Wednesday, March 4, 2009




Tropical diseases are important to us all. This section will illustrate the huge burden of mortality and morbidity that they produce. This burden is not confined to the residents of endemic countries but affects people all over the world in many ways. Malaria kills 1 million children in Africa each year; leprosy has left 4 million people with disabilities. Tropical disease also spreads beyond the tropics and may present to doctors unfamiliar with its signs and symptoms. Tourists, travellers, business people and refugees can all present with acute and chronic tropical illnesses and good physicians will ask about their patient's travel history. 

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Controlling tropical diseases has proved difficult. War can undermine good control programmes as in central Africa where trypanosomiasis is resurgent, and these programmes can be difficult to maintain. Drug resistance can emerge rapidly, as happened with malaria. Altering the environment can cause diseases such as the arboviruses Ebola and Hanta to emerge from rural habitats. Tropical disease can travel; cholera skipped continents to South America. Treatment of tropical diseases is often difficult; few new drugs have been developed and for many diseases our current treatments, such as the use of antimony for leishmaniasis, would have been familiar to physicians 50 years ago. 

Diagnosing tropical infections requires a good grasp of geography and a regular updating of disease patterns so that a patient's tropical residence can be matched against the diseases which might have been encountered. This section is organised according to the major ways in which tropical diseases present: fever, eosinophilia and skin problems. Diarrhoea is covered on pages 38-49. Running through each section is the imperative of asking your patients where they have been and what they did; this approach can make detecting tropical infections both easier and interesting.





Presentation of illness as fever is common both in patients returning from the tropics and in tropical residents. Here the presentation and management of infections that could be acquired in the tropics or during a tropical residence will be considered. Non-tropical infection may also present after tropical travel and it is important to enquire about all systems, as discussed in the investigation of a pyrexia of unknown origin (see p. 10). The common final diagnoses in febrile patients returning from the tropics are malaria, typhoid fever, viral hepatitis and dengue fever. 

In this section fevers will be considered first by their duration, acute being less than 14 days. They will then be considered by their presentation: fever without localising signs, fever and rash, fever and haemorrhage, and fever following tick bites. These categories are not mutually exclusive and diseases may have features of several categories. Disease may also have different stages of evolution; patients with leptospirosis may present with few localising signs and only develop a haemorrhagic rash later in their illness. It is only by regular re-examination of patients with fever that these evolving signs can be detected. 


Vital questions to ask anyone returning from the tropics are listed in Box 1.31. 


Where have you been?

What have you done?

How long were you there?

Did you have insect bites or contact with animals?



Geography and exposures 

It is important to establish which countries were visited and the arrival and departure dates. Most tropical infections are transmitted more easily in rural than urban centres. 


 Exposure Infection or disease

 Mosquito bite Malaria, dengue fever, filariasis

 Tsetse fly bite African trypanosomiasis

 Tick bite Typhus, Lyme disease, Crimean-Congo haemorrhagic fever, babesiosis,

   Kyasanur forest disease

 Louse bite Typhus

 Flea bite Plague, tularaemia

 Sandfly bite Visceral leishmaniasis, arboviruses

 Infected person contact Viral haemorrhagic fevers (Lassa, Ebola, Marburg, Crimean-Congo), viral hepatitis, typhoid fever, meningococcal disease

 Animal contact Q fever, brucellosis, anthrax, viral haemorrhagic fevers, histoplasmosis, rabies, plague

 Raw or uncooked foods Enteric bacterial infections, viral hepatitis

 Untreated water Enteric bacterial infections, viral hepatitis

 Unpasteurised milk Brucellosis, salmonellosis, abdominal tuberculosis

 Fresh-water swimming Schistosomiasis, leptospirosis

 Promiscuous sexual contact HIV infection, viral hepatitis B, syphilis, gonococcal bacteraemia


The potential infections acquired by an aid worker who has been working in an African rural community are different from those of a business traveller who has stayed in five-star hotels. A detailed living history should be taken, covering living and sleeping conditions, whether bed nets were used, what type of food and water was consumed, and whether there was any contact with animals, hospitals or fresh water. Sometimes there are unique exposures that point to a specific diagnosis, e.g. unprotected intercourse with a commercial sex worker. Box 1.32 lists exposures aiding diagnosis. 

Vaccinations and prophylaxis 

Ask about vaccinations and their validity; vaccinations against yellow fever, and hepatitis A and B virtually rule out these infections. Oral and injectable typhoid vaccinations are 70-90% effective. Enquire about malaria prophylaxis and establish precisely which tablets, if any, were being taken. A sexual history should always be taken. It is also useful to ask about local remedies which patients may have used, either conventional modern medicine or traditional medical preparations. Remember that locally manufactured medications may have low amounts of bio-available drugs. 


A careful examination is vital. This must be repeated regularly. Pay particular attention to the skin, throat, eyes, nail beds, lymph nodes, abdomen and heart. Patients may be unaware of tick bites or eschars (see Fig. 1.45). The temperature should be measured at least twice daily. 


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Figure 1.45 Acute fever in/from the tropics: clinical examination.


 WCC differential Potential diagnoses Further investigations

 Neutrophil leucocytosis Bacterial sepsis Blood culture

   Leptospira and  

   Borrelia infections  

     Leptospirosis Culture of blood and urine, serology

     Tick-borne relapsing fever Blood films

     Louse-borne relapsing fever Blood film

   Amoebic liver abscess Ultrasound

 Normal WCC and differential Typhoid fever Blood, stool and urine culture

   Typhus Serology

   Arboviral infection Serology (PCR and viral culture)

 Lymphocytosis Viral fevers Serology

   Infectious Monospot test

   mononucleosis Serology

   Rickettsial fevers  


Initial investigations in all settings should start with thick and thin blood films for malaria parasites, full blood count, urinalysis and chest radiograph if indicated. Box 1.33 gives the diagnoses that should be considered in acute fever with no localising signs.





In the absence of localising signs malaria is the most important diagnosis to consider. Thick and thin blood films should be taken, together with total and differential white counts and blood cultures. 


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Figure 1.46 Distribution of malaria.

Malaria is caused by Plasmodium falciparum, P. vivax, P. ovale and P. malariae. It is transmitted by the bite of female anopheline mosquitoes and occurs throughout the tropics and subtropics at altitudes below 1500 m (see Fig. 1.46). There are up to 250 million clinical cases per year and over 1 million die, mainly children. Following WHO-sponsored campaigns of prevention and effective treatment, the incidence of malaria was greatly reduced in 1950-60 but since 1970 there has been a resurgence. Furthermore, P. falciparum has now become resistant to chloroquine, notably in Asia and Africa. Due to increased travel and neglect of chemoprophylaxis, over 2000 cases are imported annually into Britain. Most are due to P. falciparum, usually from Africa, and of these 1% die because of late diagnosis. Immigrants returning home after a long residence in the UK are particularly at risk. They have lost their partial immunity and do not realise that they should be taking malaria prophylaxis. A few people living near airports in Europe have acquired malaria from accidentally imported mosquitoes. 


Life cycle of the malarial parasite 



Figure 1.47 Malarial parasites. Life cycle. Hypnozoites(*) are present only in P. vivax and P. ovale infections.

The female anopheline mosquito becomes infected when it feeds on human blood containing gametocytes, the sexual forms of the malarial parasite (see Figs 1.47 and 1.48). Development in the mosquito takes from 7-20 days. Sporozoites inoculated by an infected mosquito disappear from human blood within half an hour and enter the liver. After some days merozoites leave the liver and invade red blood cells, where further asexual cycles of multiplication take place, producing schizonts. Rupture of the schizont releases more merozoites into the blood and causes fever, the periodicity of which depends on the species of parasite. 

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Figure 1.48 Scanning electron micrograph of P. falciparum oöcysts lining the anopheline mosquito's stomach.

P. vivax and P. ovale may persist in liver cells as dormant forms, hypnozoites, capable of developing into merozoites months or years later. Thus the first attack of clinical malaria may occur long after the patient has left the endemic area, and the disease may relapse after treatment with drugs that kill only the erythrocytic stage of the parasite. 

P. falciparum and P. malariae have no persistent exoerythrocytic phase but recrudescences of fever may result from multiplication in the red cells of parasites which have not been eliminated by treatment and immune processes (see Box 1.34). 


The pathology in malaria is due to haemolysis of infected red cells and adherence of infected red blood cells to capillaries. Malaria is always accompanied by haemolysis and in a severe or prolonged attack anaemia may be profound. Anaemia is worsened by dyserythropoiesis, splenomegaly and depletion of folate stores. Haemolysis is most severe with P. falciparum, which invades red cells of all ages but especially young cells. P. vivax and P. ovale invade reticulocytes, and P. malariae normoblasts, so that infections remain lighter. 

Effects on red blood cells and capillaries 


 Cycle/feature P. vivax, P. ovale P. malariae P. falciparum

 Pre-Patent Period (Minimum Incubation) 8-25 days 15-30 days 8-25 days

 Asexual cycle 48 hrs synchronous 72 hrs synchronous <>

 Periodicity of fever 'Tertian' 'Quartan' Aperiodic

 Exo-erythrocytic cycle Persistent as hypnozoites Pre-erythrocytic only Pre-erythrocytic only

 Delayed onset Common Rare Rare

 Relapses Common up to 2 years Recrudescence many years later Recrudescence up to 1 year


In P. falciparum malaria, red cells containing schizonts adhere to capillary endothelium in brain, kidney, liver, lungs and gut. The vessels become congested and the organs anoxic. Rupture of schizonts liberates toxic and antigenic substances which may cause further damage. Thus the main effects of malaria are haemolytic anaemia and, with P. falciparum, widespread organ damage (see Box 1.35 and Fig. 1.49). P. falciparum does not grow well in red cells that contain haemoglobin F, C or especially S. Haemoglobin S heterozygotes (AS) are protected against the lethal complications of malaria. P. vivax cannot enter red cells that lack the Duffy blood group. West African and American black people are protected. 

Clinical features 

P. falciparum infection 

This is the most dangerous of the malarias. The onset is often insidious, with malaise, headache and vomiting, and is often mistaken for influenza. Cough and mild diarrhoea are also common. The fever has no particular pattern. Jaundice is common due to haemolysis and hepatic dysfunction. The liver and spleen enlarge and become tender. Anaemia develops rapidly. 

A patient with falciparum malaria, apparently not seriously ill, may develop serious complications (see Box 1.35). Cerebral malaria is the most serious complication and is manifested by either confusion or coma, usually without localising signs. Children die rapidly without any special symptoms other than fever. Immunity is impaired in pregnancy, and abortion from parasitisation of the maternal side of the placenta is frequent. Splenectomy increases the risk of severe malaria. 

P. vivax and P. ovale infection 

In many cases the illness starts with a period of several days of continued fever before the development of classical bouts of fever on alternate days. Fever starts with a rigor. The patient feels cold and the temperature rises to about 40°C. After half an hour to an hour the hot or flush phase begins. It lasts several hours and gives way to profuse perspiration and a gradual fall in temperature. The cycle is repeated 48 hours later. Gradually the spleen and liver enlarge and may become tender. Anaemia develops slowly. Herpes simplex is common. Relapses are common in the first 2 years of leaving the malarious area. 

P. malariae infection 

This is usually associated with mild symptoms and bouts of fever every third day. Parasitaemia may persist for many years with the occasional recrudescence of fever, or without producing any symptoms. P. malariae causes glomerulonephritis and the nephrotic syndrome in children. 

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 Manifestation/complication Immediate management

 Coma (cerebral malaria) Maintain airway

   Nurse on side

   Exclude other treatable causes of coma (e.g. hypoglycaemia, bacterial meningitis)

   Avoid harmful ancillary treatments such as corticosteroids, heparin and adrenaline (epinephrine)

   Intubate if necessary

 Hyperpyrexia Tepid sponging, fanning, cooling blanket

   Antipyretic drug

 Convulsions Maintain airway

   Treat promptly with diazepam or paraldehyde injection

 Hypoglycaemia Measure blood glucose

   Give 50% dextrose injection followed by 10% dextrose infusion (glucagon may be ineffective)

 Severe anaemia (packed cell volume <>

 Acute pulmonary oedema Prop up at 45°, give oxygen, venesect 250 ml of blood into donor bag, give diuretic, stop intravenous fluids

   Intubate and add PEEP/CPAP (see p. 203) in life-threatening hypoxaemia


 Acute renal failure Exclude pre-renal causes

   Check fluid balance, urinary sodium

   If urine output inadequate despite fluid replacement, give diuretic/dopamine

   Peritoneal dialysis (haemofiltration or haemodialysis if available)

 Spontaneous Bleeding And Coagulopathy Transfuse Screened Fresh Whole Blood (Cryoprecipitate/Fresh Frozen Plasma And Platelets if Available)

   Vitamin K injection

 Metabolic acidosis Exclude or treat hypoglycaemia, hypovolaemia and Gram-negative septicaemia

   Give oxygen

 Shock ('algid malaria') Suspect Gram-negative septicaemia

   Make blood cultures

   Give parenteral antimicrobials

   Correct haemodynamic disturbances

 Aspiration pneumonia Give parenteral antimicrobial drugs

   Change position


   Give oxygen

 Hyperparasitaemia (e.g. > 10% of circulating erythrocytes parasitised in non-immune patient with severe disease) Consider exchange or partial exchange transfusion, manual or haemophoresis



Thick and thin blood films should be taken whenever malaria is suspected. In the thick film erythrocytes are lysed, releasing all blood stages of the parasite. This, as well as the fact that more blood is used in thick films, facilitates the diagnosis of low-level parasitaemias. A thin film is essential to confirm the diagnosis, to identify the species of parasite and, in P. falciparum infections, to quantify the parasite load (by counting the percentage of infected erythrocytes). P. falciparum parasites may be very scanty, especially in patients who have been partially treated. With P. falciparum, only ring forms are normally seen in the early stages. With the other species all stages of the erythrocytic cycle may be found. Gametocytes appear after about 2 weeks. They persist after treatment and are harmless, but are the source for infecting mosquitoes. Immunochromatographic 'dipstick' tests for P. falciparum antigen are now marketed and provide a useful non-microscopic means of diagnosing this infection. They should be used in parallel with blood film examination but are about 100 times less sensitive than a carefully examined blood film. 


Chemotherapy of mild P. falciparum malaria 

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Figure 1.49 Organ involvement in severe malaria.

P. falciparum is now resistant to chloroquine almost worldwide, so quinine is the drug of choice as quinine dihydrochloride or sulphate 600 mg salt (10 mg/kg) 8-hourly by mouth until clinically better and the blood is free of parasites (usually 3-5 days). Reduce the dose to 12-hourly if quinine toxicity develops. This regimen should be followed by a single dose of sulfadoxine 1.5 g combined with pyrimethamine 75 mg, i.e. 3 tablets of Fansidar. In pregnancy a 7-day course of quinine alone should be given. If sulphonamide sensitivity is suspected, quinine may be followed by doxycycline 100 mg daily for 7 days. Decreased efficacy of quinine has been reported in some areas, notably the Thailand/Myanmar border. Alternatives to quinine plus Fansidar are atovaquone 250 mg plus proguanil 100 mg (Malarone) 4 tablets once daily for 3 days, or artemether 200 mg/day orally for 5 days then mefloquine 500 mg 2 doses 2 hours apart. Mefloquine may occasionally cause alarming neuropsychiatric side-effects which can persist for several days due to its plasma half-life of 14 days. 


Management of complicated P. falciparum malaria 

Severe malaria is a medical emergency and cerebral malaria is the most common presentation and cause of death in adults with malaria. Cerebral malaria is assumed when asexual parasites are present in the blood film and the patient has impaired consciousness and other encephalopathies have been excluded, particularly bacterial meningitis and locally occurring viral encephalitides. Complications of severe malaria include hypoglycaemia, severe anaemia, renal failure and metabolic acidosis (see Box 1.35). Severe malaria should be considered in any non-immune patient with a parasite count greater than 2%. 

The management of severe malaria should include early appropriate antimalarial chemotherapy, active treatment of complications, correction of fluid, electrolyte and acid-base balance, and avoidance of harmful ancillary treatments (see Box 1.36). 


Corticosteroids (dexamethasone)

Other anti-inflammatory agents

Other anti-cerebral oedema agents (urea, mannitol, invert sugar)

Low molecular weight dextran

Adrenaline (epinephrine)



Pentoxifylline (oxpentifylline)

Hyperbaric oxygen

Ciclosporin A

Hyperimmune serum

Iron-chelating agents (desferrioxamine B)

Anti-tumour necrosis factor antibodies



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Quinine is indicated if a chloroquine-resistant infection is at all likely. Although quinine resistance has increased in South-east Asia and South America, there is still no high-grade resistance that precludes its use in severe malaria. Quinine is given as an intravenous infusion over 4 hours. Treatment should be started with a loading dose infusion of 20 mg/kg quinine salt. Up to a maximum of 1.4 g quinine can be given over 4 hours, then after 8-12 hours maintenance dosage at 10 mg/kg quinine salt up to a maximum of 700 mg. The dose should be repeated at intervals of 8-12 hours until the patient can take drugs orally. The loading dose should not be given if the patient has received quinine, quinidine or mefloquine during the previous 24 hours. Quinine may instead be given intramuscularly but may cause muscle necrosis; the hydrochloride is less irritant than the dihydrochloride. Those with cardiac disease should be monitored by ECG, with special attention to QRS duration and QTc. Artemesinin derivatives may also be used as antimalarial chemotherapy. Four recently published randomised controlled trials have compared parenteral quinine and intramuscular artemether and none has shown a clear and unequivocal benefit for either drug in outcome measures as either mortality or incidence of neurological sequelae. Artesunate should be given as a loading dose 2.4 mg/kg then 1.2 mg/kg i.v. 12-hourly to a total dose of 600 mg. It can be given intramuscularly in children. Artemether is given as a loading dose 3.2 mg/kg i.m. then 1.6 mg/kg i.m. daily to a total of 640 mg. Change to an oral formulation as soon as possible. Mefloquine should not be used for severe malaria since no parenteral form is available. 

The management of severe malaria involves careful attention to all the major organ systems (see Box 1.35). Numerous ancillary treatments have been tested but none has proven beneficial (see Box 1.36). 

Exchange transfusion has not been tested in randomised controlled trials but may be beneficial for non-immune patients with persisting high parasitaemias (> 10% circulating erythrocytes). 

Cheap and affordable drugs are urgently needed for the treatment of severe malaria. A combination of chlorproguanil and dapsone (Lapdap) is in third-stage research trials in uncomplicated malaria in sub-Saharan African children. 

P. vivax, P. ovale and P. malariae infections should be treated with chloroquine; 600 mg chloroquine base followed by 300 mg base in 6 hours then 150 mg base 12-hourly for 2 more days.


Radical cure of malaria due to P. vivax and P. ovale 

Relapses can be prevented by taking one of the antimalarial drugs in suppressive doses. Radical cure is achieved in most patients by a course of primaquine (15 mg daily for 14 days), which destroys the hypnozoite phase in the liver. Haemolysis may develop in those who are glucose-6-phosphate dehydrogenase (G6PD)-deficient. Cyanosis due to the formation of methaemoglobin in the red cells is more common but not dangerous. 


Every person going to a malarious area should receive anti-malaria advice. This comprises avoiding bites and taking appropriate chemoprophylaxis. 

Avoiding mosquito bites 

This can be done by wearing long sleeves and trousers outside the house, especially at night when the anopheline mosquitoes bite. Repellent creams and sprays can be used. Screened windows, the use of a mosquito net and burning repellent coils or tablets also reduce the risk. Impregnation of bed nets with permethrin also reduces mosquito biting. 



Clinical attacks of malaria may be preventable by drugs such as proguanil which attack the pre-erythrocytic form, and also by drugs such as atovaquone 250 mg plus proguanil 100 mg (Malarone), doxycycline, chloroquine or mefloquine after the parasite has entered the erythrocyte ('suppression'). Box 1.37 gives the recommended doses for protection of the non-immune. It is important to determine the degree of risk of malaria in the area to be visited and the degree of chloroquine resistance. These factors will guide the recommendations for prophylaxis and are summarised in the British National Formulary (BNF) in the UK. Expert advice is required for individuals unable to tolerate the first-line agents listed, or in whom they are contraindicated. Doses for children vary, depending on age and body weight. Reference should be made to standard dosage recommendations (BNF). Chemoprophylaxis is begun 1 week before entering the malarious area and is continued for 4 weeks after leaving it. Resistance to the cheap and well-tolerated drug proguanil is increasing, and frequently coincides with the much more serious spread of chloroquine resistance. Chloroquine should not be taken continuously as prophylactic for over 5 years without regular ophthalmic examination, as it may cause irreversible retinopathy. Pregnant and lactating women may take proguanil or chloroquine safely. Mefloquine is contraindicated in the first trimester of pregnancy. Fansidar should not be used for chemoprophylaxis, as deaths have occurred from agranulocytosis or Stevens-Johnson syndrome (see p. 33 and 1098). Mefloquine is useful in areas of multiple drug resistance, such as East and Central Africa and Papua New Guinea. Experience shows it to be safe for at least 2 years. There are several contraindications to its use (see Box 1.37). 


 Area Antimalarial tablets Adult prophylactic dose Regimen

 Chloroquine resistance high  Mefloquine 250 mg One tablet weekly

   or Doxycycline 100 mg Daily

   or Malarone 1 tablet from 1-2 days before travelling to 1 week after return Daily

 Chloroquine resistance moderate Chloroquine 150 mg base Two tablets weekly

   plus Proguanil 100 mg Two tablets Daily

 Chloroquine resistance absent Chloroquine 150 mg base Two tablets weekly

   or Proguanil 100 mg One or two tablets daily


1Choice of regimen is determined by area to be visited, length of stay, level of malaria transmission, level of drug resistance, presence of underlying disease in the traveller and concomitant medication taken.

2Contraindicated in the first trimester of pregnancy, lactation, cardiac conduction disorders, epilepsy, psychiatric disorders; may cause neuropsychiatric disorders.

3British preparations of chloroquine usually contain 150 mg base, French preparations 100 mg base and American preparations 300 mg base. 

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Malaria control in endemic areas 

There are major initiatives under way to reduce malaria in endemic areas. The provision of permethrin-impregnated bed nets has been shown to reduce mortality in African children. WHO now has a 'Roll back malaria' programme. New combination drugs such as artemether-lumefatrine and pyronaridine are being assessed in trials. In developing new drugs known targets can be better exploited by new 4-aminoquinolones, and new targets can be identified such as the phospholipid biosynthesis inhibitors that are at an early stage of development. Trial vaccines are being evaluated in Thailand and Africa.







The combination of fever and rash in someone in or from the tropics raises a distinctive set of diagnostic possibilities (see Box 1.38). It is important to ask about and examine carefully for a rash that may be transient and minimal or may have characteristic features that aid in diagnosis, e.g. the blanching of the dengue rash. 


Ø                        1.Typhoid and paratyphoid fevers

Ø                        2.Dengue and arboviral infections

Ø      3. Leptospirosis

Ø      4.Meningococcal infections

Ø      5.Measles

Ø      6.Rickettsial infections

Ø                        7.African trypanosomiasis

Ø          8.Viral infection-EBV, CMV etc.

Ø      9.HIV seroconversion

Ø     10.Secondary syphilis

Ø     11.Connective tissue diseases

Ø      12.Cat scratch disease





In developing countries typhoid and paratyphoid fevers, which are transmitted by the faecal-oral route, are important causes of fever. Elsewhere they are relatively rare. 


The enteric fevers are caused by infection with Salmonella typhi and S. paratyphi A and B. High levels of transmission continue in India, sub-Saharan Africa and Latin America. The bacilli may live in the gallbladder of carriers for months or years after clinical recovery and pass intermittently in the stool and less commonly in the urine. The incubation period of typhoid fever is about 10-14 days; that of paratyphoid is somewhat shorter. 


After a few days of bacteraemia, the bacilli localise mainly in the lymphoid tissue of the small intestine. The typical lesion is in the Peyer's patches and follicles. These swell at first, then ulcerate and ultimately heal, but during this sequence they may perforate or bleed. 

[X] Clinical features  Typhoid fever 


Clinical features are outlined in Box 1.39. The onset may be insidious. The temperature rises in a stepladder fashion for 4 or 5 days. There is malaise, with increasing headache, drowsiness and aching in the limbs. Constipation may be present, although in children diarrhoea and vomiting may be prominent early in the illness. The pulse is often slower than would be expected from the height of the temperature, i.e. a relative bradycardia. 

At the end of the first week a rash may appear on the upper abdomen and on the back as sparse, slightly raised, rose-red spots, which fade on pressure. It is usually visible only on white skin. Cough and epistaxis occur. Around the seventh to tenth day the spleen becomes palpable. Constipation is then succeeded by diarrhoea and abdominal distension with tenderness. Severe diarrhoea has been described in HIV patients with typhoid. Bronchitis and delirium may develop. By the end of the second week the patient may be profoundly ill unless the disease is modified by antibiotic treatment. In the third week toxaemia increases and the patient may pass into coma and die. Such extreme cases are rare in countries with developed health services. 

Following recovery, up to 5% of patients become chronic carriers of S. typhi and classically such patients have gallbladder disease. 


First week

·       Fever

·       Headache

·       Myalgia

·       Relative bradycardia

·       Constipation

·       Diarrhoea and vomiting in children


End of first week

·       Rose spots on trunk

·       Splenomegaly

·       Cough

·       Abdominal distension

·       Diarrhoea


End of second week

·       Delirium, complications, then coma and death (if untreated)



Paratyphoid fever 

The course tends to be shorter and milder than that of typhoid fever and the onset is often more abrupt with acute enteritis. The rash may be more abundant and the intestinal complications less frequent. 


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§       Perforation

§       Haemorrhage

Septicaemic foci

§       Bone and joint infection

§       Cholecystitis

§       Meningitis

Toxic phenomena

§       Myocarditis

§       Nephritis



These are given in Box 1.40. Haemorrhage from, or a perforation of, the ulcerated Peyer's patches may occur at the end of the second week or during the third week of the illness. A drop in temperature to normal or subnormal levels may occur in those with intestinal haemorrhage. This can be falsely reassuring as it occurs even before there is clinical evidence of bleeding such as melaena. Additional complications may involve almost any viscus or system because of the septicaemia present during the first week; these include cholecystitis, pneumonia, myocarditis, arthritis, osteomyelitis and meningitis. Bone and joint infection is seen, especially in children with sickle-cell disease. 

[Y] Investigations  Typhoid fever 


In the first week the diagnosis may be difficult because in this invasive stage with bacteraemia the symptoms are those of a generalised infection without localising features. A white blood count may be helpful as there is typically a leucopenia. Blood culture is the most important diagnostic method in a suspected case. The faeces will contain the organism more frequently during the second and third weeks. The Widal reaction detects antibodies to the causative organisms. However, it is not a reliable diagnostic test and should be interpreted with caution, particularly in typhoid-vaccinated patients. 

[Z] Management  Typhoid fever 


Several antibiotics are effective in enteric fever. Ciprofloxacin in a dose of 500 mg 12-hourly is the drug of choice. Alternatives include co-trimoxazole (two tablets or intravenous equivalent 12-hourly), amoxicillin (750 mg 6-hourly) and chloramphenicol (500 mg 6-hourly). However, an increasing number of salmonellae, including S. typhi, are now resistant to many antibiotics and some are only sensitive to ciprofloxacin. The third generation cephalosporins, ceftriaxone and cefotaxime, are useful when the organism is resistant to ciprofloxacin. Treatment should be continued for 14 days. Pyrexia may persist for up to 5 days after the start of specific therapy. Even with effective chemotherapy there is still a danger of complications, recrudescence of the disease and the development of a carrier state. The chronic carrier should be treated for 4 weeks with ciprofloxacin; cholecystectomy may be necessary in some cases. 

[Z 1] Prevention  Typhoid fever 


Improved sanitation and living conditions reduce the incidence of typhoid. Travellers to countries where enteric infections are endemic should be inoculated with one of the three available typhoid vaccines (two inactivated injectable and one oral live attenuated). 






The dengue flavivirus is a common cause of fever in and from the tropics. It is endemic in South-east Asia and India and is also seen in Africa; there have been recent large epidemics in the Caribbean and Americas (see Fig. 1.50). The principal vector is Aedes aegypti, which breeds in standing water; collections of water in containers and tyre dumps are a particular risk in large cities. Aedes albopictus is a vector in some South-east Asian countries. There are four serotypes of dengue virus, all producing a similar clinical syndrome; homotypic immunity is life-long but heterotypic immunity between serotypes lasts only a few months. The incubation period from being bitten by an infected mosquito is usually 2-7 days. 

[X] Clinical features  DENGUE FEVER WITH RASH


The disease varies in severity. The clinical features are listed in Box 1.41. Subclinical infections are common. The morbilliform rash characteristically blanches under pressure. 



Figure 1.50 Endemic zones of yellow fever and dengue.

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·       2 days of malaise and headache

Acute onset

·       Fever, backache, arthralgias, headache, generalised pains ('breakbone fever'), pain on eye movement, lacrimation, anorexia, nausea, vomiting, relative bradycardia, prostration, depression, lymphadenopathy, scleral injection


·       Continuous or 'saddle-back', with break on fourth or fifth day; usually lasts 7-8 days


·       Transient macular in first 1-2 days. Maculo-papular, scarlet morbilliform from days 3-5 on trunk, spreading centrifugally and sparing palms and soles. May desquamate on resolution

Convalescence   (the recovery period after an illness)

·       Slow


 Dengue haemorrhagic fever or dengue shock syndrome 


This occurs mainly in children in South-east Asia (see Fig. 1.50). In mild forms there is thrombocytopenia and haemoconcentration. In the most severe form, after 3-4 days of fever, hypotension and circulatory failure develop with features of a capillary leak syndrome. Minor (petechiae, ecchymoses, epistaxis) or major (gastrointestinal bleeding) haemorrhagic signs may occur. The pathogenesis is unclear but pre-existing immunity to a dengue virus serotype heterotypic to the one causing the current infection predisposes to the syndrome. In vitro such heterotypic antibody causes enhanced virus entry and replication in monocytes; it is believed that enhancing antibody from previous dengue infection with a different serotype, or from acquired maternal antibody in infants, facilitates development of a very heavy viral load. Disseminated intravascular coagulation, complement activation and release of vasoactive mediators may contribute to the pathogenesis of the syndrome, possibly triggered by immunopathological mechanisms. Cytokine release is thought to be the cause of vascular damage at the site of post-capillary endothelial junctions. Even with good treatment the case fatality may be up to 10%. Adults rarely have classical dengue shock syndrome but may have a stormy and fatal course characterised by elevated liver enzymes, haemostatic abnormalities and gastrointestinal bleeding. 

[Y] Investigations  DENGUE FEVER WITH RASH


Diagnosis of dengue is usually easy in an endemic area when a patient has the characteristic symptoms and signs. However, mild cases may resemble other viral disease. Leucopenia is usual and thrombocytopenia common. The virus can be recovered from the blood and there are tests for viral antigen. Antibody titres rise but serological tests may detect cross-reacting antibodies from other flaviviruses, including yellow fever vaccine. 

[Z] Management and prevention DENGUE FEVER WITH RASH


There is no specific treatment. The severe pains can be relieved by paracetamol, but occasionally opiates are required. Aspirin should be avoided. Volume replacement, blood transfusions and management of shock are indicated in the capillary leak syndrome. Corticosteroids have not been shown to help. No existing antivirals are effective. 

Breeding places of Aedes mosquitoes should be abolished and the adults destroyed by insecticides. There is as yet no vaccine but a tetravalent live attenuated version is at an advanced stage of development.              








African sleeping sickness is caused by trypanosomes (see Fig. 1.51) conveyed to humans by the bites of infected tsetse flies. Two trypanosomes affect humans: Trypanosoma brucei gambiense and T. rhodesiense. Gambiense trypanosomiasis has a wide distribution in West and Central Africa reaching to Uganda and Kenya; rhodesiense trypanosomiasis is found in parts of East and Central Africa, where it is currently on the increase. In West Africa transmission is mainly at the riverside, where the fly rests in the shade of trees. Animal reservoirs of T. gambiense have not been identified. T. rhodesiense has a large reservoir in numerous wild animals and transmission takes place in the shade of woods bordering grasslands. 



Figure 1.51 Trypanosomiasis. Scanning electron micrograph showing trypanosomes swimming among erythrocytes.




A bite by a tsetse fly is painful and commonly becomes inflamed, but if trypanosomes are introduced, the site may again become painful and swollen about 10 days later ('trypanosomal chancre') and the regional lymph nodes enlarge ('Winterbottom's sign'). Within 2-3 weeks of infection the trypanosomes invade the blood stream. 

Rhodesiense infections 

In these infections the disease is more acute and severe than in gambiense infections, so that within days or a few weeks the patient is usually severely ill and may have developed pleural effusions and signs of myocarditis or hepatitis. There may be a petechial rash. The patient may die before there are signs of involvement of the central nervous system. If the illness is less acute, drowsiness, tremors and coma develop. 

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Gambiense infections 

In these infections the disease usually runs a slow course over months or years, with irregular bouts of fever and enlargement of lymph nodes. These are characteristically firm, discrete, rubbery and painless, and are particularly prominent in the posterior triangle of the neck. The spleen and liver may become palpable. After some months, in the absence of treatment, the central nervous system is invaded. This is shown clinically by headache and changed behaviour, insomnia by night and sleepiness by day, mental confusion and eventually tremors, pareses, wasting, coma and death. 




Trypanosomiasis should be considered in any febrile patient from an endemic area. In rhodesiense infections thick and thin blood films, stained as for the detection of malaria, will reveal trypanosomes. The trypanosomes may be seen in the blood or from puncture of the primary lesion in the earliest stages of gambiense infections, but it is usually easier to demonstrate them by puncture of a lymph node. Concentration methods include buffy coat microscopy and miniature anion exchange chromatography. Serological tests are useful in the diagnosis of chronic infection and are employed in fieldwork. If the central nervous system is affected, the cell count and protein content of the CSF are increased and the glucose is diminished. Very high levels of serum IgM or the presence of IgM in the CSF are suggestive of trypanosomiasis. 




The prognosis is good if treatment is begun early before the brain has been invaded. At this stage suramin or pentamidine may be used, the latter being employed only for gambiense infections. Once the nervous system is affected an arsenical or difluoromethyl ornithine will be required. 




In endemic gambiense areas various measures may be taken against tsetse flies and field teams detect and treat early human infection. In rhodesiense areas control is difficult. 



Chagas disease occurs widely in South and Central America. The cause is Trypanosoma cruzi, transmitted to humans from the faeces of a reduviid bug in which the trypanosomes have a cycle of development before becoming infective to humans. Bugs live in the mud and wattle walls and thatch roofs of simple rural houses, and emerge at night to feed on the sleeping occupants. While feeding they defaecate. Infected faeces are rubbed in through the conjunctiva, mucosa of mouth or nose or abrasions of the skin. Over 100 species of mammals, domestic, peridomestic and wild, may serve as reservoirs of infection. In some areas blood transfusion accounts for about 5% of cases. Congenital transmission occurs occasionally. 




The trypanosomes migrate via the blood stream and develop into amastigote forms in the tissues. These multiply in many sites, especially in the myocardium causing pseudocysts, in smooth muscle fibres, and also in the ganglion cells of the autonomic nervous system. 




The entrance of T. cruzi through an abrasion produces a dusky-red firm swelling and enlargement of regional lymph nodes. A conjunctival lesion, though less common, is more characteristic; the unilateral firm reddish swelling of the lids may close the eye and constitutes 'Romaña's sign'. Young children are most commonly affected. In a few patients an acute generalised infection soon appears, with a transient morbilliform or urticarial rash, fever, lymphadenopathy and enlargement of the spleen and liver. Neurological features include personality changes and signs of meningoencephalitis. The acute infection may be fatal to infants. In many patients the early infection is silent. 

After a latent period of several years features of the chronic infection appear, notably damage to Auerbach's plexus with resulting dilatation of various parts of the alimentary canal, especially the colon and oesophagus, so-called 'mega' disease. Dilatation of the bile ducts and bronchi are also recognised sequelae. Chronic low-grade myocarditis and damage to conducting fibres cause a cardiomyopathy characterised by cardiac dilatation, arrhythmias, partial or complete heart block and sudden death. Autoimmune processes may be responsible for much of the damage. There are geographical variations of the basic pattern of disease. 




T. cruzi may be seen in a blood film in the acute illness. In chronic disease it may be recovered in up to 50% of cases by xenodiagnosis in which infection-free, laboratory-bred reduviid bugs are fed on the patient; subsequently the hind gut or faeces of the bug are examined for parasites. Complement fixation, direct agglutination and fluorescent antibody tests are positive in 95% of cases. 




Nifurtimox is given orally. The dose, which has to be carefully supervised to minimise toxicity while preserving parasiticidal activity, is 10 mg/kg divided into three equal doses, daily by mouth for 60-90 days. The paediatric dose is 15 mg/kg daily. Cure rates of 80% in acute disease are obtained. Benznidazole is an alternative drug at a dose of 5-10 mg/kg daily by mouth, in two divided doses for 60 days; children receive 10 mg/kg daily. Both nifurtimox and benznidazole are toxic, with adverse reaction rates of 30-55%. Specific drug treatment of chronic Chagas disease is not usually undertaken and does not reverse established tissue damage. Surgery may be needed for 'mega' disease. 




Preventative measures include improving housing and destruction of reduviid bugs by spraying of houses with insecticides. Blood donors should be screened. 

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The major causes of fever and haemorrhage are yellow fever and the viral haemorrhagic fevers (VHF). These fevers all occur in well-recognised geographical areas and have a non-specific presentation with fever and myalgia. Diagnosis rests on being aware that the patient has travelled to a yellow fever or VHF area, together with excluding other causes of fever, principally malaria. 


Yellow fever, caused by a flavivirus, is normally a zoonosis of monkeys (zoonoses-diseases of animals which can be transmitted to man ex-rabies,bovine TB)  that inhabit tropical rainforests in West and Central Africa and South and Central America, among whom it may cause devastating epidemics (see Fig. 1.50). It is transmitted by mosquitoes living in tree-tops. Aedes africanus in Africa and the Haemagogus species in America are the vectors. The infection is brought down to humans either by infected mosquitoes when trees are felled, or by monkeys raiding human settlements. In towns yellow fever may be transmitted between humans by Aedes aegypti, which breeds efficiently in small collections of water. The distribution of this mosquito is far wider than that of yellow fever and poses a continual risk of spread. It is surprising that there is no yellow fever in Asia; this may be because there are strain differences between the Asian and African Aedes mosquitoes or there may be unrecognised demographic obstacles to transmission. 

Humans are infectious during the viraemic phase, which starts 3-6 days after the bite of the infected mosquito and lasts for 4-5 days. The incubation period is 3-6 days. 




In the liver, acute mid-zonal necrosis leads to deposits of hyalin called Councilman bodies, and intranuclear eosinophilic inclusions called Torres bodies. Another characteristic feature is the absence of inflammatory infiltrate. The kidneys show tubular degeneration, which may partly be due to reduced blood flow. Widespread petechial haemorrhages are most marked in the stomach and duodenum. Haemorrhage is due to liver damage and disseminated intravascular coagulation. 




Yellow fever is often a mild febrile illness lasting less than a week. However, the classical disease starts suddenly with rigors and high fever. Backache, headache and bone pains are severe. Nausea and vomiting then develop. The face is flushed and the conjunctivae are injected. Bradycardia and leucopenia are characteristic of this phase of the illness, which lasts 3 days and is followed by a remission lasting a few hours or days. The fever then returns with acute hepatic and renal failure. There is jaundice and a haemorrhagic diathesis with petechiae, haemorrhages into the mucosa and gastrointestinal bleeding plus oliguria. Patients commonly die in the third stage, often after a period of coma. 


·       Clinical features in endemic area

·       Virus isolation from blood in first 4 days

·       Fourfold rise in antibody titre

·       Post-mortem liver biopsy

·       Differentiate from malaria, typhoid, viral hepatitis, leptospirosis, haemorrhagic fevers, aflatoxin poisoning






Diagnostic procedures are listed in Box 1.42.(see above) 




Treatment is supportive, with meticulous attention to fluid and electrolyte balance, urine output and blood pressure. Blood transfusions, plasma expanders and peritoneal dialysis may be necessary. Patients should be isolated as their blood and body products may contain viral particles. 




A single vaccination with the 17D non-pathogenic strain of virus gives full protection for at least 10 years. The vaccine does not produce appreciable side-effects, unless there is allergy to egg protein. Vaccination is not recommended in people who are immunosuppressed, whether it be the result of immunosuppressive therapy or of underlying disease. 





The viral haemorrhagic fevers are zoonoses caused by several different viruses (see Box 1.43). They are endemic world-wide, each virus having its own niche. They are mainly rural and transmission is associated with poverty and poor medical facilities. Dengue has already been described (see p. 58). Serological surveys have shown that Lassa fever is widespread in West Africa where it accounts for 15% of adult hospital admissions and 50% of adults have antibodies. Ebola and Marburg viruses cause small epidemics but with high fatality rates. The most recent Ebola outbreak was in Uganda in 2000-2001. Lassa fever remains very rare in Britain, with about 1 case arriving in the country every 2 years. Patients returning from rural Africa with a fever should be put into isolation until a diagnosis is made. It is vital to exclude malaria in these patients. Ask about contact with potential animal vectors, hospitals and attendance at ritual funerals.                Kyasanur forest disease is a tick-borne viral haemorrhagic fever currently confined to a small focus in Karnataka, India and causing about 500 cases annually. Monkeys are the principal hosts but with forest felling there are fears that this disease will increase. 




The virus causes endothelial dysfunction with the development of leaky capillary syndrome. Hypovolaemic shock and acute respiratory distress syndrome develop (see p. 198). 

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 Disease Reservoir Transmission Geography Case mortality Clinical features

 Lassa fever Multimammate rat (Mastomys natalensis) Urine West Africa Up to 50% (responds to ribavirin) Encephalopathy ARDS

   Patient Body fluids      

 Marburg/Ebola virus disease ? Patient Via monkeys' body fluids Central Africa 25-90% Thrombocytopenia

Blood oozing

 Yellow fever Monkeys Mosquitoes Tropical Africa, South and Central America 10-60% Hepatic failure

Blood oozing

 Dengue Humans Aedes aegypti et al. Tropical and subtropical coasts Nil-10% Joint and bone pain


 Crimean-Congo Ixodes tick Ixodes tick Africa, Asia, Eastern Europe 15-70% Thrombocytopenia

Blood oozing


 Bolivian and Argentinian Rodents (Calomys spp.) Urine South America ? Thrombocytopenia


 Haemorrhagic fever with renal syndrome (Hantan fever) Rodents Faeces Northern Asia, northern Europe 30% Petechiae Renal failure ARDS


1 All have circulatory failure.

2 Mortality of uncomplicated and haemorrhagic dengue fever, respectively. 




All the haemorrhagic fevers start with high fever and severe body pains. Sore throat is another feature. In Lassa fever retrosternal pain, pharyngitis and proteinuria had a positive predictive value of 80% in West Africa. Joint and abdominal pain are prominent in Lassa fever. A macular blanching rash may be present, but bleeding is unusual, occurring in only 20% of hospitalised patients. Bradycardia and ECG abnormalities are common. Encephalopathy may develop. Deafness affects 30% of survivors. 




There is leucopenia, thrombocytopenia and proteinuria. In Lassa fever an aspartate amino transferase (AST) > 150 i.u./l is associated with a 50% mortality. 




The causative virus may be isolated, or antigen-detected, in maximum security laboratories from serum, pharynx, pleural exudate and urine. The diagnosis should be considered in the UK and other non-endemic areas in patients presenting with fever within 21 days of leaving West Africa, particularly if they have organ failure or haemorrhagic features (although most patients initially suspected of having viral haemorrhagic fevers in the UK turn out to have malaria). 




Strict isolation and general supportive measures, preferably in a special unit, are required. Ribavirin is given intravenously (100 mg/kg, then 25 mg/kg daily for 3 days and 12.5 mg/kg daily for 4 days). Isolation and good infection control practices will prevent further transmission. 




Ribavirin has been used as prophylaxis in close contacts of Lassa fever patients but there are no formal trials of its efficacy.








There is a group of acute febrile illnesses transmitted by arthropods exemplified by rickettsial fevers, Lyme disease, plague and babesiosis. It is important to ask about exposures that would put patients at risk of bites or contact with ticks, lice or fleas. 


The rickettsial fevers are the most common of the tick-borne infections and present acutely with headache, skin rash and sometimes neurological disturbance. There are three main groups of rickettsial fevers, as described below; these are compared in Box 1.44. 

[X1] Pathogenesis 

The rickettsia are intracellular Gram-negative organisms which parasitise the intestinal canal of arthropods. Infection is usually conveyed to humans through the skin from the excreta of arthropods but the saliva of some biting vectors is infected. The organisms multiply in capillary endothelial cells, producing lesions in the skin, central nervous system, heart, lungs, kidneys and skeletal muscles. Endothelial proliferation, associated with a perivascular reaction, may cause thromboses and small haemorrhages. In epidemic typhus the brain is the target organ; in scrub typhus the cardiovascular system and lungs are particularly attacked. An eschar is often found in tick- and mite-borne typhus. An eschar is a necrotic sore, often scabbed, at the site of the bite and is due to vasculitis following immunological recognition of the inoculated organism. Regional lymph nodes often enlarge. 

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 Disease Reservoir Vector Primary complex Rash Gangrene Target organs Mortality

 Rocky Mountain spotted fever Rodents, dogs, ticks Ixodes Tick Often Morbilliform Haemorrhagic Often Bronchi, Myocardium, brain, skin 2-12%

 Other tick-orne typhus Rodents, dogs, ticks Ixodes tick Usual Maculo-papular - Skin, meninges Rare3

 Scrub typhus Rodents, mites Trombicula mite Often Maculo-papular Unusual Bronchi, myocardium, brain, skin Rare3

 Epidemic typhus Humans Louse - Morbilliform Haemorrhagic Often Brain, skin, bronchi, myocardium Up to 40%

 Endemic typhus Rats Flea - Slight - - Rare3


1Eschar at bite site and local lymphadenopathy.

2Highest in adult males.

3Except in infants, elderly and debilitated. 

Spotted fever group 

Rocky Mountain spotted fever. Rickettsia rickettsii is transmitted by tick bites. It is widely distributed and increasing in western and south-eastern states of the USA and also in South America. The incubation period is about 7 days. The rash appears on about the third or fourth day, and is at first like measles, but in a few hours the typical maculo-papular eruption develops. The rash first appears on the wrists, forearms and ankles, and spreads in 24-48 hours to the back, limbs and chest and lastly to the abdomen where it is least pronounced. Larger cutaneous and subcutaneous haemorrhages may appear in severe cases. The liver and spleen become palpable. At the extremes of life the mortality is 5-10%. 

Tick-borne South African typhus. R. conorii causes Mediterranean and African tick typhus, which also occurs in the Indian subcontinent. Infected ticks may be picked up by walking on grasslands or dogs may bring ticks into the house. A careful search is needed to find the tell-tale eschar, and a maculo-papular rash on the trunk, limbs, palms and soles. There may be delirium and meningeal signs in severe infections but recovery is the rule. 

Typhus group 

Scrub typhus fever. Scrub typhus is caused by R. tsutsugamushi, transmitted by mites. It occurs in the Far East, Myanmar, Pakistan, Bangladesh, India, Indonesia, the South Pacific islands and Queensland, particularly where patches of forest cleared for plantations have attracted rats and mites. 

In many patients one eschar or more develops, surrounded by an area of cellulitis and enlargement of regional lymph nodes. The incubation period is about 9 days. 

Mild or subclinical cases are common. The onset of symptoms is usually sudden with headache, often retro-orbital, fever, malaise, weakness and cough. In severe illness the general symptoms increase, with apathy and prostration. An erythematous maculo-papular rash often appears on about the fifth to the seventh day and spreads to the trunk, face and limbs including the palms and soles, with generalised painless lymphadenopathy. The rash fades by the 14th day. The temperature rises rapidly and continues as a remittent fever with sweating until it falls by lysis on about the 12th-18th day. In severe infection the patient is prostrate with cough, pneumonia, confusion and deafness. Cardiac failure, renal failure and haemorrhage may develop. Convalescence is often slow and tachycardia may persist for some weeks. 

Epidemic (louse-borne) typhus. Epidemic typhus is caused by R. prowazekii and is transmitted by infected faeces of the human body louse usually through scratching the skin. Patients suffering from epidemic typhus infect the lice, which leave when the patient is febrile. In conditions of overcrowding the disease spreads rapidly. It is prevalent in parts of Africa, especially Ethiopia and Rwanda, and in the South American Andes and Afghanistan. Large epidemics have occurred in Europe, usually as a sequel to war. The incubation period is usually 12-14 days. 

There may be a few days of malaise but the onset is more often sudden with rigors, fever, frontal headaches, pains in the back and limbs, constipation and bronchitis. The face is flushed and cyanotic, the eyes are congested and the patient soon becomes dull and confused. 

The rash appears on the fourth to the sixth day and often resembles measles. In its early stages it disappears on pressure but soon becomes petechial with subcutaneous mottling. It appears first on the anterior folds of the axillae, sides of the abdomen or backs of hands, then on the trunk and forearms. The neck and face are seldom affected. 

During the second week symptoms increase in severity. Sores develop on the lips. The tongue becomes dry, brown, shrunken and tremulous. The spleen is palpable, the pulse feeble and the patient stuporous and delirious. The temperature falls rapidly at the end of the second week and the patient recovers gradually. In fatal cases the patient usually dies in the second week from toxaemia, cardiac or renal failure, or pneumonia. 

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Endemic (flea-borne) typhus. Flea-borne or 'endemic' typhus caused by R. mooseri is endemic world-wide. Humans are infected when the faeces or contents of a crushed flea which has fed on an infected rat are introduced into the skin. The incubation period is 8-14 days. The symptoms resemble those of a mild louse-borne typhus. The rash may be scanty and transient. 

[Y] Investigations 

Routine blood investigations are unhelpful. Diagnosis is made on clinical grounds and response to treatment. Differential diagnoses include malaria, typhoid, meningococcal sepsis and leptospirosis. 

The Weil-Felix reaction is the non-specific agglutination of the somatic antigens of non-motile Proteus species by the patient's serum. A fourfold rise in titre is diagnostic. 

Species-specific antibodies may be detected by complement fixation, microagglutination and fluorescence in specialised laboratories. 

[Z] Management of the rickettsial diseases 

The different rickettsial fevers vary greatly in severity but all respond to tetracycline or chloramphenicol. Tetracycline is given 500 mg 6-hourly for 7 days, chloramphenicol 500 mg 6-hourly for 7 days. Louse-borne typhus and scrub typhus can be treated with a single dose of 200 mg doxycycline, repeated for 2-3 days to prevent relapse. Chloramphenicol- and doxycycline-resistant strains of R. tsutsugamushi have been reported from Thailand and patients here may need treatment with rifampicin. 

Nursing care is important, especially in epidemic typhus. Sedation may be required for delirium and blood transfusion for haemorrhage. Relapsing fever and typhoid are common intercurrent infections in epidemic typhus, and pneumonia in scrub typhus. They must be sought and treated. Convalescence is usually protracted, especially in older people. 

[Z1] Prevention of rickettsial infections 

Vector and reservoir control 

Lice, fleas, ticks and mites need to be controlled with insecticides. 



See page 21. 



The human body louse, Pediculus humanus, causes itching. Borreliae (B. recurrentis) are liberated from the infected lice when they are crushed during scratching, which also inoculates the borreliae into the skin. 


The borreliae multiply in the blood, where they are abundant in the febrile phases, and invade most tissues, especially the liver, spleen and meninges. Hepatitis causing jaundice is frequent in severe infections and there may be petechial haemorrhages in the skin, mucous membranes and serous surfaces of internal organs. Thrombocytopenia is marked. 



Figure 1.52 Louse-borne relapsing fever. Injected conjunctivae.

[X] Clinical features 

Onset is sudden with fever. The temperature rises to 39.5-40.5°C and is accompanied by a rapid pulse, headache, generalised aching, injected conjunctivae (see Fig. 1.52) and frequently a petechial rash, epistaxis and herpes labialis. As the disease progresses, the liver and spleen frequently become tender and palpable and jaundice is common. There may be severe serosal and intestinal haemorrhage. Mental confusion and meningism may occur. The fever ends by crisis between the fourth and tenth days, often associated with profuse sweating, hypotension, circulatory and cardiac failure. There may be no further fever but in a proportion of patients, after an afebrile period of about 7 days, there may be one or more relapses which are usually milder and less prolonged. In the absence of specific treatment the mortality rate may be as high as 40%, especially among the elderly and malnourished. 

[Y] Investigations 

The organisms are demonstrated in the blood during fever either by dark ground illumination of a wet film or by staining thick and thin films. 

[Z] Management 

The problems of treatment are to eradicate the organism, to minimise the severe Jarisch-Herxheimer reaction (JHR-see p. 100) which inevitably follows successful chemotherapy, and to prevent relapses. The safest treatment is procaine benzylpenicillin (procaine penicillin) 300 mg intramuscularly, followed the next day by 0.5 g tetracycline. Tetracycline alone is effective and prevents relapse, but may give rise to a worse reaction. Doxycycline, 200 mg once by mouth as an alternative to tetracycline, has the advantage of also being curative for typhus, which often accompanies epidemics of relapsing fever. JHR is best managed in a high-dependency unit with expert nursing and medical care. 


The patient, clothing and all contacts must be freed from lice as in epidemic typhus. 



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Epidemics of plague, such as the 'Black Death', have attacked humans since ancient times. The disease continues to have a rat reservoir. Plague foci are widely distributed throughout the world and human cases are reported from about 10 countries per year. There was an outbreak of plague in India in 1994 centred around Surat (see Fig. 1.53). The causative organism, Yersinia pestis, is a small Gram-negative bacillus. It is spread between rodents by their fleas. If domestic rats become infected, infected fleas may bite humans. In the late stages of human plague, Y. pestis may be expectorated and spread between humans by droplets. 'Pneumonic plague' may follow. Hunters and trappers can contract plague from handling rodents. 



Organisms inoculated through the skin are taken rapidly to the draining lymph nodes where they elicit a severe inflammatory response that may be haemorrhagic. If the infection is not contained, septicaemia ensues and necrotic, purulent or haemorrhagic lesions develop in many organs. Oliguria and shock follow, and disseminated intravascular coagulation may result in widespread haemorrhage. Inhalation of Y. pestis causes alveolitis. The incubation period is 3-6 days, but less in pneumonic plague. 

Bubonic plague 

In this, the most common form of the disease, the onset is usually sudden with a rigor, high fever, dry skin and severe headache. Soon, aching and swelling at the site of the affected lymph nodes begin. The groin is the most common site of the bubo, made up of the swollen lymph nodes and surrounding tissue. Some infections are relatively mild but in the majority of patients toxaemia quickly increases with a rapid pulse, hypotension and mental confusion. The spleen is usually palpable. 

Septicaemic plague 



Figure 1.53 Foci of the transmission of plague.

Those not exhibiting a bubo usually deteriorate rapidly. Meningitis, pneumonia and expectoration of blood-stained sputum containing Y. pestis may complicate bubonic or septicaemic plague. 

Pneumonic plague 

The onset is very sudden with cough and dyspnoea. The patient soon expectorates copious blood-stained, frothy, highly infective sputum, becomes cyanosed and dies. Radiographs of the lung show a lobar opacity. 




Early diagnosis is urgent and requires a high index of clinical suspicion. Delayed diagnosis is associated with a high case fatality rate. An aspirate from a bubo, sputum or the buffy coat (leucocyte fraction) of blood is used to show the characteristic organism by staining with methylene blue or by immunofluorescence. Blood, sputum and aspirate should be cultured. Plague is notifiable under the international health regulations. 




If the diagnosis is suspected on clinical and epidemiological grounds, treatment must be started as soon as, or even before, samples have been collected for laboratory diagnosis. Streptomycin (1 g 12-hourly) or gentamicin (1 mg/kg 8-hourly) are the drugs of choice. Tetracycline (500 mg 6-hourly) and chloramphenicol (12.5 mg/kg 6-hourly) are alternatives. Treatment may also be needed for acute circulatory failure, disseminated intravascular coagulation or hypoxia. 




Rats and fleas should be controlled. In endemic areas people should avoid handling and skinning wild animals. 

A formalin-killed vaccine is available for those at occupational risk. Patients are isolated and attendants must wear gowns, masks and gloves. Contacts should be protected by tetracycline 2 g daily, or co-trimoxazole one tablet daily for a week. 

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This is caused by a tick-borne intra-erythrocytic protozoan parasite. Patients present with fever 1-4 weeks after a tick bite. Severe illness is seen in splenectomised patients. The diagnosis is made by blood film examination. Treatment is with quinine and clindamycin.






Chronic fever can be defined as a fever lasting more than 14 days. When this is in a patient in or returned from the tropics it is imperative to take and retake a careful history looking for risk factors, and to carry out repeated examinations to detect new signs. The principal infectious causes of chronic fever are listed in Box 1.45. It is especially important to consider tuberculosis and HIV infection (see Box 1.46, p. 121 and p. 532). 


*                      1.Typhoid

*                      2.Tuberculosis

*                      3.HIV

*                      4.Amoebic liver abscess

*                      5.Visceral leishmaniasis[KALA-AZAR]

*                      6.Brucellosis

*                      7.Melioidosis

*                      8.Q fever

*                      9.African trypanosomiasis




 WCC differential                            Potential diagnoses

*   Neutrophil leucocytosis                                                                                                                 Deep sepsis/abscess*

   Amoebic liver abscess


*   Eosinophilia                                                                                                                                  Invasive schistosomiasis

   Other invasive parasitic infections

*   Leucopenia                                                                                                                                                                                            Malaria

   Disseminated tuberculosis

   Visceral leishmaniasis


*   Normal WCC                                                                                                                                                    Localised tuberculosis


   Secondary syphilis



   Subacute bacterial endocarditis


   Chronic meningococcal septicaemia

*   Variable WCC                                                                                                                                         Tumours


   Drug reactions

   Connective tissue disease


*May show spiking fever. 



This often occurs without a history of recent diarrhoea. It is common in the tropics and an important cause of imported fever in Britain. The life cycle of the amoeba is shown in Figure 1.43, page 46. 




Amoebic trophozoites emerge from the vegetative cyst form in the colon and may invade the bowel mucosa. They may enter a portal venous radicle and be carried to the liver where they multiply rapidly and destroy the parenchyma, causing an amoebic abscess. The liquid contents at first have a characteristic pinkish colour which may later change to chocolate brown. 




The abscess is usually found in the right hepatic lobe. Early symptoms may be local discomfort only and malaise; later, a swinging temperature and sweating may develop. An enlarged, tender liver, cough, and pain in the right shoulder are characteristic, but symptoms may remain vague and signs minimal. The absence of toxicity in the presence of a high swinging fever is noticeable. The less common abscess in the left lobe is difficult to diagnose. There is usually neutrophil leucocytosis and a raised diaphragm, with diminished movement on the right side. A large abscess may penetrate the diaphragm and rupture into the lung, from where its contents may be coughed up. Rupture into the pleural cavity, the peritoneal cavity or pericardial sac is less common but more serious. 




An amoebic abscess of the liver is suspected from the clinical and radiographic appearances and confirmed by ultrasonic scanning. Aspirated pus from an amoebic abscess has the characteristic appearance described above but only rarely contains free amoebae. 

Antibodies are detectable by immunofluorescence in over 95% of patients with hepatic amoebiasis. 




Early hepatic amoebiasis responds promptly to treatment with metronidazole (800 mg 8-hourly for 5 days) or tinidazole (2 g daily for 3 days) as above. The luminal amoebicide diloxanide furoate (500 mg 8-hourly for 10 days) is given to eliminate the intestinal infection. If the abscess is large or threatens to burst, or if the response to chemotherapy is not prompt, aspiration is required and repeated if necessary. Rupture of an abscess into the pleural cavity, pericardial sac or peritoneal cavity necessitates immediate aspiration or surgical drainage. Small serous effusions resolve without drainage. 



Leishmaniasis may take the form of a generalised visceral febrile infection, kala-azar, or of a purely cutaneous infection, known in the Old World as oriental sore. In South America cutaneous leishmaniasis may remain confined to the skin or metastasise to the nose and mouth. The cutaneous forms are discussed on pages 83-84. The distribution of leishmaniasis is shown in Figure 1.64, page 83. 

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Figure 1.54 Leishmaniasis. A Life cycle of leishmania. (A = amastigote (Leishman-Donovan body); P = promastigote) B Bone marrow smear showing numerous intracellular, and a few extracellular, amastigotes.

Visceral leishmaniasis is caused by the protozoon Leishmania donovani and transmitted by the phlebotomine sandfly (see Fig. 1.54). It is prevalent in the Mediterranean and Red Sea littorals, Sudan, parts of East Africa, Asia Minor, mountainous regions of southern Arabia, eastern parts of India, China and South America. In India there is currently a massive epidemic centred around Bihar; here humans are the chief hosts. In most other areas, including the Mediterranean, dogs and foxes are the main reservoirs of infection. In these regions the disease is endemic and occurs chiefly in young children or tourists. In Africa various wild rodents provide the reservoir, and the disease is rural, occurring in older children and visiting hunters and soldiers. Transmission has also been reported to follow blood transfusion in northern Europe. The disease has presented unexpectedly in immunosuppressed patients-for example, after renal transplantation and in AIDS. 



Multiplication of leishmaniae takes place in macrophages, especially in the liver and spleen, the bone marrow and lymphoid tissue. The disease is accompanied by malnutrition and immunosuppression. Acute intercurrent pneumococcal infection or tuberculosis is a common complication. Granulocytopenia and thrombocytopenia occur. Anaemia is due to haemolysis, hypersplenism and ineffective erythropoiesis. Serum albumin is low and globulin, mainly IgG, high. Hepatocellular damage and bleeding are late complications. 

[X] Clinical features  KALA-AZAR CHRONIC FEVER 


The incubation period is usually about 1 or 2 months but may be up to 10 years. The onset is usually insidious with a low-grade fever, the patient remaining ambulant, or it may be abrupt with sweating and high intermittent fever, sometimes showing a double rise of temperature in 24 hours. The spleen soon becomes enlarged, often massively; hepatomegaly is less marked. If not treated, the patient will become anaemic and wasted, frequently with increased pigmentation, especially on the face. Cough and diarrhoea develop. In Africa lymphadenopathy is common, and is rarely the only clinical finding. 

After recovery post-kala-azar dermal leishmaniasis sometimes develops. It may present first as hypopigmented or erythematous macules on any part of the body or as a nodular eruption especially on the face. 

[Y] Investigations  KALA-AZAR CHRONIC FEVER 


Diagnosis is established by demonstrating the parasite in stained smears of aspirates of bone marrow, lymph node, spleen or liver, or by culture of these aspirates. PCR is also useful in confirming speciation. Amastigotes are scanty in skin biopsies from post-kala-azar dermal leishmaniasis. Antibody is detected by immunofluorescence or the direct agglutination test early in the disease. The leishmanin skin test is negative; it is performed and read in the same way as the tuberculin test, using a suspension of killed promastigotes as antigen. 



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The response to treatment varies with the geographic area in which the disease has been acquired. In Europe the disease is readily cured. Resistance to antimonials has become a problem in India and Sudan. Where resources permit, liposomal amphotericin B is the drug of choice for visceral leishmaniasis. The dosage regimen is 2-3 mg/kg per dose, equivalent to 21-24 mg/kg total dose for the course, given in seven doses over 10 days. However, pentavalent antimonials remain the drugs of choice in many areas when cost, availability, efficacy and familiarity are considered. Sodium stibogluconate contains 100 mg Sb/ml; the Indian preparation meglumine antimoniate contains 85 mg Sb/ml. The dose is 20 mg Sb/kg i.v. or i.m. daily for 20-30 days. It may be reduced progressively by 2 mg Sb/kg if not well tolerated. The principal side-effects of sodium stibogluconate are myalgia, cardiac toxicity and pancreatitis. A new oral preparation, miltefosine, has undergone trials in India where a 28-day course gave 100% cure. There was little associated toxicity but anxieties about potential teratogenicity have not yet been resolved. 

Intercurrent infection is sought and treated. Rarely, blood transfusion is needed for anaemia or bleeding. Measurement of spleen size, haemoglobin and serum albumin are useful in assessing progress. A small proportion of patients relapse, and should be retreated for 2 months with a full 20 mg Sb/kg daily. Patients with HIV and visceral leishmaniasis are particularly difficult to treat. They have a reduced response rate to therapy and invariably relapse. 



Infected or stray dogs should be destroyed in an endemic area, where they are the reservoir. Sandflies should be combated. They are extremely sensitive to insecticides. Mosquito nets treated with permethrin will keep out the tiny sandfly. Insect repellent creams may be helpful. 

Early diagnosis and treatment of human infections reduce the reservoir and control epidemic kala-azar in India. Serology is useful for case detection in the field. There is no vaccine currently available.






In many parts of the developing world diphtheria remains an important cause of illness, having been eradicated from much of the developed world by mass vaccination in the mid-20th century. Recent outbreaks have occurred in the former Soviet Union and continue to occur in South-east Asia. The disease is notifiable in all countries of Europe and North America and international guidelines have been produced by WHO for the management of infection. 

Infection with Corynebacterium diphtheriae occurs most commonly in the upper respiratory tract, and sore throat is frequently the presenting feature. The disease is usually spread by droplet infection from cases or carriers. The organisms remain localised at the site of infection and serious consequences result from the absorption of a soluble exotoxin which damages the heart muscle and the nervous system. Infection may occur rarely on the conjunctiva or in the genital tract, or may complicate wounds, abrasions or diseases of the skin, especially in chronic lesions and alcoholics. 

The average incubation period is 2-4 days. Cases must be isolated until cultures from three daily nose and throat swabs are negative. 


Acute infection

·       Membranous tonsillitis

·       or Nasal infection

·       or Laryngeal infection

·       or Skin/wound/conjunctival infection (rare)


·       Laryngeal obstruction or paralysis

·       Myocarditis

·       Peripheral neuropathy



[X] Clinical features (see Box 1.47) DIPHTHERIA

The disease begins insidiously. Fever is seldom significant although tachycardia is usually marked. The diagnostic feature is the 'wash-leather' elevated greyish-green membrane on the tonsils. It has a well-defined edge, is firm and adherent, and is surrounded by a zone of inflammation. There may be swelling of the neck ('bull-neck') and tender enlargement of the lymph nodes. In the mildest infections, especially in the presence of a high degree of immunity, a membrane may never appear and the throat is merely slightly injected. 

With anterior nasal infection there is nasal discharge, frequently blood-stained. In laryngeal diphtheria a husky voice and high-pitched cough signal potential respiratory obstruction requiring urgent tracheostomy. If infection spreads to the uvula, fauces and the nasopharynx, the patient is gravely ill. Death from acute circulatory failure may occur within the first 10 days. 

Late complications occur as a result of toxin action on heart or nervous system. About 25% of survivors of the early toxaemia may later develop myocarditis with arrhythmias or cardiac failure. These are usually reversible with no permanent damage other than heart block in survivors. 

Neurological involvement occurs in 75% of cases. After tonsillar or pharyngeal diphtheria it usually commences after 10 days with palatal palsy. Paralysis of accommodation often follows, manifest by difficulty in reading small print. Generalised polyneuritis with weakness and paraesthesia may follow in the next 10-14 days. Recovery from such neuritis is always ultimately complete. 

[Z] Management DIPHTHERIA

A clinical diagnosis of diphtheria must be notified to the public health authorities and sent urgently to a hospital for infectious diseases. Treatment should begin once appropriate swabs have been taken before waiting for microbiological confirmation. Three main areas of management are:

administration of diphtheria antitoxin

administration of antibiotics

strict isolation procedures.

Antitoxin has no neutralising effect on toxin already fixed to tissues so must be injected intramuscularly without awaiting the result of a throat swab. However, since the antitoxin is hyperimmune horse serum, undesirable reactions to this foreign protein may occur. A potentially lethal immediate anaphylactic reaction with dyspnoea, pallor and collapse is recognised. 'Serum sickness' with fever, urticaria and joint pains may occur 7-12 days after injection. A careful history of previous horse serum injections or allergic reactions should alert the physician. A small test injection of serum should be given half an hour before the full dose in every patient. Adrenaline (epinephrine) solution must be available to deal with any immediate type of reaction (0.5-1.0 ml of 1/1000 solution i.m.). An antihistamine is also given. 

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In a severely ill patient the risk of anaphylactic shock is outweighed by the mortal danger of diphtheritic toxaemia and up to 100 000 units of antitoxin are injected intravenously if the test dose has not given rise to symptoms. For disease of moderate severity, 16 000-40 000 units i.m. will suffice, and for mild cases 4000-8000 units. 

Penicillin 1200 mg 6-hourly i.v. or amoxicillin 500 mg 8-hourly should be administered for 2 weeks to eliminate C. diphtheriae. Patients allergic to penicillin can be given erythromycin. Due to poor immunogenicity all sufferers should be immunised with diphtheria toxoid following recovery. Patients must be managed in strict isolation attended by staff with a clearly documented immunisation history until three swabs 24 hours apart are culture-negative. 

[Z1] Prevention  DIPHTHERIA

Active immunisation should be given to all children (see Appendix). If diphtheria occurs in a closed community, contacts should be given erythromycin, which is more effective than penicillin in eradicating the organism in carriers. All contacts should also be immunised or given a booster dose of toxoid. Adults should be given a dilute preparation of vaccine to avoid severe reactions.






Eosinophilia is associated with parasite infections, particularly those with a tissue migration phase during their life cycle. Eosinophils have an important role in mediating antibody-dependent damage to helminths, phagocytosing immune complexes and modulating type 1 hypersensitivity reactions. Anybody with an eosinophil count of > 0.4 × 109 should be investigated for both parasitic and non-parasitic causes of eosinophilia. Box 1.48 gives the main causes of eosinophilia, Box 1.49 the main parasitic causes and Box 1.50 the tropical diseases that are not associated with eosinophilia. 

This section covers the major parasite infestations associated with eosinophilia, the soil-transmitted helminths, the filariases and schistosomiasis. A few non-eosinophil-associated worms will also be considered here. The response to parasite infections is often different when travellers and residents of endemic areas are compared. Travellers will often have recent and light infections associated with eosinophilia. Residents have often been infected for a long time, have evidence of chronic pathology and no longer have an eosinophilia. 


*                     1.Metazoan parasite infections

*                     2.Atopy and allergic drug reactions

*                     3.Skin diseases

*                     4.Pulmonary eosinophilia

*                     5.HIV, human T-cell lymphotropic virus 1 (HTLV 1)

*                     6.Lymphomas

*                     7.Leukaemias

*                     8.Polyarteritis nodosa

*                     9.Sarcoidosis

*                     10.Hypereosinophilic syndrome




 Infestation Pathogen Clinical syndrome associated with eosinophilia

 Strongyloidiasis Strongyloides stercoralis  

 Soil-transmitted helminthiases    

 Hookworm Necator americanus  

   Ancylostoma duodenale  

 Ascariasis Ascaris lumbricoides Loeffler's syndrome

 Toxocariasis Toxocara canis Visceral larva migrans

 Schistosomiasis Schistosoma  


   S. mansoni  

   S. japonicum  


 Loiasis Loa loa  

 Wuchereria bancrofti W. bancrofti  

 Brugia malayi B. malayi  

 Mansonella perstans M. perstans  

 Onchocerciasis Onchocerca volvulus  

 Cysticercosis Taenia saginata Migratory phase

   T. solium  

 Hydatid disease Echinococcus granulosus Leakage from cyst

 Liver flukes Fasciola hepatica Migratory phase

   Clonorchis sinensis  

   Opisthorchis felineus  



Ø    1.Amoebiasis

Ø    2.Arboviral infections

Ø    3.Brucellosis

Ø    4.Enteric fever

Ø    5.Giardiasis

Ø    6.Leishmaniasis

Ø    7.Leprosy

Ø    8.Malaria

Ø    9.Trypanosomiasis

Ø    10.Tuberculosis

Ø    11.Tapeworms



[X2] History 

A careful geographical history and an awareness of the overlap between where the patient has travelled to and the known endemic areas for diseases such as schistosomiasis, onchocerciasis and the filariases will indicate possible causes for the eosinophilia. Establish how long patients spent in endemic areas and ask about any occupational and behavioural risks (see Box 1.32, p. 50). Contact with fresh water in sub-Saharan Africa and particularly swimming in Lake Malawi are important risk factors for schistosomiasis. Walking barefoot is a risk factor for acquiring any of the soil-transmitted helminthiases. 

[X] Clinical features 

Symptoms that would suggest a parasitic cause for eosinophilia include transient rashes (schistosomiasis, strongyloidiasis), fever (Katayama syndrome-see p. 78), itching (onchocerciasis), haematuria, haematospermia (schistosomiasis) or migrating subcutaneous swellings (loiasis, gnathostomiasis) (see Box 1.51). 

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Urticarial rashes

·       Strongyloidiasis, onchocerciasis, fascioliasis, hydatid disease, trichinosis


Cutaneous larva migrans

·       Ancylostoma braziliense



·       Onchocerciasis


Migratory subcutaneous swellings

·       Loiasis, gnathostomiasis


Lymphangitis, orchitis

·       Lymphatic filariasis



·       Trichinosis, cysticercosis


Febrile hepatosplenomegaly

·       Schistosomiasis, toxocariasis



·       Migratory stage of larval helminths (Loeffler's syndrome), lymphatic filariasis (tropical pulmonary eosinophilia), systemic strongyloidiasis


Enteritis and colitis

·       Strongyloidiasis, capillariasis, trichinosis, rarely other intestinal worms



·       Angiostrongyliasis, strongyloidiasis



[Y] Investigations 

To establish a parasitic infestation direct visualisation of adult worms, larvae or ova is the best evidence. Serological evidence may be helpful but a serological response may not distinguish between an active and an old infection. Radiological investigations may also provide circumstantial evidence of parasite infestation. Box 1.52 gives the initial investigations for eosinophilia. 


            Investigation                          Pathogens sought

ü    1.Stool microscopy                   Ova, cysts and parasites

ü    2.Terminal urine                       Ova of Schistosoma haematobium

ü    3.Duodenal aspirate                 Filaria of Strongyloides, liver fluke ova

ü    4.Day bloods                            Microfilariae Wuchereria bancrofti, Loa loa

ü    5.Night bloods                         Microfilariae Brugia malayi

ü    6.Skin snips                              Onchocerca volvulus

ü    7.Serology                                Schistosomiasis, filariasis, strongyloidiasis, hydatid, trichinosis etc.



Pathogens sought

1.Stool microscopy                   

Ova, cysts and parasites

2.Terminal urine                       

Ova of Schistosoma haematobium

3.Duodenal aspirate                 

Filaria of Strongyloides, liver fluke ova

4.Day bloods                            

Microfilariae Wuchereria bancrofti, Loa loa

5.Night bloods                         

Microfilariae Brugia malayi

6.Skin snips                              

Onchocerca volvulus


Schistosomiasis, filariasis, strongyloidiasis, hydatid, trichinosis etc.








Soil-transmitted helminthiases are of two types: the hook worms which have a soil stage developing into larvae which then penetrate the host, and a group of nematodes which survive in the soil merely as eggs that have to be ingested for the cycle to continue. The geographical distribution of hook worms is limited by the larval requirement for warmth and humidity. 



Ancylostomiasis is caused by parasitisation of the small intestine with Ancylostoma duodenale or Necator americanus. It is one of the main causes of anaemia in the tropics. In the early stages of infection eosinophilia is common. The adult hookworm is 1 cm long and lives in the duodenum and upper jejunum. Eggs are passed in the faeces. In warm, moist, shady soil the larvae develop into the filariform infective stage; they then penetrate human skin and are carried to the lungs (see Fig. 1.55). After entering the alveoli they ascend the bronchi, are swallowed and mature in the small intestine, reaching maturity 4-7 weeks after infection. 

Hookworm infection is widespread in the tropics and subtropics. A. duodenale is endemic in the Far East and Mediterranean coastal regions and is also present in Africa, while N. americanus is endemic in West, East and Central Africa and Central and South America as well as in the Far East. 




The larvae may cause allergic inflammation at the site of entry through the skin. When infection is heavy, the passage through the lungs may cause pulmonary eosinophilia. The worms attach themselves to the mucosa of the small intestine by their buccal capsule (see Fig. 1.56) and withdraw blood. The mean daily loss of blood from one A. duodenale is 0.15 ml and for N. americanus 0.03 ml. The degree of iron and protein deficiency which develops depends not only on the load of worms but also on the nutrition of the patient and especially on the iron stores. In a light infection there may be no anaemia. 


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Figure 1.55 Ancylostomiasis. Life cycle of Ancylostoma.



Figure 1.56 Ancylostoma duodenale. Electron micrograph showing the ventral teeth.


[X] Clinical features  ANCYLOSTOMIASIS (HOOKWORM) 

Dermatitis usually on the feet (ground itch) may be experienced at the time of infection. The passage of the larvae through the lungs in a heavy infection causes a paroxysmal cough with blood-stained sputum, associated with patchy pulmonary consolidation. When the worms have reached the small intestine, vomiting and epigastric pain resembling peptic ulcer disease may occur. Sometimes frequent loose stools are passed. Iron deficiency anaemia, protein-losing enteropathy and hypoproteinaemia may develop in the undernourished. High-output cardiac failure may result from the chronic iron deficiency anaemia. The mental and physical development of children may be retarded. A well-nourished person with a light infection may be asymptomatic. 



The characteristic ovum can be recognised in the stool. If hookworms are present in numbers sufficient to cause anaemia, tests of the stool for occult blood will be positive and ova will be present in large numbers. 



Mebendazole 100 mg 12-hourly for 3 days is preferred, but for single-dose treatment albendazole (400 mg) is the best choice. Anaemia associated with hookworm infection responds well to oral iron. The management of anaemic heart disease is best accomplished by treatment with anthelmintics and iron. Blood transfusion should only be used with great care in very severely anaemic patients (< style="mso-spacerun:yes"> 



Strongyloides stercoralis is a very small nematode (2 mm × 0.4 mm) which parasitises the mucosa of the upper part of the small intestine, often in large numbers causing persistent eosinophilia. The eggs hatch in the bowel but only larvae are passed in the faeces. In moist soil they moult and become the infective filariform larvae. After penetrating human skin they undergo a development cycle similar to that of hookworms but the female worms burrow into the intestinal mucosa and submucosa. Some larvae in the intestine may develop into filariform larvae which may then penetrate the mucosa or the perianal skin and lead to autoinfection and persistent infection. Patients with Strongyloides infection persisting for more than 35 years have been described. Strongyloidiasis occurs in the tropics and subtropics and is especially prevalent in the Far East. 




In the intestine female worms burrow into the mucosa and induce an inflammatory reaction; with heavy infections the mucosa may be severely damaged, leading to malabsorption. Granulomatous changes, necrosis, and even perforation and peritonitis may occur. Eosinophilia commonly persists. Actively motile larvae are passed in the faeces. Immunosuppression may cause fatal systemic strongyloidiasis. 




These are shown in Box 1.53. The classic triad of symptoms consists of abdominal pain, diarrhoea and urticaria. Cutaneous manifestations are characteristic and occur in 66% of patients, either urticaria or larva currens. Systemic strongyloidiasis (the Strongyloides hyperinfestation syndrome) with dissemination of larvae throughout the body occurs in association with immune suppression (intercurrent disease, HTLV1 infection, corticosteroid treatment). Patients present with severe, generalised abdominal pain, abdominal distension and shock. Massive larval invasion of the lungs causes cough, wheeze and dyspnoea; cerebral involvement has manifestations ranging from subtle neurological signs to coma. Gram-negative sepsis frequently complicates the picture. 



Penetration of skin by infective larvae

Itchy rash


Presence of worms in gut

Abdominal pain, diarrhoea, steatorrhoea, weight loss


Allergic phenomena

Urticarial plaques and papules, wheezing, arthralgia



Transient itchy linear urticarial weals across abdomen and buttocks (larva currens)


Systemic (super)infection

Diarrhoea, pneumonia, meningoencephalitis, death



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The faeces should be examined microscopically for motile larvae. Excretion is intermittent so repeated examinations may be necessary. Larvae can also be found in jejunal aspirate or detected using the string test. Serology (ELISA) is helpful, but definitive diagnosis depends upon finding the larvae. Larvae may also be cultured from faeces. 




Ivermectin 200 mg/kg as a single dose, or two doses of 200 mg/kg on successive days, is effective. Albendazole is given orally in a dose of 15 mg/kg body weight 12-hourly for 3 days. A second course may be required. For the Strongyloides hyperinfestation syndrome, ivermectin is given at 200 mg/kg on days 1, 2, 15 and 16. 



This pale yellow worm is 20-35 cm long. Humans are infected by eating food contaminated with mature ova. Ascaris larvae hatch in the duodenum, migrate through the lungs, ascend the bronchial tree, are swallowed and mature in the small intestine. This tissue migration can provoke both local and general hypersensitivity reactions with pneumonitis, eosinophilic granulomata, bronchial asthma and urticaria. 



Intestinal ascariasis causes symptoms ranging from occasional vague abdominal pain through to malnutrition. The large size of the adult worm and its tendency to aggregate and migrate can result in severe obstructive complications. In endemic areas ascariasis causes up to 35% of all intestinal obstructions, most commonly in the terminal ileum. Obstruction can be complicated further by intussusception, volvulus, haemorrhagic infarction and perforation. Other complications include blockage of the bile or pancreatic duct and obstruction of the appendix by adult worms. 



The diagnosis is made microscopically by finding ova in the faeces. Adult worms are frequently expelled rectally or orally. Occasionally, the worms are demonstrated radiographically by a barium examination. 



Mebendazole 100 mg 12-hourly for 3 days, albendazole 400 mg or piperazine 4 g as a single dose, is effective for intestinal ascariasis. Patients should be warned that they may expel numerous whole, large worms. Obstruction due to ascariasis should be treated with nasogastric suction, piperazine and intravenous fluids. 



Community chemotherapy programmes have been used to reduce Ascaris infection. The whole community can be treated every 3 months and over several years. Alternatively, schoolchildren can be targeted; treating them lowers the prevalence of ascariasis in the whole community. 



Trichinella spiralis is a parasite of rats and pigs and is transmitted to humans if they eat partially cooked infected pork, usually as sausage or ham. Bear meat is another source. Symptoms result from invasion of intestinal submucosa by ingested larvae, which develop into adult worms, and the secondary invasion of tissues by fresh larvae produced by these adult worms. The main tissue invaded is striated muscle, in which the larvae encyst. Outbreaks have occurred in Britain as well as in other countries where pork is eaten. 




The clinical features of trichinosis are determined by the larval numbers. A light infection with a few worms may be asymptomatic; a heavy infection causes nausea and diarrhoea 24-48 hours after the infected meal. A few days later, the symptoms associated with larval invasion predominate: fever and oedema of the face, eyelids and conjunctivae. Invasion of the diaphragm may cause pain, cough and dyspnoea; involvement of the muscles of the limbs, chest and mouth causes stiffness, pain and tenderness in affected muscles. Larval migration may cause acute myocarditis and encephalitis. An eosinophilia is usually found after the second week. An intense infection may prove fatal but those who survive recover completely. 




Commonly, a group of people who have eaten infected pork from a common source develop symptoms at about the same time. Biopsy from the deltoid or gastrocnemius after the third week of symptoms in suspected cases may reveal encysted larvae. Serological tests are also helpful. 




Treatment is with albendazole 20 mg/kg daily for 7 days. Given early in the infection this may kill newly formed adult worms in the submucosa and thus reduce the number of larvae reaching the muscles. Corticosteroids are necessary to control the serious effects of acute inflammation. 49.10






This helminth is common throughout the world. It affects children especially. The male worm is 2-5 mm long and the female 8-13 mm. After the ova are swallowed, development takes place in the small intestine, but the adult worms are found chiefly in the colon. 



The gravid female worm lays ova around the anus and causes intense itching, especially at night. The ova are often carried to the mouth on the fingers and so reinfection takes place (see Fig. 1.57). In females the genitalia may be involved. The adult worms may be seen moving on the buttocks or in the stool. 

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Figure 1.57 Threadworm. Life cycle of Enterobius vermicularis.



Ova are detected by applying the adhesive surface of Cellophane tape to the perianal skin in the morning. This is then examined on a glass slide under the microscope. A perianal swab, moistened with saline, is an alternative method for diagnosis. 



A single dose of mebendazole 100 mg, albendazole 400 mg or piperazine 4 g is given and may be repeated after 2 weeks to control auto-reinfection. Where infection constantly recurs in a family, each member should be treated as above. During this period all nightclothes and bed linen are laundered. Fingernails must be kept short and hands washed carefully before meals. Subsequent therapy is reserved for those family members who develop recurrent infection. 



Infections with whipworm are common all over the world under unhygienic conditions. Infection takes place by the ingestion of earth or food contaminated with ova which have become infective after lying for 3 weeks or more in moist soil. The adult worm is 3-5 cm long and has a coiled anterior end resembling a whip. Whipworms inhabit the caecum, lower ileum, appendix, colon and anal canal. There are usually no symptoms, but intense infections in children may cause persistent diarrhoea or rectal prolapse, and stunting. The diagnosis is readily made by identifying ova in faeces. Treatment is with mebendazole in doses of 100 mg 12-hourly for 3-5 days or a single dose of albendazole 400 mg. 


This is achieved by preventing contact with faecally contaminated soil; the provision of adequate sewerage disposal could eliminate hookworm infestation. The use of footwear also reduces hookworm infection. Transmission of intestinal nematodes is through contaminated soil or unwashed hands. Safe disposal of faeces, the provision of clean drinking water and strict personal hygiene form the basis of control.






Filarial infections cause the highest eosinophilia of all helmintic infections. The larval stages are inoculated by biting mosquitoes or flies, each specific to a particular filarial species. The larvae develop into adult worms (2-50 cm long) which, after mating, produce millions of microfilariae (170-320 microns long) that migrate in blood or skin. The life cycle is completed when the vector takes up microfilariae while feeding on humans, normally the only host. 

Disease is due to the host's immune response to the worms, particularly dying worms, and its pattern and severity vary with the site and stage of each species (see Box 1.54). The worms are long-lived; microfilariae survive 2-3 years and adult worms 10-15 years. The infections are chronic and worst in individuals constantly exposed to reinfection. 


 Worm species Adult worm Microfilariae

 Wuchereria bancrofti and Brugia malayi Lymphatic vessels+++ Blood-

Pulmonary capillaries++

 Loa loa Subcutaneous+ Blood+

 Onchocerca volvulus Subcutaneous+ Skin+++


 Mansonella perstans Retroperitoneal- Blood-

 Mansonella streptocerca Skin+ Skin++



(+++ = severe; ++ = moderate; + = mild; - = rarely pathogenic) 



Worm species

Adult worm


1.Wuchereria bancrofti and Brugia malayi

Lymphatic vessels+++


Pulmonary capillaries++


2.Loa loa



3.Onchocerca volvulus





4.Mansonella perstans




5.Mansonella streptocerca







Infection with the filarial worms Wuchereria bancrofti and Brugia malayi is associated with a range of clinical outcomes ranging from subclinical infection to hydrocele and elephantiasis. W. bancrofti is transmitted by night-biting Culex quinquefasciatus mosquitoes. The adult worms, 4-10 cm in length, live in the lymphatics, and the females produce microfilariae which at night circulate in large numbers in the peripheral blood. In the mosquito, ingested microfilariae develop into infective larvae. The infection is widespread in tropical Africa, the North African coast, coastal areas of Asia, Indonesia and northern Australia, the South Pacific islands, the West Indies and also in North and South America. B. malayi is similar to W. bancrofti and is found in Indonesia, Borneo, Malaysia, Vietnam, South China, South India and Sri Lanka. 

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[X1]Pathology  FILARIASES

Four factors are central to the pathogenesis of lymphatic filariasis: the living adult worm, the inflammatory response caused by the death of the worm, microfilariae and secondary infections. Toxins released by the adult worm cause lymphangiectasia. Dilatation of the lymphatic vessel leads to lymphatic dysfunction and the chronic clinical manifestations of lymphatic filariasis, lymphoedema and hydrocele. Death of the adult worm results in acute filarial lymphangitis. Lymphatic obstruction persists after death of the adult worm. Secondary bacterial infections cause tissue destruction. Microfilariae are central to the pathogenesis of tropical pulmonary eosinophilia (see Fig. 1.58). 

[X]Clinical features  FILARIASES

Acute filarial lymphangitis presents with fever, pain, tenderness and erythema along the course of inflamed lymphatic vessels. Inflammation of the spermatic cord, epididymitis and orchitis are common. The whole episode lasts a few days but may recur several times a year. Temporary oedema becomes more persistent and regional lymph nodes enlarge. Progressive enlargement, coarsening, corrugation and fissuring of the skin and subcutaneous tissue develop gradually, causing irreversible 'elephantiasis'. The scrotum may reach an enormous size. Chyluria and chylous effusions are milky and opalescent; on standing, fat globules rise to the top. Elephantiasis develops only in association with repeated skin sepsis. 



Figure 1.58 Wuchereria bancrofti and Brugia malayi. Life cycle of organisms and pathogenesis of lymphatic filariasis.

The acute lymphatic manifestations of filariasis must be differentiated from thrombophlebitis and infection. The oedema and lymphatic obstructive changes must be distinguished from congestive cardiac failure, malignancy, trauma and idiopathic abnormalities of the lymphatic system. 

Tropical pulmonary eosinophilia 

This condition is seen mainly in India and is likely to be due to microfilariae trapped in the pulmonary capillaries and destroyed by allergic inflammation. Patients present with paroxysmal cough, wheeze and fever. The chest radiograph shows miliary changes or mottled opacities. Lung function tests show a restrictive picture. If untreated, this progresses to debilitating chronic interstitial lung disease. 

There is no specific therapy for this condition but the lymphatic damage can be managed actively as outlined for filarial elephantiasis. 

[Y]Investigations  FILARIASES

In the earliest stages of lymphangitis the diagnosis is made on clinical grounds, supported by eosinophilia and sometimes by positive filarial serology. Microfilariae are found in the peripheral blood at night and can be seen moving in a wet blood film or by microfiltration of a sample of lysed blood. They are usually present in hydrocele fluid which may occasionally yield an adult filaria. By the time elephantiasis develops, microfilariae become difficult to find. Calcified filariae may sometimes be demonstrable by radiography. Movement of adult worms can be seen on scrotal ultrasound. Indirect fluorescence and ELISA detect antibodies in over 95% of active cases and 70% of established elephantiasis. The test becomes negative 1-2 years after cure. Serological tests cannot distinguish the different filarial infections. In tropical pulmonary eosinophilia, serology is strongly positive and IgE levels are massively elevated but circulating microfilariae are not found. 

[Z]Management  FILARIASES

Treatment of the individual is aimed at reversing and halting disease progression. Diethylcarbamazine (DEC) kills microfilariae and adult worms. The dose is 6 mg/kg daily orally in three divided doses for 12 days. The full dose must be reached slowly, starting with 50 mg and doubling daily unless serious allergic reactions ensue. Most adverse effects seen with DEC treatment are due to the host response to dying microfilariae, and the reaction intensity is directly proportional to the microfilarial load. The main symptoms are fever, headache, nausea, vomiting, arthralgia and prostration. These usually occur within 24-36 hours of the first dose of DEC. Antihistamines or corticosteroids may be required to control these allergic phenomena. Both the 12-day course and a single dose of DEC reduce microfilaria levels by about 90% 6-12 months after treatment. No carefully controlled trials have evaluated the effects of DEC treatment alone on the chronic manifestations of lymphatic filariasis. Ivermectin may also be used. 

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 prostration-exhausted or extremely weak

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Chronic lymphatic pathology 

Experience in India and Brazil shows that active management of chronic lymphatic pathology can alleviate symptoms. Patients should be taught meticulous local care of their lymphoedematous limbs with assiduous skin care to prevent secondary bacterial and fungal infections. Tight bandaging, massage and bed rest with elevation of the affected limb may help to control the lymphoedema. Prompt diagnosis and antibiotic therapy of bacterial cellulitis are important in preventing further lymphatic damage and worsening of existing elephantiasis. Patient education is a critical feature of lymphoedema treatment, both to alter fatalistic beliefs about inevitable progression of disease and to foster motivation. Plastic surgery may be indicated in established elephantiasis. Great relief can be obtained by removal of excess tissue but recurrences are probable unless new lymphatic drainage is established. Hydroceles can be repaired surgically; chyluria can also be corrected surgically. 

[Z1]Prevention FILARIASES

Treatment of the whole population in endemic areas with annual single-dose DEC, 100 mg for adults (50 mg for children), has reduced but not eliminated the infection. Ivermectin, alone or in combination with albendazole, is under evaluation as an alternative to DEC. This mass treatment should be combined with mosquito control programmes. 



This occurs in certain filaria-free geographical areas and affects one or both legs. It is due to lymphatic damage by silicates absorbed from volcanic soil. There is no specific therapy for this condition but the lymphatic damage can be managed actively as outlined above for filarial elephantiasis. 



Loiasis is caused by infection with the filaria Loa loa. The adults, 3-7 cm × 4 mm, parasitise chiefly the subcutaneous tissue of humans. The larval microfilariae circulate harmlessly in the peripheral blood in the daytime. The vector is Chrysops, a forest-dwelling, day-biting fly. 

[X1]Pathology  LOIASIS


The adult worms move harmlessly about in the subcutaneous tissues and other interstitial planes. From time to time a short-lived, inflammatory, oedematous swelling (a Calabar swelling) is produced around an adult worm. Heavy infections, especially when treated, may cause encephalitis. The incubation period is commonly over a year but may be just 3 months. 

[X]Clinical features  LOIASIS 


The infection is often symptomless. The first sign is usually a Calabar swelling, an irritating, tense, localised swelling that may be painful, especially if it is near a joint. The swelling is generally on a limb; it measures a few centimetres in diameter but sometimes is more diffuse and extensive. It usually disappears after a few days but may persist for 2 or 3 weeks. A succession of such swellings may appear at irregular intervals, often in adjacent sites. Sometimes there is urticaria and pruritus elsewhere. Occasionally, a worm may be seen wriggling under the skin, especially of an eyelid, and may cross the eye under the conjunctiva, taking many minutes to do so. 

[Y]Investigations  LOIASIS 


Diagnosis is by demonstrating microfilariae in blood taken during the day, but they may not always be found in patients with Calabar swellings. Antifilarial antibodies are positive in 95% of patients; there is massive eosinophilia. Occasionally, a calcified worm may be seen on a radiograph. 

[Z]Management  LOIAS                                                                                                    DEC (see above) is curative, gradually increased to a dose of 9-12 mg/kg daily which is continued for 21 days. Treatment may precipitate a severe reaction in patients with a heavy microfilaraemia characterised by fever, joint and muscle pain, and encephalitis; microfilaraemic patients should be given steroid cover. 

[Z1]Prevention  LOIASIS

Protection is afforded by building houses away from trees and by having dwellings wire-screened. Protective clothing and repellents are also useful. DEC in a dose of 5 mg/kg daily for 3 days each month is partially protective. 



Onchocerciasis is the result of infection by Onchocerca volvulus. Only about 0.3 mm in diameter, the adult female may be as long as 50 cm; the male is 13 cm. The infection is conveyed by flies of the genus Simulium which inflict a painful bite. In West Africa the vector is S. damnosum, in northern Nigeria also S. bovis, and in East Africa and Zaire S. neavei. The flies breed in rapidly flowing, well-aerated water, the larvae being attached to submerged vegetation, rocks or crabs. Adult flies bite during the day both inside and outside houses. Humans are the only known definitive hosts. 

Onchocerciasis is endemic in well-defined areas throughout tropical Africa, in southern Arabia and Yemen, and also in South Mexico, Guatemala, Colombia, Venezuela and Brazil. It is estimated that over 20 million people are infected. In parts of West and Central Africa it affects the whole adult population and blindness rates of 10% are common, reaching 35% in some parts of Ghana. Due to onchocerciasis huge tracts of fertile land lie virtually untilled, and individuals and communities are impoverished. 



Infective larvae of O. volvulus are introduced into the skin by the bite of an infected Simulium fly (see Fig. 1.59). The worms mature in 2-4 months and live for up to 17 years in small colonies in subcutaneous and connective tissues. At sites of trauma, over bony prominences and around joints, fibrosis may form nodules around adult worms which otherwise cause no direct damage. Innumerable microfilariae, discharged by the female O. volvulus, move actively in these nodules and in the adjacent tissues, are widely distributed in the skin, and may invade the eye. Live microfilariae elicit little tissue reaction, but dead ones may cause severe allergic inflammation leading to hyaline necrosis and loss of collagen and elastin. Death of microfilariae in the eye causes conjunctivitis, sclerosing keratitis with pannus formation, uveitis which may lead to glaucoma and cataract and, less commonly, choroidoretinitis and optic neuritis. 

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Figure 1.59 Onchocerca volvulus. Life cycle of organism and pathogenesis of onchocerciasis.



The infection may remain symptomless for months or years. The first symptom is usually itching, localised to one quadrant of the body and later becoming generalised and involving the eyes. Evanescent oedema of part or all of a limb in Europeans is an early sign, followed by papular urticaria spreading gradually from the site of infection. This is difficult to see on dark skins, in which the most common signs are papules excoriated by scratching, spotty hyperpigmentation from resolving inflammation, and more chronic changes of a rough, thickened or inelastic, wrinkled skin. Superficial lymph nodes enlarge and may hang down in folds of loose skin at the groins. Hydrocele, femoral hernias and scrotal elephantiasis occur. Firm subcutaneous nodules occur in chronic infection (onchocercomas), which are palpable and 1 cm or more in diameter. 

Eye disease is most common in highly endemic areas and is associated with chronic heavy infections and nodules on the head. Early manifestations include itching, lacrimation, conjunctival injection and evidence of the features listed under 'Pathology'. Classically, 'snowflake' deposits are seen in the edges of the cornea. 



The finding of nodules or characteristic lesions of the skin or eyes in a patient from an endemic area, associated with eosinophilia, is suggestive. Skin snips or shavings, taken with a corneoscleral punch or scalpel blade from calf, buttock and shoulder, are placed in saline under a cover slip on a microscope slide and examined after 4 hours. Microfilariae are seen wriggling free in all but the lightest infections. If negative, a test dose of DEC is given to see if it aggravates the rash. Slit-lamp examination of the eye may reveal microfilariae moving in the anterior chamber of the eye, or trapped in the cornea. A nodule may be removed and incised, showing the coiled, thread-like adult worm. Filarial antibodies may be detected in up to 95% of patients, but antibody positivity can be much lower in lightly infected expatriates. 



Ivermectin, in a single dose of 100-200 mg/kg, kills microfilariae and prevents their return for 9 months. It is non-toxic and does not trigger severe reactions, in contrast to DEC which is no longer used for this infection. In the rare event of a severe reaction causing oedema or postural hypotension, prednisolone 20-30 mg may be given daily for 2 or 3 days. Retreatment with ivermectin may be necessary. 



Mass treatment with ivermectin is in use. It reduces morbidity in the community and prevents eye disease from getting worse. Simulium can be destroyed in its larval stage by the application of insecticide to streams. Dimethyl phthalate applied to skin or clothing will repel the fly for several hours. Long trousers, skirts and sleeves discourage the fly from biting. 



Mansonella perstans 

This filarial worm is transmitted by the midges Culicoides austeni and C. grahami. It is common throughout equatorial Africa as far south as Zambia, and also in Trinidad and parts of northern and eastern South America. 

M. perstans has never been shown to cause disease but it may be responsible for a persistent eosinophilia and occasional allergic manifestations. M. perstans is resistant to ivermectin and DEC and the infection may persist for many years. 

Dirofilaria immitis 

This dog heart worm infects humans with skin and lung lesions. It is not uncommon in the US, Japan and Australia. 49.12 




Schistosomiasis (bilharziasis) is one of the most important causes of morbidity in the tropics and is being spread by irrigation schemes. Schistosome eggs have been found in Egyptian mummies dated 1250 BC. Recent travellers, especially those overlanding through Africa, may present with eosinophilia; residents of schistosomiasis-endemic areas are more likely to present with chronic urinary tract pathology or portal hypertension. 

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There are three species of the genus Schistosoma which commonly cause disease in humans: S. haematobium, S. mansoni and S. japonicum. S. haematobium was discovered by Theodor Bilharz in Cairo in 1861 and the genus is sometimes called Bilharzia and the disease bilharziasis. The ovum is passed in the urine or faeces of infected individuals and gains access to fresh water where the ciliated miracidium inside it is liberated and enters its intermediate host, a species of freshwater snail, in which it multiplies. Large numbers of fork-tailed cercariae are then liberated into the water, where they may survive for 2-3 days. Cercariae can penetrate the skin or the mucous membrane of the mouth of their definitive host, humans. They transform into schistosomulae and moult as they pass through the lungs and are carried by the blood stream to the liver and so to the portal vein where they mature (see Fig. 1.60). The male worm is up to 20 mm in length and the more slender cylindrical female, usually enfolded longitudinally by the male, is rather longer. Within 4-6 weeks of infection they migrate to the venules draining the pelvic viscera, where the females deposit ova. 



Figure 1.60 Schistosoma. A Life cycle. B Scanning electron micrograph of adult schistosome worms showing the larger male worm embracing the thinner female.


 Stage Time S. haematobium S. mansoni and S. japonicum

 Cercarial penetration Days Papular dermatitis at site of penetration As for S. haematobium

 Larval migration and maturation Weeks Pneumonitis, myositis, hepatitis, fever, 'serum sickness', eosinophilia, seroconversion As for S. haematobium

 Early egg deposition Months Cystitis, haematuria Colitis, granulomatous hepatitis, acute portal hypertension

     Ectopic granulomatous lesions: skin, CNS etc. As for S. haematobium

     Immune complex glomerulonephritis  

 Late egg deposition Years Fibrosis and calcification of ureters, bladder; bacterial infection, calculi, hydronephrosis, carcinoma Colonic polyposis and strictures, periportal fibrosis, portal hypertension

     Pulmonary granulomas and pulmonary hypertension As for S. haematobium


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[X1]Pathology SCHISTOSOMIASIS(bilharziasis)   


The pathological changes and symptoms depend on species and stage of infection (see Box 1.55). Most of the disease is due to the passage of eggs through mucosa and to the granulomatous reaction to eggs deposited in tissues. The eggs of S. haematobium pass mainly through the wall of the bladder, but may also involve rectum, seminal vesicles, vagina, cervix and uterine tubes. S. mansoni and S. japonicum eggs pass mainly through the wall of the lower bowel or are carried to the liver. The most serious, though rare, consequences of the ectopic deposition of eggs are transverse myelitis and paraplegia. Granulomas are composed of macrophages, eosinophils, epithelioid and giant cells around an ovum. Later there is fibrosis and eggs calcify, often in sufficient numbers to become radiologically visible. Eggs of S. haematobium, and of the other two species after the development of portal hypertension, may reach the lungs. 

[X]Clinical features SCHISTOSOMIASIS(bilharziasis)     

During the early stages of infection there may be itching lasting 1-2 days at the site of cercarial penetration. After a symptom-free period of 3-5 weeks acute schistosomiasis (Katayama syndrome) may present with allergic manifestations such as urticaria, fever, muscle aches, abdominal pain, headaches, cough and sweating. On examination hepatomegaly, splenomegaly, lymphadenopathy and pneumonia may be present. There is eosinophilia and schistosomiasis serology may be positive. These allergic phenomena (Katayama syndrome) may be severe in infections with S. mansoni and S. japonicum but are rare with S. haematobium. The features subside after 1-2 weeks. Chronic schistosomiasis is due to egg deposition and occurs months to years after infection. The symptoms and signs depend upon the intensity of infection and the species of infecting schistosome. 

Schistosomiasis haematobium 

Humans are the only natural hosts of S. haematobium, which is highly endemic in Egypt and East Africa, and occurs throughout most of Africa and the Middle East. There is also a solitary focus in Maharashtra, India (see Fig. 1.61). 

Painless terminal haematuria is usually the first and most common symptom. Frequency of micturition follows, due to bladder neck obstruction. Later the disease may be complicated by frequent urinary tract infections, bladder or ureteric stone formation, hydronephrosis, renal functional abnormalities and ultimately renal failure with a contracted calcified bladder. Pain is often felt in the iliac fossa or in the loin and radiates to the groin. In several endemic areas there is a strong epidemiological association of S. haematobium infection with squamous cell carcinoma of the bladder. Disease of the seminal vesicles may lead to haemospermia. Females may develop schistosomal papillomata of the vulva, and schistosomal lesions of the cervix may be mistaken for cancer. Intestinal symptoms may follow involvement of the bowel wall. Ectopic worms cause skin or cord lesions. The severity of S. haematobium infection varies greatly, and many with a light infection suffer little. However, as adult worms can live for 20 years or more and lesions may progress, these patients should always be treated. 



Figure 1.61 Geographical distribution of schistosomiasis.

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Schistosomiasis mansoni 

S. mansoni is endemic throughout Africa, the Middle East, Venezuela, Brazil and the Caribbean (see Fig. 1.61). 

Characteristic symptoms begin 2 months or more after infection. They may be slight, no more than malaise, or consist of abdominal pain and frequent stools which contain blood-stained mucus. With severe advanced disease increased discomfort from rectal polypi may be experienced. The early hepatomegaly is reversible but portal hypertension may cause massive splenomegaly, fatal haematemesis from oesophageal varices, or progressive ascites. Liver function is initially preserved because the pathology is fibrotic rather than cirrhotic. S. mansoni infections predispose to the carriage of Salmonella. 

Schistosomiasis japonicum 

In addition to humans the adult worm infects the dog, rat, fieldmouse, water buffalo, ox, cat, pig, horse and sheep. S. japonicum is prevalent in the Yellow River and Yangtze-Jiang basins in China, where the infection is a major public health problem. It also has a focal distribution in the Philippines, Indonesia and Thailand. There is now no human transmission of this parasite in Japan. A related parasite, S. mekongi, occurs in Laos, Thailand and Myanmar. The pathology of S. japonicum is similar to that of S. mansoni, but as this worm produces more eggs, the lesions tend to be more extensive and widespread. The clinical features resemble those of severe infection with S. mansoni, with added neurological features. The small bowel as well as the large may be affected, and hepatic fibrosis with splenic enlargement is usual. Deposition of eggs or worms in the central nervous system, especially in the brain, causes symptoms in about 5% of infections, notably epilepsy, hemiplegia, blindness and paraplegia. 

[Y]Investigations SCHISTOSOMIASIS(bilharziasis)     

A history of residence in an endemic area, with characteristic symptoms, will indicate the need for investigation. Diagnosis depends on demonstrating eggs or serological evidence. In S. haematobium infection, dipstick urine testing shows blood and albumin. The terminal spined eggs can usually be found by microscopic examination of the centrifuged deposit of terminal stream urine. Ultrasound is useful for assessing the urinary tract and can be performed easily in the field. Bladder wall thickening, hydronephrosis and bladder calcification can be detected. Cystoscopy reveals 'sandy' patches, bleeding mucosa and later distortion. 

In a heavy infection with S. mansoni or S. japonicum the characteristic egg with its lateral spine can usually be found in the stool. When the infection is light, or of long duration, a rectal biopsy can be examined. Sigmoidoscopy may show inflammation or bleeding. Biopsies should be examined for ova. Serological tests (ELISA) are useful as screening tests but remain positive after chemotherapeutic cure. 

[Z]Management SCHISTOSOMIASIS(bilharziasis)     

The object of specific treatment is to kill the adult schistosomes and so stop egg-laying. It may not be possible or desirable to kill all adult worms by mass treatment campaigns in communities where reinfection is likely, but a reduction in egg output of around 90% is often achieved which significantly reduces morbidity, and possibly transmission, without impairing what little acquired immunity there may be. Praziquantel is the drug of choice for all forms of schistosomiasis. The drug is effective in producing parasitological cure in 80% of treated individuals and achieves over 90% reduction in egg counts in the remaining individuals. Side-effects are uncommon but include nausea and abdominal pain in individuals with heavy egg burdens. Praziquantel therapy in early infection will reverse pathologies such as hepatomegaly and bladder wall thickening. 

Surgery may be required to deal with residual lesions but large vesical granulomas usually respond well to chemotherapy. Ureteric stricture and the small fibrotic urinary bladder may require plastic procedures. Removal of rectal papillomas by diathermy or by other means may provide relief. Granulomatous masses in the brain or spinal cord may require neurosurgery if the manifestations do not respond to chemotherapy and corticosteroids. 

[Z1]Prevention SCHISTOSOMIASIS(bilharziasis)     

This presents great difficulties and so far no satisfactory single means of controlling schistosomiasis has been established. The life cycle is terminated if the ova in urine or faeces are not allowed to contaminate fresh water containing the snail host. The provision of latrines and of a safe water supply, however, remains a major problem in rural areas throughout the tropics. In the case of S. japonicum, moreover, there are so many hosts besides humans that the proper use of latrines would be of little avail. Mass treatment of the population helps against S. haematobium and S. mansoni but this method has so far had little success with S. japonicum. Attack on the intermediate host, the snail, presents many difficulties and has not on its own proved successful on any scale. For personal protection, contact with infected water must be avoided.






Liver flukes infect at least 20 million people and remain an important public health problem in many endemic areas. They are associated with abdominal pain, hepatomegaly and relapsing cholangitis. Clonorchis sinensis is a major aetiological agent of bile duct cancer. The three major flukes have similar life cycles and pathologies, as outlined in Box 1.56. 

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   Clonorchiasis Opisthorchiasis Fascioliasis

 Parasite Clonorchis sinensis Opisthorchis felineus Fasciola hepatica

 Other mammalian hosts Dogs, cats, pigs Dogs, cats, foxes, pigs Sheep, cattle

 Mode of spread Ova in faeces, water As for C. sinensis Ova in faeces on to wet pasture

 1st intermediate host Snails Snails Snails

 2nd intermediate host Fresh-water fish Fresh-water fish Encysts on vegetation

 Geographical distribution Far East, especially South China Far East, especially Cosmopolitan, including UK

     North-east Thailand  

 Pathology E. coli cholangitis, abscesses, biliary carcinoma As for C. sinensis Toxaemia, cholangitis, eosinophilia

 Symptoms Often symptom-free, recurrent jaundice As for C. sinensis Obscure fever, tender liver, may be ectopic, e.g. subcutaneous fluke

 Diagnosis Ova in stool or duodenal aspirate As for C. sinensis As for C. sinensis, also serology

 Prevention Cook fish Cook fish Avoid contaminated watercress

 Treatment Praziquantel 25 mg/kg 8-hourly for 2 days As for C. sinensis but for 1 day only Triclabendazole 10 mg/kg single dose; repeat treatment may be required*


* In UK available from the Hospital for Tropical Diseases, London.








Clonorchis sinensis

Opisthorchis felineus

Fasciola hepatica


Other mammalian hosts

Dogs, cats, pigs

Dogs, cats, foxes, pigs

Sheep, cattle

Mode of spread

Ova in faeces, water

As for C. sinensis

Ova in faeces on to wet pasture

1st intermediate host




2nd intermediate host

Fresh-water fish

Fresh-water fish

Encysts on vegetation

Geographical distribution

Far East, especially South China

Far East, especially     North-east Thailand  


Cosmopolitan, including UK




E. coli cholangitis, abscesses, biliary carcinoma

As for C. sinensis

Toxaemia, cholangitis, eosinophilia



Often symptom-free, recurrent jaundice

As for C. sinensis

Obscure fever, tender liver, may be ectopic, e.g. subcutaneous fluke



Ova in stool or duodenal aspirate

As for C. sinensis

As for C. sinensis, also serology



Cook fish

Cook fish

Avoid contaminated watercress


Praziquantel 25 mg/kg 8-hourly for 2 days

As for C. sinensis but for 1 day only

Triclabendazole 10 mg/kg single dose; repeat treatment may be required*


* In UK available from the Hospital for Tropical Diseases, London.








Cestodes are ribbon-shaped worms which inhabit the intestinal tract. They have no alimentary system and absorb nutrients through the tegumental surface. The anterior end, or scolex, has suckers for attaching to the host. From the scolex arises a series of progressively developing segments, the proglottides, which when shed may continue to show active movements. Cross-fertilisation takes place between segments. Ova, present in large numbers in mature proglottides, remain viable for weeks and during this period they may be consumed by the intermediate host. Larvae liberated from the ingested ova pass into the tissues. 

Humans acquire tapeworm by eating undercooked beef infected with Cysticercus bovis, the larval stage of Taenia saginata (beef tapeworm), undercooked pork containing C. cellulosae, the larval stage of T. solium (pork tapeworm), or undercooked freshwater fish containing larvae of Diphyllobothrium latum (fish tapeworm). Usually only one adult tapeworm is present in the gut but up to 10 have been reported. The life cycles of Spirometra mansoni and Dipylidium caninum involve cats and dogs; Hymenolepis nana has no intermediate host. Echinococcus granulosus is a dog tapeworm. 


Infection with T. saginata occurs in all parts of the world. The adult worm may be several metres long and produces little or no intestinal upset in human beings, but knowledge of its presence, by noting segments in the faeces or on underclothing, may distress the patient. Ova may be found in the stool. The ova of T. saginata and T. solium are indistinguishable microscopically. 

Praziquantel is the drug of choice, and prevention depends on efficient meat inspection and the thorough cooking of beef. Niclosamide is an alternative (see below). 


T. solium, the pork tapeworm, is common in central Europe, South Africa, South America and parts of Asia. It is not as large as T. saginata. The adult worm is found only in humans following the eating of undercooked pork containing cysticerci. 



Figure 1.62 Cysticercosis. Life cycle of Taenia solium.

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Human cysticercosis is acquired by ingesting tapeworm ova, either by ingesting ova from contaminated fingers or by eating contaminated food (see Fig. 1.62). The larvae are liberated from eggs in the stomach, penetrate the intestinal mucosa and are carried to many parts of the body where they develop and form cysticerci, 0.5-1 cm cysts that contain the head of a young worm. They do not grow further or migrate. Common locations are the subcutaneous tissue, skeletal muscles and brain. 

Clinical features 

When superficially placed, cysts can be palpated under the skin or mucosa as pea-like ovoid bodies. Here they cause few or no symptoms, and will eventually die and become calcified. 

Heavy brain infections, especially in children, may cause features of encephalitis. More commonly, however, cerebral signs do not occur until the larvae die, 5-20 years later. Epilepsy, personality changes, staggering gait or signs of internal hydrocephalus are the most common features. 


Calcified cysts in muscles can be recognised radiologically. In the brain, however, less calcification takes place and larvae are only occasionally demonstrated radiologically; usually CT or MRI will show them. Epileptic fits starting in adult life should suggest the possibility of cysticercosis if the patient has lived or travelled in an endemic area. The subcutaneous tissue should be palpated and any nodule excised for histology. Radiological examination of the skeletal muscles may be helpful. Antibody detection by fluorescent antibody test, ELISA or immunoblotting is available for serodiagnosis. 

Management and prevention 

Niclosamide, followed by a mild laxative (after 1-2 hours) to prevent retrograde intestinal autoinfection, is useful only for the intestinal infection. Praziquantel improves the prognosis of cerebral cysticercosis; the dose is 50 mg/kg in three divided doses daily for 10 days. Albendazole, 15 mg/kg daily for a minimum of 8 days, has now become the drug of choice for parenchymal neurocysticercosis. Prednisolone, 10 mg 8-hourly, is also given for 14 days, starting 1 day before the albendazole or praziquantel. In addition, anti-epileptic drugs should be given until the reaction in the brain has subsided. Operative intervention is indicated for hydrocephalus. Studies from India and Peru suggest that most small solitary cerebral cysts will resolve without treatment. 

Cooking pork well will prevent infection with T. solium. Cysticercosis is avoided if food is not contaminated by ova or segments. Great care must be taken by nurses and other adults while attending a patient harbouring an adult worm. 




Figure 1.63 Hydatid disease. A Life cycle of Echinococcus granulosus. B Daughter cysts removed at surgery. C Within the daughter cysts are the protoscolices.

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Dogs are the definitive hosts of the tiny tapeworm E. granulosus. The larval stage, a hydatid cyst, normally occurs in sheep, cattle, camels and other animals that are infected from contaminated pastures or water. By handling a dog or drinking contaminated water, humans may ingest eggs (see Fig. 1.63). The embryo is liberated from the ovum in the small intestine and gains access to the blood stream and thus to the liver. The resultant cyst grows very slowly, sometimes intermittently, and may outlive the patient. It may calcify or rupture, giving rise to multiple cysts. The disease is common in the Middle East, North and East Africa, Australia and Argentina. Foci of infection persist in rural Wales and Scotland. E. multilocularis, which has a cycle between foxes and voles, causes a similar but more severe infection, 'alveolar hydatid disease', which invades the liver like cancer. 

Clinical features 

A hydatid cyst is typically acquired in childhood and it may, after growing for some years, cause pressure symptoms. These vary, depending on the organ or tissue involved. In nearly 75% of patients with hydatid disease the right lobe of the liver is invaded and contains a single cyst. In others a cyst may be found in lung, bone, brain or elsewhere. 


The diagnosis depends on the clinical, radiological and ultrasound findings in a patient who has lived in close contact with dogs in an endemic area. Complement fixation and ELISA are positive in 70-90% of patients. 

Management and prevention 


 Lesion type Aetiology Clinical features


 Scabies (see p. 1085) Sarcoptes scabiei Raised linear burrows

 Insect bites Mosquito Pruritic weal, flare or papule

   Flea Discrete pruritic papule with central haemorrhagic punctum

   Tick Painful swelling with central necrosis and erythematous margin

   Bedbug Pruritic papules in a linear configuration

 Prickly heat Heat with humidity Erythematous, papular and vesicular eruption around sweat glands

 Ringworm (see p. 1083) Tinea corporis Circular, raised, sharply marginated

 Onchocerciasis (see p. 75) Onchocerca volvulus Pruritic, papular rash

 Linear lesions

 Cutaneous larva migrans Ancylostoma caninum Severely pruritic serpiginous track

 Larva currens Strongyloides stercoralis Pruritic, fast-moving erythematous band


 Ecthyma (see p. 23) Staphylococcus aureus, Vesicle or crusted pustule

   ß-haemolytic streptococcus  

 Oriental sore, Delhi boil, chiclero ulcer etc. Leishmania Indolent, slow-healing ulcer

 Anthrax (see p. 27) Bacillus anthracis Single black, oedematous, painless lesion

 Rickettsial eschar Rickettsia conorii and R. tsutsugamushi Small ulcer with black centre, systemic illness

 Buruli ulcer Mycobacterium ulcerans Nodule and ulceration

 Tropical ulcer Fusobacterium ulcerans and Sharply defined painful ulcer, usually on lower leg

   Treponema vincenti  


 Insect bites Spanish fly (Lytta vesicatoria) Blister produced from contact with insect toxins

   Rove beetle  

 Subcutaneous swellings

 Myiasis Dermatobia hominis larva, Larva protruding from subcutaneous cavity

   Cordylobia anthropophaga larva  

 Tungiasis (jiggers) Tunga penetrans Small black dot, developing into an inflammatory nodule

 Fungal infections Sporothrix schenckii Hard, non-tender subcutaneous nodules, later ulcerate

 Dracunculiasis Dracunculus medinensis Erythema, ulceration and induration; worm may protrude


Hydatid cysts should be excised wherever possible. Great care is taken to avoid spillage and cavities are sterilised with 0.5% silver nitrate or 2.7% sodium chloride. Albendazole (400 mg 12-hourly for 3 months) is used for inoperable disease, and to reduce the infectivity of cysts pre-operatively. Praziquantel 20 mg/kg 12-hourly for 14 days kills protoscolices perioperatively. 

Prevention is difficult in situations where there is a close association with dogs and sheep. Personal hygiene, satisfactory disposal of carcasses, meat inspection and deworming of dogs can greatly reduce the prevalence of disease. 


There are many other cestodes whose adult or larval stages may infect humans. Sparganosis is a condition in which an immature worm develops in humans, usually subcutaneously, as a result of eating or applying to the skin the secondary or tertiary intermediate host. 49.15




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Community-based studies in the tropics consistently show that scabies, skin infections (bacterial and fungal) and eczema are the most common skin problems in the tropics. Bacterial skin infections are discussed on pages 23-27. The other conditions are dealt with in Chapter 21. Cutaneous leishmaniasis, onchocerciasis and deep fungal infections are rare and have defined geographical distributions. In travellers secondarily infected insect bites, pyoderma, cutaneous larva migrans and non-specific dermatitis are the most common skin lesions. Enquire about habitation, work and travel when investigating these lesions. Box 1.57 lists the common lesions, their aetiology and clinical features. 


Cutaneous larva migrans (CLM) is the most common linear lesion seen in travellers. Intensely pruritic, linear serpiginous lesions result from the larval migration of the dog hookworm (Ancylostoma caninum). The track moves across the skin at a rate of 2-3 cm/day. This contrasts with the rash of Strongyloides (see p. 71), which is fast-moving and evanescent. Dog hookworms rarely establish infection in humans. The most common site for CLM is the foot but elbows, breasts and buttocks may be affected. Most patients with CLM have recently visited a beach where the affected part was exposed. The diagnosis is clinical. Treatment may be local with 12-hourly application of 15% tiabendazole cream or systemic with albendazole 400 mg daily for 3 days or a single dose of ivermectin. 


Cutaneous leishmaniasis (CL) is caused by the protozoon Leishmania. The geographical origin of the parasite is critical (see Fig. 1.64); in the Old World cutaneous disease is mild, while in the Americas the disease may involve the nose and mouth. The disease is commonly imported into Britain. CL should be considered in the differential diagnosis of an ulcerating skin lesion, especially in travellers who have visited forests in Central and South America. 

Old World cutaneous leishmaniasis (oriental sore) 



Figure 1.64 World distribution of human leishmaniasis. A Visceral leishmaniasis. B Cutaneous leishmaniasis.

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 Leishmania species Host Clinical features

 L. tropica Dogs Slow evolution, less severe

 L. major Gerbils, desert rodents Rapid necrosis, wet sores

 L. aethiopica Hyraxes Solitary facial lesions with satellites


Cutaneous leishmaniasis is found around the Mediterranean basin, throughout the Middle East and Central Asia as far as Pakistan, and in sub-Saharan West Africa and Sudan (see Fig. 1.64). The parasites L. tropica, L. major and L. aethiopica are the main species (see Box 1.58). 


Inoculated parasites are taken up by dermal macrophages where they multiply and form a focus for lymphocytes, epithelioid cells and plasma cells. Self-healing may occur with necrosis of infected macrophages, or the lesion may become chronic with ulceration of the overlying epidermis. The incubation period is 2-3 months (range 2 weeks-5 years). 

Clinical features 

Lesions, single or multiple, on exposed parts of the body, start as small red papules which increase gradually in size, reaching 2-10 cm in diameter. A crust forms, overlying an ulcer with a granular base (see Fig. 1.65). Tiny satellite papules are characteristic. Untreated, the lesions heal slowly over many months. Healing produces a depressed mottled scar which may be disfiguring or disabling. Two forms of cutaneous leishmaniasis occur which do not heal spontaneously: diffuse cutaneous leishmaniasis (L. aethiopica), in which an immune defect permits the disease to spread all over the skin, and recidivans (lupoid) leishmaniasis (L. tropica), in which apparently healed sores relapse persistently. 



Figure 1.65 Cutaneous leishmaniasis.

New World cutaneous and mucosal leishmaniasis 

In South and Central America, cutaneous leishmaniasis is endemic in hot, moist forest regions but spread is now occurring into urban areas (see Fig. 1.64). The two main parasite groups are L. mexicana and the Vianna subgenus which includes L. brasiliensis, L. panamensis and L. peruviana. The Vianna subgenus extends widely from the Amazon basin as far as Paraguay and Costa Rica and is responsible for deep sores and mucosal leishmaniasis. L. mexicana is responsible for chiclero ulcers, the self-healing sores of Mexico. 


Microscopically, the appearances are similar to Old World cutaneous leishmaniasis. Mucosal lesions begin as a perivascular infiltration; later endarteritis may cause destruction of the surrounding tissues. 

Clinical features 

Clinically, lesions of L. mexicana and L. peruviana closely resemble those seen in the Old World, but lesions on the pinna of the ear are common and are chronic and destructive. The primary lesions of L. brasiliensis are similar but between 2 and 40% of infected persons develop 'espundia', metastatic lesions in the mucosa of the nose or mouth. Mucosal lesions usually occur 1-2 years after the skin lesions but may appear many years later. Young men with chronic lesions are particularly at risk. The nasal mucosa becomes congested and ulcerates; later, all soft tissues of the nose may be destroyed. The lips, soft palate, fauces and larynx may also be invaded and destroyed, leading to considerable suffering and deformity. Secondary bacterial infection is common. 


Amastigotes can be demonstrated by making a slit skin smear (see p. 90) and staining the material obtained with Giemsa stain or culturing it. Cultured parasites may be speciated by PCR. The leishmanin skin test is positive except in diffuse cutaneous leishmaniasis. Serology is unhelpful. 


There are no good randomised controlled trials of treatment for cutaneous leishmaniasis. Small lesions may self-heal. There is no ideal therapy. Treatment should be individualised on the basis of the lesions, availability of drugs, tolerance of the patient for toxicity, and local resistance patterns. Small lesions may be treated by freezing with liquid carbon dioxide, curettage or infiltration with 1-2 ml sodium stibogluconate. When the lesions are multiple or in a disfiguring site, it is better to treat the patient by parenteral injections of pentavalent antimonials or amphotericin B as outlined under visceral leishmaniasis. If there is any chance that a lesion acquired in South America is an L. brasiliensis strain, then parenteral treatment should be given with pentavalent antimony (20 mg/kg for 20 days) to prevent the development of mucosal disease. 

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Personal protection against sandfly bites is important. No effective vaccine is yet available. 


Tropical ulcer is due to a synergistic bacterial infection between a fusobacterium (F. ulcerans), an anaerobe and Treponema vincenti. It is common in hot humid regions. 

Clinical features 

The ulcer is most common on the lower legs and develops as a papule that rapidly breaks down to a sharply defined, painful ulcer. The base of the ulcer has a foul slough. 


Penicillin and metronidazole are useful in the early stages but rest, elevation and dressings are the mainstays of treatment. 


This ulcer is caused by Mycobacterium ulcerans and occurs world-wide in tropical rainforests. In 1999 a survey in Ghana found 6500 cases; there are an estimated 10 000 cases in West Africa. 


The ulcer starts with acute necrosis. Clumps of acid-fast bacilli are present on the ulcer floor. Later, healing occurs with granuloma formation. 

Clinical features 

The initial lesion is a small subcutaneous nodule on the arm or leg. This breaks down to form a shallow, necrotic ulcer with deeply undermined edges which extends rapidly. Healing may occur after 6 months but the accompanying fibrosis causes contractures and deformity. 


Antibiotics are not clinically useful. Infected tissue should be removed surgically. 


Health campaigns in Ghana have successfully focused on early removal of the small, pre-ulcerative nodules. 


Yaws is a granulomatous disease mainly involving the skin and bones which is caused by Treponema pertenue, morphologically indistinguishable from the causative organisms of syphilis and pinta. The three infections induce similar serological changes and possibly some degree of cross-immunity. Organisms are transmitted by bodily contact from a patient with infectious yaws through minor abrasions of the skin of another patient, usually a child. The mass WHO campaigns between 1950 and 1960 treated over 60 million people and eradicated yaws from many areas, but the disease has persisted patchily throughout the tropics; there was a resurgence in the 1980s and 1990s in West and Central Africa and the South Pacific. 


A proliferative granuloma containing numerous treponemes develops at the site of the inoculation. This primary lesion is followed by secondary eruptions. In addition, there may be hypertrophic periosteal lesions of many bones, with underlying cortical rarefaction. Lesions of late yaws are characterised by destructive changes which closely resemble the osteitis and gummas of tertiary syphilis and which heal with much scarring and deformity. The incubation period is 3-4 weeks. 

Clinical features 

Early yaws 

The primary lesion or 'mother yaw' is usually on the leg or buttocks. The secondary eruption usually follows a few weeks or months later, as crops of papillomas covered with a whitish-yellow exudate, especially in the flexures and around the mouth. Sometimes a lesion erupts through the palm or sole, and walking becomes painful ('wet crab yaws'). Phalanges, nasal bones and tibiae swell and become distorted. Most of the lesions of early yaws will eventually subside, even if untreated. 

Latent yaws 

Following the spontaneous resolution of 'early yaws', serological changes may persist, to be followed by further manifestations of 'early yaws' or, after an interval of as much as 5-10 years, by the tertiary lesions or 'late yaws'. 

Late yaws 

Solitary or multiple lesions appear as nodules or ulcers in the skin, hyperkeratotic lesions of palms or soles ('dry crab yaws') and gummatous lesions of bone. They heal with scarring. Lesions of the facial and palatal bones cause terrible disfigurement (gangosa). 

Investigations and management 

See Box 1.59. 


The disease disappears with improved housing and cleanliness. In few fields of medicine have chemotherapy and improved hygiene achieved such dramatic success as in the control of yaws. 


Diagnosis of early stages

Detection of spirochaetes in exudate of lesions by dark ground microscopy


Diagnosis of latent and early stages

Positive serological tests, as for syphilis (see p. 99)


Treatment of all stages

Single intramuscular injection of 1.2 g long-acting (e.g. benzathine) penicillin G



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These two treponemal infections occur in poor rural populations with low standards of domestic hygiene, but in separate parts of the world. They have features in common, notably that they are transmitted by contact, usually within the family and not sexually, and in the case of bejel, through common eating and drinking utensils. Their diagnosis and management are as for yaws (see Box 1.59). 


Pinta is probably the oldest of the human treponemal infections and T. carateum the parent of the organism that came to Europe with the return of Christopher Columbus's sailors in 1493, starting the epidemic of venereal syphilis known as the 'Great Pox'. It is found only in South and Central America, where its incidence is declining. The early lesions are scaly papules or dyschromic patches on the skin. The late lesions are often depigmented and disfiguring. The infection is confined to the skin. 


Bejel is the Middle Eastern name for non-venereal syphilis, which has a patchy distribution across sub-Saharan Africa, the Middle East, Central Asia and Australia. It has been eradicated from Eastern Europe. Transmission is most commonly from the mouth of the mother or child and the primary mucosal lesion is seldom seen. The early and late lesions resemble those of secondary and tertiary syphilis (see pp. 96-100) but cardiovascular and neurological disease is rare.





These may be due to direct invasion of the skin (as in myiasis), due to parasite emergence through the skin (dracunculiasis) or a manifestation of immune reactivity to parasite antigens in the skin (Calabar swellings, see p. 75). 


This is widespread in tropical America and Africa and is caused by the sand flea Tunga penetrans. The pregnant flea burrows into the skin around toes and produces large numbers of eggs. The burrows are intensely irritating and the whole inflammatory nodule should be removed with a sterile needle. Secondary infection of tunga lesions is common. 


Myiasis is due to skin infestation with larvae of the South American botfly, Dermatobia hominis, and the African Tumbu fly, Cordylobia anthropophaga. The larvae develop in a subcutaneous space with a central sinus. This orifice is the air source for the larvae, and periodically the larval respiratory spiracles protrude through the sinus. Patients with myiasis feel movement within the larval burrow and experience intermittent sharp, lancinating pains. Myiasis is diagnosed clinically and should be suspected in any furuncular lesion accompanied by pain and a crawling sensation in the skin. The larva may be extruded by squeezing gently on the burrow and catching it with tweezers. Alternatively, the larva may be suffocated by blocking the respiratory orifice with petroleum jelly. Secondary infection of myiasis is remarkably infrequent and rapid healing follows removal of intact larvae. 


Guinea worm (Dracunculus medinensis) infestation manifests when the female worm, over a metre long, emerges from the skin. Humans are infected by ingesting a small crustacean, Cyclops, which inhabits wells and ponds and contains the infective larval stage of the worm. The worm was widely distributed across Africa and the Middle East. It has now nearly been eradicated from Pakistan and India and numbers have decreased spectacularly elsewhere. 


Ingested larvae mature, penetrate the intestinal wall and migrate through the host connective tissues. After 9-18 months the mature female surfaces under the skin, usually on the leg, where a vesicle is raised, ruptures and discharges worm larvae. The worm is attracted to the surface by cooling; hence the larvae are likely to be expelled into water, where they complete the life cycle. 

The disease can be extremely disabling. It is especially liable to affect those who collect water at water-holes, or farmers at the beginning of the rains, and thus seriously interferes with planting. 

Clinical features 

The adult worm may sometimes be felt beneath the skin. Some hours before the head of the worm emerges from the skin there is painful, hot, local vesicular inflammation. The larvae are discharged over 3-4 weeks; during this time the ulcer persists and there is pain and cellulitis. A marked allergic inflammation occurs if the worm dies or is broken during extraction. Secondary infection is common with cellulitis and arthritis, especially if the worm is close to an ankle or knee. Tetanus is a well-recognised complication. 


This is clinical. Discharge fluid may contain larvae. A radiograph may show calcified worms. 


Traditionally, the protruding worm is extracted by winding it out gently over several days on a matchstick. The worm must never be broken. Metronidazole or tiabendazole may reduce inflammation and aid the extraction of the worm. Antibiotics for secondary infection and prophylaxis of tetanus are also required. 


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The global elimination campaign is based on the provision of clean drinking water and eradication of water fleas from drinking water. The latter is being achieved by simple filtration of water through a plastic mesh filter and chemical treatment of water supplies. 


Mycetoma, in this restricted sense, is a chronic fungal infection of the deep soft tissues and bones, most commonly of the limbs but also of the abdominal or chest wall or head. It is produced by the fungal groups Eumycetes and Actinomycetes. Both groups produce characteristically coloured grains. 


The histology is that of a chronic granuloma with a fibrous stroma and cyst-like spaces in which lie the characteristic grains. 

Clinical features 

The fungus is usually introduced by a thorn and the infection is most common in the foot. The mycetoma begins as a painless swelling at the site of implantation, which grows and spreads steadily within the soft tissues, causing further swelling, and eventually penetrates bones. Nodules develop under the epidermis and these rupture revealing sinuses through which grains are discharged. Some sinuses may heal with scarring while fresh sinuses appear elsewhere. 

There is little pain and usually no fever or lymphadenopathy, but there is progressive disability. When the lesion is in the scalp, the skull may be affected but the dura mater appears to be an effective barrier. Nocardia brasiliensis often affects the skin of the back. It is seldom localised and may spread widely. 


Diagnosis is confirmed by demonstration of fungal grains in pus or tissue biopsy. Culture is usually necessary for species identification. Serology may be helpful. 


Localised lesions that can be excised without residual disability are best so treated. Medical treatment of fungal mycetomas is unsatisfactory. 

Among the fungal causes of mycetoma Madurella mycetomatis is the most sensitive to therapy, responding to ketoconazole in about 60% of cases. For the other cases treatment with griseofulvin or itraconazole may slow the progress of infection. Amputation should be considered carefully as in many countries it may deprive patients of their livelihood. 

Actinomycetes may be susceptible to treatment with combinations of rifampicin and dapsone for 3 months or co-trimoxazole for 4-24 months. Nocardia infection may respond to dapsone alone.




Leprosy (Hansen's disease) is a chronic granulomatous disease affecting skin and nerve; it is caused by Mycobacterium leprae. The clinical form of the disease is determined by the degree of cell-mediated immunity (CMI) expressed by that individual towards M. leprae (see Fig. 1.66). High levels of CMI with elimination of leprosy bacilli produce tuberculoid leprosy, whereas absent CMI results in lepromatous leprosy. The medical complications of leprosy are due to nerve damage, immunological reactions and bacillary infiltration. Nerve damage accompanying leprosy is a serious complication causing considerable morbidity. Leprosy patients are frequently stigmatised and using the word 'leper' is inappropriate. 

1.Organism  LEPROSY

M. leprae still cannot be grown in vitro but does grow in the nude mouse footpad and nine-banded armadillos. It grows at 30-33°C, has a doubling time of 12 days and is a stable, hardy organism which withstands drying for up to 5 months. It possesses a complex cell wall and synthesises a species-specific phenolic glycolipid (PGL). The genome of M. leprae has undergone massive gene decay and differs from M. tuberculosis by only 29 functional genes. Analysis of these proteins will be critical for understanding the survival and pathogenesis of M. leprae. 

2. Epidemiology  LEPROSY

Some 4 million people have or are disabled by leprosy. World-wide active transmission continues with 800 000 new cases annually and high rates of childhood cases. About 70% of the world's leprosy patients live in India with Brazil, Indonesia, Myanmar, Madagascar and Nepal being the next most endemic countries. Intensive week-long leprosy elimination campaigns in 1999 detected many new cases; in Nepal 11 696 new cases were found, doubling the national caseload. All new cases seen in the UK have acquired their infection abroad. Age, sex and household contact are important determinants of leprosy risk; leprosy incidence reaches a peak at 10-14 years, and an excess of male cases has been regularly found. HIV infection is not a risk factor for leprosy. HIV/leprosy coinfected patients have typical skin lesions and typical leprosy histology and granuloma formation even with low circulating CD4 counts.  

3. Transmission   LEPROSY

Untreated lepromatous patients discharge bacilli from the nose. Infection occurs through the nose followed by haematogenous spread to skin and nerve. The incubation period is 2-5 years for tuberculoid cases and 8-12 years for lepromatous cases. 

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Figure 1.66 Leprosy: mechanisms of damage and tissue affected. Mechanisms under the broken line are characteristic of disease near the lepromatous end of the spectrum and those under the solid line of the tuberculoid end. They overlap in the centre where, in addition, instability predisposes to type 1 lepra reactions. At the peak in the centre neither bacillary growth nor cell-mediated immunity has the upper hand. (BL = borderline lepromatous; BT = borderline tuberculoid)

4. Pathogenesis   LEPROSY

M. leprae has a predilection for Schwann cells and skin macrophages and the host response is critical in determining the outcome of infection. There are three important aspects of leprosy pathogenesis: the spectrum of immune responses, nerve damage and immune-mediated reactions. Figure 1.66 shows the Ridley-Jopling spectrum of response. At the tuberculoid pole, well-expressed CMI and delayed hypersensitivity control bacillary multiplication; organised epithelioid granulomata are seen in tissue biopsies. In the lepromatous form, there is cellular anergy towards M. leprae, resulting in abundant bacillary multiplication. Between these two poles is a continuum, varying from patients with moderate CMI (borderline tuberculoid) to patients with little cellular response (borderline lepromatous). The polar groups are stable but the central groups are immunologically unstable. 

Both T cells and macrophages are important in the response to M. leprae antigens. Tuberculoid patients have a Th1-type response to M. leprae, producing interleukin-2 (IL-2) and interferon-? (IFN-?), and positive lepromin (a soluble M. leprae preparation) skin test responses. This strong cell-mediated response clears antigen, but with local tissue destruction. Lepromatous patients have a specific cell-mediated T cell and macrophage anergy to M. leprae and poor lymphocyte responses to M. leprae antigens in vitro. They are negative on lepromin skin testing. They produce Th2-type cytokines. 

Nerve damage occurs across the spectrum in skin lesions and peripheral nerves. In tuberculoid disease epithelioid granulomata are found. In lepromatous leprosy bacilli are found in Schwann cells and the perineurium. Immune-mediated events are responsible for leprosy reactions (see below). 

5. Clinical features  LEPROSY


K   Skin lesions, typically anaesthetic at tuberculoid end of spectrum

K   Thickened peripheral nerves

K   Acid-fast bacilli on skin smears or biopsy



Patients commonly present with skin lesions or the effects of a peripheral nerve lesion, weakness or an ulcer in an anaesthetic hand or foot. Borderline patients may present as a reaction to nerve pain, sudden palsy, multiple new skin lesions. Box 1.60 gives the cardinal signs of leprosy. 

5. [A]  Skin. The most common skin lesions are macules or plaques. In lepromatous leprosy, papules, nodules or diffuse infiltration of the skin occurs. Tuberculoid patients have few, hypopigmented lesions whilst lepromatous patients have numerous, sometimes confluent lesions. 

5. [B] Anaesthesia. Anaesthesia occurs in skin lesions when dermal nerves are involved or in the distribution of a large peripheral nerve. In skin lesions the small dermal sensory and autonomic nerve fibres are damaged causing local sensory loss and loss of sweating within that area. 

5. [C] Peripheral neuropathy. Peripheral nerve trunks are affected at 'sites of predilection'. These are the ulnar (at the elbow), median (at the wrist), radial in the radial groove of the humerus causing wrist drop, radial cutaneous (at the wrist), common peroneal (at the knee), posterior tibial and sural nerves at the ankle, facial nerve as it crosses the zygomatic arch, and great auricular in the posterior triangle of the neck. Damage to peripheral nerve trunks produces characteristic signs with regional sensory loss and dysfunction of muscles supplied by that peripheral nerve. All these nerves should be examined for enlargement and tenderness and tested for motor and sensory function. The central nervous system is not affected. 

5. [D] Eye involvement. Blindness due to leprosy is a devastating complication for a patient with anaesthetic hands and feet. Eyelid closure is impaired when the facial nerve is affected. Damage to the trigeminal (5th) nerve causes anaesthesia of the cornea and conjunctiva. The cornea is then susceptible to trauma and ulceration. 



Figure 1.67 Tuberculoid leprosy. Single lesion with a well-defined active edge and anaesthesia within the lesion.

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Figure 1.68 Borderline tuberculoid leprosy with severe nerve damage. This boy has several well-defined, hypopigmented, macular, anaesthetic lesions. He has severe nerve damage affecting both ulnar and median nerves bilaterally and has sustained severe burns to his hands.

5. [1] Tuberculoid leprosy  

Tuberculoid leprosy (see Fig. 1.67) has a good prognosis; it may self-heal and peripheral nerve damage is limited. 

5. [2] Borderline tuberculoid  

The skin lesions (see Fig. 1.68) are similar to those in tuberculoid leprosy but are more numerous. Damage to peripheral nerves may be widespread and severe. These patients are prone to type 1 reactions with consequent nerve damage. 

5. [3] Borderline leprosy  

Borderline leprosy is unstable and patients have numerous skin lesions varying in size, shape and distribution. Annular lesions with a broad, irregular edge and a sharply defined, punched-out centre are characteristic. Nerve damage is variable. 

5. [4] Borderline lepromatous leprosy  

Borderline lepromatous leprosy is characterised by widespread small macules. They may experience both type 1 and type 2 reactions. Peripheral nerve involvement is widespread. 


5. [5] Lepromatous leprosy  


The earliest lesions are ill defined; gradually, the skin becomes infiltrated and thickened. Facial skin thickening leads to the characteristic leonine facies (see Fig. 1.69). Dermal nerves are destroyed, sweating is lost, and a 'glove and stocking' neuropathy is common. Nerve damage to large peripheral nerves occurs late in the disease. Nasal collapse occurs secondary to bacillary destruction of the bony nasal spine. Testicular atrophy is caused by diffuse infiltration and the acute orchitis that occurs with type 2 reactions. This results in azoospermia and gynaecomastia (see Box 1.61). 

5. [6] Pure neural leprosy  

This occurs principally in India and accounts for 10% of patients. There is asymmetrical involvement of peripheral nerve trunks and no visible skin lesions. On nerve biopsy all types of leprosy have been found. 


Figure 1.69 Lepromatous leprosy. Widespread nodules and infiltration with loss of the eyebrows. This man also has early collapse of the nose.


 Clinical and tissue-specific features Lepromatous Tuberculoid

 Skin and nerves

 Number and distribution Widely disseminated One or a few sites, asymmetrical

 Skin Lesions


   Clarity of margin Poor Good

   Elevation of margin Never Common


   Dark skin Slight hypopigmentation Marked hypopigmentation

   Light skin Slight erythema Coppery or red

 Surface Smooth, shiny Dry, scaly

 Central healing None Common

 Sweat and hair growth Impaired late Impaired early

 Loss of sensation Late Early and marked

 Nerve enlargement and damage Late Early and marked

 Bacilli (bacterial index) Many (5 or 6+) Absent (0)

 Natural outcome Progression Healing

 Other tissues Upper respiratory mucosa, eye, testes, bones, muscle None

 Reactions Immune complexes Cell-mediated


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6.  Leprosy reactionsLEPROSY


Leprosy reactions (see Box 1.62) are events superimposed on the cardinal features shown in Box 1.60). 

Type 1 (reversal) reactions  

These occur in 30% of borderline patients (BT, BB, BL) and are delayed hypersensitivity reactions caused by increased recognition of M. leprae antigens in skin and nerve sites. Skin lesions become erythematous (see Fig. 1.70); peripheral nerves become tender and painful. Loss of nerve function can be sudden, with foot drop occurring overnight. Reversal reactions may occur spontaneously, after starting treatment and also after completion of multidrug therapy. 


Figure 1.70 Reversal reactions. Erythematous, oedematous lesions.


   Lepra reaction type 1 (reversal) Lepra reaction type 2 (erythema nodosum leprosum)

 Mechanism Cell-mediated hypersensitivity Immune complexes

   Arthus phenomenon  

 Clinical features Painful tender nerves, loss of function Tender papules and nodules, may ulcerate

   Swollen skin lesions Painful tender nerves, loss of function

   New skin lesions Iritis, orchitis, myositis, lymphadenitis

   Rarely, fever Fever, oedema

 Management Mild: aspirin 600 mg 6-hourly Mild: aspirin 600 mg 6-hourly

   Severe1: prednisolone 40-80 mg, reducing over 3-9 months Severe1: thalidomide2 or prednisolone 20-40 mg, reducing over 1-6 months; local if eye involved3


1Includes any threat to nerve or eye function.

2See text for details.

31% hydrocortisone drops or ointment and 1% atropine drops. 

Type 2 (erythema nodosum leprosum-ENL) reactions  


These are partly due to immune complex deposition and occur in BL and LL patients who produce antibodies and have a high antigen load. They manifest with malaise, fever and crops of small pink nodules on the face and limbs. Iritis and episcleritis are common. Other signs are acute neuritis, lymphadenitis, orchitis, bone pain, dactylitis, arthritis and proteinuria. ENL may continue intermittently for several years. 

7.Investigations  LEPROSY

The diagnosis is clinical by finding a cardinal sign of leprosy, and is supported by finding acid-fast bacilli in slit skin smears or typical histology in a skin biopsy. Skin lesions should be tested for anaesthesia. The peripheral nerves should be palpated for thickening and tenderness. Neither serology nor PCR testing for M. leprae DNA is sensitive or specific enough for diagnosis. 

Slit skin smears  

The bacterial load is assessed by scraping dermal material on to a glass slide. The smears are then stained and acid-fast bacilli are scored on a logarithmic scale, the bacterial index (BI). Smears are useful for confirming the diagnosis and monitoring response to treatment. 

8.Differential diagnosis  LEPROSY


The anaesthesia of tuberculoid and borderline tuberculoid lesions differentiates them from fungal infections, vitiligo, psoriasis and eczema. The presence of acid-fast bacilli in smears differentiates lepromatous nodules from onchocerciasis, Kaposi's sarcoma and post-kala-azar dermal leishmaniasis. 


Leprosy is the most common cause of peripheral nerve thickening. Uncommon conditions such as Charcot-Marie-Tooth disease and amyloid are differentiated from leprosy by the absence of skin lesions and acid-fast bacilli. Always compare with nerves on the other side. The causes of other polyneuropathies such as HIV, diabetes, alcoholism, vasculitides and heavy metal poisoning should all be considered where appropriate. 

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Outside leprosy-endemic areas doctors often fail to diagnose leprosy. Of new patients seen between 1995 and 1999 at the Hospital for Tropical Diseases, London, diagnosis had been delayed in over 80% of cases. Patients had been misdiagnosed by dermatologists, neurologists, orthopaedic surgeons and rheumatologists. These delays had serious consequences for patients, with over half of them having nerve damage and disability. Always consider leprosy as a possible cause of peripheral neuropathy or neuropathic ulcers in patients of Indian or African origin. 

9.Management  LEPROSY

Effective treatment (see Box 1.63) can only be achieved with the patient's cooperation and confidence. All leprosy patients should be given an appropriate multidrug combination. Patients can be classified into paucibacillary (skin smear negative tuberculoid and BT) and multibacillary (skin smear positive BT, all BB, BL and LL). The first-line anti-leprosy drugs are rifampicin, clofazimine and dapsone. Box 1.64 gives the drug combinations, doses and duration of treatment. Studies from India have shown that multibacillary patients with an initial BI > 4 need longer treatment and should be treated to smear negativity. 

Rifampicin is a potent bactericidal for M. leprae. Four days after a single 600 mg dose bacilli from a previously untreated multibacillary patient were no longer viable in a mouse footpad test. As M. leprae can develop resistance to rifampicin as a single-step mutation, rifampicin should always be given in combination with other anti-leprotics. 


Stop the infection with chemotherapy

Treat reactions

Educate the patient about leprosy

Prevent disability

Support the patient socially and psychologically




 Type of leprosy* Monthly supervised drug treatment Daily self-administered drug treatment Duration of treatment

 Paucibacillary Rifampicin 600 mg Dapsone 100 mg 6 months

 Multibacillary Rifampicin 600 mg Clofazimine 50 mg 12 months

   Clofazimine 300 mg Dapsone 100 mg  

 Paucibacillary single-lesion Ofloxacin 400 mg   Single dose

   Rifampicin 600 mg    

   Minocycline 100 mg    


*WHO classification for field use when slit skin smears are not available:

paucibacillary single-lesion leprosy (one skin lesion)

paucibacillary (2-5 skin lesions)

multibacillary (more than 5 skin lesions).

In this field classification WHO recommends treatment of multibacillary patients for 12 months only. 

Dapsone is bacteriostatic. It commonly causes mild haemolysis but rarely anaemia. The 'dapsone syndrome', only occasionally seen in leprosy, starts 6 weeks after commencing dapsone and manifests as exfoliative dermatitis associated with lymphadenopathy, hepatosplenomegaly, fever and hepatitis. Clofazimine is a red, fat-soluble crystalline dye, weakly bactericidal for M. leprae. Skin discoloration (red to purple-black) and ichthyosis are troublesome side-effects, particularly on pale skins. New drugs bactericidal for M. leprae have been identified, notably the fluoroquinolones pefloxacin and ofloxacin, minocycline and clarithromycin. These agents are now established second-line drugs. Minocycline causes a black pigmentation of skin lesions and so may not be an appropriate substitute for clofazimine if pigmentation is to be avoided. 

More than 10 million patients have been treated successfully with multidrug treatment (MDT). Clinical improvement has been rapid and toxicity rare. The treatment duration has been shortened. Monthly supervision of the rifampicin component has been crucial to success. At the end of 6 months' treatment for borderline disease there may still be signs of inflammation which should not be mistaken for active infection. The distinction between relapse and reaction may be difficult. WHO studies have reported a cumulative relapse rate of 1.07% for paucibacillary leprosy and 0.77% for multibacillary leprosy at 9 years after completion of MDT. M. leprae is such a slow-growing organism that relapse only occurs after many years. A single-dose triple drug combination (rifampicin, ofloxacin and minocycline) has been tested in India for patients with single skin lesions. Although single-dose treatment is clinically less effective than the conventional 6-month treatment for paucibacillary leprosy, it is an operationally attractive field regimen and has been recommended for use by WHO. 

Treatment of reactions 

The principles of treating immune-mediated reactions are:

Control the acute inflammation and ease the pain.

Treat the neuritis.

Halt eye damage.


Type 1 reactions should be treated with oral prednisolone starting at 40 mg/day, and reduced by 5 mg/day each month. ENL is difficult to treat and requires high-dose steroids (80 mg daily, tapered down rapidly) or thalidomide. The chronicity of ENL reactions makes corticosteroid dependency a problem in these patients. Thalidomide is effective at controlling ENL but its teratogenic side-effects in early pregnancy limit its use in women of childbearing age. Chloroquine can also be used. 

Patient education 

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Educating leprosy patients about their disease is vital for successful management. Reassure patients that after 3 days of chemotherapy they are not infectious and can lead a normal social life. Emphasise that gross deformities are not inevitable, and that care of anaesthetic limbs is as important as chemotherapy. 

10.Prevention of disability  LEPROSY

The morbidity and disability associated with leprosy are secondary to nerve damage. Nerve damage produces anaesthesia, dryness and muscle weakness. These three factors lead to misuse of the affected limb, with resultant ulceration, infection and, ultimately, severe deformity. Monitoring sensation and muscle power in hands, feet and eyes should be part of the routine follow-up so that new nerve damage is detected early. The patient with an anaesthetic hand or foot needs to develop daily self-care and protection when performing dangerous tasks. Soaking dry hands and feet followed by rubbing with oil keeps the skin moist and supple. Physiotherapy can prevent contractures, muscle atrophy and over-stretching of paralysed muscles. 

Anaesthetic feet need protective footwear. For anaesthesia alone, a well-fitting 'trainer' with firm soles and shock-absorbing inners provides adequate protection. Once there is deformity, then special footwear is needed to protect pressure points and ensure even weight distribution. 

Teach patients to work out the causation of any injury so that recurrence can be avoided. Plantar ulceration occurs secondary to increased pressure over bony prominences. Ulceration is treated by rest. Unlike ulcers in diabetic feet, ulcers in leprosy heal if they are protected from weight-bearing. No weight-bearing is permitted until the ulcer has healed. Appropriate footwear should be provided to prevent recurrence. 

Social, psychological and economic rehabilitation 

The social and cultural background of the patient determines many of the problems that may be encountered. The patient may have difficulty in coming to terms with leprosy. The community may reject the patient. Education, employment, confidence in family, friends and doctor, and plastic surgery to correct stigmatising deformity all have a role to play. 

Leprosy in women 

Women with leprosy are in double jeopardy; not only may they develop post-partum nerve damage but they are also at particular risk of social ostracisation with rejection by spouse and family. 

11.Prognosis  LEPROSY

The majority of patients, especially those who have no nerve damage at the time of diagnosis, do well on MDT, with resolution of skin lesions. Borderline patients are at risk of developing type 1 reactions which may result in devastating nerve damage. 

12.Prevention and control  LEPROSY

The current strategy of leprosy control in endemic countries has been very successful. Vertical programmes provide case detection, treatment with WHO MDT and contact examination, and are supported by case-finding campaigns, especially in schools. Effective treatment is not merely restricted to chemotherapy but also involves good case management with effective monitoring and supervision. An important secondary role of leprosy control programmes is the prevention of disabilities. BCG vaccination has been shown to give good but variable protection against leprosy. Combining M. leprae with BCG does not enhance the protection from BCG. 







Splenomegaly (see p. 906) is occasionally the presenting feature of a tropically acquired infection. If it is acute and accompanied by a fever, then the causes listed in Box 1.65 should be considered. If it is moderate or massive, then endocarditis, splenic abscess, visceral leishmaniasis and hyper-reactive malarious splenomegaly should be considered. 


These will be guided by the context of the splenomegaly, particularly the travel and exposure history. Every patient should have several thick and thin blood films, blood cultures, a full blood count and film examination. Serologies where appropriate can help diagnose a viral infection. Imaging can detect a splenic abscess and indicate whether portal hypertension is present. The diagnosis of visceral leishmaniasis will require a bone marrow or splenic aspirate. 



Parasite infection


Katayama fever






















Subacute bacterial endocarditis

Splenic abscess

Portal hypertension due to schistosomiasis

Disseminated tuberculosis



Visceral leishmaniasis

Hyper-reactive malarial splenomegaly



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In some hyper-endemic areas gross splenomegaly is associated with an exaggerated immune response to malaria and is seen, unexpectedly, in adults who have high antibody titres to malaria and low parasitaemias. The condition, which is more common in females and in certain racial and family groups, is characterised by enormous over-production of IgM, levels reaching 3-20 times the local mean value. Much of the IgM is aggregated with other immunoglobulin or complement and precipitates in the cold, in vitro. IgM aggregates are phagocytosed by reticulo-endothelial cells in the spleen and liver, and the demonstration of this by immunofluorescence in a liver biopsy section is diagnostic. Light microscopy of the liver usually shows sinusoidal lymphocytosis. Anaemia and lymphocytosis can be confused with leukaemia. Portal hypertension may develop. 


Splenomegaly and anaemia usually resolve over a period of months of continuous treatment with proguanil 100 mg daily, which should be continued for life to prevent relapse. Complicating folate deficiency is treated with folic acid 5 mg daily.








This flavivirus is an important cause of encephalitis in Japan, China, South-east Asia and India. These regions are endemic for Japanese B encephalitis and epidemics also occur. In China, despite 70 million children being immunised, there are still 10 000 cases annually. Swine and birds are the virus reservoirs; transmission is by mosquitoes. 

Clinical features 

There is an initial systemic illness with fever, malaise and anorexia, followed by photophobia, vomiting, headache and changes in brain-stem function. Most children die from respiratory failure and frequently have evidence of cardiac and respiratory instability, reflecting viraemic spread via the vertebral vessels and infection of brain-stem nuclei. Other patients have evidence of multifocal CNS disease that involves the basal ganglia, thalamus and lower cortex, and develop tremors, dystonia and parkinsonian symptoms. Asymptomatic infection is common; of symptomatic infections there is a case fatality rate of 25% and 50% of survivors are left with neurological sequelae. 


Other infectious causes of encephalitis should be excluded (see p. 1197). Serological testing can be carried out. There is a CSF antigen test. 


Treatment should be supportive, anticipating and treating complications. 


In 1999 a newly discovered paramyxovirus, the Nipah virus, caused an epidemic of encephalitis amongst Malaysian pig farmers. Infection is through direct contact with pig secretions. Mortality is in the region of 30%. Antibodies to the Hendra virus are present in 76% of the cases. 


Melioidosis is caused by Burkholderia (Pseudomonas) pseudomallei, which is a saprophyte found in soil and water (paddy fields). Infection is by inoculation and inhalation. Diabetics and patients with severe burns are particularly susceptible. The disease is most common in the Far East, India, South-east Asia and Australia. 


A bacteraemia is followed by the formation of abscesses in the lungs, liver and spleen. 

Clinical features 

There is high fever, prostration and sometimes diarrhoea, with signs of pneumonia and enlargement of the liver and spleen. A chest radiograph resembles that of acute caseous tuberculosis. In more chronic forms multiple abscesses recur in subcutaneous tissue and bone. 


Culture of blood, sputum or pus may yield B. pseudomallei. Except in fulminating infections, antibodies may be detected by indirect haemagglutination, direct agglutination, and complement-fixation tests. 


In acute illness prompt treatment, without waiting for confirmation by culture, may be life-saving. Ceftazidime 120 mg/kg plus tetracycline 3 g daily are given in divided doses for about 2-3 weeks, followed by doxycycline 200 mg daily for 2-3 months, until pulmonary cavities have healed. Abscesses should be drained surgically. In chronic cases profound wasting is a major clinical problem.






Histoplasmosis is caused by Histoplasma capsulatum; this is a yeast in its parasitic phase but is a filamentous fungus of soil at other times. A variant, H. duboisii, is found in parts of tropical Africa. 

H. capsulatum multiplies in soil enriched by the droppings of birds and bats, and the spores remain viable for years. Natural infections are found in several species of small mammal, including bats. Infection is by inhalation of infected dust. The infection is an especial hazard for explorers of caves and people who clear out bird (including chicken) roosts. 

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H. capsulatum is found in all parts of the USA, especially in the east central states, and less commonly in Latin America from Mexico to Argentina, Europe, North, South and East Africa, Nigeria, Malaysia, Indonesia and Australia. Disseminated histoplasmosis is also seen in immunocompromised patients, e.g. those with AIDS (see p. 115). 


The parasite in its yeast phase multiplies mainly in monocytes and macrophages, and produces areas of necrosis in which the parasites may abound. From these foci the blood stream may be invaded, producing metastatic lesions in the liver, spleen and lymph nodes. Pulmonary histoplasmosis may cause pathological changes similar to those of tuberculosis, including the production of a primary complex with enlarged regional lymph nodes, multiple small discrete lesions and occasionally cavitation. Healed lesions may calcify. 


In an area where the disease occurs, histoplasmosis should be suspected in every obscure infection in which there are pulmonary signs or where there are enlarged lymph nodes or hepatosplenomegaly. Tissue is obtained by biopsy for an impression smear, histology and culture. Radiological examination in long-standing cases may show calcified lesions in the lungs, spleen or other organs. In the more acute phases of the disease single or multiple soft pulmonary shadows with enlarged tracheobronchial nodes are seen. 

Delayed hypersensitivity to the intradermal injection of histoplasmin develops in patients with either active or healed infections but is usually negative in acute disseminated disease. Complement-fixing antibodies are detected within 3 weeks of the onset of an acute primary infection and increase in titre as the disease progresses. Precipitating antibodies may also be detected. 


Specific treatment with amphotericin B is indicated only in severe infections; the dosage (0.5 mg/kg in 500 ml of 5% glucose) is given intravenously over a 6-hour period, gradually increasing to a maximum of 1.0 mg/kg. Treatment is given on alternate days to a total adult dose of 2 g. If badly tolerated, the dose may have to be reduced. Side-effects are anorexia, nausea, fever, headache, and venous thrombosis which may be controlled by the addition of 10 mg prednisolone to the intravenous solution. Plasma urea rises and haemoglobin falls during treatment but later they return to normal. Amphotericin may have to be continued for up to 3 months or longer, depending on the clinical response. Severe dyspnoea in histoplasmosis should be treated with prednisolone 20-40 mg daily for a few days. Itraconazole 200-400 mg daily can be used in chronic pulmonary histoplasmosis and chronic disseminated histoplasmosis. 


H. duboisii, the fungus of African histoplasmosis, is larger than the classical H. capsulatum. It is found throughout East, Central and West Africa. 

The disease differs in several ways from H. capsulatum infection. The bones, skin, lymph nodes and liver develop granulomatous lesions or cold abscesses resembling tuberculosis, but the lungs are seldom involved. The visceral form with liver and splenic invasion is often fatal, while ulcerative skin lesions and bone abscesses follow a more benign course. 

Radiological examination may show rounded foci of bone destruction, sometimes associated with abscess formation. Multiple lesions of the ribs are common and the bones of the limbs may be involved. Systemic disease is treated in the same way as H. capsulatum infections. A solitary lesion in bone may require only local surgical treatment. 


This is the most common respiratory mycosis in Britain and is discussed on page 540. 


This is caused by Coccidioides immitis and is found in the southern USA, and Central and South America. The disease is acquired by inhalation. The infection behaves like tuberculosis or histoplasmosis. In 60% of cases it is asymptomatic, but in 40% of cases it affects the lungs, lymph nodes and skin. Rarely, it may be carried by the blood stream to the bones, adrenals, meninges and other organs. Pulmonary coccidioidomycosis has two forms: primary and progressive. Primary coccidioidomycosis behaves like primary tuberculosis or histoplasmosis and is often asymptomatic. The progressive form of the disease is associated with marked systemic upset and features of lobar pneumonia. In more chronic cases it may resemble chronic tuberculosis. Infections, including subclinical attacks, are followed by immunity. 

The fungi grow readily on culture media but as they are highly infective, diagnostic investigations are usually limited to intradermal, complement fixation and precipitin tests. 

Amphotericin B (as for histoplasmosis), itraconazole, ketoconazole or fluconazole may be helpful but relapse is common. Some localised pulmonary lesions can be treated by surgery. 


This is caused by Paracoccidioides brasiliensis and occurs in South America. Mucocutaneous lesions occur early. Involvement of lymphatic nodes and the lungs is prominent and the gastrointestinal tract may also be attacked. Most patients respond to ketoconazole 200 mg/day for at least 6 months; itraconazole 100-200 mg daily is an alternative. Liver function must be monitored for either agent. For those who do not respond, amphotericin B (as for histoplasmosis) may be used. 

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North American blastomycosis is caused by Blastomyces dermatitidis. It also occurs in Africa. Systemic infection begins in the lungs and mediastinal lymph nodes and resembles pulmonary tuberculosis. Bones, skin and the genitourinary tract may also be affected. Treatment is with itraconazole 200-400 mg daily, ketoconazole 200-400 mg daily or amphotericin B (see above).  


This is caused by Cryptococcus neoformans. Its distribution is world-wide. It causes local gumma-like tumours and granulomatous lesions of the lung, bones, brain and meninges. The CSF often contains the fungus when the nervous system is affected. Immunocompromised individuals are at special risk, including those with HIV infection (see p. 124). 

The diagnosis is made by culture or recognition of spores in the CSF, biopsy and serological detection of antigen. 

Amphotericin B should be given intravenously (see above) and flucytosine orally (see p. 143). Surgical removal of local pulmonary lesions may be necessary. Recovery may be monitored by the fall in antigen titre. Cryptococcal meningitis is particularly important in HIV infection. 


Candida albicans is a cause of systemic fungal infection in the immunosuppressed (see p. 116). 





In 1999 49 million overseas visits were made by UK residents; these included almost 1 million to Africa and half a million to the Indian subcontinent. Malaria remains a major risk to travellers but the principal causes of death whilst travelling are road traffic accidents, drowning and exacerbation of chronic disease. Good travel insurance is imperative. The key principles of travel medicine are assessing the risks that the traveller will be exposed to, advising on malaria prophylaxis, and ensuring that the traveller is aware of the role of personal protection in preventing disease. Information on local disease patterns can be obtained from the WHO and CDC websites; advice on available vaccines can be obtained from the UK Department of Health book Health information for overseas travel (see p. 146). 

Assessing the risks 

Risks of encountering local disease need to be assessed so that balanced advice about vaccinations and other protection can be given. Ask about:

Type of travel-holiday or business.

Accommodation-five-star or adventurous.

Urban or rural travel. Rural travel often poses greater risks.

Itinerary. Malaria may be confined to certain areas. In Thailand the coastal areas are malaria-free but the jungle highlands have multidrug-resistant parasites.

Activities-jungle trekking, water sports.

Length of trip.


Effective vaccines are available for many diseases, including yellow fever, rabies, typhoid and hepatitis. However, some vaccines, such as Japanese B encephalitis vaccine, have adverse effects and the degree of protection needed should be balanced against potential side-effects. 

Malaria prophylaxis 

The risk of malaria is often difficult to gauge but a proxy is the entomological inoculation rate (EIR)-the number of infective Plasmodium falciparum bites received per person per year. The EIR in Tanzania is 667, which implies a risk of two infective bites per night. All travellers to malarious areas should be encouraged to take chemoprophylaxis, especially young children (see p. 56). Advice on the best combinations can be obtained from the WHO and CDC websites. Personal protection is also important in avoiding malaria. Travellers should be advised to:

sleep under bed nets

wear long-sleeved shirts and trousers, especially after dusk

use insect repellents.


Travellers should also be made aware of the importance of seeking prompt medical advice when they develop a fever so that malaria can be excluded. 

Personal protection 

Travellers can be advised on ways of reducing the risk of travellers' diarrhoea such as:

drinking bottled water wherever possible, ensuring that the seal on the bottle is intact

avoiding food exposed to flies

avoiding salads and unpeeled fruit.


Skin protection with sunscreen will reduce sunburn. 

Unplanned sexual activity often occurs when travelling. The risk of sexually transmitted diseases can be reduced for both partners by using condoms. 




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