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49TROPICAL AND INTERNATIONAL HEALTH
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
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Controlling tropical diseases has proved difficult. War can undermine good control programmes as in central
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.
49.1
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FEVER IN/FROM THE TROPICS
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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.
History
Vital questions to ask anyone returning from the tropics are listed in
1.31 KEY QUESTIONS FOR DIAGNOSING A FEVER IN THE TROPICS
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.
1.32 SPECIFIC EXPOSURES THAT ASSIST IN DIAGNOSIS OF FEVER FROM THE TROPICS
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,
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.
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.
Examination
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.
Investigations
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Figure 1.45 Acute fever in/from the tropics: clinical examination.
1.33 DIFFERENTIAL WHITE CELL COUNTS (WCC): ACUTE FEVER IN THE ABSENCE OF LOCALISING SIGNS
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.
49.2
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FEVER WITHOUT LOCALISING SIGNS
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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.
MALARIA
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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
Pathogenesis
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
Pathology
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
1.34 RELATIONSHIPS BETWEEN LIFE CYCLE OF PARASITE AND CLINICAL FEATURES OF MALARIA
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
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
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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1.35 SEVERE MANIFESTATIONS AND COMPLICATIONS OF FALCIPARUM MALARIA AND THEIR IMMEDIATE MANAGEMENT
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
Haemofilter
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
Physiotherapy
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
Diagnosis
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.
Management
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
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
1.36 INEFFECTIVENESS OF ANCILLARY TREATMENTS IN MALARIA
Corticosteroids (dexamethasone)
Other anti-inflammatory agents
Other anti-cerebral oedema agents (urea, mannitol, invert sugar)
Low molecular weight dextran
Adrenaline (epinephrine)
Heparin
Epoprostenol
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
The management of severe malaria involves careful attention to all the major organ systems (see
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.
Prevention
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.
Chemoprophylaxis
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').
1.37 CHEMOPROPHYLAXIS OF MALARIA
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
49.3
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FEVER WITH RASH
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The combination of fever and rash in someone in or from the tropics raises a distinctive set of diagnostic possibilities (see
1.38 DIAGNOSTIC POSSIBILITIES FOR FEVER AND RASH IN OR FROM THE TROPICS
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
FEVER WITH RASH49.3
[4]TYPHOID AND PARATYPHOID (ENTERIC)FEVERS
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.
Aetiology
The enteric fevers are caused by infection with Salmonella typhi and S. paratyphi A and B. High levels of transmission continue in
Pathology
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
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.
1.39 CLINICAL FEATURES OF TYPHOID FEVER
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.
Complications
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1.40 COMPLICATIONS OF TYPHOID FEVER
Bowel
§ Perforation
§ Haemorrhage
Septicaemic foci
§ Bone and joint infection
§ Cholecystitis
§ Meningitis
Toxic phenomena
§ Myocarditis
§ Nephritis
These are given in
[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).
FEVER WITH RASH49.3
[3]DENGUE
The dengue flavivirus is a common cause of fever in and from the tropics. It is endemic in
[X] Clinical features DENGUE FEVER WITH RASH
The disease varies in severity. The clinical features are listed in
Figure 1.50 Endemic zones of yellow fever and dengue.
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1.41 CLINICAL FEATURES OF DENGUE FEVER
Prodrome
· 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
Fever
· Continuous or 'saddle-back', with break on fourth or fifth day; usually lasts 7-8 days
Rash
· 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
[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.
FEVER WITH RASH49.3
[2]AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS)
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
Figure 1.51 Trypanosomiasis. Scanning electron micrograph showing trypanosomes swimming among erythrocytes.
[X] Clinical features AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS) FEVER WITH RASH
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.
[Y] Investigations AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS) FEVER WITH RASH
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.
[Z] Management AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS) FEVER WITH RASH
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.
[Z1] Prevention AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS) FEVER WITH RASH
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.
FEVER WITH RASH49.3
[1]AMERICAN TRYPANOSOMIASIS (CHAGAS DISEASE)
Chagas disease occurs widely in South and
FEVER WITH RASH
[X1] Pathology AMERICAN TRYPANOSOMIASIS (CHAGAS DISEASE)
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.
FEVER WITH RASH
[X] Clinical features AMERICAN TRYPANOSOMIASIS (CHAGAS DISEASE)
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.
FEVER WITH RASH
[Y] Investigations AMERICAN TRYPANOSOMIASIS (CHAGAS 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.
FEVER WITH RASH
[Z] Management AMERICAN TRYPANOSOMIASIS (CHAGAS DISEASE)
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.
FEVER WITH RASH
[Z1] Prevention AMERICAN TRYPANOSOMIASIS (CHAGAS 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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49.4
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FEVER WITH HAEMORRHAGE
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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
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
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.
[X1] Pathology YELLOW FEVER FEVER WITH HAEMORRHAGE
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.
[X] Clinical features YELLOW FEVER FEVER WITH HAEMORRHAGE
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.
1.42 DIAGNOSIS OF YELLOW FEVER
· 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
[Y] Investigations YELLOW FEVER FEVER WITH HAEMORRHAGE
Diagnostic procedures are listed in
[Z] Management YELLOW FEVER FEVER WITH HAEMORRHAGE
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.
[Z1] Prevention YELLOW FEVER FEVER WITH HAEMORRHAGE
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.
FEVER WITH HAEMORRHAGE
VIRAL HAEMORRHAGIC FEVERS
The viral haemorrhagic fevers are zoonoses caused by several different viruses (see
[X] Pathogenesis VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
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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1.43 COMMON VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
Disease Reservoir Transmission Geography Case mortality Clinical features
Lassa fever Multimammate rat (Mastomys natalensis) Urine
Patient Body fluids
Marburg/Ebola virus disease ? Patient Via monkeys' body fluids
Blood oozing
Yellow fever Monkeys Mosquitoes Tropical Africa, South and
Blood oozing
Dengue Humans Aedes aegypti et al. Tropical and subtropical coasts Nil-10% Joint and bone pain
Petechiae
Crimean-Congo Ixodes tick Ixodes tick
Blood oozing
Petechiae
Bolivian and Argentinian Rodents (Calomys spp.) Urine
Petechiae
Haemorrhagic fever with renal syndrome (
1 All have circulatory failure.
2 Mortality of uncomplicated and haemorrhagic dengue fever, respectively.
[X] Clinical features VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
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
[Y] Investigations VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
There is leucopenia, thrombocytopenia and proteinuria. In Lassa fever an aspartate amino transferase (AST) > 150 i.u./l is associated with a 50% mortality.
[Y1] Diagnosis VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
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).
[Z] Management VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
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.
[Z1] Prevention VIRAL HAEMORRHAGIC FEVERS FEVER WITH HAEMORRHAGE
Ribavirin has been used as prophylaxis in close contacts of Lassa fever patients but there are no formal trials of its efficacy.
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FEVER FOLLOWING ARTHROPOD BITES
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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.
RICKETTSIAL FEVERS
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
[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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1.44 ESSENTIAL FEATURES OF RICKETTSIAL INFECTIONS
Disease Reservoir Vector Primary complex Rash Gangrene Target organs Mortality
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
Tick-borne South African typhus. R. conorii causes
Typhus group
Scrub typhus fever. Scrub typhus is caused by R. tsutsugamushi, transmitted by mites. It occurs in the
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
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
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.
FEVER FOLLOWING ARTHROPOD BITES
LYME DISEASE
See page 21.
FEVER FOLLOWING ARTHROPOD BITES
LOUSE-BORNE RELAPSING FEVER
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.
Pathology
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.
Prevention
The patient, clothing and all contacts must be freed from lice as in epidemic typhus.
FEVER FOLLOWING ARTHROPOD BITES
PLAGUE
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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
[X1] Pathology PLAGUE FEVER FOLLOWING ARTHROPOD BITES
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.
[Y] Investigations PLAGUE FEVER FOLLOWING ARTHROPOD BITES
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.
[Z] Management PLAGUE FEVER FOLLOWING ARTHROPOD BITES
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.
[Z1] Prevention PLAGUE FEVER FOLLOWING ARTHROPOD BITES
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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FEVER FOLLOWING ARTHROPOD BITES
BABESIOSIS
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.
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CHRONIC FEVER
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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
1.45 INFECTIOUS CAUSES OF CHRONIC FEVER
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
1.46 DIFFERENTIAL WHITE CELL COUNTS (WCC) IN CHRONIC FEVER
WCC differential Potential diagnoses
Neutrophil leucocytosis Deep sepsis/abscess*
Amoebic liver abscess
Cholangitis
Eosinophilia Invasive schistosomiasis
Other invasive parasitic infections
Leucopenia Malaria
Disseminated tuberculosis
Visceral leishmaniasis
Brucellosis
Normal WCC Localised tuberculosis
Brucellosis
Secondary syphilis
Trypanosomiasis
Toxoplasmosis
Subacute bacterial endocarditis
SLE
Chronic meningococcal septicaemia
Variable WCC Tumours
Reticuloses
Drug reactions
Connective tissue disease
*May show spiking fever.
CHRONIC FEVER
AMOEBIC LIVER ABSCESS
This often occurs without a history of recent diarrhoea. It is common in the tropics and an important cause of imported fever in
[X1] Pathogenesis AMOEBIC LIVER ABSCESS CHRONIC FEVER
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.
[X] Clinical features AMOEBIC LIVER ABSCESS CHRONIC FEVER
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.
[Y] Investigations AMOEBIC LIVER ABSCESS CHRONIC FEVER
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.
[Z] Management AMOEBIC LIVER ABSCESS CHRONIC FEVER
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.
CHRONIC FEVER
VISCERAL LEISHMANIASIS (KALA-AZAR)
Leishmaniasis may take the form of a generalised visceral febrile infection, kala-azar, or of a purely cutaneous infection, known in the
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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
[X1] Pathology KALA-AZAR CHRONIC FEVER
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
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.
[Z] Management KALA-AZAR CHRONIC FEVER
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The response to treatment varies with the geographic area in which the disease has been acquired. In
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.
[Z1] Prevention KALA-AZAR CHRONIC FEVER
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
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DIPHTHERIA
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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
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.
1.47 CLINICAL FEATURES OF DIPHTHERIA
Acute infection
· Membranous tonsillitis
· or Nasal infection
· or Laryngeal infection
· or Skin/wound/conjunctival infection (rare)
Complications
· Laryngeal obstruction or paralysis
· Myocarditis
· Peripheral neuropathy
[X] Clinical features (see
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.
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EOSINOPHILIA AND TROPICAL INFECTIONS
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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.
1.48 CAUSES OF 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
1.49 PARASITE INFECTIONS THAT CAUSE EOSINOPHILIA
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
haematobium
S. mansoni
S. japonicum
Filariases
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
1.50 TROPICAL INFECTIONS NOT ASSOCIATED WITH EOSINOPHILIA
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
[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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1.51 EOSINOPHILIC SYNDROMES ASSOCIATED WITH HELMINTIC INFECTIONS
Urticarial rashes
· Strongyloidiasis, onchocerciasis, fascioliasis, hydatid disease, trichinosis
Cutaneous larva migrans
· Ancylostoma braziliense
Dermatitis
· Onchocerciasis
Migratory subcutaneous swellings
· Loiasis, gnathostomiasis
Lymphangitis, orchitis
· Lymphatic filariasis
Myositis
· Trichinosis, cysticercosis
Febrile hepatosplenomegaly
· Schistosomiasis, toxocariasis
Pneumonitis
· 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
Meningitis
· 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.
1.52 INITIAL INVESTIGATION OF 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.
| Investigation | 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 |
| 7.Serology | Schistosomiasis, filariasis, strongyloidiasis, hydatid, trichinosis etc. |
49.9
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PARASITIC CAUSES OF EOSINOPHILIA
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SOIL-TRANSMITTED HELMINTHIASES
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.
PARASITIC CAUSES OF EOSINOPHILIA
ANCYLOSTOMIASIS (HOOKWORM)
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
PARASITIC CAUSES OF EOSINOPHILIA
[X1] Pathology ANCYLOSTOMIASIS (HOOKWORM)
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.
PARASITIC CAUSES OF EOSINOPHILIA
[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.
[Y] Investigations ANCYLOSTOMIASIS (HOOKWORM) PARASITIC CAUSES OF EOSINOPHILIA
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.
[Z] Management ANCYLOSTOMIASIS (HOOKWORM) PARASITIC CAUSES OF EOSINOPHILIA
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">
PARASITIC CAUSES OF EOSINOPHILIA
STRONGYLOIDIASIS
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
[X1] Pathology STRONGYLOIDIASIS PARASITIC CAUSES OF EOSINOPHILIA
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.
[X] Clinical features STRONGYLOIDIASIS PARASITIC CAUSES OF EOSINOPHILIA
These are shown in
1.53 CLINICAL FEATURES OF STRONGYLOIDIASIS PARASITIC CAUSES OF EOSINOPHILIA
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
Autoinfection
Transient itchy linear urticarial weals across abdomen and buttocks (larva currens)
Systemic (super)infection
Diarrhoea, pneumonia, meningoencephalitis, death
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[Y] Investigations STRONGYLOIDIASIS PARASITIC CAUSES OF EOSINOPHILIA
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.
[Z] Management STRONGYLOIDIASIS PARASITIC CAUSES OF EOSINOPHILIA
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.
PARASITIC CAUSES OF EOSINOPHILIA
ASCARIS LUMBRICOIDES (ROUNDWORM)
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.
[X] Clinical features ROUNDWORM PARASITIC CAUSES OF EOSINOPHILIA
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.
[Y] Investigations ROUNDWORM PARASITIC CAUSES OF EOSINOPHILIA
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.
[Z] Management ROUNDWORM PARASITIC CAUSES OF EOSINOPHILIA
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.
[Z1] Prevention ROUNDWORM PARASITIC CAUSES OF EOSINOPHILIA
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.
PARASITIC CAUSES OF EOSINOPHILIA
TRICHINOSIS
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
[X] Clinical features TRICHINOSIS PARASITIC CAUSES OF EOSINOPHILIA
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.
[Y] Investigations TRICHINOSIS PARASITIC CAUSES OF EOSINOPHILIA
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.
[Z] Management TRICHINOSIS PARASITIC CAUSES OF EOSINOPHILIA
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
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HELMINTHS NOT ASSOCIATED WITH EOSINOPHILIA
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ENTEROBIUS VERMICULARIS (THREADWORM)
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.
[X] Clinical features THREADWORM HELMINTHS NOT ASSOCIATED WITH EOSINOPHILIA
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.
[Y] Investigations THREADWORM HELMINTHS NOT ASSOCIATED WITH EOSINOPHILIA
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.
[Z] Management THREADWORM HELMINTHS NOT ASSOCIATED WITH EOSINOPHILIA
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.
HELMINTHS NOT ASSOCIATED WITH EOSINOPHILIA
TRICHURIS TRICHIURA (WHIPWORM)
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.
PREVENTION OF HELMINTHIASES
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.
49.11
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FILARIASES
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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
1.54 PATHOGENICITY OF FILARIAL INFECTIONS DEPENDING ON SITE AND STAGE OF
Worm species Adult worm Microfilariae
Wuchereria bancrofti and Brugia malayi Lymphatic vessels+++ Blood-
Pulmonary capillaries++
Loa loa Subcutaneous+ Blood+
Onchocerca volvulus Subcutaneous+ Skin+++
Eye+++
Mansonella perstans Retroperitoneal- Blood-
Mansonella streptocerca Skin+ Skin++
(+++ = severe; ++ = moderate; + = mild; - = rarely pathogenic)
| 1.54 PATHOGENICITY OF FILARIAL INFECTIONS DEPENDING ON SITE AND STAGE OF | ||
| Worm species | Adult worm | Microfilariae |
| 1.Wuchereria bancrofti and Brugia malayi | Lymphatic vessels+++ | Blood- Pulmonary capillaries++ |
| 2.Loa loa | Subcutaneous+ | Blood+ |
| 3.Onchocerca volvulus | Subcutaneous+ | Skin+++ Eye+++ |
| 4.Mansonella perstans | Retroperitoneal- | Blood- |
| 5.Mansonella streptocerca | Skin+ | Skin++ |
49.11.1
LYMPHATIC FILARIASIS
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
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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
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
[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.
49.11.2
NON-FILARIAL ELEPHANTIASIS
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.
49.11.3
LOIASIS
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.
49.11.4
ONCHOCERCIASIS (RIVER BLINDNESS)
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
Onchocerciasis is endemic in well-defined areas throughout tropical
[X1]Pathology ONCHOCERCIASIS (RIVER BLINDNESS)
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.
[X]Clinical features ONCHOCERCIASIS (RIVER BLINDNESS)
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.
[Y]Investigations ONCHOCERCIASIS (RIVER BLINDNESS)
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.
[Z]Management ONCHOCERCIASIS (RIVER BLINDNESS)
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.
[Z1]Prevention ONCHOCERCIASIS (RIVER BLINDNESS)
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.
49.11.5
OTHER FILARIASES
Mansonella perstans
This filarial worm is transmitted by the midges Culicoides austeni and C. grahami. It is common throughout equatorial
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
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SCHISTOSOMIASIS
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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
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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
Figure 1.60 Schistosoma. A Life cycle. B Scanning electron micrograph of adult schistosome worms showing the larger male worm embracing the thinner female.
1.55 PATHOGENESIS OF SCHISTOSOMIASIS
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
[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
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
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
[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.
49.13
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LIVER FLUKES
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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
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1.56 DISEASES CAUSED BY FLUKES IN THE BILE DUCT
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
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
| 1.56 DISEASES CAUSED BY FLUKES IN THE BILE DUCT | |||
| | 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 | | | Cosmopolitan, including |
| 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 | |||
49.14
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CYSTICERCOSIS AND HYDATID DISEASE
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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.
TAENIA SAGINATA
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).
TAENIA SOLIUM AND CYSTICERCOSIS
T. solium, the pork tapeworm, is common in central
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.
Investigations
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
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.
ECHINOCOCCUS GRANULOSUS (TAENIA ECHINOCOCCUS) AND HYDATID DISEASE
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
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.
Investigations
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
1.57 COMMON CAUSES OF SKIN LESIONS IN THE TROPICS
Lesion type Aetiology Clinical features
Papules
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
Ulcers
Ecthyma (see p. 23) Staphylococcus aureus, Vesicle or crusted pustule
ß-haemolytic streptococcus
Oriental sore,
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
Vesicles
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.
OTHER TAPEWORMS
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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SKIN CONDITIONS IN THE TROPICS
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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.
CUTANEOUS LARVA MIGRANS
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
Cutaneous leishmaniasis (CL) is caused by the protozoon Leishmania. The geographical origin of the parasite is critical (see Fig. 1.64); in the
Figure 1.64 World distribution of human leishmaniasis. A Visceral leishmaniasis. B Cutaneous leishmaniasis.
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1.58 TYPES OF OLD WORLD LEISHMANIA
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
Pathogenesis
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.
In South and
Pathogenesis
Microscopically, the appearances are similar to
Clinical features
Clinically, lesions of L. mexicana and L. peruviana closely resemble those seen in the
Investigations
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.
Management
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
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Prevention
Personal protection against sandfly bites is important. No effective vaccine is yet available.
TROPICAL ULCER
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.
Management
Penicillin and metronidazole are useful in the early stages but rest, elevation and dressings are the mainstays of treatment.
BURULI ULCER
This ulcer is caused by Mycobacterium ulcerans and occurs world-wide in tropical rainforests. In 1999 a survey in
Pathogenesis
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.
Management
Antibiotics are not clinically useful. Infected tissue should be removed surgically.
Prevention
Health campaigns in
YAWS
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
Pathology
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
Prevention
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.
1.59 DIAGNOSIS AND TREATMENT OF YAWS, PINTA AND BEJEL
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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PINTA AND BEJEL
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
Pinta
Pinta is probably the oldest of the human treponemal infections and T. carateum the parent of the organism that came to
Bejel
Bejel is the Middle Eastern name for non-venereal syphilis, which has a patchy distribution across sub-Saharan
49.16
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SUBCUTANEOUS SWELLINGS
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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).
JIGGERS (TUNGIASIS)
This is widespread in tropical
MYIASIS
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.
DRACUNCULIASIS (GUINEA WORM)
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
Pathology
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.
Diagnosis
This is clinical. Discharge fluid may contain larvae. A radiograph may show calcified worms.
Management
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.
Prevention
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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 (MADURA FOOT)
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.
Pathology
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.
Investigations
Diagnosis is confirmed by demonstration of fungal grains in pus or tissue biopsy. Culture is usually necessary for species identification. Serology may be helpful.
Management
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.
49.17
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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
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
1.60 CARDINAL FEATURES OF 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.
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
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.
1.61 CLINICAL CHARACTERISTICS OF THE POLAR FORMS OF LEPROSY
Clinical and tissue-specific features Lepromatous Tuberculoid
Skin and nerves
Number and distribution Widely disseminated One or a few sites, asymmetrical
Skin Lesions
Definition
Clarity of margin Poor Good
Elevation of margin Never Common
Colour
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
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.
1.62 REACTIONS IN LEPROSY
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
Skin
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.
Nerves
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,
9.Management LEPROSY
Effective treatment (see
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.
1.63 PRINCIPLES OF LEPROSY TREATMENT
Stop the infection with chemotherapy
Treat reactions
Educate the patient about leprosy
Prevent disability
Support the patient socially and psychologically
1.64 MODIFIED WHO-RECOMMENDED MULTIDRUG THERAPY REGIMENS IN LEPROSY
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
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.
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SPLENOMEGALY IN/FROM THE TROPICS
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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
Investigations
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.
1.65 CAUSES OF TROPICAL SPLENOMEGALY
Mild
Parasite infection
Malaria
Katayama fever
Toxoplasmosis
Trypanosomiasis
Viral
EBV
Hepatitis
Dengue
HIV
CMV
Bacterial
Typhoid
Brucellosis
Spirochaetal
Leptospirosis
Fungal
Histoplasmosis
Moderate
Subacute bacterial endocarditis
Splenic abscess
Portal hypertension due to schistosomiasis
Disseminated tuberculosis
Massive
Visceral leishmaniasis
Hyper-reactive malarial splenomegaly
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HYPER-REACTIVE MALARIAL SPLENOMEGALY (TROPICAL SPLENOMEGALY SYNDROME)
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.
Management
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.
49.19
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OTHER SYSTEMIC INFECTIONS
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JAPANESE B ENCEPHALITIS
This flavivirus is an important cause of encephalitis in
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.
Diagnosis
Other infectious causes of encephalitis should be excluded (see p. 1197). Serological testing can be carried out. There is a CSF antigen test.
Management
Treatment should be supportive, anticipating and treating complications.
NIPAH VIRUS ENCEPHALITIS
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
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
Pathology
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.
Investigations
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.
Management
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.
49.20
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SYSTEMIC FUNGAL INFECTIONS
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HISTOPLASMOSIS
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
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
Pathology
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.
Investigations
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.
Management
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.
HISTOPLASMA DUBOISII
H. duboisii, the fungus of African histoplasmosis, is larger than the classical H. capsulatum. It is found throughout East, Central and
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.
ASPERGILLOSIS
This is the most common respiratory mycosis in
COCCIDIOIDOMYCOSIS
This is caused by Coccidioides immitis and is found in the southern
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.
PARACOCCIDIOIDOMYCOSIS
This is caused by Paracoccidioides brasiliensis and occurs in
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BLASTOMYCOSIS
North American blastomycosis is caused by Blastomyces dermatitidis. It also occurs in
CRYPTOCOCCOSIS
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.
CANDIDIASIS
Candida albicans is a cause of systemic fungal infection in the immunosuppressed (see p. 116).
49.21
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TRAVEL MEDICINE
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In 1999 49 million overseas visits were made by
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
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
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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