The International Development Research Centre is a public corpora­ tion created by the Parliament of Canada in 1970 to support research designed to adapt science and technology to the needs of developing countries. The Centre's activity is concentrated in five sectors: agriculture, food and nutrition sciences; health sciences; information sciences; publications; and social sciences. IDRC is financed solely by the Government of Canada; its policies, however, are set by an international Board of Governors. The Centre's headquarters are in Ottawa, Canada. Regional offices are located in Africa, Asia, Latin America, and the Middle East.

©1978 International Development Research Centre Postal Address: Box 8500, Ottawa, Canada KlG 3H9 Head Office: 60 Queen Street, Ottawa

Dupuis, R. Keystone, J. Losos, J. Meltzer, A. IDRC-106e Travelers to the tropics - guidelines for physicians. Ottawa, Ont., IDRC, 1978. 36p.

/IDRC publication/. Guidelines for physicians on the treatment of /tropical disease/s - discusses the importance of /immunization/s, /diagnosis/, treatment of patients with /parasitic disease/s; includes /bibliography/, /directory/ of tropical disease /information centre/s.

UDC: 616.91 ISBN: 0-88936-166-5

Microfiche edition available IDRC-106e

Travelers to the Tropics - Guidelines for Physicians

R. Dupuis/ J. Keystone, 2 J. Losos, 3 and A. Meltzer4

1M.D., F.R.C.P.(C), Colonel and Chief of Medicine and Physician in Charge, Tropical Disease Clinic, National Defence Medical Centre, Ottawa, Canada. 2M.D., MSc. (CTM), F.R.C.P.(C), Director, Tropical Disease Unit, Toronto General Hospital, Toronto, Ontario. 3M.D., D.E.C.H., Associate Director, Health Sciences Division, International De­ velopment Research Centre, Ottawa, Canada. 4M.B.Ch.B., D. OBST., D.T.M.&H., Physician, Health Unit, Carleton University, Ottawa, Canada. Contents

Introduction ...... 3

Preparing for a Visit to the Tropics ...... 4

Immunizations ...... 7

The Patient Returning from the Tropics ...... 11

The Patient with Malaria ...... 12

The Patient with a Fever ...... 18

The Patient with Diarrhea ...... 20

The Patient with Amoebiasis ...... 22

The Patient with a Worm Infection...... 24

The Patient with an Eosinophilia ...... 27

The Patient with Other Tropical and Parasitic Infections ...... 28

Acknowledgments ...... 31

Appendix A. International Immunization Requirements (1978) ...... 32

Appendix B. Canadian Reference Centres for Tropical Diseases ...... 34

Appendix C. Recommended Reading ...... 35

Index ...... 36

2 Introduction

Most physicians are now seeing patients who have traveled in many parts of the world, and there is a growing awareness that tropical and travel medicine have an important role to play as far as the health of the individual and the community is concerned. As in most branches of medicine, preventive aspects are of supreme importance: by taking adequate precautions most travelers will have few problems. The aim of these guidelines is to provide some basic information for physicians and health workers who are dealing with subjects who intend to visit the tropics or have returned from such areas. In general, only the more likely conditions that may be encountered are mentioned. In some instances patients may have to be referred to a tropical disease unit for appropriate investigation and therapy. However, in all instances it is essential that physicians should have a high index of suspicion for tropical and parasitic diseases and all subjects should be asked for details of their travels (e.g., Where have you been?). In many instances the history will yield a clue to possible parasitic infections (e.g., malaria). Many parasitic diseases continue to go undetected in patients, and it is hoped that these brief notes will assist physicians to be on the alert for such conditions. For further details the material mentioned in Appendix C, Recommended Reading, will be of use. It should be stressed that many parasitic infections may remain "asymptomatic" for a long time and that all travelers should have an appropriate checkup and investigation for parasitic diseases on their return from the tropics. This is particularly important if the subject has a history of unexplained fever, diarrhea, or weight loss. Also it must be remembered that the symptoms of such diseases as malaria may mimic other conditions (e.g., influenza) and are easily misdiagnosed. Again with many parasitic infections, symptoms may appear long after the traveler has been away from the tropics and physicians must keep this fact in mind. When possible, investigations are best carried out in a laboratory experienced in parasitic diseases.

3 Preparing for a Visit to the Tropics

The tropics impose various physical and mental stresses on all travelers, and in particular, on individuals with diseases such as mental disorders (especially depression), alcoholism, renal calculi and chronic renal diseases, chronic liver diseases, bowel conditions such as ulcerative colitis, significant cardiovascular disease (particularly unstable hyperten­ sion), and immunosuppressive conditions. Unstable diseases such as diabetes are also subject to stress as a result of changes in diet, fatigue, and alterations in circadian rhythm due to "jet lag." Although none of the above conditions constitute absolute contra­ indications to life in the tropics, they should be evaluated and discussed with the patient. Individuals on medication should be advised to take an adequate supply with them (e.g., insulin, steroids), and a summary of the medical conditions should be given to the patient before his departure to take with him. Preparation for the tropics should include a dental and complete medical examination as these services may not be available in the countries that are to be visited. Patients should be advised to carry a medical kit with them. This is not meant to delay consultation with proper medical authorities, but may be useful while awaiting medical help. This should include an antimalarial, an antidiarrhea agent (Lomotil), a broad spectrum antibiotic, an antacid, an analgesic, an antihistamine, a topical antifungal, first aid material, insect repellent, and suntan lotion. The following points should be brought to the attention of the traveler: acclimatization; food; water and drink; swimming; barefoot walking; prevention of diarrhea; protection from insects; and antimalarials.

Acclimatization On arriving in the tropics one should allow several days to adapt to the local conditions and recover from "jet lag." Exposure to the sun should initially be for short periods and then be increased gradually over the next few days. Light-coloured cotton clothing is preferable. Heat in the tropics can be intense enough to cause syncope in susceptible individuals. Heat exhaustion can occur from water depletion resulting from loss through sweating and other routes such as diarrhea. The patient is thirsty with scanty urine of high specific gravity. Treatment is by fluid replacement. Another form of heat exhaustion can occur from salt depletion, which is secondary to loss through sweating. The patient is not thirsty in the pure form of this syndrome and the sodium chloride content of urine

4 is low. Treatment consists of the replacement of salt in the body, either in drinks or intravenously (i.v.). Heatstroke occurs when temperature regulatory mechanisms do not function. Body temperature is high and successful treatment depends on lowering body temperature. Prickly heat (miliaria rubra) is associated with high humidity and appears as a rash on areas covered by clothing and subject to friction. This condition may be alleviated by moving to cooler surroundings, taking a cool shower, drying the skin, and applying calamine lotion. All of these conditions can be prevented by prudent activity in hot climates, the wearing of appropriate apparel, and sufficient salt and fluid intake.

Food Milk (and dairy products) and salads are best avoided. Vegetable, meat, or fish dishes should be well cooked. The visitor should stick to fruit that can be peeled by himself. Extra salt should be added to food.

Water and Drink In general, all water should be boiled before use. Bottled carbonated drinks are usually safe. Ice cubes should be made from purified water. If the local water is not safe for drinking, then it is not suitable for dental use. Halazone tablets may be used to purify drinking water, or a 2% tincture of iodine can be used (five drops added to 1 litre of "clear" water or 10 drops added to 1 litre of "cloudy" water). The water should be thoroughly mixed and allowed to stand for 30 minutes before being used.

Swimming Visitors to the tropics should be advised against swimming in fresh untreated water in regions endemic for schistosomiasis.

Barefoot Walking In most tropical areas barefoot walking is inadvisable because of the risk of acquiring hookworm infections. Shoes also lessen the chance of being bitten by certain insects or snakes.

Prevention of Diarrhea The best preventive measure is to take care with food and drink. "Prophylactic" drugs are not generally recommended, and preparations containing iodochlorhydroxyquin should be avoided as they are relatively ineffective, may mask infections, and have serious potential adverse reactions (optic nerve lesions). Diphenoxylate-atropine (Lomotil) is useful in controlling diarrhea, but is contraindicated when diarrhea is accompanied by a high fever or blood in the stools, and should not be used in young children. All travelers should have appropriate stool tests carried out on their return, particularly those who were symptomatic while abroad.

5 Protection from Insects A good insect repellent and a "knockdown" type of spray for the room at night are advisable. Long-sleeved clothing and long trousers offer added protection. Suitable window screens and insect nets lessen the possibility of exposure to insects.

Antimalarials See section on malaria (page 12).

6 Immunizations

A country may require international certificates of vaccination against yellow fever, cholera, and smallpox from international travelers, and the individual requirements for each country visited should always be checked before the trip. If the physician is of the opinion that vaccination should not be performed on medical grounds, the traveler should be supplied with a signed, dated statement of the reasons. Immunizations against poliomyelitis and typhoid are not required under the International Health Regulations, but are recommended when visiting tropical or developing countries. The doses and schedules mentioned below are only guides and all physicians should check with the recommendations supplied by the manufacturer for each specific vaccine.

Smallpox At present, endemic smallpox is restricted to the Somali Republic, but certain countries still require proof of smallpox vaccination. Primary vaccination and revaccination are valid for 3 years, the primary procedure being valid 8 days after vaccination and the revaccination being valid at once. Contraindications to vaccination include: (a) eczema; (b) acute illness; (c) altered immune states and blood dyscrasias; (d) pregnancy; (e) corticosteroid orimmunosuppressive therapy; and (f) radiation therapy. Revaccination is done every 3 years. (Note: Smallpox and yellow fever vaccine are usually given 2-3 weeks apart, but they may also be given simultaneously at different sites.)

Yellow Fever This is valid 10 days after the primary vaccination and remains valid for 10 years, the revaccination being valid at once. The vaccine should not be given to children under the age of 6 months. Vaccination during pregnancy is contraindicated (but pregnant women who must travel to high risk areas should be vaccinated). Yellow fever vaccination should be avoided in subjects with leukemia, lymphoma, generalized malignancy, or those on steroids, alkylating drugs, antimetabolite drugs, or those receiving radiation therapy. Hypersensitivity to eggs is a contraindication to vaccination. (Note: Smallpox and yellow fever vaccine are usually given 2-3 weeks apart, but they may also be given simultaneously at different sites.)

Cholera Cholera vaccine is not routinely recommended for all travelers visiting countries not demanding vaccination as a condition of entry. The complete primary series is only recommended for those visiting high risk

7 areas. The vaccination is valid for 6 months, beginning 6 days after the primary procedure. Revaccinations are valid from the date given (if within 6 months of the previous cholera injection).

Doses Doses may be given subcutaneously (s.c.) or intramuscularly (i.m.). Adults - First dose of 0.5 ml followed by 0.5 ml (given at least 1 week apart). The booster dose is 0.5 ml. Pregnant women should not receive the vaccine. Children - Under 5 years of age, first dose of 0.1 ml, second dose of 0.3 ml at least 1 week after the first dose; the booster dose is 0.1 ml. Five to ten years of age, first dose of 0.3 ml, second dose of 0.5 ml at least 1 week after the first dose; the booster dose is 0.3 ml. Children over the age of 10 years may receive the adult dose. (Note: The primary series need never be repeated for booster doses to be effective. Visitors to countries demanding evidence of cholera vaccination for entry should be given one injection of the vaccine.)

Poliomyelitis Travel to the tropics is accompanied by an increased risk of exposure to poliomyelitis in many areas, and all travelers should be protected against the disease. For those who have completed the primary series, a single booster dose of trivalent oral polio vaccine (TOPV) is recom­ mended. If the subject has not previously been immunized, a primary series of three doses should be given (first and second doses should be given 6-8 weeks apart, with the third dose to be given 8-12 months after the second dose). Vaccination with the live poliomyelitis vaccine should be avoided in subjects with severe underlying diseases. Those with immune deficiency conditions or impaired immune states who are at risk to the infection should be immunized with inactivated polio vaccine.

Typhoid This vaccine is not required for international travel, but is recommended for subjects who intend to visit or work in high risk areas. If the subject has been previously immunized, then only one booster dose need be given.

Doses Vaccine is administered s.c. Adults - First dose 0.5 ml, second dose 0.5 ml given 4 or more weeks after the first dose. Reinforcing doses of 0.5 ml are given every 3 years. The vaccine should not be given to pregnant women. Children - Children under the age of 10 years may be given half the adult dose.

8 Tetanus/Diphtheria All visitors to the tropics should have adequate protection against tetanus and diphtheria.

Typhus This is only recommended for those people traveling to special risk areas. It is used to prevent louse-borne (epidemic) typhus in rural or remote highland areas of Ethiopia, Ecuador, Bolivia, Peru, and mountainous parts of Asia. For vaccine dosage, the individual manufac­ turer's directions should be followed. Booster doses are given every 6-12 months. (Note: The vaccine should not be administered to those with a history of hypersensitivity to egg protein.)

Plague Most travelers do not require this vaccine. Even when used, it only offers partial protection and adverse reactions may be severe.

Gamma Globulin Infectious hepatitis is common in many tropical regions and it would appear that immunoglobulin may offer some protection against hepatitis-A for a period of about 6 months. (Note: The preparation should be administered near the departure date and at least 14-21 days after any other immunizations (Table 1).)

Rabies Preexposure immunization may be indicated for those visiting high risk areas (e.g., biologists), who may have close contact with species carrying rabies. If the vaccine is given, then the serum should be checked for antibody levels 3-4 weeks after the last injection. If no antibody is present, booster doses should be given until a response is detected. Subjects with continuing exposure are given booster doses every 2-3 years. (For details of doses, the manufacturer's recommendations for specific vaccines should be consulted.)

Calmette-Guerin Bacillus (BCG) Where indicated, BCG vaccine may be given to travelers going to high risk areas.

Immunization Routine This is only a suggested schedule and requirements should be modified to meet the needs of individual travelers (Tables 2 and 3). For vaccines such as polio, typhoid, and cholera, a single "booster" dose is only effective if the subject has previously completed the primary series. For details regarding primary series and boosters please refer to the notes on each individual vaccine. (These schedules are modifications of those mentioned in Health Guide for Travellers to Warm Climates published by the Canadian Public Health Association, 1975, by S. Seah. For further details

9 Table 1. Dosage of immunoglobulin administered intramuscularly against infectious hepatitis-A.•

Bodyweight Dose, ml Short-term travel (less than 3 months) Less than 50 lb 0.5 50-lOOlb 1.0 Over lOOlb 2.0 Long-term travel (3 months or more) Less than 50 lb 1.0 50-100 lb 2.5 OverlOO lb 5.0 •source: Health lnfrmnation for International Travel published by the Centre for Disease Control, Atlanta, Georgia, 1977.

Table 2. Suggested time intervals when vaccines should be administered before visiting the tropics.

Week

Vaccine 1 2 3 4 5 6 7 10 Polio x• Typhoid x x Cholera x x Smallpox x Yellow fever x Gamma globulin x •If a complete polio series has been previously given, then only a booster is necessary. Otherwise a complete series of three doses is needed. (For details of immunization, please see main text.)

Table 3. This schedule should only be used in cases where the traveler has to visit the tropics at short notice and it is not possible to carry out the schedule listed in Table 2.

Day

Vaccine 1 5 17 19 21 Smallpox x Yellow fever x Cholera x x Typhoid x x Polio x Gamma globulin x (For details of immunization, please see main text.) on immunizations, the booklet Health Information for International Travel, 1977, published by the Centre for Disease Control, Atlanta, Georgia, is recommended.)

10 The Patient Returning from the Tropics

Most travelers feel well on their return from the tropics, but it is advisable that they undergo basic screening tests to detect parasitic infections, particularly as some infections are asymptomatic in the early stages and there may be no clinical signs of disease.

Taking a History Physicians should ask: "Where have you been?" "Did you have a fever?" "Did you take antimalarials regularly?" "Did you have severe diarrhea?" "Did you swim or wade in fresh water?" "Did you notice blood in the stools or urine?"

Clinical Examination It is not possible to enumerate all the physical findings that may be associated with parasitic disease, but aspects to consider include the following: (1) localized edema (trypanosomiasis/ trichinosis/ filariasis ); (2) skin nodules (onchocerciasis/leprosy/leishmaniasis); (3) skin rashes (schistosomiasis/ filariasis/ strongy loides/larva migrans ); (4) respiratory signs (ascaris/ visceral larva migrans/ schistosomiasis/ paragonimus/ tuberculosis); (5) lymphadenopathy (tuberculosis/ filariasis/ trypanosomiasis/ leishmaniasis); (6) hepatomegaly (malaria/ amoebiasis/ visceral larva migrans/ hepatitis/ visceral leishmaniasis/ schistosomiasis); (7) splenomegaly - there are many causes of an enlarged spleen, but in all cases it is essential to rule out malaria.

Laboratory Investigations The history and physical findings may suggest a particular parasite, but the following tests may be considered as a "routine" screening for those returning from the tropics. (1) Examination of fresh stool samples (preferably a minimum of three) for ova/parasites and bacteriological examination. (2) Examination of the blood: film/hemoglobin (Hb)/leukocytes and differential/erythrocyte sedimentation rate (ESR). (3) Urinalysis: two to three samples, preferably collected at midday, should be obtained from travelers returning from Africa and the Middle East to exclude schistosomiasis. (4) Chest X ray (Mantoux test may be useful if there is no history of BCG or a previous positive reaction). (5) VDRL. The significance of positive findings in the stools is considered in the section on diarrhea. The blood film is useful in detecting malaria, filariasis ("day" and "night" films), or trypanosomiasis.

11 The Patient with Malaria

An increasing number of subjects from temperate climates are now visiting malarious regions, and physicians should stress the importance of taking antimalarials as prescribed when such areas are to be visited. The WHO publication Information on Malaria Risk for International Travellers, reprinted from the WHO Weekly Epidemiological Record (51, 181-200, 11 June 1976) (Table 4), provides useful information on the subject. Some of the more commonly used antimalarials are mentioned below.

Chloroquine (Aralen) When given as a suppressive for Plasmodium falciparum and P. malariae infections, the drug results in a complete cure (providing the parasite is not resistant). It does not prevent relapses in P. vivax or P. ova le infections. It should not be given to those with retinal disease or visual field defects. Adverse reactions to the drug include: retinopathies; corneal deposits; macular lesions; optic atrophy; gastrointestinal upsets; psychotic episodes; convulsions; blood dyscrasias; skin changes; and myopathies. Note that in the usual antimalarial doses the risks of adverse reactions are relatively small. The drug should be taken 2 weeks before entering the malarious region, and continued for 8 weeks after leaving the endemic area. After long-term usage (e.g., when the total dose of base exceeds 100 g) another antimalarial should be used to reduce the risk of eye damage.

Chloroguanide (Paludrine) This acts as a causal prophylactic for P. falciparum and has a suppressive effect on the other parasites associated with human malaria. It is a relatively nontoxic drug and is begun just before entering the endemic zone and continued for 8 weeks after leaving.

Pyrimethamine (Daraprim) This is administered once a week, starting just before entering the malarious zone and continuing for at least 8 weeks after leaving. In the usual doses it has few adverse reactions. (Long-term use may be associated with a megaloblastic anemia.) Note: Drugs such as chloroquine, chloroguanide, or pyrimethamine will not prevent relapses in P. vivax or P. ovale infections because these relapses are due to the secondary exo-erythrocytic stages of the parasite. To prevent relapses and provide a radical cure, a course of primaquine is given. (For details, see notes on the therapy of malaria.)

12 Table 4. Summary of antimalarial dosage for chemoprophylaxis. •

Under 1 year, 1-4 years, 5-8 years, 9-12 years, Adults, Drug mg mg mg mg mg Chloroquine, 37.50-50 base 50-100 base 150-200 base 200-300 base 300 base weekly (Note: In highly malarious regions, adults should take 300 mg of the base twice a week.)

Chloroguanide, 25-50 50 75 100 100 daily (Note: In highly malarious regions, adults should take 200 mg daily.)

Pyrimethamine, 6.25 6.25-12.50 12.50 12.50-25 25-50 weekly "Source: Information on Malaria Risk for International Travellers, WHO Weekly Epidemiological Record, 51, 181-200, 11June1976.

Antimalarials and Pregnancy It is generally accepted that the potential risk of malaria justifies the use of antimalarials in the pregnant subject.

The Drug-Resistant Parasite The resistance of P. falciparum to chloroquine has been noted in parts of Panama, South America, the Indian subcontinent, Southeast Asia, and New Guinea, but not in Africa or the Middle East. In some parts of Africa, P. falciparum is resistant to chloroguanide and pyrimethamine and similar findings have been described in Southeast Asia and South America. Resistance involving P. vivax, P. malariae, and P. ovale has also been reported. In an effort to overcome the problem, combinations of drugs have been used. For example: chloroquine 300 mg of base plus primaquine 45 mg of base, once weekly (this combination has also been used with daily doses of dapsone 25 mg, but primaquine and dapsone have serious potential adverse effects); or pyrimethamine 15 mg plus chloroquine 150 mg of base, two tablets weekly. Fansidar (a combination of pyrimethamine and sulfadoxine) is useful for the suppression of chloroquine-resistant P. falciparum malaria. It is not yet available in Canada, but is usually available in most countries where the problem exists. The adult dose is 50 mg pyrimethamine and 1000 mg sulfadoxine once every 2 weeks. The pediatric dose is: for 6-11 months of age, one-quarter of a tablet every 2 weeks; 1-3 years, one-half tablet every 2 weeks; 4-8 years, one tablet every 2 weeks; 9-14 years, one and one-half tablets every 2 weeks. However, serious adverse side effects may be associated with the use of sulfonamides and at present the drug is not recommended for long-term use. (If the traveler wishes to purchase Fansidar when in the tropics, then prophylaxis with chloroquine should be started 2 weeks before entering the malarious area and continued until a switch to pyrimethamine-sulfadoxine is made.)

13 0 •

ff•• 1r~·-.

Areas where Malaria transmission occurs or might occur. Clinical Features of Malaria From the time of the mosquito bite the period before symptoms appear varies between types of malaria. For P. falciparum, this is about 12 days; for P. vivax, it is 13-15 days or longer; and P. malariae may be up to 1 month. P. falciparum may be fatal to the nonimmune subject, and the primary attack is the most dangerous. A tertian fever may be present and is usually accompanied by a cold stage (lasting 1-2 hours), hot stage (lasting 3-4 hours), and a sweating stage (2-4 hours). P. vivax has a similar periodicity; pyrexia occurs every 4th day in P. malariae infections. In many subjects the typical fever patterns are not present; mixed infections may also occur. Other clinical features include splenomegaly, hepatomegaly, nausea and vomiting, diarrhea, headache, myalgia, and malaise. The classical picture may be modified and all the standard signs and symptoms may be absent. The most common presenting sign is fever. (In severe P. falciparum infections, associated with shock, the temperature may be subnormal.)

Complications of P. falciparum malaria These may develop at any stage of the infection. Algid malaria - There is acute shock and death may occur with little warning. Cerebral malaria - Cerebral involvement may be associated with coma, hyperpyrexia, and convulsions. Cerebral malaria may be confused with diabetic coma, alcoholism, head injuries, cerebrovascular disorders, or uremia. Renal failure and blackwater fever - Renal insufficiency can occur at any stage of the infection. In blackwater fever, hemoglobinuria, vomiting, and abdominal pain may be present. The syndrome is not common now, but was observed mainly in subjects who had taken quinine irregularly. Splenic rupture - Spontaneous rupture of the spleen may occur in the acute primary stages. Hepatic failure - This is associated with a poor prognosis. Malaria is sometimes called the great "mimic" because it can have a very broad range of atypical symptomatology. This can range from acute abdominal pain to symptoms of a mild influenza. Malaria should be kept in mind for any illness of a traveler returning from endemic malarious regions.

Diagnosis If any subject with a pyrexia, or history of pyrexia, has returned from a malarious region, then the physician should assume malaria to be present until proved otherwise. The diagnosis should always be confirmed by finding the erythrocytic forms of the parasite in a suitable blood film (parasites are most numerous during or soon after the fever). "Thick" and "thin" films should be taken; sternal marrow samples are rarely needed. Hematological findings include hemolytic anemia,

15 leucocytosis (with increase in monocytes), or leucopenia and throm­ bocytopenia; there may be evidence of hepatic or renal dysfunction. The history is important, i.e. "Where did you visit?" "Did you take antimalarials as directed?"

Treatment of Acute Malaria

Even if there is doubt as to the species of malaria parasite involved, the patient should be started on chemotherapy. Most cases of malaria will respond quite dramatically to the standard treatment with chloroquine. Usually the fever will drop and the patient will feel better within 24 to 36 hours of initiation of therapy. If this is not the case, or if the blood slide does not show a decrease in the number of parasites, the malaria could be resistant. In that case, alternate therapy should be instituted or the patient should be referred to a specialty clinic.

Doses Adults (oral)- Chloroquine phosphate: initial dose of 1.0 g (600 mg of the base) is followed by an additional 500 mg (300 mg of the base) 6-8 hours later. Then a single dose of 500 mg (300 mg of the base) is given on each of the next 2 consecutive days. Infants and children (oral) - Chloroquine phosphate: first dose of 10 mg of the base per kilogram (not exceeding a single dose of 600 mg of base). Second dose of 5 mg of base per kilogram (not exceeding a single dose of 300 mg of base) 6 hours after the first dose. Third dose of 5 mg of base per kilogram 18 hours after the second dose. Fourth dose of 5 mg of base per kilogram 24 hours after the third dose. Supportive therapy includes bed rest, correction of fluid and electrolyte imbalance, and treatment of complications (e.g., renal failure, hyperpyrexia). This treatment refers to an acute attack and should result in a radical cure for P. falciparum and P. malariae infections (providing the parasite is not resistant to the drug).

Note: For a radical cure of P. vivax or P. ovale infections, follow-up therapy with primaquine is needed.

Doses Adults - Primaquine phosphate: 15 mg of the base is given orally for 14 days. (Children may be given 0.3 mg/kg of the base for 14 days.) Primaquine is a toxic drug and must be given with care as there is a risk of hemolytic anemia, especially in subjects with a glucose-6-phosphate dehydrogenase deficiency, and methemoglobinemia.

16 Treatment of Severe Infections Chloroquine is the drug of choice (unless the parasite is resistant to chloroquine). When the subject is unable to tolerate oral medication, chloroquine may be given i. m. or i. v. but must be given with care.

Doses Adults - Chloroquine hydrochloride: 250 mg (200 mg of the base) administered i.m. every 6 hours, or quinine dihydrochloride: 600 mg in 300 ml of normal saline administered i. v. over at least 1 hour. Can repeat in 6-8 hours. (The maximum daily dose is 1800 mg.) Children - Chloroquine hydrochloride: 5 mg/kg of the base administered i.m. every 12 hours, or quinine dihydrochloride may be given i. v. Quinine dihydrochloride: 25 mg/kg per day. Half of the dose in a 1-hour infusion, and then the other half 6-8 hours later. (The maximum daily dose is 1800 mg.) (Note: Where antimalarial drugs are administered i. m. or i. v., a change to oral therapy should be made as soon as possible. In particular, i.v. quinine may be associated with severe adverse reactions.) Intravenous steroids are indicated in cerebral malaria, in addition to antimalarials. Adults may be given 4-6 mg of dexamethasone i. v. every 4-6 hours. With reference to P. falciparum malaria, if there is no prompt response to standard doses of chloroquine, then the possibility of a drug-resistant parasite being present should be kept in mind.

Treatment of Acute Attack of P. falciparum Malaria - Resistant to Chloroquine

Doses Adults - Quinine sulfate: 650 mg administered orally three times a day (t.i.d.) for 10-14 days; plus pyrimethamine: 25 mg administered orally twice a day (b.i.d.) for 3 days; plus sulfadiazine: 500 mg administered orally four times a day (q.i.d.) for 5 days. Children - Quinine sulfate administered orally, 25 mg/kg per day in three doses for 10-14 days; plus pyrimethamine administered orally for 3 days: less than 10 kg body weight, 6.25 mg/day; 10-20 kg body weight, 12.50 mg/day; 20-40 kg body weight, 25 mg/day; plus sulfadiazine administered orally, 100-200 mg/kg per day in four doses for 5 days (maximum 2 g/day). Note: For radical cure of P. vivax or P. ovale infections, follow-up therapy with primaquine is needed.

17 The Patient with a Fever

Fever may be a presenting sign in a wide variety of tropical diseases. These include viral conditions such as dengue fever; rickettsial diseases such as typhus; parasitic diseases such as malaria, schistosomiasis, or filariasis; and of course, a wide range of bacterial infections prominent in the tropics. The important fact to keep in mind when faced with a diagnostic problem of pyrexia of unknown origin is a travel history. In practical terms, any febrile patient from tropical areas should be suspected of having malaria unless proven otherwise. Malaria may present as a flu-like illness and may mimic a wide variety of medical conditions. In such cases, the history of where the person traveled and for how long can be of help. Incubation periods from first or last possible exposure can give clues as to the infecting organism. Whether or not prophylactic medications of any type were taken can be of importance. Travelers who stayed in major tourist hotels are not as likely to be exposed to indigenous diseases as those who camped in the bush. Physical examination can also give evidence of etiology. Lym­ phadenopathy, splenomegaly, rashes, and fever patterns are helpful. Clinical pointers and laboratory investigations are needed to confirm the presence of parasites. A wet blood film may show blood helminths, and a thick or thin film with staining may show intracellular malaria parasites. A white blood count and differential may indicate viral, bacterial, or parasitic etiology. Stool examinations and cultures are of course a great help in making a diagnosis. The key, therefore, is to consider tropical disease in a differential diagnosis of fever. The major causes can be screened out, and even in cases where symptoms are classic for nontropical causes, the above conditions should be suspected until recovery has been complete. All patients with a fever of uncertain origin occurring within 3 weeks of departure from Nigeria, Liberia, Sierra Leone, Sudan, or Zaire should be placed in strict isolation and diagnostic work should be held to a minimum until a specialist opinion is available. The rationale for this is that although virus diseases such as Lassa fever are rare, when they arise they may constitute a major health hazard to the community. The following are some of the ca uses of fever to be considered in subjects returning from abroad and the main diagnostic tests that should be done:

(1) malaria: blood films/serology; (2) amoebiasis/hepatic abscess: stools/sigmoidoscopy/ liver scan/serology; (3) bacillary dysentery: stools;

18 ( 4} typhoid: blood, urine, and stool culture/serology; (5) filariasis: day and night blood films/serology; (6) schistosomiasis: stools/urine/intravenous pyelogram (I. V.P .)/ biopsyI serologyI endoscopy; (7) trichinosis: muscle biopsy/X rays/serology; (8) hepatitis: liver function tests; (9) brucellosis: blood culture/serology; (10) typhus: serology; (11) tuberculosis: X rays/skin tests; (12) arboviruses: serology; (13) trypanosomiasis: blood films/lymph node smears/ culture/serology; (14) leishmaniasis: blood films/bone marrow/splenic puncture/ culture/serology; (15) Lassa fever, Marburg virus: serology/virus isolation - in isolation unit.

19 The Patient with Diarrhea

Diarrhea is the commonest symptom for which the traveler seeks medical aid on his or her return from the tropics. In all cases, a good history, physical examination, and appropriate investigations should be performed. The most important test is the stool examination for ova and parasites and bacteriological testing. Always, nontropical causes of diarrhea must be kept in mind, but tropical causes should be excluded first in the diagnosis. It is worth remembering that parasitic infections may coexist with other conditions (e.g., neoplasms or ulcerative colitis), and other investigations may be needed to exclude these possibilities, in particular sigmoidoscopy and radiological examinations. Also, several types of parasite may be present in the same host. Diarrhea often occurs in tropical areas as a result of changes in the bowel flora and dietary intake. Bacterial causes such as salmonellosis and shigellosis and other enteropathogenic organisms are not uncommon.

Examination of the stool may identify a wide variety of parasites. These include: Entamoeba histolytica, Ascaris, hookworm, Giardia lamblia, Trichuris trichiura, schistosomiasis, tapeworms, clonorchis, and stron­ gyloides (although not all of these cause diarrhea).

Sometimes the identified amoebae are noninvasive. These are Entamoeba coli, Endolimax nana, Dientamoeba fragilis (actually a flagellate), and Iodamoeba biitschlii. Some of these may be associated with relatively mild intestinal symptoms, but most authorities do not treat them. Amoebic infections are not the commonest cause of diarrhea in travelers returning from the tropics, but are worthy of extra attention, for if untreated, the infection may be associated with chronic ill health and is potentially fatal. (For diagnosis and therapy, see section on "The Patient with Amoebiasis," page 22.)

Although organisms of the Shigella group may cause bacillary dysentery, some subjects harbour the organisms without any accompany­ ing symptoms. The incubation period is usually short and most episodes are transient.

In cholera, the acute infection presents with vomiting, cramps, and watery diarrhea. Water or food are usually involved in the transmission of this infection, and the incubation period is 3-6 days. The vaccine offers only partial protection against the disease. Diagnosis is made by finding the Vibrio cholerae in the stools. Treatment is directed to rapidly correcting the dehydration, replacing lost electrolytes, and using a suitable antibiotic (e.g., tetracyclines).

Giardia lamblia is a parasite commonly seen in visitors from the tropics and clinical features include nausea, abdominal discomfort, flatulence,

20 diarrhea, fatigue, and malabsorption syndromes (floating malodorous stools). It lives in the upper part of the small intestine and duodenum. Many patients remain symptomless. Diagnosis is made by finding the cysts in the stools, by duodenal aspiration, or by small bowel biopsy.

Treatment of Giardiasis Adults are given a daily oral dose of quinacrine hydrochloride, 100 mg t.i.d. for 5-7 days. (Children may be given 2 mg/kg t.i.d. for 5-7 days, a maximum of 300 mg/day.) Metronidazole may also be used. Adults are given a daily oral dose of 250 mg t.i.d. for 10 days. (Children may be given 5 mg/kg t.i.d. for 10 days.) (Adverse effects of metronidazole include headache, nausea, rashes, and dark urine, and it has had a mutagenic effect in some animal studies. Alcohol is contraindicated several days before, during, and several days after therapy.) For therapy of other parasites associated with diarrhea, please see section on "The Patient with Other Tropical and Parasitic Infections" (page 28).

21 The Patient with Amoebiasis

Entamoeba histolytica usually infects the large bowel but may spread to other parts of the body (especially the liver). Patients become infected by swallowing the parasite in the cyst stage, which is excreted with the feces. The incubation period can be long and symptoms sometimes occur many years after initial exposure. The onset is usually insidious and the main complaints are of diarrhea and abdominal discomfort. Blood and mucus may be present in the stool and there may be tenderness over the sigmoid colon with associated tenesmus. Pyrexia is unusual but there is sometimes a moderate leucocytosis. A useful classification divides amoebiasis into asymptomatic and symptomatic. Symptomatic cases may be intestinal (which present as dysentery, colitis, amoeboma or irritable bowel syndrome), or extraintestinal (which may be hepatic, pulmonary, cutaneous, cerebral, etc.) in distribution. Most patients who excrete the infective cysts remain symptomless; therefore, the presence of the parasite in the stool is not necessarily synonymous with amoebic disease. Complications of intestinal amoebiasis include abscess formation (commonly hepatic), hemorrhage, perforation, intussusception, and strictures. Hepatic abscesses may be present long after the initial intestinal infection with pyrexia, discomfort over the liver, and weight loss. There is usually a leucocytosis and fever but liver function tests are not commonly affected. Clinical examination may reveal tender hepatomegaly, intercostal tenderness, and a high fixed hemidiaphragm in the classical case. X ray, a liver scan, and serological tests are often needed, however, to confirm the diagnosis.

Diagnosis of Amoebic Infections (1) History of diarrhea, abdominal cramps, blood and mucus in the stools. (2) Acute stage: the presence of trophozoites of E. histolytica in fresh stool samples. (3) Chronic stage: cysts of the parasite in stool samples. (4) Culture methods may be used in the acute stage (but these are not generally available). (5) Endoscopy may reveal the characteristic ulcers associated with the infection (this may be combined with biopsy and scraping of the ulcer base), but similar appearance may be present in ulcerative colitis. (6) Serology (indirect hemagglutination, complement fixation, or indirect fluorescent antibody tests).

Differential Diagnosis Other causes of diarrhea must be considered in the differential diagnosis. These include bacillary dysentery, ulcerative colitis, diver­ ticulitis, giardiasis, viral gastroenteritis, tropical sprue, balantidiosis, intestinal tuberculosis, and salmonellosis.

22 Treatment of Amoebic Infections Asymptomatic cyst carriers - Diiodohydroxyquin: orally, 650 mg t. i. d. for 20 days (should be given with care because of the risk of optic neuritis); or metronidazole: orally, 750 mg t.i.d. for 5-10 days; or diloxanide furoate: orally, 500 mg t.i.d. for 10 days. Patients with intestinal disease - Metronidazole (as above); or dehydroemetine: 1.0-1.5 mg/kg daily maximum 90 mg/day (i.m. or s.c.) for up to 5 days; plus a luminal agent (e.g., diiodohydroxyquin or diloxanide furoate). In severe dysentery, tetracyclines (500 mg q.i.d. for 5 days) are a useful adjunct to reduce the severity of the diarrhea. (Note: Emetine and its derivatives can have a toxic effect on the cardiovascular system and patients .on the drug must be carefully monitored.)

Treatment of Amoebic Liver Abscess Larger abscesses may require needle aspiration (closed drainage only in a specialized unit). Indications for aspiration include: impending rupture of the abscess (marked elevation of the right hemidiaph~agm); a large left lobe abscess with potential to rupture into the pericardium; or failure of medical management. Drugs used include: metronidazole - orally, 750 mg t.i.d. for 5-10 days, plus a luminal agent as above; or dehydroemetine - 1.0-1.5 mg/kg daily, maximum 90 mg/day (i.m. or s.c.) for up to 10 days; plus chloroquine phosphate - orally, 1.0 g (600 mg base) daily for 2 days, then 500 mg (300 mg base) daily for 21 days; plus a luminal agent (e.g., diiodohydroxyquin or diloxanide furoate). (Note: All patients who have been treated for amoebic infections should have appropriate follow-up examinations, particularly stool examina­ tions. Some drugs (e.g., diiodohydroxyquin and diloxanide furoate are not generally available and may need to be obtained from reference centres. For potential adverse effects of metronidazole see notes on treatment for Giardiasis, page 21.)

23 The Patient with a Worm Infection

Routine stool tests performed on persons returning from the tropics often reveal the presence of a helminthic infection, though in most cases the subject has no obvious symptoms. There may be an associated eosinophilia. Unless essential, antihelminthic drugs should not be used in the pregnant subject. After therapy it is essential to carry out follow-up stool tests before the patient is pronounced "cured." Some of the more common worm infections are discussed below.

Ascaris (Roundworm) This parasite is acquired by ingestion of the fertile eggs. The early stage of the infection may be associated with Loeffler's Syndrome (pulmonary manifestations and eosinophilia). Adult worms may produce biliary or intestinal colic and appendicitis; some subjects "vomit" the worm. Diagnosis is made by detecting the ova or adult worms in the stools. With reference to therapy, where mixed worm infections occur, Ascaris must always be treated first. Drugs used to treat the worm include the following. Piperazine citrate: given orally - 75 mg/kg (maximum daily dose is 3.5 g) for 2 consecutive days. Piperazines are contraindicated in those with a history of seizures or renal dysfunction. Adverse effects include dizziness, tremors, vomiting, and rashes. Pyrantel pamoate: given orally - single dose of 10 mg/kg (maximum 1 g). This drug should not be given to those below 1 year of age. Adverse effects include vomiting, headache, and dizziness. Mebendazole: given orally - 100 mg t.i. d. for 3 consecutive days (same dose for adults and children, but should not be given to children below 2 years of age). Adverse effects of the drug include drowsiness, headache, and dizziness.

Hookworm The larvae enter the human host via the skin (barefoot walking) and the adults live in the small intestine; an eosinophilia may be present. Heavy worm loads can produce an iron-deficiency anemia. Diagnosis is made by finding the eggs of the worm in the stools. The drug of choice is mebendazole (same dose as for Ascaris), or pyrantel pamoate may be used (same daily dose for Ascaris, but given for 3 days).

Strongyloides Most infections are symptomless, but diarrhea, eosinophilia, and skin rashes may be present. In immunosuppressed patients, strongy­ loides may disseminate and the infection may be fatal. Thiabendazole,

24 given orally, 25 mg/kg body weight b.i.d. for 2 days, has been used to treat the infection. Adverse effects of the drug include vomiting, dizziness, and headache.

Trichuriasis (Whipworm) This worm inhabits the cecum and colon and is acquired through ingestion of the embryonated eggs (from soil contamination). Usually there are no associated symptoms. Diagnosis is made by detecting the eggs in the stools. The drug of choice is mebendazole (same doses as for Ascaris infections). Treatment is necessary only in heavily infected or symptomatic individuals.

Clonorchis The liver fluke is found in the Far East and is acquired by ingesting raw contaminated fish. Occasionally, fever, jaundice, and cholangitis may be present. Diagnosis is made by finding the eggs of the worm in the stools or in aspirates of duodenal contents. Therapy is unsatisfactory. Oral doses of chloroquine phosphate, 250 mg t.i.d. for 2-6 weeks in adults, may diminish egg production, but the drug has potential adverse reactions and does not kill the worm, and should not be used in children. Bithionol, dehydroemetine, and emetine have also been used. Treatment is necessary only in heavily infected symptomatic individuals.

Tapeworms Taenia saginata (beef tapeworm) - Humans can become infected with this tapeworm by eating raw beef. Diagnosis is made by finding the eggs or proglottides in the stools. The drug of choice is niclosamide (Yomesan). Adults and children over 6 years are given 2 g orally, the tablets being chewed before being swallowed with a few sips of water. Children between 2 and 6 years are given 1 g. Adverse effects are rare (gastrointestinal upsets). Taenia solium (pork tapeworm) - This tapeworm is acquired by eating raw or poorly cooked pork. The larvae may cause widespread lesions. Diagnosis is made by finding the eggs or proglottides in the stools. Niclosamide is given in the same doses as for T. saginata but, to minimize the risk of autoinfection ( cysticercosis), an an tiemetic drug should be given before treatment and a purgative should be administered 2 hours after the drug is given. Diphyllobothrium latum (fish tapeworm) - Man is infected with this by eating raw fish. Occasionally it produces a megaloblastic anemia. Niclosamide is the drug of choice (same dosage as for beef tapeworm). Hymenolepis nana (dwarf tapeworm) - This tapeworm rarely gives symptoms, and treatment is with niclosamide. Adults and children over 6 years are given 2 g orally on the 1st day and then 1.0 g daily for 6 days. Children between the ages of 2 and 6 years are given one-half the adult dose. As there is a risk of reinfection, a second course may be given 3 weeks later.

25 Pinworm (Enterobiasis)

Pinworm is difficult to eradicate and may be associated with pruritus ani, vulvitis, and enuresis. All members of a family should be treated. General hygiene is also important. Pyrantel pamoate may be used (same dose as for Ascaris) or pyrvinium pamoate (Vanquin) can be given: single oral dose of 5 mg/kg (maximum 250 mg) (stains stools red). Mebendazole is also used (single oral dose of 100 mg for children over 2 years of age and adults). It is advisable to repeat the treatment after 2 weeks.

26 The Patient with Eosinophilia

One of the more perplexing diagnostic problems in the returning traveler is that of the unexplained elevation of absolute eosinophil count. Frequently, repeated stool and blood examinations fail to reveal a parasite to account for an eosinophilia. Even if the patient has no signs or symptoms, it is wise to monitor the count, and in many cases it will settle to normal by itself over a period of time. A persistent or increasing eosinophilia is always significant and warrants an extensive search for parasitic disease, particularly to exclude the following: filariasis; schistosomiasis; ascariasis; hookworm; trichinosis; larva migrans; trichuriasis; and strongyloidiasis. If the patient exhibits symptoms such as fatigue, skin swellings, fevers, or skin rashes, then blood parasites such as Filaria should be suspected. Filariasis, or the bowel parasite Strongyloides stercoralis, may cause a very high eosinophilia (50-60% of white cells). If the patient feels well and has no other physical or laboratory abnormalities, there may be time for a conservative approach to the problem (a close watch on the blood picture and other investigations as indicated). It also should be remembered that an eosinophilia may be associated with a nonparasitic condition (e.g., hay fever). Serological tests may be useful to confirm the presence of a particular parasite, but because of cross reactions between various parasites, the results of such tests must be evaluated with care. In all cases, diagnosis is best confirmed by the history and direct detection of the parasite.

27 The Patient with Other Tropical and Parasitic Infections

Bal an tidiasis This is relatively rare but on occasions may be associated with severe dysentery. The infection is acquired by ingestion of the cysts (passed in the feces of the pig). In acute infections the motile trophozoites are found in the stools, but in chronic infections the cysts are present in the stools. Tetracyclines are effective (e.g., for adults 500 mg of tetracycline q.i.d. for 10 days).

Filariasis The parasite is transmitted by the bite of infected insects (e.g., mosquitoes and blackflies). Incubation periods are long (up to 1.2 months or longer) and the short-stay visitor is rarely affected.

Wuchereria bancrofti - This is found in Africa, Asia, South America, the West Indies, and some South Pacific zones. The adult worms lie in the lymphatic tissues and the microfilariae can be observed in the peripheral blood at night (10:00 p.m. - 2:00 a.m.). Infections may be associated with fever, lymphangitis, and elephantiasis (late). Diagnosis is made by detecting the microfilariae in blood films. Eosinophilia is often present.

Brugia malayi - This is present in Asia and clinically resembles W. bancrofti infections. Diagnosis is made by blood film examination (night and day films).

Loa loa - This is confined to Africa. The adult worm lives in the subcutaneous tissues. Clinical features include "Calabar" swellings (transitory edematous swellings of the skin), fever, eosinophilia, and occasionally the movement of the worm across the eye or skin may be noticed. Diagnosis is made by detection of the microfilariae in the blood (day film).

Onchocerciasis - This is found in Africa and Central and South America and is transmitted by the blackfly. Pruritus and a skin rash are the common presenting symptoms. Blindness may follow the eye lesions. Microfilariae are sometimes seen in skin biopsies and occasionally in the anterior chamber of the eye. Eosinophilia may be high.

Therapy of Filariasis Diethylcarbamazine is used. The death of the parasite may produce severe allergic reactions, and antihistamines and steroids have been used to minimize this, particularly in onchocerciasis where steroids (systemic and local eye drops) have been used to prevent severe reactions.

28 Dose - Diethylcarbamazine citrate is given orally at a dose of 2 mg/kg t.i.d. for 14-28 days. For onchocerciasis a different dosage is used and should only be given in a tropical disease unit. (Diethylcarbamazine citrate is given orally plusi.v. suramin.)

Larva Migrans Larvae of nematodes enter the human subject and although the worms develop no further, the subject may experience a wide range of symptoms. The worm is sometimes observed in the skin. These usually respond to local freezing with ethyl chloride and topical or systemic thiabendazole (same dose as for strongyloides). Sometimes the larval forms inhabit the viscera and produce hepatosplenomegaly, fever, eosinophilia, respiratory symptoms, or retinal lesions (toxocariasis). Diagnosis is made by biopsy and serology; Thiabendazole or diethylcar­ bamazine have been used to treat the condition. In severe cases systemic steroids may be useful.

Lassa Fever The virus (arenavirus) originates in wild rodents (Mastomys natalen­ sis), and the disease was first observed in Nigeria in 1969. The incubation period ranges from 7 to 17 days. It presents as an acute febrile illness and clinical features include sore throat, cough, vomiting, abdominal pain, shock, renal failure, and encephalopathy. Albuminuria and leucopenia are often present. Fatality rates range from 30 to 50%. Asymptomatic cases appear to be common. Diagnosis is made by isolation of the virus from the blood and complement fixation and neutralization tests. Patients suspected of having the infection must be isolated (preferably in a specialized unit), and all laboratory samples must be handled with extreme care. There is no specific treatment, but convalescent plasma has been used and may have a beneficial effect.

Leishmaniasis This is due to infection with the protozoa of the genus Leishmania and is transmitted to humans by sandflies. The visceral form (kala azar) is caused by L. donovani and is found in India, Africa, and parts of the Mediterranean and South America. The incubation period is long (may be several years), and clinical features include splenomegaly, leucopenia, anemia, lymphadenopathy, and changes in the plasma proteins (reversal of A/G ratio and an increase in IgG). Diagnosis is made by finding Leishman-Donovan bodies in the marrow, lymph nodes, or liver. Serological and blood culture (in NNN media) methods are also used. Drugs used to treat the infection include sodium stibogluconate and pentamidine.

29 Cutaneous leishmaniasis (oriental sore) is caused by L. tropica and the incubation period ranges from several weeks to several months. The nodular lesions (face or limbs) lead to ulcers. There is no systemic involvement and diagnosis is confirmed by finding the parasites in samples taken from the edge of the ulcer. Local or systemic sodium stibogluconate may be used to treat the condition, or the ulcer may be left to resolve spontaneously. Mucocutaneous leishmaniasis (espundia) is found mostly in South America and is caused by L. braziliensis. Diagnosis is by detecting the parasite in aspiration samples of the lesion or in biopsy samples. Treatment is similar to that of oriental sore. In Central America (particularly in Mexico, Guatemala, and the Honduras), a lesion similar to oriental sore occurs and is caused by L. mexicana.

Leprosy It is not possible to cover this disease here, but all physicians should be on the lookout for the infection. The clinical picture includes skin macules, nodules, ulceration, thickening of the peripheral nerves (great auricular, ulnar, and lateral popliteal), sensory impairment, muscle palsies, eye lesions, keratitis, iritis, and opacities, and the sequelae of such changes. Diagnostic methods include skin smears, nasal scrapings, biopsy of nerves and skin, histamine and lepromin tests. Drugs used to treat the infection include dapsone, thiabutosine, rifampicin, and clofazimine.

Lymphogranuloma Venereum This is an infection related to the psittacosis-trachoma group. In males the primary sore· is usually on the penis, but in females the primary lesion may go unobserved. Later the regional lymph nodes are involved forming a bubo. Complications include rectal or vaginal fistulae and strictures. Diagnosis is by demonstrating the organism in a smear from the lesion or lymph nodes (aspirate). The Frei skin test and complement fixation tests are also available. Sulfonamides and tetracyclines are effective in treating this infection.

Smallpox The physician should always keep this infection in mind, particularly as eradication programs are incomplete.

Schistosomiasis (Blood Flukes) Schistosoma hematobium lives in the veins of the bladder and is found in Africa and the Middle East. S. mansoni lives in the mesenteric veins and is found in Africa, the Middle East, South America, and the Caribbean. S. japonicum lives in the veins of the small intestine and is found in the Far East. Infection is acquired by swimming or wading in contaminated fresh water. Clinical features include skin rashes, fever, eosinophilia, dysen­ tery, terminal hematuria (S. hematobium), hepatic enlargement, portal and pulmonary hypertension, and central nervous system (CNS) involve-

30 ment. Genitourinary symptoms predominate in S. hematobium infections. S. mansoni and S. japonicum may be associated with intestinal signs and symptoms. For diagnosis of S. hematobium, the eggs should be sought in the midday sample of urine, terminal portion. Biopsy of the bladder, IVP, and cystoscopy are also useful. For S. mansoni and S. japonicum, the eggs may be present in the stools and biopsies of the intestine or rectum are also used. Serological and skin tests are also useful. Niridazole (Ambilhar) is the drug of choice for S. hematobium and S. mansoni infections.

Dose - Niridazole (Ambilhar), 25 mg/kg of body weight is given orally, daily for 7-10 days (maximum daily dose is 1.5 g). Adverse effects include dizziness, mental changes, seizures, vomiting, ECG changes, skin rashes, and hemolysis (G-6-Pd deficiencies). The drug should not be used where there is hepatic dysfunction, portal hypertension, or history of seizure. S. japonicum is difficult to eradicate, and antimony potassium tartrate has been used.

Trypanosomiasis African trypanosomiasis - This is transmitted by tsetse flies. The parasite is present in the blood, lymphatics, and CNS. The incubation period may be up to several years. Clinical features include fever, rashes, edema, lymphadenopathy, headaches, drowsiness, and personality changes. Diagnosis is made by blood films, or aspiration of lymph nodes. In later stages, the parasite may be found in the cerebrospinal fluid (CSF). Serological tests are also available. The serum IgM rises rapidly in the early stages and the CSF IgM is raised in the late CNS stage. A normal serum IgM level would virtually rule out the possibility of the disease being present. Pentamidine, suramin, and melarsoprol have been used to treat the disease and pentamidine has been given for prophylaxis. American trypanosomiasis (Chagas' disease) - This is transmitted by the reduviid bug (South and Central America). Initially there may be swelling of local lymph nodes and edema. Other features include fever, tachycardia, enlargement of the liver and spleen. Cardiac arrythmias, congestive heart failure and megaesophagus and megacolon are seen later. Diagnosis is by finding Trypanosoma cruzi in the blood or leishmanoid forms in the tissues (e.g., muscles). Blood culture, xenodiagnosis, and complement fixation tests have also been used. Treatment is unsatisfactory but primaquine and Bayer 2502 have been used.

Acknowledgments We wish to express our appreciation to the members of the Tropical Medicine and International Health Division of the Canadian Public Health Association for their assistance, and to Health and Welfare Canada for their permission to reproduce the table of international immunization requirements.

31 YELLOW FEVER YELLOW FEVER YELLOW FEVER Fl~VRE JAUNE Fl~VRE JAUNE Fl~VRE JAUNE

CHOLERA CHOLERA CHOLERA CHOL£ RA CHOL£ RA CHOL£ RA

SMALLPOX - ON RETURN SMALLPOX - ON RETURN SMALLPOX - ON RETURN VARIOLE - AU RETOUR VARIOLE - AU RETOUR VARIOLE - AU RETOUR

SMALLPOX - REQUIRED TO VISIT SMALLPOX - REQUIRED TO VISIT SMALLPOX - REQUIRED TO VISIT VARIOLE - EXIG£E POUR VISITER VARIOLE - EXIG£E POUR VISITER VARIOLE - EXIG£E POUR VISITER COUNTRY- PAYS COUNTRY- PAYS COUNTRY- PAYS , I * REQUIRED/EXIG~E * REQUIRED/EXIG~E I * REQUIRED/EXIG~E R RECOMMENDED/RECOMMAND~E R RECOMMENDED/RECOMMAND~E R RECOMMENDED/RECOMMAND~E Afghanistan Comoros - Comores * Grenada - Grenade * Albania - Aloanle Congo * * Guam Algeria - Alg6rie Cook. Is. Guatemala American Samoa - Samoa am6ricain Costa Rica Guernsey, Alderney and Sark Angola * R R Cuba Guernesey, Alderney et Sark Antigua Cyprus - Chypre Guinea - Gulnlte * * Argentina - Argentine * Czechoslovakia - Tch6coslovaquie Guinea - Bissau - Gulnee - Bissau * Australia - Australie Democratic Kampuchea - Guyana - Guyane Austria - Autriche Kampuchea d6mocratlque * Haiti- Haiti * w Bahamas Democratic Yemen - Y6men d6mocratique Honduras N Bahrain - Bahreln Denmark - Oanemark Hong Kong Banglade'l/1 * R Djibouti * Hungary - Hongrie Barbados - Barbade Dominica - Dominique Iceland - lslande Belgium - Belgique Dominican Republic - R6publlque Oominlcaine India- lnde R Belize * East Timor - Timor orlental * * Indonesia - lndonesie * R Benin - B6nin * * Ecuador - a=:quateur Iran * R Bermuda - Bermudes Egypt - £gypte * Iraq - lrak * Bolivia - Bolivie * R El Salvador Ireland - lrlande . Botswana * Equatorial Guinea - Guin6e t\quatorlale * Isle of Man - lie de Man Brazil - Brasil * R Ethiopia - .=:thiople * * * Israel - Israel Brunei - Brunei * Falkland (Malvlnas). Is. Italy- ltalle Bulgaria - Bulgarle Faroe Islands- Ties Faroe Ivory Coast - COte d'Ivoire * * Burma - Birmanie R Fljl-Fldjl Jamaica - Jamaique Burundi * Finland - Finlande Japan - Japon Canada France Jersey Canal Zone - Zone du Canal French Polynesla - Polynt\sle franc;alse Jordan - Jordanie Cape Verde - Cap-Vert Gabon * Kenya * * Cayman Islands * Gambia - Gamble Kuwait - Kowelt * Central African Empire - Empire Centrafricain * * German Democratic Republic Lao People's Democratic Republic Chad- Tchad * R Rt\publlque dt\mocratlque allemande Rt\publlque dt\mocratlque populaire lao * Chile- Chili Germany, Federal Republic of Lebanon - Llban Allemagne. A~publlque f~d~rale d' China. People's Republic - Lesotho * Republique de la Chine Populaire * R Ghana R R Liberia - Li berla * R * China, Republic of (Taiwan) - Gllbraltar Libyan Arab Republic Rt\publique de la Chine (Taiwan) * Giibert, I. R Rt\publique arabe libyenne * Christmas I_ (Indian Ocean - Ocean indien) Greece - Gri!ce Liechtenstein Colombia - Colomble * R Greenland - Groenland Luxemboura YELLOW FEVER YELLOW FEVER YELLOW FEVER Fl~VRE JAUNE Fl~VRE JAUNE Fl~VRE JAUNE

CHOLERA CHOLERA CHOLERA CHOL~RA CHOL~RA CHOL~RA

SMALLPOX - ON RETURN SMALLPOX - ON RETURN SMALLPOX - ON RETURN VARIOLE - AU RETOUR VARIOLE - AU RETOUR VARIOLE - AU RETOUR

SMALLPOX - REQUIRED TO VISIT SMALLPOX - REQUIRED TO VISIT SMALLPOX - REQUIRED TO VISIT VARIOLE - EXIG~E POUR VI SITER VARI OLE - EXIG~E POUR VI SITER VARIOLE - EXIG~E POUR VISITER I COUNTRY- PAYS' COUNTRY- PAYS COUNTRY- PAYS * AEQUIAED/EXIGU 1 * AEQUIAED/EXIG~E , * AEQUIAED/EXIGU ' R AECDMMENDED/AECDMMAND~E R AECDMMENDED/RECDMMANDU R AECDMMENDED/AECDMMANDU Macao Peru P6rou R Togo * R • Madagascar * Phillpplnes * R Tonga Malawi * Pitcairn, I. Trinidad and Tobago - Trinit6-et-Tobago Malaysia - Malaisle R Poland - Pologne Tunisia - Tun Isle Maldives * * Portugal Turkey - Turqule Mali * * Puerto Rico - Porto Rico Tuvalu Malta- Malte Qatar * Uganda - Ouganda * * Mauritania - Mauritania Republic of Korea - R6publique de Corte * Union of Soviet Socialist Republics * * Union des R~publiques soclalistes sovi~tiques Mauritius - Maurice Romania - Roumanie ------United Arab Emirates - Emirats Arabes Unls Mexico - Mexique Rwanda United Kingdom - Royaume-Uni Monaco Saint Helena - Sainte-H61ene * United Republic of Cameroon Mongolia - Mongol le Saint Kitts-Nevis-Anguilla * Saint-Christophe-et-Nieves et Anguilla ~publique-Unle du Cameroun * * Montserrat Saint Lucia - Sainte-Lucie United Republic of Tanzania Morocco - Maroc R6publlque-Unle de Tanzania R Saint-Pierre et Miquelon Mozambique United States of America * R Saint Vincent Namibia - Namibie Etats-Unls d'Am6rlque * Samoa Nauru Upper Volta - Haute-Volta Sao Tome and Principe - Sao Tom6-et-Principe * * Nepal - N6pal * * Uruguay * R Saudi Arabia - Arable Saoudlte * Netherlands - Pays-Bas R Venezuela Senegal - S6n6gal Netherlands Antilles - Antilles n6erlandaises * Viet Nam Seychelles * R New Caledonia and Dependencies * * Virgin Islands (USA) Nouvelle-Cal6donle et d6pendances Sierra Leone * R lies Vierges des ~tats-Un ls d' Am8rique New Hebrides - Nouvelles-H6brides Singapore - Singapour * Wake, I. New Zealand - Nouvelle-Z61ande Solomon, I. Yemen - Y6men Nicaragua * Somalia - Somafle * * Yugoslavia - Yougoslavle Niger * * South Africa - Afrlque du Sud * Zaire - Zaire * R Nigeria - Nig6rla * R * Southern Rhodesia - Rhod6sle du Sud * Zambia - Zamble Niue Spain - Espagne Travellers are advised that the vaccination requi remen1s of Sri Lanka Norway - Norvttge * R countries in which they arrive are related to the health con- Sudan - Soudan Oman * * R ditlona in the country of departure and to health conditions Pacific Islands, Trust Territory of the USA Surinam in the countries in which travellers disembark during their lies du Paclfique Swaziland - Souaziland journey. (Terrltolre sous tutelle des Etats-Unis d'Am6rique) Sweden - Subde Lea voyageurs aont avertia que lea exigences de vaccination Pakistan Switzerland - Suisse dea Paya d'entr6e aont aoumisea aux conditions sanitalres du Panama Syrian Arab Republic paya d'origine et aux conditions aanitaires existantes dans Papua New Guinea- Papouasle-Nouvelle-Guin6e R6publlque arabe syrienne * R * * lea paya de a6jour. Paraauav Thailand - Thailande AppendixB Canadian Reference Centres for Tropical Diseases

(This list is not complete and other centres and units also offer assistance. As well, an increasing number of individual physicians and local hospitals now have information and some experience on the subject.)

Phone Number Ottawa Tropical Disease Clinic, National Defence Medical Centre (613) 733-6600 Health Unit, Carleton University (613) 231-2755 Toronto Tropical Disease Unit, Toronto General Hospital (416) 595-3600 St. Michaels Hospital (Travel Clinic) (416) 360-6620 Montreal Tropical Disease Clinic, Montreal General Hospital (514) 937-6011 Hotel-Dieu de Montreal (514) 844-0161 Vancouver Division of Laboratories, 828 W. 10 Avenue, Vancouver (604) 874-2331 Edmonton Infectious Disease Clinic, University Hospital ( 403) 439-5911 Winnipeg Infectious Disease Clinic, Winnipeg General Hospital (204) 774-6511

34 AppendixC Recommended Reading

Abramowicz, M. (ed.) 1976. The medical letter. Handbook of antimicrobial therapy. New York, N.Y., Medical Letterlnc. Adams, A.R.D., and Maegraith, B.G. 1976. Clinical tropical diseases. 6th edition. Oxford, England, Blackwell Scientific Publications. Brown, H. W. 1975. Basic clinical parasitology. 4th edition. New York, N.Y., Appleton-Century-Crofts. Jeffrey, H.C., and Leach, R.M. 1975. Atlas of medical helminthology and protozoology. 2nd edition. London, England, Churchill Livingstone. Seah, S.K.K. 1975. Health guide for travellers to warm climates. Toronto, Ontario, Canadian Public Health Association. Turner, A.C. 1975. Travel medicine; a handbook for practitioners. Edinburgh, Scotland, Churchill Livingstone. U.S. Department of Health, Education and Welfare. 1976. Health information for international travel. (DHEW publication no. (CDC) 76-8280.) U.S. Depart­ ment of Health, Education and Welfare, Public Health Service Centre for Disease Control, Bureau of Epidemiology, Atlanta, Georgia. U.S. Department of Health, Education arid Welfare. 1978. Chemoprophylaxis of malaria. (DHEW publication no. (CDC) 78-8017.) Supplement to Morbidity and Mortality Weekly Report, Centre for Disease Control, Atlanta, Georgia, Vol. 27, No. 10, 10 March 1978. Wilcocks, C., and Manson-Bahr, P.E.C. 1972. Manson's tropical diseases. 17th editio'n. London, England, Bailliere-Tindall. Woodruff, A. W. 1974. Medicine in the tropics. Edinburgh, Scotland, Churchill Livingstone.

World Health Organization. 1976. Information on malaria ris~ for international travellers. 2nd edition (updated). Weekly Epidemiological Record, 51(24), 181-200, 11June1976.

35 Index Acclimatization, 4 Niclosamide, 25 Amoebiasis, 22 Niridazole, 31 Antimalarials, 12, 13 Onchocerciasis, 28 Aralen, 12 Ascaris, 24 Paludrine, 12 Parasitic infections, 28 Balantidiasis, 28 Pentamidine, 29, 31 Barefoot walking, 5 Pinworms, 26 Bayer 2502, 31 Piperazine citrate, 24 Blood flukes, 30 Plague, 9 Brugia malayi, 28 Poliomyelitis, 8 Prickly heat (miliaria rubra), 5 Chagas' Disease, 31 Primaquine, 12, 13, 16, 17, 31 Chloroguanide, 12, 13 Primaquine phosphate, 16 Chloroquine, 12, 13, 17 Pyrantel pamoate, 24, 26 Chloroquine hydrochloride, 17 Pyrimethamine, 12, 13, 17 Chloroquine phosphate, 16, 23, 25 Pyrvinium pamoate, 26 Cholera, 7 Clofazirnine, 30 Quinacrine hydrochloride, 21 Clonorchis, 25 Quinine, 17 Quinine dihydrochloride, 17 Dapsone, 13, 30 Quinine sufate, 17 Daraprim, 12 Rabies, 9 Dehydroemetine, 23 Reference Centres for Tropical Diseases Diarrhea, 5, 20 (Canada), 34 Diethykarbamazine, 28, 29 Rifampicin, 30 Diethykarbamazine citrate, 29 Roundworm, 24 Diiodohydroxyquin, 23 Diloxanide furoate, 23 Salt depletion, 4 Diptheria', 9 Schistosomiasis, 30 Smallpox, 7, 30 Emetine, 23, 25 Sodium stibogluconate, 29, 30 Enterobiasis, 26 S trongyloides, 24 Eosinophilia, 27 Sulfadiazine, 17 Sulfadoxine, 13 Fansidar, 13 Sulfonamides, 30 Fevers, 18 Suramin, 31 Filariasis, 28 Swimming,5 Food,5 Tapeworms (beef, pork, fish, dwarf), 25 Giardiasis, 21 Tetanus, 9 Halazone tablets, 5 Tetracyclines, 28, 30 Heat exhaustion, 4 Thiabendazo)e, 24, 29 Heatstroke, 5 Thiabutosine, 30 Hookworm, 24 Trichuriasis, 25 Immunizations, 7 Trypanosomiasis (African and American), 31 Immunization Requirements, 32, 33 Typhoid, 8 Infectious hepatitis, 9 Typhus, 9 Insects, 6 Vaccines "Jet lag," 4 BCG,9 Cholera, 8 Larva migrans, 29 Gamma globulin, 9 Lassa Fever, 29 Polio, 8 Leishmaniasis, 29 Smallpox, 7 Leprosy, 30 Typhoid, 8 Loa /oa, 28 Typhus, 9 Loeffler' s Syndrome, 24 Yellow Fever, 7 Lomotil, 4, 5 Lymphogranuloma venereum, 30 Water and Drink, 5 Whipworm, 25 Malaria, 12 Worm Infections, 24 Mebendazole, 24, 25, 26 Wuchereria bancrofti, 28 Melarsoprol, 31 Metronidazole, 21, 23 Yellow Fever, 7 36