Imported African Trypanosomiasis in the United States HARRISON C. SPENCER, Jr., M.D., JAMES J. GIBSON, Jr., M.D., RICHARD E. BRODSKY, M.D. f and MYRON G. SCHULTZ, D.V.M., M.D., D.C.M.T., F.A.C.P., Atlanta, Georgia

Since 1967, six cases of African trypanosomiasis have been diagnosed and treated in the United States. Five patients were Americans infected with Trypanosoma rhodesiense, and the other was an African student with T. gambiense. Presenting signs and symptoms for all cases were typical of the disease, but often the diagnosis was delayed. The five Americans had spent only brief periods in endemic areas. All cases responded to therapy although one relapsed. Cases of imported sleeping sickness are few, and the risk of Americans acquiring the disease while traveling to endemic areas is low. However, the early diagnosis of sleeping sickness requires that physicians be cognizant of the possibility of imported tropical diseases.

T w o FORMS OF AFRICAN TRYPANOSOMIASIS (sleeping sick-

ness) are classically described: a chronic illness caused by Trypanosoma gambiense and characterized by emaciation, personality changes, progressive somnolence, and mental deterioration during a period of months or years; and a more acute infection caused by T. rhodesiense presenting with chills, fever, adenopathy, headache, and rapid involvement of the central nervous system (CNS) often progressing to death in a few months. The Gambian form is found primarily in West and Central Africa; the acute Rhodesian form, in East Africa from Ethiopia to the Republic of South Africa. This distribution is not absolute, however; acute Rhodesian-like illness can occur in West Africa and the more chronic infection in East Africa. Extensive rapid international travel has facilitated the importation of exotic diseases to nonendemic areas (1-3). While falciparum malaria is probably the most common life-threatening imported disease that can result in serious diagnostic errors (4-8), African trypanosomiasis is also easily misdiagnosed (9-11). Although sleeping sickness is a threat to the traveler in Africa as well as to the African, little is known of the traveler's risk of acquiring the disease. Cases of sleeping sickness in Americans have been infrequently reported and rarely diagnosed in the United States (12-20).

the CDC has the only supply of chemotherapeutic agents for sleeping sickness available in this country, to our knowledge these cases constitute all diagnosed here during this period. For five cases, a member of the Parasitic Diseases Branch hand-carried the drugs, examined the patient, and participated directly in the management. In the other instance, the clinical course was monitored closely by telephone. In all cases the diagnosis was made by finding trypanosomes in the peripheral blood or cerebrospinal fluid (CSF) before beginning chemotherapy. Serologic tests were done at the CDC. Either an indirect hemagglutination test using Trypanosoma cruzi as an antigen (four patients) (21) or an indirect immunofluorescence test using strain of T. rhodesiense isolated from our Patient 2 was done (2 patients) (22, 23). The chemotherapeutic agents used were melarsoprol (Arsobal®*) (commonly called Mel!B), suramin sodium (Suramin®"!") (previously known as Bayer 205®t), pentamidine isethionate (Lomidine®t), and nitrofurazone (Furacin®§). All but nitrofurazone are unlicensed in this country and are sponsored by one of the authors (Dr. Schultz) under authority of the Food and Drug Administration by Notice of Claimed Investigation Exemption for a New Drug. These drugs are supplied by the Parasitic Disease Drug Service, CDC, on request from physicians. Results EPIDEMIOLOGIC DATA

Epidemiologic characteristics of the six cases are shown in Table 1. Although T. rhodesiense and T. gambiense are morphologically indistinguishable ( 2 4 ) , the acute manifestations of illness and the areas of Africa visited suggest that the five Americans had the Rhodesian form of sleeping sickness. The other patient, an African student, had features suggestive of Gambian disease ||. Of the five T. rhodesiense infections, three were acquired in Botswana; two persons (Patients 4 and 5) had been along the Khwai River near the Okavango Swamp, a known endemic area. The other spent 19 days on a hunting trip in the bush. Patient 3, a missionary, was infected on a 1-day trip to the Kagera Game Park, Rwanda (the only day he was in a tsetse-infested area), and the patient infected in Kenya had spent time at the Serengeti Park. Two developed initial symptoms while in Africa, two in Europe, and one after returning home. Possible incubation periods in each case were compatible with the usual range observed in Europeans of 5 to 15 days (25-27). All five

Materials and Methods

From 1967 through August, 1974, six cases of African trypanosomiasis diagnosed and treated in the United States were reported to the Center for Disease Control (CDC). Because • From the Center for Disease Control, Public Health Service, U. S. Department of Health, Education, and Welfare, Atlanta, Georgia. Annals of Internal Medicine 82:633-638, 1975.

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* Rhone Poulenc, Paris, France. t Farbenfabriken Bayer AG, Leverkusen, West Germany. % May and Baker Ltd., Dagenham, England. § Eaton Laboratories, Norwich, New York. || GRUNINGER R P : Trypanosomiasis (African Sleeping Sickness) in Minnesota. A Case Presentation, Minnesota Society of Internal Medicine, Minneapolis, Minnesota, 12 May 1973.

633

Table 1 . Epiderniologi c Feattires of lm(>orted African Tryptanosomia sis in the Uniti3d States (1967 to1974)* Patient

Age

Sex

Race

Citizenship

Etiologic Agent

Year of Diagnosis;

1969

Botswana

1970 1970

Kenya Rwanda

1970 1971 1972

Botswana Botswana Liberia

Country ]Known Timec >f of Tsetse Exposu re Exposure Bite

yrs

Possible Incubation Period

Reason for Exposure

days

days

1

56

M

W

U.S.

2 3

24 57

F M

W

U.S. U.S.

Trypanosoma rhodesiense T. rhodesiense T. rhodesiense

4 5 6

19 74 24

M M M

U.S. U.S. Liberia

T. rhodesiense T. rhodesiense T. gambiense

w w w B

+

19

1 to 19

Safari



3 1

8 to 10 7

21 14

1 to 21 1 to 14

Safari Visit to game park Safari Safari Resident

+ + + -

-

Interval f

-

1 10 7 0 15 69

* + = known; — = not known. t Time between initial physician visit in the United States and correct diagnosis.

were diagnosed and treated in the United States: two in California and one each in Pennsylvania, Florida, and New York City. Four of the five could remember being bitten by tsetse flies. The patient with T. gambiense disease, an African student, had never been out of Liberia until his trip directly to the United States. He had lived in an area of rain forest in which Gambian trypanosomiasis had been endemic in the past (28). Symptoms developed less than a week after he arrived to attend college in Minnesota. The patient denied receiving prophylaxis for trypanosomiasis, knew of no cases of sleeping sickness where he lived, and could not recall ever having been bitten by a tsetse fly. Although all six patients consulted physicians within 2 weeks after developing symptoms, for three of five Americans 1 to 2 weeks elapsed between initial physician contact in the United States and correct diagnosis. In one of the four, trypanosomes were seen and correctly identified on peripheral blood smear by laboratory technicians but were ignored, and the patient was treated for nonexistent malaria for 2 weeks. Trypanosomiasis was initially suspected in Patient 4 when he developed a chancre while in Nairobi, but blood smears at that time were negative. Diagnosis could have been made earlier by scraping the lesion (26, 29). Despite his background and presenting symptoms, the African patient was followed with a variety of diagnoses for more than 2 months before the organism was identified and appropriate therapy given. CLINICAL FEATURES

Presenting symptoms and signs were markedly uniform (Tables 2 and 3). All presented with malaise, confusion, anorexia, and lethargy. Five had headache and fever, 38.3 °C [101 °F], and four had chills and personality change. On examination, four had a definite chancre, three had lymphadenopathy (two with enlarged soft posterior cervical nodes—Winterbottom's sign); and one had a transient morbilliform rash. There were no localizing neurological signs. One patient had hyperesthesia related to a secondarily infected chancre, but none showed delayed deep hyperesthesia (Kerandel's sign). One patient had a palpable spleen and a slightly enlarged liver. Only one patient had cardiomegaly, and none experienced heart failure. Jaundice was not observed. 634

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Presenting manifestations of the three patients found to have trypanosomes in the CSF were similar to those whose CSF was normal. Patient 2 was documented to have invasion of the CNS when lumbar puncture was done only 14 days after the onset of fever. Initial symptoms for the patients with T. rhodesiense included fever and chancre in four, and fever, nausea, vomiting, and headache in one. All appeared acutely ill. The African student with T. gambiense was chronically ill and presented with headache, somnolence, confusion, and personality change. LABORATORY FEATURES

Selected laboratory findings of these patients on admission to the hospital are presented in Table 4. All had trypanosomes in a peripheral blood smear. Organisms were present in the CSF of three, and CSF protein was elevated. Two patients were thrombocytopenic; one, Patient 4, as previously reported, developed changes in clotting function suggestive of disseminated intravascular coagulation (16). Four of the five T. rhodesiense patients had moderately low hemoglobin; this possibly reflects the autoimmune hemolysis previously reported (30). Marked abnormalities in serum proteins were observed. All patients demonstrated hypoalbuminemia, four had hypoproteinemia, and five had hyperglobulinemia. Hypergammaglobulinemia was seen in two of four patients tested. Two of three patients had marked elevation of quantitative IgG and IgM immunoglobulin levels but not in the 3:1 IgM-to-IgG ratio previously noted (31). Levels of IgA were also elevated in one. Liver function tests showed moderate elevations in five of six patients; the changes were nonspecific. Two patients had evidence of renal insufficiency prior to therapy. Renal function gradually returned to normal values after therapy ended. Four had proteinuria but in no instance was the loss striking. After therapy, urinalysis was normal in all. SEROLOGIC RESULTS

Serums for serologic tests were drawn 3 to 5 weeks after the onset of symptoms. Four patients had negative indirect hemagglutination tests using T. cruzi as an antigen. Patient 2 had a positive titer (1:1024) by indirect immunofluorescence using her own T. rhodesiense organisms as a source

Table 2. Presenting Symptoms of Imported African Trypanosomiasis in the United States (1967 to 1974)

of antigen. With the same source of antigen the patient with T. gambiense also had a titer of 1:1024 by indirect immunofluorescence test; the titer fell to 1:64 after his first course of therapy.

tired. Trypanosomes were present in CSF and there were 76 mononuclear cells per mm3. During this third relapse, he received a combination of melarsoprol and oral nitrofurazone (32). Because resistance to arsenical drugs is more characteristic of T. rhodesiense than of T. gambiense, this occurrence of melarsoprol resistance is unusual, but not unique (33). Toxic manifestations were surprisingly few. While receiving suramin sodium, Patient 1 developed hyponatremia, oliguria, and increasing azotemia. The drug was withheld for 2 weeks and then given once a week for 4 weeks for a total dose of 3.4 g without ill effects. Patient 5 developed tremor, increasing weakness, and hemiballismus while on melarsoprol. These disappeared when the drug was stopped. The African student had a 38.9 °C [102 °F] fever and pulse of 100 per minute for 2 hours starting 3 to 4 hours after the first injection of melarsoprol. This reaction was possibly a Herxheimer type previously reported in treating Gambian disease (34). During treatment with nitrofurazone he developed a combined sensory and motor peripheral neuropathy which caused cessation of therapy, and has persisted to the present.

Therapy

Risk

For patients with T. rhodesiense, suramin sodium was used alone unless CNS invasion was documented, in which case melarsoprol was added. A 1-g dose of suramin sodium was given intravenously on days 1, 3, 7, 14, and 21. A test dose of 0.1 g was given initially to exclude hypersensitivity. Melarsoprol was given once a day intravenously on 3 successive or alternate days in doses of 1.5, 2, and 2.2 mg/kg followed after a 7-day interval by doses of 2.5, 3, and 3.6 mg/kg; finally a third 3-day course of one daily injection of 3.6 mg/kg was given. The maximum daily dose did not exceed 200 mg. Of the three patients with CNS invasion, one received both melarsoprol and suramin sodium in full dosages (Patient 2), and one was pretreated with 2 g of suramin sodium prior to being given melarsoprol (Patient 5). Because of documented CNS invasion, low parasitemia, and generally good clinical condition, the patient with T. gambiense infection received melarsoprol alone. The patients without evidence of CNS invasion were treated with suramin sodium alone except in one instance where pentamidine was given initially because suramin sodium was not available until the day after diagnosis. All patients recovered rapidly from the initial attack after receiving appropriate therapy. All became afebrile, trypanosomes disappeared from the peripheral blood and CSF, and clinical signs as well as laboratory abnormalities improved. At present, only the patient with T. gambiense infection has relapsed. Five months after completion of therapy, the patient noted recurrence of fatigue, headache, and weakness. Organisms were again present in the blood and CSF. A second course of melarsoprol was given without toxic effect; he remained well for 8 months but then experienced a second recurrence of headache and fatigue. An occasional organism was found in the CSF only; a third course of melarsoprol was given. He remained well for 6 months, until July 1974, but then felt weak and

Persons in America at risk of acquiring African trypanosomiasis are tourists, immigrants from Africa, persons whose occupation requires foreign residence or travel, and laboratory personnel. Only indirect data are available to assess exposure. Approximately 20 000 U.S. citizens and 10 000 aliens arrive annually in the United States directly from countries with known focuses of African trypanosomiasis transmission (35). These numbers are only a proportion of the total American population at risk because only the last country of embarkation is given in the immigration data; consequently, those who return to the United States via nonendemic countries, but have previously been to endemic ones, are excluded from this count.

Symptom Malaise Confusion Anorexia Lethargy Headache Fever Personality change Chills Myalgia Somnolence Vomiting Irritability Weight loss Nocturnal insomnia

Number of Patients * 6 6 6 6 5 5 4 4 3 2 2 2 2 1

* Total patients, 6.

Table 3. Clinical Signs of Imported African Trypanosomiasis in the United States (1967 to 1974) Signs

Number of Patients*

Fever, > 38.3 °C [> 101 °F] Chancre Lymphadenopathy Axillary Posterior cervical Femoral Inguinal Tachycardia Abnormal reflexes Decreased deep tendon reflexes Increased deep tendon reflexes Grasp, suck, blepharospasm Localized edema Pedal Facial Muscle weakness Cardiomegaly Transient rash Splenomegaly Hepatomegaly Nystagmus

5

4

4 3 2 1 1 4 3 2 1 1 2 1 1 1 1 1 1 1 1

* Total patients, 6. Spencer etal. • Trypanosomiasis

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635

Table 4. Presenting Laboratory Features of irnported African Tryipanosomiasis irl the United State;s (1967 to 1974)» Tests Hematologic Hemoglobin, g/100 ml Platelets, no./mm3 Leukocytes, no. /mm3 Cerebrospinal fluid Trypanosomas Protein (15 to 45 mg/100 ml) Glucose (50 to 75 mg/100 ml) Cells (no./mm3) mononuclear, no./mm3 polymorphonuclear, no./mm3 Serum protein Albumin (3.5 to 5 g/100 ml) Globulin (2 to 3 g/100 ml) Gamma globulin (0.8 to 1.8 g/100 ml) IgA (90 to 325 mg/100 ml) IgM (45 to 150 mg/100 ml) IgG (720 to 1500 mg/100 ml) Liver function Bilirubin Serum glutamic-oxalacetic transaminase Serum glutamic-pyruvic transaminase Lactic dehydrogenase Alkaline phosphatase Renal function Blood urea nitrogen, mg/100 ml Creatinine, mg/100 ml

Patients 1

2

3

4

5

6

13.6 adequate 5000

8.8 300 000 3 800

14.1 45 900 5 200

11.5 36 000 5 200

12.5 193 000 4 200

12 adequate 4 200







22 76 1 1 0

+72 ND 24 17 7

21 ND 0 0 0

3 3.3 ND ND ND ND

1.9 3.9 2.7 ND ND ND

2.7 2.3 1.1 ND ND ND

N

rT

T T

T

N

T T

N ND

N ND

T

T

48 5.2

18 0.9

50 6.9

17 70 0 0 0

1.8 3.2 1.1 246 90 880

+59

+99

57 33 28 5

46 2 2 0

2.6 4.4 ND 620 1000 2 800

3.1 4.9 3.5 255 2 280 2600

N

N

T

T

ND

T

N

29 1.5

N ND

T 21 0.9

N N ND ND N 9 0.9

* First tests done prior to therapy; parentheses enclose normal values; + = present; — = absent; ND = not done; N = normal; f = increased.

In addition, airline crewmen, seamen, and military and diplomatic personnel are not included in this estimate. Data are not available for visits to particular regions of countries with endemic trypanosomiasis. Such figures would be important in estimating risk because trypanosomiasis occurs in discrete focuses. Although about 2500 Peace Corps Volunteers work annually in Sub-Saharan Africa, frequently, in remote areas, there has never been a proved case of African trypanosomiasis in a volunteer (conversation with I. S. Alio, Director, Health Program, U.S. Peace Corps, Washington, D.C., in May 1974). Similarly in the past 5 years no cases have been reported in employees of the U.S. Department of State working in Africa (conversation with M. S. Wolfe, Tropical Medical Unit, Department of State, Washington, D. C, in March 1974). The incidence of trypanosomiasis in a group of nonAfricans living in rural areas of Africa can be calculated from the experience of a missionary order, the White Fathers, that supports European and American priests throughout Africa. In the 14-year period of 1960 through 1973, there was one case of Gambian trypanosomiasis acquired in West Africa (Upper Volta), for an incidence of 1 case per 10 000 man-years of exposure, and in East and Central Africa no cases occurred in 20 150 man years of exposure (communication from R. Lamey, White Fathers of Africa, Rome, Italy, February 1974). Discussion SYMPTOMS

Early manifestations of sleeping sickness in non-Africans 636

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differ from those seen in Africans (26, 27, 36, 37). Commonly reported presenting features include fever, trypanosomal "chancre," transient morbilliform rash, lymphadenopathy, splenomegaly, localized edema, deep delayed hyperesthesia, headache, irritability, insomnia, and personality and mood changes (23, 24). Jaundice is rarely reported (38, 39). The only pathognomonic sign is the chancre, which is infrequent in Africans but seen in up to 70% of Europeans (26, 27, 38). Transient morbilliform rash, deep delayed hyperesthesia (Kerandel's sign), and posterior cervical adenopathy (Winterbottom's sign) are relatively specific signs. Fever or the chancre appears first, followed by other symptoms (26, 27, 29, 38). In Europeans, both Gambian and Rhodesian disease usually have an acute onset, and asymptomatic carriers have never been reported, although chronic, asymptomatic infections of both Rhodesian (40, 41) and Gambian disease (42) in Africans are well described. Differences in presentation between the Gambian and Rhodesian form are not sufficiently consistent to be of diagnostic value. Presenting symptoms and signs noted in our patients are consistent with earlier reports (26, 27, 29, 38, 39, 43) and were markedly uniform. All developed symptoms abroad or soon after entering the United States. From history of travel to Africa associated with fever, chancre, rash, or personality change, the diagnosis of sleeping sickness should have been apparent in all. Duggan and Hutchinson (27) in a review of 109 cases of African trypanosomiasis in Europeans found only 22 (20%) with mood and personality changes. All of our patients presented with confusion, and four developed distinctive changes in per-

sonality and mood. In addition to the six imported cases reported here, we are aware of three Americans treated abroad during the same time period, one with fatal outcome (19). DIAGNOSIS

The diagnosis of trypanosomiasis will not be made at the patient's first presentation unless the physician has a high index of suspicion. Appearance of the above-mentioned specific signs is a helpful clue, as is a history of tsetse fly exposure, but commonly patients do not remember the bite. A history of travel to an endemic area is of more diagnostic value (43, 44). The incubation period is usually about 8 to 10 days, but varies from a few days to 3 weeks. Diagnosis is made by detecting organisms in blood, bone marrow, fluid from enlarged lymph nodes (usually cervical), or centrifuged CSF (26, 45). For infections with low parasitemia, organisms are frequently found in a buffycoat preparation (46). If a chancre is present, trypanosomes may be shown in the lesion 48 hours before parasitemia occurs (26). Both T. gambiense and T. rhodesiense are readily cultured on isolation medium (45). Trypanosomes were present in the peripheral blood of all our patients. Animal inoculation can also be of value. T. rhodesiense infection will become patent in most common laboratory rodents within 1 to 2 weeks (26, 47). However, T. gambiense will seldom infect these animals and should be inoculated into monkeys (26, 28). The antigenic variation of these organisms has complicated serologic diagnosis (48-50). Both the indirect immunofluorescence and complement fixation tests are of value when positive in the absence of patent parasitemia. However, at present neither can be recommended as the sole diagnostic tool for imported cases. Recent work has shown that patients with sleeping sickness have an increased serum macroglobulin (IgM) level (usually 8 to 16 times normal) (31, 51). Serum IgM levels begin to rise within 1 or 2 weeks after the appearance of patent parasitemia and may remain elevated for years (52). Elevated concentrations of IgM in the CSF represent a sensitive indicator of CNS involvement. However, elevation of CSF immunoglobulin levels occurs more slowly and does not persist as long as corresponding changes in the serum (52). All patients suspected of having the disease should have a lumbar puncture even if CNS invasion is felt to be unlikely, for this is the only sure way to exclude the possibility. Invasion of the CNS can occur in the presence of minimal symptoms. If trypanosomes are found in peripheral blood, an elevated CSF protein or cell count should be considered an indication of CNS invasion even if organisms cannot be found. One of our patients (Patient 6) with trypanosomes in the CSF had a normal cell count but elevated protein. Thus, both must be examined. Lumbar puncture should be repeated after therapy. THERAPY

Drugs used for the treatment of African trypanosomiasis

in the United States can be obtained from the Parasitic Disease Drug Service, Center for Disease Control, Atlanta, Georgia*. All must be given parenterally, can be toxic, and should be used judiciously. Pentamidine isethionate is the drug of choice for Gambian disease and suramin sodium is the choice for Rhodesian disease, before the stage of CNS invasion (53). Both can be nephrotoxic. Melarsoprol is the only drug available in the U.S. for both forms when CNS disease is present (53). Melarsoprol is also effective against earlier stages of the disease but is not used because of its potential for causing encephalopathy (54). If the patient is acutely ill or has high parasitemia, 2 to 4 low-dose injections of suramin sodium on alternate days can be used to improve the patient's condition before beginning a course of the more toxic melarsoprol (55). PREVENTION

The rationale for the use of pentamidine and suramin sodium in chemoprophylaxis of African trypanosomiasis has been reviewed recently (56). Most American travelers to tsetse-infested areas do not need prophylaxis. From our data, the risk of acquiring the disease is small and is probably less than the risk of toxic effects from the drug. Tourists are more likely to be exposed to T. rhodesiense. Of the eight Americans known to have contracted African trypanosomiasis since 1967, all had the Rhodesian form and all were infected in East or South Africa. All had been to game parks at their presumed times of infection. Four of the eight Americans were infected in the small country of Botswana, probably as a result of the large number of safaris in this area. Infection with T. rhodesiense is transmitted by the Savannah group of tsetse flies and occurs in woodlands and bush country. However, efficacy of chemoprophylaxis for Rhodesian sleeping sickness has not been well shown. Clasically, infection with T. rhodesiense presents as an illness, thereby increasing the likelihood of diagnosis and treatment. The most disquieting hazard associated with chemoprophylaxis is the possible induction of "cryptic cases," in which no organisms are found in the peripheral blood or lymph nodes and CNS involvement is among the presenting symptoms. Chemoprophylaxis should be considered only for persons who will have constant, heavy exposure to the tsetse fly in areas with known transmission of Gambian disease. Routine preventive measures should include the wearing of wrist and ankle length clothing in endemic areas, avoidance of brightly colored clothing, the routine use of mosquito nets, advance contact with medical personnel in areas known to have trypanosomiasis, and the close monitoring and prompt medical attention for any acute febrile illness occurring while in an endemic area or after return home. While the risk of acquiring African sleeping sickness appears low, these cases illustrate that imported disease does occur in this country. Symptoms are often nonspecific and the travel history may be the only clue to the diagnosis. Patients may have stopped only briefly in endemic areas. •Telephone: day, (404)633-3311; night, (404)633-2176. Spencer et a/. • Trypanosomiasis

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637

The early diagnosis of trypanosomiasis does not require that all physicians be experts in tropical medicine but only that they be cognizant of the possibility of imported tropical disease. ACKNOWLEDGMENTS: The authors thank the following physicians, who were directly responsible for the care of these six patients and who permitted us to present these case reports: Robert Gruninger, M.D.; Robert Swenson, M.D.; Daniel L. Donovan, M.D.; George M. Stroud, M.D. (deceased); David Perera, M.D.; William O. Umiker, M.D.; J. Fred Young, M.D.; Philip Ottman, M.D.; A. John Zumwalt, M.D.; E. Barrett-Connor, M.D.; R. J. Ugoretz, M.D.; A. I. Braude, MD.; and Donald Hoskins, M.D. Received 17 June 1974; revision accepted 6 January 1975. • Requests for reprints should be addressed to Richard E. Brodsky, M.D., Epidemic Intelligence Service Officer, Parasitic Diseases and Public Health Division, Center for Disease Control, Atlanta, GA 30333.

28. WORLD HEALTH ORGANIZATION: African Trypanosomiasis

1. MAEGRAITH B: Unde venis? Lancet 1:401-404, 1963 2. DOROLLE P: Old plagues in the jet age. International aspects of present and future control of communicable disease. Br Med J 4:789-792, 1968 3. EDITORIAL: Exotic disease. Br Med J 3:1-2, 1971 4. EDITORIAL: Exotic holidays and malaria. Br Med J 2:604-605, 1972 5. SHUTE PG, MARYON M: Imported malaria in the United Kingdom. Br Med J 2:781-785, 1969 6. EDITORIAL: Malaria risk to travelers. Br Med J 1:691-692, 1973 7. MAEGRAITH B: Exotic Disease in Practice. New York, American Elsevier Publishing Company, Inc., 1965 8. Imported tropical disease. Br Med J 1:450, 1967 9. WILLET KC: Trypanosomiasis in Britain. Br Med J 2:167, 1965 10. Sleeping sickness presenting in Britain. Discussed at the Hospital for Tropical Diseases, London. J Trop Med Hyg 68:296299, 1965 11. SCHNEIDER J: Problemes diagnostiques et therapeutiques de medecine tropicale dans la pratique medicale courante en France. Bull Soc Pathol Exot 57:669-715, 1964 12. MOST H: Manhattan: "a tropical isle"? Am J Trop Med Hyg 17:333-354, 1968 13. MORGAN HJ: A case of trypanosomiasis treated with tryparsamide. Am J Med Sci 167:827-835, 1924 14. LEWIS KM: Trypanosomiasis: relative frequency in the United States, tryparsamide therapy in refractory cases. Boston Med Surg J 195:167-168, 1926 15. FRIEDHEIM E: The first case of highly drug resistant African sleeping sickness treated in the United States of America. Am J Trop Med Hyg 2:634-636, 1953 Disseminated

intravascular coagulation in trypanosomiasis. Arch Intern Med 131:574-577, 1973 17. PERERA DA, DONOVAN DL, STROUD GM, et al: Imported Afri-

can sleeping sickness. JAMA 209:270, 1969 18. SCHULTZ MG, WESTERN KA, PERERA D : African trypanosomia-

sis—Florida. J Infect Dis 119:307-308, 1969 19. CENTER FOR DISEASE CONTROL: An outbreak of African sleep-

(WHO

Technical Report No. 434). Geneva, Joint FAO/WHO Expert Committee, 1969 29. WILLETT KC: The 'trypanosome chancre' in Rhodesian sleeping sickness. Trans R Soc Trop Med Hyg 60:689-690, 1966 30. WOODRUFF AW, ZIEGLER JL, HATHAWAY A, et al: Anaemia in

African trypanosomiasis and big spleen disease in Uganda. Trans R Soc Trop Med Hyg 67:329-337, 1973 31. MCKELVEY EM, FAHEY JL: Immunoglobulin changes in disease: quantitation on the basis of heavy polypeptide chains IgG (yG), IgA (yA), and IgM (yM), and of light polypeptide chains, type K (I) and type L (II). J Clin Invest 44:17781787, 1965 32. EVENS F, NIEMEGEERS R, PACTCHANIAN A: Nitrofurazone ther-

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Imported African trypanosomiasis in the United States.

Since 1967, six cases of African trypanosomiasis have been diagnosed and treated in the United States. Five patients were Americans infected with Tryp...
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