Schistosomiasis in Travelers and Expatriates

Schistosomiasis in Travelers and Expatriates Tomasjelinek, Hans-Dieter Nothduft, and Thomas Loscher Background: Several outbreaks of schistosomiasis among travelers, expatriates, and military serviceman have been reported in recent years. Methods: The travel histories and anamnestic and clinical features of 62 patients with schistosomiasis, who presented to a German outpatient clinic specializing in infectious and tropical diseases, were investigated to identify risk factors that could lead to infection in travelers and expatriates. Results: All patients remembered incidents that led to a likely exposure to cercariae of Schistosoma sp. Fifty nine patients (95%) acquired infection in Africa, two (3%) in South America, and one each (2% each) in Iraq and the Mekong River, respectively. The highest proportion of infection (45%) was imported from West Africa. Patients returning from West Africa reported either contact with tributaries of the Niger (including freshwater pools in the Dogon country, Mali) or with waters of the Volta River, notably Lake Volta and/or its delta. Six patients (10%) acquired infection in little-visited areas such as Central Africa and the Congo Basin. East Africa (especially Lake Victoria) and Lake Malawi contributed 14 patients (22%) to our study group; a further nine patients (14%) became infected after contact with waters of the Zambezi River. Conclusions: The most sensitive method for detection of possible infection with schistosomiasis appeared to be a combination of thorough travel history and serologic testing by indirect hemagglutination (IHA), immunofluorescence antibody test (IFAT), and enzyme-linked immunosorbent assay (ELSA). Most infections were acquired by travelers on lengthy and adventurous journeys or by expatriates venturing outside their normal areas of activity. Most patients knew that they had traveled in an area endemic for schistosomiasis, but were uninformed about behavioral risks they had taken in specific settings. Schistosomiasis is a curable parasitic infection caused by trematodes (flukes). The disease is endemic in 74 countries in Africa, South America, the Caribbean, and Asia.' Man acquires the infection during exposure to fresh water containing cercariae, the infective form of Srhistosoma sp. Infected snails, the specific intermediate hosts, release cercariae into fresh water where they penetrate actively the intact shn of definite hosts, e.g., humans. Penetration can cause intense itching and a papular rash, cercarial dermatitis. Katayama fever, the syndrome associated with acute schistosomiasis, coincides with larval maturation, migration, and early oviposition.2,3 Katayania fever may develop 2-10 weeks following the initial infection of nonimmune individuals and is, therefore, rarely seen in indigenous populations in endemic area^.^,^ Katayania syndrome is characterized by fever, chills, weakness, weight loss, headache, anorexia, nausea, voniiting, diarrhea, abdominal cramps, tenderness and enlargement of the liver, myalgia and arthralgia, dry cough, dyspnea, and scattered soft mottling of the lung fields on Tornas Jelinek, MD, Hans-Dieter Nothdurft, MD, and Thomas Loscher, MD: Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany. Reprint requests: Dr. Tomas Jelinek, Department of Infectious Diseases and Tropical Medicine, Leopoldstrasse 5, 80802 Munchen, Germany J Travel Med 1996; 3:160-164. chest films.' Onset may be sudden, followed by a mild to severe, sometimes life threatening, disease. Hypereosinophilia is a common feature. Chronic schistosoniiasis is characterized by inflammation and subsequent fibrosis of tissues infected by schistosoine eggs. The chronic form of schistosomiasis typically develops years to decades after initial infection.' Several outbreaks of schistosomiasis among travelers, expatriates, and military serviceman have been reported in recent years.""."-"therefore, a good knowledge of endemic areas, risk groups, and risk behavior is warranted for those who give pretravel advice to tourists. To identify risk factors leading to infection in travelers and expatriates, we investigated travel histories and anamnestic and clinical features of patients with schistosoniiasis who presented at our outpatient clinic. Patients and Methods Patients Between 1990 and 1994,17,949 patients presented at the outpatient department of our infectious disease clinic for various medical reasons. Most of them had returned recently from a journey to tropical or subtropical areas. Of these 17,949 patients 31.9% had been to Africa, 34.9% to Asia, 19.3% to Central and South America, and 13.9% to other areas. Schistosoniiasis was diagnosed in 62 German patients returning from endemic countries.trave1 and case histories were analyzed for risk factors and behavior leading to infection. Individual data

Jelinek et al, Schistosomiasis in Travelers and Expatriates 161 points, stored in a coniputerized data base (Microsoft, Excel) were analyzed for statistical significance by Epi Info (World Health Organization [WHO], Geneva and the Centers for Ilisease Control [CUC], Atlanta). Methods Travelers were considered to be possibly infected if they reported an exposure to fresh water in endemic regions and/or presented with signs indicating acute or chronic schistosomiasis.' The diagnosis of schistosomiasis was considered confirnied if elevated antibody titers against Schistosomn mansoni antigens were detectable and/or living eggs of Schisfosoma sp. were present on microscopic examination of rectal snips, urine, or fecal material. '3-'h Blood saniples were collected from all 62 travelers with schistosoiniasis for hematologic and serologic testing. IgG antibodies to somatic (gut-associated polysaccharide) antigens of S. mansorii were assessed by inimunofluorescence antibody test (IFAT) and indirect heniagglutination (IHA), and antibodies to egg antigens were assessed by an immune-linked imniunosorbent assay (ELISA).I3,'' Elevated antibody titers were defined as factors (multiples of normal activity) 2 1 :64 in IFAT and IHA and factors > 10 in the ELISA. Stool samples of patients with suspected schistosomiasis were investigated for eggs by direct microscopy and formol-ether concentrati~n'~ as were the entire sediments of routine urine samples and urine samples collected over 24 hours. We suggested rectum biopsy and subsequent microscopic investigation of rectal snips for egg to all patients with positive serologic findings and negative results of stool and urine samples. However, 40 out of 55 patients declined these investigations for various reasons, chiefly because serologic testing suggested that a diagnosis of schistosomiasis was already highly likely. Treatment All 62 patients received a single dose of praziquantel (40 nig/kg) after diagnosis was established. Regular follow up examinations were performed for at least 12 months. Results Ofthe 62 investigated patients 14 (23%) were female and 48 (77%) were male.the mean age was 30 years.al1 patients were able to remember incidents that led to a likely exposure to cercariae of Schictosoma sp. Of the 62 patients 58 (95%) acquired infection in Africa, two (3%) 21% Iraq Amazon basin Figure 1 Areas of schistosome infection in travelers and expatriates (n = 62).

162 Journal of Travel Medicine, Volume 3, Number 3 in South America, and one each (2% each) in Iraq and the Mekong River, respectively (Fig. 1). The highest proportion of infection (45%) was imported from West Africa. Patients returning from this area reported either contact with tributaries of the Niger (including freshwater pools in the Dogon country, Mali) or with waters of thevolta River, notably LakeVolta and/or its delta. Six out of the 62 patients (1 0%) acquired infection in littlevisited areas such as Central Africa and the Congo Basin. East Africa (especially Lake Victoria) and Lake Malawi contributed 14 patients (22%) to our study group; a further nine (14%) became infected after contact with waters of the Zambezi River. Two groups clearly distinguishable emerged within our study population: travelers returning from a journey to an endemic area (40 patients, 65%) and expatriates returning after a lengthy professional stay (22 patients, 35%).The mean age of travelers was somewhat lower than that of the expatriates (30 years compared to 36 years). Eleven of the 40 travelers (27.5%) were female, whereas this was true for 3 out of22 expatriates (14%).Travelers stayed an average of 112 days (range 7-425 days) within endemic areas.the mean time of residence was 1057 days in expatriates (range 28-2555 days). Some differences were noticed when the areas of infection in both groups were analyzed (Table 1). One major difference was the important role of thevolta River as a cause of schistosomiasis in expatriates. Eight of 22 patients, 36%, acquired infection in this location compared to its less important role in travelers (seven out of40 patients, 17%;p=.0018).Also notable was that 17% of the travelers acquired infection in Lake Malawi and 8% in the Congo River, whereas none of the expatriates became infected in these areas (p<.001 in both cases). A large proportion of expatriates (59%) and travelers (25%) presented without symptoms that suggested a schistosomiasis (Table 2). However, 23 of the 40 travelers (57%), and seven of the 22 expatriates (32%) developed Table 2 Clinical Signs and Symptoms in 62 Patients with Sc histosomiasis Travelers Expatriates Siyns and Symptoms (n = 40) (n = 22) Cercarial dermatitis" 2 (5%) 1 (4%) Symptoms of Katayama fevert 23 (57%) 7 (32%) Unspecific gastrointestinal 5 (13%) 1 (4%) complaints No symptoms 10 (25%) I 3 (59%) *Itching and papular rash; +Fever, chills, weakness, weight loss, headache, anorexia, nausea, vomiting, diarrhea, abdominal cramps, tenderness and enlargement of the liver, myalg~a and arthralgia, dry cough and dyspnea. symptoms that were suggestive of Katayama fever, notably fever and/or diarrhea.three of the expatriates and five of the travelers suspected malaria as the cause of their symptoms, and they had treated themselves with antimalarials (halofantrine or mefloquine) prior to referral to our outpatient clinic.another three travelers, assumed to have acute amoebiasis, took metronidazole; one traveler took a combined treatment against malaria and amoebiasis (metronidazole and mefloquine); and one traveler was treated for Lyme disease with doxycycline by his family doctor after return from his journey. None of these suspected infections could be confirmed retrospectively by serologic or parasitologic testing.the mean duration of symptoms before establishment of diagnosis was 54 days in travelers (range 1-235 days) and 154 days in expatriates (range 8-677 days). Hematologic findings were helpful in 21 out of 40 travelers (53%), who presented with eosinophilia (defined as values 27% of the leukocyte count), and in 14 out of 22 expatriates (64%). Travelers had a mean eosinophil count of 11% (range 0-50%$, and expatriates had a mean value of 12% (range 0-38%). Diagnosis was established in 16 patients (11 travelers and five expatriates) by microscopic detection of schistosome eggs either in urine (three patients), stool saniples (four patients), or in rectal snips (nine patients). Table 1 Areas of Infection with Schistosoma sp - Eleven of these 16 patients were infected with S. mun- Comparison between Travelers and Expatriates soni and five by S. huemutobium.the remaining 46 patients were found to be negative on repeated parasitologic Travelers Expatriates Area oflnfection (n = 40) = 22) examination of stool and urine samples. Six of these patients were also examined by rectoscopy, without any Amazon Basin 2 (5%) 0 positive finding. Forty patients refused rectoscopic exam- Iraq 0 1 (5%) Mekong River 0 (40/o) ination, chiefly because serologic testing suggested that Volta River 7 (17%)) 8 (36%) a diagnosis of schistosomiasis was already highly likely. Niger 11 imj 2 (9%) ' Elevated antibody titers in at least one out of the three Central Africa 1 (3%) 2 (9%) serologic tests performed (IFAT, IHA and ELISA'3,'4) were Nile 0 1 (4%) detected in all patients. East Africa 4 (10%) 3 (14%) Lake Malawi 7 (17%) 0 Treatment consisted of a single dose of praziquan- Congo River 3 (8%) 0 tel (40 mg/kg).all patients were closely followed for at Zambezi 5 (13%) 4 (18%) least 12 months. Relapses were detected in six patients

Jelinek et al. Schistosomiasis in Travelers and Expatriates 163 through the finding of viable eggs in urine or stool specimens (4 patients) or through the reoccurrence of eosinophiha and a marked increase of antibody titers compared to the last control (two patients), respectively. These patients were treated by a second course of praziquantel in the same dosage. No further relapses were detected. Discussion Typically, schistosomiasis is described as an infection of either the uninformed, the inexperienced, or the adventurous traveler.. Retrospectively, all 62 patients in our study were able to remember particular incidents that brought them into possible contact with infective cercariae. Judging from our study population, travel to Africa appears to bear an increased risk of infection compared to travel to other endemic areas. Ninety-five percent of all infections were acquired in Africa (see Fig. 1). Contact with tributaries of thevolta River or the Niger in West Africa (notably freshwater pools in Dogon country, Mali) was the probable cause in 45% of our patients.these findings correspond with several recently published reports about outbreaks of schistosomiasis among travelers to Dogon country and the Niger... Although important areas of infection among travelers in our study group, they were less important for infection in expatriates. Only two of the 22 investigated expatriates (9%) became infected in these areas, compared to 11 of 40 travelers (27%) (Table 1). Similar differences were noted for thevolta River, which was an important source of infection in expatriates (36%) and a less important source in travelers (17%); Lake Malawi, where 17% of the travelers and none of the expatriates became infected; and the Congo River (8% infection in travelers, none in expatriates). Questioning of the patients fiequently revealed a specific behavior that led to infection in specific areas.the delta of thevolta River and thevolta Lake in Ghana are popular destinations of expatriates working in the surrounding countries. These areas are visited on public holidays and on short recreation trips.the water of the delta is especially assumed to be free of cercariae since it blends with salt water from the sea. One expatriate reported that a sign, close to his hotel on the beach, stated there was no danger from schistosome infection in this area. He and his family developed typical signs of Katayama fever shortly after their stay at this beach. Patients who became infected after contact with the waters of the Niger reported either bathing in freshwater pools in the Dogon country, Mali, or participating in extended boat trips on the Niger, or both.these patients were aware of the danger of acquiring schistosomiasis fiom the Niger, but they were uninformed about the same danger in freshwater pools. Lake Malawi is now a popular destination with backpackers, who use it for snorkeling and scuba diving. All patients infected at Lake Malawi report extended freshwater contacts during their diving. Due to its excellent water quality, these travelers did not suspect that Lake Malawi harbored cercariae. The analysis of the symptoms, which led to presentation in our outpatient clinic, reveals no sensitive and specific clinical sign to guide towards a diagnosis of schistosomiasis. Katayama fever, a condition believed to be caused by an allergic reaction to migrating and maturing larvae, occurs only in nonimmune patients3 Its symptoms might easily be mistaken for signs of other infections, such as malaria, amoebiasis, or even Lyme disease, as the pretreatment of 13 of our patients demonstrates. Among our patients, single or multiple symptoms of Katayama syndrome were present in 57% of travelers and 32% of expatriates (Table 2). However, 25% of the travelers and 59% of the expatriates exhibited no symptoms at all; they merely presented for a routine examination after their return to Germany.An increased blood eosinophil count suggested a parasitic infection in these patients and led to further diagnostic procedures. Only in a minority of our patients (1 6 out of 62 patients) did the parasitologic examination of urine, stool specimens, and rectal snips confirm diagnosis. The most sensitive method for detection ofschistosomiasis appeared to be a combination of thorough travel history and serologic testing of all patients with possible infection. The availability of sensitive and specific serologic tests has facilitated the diagnosis of schistosomiasis, especially in cases with limited egg secretion and during the prepatent period, before egg production begins. ** Serologic testing has obviated the need for rectal biopsies to confirm diagnosis in patients with negative results in urine and stool examination. However, serology might be negative during the early stages of disease, and testing should therefore be repeated in cases with a travel history and clinical signs suggestive of schistosomiasis. Praziquantel is the current drug of choice for the treatment of schistosomiasis. Maturing larvae of Schktosoma sp. appear to be less vulnerable to the antihelminthic activity of the drug than adult parasites; therefore, treatment during the acute stages of infection is thought to be less effective than during the chronic stages. Early treatment has also been associated with severe allergic However, treatment with praziquantel is generally considered safe and effective, with few side effects. Patients reporting fieshwater contacts in endemic regions, and with significantly elevated antibody titers against schistosonie antigens, should therefore be treated, even if a definite parasitologic diagnosis cannot be established. Treatment failures such as those in six of our patients are reported frequently and are thought to be

164 Journal of Travel Medicine, Volume 3, Number 3 due to a substantial first-pass effect ofpraziquantel in the liver, which leads to plasma concentrations of only 5-796 of the ingested dose.*" Therefore, all patients should be closely followed for several months following treatment. An important proportion of infected patients probably remains undiagnosed, possibly because these patients and their physicians are unaware of the possibility of schistosomiasis.3 Although acute infections gradually improve spontaneously, they can lead to chronic infection accompanied with granuloma formation and subsequent fibrosis. Schistosomiasis can also cause transverse myelitis and other manifestations of neuroschistosomiasis which are caused by an ectopic location of adult worm pairs or eggs in the central nervous systen~.'~'~ This form of infection can cause severe symptoms and is preventable with early diagnosis and rapid treatment.24 In our study group, most infections were acquired by travelers on a lengthy and adventurous journey or by expatriates venturing outside their normal areas of activity. Most patients knew that they had traveled in an area endemic for schistosomiasis, but were uninformed about the behavioral risks they had taken in specific settings, such as snorkeling in Lake Malawi or bathing in Dogon country. Others simply could not avoid skin exposure to freshwater, such as backpackers traveling in boats on the Niger or Congo River. Travelers to the tropics should therefore be informed thoroughly about the dangers of water-related diseases such as schistosomiasis. References 1. Anonymous. Schistosomiasis in US Peace Corps volunteers - Malawi, 1992. MMWR Morb Mortal Wkly Rep 1993; 42:565-570. 2. Stuiver PC. Acute schistosomiasis (Katayama fever). BMJ 1984; 288:221-222. 3. Visser LG, Polderman AM, Stuiver PC. Outbreak of schistosomiasis among travelers returning from Mali,West Africa. Clin Infect Dis 1995; 20:280-285. 4. Clarke V dev, Warburton B, Blair DM.The Katayaina Fyndrome: report on an outbreak in Khodesia. Cent Afr J Med 1979; 16: 123-1 26. 5. Nash TE, Cheever AW, Ottesen EA, Cook JA. Schistosonie infections in humans: perspectives and recent findings. NIH conference discussion. Ann Intern Med 1982; 97:740-754. 6. Corachan M, Ruiz L,Valls ME, Gascon J. Schistosomiasis and the Dogon Country (Mali). Am J Trop Med Hyg 1992; 47:b-9. 7. 8. 9. 10. 11. 12. 13. 14. 18. 19. 20. 21. 22. 23. 24. Junghanss T, Weiss N. Akute Schistosomiasis bei Tropenreisenden. Dtsch Med Wochenschr 1992; 117:935-940. Anonymous. Acute schistosomiasis in travelers returning from Africa. Wkly Epideniiol Rec 1990; 65:194-195. Anonyniouc.Acute tchistosomiasis in US travelers returning from Africa. MMWR Morb Mortal Wkly Rec 1990; 39:141-142. Chapman PJ, Wilkinson PR, Davidson RN. Acute schistosoniiasis (Katayama fever) among British air crew. BMJ 1988; 297:llOl. Harries AD, Fryatt K,WalkerJ, et al. Schistosomiasis in expatriates returning to Britain from the tropics: a controlled study Lancet 1986; 317:86-88. Ime GR, Fontaine KE,Tarr J, Hopkins RS. Acute schistosoniiasis among Americans rafting the Onio River, Ethiopia. JAMA 1984; 251:508-510. Nash TE. Antibody response to a polysaccharide antigen present in the schistosome gut. 1. Sensitivity and specificity Am J Trop Med Hyg 1978; 27:939-943. Deelder AM, Kornelis D. Immunodiagnosis of recently acquired Schirfosoma rnanroni infecti0n.a comparison of various immunological techniques.trop Geograph Med 1981 ; 33:36-41. Ridley DS, Hawgood BC.The value of formol-ether concentration of faecal cysts and ova. J Clin Pathol 1956; 9:74-76. Katz N, Chaves A, Pellegrino J. A simple device for quantitative stool thick-smear technique in schistoson~iasis niansoni. KKV lnst MedTrop Sao Paulo 1972; 14:397-400. Lawley TJ, Ottesen EA, Hiatt RA, Gaze LA. Circulating immune complexes in acute schictosotniasit. Clin Exp Immunol 1979; 37:221-227. Evengard B, Manimarstrom L, Smith Cl, Linder E. Early antibody responses in human sch~stosomiasis. Clin Exp Immunol 1990; 80:69-76. Hayunga EG, Mollegard I, Duncan JE et al. Development of circulating antibody antigen assay for rapid detection of acute schistosomiasis. Lancet 1986; 318:716-718. King CH, Mahmoud AAE Drugs five years later: praziquantel.ann Intern Med 1989; 110:290-296. Sabah AA, Fletcher C,Webbe G, Doenhoff MJ. Schistosoma mansoni: chemotherapy of infections of different ages. Exp Parasitol 1986; 61 :294-303. Harries AD, Cook GC. Acute schistosomiasis (Katayama fever): clinical deterioration after chemotherapy. J lnfect 1987; 14~159-161. Anonymous. Case records of the Massachusetts General Hospital: case 21-1985. N Engl J Med 1985; 312:1376-1383. Blanchard TJ, Milne LM, Pollok R, Cook GC. Early chemotherapy of imported neuroschistosomiasis [letter]. Lancet 1993: 341959.