The effect of oral and parenteral typhoid vaccination on the rate of infection with Salmonella typhi and Salmonella paratyphi A among foreigners in Nepal.

We studied the incidence of enteric fever among travelers and foreign residents who attended an expatriate clinic in Kathmandu, Nepal, from February 1987 to June 1988. There were 42 cases of enteric fever; 20 were caused by Salmonella typhi and 22 by Salmonella paratyphi A. Among 18 unvaccinated foreigners who had enteric fever, S typhi was isolated from 67%, and S paratyphi A from 33%, a ratio similar to the local Nepalese population. Among 22 vaccinated foreigners, S typhi was isolated from 35%, compared with 65% with S paratyphi A. Nine percent of tourists had received the oral Ty21A typhoid vaccine. However, among seven vaccinated tourists who became infected with S typhi, four (57%) had received the oral vaccine. Typhoid vaccine efficacy for tourists was calculated and showed an overall protective rate of 90% against enteric fever in general, 95% protection against S typhi, and 72% to 75% protection against S paratyphi A. We conclude that typhoid vaccine should be recommended to all travelers to the Indian subcontinent, and since S paratyphi A is the predominant cause of enteric fever among vaccinated travelers, consideration should be given to an effective vaccine against S paratyphi A when that becomes available.

An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in Nepal.

An unidentified organism was found in the stools of 55 immunocompetent patients who presented to the CIWEC Clinic in Kathmandu, Nepal between June and November 1989. The microscopic features of the organism share characteristics of both coccidia and cyanobacteria species. From June 26, 1989 to November 17, 1989, 55 persons were identified as having the organism in at least one stool sample. The illness was characterized by prolonged watery diarrhea, anorexia, fatigue, and weight loss. The mean +/- SD duration of illness was 43 +/- 24 days (range 4-107). Thirty-four patients received a total of 78 courses of antimicrobial treatment (2.3 courses/patient). The mean +/- SD duration of illness in 34 treated patients was 46 +/- 24 days. In 14 untreated patients, the mean +/- SD duration of illness was 35 +/- 23 days. The organism is 8.0-9.0 microns in diameter, floats in Sheather's solution, and stains red with the modified acid-fast stain. Since the agent was closely associated with a prolonged, self-limited diarrheal illness, it could easily have been misdiagnosed as Cryptosporidium. The organism should be looked for in the stools of patients with persistent diarrhea and a history of foreign travel.

Chronic diarrhea in the returned traveler.

The persistence of gastrointestinal symptoms after travel to a developing country is one of the most common and troublesome post-travel illnesses. Few data exist to document the extent of this problem, but anecdotal examples abound among travel medicine practitioners, internists, and gastroenterologists. This article presents an approach to the patient with persistent gastrointestinal symptoms after travel.

Enteric fever among Israeli travelers in Nepal: the need for typhoid vaccination.

Enteric fever is still an endemic disease in many developing countries. Most authorities recommend typhoid vaccination for travelers from developed countries to developing countries, particularly in the Indian subcontinent. The Ministry of Health in Israel, however, does not recommend typhoid vaccination to Israeli travelers going to any developing countries. In a study undertaken at a Western-run clinic in Kathmandu, Nepal, we found the rate of typhoid fever infection to be seven times higher among 243 Israeli travelers treated at the clinic for all causes than among 2,866 other Western tourists. The typhoid vaccination rate of the Israeli tourists was 6% compared with 91% for the other Western tourists. We could not detect any differences between the Israeli tourists and the others except for the vaccination status. We conclude that the high rate of enteric fever among Israelis is due to the lack of typhoid vaccination, and we recommend typhoid vaccine for all travelers to the Indian subcontinent.

The causes of death among trekkers in Nepal.

A review of trekking deaths from 1984 to mid-1987 showed a death rate of 15/100,000 trekkers. Altitude sickness deaths accounted for 3/23 (13%) of these deaths. Recently, we followed up on our original study by compiling the number and causes of trekking deaths in Nepal from mid-1987 through 1991. The overall number of deaths was 40, out of 275,950 trekkers (death rate 14/100,000). Illness accounted for 14 deaths, trauma was the cause of 12 deaths, altitude sickness was the cause of 10 deaths, 3 people were found dead after being reported missing, and one person is still missing and presumed dead. Eight out of 10 altitude sickness deaths occurred in organized trekking groups, even though only 40% of trekkers trek in organized groups. Four people were reported to have died from heart attacks, and 3 people died from apparent diabetic ketoacidosis above 4000 meters in altitude. Trekking in Nepal is a relatively safe holiday that currently attracts more than 60,000 people each year. Monitoring the causes of death among trekkers can help generate advice that could make trekking even safer.

Helicopter rescues and deaths among trekkers in Nepal.

Trekking in Nepal is a popular recreational activity that involves approximately 45,000 persons each year. The health risk of trekking in Nepal has never been calculated. We retrospectively studied all helicopter evacuations and deaths among trekkers in Nepal between Jan 1, 1984, and June 30, 1987. A total of 148,000 persons obtained trekking permits during that time. Twenty-three persons died and 111 were rescued by helicopter. The risk of dying while trekking was 15 deaths per 100,000 trekking permits. The frequency of helicopter rescue was 75 per 100,000 trekking permits. The most frequent cause of death was trauma (11 persons), followed by illness (eight persons) and acute mountain sickness (three persons). Deaths occurred equally at all altitudes from 1000 m to over 5000 m, although the number of persons at risk at different altitudes could not be calculated. These data suggest that trekking in Nepal is a relatively safe activity, but a decision to embark on a trek in Nepal should be individualized, with an understanding of the problems related to remoteness, altitude, and illness in the absence of medical facilities.

Pulmonary embolism presenting as high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a recognized risk of rapid ascent to high altitude. Since the recognition of this entity more than 30 years ago, most pulmonary deaths at high altitude have been attributed to HAPE. However, as the bodies can almost never be recovered for postmortem examination, rare diagnoses that appear clinically similar to HAPE will not be recognized. A 33-year-old woman climbing on Mt. Everest, and taking oral contraceptive pills, developed what seemed to be severe HAPE. Examination after she was evacuated from the mountain revealed a deep venous thrombosis in her left leg and multiple pulmonary emboli. We propose that multiple pulmonary emboli at high altitude can mimic HAPE, and fatal pulmonary embolism may be an explanation for some alleged victims of HAPE who died despite what should have been adequate descent.

Suddenly symptomatic brain tumors at altitude.

High-altitude cerebral edema can present with a wide variety of neurologic manifestations; these symptoms resolve with descent. The persistence of neurologic symptoms after descent suggests an intracranial lesion. Brain tumors suddenly becoming symptomatic at altitude have not been reported previously. We report three cases of previously unsuspected brain tumors that suddenly became symptomatic at high altitudes.

Is Blastocystis hominis a cause of diarrhea in travelers? A prospective controlled study in Nepal.

Although the pathogenicity of Blastocystis hominis has been extensively debated in the medical literature, controlled studies of the association between B. hominis and diarrhea are lacking. We conducted a case-control study among expatriates and tourists in Kathmandu, Nepal, in which we compared the prevalence of the organism among patients with diarrhea to that among a control group without diarrhea. B. hominis was detected in 56 (30%) of 189 patients with diarrhea, compared with 40 (36%) of 112 asymptomatic controls. Patients with diarrhea were significantly more likely to have > or = 10 B. hominis organisms per high-power (400x) field than were controls. However, among the 25 patients with this concentration of organisms, other enteric pathogens were detected in 17 (68%). Only 8 (4%) of 189 patients with diarrhea had > or = 10 B. hominis organisms per high-power field detected in the absence of other pathogens, compared with 5 (5%) of 112 asymptomatic controls. Thus, B. hominis in higher concentrations was not associated with diarrhea. There were no specific symptoms associated with B. hominis infection, and the presence of higher concentrations of the organism in stool was not associated with more-severe symptoms. Despite the high prevalence of the organism among travelers and expatriates in Nepal, the results of this study suggest that B. hominis does not cause diarrhea in this population.

Etiology of diarrhea among travelers and foreign residents in Nepal.

A bacterial pathogen was isolated from 47% of 328 expatriate patients with diarrhea seen at two medical clinics in Nepal in 1986. Enterotoxigenic Escherichia coli (24%), Shigella (14%), and Campylobacter species (9%) were isolated most frequently. Enteroinvasive and adherence factor-positive E coli were isolated from 2% and 1% of patients, respectively. Giardia lamblia was detected in 12% of patients, rotavirus in 8%, and Cryptosporidium and Entamoeba histolytica each in 5%. Blastocystis hominis was present in 33% of patients but in only 9% of those who took trimethoprim-sulfamethoxazole. More than one enteropathogen was detected in 17% of patients. Patients with prolonged symptoms (longer than two weeks) were more likely to have Giardia (27%) and less likely to have Shigella (5%) than were patients with acute symptoms. The isolation rates of bacterial pathogens decreased with length of stay in Nepal. A wide variety of enteropathogens were detected in travelers to Nepal, and Shigella and protozoa were particularly important. Length of time abroad and duration of symptoms were important diagnostic considerations.

Pathologic changes in the small bowel in nine patients with diarrhea associated with a coccidia-like body.

OBJECTIVE: To confirm a suspected small-bowel injury in patients with a syndrome of protracted diarrhea associated with a coccidia-like body (CLB). DESIGN: Investigation of an epidemic including a case-control study. SETTING: Outpatient clinic in Kathmandu serving primarily the tourist and expatriate community in Nepal. PATIENTS: Nine patients with diarrhea with at least one stool specimen that was positive for the presence of a CLB and seven noninfected volunteer controls. MEASUREMENTS: Clinical data, microscopic examination of stool, bacteriologic and viral studies on submitted stool specimens, upper gastrointestinal endoscopy including duodenal aspiration and microscopy, small-bowel biopsy with subsequent light and electron microscopy. RESULTS: Endoscopic evidence of inflammation of the distal duodenum was present in five of nine patients with CLB and in none of the seven controls. All nine patients with CLB were noted to have histologic evidence of small-bowel injury, which included acute and chronic inflammation, surface epithelial disarray, and varying degrees of villous atrophy and crypt hyperplasia. One of the seven controls had similar pathologic findings and developed CLB-related diarrhea 5 days later. The other controls had normal distal duodenal histologic results. The organism was found in two of nine duodenal aspirates but was not present in the preserved biopsy specimens as determined by light or electron microscopy. CONCLUSIONS: The pathologic basis of CLB-associated diarrhea appears to be small-bowel injury whose cause remains to be elucidated.

Epidemiology of diarrhoeal illness associated with coccidian-like organism among travellers and foreign residents in Nepal.

A newly described organism called CLB (coccidian-like or cyanobacterium-like body) has been identified in cases of prolonged diarrhoea. To confirm an association of CLB with disease and identify risk factors for transmission, we conducted a case-control study of travellers and foreign residents at two outpatient clinics in Kathmandu, Nepal. Patients without diarrhoea were matched to CLB cases by clinic and date of visit. For comparison, patients with other causes of diarrhoea were also studied. Stools were examined for enteric pathogens with standard microbiological and molecular genetic techniques. CLB was identified in 108 (11%) of 964 individuals with gastrointestinal symptoms compared with only 1 (1%) of 96 symptom-free controls (p = 0.003). 7% of residents in the US Embassy community acquired the infection. The diarrhoeal illness associated with CLB lasted a median of 7 weeks (interquartile range 4-9) compared with 9 days (4-19) for individuals with other causes of diarrhoea (p < 0.0001). The prevalence of other enteric pathogens was no higher among CLB cases than among symptom-free controls. Patients with CLB infection were more likely than controls to report consumption of untreated water (odds ratio 3.98; 95% CI 1.29-13.14); organisms of the same appearance were identified in an epidemiologically implicated water sample. The significant association of CLB with prolonged diarrhoea, and the low rate of other enteropathogens in CLB cases, strongly supports the hypothesis that CLB is a new pathogen. Epidemiological and environmental data suggest that the organism is waterborne.

Epidemiology of diarrhea among expatriate residents living in a highly endemic environment.

OBJECTIVE: To determine the etiology of diarrhea among expatriate residents living in a developing country and identify risk factors for travelers' diarrhea that are difficult to evaluate in tourist populations. DESIGN: Clinic based case-control study. SETTING: Primary care travel medicine clinic in Kathmandu, Nepal. PARTICIPANTS: A total of 69 expatriate residents with diarrhea, compared with 120 tourists with diarrhea, and 112 asymptomatic resident and tourist controls, selected systematically during a 1-year period. MAIN OUTCOME MEASURES: Risk factors for diarrhea assessed by questionnaire and pathogen prevalence assessed by microbiologic analysis of stool specimens. RESULTS: The dominant risk factors for diarrhea among expatriate residents included younger age (P = .003), shorter duration of stay in Nepal (P < .001), and eating out in restaurants (P = .01). Eating raw vegetables, salads, fresh fruit, or ice served in restaurants was not significantly associated with diarrhea. Longer duration of residence was linearly correlated with protection. Enteric pathogens were identified in 44 (64%) of 69 residents with diarrhea compared with 100 (83%) of 120 tourists with diarrhea, with enterotoxigenic Escherichia coli, Campylobacter, and Shigella predominant for both groups. Pathogens were also found in stools from 32 (37%) of 87 asymptomatic resident controls and 13 (52%) of 25 tourist controls. The attack rate of diarrhea among expatriates was estimated to be 49% (95% confidence interval, 37% to 61%) per month during the first 2 years of residence. The highest-risk months were April through July. CONCLUSIONS: Diarrhea among expatriates in a highly endemic environment is a persistent risk. The extremely high prevalence of enteric pathogens among asymptomatic persons reflects widespread exposure. The most important risk factors for travellers' diarrhea are difficult to modify, including younger age, duration of stay, eating in restaurants, and seasonality. Preventive dietary recommendations may not be fully protective, suggesting that pretravel advice should emphasize empiric treatment in addition to strategies to avoid exposure.

Persistent high risk of diarrhea among foreigners in Nepal during the first 2 years of residence.

Although numerous studies have shown that diarrhea is the most common illness occurring during the first few weeks of travel, systematic studies of the incidence of diarrhea during long-term residence in developing countries have not been performed. We conducted a cohort study of the incidence and etiology of diarrhea among 77 expatriate adults who had lived in Nepal for <2 years. Persons were followed prospectively for up to 1 year (mean, 9 months). The incidence of diarrhea during the surveillance period was 3.3 episodes of diarrhea per person per year, or 0.27 episodes per person per month. The annual attack rate of specific pathogens was 42% for enterotoxigenic Escherichia coli, 32% for Cyclospora species, 16% for Giardia lamblia, 16% for Shigella species, 10% for Campylobacter species, > or =10% for rotavirus, and 6% for Entamoeba histolytica. This study suggests that adult persons from developed countries who move to developing countries such as Nepal remain at high risk for diarrhea during their first 2 years of residence.

Prevalence of Cyclospora species and other enteric pathogens among children less than 5 years of age in Nepal.

Stools from 124 Nepalese children aged 6 to 60 months with diarrhea were examined for organisms of the coccidian genus Cyclospora and for other enteric pathogens. Enterotoxigenic Escherichia coli, Giardia Lamblia, Campylobacter species, Cyclospora species, and Cryptosporidium species were the most common pathogens identified. Cyclospora species were detected in none of 74 children < 18 months of age compared with 6 (12%) of 50 children > or = 18 months of age (P = 0.004).

Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and foreign residents in Nepal.

Cyclospora is a coccidian (previously referred to as cyanobacterium-like bodies) that has been implicated in cases of prolonged diarrhoea. The average duration of symptoms is more than three weeks, and no specific treatment has been shown to shorten the illness. A case report suggested that co-trimoxazole may be effective. Expatriate persons with gastrointestinal complaints and cyclospora detected on examination of faeces were recruited from two clinics in Kathmandu, Nepal, between May and August, 1994. Participants were assigned in a randomised, double-blinded manner to receive either cotrimoxazole (160 mg trimethoprim, 800 mg sulphamethoxazole) or placebo tablets twice daily for 7 days. Of 40 patients included in the study, 21 received cotrimoxazole and 19 placebo. There were no significant differences between these two groups in age, sex, time in Nepal, duration or severity of illness, or presence of other enteric pathogens. After 3 days, 71% of patients receiving co-trimoxazole still had cyclospora detected, compared with 100% of patients receiving placebo (p = 0.016). After 7 days, cyclospora was detected in 1 (6%) of 16 patients treated with co-trimoxazole who submitted stool specimens compared with 15 (88%) of 17 patients receiving placebo (p < 0.0001). Eradication of the organism was correlated with clinical improvement. There was no evidence of relapse of infection among treated patients followed for an additional 7 days. Treatment with co-trimoxazole for 7 days was effective in curing cyclospora infection among an expatriate population in Nepal.