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The spread of chloroquine-resistant Plasmodium falciparum malaria has led to increased use of mefloquine prophylaxis by US Peace Corps volunteers in sub-Saharan Africa. We compared long-term mefloquine with other drug regimens for effectiveness and tolerance. The incidence of Plasmodium falciparum infections and of adverse reactions was compared in Peace Corps volunteers who took chloroquine weekly, mefloquine weekly, mefloquine every other week, or weekly chloroquine plus daily proguanil. Weekly mefloquine was 94% more effective than chloroquine (95% CI 86% to 97%), 86% more effective than chloroquine plus proguanil (95% CI 67% to 94%), and 82% more effective than prophylaxis with mefloquine when taken every other week (95% CI 68% to 90%). No serious adverse reactions were observed. Mild adverse events were equally frequent in mefloquine users and chloroquine users, and the frequency of these events declined with increasing duration of prophylaxis. Mefloquine is an effective and well-tolerated drug for prophylaxis of malaria by short-term and long-term travellers.

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Pre-exposure rabies prophylaxis is recommended by the Immunization Practices Advisory Committee of the US Public Health Services (PHS) as a safe and effective method for reducing the risk of rabies in international travellers. The United States Peace Corps provides pre-exposure prophylaxis with human diploid cell rabies vaccine (HDCV) to over 2000 new volunteers each year going to rabies-endemic countries. During the year November 1987 through October 1988, 175 rabies exposures (and no deaths) were documented in Peace Corps Volunteers serving in 31 rabies-endemic countries, for an overall postexposure treatment rate of 43.6/1000 volunteers per year. Although PHS treatment protocols were strictly followed, the postexposure prophylaxis rate for these Peace Corps Volunteers was 550 times higher than that for the US general population, and 55 times higher than the average rate for 30 developing countries. The use of pre-exposure prophylaxis in travellers was not cost-effective and will not become so until the price of a dose of vaccine declines substantially to $7.00 for the Peace Corps, and even lower for groups with less rabies exposure. However, despite the high vaccine cost, pre-exposure prophylaxis continues to be recommended in the Peace Corps for important non-economic reasons which may also be applicable to other groups of travellers.

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A prospective study of US Peace Corps volunteers (PCVs) serving in Zaire, central Africa, was undertaken to determine the risk of human immunodeficiency virus (HIV) and hepatitis B virus infection in an acquired immunodeficiency syndrome-aware expatriate population living in an area of high endemicity for both diseases. Of the 338 PCVs who served in Zaire between October 1985 and May 1988, 282 (83%) were enrolled, representing 7776 volunteer-months of service. Analyses of serum samples for HIV and hepatitis B virus were performed on enrollment and at completion of service. All PCVs received extensive education and counseling regarding HIV and acquired immunodeficiency syndrome throughout their stay in Zaire. There were no documented seroconversions to HIV among 282 PCVs who lived in Zaire for periods ranging from 1 to 81 months, with a mean length of stay of 27.4 months. Of the 14 (6.2%) of 226 PCVs tested who had at least one positive serologic marker for infection with hepatitis B virus, none was documented to have seroconverted during service. During the study period, the rate of all sexually transmitted diseases among PCVs in Africa decreased from 131 to 68 per 1000 study population per year, and there were 52 cases of confirmed malaria among volunteers in Zaire. These data suggest that the risk of acquiring infection with HIV or hepatitis B virus in PCVs in Zaire is very low, and there is no evidence for unusual modes of transmission.

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To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.

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A study was undertaken to determine the incidence of subclinical infection in Peace Corps volunteers (PCVs) maintained on a routine prophylactic immune globulin (IG) regimen. Serum markers to hepatitis A virus (HAV) were detected in 172 of 1,508 (11.4%) single serum samples from a cross-sectional sample of PCVs. Of those tested prior to service, 15/298 (5%) were seropositive for HAV. Those tested at 1-12 months showed 48/417 (11.3%) seropositivity, while 72/529 (13.6%) of those with greater than 12 months of service had antibody to HAV. Only 3/80 (3.8%) of those seropositive PCVs who received their IG injections at least every 6 months were documented to have shown clinical signs of HAV infection during service. This compares to 6/30 (20%) of those who had received irregular prophylaxis (P = 0.01, Fisher's exact test, 2-tailed). Significant numbers of PCVs are subclinically infected with HAV overseas and increasingly develop active immunity with greater length of service.

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Chronic diarrhoea of unknown aetiology is increasingly recognized as a problem in international travellers, and has been reported in US Peace Corps volunteers. In December 1987, we surveyed all Peace Corps medical officers to determine the magnitude of this problem and obtain preliminary data on potential risk factors. A rate of nine cases of chronic diarrhoea per 1000 volunteers per year was reported by medical officers representing 4607 volunteers in 43 countries. The highest rates were reported in Haiti, where one-third of the volunteers reportedly developed chronic diarrhoea during their two-year stay, as well as in Central and West Africa and Nepal. Volunteers were reported to drink unpasteurized milk routinely in eight (42%) of 19 countries with greater than or equal to one case of chronic diarrhoea during the previous two years, but in only two (11%) of 19 countries where none of the volunteers had chronic diarrhoea (odds ratio = 6.2, p = 0.06, Fisher exact test). Intensive prospective studies in areas of high incidence are needed to define this syndrome further.

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Spreading from 2 countries in 1978 to at least 29 in 1988, chloroquine-resistant Plasmodium falciparum malaria has become a significant concern for travelers to Africa. The spread of chloroquine resistance has been documented by sporadic case reports and by isolated population surveys, which do not always completely reflect the risk of infection for travelers using chloroquine prophylaxis. Surveillance of Peace Corps volunteers in West Africa indicates that as of January 1, 1989, P falciparum malaria resistant to chloroquine prophylaxis had spread as far west as Liberia, with only limited risk in Sierra Leone and to the north and west of Sierra Leone. Monitoring the incidence of malaria in highly exposed expatriates provides early warning of the emergence of drug-resistant P falciparum malaria and can provide data to guide recommendations for travelers.

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In 1985, the US Peace Corps developed a computerized epidemiological surveillance system to monitor health trends in over 5500 Peace Corps Volunteers working in development projects in 62 countries worldwide. Data on 31 health conditions and events are collected monthly from each country; quarterly and annual incidence rates are then calculated, and the analysed data are distributed. In 1987, the most commonly reported health problems were diarrhoea (unclassified), 48 cases per 100 volunteers per year; amoebiasis, 24 per 100 volunteers per year; injuries, 20 per 100 volunteers per year; bacterial skin infections, 19 per 100 volunteers per year; and giardiasis 17 per 100 volunteers per year. Tracking each of these common problems, as well as other selected health conditions, guides design of more specific studies and disease control efforts. Health problems with very low rates (less than 1.0/100 volunteers/year) include hepatitis, schistosomiasis, non-falciparum malaria, and filariasis. The epidemiological surveillance system provides the health data needed to plan, implement, and evaluate health programmes for Peace Corps Volunteers, and provides a model for surveillance in other groups of temporary and permanent residents of developing countries.

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Intradermal human diploid cell rabies vaccine (ID HDCV) was licensed for preexposure use in the United States on May 30, 1986. We studied the safety and efficacy of this newly approved route and dose of administration. Serologic results were available from 112 (90%) of the 124 persons who participated in an HDCV low-dose preexposure study in which five different ID, intramuscular (IM), and subcutaneous primary immunization regimens were administered. Three 1.0-mL IM doses of vaccine resulted in titers similar to those from three 0.1-mL ID doses when compared 49 days, one year, and two years after primary immunization. Uniformly high postbooster titers occurred in all five groups when ID boosters were administered at one year or two years. Adverse reactions were similar following both ID and IM vaccination. Although ID HDCV can be a cost-effective substitute for IM vaccine, excessive use of unnecessary preexposure booster doses by any route may be inadvisable because of systemic allergic reactions. In addition, poor immune responses to HDCV have been documented in persons vaccinated in some developing countries. This may limit the use of low-dose regimens in some places.

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Persons immunized in developing countries were recently shown to have low titers after pre-exposure immunization with human diploid cell rabies vaccine (HDCV). An investigation into the response to HDCV boosters was conducted to determine if immunologic sensitization had occurred and if there was a response difference in persons immunized in and outside of the United States. Intramuscular (im) booster doses of vaccine were administered to 113 persons previously immunized outside the United States and 47 persons immunized in the United States. The post-exposure booster regimen of a single 1.0-ml im booster, as recommended by the World Health Organization for all but the most severe bites, produced a one-dilution (5-fold) rise in antibody titer in 14 (11%) of 123 persons tested 5 days after booster and in 56 (89%) of 63 persons studied 7 days after booster. Persons immunized in the United States and those immunized outside the United States had similar responses. Persons with low pre-booster titers were more likely to exhibit a 5-fold rise in antibody titer 5 days after booster (P = 0.03) than persons with higher pre-booster titers. The post-exposure booster regimen of 2 1.0-ml im doses (one each on days 0 and 3), recommended in the United States, produced a more rapid response than the single booster regimen in only some persons; a 5-fold response occurred in 6 (50%) of 12 persons 5 days after booster.(ABSTRACT TRUNCATED AT 250 WORDS)

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Following a routine 0.1 ml booster dose of Merieux rabies human diploid cell vaccine (HDCV), administered intradermally, 23(10.2%) of 226 persons had signs and symptoms compatible with an immune complex-like disease. The disease had its onset from 3-13 days after the injection, lasted 1-5 days, and consisted primarily of urticaria (78.3%), macular rash (65.2%), angiooedema (39.1%), and arthralgia (17.4%). None of the cases were considered severe, and all recovered with no sequelae. There were significant differences in attack rates between men (78.3% of all cases) and women, and between those receiving vaccinations on different days. Similar reactions have been reported following intramuscular booster doses of HDCV. Since the Merieux HDCV is used worldwide, physicians administering HDCV must be aware of these adverse reactions and warn patients. Appropriate therapy should be instituted as warranted by severity of reactions.

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In November 1982, a U.S. Peace Corps volunteer in Kenya completed pre-exposure rabies prophylaxis with a standard 3 dose intradermal (ID) series of human diploid cell rabies vaccine (HDCV). In May 1983, she was bitten by a dog and died of rabies 3 months later. An initial investigation revealed that the patient, as well as 9 of 11 others immunized at the same time, had no rabies antibody titers (less than 1:5). We therefore instituted investigations into the immunogenicity of pre-exposure HDCV both in the United States and in developing countries. A serosurvey revealed unexpectedly low rabies titers in both Peace Corps volunteers and others immunized in developing countries. Antibody titers measured 2-3 weeks after ID immunization were compared in 9 groups totaling 271 persons in the United States and Kenya. There was no statistically significant difference in antibody titers in the 6 U.S. groups immunized from 1980-1984 (P greater than 0.15); however, groups immunized in the United States had significantly higher titers than a group of Kenyan nationals (P less than or equal to 0.0001), and the Kenyans had significantly higher titers than 2 Peace Corps groups immunized in Kenya (P less than or equal to 0.0001). No single hypothesis proposed (laboratory error, vaccine potency, vaccination technique, or specific immune suppression) accounted for the observed differences. Although we cannot fully explain the poor response to HDCV, it is probably due to multiple factors. We conclude that persons immunized with ID pre-exposure HDCV in developing countries should have rabies antibody titers determined to ensure their seroconversion; for persons immunized in the United States, such titers need not be routinely determined.

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From August 22 to November 6, 1981, 989 cases of acute hemorrhagic conjunctivitis were identified in Key West, Florida. The outbreak probably began when an infected 12-year-old Key West resident returned from the Bahamas and transmitted the illness to several neighborhood playmates. The rate of illness was highest for school-aged children, and a high proportion of cases occurred among blacks living in two adjacent low-income housing tracts. A telephone survey of persons living in these two tracts showed that the risk for introduction of illness into a household was 3.8 times greater for families with school-aged children. A study of 100 case households showed that black race, living in the two low-income housing tracts, and having a high ratio of family members per bathroom were variables significantly associated with multiple case households. To limit intracommunity spread of illness, symptomatic children were excluded from school for a period of seven days. The number of reported cases steadily decreased after school exclusion was implemented.

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Most previous reports of Rocky Mountain spotted fever (RMSF) have included cases either not laboratory confirmed or confirmed by relatively weak diagnostic criteria. In the present study detailed epidemiological, clinical, and laboratory features of 262 confirmed or highly probable cases of RMSF reported from six states from 1977 to 1980 were analyzed. This analysis revealed that early clinical diagnosis of RMSF is difficult because the illness may have a gradual or an abrupt onset, the symptoms and signs may be unusual in timing or frequency, and the clinical appearance may vary depending on such factors as age and location of residence. RMSF was diagnosed later in those who died than in survivors, primarily because of atypical initial symptoms and the late onset of rash. RMSF should be considered in any individual who, during the spring and summer, has been in RMSF-endemic areas and develops a fever, regardless of the absence of rash or history of tick exposure.

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Surveillance of Rocky Mountain spotted fever (RMSF) in the United States has revealed a stable incidence of the disease from 1981 to 1983, with a median of 0.48 cases/100,000 population per year (range, 0.42-0.52). During this three-year period an increase in both the number and the percentage of total cases reported from the West South Central states was observed when compared with previous three-year periods. An expanded case report form, which was introduced in 1981 for use by state health departments, was received for 2,850 (87%) of the 3,294 cases reported in 1981-1983. Of these 2850 cases, 1375 (48%) were laboratory confirmed. Death from RMSF was more common in persons greater than or equal to 30 years of age (case-fatality ratio of 8.4%) than in persons less than 30 years (2.2%, P less than .001). Fatality was also associated with failure to obtain a history of a tick bite within 14 days before onset of illness (P less than .05) and with lack of treatment with tetracycline or chloramphenicol (P less than .01).

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Body fluids and brain tissue from rabid human patients have demonstrated only low titers of interferon. Therefore, pharmacokinetic studies of systemically administered and locally injected leukocyte interferon were performed in 2 North American patients with suspected rabies who showed no clinically important side effects of this therapy. Similar therapy was given to 5 patients with symptomatic rabies in Europe and America. Although no prolongation of the clinical course was seen in 3 patients given high-dose intraventricular and systemic therapy, treatment was not initiated until between 8 and 14 days after symptoms were seen. The intraventricular dosage regimen produced cerebrospinal fluid levels that appeared to fall progressively over the 24 hours after injection and demonstrated good but somewhat delayed distribution into the lumbar sac. Titers produced by this therapy were 30- to 10,000-fold higher than those normally observed in this infection, however. In the patients treated at the highest dosage, a diminished and delayed antirabies neutralizing antibody titer was observed, probably a result of the administration of the exogenous interferon.

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In a study to compare the immunogenicity of human diploid cell rabies vaccine (HDCV) given by intramuscular or automatic intradermal jet injection, neither method of administration resulted in antibody levels predicted by previous studies. 49 days after starting a series of three 0.1 ml doses of HDCV given intradermally, 85 volunteers had a geometric mean titre (GMT) of neutralising antibody to rabies of 1:170. 9 concurrent control subjects who received 1.0 ml doses of vaccine intramuscularly had a GMT of only 1:269. Although standard potency testing did not demonstrate that the vaccine used was subpotent , these results strongly suggest that the immunogenicity of HDCV is substantially less than previously reported.

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The increase in the incidence of RMSF observed in the 1970s appears to have plateaued at a median of 0.49 cases/100,000 for the 6-year period 1978-1983. In 1981-1983, for the first time, Oklahoma had the highest incidence of RMSF in the United States (4.10 cases/100,000/year); increased numbers of cases were also reported from two of the other three West South Central states-Texas and Arkansas. Texas, which reported 217 cases in the 3-year period, had an average incidence of 0.47 cases/100,000/year. This apparent regional increase in RMSF activity may reflect multiple factors, including increased recognition and reporting of cases and environmental factors that may be associated with a true increase in RMSF. Simultaneously, a decrease in the number of cases reported and in the incidence of RMSF have been observed in the South Atlantic states, although these states still account for most (51%) of the cases in the United States. The slight decrease in the case-fatality ratio observed over the last 9 years is unexplained. It may reflect increased awareness of RMSF and result in appropriate and timely treatment. The increasing number and percentage of cases that are laboratory confirmed suggest that the more sensitive and specific laboratory tests now required for serologic confirmation are being more widely used and are contributing to an increased accuracy of reporting of RMSF in this country.(ABSTRACT TRUNCATED AT 250 WORDS)

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