HIV-1 infection in young men in northern Thailand.

OBJECTIVES: To determine risk factors for HIV-1 infection in young men in northern Thailand. METHODS: At enrollment into a prospective study, data were collected from a self-administered questionnaire and serologic testing on a cohort of 1115 young men selected by lottery for conscription. RESULTS: The overall HIV-1 infection rate was 6.9%; however, the rate was 15.3% among the 387 (34.7%) men who had been living in the upper north subregion of Thailand compared with 2.5% for the remaining 728 men (P < 0.001). A history of sex with female prostitutes was reported by 74.7% of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease (STD) symptoms (chi 2 for trend, P < 0.001). In stratified and multivariate analyses, however, history of STD symptoms, reported by 42.5% of the cohort, was most strongly associated with HIV-1 infection. Only 42.8% of men who reported sex with prostitutes had used condoms more than half the time. CONCLUSIONS: Young men in the general population in northern Thailand are at high risk for HIV-1 infection via sex with female prostitutes; STD are highly associated with HIV-1 infection. Increasing condom use and controlling STD should be immediate goals of HIV control programs.

PIP: This study sought to determine risk factors for HIV-1 infection in young men in northern Thailand. This cohort of 1115 young men were selected by lottery for conscription and at enrollment into this prospective study, data were collected from a self-administered questionnaire and serologic testing. The overall HIV-1 infection rate was 6.9%; however, the rate was 15.3% among the 387 (34.7%) men who had been living in the upper north subregion of Thailand compared with 2.5% for the remaining 728 men (p 0.001). A history of sex with female prostitutes was reported by 74.7% of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease (STD) symptoms (chi square for trend, p 0.001). In stratified and multivariate analyses, however, history of STD symptoms, reported by 42.5% of the cohort, was most strongly associated with HIV-1 infection. Only 42.8% of men who reported sex with prostitutes had used condoms more than half the time. Young men in the general populations in northern Thailand are at high risk for HIV-2 infection via sex with female prostitutes; STDs are highly associated with HIV-2 infection. Increasing condom use and controlling STD should be immediate goals of HIV control programs.

Incidence of HIV-1 infection among young men in Thailand.

Royal Thai Army (RTA) enlistees were tested for HIV-1 seropositivity prospectively in order to explore their feasibility as a cohort in an HIV-1 preventive vaccine efficacy trial. The 17,615 seronegative enlistees, virtually all 21-year-old men, contributed 10,409 person-years (p-y) of follow-up. Cohorts were enlisted in November 1991 and May 1992 from northern Thailand and Bangkok. The follow-up rate was 50%, with loss to follow-up significantly associated with location of the base, marital status, and educational level. Seroincidence was 0.5/100 p-y for recruits stationed in Bangkok, 1.0/100 p-y in the lower north, and 3.2/100 p-y in the upper north. In a multiple regression model, the young man's birthplace was strongly associated with risk of infection, suggesting that transmission occurred during leave as well as during duty. Incidence rates were significantly lower in those who were married at the time of enlistment and in those with > or = 10 years of education. The seroincidence rates among recruits stationed in the upper north support vaccine trial feasibility, but follow-up rates need to be improved.

Genetic variants of HIV-1 in Thailand.

Serosurveys conducted prior to 1988 indicated a very low level of HIV-1 infection in Thailand, even among high-risk groups. The Ministry of Health has reported a dramatic increase in HIV-1 infection during the last three years. The geographic and demographic distribution of the epidemic is broad, involving multiple provinces and risk groups. Foci of higher incidence and prevalence have been noted in the urban center of Bangkok and in the northern provinces of Chiang Mai and Chiang Rai. Here we report the results of genetic characterization of 16 HIV-1 isolates from Thailand using a combination of polymerase chain reaction (PCR) typing and DNA sequencing. The complete sequence of gp160 (env) of five isolates, partial env sequence of six additional isolates, and the gag gene of two isolates were determined. Two highly distinct HIV-1 variants were found. One variant resembled those prevalent in North America and Europe; five of the isolates were of this type. The remaining eleven isolates were very similar to one another and represented a variant unlike any previously described. Phylogenetic tree analysis of complete env and gag genes placed the two variants on widely separated branches. Protein sequence comparisons indicate both general and specific features that distinguish the Northern Thailand variant both from the Bangkok variant and from virtually all previously sequenced HIV-1 isolates. A simple PCR test for distinguishing the two variants has been developed for use in epidemiologic surveys.

Malaria prophylaxis with proguanil in children living in a malaria-endemic area.

We studied the effects of daily proguanil compared to weekly chloroquine as malaria prophylaxis in 170 children living in a malaria-endemic area along the Thai-Burmese border. Children aged 5-10 years were matched for age, weight, and presence of splenomegaly then randomly assigned to receive either proguanil (equivalent of 200 mg daily adult dose) or chloroquine (equivalent of 300 mg base weekly). All medications were administered by the investigators and malaria smears were performed on a weekly basis. Among 85 children taking proguanil for 524 human-weeks, there were 17 cases of falciparum malaria and 11 cases of vivax. Of 85 children on chloroquine for 537 human-weeks, there were 24 cases of falciparum and 1 case of vivax. There were no statistically significant differences between the two regimens when analyzed either as suppressive or as causal Plasmodium falciparum prophylactics. The data were suggestive that proguanil may have some causal prophylactic effect against falciparum malaria. There were significantly more vivax prophylactic failures (P less than 0.01) in the proguanil group. Side effects were infrequent, mild, and comparable in both groups.

Proguanil-sulphonamide for malaria prophylaxis.

There are few safe, effective chemoprophylactic regimens for preventing Plasmodium falciparum infection in south-east Asia. In two randomized placebo-controlled trials, combinations of proguanil and sulphonamide were tested for chemoprophylactic activity in schoolchildren, aged 6-15 years, living near the Thai-Burmese border. Proguanil at an equivalent adult dose of 200 mg/d was combined with sulphafurazole (= sulfisoxazole) at 25 mg/kg/d or sulphamethoxazole at 25 and 10 mg/kg/d. Combinations of daily proguanil/sulphafurazole and proguanil/sulphamethoxazole were equally effective (greater than 75%) against both falciparum and vivax malaria when the sulphonamide component was used at 25 mg/kg/d. Proguanil and sulphamethoxazole at 10 mg/kg/d was ineffective. Approximately 1% of the children had sulphonamide-related skin rashes which resolved when treatment stopped. Proguanil/sulphonamide is a possible alternative chemoprophylactic regimen in areas with multiple drug-resistant P. falciparum.

Malaria prophylaxis during military operations in Thailand.

Thai soldiers deployed along the Thai-Kampuchean border experience high attack rates of drug-resistant falciparum malaria. Adequate drug prophylaxis has proven difficult with the failure of chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/dapsone. Under some circumstances, mefloquine, doxycycline, and proguanil/sulfamethoxazole can successfully prevent falciparum malaria in Thailand. Decisions regarding chemoprophylaxis drugs in Thailand depend on a complex interaction of effectiveness, compliance, side effects, and long-term usefulness.

Malaria in displaced persons along the Thai-Burmese border.

Malaria epidemiology in displaced Karen ethnic children along the Thai-Burmese (Myanmar) border was observed for 3 years. An active screening process in connection with malaria chemoprophylaxis trials showed a decrease in malaria prevalence over time in children not receiving chemoprophylaxis. The number of malaria cases detected at a primary health care clinic in the same area remained stable.

Prevention of Plasmodium falciparum malaria by Fansimef and Lariam in the northeastern part of Thailand.

Two studies were conduct in Thailand in order to find appropriate falciparum malaria prophylactic drug regimens. The first study was done during June - September 1987 with 363 soldiers who received Fansimef (MSP) 1 tab/week (group 1), 337 soldiers who received MSP 1 tab/2 week (group 2) and 165 soldiers who received chloroquine 300 mg base weekly plus Fansidar 1 tab/week (group 3). At the end of the study there were 9 and 13 falciparum malaria episodes in groups 1 and 2, respectively, with incidence rates of 0.8 and 1.8 cases/100 person-months (P-M). In group 3, the corresponding values were 30 episodes and an incidence of 7.2/100 P-M. For the second study which lasted from October 1987 - January 1988 in the same area, 498 soldiers were given Fansimef 1/2 tab/week (group 4), 499 soldiers were given Lariam 1/2 tab/week (group 5) and 247 soldiers were given chloroquine plus Fansidar (group 6). Thirty malaria episodes were found in group 4, for an incidence of 2.0/100 P-M. In group 5, 23 episodes were found, for an incidence of 1.6/100 P-M. In group 6, 74 episodes occurred, ie an incidence of 12.2/100 P-M. The incidence rates of malaria among Fansimef 1 tab weekly, Fansimef half dose weekly or Lariam half dose weekly were not significantly different but were different from chloroquine plus Fansidar groups. Adverse events in each group were mild.

Malaria prophylaxis with doxycycline in soldiers deployed to the Thai-Kampuchean border.

A battalion of Royal Thai Marine militia was assigned to take either 50 mg or 100 mg of doxycycline daily or pyrimethamine/dapsone weekly for malaria prophylaxis on the Thai-Kampuchean border for a 17 week period. Attack rates for the groups expressed as cases/100 men were 34 for 50 mg doxycycline, 18 for 100 mg doxycycline, and 52 for pyrimethamine/dapsone. The relative efficacy of the two doxycycline regimens compared to Maloprim were 1.6 and 1.4. Compliance with the daily drug nearly equalled that of the weekly regimen. This suggests that 100 mg of doxycycline daily can be effectively used for malaria prophylaxis by soldiers under operational conditions on the Thai-Kampuchean border.

Clinical and microbiological efficacy of a single dose of norfloxacin in the treatment of chancroid.

Forty-one men with a clinically and bacteriologically verified diagnosis of chancroid were given a single dose of 800 mg of norfloxacin and were examined clinically and bacteriologically four, seven and 14 days after treatment. Five patients were excluded from evaluation of efficacy due to concomitant infections or incomplete follow-up. Of the remaining 36 patients, 34 were cured and culture negative at follow-up controls. Another 15 men with culture-negative ulcers treated with 800 mg of norfloxacin as a single dose, were all cured clinically. The high cure rate and the good tolerability make norfloxacin a convenient and cheap alternative to intramuscular single dose therapy of chancroid.

Doxycycline prophylaxis for falciparum malaria.

188 schoolchildren aged 10-15 living in a malaria endemic area along the Thai-Burmese border were matched for age, splenomegaly, and weight and were then randomly assigned to receive either doxycycline (adult equivalent of 100 mg daily) or chloroquine (adult equivalent of 300 mg base weekly). All drugs were administered by the investigators and blood smears were done weekly. In 95 subjects taking doxycycline for 597 man-weeks there were 5 cases of falciparum malaria and in the 93 controls taking chloroquine for 488 man-weeks there were 31. Doxycycline was more effective than chloroquine in the prevention of falciparum malaria infections (p less than 0.0001). The doxycycline group did not have significantly more side-effects than the chloroquine group.

Malaria prophylaxis with proguanil and sulfisoxazole in children living in a malaria endemic area.

The effects of three separate antimalarial prophylactic regimens (proguanil, sulfisoxazole, and proguanil plus sulfisoxazole) and of vitamins in a control group were compared in a study population of 380 children living in a malaria endemic area along the Thai-Burmese border. The subjects, aged 5-16 years, were matched for age, weight, and presence of splenomegaly, then randomly assigned to one of the four groups. All medications were administered daily by the investigators and malaria smears were performed on a weekly basis. Among 99 subjects taking proguanil plus sulfisoxazole for a total of 1464 man-weeks, there was only one case of falciparum and no vivax malaria. Statistically, this regimen proved superior to each of the other groups against both Plasmodium falciparum and P. vivax. The data show that proguanil alone, as a causal or suppressive prophylatic, has poor efficacy against P. falciparum. Side-effects were infrequent and generally mild, except for two subjects whose sulfisoxazole prophylaxis was discontinued because of urticarial rash.

Etiology of urethritis in Thai men.

The etiology of urethritis was determined for 303 Thai men with urethral discharge containing 5 or more polymorphonuclear cells (PMN)/high power field (hpf) and 132 men with a discharge containing less than 5 PMN/hpf. Neisseria gonorrhoeae was isolated significantly more often from men with greater than or equal to 5 PMN/hpf than from men with less than 5 PMN/hpf (42% vs 1%, P less than .0001). Chlamydia trachomatis was also isolated more often from patients with greater than or equal to 5 PMN/hpf than from men with less than 5 PMN/hpf (16% vs 8%, P less than .03). Ureaplasma urealyticum was isolated with nearly equal frequency from both groups of patients (45% vs 37%). Among men with a urethral exudate containing greater than or equal to 5 PMN/hpf, N. gonorrhoeae was isolated as the only pathogen from 19% and in combination with C. trachomatis or U. urealyticum in 23% of these men. C. trachomatis or U. urealyticum, but not N. gonorrhoeae, was isolated from 30%, and no pathogen was isolated from 28% of these men. Among men with urethral exudate containing less than 5 PMN/hpf, N. gonorrhoeae was isolated from only 1%, C. trachomatis or U. urealyticum from 41%, and no pathogen from 58%. These findings suggest that all Thai men with urethral discharge containing greater than or equal to 5 PMN/hpf should be treated for non-gonococcal urethritis and for gonococcal urethritis if gram-negative diplococci are demonstrated on gram stain of the urethral discharge. Men with urethritis with less than 5 PMN/hpf should be treated for only non-gonococcal urethritis.

Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand.

Attenuated Vibrio cholerae oral vaccine CVD 103-HgR was well tolerated by 324 Thai soldiers and civilians. Most received a single 5 x 10(8) cfu dose, while 40 each received one or two 5 x 10(9) cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P less than .001). Increasing the vaccine dose to 5 x 10(9) cfu raised the geometric mean titer (P less than .001). A second 5 x 10(9) cfu dose one week later did not notably increase seroconversions. Likelihood of seroconversion was inversely correlated with baseline vibriocidal titer (P less than .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers less than or equal to 1:40, including 100% of civilians after one 5 x 10(8) cfu dose, 79% of soldiers after one 5 x 10(9) cfu dose, and 45% of soldiers after one 5 x 10(8) cfu dose. In persons with elevated baseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects, other measurements must be used. Study regimens in endemic areas should use a single 5 x 10(9) cfu dose.

Safety, immunogenicity and limited efficacy study of a recombinant Plasmodium falciparum circumsporozoite vaccine in Thai soldiers.

Thai soldiers were vaccinated with a recombinant protein derived from the central repeat region of the circumsporozoite (CS) protein of Plasmodium falciparum conjugated to Toxin A (detoxified) of Pseudomonas aeruginosa (R32Tox-A) to evaluate its safety, immunogenicity and efficacy. In a randomized, double-blind manner, 199 volunteers received either R32Tox-A or a control vaccine at 0, 8 and 16 weeks. Immunization was performed in a malaria non-transmission area, after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection. The vaccine was found to be safe and to elicit antibody responses in all vaccinees. Peak CS antibody (IgG) concentrations in malaria-experienced vaccinees exceeded those in malaria-naive vaccinees (mean 40.6 versus 16.1 micrograms ml-1; p = 0.005) as well as those induced by previous CS protein-derived vaccines and observed in association with natural infections. A log-rank comparison of time to falciparum malaria revealed no differences between vaccinated and non-vaccinated subjects. Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of vaccine (p = 0.06 and p = 0.014, respectively). Because antibody levels had fallen substantially before peak malaria transmission occurred, the question of whether high levels of CS antibody are protective remains to be resolved.

Correlates of HIV-1 seropositivity among young men in Thailand.

Geographic and demographic correlates of risk for HIV-1 seropositivity were studied in 120,216 young men selected by lottery for service in the Royal Thai Army (RTA). The study population consisted of men selected between November 1991 and May 1993. Venous blood was collected at induction, and a brief demographic questionnaire was administered. HIV-1 seropositivity was established by Western blot confirmation of duplicate reactive ELISAs. Geographic variable provided the strongest correlate of risk, clearly distinguishing residents of the upper north, Bangkok, and the central region from the northeast. Overall 12.2% of men from the upper north were HIV-positive. Men who had lived in rural areas were at less risk in most regions of the country, but had equal risk in the upper north. Unmarried men and those with less education were at higher risk throughout the country. These data provide valuable information on the prevalence of HIV infection in one segment of the general population. Continued surveillance of this group will facilitate evaluation of Thailand's response to the epidemic.

PIP: During November 1991 to May 1993, interviews were conducted with and blood samples drawn from 120,216 male military recruits aged 21-29 of the Royal Thai Army (RTA) from every geographic region and social stratum of Thailand. 93.5% were 21 years old. These men are somewhat more representative of the general population than the traditional high risk groups since selection for military service is by lottery and includes all regions of Thailand. The overall HIV seroprevalence was 3.5%. Men from the Upper North region had the highest HIV seroprevalence rate (12.2% vs. 2-4%). This region encompassed the following provinces: Phayao, Chiang Rai, Chiang Mai, Lamphun, Lampang, Phrae, Nan, and Mae Hong Sun. The multivariate analysis of the 97,848 men with a complete set of demographic data and confirmed serostatus (83% of all men inducted) revealed that region of residence was a significant predictor of HIV infection. The odds ratio (OR) of HIV infection among men in the Upper North region was 7.83 (p 0.01). In every region of the country except Upper North, the risk of HIV infection was higher for men from urban areas than those from rural areas (OR = 1.37). In the Upper North region, rural residents were more likely to have HIV infection than urban residents. The higher the man's educational status, the less likely he was to have HIV infection (OR = 0.31 for 13-16 years of education; p 0.01). Risk of HIV infection attributable to age was only significant in unmarried men (OR = 1.76; p 0.01). Thailand has already introduced extensive AIDS education and prevention efforts; they should continue.