Drug resistant malaria on the Thai-Myanmar and Thai-Cambodian borders.

We describe the changing epidemiology of drug resistant malaria in Thailand over the past decade. Factors determining the characteristic patterns of the development and spread of resistance to anti-malarial drugs on the Thai-Cambodian border and the Thai-Myanmar border are explored, namely, population dynamics, drug usage and malaria control measures. The introduction of artesunate-mefloquine combination in selected areas along the two borders in 1995 is believed to be one of the multiple factors responsible for stabilizing the multidrug resistance problems in Thailand today. Other control measures and inter-governmental co-operation must continue to be strengthened in order to limit the spread of drug resistance malaria in the Southeast Asian region.

Malaria as a military factor in Southeast Asia.

Malaria remains a major cause of military casualties in Southeast Asia. The numerous conflicts in the region have been greatly affected by malaria. Besides guerrilla warfare, refugees and other civilian movements across international borders contribute heavily to the continuing problem of multiple drug-resistant malaria. Drug resistance is an increasing problem with few available prophylactic options. The malaria threat to any potential deployment of United States military forces remains unsolved.

Proguanil/sulfamethoxazole malaria chemoprophy-laxis on the Thai-Cambodian border.

383 Thai soldiers on the Thai-Cambodian border were entered into a randomized malaria chemoprophylactic trial. Proguanil (200 mg/day) combined with sulfamethoxazole (1000 or 1500 mg/day) were compared to a standard combination of weekly pyrimethamine/dapsone (Maloprim). Men receiving proguanil/sulfamethoxazole had a significantly lower malaria attack rate than those taking pyrimethamine/dapsone. This was true of both the first five-week phase in which 1000 mg of sulfamethoxazole was used (0.11 vs 0.26; p less than 0.001) and in the second ten weeks in which 1500 mg of sulfamethoxazole was used (0.13 vs 0.30; p less than 0.001). Combined relative efficacy indicated that proguanil/sulfamethoxazole was better than pyrimethamine/dapsone by 64% for Plasmodium vivax and by 38% for P. falciparum. Unenforced compliance as measured by returned pills was greater than 86% in both groups. No serious drug side-effects were observed. Proguanil/sulfamethoxazole may represent a useful chemoprophylactic option in areas of multiple drug-resistant malaria.

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.

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 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.

An efficacy trial of doxycycline chemoprophylaxis against leptospirosis.

Because leptospirosis has been an important cause of morbidity in U.S. soldiers training in the Republic of Panama, we conducted a randomized, double-blind, placebo-controlled field trial during the fall of 1982 to determine whether doxycycline was an effective chemoprophylactic agent against this infection. Doxycycline (200 mg) or placebo was administered orally on a weekly basis and at the completion of training to 940 volunteers from two U.S. Army units deployed in Panama for approximately three weeks of jungle training. Twenty cases of leptospirosis occurred in the placebo group (an attack rate of 4.2 per cent), as compared with only one case in the doxycycline group (attack rate, 0.2 per cent, P less than 0.001), yielding an efficacy of 95.0 per cent. This study demonstrated the value of doxycycline as a prophylactic drug against leptospirosis.

Factors relating to transmission of viral hepatitis in a United States military population stationed in Thailand.

To determine the incidence of clinical and inapparent hepatitis in a US military population stationed in Thailand, the authors prospectively studied a cohort of 326 men during one year. Clinical hepatitis A occurred in one man (clinical attack rate = 3.1/1000 men/year), and clinical hepatitis B was found in four men (clinical attack rate = 12.3/1000 men/year). No non-A, non-B hepatitis was identified. There was no serologically identified inapparent hepatitis A but inapparent hepatitis B occurred in 17 men. The apparent/inapparent ratio for hepatitis B was 1:4.25. Serotype analysis suggested that hepatitis B virus largely originated from Thai contacts, although 23% of cases were derived from western sources. To determine the relative contribution of 16 statistically significant (out of 67 studied) behavioral variables to the transmission of HBV, a factor analysis and a multivariate correlation analysis were employed. Factor analysis indicated that social and sexual contact with the indigenous population, including prostitutes, residence within the Thai community and marijuana use were behavioral areas that were associated with the acquisition of hepatitis B. Residence in the Thai community during the first four-month period in Thailand, sexual contact with a prostitute during the third four-month period, and ever having maintained a Thai mistress were found to be significant and independent risk factors by multiple regression analysis.

Children in motor vehicles. Never too young to die.

In a series of 89 children less than 15 years old who were killed as motor vehicle occupants, children under 1 year of age were greatly overrepresented. Only three children were using child restraint systems or seat belts. Eight were traveling on their parents' laps. Head injuries predominated and were most common in the youngest children. Children under age 1 were the most likely to have reached the hospital alive. The high death rate for very young children was not explained by the circumstances of the crashes or by the age distribution of children involved in all crashes.

Transmission of hepatitis B virus to gibbons by exposure to human saliva containing hepatitis B surface antigen.

A pool of whole-mouth saliva collected from five human carriers of hepatitis B surface antigen, subtype adr, was found to contain antigen particles with mean diameters of 23.3 and 41.8 nm as seen by immune electron microscopy. Two gibbons received subcutaneous injections of the pooled saliva and developed serological and, in at least one animal, biochemical evidence of hepatitis B virus infection at 12 and 22 weeks, respectively. Although none of eight other gibbons that were exposed by the nasal or oral routes were infected, the experiment demonstrated that human saliva can serve as a vehicle for the transmission of hepatitis B virus.

Epidemic hepatitis B: a sustained outbreak in a large military population.

A sustained outbreak of viral hepatitis occurred at an Army base in Texas between January 1971 and June 1973. Seven hundred ninety-two admissions but no deaths were recorded in a military population of 35,000. Cases were sporadic, with highest attack rates in low-ranking soldiers with disciplinary problems. Twenty-nine per cent of patients had histories of intravenous drug use within six months prior to hospitalization; most of the rest had close personal contact with jaundiced persons. Of 505 patients tested, 31% were seropositive for hepatitis B antigen (HBSAg) by counterelectrophoresis. Comparison of 38 hepatitis patients (cases) to 34 orthopedic patients (controls) revealed marked differences in rates of exposure to jaundiced persons are shared needles. Sixteen (94%) of 17 antigenemic cases tested were of subtype ayw. Seven (78%) of nine NBSAg-negative cases tested were antibody (anti-HBS) positive three months later.

Hepatitis B antigen in saliva, urine, and stool.

A survey of hepatitis B patients, asymptomatic hepatitis B antigen (HBsAg) carriers, and control subjects was conducted to determine the relationship between antigenemia and antigen excretion in saliva, urine, and stool. Radioimmunoassay was used to detect HBsAg. Specificity-confirmed HBsAg was detected in the saliva of 6 (30%) of 20 antigenemic patients, 1 (5%) of 20 nonantigenemic patients, 14 (34%) of 41 carriers, and 0 of 112 controls. HBsAg was detected in urine only after 100-fold concentration of first-morning specimens. Specificity-confirmed HBsAg was present in the urine of 7 (16%) of 43 carriers; unconfirmed HBsAg was found in the urine of 5 (13%) of 38 patients and 5 (5%) of 112 controls. Unconfirmed HBsAg was detected in concentrated stool specimens from 5 (46%) of 11 patients and 3 of 8 carriers and controls. Longitudinally collected specimens from antigenemic subjects showed no consistent patterns of antigen excretion.