Mefloquine chemoprophylaxis of soldiers on the Thai-Cambodian border.

Chemoprophylaxis of malaria on the Thai-Cambodian border is difficult due to the high level of drug resistance. Thirteen separate companies of Royal Thai Marine Militia were placed on 250 mg weekly mefloquine chemoprophylaxis from August 1989 to January 1990. A mean number of 722 soldiers received two or more doses of mefloquine per month for the five month study. The medication was well tolerated and compliance averaged 91%. Substantial numbers of prophylaxis breakthroughs were seen which resulted in 3.2 cases of malaria/100 man-months. Sixty-eight falciparum malaria cases were documented in men who had taken at least two mefloquine doses in the previous four weeks. No serious neuropsychiatric reactions occurred. Mefloquine chemoprophylaxis failures exist on the Thai-Cambodian border and are one sign of the spread of mefloquine resistance.     

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.     

Amebiasis at an evacuation site on the Thai-Cambodian border

Symptomatic intestinal amebiasis was highly endemic among the Cambodians living at Green Hill, an evacuation site on the Thai-Cambodian border between June 1987 through May 1989. Monthly incidence rates of intestinal amebiasis were determined to be inversely proportional to cumulative monthly rainfall. The highest incidence of amebic dysentery was 63/1000 in children 12-23 months old. Behavioral risk factors were investigated by conducting a case-control study. A questionnaire was administered to 73 families, each having at least one member with confirmed intestinal amebiasis within the past 3 months, and to 95 randomly selected control families having no individual with diarrhea for at least 3 months. Individuals from families with greater than 4 members were at higher risk for acquiring intestinal amebiasis. No significant differences in behavioral risk factors were identified between case and control families. Eighty-six percent of 51 water samples drawn from wells where amebiasis patients obtained their drinking water had greater than 10 coliforms/100 ml. The main route of transmission of E. histolytica was not identified, but was most likely via the fecal-oral route.     

Underweight schoolchildren in a rural school near the Thai-Cambodian border

We report on the high prevalence of underweight children in a rural primary school near the Thai-Cambodian border. Ninety-five children were studied: anthropometric data were recorded and studied for their correlation with semester examination scores; 63.2% of the children (60 cases) were underweight; in addition, BMI appeared to be significantly correlated to the semester examination scores. Our findings also revealed problems of nutrition and sanitation among the schoolchildren. In conclusion, schoolchildren in rural areas should be considered a priority in the national health and nutrition promotion programs.     

Experimental studies of the potentiation of proguanil and pyrimethamine by dapsone using Plasmodium berghei in white mice.

An accurate system with stringent criteria has been established to test antimalarial drugs and drug combinations against Plasmodium berghei in mice. Minimum effective doses for a number of antimalarial drugs have been determined when used in this system. Considerable potentiation of the activity of pyrimethamine and to a somewhat less extent of proguanil by dapsone has been demonstrated. The need to extend studies of these combinations to the parasites of human malaria is discussed in terms of establishing a safe chemoprophylactic regime in the presence of drug-resistant strains of parasites.     

Malaria chemoprophylaxis with chloroquine in young Nigerian children. III. Its effect on nutrition

The nutrition of a group of Nigerian children who received weekly chemoprophylaxis with chloroquine during their first one or two years of life was compared with the nutrition of a group of children exposed frequently to malaria. Fewer episodes of severe malnutrition and fewer deaths from malnutrition occurred among protected than among control children. Protected children tended to be taller and heavier than control children and to have a larger mid-upper arm circumference. Mean serum albumin and pre-albumin levels were higher in protected than in control children. However differences between the two groups were small and only in a few instances were they statistically significant.     

Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens.

As international travel becomes increasingly common and resistance to antimalarial drugs escalates, a growing number of travelers are at risk for contracting malaria. Parasite resistance to chloroquine and proguanil and real or perceived intolerance among patients to standard prophylactic agents such as mefloquine have highlighted the need for new antimalarial drugs. Promising new regimens include atovaquone and proguanil, in combination; primaquine; and a related 8-aminoquinoline, tafenoquine. These agents are active against the liver stage of the malaria parasite and therefore can be discontinued shortly after the traveler leaves an area where malaria is endemic, which encourages adherence to the treatment regimen. Part 1 of this series reviews currently recommended chemoprophylactic drug regimens, and part 2 will focus on 8-aminoquinoline drugs.     

Malaria chemoprophylaxis with chloroquine in young Nigerian children. IV. Its effect on haematological measurements

Haematological measurements were made in 198 Nigerian children aged three months to two years who received weekly malaria chemoprophylaxis with chloroquine from shortly after birth until the age of one or two years and in 185 age-matched control children. Children protected against malaria had a higher mean haemoglobin level and a higher packed cell volume than control children, and they showed fewer abnormalities of their red cells. Total and differential white blood cell counts, mean plasma folate and mean serum ferritin concentrations were similar in both groups of children. However, the geometric mean red cell folate level of children exposed to malaria was significantly higher than the mean level of control children; and it may be that malaria raises the red cell folate through intracellular synthesis by malaria parasites. Children with malaria parasitaemia had a significantly lower haemoglobin and packed cell volume and a significantly higher geometric mean red cell folate and ferritin level than children without parasitaemia. Serum ferritin is probably an unreliable index of iron status in children with malaria.     

Malaria chemoprophylaxis with chloroquine in young Nigerian children. II. Effect on the immune response to vaccination

The immune response of 198 young Nigerian children protected against malaria by chemoprophylaxis with chloroquine to immunization with triple, poliomyelitis, measles, typhoid, meningococcal and BCG vaccines was compared with the immune response to vaccination of 185 control children. Good responses to triple, measles and BCG vaccines were shown by children in both groups; poorer responses were obtained to poliomyelitis, typhoid and meningococcal vaccines. The response to immunization of protected children was similar to that observed among control children for all the vaccines tested except for meningococcal polysaccharide vaccine. Protected children showed a significantly greater antibody response to both group A and group C meningococcal polysaccharides than control children. This finding supports the results of previous studies which have shown that the immune response to meningococcal polysaccharide vaccines is adversely affected both by acute malaria and by asymptomatic malaria parasitaemia.     

A successful supervised outpatient short-course tuberculosis treatment program in an open refugee camp on the Thai-Cambodian border

The operation of a tuberculosis treatment program in an open refugee camp of 45,000 refugees on the Thai-Cambodian border is described. Fifty-eight patients received 6 months of supervised daily, outpatient therapy with a protocol employing isoniazid, rifampin, streptomycin, and pyrazinamide. Patient compliance was high, with only 15 of 10,209 patient days being missed, despite a high incidence of minor side effects. Three patients died, 4 defaulted, and 1 moved to another camp for treatment. The therapies of 4 patients were extended because of the need for reduced doses of medications, the development of extrapulmonary disease, treatment failure, and slow resolution of infiltrates on radiographs. There was 1 late relapse. This report demonstrates the feasibility in integrating short-course therapies with program designs to produce high compliance under difficult field conditions.     

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.     

Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that may be available in the future.

All current regimens of malaria chemoprophylaxis have serious drawbacks as a result of either suboptimal efficacy, difficulty with medication compliance, or adverse events. Two 8-aminoquinolines may be approaching registration, with primaquine having completed its prophylactic field testing and tafenoquine having begun advanced field testing at the end of 2000. Primaquine has long been used for management of relapses of malaria, but in the past decade, it has been reexamined for use in malaria prevention in order to stop infection in the liver. In field trials performed in Indonesia and Colombia, the efficacy of primaquine for malaria prevention was approximately 90%, compared with that of placebo. Because of its short half-life, primaquine requires daily administration. For adults, the prevention regimen is 30 mg base daily (0.5 mg base/kg/day), and it can probably be discontinued soon after departure from an area where malaria is endemic. To kill parasites that already exist in the liver, terminal prophylaxis is given after exposure to relapses of malaria infection; for adults, such prophylaxis usually consists of 15 mg base (0.3 mg base/kg/day) given daily for 2 weeks. Primaquine-induced gastrointestinal disturbances can be minimized if the drug is taken with food. Neither primaquine nor tafenoquine should be given to persons with glucose-6-phosphate dehydrogenase deficiency, to avoid the development of potentially severe drug-induced hemolysis. Tafenoquine is an analogue of primaquine that is more potent than the parent drug. Field trials in Kenya, Ghana, Gabon, and Southeast Asia have demonstrated an efficacy rate of approximately 90% for tafenoquine. Its long half-life allows for infrequent dosing (currently tested at 200 mg base/week), and its effect on parasites at the liver stage may allow for drug discontinuation at the time of departure from the area of endemicity.     

Malaria chemoprophylaxis with chloroquine in young Nigerian children. I. Its effect on mortality, morbidity and the prevalence of malaria

One hundred and ninety-eight Nigerian children who received weekly chemoprophylaxis with chloroquine from shortly after birth until the age of one year or two years and 185 age-matched controls were studied. Chemoprophylaxis with chloroquine was partially, but not completely, effective in controlling malaria. Clinical malaria was documented significantly less frequently in protected children than in control children, and only 9% of random blood films obtained from protected children were positive for Plasmodium falciparum while 41% of random blood films from control children were positive for this parasite. Mean malaria antibody levels were lower in protected than in control children; for ELISA and precipitin antibodies the difference between the two groups was less marked at two years than at one year. Mortality was similar among protected and among control children. No rebound mortality or morbidity was observed after chemoprophylaxis was stopped.     

Malaria infection among the migrant population along the Thai-Myanmar border area

A population based case-control study was performed to determine factors associated with malaria infection among the migrant population, foreign nationals aged 15 years or over. Data were obtained from 217 malaria and 217 non-malaria patients attending the Vector-Borne Disease Control Units 6-9 (Thong Pha Phum and Sangkhla Buri districts) in Kanchanaburi Province and at the Vector-Borne Disease Control Units 1,9 (Mae Fa Luang and Mae Sai districts) in Chiang Rai Province, between June and December 2002. All study subjects were interviewed by trained interviewers using a structured interview form. The statistical analysis was carried out by the chi-square test and multivariate logistic regression: a p-value of less than 0.05 was considered to be statistically significant. The results showed that the study subjects were predominantly Thai-Yai and Myanmar. Plasmodium falciparum was the major type of the malaria (60.8%). Logistic regression analysis, controlling for possible confounding factors, revealed that residence located in the forest increased the risk of malaria infection by a factor of 6.29 (OR = 6.29, 95% CI = 1.56-25.42); outdoor stay < 7 and > 7 days prior to the blood examination also increased the risk by a factor of 4.34 and 4.13 respectively (OR = 4.34, 95% CI = 1.05-17.99; OR = 4.13, 95% CI = 1.29-13.13).     

Malaria morbidity among the nonimmune foreigners in the city of Maputo and the problem of chemoprophylaxis

In a colony with nonimmune foreigners in Maputo city (Mozambique People's Republic) active detection and treatment of patients suffering from malaria has been carried out for 1.5 years. It was shown that even in a city with some hyper- and mesoendemic regions where less than 10% of colony members were treated with chemoprophylaxis, yearly morbidity among them did not surpass 20-30 cases per 1000 population. Such index is considered to be admissible risk for health if adequate diagnosis and treatment of infection is available. Despite predominance of drug-resistant strains of tropical malaria agents among the local population, resistance to chlorochin or phancidar was observed in 3 foreign patients out of 31. In one case the clinical pattern of infection was atypical.     

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.     

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.