Immune response to Plasmodium vivax has a potential to reduce malaria severity.

Plasmodium falciparum infection causes transient immunosuppression during the parasitaemic stage. However, the immune response during simultaneous infections with both P. vivax and P. falciparum has been investigated rarely. In particular, it is not clear whether the host's immune response to malaria will be different when infected with a single or mixed malaria species. Phenotypes of T cells from mixed P. vivax-P. falciparum (PV-PF) infection were characterized by flow cytometry, and anti-malarial antibodies in the plasma were determined by an enzyme-linked immunosorbent assay. We found the percentage of CD3+delta2+-T cell receptor (TCR) T cells in the acute-mixed PV-PF infection and single P. vivax infection three times higher than in the single P. falciparum infection. This implied that P. vivax might lead to the host immune response to the production of effector T killer cells. During the parasitaemic stage, the mixed PV-PF infection had the highest number of plasma antibodies against both P. vivax and P. falciparum. Interestingly, plasma from the group of single P. vivax or P. falciparum malaria infections had both anti-P. vivax and anti-P. falciparum antibodies. In addition, antigenic cross-reactivity of P. vivax or P. falciparum resulting in antibodies against both malaria species was shown in the supernatant of lymphocyte cultures cross-stimulated with either antigen of P. vivax or P. falciparum. The role of delta2 +/- TCR T cells and the antibodies against both species during acute mixed malaria infection could have an impact on the immunity to malaria infection.

Determining cost-effectiveness and cost component of three malaria diagnostic models being used in remote non-microscope areas.

This cross-sectional experimental study developed a methodology to analyze the cost-effectiveness of three malaria diagnostic models: microscopy; on-site OptiMAL; and on-site Immunochromatographic Test (on-site ICT), used in remote non-microscope areas in Thailand, from both a public provider and patient perspective. The study covered six areas in two highly malaria-endemic areas of provinces located along the Thai-Myanmar border. The study was conducted between April and October 2000, by purposively recruiting 436 malaria suspected cases attending mobile malaria clinics. Each patient was randomly selected to receive service via the three diagnostic models; their accuracy was 95.17%, 94.48% and 89.04%, respectively. In addition, their true positive rates for all malaria species were 76.19%, 82.61% and 73.83%; for falciparum malaria 85.71%, 80.95% and 80.00%, and for vivax malaria 57.14%, 100% and 50%, respectively, with the parasitemia ranging from 80 to 58,240 microl of blood. Consequently, their costs were determined by dividing into provider and consumer costs, which were consequently classified into internal and external costs. The internal costs were the costs of the public providers, whereas the external costs were those incurred by the patients. The aggregate costs of these three models were 58,500.35, 36,685.91, and 40,714.01 Baht, respectively, or 339.53, 234.39, and 243.93, in terms of unit costs per actual case. In the case of microscopy, if all suspected malaria cases incurred forgone opportunity costs of waiting for treatment, the aggregate cost and unit cost per actual case were up to 188,110.89 and 944.03 Baht, respectively. Accordingly, the cost-effectiveness for all malaria species, using their true positive rates as the effectiveness indicator, was 446.75, 282.40, and 343.56 respectively, whereas for falciparum malaria it was 394.80, 289.37 and 304.91, and for vivax malaria 595.67, 234.39 and 487.86, respectively. This study revealed that the on-site OptiMAL was the most cost-effective. It could be used to supplement or even replace microscopy for this criteria in general. This study would be of benefit to malaria control program policy makers to consider using RDT technology to supplement microscopy in remote non-microscope areas.

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 rapid diagnostic devices: performance characteristics of the ParaSight F device determined in a multisite field study.

Microscopic detection of parasites has been the reference standard for malaria diagnosis for decades. However, difficulty in maintaining required technical skills and infrastructure has spurred the development of several nonmicroscopic malaria rapid diagnostic devices based on the detection of malaria parasite antigen in whole blood. The ParaSight F test is one such device. It detects the presence of Plasmodium falciparum-specific histidine-rich protein 2 by using an antigen-capture immunochromatographic strip format. The present study was conducted at outpatient malaria clinics in Iquitos, Peru, and Maesod, Thailand. Duplicate, blinded, expert microscopy was employed as the reference standard for evaluating device performance. Of 2,988 eligible patients, microscopy showed that 547 (18%) had P. falciparum, 658 (22%) had P. vivax, 2 (0.07%) had P. malariae, and 1,750 (59%) were negative for Plasmodium. Mixed infections (P. falciparum and P. vivax) were identified in 31 patients (1%). The overall sensitivity of ParaSight F for P. falciparum was 95%. When stratified by magnitude of parasitemia (no. of asexual parasites per microliter of whole blood), sensitivities were 83% (>0 to 500 parasites/microl), 87% (501 to 1,000/microl), 98% (1,001 to 5,000/microl), and 98% (>5,000/microl). Device specificity was 86%.

Antimalarial drug combination policy: a caveat.

PIP: This paper presents facts on malaria epidemiology and historical perspectives of antimalarial drug use in Thailand. It also suggests that the use of an artesunate-mefloquine combination for treating falciparum malaria may be one of the factors responsible for the success of the country's control strategies. It is noted that in Thailand Plasmodium falciparum has evolved resistance to chloroquine, sulfadoxine-pyrimethamine, and mefloquine in succession. In view of this, administration of oral artesunate plus mefloquine became the standard treatment for microscopically confirmed uncomplicated falciparum malaria in 1995. The regimen requires administration of 300 mg/day of artesunate for 2 days plus 750 mg mefloquine on the first day, followed by 500 mg on the second day. Overall, it is too early to assume that the addition of artesunate has halted the progression of mefloquine resistance in Thailand. In terms of applicability of the regimen worldwide, the complexity of the factors involved makes it impossible to predict the useful lifespan of the artesunate-mefloquine combination on the Thai-Myanmar border. Further research is needed into the determination and validation of the most suitable antimalarial regimens for each epidemiologically distinct area and each operationally different circumstance.^ieng

Application of log-linear models to malaria patients in Thailand.

Malaria is a common infectious disease in many tropical countries, including Thailand. The country is located geographically in a tropical zone and the transmission of malaria is particularly common in some regions, for instance in Tak province. The objective of this study is to identify risk factors causing malaria in Tak province in the rainy season by using log-linear models. Tests of independence are used (chi-square and Cramer's V-value tests) to find out the relationships between any two variables. In addition two- and three-dimensional log-linear models are used to obtain estimated parameters and expected frequencies for these models. Amongst the models fitted, the best are chosen based on the analysis of deviance. The results of this study show that most observed variables are significantly related with p-values<0.05. Causes of migration and reasons for staying overnight are highly related to personal variables. Thus, it can be concluded that two of the risk factors for malaria are causes of migration and reasons for staying overnight. Knowledge of prevention is also related to personal variables. Therefore, knowledge of prevention was concluded to be a risk factor affecting prevalence of malaria. For each set of three variables, the best model shows interaction terms of variables that have a relationship but there are no interactions of three effects in these best models.

Investigations of incidence of pretreatment, drug sensitivity in vitro, and plasma levels of pyrimethamine in patients with multidrug resistant falciparum malaria following the three combination regimens of artemether/pyrimethamine.

The study was carried out to investigate the status of in vitro susceptibility of Plasmodium falciparum to pyrimethamine (PYR) in multidrug resistant area of the Thai-Myanmar border, the incidence of unregulated use of the combination of PYR with sulfadoxine (Fansidar) in this area and the relevance of pharmacodynamic and pharmacokinetic factors in determining the treatment outcome from the three combination regimens of ART/PYR (1-, 2- and 3-day regimens), in patients with acute uncomplicated falciparum malaria. The majority of patients had baseline PYR concentrations in the range of 1-100 (50.6%) or 100-500 (34.8%) ng/ml, while concentrations of more than 500 ng/ml were found in only 1.1%. All of the isolates exhibited high grade resistance to PYR with the minimum inhibition concentration (MIC) of as high as 10(-5) M. No association was observed between treatment outcome and the presence of baseline plasma PYR concentrations. In addition, lack of association between plasma concentrations during the acute phase (day-1 and -2) and treatment outcome was found.

Compliance with a 2 day course of artemether-mefloquine in an area of highly multi-drug resistant Plasmodium falciparum malaria.

AIMS: Multi-drug resistant Plasmodium falciparum malaria is a rapidly increasing problem in the world, particularly Thailand. Practical antimalarial regimens which are highly effective against multi-drug resistant parasites with short-term course of administration are needed. In this study, we assessed the patient compliance of a short course regimen using artemether-mefloquine. METHODS: Clinical effectiveness (efficacy, tolerability and patient compliance) of a 2-day regimen of artemether-mefloquine was evaluated in 126 patients with acute uncomplicated falciparum malaria who were attending the two malaria clinics in an area of highly multi-drug resistant P. falciparum malaria (Thai-Myanmar border). Patients were treated with a single oral dose of 300 mg artemether on the day of attendance. Two additional doses of mefloquine were given for home treatment on the following day (750 and 500 mg after breakfast and lunch, respectively). RESULTS: The combination regimen was effective, with a cure rate of 92.6%. Based upon the concentrations of whole blood mefloquine on day-2, compliance for this 2 day regimen of artemether-mefloquine was 98.1% (full compliance 86.8%, partial compliance 11.3%, non-compliance 1.9%). CONCLUSIONS: We conclude that the 2 day regimen of artemether-mefloquine is, at present, a good alternative regimen for the treatment of uncomplicated multi-drug resistant falciparum malaria.

A comparative study of artesunate and artemether in combination with mefloquine on multidrug resistant falciparum malaria in eastern Thailand.

Plasmodium falciparum in Thailand is highly resistant to chloroquine, sulfadoxine-pyrimethamine and there is increasing resistance to quinine and mefloquine. The use of qinghaosu derivatives alone or in combination with mefloquine has been shown successfully effective against multidrug resistant P. falciparum in many clinical trials. However their applications with ambulatory treatment should be assessed. 394 uncomplicated falciparum malaria cases studied at Trat and Chanthaburi malaria clinics, eastern Thailand, were allocated at random to receive either one of the seven following regimens: A) artesunate 600 mg over 2 days and mefloquine 1,250 mg in divided doses. B) artemether 640 mg over 2 days and mefloquine 1,250 mg in divided doses. C) artesunate alone 700 mg over 5 days period. D) artemether alone 800 mg over 5 days period. E) quinine plus tetracycline for 7 days. F) mefloquine 1,250 mg in divided doses and G) artesunate 600 mg over 2 days period and mefloquine 750 mg. The follow-up was on Days 1, 2, 7, 14, 21 and 28. Patients tolerated all regimens very well and there was no serious side effects. The adverse effects did not differ among the seven regimens. The cure rates were 98.7, 97.1, 97.9, 96.7, 92.3, 100 and 95.2%, respectively. There was no significant difference of cure rates among various regimens. A total of 16 P. vivax and 1 P. malariae reinfections were reported among the study groups during the second half of the follow-up period, 14 of which were from the groups administered short action drugs (artesunate, artemether or quinine). The results suggested that either artesunate 600 mg or artemether 640 mg in combination with mefloquine 1,250 mg over a period of two days should be considered as alternative regimens for treating uncomplicated multi-drug resistant falciparum malaria.

Epidemiology of Malaria in Thailand.

Background: In spite of significant achievements in malaria control in the past two decades, about 150,000 malaria cases still occur in Thailand each year. Although most short-term visitors to Thailand stay in malaria-free areas, an increasing number of more adventurous travelers are exposed to the disease. Method: Since 1987, the Malaria Division of the Thai Ministry of Public Health has maintained a computerized database that includes all malaria cases recorded at malaria clinics, government health institutions, and private hospitals nationwide. In this article, we analyze the 1992 data. Results: The provinces of Trad, Tak, and Kanchanaburi had the highest incidence of locally transmitted cases. Trad Province was also responsible for the highest number of imported cases. The highest incidence rate was found to be 426.5 per 1000 persons per year in a group of villages in Maesod District, Tak Province. Districts and provinces with >= 20 cases per 1000 persons per year are listed in this report. Peak transmission seasons and species prevalence of different endemic areas are described. Analysis of case investigation, a part of this database, indirectly supported the presence of mefloquine resistant Plasmodium falciparum strains on the Thai-Cambodian border. Conclusions: This paper describes the characteristics of malaria in different parts of Thailand and pinpoints areas with significant transmission. However, in accordance with the present policy of the Thai national malaria control program, we do not recommend chemoprophylaxis, but we do strongly encourage personal protection, early diagnosis, and prompt treatment. (J Travel Med 2:59-65, 1995)

In vivo study of the response of Plasmodium falciparum to standard mefloquine/sulfadoxine/pyrimethamine (MSP) treatment among gem miners returning from Cambodia.

An in vivo study of the response of P. falciparum to the combination drug, MSP, was conducted among gem miners who contracted malaria from Cambodia in 1991-1992. High level resistance (RII, RIII responses) was observed in 22.5% of the 40 cases attending Mae Sot malaria clinic, west Thailand border, and in 28.1% of the 96 cases attending Bo Rai malaria clinic, east Thailand border. The observations on in vitro studies conducted prior to the MSP treatment and after recrudescence, together with the findings on adequate mefloquine blood levels strongly indicated the serious deterioration of mefloquine efficacy. The first line treatment for the malaria control program needs to be revised and the use of qinghaosu derivatives considered. Intensive measures to combat spreading of the highly resistant strains to other parts of the country should be taken into account.