Plasmodium vivax threatens almost 40% of the world's population, resulting in 132-391 million clinical infections each year. Most of these cases originate from Southeast Asia and the Western Pacific, although a significant number also occurs in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact, and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates, the parasite's ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies.

Abstract. The factors affecting the development of patent Plasmodium falciparum gametocytemia were assessed in 5,682 patients entered prospectively into a series of antimalarial drug trials conducted in an area of low and seasonal transmission on the western border of Thailand. Of the 4,565 patients with admission thick smear assessments, 110 (2.4%) had gametocytemia. During the follow-up period 170 (3%) of all patients developed patent gametocytemia, which in 89% had developed by day 14 following treatment. In a multiple logistic regression model five factors were found to be independent risk factors at presentation for the development or persistence of gametocytemia during follow up; patent gametocytemia on admission (adjusted odds ratio [AOR] ϭ 7.8, 95% confidence interval [CI] ϭ 3.7-16, P Ͻ 0.001), anemia (hematocrit Ͻ30%) (AOR ϭ 3.9, 95% CI ϭ 2.3-6.5, P Ͻ 0.001), no coincident P. vivax malaria (AOR ϭ 3.5, 95% CI ϭ 1.04-11.5, P Ͻ 0.04), presentation with a recrudescent infection (AOR ϭ 2.3, 95% CI ϭ 1.3-4.1, P Ͻ 0.004), and a history of illness longer than two days (AOR ϭ 3.3, 95% CI ϭ 1.7-6.6, P Ͻ 0.001). Patients whose infections responded slowly to treatment or recrudesced subsequently were also more likely to carry gametocytes than those who responded rapidly or were cured (relative risks ϭ 1.9, 95% CI ϭ 1.3-2.7 and 2.8, 95% CI ϭ 2.0-4.0, respectively; P Ͻ 0.001). These data provide further evidence of important epidemiologic interactions between P. falciparum and P. vivax, and drug resistance and transmission potential.The life cycle of Plasmodium falciparum is dependent upon the production of viable sexual stages of the parasite and their appearance in sufficient numbers in the peripheral blood of the human host. These gametocytes can then be transmitted to a feeding anopheline mosquito and on to a new human host, thus completing the life cycle of the malaria parasite. In contrast to the treatment of the three other species of human malaria, most of the antimalarial drugs used to treat the asexual stages of P. falciparum malaria have little or no effects on the viability of mature gametocytes. The rate of production of gametocytes is influenced considerably by host factors, notably immunity, 1 and this may have significant epidemiologic consequences. Integrated malaria control programs that aim to reduce malaria transmission are often based on identifying those individuals most likely to transmit malaria. We investigated the factors that influence the production of gametocytes following uncomplicated falciparum malaria in an area where there is a high prevalence of multidrug resistance, and a relatively low level of transmission and consequent background immunity. METHODSStudy site. The study took place between 1990 and 1995 in patients living in a camp for displaced person of the Karen ethnic minority situated in an area of malarious hill forest on the western border of Thailand. During the five-year period, a series of 18 antimalarial drug studies were conducted to determine the optimum treatment of ...

The Malaria Eradication Research Agenda (malERA) Consultative Group on Drugs present a research and development agenda to ensure that appropriate drugs are available for use in malaria eradication.

Abstract. In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826 patients, and mefloquine alone was used in 1,303 patients. The combined regimens of mefloquine plus an artemisinin derivative were associated with more side effects than those with an artemisinin derivative alone; acute nausea (31% versus 16%), vomiting (24% versus 11%), anorexia (51% versus 34%), and dizziness (47% versus 15%) (P Ͻ 0.001). Oral artesunate and artemether alone were very well tolerated. There was no difference in the incidence of possible adverse effects between the two drugs, and no evidence that either derivative caused allergic reactions, neurologic or psychiatric reactions, or cardiovascular or dermatologic toxicity. Blackwater fever occurred in three patients treated with mefloquine plus artesunate regimens. Oral artesunate and artemether are safe and well tolerated antimalarial drugs.

The pharmacokinetic properties of mefloquine in malaria were relatively unaffected by demographic variables (other than body weight) or disease severity. If it is assumed that apparent clearance and volume of distribution are unaffected by dose regimen, then splitting the 25 mg/kg mefloquine dose improves oral bioavailability and the therapeutic response in the treatment of acute falciparum malaria.