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 ...
Following a marked decline in the efficacy in vivo of mefloquine between 1990 and 1994, a combination of artesunate (4 mg/kg/d for 3 d) and mefloquine (25 mg/kg) has been used as first line treatment of uncomplicated falciparum malaria in camps for displaced persons located along the north-western border of Thailand. Antimalarial drug susceptibility of fresh isolates of Plasmodium falciparum from this population was evaluated using a radioisotope microdilution assay between 1995 and 1999. In total, 268 isolates were collected, of which 189 were from primary infections and 79 from recrudescent infections. The geometric mean 50% inhibitory concentration (IC50) values from primary infections were: dihydroartemisinin 1.2 ng/mL, artesunate 1.6 ng/mL, artemether 4.8 ng/mL, atovaquone 0.4 ng/mL, lumefantrine 32 ng/mL, chloroquine 149 ng/mL, quinine 354 ng/mL, mefloquine 27 ng/mL and halofantrine 4.1 ng/mL. A significant positive correlation was found between the susceptibility in vitro to artesunate and quinine (r = 0.43, P < 0.001), mefloquine (r = 0.46, P < 0.001), and halofantrine (r = 0.51, P < 0.001). These levels of resistance in vitro are among the highest reported and confirm continuing high level multidrug resistance in this area. Despite intensive use of the combination between 1995 and 1999 there has been a significant improvement in mefloquine sensitivity (P < 0.001) and artesunate sensitivity (P < 0.001). This supports observations in vivo that the combination of artesunate and mefloquine has reversed the previous decline in mefloquine sensitivity.
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