SummaryIgG extracted from the sera of African adults immune to malaria were injected intravenously into eight Plasmodium falcipamm-infected nonimmune Thai patients. Clinical and parasitological improvement was reproducibly obtained in each case. After the disappearance of the transferred Ig, recrudescent parasites were equally susceptible to the same Ig preparation. High levels of antibodies to most parasite proteins were detected by Western blots in the receivers' sera (taken before transfer) as in the donors' Ig, thus indicating that the difference was qualitative rather than quantitative between donors and receivers. In vitro, the clinically effective Ig had no detectable inhibitory effect on either penetration or intra-erythrocytec development of the parasite. On the contrary, they sometimes increased parasite growth. In contrast, these IgG, as the receivers' Ig collected 4 d after transfer, but not those collected before transfer, proved able to exert an antibodydependent cellular inhibitory (ADCI) effect in cooperation with normal blood monocytes. Results were consistent among the seven isolates studied in vitro, as with the recrudescent parasites. Thus, the results obtained in the ADCI assay correlate closely with clinical and parasitological observations.

Abstract. The factors contributing to anemia in falciparum malaria were characterized in 4,007 prospectively studied patients on the western border of Thailand. Of these, 727 patients (18%) presented with anemia (haematocrit Ͻ 30%), and 1% (55 of 5,253) required blood transfusion. The following were found to be independent risk factors for anemia at admission: age Ͻ 5 years, a palpable spleen, a palpable liver, recrudescent infections, being female, a prolonged history of illness (Ͼ 2 days) before admission, and pure Plasmodium falciparum infections rather than mixed P. falciparum and Plasmodium vivax infections. The mean maximum fractional fall in hematocrit after antimalarial treatment was 14.1% of the baseline value (95% confidence interval [CI], 13.6-14.6). This reduction was significantly greater in young children (aged Ͻ 5 years) and in patients with a prolonged illness, high parasitemia, or delayed parasite clearance. Loss of parasitized erythrocytes accounted for Ͻ 10% of overall red blood cell loss. Hematological recovery was usually complete within 6 weeks, but it was slower in patients who were anemic at admission (adjusted hazards ratio [AHR], 1.9, 95% CI, 1.5-2.3), and those whose infections recrudesced (AHR, 1.2, 95% CI, 1.01-1.5). Half the patients with treatment failure were anemic at 6 weeks compared with 19% of successfully treated patients (relative risk, 2.8, 95% CI, 2.0-3.8). Patients coinfected with P. vivax (16% of the total) were 1.8 (95% CI, 1.2-2.6) times less likely to become anemic and recovered 1.3 (95% CI, 1.0-1.5) times faster than those with P. falciparum only. Anemia is related to drug resistance and treatment failure in uncomplicated malaria. Children aged Ͻ 5 years of age were more likely than older children or adults to become anemic. Coinfection with P. vivax attenuates the anemia of falciparum malaria, presumably by modifying the severity of the infection.

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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 ...

From November 1991 to November 1992 a prospective, descriptive study of malaria epidemiology was conducted in a Karen population on the western border of Thailand. Two study groups were selected at random and more than 80% of the subjects were followed for one year. In Group 1, comprising 249 schoolchildren (aged 4-15 years), daily surveillance for illness was combined with fortnightly malaria surveys. These children experienced 1.5 parasitaemic infections per child-year (95% confidence interval [CI] 1.3-1.7), of which 68% (193/285) were symptomatic (Plasmodium falciparum 84%, P. vivax 57%). The estimated pyrogenic densities were 1460/microL for P. falciparum and 181/microL for P. vivax. In Group 2, comprising subjects of all age from 428 households, malaria was diagnosed during two-monthly surveys, at weekly home visits, and otherwise by passive case detection. Malaria and splenomegaly prevalence rates were low in all age groups (spleen index 2-9%; P. falciparum prevalence rate 1-4%; P. vivax 1-6%). Group 2 subjects had 1.0 infections per person-year (95% CI 0.9-1.1), most of which were symptomatic (312/357; 87%). Malaria infections clustered in households. Overall, P. vivax caused 53% and P. falciparum 37% of the infections (10% were mixed), but whereas P. vivax was most common in young children, with a decline in incidence with increasing age, P. falciparum incidence rates rose with age to a peak incidence between 20 and 29 years, although the risk of developing a severe malaria decreased with increasing age. There was no death from malaria during the study. P. falciparum infections were more common in males, subjects with a history of malaria before the study, and in those who had travelled outside their village. These findings suggest a higher transmission rate for P. vivax than P. falciparum, although adults still suffered symptomatic malaria due to both species. The 2 malaria parasites found in this area contribute approximately 50% of infections each, but their clinical epidemiology is very different.

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Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.