19 research outputs found
Predicting Outcome in Malaria: Correlation between Rate of Exposure to Infected Mosquitoes and Level of Plasmodium falciparum Parasitemia
No full textA new primaquine analogue, tafenoquine (WR 238605), for prophylaxis against Plasmodium falciparum malaria
No full textWe tested tafenoquine (WR 238605), a new long-acting 8-aminoquinoline, for its ability to prevent malaria in an area that is holoendemic for Plasmodium falciparum. In a double-blinded, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of 250 mg halofantrine per day for 3 days, to effect clearance of preexisting parasites. The volunteers were then assigned to 1 of 4 drug regimens: placebo throughout; 3 days of 400 mg (base) of tafenoquine per day, followed by placebo weekly; 3 days of 200 mg of tafenoquine per day, followed by 200 mg per week; and 3 days of 400 mg of tafenoquine per day, followed by 400 mg per week. Prophylaxis was continued for up to 13 weeks. Of the evaluable subjects (223 of 249 randomized subjects), volunteers who received 400 mg tafenoquine for only 3 days had a protective efficacy of 68% (95% confidence interval [CI], 53%-79%), as compared with placebo recipients; those who received 200 mg per day for 3 days followed by 200 mg per week had a protective efficacy of 86% (95% CI, 73%-93%); and those who received 400 mg for 3 days followed by 400 mg per week had a protective efficacy of 89% (95% CI, 77%-95%). A similar number of volunteers in the 4 treatment groups reported adverse events. Prophylactic regimens of 200 mg or 400 mg of tafenoquine, taken weekly for less than or equal to 13 weeks, are highly efficacious in preventing falciparum malaria and are well tolerated
Natural antibody responses against the non-repeat-sequence-based B-cell epitopes of the Plasmodium falciparum circumsporozoite protein.
No full textCenters for Disease Control.Division of Parasitic Diseases, National Center for Infectious Diseases. Malaria Branch. Atlanta, Georgia, USA.Centers for Disease Control.Division of Parasitic Diseases, National Center for Infectious Diseases. Malaria Branch. Atlanta, Georgia, USA.Papua New Guinea Institute of Medical Research. Goroka, Papua New GuineaMinistério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Kenya Medical Research Institute. Vector Biology and Control Research Center. Kisumu, Kenya.Centers for Disease Control.Division of Parasitic Diseases, National Center for Infectious Diseases. Malaria Branch. Atlanta, Georgia, USA / Kenya Medical Research Institute. Vector Biology and Control Research Center. Kisumu, Kenya.Centers for Disease Control.Division of Parasitic Diseases, National Center for Infectious Diseases. Malaria Branch. Atlanta, Georgia, USA.Synthetic peptides and human serum or plasma samples from regions of Brazil, Papua New Guinea, and Kenya in which malaria is endemic were used to identify B-cell epitopes localized outside the repeat region of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum. In agreement with recent observations, our results confirm the presence of two non-repeat-region-based B-cell epitopes of the CS protein. Of these two epitopes, only the region I epitope (KPKHKKLKQPGDGNP) was previously shown to be recognized by human sera. In this study, we show that human immune sera from malarious regions recognize another B-cell epitope, ENANANNAV, that resides carboxyl to the repeat region. The present study reveals that (i) the repeat-sequence (NANP)-based B-cell epitope of the CS protein is an immunogenic but not immunodominant epitope; (ii) the natural expression of antibody responses to the two non-repeat-region-based B-cell epitopes of the CS protein varies in different populations in which malaria is endemic; (iii) although the host immune responses to the non-repeat-region-based B-cell epitopes increase as a function of host age, this increase is not statistically significant for the region I epitope but is significant for the other epitope; and (iv) the Th1R T-cell site but not the Th2R or Th3R T-cell site induces an antibody response in the human host. This study confirms the immunogenic potential of non-repeat-region-based B-cell epitopes and suggests that antibody pressures may also contribute to the maintenance of the antigenic diversity of the CS protein
Dehydroepiandrosterone sulfate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya
No full textIn areas where Plasmodium falciparum malaria is endemic, parasite density, morbidity, and mortality decrease with increasing age, which supports the view that years of cumulative exposure are necessary for the expression of maximal protective immunity. Developmental changes in the host also have been implicated in the expression of maximal resistance. To further evaluate the contribution of host developmental factors in malaria resistance, we examined the relationship between P. falciparum parasitemia and pubertal development in a cross-sectional sample of 12 - 18-year-old schoolgirls from an area of intense transmission in western Kenya. Among pubertal girls, dehydroepiandrosterone sulfate (DHEAS) levels were significantly associated with decreased parasite density, even after adjustment for age. DHEAS levels also were related to increased hemoglobin levels, even after accounting for age and other determinants of hemoglobin level. These findings support the hypothesis that host pubertal development, independent of age and, by proxy, cumulative exposure, is necessary for maximal expression of resistance to malarial infection and morbidity, as assessed by hemoglobin leve
Effectiveness of Permethrin-Impregnated Bed Nets and Curtains for Malaria Control in a Holoendemic Area of Western Kenya
No full text
Plasmodium falciparum Gametocytemia in Kenyan Children: Associations among Age, Intensity of Exposure to Transmission, and Prevalence and Density of Subsequent Gametocytemia
No full textFactors affecting use of permethrin-treated bed nets during a randomized controlled trial in western Kenya
No full textAbstract. Adherence with permethrin-treated bed net (ITN) use and their proper deployment was directly observed in 2,178 individuals (784 households) participating in a large-scale trial of ITNs on child mortality in western Kenya. The ITNs were distributed free of charge to ensure high coverage, resulting in a ratio of 1.46 persons per ITN. Approximately 30 % of ITNs present were unused. The overall percentage adherence was 72.3%. The probability of adherence by individuals depended strongly on age (relative risk [RR] 0.86, 95 % confidence limit [CL] − 0.78–0.94), in which children less than five years of age were less likely to use ITNs than older individuals, and temperature, in which ITNs were more likely to be used in periods of cooler weather. A marginally significant diminution in adherence during the second year of the project was also observed (RR 0.83, 95 % CL 0.68–1.01). Mosquito numbers, relative wealth, number of house occupants, and the educational level of the head of the household had no effect on adherence. In unstructured questioning of house residents, excessive heat was often cited as a reason for not deploying the child’s ITN. The most important reason for non-adherence was disruption of sleeping arrangements, indicating that ITNs were not readily redeployed in the face of shifting sleeping patterns due to visitors, funerals, house construction, and other events. Challenges faced by health education programs to maximize adherence with ITN use are discussed
The efficacy of permethrin-treated bed nets on child mortality and morbidity in western Kenya I. Development of infrastructure and description of study site.
No full textRandomized controlled trials in sub-Saharan Africa have shown that permethrin-treated bed nets and curtains reduce all-cause child mortality by 15-33% in areas with low or high but seasonal malaria transmission. This report describes the study site for a community-based, group-randomized, controlled trial in an area of high and year-round malaria transmission in western Kenya. We outline the development of the human and physical infrastructure required to conduct this trial and discuss some of the difficulties encountered and lessons learned in conducting it
Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing
No full textBetween 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onwar
