Long-Lasting Insecticidal Nets Incorporating Piperonyl Butoxide Reduce the Risk of Malaria in Children in Western Kenya: A Cluster Randomized Controlled Trial

Malaria vectors have acquired an enzyme that metabolizes pyrethroids. To tackle this problem, we evaluated long-lasting insecticidal nets incorporating piperonyl butoxide (PBO-LLINs) with a community-based cluster randomized control trial in western Kenya. The primary endpoints were anopheline density and Plasmodium falciparum polymerase chain reaction (PCR)-positive prevalence (PCRpfPR) of children aged 7 months to 10 years. Four clusters were randomly selected for each of the treatment and control arms (eight clusters in total) from 12 clusters, and PBO-LLINs and standard LLINs were distributed in February 2011 to 982 and 1,028 houses for treatment and control arms, respectively. Entomological surveys targeted 20 houses in each cluster, and epidemiological surveys targeted 150 children. Cluster-level permutation tests evaluated the effectiveness using the fitted values from individual level regression models adjusted for baseline. Bootstrapping estimated 95% confidence intervals (CIs). The medians of anophelines per house were 1.4 (interquartile range [IQR]: 2.3) and 3.4 (IQR: 3.7) in the intervention and control arms after 3 months, and 0.4 (IQR: 0.2) and 1.6 (IQR: 0.5) after 10 months, respectively. The differences were –2.5 (95% CI: –6.4 to –0.6) and –1.3 (95% CI: –2.0 to –0.7), respectively. The datasets of 861 and 775 children were analyzed in two epidemiological surveys. The median PCRpfPRs were 25% (IQR: 11%) in the intervention arm and 52% (IQR: 11%) in the control arm after 5 months and 33% (IQR: 11%) and 45% (IQR: 5%) after 12 months. The PCRpfPR ratios were 0.67 (95% CI: 0.38, 0.91) and 0.74 (95% CI: 0.53, 0.90), respectively. We confirmed the superiority of PBO-LLINs

A preliminary study on designing a cluster randomized control trial of two new mosquito nets to prevent malaria parasite infection

Background: Although long-lasting insecticidal nets (LLINs) are the most effective tool for preventing malaria parasite transmission, the nets have some limitations. For example, the increase of LLIN use has induced the rapid expansion of mosquito insecticide resistance.More than two persons often share one net, which increases the infection risk. To overcome these problems, two new mosquito nets were developed, one incorporating piperonyl butoxide and another covering ceilings and open eaves. We designed a cluster randomized controlled trial (cRCT) to evaluate these nets based on the information provided in the present preliminary study. Results: Nearly 75% of the anopheline population in the study area in western Kenya was Anopheles gambiae s. l., and the remaining was Anopheles funestus s. l. More female anophelines were recorded in the western part of the study area. The number of anophelines increased with rainfall. We planned to have 80% power to detect a 50% reduction in female anophelines between the control group and each intervention group. The between-cluster coefficient of variance was 0.192. As the number of clusters was limited to 4 due to the size of the study area, the estimated cluster size was 7 spray catches with an alpha of 0.05. Of 1619 children tested, 626 (48%) were Plasmodium falciparum positive using a rapid diagnostic test (RDT). The prevalence was higher in the northwestern part of the study area. The number of children who slept under bed nets was 929 (71%). The P. falciparum RDT-positive prevalence (RDTpfPR) of net users was 45%, and that of non-users was 55% (OR 0.73; 95% CI 0.56, 0.95). Using 45% RDTpfPR of net users, we expected each intervention to reduce prevalence by 50%. The intracluster correlation coefficient was 0.053. With 80% power and an alpha of 0.05, the estimated cluster size was 116 children. Based on the distribution of children, we modified the boundaries of the clusters and established 300-m buffer zones along the boundaries to minimize a spillover effect. Conclusions: The cRCT study design is feasible.As the number of clusters is limited, we will apply a two-stage procedure with the baseline data to evaluate each intervention

Longitudinal survey of Plasmodium falciparum infection in Vietnam: characteristics of antimalarial resistance and their associated factors.

Plasmodium falciparum is the main cause of human malaria and is one of the important pathogens causing high rates of morbidity and mortality. The total number of malaria patients in Vietnam has gradually decreased over the last decade. However, the spread of pathogens with drug resistance remains a significant problem. Defining the trend in genotypes related to drug resistance is essential for the control of malaria in Vietnam. We undertook a longitudinal survey of Plasmodium falciparum malaria in 2001, 2002, and 2005 to 2007. The pfcrt, pfmdr1, pfdhfr, and pfdhps genes were analyzed by sequencing; and correlations by study year, age, gender, and genotype were identified statistically. The ratio of the chloroquine resistance genotype pfcrt 76T was found to have decreased rapidly after 2002. High numbers of mutations in the pfdhfr and pfdhps genes were observed only in 2001 and 2002, while the emergence of parasites with a new K540Y mutation in the P. falciparum dihydropteroate synthetase (PfDHPS) was observed in 2002. For males and those in younger age brackets, a correlation between vulnerability to P. falciparum infection and strains with pfcrt 76K or strains with decreased numbers of mutations in pfdhfr and pfdhps was demonstrated. The parasites with pfcrt 76T exhibited a greater number of mutations in pfdhfr and pfdhps

Novel Mutations in K13 Propeller Gene of Artemisinin-Resistant Plasmodium falciparum

We looked for mutations in the Plasmodium falciparum K13 propeller gene of an artemisinin-resistant parasite on islands in Lake Victoria, Kenya, where transmission in 2012-2013 was high. The 4 new types of nonsynonymous, and 5 of synonymous, mutations we detected among 539 samples analyzed provide clues to understanding artemis- inin-resistant parasites

Plasmodium falciparum: Differential Selection of Drug Resistance Alleles in Contiguous Urban and Peri-Urban Areas of Brazzaville, Republic of Congo

The African continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. We studied the impact of the degree of urbanization on the population genetics of Plasmodium falciparum in urban and peri-urban areas in and around the city of Brazzaville, Republic of Congo. This field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows the characterization of malaria parasites from areas where the human, parasite, and mosquito populations are shared, but where differences in the degree of urbanization (leading to dramatic differences in transmission intensity) cause the pattern of malaria transmission to differ greatly. We have investigated how these differences in transmission intensity affect parasite genetic diversity, including the amount of genetic polymorphism in each area, the degree of linkage disequilibrium within the populations, and the prevalence and frequency of drug resistance markers. To determine parasite population structure, heterozygosity and linkage disequilibrium, we typed eight microsatellite markers and performed haplotype analysis of the msp1 gene by PCR. Mutations known to be associated with resistance to the antimalarial drugs chloroquine and pyrimethamine were determined by sequencing the relevant portions of the crt and dhfr genes, respectively. We found that parasite genetic diversity was comparable between the two sites, with high levels of polymorphism being maintained in both areas despite dramatic differences in transmission intensity. Crucially, we found that the frequencies of genetic markers of drug resistance against pyrimethamine and chloroquine differed significantly between the sites, indicative of differing selection pressures in the two areas

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京都大学0048新制・課程博士博士(医学)甲第13731号医博第3246号新制||医||968(附属図書館)UT51-2008-C648京都大学大学院医学研究科内科系専攻(主査)教授 松岡 雅雄, 教授 光山 正雄, 教授 松田 文彦学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Evidence of infection with Leptospira interrogans and spotted fever group rickettsiae among rodents in an urban area of Osaka City, Japan

We examined 33 rodents captured in an urban area of Osaka City, Japan for IgG antibodies against Seoul virus, severe fever with thrombocytopenia syndrome virus, hepatitis E virus, Leptospira interrogans, Yersinia pestis, spotted fever, typhus and scrub typhus group rickettsiae. We found that 3 (9.1%) and 1 (3.0%) of the 33 rodents had antibodies against L. interrogans and spotted fever group rickettsiae, respectively. DNAs of leptospires were detected from 2 of the 3 seropositive rodents, but DNA of rickettsia was not detected. Phylogenetic analysis and multiple locus sequence typing revealed that the 2 leptospires were L. interrogans belonging to a novel sequence type. There is a potential risk for acquiring rodent-borne zoonotic pathogens even in cities in developed countries