Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-3 (of 3 Records) |
Query Trace: Onyona P [original query] |
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Assessment of submicroscopic infections and gametocyte carriage of Plasmodium falciparum during peak malaria transmission season in a community-based cross-sectional survey in western Kenya, 2012.
Zhou Z , Mitchell RM , Kariuki S , Odero C , Otieno P , Otieno K , Onyona P , Were V , Wiegand RE , Gimnig JE , Walker ED , Desai M , Shi YP . Malar J 2016 15 (1) 421 BACKGROUND: Although malaria control intervention has greatly decreased malaria morbidity and mortality in many African countries, further decline in parasite prevalence has stagnated in western Kenya. In order to assess if malaria transmission reservoir is associated with this stagnation, submicroscopic infection and gametocyte carriage was estimated. Risk factors and associations between malaria control interventions and gametocyte carriage were further investigated in this study. METHODS: A total of 996 dried blood spot samples were used from two strata, all smear-positives (516 samples) and randomly selected smear-negatives (480 samples), from a community cross-sectional survey conducted at peak transmission season in 2012 in Siaya County, western Kenya. Plasmodium falciparum parasite presence and density were determined by stained blood smear and by 18S mRNA transcripts using nucleic acid sequence-based amplification assay (NASBA), gametocyte presence and density were determined by blood smear and by Pfs25 mRNA-NASBA, and gametocyte diversity by Pfg377 mRNA RT-PCR and RT-qPCR. RESULTS: Of the randomly selected smear-negative samples, 69.6 % (334/480) were positive by 18S-NASBA while 18S-NASBA detected 99.6 % (514/516) smear positive samples. Overall, 80.2 % of the weighted population was parasite positive by 18S-NASBA vs 30.6 % by smear diagnosis and 44.0 % of the weighted population was gametocyte positive by Pfs25-NASBA vs 2.6 % by smear diagnosis. Children 5-15 years old were more likely to be parasitaemic and gametocytaemic by NASBA than individuals >15 years old or children <5 years old while gametocyte density decreased with age. Anaemia and self-reported fever within the past 24 h were associated with increased odds of gametocytaemia. Fever was also positively associated with parasite density, but not with gametocyte density. Anti-malarial use within the past 2 weeks decreased the odds of gametocytaemia, but not the odds of parasitaemia. In contrast, recent anti-malarial use was associated with lowered parasite density, but not the gametocyte density. Use of ITNs was associated with lower odds for parasitaemia in part of the study area with a longer history of ITN interventions. In the same part of study area, the odds of having multiple gametocyte alleles were also lower in individuals using ITNs than in those not using ITNs and parasite density was positively associated with gametocyte diversity. CONCLUSION: A large proportion of submicroscopic parasites and gametocytes in western Kenya might contribute to the stagnation in malaria prevalence, suggesting that additional interventions targeting the infectious reservoir are needed. As school aged children and persons with anaemia and fever were major sources for gametocyte reservoir, these groups should be targeted for intervention and prevention to reduce malaria transmission. Anti-malarial use was associated with lower parasite density and odds of gametocytaemia, but not the gametocyte density, indicating a limitation of anti-malarial impact on the transmission reservoir. ITN use had a protective role against parasitaemia and gametocyte diversity in western Kenya. |
In vitro and molecular surveillance for antimalarial drug resistance in Plasmodium falciparum parasites in western Kenya reveals sustained artemisinin sensitivity and increased chloroquine sensitivity.
Lucchi NW , Komino F , Okoth SA , Goldman I , Onyona P , Wiegand RE , Juma E , Shi YP , Barnwell JW , Udhayakumar V , Kariuki S . Antimicrob Agents Chemother 2015 59 (12) 7540-7 Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials including current artemisinin-based combination therapies.An antimalarial drug resistance surveillance study involving 203 P. falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine and artemisinin derivatives (artesunate and dihydroartemisinin), and for drug resistance allele polymorphisms in Pfcrt, Pfmdr-1 and the K13 propeller domain (K13).We observed a significant increase in the proportion of samples with the Pfcrt wild type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (p < 0.0001) and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild type N allele in Pfmdr-1 codon 86 (93.5 %), with only 7 (3.50%) samples with the mutant N86Y allele. Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%) with only 12 (6.38%) specimens with the mutant D1246Y allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean= 0.907+/-0.141). None of the sequenced parasites had mutations in the K13.Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya. |
Increasing Prevalence of a Novel Triple-Mutant Dihydropteroate Synthase Genotype in Plasmodium falciparum in Western Kenya.
Lucchi NW , Okoth SA , Komino F , Onyona P , Goldman IF , Ljolje D , Shi YP , Barnwell JW , Udhayakumar V , Kariuki S . Antimicrob Agents Chemother 2015 59 (7) 3995-4002 The molecular basis of sulfadoxine-pyrimethamine (SP) resistance lies in a combination of single-nucleotide polymorphisms (SNPs) in two genes coding for Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. The continued use of SP for intermittent preventive treatment in pregnant women in many African countries, despite SP's discontinuation as a first-line antimalarial treatment option, due to high levels of drug resistance, may further increase the prevalence of SP-resistant parasites and/or lead to selection of new mutations. An antimalarial drug resistance surveillance study was conducted in western Kenya between 2010 and 2013. A total of 203 clinical samples from children with uncomplicated malaria were genotyped for SNPs associated with SP resistance. The prevalence of the triple mutant Pfdhfr C50 I51R59N: 108I164 and the double mutant Pfdhps S436 G437E540: A581A613 genotypes was high. Two triple mutant Pfdhps genotypes were found: S436 G437E540G: 581A613 and H: 436 G437E540: A581A613, with the latter, thus far, uniquely found in western Kenya. The prevalence of the S436 G: 437 E: 540 G: 581A613 genotype was low. However, a steady increase in the triple Pfdhps H: 436 G: 437 E: 540A581A613 genotype was observed since its appearance in early 2000. These isolates shared substantial microsatellite haplotypes with the most common double mutant allele suggesting that this triple mutant allele may have evolved locally. Overall, these findings show that the triple H: 436 G437E540: A581A613 mutant may be increasing in this population and could compromise the efficacy of SP for IPTp if it increases the resistant threshold further. |
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