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

Abstract

BackgroundAlthough 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.MethodsA 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.ResultsOf 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.ConclusionA 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 transmissio...

Genetic diversity and population structure of Plasmodium falciparum in Kenyan–Ugandan border areas

“…In fact, the parasite genetic diversity increased after ACTs were introduced [12]. Explanations for the persisting high genetic diversity are the increasing number of asymptomatic malaria cases with higher gametocytaemias, vector resistance against pyrethroids which sustain transmission and the removal of antimalarial drug selection pressure following the replacement of the less effective sulphadoxine-pyrimethamine in 2006 by the highly efficacious ACT [8,12,15,16,39,40]. It is also worth noting that the P. falciparum genetic diversity reported here is similar to the genetic diversity of parasite populations from other countries in sub-Saharan Africa [22,41], and it is higher than the genetic diversity of populations from low malaria-endemic settings in the Pacific Region, Southeast Asia and South America [22,[42][43][44][45][46].…”

“…Analyses conducted 5 and 10 years after ITN introduction showed no change in the genetic diversity and population structure of P. falciparum populations from inland Kenya [13,14]. Increasing asymptomatic malaria prevalence with higher gametocytaemias [15], mosquito vector resistance to pyrethroids [16], changing mosquito biting behaviour [17,18] and high gene flow [19][20][21] are some of the prominent factors informing the resilience of P. falciparum genetic variability and population structure.…”

A Cross-Sectional Population Study of Geographic, Age-Specific, and Household Risk Factors for Asymptomatic Plasmodium falciparum Malaria Infection in Western Kenya

“…6 The well-demarcated malaria-epidemiologic zones in Kenya lend themselves to targeted malaria control, 7 but there are challenges about how to deal with > 75% of malaria infections, which are usually asymptomatic. [8][9][10] People who are asymptomatically infected constitute a major source of new infections 11,12 because they are more likely to be bitten by mosquitoes than parasite-free individuals, 13 they are usually not detected or treated, and are often mobile, 10,14 which increases their potential to establish foci of transmission in distant areas. 15 A better understanding of the dynamics of asymptomatic malaria in western Kenya may help design interventions to efficiently target high malaria burden regions.…”

Gametocyte carriage in an era of changing malaria epidemiology: A 19-year analysis of a malaria longitudinal cohort

“…Identifying prognostic indicators of gametocyte carriage is key to the successful implementation of interventions aimed at reducing malaria transmission. Several studies have examined the epidemiology of gametocyte carriage but these have largely been single surveys 14,[16][17][18] or limited to short-term follow up 19,20 . We carried out an analysis of data collected over 19 years of follow-up in a longitudinal cohort established at the Kenyan coast, during a period of changing malaria transmission and changing drug use.…”