Marked variation in MSP-119 antibody responses to malaria in western Kenyan highlands

<p>Abstract</p> <p>Background</p> <p>Assessment of malaria endemicity at different altitudes and transmission intensities, in the era of dwindling vector densities in the highlands, will provide valuable information for malaria control and surveillance. Measurement of serum anti-malarial antibodies is a useful marker of malaria exposure that indicates long-term transmission potential. We studied the serologic evidence of malaria endemicity at two highland sites along a transmission intensity cline. An improved understanding of the micro-geographic variation in malaria exposure in the highland ecosystems will be relevant in planning effective malaria control.</p> <p>Methods</p> <p>Total IgG levels to <it>Plasmodium falciparum </it>MSP-1₁₉were measured in an age-stratified cohort (< 5, 5-14 and ≥ 15 years) in 795 participants from an uphill and valley bottom residents during low and high malaria transmission seasons. Antibody prevalence and level was compared between different localities. Regression analysis was performed to examine the association between antibody prevalence and parasite prevalence. Age-specific MSP-1₁₉seroprevalence data was fitted to a simple reversible catalytic model to investigate the relationship between parasite exposure and age.</p> <p>Results</p> <p>Higher MSP-1₁₉seroprevalence and density were observed in the valley residents than in the uphill dwellers. Adults (> 15 years) recorded high and stable immune response in spite of changing seasons. Lower responses were observed in children (≤ 15 years), which, fluctuated with changing seasons particularly in the valley residents. In the uphill population, annual seroconversion rate (SCR) was 8.3% and reversion rate was 3.0%, with seroprevalence reaching a plateau of 73.3% by age of 20. Contrary, in the valley bottom population, the annual SCR was 35.8% and the annual seroreversion rate was 3.5%, and seroprevalence in the population had reached 91.2% by age 10.</p> <p>Conclusion</p> <p>The study reveals the micro-geographic variation in malaria endemicity in the highland eco-system; this validates the usefulness of sero-epidemiological tools in assessing malaria endemicity in the era of decreasing sensitivity of conventional tools.</p

Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis

<p>Abstract</p> <p>Background</p> <p>Asymptomatic carriers of <it>Plasmodium falciparum </it>serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area.</p> <p>Methods</p> <p>Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of <it>P. falciparum </it>asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell <it>et al </it>(originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions.</p> <p>Results</p> <p>The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention.</p> <p>Conclusions</p> <p>Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.</p

A cohort study of Plasmodium falciparum infection dynamics in Western Kenya Highlands

Abstract Background The Kenyan highlands were malaria-free before the 1910s, but a series of malaria epidemics have occurred in the highlands of western Kenya since the 1980s. Longitudinal studies of the genetic structure, complexity, infection dynamics, and duration of naturally acquired Plasmodium falciparum infections are needed to facilitate a comprehensive understanding of malaria epidemiology in the complex Kenyan highland eco-epidemiological systems where malaria recently expanded, as well as the evaluation of control measures. Methods We followed a cohort of 246 children residing in 3 villages at altitudes 1430 - 1580 m in western Kenya. Monthly parasitological surveys were undertaken for one year, yielding 866 P. falciparum isolates that were analyzed using 10 microsatellite markers. Results Infection complexity and genetic diversity were high (HE = 0.787-0.816), with ≥83% of infections harboring more than one parasite clone. Diversity remained high even during the low malaria transmission season. There was no significant difference between levels of genetic diversity and population structure between high and low transmission seasons. Infection turn-over rate was high, with the average infection duration of single parasite genotypes being 1.11 months, and the longest genotype persistence was 3 months. Conclusions These data demonstrate that despite the relatively recent spread of malaria to the highlands, parasite populations seem to have stabilized with no evidence of bottlenecks between seasons, while the ability of residents to clear or control infections indicates presence of effective anti-plasmodial immune mechanisms

Reduced Risk of Malaria Parasitemia Following Household Screening and Treatment: A Cross-Sectional and Longitudinal Cohort Study

BACKGROUND: In regions of declining malaria transmission, new strategies for control are needed to reduce transmission and achieve elimination. Artemisinin-combination therapy (ACT) is active against immature gametocytes and can reduce the risk of transmission. We sought to determine whether household screening and treatment of infected individuals provides protection against infection for household members. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in two areas in Southern Province, Zambia in 2007 and 2008/2009. To determine the impact of proactive case detection, households were randomly selected either to join a longitudinal cohort, in which participants were repeatedly screened throughout the year and those infected treated with artemether-lumefantrine, or a cross-sectional survey, in which participants were visited only once. Cross-sectional surveys were conducted throughout the year. The prevalence of RDT positivity was compared between the longitudinal and cross-sectional households at baseline and during follow-up using multilevel logistic regression. In the 2007 study area, 174 and 156 participants enrolled in the cross-sectional and longitudinal groups, respectively. In the 2008/2009 study area, 917 and 234 participants enrolled in the cross-sectional and longitudinal groups, respectively. In both study areas, participants and households in the longitudinal and cross-sectional groups were similar on demographic characteristics and prevalence of RDT positivity at baseline (2007: OR = 0.97; 95% CI:0.46, 2.03 | 2008/2009: OR = 1.28; 95% CI:0.44, 3.79). After baseline, the prevalence of RDT positivity was significantly lower in longitudinal compared to cross-sectional households in both study areas (2007: OR = 0.44; 95% CI:0.20, 0.96 | 2008/2009: OR = 0.16; 95% CI:0.05, 0.55). CONCLUSIONS/SIGNIFICANCE: Proactive case detection, consisting of screening household members with an RDT and treating those positive with ACT, can reduce transmission and provide indirect protection to household members. A targeted test and treat strategy could contribute to the elimination of malaria in regions of low transmission

Prevalence and risk factors of malaria among children in southern highland Rwanda

<p>Abstract</p> <p>Background</p> <p>Increased control has produced remarkable reductions of malaria in some parts of sub-Saharan Africa, including Rwanda. In the southern highlands, near the district capital of Butare (altitude, 1,768 m), a combined community-and facility-based survey on <it>Plasmodium </it>infection was conducted early in 2010.</p> <p>Methods</p> <p>A total of 749 children below five years of age were examined including 545 randomly selected from 24 villages, 103 attending the health centre in charge, and 101 at the referral district hospital. Clinical, parasitological, haematological, and socio-economic data were collected.</p> <p>Results</p> <p><it>Plasmodium falciparum </it>infection (mean multiplicity, 2.08) was identified by microscopy and PCR in 11.7% and 16.7%, respectively; 5.5% of the children had malaria. PCR-based <it>P. falciparum </it>prevalence ranged between 0 and 38.5% in the villages, and was 21.4% in the health centre, and 14.9% in the hospital. Independent predictors of infection included increasing age, low mid-upper arm circumference, absence of several household assets, reported recent intake of artemether-lumefantrine, and chloroquine in plasma, measured by ELISA. Self-reported bed net use (58%) reduced infection only in univariate analysis. In the communities, most infections were seemingly asymptomatic but anaemia was observed in 82% and 28% of children with and without parasitaemia, respectively, the effect increasing with parasite density, and significant also for submicroscopic infections.</p> <p>Conclusions</p> <p><it>Plasmodium falciparum </it>infection in the highlands surrounding Butare, Rwanda, is seen in one out of six children under five years of age. The abundance of seemingly asymptomatic infections in the community forms a reservoir for transmission in this epidemic-prone area. Risk factors suggestive of low socio-economic status and insufficient effectiveness of self-reported bed net use refer to areas of improvable intervention.</p

Cost analysis of school-based intermittent screening and treatment of malaria in Kenya

<p>Abstract</p> <p>Background</p> <p>The control of malaria in schools is receiving increasing attention, but there remains currently no consensus as to the optimal intervention strategy. This paper analyses the costs of intermittent screening and treatment (IST) of malaria in schools, implemented as part of a cluster-randomized controlled trial on the Kenyan coast.</p> <p>Methods</p> <p>Financial and economic costs were estimated using an ingredients approach whereby all resources required in the delivery of IST are quantified and valued. Sensitivity analysis was conducted to investigate how programme variation affects costs and to identify potential cost savings in the future implementation of IST.</p> <p>Results</p> <p>The estimated financial cost of IST per child screened is US$6.61 (economic cost US$ 6.24). Key contributors to cost were salary costs (36%) and malaria rapid diagnostic tests (RDT) (22%). Almost half (47%) of the intervention cost comprises redeployment of existing resources including health worker time and use of hospital vehicles. Sensitivity analysis identified changes to intervention delivery that can reduce programme costs by 40%, including use of alternative RDTs and removal of supervised treatment. Cost-effectiveness is also likely to be highly sensitive to the proportion of children found to be RDT-positive.</p> <p>Conclusion</p> <p>In the current context, school-based IST is a relatively expensive malaria intervention, but reducing the complexity of delivery can result in considerable savings in the cost of intervention.</p> <p>(Costs are reported in US$ 2010).</p