Malaria prevalence, transmission potential and efficacy of Artemisinin Combination Therapy in the Kenyan Central highlands - a zone previously characterized as malaria free

Abstract

Introduction: Emerging infectious diseases are infections that have recently appeared within a population or those whose incidence or geographic range is rapidly increasing or threatens to increase in the near future. The current study sought to re-evaluate malaria prevalence, susceptibility to ACTs, transmission patterns and the presence of malaria vectors in the Kikuyu area of the Kenyan Central highlands, a non-traditional/ low risk malaria transmission zone where there have been anecdotal reports of malaria cases The potential role of climate factors was also evaluated. The aim of the study was to generate data to inform malaria treatment policy and practice in the study area and country. Methodology: Sampling of adult mosquitoes was carried indoors by manual aspiration and using CDC light traps while mosquito larvae were sampled outdoors using larval dippers and reared to adults in the laboratory. Mosquitoes were identified by morphology and subsequently using PCR and the presence of malaria parasites in field sampled adult mosquitoes investigated using ELISA. The malaria clinical study was an open label nonrandomized clinical trial where the efficacy of one artemisinin-based antimalarial combination drug, Artemether Lumefantrine (AL) was evaluated. Two health facilities Lusigeti and Gikambura were identified for the study. Microscopy was used to identify positive cases at the health facility and nested PCR amplification targeting subunit 18s rRNA gene used to confirm positivity in the lab. P. falciparum isolates were genotyped using nested-PCR of MSP-1 (block 2) and MSP-2 (block 3) family alleles to determine the multiplicity of the infections (MOI) and characterize any subsequent infection. Antimalarial resistance gene markers Pfk13 and Pfmdr1 were analyzed Climate data for the study area was obtained from Climate Engine (http://climateengine.org) and analyzed to understand long term trends. Results: A rich repertoire of mosquito vector species was identified from the area, with the Anopheles funestus group being the predominant vector species and comprising 76.35% of all collections. Only two adult mosquitoes which were non-blood fed and negative for malaria parasites were collected. Of the 838 patients screened, 471, with a slide positivity rate of 2.1% (10) were from Lusigeti and 421, with a slide positivity rate of 7.4% (31) were from Gikambura. Parasitological analysis of microscopy outcome of the 41 cases revealed 100% (95% CI 1.96) as Adequate Clinical and Parasitological Response (ACPR). There was probable delayed parasite clearance (parasites present on Day 3) in 3(7.3%) of the cases, and no severe adverse reaction was observed. Analysis of the Pfk13 gene in the positive P. falciparum cases from the study sites revealed no SNP associated with artemisinin resistance. The pfmdr1 86Y mutation was found in 0% (0/41) of the isolates while the N86 wild allele was detected in 100%(37/37). Analysis of long term climate data showed an increase of about 1.3ºC in both the mean minimum and maximum temperatures consistent with forecasts from other sources. Conclusion: The positivity rate observed in the study site was very low but the fact that 87% of participants who tested positive did not report recent history of travel from the area and the finding of highly competent known vectors of malaria suggest a changing malaria transmission scenario requiring further investigations. That circulating parasite strains showed full sensitivity to the available treatment option indicating the absence of antimalarial drug resistance which is a positive finding.