| dc.description.abstract | Children under five years of age and pregnant women remain susceptible to malaria illness, infection and death due to rapid emergence of drug resistance. A robust surveillance system is required to monitor and help contain the drug resistance. This study reports polymorphisms in chloroquine resistant genotypes alongside demographics and parasite characteristics among symptomatic malaria cases in malaria transmission zones, Kenya. One thousand eight hundred and fifteen individuals presenting with uncomplicated malaria at hospitals selected from four malaria epidemic zones in Kenya between 2008 and 2014 were enrolled in a prospective surveillance study assessing the epidemiology of malaria drug resistance patterns. The cases were from lake endemic (n=l 148), highland epidemic (n=563), coast endemic (n=64) and semi-arid seasonal (n=40) zones. Demographic and clinical data/information was collected from each of the individuals and treatment administered in accordance with ministry of health guidelines. Further, 2mL of blood was collected for malaria diagnosis, parasitemia quantification and molecular analyses. DNA extracted from dried blood spots collected from each of the individuals was genotyped for polymorphisms in Plasmodium falciparum chloroquine transporter (Pfcrt 76), Plasmodium falciparum malaria multidrug resistant 1 (P.findr 1 86 and P.findr 1 184) regions that are putative drug resistance genes using both conventional polymerase chain reaction (PCR) and real-time PCR. The molecular and demographic data was analyzed using Stata version 13 while mapping of cases at the selected geographic zones was done in ArcGIS version 10. All the 1815 cases were positive for malaria with parasite densities per micro liter as median 10.420, IQR 9.050-11.456 and range 3.689-14.188. This density varied significantly across the four zones (p=0.0001) with the lake endemic region showing the highest parasitemia at medianl0.763 IQR 9.916-11.640 range 3.689-14.186. Individuals in age group< 5 years had highest parasitemia median 10.609, IQR 9.311-11.639 range 3.689- 13.899 compared to that of 6-15 years and > 16 years age groups (p=0.0001). There was a decline in Pfcrt 76T and P.findrl 86Y mutant genotypes from 61.9% (n=l25) to 5.2% (n=l 7) and 40.1 % (n=81) to 1.3% (n=7) respectively between 2008 and 2014. However, a threefold increase in P.findrl 184F mutant genotype was noted between 2008 and 2014 with frequencies of 13.4% (n=27) to 36.5% (n=191). A carriage of chloroquine resistance (CQR) genotypes across gender revealed an association with chloroquine resistance, by univariate model (P = 0.024) and by multivariate model (p = 0.025), female as reference group in both models. Treatment in the last 6 weeks before enrollment was associated to CQR by multivariate model (P = 0.031, reference; the group with no treatment). There was a significant relationship between travel and chloroquine resistance both by univariate model (p=0.001) and multivariate model (p=0.002), reference- not travelled. The median parasite density was high despite significant regional/zone variability. This observation appears to suggest a trend where cases delay seek treatment hence longer duration of an infection in the cases. Further, gender and travel are significantly associated with chloroquine resistance therefore underscoring role of transport network in introducing spread of resistant genotypes. The overall decline in chloroquine resistance implies that chloroquine could be reconsidered in future for malaria treatment. The increase in Pfmdrl 184F mutant genotype has been associated with increased use of lumefantrine and poses a threat to the sensitivity of lumefantrine and mefloquine. Consistent monitoring of P.findrl 184 genotypes is warranted as in this period of continued implementation of ACTs. | en_US |