Schistosoma mansoni susceptibility to praziquantel in endemic localities in Kenya
Mwangi, Ibrahim Ndung'u
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Schistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flukes of the genus Schistosoma transmitted through freshwater snails. While the disease affects as many as 249 million people worldwide, treatment largely relies on a single drug, praziquantel (PZQ), which is extremely effective against all schistosome species known to infect humans, it is well-tolerated in the body, making it suitable for mass treatment campaigns. The near exclusive use of this drug for such a prevalent disease has led to concerns regarding the potential for drug resistance to arise and the effect this would have on affected populations. The aim of this study was to investigate if S. mansoni susceptibility to PZQ is altered following repeated treatments. In this study, a modified in vitro technique by Liang et al., was used to determine the effect of PZQ on miracidia. This was achieved by hatching of miracidia from eggs obtained from fecal samples of infected individuals, subjecting the miracidia to varying concentrations of PZQ and observation of viability (dead or alive) of miracidia under a dissection microscope. Similarly, the generation of a lab strain with reduced susceptibility was achieved in vivo whereby the parasite was subjected to sub-lethal doses of PZQ and gradually increased over five generations until the parasites could withstand a normally lethal dose. A total of 72 isolates of S. mansoni from infected individuals with a history of multiple treatments with PZQ were analysed for PZQ sensitivity in the in-vitro. Similarly, 38 isolates of S. mansoni from field-collected Biomphalaria snails were analysed. The overall miracidial mortality of S. mansoni at a concentration of 10-5 M PZQ for the entire study population was between 82.1-84.6 %, with the lowest observed value being 72.7% (P >0.05%).In general, results of the present study found no evidence for the presence of such strains in the cohort of adults and children living in endemic areas of western and central Kenya who have undergone recent or historical treatment with PZQ and did not harbor S. mansoni with reduced PZQ susceptibility. However, under experimental conditions, a strain with reduced susceptibility to PZQ was produced within only 5 generations (P < 0.05%). The likelihood of this happening in the field is real, if sufficient PZQ pressure is applied. The threat of PZQ resistance remains a great public health concern in Kenya especially with intensified use of PZQ for schistosomiasis control and elimination. Regular monitoring of PZQ sensitivity in schistosomes is therefore needed in control programs for early detection of changes in parasite sensitivity to the drug.