Abstract
BackgroundTargeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes.MethodsIn this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts.ResultsInitial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal® completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls.ConclusionsThe results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatments.
Highlights
Targeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control
The transmission blocking activity of the four A. indica extracts and the G. senegalensis extract was investigated in a series of 31 membrane feeding experiments using P. falciparum gametocyte-positive blood from 18 different donors
Gametocyte densities varied among the experimental blood samples from 56 to 1760 sexual forms per microliter of blood; two thirds of the samples (12/18) displayed gametocyte densities between 96 and 416 (Table 1)
Summary
Targeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. An estimated 274 million cases and 1.1 million deaths have been averted and 50 countries with ongoing malaria transmission are on track to reduce the incidence of malaria cases by 75% by 2015 [1]. Since current and prospective international disbursements for malaria control reach not even half of the estimated yearly US$ 5.1 billion required to achieve universal coverage of malaria interventions [1], it is highly uncertain whether the international targets for reducing malaria cases and deaths can be attained in all stricken countries. A recent review of studies conducted in 7 Asian and 21 sub-Saharan African countries unveiled an alarming occurrence of falsified, substandard and degraded antimalarial drugs with about one third of the drug samples tested failing chemical analysis by pharmacopeia standards [2]
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