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FREP1 in mosquito midguts facilitates Plasmodium falciparum parasite transmission. The fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among Anopheles species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of Plasmodium berghei and Plasmodium vivax to Anopheles gambiae and Anopheles dirus, respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P. berghei to A. gambiae without triggering immunopathology. Anti-FBG serum also reduced >81% of P. falciparum infection to A. gambiae. Finally, we showed that FBG interacts with Plasmodium gametocytes and ookinetes, revealing the molecular mechanism of its antibody transmission-blocking activity. Collectively, our data support that FREP1-mediated Plasmodium transmission to mosquitoes is a conserved pathway and that targeting the FBG domain of FREP1 will limit the transmission of multiple Plasmodium species to multiple Anopheles species.

Background The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. Methods Plasmodium falciparum ( Pf ) and Plasmodium vivax ( Pv ) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv _18S rRNA genes or the multi-copy targets Pf _varATS and Pv _mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. Results In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf _18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_ varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv _18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum , at 8.0% (66/828). Use of Pv _mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. Conclusion The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.

Background A mixed methods study was conducted to look at the magnitude of residual malaria transmission (RMT) and factors contributing to low (

Basic science holds enormous power for revealing the biological mechanisms of disease and, in turn, paving the way toward new, effective interventions. Recognizing this power, the 2011 Research Agenda for Malaria Eradication included key priorities in fundamental research that, if attained, could help accelerate progress toward disease elimination and eradication. The Malaria Eradication Research Agenda (malERA) Consultative Panel on Basic Science and Enabling Technologies reviewed the progress, continuing challenges, and major opportunities for future research. The recommendations come from a literature of published and unpublished materials and the deliberations of the malERA Refresh Consultative Panel. These areas span multiple aspects of the Plasmodium life cycle in both the human host and the Anopheles vector and include critical, unanswered questions about parasite transmission, human infection in the liver, asexual-stage biology, and malaria persistence. We believe an integrated approach encompassing human immunology, parasitology, and entomology, and harnessing new and emerging biomedical technologies offers the best path toward addressing these questions and, ultimately, lowering the worldwide burden of malaria., Dyann F. Wirth and colleagues propose a research agenda for basic science and enabling technologies in malaria elimination and eradication.

Indirect clinical measures assessing anti-malarial drug transmission-blocking activity in falciparum malaria include measurement of the duration of gametocytaemia, the rate of gametocyte clearance or the area under the gametocytaemia-time curve (AUC). These may provide useful comparative information, but they underestimate dose-response relationships for transmission-blocking activity. Following 8-aminoquinoline administration P. falciparum gametocytes are sterilized within hours, whereas clearance from blood takes days. Gametocytaemia AUC and clearance times are determined predominantly by the more numerous female gametocytes, which are generally less drug sensitive than the minority male gametocytes, whereas transmission-blocking activity and thus infectivity is determined by the more sensitive male forms. In choosing doses of transmission-blocking drugs there is no substitute yet for mosquito-feeding studies.