MEFAS, a hybrid of artesunate-mefloquine active against asexual stages of Plasmodium vivax in field isolates, inhibits malaria transmission

Penna-Coutinho, Julia; Araújo, Maísa da Silva; Aguiar, Anna Caroline Campos; Sá, Paula M.; Rios, Carlos Tong; Medeiros, Jansen Fernandes; Pereira, Dhélio Batista; Boechat, Núbia; Krettli, Antoniana U.

doi:10.1016/j.ijpddr.2021.09.003

Cited by 3 publications

(3 citation statements)

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“…Data from CQ+TQ treatment should be continue investigated, considering that it is a new drug and because it is included as an option for P. vivax treatment in Brazil. A few studies have PLOS NEGLECTED TROPICAL DISEASES systematically characterized the gametocytocidal or sporontocidal properties of new antimalarial drugs [19,20,49]. The continued malaria transmission at 24 h is maybe due to the metabolism concentration of tafenoquine, since it does not reach a high level as quickly as primaquine; however, due the long half-life of tafenoquine, it probably maintains the concentration in the metabolism for more time.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…The efficacy of antimalarial drugs in blocking transmission, as well potential compounds against P . vivax has been studied in experiments with the anopheline mosquito vector [ 17 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, there are not many studies on gametocytocidal or sporontocidal activity, and because of the lack of reproducible continuous culture methods, there is no in vitro model for assessing gametocytocidal drug activity against P. vivax directly [18]. The efficacy of antimalarial drugs in blocking transmission, as well potential compounds against P. vivax has been studied in experiments with the anopheline mosquito vector [17,19,20].…”

Section: Introductionmentioning

confidence: 99%

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Transmission-blocking activity of antimalarials for Plasmodium vivax malaria in Anopheles darlingi

et al. 2023

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Malaria is caused by parasite of the genus Plasmodium and is still one of the most important infectious diseases in the world. Several biological characteristics of P. vivax contribute to the resilience of this species, including early gametocyte production, both of which lead to efficient malaria transmission to mosquitoes. This study evaluated the impact of currently used drugs on the transmission of P. vivax. Participants received one of the following treatments for malaria: i) chloroquine [10 mg/kg on day 1 and 7.5 mg/kg on day 2 and 3] co-administered with Primaquine [0.5 mg/kg/day for 7 days]; ii) Chloroquine [10 mg/kg on day 1 and 7.5 mg/kg on day 2 and 3] co-administered with one-dose of Tafenoquine [300 mg on day 1]; and iii) Artesunate and Mefloquine [100 mg and 200 mg on day 1, 2 and 3] co-administered with Primaquine [0.5 mg/kg/day for 14 days]. Patient blood was collected before treatment and 4 h, 24 h, 48 h and 72 h after treatment. The blood was used to perform a direct membrane feeding assay (DMFA) using Anopheles darlingi mosquitoes. The results showed 100% inhibition of the mosquito infection after 4 h using ASMQ+PQ, after 24 h for the combination of CQ+PQ and 48 h using CQ+TQ. The density of gametocytes declined over time in all treatment groups, although the decline was more rapid in the ASMQ+PQ group. In conclusion, it was possible to demonstrate the transmission-blocking efficacy of the malaria vivax treatment and that ASMQ+PQ acts faster than the two other treatments.

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Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transmission-blocking activity of antimalarials for Plasmodium vivax malaria in Anopheles darlingi

et al. 2023

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Optimization of Plasmodium vivax infection of colonized Amazonian Anopheles darlingi

Andrade,

Santos,

Bastos

et al. 2023

Sci Rep

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Obtaining Plasmodium vivax sporozoites is essential for in vitro culture of liver stage parasites, not only to understand fundamental aspects of parasite biology, but also for drug and vaccine development. A major impediment to establish high-throughput in vitro P. vivax liver stage assays for drug development is obtaining sufficient numbers of sporozoites. To do so, female anopheline mosquitoes have to be fed on blood from P. vivax-infected patients through an artificial membrane-feeding system, which in turns requires a well-established Anopheles colony. In this study we established conditions to provide a robust supply of P. vivax sporozoites. Adding a combination of serum replacement and antibiotics to the membrane-feeding protocol was found to best improve sporozoite production. A simple centrifugation method appears to be a possible tool for rapidly obtaining purified sporozoites with a minimal loss of yield. However, this method needs to be better defined since sporozoite viability and hepatocyte infection were not evaluated.

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Evaluation of sustainable susceptibility to Plasmodium vivax infection among colonized Anopheles darlingi and Anopheles deaneorum

Santos

Andrade²,

Santos³

et al. 2022

Malar J

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Background The colonization of mosquitoes susceptible to Plasmodium vivax via direct membrane feeding assay (DMFA) has the potential to significantly advance our knowledge of P. vivax biology, vector-parasite interaction and transmission-blocking vaccine research. Anopheles darlingi and Anopheles deaneorum are important vectors of malaria in the Western Brazilian Amazon. Since 2018, well-established colonies of these species have been maintained in order to mass produce mosquitoes destined for P. vivax infection. Plasmodium susceptibility was confirmed when the colonies were established, but susceptibility needs to be maintained for these colonies to remain good models for pathogen transmission. Thus, the susceptibility was assessed of colonized mosquitoes to P. vivax isolates circulating in the Western Amazon. Methods Laboratory-reared mosquitoes from F10-F25 generations were fed on P. vivax blood isolates via DMFA. Susceptibility was determined by prevalence and intensity of infection as represented by oocyst load seven days after blood feeding, and sporozoite load 14 days after blood feeding. The effect of infection on mosquito survival was evaluated from initial blood feeding until sporogonic development and survival rates were compared between mosquitoes fed on infected and uninfected blood. Correlation was calculated between gametocytaemia and prevalence/intensity of infection, and between oocyst and sporozoite load. Results Significant differences were found in prevalence and intensity of infection between species. Anopheles darlingi showed a higher proportion of infected mosquitoes and higher oocyst and sporozoite intensity than An. deaneorum. Survival analysis showed that An. deaneorum survival decreased drastically until 14 days post infection (dpi). Plasmodium vivax infection decreased survival in both species relative to uninfected mosquitoes. No correlation was observed between gametocytaemia and prevalence/intensity of infection, but oocyst and sporozoite load had a moderate to strong correlation. Conclusions Colonized An. darlingi make excellent subjects for modelling pathogen transmission. On the other hand, An. deaneorum could serve as a model for immunity studies due the low susceptibility under current colonized conditions. In the application of DMFA, gametocyte density is not a reliable parameter for predicting mosquito infection by P. vivax, but oocyst intensity should be used to schedule sporozoite experiments.

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MEFAS, a hybrid of artesunate-mefloquine active against asexual stages of Plasmodium vivax in field isolates, inhibits malaria transmission

Cited by 3 publications

References 38 publications

Transmission-blocking activity of antimalarials for Plasmodium vivax malaria in Anopheles darlingi

Transmission-blocking activity of antimalarials for Plasmodium vivax malaria in Anopheles darlingi

Optimization of Plasmodium vivax infection of colonized Amazonian Anopheles darlingi

Evaluation of sustainable susceptibility to Plasmodium vivax infection among colonized Anopheles darlingi and Anopheles deaneorum

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