Infection of Laboratory-Colonized Anopheles darlingi Mosquitoes by Plasmodium vivax

Moreno, Marta; Tong, Carlos; Guzmán, Mitchel; Chuquiyauri, Raúl; Llanos-Cuentas, Alejandro; Rodríguez, Hugo; Gamboa, Dionicia; Meister, Stephan; Winzeler, Elizabeth A.; Maguina, Paula; Conn, Jan E.; Vinetz, Joseph M.

doi:10.4269/ajtmh.13-0708

Cited by 52 publications

(78 citation statements)

References 25 publications

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“…albimanus ). Although we observed variability in infectivity, the numbers of observed oocysts were in line with those found with live SMFAs in disease endemic countries (Bharti et al, 2006; Zollner et al, 2006; Basseri et al, 2008; Joshi et al, 2009; Bahia et al, 2011; Solarte et al, 2011; Rios-Velásquez et al, 2013; Mathias et al, 2014; Moreno et al, 2014; Vera et al, 2015). …”

supporting

confidence: 90%

Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates

Shaw-Saliba

Clarke

Santos

et al. 2016

International Journal for Parasitology

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Plasmodium vivax is the most geographically widespread malaria parasite. Unique features of transmission biology complicate P. vivax control. Interventions targeting transmission are required for malaria eradication. In the absence of an in vitro culture, transmission studies rely on live isolates from non-human primates or endemic regions. Here, we demonstrate P. vivax gametocytes from both India and Brazil are stable during cryopreservation. Importantly, cryopreserved gametocytes from Brazil were capable of infecting three anopheline mosquito species in feedings done in the United States. These findings create new opportunities for transmission studies in diverse locales.

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supporting

confidence: 90%

Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates

Shaw-Saliba

Clarke

Santos

et al. 2016

International Journal for Parasitology

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“…aquasalis, Anopheles albitarsis, and Anopheles darlingi are the main vectors in South America and are associated with malaria transmission (11). A. aquasalis has successfully been used under laboratory conditions for P. vivax infections (10), and an infection protocol with P. vivax on A. darlingi was recently established (12). For these assays, purified gametocytes were used to prepare blood dilutions at a hematocrit level of 36% using washed uninfected fresh Oϩ blood and AB serum at a final volume of 1 ml.…”

mentioning

confidence: 99%

Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays

Vera

Brito

Albrecht

et al. 2015

Antimicrob Agents Chemother

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f Significant progress toward the control of malaria has been achieved, especially regarding Plasmodium falciparum infections. However, the unique biology of Plasmodium vivax hampers current control strategies. The early appearance of P. vivax gametocytes in the peripheral blood and the impossibility of culturing this parasite are major drawbacks. Using blood samples from 40 P. vivax-infected patients, we describe here a methodology to purify viable gametocytes and further infect anophelines. This method opens new avenues to validate transmission-blocking strategies. In a scenario of malaria elimination, strategies based on transmission control, rapid diagnosis, effective vaccines, and specific drugs are vital. Early diagnosis and prompt treatment with effective drugs have led to a considerable decrease in the number of cases of falciparum malaria worldwide (1). However, the control and elimination of Plasmodium vivax still constitute a great challenge due to specific features of the organism, including gametocytes on peripheral blood early during infection (2), occurrence of a dormant stage in the liver (hypnozoite), and the emergence of drug-resistant forms (3, 4). The development of transmissionblocking molecules to reduce transmission is crucial for malaria eradication. However, because of the lack of a robust continuous in vitro culture system (5), studies on P. vivax gametocytes have been hampered. Here, using blood samples from 40 P. vivax-infected patients and membrane feeding assays, we describe a unique methodology to purify and concentrate viable gametocytes capable of infecting anophelines. This methodology opens avenues for testing drugs or vaccines against the gametocytes, the nonreplicating sexual stage responsible for parasite transmission to mosquitoes (2).Patients were recruited at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), a tertiary care center for infectious diseases in Manaus, Amazonas State, Brazil. This study was approved by a Brazilian ethics board (CAAE 0044.0.114.000-11). Up to 9 ml of peripheral blood was collected from infected patients, with parasitemia ranging from 297.5 to 30,600 parasites/l and gametocytemia (mean Ϯ standard deviation [SD]) of 13.3% Ϯ 16.7%. White blood cells were removed from the blood using a cellulose column (Sigma), as previously described (6). Afterwards, to separate asexual and sexual parasites from noninfected erythrocytes, we used a Percoll-45% (P45) or Percoll-60% (P60) gradient (7, 8) and/or magnetic purification (MP) using MACS-Columns LD/LS (Miltenyi Biotec) (9). Blood samples were maintained at 37°C during all procedures to avoid gametocyte exflagellation. For this purpose, we used a hot plate inside the tissue culture hood and preheated solutions, and all centrifugations were performed at 37°C. The percentage of gametocytes was determined by counting parasites on thin Giemsa smears before and after the purification process. Correlations were analyzed using the Spearman test. The normality of the data was evaluated with th...

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“…darlingi colony derived from wild-caught mosquitoes obtained in the northeastern Peruvian Amazon region of Iquitos that was confirmed for its P. vivax vectorial capacity. 100 The feasibility of infecting in vitro liver hepatocyte culture with the sporozoites produced weekly in their insectary is currently being tested. One major challenge will be to continue improving sporozoite yields per mosquito, which is currently suboptimal (1000-6000 sporozoites per mosquito), in order to provide the necessary sporozoite biomass for a high-throughput screening assay.…”

Section: Source Of Sporozoitesmentioning

confidence: 99%

Killing the hypnozoite – drug discovery approaches to prevent relapse inPlasmodium vivax

Campo

Vandal

Wesche

et al. 2015

Pathogens and Global Health

101

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The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse.

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Infection of Laboratory-Colonized Anopheles darlingi Mosquitoes by Plasmodium vivax

Cited by 52 publications

References 25 publications

Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates

Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates

Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays

Killing the hypnozoite – drug discovery approaches to prevent relapse inPlasmodium vivax

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