Malaria Transmitted to Humans by Mosquitoes Infected from Cultured Plasmodium falciparum

Chulay, Jeffrey D.; Schneider, Imogene; Cosgriff, Thomas M.; Hoffman, S. L.; Ballou, W. Ripley; Quakyi, Isabella A.; Carter, R; Trosper, James H.; Hockmeyer, Wayne T.

doi:10.4269/ajtmh.1986.35.66

Cited by 134 publications

(99 citation statements)

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“…Sporozoite load was expressed as the weighted average of sporozoite load per batch; to calculate the average sporozoite loads, parasite density scores were defined as follows: 1+ (1-10 sporozoites); 2+ (11-100 sporozoites); 3+ (101-1,000 sporozoites); and 4+ (> 1,001 sporozoites). 28 To assess the sporozoite load per batch, salivary glands were dissected and pooled to determine the mean sporozoite load. Pooled salivary glands were homogenized in a cell tissue grinder with PBS.…”

Section: Methodsmentioning

confidence: 99%

Plasmodium vivax Sporozoite Production in Anopheles albimanus Mosquitoes for Vaccine Clinical Trials

Solarte¹,

Manzano²,

Rocha³

et al. 2011

The American Journal of Tropical Medicine and Hygiene

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Abstract. Vaccine development for Plasmodium vivax malaria is underway. A model to assess the protective efficacy of vaccine candidates in humans is urgently needed. Given the lack of continuous P. vivax cultures, we developed a system to infect Anopheles albimanus mosquitoes using blood from P. vivax-infected patients and determined parameters for challenge of malaria-naive volunteers by mosquito bite. Absence of co-infections in parasitized blood was confirmed by tests consistent with blood bank screening. A total of 119 experiments were conducted using batches of 900-4,500 mosquitoes fed by an artificial membrane feeding method. Optimal conditions for mosquito probing and infection were determined. Presence of oocyst and sporozoites were assessed on Days 7-8 and 14-15, respectively, and conditions to choose batches of infected mosquitoes for sporozoite challenge were established. Procedures to infect volunteers took a 2-hour period including verification of inoculum dose. Anopheles albimanus mosquitoes represent a valuable resource for P. vivax sporozoite challenge of volunteers.

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Section: Methodsmentioning

confidence: 99%

Plasmodium vivax Sporozoite Production in Anopheles albimanus Mosquitoes for Vaccine Clinical Trials

Solarte¹,

Manzano²,

Rocha³

et al. 2011

The American Journal of Tropical Medicine and Hygiene

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“…Six of the seven (five in study 115-131 and one in study 115-134) were observed in the hospital for seven days or less and then completed their follow-up evaluation as outpatients, where they were potentially exposed to the bites of infected mosquitoes. Because the prepatent period for falciparum malaria averages about 10 days and can be as short as seven days after the bite of an infected mosquito, 12 it is possible that many of these patients had a new infection rather than a recrudescent infection.…”

Section: Evaluation Of a Range Of Doses Of Atovaquone And Proguanil Hmentioning

confidence: 99%

Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group.

Looareesuwan¹,

Chulay²,

Canfield³

et al. 1999

Am J Trop Med Hyg

185

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Abstract. The continuing spread of drug-resistant malaria emphasizes the need for new antimalarial drugs. Atovaquone is a broad-spectrum antiprotozoal drug with a novel mechanism of action, via inhibition of parasite mitochondrial electron transport, and a favorable safety profile. Early studies with atovaquone alone for treatment of malaria demonstrated good initial control of parasitemia but an unacceptable rate of recrudescent parasitemia. Parasites isolated during recrudescence after treatment with atovaquone alone were resistant to atovaquone in vitro. The combination of atovaquone and proguanil is synergistic in vitro, and clinical studies demonstrated enhanced efficacy of the combination compared to either drug alone for treatment of malaria. Malarone, a fixed-dose combination of 250 mg of atovaquone and 100 mg of proguanil hydrochloride, is available in many countries for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum. At the recommended dose (in adults, four tablets once a day for three days), the overall cure rate was Ͼ 98% in more than 500 patients with falciparum malaria. In four randomized, controlled clinical trials, treatment with atovaquone and proguanil hydrochloride was significantly more effective than mefloquine (Thailand), amodiaquine (Gabon), chloroquine (Peru and the Philippines) or chloroquine plus pyrimethamine/sulfadoxine (Philippines). In clinical trials where the comparator drug was highly effective, treatment with atovaquone and proguanil hydrochloride was equally effective. Parasites isolated during recrudescence after treatment with the combination of atovaquone and proguanil were not resistant to atovaquone in vitro. The most commonly reported adverse events in clinical trials (abdominal pain, anorexia, nausea, vomiting, diarrhea and coughing) occurred with similar frequency in patients treated with a comparator drug. Malarone is a safe and effective new agent for treatment of malaria.

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“…Protective efficacy was assessed by conducting a standardized challenge of vaccinated subjects and infectivity controls with the bites of five malaria-infected mosquitoes as previously described [11,23]. Cloned, chloroquinesensitive P. falciparum (3D7 strain) parasites were expanded from a master seed lot and were used to infect laboratoryreared, specific pathogen-free Anopheles stephensi.…”

Section: Efficacymentioning

confidence: 99%

Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naïve adults at the Walter Reed Army Institute of Research

Kester

Cummings

Ockenhouse

et al. 2008

Vaccine

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121

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K.E. Kester et al.against falciparum malaria would be compatible with the Expanded Programme on Immunization, or in combination with other prevention measures, interrupt epidemic malaria or protect individuals upon sudden travel to an endemic area. Methods:We conducted an open label, Phase 2a trial of two different full dose schedules of RTS,S/AS02 in 40 healthy malaria-naïve adults. Cohort 1 (n = 20) was immunized on a 0, 1, and 3 month schedule and Cohort 2 (n = 20) on a 0, 7, and 28 day schedule. Three weeks later, 38 vaccinees and 12 unimmunized infectivity controls underwent malaria challenge. Results: Both regimens had a good safety and tolerability profile. Peak GMCs of antibody to the circumsporozoite protein (CSP) were similar in Cohort 1 (78 g/mL; 95% CI: 45-134) and Cohort 2 (65 g/mL; 95% CI: 40-104). Vaccine efficacy for Cohort 1 was 45% (95% CI: 18-62%) and for Cohort 2, 39% (95% CI: 11-56%). Protected volunteers had a higher GMC of anti-CSP antibody (114 g/mL) than did volunteers with a 2-day delay (70 g/mL) or no delay (30 g/mL) in the time to onset of parasitemia (Kruskal-Wallis, p = 0.019). A trend was seen for higher CSP-specific IFN-␥ responses in PBMC from protected volunteers only in Cohort 1, but not in Cohort 2, for ex vivo and for cultured ELISPOT assays. Conclusion: In malaria-naïve adults, the efficacy of three-dose RTS,S/AS02 regimens on either a 0, 1, and 3 month schedule or an abbreviated 0, 7, and 28 day schedule was not discernibly different from two previously reported trials of two-dose regimens given at 0, 1 month that conferred 47% (95% CI: −19 to 76%) protection and in another trial 42% (95% CI: 5-63%). A strong association of CSP-specific antibody with protection against malaria challenge is observed and confirms similar observations made in other studies. Subsequent trials of adjuvanted RTS,S in African children and infants on a 0, 1, and 2 month schedule have demonstrated a favorable safety and efficacy profile.

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Malaria Transmitted to Humans by Mosquitoes Infected from Cultured Plasmodium falciparum

Cited by 134 publications

References 0 publications

Plasmodium vivax Sporozoite Production in Anopheles albimanus Mosquitoes for Vaccine Clinical Trials

Plasmodium vivax Sporozoite Production in Anopheles albimanus Mosquitoes for Vaccine Clinical Trials

Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group.

Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naïve adults at the Walter Reed Army Institute of Research

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