Last Updated

28 Jun 2022

Experimental Vivax Transmission to Anopheles (EVITA)

Objectives

To evaluate the P. vivax induced blood stage malaria (IBSM) model with subsequent experimental mosquito feeding as a system to study infectivity to vector mosquitoes.

Principal Investigator
Rationale and Abstract

A renewed focus on malaria elimination has increased the priority of research towards development of interventions to block malaria transmission, including transmission blocking vaccines (TBVs). This Phase I clinical trial is designed test if our established malaria challenge system is suitable to study transmission to mosquitoes. A Plasmodium vivax malaria infection will be established in 6 human volunteers. Vector transmission studies will be undertaken with a laboratory strain of Anopheles stephensi mosquitoes to assess the transmission of parasites to the mosquitoes, both by direct feeding on volunteers and by artificial membrane feeding. Assessment of infection of the mosquitos will be done by mid gut dissection and microscopic visualisation, to evaluate the production of oocysts following the feeding experiments. Once feeding experiments have been completed, participants will then commence curative anti malarial treatment.              

Study Design

An experimental study to investigate the transmission of malaria from a person infected with a specific species of malaria to mosquito feeding on that infected person’s blood.

The study will be conducted in 3 cohorts, each with 2 participants. All participants will receive malaria inoculum injection of ~100 viable Plasmodium vivax-infected human erythrocytes administered intravenously. Participants will be monitored on an outpatient basis including with blood collection for quantification of parasitaemia by PCR, and for unexpected early onset of symptoms of malaria or adverse events until they are admitted to the inpatient facility for curative antimalarial chemotherapy. On the three days up to the anticipated commencement day of treatment as determined by PCR, transmission studies will be undertaken. Over those 3 days blood will be collected twice daily from each participant for membrane feeding assays with An. Stephensi, and for PCR testing and exploratory research. On the morning of those 3 days participants will then be placed in the insectary and asked to allow 30 vector mosquitoes to feed on the volar surface of their forearms or thighs for a period of 15 + 5 minutes (direct feeding assay). On the day designated for commencement of treatment, as determined by the onset of clinical manifestations of malaria infection, participants will be admitted to the study unit and confined for safety monitoring and antimalarial treatment with the antimalarial drug Riamet (artemether20mg/lumefantrine120mg). This will be administered by oral administration of 6 doses of 4 tablets (total course 24 tablets) given over a period of 60 hours following food. All doses with exception of the last will be given under direct observation of clinical staff. It is expected the last dose is taken by participants at home. Following treatment, participants will be followed up as inpatients for 36 hours to ensure tolerance of therapy and clinical response. Once clinically well, they will be followed up on an outpatient basis for continued dosing of antimalarial drug, safety and clearance of malaria parasites as assessed by sensitive quantitative PCR. Follow up visits for safety assessments will be performed on day 28 after malaria challenge and participants are required to be contactable and available up to 2 weeks following this end of study visits.

Date

2013 Oct - 2014 Sep

Funding Details

Project Site

Deep Dives