Controlled Human Malaria Infection by Mosquito Bites Using a Local Strain of Plasmodium Falciparum

NCT07816497 | Completed Phase 1 DMC

• 1 other identifier: SRC-2025-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The project aims to reproduce the malaria infection cycle using African mosquitoes, namely Anopheles gambiae and a local strain of Plasmodium parasites. The study will be conducted in two steps: (i) the production of infected mosquitoes and (ii) human infection with malaria parasites, known as Controlled Human Malaria Infection (CHMI). During the first step, Anopheles gambiae mosquitoes raised in the Centre de Recherches Médicales de Lambaréné (CERMEL) entomology laboratory in Lambaréné, Gabon, will be fed with blood collected from a person living in Lambaréné or the surrounding area who is positive for Plasmodium falciparum parasites, with the presence of asexual and sexual stages (responsible for malaria transmission) of the parasites in his/her blood. The Plasmodium-infected mosquitoes will be used two weeks later to infect healthy adult volunteers by mosquito bites under the supervision of the research team. After exposure, we will follow all exposed participants daily, starting on the fifth day after exposure. During the daily visits, we will perform malaria tests to detect the presence of malaria parasites in the blood of the participant. If participants test positive, they will receive usual antimalarial treatment if they simultaneously present malaria symptoms or if their parasitaemia is equal to or greater than 1,000 parasites per microlitre of blood. To ensure participants are effectively treated, we will perform two malaria tests after treatment, which should be negative. Otherwise, a different treatment will be administered. We will consider the process successful if we manage to infect (presence of malaria parasites in the blood) at least 50% of exposed participants. We also want the process to be safe, assuming that no unexpected clinical or biological events occur. Such an approach could contribute to a better assessment of the efficacy of antimalarial drugs and vaccine candidates, taking into account the specific characteristics of each endemic area.

Conditions

Malaria (Plasmodium Falciparum)

Keywords

CHMI; Plasmodium falciparum; Anopheles gambiae; Mosquito bites; Local strain

Outcome Measures

Primary Outcomes (1)

• Number of participants with Asexual P. falciparum blood stage infection detected by qPCR

  Until 21 days post-exposure

Secondary Outcomes (3)

• Number and frequency of adverse events

  During the 28-day follow-up period

• Number of participants with asexual P. falciparum blood stage infection detected by qPCR

  Until 28 days post-exposure

• Number of symptoms consistent with Plasmodium falciparum malaria

  During the 28-day follow-up period

Study Arms (1)

Healthy adults

EXPERIMENTAL

Participants in this arm will receive Plasmodium falciparum-infected mosquito bites each under direct supervision

Biological: Controlled Human Malaria Infection

Interventions

Controlled Human Malaria Infection BIOLOGICAL

Anopheles gambiae mosquitoes infected with a local strain of Plasmodium falciparum will be used to perform a CHMI by mosquito bites in healthy adult volunteers

Healthy adults

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult volunteers aged 18 to 45 years old
• Tympanic body temperature \< 37.5°C
• Residence in Lambaréné or surroundings for the period of the trial
• History of long-term residence (at least 5 years) in Gabon
• Willingness to take two curative anti-malarial regimens
• Reachable (24/7) by mobile phone during the CHMI and follow-up
• A body mass index \<35

You may not qualify if:

• Haemoglobin level \< 11 g/dl for female volunteers and \< 11.5 g/dl for male volunteers
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
• Prior receipt of an investigational malaria vaccine
• Immunization with more than 3 other vaccines within the past month.
• Positive for hepatitis B surface antigen (HBs-antigen)
• Seropositive for hepatitis C virus (antibodies to HCV).
• Positive HIV test
• Abnormal level of transaminase (ALAT, ASAT)
• Have been treated for malaria disease with an antimalarial drug or an antibiotic active on malaria parasites over the previous 28 days of the inoculation.
• Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe and chronic (more than 14 days) infections, immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
• Use of immunoglobulins or blood products within 3 months prior to enrolment.
• Sickle cell disease or any clinically relevant blood disorder.
• History of a serious psychiatric condition that may affect participation in the study.
• Positive urine pregnancy test or breastfeeding
• Any other serious chronic illness requiring hospital specialist supervision

Sponsors & Collaborators

• Centre de Recherche Médicale de Lambaréné: lead

Study Sites (1)

Centre de Recherches Médicales de Lambaréné

Lambaréné, Moyen-Ogooué Province, 242, Gabon

Location

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Steffen Borrmann, Prof.

  Institut für Tropenmedizin, Universitätsklinikum Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The project comprises two steps: (i) the production of mosquitoes infected with P. falciparum (Pf) by infecting laboratory-raised Anopheles gambiae mosquitoes of the Kisumu strain with blood samples taken from local carriers of Pf gametocytes; and (ii) CHMI by bites of Pf-infected A. gambiae (PfiAg) mosquitoes on healthy volunteers who will be recruited to receive a specified number of PfiAg mosquito bites under direct supervision and monitored daily from day 5 to D21 after exposure. PCR and thick blood smears (TBS) will be performed at each visit until one of the following criteria for antimalarial treatment is met: asexual parasite density ≥ 1,000 parasites/µL by TBS or malaria symptoms in the presence of a positive TBS (any parasite density). This endpoint will trigger antimalarial treatment. Participants who remain PCR-negative until D21 will be seen on days 24 and 28 for additional follow-up visits. Antimalarial treatment will be provided to all other study participants on D28

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: September 11, 2026
• Study Start: July 18, 2025
• Primary Completion: February 19, 2026
• Study Completion: February 19, 2026
• Last Updated: September 11, 2026

Record last verified: 2026-03

Locations

GA (1)