Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays

NCT04666350 | Completed Results

• 1 other identifier: CVIA 085 -- Phase 0
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Oocyst Prevalence

  Participants underwent feeding assays on two days, 24 hours apart (day 1 and Day 2). After feeding, mosquitoes were maintained in locked environmental chambers for 9 days to allow oocyst development. An oocyst is a structure that develops on the outer wall of the infected mosquito's stomach that contains developing sporozoites. Nine days after feeding mosquito midguts were dissected, stained with 1% mercurochrome and examined by optical microscopy. The number of oocysts in each midgut were recorded. Oocyst prevalence is defined as the percentage of mosquitoes in a cup with at least one oocyst detected in the mid-gut among the surviving mosquitoes (in the same cup) that underwent the feeding assays.

  Feeding assays were performed on Day 1 and Day 2; Oocyst prevalence in surviving mosquitoes was assessed 9 days after feeding (Days 9 and 10).

Secondary Outcomes (3)

• Oocyst Density

  Feeding assays were performed on Day 1 and Day 2; Oocyst density in surviving mosquitos was assessed 9 days after feeding (Days 9 and 10).

• Sporozoite Prevalence

  Feeding assays were performed on Day 1 and Day 2; Sporozoite prevalence in surviving mosquitoes was assessed 14 days after feeding (Days 14 and 15).

• Sporozoite Density

  Day 1 and Day 2

Study Arms (1)

Study Volunteers

Participants provided a blood sample on Day 1 for DMFA testing and then participated in the mosquito feeding assay. On Day 2 participants underwent a second DMFA and DSFA assay (within 24 hours of the first assays). Upon completion of Day 2 DSFA participants will receive one dose of primaquine and the first dose of a 3-day regiment of artemether/lumefantrine.

Other: Direct Skin Feeding Assay (DSFA); Drug: Primaquine; Drug: Artemether/Lumefantrine

Interventions

Direct Skin Feeding Assay (DSFA) OTHER

In the direct feeding assay a cup with 60 unfed, sterile insectary-reared Anopheles gambiae mosquitoes will be allowed to feed on a participant's calf or arm for 15 minutes.

Study Volunteers

Primaquine DRUG

Participants will receive one dose of primaquine 26.3 mg tablet on Day 2 after completion of the direct feeding assay.

Study Volunteers

Artemether/Lumefantrine DRUG

Participants will receive artemether (80 mg) and lumefantrine (480 mg) combination tablets twice a day for 3 days, starting after completion of the direct feeding assay on Day 2.

Also known as: Coartem®

Study Volunteers

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The target sample size for subjects with gametocytemia is approximately 45 individuals. Approximately 180 participants will be screened for gametocyte carriage by PCR to achieve the target sample size. Screening of subjects will continue until the desired sample size of gametocytemic individuals who undergo all study procedures is attained. Adults aged 18 - 55 years will be recruited from the villages in the Kombewa Health and Demographics Surveillance System (HDSS) consisting of half of Kisumu

You may qualify if:

• Provision of signed or thumb printed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female aged between 18 years and 55 years inclusive.
• Resident within the study area
• In good general health as evidenced by medical history and clinical examination before entering the study Ability to take oral Coartem and low-dose primaquine anti-malarials upon conclusion of day 2 (2nd direct skin feed) and be willing to adhere to the medication regimen
• For females, she must be of non-childbearing potential or use appropriate measures to prevent pregnancy for 30 days after receiving Coartem and primaquine. Non-childbearing potential means she is surgically sterilized or at least one year post-menopausal. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant or Depo-Provera).
• For males, he must be willing to ensure that he does not get his partner(s) pregnant for at least 3 months after treatment with primaquine. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions in either the participant or the partner.
• Positive for P. falciparum gametocytes as measured by polymerase chain reaction (PCR) with cycle threshold (cT) value \< 31.

You may not qualify if:

• Presence of any signs or symptoms of malaria
• Presence of contraindications to administration of Coartem and primaquine as indicated in the respective drug package inserts
• History of severe allergic reactions to mosquito bites (other than pruritus and local swelling)
• Pregnant (i.e. a positive pregnancy test)
• Current or recent (within the preceding 2 weeks) use of antimalarial treatment
• Current participation in a malaria vaccine study
• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Sponsors & Collaborators

• PATH: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Kenya Medical Research Institute: collaborator

Study Sites (1)

KEMRI

Kombewa, Kenya

Location

Related Publications (1)

• Akala HM, Aponte JJ, Achola MA, Juma DW, Opot BH, Maisiba RN, Okoth RO, Juma JA, Mwakio EW, Mwalo MA, Oullo DO, Abuom D, Garges EC, Eyase FL, Tina LO, Copeland NK, Roth A, Mutunga J, Onyango I, Johnson J, Ogutu BR, Sifuna P, Hutter J, Mercer L, Raine M, Moore V, Ivinson K, Wu Y, Andagalu B, Ockenhouse CF. Consistency and reproducibility of independent feedings using blood from two consecutive days at varying Plasmodium falciparum gametocyte densities based on both direct membrane feeding assay and direct skin feeding assay. Malar J. 2025 May 16;24(1):154. doi: 10.1186/s12936-025-05360-3.

  PMID: 40380146 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Sera collected will be assayed in membrane feeding assay (risk mitigation) only if gametocyte-positive subject fails to transmit any parasites to mosquitoes in either the DSFA or DMFA performed either on day 1 or day 2. Sera will be destroyed before study close-out.

MeSH Terms

Conditions

Malaria

Interventions

Primaquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Chris F Ockenhouse, MD, PhD
• Organization: PATH

cockenhouse@path.org

+1 (202) 716-5849

Study Officials

• Ben Andagalu, MD

  Drug Resistance Laboratory, KEMRI

  PRINCIPAL INVESTIGATOR

• Hoseah Akala, MD

  Drug Resistance Laboratory, KEMRI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 14, 2020
• Study Start: March 9, 2021
• Primary Completion: December 20, 2021
• Study Completion: December 20, 2021
• Last Updated: April 29, 2024
• Results First Posted: April 29, 2024

Record last verified: 2022-12

Locations

KE (1)