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

Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays in Adults With Varying Plasmodium Falciparum Gametocyte Densities

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Other: Direct Skin Feeding Assay (DSFA); Drug: Primaquine; Drug: Artemether/Lumefantrine

Detailed Description

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. The results will determine the type of pivotal trial design for a follow-on Phase 2b trial whose objective is to bridge the standard membrane feeding assay (SMFA) to the direct skin feeding assay (DSFA) and direct membrane feeding assay (DMFA) using a monoclonal antibody intervention, TB31F monoclonal antibody (mAb), which interrupts transmission from human to mosquito. The results from this experimental medicine study will inform whether the preferred "Before-After" trial design in which each human volunteer serves as their own internal control can be utilized for a follow-on Phase 2b trial.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Kenya
  • Kombewa, Kenya
    • KEMRI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: N/A

• 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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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); 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.; Drug: Primaquine; Participants will receive one dose of primaquine 26.3 mg tablet on Day 2 after completion of the direct feeding assay.; Drug: Artemether/Lumefantrine; 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.; Other Names: Coartem®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oocyst Density	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 density is defined as the mean number of oocysts detected in infected mosquitoes that underwent feeding assays on the same participant.	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	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 14 days to allow sporozoite development. Sporozoites are the forms of the plasmodium that are liberated from the oocysts in the mosquito, accumulate in the salivary glands of the mosquito, and are transferred to humans when the mosquito feeds. Fourteen days after feeding, salivary glands were dissected from live mosquitoes submerged in phosphate-buffered saline (PBS) in order to visualize motile sporozoites by microscopy. Sporozoite prevalence was recorded. Sporozoite prevalence is defined as the percentage of mosquitoes in a cup with at least one sporozoite detected in the salivary glands among the mosquitoes (in the same cup) that underwent feeding assays.	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	Sporozoite density is defined as the mean number of sporozoites detected in infected mosquitoes that underwent feeding assays. Due to limitation on the state of the art, it was not possible to estimate the sporozoite density using the Optical Microscopy technique.	Day 1 and Day 2

Collaborators and Investigators

• Sponsor: PATH
• Collaborators: Walter Reed Army Institute of Research (WRAIR); Kenya Medical Research Institute
• Investigators: Principal Investigator: Ben Andagalu, MD, Drug Resistance Laboratory, KEMRI; Principal Investigator: Hoseah Akala, MD, Drug Resistance Laboratory, KEMRI

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): December 20, 2021

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Lumefantrine; Artemether; Primaquine; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: CVIA 085 -- Phase 0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No