Blood-Stage Plasmodium Vivax Cell Bank
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Malaria is caused by a parasite (a type of germ called P. vivax) that is carried by
      mosquitoes. The disease is transmitted to people when they are bitten by infected mosquitoes.
      To make drugs and vaccines for malaria, researchers need malaria-infected blood. Plasmodium
      vivax cell cultures are currently not cultured in vivo, and thus establishing a blood bank
      from P. vivax infections will be vital for future research.

      Objective:

      The goal of this study is to infect people with early-stage malaria, then collect infected
      blood samples to store in a cell bank for future use.

      Eligibility:

      Healthy adults ages 18-50 who will not be living alone during the study period.

      Design:

      Participants will be screened with a physical exam, heart health test, and medical history.
      They will have blood and urine tests. They will take a mental health survey. They must pass
      an exam to prove they understand the study.

      Participants will have red blood cells infected with P. vivax injected into an arm vein. They
      will be observed for side effects. They will get a thermometer to measure their temperature
      at home.

      For the next 3 days, they will be monitored via phone call or text. Starting on day 4 after
      the infection, they will have daily study visits to give blood samples. They will likely
      develop symptoms of malaria, such as fever, chills, headache, and muscle pain.

      Participants will be admitted to the hospital for 2-3 days when either they develop symptoms
      or the daily blood tests detect a certain amount of parasites. Once malaria is confirmed, a
      sample of their blood will be collected for the cell bank. Then they will be treated for
      malaria with oral medication that will cure the infection. Those who do not develop malaria
      will begin treatment after 15 days.

      Participants will have follow-up visits 28 and 90 days after infection.

      Participation will last for 3-5 months.
    

Detailed description: 
      This is a single-center, open-label study using induced blood-stage malaria (IBSM) to produce
      a human malaria parasite (HMP) bank for use in future studies. This study will be conducted
      in up to two participants. Participants will be inoculated intravenously (IV) with human
      malaria parasite blood stage P. vivax (HMPBS02-Pv) parasite-infected erythrocytes (day 0) and
      then monitored closely via outpatient clinic visits, phone visits, and while inpatient at the
      NIH Clinical Center (CC) for symptoms and signs of malaria to characterize the safety,
      tolerability, and infectivity in healthy malaria-naive participants inoculated with P. vivax.
      Blood sampling will be done periodically to measure parasitemia via quantitative polymerase
      chain reaction (qPCR) targeting the P. vivax 18S rRNA gene.

      The threshold for the commencement of collection of blood for production of the HMP bank and
      subsequent antimalarial rescue treatment with artemether/lumefantrine will occur when the
      Malaria Clinical Score is >6 (admission within 24 hours of notification), or parasitemia is
      >20,000 parasites/mL, or at the investigator s discretion. When this threshold is reached,
      the participant will be admitted to the NIH CC for further safety assessments before
      undergoing the blood collection procedure.

      After blood collection, the first dose of artemether/lumefantrine will be administered and
      the participant will remain inpatient for 48-72 hours to monitor for safety and tolerability
      of rescue therapy, and to ensure adequate clinical and parasitological response to treatment.
      In the unlikely and unprecedented event that artemether/lumefantrine fails to clear
      parasitemia, participants will be treated with chloroquine. If oral administration of either
      artemether/lumefantrine or chloroquine is not possible (e.g., the participant is vomiting),
      the participant will receive IV treatment with artesunate. After discharge, participants will
      be followed on an outpatient basis for monitoring of safety and parasite clearance. Follow-up
      for safety assessments will be performed on day 28 plus or minus 3, day 56 plus or minus 7
      (phone call only), and day 90 plus or minus 7 (End of Study).

      Participants may also be evaluated for the presence of sexual parasite stages (gametocytes)
      and other parasite lifecycle stages in the blood during the study using quantitative reverse
      transcriptase PCR (qRT-PCR).

      Objectives: Primary Objective: The collection of blood from healthy participants
      experimentally infected with P. vivax isolate HMPBS02-Pv for the production of a P. vivax
      blood-stage parasite bank for use in future studies.

      Secondary Objective: To assess the safety and tolerability of the P.vivax IBSM model
      following inoculation of healthy malaria-naive participants with P. vivax.

      Exploratory Objective: To further characterize blood- and sexual stage parasite growth
      profiles following inoculation with P. vivax isolate and treatment with
      artemether/lumefantrine.

      Endpoints: Primary Endpoint: Collection of blood for the production of a P.vivax blood-stage
      parasite bank from study participants following experimental infection with P. vivax isolate
      HMPBS02-Pv.

      Secondary Endpoint: Occurrence of solicited and unsolicited adverse events (AEs) following P.
      vivax inoculation prior to the initiation of antimalarial treatment.

      Exploratory Endpoint: The rate of growth of blood- and sexual-stage P. vivax isolate
      following inoculation and treatment with artemether/lumefantrine as determined by blood smear
      and/or qPCR.
    

Intervention name(s): HMPBS02-Pv
Intervention type(s): Biological
Intervention description(s): The blood-stage P. vivax master cell bank HMPBS02-Pv was also produced using blood collected from a consenting patient with naturally acquired malaria infection. The malaria infection was confirmed to be P. vivax by species-specific PCR at Pathology Queensland (accredited by the Australian National Association of Testing Authorities) and further confirmed by deep sequencing at the Sanger Institute. The clinical response to antimalarial chemotherapy was also demonstrated with this donor, who was successfully cured with artemether/lumefantrine.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Malaria; Parasitemia; IBSM; inoculation; Challenge