Malaria,Falciparum
Conditions
Brief summary
Objectives: Primary: • To characterize the infectivity of the new lot of Plasmodium falciparum strain 3D7 within the standard WRAIR CHMI model as compared to the current lot (historical data) Secondary: * To assess safety of the new lot of P falciparum parasites * To assess the kinetics of detecting parasitemia and parasite clearance by quantitative polymerase chain reaction (qPCR) as compared to blood smear * To obtain plasma samples to restore the testing control pool for malaria serology testing and for future malaria research
Detailed description
This is a single center, open label CHMI study. CHMI will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. After the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Unless previously diagnosed and fully treated, subjects will be required to stay in a hotel for a maximum of 12 nights starting on or around the evening of Day 7 post challenge. All subjects diagnosed with malaria infection based on smears will be prescribed a standard malaria treatment regimen to begin on the day that parasitemia is detected. Subjects who do not become parasitemic (via smear) by Day 19 will be empirically treated for malaria. After the hotel phase, all challenged subjects will have a final scheduled follow-up visit on Day 28 (±7 days).
Interventions
BIOLOGICALPlasmodium falciparum malaria parasite
Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).
Sponsors
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* To be eligible for this study, you must meet ALL of the following conditions: * You are between the ages of 18 and 50 years old. * You are willing and able to participate in all planned study visits for the duration of the study. * You are in good general health based on your medical history, physical examination, EKG, and screening laboratories. * You are able to understand and sign this informed consent. * You pass the written test called the 'Assessment of Understanding' with a score of at least 80% (8 out of 10 questions correct). * You agree not to donate blood during the study and for 3 years after the malaria challenge. * You agree not to travel to place(s) where there is malaria during the time of the study. * If you are a female, you must agree to consistently use effective birth control (e.g., oral or implanted contraceptives, intrauterine device (IUD), diaphragm with spermicide, abstinence, cervical cap) during the period from the day of screening (today) through 3 months after the malaria challenge. * You must be willing to take anti-malarial treatment after CHMI, if indicated. * You must agree to stay in a pre-determined hotel near the NMRC CTC during the designated post-CHMI follow-up period from approximately 7 days after malaria challenge until antimalarial treatment is completed, if indicated. * If you are an active duty military or federal employee, you must have approval from your supervisory chain to participate. The appropriate approval form will be provided to you.
Exclusion criteria
* You must not have any of the following: * Any history of malaria infection or having been given a malaria vaccine * Any history travel to a country with falciparum malaria in the past 6 months, or planned travel to such an area during the course of the study * Any history of having lived in an area with falciparum malaria for more than 5 years. * Any use of medications that prevent or treat malaria during the 1 month prior to challenge or planned use during the study (outside of the drugs provided by the study team). * Any serious medical illness or condition involving the heart, liver, lungs, or kidneys * Any significant risk for developing heart disease in the next 5 years. The risk for developing heart disease in the next 5 years will be determined by a combination of the following factors: high blood pressure, smoking, weight, family history of heart disease and the presence of diabetes * Any medical illness or condition involving your blood or immune system (to include sickle cell trait or thalassemia trait) * Any abnormal (as determined by a physician) screening laboratory test results * Any history of neurologic disease (including migraines or seizures) * Any history of psoriasis (itchy skin rash) or porphyria (rare disturbance of metabolism), since these conditions could get worse after treatment with chloroquine (a medication for treating malaria). * You have had your spleen removed * Any past or current infection with HIV, Hepatitis C, or Hepatitis B * Any use of investigational drugs or vaccines within 1 month before starting the study * Any allergy to or inability to take the anti-malaria medications used in this study * Any history of allergic reaction to mosquito bites that required hospitalization * You must not be pregnant or nursing, or have any plans to become pregnant or breastfeed during the period from now through 3 months after malaria challenge * Any chronic use of steroids or other medications that affect the immune system in the 6 months before malaria challenge. Inhaled and topical (used on the skin) steroids are allowed. * You plan to have surgery between enrollment and 3 months after malaria challenge. * Any active alcohol or drug abuse * You have any other physical or psychologic condition or laboratory abnormality that the study doctor thinks may increase your risk of having side effects or compromise the results of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | Within 2 weeks | Number of challenged subjects exposed to the new lot of Plasmodium falciparum strain 3D7 parasites developing parasitemia (defined as 2 unambiguous malaria parasites on a single smear). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Efficacy; Time to Parasitemia by Blood Smear Method After the P Falciparum Challenge | Within 2-3 weeks | Time to parasitemia by blood smear method after the P falciparum challenge. Time to parasitemia is defined as the time from CHMI to a first positive malaria parasite result. Parasitemia was defined as the presence of 2 unambiguous malaria parasites on a single smear. Beginning on Day 1 after their challenge, subjects were seen and evaluated daily by a study investigator and blood was drawn for determination of parasitemia by qPCR. Beginning on Day 5 and through Day 19 after their challenge, blood from these daily draws was utilized to generate blood smears to evaluate the development of malaria infection. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. However, only blood smears were used for diagnosis during this trial and evaluation of treatment success. |
| Diagnostic Efficacy; Time to Parasitemia (Days) by qPCR Method After the P Falciparum Challenge | Within 2-3 weeks | Time to parasitemia by qPCR method after the P falciparum challenge. Time to parasitemia is defined as the time from CHMI to a first positive malaria parasite result. Parasitemia was defined as the presence of 2 unambiguous malaria parasites on a single smear. On Day 0, subjects were evaluated by qPCR once prior to challenge, to establish a baseline. Beginning on Day 1 through Day 19 after their challenge, subjects were seen and evaluated daily by a study investigator and blood was drawn for determination of parasitemia by qPCR. Beginning on Day 5 and going through Day 19 after their challenge, blood from these daily draws was utilized to generate blood smears to evaluate the development of malaria infection. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. However, only blood smears were used for diagnosis during this trial and evaluation of treatment success. |
| Diagnostic Efficacy; Quantification of Parasite Clearance Time (PCT) by Blood Smear and qPCR Methods After Initiation of Antimalarial Treatment | Within 6 weeks | Time to Clearance was determined for all subjects for both smear and qPCR. Time to Clearance was defined as the time (in Days) from malaria diagnosis to confirmed clearance of parasitemia. Confirmed clearance of parasitemia by malaria smear was defined as the observation of 3 sequential negative (no parasites observed) daily smears. Confirmed clearance of parasitemia by qPCR was defined as 2 sequential daily (approximately 24 hours apart) negative qPCR assay results. For clarity, the day of the final test in each sequence (smear, PCR) was used as the day of confirmed clearance for calculation purposes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infective Controls Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear.
Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed). | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Infective Controls |
|---|---|
| Age, Customized Age | 28.7 years STANDARD_DEVIATION 7.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model.
Number of challenged subjects exposed to the new lot of Plasmodium falciparum strain 3D7 parasites developing parasitemia (defined as 2 unambiguous malaria parasites on a single smear).
Time frame: Within 2 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infective Controls | To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | 9 Days post-challenge | 0 Participants |
| Infective Controls | To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | 10 Days post-challenge | 1 Participants |
| Infective Controls | To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | 11 Days post-challenge | 5 Participants |
| Infective Controls | To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | 12 Days post-challenge | 5 Participants |
| Infective Controls | To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | 13 Days post-challenge | 0 Participants |
| Infective Controls | To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. | 14 Days post-challenge | 1 Participants |
Secondary
Diagnostic Efficacy; Quantification of Parasite Clearance Time (PCT) by Blood Smear and qPCR Methods After Initiation of Antimalarial Treatment
Time to Clearance was determined for all subjects for both smear and qPCR. Time to Clearance was defined as the time (in Days) from malaria diagnosis to confirmed clearance of parasitemia. Confirmed clearance of parasitemia by malaria smear was defined as the observation of 3 sequential negative (no parasites observed) daily smears. Confirmed clearance of parasitemia by qPCR was defined as 2 sequential daily (approximately 24 hours apart) negative qPCR assay results. For clarity, the day of the final test in each sequence (smear, PCR) was used as the day of confirmed clearance for calculation purposes.
Time frame: Within 6 weeks
Population: Unless previously diagnosed and fully treated, subjects stayed in a hotel starting on the evening of Day 9 post challenge. Subjects diagnosed with malaria were treated on the day parasitemia was detected. Subjects not parasitemic by Day 19 were treated for malaria and released from the hotel. These subjects had clinic daily for completion of treatment and blood collection until treatment efficacy criteria were met. All challenged subjects had a final follow-up visit on Day 28 (±7 days).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infective Controls | Diagnostic Efficacy; Quantification of Parasite Clearance Time (PCT) by Blood Smear and qPCR Methods After Initiation of Antimalarial Treatment | Blood smear Method | 1.2 days | Standard Deviation 0.39 |
| Infective Controls | Diagnostic Efficacy; Quantification of Parasite Clearance Time (PCT) by Blood Smear and qPCR Methods After Initiation of Antimalarial Treatment | qPCR method | 3.0 days | Standard Deviation 0.6 |
Secondary
Diagnostic Efficacy; Time to Parasitemia by Blood Smear Method After the P Falciparum Challenge
Time to parasitemia by blood smear method after the P falciparum challenge. Time to parasitemia is defined as the time from CHMI to a first positive malaria parasite result. Parasitemia was defined as the presence of 2 unambiguous malaria parasites on a single smear. Beginning on Day 1 after their challenge, subjects were seen and evaluated daily by a study investigator and blood was drawn for determination of parasitemia by qPCR. Beginning on Day 5 and through Day 19 after their challenge, blood from these daily draws was utilized to generate blood smears to evaluate the development of malaria infection. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. However, only blood smears were used for diagnosis during this trial and evaluation of treatment success.
Time frame: Within 2-3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infective Controls | Diagnostic Efficacy; Time to Parasitemia by Blood Smear Method After the P Falciparum Challenge | 11.6 days | Standard Deviation 1 |
Secondary
Diagnostic Efficacy; Time to Parasitemia (Days) by qPCR Method After the P Falciparum Challenge
Time to parasitemia by qPCR method after the P falciparum challenge. Time to parasitemia is defined as the time from CHMI to a first positive malaria parasite result. Parasitemia was defined as the presence of 2 unambiguous malaria parasites on a single smear. On Day 0, subjects were evaluated by qPCR once prior to challenge, to establish a baseline. Beginning on Day 1 through Day 19 after their challenge, subjects were seen and evaluated daily by a study investigator and blood was drawn for determination of parasitemia by qPCR. Beginning on Day 5 and going through Day 19 after their challenge, blood from these daily draws was utilized to generate blood smears to evaluate the development of malaria infection. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. However, only blood smears were used for diagnosis during this trial and evaluation of treatment success.
Time frame: Within 2-3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infective Controls | Diagnostic Efficacy; Time to Parasitemia (Days) by qPCR Method After the P Falciparum Challenge | 7.3 days | Standard Deviation 0.65 |