Malaria Transmission Studies in Mali
Malaria Transmission Studies in Mali
Background:

 - Malaria is an illness caused by a parasite spread by mosquitoes. When a mosquito bites a
 person who is infected with a kind of parasite called a gametocyte, it is able to spread the
 infection to another person. Not everyone infected with parasites have gametocytes in their
 blood. As a result, not everyone can spread malaria to others. Researchers are interested in
 learning more about why some healthy people have gametocytes in their blood and others do
 not. Identifying the people who have gametocytes in their blood can help target treatment and
 reduce the spread of malaria. This study will focus on the people of the village of Kenieroba
 in Mali, where malaria is common.

 Objectives:

 - To study the relationship between gametocytes and malaria transmission in Mali.

 Eligibility:

 - Individuals between 6 months and 65 years of age who live in Kenieroba, Mali, and will stay
 in the area for 1 year.

 Design:

 -  For 1 year, participants will have study visits once every 2 weeks (twice a month, for a
 total of 24 visits). The visits will last 30 minutes each.

 -  At each visit, participants will provide a small blood sample. They will report any
 symptoms of malaria such as fever, headache, and body aches. Participants will be
 encouraged to seek medical treatment if they experience malaria symptoms between visits.

 -  Participants who have malaria symptoms will have a blood test for malaria parasites.
 Those who have parasites in the blood will receive antimalarial treatment.

 -  Three times over 1 year, a larger blood sample will be collected. These blood samples
 will be taken once in the dry season, once in the wet season, and once in the next dry
 season.

 -  Women between 14 and 45 years of age will also provide urine samples to test for
 pregnancy. Pregnant women will not be asked to give blood samples.
Plasmodium falciparum malaria continues to evade control efforts in part through the
 complexity of its life cycle, which involves both humans and mosquitoes. While it is known
 that the gametocyte form of the parasite transmits disease, it is unclear which individuals
 constitute the primary gametocyte reservoir in a given human population. It is also unclear
 how an individual s asexual parasite density, acquired immune responses, and red blood cell
 (RBC) polymorphisms affect the presence and transmission of gametocytes. Investigating these
 effects has been limited in part because gametocytes are often present in peripheral blood at
 densities below the limit of microscopic detection. Recent technical advances in the
 molecular detection of gametocytes have set the stage for a better understanding of
 gametocyte epidemiology and biology in humans. In a setting of highly seasonal transmission,
 we are conducting an epidemiological study to estimate gametocyte prevalence over 1 year in
 the village of Kenieroba, Mali. In a cohort of 500 individuals that represents the
 age-distribution of the entire village population, we will explore how age, asexual parasite
 prevalence, season, and RBC polymorphisms affect variation in gametocyte prevalence (detected
 by a sensitive molecular method). From these same individuals, we will purify plasma IgG and
 compare its transmission-blocking activity by age group and season. These assessments will
 provide a foundation for future studies of gametocytemia dynamics within individuals as well
 as the impact of host immunity on gametocyte infectivity in our study population. Such
 information will enable us to identify those individuals that are primarily responsible for
 malaria transmission in Kenieroba. Incorporation of such findings into new or existing
 computer-based models of parasite infection and transmission may improve our evaluation of
 existing malaria control strategies.
-  INCLUSION CRITERIA (COHORT STUDY)

 1. Age 6 months to 65 years, inclusive

 2. Resident of Kenieroba with no plans to relocate away from Kenieroba for 1 year

 3. Willingness to participate in the study as evidenced by informed consent (if <18
 years, the informed consent of parent or guardian of the child, and assent from
 children 14 to 17 years old)

 EXCLUSION CRITERIA (COHORT STUDY)

 1. Any condition that in the opinion of the investigator would render the participant
 unable to comply with the protocol (e.g., psychiatric disease)

 2. Any health condition that in the opinion of the investigator would confound data
 analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who
 are known to be HIV-infected) or to the participant (e.g., severe malnutrition)

 3. Pregnancy for venous blood collections (March 2013, October 2013, March 2014)

 INCLUSION CRITERIA (ADULT BLOOD COLLECTION STUDY)

 1. Age 18 to 65 years, inclusive

 2. Hb level greater than or equal to 8.5 g/dL

 3. Willingness to participate in the study as evidenced by informed consent

 EXCLUSION CRITERIA (ADULT BLOOD COLLECTION STUDY)

 1. Pregnancy

 2. Any condition that in the opinion of the investigator would render the participant
 unable to comply with the protocol (e.g., psychiatric disease)

 3. Any health condition that in the opinion of the investigator would confound data
 analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who
 are known to be HIV-infected) or to the participant (e.g., severe malnutrition)

 INCLUSION CRITERIA (PARASITIZED BLOOD COLLECTION STUDY):

 1. Age 2 to 17 years, inclusive

 2. Hb level greater than or equal to 8.5 g/dL

 3. Previous enrollment in cohort study on protocol #08-I-N120

 4. Uncomplicated malaria*

 5. P. falciparum density greater than or equal to 10,000/microliters

 6. Known hemoglobin type HbAA or HbAS

 7. Not enrolled in this protocol s cohort study

 8. Willingness to participate in the study as evidenced by informed consent and assent
 from children 14-17 years old)

 -  Uncomplicated malaria: axillary temperature >37.5 degrees Celcius or history of
 fever in the past few days and no criteria of SM (see next paragraph) and no
 other etiologies of febrile illness (e.g., respiratory tract infection) on
 clinical examination.

 Severe P. falciparum malaria: parasitemia of any density and any one of the following: coma

 (Blantyre coma score less than or equal to 2), convulsions (witnessed by investigator),
 severe prostration, severe anemia (hemoglobin less than or equal to 6 g/dl), respiratory
 distress, hypoglycemia (serum glucose less than or equal to less than or equal to 40
 mg/dl), jaundice/icterus, shock (systolic blood pressure less than or equal to 70 mmHg,
 rapid pulse, cool extremities), cessation of eating and drinking, repetitive vomiting.

 EXCLUSION CRITERIA (PARASITIZED BLOOD COLLECTION STUDY):

 1. Pregnancy

 2. Any condition that in the opinion of the investigator would render the participant
 unable to comply with the protocol (e.g., psychiatric disease)

 3. Any health condition that in the opinion of the investigator would confound data
 analysis or pose unnecessary risks to study participants (e.g., severe malnutrition,
 acquired or inherited immunodeficiency)