Molecular Basis of Erythrocyte Invasion by Plasmodium Vivax Into Duffy-Negative Erythrocytes in Mali

Background:

Malaria is caused by parasites carried by some mosquitos. When the mosquitos bite people, the parasites can infect them. One of these parasites is Plasmodium vivax (P. vivax). Some children have P. vivax in their blood. They did not have malaria symptoms, but some also had a blood problem called anemia. This can make people feel tired or weak. This could have been caused by P. vivax. Researchers want to know how P. vivax infects these children, and if it affects their health.

Objective:

To collect blood, stool, and urine monthly from children to look for infections with P. vivax, worms, and other parasites.

Eligibility:

Children between 6 months and 10 years old

Design:

For screening, the study will be explained to the participant s parents or guardians, who will provide consent.

Participants will have a visit once a month for about 3 months, from November to January, and then for about 6 months from June to November 2018. Visits include:

Questions about their health

Medical history

Physical exam

Blood draw by pricking the finger tip

Urine and stool collection. They may collect these at home and bring them back.

If participants have P. vivax in their blood, them may need to come back to the clinic within 3 days. They will have blood taken from their arm using a needle.

If participants feel ill during the study, they can go to the clinic for an exam and blood tests.

If participants develop malaria while on the study, they will be treated.

Participants samples will be stored for future research studies.

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Plasmodium vivax was thought not to be a problem in Duffy blood group negative Africans. However, recent research has found that P. vivax infection occurs not only in areas where Duffy-positive and -negative people live side-by-side, but also in areas where populations are predominantly Duffy-negative, such as Bandiagara, Mali. In this region, our research group recently observed 25 P. vivax infections in children, all of whom were Duffy-negative. Furthermore, some preliminary data suggest that, despite having extremely low parasitemia and no malarial symptoms (no fever, muscle aches, or chills), the children of Bandiagara with P. vivax may have a drop in hemoglobin.

The present study involves two substudies to detect P. vivax infections in children and adults of two predominantly Duffy-negative Malian populations where P. vivax infections have previously been identified. The cohort study will be conducted in the Bandiagara region. We will conduct physical exams and collect blood, urine, and stool samples at baseline and monthly (urine samples will be collected only at baseline) for about 10 months. Our goal is to detect and characterize P. vivax infections, focusing on molecularly characterizing how P. vivax invades erythrocytes in Duffy-negative individuals. Specifically, we want to identify the parasite ligands involved in this invasion. We will use RNA sequencing (RNAseq) of P. vivax in blood samples of infected subjects to define the level of expression of parasite invasion ligands. From the parasite DNA found in blood samples, we will determine whether there is gene expansion of the parasite ligand Duffy binding protein (PvDBP) (the number of copies of PvDBP in each genome), and identify the sequence of PvDBP to determine whether it can bind an erythrocyte receptor other than the Duffy blood group antigen (i.e., Duffy-negative erythrocytes). An additional focus will be whether P. vivax leads to anemia in the Duffy-negative children.

In addition, we will conduct a cross-sectional study to investigate the prevalence of P. vivax in the general population in Yirimadio, a periurban setting of Bamako, which is the sole place in Mali besides Bandiagara where P. vivax infections have been reported in Duffy-negative individuals. This will be achieved by undertaking a cross-sectional survey. Subjects will provide blood for blood smear and filter paper analyses to identify the presence of P. vivax infection at 3 different time points.

Eligibility Criteria:
* INCLUSION CRITERIA:

For inclusion in the cohort substudy, a child must meet the following criteria:

1. Is greater than or equal to 6 months and less than or equal to 10 years of age
2. Residing in Bandiagara for at least 6 months prior to screening
3. Will be available to attend visits during this study
4. Agrees to provide urine and stool samples during this study
5. Agrees to allow storage of samples for future research.

For inclusion in the cross-sectional substudy, an individual must meet the following criteria:

1. Aged greater than or equal to 6 months;
2. Residing in Yirimadio for at least 6 months prior to screening.

EXCLUISION CRITERIA:

The following criterion is exclusionary in either substudy:

1) Has any underlying conditions that, in the judgement of the clinical investigators, could increase the risk to the subject.