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

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ClinicalTrials.gov Identifier: NCT03304691
Recruitment Status : Enrolling by invitation
First Posted : October 9, 2017
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

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.


Condition or disease
Malaria

Detailed Description:
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.1 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 will detect P. vivax infections in children of 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)from January 2018 to March 2019. 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.

Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Molecular Basis of Erythrocyte Invasion by Plasmodium Vivax Into Duffy-Negative Erythrocytes in Children in Bandiagara, Mali
Estimated Study Start Date : December 20, 2018
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Group/Cohort
Children
Children of the Bandiagara region.



Primary Outcome Measures :
  1. Identify the P. vivax ligands for infection of Duffy blood group negative Africans by RNA sequencing (RNAseq) of blood from P. vivax cases. [ Time Frame: Monthly surveillance visits throughout length of the study ]

Secondary Outcome Measures :
  1. Determine the number of clones of P. vivax circulating in the community by DNA sequencing of polymorphic parasite proteins. [ Time Frame: Monthly surveillance visits throughout length of the study ]
  2. Determine by stool examinations the presence of hypnozoites in the liver that fail to cause blood infections. [ Time Frame: Monthly surveillance visits throughout length of the study ]
  3. Study the association between P. vivax parasitemia and anemia inDuffy-negative Africans. Identify the vector populations in and around the study area that may transmit malaria, including during the dry season, as well as the infection rates i... [ Time Frame: Monthly surveillance visits throughout length of the study ]
  4. Study the association between P. vivax parasitemia and anemia inDuffy-negative Africans. [ Time Frame: Monthly surveillance visits throughout length of the study ]
  5. Identify the vector populations in and around the study area that may transmit malaria, including during the dry season, as well as theinfection rates in these populations. [ Time Frame: Monthly surveillance visits throughout length of the study ]


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Ages Eligible for Study:   6 Years to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The present study will detect P. vivax infections in children of the Bandiagara region.
Criteria
  • INCLUSION CRITERIA:

For inclusion in the study, 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. Will be available to attend visits during this study
  3. Agrees to provide urine and stool samples during this study
  4. Agrees to allow storage of samples for future research.

EXCLUISION CRITERIA:

The following criterion is exclusionary:

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03304691


Locations
Mali
Bandiagara Malaria Program (BMP) Clinic
Bandiagara, Mali
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Louis H Miller, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03304691     History of Changes
Other Study ID Numbers: 999917165
17-I-N165
First Posted: October 9, 2017    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: November 7, 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Malaria
Parasitemia
Anemia
Ligand
Anopheles gambiae

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases