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

ID: NCT03304691
Status: Recruiting
Phase: N/A
Start Date: March 01, 2018
First Submitted: October 06, 2017
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Location: Mali
Conditions: Malaria
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Study Description

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.

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 monthly from November 2017 to January 2018 and from June to November 2018. 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.
Condition or disease Intervention/treatment Phase

Malaria

N/A

Tracking Information

First Submitted DateOctober 06, 2017
Last Update Posted DateFebruary 23, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateDecember 31, 2019
Anticipated Primary Completion DateNovember 30, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • 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]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • 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]

  • 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]

  • 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]

  • Study the association between P. vivax parasitemia and anemia inDuffy-negative Africans. [Time Frame: Monthly surveillance visits throughout length of the study]

  • 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]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleMolecular Basis of Erythrocyte Invasion by Plasmodium Vivax Into Duffy-Negative Erythrocytes in Children in Bandiagara, Mali
Official TitleThe Molecular Basis of Erythrocyte Invasion by Plasmodium Vivax Into Duffy-Negative Erythrocytes in Children in Bandiagara, Mali
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.

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 monthly from November 2017 to January 2018 and from June to November 2018. 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 TypeObservational
Study PhaseN/A
Estimated Enrollment
400
Allocation
Not Available
Interventional Model
Not Available
Masking
Not Available
Primary Purpose
Not Available
Conditions
Malaria
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodNon-Probability Sample
Study PopulationThe present study will detect P. vivax infections in children of the Bandiagara region.
Intervention
Not Available
Study Groups/Cohorts
Children
Children of the Bandiagara region.

Study Arms
Not Available
Arm Intervention/Treatment

Recruitment Information

Recruitment Status:Recruiting
Enrollment400
Completion DateDecember 31, 2019
Eligibility 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.
GenderAll
Age6 Years to 10 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Mali

Administrative Information

NCT Number:NCT03304691
Other Study ID Numbers
999917165
17-I-N165
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Not Available
Investigators
Principal Investigator
Louis H Miller, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)