MalariaNCT03304691
Molecular Basis of Erythrocyte Invasion by Plasmodium Vivax Into Duffy-Negative Erythrocytes in Mali
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in Mali.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months and olderHealthy volunteers can take part
- Conditions the study is for
- Malaria
- How many people
- 667 participants
- Where
- 2 sitesMali
- Study dates
- 30 Jun 2021to 30 Mar 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Subjects will be selected to enroll based on community permission and sensitization strategies for both the Bandiagara and Yirimadio sites.
Who may be able to join
- For inclusion in the cohort substudy, a child must meet the following criteria:
- Is greater than or equal to 6 months and less than or equal to 10 years of age
- Residing in Bandiagara for at least 6 months prior to screening
- Will be available to attend visits during this study
- Agrees to provide urine and stool samples during this study
- Agrees to allow storage of samples for future research.
Show all 12Show fewer
- For inclusion in the cross-sectional substudy, an individual must meet the following criteria:
- Aged greater than or equal to 6 months;
- 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.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
Mali2 sites
Yirimadio Community Health Center
Bamako
Bandiagara Malaria Program (BMP) Clinic
Bandiagara
About this study
Official title: The 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.
Read more
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.
...
Read the 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. 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.
- Conditions
- Malaria
- Keywords
- Malaria, Parasitemia, Anemia, Ligand, Anopheles gambiae, Natural History
- Medical subject headings
- Malaria, Parasitemia, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Bandiagara, Mali | Children of both sexes between 6 months and 10 years of age. | |
| Yirimadio, Bamako, Mali | Children and adults of both sexes 6 months and older. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify the P. vivax ligands for infection of Duffy blood group negative Africans by RNA sequencing (RNAseq) of blood from P. vivax cases.
Identify the P. vivax ligands for infection of Duffy blood group negative Africans by RNA sequencing (RNAseq) of blood from P. vivax cases.
Measured: Monthly surveillance visits throughout length of the study
Secondary outcomes (5)
Determine the prevalence of P. vivax in Yirimadio in Duffy negative population
Measured: Beginning, peak, and end of transmission season
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 in these populations.
Measured: Monthly surveillance visits throughout length of the study
Study the association between P. vivax parasitemia and anemia in Duffy-negative Africans.
Measured: 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.
Measured: Monthly surveillance visits throughout length of the study
Determine the number of clones of P. vivax circulating in the community by DNA sequencing of polymorphic parasite proteins.
Measured: Monthly surveillance visits throughout length of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2017
- Study start30 Jun 2021
- Primary completion1 Mar 2023
- Study completion30 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 667 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Louis H Miller, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03304691
- Sponsor's protocol ID
- 999917165
- Other IDs
- 17-I-N165
- Status last verified
- Feb 2023
- First submitted
- 6 Oct 2017
- Last updated
- 31 Oct 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gunalan K, Niangaly A, Thera MA, Doumbo OK, Miller LH. Plasmodium vivax Infections of Duffy-Negative Erythrocytes: Historically Undetected or a Recent Adaptation? Trends Parasitol. 2018 May;34(5):420-429. doi: 10.1016/j.pt.2018.02.006. Epub 2018 Mar 9.
PubMed 29530446Gunalan K, Sa JM, Moraes Barros RR, Anzick SL, Caleon RL, Mershon JP, Kanakabandi K, Paneru M, Virtaneva K, Martens C, Barnwell JW, Ribeiro JM, Miller LH. Transcriptome profiling of Plasmodium vivax in Saimiri monkeys identifies potential ligands for invasion. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7053-7061. doi: 10.1073/pnas.1818485116. Epub 2019 Mar 14.
PubMed 30872477Niangaly A, Karthigayan Gunalan, Amed Ouattara, Coulibaly D, Sa JM, Adams M, Travassos MA, Ferrero J, Laurens MB, Kone AK, Thera MA, Plowe CV, Miller LH, Doumbo OK. Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in Bandiagara, Mali. Am J Trop Med Hyg. 2017 Sep;97(3):744-752. doi: 10.4269/ajtmh.17-0254. Epub 2017 Jul 27.
PubMed 28749772
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Molecular Basis of Erythrocyte Invasion by Plasmodium Vivax Into Duffy-Negative Erythrocytes in Mali
- ClinicalTrials.gov ID
- NCT03304691
- Acronym / sponsor ID
- 999917165
- Conditions
- Malaria
- Keywords
- Malaria, Parasitemia, Anemia, Ligand, Anopheles gambiae, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 667 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 30 Jun 2021 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 9 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bandiagara, Mali | – | –Children of both sexes between 6 months and 10 years of age. |
| Yirimadio, Bamako, Mali | – | –Children and adults of both sexes 6 months and older. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects will be selected to enroll based on community permission and sensitization strategies for both the Bandiagara and Yirimadio sites.
Key inclusion criteria (12 listed)
- Is greater than or equal to 6 months and less than or equal to 10 years of age
- Residing in Bandiagara for at least 6 months prior to screening
- Will be available to attend visits during this study
- Agrees to provide urine and stool samples during this study
- Agrees to allow storage of samples for future research.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Identify the P. vivax ligands for infection of Duffy blood group negative Africans by RNA sequencing (RNAseq) of blood from P. vivax cases.
5 secondary outcomes
Determine the prevalence of P. vivax in Yirimadio in Duffy negative population
Time frame: Beginning, peak, and end of transmission season
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 in these populations.
Time frame: Monthly surveillance visits throughout length of the study
Study the association between P. vivax parasitemia and anemia in Duffy-negative Africans.
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2023.
- Background: PubMed 29530446Gunalan K, Niangaly A, Thera MA, Doumbo OK, Miller LH. Plasmodium vivax Infections of Duffy-Negative Erythrocytes: Historically Undetected or a Recent Adaptation? Trends Parasitol. 2018 May;34(5):420-429. doi: 10.1016/j.pt.2018.02.006. Epub 2018 Mar 9.
- Background: PubMed 30872477Gunalan K, Sa JM, Moraes Barros RR, Anzick SL, Caleon RL, Mershon JP, Kanakabandi K, Paneru M, Virtaneva K, Martens C, Barnwell JW, Ribeiro JM, Miller LH. Transcriptome profiling of Plasmodium vivax in Saimiri monkeys identifies potential ligands for invasion. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7053-7061. doi: 10.1073/pnas.1818485116. Epub 2019 Mar 14.
- Background: PubMed 28749772Niangaly A, Karthigayan Gunalan, Amed Ouattara, Coulibaly D, Sa JM, Adams M, Travassos MA, Ferrero J, Laurens MB, Kone AK, Thera MA, Plowe CV, Miller LH, Doumbo OK. Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in Bandiagara, Mali. Am J Trop Med Hyg. 2017 Sep;97(3):744-752. doi: 10.4269/ajtmh.17-0254. Epub 2017 Jul 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louis H Miller, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in Mali.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03304691, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2023.