Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali

NCT01168271 | Recruiting

• 2 other identifiers: 99991015610-I-N156
• Study Type: observational
• Target: 15,000
• Locations: 1 country
• Sites: 2

Brief Summary

Malaria caused by Plasmodium falciparum continues to be a global problem with devastating consequences. A greater understanding of the immunologic and parasitologic factors associated with infection and disease is badly needed, and will accelerate the development of highly protective vaccines for both mothers and children. Pregnancy malaria is associated with low birth weight, maternal anemia, and gestational hypertension, and both inflammation and the fetal response to infection may contribute to these poor outcomes. Childhood malaria is a major cause of mortality, and we have found that risk of childhood malaria is related to in utero exposure to pregnancy malaria, as well as other host factors like iron status and constitutive cytokine levels. Pregnancy malaria is caused by a distinct parasite binding phenotype, and as our primary hypothesis in this study we speculate that severe childhood malaria parasites may also have distinct features. A longitudinal cohort study will be conducted in Ouelessebougou, Mali an area of intense seasonal transmission. Up to 2000 pregnant women and their infants and 2000 children ages 0 - 3 will be enrolled and followed to age 5 years, with clinical evaluation and periodic venous and peripheral blood samples obtained. In addition, 2000 febrile children up to age 10 years will be enrolled at the Ouelessebougou district health centers or the Gabriel Toure Pediatric Hospital in Bamako, Mali, with acute and convalescent samples being obtained and 500 pregnant women enrolled at the health centers and hospital in Ouelessebougou district or the Gabriel Toure Hospital in Bamako for a case-control study on pregnancy malaria and preeclampsia. Clinical, parasitologic and host response (including immunologic) endpoints will be analyzed using appropriate statistical methods, including possible confounders, to determine factors associated with infection and disease in pregnant woman and young children.

Conditions

Malaria

Keywords

Observational; Newborns; Hospitalized; Febrile; Resistance; Natural History

Outcome Measures

Primary Outcomes (1)

• Maternal, placental, parasite and host associated with resistence to malaria infection and diseases in children

  To assess the relationship between malaria exposure during pregnancy and maternal and fetal outcomes; and to determine factors (maternal, placental, parasite, and host) associated with susceptibility or resistance to malaria infection and diseases in children

  up to 5 years for infants and children

Study Arms (5)

Children Ages 0-3 years

Children aged 0-3 years in Ouelessebougou

Febrile Hospitalized Children

Febrile hospitalized children aged 0-10 years in Ouelessebougou or the Pediatric service of Gabriel Toure Hospital in Bamako

Later Childhood and Adolescence

Re-enrollees who were originally enrolled at birth and completed the Pregnant Women and Newborn Cohort

Non-Hospitalized Children

Febrile non-hospitalized children aged 0-10 years in Ouelessebougou or the Pediatric service of Gabriel Toure Hospital in Bamako

Pregnant Women + Newborns

Pregnant women presenting for antenatal consultations and delivery and their newborns

Eligibility Criteria

• Age: 1 Day - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women presenting for antenatal consultations and delivery and their newborns; children aged 0-3 years in Ouelessebougou and Febrile children ages 0-10 years hospitalized and non-hospitalized in Ouelessebougou or the Pediatric service of Gabriel Toure Hospital in Bamako; Re-enrollees who were originally enrolled at birth and completed the Pregnant Women and Newborn Cohort

You may qualify if:

• A study participant must satisfy the following criteria to be enrolled in this study:
• Pregnant women aged 15-45 years and their newborn infants who are residents of the district of Ouelessebougou for at least one year at the time of enrollment; OR
• Children who previously participated in the 1st cohort of "pregnant women and their newborn infants", OR
• Children aged 3 years or less, who are residents of the district of Ouelessebougou for at least one year at the time of enrollment, OR
• Febrile hospitalized children (aged 0-10 years), including those with positive and negative blood smears for P. falciparum in Ouelessebougou or the pediatric service of Gabriel Toure Hospital in Bamako. Febrile non-hospitalized children (aged 0-10 years) with non-severe malaria will be recruited at outpatient clinics in Ouelessebougou district health hospital and nearby facilities, with no chronic or serious illness.
• Pregnant women aged 15-25 in Ouelessebougou district health centers or maternity unit of Gabriel Toure Hospital in Bamako and for a case-control study of pregnancy malaria and preeclampsia. Cases include women with signs/symptoms of preeclampsia. Control pregnant women without signs/symptoms of preeclampsia will be recruited sequentially after identification of individual cases, matched for parity, age (+/-2 years) and pregnancy trimester.
• The study participant or parent/guardian understands the study and gives informed consent for participation of themselves and/or their child, and agrees to have samples stored.

You may not qualify if:

• A participant will be excluded from the study if any one or more of the following criteria are met:
• Chronic, debilitating illness, other than malaria, determined by history and physical examination of mother or study participant.
• Conditions that in the judgment of the investigator could increase the risk to the volunteer.
• History of previous participation in a malaria vaccine trial.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Gabriel Toure Hospital

Bamako, Mali

RECRUITING

Ouelessebougou Clinical Research Center

Wolossébougou, Mali

RECRUITING

Related Publications (7)

• Fried M, Nosten F, Brockman A, Brabin BJ, Duffy PE. Maternal antibodies block malaria. Nature. 1998 Oct 29;395(6705):851-2. doi: 10.1038/27570. No abstract available.

  PMID: 9804416 BACKGROUND

• Ho M, Singh B, Looareesuwan S, Davis TM, Bunnag D, White NJ. Clinical correlates of in vitro Plasmodium falciparum cytoadherence. Infect Immun. 1991 Mar;59(3):873-8. doi: 10.1128/iai.59.3.873-878.1991.

  PMID: 1997437 BACKGROUND

• Muehlenbachs A, Mutabingwa TK, Edmonds S, Fried M, Duffy PE. Hypertension and maternal-fetal conflict during placental malaria. PLoS Med. 2006 Nov;3(11):e446. doi: 10.1371/journal.pmed.0030446.

  PMID: 17105340 BACKGROUND

• Doritchamou JYA, Renn JP, Jenkins B, Mahamar A, Dicko A, Fried M, Duffy PE. A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates. Elife. 2022 Feb 1;11:e76264. doi: 10.7554/eLife.76264.

  PMID: 35103596 DERIVED

• Mahamar A, Gonzales Hurtado PA, Morrison R, Boone R, Attaher O, Diarra BS, Gaoussou S, Issiaka D, Dicko A, Duffy PE, Fried M. Plasma biomarkers of hemoglobin loss in Plasmodium falciparum-infected children identified by quantitative proteomics. Blood. 2022 Apr 14;139(15):2361-2376. doi: 10.1182/blood.2021014045.

  PMID: 34871370 DERIVED

• Mahamar A, Andemel N, Swihart B, Sidibe Y, Gaoussou S, Barry A, Traore M, Attaher O, Dembele AB, Diarra BS, Keita S, Dicko A, Duffy PE, Fried M. Malaria Infection Is Common and Associated With Perinatal Mortality and Preterm Delivery Despite Widespread Use of Chemoprevention in Mali: An Observational Study 2010 to 2014. Clin Infect Dis. 2021 Oct 20;73(8):1355-1361. doi: 10.1093/cid/ciab301.

  PMID: 33846719 DERIVED

• Fried M, Kurtis JD, Swihart B, Pond-Tor S, Barry A, Sidibe Y, Gaoussou S, Traore M, Keita S, Mahamar A, Attaher O, Dembele AB, Cisse KB, Diarra BS, Kanoute MB, Dicko A, Duffy PE. Systemic Inflammatory Response to Malaria During Pregnancy Is Associated With Pregnancy Loss and Preterm Delivery. Clin Infect Dis. 2017 Oct 30;65(10):1729-1735. doi: 10.1093/cid/cix623.

  PMID: 29020221 DERIVED

MeSH Terms

Conditions

Malaria; Fever

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Patrick E Duffy, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michal Fried, Ph.D.

CONTACT

(240) 747-7880; michal.fried@nih.gov

Patrick E Duffy, M.D.

CONTACT

(301) 761-5089; duffype@niaid.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 23, 2010
• Study Start: August 30, 2010
• Last Updated: June 1, 2026

Record last verified: 2026-03-11

Data Sharing

• IPD Sharing: Will not share

Locations

MA (2)