NCT06769815

Host Immunity, Plasmodium and Pathogens Co-Infections

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 2,000 (estimated)
• Sponsor: Institut Pasteur · Industry
• Sex: All
• Age: —
• Healthy volunteers: Accepted

Summary

Few studies have focused on malaria co-infections, mainly caused by Plasmodium falciparum, occurring mainly in children under 5 years of age in sub-Saharan Africa. These studies have focused on malaria-associated bacterial sepsis, with an estimated prevalence of 9.1% and associated mortality of 15.0%. However, no study has documented infectious sites other than the blood compartment, considered viruses and parasites as possible causes of infection in addition to bacteria, and used molecular diagnostic methods based on PCRs, which are more sensitive. Thus, the prevalence of these co-infections and the spectrum of pathogens involved are probably underestimated, as is the impact of these co-infections on mortality. Furthermore, it has been shown that malaria infections can condition the immune cells of naturally exposed individuals, potentially leading to greater susceptibility to all types of infection. But these mechanisms have never been documented in the context of co-infections. The WHO recommends the use of broad-spectrum antibiotics in cases of severe malaria, in addition to antimalarial drugs, as it can be difficult to differentiate clinically between severe malaria and severe bacterial infection (bacteremia, pneumonia and meningitis). Yet this empirical use of antibiotics could be contributing to an increase in antibiotic resistance. Identifying the determinants of co-infection with malaria and severe bacterial infection would enable this treatment to be better targeted. These determinants remain undetermined as no study has considered other causes of severe bacterial infection other than bacteremia, used appropriate statistical methodology (univariate analysis only) and explored important determinants, notably the capacity of children's innate immunity to respond to severe bacterial infection.

Detailed description

This is a prospective multicenter longitudinal study. The study will focus on several populations: * febrile children: aged between 6 and 60 months consulting ; * non-febrile children: aged between 6 and 60 months consulting. * Pregnant women. * newborns: those born to mothers included in the study with or without pregnancy-associated malaria. The study will be based on : * Clinical and microbiological documentation of acute febrile episodes in recruited children * Documentation of vital status in children 3 months after recruitment * Ability of host cells to respond to infections.

Conditions

• Malaria
• Bacterial Co-infection

Interventions

Type	Name	Description
OTHER	Blood sample	For febrile children at the time of inclusion : 6.25 ml to 8.25 ml of blood ; For non febrile children at the time of inclusion : 4 ml of blood ; For pregnant women at the time of inclusion : 5 ml of peripheral blood, 5 ml of placental blood, 20 to 40 ml of umbilical cord blood ; For new borns : drop of blood on child's heel each month and 5 ml of blood the 12th and last month.
OTHER	Urine sample	For febrile children : 10 ml of urine
OTHER	oropharyngeal sample	For febrile children : oropharyngeal swab sampling
OTHER	Optionnal : stool sample	For febrile children (only as part of the care of the child) : 5g stool
OTHER	Optionnal : cerebrospinal fluid	For febrile children (only as part of the care of the child in case of suspected meningitis) : 4 additional drops of cerebrospinal fluid
OTHER	placental biopsy	For pregnant women : placental biopsy the size of 2 rice grains

Timeline

• Start date: 2025-02-15
• Primary completion: 2027-02-15
• Completion: 2027-08-15
• First posted: 2025-01-10
• Last updated: 2025-01-24