Host Immunity, Plasmodium and Pathogens Co-Infections

NCT ID: NCT06769815

Last Updated: 2025-01-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 2000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-15
• Study Completion Date: 2027-08-15

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Febrile and non febrile children, pregnant women and new borns

The study population is composed of children under the age of 5, which is also the population most at risk of malaria, living in the endemic areas of Lomé and Tsévié in Togo.

Group Type: OTHER

Blood sample

Intervention Type: OTHER

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.

Urine sample

Intervention Type: OTHER

For febrile children : 10 ml of urine

oropharyngeal sample

Intervention Type: OTHER

For febrile children : oropharyngeal swab sampling

Optionnal : stool sample

Intervention Type: OTHER

For febrile children (only as part of the care of the child) : 5g stool

Optionnal : cerebrospinal fluid

Intervention Type: OTHER

For febrile children (only as part of the care of the child in case of suspected meningitis) : 4 additional drops of cerebrospinal fluid

placental biopsy

Intervention Type: OTHER

For pregnant women : placental biopsy the size of 2 rice grains

Interventions

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.

Intervention Type: OTHER

Urine sample

For febrile children : 10 ml of urine

Intervention Type: OTHER

oropharyngeal sample

For febrile children : oropharyngeal swab sampling

Intervention Type: OTHER

Optionnal : stool sample

For febrile children (only as part of the care of the child) : 5g stool

Intervention Type: 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

Intervention Type: OTHER

placental biopsy

For pregnant women : placental biopsy the size of 2 rice grains

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Febrile children:

• aged between 6 and 60 months
• with a febrile episode lasting less than 7 days (axillary temperature >=37.5° Celsius)
• whose state of health is compatible with a minimum single blood sample volume of 6.25 ml

Non-febrile children:

• aged between 6 and 60 months
• with axillary temperature <37.5° Celsius
• no clinical signs of infection at the time of inclusion
• no infectious episode or fever for 7 days

Pregnant women :

• giving birth in the project's partner health center
• intending to reside in the study area during the newborn follow-up period
• with a mono-fetal pregnancy
• With an apparently uncomplicated delivery not requiring referral to a higher-level health facility

Newborns at delivery:

• Born at term (determined by Ballard score)
• whose parents or legal guardians reside in the study area during the newborn's follow-up period

Exclusion Criteria

For all :

• person already participating in another biomedical research project.

For febrile and non-febrile children:

• chronic non-infectious pathology (cancer, malnutrition, etc.)

For pregnant women

• scheduled caesarean section for current pregnancy
• Caesarean section in previous pregnancies
• chronic non-infectious pathology during pregnancy (diabetes, hypertension, pre-eclampsia)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role: collaborator

Institut Pasteur

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bich-Tram Huynh, PhD

Role: STUDY_DIRECTOR

Institut Pasteur

Luc Douti, MD

Role: PRINCIPAL_INVESTIGATOR

CHU-Campus de Lomé

Serge Ekoué Gbadoe, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital de district Polyclinique de Zio-Tsévié

Central Contacts

Bich-Tram Huynh, PhD

Role: CONTACT

bich-tram.huynh@pasteur.fr

+33 1 53 55 18 50

Celia Dechavanne, PhD

Role: CONTACT

celia.dechavanne@ird.fr

+229 99 35 05 98

Other Identifiers

IRB2024-01

Identifier Type: OTHER

Identifier Source: secondary_id

043/2024/CBRS

Identifier Type: OTHER

Identifier Source: secondary_id

2023-079

Identifier Type: -

Identifier Source: org_study_id