About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
aged between 6 and 60 months
Disqualifiers
scheduled caesarean section for current pregnancy
Caesarean section in previous pregnancies
chronic non-infectious pathology during pregnancy (diabetes, hypertension, pre-eclampsia)
Trial design
Single group
Treatments tested in this trial
Blood sample
Other interventionFor 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
Other interventionFor febrile children : 10 ml of urine
oropharyngeal sample
Other interventionFor febrile children : oropharyngeal swab sampling
Optionnal : stool sample
Other interventionFor febrile children (only as part of the care of the child) : 5g stool
Optionnal : cerebrospinal fluid
Other interventionFor febrile children (only as part of the care of the child in case of suspected meningitis) : 4 additional drops of cerebrospinal fluid
placental biopsy
Other interventionFor pregnant women : placental biopsy the size of 2 rice grains
Treatment groups
Trial outcomes
Primary outcomes
Determine the extent and microbiological spectrum of malaria co-infections in children under 5.
the number of malaria co-infection events in febrile children.
Secondary outcomes
Assess the impact of malaria co-infections on mortality
Number of deaths in children under 5 with malaria co-infection
Identify the underlying immunological mechanisms mediating malaria co-infections
Concentration of cytokines IL6, IL1β and TNFα and IL 10 in children under 5 years of age
Identify epigenetic and transcriptomic modifications in infant, maternal and placental blood cells mediating malaria co-infections
Expression level of transcripts according to the populations studied will be measured by RNA-seq
Identify molecules associated with epigenetic modifications (metabolome, proteome).
Expression level of proteins and metabolites according to the populations studied will be measured by RNA-seq
Locations
Sponsors and contacts
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Institut Pasteur
Lead sponsor
Institut de Recherche pour le Developpement
Collaborator
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