Host Immunity, Plasmodium and Pathogens Co-Infections

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorInstitut Pasteur

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 volunteers

Qualifiers

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

Design model

Single group

Treatments tested in this trial

  • Blood sample

    Other intervention

    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

    Other intervention

    For febrile children : 10 ml of urine

  • oropharyngeal sample

    Other intervention

    For febrile children : oropharyngeal swab sampling

  • Optionnal : stool sample

    Other intervention

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

  • Optionnal : cerebrospinal fluid

    Other intervention

    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

    Other intervention

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

Treatment groups

2,000 Participants
are divided into 1 treatment group
Group A: Febrile and non febrile children, pregnant women and new bornsOther 6 interventions

Trial outcomes

Primary outcomes

1

Determine the extent and microbiological spectrum of malaria co-infections in children under 5.

the number of malaria co-infection events in febrile children.

Time frame
3 years

Secondary outcomes

1

Assess the impact of malaria co-infections on mortality

Number of deaths in children under 5 with malaria co-infection

Time frame
2 years
2

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

Time frame
2 years
3

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

Time frame
2 years
4

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

Time frame
2 years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institut Pasteur

Lead sponsor

Institut de Recherche pour le Developpement

Collaborator

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