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NCT Number: NCT06769815

Host Immunity, Plasmodium and Pathogens Co-Infections

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.

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Key information

Conditions

Malaria Bacterial Co-infection Coinfection Infections Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

blood sample

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

Other

For febrile children : 10 ml of urine

oropharyngeal sample

Other

For febrile children : oropharyngeal swab sampling

Optionnal : stool sample

Other

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

Optionnal : cerebrospinal fluid

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

Other

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

Primary outcomes

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

    Time frame: 3 years

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

Secondary outcomes

  1. Assess the impact of malaria co-infections on mortality

    Time frame: 2 years

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

  2. Identify the underlying immunological mechanisms mediating malaria co-infections

    Time frame: 2 years

    Concentration of cytokines IL6, IL1β and TNFα and IL 10 in children under 5 years of age

  3. Identify epigenetic and transcriptomic modifications in infant, maternal and placental blood cells mediating malaria co-infections

    Time frame: 2 years

    Expression level of transcripts according to the populations studied will be measured by RNA-seq

  4. Identify molecules associated with epigenetic modifications (metabolome, proteome).

    Time frame: 2 years

    Expression level of proteins and metabolites according to the populations studied will be measured by RNA-seq

  5. Identify determinants of malaria co-infections and severe bacterial infections.

    Time frame: 2 years

    The number of malaria co-infection events associated with severe bacterial infection in febrile children under 5 years of age.

Study contacts

Contact information is provided by the study sponsor or research team.

Bich-Tram Huynh, PhD

CONTACT

[email protected]

+33 1 53 55 18 50

Celia Dechavanne, PhD

CONTACT

[email protected]

+229 99 35 05 98

Sponsors and collaborators

Lead sponsor

Institut Pasteur

Industry

Collaborators

  • Institut de Recherche pour le Developpement

Registry information

Acronym: HIPPI

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jan 10, 2025
Registry last updated
Jan 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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