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| ID | Type | Description | Link |
|---|---|---|---|
| IRB2024-01 | Other Identifier | IRB00006966 Institut Pasteur IRB #1 | |
| 043/2024/CBRS | Other Identifier | Comité de Bioéthique pour la Recherche en Santé |
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| Name | Class |
|---|---|
| Institut de Recherche pour le Developpement | OTHER_GOV |
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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.
This is a prospective multicenter longitudinal study.
The study will focus on several populations:
The study will be based on :
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Febrile and non febrile children, pregnant women and new borns | Other | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Determine the extent and microbiological spectrum of malaria co-infections in children under 5. | the number of malaria co-infection events in febrile children. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Assess the impact of malaria co-infections on mortality | Number of deaths in children under 5 with malaria co-infection | 2 years |
| Identify the underlying immunological mechanisms mediating malaria co-infections |
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Inclusion Criteria:
Febrile children:
Non-febrile children:
Pregnant women :
Newborns at delivery:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bich-Tram Huynh, PhD | Contact | +33 1 53 55 18 50 | bich-tram.huynh@pasteur.fr | |
| Celia Dechavanne, PhD | Contact | +229 99 35 05 98 | celia.dechavanne@ird.fr |
| Name | Affiliation | Role |
|---|---|---|
| Bich-Tram Huynh, PhD | Institut Pasteur | Study Director |
| Luc Douti, MD | CHU-Campus de Lomé | Principal Investigator |
| Serge Ekoué Gbadoe, MD |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| D060085 | Coinfection |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Urine sample | Other | For febrile children : 10 ml of urine |
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| oropharyngeal sample | Other | For febrile children : oropharyngeal swab sampling |
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| Optionnal : stool sample | Other | For febrile children (only as part of the care of the child) : 5g stool |
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| 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 |
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| placental biopsy | Other | For pregnant women : placental biopsy the size of 2 rice grains |
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Concentration of cytokines IL6, IL1β and TNFα and IL 10 in children under 5 years of age
| 2 years |
| 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 | 2 years |
| 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 | 2 years |
| Identify determinants of malaria co-infections and severe bacterial infections. | The number of malaria co-infection events associated with severe bacterial infection in febrile children under 5 years of age. | 2 years |
| Hôpital de district Polyclinique de Zio-Tsévié |
| Principal Investigator |
| D000079426 |
| Vector Borne Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |