Malaria co-infections in children in sub-Saharan Africa (Mal-CoChild)

Few studies have investigated malaria co-infections, mainly caused by Plasmodium falciparum, which mostly affect children under 5 years old in sub-Saharan Africa. These studies have mainly focused on malaria-associated bacteremia with an estimated prevalence of 9.1% [7.8-10.4] and an associated mortality of 15.0% [8.0-23.0]. No study has (1) documented other infectious sites in addition to the bloodstream, (2) considered viruses and parasites as possible causes of infection in addition to bacteria, and (3) used molecular diagnostic methods based on PCR, which are more sensitive. Therefore, the prevalence of these co-infections and the spectrum of pathogens involved are likely underestimated, and consequently the impact of these co-infections on mortality as well. The WHO recommends administering broad-spectrum antibiotics in severe malaria cases in addition to antimalarials because it can be difficult to clinically differentiate severe malaria from severe invasive bacterial infections (bacteremia, pneumonia, and meningitis). However, this indicriminate use of antibiotics could contribute to the growing problem of antibiotic resistance. Identifying the determinants of co-infection by malaria and severe bacterial infection in children would enable more targeted antimicrobial management. These determinants remain unknown because no study has (1) considered other causes of severe bacterial infections other than bacteremia, (2) used appropriate statistical methodology (only univariate analysis), and (3) explored important determinants such as parasitemia and the innate immunity capacity of children to respond to severe bacterial infection.

Blood, urine and oropharyngeal samples will be systematically collected. Additionaly, if clinically indicated, stool, and cerebrospinal fluid samples will also be taken. These samples will be analyzed using both conventional culture methods and PCR to detect parasitic, bacterial, and viral pathogens responsible for the febrile illness. Also, 240 afebrile children will be recruited, and a blood sample will be collected to determine their baseline malaria parasitemia and innate immune profile. Immunological analyses will measure the ability of monocytes to secrete certain cytokines after stimulation in febrile and afebrile children, allowing the evaluation of the innate monocyte response capacity related to the occurrence of severe bacterial infection. Epidemiological data concerning socio-demographic characteristics, medical history, clinical data, and anthropometric measurements will be collected. All epidemiological, microbiological, and immunological data will be integrated with appropriate statistical models to achieve the objectives. In particular, propensity score methods will be used to evaluate the impact of malaria co-infections on mortality, and multivariate logistic models will be used to identify determinants of malaria and severe bacterial co-infections. The study is expected to yield a comprehensive understanding of the prevalence and spectrum of pathogens involved in malaria co-infections, along with their impact on mortality. By guiding the development of targeted antimicrobial management strategies, the insights generated by this study have the potential to significantly improve patient outcomes. Furthermore, this study will contribute to improving the understanding of innate immunity and could open up new research avenues. Lastly, identifying others causes of non-malarial fever will provide valuable insights for prioritizing public health actions aimed at reducing infant morbidity and mortality.

Project details

Epidemiology
Vulnerable Populations

Jan 2024 — Jan 2029

$504,842

France