• Thematic field of study: Polymorphism in Toll-like receptors and cytokine response according to malaria severity in adults and children
• Supervisor(s): Prof Marielle Bouyoy Akotet, Prof Patricia Mawili Mboumba, Dr Jacques Mari Ndong Ngomo, DrNoe Patrick Mbondoukwe
• Contact details: dpmawili@gmail.com

Summary of Hosting Lab

The activities of the Joint Research Unit on Infectious Agents and Associated Pathologies (JRAIP) focus on the genetic diversity of pathogens, and studies on factors influencing the expression of known or emerging parasites, bacteria and viruses. Indeed, the expression of diseases linked to these pathogens are strongly associated with the susceptibility of the hosts, in particular with the quality of their immune response. Identifying the immunologic factors involved in the severity of infectious diseases leads to the development of vaccines. Within
UMRAIP, a team is working on molecular characterization using conventional PCR, real-time PCR and RFLP PCR. Another team is studying the cytokine response of the hosts. The UMRAIP is a research unit of the University of Health Sciences in which several students have been
introduced to basic, clinical and operational research; and carried out their research work.

Project Description

recent work by the Department of Parasitology Mycology Tropical Medicine of the USS has highlighted a change in the epidemiological profile of malaria in Gabon, with a higher susceptibility of older children, although younger children are still the most affected by malaria-
related deaths. In addition, certain clinical forms, hitherto very rarely described in adolescents and adults 20 years ago, are currently being reported. In addition, there is limited data on the factors associated with resuscitation admission in some children, compared with others
hospitalized for the same clinical forms of severe malaria. Some studies have shown an association between the genetic polymorphism of Toll-like receptors and the severity of malaria. The same applies to the cytokine response.
The objective of this project is to analyze the relationship between the polymorphism of TLR2, TLR4, and TLR6 and the cytokine response (IL-6, TNF alpha, and IL-10) and the clinical forms of malaria as well as in the case of resuscitation transfer in adults and children with malaria. TLR
polymorphism will be analyzed by qPCR, and cytokine response using ELISA and Luminex.

Publications

Guémas E, Coppée R, Ménard S, du Manoir M, Nsango S, Makaba Mvumbi D, Nakoune E, Eboumbou Moukoko CE, Bouyou Akotet MK, et al. Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central Africa: a cross-sectional study. Lancet Microbe. 2023 Dec;4(12):e983-e993.
Ndong Ngomo JM, Mawili-Mboumba DP, M'Bondoukwé NP, Ditombi BM, Koumba Lengongo JV, Batchy Ognagosso FB, Bouyou-Akotet MK. Drug Resistance Molecular Markers of Plasmodium falciparum and Severity of Malaria in Febrile Children in the Sentinel Site for
Malaria Surveillance of Melen in Gabon: Additional Data from the Plasmodium Diversity Network African Network. Trop Med Infect Dis. 2023 Mar 23;8(4):184.

M'Bondoukwé NP, Moutongo R, Gbédandé K, Ndong Ngomo JM, Hountohotegbé T, Adamou R, Koumba Lengongo JV, Pambou Bello K, Mawili-Mboumba DP, Luty AJF, Bouyou-Akotet MK. Circulating IL-6, IL-10, and TNF-alpha and IL-10/IL-6 and IL-10/TNF-alpha ratio profiles of polyparasitized individuals in rural and urban areas of gabon. PLoS Negl Trop Dis. 2022 Apr 14;16(4):e0010308.

Mawili-Mboumba DP, Mbuyi MLT, M'bondoukwe NP, Bouyou-Akotet MK. Plasmodium falciparum Allelic Diversity: A Comparison of DNA Extraction from Isolates Collected on Rapid Diagnostic Tests (Rdts) and Filter Paper. Iran J Parasitol. 2021 Oct-Dec;16(4):555-559.
Bouyou-Akotet MK, Kombila M, Kremsner PG, Mavoungou E. Cytokine profiles in peripheral, placental and cord blood in pregnant women from an area endemic for Plasmodium falciparum. Eur Cytokine Netw. 2004 Apr-Jun;15(2):120-5.

Major Lab techniques

Malaria microscopic diagnosis; Nucleic acid extraction, qPCR, Luminex Immuno, Protocol
writing, results analysis and interpretation (basic data analysis), and scientific communication.

• Thematic field of study: Blastocystis infection and Intestinal microbiota analysis
• Supervisor(s):Bouyou-Akotet Marielle, Mawili Mboumba Denise, M’Bondoukwe Noe, Ndong Ngomo Jacques-Mari
• Contact details: dpmawili@gmail.com

Summary of Hosting Lab

Department of Parasitology-Mycology, at Université des Sciences de la Santé in Gabon, is a Labreference in Parasitology-Mycology working on genetic diversity, immune response and epidemiology of endemic parasitic diseases.
Prof Bouyou the head of this department has expertise on infectious diseases and by leading the national COVID-19 scientific committee has developed experience in diagnosis, therapy, and immune response to this disease. She also supervised national guidelines in collaboration with
health authorities. On a scientific level, she has collaborated with various studies on COVID-19 disease and has been a co-investigator of networks such as Aphrocov focused on COVID-19 diagnosis and care.
Clinical trials on COVID-19 disease have been performed in Gabon and the department team has participated.
The research performed by the team of Prof Bouyou has an important impact on a scientific level and contributes to providing accurate data to the health authorities, the national programmes to adapt the control strategies and improve care. Therefore, we will use our experience in epidemiology, molecular analysis, immune response measurement, data management, and in student supervision to perform our projects as Brains partner.

Project Description

The factors influencing the severity of coronavirus disease-2019 (COVID-19), mainly the immune mechanisms remained incompletely understood. It is also admitted that the factors such as older age, which were recognized risk factors for severe COVID-19 in occident, seem to
do not be in cause in SSA. Indeed, severe disease and deaths mostly occurred in individuals aged less than 60 years old, as well as in urban settings. Thus specific immune mechanism can suspected among African population. Immune dysregulation at the transcriptional, protein and
cellular levels, which could induce an imbalance of inflammatory responses was also shown to influence the course of cOVID-19. Proinflammatory markers such as cytokine and chemokine response, as weel as Toll Like Receptors are involved in the immune response towards SARS-Cov2 infection. Moreover, the distribution of TLR agonists as adjuvant is also investigated for vaccine research. Pro-inflammatory genes (e.g., CXCL6) and serum chemokines (e.g., CXCL9) and TLR7, 9, and 10 allele and genotype frequencies were found to differ according to COVID-19 severity. Nevertheless, all these data were obtained in studies performed out of sub-Saharan Africa. Data from West and central Africa are scarce; although a better knowledge of immune response would help in the design of future vaccines.
The aim of the present project is to analyze the relationship with the hsot immune response and the severity of COVID-19 in patients living in Libreville, the epicentre of the stusy
– TNF-alpha, IL-6, CXC8 levels will be measured in plasma from COVID-19 patients and compared between severe and uncomplicated forms.
– TLR genetic polymorphism as well as interferon-stimulating gene types and frequencies will also be assessed in the different groups.

Plasma concentration of tumor necrosis factor (TNF), interleukin-6 (IL-6), chemokine ligand 2 (CCL2), C-X-C motif ligand 8 (CXCL8) will be measured with ELISA. Gene expression assay was used in the real-time PCR assays

Publications

Ayo Bivigou E et al, Early Alterations of QTc in Patients with COVID-19 Treated with Hydroxychloroquine or Chloroquine in Libreville, Gabon. Clin Pract. 12(4):482-490. doi: 10.3390/clinpract12040052. 2022
Mintsa-Nguema R et al, Could pooled samples method affect SARS-CoV-2 diagnosis accuracy using BGI and Sansure-Biotech RT-PCR kits used in Gabon, Central Africa? PLoS One 17(1):e0262733. doi: 10.1371/journal.pone.0262733. eCollection 2022.

Igala M et al, Co-infection paludisme et coronavirus 19 chez les patients admis au service d’infectiologie COVID du Centre Hospitalier Universitaire de Libreville. PAMJ. 41:101 ; 10.11604/pamj.2022.41.101.28751. 2022
Ndong Ngomo JM, Mawili-Mboumba DP, M'Bondoukwé NP, Ditombi BM, Koumba Lengongo JV, Batchy Ognagosso FB, Bouyou-Akotet MK. Drug Resistance Molecular Markers of Plasmodium falciparum and Severity of Malaria in Febrile Children in the Sentinel Site for
Malaria Surveillance of Melen in Gabon: Additional Data from the Plasmodium Diversity Network African Network. Trop Med Infect Dis. 2023 Mar 23;8(4):184.
MBondoukwé NP, Moutongo R, Gbédandé K, Ndong Ngomo JM, Hountohotegbé T, Adamou R, Koumba Lengongo JV, Pambou Bello K, Mawili-Mboumba DP, Luty AJF, Bouyou-Akotet MK. Circulating IL-6, IL-10, and TNF-alpha and IL-10/IL-6 and IL-10/TNF-alpha ratio profiles of
polyparasitized individuals in rural and urban areas of gabon. PLoS Negl Trop Dis. 2022 Apr 14;16(4):e0010308.

Major Lab techniques

Sample processing, cytokine measurement, molecular, Collaborative research, Documentation
and reporting, Data analysis