Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

Dr Justin Komguep Nono

South Africa

EDCTP portfolio: Career Development Fellowships

Dr Justin Nono Komguep aims to determine the molecular mechanisms behind differential schistosomiasis-driven liver pathology in children in Cameroon.

Mapping hepato-intestinal schistosomiasis in children

Intestinal schistosomiasis, specifically at the chronic stage, constitutes a health risk for 230 million people worldwide. The disease morbidity primarily results from the infected individuals’ poor ability to immune-regulate their response to parasite eggs trapped in their liver. A progressive fibroproliferative response ensues leading to organ impairment, pathology and - when left untreated - death. The molecular mechanisms behind schistosomiasis-driven liver fibrosis remain elusive. The challenge is to determine these mechanisms.

The challenge

Dr Nono reasons that a differential expression profile in schistosomiasis-diseased patients with a comparable egg burden but a different stage of advancement of the liver fibrosis may unveil candidate factors in the host that, by their sole differential expression, alter the progression of liver fibrosis in those patients.

The present study conducted by Dr Nono and his team investigates through full-genome mRNA sequencing of blood cells the factors which are differentially expressed by school children with schistosomiasis, factors that that associate with the rapid onset and/or fast progression of liver fibrosis.

The study takes place at a highly endemic site for schistosomiasis in the locality of Yoro in Cameroon around the Mbam river and is rooted in a cross-sectional study on 1000 school children. The study specifically aims to define the knowledge, habits and practices of school children regarding schistosomiasis and the risk the disease represents in the area. Egg-defined prevalence of the disease will be related to individual habits. Secondly, the study assesses the advancement of liver fibro-pathology in the recruited children by ultrasonography and defines comparative clusters of individuals with similar parasitological status but different fibro-pathological (liver) status. Finally, the study determines by next-generation sequencing of children’s PBMCs-derived mRNA the differences in transcriptional profiles between children with fibrotic and non-fibrotic livers.

The project

The different aims of our project are expected to yield an updated map of the prevalence of schistosomiasis in the locality of Yoro. Unprecedentedly, it will define an ultrasonographic profile of the liver pathology in the children of this hepato-intestinal schistosomiasis endemic area. Potentially, it may unveil a unique library of host factors involved in the progression of pathological liver fibrosis in general and during schistosomiasis in particular.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Intestinal schistosomiasis, specifically at the chronic stage, constitutes a health risk for 230 million people worldwide. The disease morbidity primarily results from the infected individuals’ poor ability to immune-regulate their response to parasite eggs trapped in their liver. A progressive fibroproliferative response ensues leading to organ impairment, pathology and - when left untreated - death. The molecular mechanisms behind schistosomiasis-driven liver fibrosis remain elusive. The challenge is to determine these mechanisms.

Dr Nono reasons that a differential expression profile in schistosomiasis-diseased patients with a comparable egg burden but a different stage of advancement of the liver fibrosis may unveil candidate factors in the host that, by their sole differential expression, alter the progression of liver fibrosis in those patients.

The present study conducted by Dr Nono and his team investigates through full-genome mRNA sequencing of blood cells the factors which are differentially expressed by school children with schistosomiasis, factors that that associate with the rapid onset and/or fast progression of liver fibrosis.

The study takes place at a highly endemic site for schistosomiasis in the locality of Yoro in Cameroon around the Mbam river and is rooted in a cross-sectional study on 1000 school children. The study specifically aims to define the knowledge, habits and practices of school children regarding schistosomiasis and the risk the disease represents in the area. Egg-defined prevalence of the disease will be related to individual habits. Secondly, the study assesses the advancement of liver fibro-pathology in the recruited children by ultrasonography and defines comparative clusters of individuals with similar parasitological status but different fibro-pathological (liver) status. Finally, the study determines by next-generation sequencing of children’s PBMCs-derived mRNA the differences in transcriptional profiles between children with fibrotic and non-fibrotic livers.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The different aims of our project are expected to yield an updated map of the prevalence of schistosomiasis in the locality of Yoro. Unprecedentedly, it will define an ultrasonographic profile of the liver pathology in the children of this hepato-intestinal schistosomiasis endemic area. Potentially, it may unveil a unique library of host factors involved in the progression of pathological liver fibrosis in general and during schistosomiasis in particular.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M