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Associate Professor
Kwadwo Asamoah Kusi

Ghana

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Project Title

Clinical and immunopathological consequences of chronic HBV and Plasmodium falciparum co-infections

Project Objectives

Aim 1: To determine the effect of chronic HBV infection on the outcome of Plasmodium liver stage infection. Aim 2: To determine the cytokine expression profiles of white cells from chronic HBV patients with and without Plasmodium infection over a one year period.

Host Organisation

Department Institution Country
University of Ghana GH

EDCTP Project

TMA2018SF-2456

EDCTP Program

EDCTP2

EDCTP Project Call

Senior Fellowship (SF)

Study Design

case-control design

Project Summary

Hepatitis B virus (HBV) and Plasmodium are very common pathogens in sub-Saharan Africa and sometimes occur as co-infections. Both pathogens infect liver cells and elicit pathogen-specific immune responses that may mediate both protection and immunopathology. HBV infection of the liver, even in an acute form, is usually long term, while Plasmodium liver infections are usually over a limited period after an infectious mosquito bite. Immune responses, especially against chronic HBV infections, can thus affect liver stage malaria-specific T cell responses. There is however no consensus on how HBV induced immune responses affect liver stage anti-malarial immunity. Plasmodium infection could also, in the reverse, contribute to liver pathology in chronic HBV-infected subjects. Malaria vaccine candidate trials usually exclude individuals infected with immune modulating pathogens such as HBV. However, vaccine induced responses could be compromised in HBV-infected persons if vaccines are later approved for routine immunization. Investigation of the potential impact of chronic HBV infection on malaria liver stage-specific immune response quality is therefore essential. This study will test the primary hypothesis that chronic HBV infections elicit a strong regulatory T cell environment that dampens induction of the needed pro-inflammatory response against liver stage malaria parasites. We will recruit chronic HBV-infected subjects from the Gastroenterology Clinic of the Korle Bu Teaching Hospital in Accra and followed up once a month over one year. Primary outcome measure will be Plasmodium liver stage infection, to be indirectly assessed by i) elevated antibody levels against the parasite circumsporozoite protein as evidence of infectious bite exposure, and ii) detection of asexual blood stage parasites as evidence of completed liver cycle. We will determine anti-CSP antibody seroprevalence and blood stage parasite infection every month by microscopy, RDTs and PCR. We will measure levels of selected cytokines and liver enzymes every three months and HBV viral load at study baseline and at seven months. We will also recruit a parallel cohort of healthy subjects as controls, follow up at similar time intervals and measure their anti-CSP antibody seroprevalence, parasite infection status, cytokine levels and liver enzymes for comparison. The study will provide useful data on the by-stander effects of chronic HBV infection on immunity and outcome of Plasmodium liver stage infections as well as the impact of liver stage Plasmodium infection on the clinical course of chronic HBV infection in co-infected individuals. The study will further be used to train three students at the PhD and MPhil levels.