MRC PhD students

Title of thesis: The influence of helminths on immune responses to HIV  

Promoter: Prof G Walzl (University of Stellenbosch),
Co-supervised by Dr P Kipiella (University of KZN).

Rationale
Because of their faecal-oral transmission mode, intestinal parasites (helminths) are highly prevalent in areas that are densely populated, lack sanitation and clean water supplies.  Approximately a third of the world’s population, the majority of whom are in Africa and other developing countries, harbours one or more of these parasites.. South African surveys have reported prevalence ranging from 80-100% among school children. One of the outstanding features of helminth infections include their persistence despite immune responses directed against them. The protracted interaction between the parasites’ and hosts’ immune system results in chronic activation of immune cells. Further, they induce a predominantly Th2 type of response, with subsequent down regulation of Th1 responses that are effective in controlling intracellular infections such as TB and HIV.  

Hypothesis
The current project is based on the hypothesis that prolonged exposure to and infection with intestinal parasites results in chronic activation and impairment of the individual’s immune system. The activated immune cells and associated molecules facilitate easy entry and replication of the Human Immunodeficiency Virus (HIV). Once infected with HIV, these individuals then progress faster to full-blown AIDS, owing to their impaired immune system.  

Project Objectives

• To determine whether exposure to helminths disrupts the peripheral lymphocyte populations (lymphocyte phenotype assays) in subjects with or without HIV/helminth co-infections.
• To assess whether individuals infected with helminths express high levels of immune activation markers compared with their uninfected counterparts.
• To assess the lymphoproliferative responses, Th1 and Th2 cytokine production in subjects with or without HIV/helminth co-infections.
• To determine the expression of Th1 and Th2 genes in HIV/helminth co-infections to ascertain if helminths induce a predominant Th2 profile.
• To determine if all the above are negatively associated with competent immune responses to HIV and enhance the disease progression.

Relevance to the mandate of the Nutritional Intervention Research Unit (NIRU)
Intestinal parasites are known to be a direct cause of malnutrition; however, the subtle but deleterious effects of these infections are largely ignored because of competing priorities. This creates a need for a broader focus in helminthiasis research, because nutrition is such a cross-cutting area. Since a competent immune system feeds directly from an adequate nutritional status, the Helminthiasis Group within NIRU aims to integrate nutritional and immunological research with a focus on helminthes, and to extend this to the HIV challenge.