CO-INFECTION STUDIES PROGRAMME

Head of Programme: 

The Co-Infection Studies Programme developed from interest in the immunomodulating effects of chronic helminth infection, and the impact of such effects on major infectious diseases including tuberculosis, malaria and HIV infection; it has evolved to encompass interactions between infectious and non-communicable diseases (NCDs).

In the next five years we anticipate that a major component of our work will be to further investigate the relationship between helminths and allergy, building on our results, published in January 2011, which showed that anthelminthic treatment during pregnancy was associated with increased incidence of atopic eczema in infancy.

These results support the “Hygiene Hypothesis” and also the hypothesis that prenatal and very early life exposures are critical in programming allergic disease outcomes. We will address two key questions: first, whether effective de-worming programmes are likely to lead to an increased prevalence of allergic disease in tropical developing countries, and second, whether we can identify molecular and immunological mechanisms of helminth-induced protection against allergy in humans that can be harnessed for preventive and therapeutic interventions against allergy.

Another important aspect of prenatal programming is the inverse association between birth weight and blood pressure which has been reported from developed countries. In the context of our established birth cohort, we will investigate whether birth weight shows similar associations in this setting, and explore the relationship between pre-natal and early-childhood exposure to infections and blood pressure in school age children. High blood pressure is a critical risk factor for later cardiovascular disease.

Building on capacity established through training in the last five years, more studies are being developed which will investigate the relationship between infections, poverty and cognitive development and we will examine the relationship between infections and risk of neonatal encephalopathy. We will participate, together with the EPI programme, in cross-cutting studies on cancer in Uganda. Our role will be particularly to investigate the epidemiology and immunology of oncogenic infections.

Key questions will be whether the HIV epidemic has resulted in a secondary epidemic of oncogenic infections in the general population, and whether other co-infections, including helminths and malaria, modulate immune responses and susceptibility to infection with these pathogens and subsequent cancer outcomes.

Returning to our earlier interest in the role of co-infections in determining susceptibility to tuberculosis, we will conduct a study of household contacts of tuberculosis patients to investigate the effects not only of helminths, but also of malaria and cytomegalovirus co-infection, on susceptibility to infection with Mycobacterium tuberculosis, and on the innate and adaptive immune response to mycobacteria.

Our aim is therefore to investigate the epidemiological and immunological interactions between chronic, immunomodulating infections and both NCD and infectious disease outcomes in this context.
--Our specific objectives are to understand better the interactions between:
--Helminths and allergy
--Infections and high blood pressure in childhood
--Infections and neurocognitive development
--Infections and cancer
--Helminths and susceptibility to poverty-related infectious diseases

This research programme has the following on-going projects:
1-Mother and baby trial Entebbe
2-LaVIISWA
3-CISP Laboratory
4-Other CISP studies
5-Oncogenic viruses study
--ABAaNA study