Cytomegalovirus as a risk factor for TB and leishmaniasis
Led by Dr Lisa Stockdale (University of Oxford, UK), with Dr Robindra Basu Roy (LSHTM, UK), Dr Vivian Tamietti Martins (Federal University of Minas Gerais, Brazil), Assoc Prof Eduardo Coelho (Federal University of Minas Gerais, Brazil), and Prof Helen Fletcher (LSHTM, UK)
Tuberculosis and leishmaniasis are diseases that particularly affect some of the world's poorest populations. Caused by the microbes Mycobacterium tuberculosis and the microscopic parasite Leishmania spp. respectively, control of these diseases is hampered by a lack of effective vaccines. The drugs that are available require long regimes, have significant side effects, and treatment is complicated by antimicrobial resistance. In 2018, TB overtook HIV/AIDS as the largest cause of mortality due to a single infection, and visceral leishmaniasis (VL; the most serious form of the disease) is fatal in 95% of cases if left untreated.
The role of an accompanying viral infection influencing the development of TB and VL is well-known through the increased risk in People Living With HIV. Cytomegalovirus (CMV), another virus, has also recently been implicated in increased risk of TB disease. Our current understanding of TB and leishmaniasis is that the body's protective immune responses are skewed, enabling the microbes to remain in the body and cause disease. One of the immune molecules involved in this balance between pathogen persistence and pathogen clearance for both diseases is IL-10. It is linked with shifting this balance towards disease persistence. CMV has its own viral version of this molecule which acts similarly to human IL-10.
Using three unique sample sets to investigate risk of infection with TB in Gambian children, risk of developing TB disease in Ugandan people, and severity of leishmaniasis in Brazilian people, we hope to understand if and how CMV is implicated in increased risk of infection and disease. Not only will this information help to direct future VL and TB vaccine development but it may also drive development of a CMV vaccine as a possible cross-pathogen contribution to control of both diseases.