Mansonella perstans effects on BCG vaccine-induced protection against childhood tuberculosis as well as tuberculosis disease severity and recovery in Ghana and Cameroon

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Tuberculosis (TB) is one of the most distressing infectious diseases causing more than 1.5 millions deaths per year. Control of TB is largely impeded by the lack of an effective vaccine and the necessity of a challenging long-term treatment regimen. BCG, the only available vaccine, provides only partial protection against TB manifestations. Helminth parasites are well known to polarize and suppress immune responses and may constrain protective immunity against TB e.g. induced by BCG vaccination.In the initial funding period we demonstrated that Mansonella perstans, a previously largely neglected filarial nematode, is widely distributed in Ghana and Cameroon. Wolbachia endosymbionts were found on M. perstans and first comprehensive M. perstans studies in Ghana suggested so far unknown Culicoides vector species. We detected M. perstans infection specific immune polarization and immune regulation, which modulated immune responses against mycobacterial diseases. Furthermore, we investigated TB-specific immune pathology and identified promising surrogate biomarkers of TB disease and recovery. Finally, we established doxycycline-based treatment of M. perstans infection and identified treatment-dependent changes in host immune responses. Based on these results, we hypothesize that M. perstans infection impairs the efficacy of BCG vaccination by modulating protective immunity and affects TB disease manifestation and recovery.The main aims of the next project period are to i) identify novel M. perstans vector species and characterize ecological vector niches; ii) characterize M. perstans effects on TB disease manifestation and recovery in Ghana and Cameroon; iii) determine the effect of M. perstans infection on prevention of TB progression of BCG vaccinated children with close TB patient contact. Children that are in close contact to TB patients face the highest risk of M. tuberculosis infection and of developing TB disease. Therefore, we will recruit healthy BCG-vaccinated children (n=2000) with close contact to an infectious TB index case. Children will be characterized for M. perstans infection and will be followed for one year to determine TB disease progression rates and severity within M. perstans positive and negative groups. In addition, TB patients with or without M. perstans infection will be characterized for disease severity and will be monitored for three months to determine efficient recovery under therapy. Immune biomarker candidates identified from the initial project period will be analysed for their predictive value.This is a comprehensive approach to determine the biological significance of M. perstans infection on vaccine induced protection and disease manifestation in TB. The results may lead to novel recommendations for M. perstans control by doxycycline treatment and may help to determine the impact of helminth co-infection on the limited efficacy of BCG vaccination for protection against TB.