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Background: Buruli ulcer is a disease of the skin and soft tissues caused by infection with a slow growing pathogen, Mycobacterium ulcerans. A vaccine for this disease is not available but M. ulcerans possesses a giant plasmid pMUM001 that harbours the polyketide synthase (PKS) genes encoding a multi-enzyme complex needed for the production of its unique lipid toxin called mycolactone, which is central to the pathogenesis of Buruli ulcer. We have studied the immunogenicity of enzymatic domains in humans with M. ulcerans disease, their contacts, as well as non-endemic areas controls. Methods: Between March 2013 and August 2015, heparinized whole blood was obtained from patients confirmed with Buruli ulcer. The blood samples were diluted 1 in 10 in Roswell Park Memorial Institute (RPMI) medium and incubated for 5 days with recombinant mycolactone PKS domains and mycolyltransferase antigen 85A (Ag85A). Blood samples were obtained before and at completion of antibiotic treatment for 8 weeks and again 8 weeks after completion of treatment. Supernatants were assayed for interferon-γ (IFN-γ) and interleukin-5 (IL-5) by enzyme-linked immunosorbent assay. Responses were compared with those of contacts and non-endemic controls. Results: More than 80% of patients and contacts from endemic areas produced IFN-γ in response to all the antigens except acyl carrier protein type 3 (ACP3) to which only 47% of active Buruli ulcer cases and 71% of contacts responded. The highest proportion of responders in cases and contacts was to load module ketosynthase domain (Ksalt) (100%) and enoylreductase (100%). Lower IL-5 responses were induced in a smaller proportion of patients ranging from 54% after ketoreductase type B stimulation to only 21% with ketosynthase type C (KS C). Among endemic area contacts, the, highest proportion was 73% responding to KS C and the lowest was 40% responding to acyltransferase with acetate specificity type 2. Contacts of Buruli ulcer patients produced significantly higher IFN-γ and IL-5 responses compared with those of patients to PKS domain antigens and to mycolyltransferase Ag85A of M. ulcerans. There was low or no response to all the antigens in non-endemic areas controls. IFN-γ and IL-5 responses of patients improved after treatment when compared to baseline results. Discussion: The major response to PKS antigen stimulation was IFN-γ and the strongest responses were observed in healthy contacts of patients living in areas endemic for Buruli ulcer. Patients elicited lower responses than healthy contacts, possibly due to the immunosuppressive effect of mycolactone, but the responses were enhanced after antibiotic treatment. A vaccine made up of the most immunogenic PKS domains combined with the mycolyltransferase Ag85A warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Community Based Surveillance Volunteers (CBSVs) have been instrumental in the management of Neglected Tropical Diseases (NTDs) but a concern that their services in scale up programmes may be affected due to high attrition rates has been widely acknowledged. We explored the roles and capacity needs of existing CBSVs to inform for a successful integrated NTD management programme in Ghana and similar contexts., Methods: We conducted qualitative interviews with 50 CBSVs, 21 Community Nurses, 4 Disease control officers, 7 skin NTD researchers, 2 skin NTD patients and a Director of District Health Services in Central Ghana. Interviews were digitally recorded, transcribed and coded prior to translation and thematic analysis., Results: The roles of CBSVs in NTD management were shown to have an impact on disease identification, surveillance, health seeking behaviours and status of CBSVs. Lack of motivation, inadequate structures for engagement of CBSVs within the health system and delayed management of reported cases were identified as gaps that hinder effective delivery of CBSV roles. Provision of incentives as recognition for the unpaid services rendered by CBSVs was seen as a major factor to reduce the rate of CBSV attrition in this scale up programme. Other factors included the formulation of policies by government to guide CBSV engagement, regular training of CBSV in NTD management as well as provision of resources and logistics., Conclusion: Measures including continuous training, institution of rewards and incentivization are important for ensuring the sustainability of CBSVs in the provision of skin NTD services in Ghana., (© 2023. The Author(s).)