Neglected Tropical Diseases (NTDs) are estimated to cause more than 500,000 deaths per year, almost exclusively affecting those living in impoverished rural and urban areas of low-income countries [1]. They are also characterised by a lack of research support and development of specific drugs, diagnostics, and vaccines [2,3]. For many NTDs, scientific information is lacking due to a paucity of research, often because they occur in settings with little access to the resources required to conduct high-quality research such as randomised trials. This lack of research in turn limits the development of evidence-based guidance to inform clinical and programme responses. Humanitarian organisations often work in these settings and commonly have access to the extra resources and collaborations with academic institutions needed to support such activities. Therefore, these organisations have a relatively unique opportunity to obtain important, new information on NTDs through the performance and publication of operational research using observational data. While observational studies cannot be used to make causal claims due to the inherent risk of bias and confounding, such data can nevertheless provide valuable information for health care management, hypothesis generation, and trend analysis [4]. Here we describe how operational data generated from a Medecins Sans Frontieres (MSF) Buruli ulcer (BU) management programme provided important information that contributed to the development of a global BU treatment guidance that addressed a number of complex management issues involving BU-HIV coinfection. BU is a necrotising infection of skin and subcutaneous tissue caused by Mycobacterium ulcerans. It commonly affects children in remote, resource-limited settings and, when severe, is associated with prolonged illness and long-term disability [5]. The main burden of BU is in West and Central Africa—regions also burdened with high HIV prevalence. All 15 countries in West and Central Africa reporting BU cases have an adult HIV prevalence of 1%–5%. Therefore, there is a significant potential for BU and HIV to occur in the same individual. Until recently, however, there has been very little known about the epidemiology, clinical consequences, and management implications of BU-HIV coinfection. Critical unanswered questions include the following: Is HIV a risk factor for BU? Does HIV affect BU disease presentation and severity, or does it influence outcomes such as mortality, BU cure rates, and healing times? How should BU-HIV coinfected patients be managed, when should antiretroviral treatment (ART) start, and what BU treatment regimens should be used in the face of potential interactions with antiretroviral drugs? In 2013, due to an increasing recognition of the importance and complexity of managing BU-HIV co-infection and the lack of guidance to aid in its management, World Health Organization (WHO) initiated the process of developing some core guidance principles, informed by a panel of experts [6,7]. Recommendations were based on their experience managing BU-HIV coinfection and what little scientific information was available on BU-HIV coinfection. The main body of available published information from which to draw guidance came from the Medecins Sans Frontieres BU treatment programme in Akonolinga, a town lying in the Nyong River basin in the central province of Cameroon [8]. The programme was based in a Ministry of Health district hospital and began treating BU patients in 2002. From the outset, a prospective observational database of routinely collected data was implemented for all patients treated for BU. HIV testing was initially introduced in 2002 for cases where clinical suspicion was high. However, it began to be recognised that BU-HIV coinfection was a significant issue, and in 2008 systematic HIV testing was introduced. Thus, the opportunity arose to acquire unique data on this coinfection. By May 2013, 1,130 patients had been treated for BU, and since the introduction of systematic HIV testing 29% of adults and 4% of children tested positive.