A systematic review of the noma evidence landscape: current knowledge and gaps

BackgroundNoma (cancrum oris) is a severe gangrenous disease of the mouth and oro-facial structures. Noma often presents in young children alongside extreme poverty, malnutrition and poor environmental sanitation. Gaps however remain in understanding its aetiology, pathogenesis, preventative and treatment efficacy. Methods and findingsWe systematically searched databases to find all primary research studies reporting patients of any age diagnosed with noma (including clinical trials, cohort studies, case-control, cross-sectional, other observational studies, case studies and case series) up to 7 December 2022. The 366 publications included in our review describe 15,082 noma patients, from manuscripts published between 1839 and 2022. While several cohort (n=53) and cross-sectional (n=29) studies were identified, accounting for a total of 13,489 enrolled noma patients, only 6 interventional studies enrolling a total of 101 patients (range 7 to 26 patients) were identified, with only one interventional study from the last decade. Over 380 different treatment modalities were described for noma management. Disease aetiology reports identified 117 different microorganisms across 113 publications, but none were more widespread or uniquely related to noma development. Since 2000, most (91.2%) cases have been reported in Sub-Saharan Africa, but not solely in the historical noma belt. Noma was also observed in Asia and the Americas. There were 212 different possible noma risk factors presented in 269 (73.5%) publications, with substantial heterogeneity. The definition and harmonisation of noma progression staging are poorly standardised and reported. ConclusionThe current literature provides very weak evidence to guide policy. Our thorough review also identified substantial knowledge gaps, and highlights the lack of prospective high-quality studies on the physiopathology of the disease that can guide therapeutic and preventive policies. Urgent research investment is therefore essential to improve the situation, especially as noma is now duly recognised as a Neglected Tropical Disease (NTD) by the World Health Organization (WHO). Research in contextO_ST_ABSWhat is already known on this topicC_ST_ABSNo exhaustive synthesis of the noma evidence landscape existed at the inception of this review in 2018, particularly any relating to evidence-based risk factors, microbiology, prevention, treatment, or the burden of disease. Since commencing this work, high-quality systematic and scoping reviews on noma have been published, using existing data collected from clinical trials, longitudinal patient observational studies and retrospective studies as their sources. This systematic review was designed to encompass a wider evidence landscape, including case series and case reports as well. We hypothesised that in the context of scarce noma data, case series and reports are an underutilised source of information that could potentially help address research priorities and bridge knowledge gaps. We conducted comprehensive literature searches from database inception to 7 December 2022 across 11 different global and regional databases. Searches were not restricted on language of publication. Both English and French search strings were developed. English search terms included: "noma OR cancrum oris OR necrotising ulcerative stomatitis OR necrotising stomatitis OR Gangrenous stomatitis". Noma publications on patients of any age and all primary research designs were included. Animal studies and studies on people with noma-like illnesses were excluded. What this study addsThis review includes a wider range of published material, encompassing case reports and case studies not included in previous reviews, therefore providing an exhaustive synthesis of all reported information. This work creates a comprehensive baseline knowledge of any reported risk factors, microbiology, and treatment modalities for noma from which to innovatively approach research and address gaps. From synthesis across a broad scope of study designs, we provide recommendations to guide methodology and reporting for future noma research. How this study might affect research, practice or policyThe current research evidence base has a considerable gap concerning the multi-factorial etiopathogenesis of noma. The paucity and methodological heterogeneity of high-quality studies in this area means that caution is needed in interpreting this evidence when designing future evidence-guided strategies and interventions to tackle noma. By including a broad range of study designs, this work provides valuable insights and a rich and exhaustive reference point from which to approach the design of future strategies and new robust studies that are desperately needed to address the many outstanding knowledge gaps of noma.