COVID-19 Social Science and Public Engagement Action Research in Vietnam, Indonesia and Nepal (SPEAR): Protocol for a mixed methods study exploring the experiences and impacts of COVID-19 for healthcare workers and vulnerable communities

Background: When the novel coronavirus – SARS-CoV-2 – started to spread globally, there was a call for social and behavioral scientists to conduct research to explore the wider socio-cultural contexts of coronavirus disease 2019 (COVID-19), to understand vulnerabilities, as well as to increase engagement within communities to facilitate adoption of public health measures. In this manuscript, we describe the protocol for a study conducted in Indonesia, Nepal, and Vietnam. In the study, we explore how the COVID-19 pandemic is affecting individuals and their communities. We focus on the wider health and economic impacts of COVID-19, in particular emerging and increased burden on mental health, as well as new or deepened vulnerabilities in the communities. The introduction of vaccines has added another layer of complexity and highlights differences in acceptance and inequalities around access.  Methods: We use mixed methods, combining survey methods and social media surveillance to gain a picture of the general situation within each country, with in-depth qualitative methods to gain a deeper understanding of issues, coupled with a synergistic engagement component. We also include an exploration of the role of social media in revealing or driving perceptions of the pandemic more broadly. Participants include health workers and members of communities from 13 sites across the three countries. Data collection is spread across two phases. Phase 1 is concerned with exploring lived experiences, impacts on working lives and livelihoods, mental health and coping strategies. Phase 2 is concerned with acceptance of COVID-19 vaccines, factors that increase and reduce acceptance, and factors that influence access. Conclusions: We will disseminate findings in multiple ways including short reports and policy briefs, articles in peer-reviewed journals, and digital diaries will be edited into short films and uploaded onto social media sites.</ns3:p

Exploratory urinary metabolomics of type 1 leprosy reactions

Background: Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves. Although curable with multidrug therapy, leprosy is complicated by acute inflammatory episodes called reactions, which are the major causes of irreversible neuropathy in leprosy that occur before, during, and even after treatment. Early diagnosis and prompt treatment of reactions reduces the risk of permanent disability. Methods: This exploratory study investigated whether urinary metabolic profiles could be identified that correlate with early signs of reversal reactions (RR). A prospective cohort of leprosy patients with and without reactions and endemic controls was recruited in Nepal. Urine-derived metabolic profiles were measured longitudinally. Thus, a conventional area of biomarker identification for leprosy was extended to non-invasive urine testing. Results: It was found that the urinary metabolome could be used to discriminate endemic controls from untreated patients with mycobacterial disease. Moreover, metabolic signatures in the urine of patients developing RR were clearly different before RR onset compared to those at RR diagnosis. Conclusions: This study indicates that urinary metabolic profiles are promising host biomarkers for the detection of intra-individual changes during acute inflammation in leprosy and could contribute to early treatment and prevention of tissue damage

Mycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal

Silent transmission of Mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. Therefore, the development of tools for the early diagnosis of M. leprae infection should be emphasised in leprosy research. As part of the continuing effort to identify antigens that have diagnostic potential, unique M. leprae peptides derived from predicted virulence-associated proteins (group IV.A) were identified using advanced genome pattern programs and bioinformatics. Based on human leukocyte antigen (HLA)-binding motifs, we selected 21 peptides that were predicted to be promiscuous HLA-class I T-cell epitopes and eight peptides that were predicted to be HLA-class II restricted T-cell epitopes for field-testing in Brazil, Ethiopia and Nepal. High levels of interferon (IFN)-γ were induced when peripheral blood mononuclear cells (PBMCs) from tuberculoid/borderline tuberculoid leprosy patients located in Brazil and Ethiopia were stimulated with the ML2055 p35 peptide. PBMCs that were isolated from healthy endemic controls living in areas with high leprosy prevalence (EChigh) in Ethiopia also responded to the ML2055 p35 peptide. The Brazilian EChigh group recognised the ML1358 p20 and ML1358 p24 peptides. None of the peptides were recognised by PBMCs from healthy controls living in non-endemic region. In Nepal, mixtures of these peptides induced the production of IFN-γ by the PBMCs of leprosy patients and EChigh. Therefore, the M. leprae virulence-associated peptides identified in this study may be useful for identifying exposure to M. leprae in population with differing HLA polymorphisms

Additional file 2: Figure S1. of Longitudinal immune profiles in type 1 leprosy reactions in Bangladesh, Brazil, Ethiopia and Nepal

IFN-γ in response to M.leprae-unique protein ML2478 in 6 day cultures of PBMC (see Figure 3). Simultaneously, PBMC were cultured with proteins: ML0009, ML0121, ML0141, ML0188, ML1601, ML1976, ML1989, ML1990, ML2283, ML2478, ML2531, ML2532 and ML2567 (data not shown). Figure S2. IP-10 (A), TNF (B), IL-17 (C), VEGF (D) , IL1-β (E) and G-CSF (F) production in same cultures as described in Figure S1. Figure S3. IP-10 and IL-17 (A) after stimulation with M. leprae. IP-10/ IL-10 and IL-17/ IL-10 ratios are indicated (B, C). ROC curves were calculated for IP-10/ IL-10 and IL-17 /IL-10. Ratios for patients without reactions are shown as controls (D). Figure S4. IP-10 (A), IFN-β (B) and CCL18 (C) in sera. Figure S5. Antibodies against M.leprae protein ML2028 in sera determined by ELISA. Optical density readings were performed using a 1:200 dilution. Median values are indicated by horizontal lines. Figure S6. IFN-β in sera derived from patients developing RR in the absence of clinical signs of reactions and at least three months before reaction (before RR), at diagnosis of reaction before steroids (RR) or after MDT and RR, at least one month after end of steroids (after RR). For ROC values, timepoints at least three months before RR and at RR diagnosis before steroids were considered. IFN-β levels for controls were not detectable. (DOCX 260 kb

Longitudinal immune profiles in type 1 leprosy reactions in Bangladesh, Brazil, Ethiopia and Nepal

Immunogenetics and cellular immunology of bacterial infectious disease