The NLR SkinApp: Testing a Supporting mHealth Tool for Frontline Health Workers Performing Skin Screening in Ethiopia and Tanzania.

Background: The prevalence of skin diseases such as leprosy, and limited dermatological knowledge among frontline health workers (FHWs) in rural areas of Sub-Saharan Africa, led to the development of the NLR SkinApp: a mobile application (app) that supports FHWs to promptly diagnose and treat, or suspect and refer patients with skin diseases. The app includes common skin diseases, neglected tropical skin diseases (skin NTDs) such as leprosy, and HIV/AIDS-related skin conditions. This study aimed to test the supporting role of the NLR SkinApp by examining the diagnostic accuracy of its third edition. Methods: A cross-sectional study was conducted in East Hararghe, Ethiopia, as well as the Mwanza and Morogoro region, Tanzania, in 2018-2019. Diagnostic accuracy was measured against a diagnosis confirmed by two dermatologists/dermatological medical experts (reference standard) in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The potential negative effect of an incorrect management recommendation was expressed on a scale of one to four. Results: A total of 443 patients with suspected skin conditions were included. The FHWs using the NLR SkinApp diagnosed 45% of the patients accurately. The values of the sensitivity of the FHWs using the NLR SkinApp in determining the correct diagnosis ranged from 23% for HIV/AIDS-related skin conditions to 76.9% for eczema, and the specificity from 69.6% for eczema to 99.3% for tinea capitis/corporis. The inter-rater reliability among the FHWs for the diagnoses made, expressed as the percent agreement, was 58% compared to 96% among the dermatologists. Of the management recommendations given on the basis of incorrect diagnoses, around one-third could have a potential negative effect. Conclusions: The results for diagnosing eczema are encouraging, demonstrating the potential contribution of the NLR SkinApp to dermatological and leprosy care by FHWs. Further studies with a bigger sample size and comparing FHWs with and without using the NLR SkinApp are needed to obtain a better understanding of the added value of the NLR SkinApp as a mobile health (mHealth) tool in supporting FHWs to diagnose and treat skin diseases.

Predicted Pharmacokinetic Interactions Between Hormonal Contraception and Single or Intermittently Dosed Rifampicin.

The scale-up of rifampicin-based prevention regimens is an essential part of the global leprosy strategy. Daily rifampicin may reduce the effectiveness of the oral contraceptive pill (OCP), but little is known about the effects of rifampicin at the less frequent dosing intervals used for leprosy prophylaxis. As many women of reproductive age rely on OCP for family planning, evaluating the interaction with less-than-daily rifampicin regimens would enhance the scalability and acceptability of leprosy prophylaxis. Using a semi-mechanistic pharmacokinetic model of rifampicin induction, we simulated predicted changes in OCP clearance when coadministered with varying rifampicin dosing schedules. Rifampicin given as a single dose (600 or 1200 mg) or 600 mg every 4 weeks was not predicted to result in a clinically relevant interaction with OCP, defined as a >25% increase in clearance. Simulations of daily rifampicin were predicted to increase OCP clearance within the range of observed changes previously reported in the literature. Therefore, our findings suggest that OCP efficacy will be maintained when coadministered with rifampicin-based leprosy prophylaxis regimens of 600 mg once, 1200 mg once, and 600 mg every 4 weeks. This work provides reassurance to stakeholders that leprosy prophylaxis can be used with OCP without any additional recommendations for contraception prevention.

Implementation approaches for leprosy prevention with single-dose rifampicin: A support tool for decision making.

BACKGROUND: In the past 15 years, the decline in annually detected leprosy patients has stagnated. To reduce the transmission of Mycobacterium leprae, the World Health Organization recommends single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients. Various approaches to administer SDR-PEP have been piloted. However, requirements and criteria to select the most suitable approach were missing. The aims of this study were to develop an evidence-informed decision tool to support leprosy programme managers in selecting an SDR-PEP implementation approach, and to assess its user-friendliness among stakeholders without SDR-PEP experience. METHODOLOGY: The development process comprised two phases. First, a draft tool was developed based on a literature review and semi-structured interviews with experts from various countries, organisations and institutes. This led to: an overview of existing SDR-PEP approaches and their characteristics; understanding the requirements and best circumstances for these approaches; and, identification of relevant criteria to select an approach. In the second phase the tool's usability and applicability was assessed, through interviews and a focus group discussion with intended, inexperienced users; leprosy programme managers and non-governmental organization (NGO) staff. PRINCIPAL FINDINGS: Five SDR-PEP implementation approaches were identified. The levels of endemicity and stigma, and the accessibility of an area were identified as most relevant criteria to select an approach. There was an information gap on cost-effectiveness, while successful implementation depends on availability of resources. Five basic requirements, irrespective of the approach, were identified: stakeholder support; availability of medication; compliant health system; trained health staff; and health education. Two added benefits of the tool were identified: its potential value for advocacy and for training. CONCLUSION: An evidence-informed SDR-PEP decision tool to support the selection of implementation approaches for leprosy prevention was developed. While the tool was evaluated by potential users, more research is needed to further improve the tool, especially health-economic studies, to ensure efficient and cost-effective implementation of SDR-PEP.

Prolonged delays in leprosy case detection in a leprosy hot spot setting in Eastern Ethiopia.

BACKGROUND: Leprosy or Hansen's disease is known to cause disability and disfigurement. A delay in case detection of leprosy patients can lead to severe outcomes. In Ethiopia, the disability rates caused by leprosy among new cases are relatively high compared to other endemic countries. This suggests the existence of hidden leprosy cases in the community and a delay in timely detection. To reduce disability rates, it is crucial to identify the factors associated with this delay. This study aimed to determine the extent of delay in case detection among leprosy cases in Eastern Ethiopia. METHODS: This cross-sectional explorative study was conducted in January and February 2019 among 100 leprosy patients diagnosed ≤6 months prior to inclusion. A structured questionnaire was used to collect data, including the initial onset of symptoms, and the reasons for delayed diagnosis. Descriptive statistics, including percentages and medians, were used to describe the case detection delay. Logistic regression analysis was carried out to evaluate the predictors of delay in case detection of >12 months. FINDINGS: The median age of patients was 35 years, with a range of 7 to 72 years. The majority were male (80%) and rural residents (90%). The median delay in case detection was 12 months (interquartile range 10-36 months) among the included patients. The mean delay in case detection was 22 months, with a maximum delay of 96 months. The overall prevalence of disability among the study population was 42% (12% grade I and 30% grade II). Fear of stigma (p = 0.018) and experiencing painless symptoms (p = 0.018) were highly associated with a delay in case detection of >12 months. CONCLUSIONS: Being afraid of stigma and having painless symptoms, which are often misinterpreted as non-alarming at the onset of the disease, were associated with a delay in case detection. This study showed the need to increase knowledge on early symptoms of leprosy among affected communities. Furthermore, it is important to support initiatives that reduce leprosy related stigma and promote health worker training in leprosy control activities.

Development of a questionnaire to determine the case detection delay of leprosy: A mixed-methods cultural validation study.

BACKGROUND: Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient's indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A 'Question-by-Question Guide' was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org. CONCLUSIONS/SIGNIFICANCE: It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.

PEP4LEP study protocol: integrated skin screening and SDR-PEP administration for leprosy prevention: comparing the effectiveness and feasibility of a community-based intervention to a health centre-based intervention in Ethiopia, Mozambique and Tanzania.

INTRODUCTION: Leprosy, or Hansen's disease, remains a cause of preventable disability. Early detection, treatment and prevention are key to reducing transmission. Post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) reduces the risk of developing leprosy when administered to screened contacts of patients. This has been adopted in the WHO leprosy guidelines. The PEP4LEP study aims to determine the most effective and feasible method of screening people at risk of developing leprosy and administering chemoprophylaxis to contribute to interrupting transmission. METHODS AND ANALYSIS: PEP4LEP is a cluster-randomised implementation trial comparing two interventions of integrated skin screening combined with SDR-PEP distribution to contacts of patients with leprosy in Ethiopia, Mozambique and Tanzania. One intervention is community-based, using skin camps to screen approximately 100 community contacts per leprosy patient, and to administer SDR-PEP when eligible. The other intervention is health centre-based, inviting household contacts of leprosy patients to be screened in a local health centre and subsequently receive SDR-PEP when eligible. The mobile health (mHealth) tool SkinApp will support health workers' capacity in integrated skin screening. The effectiveness of both interventions will be compared by assessing the rate of patients with leprosy detected and case detection delay in months, as well as feasibility in terms of cost-effectiveness and acceptability. ETHICS AND DISSEMINATION: Ethical approval was obtained from the national ethical committees of Ethiopia (MoSHE), Mozambique (CNBS) and Tanzania (NIMR/MoHCDEC). Study results will be published open access in peer-reviewed journals, providing evidence for the implementation of innovative leprosy screening methods and chemoprophylaxis to policymakers. TRIAL REGISTRATION NUMBER: NL7294 (NTR7503).

The State of Affairs in Post-Exposure Leprosy Prevention: A Descriptive Meta-Analysis on Immuno- and Chemo-Prophylaxis.

OBJECTIVE: Annually, over 200,000 people are diagnosed with leprosy, also called Hansen's disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy. METHODS: A systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: "leprosy" and "population" or "contacts" and "prevention" or "prophylaxis." Subsequently, Infolep.org and Google Scholar were searched and the "snowball method" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria. RESULTS: After deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months post-vaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accepted. Since 2018, SDR-PEP is included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. CONCLUSION: Progress has been made in the areas of chemoprophylaxis and immunoprophylaxis to prevent leprosy in contacts of patients. Investing in vaccine studies, like LepVax and MiP, and increasing harmonization between tuberculosis (TB) and leprosy research groups is important. SDR-PEP is promising as a chemoprophylactic agent, and further implementation should be promoted. More chemoprophylaxis research is needed on: enhanced medication regimens; interventions in varying (epidemiological) settings, including focal mass drug administration (fMDA); specific approaches per contact type; combinations with screening variations and field-friendly rapid tests, if available in the future; community and health staff education; ongoing antibiotic resistance surveillance; and administering chemoprophylaxis with SDR-PEP prior to BCG administration. Additionally, both leprosy prophylactic drug registration nationally and prophylactic drug availability globally at low or no cost are important for the implementation and further upscaling of preventive measures against leprosy, such as SDR-PEP and new vaccines.

Packaging Patients and Handing Them Over: Communication Context and Persuasion in the Emergency Department.

STUDY OBJECTIVE: Communication is commonly understood by health professional researchers to consist of relatively isolated exchanges of information. The social and organizational context is given limited credit. This article examines the significance of the environmental complexity of the emergency department (ED) in influencing communication strategies and makes the case for adopting a richer understanding of organizational communication. METHODS: This study draws on approximately 12 months (1,600 hours) of ethnographic observations, yielding approximately 4,500 interactions across 260 clinicians and staff in the EDs of 2 metropolitan public teaching hospitals in Sydney, Australia. RESULTS: The study identifies 5 communication competencies of increasing complexity that emergency clinicians need to accomplish. Furthermore, it identifies several factors-hierarchy, formally imposed organizational boundaries and roles, power, and education-that contribute to the collective function of ensuring smooth patient transfer through and out of the ED. These factors are expressed by and shape external communication with clinicians from other hospital departments. CONCLUSION: This study shows that handoff of patients from the ED to other hospital departments is a complex communication process that involves more than a series of "checklistable" information exchanges. Clinicians must learn to use both negotiation and persuasion to achieve objectives.