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BACKGROUND: Case detection delay (CDD) in leprosy is defined as the period between the onset of the first signs and symptoms and the time of diagnosis. A tool, consisting of a questionnaire and a detailed guide for researchers, which includes photos of typical skin signs and notes on establishing the timing of events, was developed to determine this period of delay in months in recently diagnosed leprosy patients. The aims of the study were to determine the reliability and consistency of this CDD assessment tool. METHODS: This study was conducted in Ethiopia, Mozambique and Tanzania. Two types of consistency were considered: over time (test-retest reliability) and across different researchers (interrater reliability). A CDD questionnaire was administered to 167 leprosy patients who were diagnosed within 6 months prior to their inclusion. One month later, the same or another researcher re-administered the CDD questionnaire to the same patients. Both test-retest and interrater reliability were assessed using the intraclass correlation coefficient (ICC), where a value greater than or equal to 0.7 is considered acceptable. RESULTS: In this study, 10 participants (6.0%) were under 15 years of age, and 56 (33.5%) were women. In the test-retest assessment, the mean CDD from the first and second interviews was 23.7 months (95% CI 14.4-34.8) and 24.0 months (95% CI 14.8-33.2), respectively. The ICC for test-retest reliability was 0.99 (95% CI 0.994-0.997). For the interrater reliability assessment, the first and second interviews revealed a mean CDD of 24.7 months (95% CI 18.2-31.1) and 24.6 months (95% CI 18.7-30.5), respectively, with an ICC of 0.90 (95% CI 0.85-0.94). A standard error of measurement of 0.46 months was found in the test-retest and 1.03 months in the interrater measurement. Most answers given by participants during the first and second interviews were matching (≥86%). Most non-matching answers were

Introduction: Suboptimal doctor-patient communication drives inappropriate prescribing of antibiotics. We evaluated a communication intervention for general practitioners (GPs) in multicultural Dutch cities to improve antibiotic prescribing for respiratory tract infections (RTI). Methods: This was a non-randomized controlled before-after study. The study period was pre-intervention November 2019 – April 2020 and post-intervention November 2021 – April 2022. The intervention consisted of a live training (organized between September and November 2021), an E-learning, and patient material on antibiotics and antibiotic resistance in multiple languages. The primary outcome was the absolute number of prescribed antibiotic courses indicated for RTIs per GP; the secondary outcome was all prescribed antibiotics per GP. We compared the post-intervention differences in the mean number of prescribed antibiotics between the intervention (N = 25) and the control group (N = 110) by using an analysis of covariance (ANCOVA) test, while adjusting for the pre-intervention number of prescribed antibiotics. Additionally, intervention GPs rated the training and their knowledge and skills before the intervention and 3 months thereafter. Results: There was no statistically significant difference in the mean number of prescribed antibiotics for RTI between the intervention and the control group, nor for mean number of overall prescribed antibiotics. The intervention GPs rated the usefulness of the training for daily practice a 7.3 (on a scale from 1–10) and there was a statistically significant difference between pre- and post-intervention on four out of nine items related to knowledge and skills. Discussion: There was no change in GPs prescription behavior between the intervention and control group. However, GPs found the intervention useful and showed some improvement on self-rated knowledge and communication skills.

Background: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. Methods: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. Discussion: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the d

Background Contact tracing has been a key component of COVID-19 outbreak control. Backward contact tracing (BCT) aims to trace the source that infected the index case and, thereafter, the cases infected by the source. Modelling studies have suggested BCT will substantially reduce SARS-CoV-2 transmission in addition to forward contact tracing.AimTo assess the feasibility and impact of adding BCT in practice. Methods We identified COVID-19 cases who were already registered in the electronic database between 19 February and 10 March 2021 for routine contact tracing at the Public Health Service (PHS) of Rotterdam-Rijnmond, the Netherlands (pop. 1.3 million). We investigated if, through a structured questionnaire by dedicated contact tracers, we could trace additional sources and cases infected by these sources. Potential sources identified by the index were approached to trace the source's contacts. We evaluated the number of source contacts that could be additionally quarantined. Results Of 7,448 COVID-19 cases interviewed in the study period, 47% (n = 3,497) indicated a source that was already registered as a case in the PHS electronic database. A potential, not yet registered source was traced in 13% (n = 979). Backward contact tracing was possible in 62 of 979 cases, from whom an additional 133 potential sources were traced, and four were eligible for tracing of source contacts. Two additional contacts traced had to stay in quarantine for 1 day. No new COVID-19 cases were confirmed. Conclusions The addition of manual BCT to control the COVID-19 pandemic did not provide added value in our study setting.

Background: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. Methods: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. Results: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds. Conclusions: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relat

Background: Leprosy is a public health burden in Indonesia with a high number of new cases every year and a high proportion of disability among new cases. Case detection delay (CDD) can contribute to ongoing transmission and increased disability chances among leprosy patients. This study aimed to establish the CDD of leprosy and the factors associated with detection delay in Indonesia. Method: Community-based study with a cross-sectional design. Data were collected through interviews about sociodemographic and behavioral factors, anticipated stigma, and duration of CDD. Leprosy classification and case detection methods were obtained from health service records. A random sample was taken of 126 leprosy patients registered between 1st October 2020 and 31st March 2022 in the Tegal regency in the Central Java Province. Data were analysed by descriptive and analytical statistics using multiple linear regression. Results: The mean CDD, patient delay, and health system delay were 13.0 months, 9.7 months, and 3.2 months, respectively. Factors associated with longer CDD are younger age (below 35 years), male, found through passive case detection, and not having a family member with leprosy. Factors associated with longer patient delay were being younger (below 35 years), being male, not having a family member with leprosy, and anticipated stigma of leprosy. It was not possible to reliably identify factors associated with health system delay. Conclusion: CDD in leprosy should be reduced in Indonesia. The Indonesian National Leprosy Control Program (NLCP) is advised to adopt an integrated intervention programme combining active case detection with targeted health education to reduce CDD and thereby preventing disabilities in people affected by leprosy.

Objectives Areas with high sexually transmitted infection (STI) testing rates may not require additional strategies to improve testing. However, it may be necessary to intervene in areas with elevated STI risk, but with low STI testing rates. We aimed to compare STI-related risk profiles and STI testing rates by geographical area to determine areas for improvement of sexual healthcare access. Design Cross-sectional population-based study. Setting Greater Rotterdam area, the Netherlands (2015-2019). Participants All residents aged 15-45 years. Individual population-based register data were matched with laboratory-based STI testing data of general practitioners (GPs) and the only sexual health centre (SHC). Outcome measures Postal code (PC) area-specific STI risk scores (based on age, migratory background, education level and urbanisation), STI testing rates and STI positivity. Results The study area consists of approximately 500 000 residents aged 15-45 years. Strong spatial variation in STI testing, STI positivity and STI risk was observed. PC area testing rate ranged from 5.2 to 114.9 tests per 1000 residents. Three PC clusters were identified based on STI risk and testing rate: (1) high-high; (2) high-low; (3) low, independently of testing rate. Clusters 1 and 2 had comparable STI-related risk and STI positivity, but the testing rate differed greatly (75.8 vs 33.2 per 1000 residents). Multivariable logistic regression analysis with generalised estimating equation was used to compare residents in cluster 1 and cluster 2. Compared with cluster 1, residents in cluster 2 more often did not have a migratory background, lived in less urbanised areas with higher median household income, and more distant from both GP and SHC. Conclusion The determinants associated with individuals living in areas with high STI-related risk scores and low testing rates provide leads for improvement of sexual healthcare access. Opportunities for further exploration include GP education

Background Case detection delay (CDD) is associated with grade 2 disability (G2D) in leprosy, a substantial disease burden worldwide. The standardized CDD questionnaire was developed to determine the period of CDD and its related factors. In Indonesia, the incidence of leprosy and G2D is high and an instrument to measure CDD is lacking. This study describes the translation and cross-cultural adaptation process and evaluates the CDD questionnaire in the Indonesian context. Methods We first did forward–backward translation into Bahasa Indonesia and cross-culturally adapted the CDD questionnaire. We then performed face-to-face three-step test interviews in a pilot test to evaluate the understanding of leprosy patients and the content validity of the CDD questionnaire (n = 15). Finally, the reliability and construct validity of the CDD questionnaire were tested in 50 leprosy patients in Tegal Regency, Indonesia. Results The interviews showed that leprosy patients understood the CDD questionnaire well. The content and construct validity were adequate according to linguistic validation and statistical hypothesis testing. The internal consistency test with a Cronbach alpha showed that the CDD questionnaire measures one underlying construct. The reproducibility test, including the test–retest reliability and agreement test, indicated excellent reliability. Conclusions The version of the CDD questionnaire in Bahasa Indonesia is an instrument with good validity and reliability to determine CDD in Indonesia. We recommend its implementation in the leprosy control programme of Indonesia for monitoring early case detection and thereby avoiding leprosy disability.

Background: Leprosy is an infectious disease caused by Mycobacterium leprae and remains a source of preventable disability if left undetected. Case detection delay is an important epidemiological indicator for progress in interrupting transmission and preventing disability in a community. However, no standard method exists to effectively analyse and interpret this type of data. In this study, we aim to evaluate the characteristics of leprosy case detection delay data and select an appropriate model for the variability of detection delays based on the best fitting distribution type. Methods: Two sets of leprosy case detection delay data were evaluated: a cohort of 181 patients from the post exposure prophylaxis for leprosy (PEP4LEP) study in high endemic districts of Ethiopia, Mozambique, and Tanzania; and self-reported delays from 87 individuals in 8 low endemic countries collected as part of a systematic literature review. Bayesian models were fit to each dataset to assess which probability distribution (log-normal, gamma or Weibull) best describes variation in observed case detection delays using leave-one-out cross-validation, and to estimate the effects of individual factors. Results: For both datasets, detection delays were best described with a log-normal distribution combined with covariates age, sex and leprosy subtype [expected log predictive density (ELPD) for the joint model: −1123.9]. Patients with multibacillary (MB) leprosy experienced longer delays compared to paucibacillary (PB) leprosy, with a relative difference of 1.57 [95% Bayesian credible interval (BCI): 1.14–2.15]. Those in the PEP4LEP cohort had 1.51 (95% BCI: 1.08–2.13) times longer case detection delay compared to the self-reported patient delays in the systematic review. Conclusions: The log-normal model presented here could be used to compare leprosy case detection delay datasets, including PEP4LEP where the primary outcome measure is reduction in case detection delay. We recommend the

Yaws is a chronic, highly contagious skin and bone infection caused by Treponema pallidum subspecies pertenue, usually affecting children in impoverished and remote communities. Yaws lesions have thick yellow crusts on pink papillomas that ulcerate and leave deep scars. Yaws cases were confirmed in the Liguasan Marsh, Mindanao Island group, Southern Philippines, in 2017, but there were no cases confirmed in the Luzon and Visayas Island groups. We aimed to detect at least one active or latent yaws case in the island groups of Luzon and Visayas. Active yaws surveillance was conducted by inviting healthcare providers to report yaws suspects. Five remote villages were included in the case detection surveys: three in Luzon and two in the Visayas Island groups. Two indigenous peoples communities were included: Aetas of Quezon and Dumagat/Remontados of Rizal provinces. Trained field personnel conducted free skin check-ups of children, household contacts, and community members. Yaws suspects underwent point-of-care serologic tests for T. pallidum and nontreponemal antibodies. A total of 239 participants were screened for skin diseases, and 103 had serologic tests. Only the Aetas of Quezon province, Luzon, had confirmed yaws cases. Nineteen cases (54.3%) were detected among 35 Aetas: five active yaws (four children, one adult), two latent yaws (adults), and 12 past yaws (1 child, 11 adults). An 8-year-old boy had yaws with skeletal deformities. We report the first yaws cases among the Aetas of Quezon, Luzon Island group. Active yaws surveillance and case detection in remote areas and among indigenous peoples should continue.

SETTING: India has the highest number of new TB cases worldwide. The participation of private providers (PPs) in the National TB Elimination Programme (NTEP) has remained suboptimal. OBJECTIVE: To explore the experiences, barriers and facilitators about their participation in the NTEP as perceived by PPs working in varied settings. DESIGN: Focus group discussions and in-depth interviews were used to engage PPs to obtain their views on participation in the NTEP. Framework and thematic content analysis was used to analyse qualitative data. RESULTS: Non-availability of a comprehensive range of diagnostics and lack of flexibility in the NTEP were barriers to participation in NTEP. PPs were predisposed to think that NTEP was for those who could not afford to purchase medications. Attitudes and previous experiences with NTEP made them sceptical about the NTEP regimen. Although more frequent interactions were sought with NTEP, some bitterness about previous interactions was perceived. CONCLUSION: Challenges identified by PPs for the NTEP include improvement of the quality of TB care, especially at the lower levels of care, availability of a comprehensive range of diagnostics, being friendly to PPs and patients, more frequent interactions with PPs, and more caring conversations with patients at NTEP centres.

Tegal Regency in Central Java Province, Indonesia, is a leprosy endemic area. In 2021, the leprosy prevalence was 0.82 per 10,000 population. The total number of new cases was 133, of whom 11% had Grade 2 disability (G2D). The high number with G2D indicates substantial case detection delay (CDD). This delay can be caused by personal, societal and health service-related factors. The aim of this study was to describe the association of disability grade with health-seeking behavior. We employed a cross-sectional research design involving 126 patients with leprosy selected by random sampling among 171 patients with leprosy registered from the 4th quarter of 2020 until the 1st quarter of 2022. Data were collected using a structured questionnaire translated from an international standardized questionnaire (ie, CDD questionnaire) through interviews with leprosy patients. Data were analyzed by descriptive and inferential statistics. We found nearly half (46.8%) of the patients aged 35-50 years, and almost two-thirds were male. Of all, 75.4% had completed primary or secondary education. At diagnosis, more than half had no disability at all, and 10.3% had G2D. Nearly half (45.2%) had used ‘self-medication’ and did not seek appropriate health care services before being diagnosed with leprosy. There was a statistically significant association between health-seeking behavior and the disability grade at diagnosis (p=0.01). In summary, disability caused by leprosy constitutes a significant public health burden in Tegal Regency, which could be lowered through supporting appropriate health seeking behavior.

Summary Objective Although elimination of leprosy was achieved in Nepal at national level in 2009, around 3000 new cases are still detected every year and 5% of these cases have Grade 2 disability (G2D). This study aims to describe the geographical distribution of leprosy new case detection (NCD) and G2D from 2010 to 2021 in two leprosy endemic provinces in Nepal. Methods We collected the geolocations and leprosy-related data of patients registered from 2010 to 2021 in Provinces 1 and 7. The geographical distribution of NCD and G2D was analysed in Quantum Geographic Information Systems (QGIS) at district, municipality and ward level, and we calculated the trends in Eye Hand Foot (EHF) impairment scores among cases with disabilities. Results From 2010 to 2021, a decrease in NCD and G2D cases was identified in Province 1, and an increase in NCD and G2D cases in Province 7. Geographical variations were visible between wards within highly endemic districts in both provinces. The mean EHF score in cases with disability increased from 1.7 in 2017 to 2.5 in 2020 in Province 1 and fluctuated between 2.3 and 4.5 in Province 7. Conclusions This study shows that the leprosy problem is still current in Nepal. Geographic variations in case detection and disability indicators are seen best when mapping at ward level. Leprosy programme managers can use the maps to develop long-term strategies at district, municipality or ward level that include intensified active case finding, preventive treatment and disability services, while considering costs and efficient use of resources.

BACKGROUND: Preventive interventions with post-exposure prophylaxis (PEP) are needed in leprosy high-endemic areas to interrupt the transmission of Mycobacterium leprae. Program managers intend to use Geographic Information Systems (GIS) to target preventive interventions considering efficient use of public health resources. Statistical GIS analyses are commonly used to identify clusters of disease without accounting for the local context. Therefore, we propose a contextualized spatial approach that includes expert consultation to identify clusters and compare it with a standard statistical approach. METHODOLOGY/PRINCIPAL FINDINGS: We included all leprosy patients registered from 2014 to 2020 at the Health Centers in Fatehpur and Chandauli districts, Uttar Pradesh State, India (n = 3,855). Our contextualized spatial approach included expert consultation determining criteria and definition for the identification of clusters using Density Based Spatial Clustering Algorithm with Noise, followed by creating cluster maps considering natural boundaries and the local context. We compared this approach with the commonly used Anselin Local Moran's I statistic to identify high-risk villages. In the contextualized approach, 374 clusters were identified in Chandauli and 512 in Fatehpur. In total, 75% and 57% of all cases were captured by the identified clusters in Chandauli and Fatehpur, respectively. If 100 individuals per case were targeted for PEP, 33% and 11% of the total cluster population would receive PEP, respectively. In the statistical approach, more clusters in Chandauli and fewer clusters in Fatehpur (508 and 193) and lower proportions of cases in clusters (66% and 43%) were identified, and lower proportions of population targeted for PEP was calculated compared to the contextualized approach (11% and 11%). CONCLUSION: A contextualized spatial approach could identify clusters in high-endemic districts more precisely than a standard statistical approach. Therefore

Background: Yaws is a chronic, non-venereal, highly contagious skin and bone infection affecting children living in impoverished, remote communities and caused by Treponema pallidum subspecie pertenue. Social stigma and economic losses due to yaws have been reported anecdotally in the Southern Philippines but have not been well-documented. Objective: To describe and compare the psychological, social, and economic effects of yaws from the perspective of patients, contacts, and key informants in two areas of the Philippines. Materials and methods: Yaws and contacts were identified through clinicoseroprevalence surveys conducted in the Liguasan Marsh area, Mindanao, Southern Philippines in 2017 and among the Aetas, an indigenous people community in Quezon province, Luzon region in 2020. Skin examinations and serologic tests confirmed the diagnosis of active, latent, or past yaws among the children and adults. Trained health personnel conducted in-depth interviews of those affected by yaws and their guardians, household contacts, and key informants, such as health workers regarding their perceptions, feelings, health-seeking behaviors, and effects of yaws on their lives. Results: A total of 26 participants were interviewed: 17 from Mindanao and 9 from Luzon. Aside from the physical discomforts and embarrassment, yaws was considered stigmatizing in Mindanao, because positive non-treponemal tests or treponemal antibody tests were associated with syphilis and promiscuity. These have led to loss of employment and income opportunities for adults with latent or past yaws. In contrast, the Aetas of Luzon did not perceive yaws as stigmatizing, because it was a common skin problem. Plantar yaws interfered with the Aeta’s gold panning livelihood due to the pain of wounds. Conclusions: Yaws is not merely a chronic skin and bone disease. It can lead to significant psychosocial and economic problems as well. Yaws is a generally forgotten disease in the Philippines. There is no ya

Immigrants constitute large proportions of the population in many high-income countries. Knowledge about their perceptions of antibiotics, in comparison to native populations, is limited. We explored these perceptions by organizing nine homogeneous focus group discussions (FGDs) with first-generation immigrant and native Dutch participants (N = 64) from Rotterdam and Utrecht, who were recruited with the assistance of immigrant (community support) organizations. The FGDs were audio-recorded and transcribed verbatim. Inductive thematic analyses were performed with the qualitative analysis software Atlas.ti, using open and axial coding. We did not find noteworthy differences between immigrants and native Dutch participants; all participants had an overall reluctant attitude towards antibiotics. Within-group differences were larger than between-group differences. In each FGD there were, for instance, participants who adopted an assertive stance in order to receive antibiotics, who had low antibiotic-related knowledge, or who used antibiotics incorrectly. Native Dutch participants expressed similar difficulties as immigrant participants in the communication with their GP, which mainly related to time constraints. Immigrants who encountered language barriers experienced even greater communicational difficulties and reported that they often feel embarrassed and refrain from asking questions. To stimulate more prudent use of antibiotics, more attention is needed for supportive multilingual patient materials. In addition, GPs need to adjust their information, guidance, and communication for the individual's needs, regardless of the patient's migration background.

Background Yaws is a chronic, highly contagious skin and bone infection affecting children living in impoverished, remote communities. It is caused by Treponema pallidum subsp. pertenue. We report the prevalence of active yaws among elementary schoolchildren based on clinical and serological criteria in selected municipalities of Southern Philippines. Methods From January to March 2017, exploratory cross-sectional surveys and screening of skin diseases were conducted in the Liguasan Marsh area of the provinces Maguindanao, Sultan Kudarat, and Cotabato. We included 9 municipalities and randomly selected one public elementary school per municipality. Members of students’ households and the communities were also examined and treated. Yaws suspects and contacts had blood tests for trepone-mal and non-treponemal antibodies using Dual Pathway Platform and Treponema pallidum particle agglutination (TPPA) tests. Results A total of 2779 children and adults were screened for any skin disease: 2291 students, 393 household members, and 95 community members. Among 210 yaws suspects and con-tacts, 150 consented to serologic tests. The estimated prevalence of active yaws among schoolchildren screened was 1 out of 2291 (0.04%). Among 2532 children who were 14 years old and younger, 4 (0.2%) had active yaws. Eight adult household contacts and community members had latent yaws and 2 had past yaws. Five out of 9 municipalities were endemic for yaws. Conclusions This study confirmed that the Philippines is endemic for yaws but at a low level in the schools surveyed. This is an under-estimation due to the limited sampling. The lack of proper disease surveillance after the eradication campaign in the 1960’s has made yaws a forgotten disease and has led to its resurgence. Yaws surveillance is needed to determine the extent of yaws in the Philippines and to help develop a strategy to eradicate yaws by 2030.

Objectives Leprosy is a chronic infectious disease caused by Mycobacterium leprae and one of the world’s most neglected tropical diseases. The post-exposure prophylaxis for leprosy study (PEP4LEP) compares two integrated skin-screening approaches combined with single dose rifampicin administration to contacts of leprosy patients. The aim of this baseline survey was to describe the epidemiological trends of leprosy and estimate case detection delay in the Ethiopian study districts before the start of the intervention. Methods The study was conducted in three districts of East Hararghe zone, Oromia Region, Ethiopia. We applied descriptive retrospective study design to describe epidemiological trends of leprosy between 2010 and 2019. Fifty patients diagnosed in the six months prior to their inclusion in the study were interviewed to establish the case detection delay at baseline. The healthcare delivery system and National Leprosy Control Program are also described. Results Trends in the number of new leprosy patients detected decreased slightly over the past ten years, although the number of new child cases increased overall, suggesting ongoing transmission. The mean case detection delay was 22.4 months (95% CI: 18.6–26.3), while the median was 19.5 months. The mean patient and health system delay were 19.6 months (95% CI: 15.8–23.4) and 2.6 months (95% CI: 1.5–3.6), respectively. Conclusion Considerable leprosy case detection delays were found in the PEP4LEP study districts in Ethiopia. Efforts to reduce delay and interrupt the transmission should focus on integrating prevention and active case finding, contact tracing and providing post-exposure prophylaxis to contacts of leprosy patients.

Objectives Leprosy, also known as Hansen’s disease, is a slowly progressive and chronic infectious neglected tropical disease (NTD) caused by Mycobacterium leprae. This study was performed to assess the epidemiological trend of leprosy in the past five years in the three study districts in Tanzania in which a leprosy prevention intervention study (PEP4LEP) is implemented, and to determine the case detection delay at baseline. Methods Secondary data from the leprosy registry of the National Tuberculosis and Leprosy Program of Tanzania from 2015 to 2019 were used to describe the epidemiological trends of leprosy for the three study districts: Morogoro, Mvomero, and Lindi district council. A cross-sectional study was also conducted to assess the delay in leprosy diagnosis at baseline. The chi-square test was used to calculate statistical significance. Results Between 2015 and 2019, 657 new leprosy cases were detected in three districts. Of those cases, 247 (37.6%) were female patients, 5 (0.8%) had a grade 2 disability (G2D) and 516 (78.5%) had multibacillary (MB) leprosy. From the 50 adult leprosy patients interviewed for detection delay, 16 (32.0%) were females and 38 (76.0%) had MB leprosy. Overall, a mean case detection of 28.1 months (95% CI 21.5–34.7) and a median of 21.5 months were observed. Conclusion The three PEP4LEP study districts remain highly endemic, with long case detection delays observed that increase the risk of disabilities and contribute to ongoing leprosy transmission. Integrating activities such as contact screening and provision of post-exposure prophylaxis are therefore a necessary strategy in these endemic areas.

Introduction: Engagement is essential to achieve intended outcomes of online interventions, but achieving such engagement is a key challenge for many researchers and practitioners. This systematic literature review aims to identify strategies and tools to promote the use of online health interventions for early detection and raising awareness of chronic diseases among the public, and to investigate the evidence regarding the effectiveness of such strategies. Materials and methods: We performed a systematic search of seven electronic databases: Embase, Medline All Ovid, Web of Science, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL and Google Scholar. The study protocol is registered in PROSPERO (CRD42020200471). Results: The database search identified 8,526 articles, 47 were included in the review. Thirty-two studies reported strategies to promote the use of their online intervention, including online advertisements on social media (n = 17), a dating application (n = 10), and a website (n = 3). Social media were not only used for promotion of the intervention, but also as main intervention platform (n = 18). Seven studies reported traditional promotion methods such as printed advertisement and (offline) campaigns. Twenty-seven studies reported strategies to keep users engaged, including reminders (n = 12), sharing of posts on social media (n = 4), rewards (n = 3), weekly group discussions (n = 2), follow-up phone calls (n = 2), interactive games (n = 1), monthly quizzes (n = 1), links to provision of a test kit (n = 1), and a deposit-return system (n = 1). Conclusions: No study conducted a formal evaluation of the effectiveness of the engagement strategies. Examining the effectiveness of engagement strategies is an important area for further research.

Objectives Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The PEP4LEP project will compare two integrated skin-screening interventions combined with the distribution of a single dose of rifampicin as post exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. To implement the study in Mozambique, it was necessary to assess recent epidemiological indicators of leprosy and to estimate case detection delay as a main outcome indicator at baseline. Methods This was a descriptive study to establish the trend of epidemiological indicators of leprosy in the Nampula province districts Murrupula, Meconta and Mogovolas in Mozambique, between 2015 and 2019; and to calculate the average delay to diagnose leprosy cases in these districts. The National Leprosy Control Programme was also described. For the estimation of the case detection delay, 81 recently diagnosed patients were interviewed. Results There were 939 new leprosy cases detected in the three districts from 2015 to 2019, with a high proportion of disability (17.0%). The mean diagnosis delay was 26.6 months (95% CI: 18.4–34.7), while the median was 17.0 months. Multibacillary cases had an average delay of 27.9 months (95% CI: 18.6–37.1), while those with grade 2 disability had an average delay of 47.8 months (95% CI: 15.4–80.2). Conclusion The long case detection delay and high grade 2 disability rates indicate that there is a need for active case finding and chemoprophylaxis with SDR-PEP to help interrupt the chain of Mycobacterium leprae transmission in Nampula province.

BACKGROUND: In new leprosy cases, grade 2 disability (G2D) is still a public health burden worldwide. It is often associated with the delayed leprosy diagnoses that healthcare systems should play a crucial role in preventing. The aim of this systematic review was to identify healthcare factors related to delays in case detection in leprosy. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) was used as a guideline in this research. The study protocol was registered in the PROSPERO (International Prospective Register of Systematic Reviews) with reference code CRD42020189274. Data was collected from five electronic databases: Embase, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library. RESULTS: After applying the selection criteria for original empirical studies, and after removing duplicates, we included 20 papers from 4313 records. They had been conducted in ten countries and published between January 1, 2000, and January 31, 2021. We identified three categories of healthcare factors related to delayed case. 1) Structural factors, such as i) financial and logistic issues, and geographical circumstances (which we classified as barriers); ii) Health service organization and management including the level of decentralization (classified as facilitators). 2) Health service factors, such as problems or shortages involving referral centers, healthcare personnel, and case-detection methods. 3) Intermediate factors, such as misdiagnosis, higher numbers of consultations before diagnosis, and inappropriate healthcare services visited by people with leprosy. CONCLUSIONS: Delays in leprosy case detection are due mainly to misdiagnosis. It is crucial to improve the training and capacity of healthcare staff. To avoid misdiagnosis and reduce detection delays, national leprosy control programs should ensure the sustainability of leprosy control within integrated health services.

Background In India, leprosy clusters at hamlet level but detailed information is lacking. We aim to identify high-incidence hamlets to be targeted for active screening and post-exposure prophylaxis. Methodology We paid home visits to a cohort of leprosy patients registered between April 1st, 2020, and March 31st, 2022. Patients were interviewed and household members were screened for leprosy. We used an open-source app(ODK) to collect data on patients’ mobility, screening results of household members, and geographic coordinates of their households. Clustering was analysed with Kulldorff’s spatial scan statistic(SaTScan). Outlines of hamlets and population estimates were obtained through an open-source high-resolution population density map(https://data.humdata.org), using kernel density estimation in QGIS, an open-source software. Results We enrolled 169 patients and screened 1,044 household contacts in Bisfi and Benipatti blocks of Bihar. Median number of years of residing in the village was 17, interquartile range (IQR)12-30. There were 11 new leprosy cases among 658 household contacts examined (167 per 10,000), of which seven had paucibacillary leprosy, one was a child under 14 years, and none had visible disabilities. We identified 739 hamlets with a total population of 802,788(median 163, IQR 65–774). There were five high incidence clusters including 12% of the population and 46%(78/169) of the leprosy cases. One highly significant cluster with a relative risk (RR) of 4.7(p<0.0001) included 32 hamlets and 27 cases in 33,609 population. A second highly significant cluster included 32 hamlets and 24 cases in 33,809 population with a RR of 4.1(p<0.001). The third highly significant cluster included 16 hamlets and 17 cases in 19,659 population with a RR of 4.8(p<0.001). High-risk clusters still need to be screened door-to-door. Conclusions We found a high yield of active household contact screening. Our tools for identifying high

Background: The Public Health Services in the Rotterdam region, the Netherlands, observed a substantial decrease of non-COVID-19 notifiable infectious diseases and institutional outbreaks during the first wave of the COVID-19 epidemic. We describe this change from mid-March to mid-October 2020 by comparing with the pre-COVID-19 situation. Methods: All cases of notifiable diseases and institutional outbreaks reported to the Public Health Services Rotterdam-Rijnmond between 1st January and mid-October 2020 were included. Seven-day moving averages and cumulative cases were plotted against time and compared to those of 2017–2019. Additionally, Google mobility transit data of the region were plotted, as proxy for social distancing. Results: Respiratory, gastrointestinal, and travel-related notifiable diseases were reported 65% less often during the first wave of the COVID-19 epidemic than in the same weeks in 2017–2019. Reports of institutional outbreaks were also lower after the initially imposed social distancing measures; however, the numbers rebounded when measures were partially lifted. Conclusions: Interpersonal distancing and hygiene measures imposed nationally against COVID-19 were in place between mid-March and mid-October, which most likely reduced transmission of other infectious diseases, and may thus have resulted in lower notifications of infectious diseases and outbreaks. This phenomenon opens future study options considering the effect of local outbreak control measures on a wide range of non-COVID-19 diseases. Targeted, tailored, appropriate and acceptable hygiene and distancing measures, specifically for vulnerable groups and institutions, should be devised and their effect investigated.

Background: If healthcare professionals perceive that patients strongly expect to be prescribed antibiotics, inappropriate prescriptions may result. As it is unknown whether this happens more often with certain patient groups, we explored whether general practitioners (GPs) and pharmacists perceived such expectations when they provided antibiotics to immigrant patients. Methods: Ten GPs and five pharmacists from Rotterdam, the Netherlands, were interviewed on the basis of a semi-structured topic guide. Atlas.ti software was then used to conduct a thematic analysis. Results: GPs felt that immigrant patients, especially those who had arrived recently, were more likely to expect to receive antibiotics than native Dutch patients. However, these expectations had decreased over the last years and did not always lead immigrants to exert pressure on them. Except for language barriers, the factors reported by GPs to influence their antibiotic prescribing behaviour were unrelated to patients’ immigrant background. If there was a language barrier, GPs experienced greater diagnostic uncertainty and needed additional time to obtain and communicate correct information. To overcome language barriers, they often used point-of-care testing to convince patients that antibiotics were unnecessary. Although pharmacists rarely experienced problems dispensing antibiotics to immigrants, they and GPs both struggled to find effective ways of overcoming language barriers, and stressed the need for multi-language support materials. Conclusion: While pharmacists rarely experience any problems providing antibiotics to immigrants, GPs regularly face language barriers with immigrant patients, which complicate the diagnostic process and communicating information in the limited available time. This sometimes leads antibiotics to be prescribed inappropriately.

Background Worldwide, around 210,000 new cases of leprosy are detected annually. To end leprosy, i.e. zero new leprosy cases, preventive interventions such as contact tracing and post-exposure prophylaxis (PEP) are required. This study aims to estimate the number of people requiring PEP to reduce leprosy new case detection (NCD) at national and global level by 50% and 90%. Methodology/Principal findings The individual-based model SIMCOLEP was fitted to seven leprosy settings defined by NCD and MB proportion. Using data of all 110 countries with known leprosy patients in 2016, we assigned each country to one of these settings. We predicted the impact of admin-istering PEP to about 25 contacts of leprosy patients on the annual NCD for 25 years and estimated the number of contacts requiring PEP per country for each year. The NCD trends show an increase in NCD in the first year (i.e. backlog cases) followed by a significant decrease thereafter. A reduction of 50% and 90% of new cases would be achieved in most countries in 5 and 22 years if 20.6 and 40.2 million people are treated with PEP over that period, respectively. For India, Brazil, and Indonesia together, a total of 32.9 million people requiring PEP to achieve a 90% reduction in 22 years. Conclusion/Significance The leprosy problem is far greater than the 210,000 new cases reported annually. Our model estimates of the number of people requiring PEP to achieve significant reduction of new leprosy cases can be used by policymakers and program managers to develop long-term strategies to end leprosy.

Background Leprosy is a chronic bacterial infection caused by Mycobacterium leprae, which may lead to physical disability, stigma, and discrimination. The chronicity of the disease and disabilities are the prime contributors to the disease burden of leprosy. The current figures of the disease burden in the 2017 global burden of disease study, however, are considered to be under-estimated. In this study, we aimed to systematically review the literature and perform individual patient data meta-analysis to estimate new disability weights for leprosy, using Health-Related Quality of Life (HRQOL) data. Methodology/principal findings The search strategy included all major databases with no restriction on language, setting, study design, or year of publication. Studies on human populations that have been affected by leprosy and recorded the HRQOL with the Short form tool, were included. A consortium was formed with authors who could share the anonymous individual-level data of their study. Mean disability weight estimates, sorted by the grade of leprosy disability as defined by WHO, were estimated for individual participant data and pooled using multivariate ran-dom-effects meta-analysis. Eight out of 14 studies from the review were included in the meta-analysis due to the availability of individual-level data (667 individuals). The overall estimated disability weight for grade 2 disability was 0.26 (95%CI: 0.18–0.34). For grade 1 disability the estimated weight was 0.19 (95%CI: 0.13–0.26) and for grade 0 disability it was 0.13 (95%CI: 0.06–0.19). The revised disability weight for grade 2 leprosy disability is four times higher than the published GBD 2017 weights for leprosy and the grade 1 disability weight is nearly twenty times higher. Conclusions/significance The global burden of leprosy is grossly underestimated. Revision of the current disability weights and inclusion of disability caused in individuals with grade 0 leprosy disability will contribute towards a mor

Background: Leprosy is known to be unevenly distributed between and within countries. High risk areas or ‘hotspots’ are potential targets for preventive interventions, but the underlying epidemiologic mechanisms that enable hotspots to emerge, are not yet fully understood. In this study, we identified and characterized leprosy hotspots in Bangladesh, a country with one of the highest leprosy endemicity levels globally. Methods: We used data from four high-endemic districts in northwest Bangladesh including 20 623 registered cases between January 2000 and April 2019 (among ~ 7 million population). Incidences per union (smallest administrative unit) were calculated using geospatial population density estimates. A geospatial Poisson model was used to detect incidence hotspots over three (overlapping) 10-year timeframes: 2000–2009, 2005–2014 and 2010–2019. Ordinal regression models were used to assess whether patient characteristics were significantly different for cases outside hotspots, as compared to cases within weak (i.e., relative risk (RR) of one to two), medium (i.e., RR of two to three), and strong (i.e., RR higher than three) hotspots. Results: New case detection rates dropped from 44/100 000 in 2000 to 10/100 000 in 2019. Statistically significant hotspots were identified during all timeframes and were often located at areas with high population densities. The RR for leprosy was up to 12 times higher for inhabitants of hotspots than for people living outside hotspots. Within strong hotspots (1930 cases among less than 1% of the population), significantly more child cases (i.e., below 15 years of age) were detected, indicating recent transmission. Cases in hotspots were not significantly more likely to be detected actively. Conclusions: Leprosy showed a heterogeneous distribution with clear hotspots in northwest Bangladesh throughout a 20-year period of decreasing incidence. Findings confirm that leprosy hotspots represent areas of higher transmission activ

This study aims to assess private and public sector contributions to Tuberculosis (TB) notification in Bengaluru city (2011 to 2016) and identify challenges of program personnel in their interaction with private practitioners and procedural barriers for TB notification from the private sector as perceived by them. A mixed methods study was carried out in Bengaluru city, India with TB notification data obtained from TB Units in addition to in-depth interviews with key program implementers. Results showed the contribution of private practitioners to TB notification to be about 20%. Barriers and challenges were: the private practitioners’ hesitancy to refer the patients to public sector due to their fear of losing patients and dishonoring of diagnosis from private practitioners, lack of awareness about TB notification, lack of legal punitive measures and constant glitches on the notification website. These need to be resolved on priority to achieve the national target of TB elimination by 2025.

Background The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. Methodology The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continua-tion of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. Principal findings In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction after-wards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. Conclusions The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

The COVID-19 pandemic has created an unprecedented health crisis and a substantial socioeconomic impact. It also affects tuberculosis (TB) control severely worldwide. Interruptions of many TB control programs because of the COVID-19 pandemic could result in significant setbacks. One of the targets that can be affected is the WHO's End TB Strategy goal to eliminate catastrophic costs of TB-affected households by 2030. Disruptions to TB programs and healthcare services due to COVID-19 could potentially prolong diagnostic delays and worsen TB treatment adherence and outcomes. The economic recession caused by the pandemic could significantly impact household financial capacity because of the reduction of income and the rise in unemployment rates. All of these factors increase the risk of TB incidence and the gravity of economic impact on TB-affected households, and hamper efforts to eliminate catastrophic costs and control TB. Therefore, efforts to eliminate the incidence of TB-affected households facing catastrophic costs will be very challenging. Because financial constraint plays a significant role in TB control, the improvement of health and social protection systems is critical. Even before the pandemic, many TB-high-burden countries (HBCs) lacked robust health and social protection systems. These challenges highlight the substantial need for a more robust engagement of patients and civil society organizations and international support in addressing the consequences of COVID-19 on the control of TB.

Background Leprosy is an infectious disease caused by Mycobacterium leprae. As incidence begins to decline, the characteristics of new cases shifts away from those observed in highly endemic areas, revealing potentially important insights into possible ongoing sources of transmission. We aimed to investigate whether transmission is driven mainly by undiagnosed and untreated new leprosy cases in the community, or by incompletely treated or relapsing cases. Methodology/Principal findings A literature search of major electronic databases was conducted in January, 2020 with 134 articles retained out of a total 4318 records identified (PROSPERO ID: CRD42020178923). We presented quantitative data from leprosy case records with supporting evidence describing the decline in incidence across several contexts. BCG vaccination, active case finding, adherence to multidrug therapy and continued surveillance following treatment were the main strategies shared by countries who achieved a substantial reduction in incidence. From 3950 leprosy case records collected across 22 low endemic countries, 48.3% were suspected to be imported, originating from transmission outside of the country. Most cases were multibacillary (64.4%) and regularly confirmed through skin biopsy, with 122 cases of suspected relapse from previous leprosy treatment. Family history was reported in 18.7% of cases, while other suspected sources included travel to high endemic areas and direct contact with armadillos. None of the countries included in the analysis reported a distinct increase in leprosy incidence in recent years. Conclusions/Significance Together with socioeconomic improvement over time, several successful leprosy control programmes have been implemented in recent decades that led to a substantial decline in incidence. Most cases described in these contexts were multibacillary and numerous cases of suspected relapse were reported. Despite these observations, there was no indication that these cas

Background Leprosy and cutaneous leishmaniasis (CL) are neglected tropical diseases (NTDs) affecting the skin. Their control is challenging but the integration of skin NTDs control programs is recommended to improve timely detection and treatment. However, little is known about the occurrence of leprosy and CL in the same individuals, and what are the characteristics of such patients. This study aimed to identify and characterize patients diagnosed with both leprosy and CL (i.e., outcome) in the hyperendemic state of Mato Grosso, Brazil. Also, we investigated the demographic risk factors associated with the period between the diagnosis of both diseases. Methodology/principal findings A retrospective cohort study was conducted with patients diagnosed between 2008 and 2017. From the leprosy (n = 28,204) and CL (n = 24,771) databases of the national reporting system, 414 (0.8%; 414/52,561) patients presenting both diseases were identified through a probabilistic linkage procedure. This observed number was much higher than the number of patients that would be expected by chance alone (n = 22). The spatial distribution of patients presenting the outcome was concentrated in the North and Northeast mesoregions of the state. Through survival analysis, we detected that the probability of a patient developing both diseases increased over time from 0.2% in the first year to 1.0% within seven years. Further, using a Cox model we identified male sex (HR: 2.3; 95% CI: 1.7–2.9) and low schooling level (HR: 1.5; 95% CI: 1.2–1.9) as positively associated with the outcome. Furthermore, the hazard of developing the outcome was higher among individuals aged 40–55 years. Conclusions/significance Leprosy and CL are affecting the same individuals in the area. Integration of control policies for both diseases will help to efficiently cover such patients. Measures should be focused on timely diagnosis by following-up patients diagnosed with CL, active case detection, and training of heal

Background: The central sexual health centre (SHC) in the greater Rotterdam area in the Netherlands helps finding people unaware of their STI/HIV status. We aimed to determine a possible association between SHC utilization and travel distance in this urban and infrastructure-rich area. Insight in area-specific utilization helps adjust outreach policies to enhance STI testing. Methods: The study population consists of all residents aged 15-45 years in the greater Rotterdam area (2015-17). We linked SHC consultation data from STI tested heterosexual clients to the population registry. The association between SHC utilization and distance was investigated by multilevel modelling, adjusting for sociodemographic and area-specific determinants. The data were also stratified by age (aged < 25 years) and migratory background (non-Western), since SHC triage may affect their utilization. We used straight-line distance between postal code area centroid and SHC address as a proxy for travel distance. Results: We found large area variation in SHC utilization (range: 1.13-48.76 per 1000 residents). Both individual- A nd area-level determinants determine utilization. Travel distance explained most area variation and was inversely associated with SHC utilization when adjusted for other sociodemographic and area-specific determinants [odds ratio (OR) per kilometre: 0.95; 95% confidence interval (CI): 0.93-0.96]. Similar results were obtained for residents <25 years (OR: 0.95; 95% CI: 0.94-0.96), but not for non-Western residents (OR: 0.99; 95% CI: 0.99-1.00). Conclusions: Living further away from a central SHC shows a distance decline effect in utilization. We recommend to enhance STI testing by offering STI testing services closer to the population.

We investigated whether an intervention to improve hand hygiene compliance in nursing homes changed glove use. Hand hygiene compliance increased, but substitution of hand hygiene with gloves did not decrease. We observed a reduction of inappropriately unchanged gloves after exposure to body fluids. Clinical trials identifier: Netherlands Trial Register, trial NL6049 (NTR6188): https://www.trialregister.nl/trial/6049.

Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.

Objectives To document serious adverse events (SAE) of prolonged prednisolone use in two double-blind randomized clinical trials (RCT). In the first RCT, treatment effectiveness on restoring nerve function of a 20-week prednisolone regimen was compared with a 32-week course. In the second RCT, patients with subclinical neuropathy received either 20 weeks prednisolone or placebo to assess whether prednisolone could prevent the development of clinical neuropathy. In both trials, patients received a prednisolone starting dose according to weight: high weight (≥50 kg) started at 60 mg and low weight (<50 kg) at 45 mg. In both trials, the occurrence of serious adverse events (SAE) was an important secondary outcome. Results In the first RCT, 868 patients were enrolled, of whom 16 (1.8%) developed a serious adverse event (SAE). There were 12 SAEs in the longer treatment arm (N = 439, event rate of 2.7%), and four in the shorter arm (N = 429, event rate of 0.9%) (p = 0.041). In the second RCT 4/364 (1.1%) developed an SAE, of which one was in the placebo arm. In both trials, minor adverse events were quite common and varied greatly in frequency and between centres. Conclusions When searching for the optimum dose and duration of prednisolone in the treatment and prevention of neuropathy in leprosy patients, one must weigh possible advantages against the possible serious adverse events. Although our trials showed a significantly increased percentage of SAE in the longer treatment arm in the first RCT and in the treatment arm of the second RCT, the overall event rate was very low.

Introduction Although antibiotic use and antimicrobial resistance in the Netherlands is comparatively low, inappropriate prescription of antibiotics is substantial, mainly for respiratory tract infections (RTIs). General practitioners (GPs) experience pressure from patients with an immigration background to prescribe antibiotics and have difficulty communicating in a culturally sensitive way. Multifaceted interventions including communication skills training for GPs are shown to be most effective in reducing antibiotic prescription. The PARCA study aims to reduce the number of antibiotic prescriptions for RTIs through implementing a culturally sensitive communication intervention for GPs and evaluate it in a randomised controlled trial (RCT). Methods and analysis A non-blinded RCT including 58 GPs (29 for each arm). The intervention consists of: (1) An E-learning with 4 modules of 10-15 min each; (2) A face-to-face training session in (intercultural) communication skills including role plays with a training actor and (3) Availability of informative patient-facing materials that use simple words (A2/B1 level) in multiple languages. The primary outcome measure is the number of dispensed antibiotic courses qualifying for RTIs in primary care, per 1000 registered patients. The secondary outcome measure is the number of all dispensed antibiotic courses, per 1000 registered patients. The intervention arm will receive the training in Autumn 2021, followed by an observation period of 6 winter months for which numbers of antibiotics will be collected for both trial arms. The GPs/practices in the control arm can attend the training after the observation period. Ethics and dissemination The study protocol was approved by the Medical Ethics Review Committee of Erasmus MC, University Medical Center Rotterdam (MEC-2020-0142). The results of the trial will be published in international peer-reviewed scientific journals and will be disseminated through national and international

Background Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and burden in leprosy lacks a uniform approach. As a result, the assessment of leprosy endemicity or burden are not comparable over time and across countries and regions. This can make program planning and evaluation difficult. This study aims to identify relevant metrics and methods for measuring and classifying leprosy endemicity and burden at (sub)national level. Methods We used a mixed-method approach combining findings from a systematic literature review and a Delphi survey. The literature search was conducted in seven databases, searching for endemicity, burden and leprosy. We reviewed the available evidence on the usage of indica-tors, classification levels, and scoring methods to measure and classify endemicity and bur-den. A two round Delphi survey was conducted to ask experts to rank and weigh indicators, classification levels, and scoring methods. Results The literature review showed variation of indicators, levels, and cut-off values to measure leprosy endemicity and/or burden. The most used indicators for endemicity include new case detection rate (NCDR), new cases among children and new cases with grade 2 disabil-ity. For burden these include NCDR, MB cases, and prevalence. The classification levels ‘high’ and ‘low’ were most important. It was considered most relevant to use separate scoring methods for endemicity and burden. The scores would be derived by use of multiple indicators. Conclusion There is great variation in the existing method for measuring endemicity and burden across countries and regions. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies.

Background: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is often late- or misdiagnosed leading to irreversible disabilities. Blood transcriptomic biomarkers that prospectively predict those who progress to leprosy (progressors) would allow early diagnosis, better treatment outcomes and facilitate interventions aimed at stopping bacterial transmission. To identify potential risk signatures of leprosy, we collected whole blood of household contacts (HC, n=5,352) of leprosy patients, including individuals who were diagnosed with leprosy 4-61 months after sample collection. Methods: We investigated differential gene expression (DGE) by RNA-Seq between progressors before presence of symptoms (n=40) and HC (n=40), as well as longitudinal DGE within each progressor. A prospective leprosy signature was identified using a machine learning approach (Random Forest) and validated using reverse transcription quantitative PCR (RT-qPCR). Findings: Although no significant intra-individual longitudinal variation within leprosy progressors was identified, 1,613 genes were differentially expressed in progressors before diagnosis compared to HC. We identified a 13-gene prospective risk signature with an Area Under the Curve (AUC) of 95.2%. Validation of this RNA-Seq signature in an additional set of progressors (n=43) and HC (n=43) by RT-qPCR, resulted in a final 4-gene signature, designated RISK4LEP (MT-ND2, REX1BD, TPGS1, UBC) (AUC=86.4%). Interpretation: This study identifies for the first time a prospective transcriptional risk signature in blood predicting development of leprosy 4 to 61 months before clinical diagnosis. Assessment of this signature in contacts of leprosy patients can function as an adjunct diagnostic tool to target implementation of interventions to restrain leprosy development. Funding: This study was supported by R2STOP Research grant, the Order of Malta-Grants-for-Leprosy-Research, the Q.M. Gastmann-Wichers Foundation and the Lepros

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).

Introduction Since ancient times leprosy has had a negative perception, resulting in stigmatization. To improve the lives of persons affected by leprosy, these negative perceptions need to change. The aim of this study is to evaluate interventions to change perceptions and improve knowledge of leprosy. Methodology/Principal findings We conducted a pre-post intervention study in Fatehpur and Chandauli districts, Uttar Pra-desh, India. Based on six steps of quality intervention development (6SQuID) two interventions were designed: (1) posters that provided information about leprosy and challenged misconceptions, and (2) meetings with persons affected by leprosy, community members and influential people in the community. The effect of the interventions was evaluated in a mixed-methods design; in-depth interviews, focus group discussions, and questionnaires containing a knowledge measure (KAP), two perception measures (EMIC-CSS, SDS) and an intervention evaluation tool. 1067 participants were included in Survey 1 and 843 in Survey 2. The interventions were effective in increasing knowledge of all participant groups, and in changing community and personal attitudes of close contacts and community members (changes of 19%, 24% and 13% on the maximum KAP, EMIC-CSS and SDS scores respectively, p<0.05). In Survey 1, 13% of participants had adequate knowledge of leprosy versus 53% in Survey 2. Responses showed stigmatizing community attitudes in 86% (Sur-vey 1) and 61% (Survey 2) of participants and negative personal attitudes in 37% (Survey 1) and 19% (Survey 2). The number of posters seen was associated with KAP, EMIC-CSS and SDS scores in Survey 2 (p<0.001). In addition, during eight post-intervention focus group discussions and 48 interviews many participants indicated that the perception of leprosy in the community had changed. Conclusions/Significance Contextualized posters and community meetings were effective in changing the perception of leprosy and in increa

Background The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection. Methods This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROS-PERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library. Results We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, perform-ing agricultural labor, and being unemployed. Stigma was the most common social and community factor. Conclusions Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider rele-vant individual, socioeconomic, and community factors, including stigmatization. Further study is requ

Leishmania infantum is transmitted by sand flies and causes visceral leishmaniasis (VL) in humans, as well as canine leishmaniosis (CanL) in dogs, the main reservoir of infection in Europe. The infection spread northwards in the last two decades, but case data are scarce, hindering monitoring and evaluation of incidence as is required by European WHO guidelines. We aim to identify the current geographical distribution of CanL incidence in Spain, which has been endemic for CanL, and France, where CanL is emerging. An online survey was conducted among veterinarians in Spain and France questioning CanL incidence in the years 2016—2017. These data were interpolated to estimate incidence in both countries using the geographical analysis ordinary kriging. Two hundred and seventy-three (273) veterinarians from 81 out of 148 French and Spanish districts completed the survey. The mean incidence in veterinary practices was 21 CanL cases per 1000 dogs during the past year, which was higher in Spain (31/1000 dogs/year) than in France (6/1000 dogs/year). Incidence rates were highest in south-eastern Spain, but sporadic cases were found up to the most northern regions of France. Our study confirms the northward spread of CanL in Spain and France, as the incidence rates were higher than reported in previous studies and cases were found in areas formerly considered non-endemic for L. infantum. Monitoring the reservoir of infection in dogs is essential for implementing timely and geographically-targeted interventions to prevent further spread of CanL and VL in Europe.

To end the decade-long, obstinately stagnant number of new leprosy cases, there is an urgent need for field-applicable diagnostic tools that detect infection with Mycobacterium leprae, leprosy's etiologic agent. Since immunity against M. leprae is characterized by humoral and cellular markers, we developed a lateral flow test measuring multiple host proteins based on six previously identified biomarkers for various leprosy phenotypes. This multi-biomarker test (MBT) demonstrated feasibility of quantitative detection of six host serum proteins simultaneously, jointly allowing discrimination of patients with multibacillary and paucibacillary leprosy from control individuals in high and low leprosy endemic areas. Pilot testing of fingerstick blood showed similar MBT performance in point-of-care (POC) settings as observed for plasma and serum. Thus, this newly developed prototype MBT measures six biomarkers covering immunity against M. leprae across the leprosy spectrum. The MBT thereby provides the basis for immunodiagnostic POC tests for leprosy with potential for other (infectious) diseases as well.