The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

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 dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.

Measuring leprosy case detection delay and associated factors in Indonesia: a community-based study.

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.

Testing for sexually transmitted infection: who and where? A data linkage study using population and provider data in the Rotterdam area, the Netherlands.

BACKGROUND: In the Netherlands, insight into sexually transmitted infection (STI) testing and characteristics of those tested by general practitioners (GPs) and sexual health centres (SHC) is limited. This is partly due to lacking registration of socio-demographics at GPs. We aimed to fill this gap by linking different registers. METHODS: Individual STI testing data of GPs and SHC were linked to population register data (aged ≥15 years, Rotterdam area, 2015-2019). We reported population-specific STI positivity, proportion STI tested, and GP-SHC testing rate comparison using negative binomial generalised additive models. Factors associated with STI testing were determined by the provider using logistic regression analyses with generalised estimating equations. RESULTS: The proportion of STI tested was 2.8% for all residents and up to 9.8% for younger and defined migrant groups. STI positivity differed greatly by subgroup and provider (3.0-35.3%). Overall, GPs performed 3 times more STI tests than the SHC. The smallest difference in GP-SHC testing rate was for 20-24-year-olds (SHC key group). Younger age, non-western migratory background, lower household income, living more urbanised, and closer to a testing site were associated with STI testing by either GP or SHC. GPs and SHC partly test different groups: GPs test women and lower-educated more often, the SHC men and middle/higher educated. CONCLUSIONS: This study highlights GPs' important role in STI testing. The GPs' role in the prevention, diagnosis, and treatment of STIs needs continued support and strengthening. Inter-professional exchange and collaboration between GP and SHC is warranted to reach vulnerable groups.

The roles of the general practitioner and sexual health centre in HIV testing: comparative insights and impact on HIV incidence rates in the Rotterdam area, the Netherlands - a cross-sectional population-based study.

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 relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.

The value of manual backward contact tracing to control COVID-19 in practice, the Netherlands, February to March 2021: a pilot study.

BackgroundContact 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.MethodsWe 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.ResultsOf 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.ConclusionsThe addition of manual BCT to control the COVID-19 pandemic did not provide added value in our study setting.

A sharp decrease in reported non-COVID-19 notifiable infectious diseases during the first wave of the COVID-19 epidemic in the Rotterdam region, the Netherlands: a descriptive study.

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.

Obtaining nasal and rectal swabs from general practice patients to assess carriage of antibiotic resistant microorganisms: a feasibility study.

PURPOSE: The aim of this study was to assess the feasibility of obtaining nasal and rectal swabs from general practice patients for measuring carriage of antibiotic resistant microorganisms in an area in Rotterdam (the Netherlands) with low socioeconomic status and a large immigrant population. METHODS: Data collection was from May to December 2017, in one general practice in Rotterdam. We asked adults (≥18 years) visiting the general practitioner (GP) with complaints not related to infections for one nasal and two rectal swabs and tested these for highly resistant microorganisms (HRMOs). Indicators for feasibility were recruitment rate, implementation and acceptation of data collection procedures by the participants. RESULTS: We obtained a nasal swab from all included 234 patients and 164 (70%) also gave rectal swabs. On average, 3 out of 30 invited patients (10%) were recruited per day. The GPs considered the workload high to inform and refer to eligible patients for the study and did this inconsistently. Most participants experienced the rectal swab procedure as burdensome and preferred assistance of a medical assistant above self-swabbing. A monetary incentive increased the willingness to provide rectal swabs. CONCLUSIONS: Obtaining (nasal and) rectal swabs from general practice patients for study purposes proved difficult. Lessons learnt from this feasibility study will help increase participation in HRMO prevalence studies among asymptomatic general practice patients.

Distance as explanatory factor for sexual health centre utilization: an urban population-based study in the Netherlands.

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- and 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.

Low antimicrobial resistance in general practice patients in Rotterdam, the city with the largest proportion of immigrants in the Netherlands.

Antimicrobial resistance (AMR) is an increasing problem. The prevalence of antimicrobial resistance in general practice patients is expected to be relatively high in Rotterdam, the Dutch city with the largest proportion non-Western immigrants. The aim of this study was to assess the prevalence of antibiotic-resistant uropathogens (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) in general practices in Rotterdam, and to find a possible association between the prevalence of antibiotic-resistant E. coli and age, gender, and socioeconomic status (SES). A retrospective analysis was performed of urine samples from general practice patients in 2016. The prevalence of AMR in uropathogens was compared with national resistance data, as was the prevalence of highly and multidrug resistant and extended spectrum ß-lactamase (ESBL) producing E. coli and K. pneumoniae. Univariate logistic regression was used to study associations between antibiotic-resistant E. coli and age, gender, and SES area score. No clinically relevant differences were observed in the prevalence of antibiotic-resistant uropathogens in Rotterdam compared with the national prevalence. For E. coli and K. pneumoniae, the prevalence was 3.6% for ESBL production (both pathogens together), while the prevalence ranged between 4.2%-5.0% for high resistance and between 1.2%-3.3% for multidrug resistance. Ciprofloxacin-resistant E. coli was significantly associated with higher age. Although Rotterdam has a high percentage of non-western immigrants and a low SES, AMR is low among general practice patients. This indicates that adherence to national guidelines in general practice enables maintenance of low AMR, even in high-risk populations.

Cost of seeking care for tuberculosis since the implementation of universal health coverage in Indonesia.

BACKGROUND: Although tuberculosis (TB) patients often incur high costs to access TB-related services, it was unclear beforehand whether the implementation of universal health coverage (UHC) in Indonesia in 2014 would reduce direct costs and change the pattern of care-seeking behaviour. After its introduction, we therefore assessed TB patients' care-seeking behaviour and the costs they incurred for diagnosis, and the determinants of both. METHODS: In this cross sectional study, we interviewed adult TB patients in urban, suburban, and rural districts of Indonesia in July-September 2016. We selected consecutively patients who had been treated for TB in primary health centers for at least 1 month until we reached at least 90 patients in each district. After establishing which direct and indirect costs they had incurred during the pre-diagnostic phase, we calculated the total costs (in US Dollars). To identify the determinants of these costs, we applied a general linear mixed model to adjust for our cluster-sampling design. RESULTS: Ninety-three patients of the 282 included in our analysis (33%) first sought care at a private clinic. The preference for such clinics was higher among those living in the rural district (aOR 1.88, 95% CI 0.85-4.15, P = 0.119) and among those with a low educational level (aOR 1.69, 95% CI 0.92-3.10, P = 0.090). Visiting a private clinic as the first contact also led to more visits (ß 0.90, 95% CI 0.57-1.24, P < 0.001) and higher costs than first visiting a Primary Health Centre, both in terms of direct costs (ß = 16.87, 95%CI 10.54-23.20, P < 0.001) and total costs (ß = 18.41, 95%CI 10.35-26.47, P < 0.001). CONCLUSION: Despite UHC, high costs of TB seeking care remain, with direct medical costs contributing most to the total costs. First seeking care from private providers tends to lead to more pre-diagnostic visits and higher costs. To reduce diagnostic delays and minimize patients' costs, it is essential to strengthen the public-private mix and reduce the fragmented system between the national health insurance scheme and the National TB Programme.

Client perspectives on an outreach approach for HIV prevention targeting Indonesian MSM and transwomen.

This study explored clients' perspective on an outreach approach to promote HIV testing in Indonesia targeting men who have sex with men (MSM) and transgender women (transwomen or waria). Semi-structured qualitative interviews were conducted with 32 individuals (21 MSM and 11 waria) who had received services from outreach workers (OWs) in five cities in Indonesia. Participants in this study reported positive experiences with the outreach approach and perceived OWs as their motivators in accessing HIV testing as well as HIV care and treatment. OWs provided easy-to-understand HIV information. Clients expected OWs to be well-trained and more creative in performing outreach. They perceived that the Internet and social media have helped them considerably to stay in touch with OWs. Yet, they expressed that such virtual contacts could not simply replace the face-to-face contact, especially for waria. Furthermore, clients suggested outreach to be delivered in a more appealing manner, for example through activities that may facilitate clients learning professional or life skills. They also asserted that as an HIV prevention approach, outreach needs to use more positive framing and go beyond HIV and health contents, chiefly for the youth. Future outreach programmes should facilitate OWs in providing tailored services based on the level and type of support that the clients need, and in applying varied proportion and levels of sophistication in the use of online and virtual platforms for outreach.

Leprosy services in primary health care in India: comparative economic cost analysis of two public-health settings.

OBJECTIVES: The WHO recommends inclusion of post-exposure chemoprophylaxis with single-dose rifampicin in national leprosy control programmes. The objective was to estimate the cost of leprosy services at primary care level in two different public-health settings. METHODS: Ingredient-based costing was performed in eight primary health centres (PHCs) purposively selected in the Union Territory of Dadra and Nagar Haveli (DNH) and the Umbergaon block of Valsad district, Gujarat, India. All costs were bootstrapped, and to estimate the variation in total cost under uncertainty, a univariate sensitivity analysis was performed. RESULTS: The mean annual cost of providing leprosy services was USD 29 072 in the DNH PHC (95% CI: 22 125-36 020) and USD 11 082 in Umbergaon (95% CI: 8334-13 830). The single largest cost component was human resources: 79% in DNH and 83% in Umbergaon. The unit cost for screening the contact of a leprosy patient was USD 1 in DNH (95% CI: 0.8-1.2) and USD 0.3 in Umbergaon (95% CI: 0.2-0.4). In DNH, the unit cost of delivering single-dose of rifampicin (SDR) as chemoprophylaxis for contacts was USD 2.9 (95% CI: 2.5-3.7). CONCLUSIONS: The setting with an enhanced public-health financing system invests more in leprosy services than a setting with fewer financial resources. In terms of leprosy visits, the enhanced public-health system is hardly more expensive than the non-enhanced public-health system. The unit cost of contact screening is not high, favouring its sustainability in the programme.

Clustering of leprosy beyond the household level in a highly endemic setting on the Comoros, an observational study.

BACKGROUND: The island of Anjouan (Comoros) is highly endemic for leprosy with an annual incidence of 5-10/10,000. In May/June, 2015 single-dose Rifampicin post-exposure prophylaxis (SDR-PEP) was administered to 269 close contacts of 70 leprosy-patients in four villages as a pilot programmatic intervention. Two years later we revisited the villages for follow-up investigations. The main aim of our study was to quantify spatial associations between reported leprosy cases before and after PEP implementation. A secondary aim was to assess the effect of this single round of SDR-PEP at the individual level. METHODS: We conducted door-to-door leprosy screening in all four villages in August/September, 2017. We screened all consenting individuals for leprosy and recorded geographic coordinates of their household. We also recorded whether they had received SDR-PEP and whether they had been diagnosed with leprosy, before or after the 2015 intervention. We fitted a Poisson model with leprosy as outcome and distance to the nearest pre-intervention case and SDR-PEP as predictors. RESULTS: During the survey we found 114 new cases among 5760 contacts screened (2.0% prevalence), in addition to the 39 cases detected in the two preceding years. We found statistically significant associations of incident leprosy with physical distance to index cases ranging from 2.4 (95% confidence interval (95% CI) 1.5-3.6) for household contacts to 1.8 (95% CI 1.3-2.5) for those living at 1-25 m, compared to individuals living at ≥75 m. The effect of SDR-PEP appeared protective but did not reach statistical significance due to the low numbers, with an incidence rate ratio (IRR) of 0.6 (95% CI 0.3-1.2) overall, and 0.5 (95% CI 0.2-1.3) when considering only household contacts. CONCLUSIONS: This pilot demonstrated an increased risk of leprosy in contacts beyond the household, therefore a wider circle should be considered for chemoprophylaxis. Baseline surveys and extended contact definitions are essential for improving SDR-PEP effectiveness.

Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts.

BACKGROUND: Leprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar. METHODS: PEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-to-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. DISCUSSION: Different trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP. TRIAL REGISTRATION: Clinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018.

Evaluation of a training aimed at building capacity for outreaching to men who have sex with men and transgender women in Indonesia.

Implementers of outreach program in Indonesia often provide formal training for their outreach workers (OWs) only at the startup. We believe continuous training can be provided by experienced OWs at any time if an appropriate training package is available. Using a one-group pre-test-post-test study design; we developed, implemented and evaluated an OW-informed training program aimed at increasing OWs' knowledge and skills for outreaching to men who have sex with men and transgender women. We analyzed longitudinal data from 75 OWs from 7 Indonesian cities using one-way within-subjects ANOVA to examine the effects of the training program on participants' knowledge and perceived skills over time Average overall knowledge among participants increased from pre-test to immediate post-test (P < 0.001) and from pre-test to 2-month post-test (P < 0.001), especially in basic human immunodeficiency virus and sexual transmitted infections; condoms and lubricants; sexual and reproductive health and rights; sexual orientation and gender identity and expression; and stages of behavior change. Average overall perceived skills increased significantly from pre-test to 2-month post-test (P = 0.018), especially in creating innovative outreach approaches; building effective teamwork; and coordinating with healthcare providers. This training package increased knowledge and perceived skills among OWs. Thus, if consistently applied, it could help maintaining quality of the outreach program.

Policy Lessons From Quantitative Modeling of Leprosy.

Recent mathematical and statistical modeling of leprosy incidence data provides estimates of the current undiagnosed population and projections of diagnosed cases, as well as ongoing transmission. Furthermore, modeling studies have been used to evaluate the effectiveness of proposed intervention strategies, such as postleprosy exposure prophylaxis and novel diagnostics, relative to current approaches. Such modeling studies have revealed both a slow decline of new cases and a substantial pool of undiagnosed infections. These findings highlight the need for active case detection, particularly targeting leprosy foci, as well as for continued research into innovative accurate, rapid, and cost-effective diagnostics. As leprosy incidence continues to decline, targeted active case detection primarily in foci and connected areas will likely become increasingly important.

Population-wide administration of single dose rifampicin for leprosy prevention in isolated communities: a three year follow-up feasibility study in Indonesia.

BACKGROUND: Indonesia ranking third in the world, regarding leprosy burden. Chemoprophylaxis is effective in reducing risk of developing leprosy among contacts. 'Blanket approach' is an operational strategy for leprosy post-exposure prophylaxis in which all members of an isolated community, high endemic for leprosy are screened and given a single dose of rifampicin (SDR) in the absence of signs and symptoms of leprosy. The objective is to assess the operational feasibility of a population-wide 'blanket' administration of SDR for leprosy prevention in isolated communities in a remote island. METHODS: A prospective follow-up study was conducted in the year 2014, 2015 and 2016 in Lingat village of Selaru Island, Indonesia. During the first two visits, screening and SDR were provided, whereas only screening was conducted during the third visit. The demographic and clinical data were used for a descriptive analysis of the project coverage and leprosy epidemiology. RESULTS: During the first two visits, 1671 persons (88%) were screened, 1499 (79%) received SDR, and 213 (11%) were excluded based on the exclusion criteria. During the first two visits, 43 (2.6%) cases were diagnosed with leprosy with a rate of 2263 per 100,000 population. The prevalence was highest in the age groups 15-24 and 25-49 years. Total, 14 (33%) cases had MB and 29 (67%) PB leprosy. Two cases (5%) had grade 2 disability. During the third visit, 10 new leprosy cases, with no grade 2 disability, were detected out of 1481 screened persons at the rate of 484 cases per 100,000 population (n = 2065 population in 2016). Among those screened during the third visit, there was a 50% reduction of leprosy among those who had previously received SDR compared to those who had not. CONCLUSION: With adequate planning and some additional investment, it is feasible to implement a blanket approach of chemoprophylaxis in a remote island of Indonesia, although effort needs to be made to cover as many people as possible in the first visit. Contingency plans need to be made to actively follow this village closely in the coming years and continue leprosy elimination efforts until no new cases are found any more.

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

Ebola Preparedness in the Netherlands: The Need for Coordination Between the Public Health and the Curative Sector.

CONTEXT: During the Ebola outbreak in West Africa in 2014-2015, close cooperation between the curative sector and the public health sector in the Netherlands was necessary for timely identification, referral, and investigation of patients with suspected Ebola virus disease (EVD). OBJECTIVE: In this study, we evaluated experiences in preparedness among stakeholders of both curative and public health sectors to formulate recommendations for optimizing preparedness protocols. Timeliness of referred patients with suspected EVD was used as indicator for preparedness. DESIGN: In focus group sessions and semistructured interviews, experiences of curative and public health stakeholders about the regional and national process of preparedness and response were listed. Timeliness recordings of all referred patients with suspected EVD (13) were collected from first date of illness until arrival in the referral academic hospital. RESULTS: Ebola preparedness was considered extensive compared with the risk of an actual patient, however necessary. Regional coordination varied between regions. More standardization of regional preparation and operational guidelines was requested, as well as nationally standardized contingency criteria, and the National Centre for Infectious Disease Control was expected to coordinate the development of these guidelines. For the timeliness of referred patients with suspected EVD, the median delay between first date of illness until triage was 2.0 days (range: 0-10 days), and between triage and arrival in the referral hospital, it was 5.0 hours (range: 2-7.5 hours). In none of these patients Ebola infection was confirmed. CONCLUSIONS: Coordination between the public health sector and the curative sector needs improvement to reduce delay in patient management in emerging infectious diseases. Standardization of preparedness and response practices, through guidelines for institutional preparedness and blueprints for regional and national coordination, is necessary, as preparedness for emerging infectious diseases needs a multidisciplinary approach overarching both the public health sector and the curative sector. In the Netherlands a national platform for preparedness is established, in which both the curative sector and public health sector participate, in order to implement the outcomes of this study.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.