Number of people requiring post-exposure prophylaxis to end leprosy: A modeling study.
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ABSTRACT: 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 administering 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.
SUBMITTER: Taal AT
PROVIDER: S-EPMC7906365 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Number of people requiring post-exposure prophylaxis to end leprosy: A modeling study.
Taal Anneke T AT Blok David J DJ van Brakel Wim H WH de Vlas Sake J SJ Richardus Jan Hendrik JH
PLoS neglected tropical diseases 20210225 2
<h4>Background</h4>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%.<h4>Methodology/principal findings</h4>The individual-based model SIMCOLEP was fitted to seven leprosy settings defin ...[more]
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Project description: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.
| S-EPMC6896699 | biostudies-literature
Project description:BackgroundThe 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.MethodologyThe 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) continuation 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 findingsIn 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 afterwards 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.ConclusionsThe 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.
| S-EPMC8011751 | biostudies-literature
Project description:India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.
| S-EPMC7428216 | biostudies-literature
Project description:BackgroundLeprosy has a wide range of clinical and socio-economic consequences. India, Indonesia and Nepal contribute significantly to the global leprosy burden. After integration, the health systems are pivotal in leprosy service delivery. The Leprosy Post Exposure Prophylaxis (LPEP) program is ongoing to investigate the feasibility of providing single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) to the contacts of leprosy cases in various health systems. We aim to compare national leprosy control programs, and adapted LPEP strategies in India, Nepal and Indonesia. The purpose is to establish a baseline of the health system's situation and document the subsequent adjustment of LPEP, which will provide the context for interpreting the LPEP results in future.MethodsThe study followed the multiple-case study design with single units of analysis. The data collection methods were direct observation, in-depth interviews and desk review. The study was divided into two phases, i.e. review of national leprosy programs and description of the LPEP program. The comparative analysis was performed using the WHO health system frameworks (2007).ResultsIn all countries leprosy services including contact tracing is integrated into the health systems. The LPEP program is fully integrated into the established national leprosy programs, with SDR and increased documentation, which need major additions to standard procedures. PEP administration was widely perceived as well manageable, but the additional LPEP data collection was reported to increase workload in the first year.ConclusionsThe findings of our study led to the recommendation that field-based leprosy research programs should keep health systems in focus. The national leprosy programs are diverse in terms of organizational hierarchy, human resource quantity and capacity. We conclude that PEP can be integrated into different health systems without major structural and personal changes, but provisions are necessary for the additional monitoring requirements.
| S-EPMC5622547 | biostudies-literature
Project description:With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.
| S-EPMC2794871 | biostudies-other
Project description:Pre-exposure prophylaxis (PrEP) has emerged as a promising strategy for preventing the transmission of HIV. Although only one formulation is currently approved for PrEP, research into both new compounds and new delivery systems for PrEP regimens offer intriguing challenges from the perspective of pharmacokinetic and pharmacodynamic modeling. This review aims to provide an overview the current modeling landscape for HIV PrEP, focused on PK/PD and QSP models relating to antiretroviral agents. Both current PrEP treatments and new compounds that show promise as PrEP agents are highlighted, as well as models of uncommon administration routes, predictions based on models of mechanism of action and viral dynamics, and issues related to adherence to therapy. The spread of human immunodeficiency virus (HIV) remains one of the foremost global health concerns. In the absence of a vaccine, other prophylactic strategies have been developed to prevent HIV transmission. One approach, known as pre-exposure prophylaxis (PrEP), allows HIV-negative individuals who are at high risk of exposure to the virus, be it through an HIV-positive sexual partner or through the shared use of drug injection equipment, to substantially reduce the risk of developing an HIV infection. PrEP is a relatively recent approach to combating the HIV epidemic, with the only currently approved treatment being Truvada, a daily oral antiretroviral (ARV) therapy initially indicated in the treatment of active HIV-1 infections, but approved for HIV PrEP in 2012. Although PrEP therapy has consistently demonstrated high efficacy in preventing HIV infection, this efficacy is dependent on patient adherence to the prescribed treatment regimen. This can present a significant problem in low- and middle-income countries, which may lack the infrastructure to provide sufficient access to PrEP medication to maintain daily dosing regimens. Furthermore, while the conventional approach has generally been to advocate for continuous administration akin to regimens used for viral suppression in infected patients, there has been some discussion of whether a better treatment paradigm might be to push for PrEP therapy primarily during those known periods of heightened exposure risk, while relying on post-exposure prophylaxis regimens to prevent infection after unanticipated exposures during low-risk periods. These considerations have led to a push for the development of long-duration and on-demand PrEP formulations, including subdermal and subcutaneous implants, slow-release intramuscular depot injections, vaginal and rectal antimicrobial gels, and intravaginal rings and dissolving films. PrEP therapy is a quickly evolving field, with a variety of antiretroviral compounds and formulations under investigation. This review aims to report on notable drugs and formulations from a pharmacokinetic/pharmacodynamic (PK/PD) modeling perspective. Given the nature of PrEP as a preventive therapy designed for long-term use, clinical trials for PrEP therapies can last for months or even years, particularly in the case of long-duration formulations. Furthermore, in contrast to antiretroviral trials in infected patients, pharmacodynamic endpoints in PrEP therapies are difficult to quantify, as the primary endpoint for efficacy is generally the rate of seroconversion. Computational modeling approaches offer flexible and powerful tools to provide insight into drug behavior in clinical settings, and can ultimately reduce the time, expense, and patient burden incurred in the development of PrEP therapies.
| S-EPMC7005100 | biostudies-literature
Project description:The incidence of human immunodeficiency virus (HIV) infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP) is the use of short-term antiretroviral therapy (ART) to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36-72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE), has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines.
| S-EPMC4216036 | biostudies-other
Project description:From a healthcare perspective, infection due to the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and the ensuing syndrome called COVID-19 (coronavirus disease 2019) represents the biggest challenge the world has faced in several decades. Particularly worrisome are the high contagiousness of the virus and the saturation of hospitals' capacity due to overwhelming caseloads. Non-pharmaceutical interventions such as quarantine and inter-personal distancing are crucial to limiting the spread of the virus in the general population, but more tailored interventions may be needed at an individual level on a case-by-case basis. In this perspective, the most insidious situation is when an individual has contact with a contagious subject without adequate protection. If rapidly recognized afterwards, this occurrence may be promptly addressed through a post-exposure chemoprophylaxis (PEP) with antiviral drugs. This strategy has been implemented for other respiratory viruses (influenza above all) and was successfully used in South Korea among healthcare workers against the Middle East respiratory syndrome (MERS) coronavirus, by providing people who were exposed to high-risk contacts with lopinavir-ritonavir plus ribavirin. Initial experiences with the use of hydroxychloroquine to prevent COVID-19 also seem promising. Post-exposure chemoprophylaxis might help mitigate the spread of SARS-CoV-2 in the current phase of the COVID-19 pandemic.
| S-EPMC7312384 | biostudies-literature
Project description:IntroductionSenegal is a leprosy low-endemic country with nine villages known to be hyperendemic with a leprosy incidence rate above 1,000 per million inhabitants. We aim to implement a door-to-door screening strategy associated with the administration of a single-dose-rifampicin (SDR) as post-exposure prophylaxis (PEP) to household and social contacts in these villages and to identify spatial clustering and assess the risk of leprosy in population according to the physical distance to the nearest index-case.MethodsFrom October/2020 to February/2022 active door-to-door screening for leprosy was conducted in nine villages. Using an open-source application, we recorded screening results, demographic and geographic coordinate's data. Using Poisson model we analysed clustering and estimated risk of contracting leprosy in contacts according to the distance to the nearest new leprosy patient.ResultsIn nine villages, among 9086 contacts listed, we examined 7115. Among 6554 eligible contacts, 97.8% took SDR. We found 39(0.64%) new leprosy cases among 6,124 examined in six villages. Among new cases, 21(53.8%) were children, 10(25.6%) were multibacillary and 05(12.8%) had grade 2 disability. The prevalent risk ratio and 95% confidence intervale(95%CI) adjusted by village were 4.2(95%CI 1.7-10.1), 0.97(95%CI 0.2-4.4), 0.87(95%CI 0.2-25), 0.89(95%CI 0.3-2.6) and 0.70(95%CI 0.2-2.5) for the contacts living in the same household of an index case, 1-25m, 26-50m, 51-75m and 76-100m compared to those living at more than 100m respectively. We identified nine high prevalent clusters including 27/39(69%) of new cases in 490/7,850(6%) inhabitants, with relative risks of 46.6(p-value = 0.01), and 7.3, 42.8, 8.2, 12.5, 11.4, 23.5, 22.3, and 14.6 (non-significant p-values).ConclusionsOur strategy has proved the feasibility of active screening for leprosy in contacts and the introduction of PEP for leprosy under programmatic conditions. Only individuals living in the same household as the leprosy patient had a significant risk of contracting leprosy. We documented nine clusters of leprosy that could benefit from tailored control activities while optimizing resources.
| S-EPMC10863860 | biostudies-literature
Project description:BackgroundDoxycycline post-exposure prophylaxis (DoxyPEP) has demonstrated efficacy for prevention of bacterial sexually transmitted infections. To inform policy decisions on the use of DoxyPEP for gonorrhea prevention, we used a mathematical model to investigate its impact on resistance dynamics and the burden of infection in men who have sex with men (MSM).Methods and findingsUsing a deterministic compartmental model of gonorrhea transmission in an MSM population, we introduced DoxyPEP at various uptake levels (10-75%) and compared 20-year prevalence and resistance dynamics relative to those at baseline (i.e., no DoxyPEP introduction). Uptake of DoxyPEP resulted in initial drops in the prevalence and incidence of gonorrhea infection, but also accelerated the spread of doxycycline resistance, with increasing DoxyPEP use driving steeper initial declines followed by faster spread of resistance. This resulted in the total loss of DoxyPEP's clinical efficacy within 1-2 decades in almost all scenarios explored. The magnitude by which DoxyPEP initially reduced the prevalence of infection was constrained by the extent of pre-existing doxycycline resistant strains in the population. De novo emergence of doxycycline resistance did not influence these dynamics. Additionally, the implementation of DoxyPEP had minimal impact on extending the clinically useful lifespan of ceftriaxone monotherapy.ConclusionsModel findings suggest DoxyPEP can be an effective but short-term solution for reducing the burden of gonorrhea infection, as its selection for doxycycline-resistant strains results in loss of its prophylaxis benefit. Increasing levels of DoxyPEP uptake and higher starting prevalence of doxycycline resistance resulted in faster loss of its efficacy and had little change on extending the clinical lifespan of ceftriaxone for treatment of N. gonorrhoeae infections.
| S-EPMC10168514 | biostudies-literature