Leprosy Contacts Research Articles

Anti‑phenolic glycolipid‑I seropositivity among household contacts of leprosy patients in Egypt.

Leprosy is a chronic, debilitating disease lacking a definitive diagnostic biomarker. Serum anti-phenolic glycolipid-I (PGL-I) IgM antibody level is considered an important diagnostic and prognostic marker for leprosy patients. However, there is limited evidence on the role of anti-PGL-I IgM antibody level as early predictive biomarker of subclinical infection among Egyptian household contacts of leprosy patients. This study investigates the relationship between specific leprosy risk factors, diagnostic parameters of eighty-three leprosy cases, and serum anti-PGL-I IgM antibody levels in their corresponding household contacts. Our results demonstrate that anti-PGL-I IgM antibody level was significantly higher among contacts when more than four residents shared the same room with a leprosy case (p = 0.032). Additionally, anti-PGL-I IgM antibody level markedly increased in contacts of leprosy cases with disabilities (p = 0.001) or damaged nerves (p = 0.001). Our ROC curve analysis of anti-PGL-I antibody level as a predictor of exposure or infection among contacts revealed a cut-off value of 0.1, with a sensitivity of 75.0% and a specificity of 54.5%, indicating that most exposed household contacts are correctly identified. The overall accuracy of the ROC curve analysis was 72.3%, highlighting the practical utility of anti-PGL-I antibody level as a predictor for exposure or infection among household leprosy contacts. In conclusion, seropositivity of anti-PGL-I antibodies (> 0.1) among household leprosy contacts may be associated with a higher leprosy exposure risk. Continuous monitoring of anti-PGL-I antibody level in household leprosy contacts may potentially contribute to early detection and management of leprosy.

Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

MIP vaccine in leprosy: A scoping review and future horizons.

Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier known as Mycobacterium welchii, is a rapidly growing non-pathogenic mycobacterium. The novelty of this bacterium is due to its translational application as an immunotherapeutic agent. When administered intradermally, the vaccine induces cell-mediated immunity in the host towards Mycobacterium leprae. It leads to faster clinical and histopathological improvement, rapid bacillary clearance, and also lepromin conversion in anergic leprosy patients. The beneficial role of the MIP vaccine in augmenting the therapeutic efficacy of Multidrug Therapy (MDT), particularly in highly bacillated leprosy patients, is well documented in various studies from India. The role of the vaccine in reactional states is controversial, with varied results in different studies. Overall, it is found to decrease the frequency of type 2 lepra reactions and is useful in recalcitrant erythema nodosum leprosum. Even though there may be an increased likelihood of type 1 reactions, no additional nerve function impairment is attributed to the vaccine in various studies. In household contacts of leprosy who are administered MIP, it is noted to confer protection from disease lasting up to 10 years. It may prove to be a cost-effective strategy in national leprosy programmes. Apart from local injection site reactions, the vaccine is relatively safe, but it is not recommended in pregnancy and lactation. This article provides an overview of the MIP vaccine's clinical application in the context of leprosy spanning over 40 years. It also considers the vaccine's possible future applications in the management of disease-related complications and achieving the long-term goal of zero leprosy.

Comparative analysis of natural resistance-associated macrophage protein 1 gene expression and anti-PGL-1 antibodies in multibacillary leprosy and household contacts.

Leprosy continues to pose a significant challenge to public health, particularly in certain global regions. Accurate diagnosis and understanding of the disease's etiology are crucial for effective management and prevention. This study aimed to explore the contribution of Natural resistance-associated macrophage protein 1 (NRAMP1) and its genetic variations, as well as the levels of anti-PGL-1 antibodies, to the pathology of multibacillary leprosy in affected individuals and their household contacts. The study included 23 multibacillary leprosy patients and 28 household contacts. NRAMP1 protein expression and anti-PGL-1 IgG and IgM levels were measured using PCR and ELISA techniques, respectively. Genotypic variants of the NRAMP1 gene were also examined. Statistical analyses, including Mann-Whitney tests and univariate logistic regression, were employed to evaluate the data. Significant differences were observed in NRAMP1 protein expression and IgG and IgM levels between the patient and household contact groups. The study also highlighted the role of the NRAMP1 gene and its D543N and 3'UTR polymorphisms in leprosy susceptibility. No significant differences were observed in the genotype variants of INT4 between the two groups. These findings emphasize the potential of integrating PCR technology with serological tests to enhance diagnostic precision in leprosy. They also suggest the need for further research to clarify the role of NRAMP1 and its polymorphisms in leprosy susceptibility and resistance.

Asymptomatic leprosy contacts present asymmetrical skin temperature in hands by infrared thermography

Asymptomatic leprosy contacts present asymmetrical skin temperature in hands by infrared thermography

Community-Based Intervention for Active Detection and Provision of Single-Dose Rifampicin Post-Exposure Prophylaxis to Household Contacts of Leprosy in Bolivia.

To achieve zero leprosy cases in Santa Cruz, Bolivia, we designed a community-based active detection and provision of single-dose rifampicin post-exposure prophylaxis (SDR-PEP) to household contacts with new leprosy patients. From July to August 2021, we assessed the current knowledge, attitude, and practices through structured interviews and focus group discussions with community representatives and health staff. This was followed by sensitization sessions, the training of health staff, and the reinforcement of referral mechanisms. Teams, including health staff and community volunteers, visited all new leprosy patients detected in 2021-2023 and household contacts. Among 115 community representatives, knowledge about leprosy etiology was attributed to non-biological factors (74%); fear accounted for 77%, and access to care was perceived as weak (74%), but the outlook was improved by SDR-PEP (80%). Among the 217 health staff interviewed, the programmatic barriers identified were a lack of referral feedback (67%), limited supplies for diagnosis and prevention, and ineffective training (64%). We visited 70 new patients and 258 household contacts. The median age in household contacts was 25 years old; 49% were women, 98% were eligible for SDR-PEP, and all who were eligible accepted it. Those who were non-eligible included one tuberculosis patient and six newly detected leprosy patients (23‱). A community-based intervention was successful in Santa Cruz, Bolivia. Misbeliefs and a lack of knowledge were identified as barriers. Programmatic components should be reinforced for SDR-PEP extension.

Role of predictors in acceptance of post-exposure prophylaxis with single-dose rifampicin among contacts of leprosy in rural area of Bankura: An explanatory mixed-method study

Background: India achieved the elimination of leprosy two decades ago although its sustenance continues to be threatened by ongoing active transmission in few remaining pockets. There is a paucity of data regarding the acceptance of single-dose rifampicin (SDR) prophylaxis among healthy contacts. Aims and Objectives: The aims and objectives of the study are to assess the factors influencing the acceptability of SDR among contacts. Materials and Methods: A community-based, sequential, explanatory mixed-method study was conducted over 6 months from September 2022 to February 2023 among 168 contacts of leprosy patients from two blocks in Bankura district, West Bengal. Quantitative analysis was done for SDR acceptance and its predictors among contacts using the Chi-square test, Mann–Whitney U test, and Logistic regression. This was followed by qualitative assessment using focus group discussions and in-depth interviews among contacts to explain the findings through a thematic approach. Results: Household contacts (aOR=13.72, 95% CI=2.09–90.19), increasing knowledge score of contacts (aOR=3.18, 95% CI=1.88–5.38), counseling by health workers (aOR=11.98, 95% CI=2.20–65.15), trust in health workers (aOR=152.96, 95% CI=13.17–1776.09), and not taking other medicines for comorbidity (aOR=35.82, 95% CI=2.94–436.02) were associated with increased SDR uptake among leprosy contacts. Barriers and facilitators of post-exposure prophylaxis (PEP)-SDR were categorized as contact, health workers, and program-related factors. Conclusion: SDR acceptability among contacts was 77.4%. Facilitators of SDR-PEP were awareness of side-effects, follow-up, prompt support by health workers, IEC, belief in National programs, etc. Lack of knowledge of PEP-SDR and contraindications, ineffective counseling by health workers, stigma of the disease, the increased workload of health workers, etc., were the barriers to SDR-PEP implementation.

Single-Dose Rifampicin Leprosy Chemoprophylaxis for Household Contacts in Kiribati: An Audit of a Combined Retrospective and Prospective Approach.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, an SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases retrospectively (2010-2017) and prospectively (2018-2022). We conducted a retrospective audit to determine the comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,641 household contacts were identified (9791 in the retrospective and 3850 in the prospective cohort). In the retrospective cohort, 1044 (11%) contacts were absent, 403 (4%) were ineligible for SDR, and 42 new cases were detected (0.4%) Overall, SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR, and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were 23 SDR refusals. The median time to SDR administration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts, respectively. SDR was readily accepted in both cohorts. The new case detection rate (0.5%) is consistent with that in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Relationship between Leprosy Suspicion Questionnaire with IgM anti-PGL-1 antibody levels in household contacts of leprosy

Introduction: Leprosy is a chronic granulomatous disease affecting mainly the skin and peripheral nerves caused by the obligate intracellular pathogen Mycobacterium leprae. This study aimed to determine the relationship between Leprosy Suspicion Questionnaire (LSQ) and anti-PGL-1 IgM antibody levels in household contacts of leprosy patients. Methods: This research was an observational analytical study with a cross-sectional design. The sample consisted of 30 subjects who were household contacts of leprosy patients. Anti-PGL-1 IgM antibody levels were examined using the ELISA method at the Cito Laboratory, Yogyakarta. Results: Regarding demographic characteristics, there were 18 female subjects (60%) and 12 male subjects (40%). LSQ+ results were found in 22 (73.3%) subjects, while LSQ- results were found in 8 (26.7%) subjects. The results of the anti-PGL-1 IgM examination were classified into three categories, namely seronegative (<605 U/ mL) totaling 25 people (83.3%), low titer seropositivity (605–1000 U/mL) totaling four people (13.3 %), and high titer seropositivity (>1000 U/mL) was one person (3.3%). The mean value of IgM anti-PGL-1 was 383.63 U/mL, with the lowest value being 0 and the highest being 1593 U/mL. Using Fischer's Exact showed no relationship between LSQ and IgM Anti-PGL-1 (p=0.287). Conclusions: No relationship was found between LSQ and anti-PGL-1 IgM antibody levels in household contacts of leprosy patients. The results of the LSQ answers correlated with anti-PGL-1 IgM antibodies found in only five subjects.

Feasibility of post-exposure-prophylaxis with single-dose rifampicin and identification of high prevalent clusters in villages' hyperendemic for leprosy in Senegal.

Senegal 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. From 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. In 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). Our 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.

Whole mitogenome sequencing uncovers a relation between mitochondrial heteroplasmy and leprosy severity

BackgroundIn recent years, the mitochondria/immune system interaction has been proposed, so that variants of mitochondrial genome and levels of heteroplasmy might deregulate important metabolic processes in fighting infections, such as leprosy.MethodsWe sequenced the whole mitochondrial genome to investigate variants and heteroplasmy levels, considering patients with different clinical forms of leprosy and household contacts. After sequencing, a specific pipeline was used for preparation and bioinformatics analysis to select heteroplasmic variants.ResultsWe found 116 variants in at least two of the subtypes of the case group (Borderline Tuberculoid, Borderline Lepromatous, Lepromatous), suggesting a possible clinical significance to these variants. Notably, 15 variants were exclusively found in these three clinical forms, of which five variants stand out for being missense (m.3791T > C in MT-ND1, m.5317C > A in MT-ND2, m.8545G > A in MT-ATP8, m.9044T > C in MT-ATP6 and m.15837T > C in MT-CYB). In addition, we found 26 variants shared only by leprosy poles, of which two are characterized as missense (m.4248T > C in MT-ND1 and m.8027G > A in MT-CO2).ConclusionWe found a significant number of variants and heteroplasmy levels in the leprosy patients from our cohort, as well as six genes that may influence leprosy susceptibility, suggesting for the first time that the mitogenome might be involved with the leprosy process, distinction of clinical forms and severity. Thus, future studies are needed to help understand the genetic consequences of these variants.

Serological IgM antibody profile of <i>M. Leprae</i> PGL-1 and characteristics of leprosy contacts from an endemic area in East Java, Indonesia

Background: Indonesia has the third-highest leprosy prevalence, and the transmission continues. Objectives: the present study aimed to describe some of the characteristics of leprosy contacts, such as the profile of the serological antibody IgM anti-PGL-1, socioeconomic factors, environmental factors, and behavioral factors. Materials and Methods. We conducted a cross-sectional study involving 77 leprosy contacts from an endemic area in Winongan, Pasuruan, East Java, Indonesia. The households or neighbors of the leprosy case recorded at Winongan Health Center, voluntarily participated in this study. Informed consent was obtained before starting the study. Three of them were excluded because they showed skin lesions as leprosy symptoms. Serum samples were assayed for IgM antibodies PGL-1 titers using enzyme-linked immunosorbent assay (ELISA). The questionnaire was used to collect information about demographic, socioeconomic, environmental, and behavioral aspects of contact. The data were analyzed descriptively using Fisher’s Exact Test. Results. Of 74 contacts, all of them were contacts of MB cases, and 6 (8.11%) were seropositive, with a cut-off point ≥ 605 ug/ml. Although none of the contact characteristics were significantly associated with IgM anti-PGL-1 seropositivity, potential risk markers and indirect transmission of leprosy were identified, including 56.76% manual labor, 90.54% living in poverty, 83.78% drinking from unprotected springs, only 20.27% boiling water to drink, and 48.65% bathing in open water bodies. Conclusions. The seropositivity among contacts, especially perimeter contacts, may identify potential active infection and transmission of leprosy in this population. Identified potential risk markers of leprosy should be noticed for prevention programs supporting leprosy elimination.

Protocol, rationale and design of BE-PEOPLE (Bedaquiline enhanced exposure prophylaxis for LEprosy in the Comoros): a cluster randomized trial on effectiveness of rifampicin and bedaquiline as post-exposure prophylaxis of leprosy contacts

BackgroundLeprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP.MethodsBE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150–600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial.DiscussionThe COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone.Trial registrationNCT05597280. Protocol version 5.0 on 28 October 2022.

Comparison of antiphenolic glycolipid-1 antibody levels in seropositive contacts of leprosy after 2 years of single-dose rifampicin as postexposure prophylaxis.

Leprosy is still a global problem, especially in developing countries, including Indonesia. Ineffective prevention of leprosy leads to active transmission of the disease. World Health Organization (WHO) recommend post-exposure prophylaxis (PEP) with single dose of rifampicin (SDR) for leprosy patients. Previous study showed protective effect of SDR against leprosy, especially for the first 2 years. Hence, the use of PEP and IgM anti PGL-1 examination are required to suspend the chain of leprosy transmission. This study evaluated the effectiveness of SDR administration by comparing IgM anti-PGL-1 antibody levels in seropositive household contacts before and after 2 years of SDR administration. Analytical observational laboratory study comparing IgM anti PGL-1 antibody levels before and after 2 years of SDR administration in leprosy contacts, with a prospective follow-up study design. We conducted this study from December 2022 to January 2023 at Dr. Mohammad Hoesin General Hospital Palembang. All seropositive household contacts of leprosy who had been administrated SDR 2 years ago were included, then PGL-1 antibody levels were examined. The use of SDR showed significant improvement in leprosy contacts after 2 years (P=0.000). The median antibody level before SDR administration was 1,209.20 (615.81 - 4,353.60), which decrease to 146.03 (0 - 2,487.80) U/mL after 2 years. There was statistically significant relationship between history of BCG vaccination (P=0.003) and IgM PGL-1 antibody levels after 2 years of SDR administration. There is a significant decrease in IgM anti PGL-1 antibody levels among leprosy contacts after 2 years of SDR chemoprophylaxis administration.

The application of digital health as a nursing solution for leprosy patients during the COVID-19 pandemic: a systematic review

To analyse the effect of using digital health technology on leprosy control programmes. The systematic review comprised search on PubMed, Scopus, ScienceDirect, SAGE and ProQuest databases for interventional studies published in English language from 2013 to 2021 which used digital health technology for leprosy contact tracing, active leprosy detection, monitoring of multi-drug therapy and treatment management during the corona virus disease-2019 pandemic A standard risk of bias tool was used to evaluate bias in the studies, and the Joanna Briggs Institute protocol was used to assess the quality of the studies analysed. Of the 205 studies initially identified, 15(7.3%) were analysed in detail. Quasi-experimental studies had a low risk of bias compared to the rest. The e-leprosy framework was being used along with applications based on smartphones and artificial intelligence Digital health technology was found to be practical, accessible and effective in leprosy control programmes. Studies reported favourable findings regarding the use of digital health technology in services related to leprosy patients.

Clinicoepidemiological Profile of Childhood Leprosy in a Tertiary Care Hospital of North Karnataka

Abstract Background: Childhood leprosy is an indicator of ongoing transmission of the disease. The prevalence rate of pediatric leprosy is considered an important epidemiological index for determining the level of transmission of the disease. Our aim was to estimate the proportion of leprosy cases among children aged 0–14 years in our tertiary care hospital. Methods: A retrospective study was carried out for a period of 4 years from January 2017 to December 2020. Secondary data were collected from leprosy records pertaining to childhood leprosy (aged between 0 and 14 years). Only new cases presented during the period were included. Details of the patients such as age, sex, family history, number and site of lesions, nerve involvement, reactions, and deformities were noted. Slit-skin smear and biopsy findings were tabulated and descriptive analysis was done. Results: Fifty-five cases (9.54%) of childhood leprosy were diagnosed. Majority of the cases were in the age group of 10–14 years. The most common leprosy type was borderline tuberculoid found in 42 patients (76.36%). Forty-nine patients (89.09%) had paucibacillary (PB) and 6 (10.91%) had a multibacillary type. The most common presenting symptom was patch (61.8%). Eleven patients had a family history. Clinicopathological correlation was observed in 50 (90%) patients. Lepra reactions were seen in six (10.9%) patients and two deformities in three patients. Conclusion: The proportion of pediatric leprosy cases was 11.61% in 2017 and decreased to 6.45% in 2020. PB type is the most common type. To achieve zero childhood leprosy cases, thorough follow-up and contact tracing of adult leprosy patients, early diagnosis of childhood leprosy to prevent disabilities is the need of the hour.

ELISA Test Based on the Phenolic Glycolipid-I (PGL-I) of Mycobacterium leprae: A Reality of a Laboratory from a Non-Endemic Country

Background: Leprosy is a neglected tropical disease caused by Mycobacterium leprae, leading to disabilities if untreated. The ELISA based on phenolic glycolipid I (PGL-I), or its synthetic version ND-O-BSA, is almost universally positive in multibacillary leprosy and thus extensively used in endemic countries. Household contacts with a positive antibody titer have ~6-fold higher probability to develop the disease than those with a negative titer. Thus, the aim of the study was to evaluate the performance of this ELISA in the setting of a non-endemic country. Methods: We calculate the cut-off using optimized O.D. thresholds, generated by receiver operating characteristics (ROC) curve analysis, testing 39 well-characterized sera obtained from lepromatous leprosy patients with strongly positive ND-O-BSAELISA titer and 39 sera from healthy non-endemic patients never exposed to M. leprae or M. tuberculosis. Indeed, we tested a second set of sera from suspected or confirmed leprosy or household contacts (SLALT group, n=50), and patients with tuberculosis (control group, n=40). Results: We detected 56.4% of SLALT and 22.5% of tuberculosis as positive, consistent with the literature. Conclusion: The ELISA based on ND-O-BSA may thus be considered a good option to be used in a non-endemic area as a screening tool in at risk population usually coming to our center.

Laboratory perspectives for Leprosy: Diagnostic, prognostic and predictive tools.

The diagnosis of leprosy poses several challenges. The bacillary load, serology, and tissue response are determined by the host immune status, which make individual tests unsuitable across the spectrum. The sensitivity of tests for identifying paucibacillary cases remains limited, on the other hand, many tests lack specificity in differentiating contacts from diseased cases. Nonetheless, a plethora of laboratory tests have been added to the armamentarium of the clinicians dealing with leprosy. In the current review, we critically analyze the tests available for diagnosis, prognostication, and prediction of treatment response in leprosy. We discuss in brief the conventional tests available and detail the newer serologic and molecular tests added over the past few years with an attempt to suggest the pros and cons of each, and the tests best fit for each clinical scenario. Slit skin smears and skin or nerve biopsies are primarily performed to exclude clinical mimics, confirm a diagnosis, and immunologically subtype the case. Antibody titres of phenolic glycolipid-1 and its synthetic variants can be measured in serum and saliva and provide noninvasive means to detect leprosy with good specificity. Conventional, quantitative, real-time, and other variants of PCR can detect M. leprae DNA and have been used to effect in blood, tissue, and urine samples. T helper I and II cytokine signatures can be used to differentiate the subtypes of leprosy. Newer machine learning algorithms use combinations of these tests to predict the development of leprosy in contacts. Tests to detect treatment response, antimicrobial drug resistance, and predict the onset of reactions in leprosy can be used to advantage. We compare the characteristics of these tests and suggest an algorithm for leprosy diagnosis optimally utilizing them in various clinical settings.

Algorithm Design for a Cytokine Release Assay of Antigen-Specific In Vitro Stimuli of Circulating Leukocytes to Classify Leprosy Patients and Household Contacts.

BackgroundImmunological biomarkers have often been used as a complementary approach to support clinical diagnosis in several infectious diseases. The lack of commercially available laboratory tests for conclusive early diagnosis of leprosy has motivated the search for novel methods for accurate diagnosis. In the present study, we describe an integrated analysis of a cytokine release assay using a machine learning approach to create a decision tree algorithm. This algorithm was used to classify leprosy clinical forms and monitor household contacts.MethodsA model of Mycobacterium leprae antigen-specific in vitro assay with subsequent cytokine measurements by enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor (TNF), interferon-γ, interleukin 4, and interleukin 10 (IL-10) in culture supernatants of peripheral blood mononuclear cells from patients with leprosy, healthy controls, and household contacts. Receiver operating characteristic curve analysis was carried out to define each cytokine’s global accuracy and performance indices to identify clinical subgroups.ResultsData demonstrated that TNF (control culture [CC]: AUC = 0.72; antigen-stimulated culture [Ml]: AUC = 0.80) and IL-10 (CC: AUC = 0.77; Ml: AUC = 0.71) were the most accurate biomarkers to classify subgroups of household contacts and patients with leprosy, respectively. Decision tree classifier algorithms for TNF analysis categorized subgroups of household contacts according to the operational classification with moderate accuracy (CC: 79% [48/61]; Ml: 84% [51/61]). Additionally, IL-10 analysis categorized leprosy patients’ subgroups with moderate accuracy (CC: 73% [22/30] and Ml: 70% [21/30]).ConclusionsTogether, our findings demonstrated that a cytokine release assay is a promising method to complement clinical diagnosis, ultimately contributing to effective control of the disease.

Factors associated with the development of leprosy in Brazilian contacts: a systematic review.

ABSTRACTPeople who interact with leprosy patients in their environment, neighborhood, family, or social relationships are at risk to develop the disease. This systematic review investigated the risk and protective factors associated with the development of leprosy in Brazilian contacts. The studies were found in Cochrane Library, PubMed (MEDLINE), Embase, Virtual Health Library, grey literature and hand search until July 2021. The study selection, data extraction and quality assessment were independently performed by two investigators. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). This review was registered in PROSPERO (CRD42020160680). Seventeen articles fulfilled the inclusion criteria (n=544). The immunological and molecular factors, such as Anti-phenolic Glycolipid Antibodies (Anti-PGL-1) seropositivity, negative Mitsuda test, absence of Bacillus Calmette-Guérin (BCG) scar, positive Polymerase Chain Reaction (PCR) in blood; age and race; conviviality, education, contact time and type of contact, as well as elements related to the index case (bacilloscopic index; genetic conditions, family relationships), and some combined factors were shown to be relevant risk factors associated with the development of the disease in Brazilian leprosy contacts. The protective factors reported were the presence of one or more BCG scars, positive Mitsuda test, and education level. All selected studies were considered of high quality according to NOS. The knowledge of disease-related risk and protective factors provides the scientific basis for decision-making in the management of the disease in leprosy contacts.