Risk factors for physical disability in patients with leprosy disease in Yunnan, China: Evidence from a retrospective observational study.

BACKGROUND: Leprosy is potentially debilitating. The risk factors related to physical disabilities associated with leprosy disease in Yunnan, China was not clear. METHODOLOGY/PRINCIPAL FINDINGS: We studied 10644 newly detected leprosy patients from Yunnan, China, from 1990 to 2019. Factors associated with Grade 1 (G1D) and Grade 2 (G2D) physical disabilities or overall physical disabilities (combined G1D and G2D) associated with leprosy were analyzed using multinomial and ordinal logistic regression analyses. The following factors were associated with the development of physical disability in these patients with leprosy: delayed diagnosis [odds ratio (OR): 5.652, 4.399, and 2.275; 95% confidence intervals (CIs): 4.516-7.073, 3.714-5.212, and 2.063-2.509; for ≥ 10, 5-10 y, and 2-5 years, respectively], nerve damage (OR: 3.474 and 2.428; 95% CI: 2.843-4.244, and 1.959-3.008; for 2 and 1 damaged nerves, respectively), WHO classification of PB (OR: 1.759; 95% CI: 1.341-2.307), Ridley-Jopling classification (OR: 1.479, 1.438, 1.522 and 1.239; 95% CI: 1.052-2.079, 1.075-1.923, 1.261-1.838, and 1.072-1.431; for TT, BT, BB, and BL when compared with LL, respectively), advanced age (OR: 1.472 and 2.053; 95% CI: 1.106-1.960 and 1.498-2.814; for 15-59 and over 60 years old, respectively), zero skin lesions (OR: 1.916; 95% CI: 1.522-2.413), leprosy reaction (OR: 1.528; 95% CI: 1.195-1.952), rural occupation (OR: 1.364; 95% CI: 1.128-1.650), Han ethnicity (OR: 1.268; 95% CI: 1.159-1.386), and male sex (OR: 1.128; 95% CI: 1.024-1.243). CONCLUSIONS: Delayed diagnosis, nerve damage, no skin lesions, WHO and Ridley-Jopling classifications, leprosy reactions, advanced age, rural occupation, Han ethnicity, and male sex were associated with disability in leprosy patients. Identifying risk factors could help to prevent physical disability.

Evaluation of the Reproducibility of Lauge-Hansen, Danis-Weber, and AO Classifications for Ankle Fractures / Avaliação da reprodutibilidade das classificações Lauge-Hansen, Danis-Weber e AO para fraturas do tornozelo

Abstract Objective The present study aims to analyze the intra- and interobserver reproducibility of the Lauge-Hansen, Danis-Weber, and Arbeitsgemeinschaft für Osteosynthesefragen (AO) classifications for ankle fractures, and the influence of evaluators training stage in these assessments. Methods Anteroposterior (AP), lateral and true AP radiographs from 30 patients with ankle fractures were selected. All images were evaluated by 11 evaluators at different stages of professional training (5 residents and 6 orthopedic surgeons), at 2 different times. Intra- and interobserver agreement was analyzed using the weighted Kappa coefficient. Student t-tests for paired samples were applied to detect significant differences in the degree of interobserver agreement between instruments. Results Intraobserver analysis alone had a significant agreement in all classifications. Moderate to excellent interobserver agreement was highly significant (p ≤ 0.0001) for the Danis-Weber classification. The Danis-Weber classification showed, on average, a significantly higher degree of agreement than the remaining classification systems (p ≤ 0.0001). Conclusion The Danis-Weber classification presented the highest reproducibility among instruments and the evaluator's little experience had no negative influence on the reproducibility of ankle fracture classifications. Level of Evidence II, Diagnostic Studies - Investigating a Diagnostic Test.

Resumo Objetivo Avaliar a reprodutibilidade intra- e interobservador das classificações de Lauge-Hansen, Danis-Weber e Arbeitsgemeinschaft für Osteosynthesefragen (AO) para as fraturas de tornozelo, e a influência do estágio de formação dos participantes na avaliação. Métodos Foram selecionadas radiografias de 30 pacientes com fratura de tornozelo nas incidências anteroposterior (AP), perfil e AP verdadeiro. Todas as imagens foram avaliadas por 11 participantes em diferentes estágios de formação profissional (cinco residentes e seis cirurgiões ortopédicos), em dois momentos distintos. Analisou-se a concordância inter- e intraobservador por meio do coeficiente Kappa ponderado. O teste t de Student para amostras pareadas foi aplicado para verificar se havia diferença significativa no grau de concordância interobservador entre os instrumentos. Resultado Observou-se que existe concordância significativa em todas as classificações quando da análise intraobservador isolada. Existe concordância interobservador altamente significativa de grau moderado a ótimo na classificação de Danis-Weber (p ≤ 0,0001). A classificação de Danis-Weber apresentou, em média, grau de concordância significativamente maior que as outras classificações (p ≤ 0,0001). Conclusão A classificação de Danis-Weber se mostrou a mais reprodutiva entre os instrumentos avaliados, e a pouca experiência do avaliador não influencia negativamente a reprodutibilidade das classificações das fraturas do tornozelo. Nível de Evidência II, Estudos Diagnósticos - Investigação de um Exame para Diagnóstico.

Synthetic Phenolic Glycolipids for Application in Diagnostic Tests for Leprosy.

Point-of-care (POC) diagnostic tests for the rapid detection of individuals infected with Mycobacterium leprae, the causative pathogen of leprosy, represent efficient tools to guide therapeutic and prophylactic treatment strategies in leprosy control programs, thus positively contributing to clinical outcome and reducing transmission of this infectious disease. Levels of antibodies directed against the M. leprae-specific phenolic glycolipid I (PGL-I) closely correlate with an individual's bacterial load and a higher risk of developing leprosy. We describe herein the assembly of a set of PGL glycans carrying the characteristic phenol aglycon and featuring different methylation patterns. The PGL trisaccharides were applied to construct neoglycoproteins that were used to detect anti-PGL IgM antibodies in leprosy patients. ELISAs and quantitative lateral-flow assays based on up-converting nanoparticles (UCP-LFAs) showed that the generated PGL-I and PGL-II trisaccharide neoglycoconjugates can be applied for the detection of anti M. leprae IgM antibodies in POC tests.

Validation of in-house liquid direct agglutination test antigen: the potential diagnostic test in visceral Leishimaniasis endemic areas of Northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis in Ethiopia is a re-emerging threat to public health, with increased geographical distribution and number of cases. It is a fatal disease without early diagnosis and treatment; thus, the availability of affordable diagnostic tools is crucial. However, due to delays caused by import regulations, procurement and late delivery of imported test kits, accessibility remains a problem in the control program. Therefore, we aimed to produce and evaluate the performance of an in-house liquid (AQ) direct agglutination test (DAT) antigen. RESULT: The AQ-DAT was produced at the Armauer Hansen Research Institute, using Leishmania donovani strain (MHOM/ET/67/L82). Sera from 272 participants; 110 microscopically confirmed cases of VL, 76 apparently healthy and 86 patients who had infectious disease other than VL were tested with AQ-DAT, and standard kits: Freeze-dried DAT (FD-DAT) and rK39. Taking microscopy as a gold standard; the sensitivity and specificity of the AQ-DAT were 97.3 and 98.8%, respectively. It had high degrees of agreement (k > 0.8), with a significant (P < 0.05) correlation compared to microscopy, FD-DAT, and rK39. CONCLUSION: Although further standardization is required, the in-house AQ-DAT could improve diagnostic accessibility, minimize intermittent stock outs and strengthen the national VL control program.

Evaluation of anti-gal enzyme-linked immunosorbent assay for the diagnosis of Indian post-kala-azar dermal leishmaniasis.

BACKGROUND: Elimination of kala azar from India is challenging as there are potential reservoirs of Leishmania donovani in patients with post-kala-azar dermal leishmaniasis (PKDL). The vast repertoire of carbohydrate moieties on L. donovani is known to elicit specific and strong humoral responses in patients with kala azar. AIM: The present study was undertaken to evaluate the diagnostic performances of anti-gal antibodies using enzyme-linked immunosorbent assay for successful serological diagnosis of PKDL in Indian patients and to differentiate cases of past cured visceral leishmaniasis infections. METHODS: We developed Gal enzyme-linked immunosorbent assay to measure specific anti-gal IgG isotype in the sera of 71 Indian patients with PKDL. The diagnostic efficacy of the newly developed assay was evaluated for precision, sensitivity and accuracy. RESULTS: Gal2 enzyme-linked immunosorbent assay revealed three-fold increased anti-gal titers in 71 patients with active PKDL compared to controls. Subclass enzyme-linked immunosorbent assay analysis further revealed enhanced IgG2 and IgG3 anti-gal titers in patients with PKDL compared to control subjects. The rank order for specificity and sensitivity for IgG subclasses was IgG3>IgG2>IgG4>IgG1. The area under the curve values of 0.98 and 0.99 were obtained for IgG and IgG3 Gal2 enzyme-linked immunosorbent assays respectively. Overall sensitivity and specificity were 95.7% (95% CI: 88.1-99.1) and 98.1% (95% confidence interval: 90.1-99.9), and 98.5% (95% CI: 92.4-99.9) and 98.1% (95% CI: 90.1-99.9), respectively. Intra-assay coefficient of variation was 1.5% and inter-assay coefficient of variation was 11.7%. LIMITATIONS: The Gal2 enzyme-linked immunosorbent assay needs to be further investigated in mass surveys. CONCLUSION: Taken together, anti-gal titers detected through Gal2 enzyme-linked immunosorbent assay can serve as an effective diagnostic tool in disease elimination setting and help in better case management in endemic districts.

Utility of multiplex PCR for early diagnosis and household contact surveillance for leprosy.

Early diagnosis of leprosy is important for limiting the severity of disease, which may lead to disabilities and deformities if not treated timely. Multiplex PCR employing more than one gene, specific to target DNA, is more efficient detection tool. In the present study, slit skin scrapings, blood, nasal swabs and saliva from Paucibacillary (PB) and Multibacillary (MB) cases as well as household contacts of PB cases were tested by multiplex PCR using three different gene targets namely RLEP, 16SrRNA and sodA. We found an increase in overall diagnostic positivity for M. leprae DNA detection by M-PCR as compared to individual PCR. In case of nasal swabs using M-PCR the PPV, NPV were 0.5454, 0.8333 respectively. There is remarkable increase in PPV in SSS of PB cases and nasal swabs of HHCs using M-PCR. Conclusively, our finding suggests the utility of M-PCR for early diagnosis and household contact surveillance for leprosy.

Diagnostic accuracy of tests for leprosy: a systematic review and meta-analysis.

OBJECTIVES: Owing to difficulties in the clinical diagnosis of leprosy, several complementary tests have been developed and used. The aim was to systematically summarize the accuracy of diagnostic tests for leprosy. METHODS: We searched for relevant articles in Embase, Medline, and Global Health databases, until June 2017. Studies evaluating the accuracy of any diagnostic techniques for differentiating between people with and without leprosy were included. Studies solely focusing on differentiating between the separate forms of leprosy were excluded. Our protocol was registered on PROSPERO (CRD42017071803). We assessed study quality using the QUADAS-2 checklist. A bivariate random effects regression model was used for the meta-analyses. RESULTS: We included 78 studies, most of those evaluating the detection of IgM antibodies against phenolic glycolipid I using ELISA. Sensitivity of the 39 studies evaluating ELISA was 63.8% (95% CI 55.0-71.8); specificity 91.0% (95% CI 86.9-93.9). The lateral flow test (nine studies) and the agglutination test (five studies) had a slightly higher sensitivity and a slightly lower specificity. Sensitivity of qPCR was (five studies) 78.5% (95% CI 61.9-89.2) and specificity 89.3% (95% CI 61.4-97.8). Sensitivity of conventional PCR was (17 studies) 75.3% (95% CI 67.9-81.5) and specificity 94.5% (95% CI 91.4-96.5). CONCLUSIONS: Although the test accuracy looks reasonable, the studies suffered from heterogeneity and low methodological quality.

Host immune responses induced by specific Mycobacterium leprae antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China.

BACKGROUND: Leprosy, caused by Mycobacterium leprae, affects over 200,000 people annually worldwide and remains endemic in the ethnically diverse, mountainous and underdeveloped southwestern provinces of China. Delayed diagnosis of leprosy persists in China, thus, additional knowledge to support early diagnosis, especially early diagnosis of paucibacillary (PB) patients, based on the host immune responses induced by specific M. leprae antigens is needed. The current study aimed to investigate leprosy patients and controls in Southwest China by comparing supernatants after stimulation with specific M. leprae antigens in an overnight whole-blood assay (WBA) to determine whether host markers induced by specific M. leprae antigens improve the diagnosis or discrimination of PB patients with leprosy. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy patients [13 multibacillary (MB) patients and 7 PB patients] and nonleprosy controls [21 healthy household contacts (HHCs), 20 endemic controls (ECs) and 19 tuberculosis (TB) patients] were enrolled in this study. The supernatant levels of ten host markers stimulated by specific M. leprae antigens were evaluated by overnight WBA and multiplex Luminex assays. The diagnostic value in PB patients and ECs and the discriminatory value between PB patients and HHCs or TB patients were evaluated by receiver operator characteristics (ROC) analysis. ML2044-stimulated CXCL8/IL-8 achieved the highest sensitivity of 100%, with a specificity of 73.68%, for PB diagnosis. Compared to single markers, a 3-marker combination model that included ML2044-induced CXCL8/IL-8, CCL4/MIP-1 beta, and IL-6 improved the diagnostic specificity to 94.7% for PB patients. ML2044-stimulated IL-4 and CXCL8/IL-8 achieved the highest sensitivity (85.71% and 100%) and the highest specificity (95.24% and 84.21%) for discriminating PB patients from HHCs and TB patients, respectively. CONCLUSIONS: Our findings suggest that the host markers induced by specific M. leprae antigens in an overnight WBA increase diagnostic and discriminatory value in PB patients with leprosy, with a particularly strong association with interleukin 8.

Evaluation of Auramine O staining and conventional PCR for leprosy diagnosis: A comparative cross-sectional study from Ethiopia.

BACKGROUND: Diagnosis of leprosy mainly relies on clinical examination due to the inconsistent sensitivity and poor reproducibility of the current laboratory tests. Utilisation of alternative methods to the standard Ziehl Neelsen (ZN), Fite-Faraco (FF) and Haematoxylin and Eosin (H&E) staining procedures may eventually improve leprosy diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this comparative study, the performance of the fluorescent Auramine O (AO) staining and polymerase chain reaction (PCR) was assessed with different skin samples using a combination of ZN, FF and H&E staining as the gold standard. AO, ZN, FF, H&E and PCR tests were performed on slit skin smears (SSS) and/or punch biopsies collected from 141 clinically confirmed leprosy cases and 28 non-leprosy skin samples. DNA was extracted from punch biopsies using two different methods with or without mechanical lysis. Sensitivities were 87.6%, 59.3% and 77% for H&E, ZN and FF, respectively, whereas it reached 65.5% and 77.9% for AO in SSS and tissue sections and 91.1% for PCR in tissue samples. Morover, samples with low bacillary index, sensitivity of AO staining (61.8%) was similar to FF (60%, p>0.05) and lower than PCR (86.6%, p<0.05). Sensitivity of PCR also increased (96.8%, p<0.05) when mechanical lysis was used during DNA extraction compared to enzymatic treatment alone (84.6%). CONCLUSIONS/SIGNIFICANCE: Our results showed that for diagnostic purposes, analysis of skin section is more sensitive than SSS, especially for samples with low bacillary load. AO staining on SSS and tissue sections was not significantly better than other routine diagnostic tests but considerably more user friendly. The sensitivity of PCR was higher than current standard methods and increased when combined with more efficient DNA extraction using mechanical and chemical lysis. Therefore, we recommend AO staining for the diagnosis of leprosy in lower health facilities such as health centres and district hospitals and PCR diagnosis at referral level and research centres.

A scoping review on the field validation and implementation of rapid diagnostic tests for vector-borne and other infectious diseases of poverty in urban areas.

BACKGROUND: Health personnel face challenges in diagnosing vector-borne and other diseases of poverty in urban settings. There is a need to know what rapid diagnostic technologies are available, have been properly assessed, and are being implemented to improve control of these diseases in the urban context. This paper characterizes evidence on the field validation and implementation in urban areas of rapid diagnostics for vector-borne diseases and other diseases of poverty. MAIN BODY: A scoping review was conducted. Peer-reviewed and grey literature were searched using terms describing the targeted infectious diseases, diagnostics evaluations, rapid tests, and urban setting. The review was limited to studies published between 2000 and 2016 in English, Spanish, French, and Portuguese. Inclusion and exclusion criteria were refined post hoc to identify relevant literature regardless of study design and geography. A total of 179 documents of the 7806 initially screened were included in the analysis. Malaria (n = 100) and tuberculosis (n = 47) accounted for the majority of studies that reported diagnostics performance, impact, and implementation outcomes. Fewer studies, assessing mainly performance, were identified for visceral leishmaniasis (n = 9), filariasis and leptospirosis (each n = 5), enteric fever and schistosomiasis (each n = 3), dengue and leprosy (each n = 2), and Chagas disease, human African trypanosomiasis, and cholera (each n = 1). Reported sensitivity of rapid tests was variable depending on several factors. Overall, specificities were high (> 80%), except for schistosomiasis and cholera. Impact and implementation outcomes, mainly acceptability and cost, followed by adoption, feasibility, and sustainability of rapid tests are being evaluated in the field. Challenges to implementing rapid tests range from cultural to technical and administrative issues. CONCLUSIONS: Rapid diagnostic tests for vector-borne and other diseases of poverty are being used in the urban context with demonstrated impact on case detection. However, most evidence comes from malaria rapid diagnostics, with variable results. While rapid tests for tuberculosis and visceral leishmaniasis require further implementation studies, more evidence on performance of current tests or development of new alternatives is needed for dengue, Chagas disease, filariasis, leptospirosis, enteric fever, human African trypanosomiasis, schistosomiasis and cholera.

Routine Follow-Up Radiographs for Ankle Fractures Seldom Add Value to Clinical Decision-Making: A Retrospective, Observational Study.

Currently, the routine use of radiographs for uncomplicated ankle fractures represents good clinical practice. However, radiographs are associated with waiting time, radiation exposure, and costs. Studies have suggested that radiographs seldom alter the treatment strategy if no clinical indication for the imaging study was present. The objective of the present study was to evaluate the effect of routine radiographs on the treatment strategy during the follow-up period of ankle fractures. All patients aged ≥18 years, who had visited 1 of the participating clinics with an eligible ankle fracture in 2012 and with complete follow-up data were included. The data were retrospectively analyzed. The sociodemographic and clinical characteristics and the number of, and indications for, the radiographs taken were collected from the medical records of the participating clinics. We assessed the changes in treatment strategy according to the radiographic findings. In 528 patients with an ankle fracture, 1174 radiographs were performed during the follow-up period. Of these radiographs, 936 (79.7%) were considered routine. Of the routine radiographs taken during the follow-up period, only 11 (1.2 %) resulted in changes to the treatment strategy. Although it is common practice to take radiographs routinely during the follow-up period for ankle fractures, the results from the present study suggest that routine radiographs seldom alter the treatment strategy. This limited clinical relevance should be weighed against the health care costs and radiation exposure associated with the use of routine radiographs. For a definitive recommendation, however, the results of our study should be confirmed by a prospective trial, which we are currently conducting.

Minimum requirements and optimal testing strategies of a diagnostic test for leprosy as a tool towards zero transmission: A modeling study.

BACKGROUND: The availability of a diagnostic test to detect subclinical leprosy cases is crucial to interrupt the transmission of M. leprae. In this study we assessed the minimum sensitivity level of such a (hypothetical) diagnostic test and the optimal testing strategy in order to effectively reduce the new case detection rate (NCDR) of leprosy. METHODS AND FINDINGS: We used the individual-based model SIMCOLEP, and based it on previous quantification using COLEP data, a cohort study of leprosy cases in Bangladesh. The baseline consisted of treatment with Multidrug therapy of clinically diagnosed leprosy cases, passive case detection and household contact tracing. We examined the use of a leprosy diagnostic test for subclinical leprosy in four strategies: testing in 1) household contacts, 2) household contacts with a 3-year follow-up, 3) a population survey with coverage 50%, and 4) a population survey (100%). For each strategy, we varied the test sensitivity between 50% and 100%. All analyses were conducted for a high, medium, and low (i.e. 25, 5 and 1 per 100,000) endemic setting over a period of 50 years. In all strategies, the use of a diagnostic test further reduces the NCDR of leprosy compared to the no test strategy. A substantial reduction could already be achieved at a test sensitivity as low as 50%. In a high endemic setting, a NCDR of 10 per 100,000 could be reached within 8-10 years in household contact testing, and 2-6 years in a population testing. Testing in a population survey could also yield the highest number of prevented new cases, but requires a large number needed to test and treat. In contrast, household contact testing has a smaller impact on the NCDR but requires a substantially lower number needed to test and treat. CONCLUSIONS: A diagnostic test for subclinical leprosy with a sensitivity of at least 50% could substantially reduce M. leprae transmission. To effectively reduce NCDR in the short run, a population survey is preferred over household contact tracing. However, this is only favorable in high endemic settings.

Early detection of neuropathy in leprosy: a comparison of five tests for field settings.

BACKGROUND: Early detection and treatment of neuropathy in leprosy is important to prevent disabilities. A recent study showed that the Nerve Conduction Studies (NCS) and Warm Detection Thresholds (WDT) tests can detect leprosy neuropathy the earliest. These two tests are not practical under field conditions, however, because they require climate-controlled rooms and highly trained staff and are expensive. We assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early stage. METHODS: Through a literature search we identified five alternative devices that appeared user-friendly, more affordable, portable and/or battery-operated: the Neuropad®, Vibratip™, NC-Stat®DPNCheck™, NeuroQuick and the Thermal Sensibility Tester (TST), assessing respectively sweat function, vibration sensation, nerve conduction, cold sensation and warm sensation. In leprosy patients in Bangladesh, the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard tests. The alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected nerves. Sensitivity and specificity were the main outcomes. RESULTS: The NeuroQuick and the TST showed very good sensitivity and specificity. On the sural nerve, the NeuroQuick had both a sensitivity and a specificity of 86%. The TST had a sensitivity of 83% and a specificity of 82%. Both the NC-Stat®DPNCheck™ and Vibratip™ had a high specificity (88% and 100%), but a low sensitivity (16% and 0%). On the posterior tibial nerve, the NeuroQuick and the TST also showed good sensitivity, but the sensitivity was lower than for the sural nerve. The Neuropad® had a sensitivity of 56% and a specificity of 61%. CONCLUSIONS: The NeuroQuick and TST are good candidates for further field-testing for reliability and reproducibility. The feasibility of production on a larger scale should be examined.

Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test.

BACKGROUND: Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. METHODS: A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. RESULTS: Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36-1.22). CONCLUSIONS: The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring.

Application of Mycobacterium Leprae-specific cellular and serological tests for the differential diagnosis of leprosy from confounding dermatoses.

Mycobacterium leprae-specific serological and cell-mediated-immunity/CMI test were evaluated for the differential diagnosis of multibacillary/MB, and paucibacillary/PB leprosy from other dermatoses. Whole-blood assay/WBA/IFNγ stimulated with LID-1 antigen and ELISA tests for IgG to LID-1 and IgM to PGL-I were performed. WBA/LID-1/IFNγ production was observed in 72% PB, 11% MB leprosy, 38% dermatoses, 40% healthy endemic controls/EC. The receiver operating curve/ROC for WBA/LID-1 in PB versus other dermatoses showed 72.5% sensitivity, 61.5% specificity and an area-under-the-curve/AUC=0.75; 74% positive predictive value/PPV, 59% negative predictive value/NPV. Anti PGL-I serology was positive in 67% MB, 8% PB leprosy, 6% of other dermatoses; its sensitivity for MB=66%, specificity=93%, AUC=0.89; PPV=91%, NPV=72%. Anti-LID-1 serology was positive in 87% MB, 7% PB leprosy, all other participants were seronegative; 87.5% sensitivity for MB, 100% specificity, AUC=0.97; PPV=100%, NPV=88%. In highly endemic areas anti-LID-1/PGL-I serology and WBA/LID-1-represent useful tools for the differential diagnosis of leprosy from other confounding dermatoses.