Forecasting models for leprosy cases: a scoping review protocol.

INTRODUCTION: Leprosy is a neglected tropical disease caused by Mycobacterium leprae that mainly affects the skin, the peripheral nerves, the mucosa of the upper respiratory tract and the eyes. Mathematical models and statistical methodologies could play an important role in decision-making and help maintain the gains in elimination programmes. Various models for predicting leprosy cases have been reported in the literature, but they have different settings and distinct approaches to predicting the cases. This study describes the protocol for a scoping review to identify and synthesise information from studies using models to forecast leprosy cases. METHODS AND ANALYSIS: A scoping review methodology will be applied following the Joanna Briggs Institute methodology for scoping reviews and will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews. We will perform a systematic search from when each database started until April 2022 and we will include the following electronic databases: MEDLINE via PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Science Literature Database. Data will be extracted and recorded on a calibrated predefined data form and will be presented in a tabular form accompanied by a descriptive summary. The Prediction Model Study Risk of Bias Assessment Tool (PROBAST) will be used. ETHICS AND DISSEMINATION: No ethical approval is required for this study. This scoping review will identify and map the methodological and other characteristics of modelling studies predicting leprosy cases. We hope that the review will contribute to scientific knowledge in this area and act as a basis for researchers designing and conducting leprosy models. This information can also be used to enhance national surveillance systems and to target specific policies. The protocol and consequent publications of this scoping review will be disseminated through peer-reviewed publications and policy briefs. SYSTEMATIC REVIEW REGISTRATION: This scoping review was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/W9375).

Association of the polymorphism of the vitamin D receptor gene (VDR) with the risk of leprosy in the Brazilian Amazon.

The transmission and evolution of leprosy depends on several aspects, including immunological and genetic factors of the host, as well as genetic factors of Mycobacterium leprae. The present study evaluated the association of single nucleotide polymorphisms (SNPs) on the FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) regions of the vitamin D receptor (VDR) gene with leprosy. A total of 405 individuals were evaluated, composed by groups of 100 multibacillary (MB) and 57 paucibacillary (PB) patients, and 248 healthy contacts. Blood samples were collected from patients and contacts. The genotyping was performed by sequencing of the interest regions. The alleles of the studied SNPs, and SNP FokI genotypes, were not associated with leprosy. For the SNP on TaqI region, the relationship between the tt genotype, and for the SNP ApaI, the AA genotype, revealed an association with susceptibility to MB form, while Aa genotype with protection. The extended genotypes AaTT and AaTt of ApaI and TaqI were associated with protection against MB form. Further studies analyzing the expression of the VDR gene and the correlation with its SNPs might help to clarify the role of polymorphisms on the immune response in leprosy.

Patients with psoriasis have a higher risk of dementia: A systematic review and meta-analysis.

BACKGROUND: Patients with psoriasis may have a higher risk of dementia because of the higher inflammatory burden, although results from previous epidemiological studies have been inconsistent. AIMS: To determine the association between psoriasis and risk of dementia by pooling the evidence from previous studies. METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to July 2019 using a search that comprised terms for "psoriasis" and "dementia." Studies were eligible for the meta-analysis if they were cohort studies that included psoriatic patients and individuals without psoriasis and followed them for incident dementia. Studies were also required to report standardized incidence ratio, hazard risk ratio or relative risk with related 95% confidence intervals (CI) comparing the incidence of dementia between the two cohorts. The retrieved point estimates with standard errors from each study were pooled into the final result by the random-effect model, generic inverse variance method. RESULTS: A total of 8,861 articles were identified. After two rounds of independent review by three investigators, we included six cohort studies that met the eligibility criteria in the meta-analysis. The risk of dementia was significantly higher among psoriatic patients than in those without psoriasis with a pooled risk ratio of 1.16 (95% CI, 1.04-1.30; I2 95%). A funnel plot was relatively symmetric and was not suggestive of the presence of publication bias. LIMITATIONS: Limited accuracy of diagnosis of psoriasis and dementia as four included studies were coding-based studies, and high statistical heterogeneity among studies. CONCLUSION: This systematic review and meta-analysis indicates that psoriatic patients have a significantly elevated risk of developing dementia.

Association of MBL2 Exon 1 Polymorphisms With Multibacillary Leprosy.

Mannose-binding lectin (MBL) is a serum protein of innate immunity, with a central role in the activation of the complement system through the lectin pathway. This protein is encoded by MBL2 gene, and single-nucleotide polymorphisms located at exon 1, such as rs5030737 C>T (D variant), rs1800450 G>A (B variant), and rs1800451 G>A (C variant), may change the MBL structure and the serum concentration. MBL2 polymorphisms have been associated with several infectious diseases, including leprosy. Host immune response has a major impact on the clinical manifestation of leprosy since only a few individuals infected with Mycobacterium leprae will develop the disease. Therefore, the aim of this study was to evaluate the influence of MBL2 exon 1 polymorphisms (rs5030737, rs1800450, and rs1800451) on the MBL levels and leprosy immunopathogenesis. This case-control study included 350 leprosy patients from Southern Brazil, with 279 classified as multibacillary (MB) and 71 as paucibacillary (PB). The control group consisted of 350 non-consanguineous individuals, who were not diagnosed with leprosy or other infectious and autoimmune diseases. Genotyping was performed by PCR-sequence specific primers, and the MBL serum concentrations were evaluated by ELISA. MBL2 exon 1 polymorphisms were analyzed individually and grouped as genotypes, considering "A" as the wild allele and "O" as the presence of at least one polymorphism (D, B, or C variants). Differences were not observed in the distribution of genotypic and allelic frequencies between leprosy per se patients and controls. However, in a haplotypic analysis, the TGG haplotype presented a risk for development of leprosy per se in women when compared to the wild haplotype (CGG) (OR = 2.69). Comparing patients with MB and PB, in a multivariate analysis, the B variant was associated with the susceptibility of developing the MB form of leprosy (OR = 2.55). Besides that, the CAG haplotype showed an increased susceptibility to develop MB leprosy in women compared to men. It was observed that the A/O genotype in women was associated with a susceptibility to leprosy development per se (OR = 1.66) and progression to MB leprosy (OR = 3.13). In addition, the MBL serum concentrations were in accordance with the genotyping analysis. In summary, our data suggest that MBL2 exon 1 polymorphisms are associated with an increased risk to leprosy development and progression.

Validation study of HLA-B*13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia.

Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.

Leprosy in urban space, areas of risk for disability and worsening of this health condition in Foz Do Iguaçu, the border region between Brazil, Paraguay and Argentina.

BACKGROUND: Leprosy is a public health problem and a challenge for endemic countries, especially in their border regions where there are intense migration flows. The study aimed to analyse the dynamics of leprosy, in order to identify areas of risk for the occurrence of the disease and disability and places where this health condition is worsening. METHOD: This ecological study considered the new cases of leprosy reported in the municipality of Foz do Iguaçu from 2003 to 2015. Spatial and spatial-temporal scan statistics were used to identify the risk areas for the occurrence of leprosy, as well as the Getis-Ord Gi and Getis-Ord Gi* methods. Areas of risk for disabilities were identified by the scan statistic and kernel density estimation. RESULTS: A total of 840 cases were reported, of which 179 (21.3%) presented Grade 1 or 2 disabilities at the time of diagnosis. Leprosy risk areas were concentrated in the Southern, Eastern and Northeastern Health Districts of the municipality. The cases of Grade 2 disability were observed with higher intensity in regions characterized by high population density and poverty. CONCLUSION: The results of the study have revealed changes in the pattern of areas at risk of leprosy according to the investigated periods. In addition, it was possible to verify disabilities as a condition present in the investigated cases, or that may be related to the late diagnosis of the disease. In the areas of risk identified, patients have reported worse physical disability after diagnostic confirmation, or indicate inadequate clinical examination, reinforcing the need for structuring leprosy control services in a qualified manner.

Análise espacial do risco de adoecimento da hanseníase em um estado do nordeste brasileiro / Análisis espacial del riesgo de enfermedad de la lepra en un estado del noreste brasileño / Spatial analysis of the risk of leprosy disease in a northeastern brazilian state

Objetivo analisar a distribuição espacial do risco para o adoecimento de hanseníase nos municípios do estado da Paraíba, Brasil. Método trata-se de estudo ecológico de análise espacial. Foram incluídos casos novos de hanseníase residentes na Paraíba, registrados no Sistema de Informação de Agravos de Notificação de 2001 a 2016. Foi realizada análise espacial descritiva nos períodos de 2001-2008 e 2009-2016 do índice composto de indicadores epidemiológico e análise de dependência espacial por meio dos índices de Moran global e local. Resultados foram registrados 12.134 casos novos no período estudado. Identificou-se no primeiro período clusters com classificação alto/alto nas regiões leste, oeste e noroeste. No segundo período, os clusters concentram-se nas regiões leste e sudeste e decresceu no oeste e noroeste. Conclusão o risco para o adoecimento de hanseníase está presente nos municípios da Paraíba. A distribuição espacial é dessemelhante no estado. Ações de vigilância devem ser prioritárias para o controle da endemia.

Objetivo analizar la distribución espacial del riesgo de enfermedad de la lepra en los municipios del estado de Paraíba, Brasil. Método este es un estudio ecológico del análisis espacial. Se incluyeron nuevos casos de lepra que viven en Paraíba, inscritos en el Sistema de Información sobre Enfermedades Notificabbles de 2001 a 2016. El análisis espacial descriptivo se realizó en los períodos 2001-2008 y 2009-2016 del índice compuesto de indicadores epidemiológicos y análisis de dependencia espacial a través de los índices globales y locales de Moran. Resultados se registraron 12.134 nuevos casos en el período estudiado. En el primer período se identificaron los clusters con clasificación alta/alta en las regiones este, oeste y noroeste. En el segundo período, los clusters se concentran en las regiones este y sureste y disminuyen en el oeste y noroeste. Conclusión el riesgo de enfermedad de la lepra está presente en los municipios de Paraíba. La distribución espacial es diferente en el estado. Las acciones de vigilancia deben ser una prioridad para el control de la enfermedad endémica.

Objective to analyze the spatial distribution of the risk for leprosy disease in the municipalities of the state of Paraíba, Brazil. Method this is an ecological study of spatial analysis. New cases of leprosy living in Paraíba, registered in the Notifiable Diseases Information System from 2001 to 2016, were included. Descriptive spatial analysis was performed in the periods of 2001-2008 and 2009-2016 of the composite index of epidemiological indicators and spatial dependence analysis through the global and local Moran indices. Results 12,134 new cases were recorded in the period studied. Clusters with high/high classification in the east, west and northwest regions were identified in the first period. In the second period, clusters are concentrated in the east and southeast regions and decreased in the west and northwest. Conclusion the risk for leprosy disease is present in the municipalities of Paraíba. Spatial distribution is dissimilar in the state. Surveillance actions should be a priority for the control of the endemic disease.

Assisted reproductive technology treatment and risk of ovarian cancer-a nationwide population-based cohort study.

STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

Leprosy in the post-elimination era: a clinico-epidemiological study from a northern Indian tertiary care hospital.

INTRODUCTION: Leprosy is a chronic disease caused by Mycobacterium leprae. Despite being eliminated from India in 2005, there are still a considerable number of leprosy cases. METHODS: A prospective hospital-based study involving all leprosy patients attending the leprosy clinic at the Department of Dermatology from January 2015 to December 2016. RESULTS: A total of 220 patients visited the leprosy clinic during the study period. Most of the patients (48.7%) were 20 to 40 years old. Multibacillary disease was more common in females (84.7%) than males (67.6%), and in rural patients (80.9%) than urban patients (64.8%). Borderline lepromatous leprosy was the most common (38.2%) type of leprosy seen, followed by lepromatous leprosy (28.2%) and borderline tuberculoid leprosy (21.4%). CONCLUSIONS: Despite elimination, leprosy continues to be a health problem in this part of the world. We have shown that females and the rural population are more susceptible to multibacillary disease.

CT Analysis of the Posteromedial Fragment of the Posterior Malleolar Fracture.

BACKGROUND: To date, there have been no studies describing the characteristics of posteromedial fragment in the posterior malleolus fracture. The aim was to investigate the variability of posteromedial fracture fragments to enable better surgical planning. METHODS: All Mason and Molloy type 2B fractures, defined as fracture of both the posterolateral and the posteromedial fragments of the posterior malleolus, from our database were identified to analyze the preoperative computed tomography scan. The posteromedial fragment was investigated in 47 cases (mean age, 46.6 years; 11 male, 36 female). RESULTS: Morphologically, the fracture could be divided into 2 subtypes: (1) a large pilon intra-articular fragment (mean of X axis: 33.0 mm, Y: 30.7 mm, Z: 31.7 mm) presented in 29 cases with mean interfragmentary angle of 32.1 and back of tibia angle of 32.7 degrees (this was seen in 25 of 27 cases with supination injury pattern); and (2) a small extra-articular avulsion fragment (mean of X axis: 9.6 mm, Y: 13.2 mm, Z: 11.5 mm) present in 18 cases with a mean interfragmentary angle of 11.0 and back of tibia angle of 10.1 degrees. It was seen in 80% of pronation injuries. CONCLUSION: The avulsion type of the posteromedial fragment of posterior malleolus fracture was more common in pronation injuries, likely the result of traction by the intermalleolar ligament, and the pilon type was more common in supination injuries, likely the result of the rotating talus impaction. Because of the intra-articular involvement, we believe the pilon type should undergo fixation to achieve articular congruity, unlike the avulsion type which may only function as a secondary syndesmotic stabilizer. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Predictors of serological cure after treatment in patients with early syphilis: A retrospective observational study in Thailand.

BACKGROUND: Some patients with early syphilis who receive appropriate treatment do not reach a serological cure and have a persistent titer which does not meet the criteria for treatment failure (serofast state). AIMS: This retrospective study aimed to determine the prevalence of serological cure and the serofast state as well as the factors associated with serological cure after treatment of patients with early syphilis. METHODS: A serological cure was defined as occurring when there was a ≥4-fold decrease in nontreponemal titer, whereas patients with a ≥4-fold increase were considered as having either a treatment failure or reinfection. Nontreponemal titers that neither increased nor decreased ≥4-fold after treatment were considered to be in a serofast state. Seroreversion was defined as occurring when there was a negative test within 12 months of treatment. RESULTS: There were 179 patients with a mean age of 31.9 years; 174 (97.2%) were men, and 125 (70%) were HIV patients. Of the total, 174 (98%; 95% confidence interval 94.82-99.42%) patients achieved a serological cure, whereas five were in a serofast state 12 months after treatment. Those five serofast patients were all HIV-positive men, of which 4 (80%) had secondary-stage syphilis, a CD4 count ≤200 cells/µl and a titer <1:8. In a bivariate analysis, a serological cure was associated with a baseline Venereal Disease Research Laboratory >1:16 titers (P = 0.018), and a CD4 cell count >200 cells/µl in 6 months preceding treatment (P = 0.016). The median time to a serological cure was 96 days. Only 22 (12.3%) of the patients achieved seroreversion at 12 months after treatment. LIMITATIONS: A retrospective medical record review is likely to have a selection bias, and in our study, 196 (52%) patients were excluded due to missing information. CONCLUSIONS: Most patients with early syphilis who achieved a serological cure at 12 months after treatment had high baseline Venereal Disease Research Laboratory titers and CD4 cell counts. However, only 22 (12.3%) had a negative Venereal Disease Research Laboratory titer after 1 year of treatment.