Antimicrobial Resistance among Leprosy Patients in Brazil: Real-World Data Based on the National Surveillance Plan.

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (folP1), rifampin (rpoB), and ofloxacin resistance (gyrA) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relationship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group.

Antimicrobial resistance among leprosy patients in Brazil: real-world data based on the National Surveillance plan

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (folP1), rifampin (rpoB), and ofloxacin resistance (gyrA) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relation ship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group

Leprosy detection rate in patients under immunosuppression for the treatment of dermatological, rheumatological, and gastroenterological diseases: a systematic review of the literature and meta-analysis.

BACKGROUND: Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. METHODS: We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. RESULTS: The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I2 = 0%, p = 0.55). CONCLUSION: Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. TRIAL REGISTRATION: This review is registered in PROSPERO with the registry number CRD42018116275 .

A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy.

Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6-87.9) and a specificity of 97.0% (95% CI = 94.0-98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0-93.9) and 97.3% (95% CI = 94.3-98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1-92.3) and 96.1% (95% CI = 90.2-98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern.

A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy

Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6−87.9) and a specificity of 97.0% (95% CI = 94.0−98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0−93.9) and 97.3% (95% CI = 94.3−98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1−92.3) and 96.1% (95% CI = 90.2−98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern(AU).

[Mortality from leprosy in highly endemic contexts: integrated temporal-spatial analysis in BrazilMortalidad por lepra en zonas de alta endemicidad: análisis espacio-temporal integrado en Brasil]. / Mortalidade por hanseníase em contextos de alta endemicidade: análise espaço-temporal integrada no Brasil.

OBJECTIVE: To describe temporal trends and spatial patterns of leprosy-related mortality in the North and Northeast of Brazil from 2001 to 2017. METHODS: This population-based, mixed ecological study employed secondary data obtained from the Health Ministry's Mortality Information System. Death certificates were examined for extraction of information on leprosy as underlying or contributing cause of death. RESULTS: In the period of interest, 4 907 leprosy-related deaths were recorded. In 59.3%, leprosy was a contributing cause. "Leprosy, unspecified" (ICD-10 A30.9) was the most common cause recorded (72.7% as underlying cause; 76.1% as contributing cause). Increased risk of mortality by leprosy was observed in males, age ≥ 60 years and brown or black race/color. Joinpoint regression analysis of time trends revealed an increased overall mortality trend in the Northeast and in the states of Tocantins, Maranhão, Alagoas, and Bahia, as well as in the male sex. Regarding the spatial distribution of mortality rates adjusted by age and sex, as well as the analysis of moving spatial means and standardized mortality ratio, patterns that were above the mean for the area under study were identified for the states of Acre and Rondônia, the southern part of Pará, Tocantins, Maranhão, Piauí, south of Ceará, and north and south of Bahia. CONCLUSIONS: Leprosy mortality in the Brazilian North and Northeast is expressive and persistent, with a focal pattern of distribution in more vulnerable territories and populations. Comprehensive leprosy care must be strengthened in the Unified Health System in these regions.

OBJETIVO: Describir las tendencias temporales y los patrones espaciales de la mortalidad relacionada con la lepra en las regiones norte y nordeste de Brasil del 2001 al 2017. MÉTODOS: Estudio ecológico mixto basado en la población, con análisis de las tendencias temporal y espacial, hecho a partir de datos secundarios tomados de las declaraciones de defunción del Sistema de Información de Mortalidad (SIM) del Ministerio de Salud. Dichas declaraciones se examinaron para extraer los registros de lepra como causa básica y asociada de defunción. RESULTADOS: Se registraron 4 907 defunciones relacionadas con la lepra en el período de interés, en 59,3% de las cuales se la citó como causa asociada. La "lepra no especificada" (A30.9) fue la causa más citada en las declaraciones de defunción (causa básica: 72,7%; causa asociada: 76,1%). Se verificó un mayor riesgo de mortalidad por lepra en personas de sexo masculino, mayores de 60 años y de raza o de piel negra o morena. La tendencia temporal por análisis de puntos de inflexión (joinpoints) mostró un incremento en la tendencia general de la mortalidad en la región nordeste y en los estados de Tocantins, Maranhão, Alagoas y Bahía, así como en personas de sexo masculino. En lo referente a la distribución espacial de las tasas de mortalidad ajustadas por edad y sexo, así como a los análisis de las medias móviles espaciales y de la razón de mortalidad normalizada, se identificaron patrones superiores a la media de la zona de estudio en Acre, Rondônia, el Sur del estado de Pará, Tocantins, Maranhão, Piauí, el Sur de Ceará y las regiones del Norte y Sur de Bahía. CONCLUSIONES: La mortalidad por lepra en las regiones norte y nordeste es significativa y persistente, con un patrón focal de incidencia en los territorios y poblaciones con mayor vulnerabilidad. Se hace hincapié en la necesidad de fortalecer la atención integral a esta enfermedad en la red de atención del Sistema Único de Salud de esas regiones.

Mortalidade por hanseníase em contextos de alta endemicidade: análise espaço-temporal integrada no Brasil

[RESUMO]. Objetivo. Descrever as tendências temporais e os padrões espaciais da mortalidade relacionada à hanseníase nas regiões Norte e Nordeste do Brasil de 2001 a 2017. Métodos. Estudo ecológico misto de base populacional, de tendência temporal e espacial, baseado em dados secundários de declarações de óbito (DO) do Sistema de Informação de Mortalidade do Ministério da Saúde (SIM). As DO foram examinadas para extração dos registros de hanseníase como causa básica e associada de morte. Resultados. Foram registrados 4 907 óbitos relacionados à hanseníase no período de interesse, 59,3% como causa associada. A hanseníase não especificada (A30.9) foi a causa mais citada nas declarações de óbito (causa básica: 72,7%; causa associada: 76,1%). Verificou-se risco acrescido de mortalidade por hanseníase em pessoas do sexo masculino, com idade ≥60 anos e de raça/cor preta ou parda. A tendência temporal por análise de pontos de inflexão (joinpoints) apresentou incremento na tendência geral da mortalidade na região Nordeste e nos estados de Tocantins, Maranhão, Alagoas e Bahia, assim como no sexo masculino. Para a distribuição espacial das taxas de mortalidade ajustadas por idade e sexo, assim como para as análises das médias móveis espaciais e da razão de mortalidade padronizada, padrões acima da média da área de estudo foram identificados para Acre, Rondônia, sul do estado do Pará, Tocantins, Maranhão, Piauí, sul do Ceará e regiões do norte e sul da Bahia. Conclusões. A mortalidade por hanseníase nas regiões Norte e Nordeste é expressiva e persistente, com padrão focal de ocorrência em territórios e populações com maior vulnerabilidade. Ressalta-se a necessidade de fortalecer a atenção integral à hanseníase na rede de atenção do Sistema Único de Saúde dessas regiões.

[ABSTRACT]. Objective. To describe temporal trends and spatial patterns of leprosy-related mortality in the North and Northeast of Brazil from 2001 to 2017. Methods. This population-based, mixed ecological study employed secondary data obtained from the Health Ministry’s Mortality Information System. Death certificates were examined for extraction of information on leprosy as underlying or contributing cause of death. Results. In the period of interest, 4 907 leprosy-related deaths were recorded. In 59.3%, leprosy was a contributing cause. “Leprosy, unspecified” (ICD-10 A30.9) was the most common cause recorded (72.7% as underlying cause; 76.1% as contributing cause). Increased risk of mortality by leprosy was observed in males, age ≥ 60 years and brown or black race/color. Joinpoint regression analysis of time trends revealed an increased overall mortality trend in the Northeast and in the states of Tocantins, Maranhão, Alagoas, and Bahia, as well as in the male sex. Regarding the spatial distribution of mortality rates adjusted by age and sex, as well as the analysis of moving spatial means and standardized mortality ratio, patterns that were above the mean for the area under study were identified for the states of Acre and Rondônia, the southern part of Pará, Tocantins, Maranhão, Piauí, south of Ceará, and north and south of Bahia. Conclusions. Leprosy mortality in the Brazilian North and Northeast is expressive and persistent, with a focal pattern of distribution in more vulnerable territories and populations. Comprehensive leprosy care must be strengthened in the Unified Health System in these regions.

[RESUMEN]. Objetivo. Describir las tendencias temporales y los patrones espaciales de la mortalidad relacionada con la lepra en las regiones norte y nordeste de Brasil del 2001 al 2017. Métodos. Estudio ecológico mixto basado en la población, con análisis de las tendencias temporal y espacial, hecho a partir de datos secundarios tomados de las declaraciones de defunción del Sistema de Información de Mortalidad (SIM) del Ministerio de Salud. Dichas declaraciones se examinaron para extraer los registros de lepra como causa básica y asociada de defunción. Resultados. Se registraron 4 907 defunciones relacionadas con la lepra en el período de interés, en 59,3% de las cuales se la citó como causa asociada. La “lepra no especificada” (A30.9) fue la causa más citada en las declaraciones de defunción (causa básica: 72,7%; causa asociada: 76,1%). Se verificó un mayor riesgo de mortalidad por lepra en personas de sexo masculino, mayores de 60 años y de raza o de piel negra o morena. La tendencia temporal por análisis de puntos de inflexión (joinpoints) mostró un incremento en la tendencia general de la mortalidad en la región nordeste y en los estados de Tocantins, Maranhão, Alagoas y Bahía, así como en personas de sexo masculino. En lo referente a la distribución espacial de las tasas de mortalidad ajustadas por edad y sexo, así como a los análisis de las medias móviles espaciales y de la razón de mortalidad normalizada, se identificaron patrones superiores a la media de la zona de estudio en Acre, Rondônia, el Sur del estado de Pará, Tocantins, Maranhão, Piauí, el Sur de Ceará y las regiones del Norte y Sur de Bahía. Conclusiones. La mortalidad por lepra en las regiones norte y nordeste es significativa y persistente, con un patrón focal de incidencia en los territorios y poblaciones con mayor vulnerabilidad. Se hace hincapié en la necesidad de fortalecer la atención integral a esta enfermedad en la red de atención del Sistema Único de Salud de esas regiones.