A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

PURPOSE: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. METHODS: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. RESULTS: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. CONCLUSION: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

The impact of the SARS-CoV-2 pandemic on tuberculosis notifications and deaths in the state of São Paulo, Brazil: a cross-sectional study.

Background: The state of São Paulo reports the highest number of tuberculosis cases in Brazil. We aimed to analyze the SARS-CoV-2 pandemic's impact on tuberculosis notifications and identify factors associated with reduced notifications and tuberculosis deaths in 2020-2021. Methods: This retrospective cross-sectional study analyzed data from 126,649 patients with tuberculosis notified in São Paulo from 2016 to 2021. Interrupted time series analysis assessed the pandemic's impact on notifications. Descriptive statistics and logistic regressions identified factors associated with decreased tuberculosis notifications and deaths during the pandemic (2020-2021) compared to the pre-pandemic period (2019). Findings: Tuberculosis notifications decreased by 10% and 8% in 2020 and 2021, respectively, with declines 2-3 times higher among individuals with no education or deprived of liberty. Contrastingly, tuberculosis notifications increased 68% among corrections workers in 2021. Diagnostics and contact tracing were compromised. Individuals with HIV, drug addiction, or deprived of liberty had lower odds of notification during the pandemic. Black and Pardo individuals or those with diabetes, treatment interruption history, or treatment changes post-adverse events had higher odds of notification. However, adverse events and tuberculosis-diabetes cases have been increasing since 2016. During the pandemic, tuberculosis-related deaths rose 5.0%-12.7%. Risk factors for mortality remained similar to 2019, with Pardo ethnicity, drug addiction and re-treatment post-adverse events emerging as risk factors in 2020/2021. Interpretation: The pandemic affected tuberculosis notifications and deaths differently among populations, exacerbating inequalities. Treatment interruption, loss of follow-up, and challenges in accessing healthcare led to increased mortality. Funding: FAPESP, CNPq and CAPES, Brazil.

The impact of the SARS-CoV-2 pandemic on tuberculosis notifications and deaths in the state of São Paulo, Brazil: a cross-sectional study

Background The state of São Paulo reports the highest number of tuberculosis cases in Brazil. We aimed to analyze the SARS-CoV-2 pandemic's impact on tuberculosis notifications and identify factors associated with reduced notifications and tuberculosis deaths in 2020­2021. Methods This retrospective cross-sectional study analyzed data from 126,649 patients with tuberculosis notified in São Paulo from 2016 to 2021. Interrupted time series analysis assessed the pandemic's impact on notifications. Descriptive statistics and logistic regressions identified factors associated with decreased tuberculosis notifications and deaths during the pandemic (2020­2021) compared to the pre-pandemic period (2019). Findings Tuberculosis notifications decreased by 10% and 8% in 2020 and 2021, espectively, with declines 2­3 times higher among individuals with no education or deprived of liberty. Contrastingly, tuberculosis notifications increased 68% among corrections workers in 2021. Diagnostics and contact tracing were compromised. Individuals with HIV, drug addiction, or deprived of liberty had lower odds of notification during the pandemic. Black and Pardo individuals or those with diabetes, treatment interruption history, or treatment changes post-adverse events had higher odds of notification. However, adverse events and tuberculosis-diabetes cases have been increasing since 2016. During the pandemic, tuberculosis-related deaths rose 5.0%­12.7%. Risk factors for mortality remained similar to 2019, with Pardo ethnicity, drug addiction and re-treatment post-adverse events emerging as risk factors in 2020/2021. Interpretation The pandemic affected tuberculosis notifications and deaths differently among populations, exacerbating inequalities. Treatment interruption, loss of follow-up, and challenges in accessing healthcare led to increased mortality. (AU)

Implantação da rede laboratorial para realização do ensaio de liberação de interferon-gama (IGRA) para detecção de tuberculose latente no Estado de São Paulo: primeiros passos e desafios / Implementation of the laboratory network to carry out the interferon-gamma release assay (IGRA) to detect latent tuberculosis in the State of Sao Paulo: first steps and challenges

A tuberculose (TB) continua sendo um grande desafio para a saúde pública mundial e, para um controle eficiente, também é essencial identificar pessoas com tuberculose latente (ILTB). O ensaio de liberação de interferon-gama (IGRA), incorporado pelo SUS em 2021, permitirá ampliar o diagnóstico de ILTB, em complemento à prova tuberculínica. Para essa implantação, as coordenações do Programa Estadual e da Rede de Laboratórios de TB/SP iniciaram a identificação de executores do IGRA a partir da rede de laboratórios de TB e/ou CD4, para verificar possíveis barreiras para implantação do teste. Foram avaliados os insumos e os profissionais para execução do ensaio, a infraestrutura laboratorial e a disponibilidade de equipamentos. Dez laboratórios avaliaram amostras de sangue total com o kit QuantiFERON®-TB Gold Plus e relataram sua experiência quanto à logística de amostras, execução do ensaio e liberação de laudos. Para otimizar o exame, a coleta ocorreu em tubos heparinizados (sódio ou lítio). Foi sugerida a logística da rede de laboratórios de CD4, que foi utilizada por 20% dos laboratórios participantes, enquanto 50% optaram pelo agendamento. Não foram reportadas dificuldades na liberação de laudo. Dois laboratórios avaliaram o número de células T CD4+ prévio e no momento do IGRA, observando diferença em 10% dos pacientes, fator que pode ser relevante na análise do resultado. Ao todo, foram analisadas 383 amostras, 81 (21,1%) reagentes, 297 (77,5%) não reagentes e cinco (1,3%) indeterminados. Foi observada grande variação de positividade (3,6-50,0%) entre os laboratórios, provavelmente devido à população atendida. Apesar dos desafios encontrados, consideramos que a taxa média de positividade (~20%) sugere que a oferta do IGRA na rede pública possibilitará o aumento do diagnóstico de ILTB e melhor controle da TB.

Aspectos clínicos e tratamento de pacientes com tuberculose ocular presumida em centro de referência de São Paulo, Brasil. Estudo retrospectivo / Clinical description and treatment of patients with presumed ocular tuberculosis in São Paulo, Brazil. Retrospective study

Resumo Objetivo: Descrever aspectos clínicos e esquema terapêutico dos pacientes com tuberculose ocular presumida tratados em um centro de referência em tuberculose de São Paulo. Métodos: Estudo retrospectivo descritivo. O teste exato de Fisher foi realizado quando apropriado. Resultados: A queixa mais comum foi baixa acuidade visual (83,1%), seguida por dor ocular generalizada (25,3%) e visão turva (22,8%). A uveíte posterior foi a apresentação mais comum (35,7%). O tratamento consistiu no esquema atualmente recomendado de rifampicina, isoniazida, pirazinamida e etambutol (RHZE). A prednisona oral foi incluída no tratamento de 37 pacientes, para tratamento da inflamação aguda, embora não tenha diminuído a prevalência de complicações crônicas, em comparação com a recuperação completa (p = 0,1). O diagnóstico precoce (<70 dias) foi associado a maiores taxas de recuperação total (p = 0,005). Não houve significância estatística quando se comparou a terapia de 6 a 9 meses (p = 0,7). Conclusão: A uveíte tuberculosa pode ser tratada por uma terapia com duração de seis meses. Um breve curso de esteroides melhora os sintomas agudos, embora não reduza as complicações a longo prazo.

Abstract Purpose: To analyze and describe the therapy used in presumed ocular tuberculosis in a referral center in São Paulo, Brazil. Methods: Retrospective, descriptive study. Fisher's exact test was performed when appropriate. Results: The most common complaint was low visual acuity (83.1%), followed by generalized ocular pain (25.3%) and blurred vision (22.8%). Posterior uveitis was the most common presentation (35.7%). Treatment consisted of the currently recommended association of rifampin, isoniazid, pyrazinamide, ethambutol (RHZE) regimen. Oral prednisone was included in the treatment of 37 patients for acute inflammation, although it did not significantly decrease the prevalence of chronic complications compared to full recovery (p = 0,1). Early diagnosis (< 70 days) was associated with higher rates of full recovery (p = 0.005). No statistical significance was observed when comparing 6 to 9-month therapy (p = 0.7). Conclusion: Tuberculous uveitis can be treated with a 6-month duration RHZE therapy. A brief course of steroids may improve acute symptoms, although it did not reduce long-term disabilities.

Profile of tuberculosis patients progressing to death, city of São Paulo, Brazil, 2002.

OBJECTIVE: To profile adult patients dying of tuberculosis in the city of São Paulo with respect to biological, environmental and institutional factors. METHODS: Descriptive study covering all tuberculosis deaths (N=416) among individuals aged over 15 years in 2002. Data were obtained from hospital records, the local Mortality Information System, Coroner's Service, and tuberculosis Surveillance System. The estimates of relative risk and 95% confidence intervals (95% CI) were based on the reference group, i.e., females aged 15 to 29 years, originally from the State of São Paulo (Brazil). A comparative analysis was conducted using Pearson's chi-square test and Fisher's exact test for categorical variables and Kruskal-Wallis test for continuous variables. RESULTS: Of all tuberculosis deaths identified, 78% had pulmonary form. Tuberculosis diagnosis was made after death in 30% and in primary health care units in 14%. Of them, 44% had not started treatment; 49% were not notified; and 76% were men. The median age was 51 years; 52% had up to four years of schooling; 4% were probably living in the streets. Mortality rate increased with age; it was 5.0/100,000 for the entire city, ranging between zero to 35 according to the district. Previous treatment was reported for 82 out of 232 patients, and of them, 41 defaulted treatment. Diabetes (16%), chronic obstructive pulmonary disease (19%), HIV infection (11%), smoking (71%), and alcohol abuse (64%) were also reported. CONCLUSIONS: Adult males over 50, migrants and living in lower Human Development Index districts were more likely to die of tuberculosis. Low schooling and comorbidities are relevant characteristics. Low involvement of primary care units in tuberculosis diagnosis and high underreporting of cases were also seen.

Perfil de pacientes que evoluem para óbito por tuberculose no município de São Paulo, 2002 / Profile of tuberculosis patients progressing to death, city of São Paulo, Brazil, 2002 / Perfil de pacientes que evolucionan a óbito por tuberculosis en el municipio de São Paulo, 2002

OBJETIVO: Descrever o perfil de pacientes adultos residentes no município de São Paulo que evoluíram para óbito associado à tuberculose, segundo fatores biológicos, ambientais e institucionais. MÉTODOS: Estudo descritivo, abrangendo todos os óbitos por tuberculose (N=416) ocorridos em 2002, entre maiores de 15 anos. Os dados analisados foram obtidos do Sistema Municipal de Informações de Mortalidade, prontuários hospitalares, Serviço de Verificação de Óbitos e Sistema de Vigilância de Tuberculose. Os cálculos dos riscos relativos e intervalos de confiança de 95 por cento (IC 95 por cento) tiveram como referência o sexo feminino, grupo de 15 a 29 anos, e os naturais do Estado de São Paulo. A análise comparativa usou o teste do qui-quadrado de Pearson e o exato de Fisher para variáveis categóricas e o teste Kruskal-Wallis para variáveis contínuas. RESULTADOS: Do total de óbitos, 78 por cento apresentavam a forma pulmonar; o diagnóstico foi efetuado após a morte em 30 por cento e em unidades de atendimento primário em 14 por cento dos casos; 44 por cento não iniciaram tratamento; 49 por cento não foram notificados; 76 por cento eram homens e a mediana da idade foi de 51 anos; 52 por cento tinham até quatro anos de estudo, 4 por cento eram prováveis moradores de rua. As taxas de mortalidade aumentavam com a idade, sendo de 5,0/100.000 no município, variando de zero a 35, conforme o distrito. Para 82 de 232 pacientes com registro de tratamento, havia referência de tratamento anterior, e desses, 41 o haviam abandonado. Constatou-se presença de diabetes (16 por cento), doença pulmonar obstrutiva crônica (19 por cento), HIV (11 por cento), tabagismo (71 por cento) e alcoolismo (64 por cento) nos pacientes. CONCLUSÕES: Homens acima de 50 anos, migrantes e residentes em distritos com baixo Índice de Desenvolvimento Humano apresentam maiores riscos de óbito. A pouca escolaridade e apresentar co-morbidades são características importantes. Observou-se baixa participação d...

Fatores preditivos para morte por tuberculose pulmonar no município de São Paulo, SP, 2002 / Predictors to death from tuberculosis pulmonary in Sao Paulo City, 2002

INTRODUÇÃO: A mortalidade por tuberculose (TBC) no município de São Paulo permanece em níveis elevados, se considerarmos seus indicadores de desenvolvimento socioeconômico, com seis óbitos por 100.000 habitantes em 2000. OBJETIVO: Caracterizar os pacientes que morreram por TBC, no municipio de São Paulo, em 2002, e identificar fatores preditivos para o óbito por TBC pulmonar. MATERIAL E MÉTODOS: No estudo descritivo, analisou-se todos os óbitos por TBC, segundo variáveis sócio-demográficas, forma clínica, critério diagnóstico, história pregressa da tuberculose e co-morbidades. Os preditores para óbito por TBC foram avaliados no estudo de caso-controle pareado segundo época do início do tratamento. Os casos foram óbitos por TBC pulmonar, notificados à vigilância, com confirmação diagnóstica, idade igual ou maior do que 15 anos, não infectados pelo HIV e os controles os que evoluíram para cura. A existência da associação entre óbito e as exposições de interesse foi investigada pelas estimativas não ajustadas e ajustadas do "odds ratio", com os respectivos intervalos de 95% de confiança, usando regressão logística condicional para considerar o efeito do pareamento. RESULTADOS: As seguintes variáveis mantiveram associação com óbito por TBC pulmonar, independentemente das demais: Pertencer ao grupo etário de 60 anos ou mais OR = 7,8 ajustado (IC 95%: 1,2 - 363,2; p = 0,02); história de TBC no passado OR = 11,4 ajustado (IC 95%: 2,4 - 54,5; p =< 0,001); o diagnóstico de TBC sido feito em hospital ou pronto socorro OR = 6,0 ajustado (IC 95%: 1,6 - 23,0; p = 0,001); ser diabético OR = 11,4 ajustado (IC 95%: 1,4 - 94,1; p =< 0,01); apresentar história de alcoolismo OR = 7,0 ajustado (IC 95%: 1,5 - 32,1; p =< 0,001). CONCLUSÕES: Os resultados apontam como preditores pertencer a alguns grupos de risco, ser idoso e diabético; fatores, em boa parte, ligados a problemas sociais como alcoolismo e outros dois, história pregressa de TBC efetuado em unidades hospitalares e pronto socorro sugerindo falhas no controle da TBC. Tais resultados podem contribuir para o aperfeiçoamento das estratégias de controle da doença em nosso meio