Vaccination in post-tuberculosis lung disease management: A review of the evidence.

INTRODUCTION AND OBJECTIVES: Post-tuberculosis lung disease (PTLD), as other chronic respiratory disorders, may have infectious complications; some of them can be prevented with vaccinations. So far, no document has discussed the potential role of vaccination in PTLD. Therefore, the objective of this review was to describe vaccination recommendations to prevent infections potentially capable of complicating PTLD. MATERIALS AND METHODS: A non-systematic review of the literature was conducted. The following keywords were used: tuberculosis, vaccination, vaccines and PTLD. PubMed/MEDLINE and Embase were used as the search engine, focusing on English-language literature only. RESULTS: We identified 9 vaccines potentially useful in PTLD. Influenza, pneumococcal and anti-COVID-19 vaccinations should be recommended. Patients with PTLD can also benefit from vaccination against shingles. Vaccination against pertussis is mainly relevant during childhood. Diphtheria, tetanus and measles vaccination are recommended for general population and should be considered in patients with PTLD not previously vaccinated. Tdap (Tetanus, diphtheria, and pertussis) booster should be repeated in every adult every ten years. Vaccination against BCG retains its importance during early childhood in countries where TB is endemic. CONCLUSIONS: Vaccination deserves to be considered among the strategies to prevent and/or mitigate PTLD complications. Further evidence is necessary to better understand which vaccines have the greatest impact and cost-benefit.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Tuberculosis incidence among contacts of active pulmonary tuberculosis.

BACKGROUND: Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients agedor=10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST>or=15 mm regardless of previous BCG vaccination. OBJECTIVE: To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN: Retrospective cohort study. Contacts aged between 12 and 15 years and those aged>or=15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS: TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100000 population. Risk of TB was greater among the 349 contacts with TST>or=5 mm (5.4%) compared to the 318 contacts with TST<5 mm (0.9%; RR 6.04, 95%CI 1.7-20.6). CONCLUSION: The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration>or=5 mm was the only variable that predicted the development of TB disease within 2years.

Molecular epidemiology of hepatitis B virus in an isolated Afro-Brazilian community.

This study was conducted in an Afro-Brazilian, slave-descendant community with high (42.4%) hepatitis B virus (HBV) prevalence. Twenty (8.4%) out of the 239 subjects under study were HBsAg-positive, and HBV-DNA was detected in 59 (25%) individuals. A high rate (18.3%) of occult infection was therefore observed that was associated to low HBV loads (mean, 1.8 x 10(4) copies/ml) and to a specific amino acid substitution (C100Y) in the small surface antigen. Genotyping of 50 isolates showed that 43 (86%) were of subgenotype A1, one (2%) from subgenotype A2, and five (10%) from subgenotype D. Mixed genotypes A1 and E were observed in one (2%) sample. The genetic distance (0.8 +/- 0.3%) among the HBV/A1 isolates from the community was smaller than the intragroup divergence among A1 isolates from Brazil as a whole, but it was similar to that found between A2 isolates from different countries, suggesting that HBV/A1 was introduced in the community through different sources. The substitution W501R (polymerase), previously reported only in Gambia, was observed in 46% of the HBV/A1 isolates. The precore/core promoter region of HBsAg-positive isolates showed several substitutions that could explain the anti-HBe phenotype found in 18 of 20 (90%) of the HBsAg-positive subjects.

Migration, TB control and elimination: Whom to screen and treat.

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease.

Prevalence of pulmonary tuberculosis among respiratory symptomatic subjects in an out-patient primary health unit.

SETTING: Out-patient primary health unit (OPHU) in Rio de Janeiro City, Brazil. OBJECTIVE: To evaluate the impact on the detection of tuberculosis (TB) cases of reducing the time of respiratory symptoms from 'cough > or = 3 weeks' to 'cough > or = 1 week' as a criteria for TB case finding among individuals visiting an OPHU for any other reason. DESIGN: Cross-sectional study. RESULTS: During the period of the study, 10.7% (765/ 7174) of subjects reported cough > or = 1 week. Among 542 subjects enrolled in the study with cough > or = 1 week, 15 (2.7%) cases were diagnosed with pulmonary tuberculosis (PTB, 2767/100000). The probability of detecting TB in the OPHU setting among subjects seeking care for respiratory symptoms was significantly higher than among those presenting to the OPHU for other reasons (OR 31.5, 95% CI 4.1-241.9; P < 0.0001). The probability of identifying TB among patients seeking care due to respiratory symptoms was not influenced by the duration of cough (P = 0.7). CONCLUSION: These findings suggest that the screening criteria for TB case finding of cough for less than the usual 3 weeks among patients who attend a health facility due to respiratory symptoms in settings with a high prevalence of TB may significantly improve the proportion of TB cases diagnosed.

Multicentre evaluation of an automated BACTEC 960 system for susceptibility testing of Mycobacterium tuberculosis.

SETTING: Three mycobacteria reference laboratories in the south-eastern part of Brazil. OBJECTIVE: To evaluate the automated Mycobacteria Growth Indicator Tube (MGIT) for drug susceptibility testing of Mycobacterium tuberculosis. DESIGN: Performance of the automated BACTEC MGIT 960 (M960) system for testing M. tuberculosis susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) was evaluated with 95 clinical isolates and compared to the results of the radiometric BACTEC 460TB (B460) system, the proportion method (PM), and the resistance ratio method (RRM). Judicial susceptibility profiles of 88 isolates were defined based on two or more concordant results among B460, PM and RRM, and used as a reference for comparison with M960 results. RESULTS: Agreement rates between M960 and conventional methods were 95.2% with B460, 96.6% with the PM and 93.4% with the RRM. The lowest agreement rates were obtained for SM with the RRM and for EMB with B460. When comparing M960 with judicial susceptibility profiles, the agreement rate was 97.9%. The agreement rates obtained for INH and RMP were 99.2% and for SM and EMB they were 96.2% and 96.9%, respectively. The mean time to reporting the M960 results was 6.9 days. CONCLUSION: M960 offers great improvements when compared to the proportion and resistance ratio methods and would benefit patient treatment.

Improvements in treatment success rates with directly observed therapy in Rio de Janeiro City.

SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To evaluate the effect of directly observed therapy (DOT) on treatment success, by comparing the treatment success rates between patients treated under DOT with those who received self-administered therapy (SAT). DESIGN: A longitudinal study in a cohort of tuberculosis (TB) patients. Of 9929 new pulmonary TB cases, 1190 (12%) were treated under DOT and 8739 (88%) under SAT. All patients received a three-drug regimen consisting of rifampicin (RMP), isoniazid (INH) and pyrazinamide for 2 months followed by 4 months of RMP and INH. RESULTS: Patients under DOT were more likely to convert to sputum-negative at the end of the second month than those treated under SAT (86.3% vs. 61.9%, P < 0.001). DOT alone was significantly associated with successful treatment (OR 1.6, 95%CI 1.37-1.86, P < 0.001), even when controlled by sex, age and positive smear or culture at enrollment (OR 1.56, 95%CI 1.33-1.82, P < 0.001). CONCLUSION: This pilot DOTS implementation phase showed that DOT is highly effective and feasible in a large urban centre of a developing country.

Detection of Mycobacterium tuberculosis by a polymerase chain reaction colorimetric dot-blot assay.

SETTING: A public health laboratory in a tuberculosis-endemic region in Brazil. OBJECTIVE: To evaluate the accuracy of a combined polymerase chain reaction (PCR) colorimetric dot-blot protocol for Mycobacterium tuberculosis detection in clinical samples in a public health laboratory. DESIGN: Eighty clinical samples (13 cerebrospinal fluid, 31 induced sputum, 17 expectorated sputum, eight bronchoalveolar lavage and 11 pleural fluid) were assayed with the developed protocol. The accuracy of polymerase chain reaction (PCR) dot-blot methodology was compared to PCR agarose gel electrophoresis (PCR-AG) using as a gold standard the bacteriological result (culture and biochemical identification) combined with clinical follow-up. One internal region of the IS6110 repetitive element of the M. tuberculosis complex was selected for amplification and the amplified product transferred to nylon membranes to be detected by biotinylated DNA probe. RESULTS: Overall sensitivity and specificity obtained were respectively 90% and 97% for PCR-AG and 95% and 97% for the PCR dot-blot. Among the 56 respiratory specimens, the sensitivity and specificity results for PCR-AG were respectively 88% and 95%, and for PCR dot-blot they were 94% and 95%. Among the 24 non-respiratory specimens the sensitivity and specificity results were respectively 83% and 100% for PCR-AG, and 100% and 100% for the PCR dot-blot protocol. CONCLUSION: The results demonstrated that the PCR dot-blot assay may be helpful in the diagnosis of tuberculosis, and feasible even in resource-poor countries.

Tuberculosis is associated with non-tuberculosis-related deaths among HIV/AIDS patients in Rio de Janeiro.

SETTING: Human immunodeficiency virus (HIV) infected patients followed in a large cohort in Rio de Janeiro, Brazil. OBJECTIVE: To evaluate the association of tuberculosis (TB) and other covariables with non-TB-related (NTR) causes of death (CODs). DESIGN: Patients aged >18 years were followed from 1997 to 2009, until death or 31 December 2009, whichever was earlier. CODs were ascertained using a standardised algorithm. TB diagnosis and prophylaxis followed Brazilian guidelines. Poisson models were used to calculate adjusted rate ratios (aRRs). RESULTS: Of 2887 patients included in the study, 761 had TB (26.4%). NTR death rates were twice as high among patients with TB (4/100 vs. 2.09/100 patient-years). TB was associated with NTR deaths (aRR 1.4, 95%CI 1.05-1.86, P = 0.01). Highly active antiretroviral treatment (HAART) was protective against NTR (aRR 0.46, 95%CI 0.34-0.61, P < 0.001). Among patients who had never had active TB, prophylaxis was also protective against NTR (aRR 0.45, P = 0.04). The CD4 cell count increase was very modest for both TB and NTR CODs compared to those who did not die (0 vs. 249 cells, P < 0.001). CONCLUSIONS: TB was significantly associated with increased NTR CODs, indicating rapid progression of disease and increased long-term risk of mortality, probably related to persistent immunodeficiency or incomplete immune recovery. Our results confirm the benefits of HAART and TB prophylaxis.

Safety and effectiveness of HAART in tuberculosis-HIV co-infected patients in Brazil.

BACKGROUND: Antiretroviral therapy (ART) significantly reduces tuberculosis (TB) incidence among persons with human immunodeficiency virus (HIV), but the safety and effectiveness of concomitant treatment for both diseases remain unclear. OBJECTIVE: To evaluate the impact of ART and anti-tuberculosis treatment on survival and risk of adverse events (AE) among co-infected individuals. METHODS: In a retrospective cohort study, clinical data were collected from 618 TB-HIV patients treated with rifampin, isoniazid and pyrazinamide ± ethambutol between 1 January 1995 and 31 December 2003. Patients were categorized into two groups: highly active ART (HAART) or no ART. Different HAART regimens were evaluated. Bivariate analysis, multivariate logistic regression and survival analysis using Cox proportional hazards regression were used. RESULTS: One-year mortality was lower for patients receiving HAART (adjusted hazard ratio [aHR] 0.17, 95%CI 0.09-0.31) compared to no ART. HAART increased the risk of AE (aHR 2.08, 95%CI 1.29-3.36). The odds of AE when receiving a ritonavir + saquinavir HAART regimen was eight-fold higher compared to no ART (OR 8.31, 95%CI 3.04-22.69), while efavirenz-based HAART was not associated with a significantly increased risk of AE (OR 1.42, 95%CI 0.76-2.65). CONCLUSION: HIV patients with TB have significantly better survival if they receive HAART during anti-tuberculosis treatment. Efavirenz-based HAART is associated with fewer AEs than protease inhibitor-based HAART.

Egg production evaluation of laying hens by multivariate analysis / Avaliação da produção de ovos de poedeiras por análise multivariada

This study aimed to verify the existence of differences between hens from the Barred Plymouth Rock (PRB) breed and White Plymouth Rock (PRW) breed by multivariate analysis of weekly egg production and cumulative during the years of 1998 and 2010, from the Laboratório de Avicultura (LAVIC) of the Departamento de Zootecnia at the Universidade Federal de Santa Maria (UFSM). For the analysis of the univariate and multivariate variance, the experimental design was completely randomized with two treatments (breed) and 299 repetitions of the PRW breed and 350 of the PRB breed. The parameters analyzed were the weekly productions of eggs per bird from the 21st to the 50th week of age (P21, P22, ..., P50) and production of eggs accumulated being from the 21st to the 25th (PA1), 21st to the 30th (PA2), 21st to the 35th (PA3), 21st to the 40th (PA4), 21st to the 45th (PA5) and 21st to 50th (PA6). Analyzes of univariate and multivariate variance were conducted and the comparison of means were made by "T" Student and Wilks respectively (P < 0, 05). Based on the results, an analysis of the principal components was performed with parameters PA1, PA2, PA4, PA5 and PA6. With the average egg production per family accumulated, a cluster analysis using Euclidean distance and single linkage method (nearest neighbors) was performed. The first two principal components meet the total variation in egg production accumulated from the 21st to 25th, 21st to 30th, 21st to 40th, 21st to 45th and 21st to 50th weeks of age. Most of the phenotypic variation of the layers can be explained by the production of eggs accumulated from the 21st until the 40th week of age, and this variable is highly correlated with total egg production. Families from the PRW and PRB breed form seven distinct groups, but homogeneous by the similarity between them. This allows direct crossings between different groups, in the pursuit for heterosis.(AU)

Objetivou-se verificar a existência de divergência entre poedeiras das raças Plymouth Rock Barrada (PRB) e Plymouth Rock Branca (PRW) por meio da análise multivariada da produção de ovos semanal e acumulada dos anos de 1998 e 2010, do Laboratório de Avicultura (Lavic) do Departamento de Zootecnia da Universidade Federal de Santa Maria (UFSM). Para as análises de variância uni e multivariada, o delineamento experimental foi inteiramente ao acaso, com dois tratamentos (raças) e 299 repetições da raça PRW e 350 da raça PRB. Os parâmetros analisados foram a produção de ovos semanal por ave da 21ª à 50ª semana de idade (P21, P22,..., P50) e a produção de ovos acumulada, sendo da 21ª à 25ª (PA1), 21ª à 30ª (PA2), 21ª à 35ª (PA3), 21ª à 40ª (PA4), 21ª à 45ª (PA5) e 21ª à 50ª (PA6). Realizaram-se as análises de variância uni e multivariada, e a comparação de médias foi feita pelos testes "T" de Student e de Wilks, respectivamente (P<0,05). Com base nos resultados, foi realizada a análise de componentes principais, com os parâmetros PA1, PA2, PA4, PA5 e PA6. E, com as médias de produção de ovos acumulada por família, foi realizada a análise de agrupamento por meio da distância euclidiana e pelo método de encadeamento único (vizinhos mais próximos). Os dois primeiros componentes principais reúnem a variação total da produção de ovos acumulada da 21ª à 25ª, 21ª à 30ª, 21ª à 40ª, 21ª à 45ª e 21ªá 50ª semanas de idade. A maior parte da variação fenotípica das poedeiras pode ser explicada pela produção de ovos acumulada da 21ª até a 40ª semana de idade, e essa variável tem alta correlação com a produção de ovos total. As famílias da raça PRW e da raça PRB formam sete grupos distintos, mas homogêneos, pela similaridade existente entre elas, o que permite direcionar cruzamentos entre os diferentes grupos, em busca da heterose.(AU)

Prevalence of hepatitis B virus infection among tuberculosis patients with or without HIV in Goiânia City, Brazil.

BACKGROUND: Hepatitis B virus (HBV) and tuberculosis (TB) represent major public health problems. There is currently little data on HBV infection among TB patients with and without human immunodeficiency virus (HIV). OBJECTIVES: To assess HBV prevalence among TB patients with and without HIV. STUDY DESIGN: From April 2008 to March 2010, a cross-sectional study was conduct among TB patients attended at a reference hospital in Goiânia City, Brazil. The participants were tested for serological markers of HBV infection and HIV antibodies. HBV DNA was detected in HBsAg-positive samples, and also in HBsAg-negative/anti-HBc-positive samples to look for HBV occult infection. RESULTS: Of 425 patients, 402 (94.6%) agreed to participate in the study. The overall prevalence of HBV (HBsAg and/or anti-HBc positive) and HIV infections were 25.6% (103/402) and 27.6% (111/402), respectively. A higher HBV infection rate was found among HIV-infected patients (36.9%; 41/111) compared to patients infected with TB only (20.0%; 57/285). A multivariate analysis of risk factors showed that age ≥ 50 years (p=0.03), non-injecting (p<0.01) and injecting (p<0.01) drugs use were associated with HBV infection. Among the HBsAg-positive samples (n=13), HBV DNA was detected in 10 (76.9%) samples. Of the 90 anti-HBc-positive samples, 13 were HBV DNA positive (with very low levels) resulting in an occult HBV infection rate of 14.4%. PCR-RFLP was successfully performed in 20 HBV DNA-positive samples: 15 were genotype A and 5 were genotype D. CONCLUSIONS: HBV infection was common, particularly among this with HIV infection.

Drug-resistant tuberculosis in six hospitals in Rio de Janeiro, Brazil.

SETTING: Tuberculosis (TB) drug resistance survey in six hospitals in Rio de Janeiro, Brazil. OBJECTIVE: To estimate resistance to at least one drug (DR) and multidrug resistance (MDR) and identify associated factors. DESIGN: One-year cross-sectional survey. Hospitals were included as a convenience sample. RESULTS: Of 595 patients investigated, 156 (26.2%) had previously undergone anti-tuberculosis treatment, 433 (72.8%) were not previously treated and information on the remaining 6 was not available. Overall, DR and MDR rates were high, at respectively 102 (17.1%, 95%CI 14.3-20.5) and 44 (7.4%, 95%CI 5.5-9.9) cases. Among individuals not previously treated, 17 had MDR (3.9%, 95%CI 2.4-6.3) and diagnosis in a TB reference hospital was independently associated with MDR (prevalence ratio [PR] 3.3, 95%CI 1.2-8.7) after multivariate analysis. Among previously treated individuals, 27 had MDR (17.3%, 95%CI 11.7-24.2). MDR-TB was independently associated with diagnosis in a TB reference hospital (PR 3.6, 95%CI 1.5-8.7), male sex (PR 2.3, 95%CI 1.2-4.4) and dyspnoea (PR 0.3, 95%CI 0.1-0.7). CONCLUSION: We found high levels of DR- and MDR-TB. Our study design did not permit us to determine the contribution of community versus nosocomial transmission. Further studies are needed to establish this. Nevertheless, hospitals should be recognised as a potential source of transmission of resistant TB strains and urgent measures to avoid nosocomial TB transmission should be taken.