Multidrug resistant tuberculosis co-existing with aspergilloma and invasive aspergillosis in a 50 year old diabetic woman: a case report

Aspergilloma and invasive aspergillosis coexisting with multidrug resistant Mycobacterium tuberculosis (MDR-TB) in the same patient is a rare entity. We report a 50 year old South Indian woman, a diabetic, who presented to us with complaints of productive cough and hemoptysis for the past 2 months. She was diagnosed to have pulmonary tuberculosis 2 years ago for which she took irregular treatment. Lung imaging showed features of a thick walled cavity in the right upper lobe with an indwelling aspergilloma. She underwent a right lung upper lobe resection. Biopsy and culture of the resected specimen showed the coexistence of Aspergillus fumigatus and multi-drug resistant Mycobacterium tuberculosis. 2 blood cultures grew Aspergillus fumigatus. She was successfully treated with Voriconazole and anti tuberculous therapy against MDR-TB

Selective Inactivity of Pyrazinamide against Tuberculosis in C3HeB/FeJ Mice Is Best Explained by Neutral pH of Caseum

Pyrazinamide (PZA) is one of only two sterilizing drugs in the first-line antituberculosis regimen. Its activity is strongly pH dependent; the MIC changes by several orders of magnitude over a range of pH values that may be encountered in various in vivo compartments. We recently reported selective inactivity of PZA in a subset of C3HeB/FeJ mice with large caseous lung lesions. In the present study, we evaluated whether such inactivity was explained by poor penetration of PZA into such lesions or selection of drug-resistant mutants. Despite demonstrating similar dose-proportional PZA exposures in plasma, epithelial lining fluid, and lung lesions, no dose response was observed in a subset of C3HeB/FeJ mice with the highest CFU burden. Although PZA-resistant mutants eventually replaced the susceptible bacilli in BALB/c mice and in C3HeB/FeJ mice with low total CFU burdens, they never exceeded 1% of the total population in nonresponding C3HeB/FeJ mice. The selective inactivity of PZA in large caseous lesions of C3HeB/FeJ mice is best explained by the neutral pH of liquefying caseum

Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guerin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Background Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. Objectives To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. Methods Two case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression. Results In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5–10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10–15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. Limitations The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. Conclusions Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading

Interventions to improve contact tracing for tuberculosis in specific groups and in wider populations: an evidence synthesis

Background The tracing and screening of people who have had contact with an active case of tuberculosis (TB) is an important element of TB control strategies. Objectives This study aimed to carry out a review of evidence regarding TB contact tracing, with a particular emphasis on research that was applicable to TB contact tracing in specific population groups in the UK. Design An evidence synthesis of literature of any study design on TB contact tracing in developed countries was carried out. Setting Any setting. Population Individuals found to have active TB disease, and people who have come into contact with them. Interventions Contact-tracing investigations. Main outcome measures Any outcome related to TB infection, contact investigations and/or the views of staff, people with TB disease, or their contacts. Data sources Searches for research published 1995 onwards were undertaken in the following databases: MEDLINE via Ovid SP, EMBASE via Ovid SP, EconLit via Ovid SP, PsycINFO via Ovid SP, Social Policy and Practice via Ovid SP, Cumulative Index to Nursing and Allied Health Literature via EBSCOhost, Science and Social Science Citation Indices via Web of Science and The Cochrane Library via Wiley Online Library. Review methods The study comprised a review of TB contact tracing in specific population groups and a review in wider populations. A narrative synthesis was completed and a logic model was developed from the literature. Results There were 112 articles in the review: 23 related to specific populations and 89 related to wider populations. The literature was of limited quality, with much general description of investigations. We identified only two (uncontrolled) studies that could be considered evaluative. Although the limitations of the evidence should be recognised, the review suggested the following: the value of a location-based approach, working with local communities and the media, partnership working, using molecular epidemiological testing, ensuring adequate systems and addressing fear of stigma. The literature on investigations for specific populations has much concordance with that reporting findings from wider population groups. The recognised limitations of conventional investigation methods may, however, be exacerbated in specific populations. Limitations The English-language inclusion criterion may have limited the breadth of countries represented. A meta-analysis was not possible owing to the nature of the literature. Relevant studies may have been missed by our searches, which used terminology relating to contact tracing rather than to active case finding or screening. Conclusions The review identified a sizeable volume of literature relating to contact investigations. However, it is currently predominantly descriptive, with little evaluative work underpinning investigations in either specific or wider populations. Our findings are, therefore, based on limited evidence. Further research is required if robust conclusions are to be made. Future work Research should further explore the development of measures that can be used to compare the effectiveness of different contact investigations, in studies using evaluative designs