Coverage of clinic-based TB screening in South Africa may be low in key risk groups

The South African Ministry of Health has proposed screening all clinic attendees for tuberculosis (TB). Amongst other factors, male sex and bar attendance are associated with higher TB risk. We show that 45% of adults surveyed in Western Cape attended a clinic within 6 months, and therefore potentially a relatively high proportion of the population could be reached through clinic-based screening. However, fewer than 20% of all men aged 18–25 years, or men aged 26–45 who attend bars, attended a clinic. The population-level impact of clinic-based screening may be reduced by low coverage among key risk groups

Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis

Background Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity. Methods From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo. Results A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. Conclusions Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598. opens in new tab.

Diagnosis of rifampicin-resistant tuberculosis: Discordant results by diagnostic methods.

The performance of the Xpert© MTB/RIF and MTBDRplus assays for the detection of rifampicin resistant Mycobacterium tuberculosis was compared to culture-based drug susceptibility testing in 30 specimens with rifampicin-resistant and rifampicin-indeterminate Xpert MTB/RIF results collected between March 2012 and March 2014. Xpert MTB/RIF and MTBDRplus were 100% sensitive and 100% concordant for rifampicin resistance detection, but 3 of 13 samples (23%) positive for rifampicin resistance on Xpert MTB/RIF and MTBDRplus were negative for rifampicin resistance on mycobacteria growth indicator tube drug susceptibility testing. Specificity was 72% for Xpert MTB/RIF and 80% for MTBDRplus. Positive predictive value for Xpert MTB/RIF for multidrug resistant tuberculosis was 47.8% for new patients and 77.8% for previously treated patients; negative predictive value was 100% for both new and previously treated patients. The discordant rifampicin resistance test results indicate a need to fully characterise circulating rifampicin resistant Mycobacterium tuberculosis strains in Zambia and to inform the development of guidelines for decision-making in relation to diagnosis of drug-resistant tuberculosis

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings

Prevalence of tuberculous lesion in cattle slaughtered in Mubende district, Uganda

BACKGROUND: The aim of this study was to estimate the prevalence of gross pathology suggestive of bovine tuberculosis (TB-like lesions) and evaluate animal’s characteristics associated with the risk of having bovine TB-like lesions among cattle slaughtered in Mubende district in the Uganda cattle corridor. METHOD: We conducted a cross sectional study in which 1,576 slaughtered cattle in Mubende district municipal abattoir underwent post-mortem inspection between August 2013 and January 2014. The presence of bovine TB-like lesions in addition to the animal’s sex, age, breed, and sub-county of origin prior to slaughter were recorded. Associations between the presence of bovine TB-like lesions and animal’s age, sex, breed, and sub-county of origin prior to slaughter were initially analysed using a univariable approach with the chi-square test, and subsequently with a multivariable logistic regression model to assess the combined impact of these animal characteristics with the risk of having a bovine TB-like lesion. Additionally, and as a secondary objective, tissue samples were collected from all carcases that had a bovine TB-like lesion and were processed using standard Mycobacterium culture and identification methods. The culture and acid fast positive samples were tested using Capilia TB-neo® assay to identify Mycobacterium tuberculosis complex (MTC). RESULTS: Of 1,576 carcasses inspected, 9.7% (153/1,576) had bovine TB-like lesions from which Mycobacterium spp and Mycobacterium Tuberculosis Complex (MTC) were isolated in 13 (8.4%) and 12 (7.8%) respectively. Bovine TB-like lesions were more likely to be found in females (OR = 1.49, OR 95% CI: 1.06–2.13) and in older cattle (OR = 2.5, 95% CI: 1.64–3.7). When compared to Ankole cattle, Cross breed (OR = 6.5, OR 95% CI: 3.37–12.7) and Zebu cattle (OR = 2.57, 95% CI: 1.78–3.72) had higher odds of having bovine TB-like lesions. Animals from Kasanda (OR = 2.5, 95% CI: 1.52–4.17) were more likely to have bovine TB-like lesions than cattle from Kasambya. CONCLUSIONS: The findings of study reveals that approximately one in ten slaughtered cattle presents with gross pathology suggestive of bovine TB in Mubende district in the Uganda cattle corridor district, however, we isolated MTC in only 8.4% of these bovine TB-like lesions. Therefore, there is a need to understand the cause of all the other bovine TB-like lesions in order to safe guard diagnostic integrity of meat inspection in Uganda

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

Persons deprived of liberty (PDLs) are disproportionately impacted by tuberculosis, with high incidence rates and often limited access to diagnostics, treatment, and preventive measures. The World Health Organization (WHO) expanded its recommendations for tuberculosis preventive treatment (TPT) to many high-risk populations, but their guidance does not include PDL, and most low- and middle-income countries do not routinely provide edforthoseusedthroughoutthetext TPT in prisons. :Pleaseverifythatallentriesarecorrectlyabbreviated: Recent studies demonstrate high acceptability and completion rates of short-course TPT regimens in jails and prisons; costs of these regimens have been markedly reduced through international agreements, making this an opportune for further expanding their use. We argue that PDL should be a priority group for TPT in national guidelines and discuss implementation considerations and resource needs for TPT programs in carceral facilities. Scaling access to TPT for PDL is important for reducing disease and transmission in this population; it is also critical to advancing an equitable response to tuberculosis

Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis.

BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .)

Costs and cost-effectiveness of tuberculosis cultures using solid and liquid media in a developing country.

SETTING: The expansion of culture has been proposed to aid tuberculosis (TB) control in developing countries. OBJECTIVES: To examine the cost and cost-effectiveness at the Zambian National TB Reference Laboratory of homemade and commercially produced Löwenstein-Jensen culture (HLJ and CLJ) as well as automated and manually read liquid culture (AMGIT and MMGIT). DESIGN: Costs were estimated from the provider's perspective and based on the average monthly throughput. Cost-effectiveness estimates were based on yield during the study period. RESULTS: All techniques show comparable costs per culture (between US$28 and$32). Costs per Mycobacterium tuberculosis specimen detected were respectively US$197,$202, $312 and$340 for MMGIT, AMGIT, CLJ and HLJ. When modelled for the maximum throughput, costs were above US$95 per M. tuberculosis specimen detected for all techniques. When only performed among smear-negative specimens, costs per additionally identified M. tuberculosis would be US$487 for MMGIT and higher for other methods. CONCLUSION: Based on cost-effectiveness grounds, liquid media compare well with conventional solid media, especially where yield of MGIT is substantially higher than that of LJ media. The results indicate high overall costs per culture; the expansion of culture to decentralised levels with lower throughputs may result in even higher costs

BOVINE CLOSTRIDIAL INFECTIONS IN ZAMBIA (1985-1994)

Retrospective surveillance study of clostridial infections of cattle in Zambia, for the period 1985 to 1994,showed that out of the 318 cases observed, 62.8% and 24.2% were from Western and Southern provinces, respectively. Of the 6 clostridia species identified, Clostridium septicum (38.1%) followed by C. chauvoei (36.2%) and C. perfringens (13.2%) were dominant. Although the highest incidence for clostridial infections was in 1989 (75 cases) and 1990 (77 cases), the number of C. perfringens cases seemed to increase. More cases were found in the dry season until the onset of the rains, that is, the period August to December