Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome.
Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits.
Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.
METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.
FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.
INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.
FUNDING: Bill & Melinda Gates Foundation.
METHODS: A retrospective study was conducted to recognize the epidemiology facts of EPTB. Individual data for EPTB patients were collected from TB registers, laboratory TB registers, treatment cards and TB medical personal files into a standardized study questionnaire. Crude (COR) and adjusted odds ratios (AOR) and 95% confidence intervals (CI) were determined to assess the risk factors for EPTB and unsuccessful treatment outcomes.
RESULTS: There were 1222 EPTB patients presenting 13.1% of all TB cases during 2006-2008. Pleural effusion and lymph node TB were the most frequent types and accounted for 45.1% of all EPTB cases among study participants. Treatment success rate was 67.6%. The best treatment completion rates were found in children ≤15 years (0.478 [0.231-1.028]; p = 0.05). On multivariate analysis, age group 56-65 years (1.658 [1.157-2.376]; p = 0.006), relapse cases (7.078 [1.585-31.613]; p = 0.010), EPTB-DM (1.773 [1.165-2.698]; p = 0.008), patients with no formal (2.266 [1.254-4.095]; p = 0.001) and secondary level of education (1.889 [1.085-3.288]; p = 0.025) were recorded as statistically positive significant risk factors for unsuccessful treatment outcomes. Patients at the risk of EPTB were more likely to be females (1.524 [1.311-1.746]; p
METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.
RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.
CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.
DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.
CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.
METHODS: We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB after randomization. Baseline factors associated with TB were analyzed using Cox regression stratified by site.
RESULTS: TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa, and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI: 2.1 to 5.1). Increased TB risk was associated with a low CD4+-cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (<150 ×109/L), and low total serum cholesterol (≤4.5 mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+-cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure.
DISCUSSION: The risk of TB remains elevated in PLHIV in the setting of second-line HIV therapy in TB endemic regions. TB was associated with a greater risk of death. Finding that low CD4+ T-cell count was significantly associated with poor outcomes in this population supports the value of CD4+ monitoring in HIV clinical management.