Reduce Tuberculosis Incidence Research Articles

Evaluating strategies for control of tuberculosis in prisons and prevention of spillover into communities: An observational and modeling study from Brazil.

BackgroundIt has been hypothesized that prisons serve as amplifiers of general tuberculosis (TB) epidemics, but there is a paucity of data on this phenomenon and the potential population-level effects of prison-focused interventions. This study (1) quantifies the TB risk for prisoners as they traverse incarceration and release, (2) mathematically models the impact of prison-based interventions on TB burden in the general population, and (3) generalizes this model to a wide range of epidemiological contexts.Methods and findingsWe obtained individual-level incarceration data for all inmates (n = 42,925) and all reported TB cases (n = 5,643) in the Brazilian state of Mato Grosso do Sul from 2007 through 2013. We matched individuals between prisoner and TB databases and estimated the incidence of TB from the time of incarceration and the time of prison release using Cox proportional hazards models. We identified 130 new TB cases diagnosed during incarceration and 170 among individuals released from prison. During imprisonment, TB rates increased from 111 cases per 100,000 person-years at entry to a maximum of 1,303 per 100,000 person-years at 5.2 years. At release, TB incidence was 229 per 100,000 person-years, which declined to 42 per 100,000 person-years (the average TB incidence in Brazil) after 7 years. We used these data to populate a compartmental model of TB transmission and incarceration to evaluate the effects of various prison-based interventions on the incidence of TB among prisoners and the general population. Annual mass TB screening within Brazilian prisons would reduce TB incidence in prisons by 47.4% (95% Bayesian credible interval [BCI], 44.4%–52.5%) and in the general population by 19.4% (95% BCI 17.9%–24.2%). A generalized model demonstrates that prison-based interventions would have maximum effectiveness in reducing community incidence in populations with a high concentration of TB in prisons and greater degrees of mixing between ex-prisoners and community members. Study limitations include our focus on a single Brazilian state and our retrospective use of administrative databases.ConclusionsOur findings suggest that the prison environment, more so than the prison population itself, drives TB incidence, and targeted interventions within prisons could have a substantial effect on the broader TB epidemic.

РЕСУРСЫ МЕДИЦИНСКИХ ОРГАНИЗАЦИЙ РОССИИ, ОКАЗЫВАЮЩИХ ПОМОЩЬ ПРИ ИНФЕКЦИОННЫХ СОЦИАЛЬНО ЗНАЧИМЫХ ЗАБОЛЕВАНИЯХ

The objective of the study: to assess the provision of the Russian medical units with resources that provide medical care for infectious socially important diseases and compare this provision with the current epidemic situation. Subjects and methods. Data from FGSN Forms no. 8, 14, 14 DS, 33, 61, 30, 47 for the Russian Federation were analyzed. The number of those died is presented as per the data of Rosstat. Results. At the working age, the mortality rate of the population is significantly affected by HIV infection, tuberculosis, viral hepatitis B and C, and the combination of these socially significant diseases (9.3%). It is difficult to determine the cause of death of the patient with multiple co-morbidities. The incidence of tuberculosis is declining more rapidly than the number of tuberculosis beds. As a result, the number of patients with tuberculosis per 1 adult tuberculosis bed decreased from 4.0 in 2005 to 2.9 in 2017; and per 1 tuberculosis bed for children aged 0-17 years – from 1.2 to 0.7 respectively. As of December 31, 2017, the average number of patients per 1 position occupied by a district phthisiologist in the Russian Federation made 306 people, including 35 people with active tuberculosis, and 8 people with multiple drug resistant tuberculosis. The existing facilities and personnel of medical tuberculosis units allow expanding their functions. Given the reduction in tuberculosis incidence, growing incidence of HIV infection, a high proportion of concurrent tuberculosis, HIV infection and viral hepatitis B and C, the best option could be the establishment of Centers for socially important infectious diseases using the facilities of medical tuberculosis units.

Tuberculosis incidence in England hits 30-year low

Tuberculosis incidence in England hits 30-year low

Isoniazid for the Prevention of Tuberculosis in HIV-Infected Children: A Systematic Review and Meta-Analysis.

Isoniazid is recommended for prevention of tuberculosis (TB) in HIV-infected adults, but its efficacy in children living with HIV (CLHIV) is not known. We performed a systematic review to assess the efficacy of isoniazid for the prevention of TB in CLHIV. We searched PubMed, Cochrane Clinical Trial Registry and Google Scholar from inception to December 2016. Any randomized controlled trial assessing the role of isoniazid for the prevention of TB in CLHIV was eligible for inclusion. The primary endpoint was TB incidence; secondary end points were mortality, overall survival and severe adverse events. Dual independent extraction of all data was performed. Data were pooled under a random effects model and summarized either as risk ratio (RR) or hazard ratio along with 95% confidence intervals (CIs). Of 931 references, 3 randomized controlled trials enrolling 977 patients met the inclusion criteria. Pooled results showed a statistically nonsignificant reduction in TB incidence (RR: 0.70; 95% CI: 0.47-1.04; P = 0.07) and mortality (RR: 0.94; 95% CI: 0.39-2.23; P = 0.88) with the use of isoniazid compared with placebo. One study was stopped early because of excess deaths in the placebo arm. However, results from subgroup analysis restricted to only completed trials did not change the overall findings. Isoniazid did not reduce the incidence of TB in CLHIV. All included studies were performed in regions with high prevalence of TB making the overall generalizability limited.

What can National TB Control Programmes in low- and middle-income countries do to end tuberculosis by 2030?

The international community has committed to ending the tuberculosis (TB) epidemic by 2030. This will require multi-sectoral action with a focus on accelerating socio-economic development, developing and implementing new tools, and expanding health insurance coverage. Within this broad framework, National TB Programmes (NTPs) are accountable for delivering diagnostic, treatment, and preventive services. There are large gaps in the delivery of these services, and the aim of this article is to review the crucial activities and interventions that NTPs must implement in order to meet global targets and milestones that will end the TB epidemic. The key deliverables are the following: turn End TB targets and milestones into national measurable indicators to make it easier to track progress; optimize the prompt and accurate diagnosis of all types of TB; provide rapid, complete, and effective treatment to all those diagnosed with TB; implement and monitor effective infection control practices; diagnose and treat drug-resistant TB, associated HIV infection, and diabetes mellitus; design and implement active case finding strategies for high-risk groups and link them to the treatment of latent TB infection; engage with the private-for-profit sector; and empower the Central Unit of the NTP particularly in relation to data-driven supportive supervision, operational research, and sustained financing. The glaring gaps in the delivery of TB services must be remedied, and some of these gaps will require new paradigms and ways of working which include patient-centered and higher-quality services. There must also be fast-track ways of incorporating new diagnostic, treatment, and prevention tools into program activities so as to rapidly reduce TB incidence and mortality and meet the goal of ending TB by 2030.

Global tuberculosis targets and milestones set for 2016-2035: definition and rationale.

>BACKGROUND:Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016–2035) and the Sustainable Development Goals (2016–2030).>OBJECTIVE:To define and explain the rationale for these targets.>DESIGN:Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States.>RESULTS:The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target—that no TB-affected households experience catastrophic costs due to the disease by 2020—was also agreed.>CONCLUSION:The global TB targets and milestones set for the period 2016–2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected.

Reduction in tuberculosis incidence in the UK from 2011 to 2015: a population-based study

BackgroundFollowing nearly two decades of increasing tuberculosis in the UK, TB incidence decreased by 32% from 2011 to 2015. Explaining this reduction is crucial to informing ongoing TB control efforts.MethodsWe...

Determinants of tuberculosis trends in six Indigenous populations of the USA, Canada, and Greenland from 1960 to 2014: a population-based study

Tuberculosis continues to disproportionately affect many Indigenous populations in the USA, Canada, and Greenland. We aimed to investigate whether population-based tuberculosis-specific interventions or changes in general health and socioeconomic indicators, or a combination of these factors, were associated with changes in tuberculosis incidence in these Indigenous populations. For this population-based study we examined annual tuberculosis notification rates between 1960 and 2014 in six Indigenous populations of the USA, Canada, and Greenland (Inuit [Greenland], American Indian and Alaska Native [Alaska, USA], First Nations [Alberta, Canada], Cree of Eeyou Istchee [Quebec, Canada], Inuit of Nunavik [Quebec, Canada], and Inuit of Nunavut [Canada]), as well as the general population of Canada. We used mixed-model linear regression to estimate the association of these rates with population-wide interventions of bacillus Calmette-Guérin (BCG) vaccination of infants, radiographic screening, or testing and treatment for latent tuberculosis infection (LTBI), and with other health and socioeconomic indicators including life expectancy, infant mortality, diabetes, obesity, smoking, alcohol use, crowded housing, employment, education, and health expenditures. Tuberculosis notification rates declined rapidly in all six Indigenous populations between 1960 and 1980, with continued decline in Indigenous populations in Alberta, Alaska, and Eeyou Istchee thereafter but recrudescence in Inuit populations of Nunavut, Nunavik, and Greenland. Annual percentage reductions in tuberculosis incidence were significantly associated with two tuberculosis control interventions, relative to no intervention, and after adjustment for infant mortality and smoking: BCG vaccination (-11%, 95% CI -6 to -17) and LTBI screening and treatment (-10%, -3 to -18). Adjusted associations were not significant for chest radiographic screening (-1%, 95% CI -7 to 5). Declining tuberculosis notification rates were significantly associated with increased life expectancy (-37·8 [95% CI -41·7 to -33·9] fewer cases per 100 000 for each 1-year increase) and decreased infant mortality (-9·0 [-9·5 to -8·6] fewer cases per 100 000 for each death averted per 1000 livebirths) in all six Indigenous populations, but no significant associations were observed for other health and socioeconomic indicators examined. Population-based BCG vaccination of infants and LTBI screening and treatment were associated with significant decreases in tuberculosis notification rates in these Indigenous populations. These interventions should be reinforced in populations still affected by tuberculosis, while also addressing the persistent health and socioeconomic disparities. Public Health Department of the Cree Board of Health and Social Services of James Bay.

Incidence of Tuberculosis Among HIV-Positive Individuals Initiating Antiretroviral Treatment at Higher CD4 Counts in the HPTN 071 (PopART) Trial in South Africa.

Antiretroviral treatment (ART) guidelines recommend life-long ART for all HIV-positive individuals. This study evaluated tuberculosis (TB) incidence on ART in a cohort of HIV-positive individuals starting ART regardless of CD4 count in a programmatic setting at 3 clinics included in the HPTN 071 (PopART) trial in South Africa. A retrospective cohort analysis of HIV-positive individuals aged ≥18 years starting ART, between January 2014 and November 2015, was conducted. Follow-up was continued until 30 May 2016 or censored on the date of (1) incident TB, (2) loss to follow-up from HIV care or death, or (3) elective transfer out; whichever occurred first. The study included 2423 individuals. Median baseline CD4 count was 328 cells/μL (interquartile range 195-468); TB incidence rate was 4.41/100 person-years (95% confidence interval [CI]: 3.62 to 5.39). The adjusted hazard ratio of incident TB was 0.27 (95% CI: 0.12 to 0.62) when comparing individuals with baseline CD4 >500 and ≤500 cells/μL. Among individuals with baseline CD4 count >500 cells/μL, there were no incident TB cases in the first 3 months of follow-up. Adjusted hazard of incident TB was also higher among men (adjusted hazard ratio 2.16; 95% CI: 1.41 to 3.30). TB incidence after ART initiation was significantly lower among individuals starting ART at CD4 counts above 500 cells/μL. Scale-up of ART, regardless of CD4 count, has the potential to significantly reduce TB incidence among HIV-positive individuals. However, this needs to be combined with strengthening of other TB prevention strategies that target both HIV-positive and HIV-negative individuals.

Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis.

The burgeoning epidemic of diabetes mellitus (DM) is one of the major global health challenges. We systematically reviewed the published literature to provide a summary estimate of the association between DM and active tuberculosis (TB). We searched Medline and EMBASE databases for studies reporting adjusted estimates on the TB–DM association published before December 22, 2015, with no restrictions on region and language. In the meta-analysis, adjusted estimates were pooled using a DerSimonian-Laird random-effects model, according to study design. Risk of bias assessment and sensitivity analyses were conducted. 44 eligible studies were included, which consisted of 58,468,404 subjects from 16 countries. Compared with non-DM patients, DM patients had 3.59–fold (95% confidence interval (CI) 2.25–5.73), 1.55–fold (95% CI 1.39–1.72), and 2.09–fold (95% CI 1.71–2.55) increased risk of active TB in four prospective, 16 retrospective, and 17 case-control studies, respectively. Country income level (3.16–fold in low/middle–vs. 1.73–fold in high–income countries), background TB incidence (2.05–fold in countries with >50 vs. 1.89–fold in countries with ≤50 TB cases per 100,000 person-year), and geographical region (2.44–fold in Asia vs. 1.71–fold in Europe and 1.73–fold in USA/Canada) affected appreciably the estimated association, but potential risk of bias, type of population (general versus clinical), and potential for duplicate data, did not. Microbiological ascertainment for TB (3.03–fold) and/or blood testing for DM (3.10–fold), as well as uncontrolled DM (3.30–fold), resulted in stronger estimated association. DM is associated with a two- to four-fold increased risk of active TB. The association was stronger when ascertainment was based on biological testing rather than medical records or self-report. The burgeoning DM epidemic could impact upon the achievements of the WHO “End TB Strategy” for reducing TB incidence.

Injecting drug use predicts active tuberculosis in a national cohort of people living with HIV.

Tuberculosis (TB) is common in people living with HIV, leading to worse clinical outcomes including increased mortality. We investigated risk factors for developing TB following HIV diagnosis. Adults aged at least 15 years first presenting to health services for HIV care in England, Wales or Northern Ireland from 2000 to 2014 were identified from national HIV surveillance data and linked to TB surveillance data. We calculated incidence rates for TB occurring more than 91 days after HIV diagnosis and investigated risk factors using multivariable Poisson regression. A total of 95 003 adults diagnosed with HIV were followed for 635 591 person-years; overall incidence of TB was 344 per 100 000 person-years (95% confidence interval 330-359). TB incidence was high for people who acquired HIV through injecting drugs [PWID; men 876 (696-1104), women 605 (365-945)] and black Africans born in high TB incidence countries [644 (612-677)]. The adjusted incidence rate ratio for TB amongst PWID was 4.79 (3.35-6.85) for men and 6.18 (3.49-10.93) for women, compared with MSM. The adjusted incidence rate ratio for TB in black Africans from high-TB countries was 4.27 (3.42-5.33), compared with white UK-born individuals. Lower time-updated CD4 cell count was associated with increased rates of TB. PWID had the greatest risk of TB; incidence rates were comparable with those in black Africans from high TB incidence countries. Most TB cases in PWID were UK-born, and likely acquired TB through transmission within the United Kingdom. Earlier HIV diagnosis and quicker initiation of antiretroviral therapy should reduce TB incidence in these populations.

Are global tuberculosis control targets overlooking an essential indicator? Prolonged delays to diagnosis despite high case detection rates in Yunnan, China.

Delay in treating active tuberculosis (TB) impedes disease control by allowing ongoing transmission, and may explain the unexpectedly modest declines in global TB incidence. Even though China has achieved TB control targets under the global Directly Observed Treatment, Short course (DOTS) strategy, TB prevalence in western provinces, including Yunnan, is not decreasing. This cross-sectional study investigates whether prolonged delay in identifying and correctly treating TB patients, which is not routinely monitored, persists even when there is a well-functioning TB control programme and global targets are being met. Records of adult smear-positive pulmonary TB patients diagnosed with between 2006 and 2013 were extracted from the Yunnan Centre for Disease Control electronic database, which contains information on the entire population of TB patients managed across 129 diagnostic centres. Delay was investigated at three stages: delay to DOTS facility (period between symptom onset and first visit to at a CDC unit providing standardized treatment); delay to TB confirmation (period between reaching a CDC unit and confirmation of smear-positive TB) and delay to treatment (period between confirmation of TB and initiation of treatment). Data from 76 486 patients was analysed. Delay to reaching a DOTS facility was by far the largest contributor to total delay to treatment initiation. The median delay to reaching a DOTS facility, to TB confirmation and to treatment was 57 days (IQR 25-112), 2 days (IQR 1-6) and 1 day (IQR 0-1) respectively. Prolonged delays to reaching a facility providing standardized TB care occurred in a substantial subset of the population despite all TB control targets being met; overall, 32% (24 676) of patients experienced a delay of more than 90 days to reaching a DOTS facility. Policies that focus on reducing delays in accessing appropriate health services, rather than only on increasing overall case-detection rates, may result in greater progress towards reducing TB incidence.

Assessing the effects of the first 2years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle in 2013-2015.

Culling badgers to control the transmission of bovine tuberculosis (TB) between this wildlife reservoir and cattle has been widely debated. Industry‐led culling began in Somerset and Gloucestershire between August and November 2013 to reduce local badger populations. Industry‐led culling is not designed to be a randomized and controlled trial of the impact of culling on cattle incidence. Nevertheless, it is important to monitor the effects of the culling and, taking the study limitations into account, perform a cautious evaluation of the impacts. A standardized method for selecting areas matched to culling areas in factors found to affect cattle TB risk has been developed to evaluate the impact of badger culling on cattle TB incidence. The association between cattle TB incidence and badger culling in the first 2 years has been assessed. Descriptive analyses without controlling for confounding showed no association between culling and TB incidence for Somerset, or for either of the buffer areas for the first 2 years since culling began. A weak association was observed in Gloucestershire for Year 1 only. Multivariable analysis adjusting for confounding factors showed that reductions in TB incidence were associated with culling in the first 2 years in both the Somerset and Gloucestershire intervention areas when compared to areas with no culling (incidence rate ratio (IRR): 0.79, 95% CI: 0.72–0.87, p < .001 and IRR: 0.42, 95% CI: 0.34–0.51, p < .001, respectively). An increase in incidence was associated with culling in the 2‐km buffer surrounding the Somerset intervention area (IRR: 1.38, 95% CI: 1.09–1.75, p = .008), but not in Gloucestershire (IRR: 0.91, 95% CI: 0.77–1.07, p = .243). As only 2 intervention areas with 2 years of data are available for analysis, and the biological cause–effect relationship behind the statistical associations is difficult to determine, it would be unwise to use these findings to develop generalizable inferences about the effectiveness of the policy at present.

Individual- and neighborhood-level contextual factors are associated with Mycobacterium tuberculosis transmission: genotypic clustering of cases in Michigan, 2004–2012

PurposeUsing genotyping data of Mycobacterium tuberculosis isolates from new cases reported to the tuberculosis (TB) surveillance program, we evaluated risk factors for recent TB transmission at both the individual- and neighborhood- levels among U.S.-born and foreign-born populations. MethodsTB cases (N = 1236) reported in Michigan during 2004 to 2012 were analyzed using multivariable Poisson regression models to examine risk factors for recent transmission cross-sectionally for U.S.-born and foreign-born populations separately. Recent transmission was defined based on spoligotype and 12-locus-mycobacterial interspersed repetitive unit–variable number tandem repeat typing matches of bacteria from cases that were diagnosed within 1 year of each other. Four classes of predictor variables were examined: demographic factors, known TB risk factors, clinical characteristics, and neighborhood-level factors. ResultsOverall, 22% of the foreign-born cases resulted from recent transmission. Among the foreign-born, race and being a contact of an infectious TB case were significant predictors of recent transmission. More than half (52%) of U.S.-born cases resulted from recent transmission. Among the U.S.-born, recent transmission was predicted by both individual- and neighborhood-level sociodemographic characteristics. ConclusionsInterventions aimed at reducing TB incidence among foreign-born should focus on reducing reactivation of latent infection. However, reducing TB incidence among the U.S.-born will require decreasing transmission among socially disadvantaged groups at the individual- and neighborhood- levels. This report fills an important knowledge gap regarding the contemporary social context of TB in the United States, thereby providing a foundation for future studies of public health policies that can lead to the development of more targeted, effective TB control.

Tuberculosis control programs and challenges in developed cities with intermediate disease burden: China experience.

Tuberculosis (TB) remains one of the world’s deadliest infectious disease (1). Historically, it not only posed threats in developing countries, but also affected population in the developed world. From a global perspective, more guidance and focus were prioritized in low-income countries and rural areas due to their high TB burdens. Recently, the World Health Organization (WHO) proposed the End TB Strategy targets (90% reduction in TB incidence and 95% reduction in TB deaths by 2035) and the action framework in low-incidence countries (1,2). However, how to strive for TB elimination in urban areas with intermediate disease burden is still not well understood.

Effectiveness of isoniazid preventative therapy in reducing incidence of active tuberculosis among people living with HIV/AIDS in public health facilities of Addis Ababa, Ethiopia: a historical cohort study

BackgroundHuman Immunodeficiency Virus (HIV) pandemic has exacerbated tuberculosis disease especially in Sub-Saharan African countries. The World Health Organization (WHO) and Joint United Nations Program on HIV/AIDS (UNAIDS) have recommended Isoniazid Preventive Therapy (IPT) for HIV infected patients to reduce the burden of tuberculosis (TB). Ethiopia has been implementing IPT since 2007. However, effectiveness of IPT in averting occurrence of active tuberculosis among HIV infected patients has not been assessed.MethodsRetrospective cohort study was employed using secondary data from public health institutions of Addis Ababa. Descriptive statistics and Generalized Linear Model based on Poisson regression was used for data analysis.ResultsFrom 2524 HIV infected patients who were followed for 4106 Person-Years, a total of 277 incident Tuberculosis (TB) cases occurred. TB Incidence Rate was 0.21/100 Person-Year, 0.86/100 Person-Year & 7.18/100 Person-Year among IPT completed, in-completed and non-exposed patients, respectively. The adjusted Incidence Rate Ratio (aIRR) among IPT completed vs. non-exposed patients was 0.037 (95% CI, 0.016-0.072). Gender, residence area, employment status, baseline WHO stage of the disease (AIDS) and level of CD4 counts were identified as risk factors for TB incidence. The aIRR among patients who took Highly Active Anti- Retroviral Therapy (HAART) with IPT compared to those who took HAART alone was 0.063 (95% CI 0.035-0.104). IPT significantly reduced occurrence of active TB for 3 years.ConclusionsIPT significantly reduced tuberculosis incidence by 96.3% compared to IPT non-exposed patients. Moreover concomitant use of HAART with IPT has shown a significant reduction in tuberculosis incidence by 93.7% than the use of HAART alone. Since IPT significantly protected occurrence of active TB for 3 years, its implementation should be further strengthened in the country.

Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model.

BackgroundNovel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen’s ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective.Methods and FindingsWe developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care.For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113–187) and 16 (95% UR: 9–23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4–10) and 0.6 (95% UR: 0.3–1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%–20%) and 11% (95% UR: 6%–20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%–46%) and RR TB mortality by 30% (95% UR: 18%–44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%–13%, half the impact of a fully optimized regimen), and increasing the efficacy against RR TB from 76% to 94% lowered RR TB mortality by 13% (95% UR: 6%–23%). Reducing treatment duration or improving ease of adherence had smaller but still substantial impact: shortening RS TB treatment duration from 6 to 2 mo lowered TB mortality by 3% (95% UR: 1%–6%), and shortening RR TB treatment from 20 to 6 mo reduced RR TB mortality by 8% (95% UR: 4%–13%), while reducing nonadherence to the corresponding regimens by 50% reduced TB and RR TB mortality by 2% (95% UR: 1%–4%) and 6% (95% UR: 3%–10%), respectively. Limitations include sparse data on key model parameters and necessary simplifications to model structure and outcomes.ConclusionsIn designing clinical trials of novel TB regimens, investigators should consider that even small changes in treatment efficacy may have considerable impact on TB-related incidence and mortality. Other regimen improvements may still have important benefits for resource allocation and outcomes such as patient quality of life.

Tuberculosis along the continuum of HIV care in a cohort of adolescents living with HIV in Ethiopia.

Eight health facilities in Ethiopia. To determine tuberculosis (TB) incidence rates and associated factors among adolescents living with the human immunodeficiency virus (ALHIV). This was a retrospective cohort study. Adolescents enrolled in HIV care between January 2005 and 31 December 2013 constituted the study population. The main outcome variable was TB diagnosis during follow-up. Baseline World Health Organization (WHO) clinical stage, CD4 count, previous history of TB and use of isoniazid preventive therapy (IPT) were the main independent variables. We estimated TB incidence rates as incident cases per 100 person-years of observation (PYO). Cox regression analysis was used to control for confounders. Of the 1221 adolescents screened, 1072 were studied; 60.1% were girls. TB incidence rate was 16.32 per 100 PYO during pre-antiretroviral therapy (pre-ART) follow-up but declined to 2.25 per 100 PYO after initiation of ART. Advanced WHO clinical stage (adjusted hazard ratio [aHR] 2.71, 95%CI 1.69-4.33) and CD4 count <350 cells/μl (aHR 2.28, 95%CI 1.10-4.81) predicted TB incidence in the pre-ART cohort. IPT use was associated with a significant reduction in TB incidence in the ART cohort, but not in the pre-ART group. Although TB was a significant problem in ALHIV, timely administration of ART and IPT had a significant protective effect.

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

SummaryBackgroundThe post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements.Methods11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy.FindingsAggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis.InterpretationMajor reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level.FundingBill and Melinda Gates Foundation

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. Bill & Melinda Gates Foundation.