Outlook for tuberculosis elimination in California: An individual-based stochastic model.

RationaleAs part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).ObjectivesTo estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.MethodsWe created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.Measurements and main resultsIn the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to$48 billion. These had an incremental cost per QALY of $657,000 to$3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.ConclusionsSubstantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks

End TB strategy: the need to reduce risk inequalities

Background Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. Discussion Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. Summary We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle

Hasil Diagnostik Mycobacterium Tuberculosis Dari Sputum Penderita Batuk ≥ 2 Minggu Dengan Pewarnaan Ziehl-Neelsen Di Puskesmas Minanga Malalayang Dua, Puskesmas Bahu, Dan Puskesmas Teling Atas Manado

: Tuberculosis (TB) is an infectious disease which still commonly found at puskesmas (primary health care) in Manado. WHO has proclaimed “The End TB Strategy” program to reduce the incidence of TB. The TB germ can be identified with the Ziehl-Neelsen staining. This study was aimed to identify Mycobacterium tuberculosis in the sputum of patients that were suffered from cough for ≥2 weeks and had not received specific therapy and of relapsed pulmonary TB patients at Puskesmas Minanga Malalayang Dua, Puskesmas Bahu, and Puskesmas Teling Atas Manado by using Ziehl-Neelsen staining. This was a descriptive prospective study with a cross-sectional design. The results showed that of 30 samples of patients, the highest percentages were as follows: at Puskesmas Teling Atas, males (60%), ages 35-59 years old (60%), M. tuberculosis (-) (90%); at Puskesmas Bahu, females (60%), ages 15-34 years old (60%), M. tuberculosis (-) (100%); at Puskesmas Minanga Malalayang Dua, males (60%), ages 15-34 years old (70%), M. tuberculosis (-) (100%). Conclusion: Most patients had sputum with negative results of Mycobaterium tuberculosis which met the The End TB Strategy of WHO

Efficacy of DOTS strategy in treatment of respiratory tuberculosis in Gorgan, Islamic Republic of Iran

We carried out a follow-up cohort study of 260 smear-positive patients (178 on directly observed treatment, short-course (DOTS); 82 on non-DOTS] over a 2-year period to evaluate the efficacy of the DOTS strategy in treatment of tuberculosis (TB). All the patients had had cough for > 3 weeks; 91.9% had fever, 60.8% of them with sputum; and 27.7% had a positive family history. The rate of treatment failure with DOTS was 9.0% at the end of the 2nd month and 1.7% at the beginning of the 5th month. In the control group these rates were 18.3% and 7.3% respectively. The DOTS strategy significantly increased the success rate of TB treatment (P < 0.05)

TB vaccine development and the End TB Strategy: importance and current status.

TB is now the leading, global cause of death due to a single infectious microbe. To achieve the End TB vision of reducing TB by 90% by 2035 we will need new interventions. The objectives of this manuscript are to summarize the status of the clinical TB vaccine pipeline; to assess the challenges facing the TB development field; and to discuss some of the key strategies being embraced by the field to overcome these challenges. Currently, 8 of the 13 vaccines in clinical development are subunit vaccines; 6 of these contain or express either Ag85A or Ag85B proteins. A major challenge to TB vaccine development is the lack of diversity in both the antigens included in TB vaccines, and the immune responses elicited by TB vaccine candidates. Both will need to be expanded to maximise the potential for developing a successful candidate by 2025. Current research efforts are focused on broadening both antigen selection and the range of vaccine-mediated immune responses. Previous and ongoing TB vaccine efficacy trials have built capacity, generated high quality data on TB incidence and prevalence, and provided insight into immune correlates of risk of TB disease. These gains will enable the design of better TB vaccines and, importantly, move these vaccines into efficacy trials more rapidly and at a lower cost than was possible for previous TB vaccine candidates

Factors Associated with Tuberculosis and Rifampicin-Resistant Tuberculosis amongst Symptomatic Patients in India: A Retrospective Analysis

Background Tuberculosis remains a major public health challenge for India. Various studies have documented different levels of TB and multi-drug resistant (MDR) TB among diverse groups of the population. In view of renewed targets set under the End TB strategy by 2035, there is an urgent need for TB diagnosis to be strengthened. Drawing on data from a recent, multisite study, we address key questions for TB diagnosis amongst symptomatics presenting for care: are there subgroups of patients that are more likely than others, to be positive for TB? In turn, amongst these positive cases, are there factors—apart from treatment history—that may be predictive for multi-drug resistance? Methods We used data from a multi-centric prospective demonstration study, conducted from March 2012 to December 2013 in 18 sub-district level TB programme units (TUs) in India and covering a population of 8.8 million. In place of standard diagnostic tests, upfront Xpert MTB/RIF testing was offered to all presumptive TB symptomatics. Here, using data from this study, we used logistic regression to identify association between risk factors and TB and Rifampicin-Resistant TB among symptomatics enrolled in the study. Results We find that male gender; history of TB treatment; and adult age compared with either children or the elderly are risk factors associated with high TB detection amongst symptomatics, across the TUs. While treatment history is found be a significant risk factor for rifampicin-resistant TB, elderly (65+ yrs) people have significantly lower risk than other age groups. However, pediatric TB cases have no less risk of rifampicin resistance as compared with adults (OR 1.23 (95% C.I. 0.85–1.76)). Similarly, risk of rifampicin resistance among both the genders was the same. These patterns applied across the study sites involved. Notably in Mumbai, amongst those patients with microbiological confirmation of TB, female patients showed a higher risk of having MDR-TB than male patients. Conclusion Our results cast fresh light on the characteristics of symptomatics presenting for care who are most likely to be microbiologically positive for TB, and for rifampicin resistance. The challenges posed by TB control are complex and multifactorial: evidence from diverse sources, including retrospective studies such as that addressed here, can be invaluable in informing future strategies to accelerate declines in TB burden

Treatment Outcome of Multi-Drug Resistant Tuberculosis Treated As Outpatient in a Tertiary Care Center

INTRODUCTION: Community-based out-patient treatment for multidrug-resistant tuberculosis (MDR TB) is relatively new concept with reported successful outcomes. OBJECTIVE: To assess the treatment outcomes of HIV negative multidrug-resistant tuberculosis (MDR TB) patients treated as outpatient at a tertiary care center in Karachi, Pakistan. METHODS: A retrospective observational study of 53 consecutive, culture proven HIV negative MDR TB patients (resistant at least to both Isoniazid (H) and Rifampin(R) treated at Aga Khan University Hospital, Karachi between August 1999 and March 2007. Data were collected on predesigned performa regarding patient’s demography, clinical features, radiological findings, drug sensitivity, treatment and outcome. RESULTS: A total of 53 HIV negative patients (27 males), with mean age of 37±15 years (range 15-76 years), received treatment as outpatient for culture proven MDR TB. 51 patients (96.2%) had pulmonary while 3 patients (5.6%) had extra-pulmonary TB. History of exposure to tuberculosis patients was found in 36 (67.9%) patients. Treatment regimen with 2nd line drugs was decided on individual basis according to DST on sputum culture results. The mean duration of treatment was 18 months. Successful outcome was seen in 25 patients (47.2%), 25 patients (47.2%) were loss to follow up and defaulted while 3 (5.6%) patients remain smear positive at the end of treatment. Success rate was 89 .2% in those who completed the treatment. CONCLUSION: Community-based out-patient treatment strategy is both feasible and safe for the treatment of MDR-TB patients in resource limited country like Pakistan and this strategy should be integrated into the routine approach to treatment of MDR-TB patients in the country where the expertise are available. High default rate is this strategy is the main challenge which should be addressed

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

Background The 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. Methods 11 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-specifi c intervention scenarios, which included screening for symptoms, active case fi nding, and preventive therapy. Findings Aggressive 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. Interpretation Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specifi c tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level

Towards cash transfer interventions for tuberculosis prevention, care and control: key operational challenges and research priorities.

BACKGROUND: Cash transfer interventions are forms of social protection based on the provision of cash to vulnerable households with the aim of reduce risk, vulnerability, chronic poverty and improve human capital. Such interventions are already an integral part of the response to HIV/AIDS in some settings and have recently been identified as a core element of World Health Organization's End TB Strategy. However, limited impact evaluations and operational evidence are currently available to inform this policy transition. DISCUSSION: This paper aims to assist national tuberculosis (TB) programs with this new policy direction by providing them with an overview of concepts and definitions used in the social protection sector and by reviewing some of the most critical operational aspects associated with the implementation of cash transfer interventions. These include: 1) the various implementation models that can be used depending on the context and the public health goal of the intervention; 2) the main challenges associated with the use of conditionalities and how they influence the impact of cash transfer interventions on health-related outcomes; 3) the implication of targeting diseases-affected households and or individuals versus the general population; and 4) the financial sustainability of including health-related objectives within existing cash transfer programmes. We aimed to appraise these issues in the light of TB epidemiology, care and prevention. For our appraisal we draw extensively from the literature on cash transfers and build upon the lessons learnt so far from other health outcomes and mainly HIV/AIDS. CONCLUSIONS: The implementation of cash transfer interventions in the context of TB is still hampered by important knowledge gaps. Initial directions can be certainly derived from the literature on cash transfers schemes and other public health challenges such as HIV/AIDS. However, the development of a solid research agenda to address persisting unknowns on the impact of cash transfers on TB epidemiology and control is vital to inform and support the adoption of the post-2015 End TB strategy

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