Katherine Floyd

Tuberculosis control and elimination 2010–50: cure, care, and social development

Rapid expansion of the standardised approach to tuberculosis diagnosis and treatment that is recommended by WHO allowed more than 36 million people to be cured between 1995 and 2008, averting up to 6 million deaths. Yet tuberculosis remains a severe global public health threat. There are more than 9 million new cases every year worldwide, and the incidence rate is falling at less than 1% per year. Although the overall target related to the Millennium Development Goals of halting and beginning to reverse the epidemic might have already been reached in 2004, the more important long-term elimination target set for 2050 will not be met with present strategies and instruments. Several key challenges persist. Many vulnerable people do not have access to affordable services of sufficient quality. Technologies for diagnosis, treatment, and prevention are old and inadequate. Multidrug-resistant tuberculosis is a serious threat in many settings. HIV/AIDS continues to fuel the tuberculosis epidemic, especially in Africa. Furthermore, other risk factors and underlying social determinants help to maintain tuberculosis in the community. Acceleration of the decline towards elimination of this disease will need invigorated actions in four broad areas: continued scale-up of early diagnosis and proper treatment for all forms of tuberculosis in line with the Stop TB Strategy; development and enforcement of bold health-system policies; establishment of links with the broader development agenda; and promotion and intensification of research towards innovations.

Cost-effectiveness of HIV / AIDS interventions in Africa: a systematic review of the evidence.

BACKGROUND Evidence for cost-effectiveness of interventions for HIV/AIDS in Africa is fragmentary. Cost-effectiveness is, however, highly relevant. African governments face difficult choices in striking the right balance between prevention, treatment, and care, all of which are necessary to deal comprehensively with the epidemic. Reductions in drug prices have raised the priority of treatment, though treatment access is restricted. We assessed the existing cost-effectiveness data and its implications for value-for-money strategies to combat HIV/AIDS in Africa. METHODS We undertook a systematic review using databases and consultations with experts. We identified over 60 reports that measured both the cost and effectiveness of HIV/AIDS interventions in Africa. 24 studies met our inclusion criteria and were used to calculate standardised estimates of the cost (US

Scaling up interventions to achieve global tuberculosis control: progress and new developments

for year 2000) per HIV infection prevented and per disability-adjusted life-year (DALY) gained for 31 interventions. FINDINGS Cost-effectiveness varied greatly between interventions. A case of HIV/AIDS can be prevented for

WHO's new end TB strategy.

11, and a DALY gained for

Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru

1, by selective blood safety measures, and by targeted condom distribution with treatment of sexually transmitted diseases. Single-dose nevirapine and short-course zidovudine for prevention of mother-to-child transmission, voluntary counselling and testing, and tuberculosis treatment, cost under

Tuberculosis control in the era of HIV

75 per DALY gained. Other interventions, such as formula feeding for infants, home care programmes, and antiretroviral therapy for adults, cost several thousand dollars per infection prevented, or several hundreds of dollars per DALY gained. INTERPRETATION A strong economic case exists for prioritisation of preventive interventions and tuberculosis treatment. Where potentially exclusive alternatives exist, cost-effectiveness analysis points to an intervention that offers the best value for money. Cost-effectiveness analysis is an essential component of informed debate about priority setting for HIV/AIDS.

Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007-2010

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination.

Interventions to reduce tuberculosis mortality and transmission in low- and middle-income countries

On May 19, 2014, the 67th World Health Assembly (WHA) adopted WHO’s “Global strategy and targets for tuberculosis prevention, care and control after 2015”. This post-2015 global tuberculosis strategy, labelled the End TB Strategy, was shaped during the past 2 years. A wide range of stakeholders—from ministries of health and national tuberculosis programmes to technical and scientifi c institutions, fi nancial and development partners, civil society and health activists, non-governmental organisations, and the private sector—contributed to its development. The strategy has a vision of making the world free of tuberculosis, with zero deaths, disease, and suff ering due to the disease (see appendix p 1 for summary of the End TB Strategy). In 2013, 9 million people fell ill with tuberculosis and 1·5 million died; about a quarter of them were HIV positive. Poor and deprived groups also bore the brunt of the enormous socioeconomic burden imposed by the disease and deaths. Concerned by this persistent human suff ering due to tuberculosis, but encouraged by the progress achieved during the past two decades and recognising the need to mount a multisectoral response to eff ectively address the problem, the health ministers at the WHA approved WHO’s proposal to push the limit of ambition to “end the global tuberculosis epidemic” by 2035, marked by well defi ned milestones and targets set along the way. Ending the tuberculosis epidemic implies bringing the levels of tuberculosis in the whole world down to converge with those already attained by many rich countries: fewer than ten new tuberculosis cases occurring per 100 000 population per year amounting to 90% reduction in tuberculosis incidence and tuberculosis deaths reduced by 95%. The rich countries achieved remarkable reductions in the tuberculosis burden not only by delivering adequate tuberculosis services, but also by pursuing universal access to health care and social protection while rapidly improving nutrition and economic conditions. Ending the tuberculosis epidemic in high-incidence countries needs a similar approach that guarantees access to high-quality tuberculosis care and prevention to all while simul taneously addressing the social determinants of tuberculosis. To this eff ect, elimination of catastrophic costs that tuberculosis-aff ected families face is an important milestone to be achieved under the End TB Strategy well within the next decade. Importantly, though, achievement of universal access to currently available methods of tuberculosis care and prevention will not be enough to end the epidemic within two decades. Global investments and eff orts are also essential to develop improved methods to diagnose, treat, and prevent tuberculosis. Equal emphasis on achievement of universal access to tuberculosis care and prevention, addressing of weaknesses in health systems and social determinants of tuberculosis, and pursuing of research and innovation for improved approaches and strategies constitute the core of the End TB Strategy. The achievements of the past two decades provide the basis for further progress. The DOTS (directly observed treatment, short-course) strategy of 1995 expanded access to high-quality tuberculosis care. The Stop TB Strategy of 2006 widened its scope to address management of all forms of tuberculosis including HIV-associated and drug-resistant tuberculosis, through engagement of communities, involvement of all care providers, strengthening of health systems, and fostering of research. Subsequently, the tuberculosis-related Millennium Development Goal to “halt and begin to reverse the incidence of tuberculosis” was achieved; 37 million lives were saved between 2000 and 2013; and a new rapid molecular test to simultaneously diagnose tuberculosis and rifampicin resistance was developed and two novel drugs were introduced. These achievements notwithstanding, the enormity of the task ahead cannot be overemphasised. Overall, the current 2% annual reduction in the global tuberculosis incidence is too slow to achieve an end to the epidemic in the foreseeable future. Tuberculosis remains a top infectious killer of men and women. A third of estimated incident tuberculosis cases go un-notifi ed or undiagnosed and close to half a million multidrug-resistant cases emerge each year. HIV-associated tuberculosis aff ects more than a million people a year. An estimated 2 billion people with latent tuberculosis infection form a reservoir that sustains the global epidemic. Analyses of constraints to global tuberculosis control bring four major persisting barriers to the fore. First, weak health systems including the unregulated non-state sector prevent reaching the currently available methods of diagnosis and treatment to all sections of the populations and a lack of universal health coverage and social protection inhibit provision of comprehensive tuberculosis care and prevention without further impoverishment to those who need it most. Second, determinants such as poverty, under nutrition, migration, and ageing populations enhance vulnerability and maintain the cycle of infection and disease. The risk of tuberculosis is further enhanced by non-communicable health problems such as diabetes, harmful use of alcohol, and tobacco smoking. Third, the lack of optimum methods—a point-of-care test for rapid diagnosis of disease and latent infection; better and safer drug regimens to shorten treatment; and a vaccine to prevent Lancet 2015; 385: 1799–801

Prospects for Tuberculosis Elimination

BACKGROUND There are no data on the feasibility and cost-effectiveness of using second-line drugs to treat patients with chronic tuberculosis, many of whom are infected with multidrug resistant (MDR) strains of Mycobacterium tuberculosis, in low or middle-income countries. METHODS A national programme to treat chronic tuberculosis patients with a directly observed standardised 18-month daily regimen, consisting of kanamycin (3 months only), ciprofloxacin, ethionamide, pyrazinamide, and ethambutol, was established in Peru in 1997. Compliance and treatment outcomes were analysed for the cohort started on treatment between October, 1997, and March, 1999. Total and average costs were assessed. Cost-effectiveness was estimated as the cost per DALY gained. FINDINGS 466 patients were enrolled; 344 were tested for drug susceptibility and 298 (87%) had MDR tuberculosis. 225 patients (48%) were cured, 57 (12%) died, 131 (28%) did not respond to treatment, and 53 (11%) defaulted. Of the 413 (89%) patients who complied with treatment, 225 (55%) were cured. Among MDR patients, resistance to five or more drugs was significantly associated with an unfavourable outcome (death, non-response to treatment, or default; odds ratio 3.37, 95% CI 1.32-8.60; p=0.01). The programme cost US

Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF

0.6 million per year, 8% of the National Tuberculosis Programme budget, and US