Reaching the targets for tuberculosis control: the impact of HIV
KF Lasersona, CD Wellsb
In 1991, the 44th World Health Assembly (WHA) recognized the importance and previous neglect of tuberculosis (TB), and set two key global targets to be reached by 2000: 70% case detection of acid-fast bacilli smear-positive TB patients under the then-new DOTS strategy recommended by WHO, and 85% treatment success for those detected.1,2 Achieving these targets would significantly decrease TB prevalence and reduce TB incidence by approximately 10% per year in the absence of any major change in TB epidemiology.3–6 By 2000, 148 countries had adopted the WHO DOTS strategy and 27% of the estimated global TB cases were being treated in a DOTS programme.2 Despite this progress, it became clear that the WHA targets would not be met by 2000, and the achievement date was deferred to 2005.2
Setting the stage: scaling up TB control
In an effort to scale up global TB control to reach the WHA targets, the STOP TB Partnership was launched in 2000 and the first Global Plan to Stop TB, covering the years 2001–2005, was implemented.3 Between 1990 and 2004, the global TB prevalence decreased from 297 to 229 per 100 000 (including those positive for HIV).7 During this time, many countries received technical assistance to improve their national TB programmes, and 4.5 million patients were treated with anti-TB drugs procured through the Global Drug Facility, which was established to facilitate treatment with good quality, inexpensive TB drugs.8 Second-line drug prices were reduced by 95% via the Green Light Committee, which promotes access to, and rational use of, second-line drugs for multidrug-resistant TB (MDR-TB).9 By July 2005, more than 36 projects managing drug-resistant TB in the context of DOTS programmes had been initiated, with more than 10 000 patients treated appropriately for MDR in more than 27 countries.4
As HIV continued to worsen the burden of TB, the TB/HIV working group of the STOP TB partnership provided guidance to help countries design and implement collaborative TB/HIV activities.10 By the end of 2003, 29 of the 41 countries with the highest prevalence of HIV-associated TB had a national policy for collaboration between their TB and HIV programmes, and 16 had a national TB/HIV coordinating body – key steps towards implementation.4 In 2006, progress in meeting the target numbers was substantial: case detection reached 59% (more than 57 countries met the case detection target), and treatment success reached 84% (more than 60 countries met the treatment target) (Chris Dye, WHO, unpublished data). By late 2006, the global TB epidemic was at the threshold of decline (Chris Dye, WHO, unpublished data); however, only 25 countries have reached both of the 1991 WHA targets for TB control; particularly problematic are the low treatment success rates reported from Africa (72%) and Europe (75%).7
To meet the 1991 WHA targets, the US $56 billion Global Plan to STOP TB, 2006–2015 was formulated and disseminated.4 Fulfilling this second plan will reach the 1991 targets. It will also achieve target 8 of Millennium Development Goal (MDG) 6 — “to have halted by 2015, and begun to reverse, the incidence of [all forms] of TB”. It will also meet the STOP TB Partnership’s 2015 targets, which are to halve TB prevalence and death rates from the 1990 baseline, and eliminate TB (incidence < 1/1 000 000) as a global public health problem by 2050.
Successful implementation of the Global Plan depends on implementation of the new 6-point STOP TB strategy recommended by WHO. This strategy promotes use of the new International Standards for Tuberculosis Care11,12 to engage all care providers (including those in the private sector) in delivering high-quality care. It specifically addresses HIV-associated TB, MDR-TB and other challenges, and strengthens human rights and health systems. However, the plan also relies on new diagnostic tests, new drugs and TB vaccines being developed by or before 2015.
Through the successful implementation of the new plan, 50 million patients will be treated using DOTS and/or tested for drug-resistant TB in the context of DOTS programmes. Countries will achieve comprehensive TB control for their entire populations, through improved quality of TB treatment and care services (including TB laboratories) and implementation of community DOTS initiatives. Although the second global plan lays out an ambitious strategy for achieving the global TB targets, it acknowledges that these targets may not be reached in eastern Europe or Africa, due to the complexities of managing and treating both MDR-TB and HIV and their implications for case detection and treatment success, as described below.
Barriers to meeting the TB control targets
Long-standing barriers to the achievement of the global targets include neglect of TB control by governments, lack of financial and human resources to provide supervision and quality control, weakened health systems, poorly managed TB control programmes, poverty, population growth and a significant increase in drug-resistant TB (particularly MDR-TB) and recently, extensively drug-resistant TB (XDR-TB).13 A lack of new diagnostic tools has impeded progress in global TB control. Perhaps the greatest challenge to achieving the global TB targets, however, has been the ever-expanding HIV epidemic and the resulting increases in HIV-associated TB.
In 2005, in large part due to Africa’s uncontrolled epidemic of HIV-associated TB, African health ministers declared TB a regional emergency.4 Approximately 38% of African TB patients are estimated to be HIV-infected.7,14 This TB/HIV syndemic has seriously compromised even historically strong national TB programmes in many countries.7 TB programmes are overwhelmed by an increasing volume of HIV-associated TB cases and by the need to manage cases and ensure treatment completion. Furthermore, TB is the leading cause of death among HIV-infected persons, and HIV is the strongest predictor of progression from latent TB infection to active disease.4,15–17 Thus, TB programmes that were nearing the WHA-set global TB targets have seen their cure and completion rates worsen.7
The TB/HIV syndemic has also had a tremendous impact on human resources.4,18–20 In a workforce that has remained the same or decreased, the increased overall number of TB patients has weakened TB programmes’ infrastructure and increased poor TB outcomes such as treatment default, death and the emergence of XDR-TB.21 The HIV-associated TB epidemic has led to an increasing incidence of smear-negative and extrapulmonary TB;7 these forms of TB do not contribute to the case-detection targets and are more complicated to diagnose. Furthermore, smear-negative TB has a worse prognosis than smear-positive TB among those who are also HIV-infected.16,22,23
TB/HIV collaborative activities
To address the impact of HIV-associated TB and facilitate the achievement of both old and new global TB targets, we must scale up the WHO-recommended TB/HIV collaborative activities and push for closer coordination of these activities between HIV and TB control programmes. The WHO 2006 report on global TB control notes that 32 of 41 countries with a high burden of HIV-positive TB cases have reported on their TB/HIV collaborative activities for the last three years.7 In 2004, 23 countries had appointed a TB/HIV focal person within their national TB programme, 17 had a formal system for referring patients from HIV to TB services, 20 had a policy to carry out intensified TB case-finding among people with HIV, 18 had a policy to provide HIV testing and counselling for all TB patients, 20 had a policy to provide cotrimoxazole preventive therapy to HIV-positive TB patients and 21 had a policy to provide antiretroviral therapy to HIV-positive TB patients.7
Progress has been made, but in reality we are dismally behind in all countries.17 WHO estimates that 125 000 TB patients were HIV tested in high-HIV-prevalence settings in Africa by the end of 2005 (Chris Dye, WHO, unpublished data). For 2006, however, the new global plan calls for 600 000 TB patients to be counselled and tested in these settings, and for 29 million TB patients to be counselled and tested overall by the end of 2015.4 Furthermore, once detected, these HIV-infected TB patients must receive cotrimoxazole preventive therapy and antiretroviral treatment.10
Although isoniazid preventive therapy (IPT) has been demonstrated to reduce the risk for TB among those with HIV infection,24 only Botswana has attempted nationwide scale-up of this important intervention.25 Many national programmes are reluctant to implement this activity due to cost, fear of not excluding active disease and logistic challenges. Successful achievement of the new global plan will require approximately 3 million HIV-positive individuals to be treated with IPT.4
HIV care settings, such as voluntary counselling and testing centres, comprehensive care clinics and centres to prevent mother-to-child transmission of HIV represent ideal settings for identifying persons with active TB; screening for active TB should be increasingly incorporated into these areas.10,26,27 Indeed, addressing TB should be a core function of HIV services. The second global plan calls for the TB screening of 210 million people living with HIV/AIDS by the end of 2015.4 However, to properly screen for TB among HIV-positive individuals, TB diagnostic capability needs to be strengthened, far beyond direct sputum-smear microscopy.23,28 Microscopy often performs poorly even when correctly executed, and is less useful among HIV-positive individuals than among those uninfected, because of the high proportion of smear-negative TB among those infected with HIV.23,29 WHO has proposed a new smear-negative TB screening algorithm in the context of HIV;29 however, this algorithm relies on the availability of chest X-ray and sputum culture for these patients. Thus, to properly diagnose and reduce TB in the context of HIV, improved and higher-quality diagnostic services, including sputum cultures, will have to be made widely available.30 Such strengthening of TB laboratory capacity will also greatly improve the ability to detect MDR-TB and XDR-TB, which in turn will help to achieve the 1991 and global plan targets in those countries where MDR-TB is preventing TB control progress, such as in eastern Europe. Furthermore, the HIV care setting is key for the initiation of urgently needed IPT programmes.
Finally, one of the most important interventions for the control of HIV-associated TB is the provision of universal access to antiretroviral (ARV) treatment for all eligible HIV-infected individuals.4,31 Treatment for HIV prevents or slows progression from latent infection to TB disease, and also leads to better treatment outcomes in patients who already have TB.16,17 However, ARV treatment must be initiated early in the course of an HIV infection, and the coverage and compliance with ARV treatment must be extremely high to truly prevent additional TB cases.32 Currently, 15 000 HIV-infected TB patients are reported to be on ARV treatment in high-HIV settings in Africa (Chris Dye, WHO, unpublished data). The global plan calls for 200 000 coinfected persons to be on ARV in 2006 in these settings, and the enrolment of 3 million HIV-positive TB patients into ARV treatment programmes by the end of 2015.4
TB-HIV service integration’s impact
Integration of TB and HIV services in all facilities (i.e. in HIV-care settings and in TB clinics), especially at the periphery, is needed to treat effectively those infected with both diseases, to prolong their survival and to maximize limited human resources.33 Diagnosing and treating TB disease in HIV-care settings will help to increase case detection and improve rates of TB treatment completion; infection control will be paramount in this context. Likewise, treating HIV (with cotrimoxazole and/or ARV) and TB together in TB treatment and care settings is logistically easier for the patient, and will also help to strengthen the follow-up and treatment completion rates for TB treatment. It is often difficult to achieve this integration operationally at the programme level, given differing resources and agendas of control programmes for TB and HIV/AIDS. Yet strengthening basic TB control in this way is critical to managing TB in the context of HIV, and will also help to “turn off the faucet” of MDR-TB, a product of poor TB control and incomplete treatment.34
The actions described above for scaling-up TB/HIV activities will also help to address the action plan put forward by the recently convened WHO Global Task Force on XDR-TB.35 Integrated services and overall better TB control, including manual laboratory services, will help to manage and treat MDR- and XDR-TB patients and will allow better investigation of cases and contacts. Scaling-up TB/HIV collaborative activities will also help to promote universal access to ARV treatment for all TB patients, another critical action for managing and controlling XDR-TB.35
Implementation of the above activities is the only way to achieve the global targets. Implementation and scale-up of these activities is critical if these targets are to be reached in eastern Europe and Africa, two places that the Global Plan to STOP TB 2006–2015 has suggested will not meet the targets. Failure to meet the targets in eastern Europe and Africa would be disastrous for global TB control overall. All targets can be met in all countries through these activities, provided that renewed attention to TB/HIV collaborative activities is combined with political commitment and will. ■
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- An expanded DOTS framework for effective tuberculosis control. Geneva: WHO; 2002 (WHO/CDS/TB/2002.297).
- Global Plan to Stop Tuberculosis. Phase 1: 2001-2005. Geneva: WHO; 2001 (WHO/HTM/STB/2001.16).
- WHO/Stop TB Partnership. Actions for life. Towards a world free of tuberculosis. The Global Plan to Stop Tuberculosis 2006-2015. Geneva: WHO; 2006 (WHO/HTM/STB/2006.35).
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- C Dye, GP Garnett, K Sleeman, BG Williams. Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Lancet 1998; 352: 1886-91.
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- WHO/Stop TB Partnership. Sustaining the gains: National self-sufficiency for TB drug access: a global drug facility strategy. Geneva: WHO; 2005 (WHO/HTM/STB/2005.34).
- R Gupta, P Cegielski, MA Espinal, M Henkens, JY Kim, CS Lambregts-Van Weezenbeek, et al. Increasing transparency in partnerships for health- introducing the Green Light Committee. Trop Med Int Health 2002; 7: 970-6.
- Interim policy on collaborative TB/HIV activities. Geneva: WHO; 2004 (WHO/HTM/TB/2004.330; WHO/HTM/HIV/2004.1).
- Tuberculosis Coalition for Technical Assistance. International standards for tuberculosis care (ISTC). The Hague: TB Coalition for Technical Assistance; 2006.
- Hopewell PC, Pai M, Maher D, Uplekar M, Raviglione MC. International standards for tuberculosis care. Lancet Infect Dis 2006; Nov; 6(11):710-25.
- US Centers for Disease Control and Prevention. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs worldwide, 2002-2004. MMWR 2006; 55: 301-5.
- EL Corbett, CJ Watt, N Walker, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 2003; 163: 1009-21.
- G Antonucci, F Girardi, MC Raviglione, G Ippolito. Risk factors for tuberculosis in HIV-infected persons: a prospective cohort study. JAMA 1995; 274: 143-8.
- EL Corbett, B Marston, G Churchyard, K DeCock. Tuberculosis in sub-Saharan Africa: opportunities, challenges and change in the era of antiretroviral treatment. Lancet 2006; 367: 926-37.
- A Reid, F Scano, H Getahun, et al. Towards universal access to HIV prevention, treatment, care and support: the role of tuberculosis/HIV collaboration. Lancet Infect Dis 2006; 6: 483-95.
- AD Harries, R Zachariah, K Bergstrom, et al. Human Resources for control of tuberculosis and HIV-associated tuberculosis. Int J Tuberc Lung Dis 2005; 9: 128-37.
- A Reid, M Dedicoat, D Lalloo, CF Gilks. Trends in adult medical admissions in a rural South African hospital between 1991 and 2002. J Acquir Immune Defic Syndr 2005; 40: 53-6.
- D Chanda, DJ Gosnell. The impact of tuberculosis on Zambia and the Zambian nursing workforce. Online J Issues Nurs 2006; 11: 4-.
- NR Ghandi, A Moll, AW Sturm, R Pawinski, T Govender, U Lalloo, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006; ▪▪▪: .
- NJ Hargreaves, O Kadzakumanja, CJ Whitty, FM Salaniponi, AD Harries, SB Squire. ‘Smear-negative’ pulmonary tuberculosis in a DOTS programme: poor outcomes in an area of high HIV seroprevalence. Int J Tuberc Lung Dis 2001; 5: 847-54.
- H Getahun, M Harrington, R O’Brien, P Nunn. Diagnosis of smear-negative pulmonary TB in people living with HIV/AIDS in resource-constrained settings: informing urgent policy changes. Lancet .
- HC Bucher, LE Griffith, GH Guyatt, P Sudre, M Naef, P Sendi, et al. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of radomized control trials. AIDS 1999; 13: 501-7.
- B Mosimaneotsile, EA Talbot, TL Moeti, NM Hone, G Moalosi. Value of chest radiography in a tuberculosis prevention programme for HIV-infected people, Botswana. Lancet 2003; 362: 1551-2.
- Kali PB, Gray GE, Violari A, Chaisson RE, McIntyre JA, Martinson NA. Combining PMTCT with active case finding for tuberculosis. J Acquir Immune Defic Syndr. 2006; Jul; 42(3):379-81.
- Nachega J, Coetzee J, Adendorff T, Msandiwa R, Gray GE, McIntyre JA, Chaisson RE. Tuberculosis active case-finding in a mother-to-child HIV transmission prevention programme in Soweto, South Africa. AIDS 2003; Jun 13;17(9):1398-400.
- Strategic approach for the strengthening of laboratory services for tuberculosis control, 2006-2009. Geneva: WHO; 2006 (WHO/HTM/TB/2006.364).
- Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents: Recommendations for HIV-prevalent and resource-constrained settings. Geneva: WHO; 2006.
- DW Dowdy, RE Chaisson, LH Moulton, SE Dorman. The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model. AIDS 2006; 20: 751-62.
- Emergency scale-up of antiretroviral therapy in resource-limited settings: technical and operational recommendations to achieve 3X5. Geneva: WHO; 2004.
- BG Williams, C Dye. Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS. Science 2003; 301: 1535-7.
- A Harries, M Boxshall, S Phiri, J Kwanjana. Managing HIV and tuberculosis in sub-Sharan Africa. Lancet 2006; 367: 1817-.
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- KEMRI/CDC Field Research Station, Centers for Disease Control and Prevention-Kenya, Kisumu, Kenya.
- Division of TB Elimination, Centers for Disease Control and Prevention, Atlanta, USA.