Testimony on Tuberculosis before the Subcommittee on Africa and Global Health, Committee on Foreign Affairs, House of Representatives

Ambassador Mark Dybul, U.S. Global AIDS Coordinator
Testimony on Multi-drug Resistant Tuberculosis before the Subcommittee on Africa and Global Health, Committee on Foreign Affairs, House of Representatives
Washington, DC
February 27, 2008

Mr. Chairman, Ranking Member Smith, and Members of the Subcommittee:

Thank you for this opportunity to discuss the President’s Emergency Plan for AIDS Relief and our efforts to combat the spread of multi-drug resistant tuberculosis (MDR-TB) globally. The partnership between PEPFAR and the Committee on Foreign Affairs over the years is one for which I am very grateful. Chairman Payne, Ranking Member Smith and Members of the Subcommittee, thank you for your commitment to the U.S. leadership in the fight against HIV/AIDS. Bipartisan support for this historic initiative has been a key to its success.

Thanks to the commitment of President Bush, Congress and the American people, PEPFAR is on track to meet its ambitious goals, and efforts are now underway to reauthorize PEPFAR for another five years. The majority of those resources are being invested directly into partnerships with host nations. By working with our host countries to build high-quality health care networks and increase capacity, we are laying the foundation for nations and communities to sustain their efforts against not just HIV/AIDS, but a wide range of other diseases, including MDR- and extensively drug-resistant (XDR)-TB – long after the initial five years of the Emergency Plan.

Because its effect on the immune system makes HIV-infected people more susceptible to infection, HIV is the greatest risk factor for developing tuberculosis. In Africa, TB is in lock step with the increase in HIV/AIDS. In fact, TB is the number one killer of people living with HIV – which is why PEPFAR is leading a unified U.S. Government (USG) global response to fully integrate HIV and TB services at the country level and build the capacity, particularly in Africa, to detect and treat MDR- and XDR-TB. Our goal is to ensure that people who are infected with HIV receive the best treatment and care possible, in order to reduce their risk of contracting or developing TB in the first place. This is critical to the long-term control of TB at the global level. Antiretroviral treatment (ART) is a powerful deterrent to the development of TB, because it restores immune function. A strong immune system means that an HIV-positive person on ART is much less likely to contract TB; and even if he or she already has been infected with tuberculosis, the bacteria are more likely to remain dormant.

PEPFAR also supports the full range of HIV treatment and care for people who already are co-infected with HIV and active TB. Appropriate and full treatment of TB is vital, not only to prevent HIV-positive people from dying but also to alleviate the risk of them developing drug-resistant TB. One study reported an 80 percent reduction in the incidence of TB among HIV-positive people who are on anti-retroviral treatment, as compared to those who are not receiving anti-retroviral therapy. Thus, in a country where 60 percent of all TB patients also have HIV, if all those who needed antiretroviral therapy received it, it is possible that overall TB rates could drop by as much as 50 percent. HIV drug therapy is a powerful tool in the fight against TB.

PEPFAR Activities to Thwart MDR-TB

Our most important work in combating TB and thwarting the development of MDR-TB takes place through partnerships at the country level to support national health authorities, non-governmental organizations, and community- and faith-based organizations to implement more effective TB/HIV activities. PEPFAR increased its funding for HIV/TB five-fold, from $26 million to $131 million, from fiscal year 2005 to fiscal year 2007, and a planned level of $150 million for fiscal year 2008. By the end of September 2007, PEPFAR had supported care for more than 367,000 TB/HIV co-infected people in the 15 PEPFAR focus countries.

Accelerated activities include supporting HIV services for people with TB and improving TB diagnosis and treatment for people with HIV. Within these categories, specific activities supported by PEPFAR include:

Providing HIV testing for TB patients;
Supporting cotrimoxazole and isoniazid preventive therapy to HIV-infected people in order to reduce their risk of developing TB;
Ensuring that routine TB screening is an integral part of PEPFAR-supported preventive care package for HIV-infected people;
Implementing effective TB infection control to reduce the risk of transmission of TB to people living with HIV/AIDS (PLWHA) in settings where they access HIV care as well as to healthcare workers, a scarce and valuable cadre that must be protected;
Implementing the World Health Organization (WHO)-recommended International Standards for TB Care, which build on Directly Observed Therapy-Short Course (DOTS) strategy, in PEPFAR HIV care settings, in order to ensure that patients complete their TB treatment;
Funding for drug resistance surveillance in six countries (Lesotho, Namibia, Nigeria, Swaziland, Russia, and Uganda);
Improving laboratory surveillance systems in order to detect outbreaks of MDR- and XDR-TB
Supporting the development of strong, tiered public health laboratory networks for diagnosing and managing drug-resistant TB and other opportunistic infections; we are strengthening capacity to diagnose both smear negative and extrapulmonary TB among PLWHA, which are critical elements in TB detection and control in the PLWHA population.

PEPFAR also supports expanding the capacity of the local health workforce to deal with these dual epidemics. Efforts include protecting healthcare workers – many of whom are also HIV-infected – from exposure to TB as an important aspect of TB infection control; supporting improvements to supply chain management systems for medications and other commodities; and establishing linkages between TB treatment and ART so that people who are co-infected receive the medical attention they need. We also work with partners to train health care providers in DOTS, the expansion and successful implementation of which helps prevent the development of drug resistance.

As an initial step in addressing MDR- and XDR-TB, the USG reconvened the U.S. Federal TB Task Force to develop a coordinated response by USG agencies to the looming threat of MDR- and XDR-TB. This Federal Task Force has formulated a comprehensive, coordinated USG response to both domestic and international aspects of MDR and XDR-TB. The USG also participates in the WHO Global XDR-TB Task Force, which has formulated the global plan to respond to XDR-TB, which Dr Raviglione can go into more detail about.

The Evolution of Drug-Resistant TB

In discussing XDR-TB, let me make two observations: (1) the development of drug resistant tuberculosis is of concern, but not surprising; and (2) it is not new. The combination of poverty, overcrowding, and HIV, particularly in high HIV prevalence countries in Africa, has led to dramatic increases in TB infection. Beginning in the 1990s, the number of TB cases exceeded the capacity of poorly-financed, under-staffed TB control programs to deliver effective TB management. Drug-resistant TB is the direct result of improperly-implemented TB control programs. This is why there is a saying in TB circles that poor TB treatment is worse than no treatment at all.

On an individual patient level, drug resistance can develop when someone is infected with an already-resistant organism. [It also can develop if a person infected with TB and the disease progresses to active TB, which can happen very quickly among people who are immuno-compromised.] This is what has happened in the well-publicized outbreak in South Africa. Another way to develop drug-resistant TB is through inadequate TB treatment, or by not completing a full course of TB therapy. The more this happens, the more TB drug-resistance will develop. We have seen the same problem with resistance to HIV medications when antiretroviral treatment is improperly prescribed or taken.

The implications of MDR- and XDR-TB, particularly for people with HIV, are serious. Most cases of TB are drug-sensitive and can be cured in someone with or without HIV infection after six months of treatment and for just a few hundred dollars. However, people with MDR-TB have a much poorer prognosis, requiring as much as 18 months of treatment, and costing many thousands of dollars. When the second-line drugs for MDR-TB are misused or mismanaged and therefore also become ineffective, XDR-TB can develop. Because XDR-TB is resistant to both first- and three of the six classes of second-line drugs, it is – for the time being at least – almost untreatable.

There has been growing concern recently about the incidence of drug-resistant TB, and we should be concerned. As cited in the new WHO Fourth Global Drug Resistance Report being launched yesterday in Washington and Brussels, there are an estimated 500,000 cases of MDR-TB per year globally resulting in 110,000 deaths. Data on the true extent to which XDR-TB in high-burden countries are generally unavailable due to inadequate lab capacity for diagnosis and surveillance. However, the fact that XDR-TB has now been detected in 45 countries is of particular concern to us because it is almost universally fatal to people who are HIV-positive.

Drug-resistant TB and sub-Sahara Africa

The explosive potential of XDR-TB in settings of high HIV prevalence, such as sub-Saharan Africa, has been well documented. In the U.S. during the early 1990s, we saw numerous outbreaks of MDR-TB in people with HIV/AIDS, but drug-resistant TB has not been seen among HIV-positive people in sub-Saharan Africa until recently. To date, little surveillance data have been available from sub-Saharan Africa on MDR- and XDR-TB, but it appears that new cases may be rapidly increasing. The recently-reported outbreak of XDR-TB in South Africa is especially troubling. It appears that people with MDR-TB had received inadequate treatment and developed XDR-TB. They then subsequently spread their XDR-TB to people with HIV/AIDS in the community or in the local hospital. Because their immune systems were so weak, the people with HIV/AIDS rapidly developed XDR-TB and the consequences have been devastating -- 52 out of 53 XDR-TB patients in the original report have died. Of these, 44 patients had been tested for HIV, and all were positive. USG agencies, including HHS/CDC and USAID, along with the WHO and local authorities, took the lead in alerting the world to this potential threat.

Addressing HIV and Drug-Resistant TB

PEPFAR-supported ARV programs have not reported a decline in the uptake of ART or changes in patient outcomes or non-attendance in care settings due to concerns about transmission of drug-resistant TB. However, given the importance of drug-resistant TB to HIV programs, guidance on TB/HIV activities supported by PEPFAR has been included in our technical guidance since 2004. In response to the XDR-TB outbreak in South Africa, PEPFAR has alerted all focus countries to the problem, and we have advised them to take it into account during the development of their Country Operational Plans, in partnership with national TB and HIV control programs. Teams of epidemiologists, laboratory scientists, and environmental engineers have been dispatched to a range of countries to develop response plans, conduct local assessments and training, and support implementation. Six teams of USG staff along with local staff from TB and HIV control programs in focus countries (Kenya, Rwanda, Ethiopia, Zambia, Namibia, and South Africa) were brought to Washington in March 2007, in collaboration with the WHO and the Bill and Melinda Gates Foundation, to develop accelerated TB/HIV plans. These plans helped define priority actions for integration into PEPFAR operational plans.

PEPFAR recognizes the significance of these dual epidemics and the danger they pose for societies worldwide, particularly in settings of high HIV prevalence, and as mentioned earlier, this is why our support for TB/HIV has increased five-fold in just three years – from $26 million to $131 million, from fiscal year 2005 to fiscal year 2007. As of September 2007, PEPFAR had supported care for approximately more than 367,000 TB/HIV co-infected people in the focus countries.

Leveraging Multinational Partners

Collaboration among USG agencies, including those working domestically, has been strengthened -- as have PEPFAR’s ties with our multilateral partners, including the WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria. Such collaborations are essential for mounting an effective response.

Our in-country partnerships include leveraging PEPFAR resources to amplify the effects of other global health initiatives, especially the Global Fund. The USG remains the largest contributor to the Global Fund. Of the approximately $3.5 billion the USG has contributed to date 17% or $595 million is being used to prevent and treat TB. Through PEPFAR, the USG has provided approximately one-third of the Fund’s resources - and through 2007, the Global Fund will have committed $1.4 billion to TB grants.

To date the Global Fund has approved 153 TB grants in 106 countries for a total of $2.2 billion. Moreover, the Global Fund reports remarkable results achieved from its financing of TB programs: more than 3.3 million people with TB have been treated under DOTS with Global Fund support. According to the Global Fund’s primary recipients, approximately 9,700 of those people are being treated for MDR-TB.

Much of the Global Fund’s success comes as a result of its focus on the expansion of DOTS programs, leveraging efforts of the TB community to develop a consistent and comprehensive strategy for TB control.

Global Fund TB grants also benefit from technical assistance from USAID as well as major partners like the Stop TB Partnership and WHO which provide in-country support to Global Fund grants.

The Global Fund has played a critical role in increasing the availability of MDR-TB drugs in resource-poor settings. In several countries, Global Fund TB financing has led to ground-breaking progress in the scale up of DOTS programs and the roll out of MDR-TB treatment. To date, Global Fund has committed approximately $750 million dollars to fight MDR-TB.

In addition, many African countries can only now address the issue of MDR-TB thanks to funding for the expensive drugs needed through Global Fund grants.

The Emergency Plan also provides support for the WHO (both the STOP TB and HIV Departments) as well as the Green Light Committee for multi-drug resistant TB, which supports a variety of interventions aimed at strengthening TB control as well as preventing, detecting, and treating drug-resistant TB. Funding for technical assistance supports countries’ ability to develop applications to the Green Light Committee and supports country programs to improve their capacity to provide treatment for MDR-TB. Some of the U.S. funding for the Green Light Committee specifically supports provision of technical assistance to Global Fund grants that treat MDR-TB. We also work with the World Bank, UNAIDS, the International Union Against TB and Lung Disease, and the private sector.

Efficacy and Investment of PEPFAR Programming

Addressing HIV/TB and drug-resistant TB is particularly challenging—especially in impoverished settings that are heavily impacted by HIV/AIDS. In sub-Saharan Africa and elsewhere, TB control programs are already overburdened and unable to deal with the emerging threat of drug-resistant TB.

The first step in accelerating TB/HIV collaborative activities and preventing the emergence of drug-resistant TB is to strengthen weak and struggling TB programs. For years, TB programs have been under-resourced and they now face incredible challenges in delivering care to thousands of TB patients, many of whom also have HIV. There are a number of essential components for a strong TB program. Through our focus on supporting and building host country capacity, PEPFAR is focusing on a few of the most important elements.

Laboratories are the most important but weakest link in the fight against TB/HIV. The diagnosis and the provision of high-quality care depend on an efficient public health lab network. International recommendations for diagnosing TB have changed and now include sophisticated investigations such as culture, and effective high-quality microscopy, including fluorescent microscopy. All this requires an effective and efficient laboratory system. The emergence of XDR-TB has further highlighted the need for strong lab systems. Finally, lab support is essential for the delivery of high-quality HIV testing and treatment services. PEPFAR is working closely with host country partners to ensure the establishment of well-functioning public health laboratory networks to diagnose and manage TB among people living with HIV/AIDS.

Despite being one of the 12 WHO-recommended collaborative TB/HIV activities, TB infection control has been heretofore neglected. Given the recent emergence of XDR-TB and increasing evidence of infection risk among not only HIV-infected people but also among health care workers, it is becoming clear that countries must develop the capacity to provide appropriate care and treatment for large numbers of co-infected people. Whether it is drug-resistant or not, TB is an airborne, potentially deadly disease. PEPFAR is mobilizing our resources to meet this challenge head-on, so that health care facilities do not become “amplifiers” of the TB epidemic.

An old public health axiom is “what is measured is done.” A strong HIV/TB program relies on a well-functioning monitoring and evaluation (M and E) system. M and E are critical activities, and building an effective M and E system is essential if we hope to capture what is going on in countries and use that information to inform and accelerate implementation of HIV/TB activities. PEPFAR is working closely with host countries and international partners to ensure that an effective M and E system for collaborative TB/HIV activities is central in program implementation.

In tackling the problem of HIV/TB and drug-resistant TB, a key entry point is HIV testing for TB patients. Estimates are that more than half of the people infected with TB in sub-Saharan Africa are co-infected with HIV. For example, in South Africa, 58 percent of all TB patients are HIV-positive – and in Botswana and Swaziland, 80 percent of all TB cases are co-infected. Unfortunately, by the end of 2005, only 10 percent of all TB patients throughout the African region had been tested for HIV.

However, progress is being made through PEPFAR partnerships. Through a PEPFAR-funded WHO collaboration in three countries, compelling results bear this out: in Kenya, 84 percent of TB patients were tested for HIV by the second quarter of 2007, up from 41 percent; and in Rwanda, 88 percent of TB patients were tested, up from 45 percent.

Similarly, data from Namibia indicate an increase in testing from 16 percent in 2005 to 47 percent in the first half of 2007. Data from Botswana’s national TB program suggest that 68 percent of all registered TB patients now undergo HIV testing. In some districts of Tanzania with provider-initiated HIV counseling and testing, more than 80 percent of all TB patients opt for HIV testing and learn their status.

Another goal is to ensure that eligible TB/HIV patients are placed on ART. The same PEPFAR-WHO collaboration demonstrated positive results: in Kenya, 42 percent of HIV-positive TB patients identified were started on ART by the end of 2007; in Ethiopia, 28 percent of HIV-positive TB patients received ART by mid-2007 from a baseline of 19 percent; and in Rwanda, 36 percent of HIV-positive TB patients received ART by the end 2007 from a baseline of 13 percent.

Important investments in the requisite infrastructure to scale-up HIV/TB activities are also being made. Funds have been made available for numerous PEPFAR host countries to increase access to rapid methods of diagnosing TB and detecting drug resistance. To facilitate this process, a Center for Integrated TB/HIV Lab Training has been launched in South Africa and the WHO’s Global Lab Initiative will be supported.

We know that the percentage of TB patients who are tested for HIV continues to vary widely. Often, this is a matter of logistics: even when referred, a TB patient may not go for HIV testing if the HIV counseling and testing center is not in close proximity to the TB clinic. Because of this, PEPFAR is working with partners in many countries -- including Botswana, Ethiopia, Kenya, Rwanda, and Tanzania -- to expand provider-initiated HIV counseling and testing services, either right in the TB clinics or nearby. We are also supporting efforts to integrate services for people living with HIV/AIDS (PLWHA). For instance, in Côte d’Ivoire, where ART programs are being decentralized, efforts are underway to co-locate TB and HIV care in the same facilities.

Diagnosing and managing TB in patients with HIV can be a challenge—but it is vital to prevent the high morbidity and mortality associated with TB.

Next Steps: the Road Ahead

In partnership with host nations and the international community, PEPFAR has taken substantial steps toward combating global HIV/TB and drug resistant TB, and we will continue to do so. In 2007, we co-sponsored a meeting of the WHO’s Stop TB partnership, local Ministers of Health, and other key USG and international partners to accelerate the implementation of HIV/TB activities in Ethiopia, Kenya, Namibia, Rwanda, South Africa, and Zambia. One of our first tasks following the meeting was to work with PEPFAR missions to use additional HIV/TB resources to support host country HIV/AIDS and TB program managers to implement collaborative HIV and TB services.

Another exciting development with enormous potential for fighting TB is PEPFAR’s public-private partnership, the Phones for Health program. It joins African entrepreneurs with local NGOs and multi-national corporations to use cell phone technology to connect health systems in 10 PEPFAR-supported countries by 2010. Working closely with national Ministries of Health and global health organizations, the Phones for Health partnership develops an integrated set of standard information solutions that support the scale-up of HIV/AIDS, TB, malaria, and other infectious disease initiatives in a cost-effective manner that builds local capacity.

Moreover, PEPFAR will continue to maximize its resources with our international and country partners to support the global response in combating and ultimately conquering both HIV/AIDS and tuberculosis around the world.

PEPFAR takes the issue of MDR- and XDR-TB very seriously, and in response, have increased the Fiscal Year 2008 commitment for TB/HIV efforts to $150 million. It is a clear priority of the Emergency Plan to increase cooperation and effective linkages between TB and HIV programs. In partnership with Congress and strong coordination within the Executive Branch, the U.S. Government and the American people are doing their part. Mr. Chairman and Ranking Member Smith, thank you again for your interest in this important issue. I look forward to your questions.