Tackling TB/HIV co-infection in Africa: An interview with CDC’s Dr. Bess Miller

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Bess Miller, MD, MSc

Science Speaks continues its interview series exploring the global HIV and tuberculosis research and development efforts at the U.S. Centers for Disease Control and Prevention (CDC) with a conversation with Bess Miller, MD, MSc, who works in the Division of Global HIV/AIDS. Dr. Miller has served as associate director and team lead for HIV/TB, providing leadership in policy and implementation of TB/HIV activities in 43 resource-limited countries supported by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR).  She has worked to align PEPFAR TB/HIV priorities with the World Health Organization (WHO) policies on TB/HIV, and on the use of antiretroviral therapy (ART) in people living with HIV (PLHIV). 

In this interview Dr. Miller discusses the successes and challenges in implementing TB infection control in Africa, progress in deploying the GeneXpert MTB/RIF rapid TB diagnostic on the ground there, and how efforts to scale up access to ART are helping achieve goals in TB control and elimination.

I know you have a background in infection control – what activities and progress are you  making in ensuring that PEPFAR-funded HIV clinics are not a good place to contract TB?
I think infection control as we know it in the U.S. is still in the very early stages in Africa. Not much attention had been paid to infection control overall, including hand washing, basic universal precautions and blood borne precautions. This field is now burgeoning.  Ministries of health, non-governmental organizations, hospitals and outpatient facilities are gearing up now in many countries.

TB infection control involves special efforts. TB is an airborne infection spread person-to-person, but it’s different even than other respiratory infections, because TB bacilli float in the air for long periods of time. To control TB, you need to initiate special interventions. The key is to remove the transmitters (coughing patients with TB) from the common space, to increase air ventilation to dilute out the floating TB bacilli, and to promote so-called cough-etiquette (cover the cough) and use of special masks for health care workers when necessary. In previous decades, policymakers did not emphasize TB infection control because TB was so common. It wasn’t so much about controlling the spread of disease in facilities but rather about finding cases and curing disease.  So treatment was prevention and infection control too.

Through various initiatives – the WHO “3 x 5” Initiative, PEPFAR, The Global Fund to Fight AIDS, TB and Malaria and other initiatives – immune-suppressed people began coming into health facilities.  Now, TB infection control became an urgent matter. These really sick folks previously had been sick and dying at home, now they were flocking into health care settings for life-saving medications. Now we were bringing the two epidemics, AIDS and tuberculosis, together under one roof.

Everything we’ve done in PEPFAR really has been based on WHO polices and strategies. In their 2004 interim policy on Collaborative TB/HIV activities, TB infection control was one of the areas that was emphasized. We took that on at CDC in both the Division of Global HIV/AIDS and the Division of TB Elimination. We worked with WHO and other partners to help develop global TB infection control guidance, and then country-level TB infection control guidelines.  We helped train ministry of health leadership on the critical elements of TB infection control, consulted on engineering controls (windows, fans, building design), and then assisted with the basic work to help countries implement TB infection control measures.

That’s where we are now. Working with international partners and agencies, we developed more practical guidance tools.  We have recently piloted and are rolling out a TB infection control package for facilities.  This includes a video (including a French version), job tools and aides, PowerPoint presentations, facility assessments, posters, and more.  The whole package is available online. We are helping countries, one by one, to begin adopting these TB infection control activities. The focus is to get simple infection control behaviors into routine practice in the clinic. It’s not so much that previous guidelines changed, it’s more a matter of operationalizing simple infection control practices that health care workers should be incorporating into their daily routines. For example, in the clinical setting screening patients for cough or having a cough monitor in the clinic, so that a person with a cough can be removed from the waiting area and “fast-tracked” to see a provider and is therefore not continuing to spread infection; keeping windows open; having waste baskets and basic surgical masks for patients; special respiratory masks for health workers, etcetera. That is slowly beginning to happen – it’s still new in many places but we are seeing best practices starting to take place. It’s exciting – getting these incorporated as part of quality improvement programs and  included as indicators of good program performance,  in  outpatient ART clinics, but also in general outpatient clinics and on hospital wards.

I think a lot of countries are beginning to move forward on TB infection control – countries such as South Africa, Rwanda, Zambia, and Botswana – and many other countries that we are working with are making dramatic improvements.  PEPFAR funds $160 million for TB/HIV activities in the countries each year, and some of these funds are being used to implement TB infection control.

What progress have you seen in the universal adoption of periodic TB screening at PEPFAR funded HIV clinics? What about use of isoniazid preventive therapy (IPT) in HIV-infected individuals?
We’re getting there, a bit slowly, but surely. During the early years of scaling up ART in Africa and other resource-limited settings, the ART clinics were swamped with very ill patients.  There was an urgency to develop systems to get ART to of PLHIV.  This involved infrastructure – actually identifying, building, reconstructing ART clinics or other outpatient facilities to deliver the medicines; supply chain management – getting HIV tests kits and drugs to the facilities; developing laboratory systems and assessing quality of new diagnostic tests;  monitoring adherence to treatment and developing systems to do that.  TB screening was seen as important, but not the first priority.

TB is the leading killer of people with HIV in Africa; up to one-third of PLHIV will get tuberculosis.  But getting systems in place to assure TB screening, and to assure documenting that screening has taken place, is the effort we are working on even now.  Studies showed that for PLHIV, screening for cough alone was not enough – so there is a four-symptom screen that was added into the WHO’s more recent TB/HIV and ART treatment guidance.  But of course, screening is not enough; we need to get patients with a positive screen the lab services needed to diagnose TB, and then get them into TB treatment, which lasts six to nine months for drug sensitive TB.

Conversely, by the way, all TB patients in these settings need to get routine, opt-out HIV testing and counseling, and if positive, need to access ART.  In the 2010 WHO ART treatment guidelines, HIV-infected patients with TB are automatic candidates for ART.

In this regard, PEPFAR has recently increased its targets for ART from 4 to 6 million people on ART by the end of 2013.There is going to be a lot more effort to get the TB patients tested and counseled for HIV and into ART treatment—something that will help reduce TB and HIV/AIDS mortality and morbidity.

Another direction that’s been taking place in the last two years but will be emphasized more is integrating HIV and TB services. Countries are trying to get HIV services into antenatal clinics, trying to get ART administered in the TB clinics and in other settings, and when the TB patient is no longer infectious, getting TB treatment into the HIV clinic. Kenya, Rwanda, Tanzania, Uganda are all doing programs where they are giving ART to HIV-infected TB patients right in the TB clinic. So it’s really easy to manage patients with TB and HIV/AIDS if the services for both diseases are right there in one clinic.

Regarding isoniazid preventive therapy (IPT), that is a program that is still in the early stages in most of the African countries we are working in.  IPT has been shown to confer benefit in reducing TB morbidity in PLHIV – and is additive to the benefit of ART.  However, there are many barriers to implementation: provider concerns about promoting isoniazid-resistant disease (unlikely); confusion regarding duration of treatment (six months, 36 months, lifetime?) and concerns regarding the apparent loss of benefit to the individual patient after cessation of IPT; difficulty of implementing tuberculin skin-testing programs (skin-test positive patients have been shown to get the benefit from IPT).  A number of countries are successfully implementing IPT programs and we are following this with interest.

What are you seeing on the ground in terms of deployment of the GeneXpert MTB/RIF rapid TB diagnostic? How many machines have been deployed and where? Are you collaborating with the U.S. Agency for International Development (USAID) in this effort?
The GeneXpert machine and the Xpert MTB/RIF are beginning to be implemented in many of the countries we are working in, since the WHO endorsed it at the end of 2010, for initial TB diagnosis in people suspected of having multidrug-resistant (MDR)- TB and those with HIV infection. The machine is fabulous; it has so much promise because it can make the diagnosis in two hours and all of the reagents are located right in the cartridges. We are working with many countries to get their systems in place to be able to use it. Right now it’s costly, the machine and the cartridges cost approximately $100,000 for one year. It takes a certain amount of infrastructure to be used – a relatively constant supply of electricity, a specific temperature range in the clinic, for example. Since it’s not quite a point-of-care test, while it’s not intended for use at the central reference lab, it does require the capabilities of a district or a sub-district facility, in most cases. That means there still needs to be transport of specimens from the clinic to these sites, for example and attention to fast-track reporting of results.

In a number of countries, we are working with ministries of health – lab programs, TB programs, AIDS control programs – to find out where they would place the machines, whether they have the capability to use the machines fully, and whether they have functional transport and communication systems, and quality assurance programs for microscopy networks (which are still necessary).  That’s where we are now. Through PEPFAR we’ve already distributed about 55 machines, and we’ll probably be giving out 30 or 40 more in the next year. It is a joint USAID/CDC venture and we are working closely together, according to guidance provided by WHO, to assist countries in deploying this new diagnostic tool and conducting program evaluations of its roll-out and scale-up in these PEPFAR-supported countries.

It’s thrilling – it’s the first new TB diagnostic test to come along in the past 100 years or so. But it’s not a dip stick or a matter of even a finger prick, though, and there will need to be a lot of training and technical assistance to make it work. The machines are all over the African countries we’re supporting –and also India, Indonesia, Bangladesh, China and many other countries. A variety of non-governmental organizations and donors and academicians are supplying them, not just the USG.

What about GeneXpert MTB/RIF use in pediatric clinics in particular?
For pediatric diagnosis of TB, we’re not there yet. The specimens have to be tested and the approach has to be looked at – but it’s not there yet. I think we don’t have the technology yet to use it in pediatrics and the WHO guidance emphasizes HIV/AIDS as the initial population to be used for GeneXpert, as well as those suspected with MDR-TB.

The difficulty with getting a lab diagnosis in children is in obtaining the specimen and the number of mycobacteria in the specimen. Children don’t produce as much sputum and they have fewer organisms to test for. At young ages, they can’t usually cough up enough sputum to test. You have to use what’s called gastric washings to test them, which involves putting a tube into the stomach, etc. It’s not an easy or pleasant experience for the child. So at this stage Xpert MTB/RIF doesn’t address the overall problem of diagnosing TB in children. But folks in diagnostic research are working on this.

Are people with HIV who have TB being prioritized for ART? Is PEPFAR pushing for countries to adopt the WHO HIV treatment guidelines?
That was included in the WHO 2010 ART guidelines – persons with TB regardless of CD4 count are eligible for ART. Where that would start is in the TB clinics, which are usually ministry of health clinics. The answer is yes, that is a priority for countries and we are seeing this happening.

What tracking are you doing to make sure these milestones are happening? Do you know how many clinics are routinely screening HIV infected persons for TB and/or starting them on IPT?
That is one of the biggest, most difficult issues, but yes we are tracking this. Just last week, we had a meeting of the PEPFAR TB/HIV Technical Working Group in Washington about how we can improve the tracking systems. It’s not easy. There is a WHO approach toward patient monitoring in HIV clinics. Their reporting documents are available in many countries and TB variables are included on them, but they may or may not be used.

Many countries have international partners that have created electronic versions of the AIDS patient management facility registers; these are usually easier to access to determine   whether or not TB screening is happening routinely. And then there are also facility-based quality assurance programs where they try to include TB screening as something they track. All of those are areas we are helping countries with. The TB side is easier because every country has a TB surveillance system. But the HIV surveillance and monitoring tools are still being built. That’s been a key effort in the last year or two, is to improve monitoring of TB in HIV clinics. It’s a collaboration of two systems – two clinical systems and two surveillance and monitoring and evaluation systems – so obviously it’s complicated.

The big efforts are aimed at getting TB patients on ART early. They are priority candidates. The attempts to try and have integrated care – that’s a big part of where everyone’s going – to try and provide both HIV and TB in the same setting if possible.

The other thing – you’re probably aware of President Obama’s emphasis on the AIDS-free generation in his speech on World AIDS Day. As part of that initiative there is a big push to scale up the prevention of mother-to-child transmission (PMTCT) of HIV, and TB screening, prevention and treatment will be part of this initiative as well. That’s going to be a way to address screening women for TB and getting them on appropriate treatment for TB or preventive treatment.   

I can’t convey how amazing it has been to be a part of the early investigations of what would be known as HIV/AIDS, to watch the TB and AIDS epidemics explode and then to remain in this field and see how people can work together to change the course of these epidemics.  It has been a true privilege to be able to witness and to provide technical assistance during all the phases of this epidemic – and especially to watch the resurrection of communities as life-saving drugs became available and systems were developed to treat patients for both HIV/AIDS and tuberculosis.

What got you interested in public health?
I majored in biology in college, and I was always interested in public health. My dad was a rabbi in the small town of Gary, Indiana, and we grew up with the perspective of serving the community.  I got a Master’s Degree in Public Health at Harvard University after college and I worked for a number of years as a public health nutritionist. Then I did medical school and a residency in internal medicine – so I didn’t come to the CDC until 1981.

I was in the CDC Epidemic Intelligence Service (EIS) program and it was July 1981 – one month after that first article appeared in Morbidity and Mortality Weekly Report (MMWR) about the five cases of pneumocystis pneumonia  among single men in San Francisco, what turned out to be the start of the AIDS epidemic in the United States.   I was fascinated by this and  started going to some of the early discussions on this  (known as the Task Force on Kasposi’s Sarcoma and Opportunistic Infections ) very early in my first year of EIS.

My EIS assignment was in Atlanta – in the Division of Viral Diseases. There were two events that initiated my work on HIV/AIDS. The first was in 1982– where I spent weeks at a time working in New York City, investigating the “lymphadenopathy syndrome” among gay men.  I ended up reviewing hundreds of pathology records at seven New York City hospitals and interviewing dozens of men with unexplained generalized lymphadenopathy.  The review and interviews revealed that there was an increase in this condition in single men during the previous several years.  Risk factors for this syndrome included a history of multiple sexual partners and being a man who has sex with men (MSM). Later, we would know that this was an early presentation of HIV/AIDS.  I was involved in a similar investigation in Atlanta.

Second, as an EIS officer I investigated the case of a child in Pennsylvania with multiple opportunistic infections in the lungs. I evaluated the child’s history, the family, the home, the environment, etc. This child was a hemophiliac and had received blood and blood product transfusions, which we later understood to be a source for transmitting the AIDS virus.

After EIS, I left CDC for two years and worked as an internist in clinical medicine.   I took care of my first patient with HIV/AIDS –but we didn’t have a name or blood test for it then.   The patient died of pneumocystis pneumonia—a very tragic case.  When I came back to the CDC I knew I wanted to focus on something that was very clinically oriented….ideally this “new disease,” AIDS. There was an opening in the Division of TB Elimination– and again it happened to be the right timing, because it was the end of 1985 and there had been an unusual increase in TB incidence in the U.S.  I began immediately studying the links between AIDS and tuberculosis…. and I’ve concentrated on this unholy alliance for more than 25 years.

Tell me about some of the positions you have held at the CDC and where.
I worked primarily in the U.S. until the 1990s when I began to do international work.  I was still in the Division of TB Elimination. It started with an evaluation in Ho Chi Minh City, Vietnam of the screening program for refugees coming to the U.S.  This was in the early ‘90’s, even before there was a U.S. Embassy in Vietnam.  They had an outstanding refugee screening program; later I had the chance to experience the benefits of this program, because I took care of many Vietnamese refugees in my tuberculosis clinic in Atlanta (where I have had the opportunity to provide clinical care for more than 20 years).  Then I started working some on TB and the links with AIDS in Africa, where many countries were experiencing an exponential increase in TB.  At that time we started working with global partners, including WHO and the International Union Against TB and Lung Disease (the Union)to establish  the Stop TB Partnership, which now has more than 400 partners.

It wasn’t until 2001 when I moved from the Division of TB Elimination over to the “LIFE (Leadership and Investment in Fighting an Epidemic) Initiative,” which now is the CDC’s Division of Global HIV/AIDS, that I started doing a lot of international work.

I continued to be interested in the connection between TB and AIDS. As the seroprevalence of HIV began sky-rocketing in Africa in the ‘80s and ‘90s, so the rates of TB followed with as much as five-fold increases…especially in Southern and Eastern Africa.  In 2003, President George W. Bush announced the formation of the President’s Emergency Plan for AIDS Relief (PEPFAR) program, initially a $15 billion, three-year initiative. In the early years of PEPFAR, I worked with others to get TB included as part of PEPFAR. I wanted to include the country ministry of health national TB programs as part of the country-wide efforts to address HIV/AIDS – because initially TB and AIDS control programs were two different worlds and TB was not a part of the early AIDS efforts.  Yet TB was the leading killer PLHIV in Africa, as many as one third of AIDS patients had TB.

It was absolutely overwhelming to see how much TB there was in Africa. In a country like South Africa there would be 400,000 cases of TB a year (in contrast to less than 12,000 cases of TB in the U.S. at that time). The magnitude of the disease burden was incredible. The other terrible fact of life in the early 2000s, before antiretroviral therapy (ART) became available in Africa, was the death. We would visit AIDS clinics and TB clinics and see people emaciated and dying, see people in the hospitals dying.  But now how much that has changed both for TB and AIDS and how things have turned around with the introduction of ART. The incidence rates of TB in countries in Africa started declining a few years after the HIV incidence (new cases) started declining.  It’s been a real privilege to be a part of this turn-around.  It has been a very, very dramatic experience.

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