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Posted by on Jul 29, 2018 in Conference coverage, News | 0 comments

TB2016: The HIV and TB community’s causes are inextricably linked: Success happens together

TB2016: The HIV and TB community’s causes are inextricably linked: Success happens together

TB2016 was a two-day conference dedicated exclusively to TB that immediately preceded the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa. It convened TB implementers, TB scientists, infectious disease clinicians and scientists, health policy makers, and advocacy — but was held in conjunction with AIDS2016 in the hope that it would attract many of the HIV community who otherwise don’t attend TB meetings. TB2016 was a signal to both the HIV and TB communities that our causes are inextricably linked and that success happens together.

The International AIDS Society launched #TB2016 in order to:

  • Galvanise political leadership and commitment to end TB by 2035
  • Bring together experts to advance knowledge and innovation about TB
  • Promote and share best practices and aspirations to reinvigorate and expand the global TB response

This first-ever IAS sponsored TB pre-meeting was held before an international AIDS conference in order to leverage the political and media attention that World AIDS Conferences receive.

The following report is the product of four rapporteurs, and contains brief summaries, excerpts from transcripts, and vignettes — as well as more complete reviews of some selected presentations. It is by no means complete, but the hope is to convey a sense of this ground-breaking meeting.

Day One, Saturday 16 July 2016

Opening session:

Valerie Mizrahi of the University of Cape Town and conference co-chair gave the introduction at the start of the meeting:

“After many years of working in the field of TB myself, I believe firmly that we are at a pivot point. I am a basic scientist, and I am committed to new tools for TB control. But I realize that impacting upon this epidemic will require communication and cooperation between role-players at a level that is unprecedented. We need to listen to each other, to learn from each other, and find new ways of working together, so that the whole can be much greater than the sum of its parts.”

She and the other conference organizers put together a conference containing a series of plenary, breakout and poster sessions showcasing the advances in the discovery, development and implementation of new TB tools. Some sessions were devoted to discussion of how to tackle challenging issues ranging from ending TB drug shortages, to insuring access to treatment for children with TB, to aligning and achieving the targets for HIV and TB diagnosis, treatment care and prevention — as well fighting for the human right to TB research and TB service delivery and the centrality engaging key and vulnerable populations in the TB response.

South African Minister of Health Dr Aaron Motsoaledi

“For many countries, including mine, TB and HIV are two sides of the same coin,” South African Minister of Health Dr Aaron Motsoaledi said in the inaugural plenary address for TB 2016, the first time the International AIDS Society has organized an AIDS conference pre-meeting devoted to tuberculosis.

“I’m very pleased that even as we focus on HIV, that we prioritize TB as well,” said the Minister, who also serves as chairperson of the STOP TB Partnership board. “At the international AIDS Society Conference, my message will be clear: We will not end AIDS without ending TB. We will either succeed or fail together and so working alone is not an option.”

Minister Motsoaledi’s words paraphrased the late President Nelson Mandela’s call to action made at the Union Lung Health meeting in Kuala Lumpur in 2004, stressing that AIDS and TB must be fought together — “the two diseases are inextricably linked”.

He stressed some of the challenges in the fight against TB. Out of more than 9.6 million people who develop active TB each year, only around 6 million are treated — at least 3 million are missed. In 2015, TB surpassed HIV/AIDS as the world’s leading infectious killer. Since the year 2000 17 million people have been put on antiretroviral treatment (ART) compared to one million in the year 2000 — a 1,600% increase. Over the same period of time, however, there was only a 65% increase in people infected with TB receiving treatment. Meanwhile, there has been a steady increase of multidrug resistance.

But in comparison to other diseases, drug development and TB research in general, has not received the funding and attention that it desperately needs. Without new tools, the World Health Organisation’s Global Strategy to End TB by 2035 will not be achieved — if TB control continues at the current trajectory, the world will not see the end of TB before 2180. The minister pointed out that this plan will require US$ 13 billion each year to fund — but current funding is at half that level.

“We want the world to respond with the same sense of urgency, if not more, demonstrated to recent outbreaks of Ebola and the Zika virus,” the Minister said.

Minister Motsoaledi himself has been a particularly powerful force in the fight against TB. He has championed bold initiatives in his country, the region and globally to screen, treat and prevent of HIV, HIV/TB and drug resistant TB.

In his own country, his leadership was essential to universal adoption of collaborative HIV/TB activities, the ambitious and rapid country-wide scale-up of new diagnostics — the Xpert MTB/Rif test — as the frontline TB test, the adoption of community-based MDR-TB care, and 60% of the world’s uptake of the new TB drug bedaquiline.

In 2014, as Chair of the Stop TB Partnership he proposed ambitious 90/90/90 targets for TB control:

  • 90% of vulnerable groups screened,
  • 90% diagnosed and started on treatment, and
  • 90% treatment success.

He stressed the need to address key and vulnerable populations as a human rights and a social justice imperative.

“It is unacceptable that nearly half of the world’s seven billion people are still unable to afford or access quality healthcare because of their vulnerability mainly caused by poverty and neglect,” he said.

One of his efforts to increase the political will supporting TB targets and universal access to healthcare, based on need rather than the ability to pay, is via his role as co-chair of the Global TB Caucus. The Caucus is an association of one thousand-four hundred parliamentarians from 126 countries around the world who are committed to the fight against TB and the drivers of TB. The Caucus formally endorsed the Global Plan and adopted the 90/90/90 TB targets last year in Cape Town, and some of its African chapter would the next day speak at the closing session of TB2016.

Dr Eric Goosby, UN Special Envoy on TB

Dr Eric Goosby , the UN Special Envoy on TB also focused on the movement to adopt universal health care as being critical to a more effective TB response.

“Together 7100 people die of HIV and TB every day,” said Eric Goosby, the UN Special Envoy for TB. “We have a disease that we have known how to prevent, diagnose, and treat for over forty years — but have been unable to put delivery systems in place that effectively identify, enter and retain people in care for a six month period of time.”

Financial constraints and social exclusion deny access to TB services to the most poor and vulnerable at TB. We collectively share the blame in our failure to take our healthcare systems to task, placing TB programmes into separate silos “that diluted our ability to address this problem, in the segregation of services,” he said.

Goosby believes that universal health care is not going to be achievable until each country ‘unpacks’ the specifics of each of their epidemics, and identifies the barriers to care preventing those most at risk from reaching services.

He also said that the chronic care platforms that have been created to respond to HIV are strong enough to incorporate the oncoming threat of non-communicable diseases (NCDs) that will inevitably have to be integrated, and to be expanded into universal health care.

To achieve this, donor policies may have to become more flexible in order to fund integrated models of care that have adequate feedback information systems to demonstrate impact. As the universal healthcare movement moves forward, it is critical that the TB community make its voice heard and be included.

José Luis Castro of the International Union Against Tuberculosis and Lung Disease

“12 years since Mandela gave that call to action, TB is still the main cause of hospitalization, and the main cause of death among people living with HIV. Nearly half the time someone living with HIV dies from TB, TB is undetected at the time of their death,” said José-Luis Castro of the International Union Against Tuberculosis and Lung Disease (henceforth referred to as the Union).

He recounted the various strategies, plans and calls over the last decade for a dramatic change in the business as usual approach to fighting TB.

“A new agenda, a new global attitude, a ‘paradigm shift’ – yet, here is where we are today: We have built goals that we are not on track to meet.  Even though we all seem to agree that we need to do things radically different, little has changed,” he said.

He called for a better union of the global TB and HIV communities — and for both communities to be bold and visible about the plight of TB

“We must tell the world that TB is here – it affects all of us and we can and must end it! TB is a scourge and drug resistance is a crisis. TB/HIV is killing people every day,” he said.

He also called for active screening to become the norm everywhere and for programmes to begin addressing the comorbidities of TB and HIV more aggressively. He also called on the joint communities to address the root causes of the TB/HIV epidemic: Poverty, malnutrition, poor housing conditions, injustices from stigma to gender discrimination and the denial of basic human rights.

“We need a fundamental change in the way we approach TB – we can adopt the same approach that the AIDS Community has followed for years. We must abandon that approach to TB that is based on our current resource supply and begin a new approach that is based on demand. When we do that we will feel the landscape shifted beneath our feet,” he said.

Thokozile Phiri of the Facilitators of Community Transformation

At the conclusion of the session, a representative of the affected communities, Thokozile Phiri of the Facilitators of Community Transformation in Malawi, rose to express her anger and frustration at hearing that the years of ambitious goals and calls to action had had so little effect.

She reminded the attendees that each person dying of TB has a name and a face. People in her own family had died of TB, even though they were receiving treatment for HIV.

“We are talking about our brothers, our sisters, our uncles. We are talking about people who are mentors, people who are parents, and children who are the future,” she said.

Phiri believes that even though the TB community has said it was committed to engaging communities in the TB response, it was missing opportunities to involve all the critical stakeholders — people such as religious, traditional and community leaders are being left out. “Political engagement must be at all levels,” she said. “Champions are needed.”

Moreover, in the communities, people are educated about HIV and its treatment, but they have received little education about TB. She stressed that programmes have to invest in the communities to develop the capacity for them to become meaningfully engaged.

Plenary Session #1

Plenary session one gave an overview of some of the basic science that could lead to advances in the treatment and prevention of both active and latent TB and concluded with a powerful case supporting a human rights-based approach to TB research and service delivery.

The biology of tuberculosis and its impact on drug discovery and development

“TB is an extremely complex disease, and moving things from basic science into the clinic in a way that makes actual impacts on patient lives is an extremely difficult challenge,” said Clifton Barry of the United States National Institutes of Allergy and Infectious Diseases. “It is not for lack of trying that we are not having a big impact in the drug’s space.”

He explained how in late 2014, the results of three extremely and expensive phase III studies, which had the modest goal of shortening therapy from six down to four months for patients, were published in the same issue of the New England Journal of Medicine.

“All three of them were robust failures at meeting that primary goal… and that was a bit of a wake up call for many of us [in the field],” he said. Paraphrasing the conclusion of an editorial in the same journal by Digby and Misrahi, he added “Our understanding of the science underlying positive clinical outcomes remains rudimentary and it is really time to go back to basics to understand what we know and what we don’t.”

Barry reviewed how the exhaustive clinical trial process (over 200 different trials of the seven available drugs in the 1950’s and 60’s) that had led to the current standard of care first-line TB regimen, which usually involves four drugs (rifampicin, isoniazid, ethambutol and pyrazinamide given for the first two months), followed by four months of rifampicin and isoniazid. Thirty years ago, a hypothesis was put forward to explain why this complex regimen was necessary: at the start of treatment, the bacterial population is mixed, and the different drugs work better in bacilli growing at different rates (with pyrazinamide clearing dormant bacilli). However, the shortened TB regimens were selected with this hypothesis in mind — and their failure suggested that the hypothesis might require revision.

Conventional wisdom suggests that the response to TB treatment is biphasic — the bacilli that are present in the sputum are cleared very rapidly during the intensive phase of treatment, but treatment has to continue long after that or the TB will relapse.

He cited a recent analysis of two of the four-month study arms found that even though regimens might achieve very similar rates of culture conversion, they could have a very different rate of relapse — suggesting that the bacteria contributing to relapse were not being captured in sputum. Even more striking is that more than half of those people who relapsed had experienced early culture conversion.

This has led to a counter-hypothesis: that instead of having persistent bacilli that are difficult to kill, it might be the pathology that is persistent — the TB lesions, which can be diverse in size and type, ranging from surface cavities to large nodules and thick granulomas may be what is difficult to clear. In fact, modern imaging studies over the course of treatment show there can indeed be a different response to treatment of the infection at the surface of the lung to what is happening to different types of lesions. Further studies using imaging mass spectrometry on nodular lesions that had been surgically removed from patients with multidrug resistant TB have shown that different drugs penetrate lesions differently.

He said that they were now trying to introduce these sorts of imaging studies into TB clinical trials in order to determine which regimens may be better at curing harder to reach TB in the more persistent TB lesions.

Critical questions and new approaches in TB vaccinology

“Will we be able to control TB without an effective vaccine… or new tools? The answer is unequivocally no,” said Willem Hanekom of The Gates Foundation. The good news is that there are twenty experimental TB vaccines in the pipeline, and some major advances in the basic science that could lead to better vaccines in the future.

There have been some major changes in the last few years in TB vaccinology, according to Hanekom.

One thing that has changed is that, unlike the BCG vaccine given to infants, the current strategy primarily targets TB in adults and adolescents. As Hanekom pointed out, young children do not transmit TB (they do not expectorate enough), but adults and adolescents do. Modeling studies suggest a vaccine strategy targeting adults (even if the effect is modest and short-lived) would prevent more new infections that the current BCG vaccine, which works well in HIV-negative children — and thus have a greater impact on the epidemic.

Some of vaccines are in fairly late phase. One, in which a non-tuberculous mycobacterium is being used, is in a 10,000-person study in China, with results expected later this year. There is also a trial of a sub-unit vaccine, M72, which is being conducted in South Africa and other countries in Africa, which should produce results in 2017.

Another new approach is that while most of the vaccines have been aimed at preventing latent TB infections from becoming active TB disease, two vaccine candidates that are being tested in Cape Town attempt to prevent initial infection — which modeling studies also show could have a major impact on the epidemic.

Unfortunately, there isn’t much clear pre-clinical evidence that any of these vaccines in clinics will actually work, partly because this is a new field (about 15 years old) and preclinical models are still being refined.

Other new approaches?

  1. Advances in aerosol vaccination that could induce a protective immune response in lung tissue.
  2. Although current vaccine strategies all address one (albeit critical) mechanism of protection — induction of conventional T cells — and all more or less targeting the same m.TB antigens. Basic science studies are looking whether there might be more effective ways to target these T cells, perhaps by using different antigens.
  3. There is a lead pre-clinical CMV-Tb vaccine from Professor Louis Picker of Oregon Health and Science University that seems much more effective in the monkey than any other vaccine yet seen. Picker has analysed the results, and found that the vaccine induces quite a unique immune response.
  4. This suggests that we should explore inducing unconventional, even unnatural immunity perhaps. For instance, why do some of those people highly exposed to TB never become infectious with active TB disease? Professor Gavin Churchyard of Aurum Health in South Africa is conducting studies looking to see what are the correlates of immunity among highly exposed miners who never become infected. Other studies in Uganda seem to suggest that some individuals have very unique antibody responses that are protective.

How latent is latent TB?

Professor Robert Wilkinson of the Crick Institute and the University of Cape Town spoke about basic science research that is trying to develop a better understanding of latent TB — including whether it might be possible to detect which cases might be on the cusp of becoming active.

So how latent is latent tuberculosis? There appears to a spectrum of latent TB infection — “at least 3 flavours” joked Prof Wilkinson.

Imaging studies (PET scanner/CT scanner hybrid with functional imaging) appear to be able to distinguish who is at high risk of progressing to active disease — showing the difference between lungs discrete nodules (low risk of activation), and active nodules in a military pattern and infiltrates scars with upper lobe activation. In addition, there appears to be a unique transcriptional profile of subclinical tuberculosis that has become active and specific cytokine mediators that are elevated — both of which could form a basis of a more predictive test for latent disease that is on the verge of becoming active.

Using Rights to Health and Scientific Progress to Advance TB Research and Access

Michael Frick of the Treatment Action Group presented an analysis of the human rights to better TB policy, care, research and putting into practice TB research findings. It is indeed a grave human rights violation for anyone to die of treatable TB.

The human right to health means that there is also a human right to TB research and to the effective distribution of the results of that research.

To achieve the human right to health, people at risk of TB require the development of new TB tools and their effective distribution and delivery.

Where inadequate and out dated tools hinder a vigorous public health response, fulfilling the right to health may require states to ensure the availability of health technologies through the promotion of research.

The human right to scientific progress extends to the actual application of the discoveries. Failure to implement significant advances are also human rights violations — for instance, developing a new TB drug such as delamanid, and failing to make it available to programmes.

“TB research and access to its benefits can either reinforce or resolve ethical dilemmas in TB prevention, diagnosis, treatment, and care. Consider the ways that an underfunded R&D environment, slow progress in the clinical pipelines, have left TB patients reliant on poorly performing, poorly tolerated regimens that complicate adherence in a number of ways that raise a whole host of ethical issues that TB programs must navigate day to day. TB research can also change the way that TB is culturally perceived. Imagine the power to work against fear and stigma if the message that TB is preventable, treatable, and curable is widely known. And the corollary: the gains against stigma and fear that can be rolled back if, due to a lack of research, what was once curable becomes more chronic and deadly, as is happening with the rise of drug-resistant TB,” said Frick.

Breakout Session 1: New Approaches in Prevention Research

Towards a correlate of protective immunity to TB

On our understanding of what constitutes protective immunity has resulted in failed vaccine efforts. But according to David Russell of Cornell University our understanding of the correlates of immunity may be based on a faulty premise. We have looked at models of TB infection, and defined success as control (containment of TB in granulomas), and assumed that that loss of control was associated with disease progression. However, infected phagocytes can be involved either in restricting bacterial growth and killing the bacteria or promoting or permitting bacteria to grow and spread. What if these functions are somewhere on the same continuum, and spread of disease is actually associated with the induction of permissiveness in the cells? Vaccines based upon the wrong understanding of immunity could promote bacterial growth and actually lead to disease progression.

Russell shared some preliminary basic science work including the use of reporter strains of M.tb that may show whether an approach is having an effect on bacterial growth and fitness. The goal should be to develop better in vitro and animal models making no assumptions about the immune pathways required for control — but rather to measure the effects on bacteria directly.

Potential indications and target populations for a new TB vaccine

Mark Hatherill (SATVI, UCT)

The update on target populations for a new vaccine highlighted that the development of a vaccine for adults is likely to prevent more infant TB cases than an infant vaccine due to reduction in transmission (since adults are the main TB disease transmitters). High TB incidence rates make Prevention of Disease (POD) trials in M.tb infected adults cost-effective but this population may be the most difficult in which to demonstrate vaccine efficacy. Low TB incidence in Mtb uninfected adults would make pre-exposure POD trials larger and longer than equivalent trials in infants.

Drivers of Tuberculosis Transmission

Professor Robin Wood of the Desmond Tutu HIV Centre, University of Cape Town presented a mathematical model to predict the annual risk of TB infection.

TB epidemic in high burdened settings is a result of high volumes of exchanged air and prevalence of infectious cases. Viable TB colony forming units (cfu) in untreated TB case aerosols is 1,000 fold higher than estimated in the 1950’s. Non-culturable M.tb may be even higher. Extremely high concentration of M.tb in bio-aerosols may enable new approaches to TB control such as:

  • The development of newer exhaled breath diagnostics
  • Congregate setting environmental screening programmes
  • Active TB screening at population level

Serial Quantiferon testing predicts disease risk among infants in high transmission settings

Jason Andrews of Stanford University School of Medicine presented an analysis of a sub-study of the MVA85A 020 trial that evaluated whether the Quantiferon values (which measures interferon gamma levels that are elevated following a TB infection) could be used to predict the risk of developing TB in high transmission settings.

The study included HIV-negative and QFT-negative infants aged 4-6 months, and patients were followed every 3 months for up to 37 months. The study questioned whether a) Routine QFT testing can identify young children at risk of tuberculosis progression in high-transmission settings b) Quantitative QFT values can provide additional prognostic information and c) Durability of QFT conversion among infants, and d) Can quantitative values predict reversion risk?

Conclusions included that routine QFT testing in infants could be an approach for identifying high-risk children for targeted diagnostic evaluation and prophylaxis, and high QFT conversion values in this population may be a strong predictor of TB in this population.

Breakout Session 2: Ending TB Drug Shortages

At the start of this session, co-chairs Sharonann Lynch of Doctors Without Borders and Jennifer Furin of Harvard University shared a petition being circulated by the Stop TB Partnership and MSF demanding that all countries upgrade their responses to TB to utilize currently available tools, including the latest diagnostic technology, medicines, and treatment guidelines within 500 days. This includes maintaining adequate stock of WHO recommended DR-TB drugs, and that new drugs are available via import waivers until full registration. See the petition at http://www.stoptb.org/global/advocacy/stepupfortb/.

Supply challenges in endemic settings

Welile Sikhondze, of the National TB Control Programme in Swaziland described efforts in her country to address TB drug and commodities supply problems.

Historically, they had used a vertical system, parallel to the central medical stores — which was handled by the TB programme. This system had various procurement mechanisms and funding sources — but ad hoc requests from health facilities lead to overstocking, expiry, and stock-outs. There were no defined mechanisms for reporting on logistics data to central level, making key logistics decision guesswork. So a TB Logistics Management and Information System (LMIS) was introduced in 2011 to enable collection of logistics data on a monthly basis from health facilities and organizations offering TB services.

Sikhondze and her colleagues also created a model forecasting a supply plan for all TB drugs with the assistance from Management Sciences for Health/Systems for Improved Access to Pharmaceuticals and Services (SIAPS).

Sikhondze highlighted the problems smaller countries have with a lack of bidding power dealing with pharmaceutical companies. Even though they have a budget to pay for the drugs, they simply aren’t prioritized by pharma— and this is particularly a challenge for second-line drugs. Keeping a steady supply of commodities such as TB testing supplies (Xpert MTB/Rif cartridges) can also be challenging.

Supply challenges in the US

TAG’s Kenyon Farrow gave a presentation on behalf of Neha Shah of the CDC on TB supply challenges in the US. TB management isn’t silo’d in the country, but that is because there is no national TB program. There is no such thing as centralized procurement to stabilize supply in the US. There is stock-piling of TB medication but it is extremely wasteful. There are too few API (active pharmaceutical ingredient) suppliers. On a number of occasions companies have simply discontinued manufacturing TB drugs because the market is too small — and FDA registration fees are too expensive for other companies to consider entering the market. Consequently, some predatory companies have come in and bought the rights to a drug, cornered the market and then jacked up the drug’s prices. For example: the manufacturer of cycloserine 250mg CAP 30 UD (blister pack) raised the price from $460 to $10,800 in 2015 — a 2000%+ increase over the previous price.

The impact of supply shortages on people living with TB

Yuliia Kalancha of AIDS Healthcare Foundation in Ukraine spoke about how government corruption or incompetence led to prolonged stock outs of MDR-TB — which is a huge issue in Ukraine (see more in community track).

Parallel Session 1 (Abstracts): MDR and XDR: diagnosis and impact

Chairs:

Gavin Churchyard (The Aurum Institute)

Neil Martinson (Perinatal HIV Research Unit)

Higher cost of implementing Xpert MTB/RIF in peripheral settings in Uganda: implications for cost-effectiveness

David Dowdy of Johns Hopkins Bloomberg School of Public Health presented a case demonstrating the Xpert MTB/Rif test can be implemented in peripheral health clinics in Uganda — but at too great to be widely scaled up at this level.

Large-scale expansion of drug-resistant tuberculosis case-finding in Mumbai via private provider engagement

For better or worse, the private sector is very involved in health delivery in India… with very uneven unregulated results. Regardless, this is not something what will change soon, so Rishabh Chopra of PATH in India described a project that explored whether the private sector providers could be engaged in MDR-TB case detection, diagnosis and standardized treatment. They appeared to have some success improving the quality of MDR-TB case detection by the private sector to match the standards of diagnosis and treatment offered by the public sector. The project excelled in some regards, for instance where they had access to Xpert MTB/Rif test.

Development of a reporter mycobacteriophage assay to detect emergent drug-resistant M.tb subpopulations

Lorenzo Uccellini of Columbia University has developed a highly sensitive assay using fluorescence-tagged mycobacteriaphages that infect M.tb for the early detection of breakout drug-resistance.

Significant and sustained decline in extensively and multiple drug resistant tuberculosis (XDR/MDR TB) from 2005-2014 in Tugela Ferry, KwaZulu-Natal South Africa

Professor Gerald Friedland of Yale University told the audience that there has been a significant sustained decline in the extensively drug resistant (XDR)-TB epidemic in Tugela Ferry since 2008, probably due to an array of interventions that were implemented — including:

1) Strengthening the local TB DOTS programme, with enhanced human and facility resources… some of which allowed for much better contact tracing,

2) Improving in- and out-patient TB infection control,

3) Integrating TB/HIV treatment and prevention services, and

4) A focus on a community-based prevention and treatment strategy that found a lot of the cases in the community.

Results: a sustained decline in incidence (and one hopes) transmission. As long as these efforts are sustained, it would appear that the region’s XDR-TB epidemic is contained. Clearly, however, continued vigilance is warranted — there could be a lot of latent XDR-TB in the community.

Breakout Session 3: Understanding and Intervening in Progression from Infection to Disease

Advantage of rifamycin containing regimens over isoniazid in high transmission settings: what is the evidence?

Tom Sumner (London School of Hygiene & Tropical Medicine)

Treating latent infection is a mainstay of TB control strategy — WHO recommends isoniazid preventive therapy a short course in low burden settings, and continuous in high burden ones. Studies now show short courses of rifamycin-containing regimens are more curative of latent TB that isoniazid alone — and may provide more durable protection in low-burden settings. However, there can be safety and drug interaction concerns when given together with ART.

However, as shown by a study of IPT plus ART in Cape Town, in very high burden settings, after the first year of discontinuing IPT, most of TB that occurred was due to re-exposure. Therefore, in high burden settings continuous IPT together with efforts to improve infection control may be necessary to provide long-term protection.

Advances in LTBI regimens: an update on ongoing clinical trials

Tim Sterling (Vanderbilt Tuberculosis Centre)

An update on ongoing clinical trials for LTBI showed that a) several trials are planned or underway on short-course rifamycin-based therapy to prevent drug-susceptible TB b) more trials to prevent MDR-TB are underway and c) several trials on optimal treatment strategy are underway.

High-dose rifampicin tuberculosis treatment regimen to reduce 12-month mortality of TB/HIV co-infected patients: The RAFA trial results

Dr. Corinne Merle of WHO who presented the RAFA study results at both the TB2016 pre-meeting, and the AIDS 2016 conference

The RAFA trial was a three parallel arm multicenter open-label randomized controlled trial that enrolled ARV-naïve adults living with HIV with CD4 ≥50 cells were enrolled. 778 patients (212 from Benin, 468 from Guinea, 98 from Senegal) were randomized to three arms: A) ARV 2 weeks (N=262), B) ART 8 weeks (N=258), C) High dose Rif (N=258). The primary outcome was mortality at 12 months after TB treatment initiation. Patients were followed up with clinical visits and 2 sputum samples taken: every 2 weeks during 2 months, every month until the end of TB treatment and every 3 months until the end of follow-up. Total follow-up per patient: 18 months post randomization.

Overall, there was no difference in 12-month survival between the three groups. However, for patients with CD4 less than 100 cell, mortality was significantly decreased in the high-dose rifampicin arm. Conclusions included:

  • More aggressive TB treatment using high dose Rif, in addition to ARV, could reduce TB/HIV mortality among co-infected TB/HIV patients with severe immunosuppression.
  • No evidence of an increased risk of hepatotoxicity with higher dosage of rifampicin (15mg/kg) given daily for 2 months to TB/HIV patients.
  • Further study is needed to explain more precisely these results and findings from pharmacokinetic/pharmacodynamics studies will be important to consider. As suggested by the plenary talk given by Clifton Barry, it is possible that a higher dose of rifampicin better penetrates and clears TB from deep within lesions in the lungs.

Breakout Session 4: Transitioning from Research and Development to Access for Children with TB

Chairs:

Eliud Wandwalo (Global Fund)

Carol Dukes Hamilton (Duke University & fhi360)

Filling research gaps for children with TB

“Outrage,” said Dr Jennifer Furin of Harvard Medical School who served a stint with MSF in Khayelitsha, ‘is one of the ingredients that’s really been missing from TB as opposed to HIV.”

She brought the outrage to her session with an impassioned plea to fill the research and implementation gaps to save the lives of children with TB.

“When it comes to our approaches to paediatric tuberculosis, we practice what I refer to as: ‘a trickle-down paediatrics’. We assume everything good that happens up here with the adults will somehow make it’s way down to the children. We have really gotten almost nowhere in terms of implementing advances for children or even advocating that children be a primary focus when it comes to tuberculosis!” she said

What is needed?

  • A point-of-care test on that can be performed on easily accessible sample
  • Non-invasive sampling methods,
  • Sensitive screening tools and techniques,
    Effective, non-toxic treatment for TB infection,
  • An ‘all oral’ short-course potent regimen for all forms of TB including MDR-TB, Paediatric formulations and
  • A family-centred approach.

She also made three recommendations which she believes could further TB research in children:

1) Establish Long-Term Family Cohorts

  • Pediatric TB studies tend to be short term and can be difficult to recruit
  • Household studies happen but are usually limited in interventions and the follow-up time is relatively short… when what is really needed would be to follow children from the time that they are exposed for four to five years to see if vaccines work, to test better diagnostics, point-of-care tests and so on
  • Need four to five established “family-centred sites” for TB — she noted that anthropological research has shown that it is possible to establish long-term family centred cohorts over a twenty to thirty year period.

2) Establish rapid response and epidemic response protocols

  • Providers on the front-line are often confronted by crises, such as a community wide outbreak of MDR-TB among children, or an outbreak in a nursery home or orphanage, and by the time they can develop and get a protocol approved, the crises may be over.
  • If there were established protocols, they could can be rapidly adapted and approved in advance for such crises

3) Commit to childhood TB as an essential part of the “End TB” Strategy

“Establishing paediatric cohorts — in which we have a clear understanding of what’s happening with TB in children —is essential if we are actually serious about meeting our goals to eliminate tuberculosis,” said Furin. She added that TB is a disease where the full impact of an intervention, such as a vaccine may only be seen 10 years later in adults. She believes children could represent a sentinel, “the harbingers of where we are going in TB Control in general and if we don’t know what is going on with them we will be ten years behind this epidemic all along.”

She did not mean that children should be the first population in which drugs should be tested, but the delays getting interventions introduced into children can be extreme. For instance, bedaquiline was approved by the US FDA in 2012, and recommended by the WHO in 2013, but there still has not been a study in children, not even in adolescents. Meanwhile, there was a paediatric development programme for delamanid, but there is still no recommendation from WHO regarding its use in the population.

Developing and registering paediatric formulations for TB

The next speaker, Vijay Agarwal of Macleods Pharmaceuticals Ltd, said he was moved by one of Jennifer Furin’s presentations at a conference a few years back on the need for generic child-friendly formulations of paediatric TB drugs, which no company had developed previously. So he spearheaded a programme at his company, and they have produced child-friendly formulations now available via the Global Drug Facility or directly from MacLeods. All of the products are tast-masked and fully dispersible. However, there has been a significant delay getting the products registered and approved, which could delay access to these in many countries for another 3-4 years. In South Africa, it is possible to apply on an individual basis to the Medicines Control Council for section-21 access to the drugs, but that is not the same as making these essential medicines widely available. This case serves to illustrate that the development and availability of new TB tools must be matched by regulatory and bureaucratic action in order to provide access to treatment.

Programme considerations for integrating new tools

John Ditekemena of the Elizabeth Glazer Pediatric AIDS Foundation (EGPAF) spoke on the programmatic considerations new tools — and the gaps between policy and implementation.

BS5, Breakout Session 5: TB Drug Discovery and Development – Where are we Heading?

Chairs:

Clifton Barry (NIAID)

Luis Soto-Ramirez (Instituto Nacional)

New TB treatment targets are needed. Among new anti-TB drugs, there are a couple of promising ones:

Opportunities and challenges in TB drug discovery: lessons from the benzothiazinones

Stewart Cole (EPFL)

Benzothiazinones are highly active against Mycobacterium tuberculosis, including MDR and XDR strains. It seems that it doesn’t have any antagonism with known (or other potential) TB drugs and has an additive effect with them all.

Prospects for antimicrobial drug re-purposing

Florian Von Groote-Bidlingmaier (TASK Applied Science)

Carbopenems in combination with clavulanic acid are currently in use for treatment of XDR-TB together with other anti-TB drugs and show some promising results. There is, however, need for further research on their efficacy and there is a need for development of an effective oral formulation.

Novel pathways for host-targeted therapy

Jerrold Ellner (Boston University)

Key take away: Research should be directed on host-targeted therapy as well as on new bacterial targets.

Lesion penetration as a critical determinant of TB drug efficacy

Rada Savic (UCSF)

Drug penetration in the TB lesions varies greatly not only between patients, but also within the same patient. Therefore there is room for improvement of old, well known drug regimens in terms of dose, frequency and treatment duration. Based on this, TB treatment regimens should be personalised

Breakout Session 6: Aligning and Achieving Targets for HIV/AIDS and TB Control

90-90-90 targets for TB

“We’ve been talking about tuberculosis — it’s been around for millennia — for many years, but why is it that we are now able to think about ‘ending’ tuberculosis?” asked Dr Paula Fujiwara rhetorically at the start of the session. Dr Fujiwara is a long time TB expert who was working in New York during the MDR-TB epidemic of the 1990s, who then joined the Union and recently became its scientific director.

The reason is that there has been a paradigm shift in the TB world in a number of areas — but chief of which is the mind shift to adopt a human rights approach to TB — which requires that we attempt to eliminate TB.

“We have a human rights and a gender-based approach to the problem and also have a more inclusive leadership, not just governments but also involving the community and the patient to have a ‘patient-driven approach’,” she said.

Her talk described the initiatives, plans and targets that could put some substance into this aspiration.

“In 2014, the World Health Assembly said: ‘We don’t want to talk about controlling tuberculosis anymore we want to talk about ‘Ending tuberculosis!’ The vision here is a world free of tuberculosis – no more deaths, no more disease and no more suffering with the goal of ending the global TB epidemic,” she said

This change was reflected in the recent ‘Sustainable Development Goals’ (SDGs) that were drafted after the conclusion of the Millennium Development Goals. The SDGs contains 17 goals and hundreds of targets. SDG number#3 concerns health, however, and one of the sub-targets is the ‘end’ of TB, HIV and Malaria within the timeframe for the SDGs, which runs from 2015 to 2030.

The Global Plan to ‘End TB’ was requested by the World Health Assembly and is a costed investment plan. It will require aggressive front-loaded investments peaking at US$ 12.3 billion globally in 2018, about twice what is currently being invested.

“Going at the rate we’ve been doing now, we will never get to the end of tuberculosis,” she said. “If we could optimize the use of what we have currently, and also to start to put together some of the emerging tools that have been developed, by 2020, then we have a chance of actually going down by 10% per year by 2025.”

But eliminating TB by the Global Plan’s goal of 2035 will require the development of major new tools — like an effective vaccine or profoundly better diagnostics and treatments. All this will require an innovative approach to funding, health systems and TB programmes optimized to roll these tools out effectively.

‘90-(90)-90’ came about after a meeting with the health ministers of the BRICS countries who requested tangible targets to work towards. The first 90 is to treat 90% of all people with TB — the 90 in parentheses is to address TB risk in 90% of people in key affected populations. The final target is to achieve treatment success in 90%.

How far away are we from ’90-90-90’?

“I think this is a little worrying because in terms of detection we are still missing one-third of all of the cases that we estimate to be having tuberculosis. When it comes to drug-resistant tuberculosis we’re doing an even worse job. In terms of doing drug susceptibility testing for tuberculosis — again, not doing very well,” said Fujiwara, who continued to go down a list of deliverables. “So we have a ways to go before we can get to any of the 90-(90)-90’s.”

Aligning HIV and TB targets in Eastern Europe and Central Asia

“When it comes to HIV/AIDS, [Eastern Europe and Central Asia] is the only region of the world where the epidemic continues to grow, with a 57% increase in new cases in the last 5 years,” said Michel Kazatchkine, the UN Secretary-General’s Special Envoy on HIV/AIDS in Eastern Europe and Central Asia.

The HIV epidemic is largely driven by injection drug use, though with an increasing contribution of sexual transmission. Access to treatment is low. HIV prevention efforts have not been scaled up sufficiently, and access to harm reduction is extremely limited — “non-existent in a number of countries,” remarked Kazatchkine.

In addition, health systems are vertical and provider-centred. There are high levels of stigma and discrimination with numerous structural, cultural, societal and political obstacles to the AIDS response. Finally, there are low levels of co-operation between government and the non-governmental sector.

The region also accounts for the majority of TB within Europe, with

  • 83% of new TB cases
  • 92% of TB deaths
  • 5% of MDR-TB cases
  • 88% of TB/HIV co-infections

The region contains 9 of the 30 high burden MDR-TB countries: Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, Tajikistan, Ukraine and Uzbekistan.

MDR-TB is increasing — and the percentage of MDR-TB among new TB cases has increased from 12% in 2009 to 18% in 2014. HIV coinfection has increased from 3.4% to 8% at an average yearly increase of 15%. In the region, the highest HIV prevalence in new TB cases is in Ukraine (approaching 20%).

Recently Kazatchkine said that he was in one TB centre in Ekaterinburg, Russia, where 35% of new TB cases were in people living with HIV, and 56% in retreatment cases.  In Belorussia, 50% of TB cases in people coinfected with HIV are MDR-TB, and among the retreatment cases in people living with HIV, 81% are MDR-TB and 19% are XDR-TB.

Key populations in the region that are at risk of HIV have an overlapping risk of TB, particularly persons who inject drugs (and their sexual partners), prisoners and migrants.

The highest risk factor for acquiring MDR-TB is among people who inject drugs, a quarter of whom are HIV-positive, and two-thirds of whom are infected with HCV.

“If you are an HIV-positive injecting drug user, and you are incarcerated, your risk of acquiring HIV is 25 fold-greater than the general population,” said Kazatchkine.

There is one primary reason for why these epidemics are expanding — the punitive approach to drug use and regressive drug policies. Fear for violence and arrest increases risk, and leads people to go underground and inject in unsafe conditions. The proportion of people incarcerated for drug possession without intent to supply is extremely high in the region — in Russia it is 72% and in Ukraine it is 61%. Unsafe injection drug use continues in prison.

Another issue is that cooperation with NGOs is limited. Civil society organizations do most of the outreach and harm reduction work, but these organizations are becoming fewer and fewer because of restrictions on funding from international sources.

Vital gaps in reaching TB targets

Shannon Hader of the US Centers for Disease Control (CDC) noted that the current TB/HIV metrics (indicating high performance on the key TB/HIV indicators such as HIV testing of people diagnosed with TB, and the numbers of those who are HIV-positive who are being put on ARVs).

“But then, if you get to know the TB language further, you’ll realize that this is hardly the whole picture,” said Hader. The metrics leave out the missing 3 million who are never diagnosed or make it onto treatment.

So the CDC has started to take a look at the TB prevalence surveys, and the HIV estimates to show it’s staff what they might be missing.

Hader said that if one uses South Africa as an example — which has quite progressive policies — and includes those who are uncounted, “rather than having 93% of notified cases who are tested for HIV, it is closer to 67% of all TB cases that are tested for HIV. And that brings the treatment initiation rate of 79% to only 51% of actual estimated TB cases,” she said.

These figures are important for the HIV partners to understand, because if the missing people with TB are being lost before being counted by those metrics, the HIV and TB programmes won’t be able to design interventions to get to those individuals.

Innovative financing in the fight to end TB

Robert Matiru described Unitaid’s efforts not only to fund new tools innovations within TB programmes. They are particularly interested in integrated health products that address more than one condition or disease or address the needs of people affected by more than one condition or disease — and thus can leverage other programmes.

 

Day Two, Saturday 17 July 2016

Morning Plenary Session

Why TB 2016? Why now?

Professor Jens Lundgren of the University of Copenhagen had planned to give a talk at the opening plenary describing why TB 2016 was being held as a pre-meeting to AIDS 2016, but due to a flight delay gave an overview of what he had heard after he had arrived on the previous day, from the perspective of an HIV doctor who doesn’t normally attend TB meetings.

He began with a slide with data from the 2015 WHO Global Report, which showed that despite substantial reductions in TB-related deaths since 2000 (43 million lives saved), it was clear that TB was not yet under control.

In 2014:

  • 6 million new cases of TB
    • Highest incidence countries: Lesotho, SA, Swaziland, Djibuti, Namibia, Mozambique
    • One-in-eight (12%) associated with HIV
  • 000 MDR TB
    • More than doubled in last 5 years
  • 5 million deaths due to TB (HIV-negative: HIV-positive: 73%: 27%)
    • One-third of all HIV deaths are due to TB

These stats, he said, were more than enough justification for this meeting.

Evolution and spread of drug resistance – a slow moving process with great public health impact

Sebastién Gagneux of the Swiss Tropical and Public Health Institute gave a presentation on the evolution and spread of TB drug resistance. There is a popular misconception that drug resistance makes M.tb less fit — but this is an over-simplification according to Gagneux. Over time, the mycobacterium can make compensatory mutations, and Gagneux presented data showing that this has indeed occurred in clinical strains, and that there is a high frequency of compensatory mutations in MDR ‘hotspots’, which are associated with ongoing transmission. In clinical settings, fit strains will evolve and be transmitted even in the context of XDR-TB.

Diagnosis of HIV-associated TB: Translating new knowledge and tools to maximise clinical impact

Professor Robin Wood of the University of Cape Town gave a presentation on behalf of Dr Stephen Lawn of the London School of Hygiene and Tropical Medicine exploring why the lateral flow urine lipoarabinomannan (LAM) assay, which only seems to be sensitive for TB in the most advanced, and often non-ambulatory people living with HIV. Recent autopsy studies suggest that, in most cases a positive urine LAM result may in fact indicate TB disease in the kidneys — though a minority of cases may reflect other disseminated TB disease without kidney involvement. Even so, “renal TB disease occurs in the sickest TB/HIV co-infected patients and is strongly associated with very poor prognosis,” said Professor Wood. This would seem to provide an even stronger rationale to use routine urine LAM testing to aid management of sick hospitalised HIV-positive people — and indeed, it’s use is recommended in the most recent WHO TB algorithm to speed up the treatment of suspected TB in seriously ill people living with HIV.

Better evidence, better policy

Yogan Pillay of the National Department of Health (DOH) told the audience how South Africa, which has a wealth of experience in tuberculosis and some of the world’s leading TB researchers, has established a TB ‘think tank’.

The rationale was that a dedicated DOH-led TB Think Tank could help facilitate evidence based TB policy decision-making through improved data utilization and consideration of programme interventions and research gaps. The think tank brings together the DOH, the South African Department of Finance, and researchers providing economic and epidemiological modelling and analysis, with support from the Bill and Melinda Gates Fund among other funders.

“We are trying to rebuild the TB programme from the bottom up,” said Pillay.

In addition to advising DOH on TB policy, the think tank is assisting in developing operational guidelines, and advising the DOH on key implementation activities.

In the last two years, they have developed South Africa’s first ever investment cases for TB-HIV showing what interventions will have the most impact for the money spent — and this was used to get more money from the Treasury for the TB programme — which could be a good lesson for other countries to consider. The think tank helped push DOH how to implement bedaquiline (currently South Africa is using more of the drug than any other country, and plans to scale up its use in a 9 month regimen for all people with MDR-TB in the country if it can negotiate lower prices on the drug), and to use three months of isoniazid/rifapentine (3HP) treatment in child contacts of people who have TB.

South Africa is also going to launch a national TB investment plan that ring-fences funds for TB research.

Nevertheless, during the discussion, Erica Lessem of TAG criticized the think tank for not yet rolling out the LAM assay as recommended by WHO.

Leaving No One Behind – Key Populations in TB

“No one can be left behind if we are to end TB,” said Dr Lucica Ditiu of the Stop TB Partnership, adding that just as in the HIV world, the TB response must meaningfully engage its key populations most at risk and most neglected: migrants, internally displaced people or refugees, prisoners, miners, children under the age of five, those poor and living in rural and in urban areas, the healthcare workers, people who use drugs, and of course, people living with HIV.

“We are trying at STOP TB Partnership to foster a movement in which we are raising, empowering and creating the space for key populations and vulnerable groups,” she said.

Challenges energizing those working in the TB field to care

The importance of empowering and creating a space for key populations and vulnerable groups in the TB response can be difficult to convey to people working in the TB field. Part of the reason for this, she said is that people working in TB have become a bit defeatist because TB doesn’t get enough attention or funding. But she stressed that the TB community is going to have to move beyond that in order to reach the targets for ending TB in the 2030 sustainable development goals.

“That will mean ‘leaving no one behind’ — a phrase used in the 2030 Agenda for Sustainable Development,” Ditiu said, reminding the audience that the phrase had its origins in military parlance during World War II.

“It was linked to an action,” said Ditiu. “It was not just ‘leave no one behind’, it was linked to search and rescue. And search and rescue is what is extremely important for us to understand — as you have heard from the previous speakers here — every year in TB for the last eight or nine years, we have missed three million people.”

The search and rescue of the most vulnerable populations not accessing TB prevention, diagnosis and treatment will take time, money and energy.

Meeting with key populations

She stressed the importance of meeting with the right people to the table — rather than people claiming to speak for them, which had been a problem at some of the first meetings the STOP TB Partnership held with vulnerable groups and key population representatives.

“I want to deal with prisoners or ex-prisoners; I want to deal with drug users; I want to deal with sex-workers and so on! Until we wake up and empower these groups, we will go nowhere,” she said.

Consequently, the Stop TB Partnership developed a set of brief guides with ideas on how programmes can access, can ensure that interventions are tailored for these groups — and especially for applying to the Global Fund.

Another challenge is the lack of data on these populations — partly because none of the local national governments are funding work with these communities.

“We have very little evidence on the key populations — numbers for what works, what doesn’t work. But to build up a strong programme and to show cost-effectiveness, we need to build on stronger evidence than just extrapolations. Nobody [read, donor], will believe us if we don’t have data” she said.

This could be difficult for the TB community to do alone — so Ditiu believes that it will need to be a joint effort with the HIV community. While not all of the key populations at risk of HIV are known as having a greater TB risk — there is probably significant overlap whenever a population has a high burden of HIV in regions where HIV-TB co-infection is common.

Reaching key populations and vulnerable groups will not be possible without dialogue and their engagement — which can be difficult when they lack resources and capacity.

“We cannot create interventions for ex-prisoners, interventions for people that use drugs, interventions for migrants or for miners if they are not there,” she said. But the communities working with these vulnerable groups are often weak and lack financial capacity. Consequently, other larger institutions tend to come in to collect the money, which then only trickles down to the actual vulnerable group networks.

If we want to have key and vulnerable groups not left behind then let’s fund and empower them to decide what is the best for them,” she said.

Parallel Session 3 (Abstracts): Transmission and Diagnosis

Deterministic linkage to evaluate the burden of recurrent TB disease in Cape Town, South Africa

Sabine Hermans, who is currently post-doctoral at the Amsterdam Institute for Global Health and Development but recently spent three years at the Desmond Tutu HIV Centre at the University of Cape Town presented the results of a study of the incidence of recurrent TB disease within the Cape Town metropolitan area over a 12 year period (2003-2015). This has largely been unstudied because many of the TB registers do not use unique patient identifiers to identify TB in the same individuals.

However, Hermans and colleagues were able to use deterministic record linkage (matching names, dates of birth, etc.) to assess a very high burden of recurrent TB. Among a cohort of 245,495 individuals there were 287,003 episodes of TB. 16% of individuals had two or more episodes of TB, and the likelihood of having recurrent TB increased over time — 35% of the individuals with TB in 2003 had one or more episodes of recurrent TB. At present, it is unclear to what extent this has been due to reactivation or reinfection, or whether there are biological, immunological, socio-economic reasons that put these individuals at increased risk of infection or progression to disease. However, further analyses are planned that will stratify by HIV status, age, sex, and smear status. In the future, they will also look at resistant cases, which are recording in different databases.

Mycobacterium tuberculosis molecular screening assay with sensitivity equivalent to culture

Sally McFall of Northwestern University in the US described work to develop an M.tb molecular screening assay as sensitive as culture that could be used at point-of-care (POC). So a test was designed to reduce human DNA extraction, which can inhibit the qPRC reaction in sputum and to be highly sensitive working with a small volume of sputum (detecting as few as 10 colony forming units in 1 ml of sputum) without being diluted or centrifuged, and without requiring guanidinium/or alcohol or a cold chain (refrigeration). In tests using blinded samples from the Foundation for Innovative New Diagnostics (FIND) specimen repository, the assay had an overall sensitivity of 97% (whether in smear negative or culture negative specimens). McFall believes the technique could be easily ported into a POC or high throughput test platform.

Development of a multi-analyte panel for non-invasive pharmacokinetic monitoring of second-line anti-tuberculosis drugs in small hair samples

John Metcalfe of the University of California San Francisco (UCSF) described the development of a system that could monitor the pharmacokinetics (pk) of TB drugs in small hair samples — which unlike plasma pk, would not require phlebotomy or a cold chain. Hair samples can provide evidence of cumulative exposure, and might be particularly useful to assess exposure to drugs used in MDR-TB treatment — as sub-therapeutic concentrations of anti-TB drugs are common whether to do adherence or for other reasons.

At present, a pk panel that he and his colleagues have designed can detect levels of most of the key drugs being used in MDR-TB treatment, with the exception of kanamycin, which will require a separate panel. There are some limitations however — the method cannot show patterns of adherence over a month… but routine use could still flag when there is a problem. Also, in general, TB pk has been understudied, and some work will be required to carefully determine cut-off levels that indicate adequate drug exposure.

Diagnostic accuracy of Xpert MTB/Rif, experience at district hospital of Buenos Aires for tuberculosis diagnosis

Omar Sued of Hospital General de Agudos Juan A. Fernandez in Buenos Aires, Argentina shared the experience of introducing the Xpert MTB/Rif test into a district hospital to improve diagnostic accuracy for TB — particularly smear-negative TB as the facility serves a fair number of people living with HIV. There were few surprises here — the test is as sensitive and specific in Argentina as it has been in other countries. Consequently, Sued recommended that the Argentinean National TB Program should consider the incorporation of this technology in all hospitals and adapt algorithms, he added one of most notable hurdles to doing this in practice is that, initially at least, it can be difficult to convince the laboratory technicians to change their flow/culture.

Breakout Session 7: MDR/XDR-TB

Evolution of Drug Resistance in KwaZulu-Natal and implications for TB control

Dr Alex Pym of the KwaZulu-Natal Research Institute for Global Health presented two studies on drug resistance — one on the history of TB drug resistance in KwaZulu-Natal — and the other on the clinical relevance of isoniazid mono-resistance.

XDR-TB is TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). The outbreak of XDR-TB at the Church of Scotland Hospital in Tugela Ferry was first reported in 2006.

“Subsequent work showed that even in 2007, that XDR-TB was already widespread throughout the province,” said Pym. “But why XDR-TB, and how did it emerge in KwaZulu Natal?”

To find out, Pym and colleagues performed population-based whole genome sequencing of TB clinical isolates from 337 individuals with TB from across the province, with varying patterns of resistance. Most of the isolates were collected recently, some between 2008 and 2010, and a handful of isolates were from the 1990s.

Looking at the phylogeny of one region of the bacterium in the XDR-TB isolates, it was clear that there was a clonal group involved in the Tugela Ferry outbreak (with identical mutations). Then they assessed how this resistance pattern had evolved, and found that resistance had been acquired sequentially, beginning with isoniazid and streptomycin resistance (subsequent dating studies suggested sometime in the 1950s when those drugs first became available), followed by further isoniazid or potentially ethionamide resistance (inhA), followed by resistance to ethambutol resistance and then resistance to rifampicin and pyrazinamide.

Again, dating analysis suggested resistance to these drugs began to appear at roughly the time that they were introduced into clinical practice. XDR-TB resistance evolved long before the outbreak in Tugela Ferry (which likely explains why it was already widespread by 2007. It may have evolved before HIV became epidemic in South Africa — Pym estimated it emerged sometime around 1995.

“One of the major public health implications of this, is, given the inevitable evolution of resistance and the introduction of new drugs like bedaquiline and delamanid, resistance will evolve and we need to think about how we can introduce these drugs in a more effective way,” he said. “Particularly when considering use of a new drug in individuals who only have a single drug option — and how and whether one should use that.

Another observation was that isoniazid mono-resistance always occurred before rifampicin resistance, but it is not detected with the current Xpert MTB/Rif test. Pym expressed concern that if routine screening for isoniazid resistance was not performed, “in a sense, we are sowing the seeds of further resistance.”

He and his colleagues then performed a retrospective cohort analysis of 79,366 people treated with standard treatment (or a modified regimen in cases of retreatment) at Prince Cyril Zulu Communicable Disease Centre, in Durban from 2000-2012  to determine what was the clinical impact of isoniazid mono-resistance. Resistance test results were available in close to 19,979 episodes over 3000 of which had resistance profiles other than isoniazid mono-resistance. Outcomes of 16,311 drug susceptible episodes were compared to 557 episodes of isoniazid mono-resistance.

Isoniazid had a clear impact on outcome, significantly reducing the odds of successful treatment, increasing the risk of death almost 2-fold — there was a 3-fold increase in combined death or failure.

“Not only is the detection of isoniazid-resistance important for preventing further evolution of TB, it is also important clinically,” he concluded.

Advances in improving treatment outcomes for MDR/XDR TB

Professor Gunar Günther of the University of Namibia School of Medicine presented a report on advances in treatment of MDR/XDR TB — and how applicable they are in the most resource limited settings.

Currently, global treatment success rate of patients with MDR-TB is only around 50% (and in truth, this figure simply represents treatment completion). There is urgent need to improve it. WHO has developed standardised short course treatment guidelines for MDR-TB. However, studies have shown that only a small proportion of patients with MDR-TB would be eligible for short-course therapy. Strategies to improve outcomes of MDR (and XDR) TB patients should include:

  • scale up of rapid diagnostic tests and culture
  • new drugs development and research in repurposed drugs
  • shorter, more tolerable regimens
  • individualised therapy
  • therapeutic drug monitoring
  • improvement in health care
    • decentralisation of TB care
    • integrated TB/HIV (and other comorbidities) care
    • dedicated health care workers
    • dedicated politicians
    • funding
  • In addition, more research is needed in:
    • host directed therapy
    • prognostic biomarkers

Günther stressed that whenever treating TB patients, clinicians should be mindful about comorbidities, pulmonary consequences/ complications after TB has been treated, and other pulmonary bacterial infections that patients might have together with TB.

Diagnostic advances in MDR/XDR-TB and their impact on clinical outcomes

Susan Dorman of the Johns Hopkins University School of Medicine presented the results of a prospective study evaluating a new test cartridge for the Gene-Xpert platform that was designed to diagnose TB and to distinguish whether it is susceptible or resistant to isoniazid (katG and inhA), the fluoroquinolones and/or second-line injectables. The assay contains 10 molecular probes, 9 for mutations associated with resistance and one an internal control, and undergoes a 3-phase amplification process to detect as few as 300 colony forming units/ml. The test takes roughly the same time to run (2 hours) as the standard Xpert MTB/Rif.

The study enrolled over 400 participants from China and South Korea with signs and symptoms of TB (with an emphasis on those with suspected drug resistance). The new Xpert cartridge results were compared to standard MGIT phenotypic drug sensitivity testing (DST) and Sanger DNA sequencing for the same specific target genes (which take much longer and cannot be performed at or near the point of care).

About 80% of the participants were culture positive for TB, about three quarters of which were smear positive. MGIT DST results were available for 321, and results between the various tests could be compared for 306 individuals — a little over half of which were rifampicin resistant on Xpert MTB/Rif. The sensitivity for TB case detection for the new cartridge was indistinguishable from that of the Xpert MTB/Rif test.

MGIT DST results were positive for mono-resistance to one drug or other for around 12%., and 3% were poly-resistant. MDR-TB was detected in 17.8%, pre-XDR-TB (MDR-TB plus resistance to either a fluoroquinolone or an injectable) was identified in 17.5%, and XDR-TB was detected in 12.8%. More than a third had no resistance.

The specificity and sensitivity of the new Xpert cartridge were high (over 95%) on most of the probes (the ones with the most positive results) compared to Sanger DNA testing, though somewhat lower on a couple probes where there were few resistant cases (and this discordance appeared largely driven by samples with mixed populations of resistant and wildtype microbe). The Xpert test sensitivity compared to phenotypic culture DST — though in the cases where there was discordance, the performance of the Xpert test was similar to DNA sequencing.

Again, the chief advantage of this test is that it could be performed soon afterwards on specimens from someone who tested rifampicin resistant on Xpert MTB/Rif — which could dramatically cut the time that it would take to put someone with MDR, pre-XDR or XDR-TB onto a clinically active regimen.

At present the status of the test is in internal review at Cepheid, which produces the Gene Xpert systems and the Xpert MTB/Rif test.

Decentralization of MDR-TB: a case study from South Africa

Dr Virginia de Azavedo, of the City of Cape Town Department of Health described how, since 2012, care and treatment for drug-resistant TB has been fully decentralized in Cape Town with relatively small investments in its existing infrastructure and human resources.

The programme has developed clear patient care pathways and clinical management meetings are held each month. In each of the sub districts, patients are being provided with clinical advice and support from a senior doctor, a DR-TB nurse and DR-TB counsellor. Reporting and recording systems have also been put in place.

According to Dr de Azavedo, decentralization has significantly increased prompt access to DR-TB care, improved the overall quality of patient management and decreased the spread of DR-TB in the community.

“But unfortunately treatment outcomes remain abysmal,” she concluded. “We need shorter treatment regimens with more effective drugs.”

Breakout Session 8: Human Rights and TB Research: Realizing the Right to Scientific Progress for TB

This session built upon Michael Frick’s presentation on the human rights framework for TB research. Session co-chair Diana Elizabeth Weil of WHO recalled that the STOP TB Partnership and WHO had called for ‘human rights based approach’ to TB in 2001, and that in 2006 the STOP TB Strategy had as one of it’s five objectives: Protecting and Promoting Human Rights.

“What’s been changing things more recently?” The advocates. Standing here with the HIV and TB and key population advocates. That voice simply wasn’t there for years, we didn’t have a strong enough voice and we still need many more people. But that voice makes a huge difference,” she said.

Returning to Durban: Science, Human Rights and Activism at the Centre of the TB/HIV epidemics

Dr Eric Goosby, the UN Special Envoy on TB recounted how he was a young doctor in San Francisco at the start of the HIV epidemic.

“The community was mad, angry at the lack of response, and the need to demand care and treatment. The demand for research and for the response to be enhanced and improved became the focus of the dialogue,” he said. After some initial hesitation on the part of the government, by the late 80’s and early 90’s, the value of engaging the activists — those who were affected by and living with HIV to be part of the planning and implementation process had become apparent.

“It kept the services relevant and responsive to the changing needs of the population. It was with the health response matched with a community response that we began to define was the most effective response in alleviating morbidity and prolonging life, and preventing death,” he said. He added that, ‘over and over again’, those working in the health system saw that identification, entry and retention strategies were best done by those in and of the community.

All of this had been orchestrated by the community’s involvement — demanding a place at the table, in the planning and implementation discussions. But he stressed that the community’s continued engagement in the response must be funded.

Developing a Rights-Based Approach to TB: Concepts, Case Law and Legislation

“The human rights-based approach to TB — to health — is founded on the dignity and autonomy of the individual which can be distinguished from a traditional public health approach that looks at population health. There are legal entitlements, freedoms and protections and rights related to prevention —human rights laws and other laws — that are relevant to fighting the disease, to protect who live with it,” said Brian Citro who is a clinical researcher in Law and an associate director of the International Human Rights Clinic at the University of Chicago Law School, and is involved in projects in India and globally on using the law to support a human-rights approach to both the HIV and TB response.

These rights and laws, he added, “establish obligations on the part of government and non-state actors.”

He highlighted a number of cross-cutting principles integral to the human rights approach to health:

  • The principle of non-discrimination / right to equality: People shouldn’t be discriminated against because of the disease, or in gaining access to services because of being members of other certain groups or populations — people need to be treated equally.
  • A focus on vulnerable and marginalized groups: “None of the initiatives, no money is going to solve the problem if we don’t focus on those who are most at risk. And that was a key development in the fight against HIV, that really to start moving things forward. We haven’t really done that yet with TB – we haven’t started to think that way enough,” he said.
  • Participation in decision-making: As Dr Goosby had noted, until there is meaningful participation of people who suffer from the disease and who were at risk there will be limited progress fighting the disease.
  • Accountability and remedies — “People must be held accountable for failures to move things forward, failures to fund research, failures to provide access to treatment and testing etc.,” said Citro. People also need remedies — which should be the approach to take rather than depending on the benevolence of government.

“We need to change that relationship so that government has an obligation — all different parts of government, also pharmaceutical companies, donors etc. This is a different relationship between the people who need access and the people who are there and have an obligation to provide it.,” said Citro.

He described the following as being foundational in a rights-based framework:

  1. Individual Entitlements (rights to life, health and to benefit from scientific progress)
  2. Individual Freedoms and Protections (non-discrimination, privacy/confidentiality, torture, informed consent, liberty/movement)
  3. Rights Related to Prevention (housing, food/nutrition, water/sanitation)

Citro then cited a number of international cases where lawsuits have been used to fight for the rights of people with TB, and where legislation has been introduced (in Peru) to confirm the human right to accessible treatment and prevention, the right to be free of discrimination, and the right to information about TB services.

“People with TB have a right to be free from discrimination, they have a right to access information – which is also critical – they have a right to privacy, there is a right to receive nutritional and other kinds of support and if they are patients with XDR-TB they have a right to receive treatment at home or in a treatment shelter,” he said.

“We have some good cases, we have one good law but we have a lot of work to do to develop and promote a ‘human rights-based approach’ to TB in the courts and also through legislation,” he concluded.

Keynote speech: TB and HIV: A call to action

So why isn’t the HIV community fully mobilized to fight TB?

As Stephen Lewis, co-director of AIDS-Free World, pointed out in his keynote address, TB remains neglected — and the UN body in charge of the fight against AIDS hardly mentions TB in its recent reports and strategies.

The TB world, however, has woken up to the need to set more aggressive targets, with new strategies to actually end TB by 2035, but as Lewis pointed out, the Global Plan to End TB will require $13 billion a year in funding — but again the current funding levels are one-half of that.

He argued that the HIV world was not being adequately supportive.

“I received, this morning, a copy of UNAIDS’ latest report, just released, titled ‘90-90-90: On the Right Track Towards the Global Target’. In 54 pages of text, TB is mentioned three times, entirely in passing, as though it were utterly inconsequential,” he said.

“This room is filled with principled advocates and activists who would move heaven and earth to defeat this disease, but the collective efforts are compromised by indifference in high places, by an absence of political leadership, and by strangulated shortfalls in resources.

He said that TB needs a stronger voice in the UN agencies — something on a similar level as UNAIDS — perhaps the UNDP. TB also needs new lines of dedicated funding — it is far too dependent upon the Global Fund. He urged the TB community to approach the World Bank, headed by Jim Kim who has worked in TB, to discuss, concretely, innovative forms of financing to fund tuberculosis.

Breakout Session 9: Diagnostics and Biomarkers

Chairs:

Robert Wallis (The Aurum Institute)

Graeme Meintjes (University of Cape Town)

Lessons from the rollout of Xpert MTB/RIF in South Africa

Wendy Stevens of South Africa’s National Health Laboratory Service (NHLS), described how the country successfully rolled the Xpert MTB/RIF test out to become the country’s first-line TB diagnostic, replacing the use of smear-microscopy which had failed to be sensitive enough in the country’s population living with HIV.

Stevens stressed that key to success of the programme was high level political commitment from South Africa’s Minister of Health, Dr Aaron Motsoaledi. The NHLS also benefitted from the experience it had gained in rapidly scaling up laboratory services in response to the country’s HIV epidemic. They developed a national plan to roll out the test in stages guided by geographical information system mapping based on estimated number of tests and patients per site. It was an effort that required a multidisciplinary team including donors, the Treasury, NHLS staff, engineers, costing and modelling experts and advocates. Costing, modeling, forecasting, procurement models led to a full investment case for HIV and TB together.

However, the effort paid off by significantly improving TB diagnosis and reduced time to treatment initiation for those with MDR-TB — although a clinical impact study showed that it had not significantly shortened the time to treatment for people with drug sensitive TB. Stevens believes that this was because the study occurred too soon after the introduction of the test to see its full impact on clinical practice. In addition, the study also revealed some shortcomings in the health system (adherence of health facility staff to the full diagnostic algorithm was poor — followed in only about 50% of the cases). Also, since the equipment for the test has been too expensive to install at the point of care — results cannot be provided to tested individuals while they wait. Rather, specimens are sent to the nearest NHLS site for testing and results returned to the clinic — which then must track down people who have been tested to give them their results and initiate them on treatment if necessary. The NHLS has been looking into ways to expedite the communication of results, however.

Nevertheless, in those with rifampicin resistance, the median time to treatment with an appropriate regimen was reduced from 73 down to 7 days. Rifampicin resistance positivity in the country remains stable at around 6%.

After the clinical impact study, the country introduced the use of the test for paediatric and extra-pulmonary TB. South Africa is now rolling out testing to those in the correctional facilities and with mobile testing facilities for peri-mining communities — though undirected testing yield has been low. Contact tracing and directing the service to hot spots may be more cost-effective.

Stevens believes the TB, MDR and XDR-TB treatment algorithm is still too complex and there is a need to move beyond culture labs which are expensive and present biosafety risks. Looking ahead, the next generation of Xpert cartridge — Xpert-Ultra promises sensitivity that could reduce the need for culture dramatically. In addition, there are moves towards developing a polyvalent platform — which could perform HIV PCR at birth testing, HIV viral load and TB sputum and stool testing using the same modules.

“Among the lessons learned: the rollout disrupted every aspect of the National TB programme — and exposed strengths and weaknesses,” said Stevens. “It also defined a sophisticated model for diagnostics implementation.”

RePORT International: Advancing TB Research Using a Common Platform across Global Networks

Professor Carol Dukes Hamilton of Duke University who works with FHI 360 is the Principal Investigator and Director of the Regional Prospective Observational Research in Tuberculosis (RePORT) International. RePORT is a common platform for TB research across global networks — with the participation of US National Institutes of Health (NIH), Division of AIDS (DAIDS) and governments of India, Brazil, Indonesia and South Africa (and potentially China and the Philippines). Its goals are to increase the speed of progress toward TB elimination and to increase capacity of scientists and institutions in high-burden settings to do high quality clinical research.

Among its expected results: the platform should allow for the collection of hundreds of key and sometimes rare, informative endpoints on biomarkers, treatment relapse, the evolution of resistance and progression from exposure to active disease, etc. It will allow for longitudinal data to be collected on key, poorly studied populations, including children and pregnant women. The common platform will lead to standardization of definitions, data, and specimen collection — which will allow for data to be shared and compared across sites. It will create local owned repositories of samples linked to data for local research, and build research infrastructure and experience.

The research will start with observational studies and move onto randomized controlled trials.

Biomarkers with diagnostic accuracy in persons suspected for active TB

Jayne Sutherland (MRC, Gambia)

&

Novel biomarkers for monitoring treatment response

Gerhard Walzl (Stellenbosch University)

There is a need for further research and development of new diagnostic tests. These two presentations described research on the biomarkers of TB. Currently there are ongoing studies on various clinical biomarkers that can be used for the diagnosis of TB as well as for monitoring of treatment duration.

Parallel Session 5 (Abstracts): Community Engagement and Innovations

Co-chair of the session, Erica Lessem of TAG opened this final community session of TB2016 with a brief complaint.

“I wish that [the community presentations] weren’t in a separate room here, I think that this would be really important for everybody in the conference to be hearing. I think too often the community initiatives tend to get siloed. Next year or next time we can ask to actually be front-centred and have some more of the community speakers on the plenaries.”

Integrating HIV and TB interventions in the community to increase TB and HIV case detection, treatment adherence and TB treatment completion in Malawi and Zimbabwe

“The HIV and TB integration that is happening is happening mostly at the clinic level but at the community level you then have the HIV worker doing his own bit of work and you have the tuberculosis worker doing his own bit of work, and never the two shall meet,” said Sameer Sah, the International Programme Director at TB Alert UK.

His organization, which has been working on TB programmes in the UK and internationally, has more recently set up integrated community-based TB/HIV programmes in Malawi and Zimbabwe partnering with a network of national organizations known locally as Humana, People to People (DAPP or ADPP) with decades of experience working on HIV testing and care in communities. Their joint work has been funded through the UK Department for International Development (DFID) and UK Comic Relief, for Malawi and Zimbabwe. At the same time, TB Alert is the technical partner of ADPP in Mozambique – which is the sub-recipient for eight countries in the ‘TB in the Mining Sector Regional Programme (TIMS)’ proposal.

Sah described projects that have grown to meet the needs of the communities where they have been working.

The projects started off using a door-to-door approach in which a field officer or the community volunteers go door-to-door screening people for TB, collecting sputum (and when necessary providing contact tracing), while at the same visit providing HIV rapid testing and counselling in the countries that permit workers from community based organisations to provide that service (at present, Zimbabwe disallows these workers).

As a rule, this work requires close coordination with district health authorities — however, they noted that in these most resource poor settings, the impact of their efforts could be limited by weaknesses in the local health system.

“We realized that we didn’t have the support in terms of the diagnostic services. In resource-poor countries sometimes the distance is too much, sometimes the microscopes and CD4 machines have broken down and they are not being serviced, sometimes there is a training gap because people are trained but then they don’t get refresher training,” he said.

So in subsequent projects, they began by supporting the local health department by servicing all of the CD4 machines and microscopes, providing training for new microscopists, training TB coordinators in monitoring and evaluation, training the TB nurses and HIV nurses, and supporting the creation of newly combined HIV/TB/MCH registers.

In other projects, they noted that some of the people on TB treatment had extremely low BMIs, which made it difficult if not impossible to recover from their illness. So they set up programmes to provide food and nutritional support — with innovations including cooking demonstrations and community gardens.

In other settings, they found other community based organisations doing excellent HIV treatment adherence work, so they trained them on TB so that family-based counselling and treatment adherence was for both HIV and tuberculosis. Whenever possible, their programmes try to set up a trio composed of a family member and someone else the patient identifies to provide treatment support, help them make clinic appointments or to collect their medicine, and help with meal preparation if necessary.

The programmes have engaged in operational research to evaluate whether door-to-door versus group-based approaches work better for service provision — and concluded that each approach had strengths and weaknesses and that a combined approach tailored to each setting would work best.

Results? In their longest established project in Mulanje, Malawi over the last two years., they have reduced losses to follow-up and contributed greatly to case detection — 46.7% of the TB cases in the district have been identified by community health workers and volunteers.

In the future, they hope to partner with other NGOs and CSOs and share their lessons learned with national TB programmes and others — while redoubling efforts to collect data to document their work and perform more operational research to determine which approaches and interventions have the greatest impact.

Anti-corruption actions of patients of Ukraine increase access to TB treatment for additionally more than 28,000 patients in 2016

Olha Stefanyshyn of ‘Patients of Ukraine’ gave a presentation on activism to address shortages of essential TB medications. Each year, there are 30,000 new (previously untreated) TB cases in Ukraine — and many more retreatment cases with one of the world’s highest burdens of drug-resistant TB. Annually, close to 6,000 people die of TB in the country. The procurement process is corrupt and has led to extremely high prices being paid for TB medications.

In response, activists developed a plan to transfer state MoH procurements to international organizations, UN Agencies (primarily UNDP), to develop legislation to change the procurement process and lobby for the law’s success. In the meantime, they mobilized the community, held a series of press briefings and round-tables and several high profile actions.

Their work continues, but so far UNDP procurement has increased access to TB treatment for additionally more than 45 000 patients in 2016. 

Social support to TB patients by forming self help groups (SHGs) and facilitating skills development for sustainable livelihoods

Dr Archana Trivedi works as technical officer at the Union’s Southeast Asia office and is managing a project funded by ‘Lilly’/MDR-TB Partnership to systematically involve private health care providers in delivering effective and quality TB services in India.

She described a project to support people diagnosed with TB in underserved areas of Khunti district, home to more than half a million people, in the eastern state of Jharkhand. The region is poor and isolated — with at least 100,000 people living below India’s poverty line.

In areas of the district identified to have low symptomatic referrals, rural health care providers (RHCPs) were trained to screen people for TB symptoms, refer them for diagnosis and provide treatment support. One of the project’s chief goals was to support people diagnosed with TB to form self help groups (SHGs) where they would be given training on skills development to generate income for sustainable likelihoods, while at the same time providing peer support to each other to adhere to TB treatment.

A needs assessment was performed on people diagnosed with TB to identify candidates for the SHGs on the basis of economic and health status as well as their willingness for skills training. Groups were formed and trained in income generation projects such as incense making as well as marketing. SHGs are provided with an initial grant of materials. The sales generate enough income for the project to become self-sustaining, and SHG members share the remaining profit — all while supporting each other to adhere to their treatment.

The project continues to explore new innovations for SHG-support.

Community advisory boards on repeat: what’s missing from TB clinical trials protocols

Lindsay McKenna of the Treatment Action Group, New York, United States gave a presentation on some of the current shortcomings of TB clinical trials protocols (in short lack of adequate community engagement). This has led to routine problems:

  • No plans for results dissemination
  • No plans for post-trial access
  • Inadequate composition (or even presence) of control arm
  • Use of stigmatizing language in study documents
  • Lack of appropriate inclusion of key affected groups

“All TB trials should engage communities in protocol development to ensure that research better reflects their needs and priorities,” said McKenna. This could be addressed by the inclusion of a CAB member on the protocol team or trial steering group, and planning for time for the CAB to review protocols and provide feedback. 

Closing Session: Next Steps and Call to Action

Chairs:

Haileyesus Getahun (WHO)

“It is clear that we’ve come a long way. The fact that we’re now having TB2016 as an integral pre-conference of an IAS conference is a clear indication of that progress. However, we are still lagging behind,” said WHO’s Haileyesus Getahun towards the close of the meeting. “Eliminating TB cases in people living with HIV should be the starting point. TB is a curable disease, and it is unacceptable, in 2016, that a person living with HIV is dying of TB.”

Closing keynote speech: Trevor Mundel

Trevor Mundel is President of Global Health at the Gates Foundation, which has for the last several years been one of the primary funders in TB research — in the discovery of drugs, diagnostics and vaccine work but also in delivery partnering with the governments of India, China and South Africa. Many big questions remain, according to Mundel.

“I was really surprised about four years ago that we had two big, quite singular failures in the TB community in the R&D front. One was the MVA85 vaccine programme that many people were hopeful about, and I certainly felt [hopeful that it would show something that could be built on], and the other was the REMOX programme could shorten the treatment course in TB to four months. And that didn’t work out. And that really set us thinking,” he said.

He was describing a shift at the foundation to alter their funding strategy to defeat TB.

“I got together with [Dr] Gilla Kaplan… and we thought that we need to really go back to the drawing board to think about what we are doing in R&D in TB. We needed to get back to the pathobiology of TB and to really understand that. We needed to understand that basic science,” he said.

This new strategy has already begun to bear fruit, in terms of new treatment targets, approaches in vaccinology, and advances in the understanding of latency — as much of the scientific content of the TB2016 demonstrated.

Panel discussion: Leadership in the fight to end TB

Moderator: Lucica Ditiu, STOP TB Partnership

To close the meeting, Lucica Ditiu introduced a panel of parliamentarian representatives from the African TB Caucus:

Stephen Mule of Kenya:

Fatima Zohra Bourouis of Algeria

Pierre Falmbeau Ngayap: Cameroon

David Emmanuel: Nigeria

Ruth Labode: Zimbabwe

Each shared their commitments to raise the profile of TB in their countries’ governments and within their regions. They also committed to work for legislation to increase funding for TB and to address the drivers of TB in their population.

In retrospect, their leadership would provide an example to other national programs that may ultimately fruition with upcoming UN General Assembly High-Level Meeting on Ending TB, to be held on 26 September 2018 in New York. This will be the first-ever high-level meeting on tuberculosis (TB) to accelerate efforts in ending TB and reach all affected people with prevention and care. The theme of the meeting is “United to end tuberculosis: an urgent global response to a global epidemic” — which we hope to be able to cover either on this site, or on some other medical news website.

 

 

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