Interview: Mario Raviglione, Director WHO Stop TB Department



Mario Raviglione, Director of WHO Stop TB Department

GESPAM had the pleasure to interview Mr. Mario Raviglione as Director of the Stop Tuberculosis (TB) Department at the World Health Organization (WHO) since 2003.

Mario Raviglione joined WHO in 1991 to work on TB/HIV research and TB epidemiology in Europe. He contributed to the development of the DOTS (Directly Observed Treatment Short course) strategy in 1994, and set up the global drug-resistance surveillance project (1994) and the global TB surveillance & monitoring system (1995). In his first decade at WHO, he also worked on experimental regimens for treatment of latent infection in the mouse model (early 1990s), described the feasibility of preventive therapy in Africa (1995), first reported the TB control crisis in Eastern Europe (1993), and co-developed estimates and projections of the global TB epidemic. Between 1999 and 2003, Raviglione  was Coordinator for Strategy and Operations globally, taking charge particularly of surveillance and programme monitoring; operational research; TB/HIV and multi drug-resistant TB responses; and DOTS expansion worldwide.
Currently, as Stop TB Department Director, he is responsible for setting norms, policies and standards on global TB control, coordinating technical support, monitoring the global situation, and developing innovative interventions through translation of new evidence into policies & practice and through addressing system challenges such as community and private sector engagement.
He has published over 250 articles and chapters on the topics of infectious diseases, HIV/AIDS and TB in the most influential health journals and books, including in the last five editions of the prestigious Harrison's Principles of Internal Medicine. He is among the top 10 most cited authors in the TB field.
Mario Raviglione graduated from the University of Turin in Italy in 1980, and trained in internal medicine and infectious diseases in New York (where he was Chief Medical Resident at Cabrini's Medical Centre) and Boston, where he was appointed an AIDS Clinical Research Fellow at Beth Israel Hospital, Harvard Medical School. In 2005, he received the Princess Chichibu TB Global Award for his achievements in TB control. In 2009 he was nominated Fellow of the Royal Academy of Physicians (F.R.C.P., London, UK). In 2010 he received the Wolfheze 20 Year Jubilee Award for his contributions to modern TB control practices in Europe. As a leading expert in TB, Mario Raviglione  has served as a visiting professor at Johns Hopkins and Geneva Universities. He has been visiting professor at the medical schools of the University of Brescia and the University of Modena & Reggio Emilia in Italy, as well as at the Faculty of Science of the University of Pavia.

Background information from WHO Global Tuberculosis Report 2012  

... the global burden of TB remains enormous. In 2011, there were an estimated 8.7 million new cases of TB (13% co-infected with HIV) and 1.4 million people died from TB, including almost one million deaths among HIV-negative individuals and 430 000 among people who were HIV-positive....Globally, 40% of TB patients had a documented HIV test result... Almost 80% of TB cases among people living with HIV reside in Africa. 
....There were an estimated 0.5 million cases [of TB] and 64 000 deaths among children in 2011....
 The burden of TB is highest in Asia and Africa. India and China together account for almost 40% of the world'€™s TB cases. About 60% of cases are in the South-East Asia and Western Pacific regions. The African Region has 24% of the world'€™s cases, and the highest rates of cases and deaths per capita. Worldwide, 3.7% of new cases and 20% of previously treated cases were estimated to have MDR (multidrug resistant)-TB. India, China, the Russian Federation and South Africa have almost 60% of the world'€™s cases of MDR-TB. The highest proportions of TB patients with MDR-TB are in eastern Europe and central Asia. ...Extensively drug-resistant TB, or XDR-TB, has been reported by 84 countries; the average proportion of MDRTB cases with XDR-TB is 9.0%..... 

GESPAM:  Mr. Raviglione, the WHO-developed Stop TB Strategy aims to dramatically reduce the global burden of tuberculosis by 2015 by ensuring all TB patients, including for example, those co-infected with HIV and those with drug-resistant TB, benefit from universal access to high-quality diagnosis and patient-centered treatment. Which progress so far?

Mario Raviglione: The implementation of DOTS, later enhanced to the Stop TB Strategy, began in the mid-1990s. At that time, the global targets were to achieve everywhere 70% case detection and 85% cure rate. The case detection is today at around 65%, while the treatment success has been consistently above 85% over a number of years.  This means that despite a major increase in detecting cases worldwide, still one third of the estimated cases are not in the system. More importantly, impact targets have been achieved. The TB-related Millennium Development Goal of reversing the incidence trend has been achieved years ago and the other two international targets of halving prevalence and mortality in 2015 compared to 1990 are on track globally, although not in Africa and Europe. Overall, there is huge progress compared to the disastrous situation of the mid-1990s. However, with still 1.4 million deaths and 8.7 million cases every year, there is no room for complacency and TB remains a major killer worldwide.

GESPAM: MDR and XDR-TB:  please, add information about definitions, trends and latest treatment results.

Mario Raviglione: WHO defines MDR-TB as a form of tuberculosis that is resistant to at least isoniazid and rifampicin. Extensively drug-resistant TB (XDR-TB) is defined as MDR-TB + additional resistance to at least any fluoroquinolone and any of the 3 injectable agents. MDR-TB is estimated to affect nearly half a million cases every year, but we do not know exactly the figure since only 4% of TB patients worldwide today are exposed to drug susceptibility testing. If all cases detected had such testing, at least 310,000 patients would be detected. In reality, only 60,000 were reported in 2011 and the treatment success today is less than 50%. This means that these patients are likely to die frequently and spread the resistant strains to their communities.  Although we do not know global trends, we are aware that in some settings, MDR-TB is declining while in others, especially countries with an overlapping HIV epidemic, MDR-TB is on the increase. Major concerns are in the countries of the former Soviet Union where MDR-TB and XDR-TB are widespread.

GESPAM: The Stop TB Department functions include facilitating and engaging in partnerships for TB action. As such, what about factual collaboration with, and contributions from counterparts like the Global Fund, the European Union, BRICS countries, and the Gates Foundation, among others?

Mario Raviglione: WHO works closely with the Global Fund, especially in the past few months when we have been involved much more strategically than in the past as part also of a newly established TB committee that helps the GF secretariat to strategize on TB. It is in the common interest to collaborate since WHO has the mandate to support technically our Member States while the Global Fund is a financing mechanism providing the vast majority of external resources for TB control. With the European Union, it has not proven easy to develop a common agenda, and there isn’€™t one today. This may also be due to the lack of prioritization of tuberculosis, a killer of 4,000 patients every day, by most European countries. Paradoxically, the US Government is much more concerned about the threat of MDR-TB and XDR-TB coming from the EU neighboring countries that the EU itself. We work instead very closely with the BRICS. This year I visited China, India and South Africa, noticing how concerned and more and more committed they are about the TB problem. We also work closely with Brazil on their revolutionary social protection mechanism, truly providing access to the poorest, that we intend to further prioritize and disseminate. We are in constant contact with the Gates Foundation as they provide some support to our Department, although 90% of their investment in TB are focused on research.

GESPAM: As per the Global Tuberculosis Report 2012 mentioned before…..there are critical funding gaps for TB care and control. Between 2013 and 2015 up to US$ 8 billion per year is needed in low- and middle-income countries, with a funding gap of up to US$ 3 billion per year. International donor funding is especially critical to sustain recent gains and make further progress in 35 low-income countries (25 in Africa), where donors provide more than 60% of current funding…..There are also critical funding gaps for research and development. US$ 2 billion per year is needed; the funding gap was US$ 1.4 billion in 2010.

Inherently, do you think revenues from a Financial Transaction Tax (a quorum for which was just reached in the European Union through “€œenhanced cooperation procedure”€, could be a resource to partly channel towards TB funding gaps?

Mario Raviglione: Funding gaps, in my philosophy, are not just a matter for international donors. I believe that sustainable development requires domestic commitment and investment. The BRICS now cover more than 95% of their financial needs, but low-income countries, especially in Africa, still rely largely on external resources and the Global Fund covers 90% of these resources. We must therefore support these countries with a plan for progressive take-over by the Governments themselves over the next few years. The financial transaction tax is one way. The problem is that tuberculosis is too often forgotten when it comes to benefit from such initiative. This is why financial gaps exist.

GESPAM: What about WHO role and position regarding cheap TB medicines rolled out by India for poor countries’€™ needs?

Mario Raviglione: WHO’€™s position is that medicines can come from anywhere as long as they are of proven quality. In tuberculosis and in infectious diseases in general, this is key, as poor quality antibiotics not only do not help patients but in fact help create drug resistance.

GESPAM: As per a recent MSF report….South Africa has one of the highest burdens of drug-resistant tuberculosis (DR-TB) worldwide, with a conservative estimate of 13,000 new cases emerging each year. A new drug, bedaquiline (formerly known as TMC207) now offers hope for these patients. Yet despite positive outcomes in early clinical trials and recent agreement for a fast-track regulatory review in the United States and compassionate use in several European countries where the DR-TB burden is comparably low, the drug is not yet made available for patients in desperate need in South Africa....

What do you think about MSF call that bedaquiline (TMC207) be prioritized for drug-resistant TB patients in South Africa?

Mario Raviglione: We are working towards policy recommendations for Member States on how to introduce this new drug rationally (a second one will likely come out in late 2013), starting with the crafting of a proper regimen where the new drug is not administered alone, else drug resistance will develop quickly. We are also developing broader recommendations on how to provide wide access through accredited physicians and institutions who guarantee rational use.  We have been working also with South Africa that has asked WHO for a technical opinion on the issue.  If everything works as foreseen, we should be able to provide rapid advice to all countries in early 2013.

GESPAM: Children are often overlooked or misdiagnosed in National TB Programmes, and few child-friendly TB medicines exist   How is WHO tackling the gap of appropriate TB paediatric formulations?

Mario Raviglione: Paediatric TB has been clearly neglected by all as an important part of the response to TB. For the first time, the WHO global report 2012 included very detailed estimates of the burden, speaking of some half a million new cases every year and of some 70,000 deaths. This is a very large burden. Recently, WHO re-visited the existing drug dosages for children and issues specific recommendations on the correct formulations of fixed-dose combinations for children. Not surprisingly, at the moment, the pharmaceutical industry is not yet producing the correct formulations. A lot of efforts have to be made to work on the appropriate procedures to obtain new paediatric formulations including pharmacokinetic studies. We have encountered some difficulties to pursue the appropriate direction but it looks like, thanks to potential new grants, we may be able to overcome the obstacles and provide the pharmaceutical industry with the guidance and the support necessary for drug companies to start producing the correct formulations as defined by WHO. I am optimistic that this will happen within the next few months.

GESPAM: Thank you Mr. Raviglione for your enlightening answers.