Rheumatic heart disease back in the limelight

Abstract

Rheumatic heart disease is drawing renewed attention from the health community and from the low-income countries most burdened by the disease. John Maurice reports. In the USA, UK, and most other high-income countries, a sore throat is nearly always just that: a sore throat. In many low-income countries, though, it is far more likely to be the harbinger of a disease—rheumatic heart disease—that kills at least 233 000 people every year. The culprit is the group A streptococcus, with its tendency, given the right conditions, to trigger a pathogenic sequence starting with pharyngitis (strep throat), followed, in a small proportion of cases, by acute rheumatic fever, and ending, in about 60% of rheumatic fever cases, with the life-threatening heart valve damage characteristic of rheumatic heart disease. The right conditions are those of low-income countries where children and young adults, the main victims of streptococcus A, live in overcrowded housing and lack adequate access to health care. Between 15 million and 20 million people are believed to have rheumatic heart disease and nearly 300 000 new cases occur every year, mostly in sub-Saharan Africa, central Asia, the Pacific Islands, and among the indigenous populations of Australia and New Zealand. The problem, though, as most cardiologists see it, is that despite the toll of death, disease, and disability that the disorder causes, and despite the fact that, if caught in time, it can be easily and inexpensively prevented and cured by simple penicillin treatment, little or nothing is being done to lower its burden on the developing world. One reason often invoked is that by the 1970s, the disease had largely dropped out of mind and out of sight in the wealthy countries, where efficient health services, improved living conditions, and the wide use of penicillin had virtually stamped it out. Another reason is that by the end of the past century other diseases, such as HIV/AIDS, malaria, and tuberculosis, were pushing rheumatic heart disease off the radar of the international health community. Bongani Mayosi, who is head of the Department of Medicine at the Faculty of Health Science at the University of Cape Town, South Africa, and President of the Pan African Society of Cardiology, compares rheumatic heart disease to cancer: “A growing number of cancers are triggered by an infectious organism and become chronic non-communicable diseases, just like rheumatic heart disease”, he says. “The big difference is that everyone agrees that cancer is a major chronic condition to be tackled. Why is rheumatic heart disease not getting the same attention? Because it is a disease of the bottom billion of the poorest people in the world—one of the most neglected of the neglected diseases.” The past decade, however, has seen a resurgence of interest in rheumatic heart disease. Srinath Reddy, president of the World Heart Federation, is upbeat: “Rheumatic heart disease is a marker of inequity, of social injustice, and of neglect of vast populations living in poverty. In recent years, advocacy groups, including the World Heart Federation, have put greater efforts into rectifying this inequity.” Rectifying the neglect, in his view, calls for a commitment by concerned countries to a strategy based on early detection of strep throat in children, early treatment with penicillin to prevent rheumatic fever, and long-term treatment with benzathine penicillin G for children already with, or with a history of, rheumatic fever. “The streptococcus”, says Reddy, “is still exquisitely sensitive to penicillin. So we have in our hands one of the oldest antibiotics that still works against one of the oldest heart diseases.” For most low-income or middle-income countries, he says, the strategy must include training of health workers and schoolteachers to recognise strep throat and for health workers to administer the treatment. To date, at least 20 countries, mostly in Africa, have signed on to this strategy and to the World Heart Federation's campaign to cut, by 25% by the year 2025, the number of premature deaths caused by the disease in people younger than 25 years of age. Reddy is also encouraged by the renewed commitment of WHO to tackling the disease. The Rheumatic Heart Disease Programme, which WHO set up in 1984 was subsumed in 2001 into the organisation's non-communicable disease (NCD) initiative. “Putting rheumatic heart disease into our NCD programme and integrating it with primary health care NCD interventions really strengthened our efforts to control the disease”, says Shanthi Mendis, who heads the NCD programme. “Our main objective is to strengthen health systems so that they can deliver the penicillin needed to prevent rheumatic fever. Our 2013 NCD action plan also focuses on alleviating poverty. With rheumatic heart disease the medical approach is not enough. Poverty is the basic problem.” A key player in the renewed focus on rheumatic heart disease is Jonathan Carapetis, director of the Telethon Institute for Child Health Research in Perth, WA, and a member of the World Heart Federation's Working Group on Rheumatic Heart Disease. “Right now I'm very excited about the current developments taking place around the world”, he tells The Lancet. “I'm particularly heartened by the resurgence of interest being shown by developing-country advocates. We still need to get traction with some of the international organisations like WHO and the Bill & Melinda Gates Foundation but I'm sure that will come. We face a big challenge, though. We now know a lot about how to get rheumatic heart disease under control but the challenge is converting that knowledge into action.” Another key player is the University of Cape Town's Bongani Mayosi, who, together with Salim Yusuf from Canada and others, is creating an international rheumatic heart disease registry which aims to collect data on a multitude of diagnostic, therapeutic, and pathological details in patients attending care centres in Asia, Latin America, the Middle East, Eastern Europe, and the Pacific. “Our objective”, he says, “is to have enough evidence to convince governments to invest in battling the disease wherever it exists and to ensure that every child in every village has access to penicillin. The real breakthrough though would be a vaccine against the streptococcus A, but that's a long way off.” It may not be such a long way off. The search for a vaccine began in the 1950s and has to date produced about 20 different products, of which none has reached clinical use. Until recently, though, progress had been curbed by several hurdles. One was concern by researchers that a vaccine might actually cause rheumatic fever, which develops through an autoimmune mechanism. The fear was that the antigens used in a vaccine might induce a reaction against the same antigens present in the heart and other tissues. Another hurdle has been the plethora of different strains of group A streptococcus—130 by the latest count. Yet another is concern by the pharmaceutical industry that a vaccine to be used mainly in low-income countries would not be commercially viable. Current developments raise hopes of disproving this concern. For one thing, streptococcus A has several strings to its bow that may enhance its commercial attractiveness. In addition to sore throat and rheumatic fever it can cause a spectrum of other severe ailments, including pneumonia, bacteraemia, necrotising fasciitis, streptococcal toxic shock syndrome, arthritis, and glomerulonephritis. Altogether, these conditions bring the estimated annual number of deaths attributable to this bacterium to more than 500 000. Currently, the list of potential vaccines is headed by four candidates, of which one is in early clinical trials and a second is expected to be by the end of this year. Australia's Jonathan Carapetis, a leading participant in the quest for a vaccine, is optimistic: “We have a much better understanding today of the pathogenesis of the disease and we've successfully addressed the safety issues. We're also starting to overcome some of the commercial barriers.” A major boost to this vaccine work has recently come from an announcement this February that the Prime Ministers of Australia and New Zealand have agreed to provide NZ$3 million (£1 500 000) over 2 years to speed the search for a vaccine. Part of the so-called Trans-Tasman Initiative, this support, which will possibly be followed by far greater funding further down the track, should allow fast-track development of at least one candidate vaccine into clinical trials and thus help to end the strangle-hold of rheumatic fever and rheumatic heart disease on most of the world's poorest countries.