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Eliminating rheumatic heart disease in Nepal

Rheumatic heart disease is the most common acquired heart disease in children and adolescents, and is disproportionately prevalent in marginalised communities across sub-Saharan Africa, South Asia, and the Pacific Islands.


Prof Thomas Pilgrim, Dr Prahlad Karki, and colleagues at BP Koirala Institute of Health Sciences in Nepal report on the successes,  costs, and challenges of detecting early stages of rheumatic heart disease among children with echocardiographic screening followed by timely treatment with antibiotic prevention.


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Hello and welcome to ResearchPod. Thank you for listening and joining us for this episode!


Today we shall be focusing on how a novel approach can solve a long-standing problem of a serious disease: detecting early stages of rheumatic heart disease among children with echocardiographic screening followed by timely treatment with antibiotic prevention.


Rheumatic heart disease is the most common acquired heart disease in children and adolescents. It often goes undetected during childhood , only to manifest later on in life with advanced stages of disease. According to recent figures, there are over 33 million current cases of rheumatic heart disease all over the world, accounting for the majority of deaths from valvular heart disease worldwide.


Scientists Dr Prahlad Karki, and colleagues from the B.P. Koirala Institute of Health Sciences in Nepal highlight that “the burden of rheumatic heart disease is disproportionately prevalent in marginalised communities across sub-Saharan Africa, South Asia, and the Pacific Islands, where endemic patterns of disease prevail”.


Acute rheumatic fever, caused by an untreated bacterial infection, gradually starts affecting the connective tissues, and often causes inflammation in the heart valves which then become scarred. The scarring results in leaking or narrowing of the valve. This then impedes the heart valve to function properly, and causes heart failure or cerebrovascular events if left untreated which can eventually lead to premature death.


To prevent this, secondary antibiotic prophylaxis is given to children after an episode of acute rheumatic fever to prevent repeated bouts of infection and stop the disease from progressing. Often what happens, though, is that affected individuals may show little symptoms of rheumatic fever, or no symptoms at all. This leads to so-called “latent rheumatic heart disease”. This means that children develop rheumatic heart disease without documentation of a prior episode of rheumatic fever.


Rheumatic heart disease progresses insidiously. At the outset, children have no symptoms of valve dysfunction and only rarely have a heart murmur, despite changes in the appearance and the function of the heart valves when examined by ultrasound. For example, a 2014 study discovered that among 21 out of 1000 children that suffered from the disease, only 3 out of 1000 had a heart murmur. This makes the disease, what is called, “clinically silent”. The silent stage of the disease provides a window of opportunity for early intervention, before symptoms of valvular dysfunction develop.


“Now we need to take bold action to accelerate the prevention, control, and improve care for patients living with this devastating disease.” – says Prof Karen Sliwa, the president of the World Heart Foundation, in an interview about researching the rheumatic heart disease last year.


Dr Karki and his colleagues have recently published results from a cluster randomized trial exploring whether echocardiographic screening would be an effective strategy for detecting rheumatic heart disease at an early, clinically silent stage. This would help doctors identify patients needing secondary antibiotic prophylaxis on time, and eventually prevent the disease from progressing and spreading.


The researchers approached 35 random schools from different social backgrounds that corresponded to the distribution of all children in the education system in Nepal – a mix of schools in rural and urban environments as well as both public and private schools – to remove any socioeconomic and health status biases that might influence the results.


Children were eligible to participate if they were between 5 and 12 years old at the time of enrolment. Participating schools were then sorted into experimental and control sets.


In the experimental set, the groups of children underwent a systematic echocardiographic examination. Those who were found to have changes in the appearance or the function of heart valves consistent with rheumatic heart disease, were then treated with antibiotics. On the other hand, in the control set up the children were not screened.


Four years later, when the children were between 9 and 16 years of age, the groups from both sets were exposed to a follow-up echocardiographic screening to track their development and assess the prevalence of rheumatic heart disease in both groups.


Upon this follow-up screening, the children were diagnosed with either definitive or borderline rheumatic heart disease, depending on the appearance and the function of the heart valves away from the normal state. In the follow-up screening, there was a lower prevalence of the disease among children in the experimental group, compared to the control group.


The estimated disease occurrence across the experimental groups was found to be 3.8 per 1000 children. This means that out of 1000 children, only just about 4 were diagnosed with rheumatic heart disease on their follow-up screening, after they had already been exposed to previous echocardiography and antibiotic treatment if needed.


In the meantime, in the control groups, where no previous screening was done, the prevalence was  10.8 per 1000 children. In other words, the combination of echocardiographic screening followed by antibiotic treatment in children with rheumatic heart disease substantially reduces the commonness of the disease across individuals.


The effect of screening emerged even more importantly in a comparison across time. In the experimental group, prevalence of rheumatic heart disease at baseline was 12.9 per 1000 children and decreased to 3.8 per 1000 children after implementation of systematic screening and prophylaxis.


Overall, scientists tracked a 71% decrease in the cases of rheumatic heart disease after implementing a strategy of early detection of clinically silent valvular lesions by means of echocardiography and timely initiation of secondary antibiotic prophylaxis in children found to have early stages of rheumatic heart disease.


This means that not only the rheumatic heart disease can be discovered in early stages, but also that, if treated correctly, damage can be slowed, or even reversed.  Crucially, the neither the types of schools the children attended, nor sex or age of the children made a difference on the effectiveness of this approach. Essentially, it did not matter where a child came from, or what school they went to – every child could benefit from the intervention.


Another important aspect about this whole approach is that it can be implemented fairly cheaply. For instance, a 10-year systematic screening plan for all of Nepal could cost on average only $4.67 per examined child. This could provide a brilliant opportunity for detecting the rheumatic heart disease in the poorer regions where it accounts for substantial proportion of morbidity and mortality. It can be applied to a larger portion of the population as well. However, logistical challenges would need to be addressed in order to justify and monitor adherence to a secondary antibiotic course, and longitudinal follow-up of children with latent rheumatic heart disease.


The research team acknowledges a few limitations in their work. Not as many school groups were tested as planned with drop out groups limiting the amount of data gathered. Further administrative and resource challenges they faced, the team worked through two major earthquakes and a period of civil unrest during the course of the study. Understandably, this led to some delays in the follow-up screenings and lost to follow-up of children originally enrolled.


Also, despite trying to mimic the natural social distribution of the population with the types of schools chosen for the study, the scientists did not include children who dropped out of school early – in Nepal this is a considerable part of the population.


Overall, screening programs are considered to be successful if implemented more broadly. What we can take from this study is that echocardiographic screening gives a reliable diagnosis of the presence of early stages of rheumatic heart disease in children. In fact, rheumatic heart disease can be detected at a stage when damage to the heart valves is still reversible in a significant proportion of children. This can be used to then prescribe antibiotic treatment earlier, which can have greater recovery rates.  


Prof Thomas Pilgrim, senior author of the study concludes that “The results support the hypothesis that early detection of clinically silent stages of rheumatic heart disease and timely initiation of secondary antibiotic prophylaxis are an effective approach to control rheumatic heart disease in endemic regions.”


Clinical studies like these are crucial for emphasising the importance of using contemporary approaches to prevent heart diseases and heart failure, despite some of the challenges the researchers meet during the trials.


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