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Prevalence of rheumatic heart disease in African school-aged population: Extrapolation from echocardiography screening using the 2012 World Heart Federation Guidelines
International Journal of Cardiology 202 (2016) 238–239
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Prevalence of rheumatic heart disease in African school-aged population: Extrapolation from echocardiography screening using the 2012 World Heart Federation Guidelines Jacqueline Weinberg a, Andrea Beaton b, Twalib Aliku c, Peter Lwabi d, Craig Sable b a
Children's Hospital of Pittsburgh, Pittsburgh, PA, USA Children's National Health System, Washington, DC, USA c Gulu University, Gulu, Uganda d Uganda Heart Institute, Kampala, Uganda b
a r t i c l e
i n f o
Article history: Received 11 August 2015 Accepted 14 August 2015 Available online 12 September 2015
Determining the true burden of rheumatic heart disease (RHD) in sub-Saharan Africa is of upmost importance for disease prioritization and public health planning. The 2012 World Heart Federation (WHF) echocardiography criteria provide an evidence-based, standardized approach [1]. Ideally, RHD prevalence data would be collected across Africa, but this is unlikely to occur in the next 5 years. The first two studies in Africa to prospectively use WHF criteria provide a new and important opportunity to update the estimated burden of latent RHD in school-aged children throughout sub-Saharan Africa [2,3]. These studies reported a RHD prevalence of 40.2/1000 (10.9/1000 definite), 30.5/1000 (16.5/1000 definite) and 20.2/1000 (3.4/1,000 definite) in children in Uganda, Ethiopia and South Africa respectively. In this letter, we conduct a brief analysis, extrapolating data from these studies to 42 low-income and low-middle income countries in sub-Saharan Africa. We provide estimated ranges of definite and borderline RHD of school-aged children in these countries. Estimates for definite and borderline RHD are considered separately as there is greater confidence surrounding the significance of definite RHD; the implications of borderline RHD remain unclear. Data from South Africa (upper middle-income country) represents the most conservative estimate, while data from Uganda and Ethiopia (low-income countries) represents the likely upper-boundary of RHD prevalence. Methods and results: Of 50 sub-Saharan African countries, 30 are considered low-income (gross national income per capita (GNIPC) ≤ $1045) and 12 lower-middle income (GNIPC N$1045 and ≤$4125) nations, as defined by the World Bank (http://data.worldbank.org/news/ 2015-country-classifications). South Africa was also included, but estimates were based solely on South African prevalence data. The GNIPC and the poverty headcount ratio (% of population living on b$1.25/ day) are reported along with national population data (https://www. cia.gov/library/publications/the-world-factbook/index.html) for
http://dx.doi.org/10.1016/j.ijcard.2015.08.128 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
children aged 5–19 for included countries (Table 1). Prevalence ranges of RHD for each country were calculated by multiplying the population of school-aged children by prevalence from South Africa, Ethiopia, and Uganda [2,3]. The cumulative population of the 42 selected countries is 874.7 million persons, including an estimated 328.3 million children. Applying the conservative estimate of 3.4/1000 children with definite RHD (South Africa), there are at least 1.11 million children currently living with latent, definite RHD in these nations. Using the higher, and likely more reflective prevalence found in Uganda/Ethiopia (10.9–16.5/ 1000), there are between 3.56 and 5.42 million children with definite latent RHD. If we expand our estimates to include borderline RHD, then an additional 5.42–9.62 million children are currently affected — with total prevalence of latent RHD between 6.63 and 13.2 million children. The table provides detailed results for the 17 most populated countries (and South Africa). Data from the other 25 countries are combined for ease of display. Note that screening in Ethiopia showed higher estimates of definite than borderline RHD while South Africa and Uganda had more borderline RHD. Discussion: The 2004 World Health Organization (WHO) report and 2005 publication on the global burden of Group A Streptococcal Disease estimated the global prevalence of RHD to be 15.6 million [4,5]. This included approximately 1.01 million children in sub-Saharan Africa [5]. The 2013 Global Burden of Disease (GBD) study doubles this estimate of global RHD — 32.9 million persons [6]. The Data Representative Index (DRI) was only 18.6% for RHD for the period 2006–2013 [6], meaning that less than 20% of countries with a significant burden of disease had reliable incidence, prevalence and mortality data. This paucity of data is most pronounced in sub-Saharan Africa, likely contributing to a vast underestimation of the prevalence of RHD. Echocardiography screening of school-aged children has contributed to a better understanding of RHD prevalence [7–9]. The pooled prevalence in a 2014 meta-analysis by Rothenbuhler et al. [10] was 23.8/1,000, with prevalence in children in Senegal, Uganda and Mozambique of 5.4/1000, 14.9/1000 and 30.4/1000 respectively. These data pre-dated the 2012 WHF guidelines; there was considerable variability in echocardiography protocols and definitions used to classify RHD. Extrapolating data from WHF standardized echocardiographic screening, we estimate a prevalence of latent, but definite RHD in sub-
Correspondence
239
Table 1 Estimated RHD prevalence in low and lower middle income sub-Saharan African countries extrapolated from WHF echocardiography screening in Uganda, Ethiopia, and South Africa. South Africa is also included for reference. Range of estimate of definite RHD cases (thousands)
Range of estimate of borderline RHD cases (thousands)
Economic indicators
Country
Population estimate (millions)
Population 5–19 years (millions)
South Africa (prevalence 3.4/1000)
Uganda (prevalence 10.9/1000)
Ethiopia (prevalence 16.5/1000)
Ethiopia (prevalence 14.0/1000)
South Africa (prevalence 16.8/1000)
Uganda (prevalence 29.3/1000)
GNI per capita
PHR: % b $1.25 per day
South Africa Nigeria Ethiopia Congo Tanzania Kenya Uganda Sudan Ghana Mozambique Madagascar Cameroon Cote d'Ivoire Burkina Faso Niger Malawi Mali Zambia Other: 25 countries⁎ Total (millions)
48.4 177.2 96.6 77.4 49.6 45.0 35.9 35.5 25.8 24.7 23.2 23.1 22.8 18.4 17.5 17.4 16.5 14.6 168.1 874.7
13.2 65.9 36.8 29.4 19.0 16.7 14.4 13.2 8.7 9.9 8.3 8.6 8.1 7.0 7.3 6.5 6.5 5.7 61.2 328.3
44.9 224.1 125.0 99.9 64.7 56.6 49.0 44.9 29.5 33.6 28.3 29.1 27.5 23.9 24.7 22.3 22.3 19.4 210.8 1.11
N/A 718.6 400.8 320.4 207.5 181.6 156.9 144.0 94.7 107.7 90.8 93.4 88.2 76.5 79.1 71.3 71.3 62.3 675.8 3.56
N/A 1087.8 606.7 485.0 314.2 274.9 237.6 217.9 143.3 163.0 137.4 141.4 133.5 115.8 119.8 108.0 108.0 94.2 1023.0 5.42
N/A 923.0 514.8 411.5 266.6 233.2 201.6 184.9 121.6 138.3 116.6 120.0 113.3 98.3 101.6 91.6 91.6 80.0 868.0 4.60
221.9 1107.6 617.8 493.8 319.9 279.9 241.9 221.9 145.9 165.9 139.9 143.9 135.9 118.0 122.0 110.0 110.0 96.0 1041.6 5.52
N/A 1931.6 1077.4 861.2 557.9 488.1 421.9 387.0 254.5 289.4 244.1 251.0 237.1 205.7 212.7 191.8 191.8 167.4 1816.6 9.62
$7410 $2710 $470 $430 $860 $1160 $600 $1550 $1770 $610 $440 $1290 $1450 $750 $400 $270 $670 $1810
9 62 37 88 43 43 38 20 29 61 88 28 35 44 41 72 51 74
Abbreviations: GNI — Gross National Income; PHR — Poverty Headcount Ratio. ⁎ Other: Zimbabwe, Senegal, Rwanda, South Sudan, Guinea, Chad, Burundi, Somalia, Benin, Togo, Eritrea, Sierra Leone, Central African Republic, Republic of Congo, Liberia, Mauritania, The Gambia, Lesotho, Guinea-Bissau, Swaziland, Comoros, Western Sahara, Cabo Verde, Sao Tome & Principe, St. Helena, Ascension & Tristan da Cunha.
Saharan Africa to be 3.6 to 5.4 times greater than the 2004 WHO report [5] and likely double that in the GBD study [6]. Applying the premise that children in sub-Saharan Africa represent 6–7% of total global RHD burden [5], there may be 50–80 million persons currently affected with RHD worldwide. We acknowledge that the 2004 Group A Strep and GBD reports base RHD estimates on symptomatic RHD, while our prevalence data is based mainly on asymptomatic schoolchildren. Nonetheless, we are in agreement with Zuhlke and Steer that we need to change how we think about RHD, accepting a model that includes both symptomatic and latent disease [11]. Other factors contribute to even these numbers being an underestimate of disease burden. The high-risk group of children too poor or sick to attend school is not included. Previous studies have estimated a multiplication factor of between 5.5 and 7.2 to extrapolate school-aged prevalence data to adult populations [11]. If this is applied to our data, the prevalence of RHD in sub-Saharan Africa, alone, could exceed 30 million. We cannot account for children and adults with symptomatic or advanced RHD. Finally, there is no doubt that at least some children with borderline RHD represent additional, meaningful RHD burden. If even a small fraction of borderline RHD represents true RHD, the global burden could exceed 100 million. Despite the assumptions made in this analysis and paucity of data, the epidemic scale of RHD is unquestionable. RHD burden is likely over 50 million and could exceed 100 million persons. The global community has successfully united to fund research and implement programs aimed at reducing the burden of other diseases that disproportionately affect those living in low-resource settings (such as HIV and tuberculosis). It is clear that the global RHD epidemic is on the same scale and we must not wait on further data to act. Implementation of prevention and early detection programs and funding of further research is critical and must be proportional to the burden of disease.
We can no longer accept RHD's status as the “World's Forgotten Disease”.
References [1] B. Remenyi, N. Wilson, A. Steer, B. Ferreira, J. Kado, K. Kumar, et al., World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline, Nat. Rev. Cardiol. 9 (2012) 297–309. [2] A. Beaton, J.C. Lu, T. Aliku, P. Dean, L. Gaur, J. Weinberg, et al., The utility of handheld echocardiography for early rheumatic heart disease diagnosis: a field study, Eur. Heart J. Cardiovasc. Imaging 16 (2015) 475–482. [3] M.E. Engel, A. Haileamlak, L. Zuhlke, C.E. Lemmer, S. Nkepu, M. van de Wall, et al., Prevalence of rheumatic heart disease in 4720 asymptomatic scholars from South Africa and Ethiopia, Heart 101 (17) (2015) 1389–1394. [4] J.R. Carapetis, A.C. Steer, E.K. Mulholland, M. Weber, The global burden of group A streptococcal diseases, Lancet Infect. Dis. 5 (2005) 685–694. [5] J. Carapetis, The Current Evidence for the Burden of Group A Streptococcal Diseases, World Health Organization, Geneva, 2004. [6] Global Burden of Disease Study C, Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study, Lancet (2013) 2015. [7] E. Marijon, P. Ou, D.S. Celermajer, B. Ferreira, A.O. Mocumbi, D. Jani, et al., Prevalence of rheumatic heart disease detected by echocardiographic screening, N. Engl. J. Med. 357 (2007) 470–476. [8] A. Beaton, E. Okello, P. Lwabi, C. Mondo, R. McCarter, C. Sable, Echocardiography screening for rheumatic heart disease in Ugandan schoolchildren, Circulation 125 (2012) 3127–3132. [9] A. Kane, M. Mirabel, K. Toure, M.C. Perier, S. Fazaa, M. Tafflet, et al., Echocardiographic screening for rheumatic heart disease: age matters, Int. J. Cardiol. 168 (2013) 888–891. [10] M. Rothenbuhler, C.J. O'Sullivan, S. Stortecky, G.G. Stefanini, E. Spitzer, J. Estill, et al., Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents, Lancet Glob. Health 2 (2014) e717–e726. [11] L.J. Zuhlke, A.C. Steer, Estimates of the global burden of rheumatic heart disease, Glob. Heart 8 (2013) 189–195.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Prevalence of rheumatic heart disease in African school-aged population: Extrapolation from echocardiography screening using the 2012 World Heart Federation Guidelines Jacqueline Weinberg a, Andrea Beaton b, Twalib Aliku c, Peter Lwabi d, Craig Sable b a
Children's Hospital of Pittsburgh, Pittsburgh, PA, USA Children's National Health System, Washington, DC, USA c Gulu University, Gulu, Uganda d Uganda Heart Institute, Kampala, Uganda b
a r t i c l e
i n f o
Article history: Received 11 August 2015 Accepted 14 August 2015 Available online 12 September 2015
Determining the true burden of rheumatic heart disease (RHD) in sub-Saharan Africa is of upmost importance for disease prioritization and public health planning. The 2012 World Heart Federation (WHF) echocardiography criteria provide an evidence-based, standardized approach [1]. Ideally, RHD prevalence data would be collected across Africa, but this is unlikely to occur in the next 5 years. The first two studies in Africa to prospectively use WHF criteria provide a new and important opportunity to update the estimated burden of latent RHD in school-aged children throughout sub-Saharan Africa [2,3]. These studies reported a RHD prevalence of 40.2/1000 (10.9/1000 definite), 30.5/1000 (16.5/1000 definite) and 20.2/1000 (3.4/1,000 definite) in children in Uganda, Ethiopia and South Africa respectively. In this letter, we conduct a brief analysis, extrapolating data from these studies to 42 low-income and low-middle income countries in sub-Saharan Africa. We provide estimated ranges of definite and borderline RHD of school-aged children in these countries. Estimates for definite and borderline RHD are considered separately as there is greater confidence surrounding the significance of definite RHD; the implications of borderline RHD remain unclear. Data from South Africa (upper middle-income country) represents the most conservative estimate, while data from Uganda and Ethiopia (low-income countries) represents the likely upper-boundary of RHD prevalence. Methods and results: Of 50 sub-Saharan African countries, 30 are considered low-income (gross national income per capita (GNIPC) ≤ $1045) and 12 lower-middle income (GNIPC N$1045 and ≤$4125) nations, as defined by the World Bank (http://data.worldbank.org/news/ 2015-country-classifications). South Africa was also included, but estimates were based solely on South African prevalence data. The GNIPC and the poverty headcount ratio (% of population living on b$1.25/ day) are reported along with national population data (https://www. cia.gov/library/publications/the-world-factbook/index.html) for
http://dx.doi.org/10.1016/j.ijcard.2015.08.128 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
children aged 5–19 for included countries (Table 1). Prevalence ranges of RHD for each country were calculated by multiplying the population of school-aged children by prevalence from South Africa, Ethiopia, and Uganda [2,3]. The cumulative population of the 42 selected countries is 874.7 million persons, including an estimated 328.3 million children. Applying the conservative estimate of 3.4/1000 children with definite RHD (South Africa), there are at least 1.11 million children currently living with latent, definite RHD in these nations. Using the higher, and likely more reflective prevalence found in Uganda/Ethiopia (10.9–16.5/ 1000), there are between 3.56 and 5.42 million children with definite latent RHD. If we expand our estimates to include borderline RHD, then an additional 5.42–9.62 million children are currently affected — with total prevalence of latent RHD between 6.63 and 13.2 million children. The table provides detailed results for the 17 most populated countries (and South Africa). Data from the other 25 countries are combined for ease of display. Note that screening in Ethiopia showed higher estimates of definite than borderline RHD while South Africa and Uganda had more borderline RHD. Discussion: The 2004 World Health Organization (WHO) report and 2005 publication on the global burden of Group A Streptococcal Disease estimated the global prevalence of RHD to be 15.6 million [4,5]. This included approximately 1.01 million children in sub-Saharan Africa [5]. The 2013 Global Burden of Disease (GBD) study doubles this estimate of global RHD — 32.9 million persons [6]. The Data Representative Index (DRI) was only 18.6% for RHD for the period 2006–2013 [6], meaning that less than 20% of countries with a significant burden of disease had reliable incidence, prevalence and mortality data. This paucity of data is most pronounced in sub-Saharan Africa, likely contributing to a vast underestimation of the prevalence of RHD. Echocardiography screening of school-aged children has contributed to a better understanding of RHD prevalence [7–9]. The pooled prevalence in a 2014 meta-analysis by Rothenbuhler et al. [10] was 23.8/1,000, with prevalence in children in Senegal, Uganda and Mozambique of 5.4/1000, 14.9/1000 and 30.4/1000 respectively. These data pre-dated the 2012 WHF guidelines; there was considerable variability in echocardiography protocols and definitions used to classify RHD. Extrapolating data from WHF standardized echocardiographic screening, we estimate a prevalence of latent, but definite RHD in sub-
Correspondence
239
Table 1 Estimated RHD prevalence in low and lower middle income sub-Saharan African countries extrapolated from WHF echocardiography screening in Uganda, Ethiopia, and South Africa. South Africa is also included for reference. Range of estimate of definite RHD cases (thousands)
Range of estimate of borderline RHD cases (thousands)
Economic indicators
Country
Population estimate (millions)
Population 5–19 years (millions)
South Africa (prevalence 3.4/1000)
Uganda (prevalence 10.9/1000)
Ethiopia (prevalence 16.5/1000)
Ethiopia (prevalence 14.0/1000)
South Africa (prevalence 16.8/1000)
Uganda (prevalence 29.3/1000)
GNI per capita
PHR: % b $1.25 per day
South Africa Nigeria Ethiopia Congo Tanzania Kenya Uganda Sudan Ghana Mozambique Madagascar Cameroon Cote d'Ivoire Burkina Faso Niger Malawi Mali Zambia Other: 25 countries⁎ Total (millions)
48.4 177.2 96.6 77.4 49.6 45.0 35.9 35.5 25.8 24.7 23.2 23.1 22.8 18.4 17.5 17.4 16.5 14.6 168.1 874.7
13.2 65.9 36.8 29.4 19.0 16.7 14.4 13.2 8.7 9.9 8.3 8.6 8.1 7.0 7.3 6.5 6.5 5.7 61.2 328.3
44.9 224.1 125.0 99.9 64.7 56.6 49.0 44.9 29.5 33.6 28.3 29.1 27.5 23.9 24.7 22.3 22.3 19.4 210.8 1.11
N/A 718.6 400.8 320.4 207.5 181.6 156.9 144.0 94.7 107.7 90.8 93.4 88.2 76.5 79.1 71.3 71.3 62.3 675.8 3.56
N/A 1087.8 606.7 485.0 314.2 274.9 237.6 217.9 143.3 163.0 137.4 141.4 133.5 115.8 119.8 108.0 108.0 94.2 1023.0 5.42
N/A 923.0 514.8 411.5 266.6 233.2 201.6 184.9 121.6 138.3 116.6 120.0 113.3 98.3 101.6 91.6 91.6 80.0 868.0 4.60
221.9 1107.6 617.8 493.8 319.9 279.9 241.9 221.9 145.9 165.9 139.9 143.9 135.9 118.0 122.0 110.0 110.0 96.0 1041.6 5.52
N/A 1931.6 1077.4 861.2 557.9 488.1 421.9 387.0 254.5 289.4 244.1 251.0 237.1 205.7 212.7 191.8 191.8 167.4 1816.6 9.62
$7410 $2710 $470 $430 $860 $1160 $600 $1550 $1770 $610 $440 $1290 $1450 $750 $400 $270 $670 $1810
9 62 37 88 43 43 38 20 29 61 88 28 35 44 41 72 51 74
Abbreviations: GNI — Gross National Income; PHR — Poverty Headcount Ratio. ⁎ Other: Zimbabwe, Senegal, Rwanda, South Sudan, Guinea, Chad, Burundi, Somalia, Benin, Togo, Eritrea, Sierra Leone, Central African Republic, Republic of Congo, Liberia, Mauritania, The Gambia, Lesotho, Guinea-Bissau, Swaziland, Comoros, Western Sahara, Cabo Verde, Sao Tome & Principe, St. Helena, Ascension & Tristan da Cunha.
Saharan Africa to be 3.6 to 5.4 times greater than the 2004 WHO report [5] and likely double that in the GBD study [6]. Applying the premise that children in sub-Saharan Africa represent 6–7% of total global RHD burden [5], there may be 50–80 million persons currently affected with RHD worldwide. We acknowledge that the 2004 Group A Strep and GBD reports base RHD estimates on symptomatic RHD, while our prevalence data is based mainly on asymptomatic schoolchildren. Nonetheless, we are in agreement with Zuhlke and Steer that we need to change how we think about RHD, accepting a model that includes both symptomatic and latent disease [11]. Other factors contribute to even these numbers being an underestimate of disease burden. The high-risk group of children too poor or sick to attend school is not included. Previous studies have estimated a multiplication factor of between 5.5 and 7.2 to extrapolate school-aged prevalence data to adult populations [11]. If this is applied to our data, the prevalence of RHD in sub-Saharan Africa, alone, could exceed 30 million. We cannot account for children and adults with symptomatic or advanced RHD. Finally, there is no doubt that at least some children with borderline RHD represent additional, meaningful RHD burden. If even a small fraction of borderline RHD represents true RHD, the global burden could exceed 100 million. Despite the assumptions made in this analysis and paucity of data, the epidemic scale of RHD is unquestionable. RHD burden is likely over 50 million and could exceed 100 million persons. The global community has successfully united to fund research and implement programs aimed at reducing the burden of other diseases that disproportionately affect those living in low-resource settings (such as HIV and tuberculosis). It is clear that the global RHD epidemic is on the same scale and we must not wait on further data to act. Implementation of prevention and early detection programs and funding of further research is critical and must be proportional to the burden of disease.
We can no longer accept RHD's status as the “World's Forgotten Disease”.
References [1] B. Remenyi, N. Wilson, A. Steer, B. Ferreira, J. Kado, K. Kumar, et al., World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline, Nat. Rev. Cardiol. 9 (2012) 297–309. [2] A. Beaton, J.C. Lu, T. Aliku, P. Dean, L. Gaur, J. Weinberg, et al., The utility of handheld echocardiography for early rheumatic heart disease diagnosis: a field study, Eur. Heart J. Cardiovasc. Imaging 16 (2015) 475–482. [3] M.E. Engel, A. Haileamlak, L. Zuhlke, C.E. Lemmer, S. Nkepu, M. van de Wall, et al., Prevalence of rheumatic heart disease in 4720 asymptomatic scholars from South Africa and Ethiopia, Heart 101 (17) (2015) 1389–1394. [4] J.R. Carapetis, A.C. Steer, E.K. Mulholland, M. Weber, The global burden of group A streptococcal diseases, Lancet Infect. Dis. 5 (2005) 685–694. [5] J. Carapetis, The Current Evidence for the Burden of Group A Streptococcal Diseases, World Health Organization, Geneva, 2004. [6] Global Burden of Disease Study C, Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study, Lancet (2013) 2015. [7] E. Marijon, P. Ou, D.S. Celermajer, B. Ferreira, A.O. Mocumbi, D. Jani, et al., Prevalence of rheumatic heart disease detected by echocardiographic screening, N. Engl. J. Med. 357 (2007) 470–476. [8] A. Beaton, E. Okello, P. Lwabi, C. Mondo, R. McCarter, C. Sable, Echocardiography screening for rheumatic heart disease in Ugandan schoolchildren, Circulation 125 (2012) 3127–3132. [9] A. Kane, M. Mirabel, K. Toure, M.C. Perier, S. Fazaa, M. Tafflet, et al., Echocardiographic screening for rheumatic heart disease: age matters, Int. J. Cardiol. 168 (2013) 888–891. [10] M. Rothenbuhler, C.J. O'Sullivan, S. Stortecky, G.G. Stefanini, E. Spitzer, J. Estill, et al., Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents, Lancet Glob. Health 2 (2014) e717–e726. [11] L.J. Zuhlke, A.C. Steer, Estimates of the global burden of rheumatic heart disease, Glob. Heart 8 (2013) 189–195.