REVIEW URRENT C OPINION
Controlling acute rheumatic fever and rheumatic heart disease in developing countries: are we getting closer? Jessica L. de Dassel a,b, Anna P. Ralph a,b, and Jonathan R. Carapetis c
Purpose of review To describe new developments (2013–2014) in acute rheumatic fever (ARF) and rheumatic heart disease (RHD) relevant to developing countries. Recent findings Improved opportunities for the primary prevention of ARF now exist, because of point-of-care antigen tests for Streptococcus pyogenes, and clinical decision rules which inform management of pharyngitis without requiring culture results. There is optimism that a vaccine, providing protection against many ARF-causing S. pyogenes strains, may be available in coming years. Collaborative approaches to RHD control, including World Heart Federation initiatives and the development of registers, offer promise for better control of this disease. New data on RHD-associated costs provide persuasive arguments for better government-level investment in primary and secondary prevention. There is expanding knowledge of potential biomarkers and immunological profiles which characterize ARF/RHD, and genetic mutations conferring ARF/RHD risk, but as yet no new diagnostic testing strategy is ready for clinical application. Summary Reduction in the disease burden and national costs of ARF and RHD are major priorities. New initiatives in the primary and secondary prevention of ARF/RHD, novel developments in pathogenesis and biomarker research and steady progress in vaccine development, are all causes for optimism for improving control of ARF/RHD, which affect the poorest of the poor. Keywords acute rheumatic fever, developing countries, disease control, rheumatic heart disease
INTRODUCTION Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain significant issues in developing countries and in some indigenous and migrant populations in developed countries. Leading physician and researcher Professor Bongani Mayosi suggests that because those affected are the ‘poorest people in the world’, ARF and RHD control are not receiving the attention they require [1]. Recent gatherings of individuals and organizations working towards RHD control have increased international awareness and collaboration, namely the second RHD Forum (Cape Town, 2013), the World Health Assembly (Geneva, 2013) and the third RHD Forum (Melbourne, 2014). Efforts are now focussed on the World Heart Federation (WHF) target to reduce premature deaths from RHD in people under 25 years by 25% by 2025. The WHF position statement promotes five key strategic areas: comprehensive www.co-pediatrics.com
register-based control programmes, global access to benzathine penicillin G, identification and development of public figures as RHD champions, expansion of RHD training hubs and support for vaccine development [2 ]. By September 2013, 20 countries had implemented control activities in line with these strategies [1]. In this review, we summarize &&
a
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Australia, bInstitute of Advanced Studies, Charles Darwin University, Darwin, Australia and cTelethon Kids Institute, Centre for Child Health Research, University of Western Australia, Perth Australia and Department of Paediatric and Adolescent Medicine, Princess Margaret Hospital for Children, Perth, Australia Correspondence to Jessica L. de Dassel, Menzies School of Health Research, PO Box 41096, Casuarina, Darwin, Northern Territory 0811, Australia. Tel: +61 8 8946 8600; e-mail: jess.dedassel@menzies. edu.au Curr Opin Pediatr 2015, 27:116–123 DOI:10.1097/MOP.0000000000000164 Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al.
KEY POINTS Estimates of the global burden of ARF and RHD remain unreliable, hampered by missing data in many countries and the use of different methods and populations for diagnosis. Findings from genetics studies and investigations into the autoimmune response increase our chances of eradicating ARF and RHD in the future. Primary prevention of ARF is being strengthened by the use of rapid antigen detection tests and the refinement of clinical decision rules. Most developing countries lack the financial and human resources required for comprehensive disease prevention programmes – increased utilization of existing infrastructure is needed.
developments during 2013–2014 in ARF and RHD relevant to developing countries.
LITERATURE REVIEW METHOD Medical databases were searched (Academic Search Premier, CINAHL, Grey Lit, Health Source: Nursing/ academic edition, LILACS, MedCarib, Medline, Scopus and Web of Science); grey literature was identified through Internet searches. Exclusion criteria: articles published prior to 1 January 2013, case studies, articles not in English, articles included in review articles/meta-analyses. The Millennium Development Goal definition of developing countries was used [3].
EPIDEMIOLOGY The Global Burden of Disease, Injuries and Risk Factors study (GBD) estimated that, in 2010, there were 34.2 million people with RHD (data provided
Table 1. Estimated global burden of rheumatic heart disease 1990
2005
2010
Prevalence
29 172 383
33 468 203
34 232 795
YLL
13 267 810
9 670 605
8 720 292
YLD [7] DALY [5] Deaths [4]
1 150 422
1 365 502
1 429 575
14 418 232
11 036 107
10 149 867
462 579
363 864
345 110
DALY, disability adjusted life years; YLD, years lived with disability; YLL, years of life lost. Data provided by the Institute for Health Metrics and Evaluation. Adapted from [6].
by the Institute for Health Metrics and Evaluation), resulting in 345 110 deaths [4] and 10.1 million disability adjusted life years lost during that year [5] (see Table 1). These compare with the most widely cited previous estimate, published in 2005, of 15.6 million cases and 233 000 deaths [8]. Although the GBD estimates are thought to come closer to the true RHD burden, there remains considerable uncertainty, largely because of limited data, underdiagnosis and lack of formal reporting systems from low-income and middle-income countries [9]. Underdiagnosis of ARF remains a major challenge; in Ethiopian children with RHD, only a quarter recalled any symptoms of ARF [10]. For RHD, the Rheumatic Heart Disease Global Registry (REMEDY) project is developing an international register to collate the data needed to advocate for governments to invest in disease-control strategies [1]. Increasing echocardiographic screening is also contributing key data [9].
New data on the prevalence of rheumatic heart disease The decreasing cost of echocardiography has enabled the proliferation of screening initiatives in developing countries. Important recent findings are summarized in Table 2. Late presentation to health facilities means the proportion of severe cases is high in developing countries [22,23]. Data from Uganda suggest HIV infection may be associated with increased RHD rates, which requires further investigation [24]. In promising new data from Brazil, hospitalization rates for both ARF and RHD have fallen, with a corresponding fall in RHD mortality [25].
Morbidity and mortality associated with rheumatic heart disease RHD remains a significant cause of heart failure and stroke in developing countries – RHD patients represented 12% of heart failure cases in a Tanzanian study [26] and up to 23.2% of strokes in Asia [27]. Complications arising from RHD during pregnancy also cause significant morbidity and mortality; in Nepal, pregnant women with RHD had a mortality rate of 4% and foetal and neonatal mortality was 16% [28]. Parks et al. [29] measured the mortality of RHD patients in Fiji; the standardized mortality ratio was 8.8 compared with the general population. Young indigenous Fijian men with RHD had the highest standardized mortality ratio at 50.0.
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
117
Infectious diseases and immunization Table 2. New data on the prevalence of rheumatic heart disease Country (region)
Population
Sample size
Diagnosis method
Prevalence
Egypt [11]
Schoolchildren (6–18 years)
48 930
Echocardiogram
0.7/1000
Fiji [12]
Schoolchildren (5–14 years, Indigenous Fijian)
1666
Echocardiogram (WHF criteria)
8.4/1000
India (north) [13]
Schoolchildren (5–15 years)
15 145
Auscultation or reported symptoms, followed up by echocardiogram
0.46/1000
India (south, rural) [14]
Over 15 years
44 164
Auscultation, followed up by echocardiogram
9.7/1000
Nepal (eastern Nepal) [15]
Schoolchildren (5–15 years)
2043
Auscultation, abnormal results followed up by echocardiogram
2.5/1000
Nepal [16]
Schoolchildren (5–15 years)
Target: 10 000
Auscultation followed by echocardiogram
Study underway
New Caledonia [17]
Schoolchildren (9–10 years)
12 728
Echocardiogram
8.9/1000
Samoa [18]
Schoolchildren (3–16 years)
8457
Echocardiogram
14/1000
Solomon Islands (Honiara) [19]
Schoolchildren (5–16 years)
700
Echocardiogram (WHF criteria)
24/1000
South Africa [20]
All ages
Undefined
Literature review of existing studies
Study underway
South Korea [21]
National insurance database
Not provided
Insurance claims for services linked to a RHD diagnosis
0.74/1000
RHD, rheumatic heart disease; WHF, World Heart Federation. Abnormalities were detected in 2712, only 1603 had an echocardiogram of sufficient quality for diagnosis.
THE COST OF RHEUMATIC HEART DISEASE The most recent calculations of the national cost of ARF and RHD are for South Korea and Fiji. In South Korea, the 2008 economic burden of RHD was estimated to be USD$67 250 000; 39% of these costs were indirect (associated with loss of productivity and premature death) [30]. The cost of ARF and RHD in Fiji was estimated to be USD$62 291 067 over 5 years; 97% of the total were indirect costs [31 ]. &
PATHOGENESIS OF ACUTE RHEUMATIC FEVER Recent studies have refined our understanding of the organism and host factors contributing to ARF pathogenesis. Evidence from a new systematic review identified 57 rheumatogenic Group A b haemolytic Streptococcus (GAS) emm types, more than previously appreciated [32]. It has been recognized that GAS virulence is linked to the hyaluronic acid capsule; serotype M18, classically associated with ARF, has a highly encapsulated phenotype. Lynskey et al. [33] have now identified that natural truncation of protein RocA causes this hyperencapsulation and the associated characteristics of carriage longevity and transmissibility. Studies of cytokine responses and monocyte expression provide clues to the aberrant host responses occurring in ARF [34–36], including elevated levels of tumour necrosis factor (TNF) a and interleukin-8 [37]. Findings regarding interleukin10 are inconsistent [35,36,38]. 118
www.co-pediatrics.com
There are two hypotheses regarding the development of autoimmunity in ARF: collagen mediated, as supported by Tandon et al. [39 ]; and molecular mimicry of myocellular proteins (although these concepts are not necessarily mutually exclusive [40]). A new development supporting molecular mimicry is the identification of antibodies to vimentin (a valve-associated protein) in RHD patients, which are cross-reactive with GAS, and could explain the inflammatory response in heart valves [41]. &
GENETIC PREDISPOSITION TO ACUTE RHEUMATIC FEVER Evidence for genetic susceptibility to ARF and RHD is growing. Recent findings are summarized in SDC1, http://links.lww.com/MOP/A22. Studies are underway in Samoa [42], Nigeria, Uganda and Rwanda [43] and our own study in Australia.
PREVENTION In 2004, the WHO published recommendations for ARF/RHD control [44]. Additional support for developing countries seeking to develop/strengthen their control programme is now available from the TIPS Handbook [45 ]. Of the recommended activities, Mayosi [46] nominates primary prevention (the treatment of GAS pharyngitis), and the establishment of register-based secondary prevention programmes as two of the 10 best buys for combating heart disease in Africa. Despite the advantages of &&
Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al.
disease prevention, some countries have no prevention or screening programme in place (e.g. Brazil) [47]. In Nepal, however, a national programme has been integrated into primary healthcare since 2007 and in 2013 a pilot primary prevention project was initiated at 42 primary healthcare centres, using a ‘treat all’ approach for GAS pharyngitis [48]. In Nepal, the Government’s commitment and centralized coordination by the Nepal Heart Foundation have been key to the programme’s success and sustainability [48]. Sudan and Rwanda also have programmes based on successful collaborations with government and nongovernment organizations [49,50]. Unfortunately, many countries spend the majority of their RHD funding on tertiary interventions, impeding the implementation of prevention programmes [51]. An innovative suggestion is to integrate RHD care into existing chronic disease management by utilizing infrastructure for HIV/ AIDS care; this approach is being trialled in Uganda and if successful, could be implemented in settings wherein HIV/AIDS infrastructure is well established [52 ]. &
Primary prevention Limited awareness of ARF and RHD is a major barrier to effective primary prevention [53], but progress is being made; new interactive computer-based resources targeting schoolchildren have been shown to increase knowledge in Kenyan children and could be used in similar settings [54 ]. When children present to health services with sore throat, throat culture remains the gold standard for the diagnosis of GAS pharyngitis. However, the emergence of rapid antigen detection tests (RADTs) and the proliferation of clinical decision rules allow for new diagnostic approaches. RADTs can be reliable, however, their performance varies; specificity ranges from 8.3 to 98.2% [55] and sensitivity 42–95% [56,57]. In one study, inadequate staff training substantially reduced the accuracy of the tests [55]. The use of RADTs in developing countries is likely to be limited by cost. The illumigene GAS assay was very effective in diagnosing GAS in children with 99% sensitivity and 99.6% specificity [58]. DNA biosensors, which stimulate an electrochemical signal when a DNA-labelled probe hybridizes with the DNA of target bacteria, have been proposed as an affordable, effective method for diagnosing GAS; results are available in 30 min and 100% specificity has been reported [59 ]. Clinical decision rules (CDRs) can be used in conjunction with culture or RADTs, or as a standalone approach. A meta-analysis of seven CDRs &
&
recommends the Joachim rules (see SDC2, http:// links.lww.com/MOP/A22), these were validated in a Brazilian population (sensitivity: 88%, specificity: 35%) [60 ]. Another comparison of CDRs, also in Brazil, recommended the Abu Reesh criteria [purulent oropharyngeal exudate or tender enlarged anterior cervical lymph nodes ¼ bacterial pharyngitis [61] (sensitivity: 85.2%, specificity: 25.8% [62])]. Two Cochrane reviews found no evidence to change the recommendation of penicillin for the treatment of GAS pharyngitis and the prevention of recurrent ARF; however, further studies in low-income, high-risk populations are needed [63 ,64 ]. There is still no reported evidence of GAS developing resistance to penicillin [65]. Irlam et al. [66] report on the cost-effectiveness of primary prevention approaches in South Africa and recommend the diagnosis of GAS pharyngitis using a clinical decision rule, and subsequent treatment with antibiotics (without culture confirmation), accompanied by primordial and secondary prevention activities. Assessment of the best approach in other settings should consider the local incidence of sore throat, CDRs with higher specificity and RADTs [67]. Manji et al. [68] compared the cost of primary and secondary prevention approaches and concluded that echocardiography followed by secondary prophylaxis for patients with evidence of RHD is the most cost-effective strategy. &&
&&
&&
Vaccine Vaccine research, underway since 1923, has investigated many candidates, targeting M proteins, GAS carbohydrate or non-M protein antigens [69 ]. Vaccine development faces several challenges: the limited commercial viability, the plethora of GAS strains (as many as 250 [70]) and the risk of stimulating an autoimmune response [1]. A study in Mali tested a 30-valent vaccine against 42 emm types (including 14 vaccine emm types) and a similar study in South Africa tested a 30-valent vaccine against 26 emm types (including 17 vaccine emm types). In both studies, immunological cross reactivity with nonvaccine serotypes extended the potential coverage of the vaccines to 95% of the tested emm types [71,72]. Funding awarded by the Australian and New Zealand Governments has assisted efforts, and clustering the emm types according to similar function may reduce the number of targets required [73]. &&
Secondary prevention Benzathine penicillin G (BPG) remains the recommended drug for secondary prophylaxis of ARF [63 ]; unfortunately, adherence is low in many &&
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
119
Infectious diseases and immunization
settings. For example, 46% of patients at Mulago Hospital in Uganda received less than 80% of their needles over a 6-month period, with pain the most commonly cited reason for missing a needle [74]. A new vibrating device from Buzzy has been trialled for pain minimization in New Zealand. Buzzy, in addition to lignocaine, reduced pain and fear reported by children compared with lignocaine alone [75 ]. This innovative low-cost device may improve adherence to secondary prophylaxis in developing settings. Concern about penicillin allergy/anaphylaxis can be an impediment to secondary prophylaxis delivery; a survey found that 25% of healthcare providers in high-prevalence countries reported that one or more of their patients had experienced anaphylaxis to BPG, and 20% reported a patient death due to BPG anaphylaxis [76]. However, the limited data on this matter indicate very low rates of true allergy; the most recent study reported suspected allergy in 2% and confirmed allergy in just 0.18% [77]. The only large scale study conducted to date (published in 1991) documented a 3.2% rate of allergic reactions but an incidence of true anaphylaxis of only 0.2% [78]. An additional challenge is the reliance on international producers and suppliers of BPG. Forty-two percent of survey respondents reported issues maintaining their supply; 33% reported difficulties with international suppliers [76]. &
Tertiary prevention Two meta-analyses confirm that heart valve repair is preferable to replacement in developing settings [79 ,80 ]; patient survival is better and anticoagulation is not required. However, in some settings, the limited opportunity for reoperation (eventually required after most valve repairs), means that replacement is used in preference to repair (e.g. in Rwanda), even though complication rates after replacement can be very high [50]. Most sub-Saharan African countries do not have cardiac surgery facilities so patients either travel overseas for procedures, or await international teams who visit on short-term bases [81]. In Fiji, an international team flies in to perform valve surgery, which is more cost-effective than transferring patients overseas for surgery. The mortality rate for patients who underwent valve replacement was 25.7%; 32.5% of deaths occurred within 90 days of the operation. The authors suggest greater collaboration between the surgical team and local health staff, and enhanced support for patients, including education and reminders for follow up appointments would improve patient outcomes [82]. &
120
&&
www.co-pediatrics.com
Locally performed surgery is also cheaper in Nigeria, where a mitral valve replacement costs USD$11 200 in country, and USD$20 000–USD$40 000 if done abroad [83]. Patients with mechanical valve replacements require lifelong anticoagulation. The challenges of warfarin are significant, and there is a pressing need for alternative therapies. Direct thrombin inhibitors (e.g. dabigatran etexilate) show promise; although more expensive, they have fewer interactions with other drugs or food and do not require monitoring or dose adjustments [80 ]. Surgery for patients from developing countries remains prohibitively expensive for most governments and patients. A key priority is to increase the number of surgeons who can perform valve repairs, but most benefit will be gained from primary and secondary prevention activities [84]. &&
ADVANCES IN DIAGNOSIS OF ACUTE RHEUMATIC FEVER The Jones Criteria for ARF diagnosis, first published in 1944, have been revised several times and are again under review. A further revision of the Jones Criteria from the American Heart Association is due for release in the near future (Gewitz M, personal communication, 29 September 2014). Over time the criteria have become more specific and less sensitive and their application in high-risk populations will result in missed cases [85], so localized guidelines are necessary in some countries. Investigation for improved diagnostic tests continues. Elevated levels of ischaemia-modified albumin could be a biomarker for ARF [86], and the detection of accelerated junctional rhythm may assist with differential diagnosis during the acute phase of ARF (specificity: 100%, sensitivity: 15.6%) [87].
ADVANCES IN DIAGNOSIS OF RHEUMATIC HEART DISEASE Echocardiograms have consistently proved to be superior to auscultation for RHD diagnosis [88] – most recently in Fiji where auscultation sensitivity was just 30% [12]. The accuracy of echocardiograms was substantially improved with the publication of the WHF echocardiographic criteria for RHD in 2012. An evaluation of the criteria found satisfactory levels of agreement in diagnoses made by experienced physicians [89 ]. The role of echocardiographic screening remains undecided. RHD only partially meets the Council of Europe Criteria for disease screening so until we strengthen the delivery of secondary &&
Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al.
prophylaxis and understand the natural history of subclinical RHD, screening cannot be endorsed [90 ]. The appropriate age for screening is also under discussion, with a report from Senegal advocating for inclusion of 16–18-year olds [91]. The limited availability of equipment and appropriately trained staff is a challenge, and work is underway to identify more cost-effective solutions. Hand-held devices are becoming more affordable and have been used by trained medical staff with high specificity and sensitivity (95 and 81%, respectively) [92]. Portable echocardiograms have been used by trained nurses with 73.2% specificity and 91.5% sensitivity [93 ]. A neural network (a decision support toolkit) could facilitate diagnosis in resource-poor settings. The tool analyses data, including ECG results, without the need for physician review and has resulted in 92.13% accuracy [94]. However, before more is invested in implementing screening activities in developing countries, the cost-effectiveness should be established [90 ]. Identifying additional biomarkers could enhance diagnosis and numerous proteins have recently been reported as possible indicators of RHD (see SDC3, http://links.lww.com/MOP/A22).
Acknowledgements None.
&&
Financial support and sponsorship Jessica de Dassel is supported by an Australian Postgraduate Award scholarship. Anna Ralph is supported by a National Health and Medical Research Council fellowship (1016567). Conflicts of interest None.
&
&&
TREATMENT A gap remains in our understanding of the progression of subclinical RHD and whether secondary prophylaxis would benefit these patients. In New Caledonia, 35% of subclinical cases proceeded to definite RHD within 2 years follow up, 43% to borderline RHD and 22% reverted to normal [95]. These findings suggest that there are some subclinical cases that would benefit from secondary prophylaxis; however, it is unclear what the features of those cases are, and whether these results can be extrapolated to other populations.
CONCLUSION ARF and RHD continue to impose a significant burden on the people and health systems of developing countries. Progress in disease control is hampered by limited community awareness, inadequate provision of secondary prophylaxis and limited availability of tertiary interventions. A vaccine for GAS infection should dramatically reduce the incidence of ARF. For those already affected by RHD, greater investment in training and retaining health staff is key, as is the development of sustainable partnerships which enable prevention programmes to operate independently of international funding and expertise.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Maurice J. Rheumatic heart disease back in the limelight. Lancet 2013; 382:1085–1086. 2. Remenyi B, Carapetis J, Wyber R, et al. Position statement of the World Heart && Federation on the prevention and control of rheumatic heart disease. Nat Rev Cardiol 2013; 10:284–292. This statement outlines key strategic areas for improving disease control and meeting WHF targets. 3. United Nations Statistics Division. Millennium Development Indicators: World and regional groupings 2014. http://mdgs.un.org/unsd/mdg/Host.aspx? Content=Data/REgionalGroupings.htm. [Accessed 17 November 2014]. 4. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380:2095– 2128. 5. Murray CJL, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380:2197–2223. 6. Schodel F. Group A streptococcal vaccines: challenges and progress. The Global Vaccine and Immunization Research Forum (GVIRF) [Internet]. 2014. http://www.who.int/immunization/research/forums_and_initiatives/03_Schodel_GVIRF14_GAS_Vaccinedev.pdf. [Accessed 17 November 2014]. 7. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380: 2163–2196. 8. Carapetis JR, Steer AC, Mulholland EK, et al. The global burden of group A streptococcal diseases. Lancet Infect Dis 2005; 5:685–694. 9. Zuhlke LJ, Steer A. Estimates of the global burden of rheumatic heart disease. Global Heart 2013; 8:189–195. 10. Tadele H, Mekonnen W, Tefera E. Rheumatic mitral stenosis in children: more accelerated course in sub-Saharan Patients. BMC Cardiovasc Disord 2013; 13:95. 11. Farrag AAM, Aroussy WAE, Hagracy NE, et al. Echocardiographic screening for rheumatic valvular heart disease among Egyptian school children. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 12. Colquhoun SM, Kado JH, Remenyi B, et al. Echocardiographic screening in a resource poor setting: Borderline rheumatic heart disease could be a normal variant. Int J Cardiol 2014; 173:284–289. 13. Negi PC, Kanwar A, Chauhan R, et al. Epidemiological trends of RF/RHD in school children of Shimla in north India. Indian J Med Res 2013; 137:1121– 1127. 14. Sriharibabu M, Himabindu Y, Kabir Z. Rheumatic heart disease in rural south India: a clinico-observational study. J Cardiovasc Dis Res 2013; 4:25–29. 15. Gautam S. Prevalence and pattern of rheumatic heart disease in school children from eastern part of underdeveloped, poor country Nepal: A crosssectional, observational study. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 16. Pilgrim T, Kalesan B, Karki P, et al. Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal. BMJ Open 2012; 2:e001320. 17. Baroux N, Rouchon B, Huon B, et al. High prevalence of rheumatic heart disease in schoolchildren detected by echocardiography screening in New Caledonia. J Paediatr Child Health 2013; 49:109–114. 18. Viali S. Rheumatic heart disease in Samoa and the Pacific Nations. J Prim Healthcare 2014; 6:84–85.
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
121
Infectious diseases and immunization 19. Kennedy L, Nasi T, Ludawane B, et al. Burden of rheumatic heart disease in the Solomon Islands. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 20. Zu¨hlke L, Watkins D, Engel ME. Incidence, prevalence and outcomes of rheumatic heart disease in South Africa: a systematic review protocol. BMJ Open 2014; 4:e004844. 21. Jang SY, Ju E-Y, Seo SR, et al. Changes in the etiology of valvular heart disease in the rapidly aging Korean population. Int J Cardiol 2014; 174:355– 359. 22. Zhang WZ, Mondo C, Okello E, et al. Presenting features of newly diagnosed rheumatic heart disease patients in Mulago Hospital: a pilot study. Cardiovasc J Afr 2013; 24:28–33. 23. Akinwusi PO, Peter JO, Oyedeji AT, et al. The new face of rheumatic heart disease in South West Nigeria. Int J Gen Med 2013; 6:375–381. 24. Gleason B, Mirembe G, Namuyonga J, et al. Does HIV infection modify the risk of RHD? Initial echocardiographic screening experience at the Joint Clinical Research Centre in Kampala, Uganda. Global Heart 2014; 9 (1S):e55. 25. Azevedo VMP, Mu¨ller RE, Kaufman R, et al. Is rheumatic fever already controlled in Brazilian children and adolescents? An overview about the last 21 years epidemiological data. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 26. Makubi A, Hage C, Lwakatare J, et al. Contemporary aetiology, clinical characteristics and prognosis of adults with heart failure observed in a tertiary hospital in Tanzania: the prospective Tanzania Heart Failure (TaHeF) study. Heart 2014; 100:1235–1241. 27. Wang D, Liu M, Lin S, et al. Stroke and rheumatic heart disease: a systematic review of observational studies. Clin Neurol Neurosurg 2013; 115:1575– 1582. 28. Chhetri S, Shrestha NR, Pilgrim T. Pregnancy complicated by heart disease in Nepal. Global Heart 2014; 9 (1S):e39. 29. Parks T, Kado J, Miller AE, et al. Mortality amongst patients with rheumatic heart disease in Fiji: a national historic data-linkage cohort study. Global Heart 2014; 9 (1S):e158. 30. Seo H-Y, Yoon S-J, Kim E-J, et al. The economic burden of rheumatic heart disease in South Korea. Rheumatol Int 2013; 33:1505–1510. 31. Heenan RC, Ba¨rnighausen T, O’Brien J, et al. The cost-of-illness of rheumatic & heart disease: a national estimation in Fiji. Global Heart 2014; 9 (1S):e30. This is an important contribution to our knowledge of cost of ARF and RHD in a high-prevalence developing country, where indirect costs accounted for 97% of the total. 32. Baroux N, D’Ortenzio E, Smeesters P, et al. GAS emm-types probably involved in acute rheumatic fever. Global Heart 2014; 9 (1S):e37. 33. Lynskey NN, Goulding D, Gierula M, et al. RocA truncation underpins hyperencapsulation, carriage longevity and transmissibility of serotype M18 Group A Streptococci. PLoS Pathog 2013; 9:15. 34. Martin WJ, Minigo G, Keeble J, et al. Involvement of Th17 cytokines in acute rheumatic fever. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 35. Bryant PA, Smyth GK, Gooding T, et al. Susceptibility to acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis. Infect Immun 2014; 82:753–761. 36. Rehman S, Akhtar N, Saba N, et al. A study on the association of TNF-a-308, IL-6-174, IL-10-1082 and IL-1RaVNTR gene polymorphisms with rheumatic heart disease in Pakistani patients. Cytokine 2013; 61:527–531. 37. Abul-fadl A, Hady SA, Gad N. Cytokines as a predictor of progression to valvular disease in children with rheumatic fever. J Saudi Heart Assoc 2013; 25:127. 38. Lea˜o SC, Lima MRM, Nascimento HM, et al. IL-10 and ET-1 as biomarkers of rheumatic valve disease. Rev Bras Cir Cardiovasc 2014; 29:25–30. 39. Tandon R, Sharma M, Chandrashekhar Y, et al. Revisiting the pathogenesis of & rheumatic fever and carditis. Nat Rev Cardiol 2013; 10:171–177. This review summarizes and analyses proposed mechanisms of autoimmunity in ARF to date, and concludes that collagen-mediated autoimmunity is the most likely mechanism. 40. Cunningham MW. Rheumatic fever revisited. Nat Rev Cardiol 2014; 11:123. 41. Delunardo F, Scalzi V, Capozzi A, et al. Streptococcal-vimentin cross-reactive antibodies induce microvascular cardiac endothelial proinflammatory phenotype in rheumatic heart disease. Clin Exp Immunol 2013; 173:419–429. 42. Kauwe JK, Allen LB, Allen M, et al. Rheumatic Rescue: Genetic basis for elevated rheumatic heart disease susceptibility in Samoa. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 43. United States National Institutes of Health. clinicaltrials.gov. http://clinical trials.gov/ct2/home. [Accessed 29 July 2014] 44. World Health Organization. Rheumatic fever and rheumatic heart disease. Report of a WHO expert consultation; October–November 2001. Geneva: World Health Organization; 2004. 45. Wyber R, Grainger Gasser A, Thompson D, et al. Tools for Implementing && RHD Control Programmes (TIPS) Handbook. Perth, Australia: World Heart Federation and RhEACH; 2014. This handbook is a key evidence-based guide for the development and strengthening of ARF and RHD disease control programmes. 46. Mayosi BM. The 10 ‘Best Buys’ to combat heart disease, diabetes and stroke in Africa. Heart 2013; 99:973–974.
122
www.co-pediatrics.com
47. Bocchi EA. Heart failure in South America. Curr Cardiol Rev 2013; 9:147– 156. 48. Regmi PR, Wyber R. Prevention of rheumatic fever and heart disease: Nepalese experience. Global Heart 2013; 8:247–252. 49. Shetty P. Sulafa Ali: a pioneer of paediatric cardiology in Sudan. Lancet 2014; 383:687. 50. Swain JD, Pugliese DN, Mucumbitsi J, et al. Partnership for sustainability in cardiac surgery to address critical rheumatic heart disease in subSaharan Africa: the experience from Rwanda. World J Surg 2014; 38: 2205–2211. 51. Ramokgopa G. Public sector prevention of RF and RHD in South Africa. Global Heart 2013; 8:187–188. 52. Longenecker C, Lwabi P, Kityo C, et al. Leveraging existing HIV/AIDS & infrastructure for rheumatic heart disease care in Uganda: a collaborative disease surveillance and management program. Global Heart 2014; 9 (1S):e55. This study describes a new approach for control in developing settings: using infrastructure from HIV/AIDS programmes to improve ARF and RHD control. 53. Zu¨hlke L J, Engel ME. The importance of awareness and education in prevention and control of RHD. Global Heart 2013; 8:235–239. 54. Matheka DM, Murgor M, Kibochi E, et al. Role of technology in creating & rheumatic heart disease awareness among school-going children in Kenya. Global Heart 2014; 9 (1S):e7–e8. This study reports on the effective use of new free computer-based education resources with schoolchildren in Kenya. 55. Toepfner N, Henneke P, Berner R, et al. Impact of technical training on rapid antigen detection tests (RADT) in group A streptococcal tonsillopharyngitis. Eur J Clin Microbiol Infect Dis 2013; 32:609–611. 56. Upton A, Lennon D, Stewart J, et al. Disappointing performance of rapid antigen detection tests for group A streptococcus in the Auckland schoolbased sore throat programme. N Z Med J 2014; 127:103–105. 57. Little P, Hobbs FDR, Moore M, et al. Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management). BMJ 2013; 347:f5806. 58. Henson AM, Carter D, Todd K, et al. Detection of Streptococcus pyogenes by use of Illumigene group A Streptococcus assay. J Clin Microbiol 2013; 51:4207–4209. 59. Singh S, Kaushal A, Khare S, et al. Gold-mercaptopropionic acid-polyethy& lenimine composite based DNA sensor for early detection of rheumatic heart disease. Analyst 2014; 139:3600–3606. This study proposes the use of biosensors as a cost-effective method for diagnosing GAS infection. 60. Le Marechal F, Martinot A, Duhamel A, et al. Streptococcal pharyngitis in && children: a meta-analysis of clinical decision rules and their clinical variables. BMJ Open 2013; 3:10. This is an important comparison of the accuracy of several clinical decision rules for diagnosing GAS pharyngitis. 61. Steinhoff MC, Khalek MKAEI, Khallaf N, et al. Effectiveness of clinical guidelines for the presumptive treatment of streptococcal pharyngitis in Egyptian children. Lancet 1997; 350:918–921. 62. Orofino DHG, Passos SRL, de Andrade CAF, et al. Accuracy and interobserver variation of three clinical decision rules for the diagnosis of streptococcal pharyngitis. Pediatr Infect Dis J 2013; 32:686–687. 63. Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane && Database Syst Rev 2013; 11:CD000023. This Cochrane review confirms that penicillin is the best choice for treatment of GAS pharyngitis. 64. van Driel ML, De Sutter AIM, Keber N, et al. Different antibiotic treatments for && group A streptococcal pharyngitis. Cochrane Database Syst Rev 2013; 4:CD004406. This Cochrane review that confirms penicillin is the most effective medication for prevention of ARF recurrences. 65. Dhanda V, Chaudhary P, Toor D, et al. Antimicrobial susceptibility pattern of bhaemolytic group A, C and G streptococci isolated from North India. J Med Microbiol 2013; 62 (Pt 3):386–393. 66. Irlam JH, Mayosi BM, Engel ME, et al. A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis. S Afr Med J 2013; 103:894–895. 67. Steer A. Primary prevention of rheumatic fever in children: key factors to consider. S Afr Med J 2014; 104:156. 68. Manji RA, Witt J, Tappia PS, et al. Cost-effectiveness analysis of rheumatic heart disease prevention strategies. Expert Rev Pharmacoecon Outcomes Res 2013; 13:715–724. 69. Sharma A, Nitsche-Schmitz DP. Challenges to developing effective strepto&& coccal vaccines to prevent rheumatic fever and rheumatic heart disease. Vaccine: Development & Therapy 2014; 4:39–54. This is a summary of the GAS vaccines in development and outlines the advantages and disadvantages of each. 70. Tandon R. Preventing rheumatic fever: M-protein based vaccine. Indian Heart J 2014; 66:64–67. 71. Dale JB, Penfound TA, Tamboura B, et al. Potential coverage of a multivalent M protein-based group A streptococcal vaccine. Vaccine 2013; 31:1576– 1581.
Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al. 72. Engel ME, Muhamed B, Whitelaw AC, et al. Group A streptococcal emm type prevalence among symptomatic children in Cape Town and potential vaccine coverage. Pediatr Infect Dis J 2014; 33:208–210. 73. Sanderson-Smith M, De Oliveira DMP, Guglielmini J, et al. A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis. 2014;210:1325– 1338. 74. Musoke C, Mondo CK, Okello E, et al. Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital. Cardiovasc J Afr 2013; 24:124–129. 75. Russell K, Nicholson R, Naidu R. Reducing the pain of intramuscular ben& zathine penicillin injections in the rheumatic fever population of Counties Manukau District Health Board. J Paediatr Child Health 2014; 50:112–117. Important evaluation of a pain minimisation device that shows it reduced children’s reported pain and fear associated with BPG injections. 76. Taubert K, Marko SB. Access to essential medicines: illuminating disparities in the global supply of benzathine penicillin g in the context of rheumatic fever/ rheumatic heart disease prevention. In: American College of Cardiology Conference. San Francisco: Journal of the American College of Cardiology; 2013; 6: E2004. 77. Kaya A, Erkoc¸og˘lu M, Senkon OG, et al. Confirmed penicillin allergy among patients receiving benzathine penicillin prophylaxis for acute rheumatic fever. Allergol Immunopathol (Madr) 2014; 42:289–292. 78. International Rheumatic Fever Study Group. Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group. Lancet 1991; 337:1308–1310. 79. Wang Z, Zhou C, Gu H, et al. Mitral valve repair versus replacement in patients & with rheumatic heart disease. J Heart Valve Dis 2013; 22:333–339. This is a meta-analysis concluding that heart valve repair is preferable over valve replacement. 80. Michota F. Transitions of care in anticoagulated patients. J Multidiscip Healthc && 2013; 6:215–228. This is a summary of recent developments in anticoagulation, including the new drug dabigatran which could improve anticoagulation for patients in developing countries. 81. Ferratini M, Marianeschi S, Santoro F, et al. Valvulopathies in sub-Saharan African children: patterns, humanitarian interventions and cardiac surgical problems. Int J Cardiol 2013; 165:237–241. 82. Thomson Mangnall L, Sibbritt D, Fry M, et al. Short- and long-term outcomes after valve replacement surgery for rheumatic heart disease in the South Pacific, conducted by a fly-in/fly-out humanitarian surgical team: a 20-year retrospective study for the years 1991 to 2011. J Thorac Cardiovasc Surg 2014; pii: S0022-5223(14)00162-7. doi: 10.1016/j.jtcvs.2014.02.006. [Epub ahead of print] 83. Falase B, Sanusi M, Majekodunmi A, et al. The cost of open heart surgery in Nigeria. Pan Afr Med J 2013; 14:61.
84. Finucane K, Wilson N. Priorities in cardiac surgery for rheumatic heart disease. Global Heart 2013; 8:213–220. 85. Lilic N, Kumar P. A timely reminder: rheumatic fever. N Z Med J 2013; 126:88–90. 86. Toker A, Karatas Z, Altin H, et al. Evaluation of serum ischemia modified albumin levels in acute rheumatic fever before and after therapy. Indian J Pediatr 2014; 81:120–125. 87. Ceviz N, Celik V, Olgun H, et al. Accelerated junctional rhythm in children with acute rheumatic fever: is it specific to the disease? Cardiol Young 2014; 24:464–468. 88. Roberts KV, Brown ADH, Maguire GP, et al. Utility of auscultatory screening for detecting rheumatic heart disease in high-risk children in Australia’s Northern Territory. Med J Aust 2013; 199:196–199. 89. Remenyi B, Carapetis J, et al., on behalf of Working group on international && standardization of echocardiographic criteria for Rheumatic Heart Disease. World Heart Federation evidence-based echocardiographic criteria for rheumatic heart disease allows for reproducible diagnosis. Global Heart 2014; 9 (1S):e25–e26. This is an important evaluation of the WHF echocardiogram criteria which reports that these criteria can be used with satisfactory levels of agreement between experienced physicians. 90. Zu¨hlke L, Mayosi BM. Echocardiographic screening for subclinical rheumatic && heart disease remains a research tool pending studies of impact on prognosis. Curr Cardiol Rep 2013; 15:343. This is a discussion of the use of echocardiographic screening for the prevention of RHD which concludes that we need to know more about the natural history of RHD and need to strengthen health systems before it can be recommended in developing settings. 91. Kane A, Mirabel M, Toure´ K, et al. Echocardiographic screening for rheumatic heart disease: Age matters. Int J Cardiol 2013; 168:888–891. 92. Shmueli H, Burstein Y, Sagy I, et al. Briefly trained medical students can effectively identify rheumatic mitral valve injury using a hand-carried ultrasound. Echocardiography 2013; 30:621–626. 93. Colquhoun SM, Carapetis JR, Kado JH, et al. Pilot study of nurse-led & rheumatic heart disease echocardiography screening in Fiji – a novel approach in a resource-poor setting. Cardiol Young 2013; 23:546–552. This is an important pilot showing that trained nurses can effectively perform echocardiograms. 94. Iftikhar F, Shams A, Dilawari A. RCD: a toolkit for rheumatic valvular and congenital heart defect diagnosis. Neural Computing & Applications 2013; 23:1729–1735. 95. Mirabel M, Fauchier T, Tafflet M, et al. Follow-up of subclinical rheumatic heart disease in children. Poster session presented at: American Heart Association Scientific Sessions; 16–20 November 2013; Dallas. http://circ.ahajournals. org/cgi/content/meeting_abstract/128/22_MeetingAbstracts/A16421. [Accessed 17 November 2014].
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
123
Controlling acute rheumatic fever and rheumatic heart disease in developing countries: are we getting closer? Jessica L. de Dassel a,b, Anna P. Ralph a,b, and Jonathan R. Carapetis c
Purpose of review To describe new developments (2013–2014) in acute rheumatic fever (ARF) and rheumatic heart disease (RHD) relevant to developing countries. Recent findings Improved opportunities for the primary prevention of ARF now exist, because of point-of-care antigen tests for Streptococcus pyogenes, and clinical decision rules which inform management of pharyngitis without requiring culture results. There is optimism that a vaccine, providing protection against many ARF-causing S. pyogenes strains, may be available in coming years. Collaborative approaches to RHD control, including World Heart Federation initiatives and the development of registers, offer promise for better control of this disease. New data on RHD-associated costs provide persuasive arguments for better government-level investment in primary and secondary prevention. There is expanding knowledge of potential biomarkers and immunological profiles which characterize ARF/RHD, and genetic mutations conferring ARF/RHD risk, but as yet no new diagnostic testing strategy is ready for clinical application. Summary Reduction in the disease burden and national costs of ARF and RHD are major priorities. New initiatives in the primary and secondary prevention of ARF/RHD, novel developments in pathogenesis and biomarker research and steady progress in vaccine development, are all causes for optimism for improving control of ARF/RHD, which affect the poorest of the poor. Keywords acute rheumatic fever, developing countries, disease control, rheumatic heart disease
INTRODUCTION Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain significant issues in developing countries and in some indigenous and migrant populations in developed countries. Leading physician and researcher Professor Bongani Mayosi suggests that because those affected are the ‘poorest people in the world’, ARF and RHD control are not receiving the attention they require [1]. Recent gatherings of individuals and organizations working towards RHD control have increased international awareness and collaboration, namely the second RHD Forum (Cape Town, 2013), the World Health Assembly (Geneva, 2013) and the third RHD Forum (Melbourne, 2014). Efforts are now focussed on the World Heart Federation (WHF) target to reduce premature deaths from RHD in people under 25 years by 25% by 2025. The WHF position statement promotes five key strategic areas: comprehensive www.co-pediatrics.com
register-based control programmes, global access to benzathine penicillin G, identification and development of public figures as RHD champions, expansion of RHD training hubs and support for vaccine development [2 ]. By September 2013, 20 countries had implemented control activities in line with these strategies [1]. In this review, we summarize &&
a
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Australia, bInstitute of Advanced Studies, Charles Darwin University, Darwin, Australia and cTelethon Kids Institute, Centre for Child Health Research, University of Western Australia, Perth Australia and Department of Paediatric and Adolescent Medicine, Princess Margaret Hospital for Children, Perth, Australia Correspondence to Jessica L. de Dassel, Menzies School of Health Research, PO Box 41096, Casuarina, Darwin, Northern Territory 0811, Australia. Tel: +61 8 8946 8600; e-mail: jess.dedassel@menzies. edu.au Curr Opin Pediatr 2015, 27:116–123 DOI:10.1097/MOP.0000000000000164 Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al.
KEY POINTS Estimates of the global burden of ARF and RHD remain unreliable, hampered by missing data in many countries and the use of different methods and populations for diagnosis. Findings from genetics studies and investigations into the autoimmune response increase our chances of eradicating ARF and RHD in the future. Primary prevention of ARF is being strengthened by the use of rapid antigen detection tests and the refinement of clinical decision rules. Most developing countries lack the financial and human resources required for comprehensive disease prevention programmes – increased utilization of existing infrastructure is needed.
developments during 2013–2014 in ARF and RHD relevant to developing countries.
LITERATURE REVIEW METHOD Medical databases were searched (Academic Search Premier, CINAHL, Grey Lit, Health Source: Nursing/ academic edition, LILACS, MedCarib, Medline, Scopus and Web of Science); grey literature was identified through Internet searches. Exclusion criteria: articles published prior to 1 January 2013, case studies, articles not in English, articles included in review articles/meta-analyses. The Millennium Development Goal definition of developing countries was used [3].
EPIDEMIOLOGY The Global Burden of Disease, Injuries and Risk Factors study (GBD) estimated that, in 2010, there were 34.2 million people with RHD (data provided
Table 1. Estimated global burden of rheumatic heart disease 1990
2005
2010
Prevalence
29 172 383
33 468 203
34 232 795
YLL
13 267 810
9 670 605
8 720 292
YLD [7] DALY [5] Deaths [4]
1 150 422
1 365 502
1 429 575
14 418 232
11 036 107
10 149 867
462 579
363 864
345 110
DALY, disability adjusted life years; YLD, years lived with disability; YLL, years of life lost. Data provided by the Institute for Health Metrics and Evaluation. Adapted from [6].
by the Institute for Health Metrics and Evaluation), resulting in 345 110 deaths [4] and 10.1 million disability adjusted life years lost during that year [5] (see Table 1). These compare with the most widely cited previous estimate, published in 2005, of 15.6 million cases and 233 000 deaths [8]. Although the GBD estimates are thought to come closer to the true RHD burden, there remains considerable uncertainty, largely because of limited data, underdiagnosis and lack of formal reporting systems from low-income and middle-income countries [9]. Underdiagnosis of ARF remains a major challenge; in Ethiopian children with RHD, only a quarter recalled any symptoms of ARF [10]. For RHD, the Rheumatic Heart Disease Global Registry (REMEDY) project is developing an international register to collate the data needed to advocate for governments to invest in disease-control strategies [1]. Increasing echocardiographic screening is also contributing key data [9].
New data on the prevalence of rheumatic heart disease The decreasing cost of echocardiography has enabled the proliferation of screening initiatives in developing countries. Important recent findings are summarized in Table 2. Late presentation to health facilities means the proportion of severe cases is high in developing countries [22,23]. Data from Uganda suggest HIV infection may be associated with increased RHD rates, which requires further investigation [24]. In promising new data from Brazil, hospitalization rates for both ARF and RHD have fallen, with a corresponding fall in RHD mortality [25].
Morbidity and mortality associated with rheumatic heart disease RHD remains a significant cause of heart failure and stroke in developing countries – RHD patients represented 12% of heart failure cases in a Tanzanian study [26] and up to 23.2% of strokes in Asia [27]. Complications arising from RHD during pregnancy also cause significant morbidity and mortality; in Nepal, pregnant women with RHD had a mortality rate of 4% and foetal and neonatal mortality was 16% [28]. Parks et al. [29] measured the mortality of RHD patients in Fiji; the standardized mortality ratio was 8.8 compared with the general population. Young indigenous Fijian men with RHD had the highest standardized mortality ratio at 50.0.
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
117
Infectious diseases and immunization Table 2. New data on the prevalence of rheumatic heart disease Country (region)
Population
Sample size
Diagnosis method
Prevalence
Egypt [11]
Schoolchildren (6–18 years)
48 930
Echocardiogram
0.7/1000
Fiji [12]
Schoolchildren (5–14 years, Indigenous Fijian)
1666
Echocardiogram (WHF criteria)
8.4/1000
India (north) [13]
Schoolchildren (5–15 years)
15 145
Auscultation or reported symptoms, followed up by echocardiogram
0.46/1000
India (south, rural) [14]
Over 15 years
44 164
Auscultation, followed up by echocardiogram
9.7/1000
Nepal (eastern Nepal) [15]
Schoolchildren (5–15 years)
2043
Auscultation, abnormal results followed up by echocardiogram
2.5/1000
Nepal [16]
Schoolchildren (5–15 years)
Target: 10 000
Auscultation followed by echocardiogram
Study underway
New Caledonia [17]
Schoolchildren (9–10 years)
12 728
Echocardiogram
8.9/1000
Samoa [18]
Schoolchildren (3–16 years)
8457
Echocardiogram
14/1000
Solomon Islands (Honiara) [19]
Schoolchildren (5–16 years)
700
Echocardiogram (WHF criteria)
24/1000
South Africa [20]
All ages
Undefined
Literature review of existing studies
Study underway
South Korea [21]
National insurance database
Not provided
Insurance claims for services linked to a RHD diagnosis
0.74/1000
RHD, rheumatic heart disease; WHF, World Heart Federation. Abnormalities were detected in 2712, only 1603 had an echocardiogram of sufficient quality for diagnosis.
THE COST OF RHEUMATIC HEART DISEASE The most recent calculations of the national cost of ARF and RHD are for South Korea and Fiji. In South Korea, the 2008 economic burden of RHD was estimated to be USD$67 250 000; 39% of these costs were indirect (associated with loss of productivity and premature death) [30]. The cost of ARF and RHD in Fiji was estimated to be USD$62 291 067 over 5 years; 97% of the total were indirect costs [31 ]. &
PATHOGENESIS OF ACUTE RHEUMATIC FEVER Recent studies have refined our understanding of the organism and host factors contributing to ARF pathogenesis. Evidence from a new systematic review identified 57 rheumatogenic Group A b haemolytic Streptococcus (GAS) emm types, more than previously appreciated [32]. It has been recognized that GAS virulence is linked to the hyaluronic acid capsule; serotype M18, classically associated with ARF, has a highly encapsulated phenotype. Lynskey et al. [33] have now identified that natural truncation of protein RocA causes this hyperencapsulation and the associated characteristics of carriage longevity and transmissibility. Studies of cytokine responses and monocyte expression provide clues to the aberrant host responses occurring in ARF [34–36], including elevated levels of tumour necrosis factor (TNF) a and interleukin-8 [37]. Findings regarding interleukin10 are inconsistent [35,36,38]. 118
www.co-pediatrics.com
There are two hypotheses regarding the development of autoimmunity in ARF: collagen mediated, as supported by Tandon et al. [39 ]; and molecular mimicry of myocellular proteins (although these concepts are not necessarily mutually exclusive [40]). A new development supporting molecular mimicry is the identification of antibodies to vimentin (a valve-associated protein) in RHD patients, which are cross-reactive with GAS, and could explain the inflammatory response in heart valves [41]. &
GENETIC PREDISPOSITION TO ACUTE RHEUMATIC FEVER Evidence for genetic susceptibility to ARF and RHD is growing. Recent findings are summarized in SDC1, http://links.lww.com/MOP/A22. Studies are underway in Samoa [42], Nigeria, Uganda and Rwanda [43] and our own study in Australia.
PREVENTION In 2004, the WHO published recommendations for ARF/RHD control [44]. Additional support for developing countries seeking to develop/strengthen their control programme is now available from the TIPS Handbook [45 ]. Of the recommended activities, Mayosi [46] nominates primary prevention (the treatment of GAS pharyngitis), and the establishment of register-based secondary prevention programmes as two of the 10 best buys for combating heart disease in Africa. Despite the advantages of &&
Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al.
disease prevention, some countries have no prevention or screening programme in place (e.g. Brazil) [47]. In Nepal, however, a national programme has been integrated into primary healthcare since 2007 and in 2013 a pilot primary prevention project was initiated at 42 primary healthcare centres, using a ‘treat all’ approach for GAS pharyngitis [48]. In Nepal, the Government’s commitment and centralized coordination by the Nepal Heart Foundation have been key to the programme’s success and sustainability [48]. Sudan and Rwanda also have programmes based on successful collaborations with government and nongovernment organizations [49,50]. Unfortunately, many countries spend the majority of their RHD funding on tertiary interventions, impeding the implementation of prevention programmes [51]. An innovative suggestion is to integrate RHD care into existing chronic disease management by utilizing infrastructure for HIV/ AIDS care; this approach is being trialled in Uganda and if successful, could be implemented in settings wherein HIV/AIDS infrastructure is well established [52 ]. &
Primary prevention Limited awareness of ARF and RHD is a major barrier to effective primary prevention [53], but progress is being made; new interactive computer-based resources targeting schoolchildren have been shown to increase knowledge in Kenyan children and could be used in similar settings [54 ]. When children present to health services with sore throat, throat culture remains the gold standard for the diagnosis of GAS pharyngitis. However, the emergence of rapid antigen detection tests (RADTs) and the proliferation of clinical decision rules allow for new diagnostic approaches. RADTs can be reliable, however, their performance varies; specificity ranges from 8.3 to 98.2% [55] and sensitivity 42–95% [56,57]. In one study, inadequate staff training substantially reduced the accuracy of the tests [55]. The use of RADTs in developing countries is likely to be limited by cost. The illumigene GAS assay was very effective in diagnosing GAS in children with 99% sensitivity and 99.6% specificity [58]. DNA biosensors, which stimulate an electrochemical signal when a DNA-labelled probe hybridizes with the DNA of target bacteria, have been proposed as an affordable, effective method for diagnosing GAS; results are available in 30 min and 100% specificity has been reported [59 ]. Clinical decision rules (CDRs) can be used in conjunction with culture or RADTs, or as a standalone approach. A meta-analysis of seven CDRs &
&
recommends the Joachim rules (see SDC2, http:// links.lww.com/MOP/A22), these were validated in a Brazilian population (sensitivity: 88%, specificity: 35%) [60 ]. Another comparison of CDRs, also in Brazil, recommended the Abu Reesh criteria [purulent oropharyngeal exudate or tender enlarged anterior cervical lymph nodes ¼ bacterial pharyngitis [61] (sensitivity: 85.2%, specificity: 25.8% [62])]. Two Cochrane reviews found no evidence to change the recommendation of penicillin for the treatment of GAS pharyngitis and the prevention of recurrent ARF; however, further studies in low-income, high-risk populations are needed [63 ,64 ]. There is still no reported evidence of GAS developing resistance to penicillin [65]. Irlam et al. [66] report on the cost-effectiveness of primary prevention approaches in South Africa and recommend the diagnosis of GAS pharyngitis using a clinical decision rule, and subsequent treatment with antibiotics (without culture confirmation), accompanied by primordial and secondary prevention activities. Assessment of the best approach in other settings should consider the local incidence of sore throat, CDRs with higher specificity and RADTs [67]. Manji et al. [68] compared the cost of primary and secondary prevention approaches and concluded that echocardiography followed by secondary prophylaxis for patients with evidence of RHD is the most cost-effective strategy. &&
&&
&&
Vaccine Vaccine research, underway since 1923, has investigated many candidates, targeting M proteins, GAS carbohydrate or non-M protein antigens [69 ]. Vaccine development faces several challenges: the limited commercial viability, the plethora of GAS strains (as many as 250 [70]) and the risk of stimulating an autoimmune response [1]. A study in Mali tested a 30-valent vaccine against 42 emm types (including 14 vaccine emm types) and a similar study in South Africa tested a 30-valent vaccine against 26 emm types (including 17 vaccine emm types). In both studies, immunological cross reactivity with nonvaccine serotypes extended the potential coverage of the vaccines to 95% of the tested emm types [71,72]. Funding awarded by the Australian and New Zealand Governments has assisted efforts, and clustering the emm types according to similar function may reduce the number of targets required [73]. &&
Secondary prevention Benzathine penicillin G (BPG) remains the recommended drug for secondary prophylaxis of ARF [63 ]; unfortunately, adherence is low in many &&
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
119
Infectious diseases and immunization
settings. For example, 46% of patients at Mulago Hospital in Uganda received less than 80% of their needles over a 6-month period, with pain the most commonly cited reason for missing a needle [74]. A new vibrating device from Buzzy has been trialled for pain minimization in New Zealand. Buzzy, in addition to lignocaine, reduced pain and fear reported by children compared with lignocaine alone [75 ]. This innovative low-cost device may improve adherence to secondary prophylaxis in developing settings. Concern about penicillin allergy/anaphylaxis can be an impediment to secondary prophylaxis delivery; a survey found that 25% of healthcare providers in high-prevalence countries reported that one or more of their patients had experienced anaphylaxis to BPG, and 20% reported a patient death due to BPG anaphylaxis [76]. However, the limited data on this matter indicate very low rates of true allergy; the most recent study reported suspected allergy in 2% and confirmed allergy in just 0.18% [77]. The only large scale study conducted to date (published in 1991) documented a 3.2% rate of allergic reactions but an incidence of true anaphylaxis of only 0.2% [78]. An additional challenge is the reliance on international producers and suppliers of BPG. Forty-two percent of survey respondents reported issues maintaining their supply; 33% reported difficulties with international suppliers [76]. &
Tertiary prevention Two meta-analyses confirm that heart valve repair is preferable to replacement in developing settings [79 ,80 ]; patient survival is better and anticoagulation is not required. However, in some settings, the limited opportunity for reoperation (eventually required after most valve repairs), means that replacement is used in preference to repair (e.g. in Rwanda), even though complication rates after replacement can be very high [50]. Most sub-Saharan African countries do not have cardiac surgery facilities so patients either travel overseas for procedures, or await international teams who visit on short-term bases [81]. In Fiji, an international team flies in to perform valve surgery, which is more cost-effective than transferring patients overseas for surgery. The mortality rate for patients who underwent valve replacement was 25.7%; 32.5% of deaths occurred within 90 days of the operation. The authors suggest greater collaboration between the surgical team and local health staff, and enhanced support for patients, including education and reminders for follow up appointments would improve patient outcomes [82]. &
120
&&
www.co-pediatrics.com
Locally performed surgery is also cheaper in Nigeria, where a mitral valve replacement costs USD$11 200 in country, and USD$20 000–USD$40 000 if done abroad [83]. Patients with mechanical valve replacements require lifelong anticoagulation. The challenges of warfarin are significant, and there is a pressing need for alternative therapies. Direct thrombin inhibitors (e.g. dabigatran etexilate) show promise; although more expensive, they have fewer interactions with other drugs or food and do not require monitoring or dose adjustments [80 ]. Surgery for patients from developing countries remains prohibitively expensive for most governments and patients. A key priority is to increase the number of surgeons who can perform valve repairs, but most benefit will be gained from primary and secondary prevention activities [84]. &&
ADVANCES IN DIAGNOSIS OF ACUTE RHEUMATIC FEVER The Jones Criteria for ARF diagnosis, first published in 1944, have been revised several times and are again under review. A further revision of the Jones Criteria from the American Heart Association is due for release in the near future (Gewitz M, personal communication, 29 September 2014). Over time the criteria have become more specific and less sensitive and their application in high-risk populations will result in missed cases [85], so localized guidelines are necessary in some countries. Investigation for improved diagnostic tests continues. Elevated levels of ischaemia-modified albumin could be a biomarker for ARF [86], and the detection of accelerated junctional rhythm may assist with differential diagnosis during the acute phase of ARF (specificity: 100%, sensitivity: 15.6%) [87].
ADVANCES IN DIAGNOSIS OF RHEUMATIC HEART DISEASE Echocardiograms have consistently proved to be superior to auscultation for RHD diagnosis [88] – most recently in Fiji where auscultation sensitivity was just 30% [12]. The accuracy of echocardiograms was substantially improved with the publication of the WHF echocardiographic criteria for RHD in 2012. An evaluation of the criteria found satisfactory levels of agreement in diagnoses made by experienced physicians [89 ]. The role of echocardiographic screening remains undecided. RHD only partially meets the Council of Europe Criteria for disease screening so until we strengthen the delivery of secondary &&
Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al.
prophylaxis and understand the natural history of subclinical RHD, screening cannot be endorsed [90 ]. The appropriate age for screening is also under discussion, with a report from Senegal advocating for inclusion of 16–18-year olds [91]. The limited availability of equipment and appropriately trained staff is a challenge, and work is underway to identify more cost-effective solutions. Hand-held devices are becoming more affordable and have been used by trained medical staff with high specificity and sensitivity (95 and 81%, respectively) [92]. Portable echocardiograms have been used by trained nurses with 73.2% specificity and 91.5% sensitivity [93 ]. A neural network (a decision support toolkit) could facilitate diagnosis in resource-poor settings. The tool analyses data, including ECG results, without the need for physician review and has resulted in 92.13% accuracy [94]. However, before more is invested in implementing screening activities in developing countries, the cost-effectiveness should be established [90 ]. Identifying additional biomarkers could enhance diagnosis and numerous proteins have recently been reported as possible indicators of RHD (see SDC3, http://links.lww.com/MOP/A22).
Acknowledgements None.
&&
Financial support and sponsorship Jessica de Dassel is supported by an Australian Postgraduate Award scholarship. Anna Ralph is supported by a National Health and Medical Research Council fellowship (1016567). Conflicts of interest None.
&
&&
TREATMENT A gap remains in our understanding of the progression of subclinical RHD and whether secondary prophylaxis would benefit these patients. In New Caledonia, 35% of subclinical cases proceeded to definite RHD within 2 years follow up, 43% to borderline RHD and 22% reverted to normal [95]. These findings suggest that there are some subclinical cases that would benefit from secondary prophylaxis; however, it is unclear what the features of those cases are, and whether these results can be extrapolated to other populations.
CONCLUSION ARF and RHD continue to impose a significant burden on the people and health systems of developing countries. Progress in disease control is hampered by limited community awareness, inadequate provision of secondary prophylaxis and limited availability of tertiary interventions. A vaccine for GAS infection should dramatically reduce the incidence of ARF. For those already affected by RHD, greater investment in training and retaining health staff is key, as is the development of sustainable partnerships which enable prevention programmes to operate independently of international funding and expertise.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Maurice J. Rheumatic heart disease back in the limelight. Lancet 2013; 382:1085–1086. 2. Remenyi B, Carapetis J, Wyber R, et al. Position statement of the World Heart && Federation on the prevention and control of rheumatic heart disease. Nat Rev Cardiol 2013; 10:284–292. This statement outlines key strategic areas for improving disease control and meeting WHF targets. 3. United Nations Statistics Division. Millennium Development Indicators: World and regional groupings 2014. http://mdgs.un.org/unsd/mdg/Host.aspx? Content=Data/REgionalGroupings.htm. [Accessed 17 November 2014]. 4. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380:2095– 2128. 5. Murray CJL, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380:2197–2223. 6. Schodel F. Group A streptococcal vaccines: challenges and progress. The Global Vaccine and Immunization Research Forum (GVIRF) [Internet]. 2014. http://www.who.int/immunization/research/forums_and_initiatives/03_Schodel_GVIRF14_GAS_Vaccinedev.pdf. [Accessed 17 November 2014]. 7. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study. Lancet 2012; 380: 2163–2196. 8. Carapetis JR, Steer AC, Mulholland EK, et al. The global burden of group A streptococcal diseases. Lancet Infect Dis 2005; 5:685–694. 9. Zuhlke LJ, Steer A. Estimates of the global burden of rheumatic heart disease. Global Heart 2013; 8:189–195. 10. Tadele H, Mekonnen W, Tefera E. Rheumatic mitral stenosis in children: more accelerated course in sub-Saharan Patients. BMC Cardiovasc Disord 2013; 13:95. 11. Farrag AAM, Aroussy WAE, Hagracy NE, et al. Echocardiographic screening for rheumatic valvular heart disease among Egyptian school children. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 12. Colquhoun SM, Kado JH, Remenyi B, et al. Echocardiographic screening in a resource poor setting: Borderline rheumatic heart disease could be a normal variant. Int J Cardiol 2014; 173:284–289. 13. Negi PC, Kanwar A, Chauhan R, et al. Epidemiological trends of RF/RHD in school children of Shimla in north India. Indian J Med Res 2013; 137:1121– 1127. 14. Sriharibabu M, Himabindu Y, Kabir Z. Rheumatic heart disease in rural south India: a clinico-observational study. J Cardiovasc Dis Res 2013; 4:25–29. 15. Gautam S. Prevalence and pattern of rheumatic heart disease in school children from eastern part of underdeveloped, poor country Nepal: A crosssectional, observational study. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 16. Pilgrim T, Kalesan B, Karki P, et al. Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal. BMJ Open 2012; 2:e001320. 17. Baroux N, Rouchon B, Huon B, et al. High prevalence of rheumatic heart disease in schoolchildren detected by echocardiography screening in New Caledonia. J Paediatr Child Health 2013; 49:109–114. 18. Viali S. Rheumatic heart disease in Samoa and the Pacific Nations. J Prim Healthcare 2014; 6:84–85.
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
121
Infectious diseases and immunization 19. Kennedy L, Nasi T, Ludawane B, et al. Burden of rheumatic heart disease in the Solomon Islands. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 20. Zu¨hlke L, Watkins D, Engel ME. Incidence, prevalence and outcomes of rheumatic heart disease in South Africa: a systematic review protocol. BMJ Open 2014; 4:e004844. 21. Jang SY, Ju E-Y, Seo SR, et al. Changes in the etiology of valvular heart disease in the rapidly aging Korean population. Int J Cardiol 2014; 174:355– 359. 22. Zhang WZ, Mondo C, Okello E, et al. Presenting features of newly diagnosed rheumatic heart disease patients in Mulago Hospital: a pilot study. Cardiovasc J Afr 2013; 24:28–33. 23. Akinwusi PO, Peter JO, Oyedeji AT, et al. The new face of rheumatic heart disease in South West Nigeria. Int J Gen Med 2013; 6:375–381. 24. Gleason B, Mirembe G, Namuyonga J, et al. Does HIV infection modify the risk of RHD? Initial echocardiographic screening experience at the Joint Clinical Research Centre in Kampala, Uganda. Global Heart 2014; 9 (1S):e55. 25. Azevedo VMP, Mu¨ller RE, Kaufman R, et al. Is rheumatic fever already controlled in Brazilian children and adolescents? An overview about the last 21 years epidemiological data. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 26. Makubi A, Hage C, Lwakatare J, et al. Contemporary aetiology, clinical characteristics and prognosis of adults with heart failure observed in a tertiary hospital in Tanzania: the prospective Tanzania Heart Failure (TaHeF) study. Heart 2014; 100:1235–1241. 27. Wang D, Liu M, Lin S, et al. Stroke and rheumatic heart disease: a systematic review of observational studies. Clin Neurol Neurosurg 2013; 115:1575– 1582. 28. Chhetri S, Shrestha NR, Pilgrim T. Pregnancy complicated by heart disease in Nepal. Global Heart 2014; 9 (1S):e39. 29. Parks T, Kado J, Miller AE, et al. Mortality amongst patients with rheumatic heart disease in Fiji: a national historic data-linkage cohort study. Global Heart 2014; 9 (1S):e158. 30. Seo H-Y, Yoon S-J, Kim E-J, et al. The economic burden of rheumatic heart disease in South Korea. Rheumatol Int 2013; 33:1505–1510. 31. Heenan RC, Ba¨rnighausen T, O’Brien J, et al. The cost-of-illness of rheumatic & heart disease: a national estimation in Fiji. Global Heart 2014; 9 (1S):e30. This is an important contribution to our knowledge of cost of ARF and RHD in a high-prevalence developing country, where indirect costs accounted for 97% of the total. 32. Baroux N, D’Ortenzio E, Smeesters P, et al. GAS emm-types probably involved in acute rheumatic fever. Global Heart 2014; 9 (1S):e37. 33. Lynskey NN, Goulding D, Gierula M, et al. RocA truncation underpins hyperencapsulation, carriage longevity and transmissibility of serotype M18 Group A Streptococci. PLoS Pathog 2013; 9:15. 34. Martin WJ, Minigo G, Keeble J, et al. Involvement of Th17 cytokines in acute rheumatic fever. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 35. Bryant PA, Smyth GK, Gooding T, et al. Susceptibility to acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis. Infect Immun 2014; 82:753–761. 36. Rehman S, Akhtar N, Saba N, et al. A study on the association of TNF-a-308, IL-6-174, IL-10-1082 and IL-1RaVNTR gene polymorphisms with rheumatic heart disease in Pakistani patients. Cytokine 2013; 61:527–531. 37. Abul-fadl A, Hady SA, Gad N. Cytokines as a predictor of progression to valvular disease in children with rheumatic fever. J Saudi Heart Assoc 2013; 25:127. 38. Lea˜o SC, Lima MRM, Nascimento HM, et al. IL-10 and ET-1 as biomarkers of rheumatic valve disease. Rev Bras Cir Cardiovasc 2014; 29:25–30. 39. Tandon R, Sharma M, Chandrashekhar Y, et al. Revisiting the pathogenesis of & rheumatic fever and carditis. Nat Rev Cardiol 2013; 10:171–177. This review summarizes and analyses proposed mechanisms of autoimmunity in ARF to date, and concludes that collagen-mediated autoimmunity is the most likely mechanism. 40. Cunningham MW. Rheumatic fever revisited. Nat Rev Cardiol 2014; 11:123. 41. Delunardo F, Scalzi V, Capozzi A, et al. Streptococcal-vimentin cross-reactive antibodies induce microvascular cardiac endothelial proinflammatory phenotype in rheumatic heart disease. Clin Exp Immunol 2013; 173:419–429. 42. Kauwe JK, Allen LB, Allen M, et al. Rheumatic Rescue: Genetic basis for elevated rheumatic heart disease susceptibility in Samoa. Poster session presented at World Congress of Cardiology 2014; May 4–7; Melbourne. 43. United States National Institutes of Health. clinicaltrials.gov. http://clinical trials.gov/ct2/home. [Accessed 29 July 2014] 44. World Health Organization. Rheumatic fever and rheumatic heart disease. Report of a WHO expert consultation; October–November 2001. Geneva: World Health Organization; 2004. 45. Wyber R, Grainger Gasser A, Thompson D, et al. Tools for Implementing && RHD Control Programmes (TIPS) Handbook. Perth, Australia: World Heart Federation and RhEACH; 2014. This handbook is a key evidence-based guide for the development and strengthening of ARF and RHD disease control programmes. 46. Mayosi BM. The 10 ‘Best Buys’ to combat heart disease, diabetes and stroke in Africa. Heart 2013; 99:973–974.
122
www.co-pediatrics.com
47. Bocchi EA. Heart failure in South America. Curr Cardiol Rev 2013; 9:147– 156. 48. Regmi PR, Wyber R. Prevention of rheumatic fever and heart disease: Nepalese experience. Global Heart 2013; 8:247–252. 49. Shetty P. Sulafa Ali: a pioneer of paediatric cardiology in Sudan. Lancet 2014; 383:687. 50. Swain JD, Pugliese DN, Mucumbitsi J, et al. Partnership for sustainability in cardiac surgery to address critical rheumatic heart disease in subSaharan Africa: the experience from Rwanda. World J Surg 2014; 38: 2205–2211. 51. Ramokgopa G. Public sector prevention of RF and RHD in South Africa. Global Heart 2013; 8:187–188. 52. Longenecker C, Lwabi P, Kityo C, et al. Leveraging existing HIV/AIDS & infrastructure for rheumatic heart disease care in Uganda: a collaborative disease surveillance and management program. Global Heart 2014; 9 (1S):e55. This study describes a new approach for control in developing settings: using infrastructure from HIV/AIDS programmes to improve ARF and RHD control. 53. Zu¨hlke L J, Engel ME. The importance of awareness and education in prevention and control of RHD. Global Heart 2013; 8:235–239. 54. Matheka DM, Murgor M, Kibochi E, et al. Role of technology in creating & rheumatic heart disease awareness among school-going children in Kenya. Global Heart 2014; 9 (1S):e7–e8. This study reports on the effective use of new free computer-based education resources with schoolchildren in Kenya. 55. Toepfner N, Henneke P, Berner R, et al. Impact of technical training on rapid antigen detection tests (RADT) in group A streptococcal tonsillopharyngitis. Eur J Clin Microbiol Infect Dis 2013; 32:609–611. 56. Upton A, Lennon D, Stewart J, et al. Disappointing performance of rapid antigen detection tests for group A streptococcus in the Auckland schoolbased sore throat programme. N Z Med J 2014; 127:103–105. 57. Little P, Hobbs FDR, Moore M, et al. Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management). BMJ 2013; 347:f5806. 58. Henson AM, Carter D, Todd K, et al. Detection of Streptococcus pyogenes by use of Illumigene group A Streptococcus assay. J Clin Microbiol 2013; 51:4207–4209. 59. Singh S, Kaushal A, Khare S, et al. Gold-mercaptopropionic acid-polyethy& lenimine composite based DNA sensor for early detection of rheumatic heart disease. Analyst 2014; 139:3600–3606. This study proposes the use of biosensors as a cost-effective method for diagnosing GAS infection. 60. Le Marechal F, Martinot A, Duhamel A, et al. Streptococcal pharyngitis in && children: a meta-analysis of clinical decision rules and their clinical variables. BMJ Open 2013; 3:10. This is an important comparison of the accuracy of several clinical decision rules for diagnosing GAS pharyngitis. 61. Steinhoff MC, Khalek MKAEI, Khallaf N, et al. Effectiveness of clinical guidelines for the presumptive treatment of streptococcal pharyngitis in Egyptian children. Lancet 1997; 350:918–921. 62. Orofino DHG, Passos SRL, de Andrade CAF, et al. Accuracy and interobserver variation of three clinical decision rules for the diagnosis of streptococcal pharyngitis. Pediatr Infect Dis J 2013; 32:686–687. 63. Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane && Database Syst Rev 2013; 11:CD000023. This Cochrane review confirms that penicillin is the best choice for treatment of GAS pharyngitis. 64. van Driel ML, De Sutter AIM, Keber N, et al. Different antibiotic treatments for && group A streptococcal pharyngitis. Cochrane Database Syst Rev 2013; 4:CD004406. This Cochrane review that confirms penicillin is the most effective medication for prevention of ARF recurrences. 65. Dhanda V, Chaudhary P, Toor D, et al. Antimicrobial susceptibility pattern of bhaemolytic group A, C and G streptococci isolated from North India. J Med Microbiol 2013; 62 (Pt 3):386–393. 66. Irlam JH, Mayosi BM, Engel ME, et al. A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis. S Afr Med J 2013; 103:894–895. 67. Steer A. Primary prevention of rheumatic fever in children: key factors to consider. S Afr Med J 2014; 104:156. 68. Manji RA, Witt J, Tappia PS, et al. Cost-effectiveness analysis of rheumatic heart disease prevention strategies. Expert Rev Pharmacoecon Outcomes Res 2013; 13:715–724. 69. Sharma A, Nitsche-Schmitz DP. Challenges to developing effective strepto&& coccal vaccines to prevent rheumatic fever and rheumatic heart disease. Vaccine: Development & Therapy 2014; 4:39–54. This is a summary of the GAS vaccines in development and outlines the advantages and disadvantages of each. 70. Tandon R. Preventing rheumatic fever: M-protein based vaccine. Indian Heart J 2014; 66:64–67. 71. Dale JB, Penfound TA, Tamboura B, et al. Potential coverage of a multivalent M protein-based group A streptococcal vaccine. Vaccine 2013; 31:1576– 1581.
Volume 27 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Controlling ARF & RHD in developing countries de Dassel et al. 72. Engel ME, Muhamed B, Whitelaw AC, et al. Group A streptococcal emm type prevalence among symptomatic children in Cape Town and potential vaccine coverage. Pediatr Infect Dis J 2014; 33:208–210. 73. Sanderson-Smith M, De Oliveira DMP, Guglielmini J, et al. A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis. 2014;210:1325– 1338. 74. Musoke C, Mondo CK, Okello E, et al. Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital. Cardiovasc J Afr 2013; 24:124–129. 75. Russell K, Nicholson R, Naidu R. Reducing the pain of intramuscular ben& zathine penicillin injections in the rheumatic fever population of Counties Manukau District Health Board. J Paediatr Child Health 2014; 50:112–117. Important evaluation of a pain minimisation device that shows it reduced children’s reported pain and fear associated with BPG injections. 76. Taubert K, Marko SB. Access to essential medicines: illuminating disparities in the global supply of benzathine penicillin g in the context of rheumatic fever/ rheumatic heart disease prevention. In: American College of Cardiology Conference. San Francisco: Journal of the American College of Cardiology; 2013; 6: E2004. 77. Kaya A, Erkoc¸og˘lu M, Senkon OG, et al. Confirmed penicillin allergy among patients receiving benzathine penicillin prophylaxis for acute rheumatic fever. Allergol Immunopathol (Madr) 2014; 42:289–292. 78. International Rheumatic Fever Study Group. Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group. Lancet 1991; 337:1308–1310. 79. Wang Z, Zhou C, Gu H, et al. Mitral valve repair versus replacement in patients & with rheumatic heart disease. J Heart Valve Dis 2013; 22:333–339. This is a meta-analysis concluding that heart valve repair is preferable over valve replacement. 80. Michota F. Transitions of care in anticoagulated patients. J Multidiscip Healthc && 2013; 6:215–228. This is a summary of recent developments in anticoagulation, including the new drug dabigatran which could improve anticoagulation for patients in developing countries. 81. Ferratini M, Marianeschi S, Santoro F, et al. Valvulopathies in sub-Saharan African children: patterns, humanitarian interventions and cardiac surgical problems. Int J Cardiol 2013; 165:237–241. 82. Thomson Mangnall L, Sibbritt D, Fry M, et al. Short- and long-term outcomes after valve replacement surgery for rheumatic heart disease in the South Pacific, conducted by a fly-in/fly-out humanitarian surgical team: a 20-year retrospective study for the years 1991 to 2011. J Thorac Cardiovasc Surg 2014; pii: S0022-5223(14)00162-7. doi: 10.1016/j.jtcvs.2014.02.006. [Epub ahead of print] 83. Falase B, Sanusi M, Majekodunmi A, et al. The cost of open heart surgery in Nigeria. Pan Afr Med J 2013; 14:61.
84. Finucane K, Wilson N. Priorities in cardiac surgery for rheumatic heart disease. Global Heart 2013; 8:213–220. 85. Lilic N, Kumar P. A timely reminder: rheumatic fever. N Z Med J 2013; 126:88–90. 86. Toker A, Karatas Z, Altin H, et al. Evaluation of serum ischemia modified albumin levels in acute rheumatic fever before and after therapy. Indian J Pediatr 2014; 81:120–125. 87. Ceviz N, Celik V, Olgun H, et al. Accelerated junctional rhythm in children with acute rheumatic fever: is it specific to the disease? Cardiol Young 2014; 24:464–468. 88. Roberts KV, Brown ADH, Maguire GP, et al. Utility of auscultatory screening for detecting rheumatic heart disease in high-risk children in Australia’s Northern Territory. Med J Aust 2013; 199:196–199. 89. Remenyi B, Carapetis J, et al., on behalf of Working group on international && standardization of echocardiographic criteria for Rheumatic Heart Disease. World Heart Federation evidence-based echocardiographic criteria for rheumatic heart disease allows for reproducible diagnosis. Global Heart 2014; 9 (1S):e25–e26. This is an important evaluation of the WHF echocardiogram criteria which reports that these criteria can be used with satisfactory levels of agreement between experienced physicians. 90. Zu¨hlke L, Mayosi BM. Echocardiographic screening for subclinical rheumatic && heart disease remains a research tool pending studies of impact on prognosis. Curr Cardiol Rep 2013; 15:343. This is a discussion of the use of echocardiographic screening for the prevention of RHD which concludes that we need to know more about the natural history of RHD and need to strengthen health systems before it can be recommended in developing settings. 91. Kane A, Mirabel M, Toure´ K, et al. Echocardiographic screening for rheumatic heart disease: Age matters. Int J Cardiol 2013; 168:888–891. 92. Shmueli H, Burstein Y, Sagy I, et al. Briefly trained medical students can effectively identify rheumatic mitral valve injury using a hand-carried ultrasound. Echocardiography 2013; 30:621–626. 93. Colquhoun SM, Carapetis JR, Kado JH, et al. Pilot study of nurse-led & rheumatic heart disease echocardiography screening in Fiji – a novel approach in a resource-poor setting. Cardiol Young 2013; 23:546–552. This is an important pilot showing that trained nurses can effectively perform echocardiograms. 94. Iftikhar F, Shams A, Dilawari A. RCD: a toolkit for rheumatic valvular and congenital heart defect diagnosis. Neural Computing & Applications 2013; 23:1729–1735. 95. Mirabel M, Fauchier T, Tafflet M, et al. Follow-up of subclinical rheumatic heart disease in children. Poster session presented at: American Heart Association Scientific Sessions; 16–20 November 2013; Dallas. http://circ.ahajournals. org/cgi/content/meeting_abstract/128/22_MeetingAbstracts/A16421. [Accessed 17 November 2014].
1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-pediatrics.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
123
