Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide, with global estimates of more than 34 million people affected and > 345,000 annual deaths, mainly in Sub-Saharan Africa [1‐3]. RHD is a chronic complication of acute rheumatic fever (ARF), an exaggerated immune response to Group A Streptococcus infections, mostly of the throat, occuring usually during childhood and adolescence [4, 5]. RHD complications include heart failure, atrial fibrillation, infective endocarditis, cardio-embolic stroke and adverse pregnancy outcomes [3, 6]. Secondary prophylaxis with 4-weekly injection of benzathine penicillin G (BPG) remains the most effective intervention for preventing RHD progression [7]. However, there are numerous and poorly understood barriers to effective control programmes [8].

RHD thrives in poor, over-crowded communities in low- and middle-income countries (LMICs) with limited access to basic social amenities, including housing and health care [1‐3]. Despite its high morbidity and mortality, RHD became largely neglected after it was virtually eliminated in high-income countries (HICs) by the end of the twentieth century [9]. In May 2018, following years of campaigning and advocacy from the RHD community [10] the World Health Organisation (WHO) launched the “Global Resolution on Rheumatic Fever and Rheumatic Heart Disease” which was unanimously adopted by member states [11]. This resolution calls for action to strengthen primary and secondary prevention of ARF and RHD, integrate RHD services into primary health care, secure a reliable supply of BPG, and ensure a well-resourced and trained health workforce to provide RHD services. Indeed, the main barriers to RHD prevention, control and elimination in endemic countries are: the neglect of ARF and RHD in national health policies and budgets; the paucity of data to enable targeting of prevention efforts; poor primary and secondary prevention and access to primary health care; inadequate numbers and training of health workers at all levels; limited understanding of ARF/RHD in affected communities, and inaction on the social determinants of the disease and inequities in health [11]. Although further research in some areas is needed, the biggest gap in RHD control is in the implementation of effective primary and secondary preventive measures. On 6th January 2020, the World Heart Federation (WHF) President met with the WHO Director General to share ambitions and actions which would lead to the elimination of RHD in a generation [11, 12].

In The Gambia, the burden of RHD is thought to be high given the substantial number of children presenting at referral hospitals at an advanced stage of the disease. Indeed, there are more than 250 children with RHD currently being managed as outpatients at the paediatrics department of the Edward Francis Small Teaching Hospital (EFSTH), the main referral and only teaching hospital in The Gambia, and at the Clinical Services Department (CSD) of the Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine (MRCG). Despite this, no high-quality data are available and no control programme is currently implemented.

In both institutions, care for children with RHD (including consultation, laboratory, imaging and medications) is provided free of charge. Echocardiography is available at the MRCG and is provided free of charge for children while adults are charged ~ US$4. There are three private echocardiography service centres, all of them based at the coast near the capital city, whose services are charged $30 to $40 per patient.

As a first step towards larger, collaborative, multi-disciplinary research projects between the Gambian Health Services and the MRCG to inform the development of an effective national RHD control programme, we conducted a baseline study to review all patients registered as having ARF or RHD at the MRCG and/or EFSTH. The objective was to describe the clinical and valvular characteristics of known RHD patients at first presentation, at last evalution during the present study, adherence to penicillin prophylaxis and the evolution of clinical and valvular lesions over time.

“This is the first publication of the RHD burden in The Gambia, reporting on the clinical and valvular evolution of RHD with related challenges to effective penicillin prophylaxis in a retrospective cohort of 111 RHD patients. While documenting a high burden, we have detected only those who presented to the health care system, largely with symptoms of heart failure suggesting severe disease. These findings suggest that there are many more cases of undetected disease, particularly in adolescents and young adults. For example, in Australia where RHD registration is the most comprehensive in the world, only 19% of cases are severe, 28% are moderate and 53% are mild [21]. Hence in the Gambia the true RHD burden is likely several-fold higher than reported here. This first Gambian report allowed us to highlight key challenges (Fig. 2) to be addressed for the control and elimination of RHD in a generation [12, 22, 23].”

It is important to highlight the high case fatality rate, particularly in young patients, in the face of unavailable cardiac surgery in the country. Our case fatality rate in 2017 was estimated at almost 20% and this was similar (17.8%) to the one reported the same year in a prospective cohort study conducted in Uganda by Okello et al. [24]. The REMEDY study which compiled data from 14 LMICs between 2010 and 2012 reported a 2-year case fatality rate of 16.9% [25]. A prior study conducted in Ethiopia in 2005 reported an annual case fatality rate of 12.5% [26]. These data highlight what has been described elsewhere as the”stark reality of rheumatic heart disease” in Africa [27], and other developing countries [28, 29]. Most of our patients (86%) died before their 25th birthday, at a median age of 17 years, showing the high human and socio-economic burden of premature deaths in The Gambia. This calls for the urgent implementation of effective control measures to achieve by 2025 the WHF strategic goal of reducing by 25% RHD mortality in individuals aged < 25 years [8].

The high case fatality rate is consistent with the finding that most patients only seek health care at an advanced stage of heart failure (Ross 3–4) and severe mitral valve lesions are often associated with other valvular lesions. This is a common finding in RHD endemic countries. Indeed, in Uganda, 85% of newly diagnosed RHD patients at the national referral hospital had cardio-vascular symptoms and half of them had complications such as congestive cardiac failure, including 32.7% with pulmonary hypertension [30]. In a later cohort study [24] Okello et al. also showed that both morbidity and mortality were significantly higher in patients presenting late with advanced disease. Similar characteristics at presentation were reported by the multi-country REMEDY study [25]. In another report of the REMEDY study [6] atrial fibrillation was documented in 21% of the patients; stroke, systemic embolism, bleeding and infective endocarditis were reported in all countries.

The main reason for late presentation in LMICs is the limited understanding of ARF and/or RHD in the affected communities [31, 32]. In our study, history of recurrent sore throat was reported by more than half of the patients but only a few of them had sought medical treatment, missing the opportunity for primary prophylaxis of ARF. Most patients were unaware of the link between sore throat, ARF and RHD, and believed traditional remedies were more appropriate. This has already been observed in other endemic countries, both within [33‐35] and outside [36‐38] Africa. Interestingly, about half of our patients reported a history of ARF before developing signs of heart failure and most of them had consulted a health facility. Unfortunately, this opportunity for secondary prophylaxis was missed by the local health staff as only 6 patients were diagnosed and treated for ARF. This is not surprising as ARF is usually underdiagnosed in endemic settings [3, 30, 35, 36]. ARF remains a diagnostic challenge for most clinicians due to the multi-systemic nature of the condition and diversity in presentations [39]. The diagnosis of ARF, given the high occurrence of atypical presentations, is often based on clinical suspicion. Treatment should be started without delay to avoid misdiagnosis, the risk of disease progression and cardiac sequelae. In The Gambia, primary health care staff (mostly nurses) are usually unaware of the moderate to high risk of ARF/RHD in local communities. This explains their low level of suspicion when dealing with aseptic mono-arthritis, polyarthralgia or sub-clinical carditis, a relatively common occurrence [39, 40]. Such a problem has been internationally recognized and the 2015 revision of Jones Criteria now includes echocardiographically diagnosed subclinical endocarditis as a major criterion and recommends echocardiography in all proven and suspect cases [41, 42]. About half of our patients reported signs and symptoms compatible with ARF, offering the opportunity to improve secondary prophylaxis if health staff are adequately trained. This calls for an urgent update of the current medical and nursing curricula to improve ARF case management and provide a more accurate estimation of the ARF/RHD burden.

A few of our patients were diagnosed with heart failure during adulthood. These were predominantly women, about half of them multiparous, with multiple severe valvular lesions, often including mitral valve stenosis, and pulmonary hypertension. This suggests a different pattern of evolution, compared to patients diagnosed during childhood, as RHD lesions may have developed at sub-clinical level very slowly, allowing the heart to progressively adapt to new valvular lesions and cope with related hemodynamic changes until decompensation, i.e. after several pregnancies. The physiological hemodynamic changes during pregnancy, including increased stroke volume, heart rate and cardiac output, are poorly tolerated in patients with rheumatic valve disease. Indeed, in LMICs, RHD is the most frequent cardiac condition during pregnancy and the first cause of maternal death [43‐45]. A recent international registry study on 390 pregnant women has shown that women with moderate, severe or symptomatic rheumatic mitral valve disease, especially those with severe mitral stenosis, are at very high risk of heart failure during pregnancy, while those with mild or asymptomatic mitral valve disease tolerated pregnancy well [46]. Systematic screening for RHD among pregnant women in LMICs, especially primigravidae, could significantly improve the pregnancy outcomes and the prevention of further valve damage with adequate secondary prophylaxis.

Secondary penicillin prophylaxis is essential for the management of ARF and the prevention of recurrences [7] and intramuscular BPG is superior to oral penicillin. Secondary prophylaxis reduces the severity of RHD by preventing disease progression [47, 48], and even by increasing the rate of regression of mitral regurgitation. Since 2013, our patients were given oral secondary PP although only half of them were taking it as recommended. This is not surprising given that in RHD patients with persistent valvular disease oral penicillin should be taken twice daily at least until the age of 40 years [49]. It is difficult to estimate adherence retrospectively as this may vary over time and patient’s age. Indeed, some patients adhered strictly to the treatment for several years before defaulting. The main reported reasons for low adherence or defaulting among children were either financial constraints (transport costs for monthly reviews, or costs for medicine following regular drug shortages), lack of time or motivation of the parents/caretaker for monthly reviews, or the geographical distance from the clinic. Adherence to monthly BPG injections may not necessarily be better as it has other disadvantages (i.e. pain, fear of anaphylactic shock) [50]. Interventions to improve adherence to secondary prophylaxis should consider several factors, e.g. age, socio-cultural factors, and the health system capacity and may include an active recall system, provision of holistic care, involvement of community health workers and delivery of ARF/RHD health education.

“Although valvular lesions worsened in less than 25% of our patients, such estimation does not include those who died (n=35) and those who underwent surgery (n=17). This proportion can also be explained by the fact that most of our patients presented with already severe valvular disease. Concerning the clinical evolution of the 111 patients, almost half of them showed some degree of worsening since presentation.”

. In our context, this is likely due to the combination of late presentation leading to unfavorable outcomes [24, 51], and poor adherence to secondary prophylaxis. Therefore, in The Gambia BPG should be recommended for both primary and secondary prophylaxis. However, given the past history of sudden deaths and current fear of anaphylactic shock, many health care workers still feel anxious about its use. Therefore, we need substantial health education and training about the safe delivery of intramuscular BPG for both primary and secondary prophylaxis. Experience from other countries have shown that improved delivery of BPG can be achieved and results in good adherence by patients [50, 52, 53].

Cardiac surgery is not available in The Gambia, therefore only a very small proportion of RHD patients can benefit from it abroad with the support of private sponsors. The international non-governmental organization (NGO) “Chain of Hope” (https://​www.​chainofhope.​org/​) has been supporting cardiac surgery for Gambian children since 2007 but only 3–5 children on average per year are selected. On a positive note, the recent development of cardiac surgery in neighboring Senegal may improve access in the near future to life-saving interventions for our young Gambian patients.

The study had some important limitations due to the retrospective data collection. First, the study design (hospital-based retrospective cohort) did not allow estimating the RHD burden in the local communities. However, the high number of RHD patients presenting at an advanced stage of heart failure and the fact that some of them are diagnosed during adulthood, particularly multigravidae, suggests a high and largely undetected burden of RHD.

Secondly, the absence of EMRS and specific record keeping for ARF/RHD patients at the Teaching Hospital led to an under-representation of their patients (i.e. only 10 versus 101 patients from MRCG) while they are both referral centers. However, clinical and valvular characteristics at first presentation, evolution, poor access to cardiac surgery and high mortality are probably similar across institutions.. Adherence to penicillin, as well as to anti-failure treatment, might be slightly worse at ESFTH as compared to MRCG, due to frequent stockouts, requiring patients to buy treatment in private pharmacies outside the hospital.

This study highlights for the first time the devastating consequences of RHD on the health of Gambian adolescents and young adults. Our findings suggest a high and largely undetected burden of disease that is not addressed by appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control program to decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease. As recommended by the World Heart Federation, The Gambia needs a national RHD registry based on echocardiography screening (including pregnant women), the provision of safe and high quality BPG, and improved access to cardiac surgery in order to achieve the “25 by 25” strategic goal.