Review of pericarditis in Sub-Saharan Africa over the past 30 years, knowledge gaps and future perspectives.
La péricardite en Afrique subsaharienne : Évolution sur les 30 dernières années, lacunes dans les connaissances et perspectives d'avenir.
KINGUE S1, MENANGA AP2, BOOMBHI J3.
RESUME
Au cours des trois dernières décennies, l'évolution de la péricardite en Afrique subsaharienne (ASS) a été profondément marquée par la persistance des étiologies infectieuses, en particulier la tuberculose (TB), exacerbée par l'épidémie du Virus de l'Immunodéficience Humaine (VIH). La région fait face à un "double fardeau" de maladies transmissibles persistantes et d'une augmentation rapide des maladies non transmissibles (MNT), y compris l'insuffisance cardiaque et des conditions associées comme la péricardite.
Malgré quelques avancées dans les diagnostics et les traitements, des défis majeurs subsistent. La péricardite tuberculeuse (PTB) reste la forme prédominante, et bien que l'accès accru aux thérapies antirétrovirales (TAR) ait amélioré la mortalité chez les patients co-infectés par le VIH, la maladie continue de peser lourdement, notamment en raison de sa complication dévastatrice : la péricardite constrictive.
Les lacunes critiques incluent le manque persistant de données épidémiologiques robustes basées sur la population, limitant une évaluation précise de la charge de la maladie. L'accès aux outils diagnostiques essentiels comme l'échocardiographie, ainsi qu'aux méthodes moléculaires et d'imagerie avancées, reste très limité en raison de contraintes économiques et infrastructurelles. De même, l'efficacité des traitements antituberculeux standards est compromise par une faible pénétration des médicaments dans le péricarde. L'essai clinique IMPI, une étude africaine majeure, a apporté des preuves nuancées sur l'utilisation des corticostéroïdes, montrant qu'ils réduisent la constriction mais augmentent le risque de cancer chez les patients séropositifs au VIH, soulignant la nécessité d'une approche stratifiée. L'accès aux interventions chirurgicales définitives, comme la péricardectomie, demeure également un obstacle majeur.
Pour l'avenir, il est impératif de combler ces lacunes en générant des données épidémiologiques fiables, en améliorant la rapidité et la précision du diagnostic étiologique, en optimisant les schémas thérapeutiques pour prévenir les complications à long terme, et en renforçant les infrastructures de santé et les capacités humaines. Une recherche "centrée sur l'Afrique" est essentielle pour développer des interventions adaptées aux réalités uniques du continent, afin d'améliorer les résultats pour les patients et de progresser vers l'équité en matière de santé.
SUMMARY
Pericarditis in Sub-Saharan Africa (SSA) has undergone a complex evolution over the past three decades, predominantly shaped by the enduring impact of infectious etiologies, particularly tuberculosis (TB) exacerbated by the Human Immunodeficiency Virus (HIV) epidemic. While global cardiovascular disease (CVD) patterns are shifting, SSA faces a unique "double burden" of persistent communicable diseases alongside a rapidly escalating non-communicable disease (NCD) burden, including heart failure and its associated conditions like pericarditis. Despite some advancements in diagnostic modalities and treatment strategies, significant challenges persist in accurately diagnosing and effectively managing pericarditis, especially its long-term complications such as constrictive pericarditis. Critical knowledge gaps remain, notably the pervasive lack of robust population-based epidemiological data and the limited accessibility of advanced diagnostic and therapeutic interventions. Addressing these gaps necessitates a concerted effort towards Africa-centric research, substantial capacity building within healthcare systems, and the implementation of integrated, context-specific public health strategies to improve patient outcomes and achieve health equity across the region.
1. Honorary Professor of Cardiology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I
2. Professor of Cardiology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I
3. Associate Professor of Cardiology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I
Adresse pour correspondance
Samuel KINGUE, Honorary Professor of Cardiology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I.
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INTRODUCTION: PERICARDITIS IN SUB-SAHARAN AFRICA – A PUBLIC HEALTH IMPERATIVE
Context of Cardiovascular Disease Burden in the Region
Sub-Saharan Africa is currently grappling with a significant and escalating epidemic of cardiovascular diseases (CVDs). This shift is profound, as CVDs have emerged as the leading cause of death in the region since 2019, a striking change from the historical dominance of infectious diseases like HIV/AIDS and malaria. [1] This transformation underscores a pivotal reorientation in the health landscape, moving beyond a singular focus on communicable diseases. [2] Over the last three decades, the absolute number of CVD-related deaths in SSA has surged by over 50%. [2] This alarming increase is driven by a confluence of factors, including demographic transitions, rapid urbanization, and socioeconomic development, which have concurrently led to a rising prevalence of traditional CVD risk factors such as hypertension, obesity, and diabetes. [2]
This concurrent rise of non-communicable diseases, including various forms of CVD, alongside the persistent high burden of infectious diseases, creates what is often termed a "double burden" of disease. [2] This simultaneous challenge places immense strain on already stretched healthcare systems, which are characterized by limited capital and inadequate human resources. [3] The allocation of funding, the scope of training initiatives, and the development of essential infrastructure are all significantly impacted. This situation can lead to a dilution of efforts across multiple critical health areas, making it increasingly difficult to achieve substantial gains in any single domain, including the comprehensive management of pericarditis.
Significance of Pericarditis within the African Health Landscape
Within this evolving health landscape, pericarditis, particularly its tuberculous form, stands out as an endemic disease and a major contributor to the clinical syndrome of heart failure in SSA. It accounts for approximately 10% of all heart failure cases observed in hospital admissions. [4] The challenge of heart failure has been recognized in SSA for over six decades. [4] However, a significant limitation in understanding its true scope, and by extension, the burden of pericarditis, is the notable absence of population-based incidence or prevalence studies. Consequently, most available epidemiological information is derived from hospital-based studies, which may not fully capture the community-level burden. [4] This data limitation critically impacts accurate disease burden assessment and effective policy planning.
The prominence of pericarditis, particularly tuberculous pericarditis (TBP), as a significant cause of heart failure in SSA [4] extends beyond being solely a cardiac issue; it reflects broader systemic public health challenges. The strong epidemiological link between pericarditis and tuberculosis, further exacerbated by HIV co-infection [4], means that the trajectory of pericarditis is intrinsically tied to the success or failure of TB and HIV control programs. Therefore, pericarditis serves as a critical indicator of the effectiveness of infectious disease control measures and the overall resilience of the public health system in SSA. Its persistent high mortality rates [5] highlight fundamental systemic vulnerabilities that extend beyond the immediate realm of cardiovascular care.
EPIDEMIOLOGICAL EVOLUTION OF PERICARDITIS (PAST 30 YEARS)
Trends in Incidence and Prevalence: Challenges in Data Collection
Over the past three decades, the precise trends in the incidence and prevalence of pericarditis in SSA have been obscured by significant challenges in data collection. While heart failure has been acknowledged as a substantial health problem for many decades, population-based incidence and prevalence studies specifically for heart failure and pericarditis in Africa are remarkably scarce. [4] The majority of available epidemiological information is consequently derived from hospital-based studies, which, while valuable, may not fully represent the broader community burden. [4] A systematic review indicates that the prevalence of pericardial diseases can vary widely, from approximately 1.1% among individuals presenting with cardiac complaints to as high as 46.5% in HIV-infected populations exhibiting cardiac symptoms. [14] Although not specific to pericarditis, the overall absolute number of CVD deaths in SSA has increased by over 50% in the past three decades [2], suggesting a general rise in the burden of cardiac conditions.
The consistent observation of a lack of population-based incidence or prevalence studies [4] and the heavy reliance on hospital-based data [4] implies an "invisible burden" of pericarditis within the community. Without accurate, population-level data, the true scale of the problem, its geographical variations, and the efficacy of public health interventions cannot be precisely measured. This fundamental absence of robust epidemiological data significantly hinders effective resource allocation, informed policy development, and the appropriate prioritization of public health initiatives. In essence, this data scarcity renders the true disease burden less discernible to policymakers and international funders, potentially leading to under-resourcing and a perpetuation of suboptimal outcomes.
Shifting Etiological Landscape: The Enduring Dominance of Tuberculous Pericarditis
In Sub-Saharan Africa, the etiological landscape of heart failure and pericarditis remains distinct from that of developed regions, characterized by the enduring dominance of infectious causes. Heart failure in SSA is predominantly due to non-ischemic causes, accounting for 98% of cases, with infectious diseases remaining a major contributor. [4] Pericarditis, in particular, is overwhelmingly attributed to active tuberculous involvement. [4] A retrospective study from Cote d'Ivoire (1977-2012) on chronic constrictive pericarditis (CCP) found tuberculosis to be the main etiology in 99% of cases. [15] This stands in stark contrast to Western countries, where idiopathic, post-surgical, or radiation injury are the primary causes. [15]
A comparative study from 1995-2001 in Africa revealed that tuberculous pericarditis accounted for a staggering 69.5% of large pericardial effusions in the region, whereas a contemporary non-African series (1996-2004) reported only 3.8%. [4] This stark and persistent etiological divergence highlights the unique epidemiological context of pericarditis in SSA.
Despite the overwhelming dominance of tuberculosis as the cause of pericarditis in SSA [4], the disease has often been considered a "neglected" condition. [5] This situation presents a paradox: a highly prevalent and serious condition that has not received systematic research or structured control programs commensurate with its significant burden. [5] This relative neglect is partly attributable to the overshadowing of pericarditis by other major public health problems, such as malaria and HIV [5], and a historical funding bias that has primarily focused on acute infectious diseases. [5] This pattern suggests a systemic failure to translate the known high burden of TBP into proportionate policy and research investment, thereby perpetuating poor patient outcomes.
Au Sénégal, et de manière générale en Afrique subsaharienne, la plupart des études rapportant des différences entre les sexes dans la présentation des symptômes et le fardeau des facteurs de risque ont surtout examiné des populations souffrant de douleurs thoraciques aiguës, de syndrome coronarien aigu (SC).
The Profound Impact of the HIV Epidemic on Pericarditis Presentation and Burden
The HIV epidemic has profoundly influenced the incidence and presentation of pericarditis in SSA over the past three decades. The incidence of pericarditis in the region has demonstrably increased as a direct consequence of the HIV epidemic. [4] HIV-related cardiac pathology, manifesting primarily as dilated cardiomyopathy and tuberculous pericarditis, has emerged as a significant cause of heart failure in many African countries. [4]
Mycobacterium tuberculosis is identified as the underlying cause in up to 70% of pericardial effusion cases in HIV patients, with this proportion rising to over 90% in HIV-infected individuals residing in TB-endemic regions. [9]
HIV infection also modifies the clinical presentation of pericardial effusion, with a higher proportion of HIV-infected patients presenting with dyspnea and hemodynamic instability. [9] Earlier studies indicated a significantly higher mortality from TBP in HIV-infected individuals, with reported mortality rates of 40% at six months for those with HIV co-infection compared to 17% for those without HIV, suggesting a mortality rate twice as high in HIV-positive patients. [5] However, more recent findings from the Investigation of the Management of Pericarditis (IMPI) trial, a landmark African-led study, suggest a changing landscape. The IMPI trial found no significant difference in the 1-year case fatality rate between HIV-infected and HIV-uninfected patients with TBP in the modern Antiretroviral Therapy (ART) era. [18]
This evolution in HIV treatment, particularly the increased access to and uptake of ART, has significantly altered the landscape of HIV-associated pericarditis. While HIV initially exacerbated the incidence and mortality associated with TBP [4], the IMPI trial's later findings indicate that with progressive ART uptake, the 1-year case fatality rate for HIV-infected patients with TBP is now comparable to that of HIV-uninfected patients. [18] This represents a positive shift in outcomes attributable to improved HIV management. However, it also highlights the continued challenge posed by TBP itself, irrespective of HIV status, and underscores the ongoing need for integrated care strategies that comprehensively address both infections.
ADVANCEMENTS IN DIAGNOSIS OF PERICARDITIS IN SUB-SAHARAN AFRICA
Clinical Presentation and Initial Diagnostic Approaches
The diagnosis of pericarditis in Sub-Saharan Africa continues to rely heavily on a thorough clinical assessment. Clinical history and physical examination remain crucial for raising suspicion of tuberculous pericarditis. Key symptoms include retrosternal chest pain, which may be aggravated by deep breathing, coughing, and lying supine, and typically does not occur with exercise. [5] A pericardial friction rub may be audible, particularly over the lower sternal area, and can be loudest during full expiration, sitting up, and leaning forward; importantly, this rub may disappear as pericardial fluid accumulates. [5] Systemic symptoms such as malaise, fever, and nocturnal sweating are also common. [5] As pericardial fluid collects, patients often experience breathlessness on exertion, accompanied by physical signs such as tachycardia, falling blood pressure, pulsus paradoxus (a weaker arterial pulse and falling systolic blood pressure with inspiration), and a raised jugular venous pressure with Kussmaul’s sign (a paradoxical rise in JVP with inspiration). [5] Heart sounds may become less audible, and an added third heart sound may be present. [5]
A clinical diagnosis of pericarditis can generally be established when at least two of the following criteria are present: pericarditic chest pain, a pericardial friction rub, characteristic electrocardiogram (ECG) changes, or pericardial effusion. [6] Initial investigations universally recommended for suspected pericarditis include a 12-lead ECG, a chest radiograph, inflammatory markers (such as C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)), and a transthoracic echocardiogram. [6]
Despite global advancements in diagnostic technologies, the core diagnostic process for pericarditis in SSA remains heavily reliant on astute clinical history and physical examination. [5] This is not merely a historical legacy but a necessity imposed by existing resource limitations. [5] The ability of clinicians to recognize subtle signs and symptoms, especially in settings where advanced imaging or comprehensive laboratory tests are unavailable, becomes paramount. This situation highlights a continuous need for medical education and training to ensure that healthcare professionals maintain high diagnostic suspicion and strong clinical skills, as these are often the primary, and sometimes only, tools for initial diagnosis in many parts of SSA.
Evolution and Accessibility of Conventional Imaging (ECG, Chest X-ray, Echocardiography)
The evolution of conventional imaging in SSA for pericarditis diagnosis has seen varying degrees of progress and accessibility. Electrocardiogram (ECG) findings often include a falling QRS voltage as an effusion collects, while early stages of pericarditis may show an upward curvature of the elevated ST segment. [5] Typical ECG findings are observed in up to 60% of patients. [6] Chest X-rays can provide clues, potentially showing evidence of pulmonary TB, including pleural effusion. With significant pericardial fluid accumulation (typically >300 mL), the heart silhouette may enlarge and appear globular. In cases of longer-standing disease, pericardial calcification may be visible on the X-ray, outlining the heart. [5]
Echocardiography is a critical tool, as it directly confirms the presence of a pericardial effusion and helps determine its size. [5] It is considered essential for objective measurement of cardiac function and for reducing false positives in the diagnosis of heart failure. [20] However, despite its importance, echocardiography is not widely available across SSA. Its use is often restricted to a limited number of referral centers, primarily in urban areas, due to a scarcity of trained human resources for cardiovascular care. [5] Efforts to improve accessibility have included training nurses and mid-level providers in simplified echocardiographic protocols, a strategy that has shown promise in improving heart failure diagnosis and management. [20] Nevertheless, the high cost of equipment and ongoing challenges with training and retention of skilled personnel remain substantial barriers. [20]
The limited accessibility of echocardiography across SSA means that a fundamental diagnostic advancement, widely adopted in developed countries, remains an "unmet promise" for many patients in the region. This gap often compels clinicians to rely on less precise diagnostic methods or to initiate empirical treatment, which can lead to delayed or inaccurate diagnoses and, ultimately, worse patient outcomes. While adaptive strategies like training mid-level providers are being pursued to bridge this gap, the underlying issues of equipment cost and human resource retention continue to impede widespread access to this essential diagnostic tool.
Emergence of Molecular and Biomarker Diagnostics for Tuberculous Pericarditis
The definitive diagnosis of tuberculous etiology in pericarditis remains a significant challenge in SSA, despite scientific advancements. Traditional methods such as fluid and tissue microscopy and culture often yield poor results, and pericardial biopsy, while definitive, is invasive and carries inherent risks, leading to its infrequent performance. [11] It is noteworthy that only 17% of definite TBP cases in the IMPI trial were confirmed by current diagnostic criteria, suggesting that existing methods may not effectively detect the bacterial burden. [28]
In response to these diagnostic limitations, biochemical and biomarker-based approaches have emerged. Adenosine Deaminase (ADA) has demonstrated good diagnostic accuracy for TBP, with a pooled sensitivity of 0.90 and specificity of 0.85 in meta-analyses, and its performance is not diminished in HIV/AIDS patients. [11] Interferon-gamma (IFN-γ) shows even higher diagnostic accuracy, with reported sensitivities and specificities approximating 98% and 99% respectively. [11] However, the widespread clinical use of IFN-γ is constrained by the lack of easily accessible and inexpensive commercial assays. [11]
Advances in molecular techniques are advocated for earlier diagnosis of TBP. [21] The Xpert MTB/RIF assay, a WHO-endorsed PCR rapid test widely used for pulmonary TB, has shown an unacceptable sensitivity of 53-70% for TBP. [11] Nevertheless, the newer Xpert MTB/RIF Ultra assay, designed for extrapulmonary and paucibacillary disease, holds promise, though its performance in TBP requires further evaluation. [11] A combined two-test approach, initiating with Xpert MTB/RIF followed by either ADA or IFN-γ, has the potential to achieve high sensitivity and specificity (>97%). [11] However, the practicality and cost-effectiveness of this combined strategy present major limitations in resource-constrained settings. [11] The development of Africa-centric diagnostic prediction models for primary healthcare settings is also a valuable area of focus. [22]
The emergence of highly accurate molecular and biomarker diagnostics, such as IFN-γ and advanced Xpert MTB/RIF assays [11], represents significant scientific advancements. However, their limited clinical utility in SSA due to the "lack of an easily accessible and inexpensive commercial assay" [11] and broader cost-effectiveness concerns [11] creates a "technology-access-cost" trilemma. The scientific knowledge and tools exist, but the ability to translate them into widespread, routine clinical practice is severely hampered by economic and infrastructural realities. This means that despite knowing how to diagnose TBP more accurately, many patients in SSA continue to receive empirical treatment due to persistent diagnostic limitations [9], which can lead to misdiagnosis or suboptimal care.
Role of Advanced Multimodality Imaging and its Limitations in Resource-Limited Settings
In high-income countries, there have been many recent advances in multimodality cardiac imaging for pericardial diseases, leading to a "renaissance" in the field. [23] Recent guidelines support the use of advanced imaging modalities such as Computed Tomography (CT), Cardiac Magnetic Resonance Imaging (MRI), and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET). [11] Cardiac MRI, for instance, can more accurately delineate pericardial inflammation and constriction, aiding in diagnosis and guiding therapy. [6] FDG-PET imaging has shown promise in differentiating tuberculous pericarditis from idiopathic pericarditis, with active TBP typically exhibiting more multifocal FDG uptake. [11]
However, the applicability of these advanced imaging techniques in SSA is severely constrained. In resource-limited settings, specialized imaging modalities like cardiac MRI and FDG-PET are often unavailable, or access is limited by long waiting periods. [11] This significantly curtails their functional utility in routine clinical practice for the majority of patients in the region.
The stark contrast between the "renaissance" in pericardial imaging observed in developed countries [23] and the limited availability of these advanced modalities in SSA [11] highlights a profound disparity in diagnostic capabilities. This means that patients in SSA are frequently unable to benefit from the most accurate and comprehensive diagnostic tools, which can lead to less precise diagnoses, potentially delayed interventions, and ultimately, worse outcomes compared to patients in high-income countries. This gap is not solely a matter of technology; it also encompasses the critical shortage of trained personnel required to operate and interpret these complex images. [5]
EVOLUTION OF MANAGEMENT STRATEGIES FOR PERICARDITIS IN SUB-SAHARAN AFRICA
Standard Anti-Tuberculosis Chemotherapy and its Efficacy
The treatment of tuberculous pericarditis (TBP) in Sub-Saharan Africa is primarily based on the standard four-drug anti-TB chemotherapy regimen, which includes isoniazid, rifampicin, ethambutol, and pyrazinamide. This intensive phase typically lasts for two months, followed by a continuation phase of isoniazid and rifampicin for an additional four months. [11] This regimen is consistent with the treatment protocols for pulmonary tuberculosis and is applied regardless of the patient's immune status. [25]
Despite the widespread use of these established regimens, mortality rates for TBP remain persistently high, with estimates ranging from 8% to 18%. [26] This continued high mortality, even with seemingly appropriate systemic treatment, points to a critical underlying issue: the inadequate concentrations of anti-TB drugs, particularly rifampin and pyrazinamide, achieved within the pericardial fluid. [28] This "penetration problem" suggests that while the standard regimens are effective for pulmonary TB, the local drug levels at the site of pericardial infection may be insufficient to effectively clear the mycobacterial burden. This is a significant factor contributing to the persistent high mortality [28] and indicates that current standard regimens may not be optimally tailored for extrapulmonary manifestations like TBP, necessitating a re-evaluation of dosing or drug combinations. [11]
The Controversial Role of Adjunctive Corticosteroids: Key Findings from the IMPI Trial
The role of adjunctive corticosteroids in the treatment of tuberculous pericarditis has been a subject of considerable debate and conflicting trial results for decades. [25] To address this critical clinical question, the Investigation of the Management of Pericarditis (IMPI) trial, a large, multi-country randomized study, was conducted in SSA between 2007 and 2012. [29] This trial, notably an African-led initiative that faced initial funding challenges [13], aimed to provide definitive evidence.
The key findings from the IMPI trial were nuanced:
- Overall Mortality: Adjunctive prednisolone (60 mg, tapered over six weeks) did not significantly reduce the composite primary endpoint of death, recurrent cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. [18]
- Constrictive Pericarditis: Importantly, prednisolone was found to significantly lower the incidence of constrictive pericarditis in both HIV-infected and uninfected participants. [11]
- HIV-Positive Patients: A critical finding was that in HIV-positive patients, the addition of steroids was associated with a significantly higher risk of cancer, including Kaposi sarcoma and non-Hodgkin lymphoma. [14] This adverse effect is attributed to the immunosuppressive nature of steroids further depressing an already compromised immune system. [26]
- HIV-Negative Patients: The results suggested that it may be reasonable to add steroids to regular treatment in TB pericarditis patients without HIV infection to prevent constriction and reduce hospitalization. [13]
- Mortality in HIV-positive patients: Contrary to earlier observational studies, the IMPI trial found no significant difference in the 1-year case fatality rate between HIV-infected (14.9%) and HIV-uninfected (12.2%) patients. [18] This favorable shift in outcomes for HIV-positive patients was attributed to the increased access to Antiretroviral Therapy (ART) during the trial period. [18]
The IMPI trial represents a landmark achievement because it generated high-quality evidence directly from the SSA context. Its nuanced findings, particularly the differential impact of corticosteroids based on HIV status [14], powerfully demonstrate why context-specific research is critical. This evidence challenges the direct applicability of universal guidelines [6] and necessitates a stratified approach to TBP management in SSA, where HIV co-infection is highly prevalent. [6] This shift from a one-size-fits-all approach to a more tailored, evidence-based strategy, grounded in local epidemiological realities, marks a significant evolution in patient care.
Interventional and Surgical Management: Pericardiocentesis and Pericardiectomy
Pericardiocentesis remains the gold standard for managing compressive pericardial fluid and its adverse hemodynamic sequelae. [11] It is recommended for virtually all patients presenting with moderate and large effusions. [11] The IMPI trial observed a notable increase in pericardiocentesis rates, from less than 25% prior to the trial to over 60%, indicating improved adherence to guidelines for fluid drainage. [11]
Pericardiectomy is the definitive surgical intervention indicated for chronic constrictive pericarditis (CCP). CCP represents the main long-term complication of TBP, occurring in up to 25% of patients, and is a significant cause of heart failure in SSA. [5] Despite its critical role in resolving constriction, surgical experience with CCP is rarely documented in Africa. [15] Access to definitive surgical therapy for CCP is generally low across the continent and is often associated with significant perioperative risks. [11] Cardiac surgery, including pericardiectomy, is not readily available in most SSA countries, frequently relying on collaborative partnerships with international teams. [5]
While pericardiocentesis has seen increased utilization [11], the definitive treatment for the severe complication of constrictive pericarditis—pericardiectomy—faces a significant "treatment-access chasm" in SSA. [5] The pervasive lack of readily available cardiac surgical services and the heavy reliance on external partnerships [5] mean that many patients who could benefit from this life-saving surgery are unable to access it. This situation perpetuates high morbidity and mortality from a condition that is otherwise treatable, underscoring a critical gap in healthcare infrastructure and overall capacity building within the region. [3]
Newer Therapeutic Agents and their Potential Applicability
Globally, there have been significant advancements in targeted therapeutics for pericardial diseases, particularly for recurrent pericarditis. These include anti-interleukin (IL)-1 agents such as anakinra, rilonacept, and goflikicept, which have demonstrated efficacy in clinical trials. [23] Colchicine has also emerged as a first-line treatment for both acute and recurrent pericarditis. [6]
However, the applicability and adoption of these newer therapeutic agents in SSA are largely limited. While these agents represent the state-of-the-art in high-income countries, their high cost and the logistical complexities associated with their administration (e.g., requiring injections and specialized monitoring) significantly restrict their widespread use in resource-constrained SSA settings. In this region, the primary focus remains on managing the high burden of infectious etiologies, particularly tuberculous pericarditis. [4] The available evidence does not indicate significant adoption or widespread clinical use of these newer biologics in SSA.
The emergence of advanced biologic therapies, such as anti-IL-1 agents, for pericarditis globally [23] highlights an "innovation-equity gap" in SSA. While these therapies represent the pinnacle of current treatment in high-income countries, their prohibitive cost and complex logistical requirements render them largely inaccessible or impractical for the majority of the SSA population. This disparity is particularly stark given that pericarditis in SSA is predominantly infectious in origin. [4] Consequently, the benefits of global therapeutic innovations are not equitably distributed, further exacerbating existing health disparities and compelling SSA to continue relying on more basic, often less effective, or less targeted interventions.
KNOWLEDGE GAPS AND FUTURE PERSPECTIVES
Critical Deficiencies in Population-Based Epidemiological Data
A pervasive and critical challenge in understanding and addressing pericarditis in SSA is the enduring lack of fundamental population-based data. There are significant deficiencies in information regarding the overall disease burden, incidence, survival rates, and long-term outcomes of cardiovascular diseases, including pericarditis, across SSA. [2] This data scarcity is so profound that most global burden of disease (GBD) estimates for SSA rely on structural modeled estimates due to the extremely limited primary information available from the region. [2]
To address this, a key research priority is to conduct targeted community surveys for specific CVDs to fill these missing data points. This includes establishing new population-based community cohorts and organizing existing ones to capture disease incidence and trends more accurately. [30] Furthermore, leveraging the vast amount of "big data" available from daily hospital records, through systematic collection and analysis, is crucial for gaining insights into disease patterns and outcomes. [30]
The pervasive lack of robust, population-level epidemiological data [2] is not merely a scientific inconvenience; it represents a fundamental barrier to effective health policy formulation and funding advocacy. Without concrete, reliable data on prevalence, incidence, and outcomes, it becomes exceedingly challenging to persuade national governments, international donors, and global health organizations to prioritize and adequately fund interventions for pericarditis and other CVDs in SSA. This data gap perpetuates a cycle where the true burden of disease remains underestimated, leading to chronic under-resourcing and a continuation of suboptimal health outcomes. Therefore, the generation of this foundational data is an indispensable prerequisite for informed decision-making and for mobilizing the necessary resources to combat pericarditis effectively.
Unmet Needs in Rapid and Accurate Etiological Diagnosis
Despite some advancements in diagnostic tools, the rapid and accurate etiological diagnosis of pericarditis, particularly distinguishing tuberculous pericarditis (TBP) from other causes, remains an unmet need in SSA. Traditional diagnostic methods, such as microscopy and culture, often yield poor results for confirming a tuberculous etiology, and pericardial biopsy, while definitive, is invasive and carries risks, leading to its infrequent use. [11] Even the WHO-endorsed Xpert MTB/RIF assay has shown insufficient sensitivity for TBP. [11]
Future research must prioritize improving the rapidity and accuracy of diagnosing a tuberculous etiology. [11] This includes further investigation into the performance of newer molecular assays, such as Xpert MTB/RIF Ultra, specifically for TBP [11], and the development of cost-effective, easily accessible biomarker assays. [11] Additionally, the creation of Africa-centric diagnostic prediction models tailored for primary healthcare settings holds significant value in improving diagnostic accuracy in resource-limited environments. [22]
The existence of scientific knowledge and technologies for more accurate TBP diagnosis (e.g., IFN-γ, advanced molecular tests) [11] juxtaposed with their limited widespread implementation in SSA due to cost and accessibility [11] creates a "diagnostic translation gap." This refers to the inability to effectively translate scientific innovation into routine clinical practice due to systemic barriers. Future research must therefore focus not only on developing novel diagnostic tools but critically on implementation science: how to make these tools affordable, scalable, and sustainable within the existing healthcare infrastructure of SSA, potentially through the development and deployment of point-of-care solutions. [20]
Optimizing Treatment Regimens and Preventing Long-Term Complications (e.g., Constrictive Pericarditis)
The persistent high mortality associated with tuberculous pericarditis (TBP), despite the use of standard anti-TB chemotherapy, is a critical knowledge gap. This outcome is partly attributed to inadequate concentrations of anti-TB drugs in the pericardial fluid. [28] Furthermore, constrictive pericarditis remains a significant long-term complication, affecting up to 25% of TBP patients and contributing substantially to the burden of heart failure in the region. [11]
Future research priorities include a deeper understanding of the pharmacokinetics and pharmacodynamics of anti-TB drugs within the pericardium. This may involve assessing higher doses or alternative drug combinations to improve drug penetration and effectively reduce the bacillary load at the site of infection. [11] There is also a pressing need to investigate targeted therapies aimed at interrupting the profibrotic pathways and mediators of tissue damage that drive the progression to pericardial constriction. [11] Further research is also required to establish the value of effective pericardiocentesis in reducing pro-inflammatory and pro-fibrotic cytokines, with the aim of preventing pericardial constriction. [11]
The current approach to TBP treatment in SSA largely focuses on eradicating the infection and managing acute complications like pericardial effusion. [11] However, the high rate of progression to constrictive pericarditis [11] and persistent mortality [28] indicate a need to shift towards "disease modification." This involves understanding the profibrotic mechanisms that lead to constriction [11] and optimizing drug delivery to the pericardium. [28] This represents a crucial future direction, moving beyond simply treating the infection to actively preventing the devastating long-term sequelae that significantly contribute to the burden of heart failure in SSA.
Addressing Healthcare Infrastructure Limitations and Enhancing Capacity Building
The effectiveness of pericarditis management in SSA is profoundly impacted by systemic healthcare infrastructure limitations. The healthcare environment is characterized by limited capital, inadequate human resources, a short supply of well-equipped screening facilities, delayed diagnoses, and suboptimal care delivery at all levels—primary, secondary, and tertiary. [3] Specialized services, such as interventional cardiology and cardiac surgery, are largely unavailable in most SSA countries, often relying on sporadic collaborative partnerships with external entities. [5]
Addressing these systemic deficiencies is a critical research priority. This involves robust capacity building within the healthcare sector, encompassing comprehensive training for CVD researchers and clinicians, as well as significant improvements in infrastructure for both research and clinical training. [30] Strategies such as task sharing and task shifting, where responsibilities are appropriately distributed among different levels of healthcare professionals, are vital. [3] Improving salaries and working conditions is also essential to retain highly trained professionals within the public sector. [3] Furthermore, increasing and ensuring equitable access to essential medicines, potentially through simplified regimens and generic drugs, is paramount. [5]
The persistent challenges in pericarditis management are not solely clinical; they are deeply rooted in these systemic healthcare infrastructure limitations. [3] The lack of adequate funding, trained personnel, diagnostic equipment, and affordable drugs creates a cascading effect that undermines even the most well-intentioned clinical guidelines. Therefore, future perspectives must emphasize a holistic approach that recognizes the systemic nature of health outcomes. Strengthening healthcare systems, from primary care to tertiary referral centers, is not merely a supportive measure but a direct intervention to improve pericarditis outcomes. This necessitates strong political will, innovative financing mechanisms, and sustained international and local collaboration. [1]
Priorities for Africa-Centric Research and Policy Development
A fundamental priority for the future of pericarditis management in SSA is the development of context-specific guidelines and interventions, moving beyond a sole reliance on models derived from high-income countries. [30] This approach acknowledges the unique epidemiological, genetic, environmental, and socioeconomic factors prevalent in the region.
Key research priorities include the development of Africa-centric nomograms, thresholds, and clinical practice guidelines that are tailored to the specific needs and realities of SSA populations. [30] Generating robust evidence on preventative and control strategies that are culturally appropriate and logistically feasible for implementation into practice is also crucial. [30] Further exploration of the complex interplay between infectious diseases and non-communicable diseases, as well as the role of genetic factors in African populations, is vital for a comprehensive understanding of disease pathogenesis and progression. [1] A strong emphasis must be placed on fostering "research in Africa by Africa" [30], empowering local leadership and expertise to drive the research agenda and ensure relevance and sustainability.
The call for "Africa-centric" research and guidelines [30] signifies a push towards greater "health sovereignty." This acknowledges that the unique genetic, environmental, socioeconomic, and disease burden profile of SSA necessitates solutions tailored to its specific context, rather than simply adapting Western models. This approach involves empowering local leadership and expertise [1], fostering multidisciplinary collaboration across various health domains, and ensuring that research outputs are directly applicable, scalable, and sustainable within African health systems. This strategic shift is crucial for developing truly effective and equitable strategies for pericarditis and other cardiovascular diseases in the region, ultimately leading to improved health outcomes for its populations.
CONCLUSION
The evolution of pericarditis in Sub-Saharan Africa over the past three decades presents a complex and multifaceted challenge. The region continues to grapple with a unique epidemiological profile where tuberculous pericarditis, profoundly influenced by the HIV epidemic, remains the predominant etiology, contrasting sharply with global trends. While the increased access to Antiretroviral Therapy (ART) has positively impacted mortality rates for HIV-associated TBP, the disease continues to pose a significant burden, particularly through its devastating long-term complication of constrictive pericarditis.
Significant advancements have been made in understanding the clinical presentation and initial diagnostic approaches for pericarditis. However, the widespread adoption and accessibility of essential diagnostic tools like echocardiography, and newer molecular and advanced imaging modalities, remain severely limited by economic and infrastructural constraints. Similarly, while standard anti-TB chemotherapy forms the cornerstone of treatment, its efficacy is hampered by issues such as poor drug penetration into the pericardium. The landmark IMPI trial has provided crucial, context-specific evidence regarding adjunctive corticosteroids, highlighting the imperative for stratified care based on HIV status, yet access to definitive surgical interventions like pericardiectomy remains a profound barrier.
The identified knowledge gaps underscore the urgent need for a concerted, multi-pronged approach to improve outcomes for pericarditis patients in SSA. Foremost among these is the critical deficiency in population-based epidemiological data, which hinders accurate burden assessment and effective policy formulation. Bridging the diagnostic translation gap, optimizing treatment regimens to prevent long-term complications, and fundamentally strengthening healthcare infrastructure and human resource capacity are paramount. Ultimately, fostering Africa-centric research and policy development is essential to ensure that interventions are tailored to the unique realities of the continent, moving towards greater health sovereignty and equitable access to care. Addressing these interconnected challenges is not merely a clinical imperative but a fundamental step towards achieving health equity and reducing the burden of cardiovascular disease in Sub-Saharan Africa.
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Table 1 Key Clinical and Diagnostic Features of Tuberculous Pericarditis
Source: [5] |
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Table 2 Etiologies of Large Pericardial Effusion in African vs. Non-African Settings (1995-2004)
Source: [4]
Table 3 Summary of IMPI Trial Findings on Adjunctive Corticosteroids in Tuberculous Pericarditis (HIV-positive vs. HIV-negative)
Source: [14]
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Table 4 Identified Knowledge Gaps and Corresponding Research Priorities in Pericarditis in SSA
Source: [2]
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