Project description:Rheumatic heart disease (RHD) continues to affect developing countries with low income, due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis of progression from its prequel disease state, acute rheumatic fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD as compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be associated with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited NK cell gene signatures reflected the drivers of the inflammatory process being common to both the disease conditions.
Project description:We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000-2018 and RHD mortality rates during 2000-2016. We found elevated rates of initial ARF hospitalizations for persons of Māori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0-14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9-27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Māori (aRR 3.2, 95% CI 2.9-3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2-5.1) groups and RHD deaths among these groups (Māori aRR 12.3, 95% CI 10.3-14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1-13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.
Project description:BackgroundRheumatic heart disease (RHD) is endemic in sub-Saharan Africa where it is the leading cause of cardiovascular mortality in the young. Rheumatic heart disease results from recurrent episodes of acute rheumatic fever (ARF), which are often difficult to diagnose clinically. Acute rheumatic fever may be diagnosed based on the revised Jones Criteria 2015 for the diagnosis of ARF. Histologically, acute rheumatic valvulitis manifests with active inflammation characterized by lymphocytic infiltration, Aschoff bodies, and Anitschkow cells. Chronic rheumatic valvulitis is associated with neovascularization, and/or dystrophic calcification. The combination of histological features of both ARF and chronic RHD is a rare finding.Case summaryHere we report on a case of a 59-year-old woman with mixed aortic and mitral valve disease of probable rheumatic aetiology (elevated C-reactive protein and prolonged PR interval) and with histological evidence of lymphocytic infiltration, Aschoff bodies, and fibrinoid necrosis admixed with features of chronic RHD.DiscussionCases of chronic RHD admixed with ARF are very rare; however, they should be considered in regions with a high prevalence of RHDs.
Project description:BackgroundOptimal delivery of regular benzathine penicillin G (BPG) injections prescribed as secondary prophylaxis for acute rheumatic fever (ARF) and rheumatic heart disease (RHD) is vital to preventing disease morbidity and cardiac sequelae in affected pediatric and young adult populations. However, poor uptake of secondary prophylaxis remains a significant challenge to ARF/RHD control programs.ObjectiveIn order to facilitate better understanding of this challenge and thereby identify means to improve service delivery, this systematic literature review explored rates of adherence and factors associated with adherence to secondary prophylaxis for ARF and RHD worldwide.MethodsMEDLINE was searched for relevant primary studies published in the English language from 1994-2014, and a search of reference lists of eligible articles was performed. The methodological quality of included studies was evaluated using a modified assessment tool.ResultsTwenty studies were included in the review. There was a range of adherence to varying regimens of secondary prophylaxis reported globally, and a number of patient demographic, clinical, socio-cultural and health care service delivery factors associated with adherence to secondary prophylaxis were identified.ConclusionInsights into factors associated with lower and higher adherence to secondary prophylaxis may be utilized to facilitate improved delivery of secondary prophylaxis for ARF and RHD. Strategies may include ensuring an effective active recall system, providing holistic care, involving community health workers and delivering ARF/RHD health education.
Project description:Rheumatic heart disease (RHD) continues to affect developing countries with low income due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis common to both the diseases and that of progression from its prequel disease state, Acute Rheumatic Fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, in this pilot study, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis approach, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated, while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be linked with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found a significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited Natural Killer cell gene signatures reflected the drivers of the inflammatory process typical to both disease conditions.
Project description:Nearly a century after rheumatic fever (RF) and rheumatic heart disease (RHD) was eradicated from the developed world, the disease remains endemic in many low- and middle-income countries (LMICs), with grim health and socioeconomic impacts. The neglect of RHD which persisted for a semi-centennial was further driven by competing infectious diseases, particularly the human immunodeficiency virus (HIV) pandemic. However, over the last two-decades, slowly at first but with building momentum, there has been a resurgence of interest in RF/RHD. In this narrative review, we present the advances that have been made in the RF/RHD continuum over the past two decades since the re-awakening of interest, with a more concise focus on the last decade's achievements. Such primary advances include understanding the genetic predisposition to RHD, group A Streptococcus (GAS) vaccine development, and improved diagnostic strategies for GAS pharyngitis. Echocardiographic screening for RHD has been a major advance which has unearthed the prevailing high burden of RHD and the recent demonstration of benefit of secondary antibiotic prophylaxis on halting progression of latent RHD is a major step forward. Multiple befitting advances in tertiary management of RHD have also been realized. Finally, we summarize the research gaps and provide illumination on profitable future directions towards global eradication of RHD.
Project description:Rheumatic heart disease (RHD) as a chronic sequela of repeated episodes of acute rheumatic fever (ARF), remains a cause of cardiac morbidity in Egypt although it is given full attention through a national RHD prevention and control program. The present report reviews our experience with subjects presenting with ARF or its sequelae in a single RHD centre and describes the disease pattern over the last decade. A cross-sectional study was conducted in El-Mahalla RHD centre between 2006 and 2018. A total of 17014 individual were enrolled and evaluated. Diagnosis ARF was based on the 2015 revised Jones criteria and RHD was ruled in by echocardiography. The majority of the screened subjects were female (63.2%), in the age group 5-15 years (64.6%), rural residents (61.2%), had primary education (43.0%), and of low socioeconomic standard (50.2%). The total percentage of cases presenting with ARF sequelae was 29.3% [carditis/RHD (10.8%), rheumatic arthritis (Rh.A) (14.9%), and Sydenham's chorea (0.05%)]. Noticeably, 72% were free of any cardiac insult, of which 37.7% were victims of misdiagnoses made elsewhere by untrained practitioners who prescribed for them long term injectable long-acting penicillin [Benzathine Penicillin G (BPG)] without need. About 54% of the study cohort reported the occurrence of recurrent attacks of tonsillitis of which 65.2% underwent tonsillectomy. Among those who experienced tonsillectomy and/or received BPG in the past, 14.5% and 22.3% respectively had eventually developed RHD. Screening of family members of some RHD cases who needed cardiac surgery revealed 20.7% with undiagnosed ARF sequalae [RHD (56.0%) and Rh.A (52.2%)]. Upon the follow-up of RHD cases, 1.2% had improved, 98.4% were stable and 0.4% had their heart condition deteriorated. Misdiagnosis of ARF or its sequelae and poor compliance with BPG use may affect efforts being exerted to curtail the disease. Updating national guidelines, capacity building, and reliance on appropriate investigations should be emphasized. Since the genetic basis of RHD is literally confirmed, a family history of RHD warrants screening of all family members for early detection of the disease.
Project description:Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD.A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis.This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls.The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.
Project description:BackgroundMeasurement of health-related quality of life (HRQOL) of people with chronic illnesses has become extremely important as the mortality rates associated with such illnesses have decreased and survival rates have increased. Thereby, such measurements not only provide insights into physical, mental and social dimensions of patient's health, but also allow monitoring of the results of interventions, complementing the traditional methods based on morbidity and mortality.ObjectiveThe present study was conducted to describe the HRQOL of patients suffering from Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD), and to identify socio-demographic and clinical factors as predictors of HRQOL.MethodologyA cross-sectional study was conducted to assess the HRQOL among 702 RF and RHD patients using EuroQol 5-dimensions 5-levels instrument (EQ-5D-5L), EuroQol Visual Analogue Scale and Time Trade off method. Mean EQ-5D-5L quality of life scores were calculated using EQ5D index value calculator across different stages of RF and RHD. Proportions of patients reporting problems in different attributes of EQ-5D-5L were calculated. The impact of socio-economic determinants on HRQOL was assessed.ResultsThe mean EQ-5D-5L utility scores among RF, RHD and RHD with Congestive heart failure patients (CHF) were estimated as 0.952 [95% Confidence Interval (CI): 0.929-0.975], 0.820 [95% CI: 0.799-0.842] and 0.800 [95% CI: 0.772-0.829] respectively. The most frequently reported problem among RF/RHD patients was pain/discomfort (33.8%) followed by difficulty in performing usual activities (23.9%) patients, mobility (22.7%) and anxiety/depression (22%). Patients with an annual income of less than 50,000 Indian National Rupees (INR) reported the highest EQ-5D-5L score of 0.872, followed by those in the income group of more than INR 200,000 (0.835), INR 50,000-100,000 (0.832) and INR 100,000-200,000 (0.828). Better HRQOL was reported by RHD patients (including RHD with CHF) who underwent balloon valvotomy (0.806) as compared to valve replacement surgery (0.645).ConclusionRF and RHD significantly impact the HRQOL of patients. Interventions aiming to improve HRQOL of RF/RHD patients should focus upon ameliorating pain and implementation of secondary prevention strategies for reducing the progression from ARF to RHD and prevention of RHD-related complications.