Burden of disease and barriers to comprehensive care for rheumatic heart disease in South Africa: an updated systematic review protocol.

INTRODUCTION: Rheumatic heart disease (RHD) is responsible for a significant burden of cardiovascular morbidity and mortality, and remains the most common cause of acquired heart disease among children and young adults in low-income and middle-income countries. Additionally, the global COVID-19 pandemic has forced the emergency restructuring of many health systems, which has had a broad impact on health in general, including cardiovascular disease. Despite significant cost to the health system and estimates from 2015 indicating both high incidence and prevalence of RHD in South Africa, no cohesive national strategy exists. An updated review of national burden of disease estimates, as well as literature on barriers to care for patients with RHD, will provide crucial information to assist in the development of a national RHD programme. METHODS AND ANALYSIS: Using predefined search terms that capture relevant disease processes from Group A Streptococcal (GAS) infection through to the sequelae of RHD, a search of PubMed, Scopus, ISI Web of Science, Sabinet African Journals, SA Heart and Current and Completed Research databases will be performed. All eligible studies on RHD, acute rheumatic fever and GAS infection published from April 2014 to December 2022 will be included. Vital registration data for the same period from Statistics South Africa will also be collected. A standardised data extraction form will be used to capture results for both quantitative and qualitative analyses. All studies included in burden of disease estimates will undergo quality assessment using standardised tools. Updated estimates on mortality and morbidity as well as a synthesis of work on primary, secondary and tertiary prevention of RHD will be reported. ETHICS AND DISSEMINATION: No ethics clearance is required for this study. Findings will be disseminated in a peer-reviewed journal and submitted to national stakeholders in RHD. PROSPERO REGISTRATION NUMBER: CRD42023392782.

Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study.

BACKGROUND: Ethiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention. METHODS: A multicenter, prospective study was performed on children aged 5-17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated. RESULTS: A total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence. CONCLUSION: Poor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.

Comparison of approaches to determine echocardiographic outcomes for children with latent rheumatic heart disease.

BACKGROUND: Screening programmes using echocardiography offer opportunity for intervention through identification and treatment of early (latent) rheumatic heart disease (RHD). We aimed to compare two methods for classifying progression or regression of latent RHD: serial review method and blinded, side-by-side review. METHODS: A four-member expert panel reviewed 799 enrolment (in 2018) and completion (in 2020) echocardiograms from the GOAL Trial of latent RHD in Uganda to make consensus determination of normal, borderline RHD or definite RHD. Serial interpretations (enrolment and completion echocardiograms read at two different time points, 2 years apart, not beside one another) were compared with blinded side-by-side comparisons (enrolment and completion echocardiograms displayed beside one another in random order on same screen) to determine outcomes according to prespecified definitions of disease progression (worsening), regression (improving) or no change. We calculated inter-rater agreement using Cohen's kappa. RESULTS: There were 799 pairs of echocardiogram assessments included. A higher number, 54 vs 38 (6.8% vs 4.5%), were deemed as progression by serial interpretation compared with side-by-side comparison. There was good inter-rater agreement between the serial interpretation and side-by-side comparison methods (kappa 0.89). Disagreement was most often a result of the difference in classification between borderline RHD and mild definite RHD. Most discrepancies between interpretation methods (46 of 47, 98%) resulted from differences in valvular morphological evaluation, with valves judged to be morphologically similar between enrolment and final echocardiograms when compared side by side but classified differently on serial interpretation. CONCLUSIONS: There was good agreement between the methods of serial and side-by-side interpretation of echocardiograms for change over time, using the World Heart Federation criteria. Side-by-side interpretation has higher specificity for change, with fewer differences in the interpretation of valvular morphology, as compared with serial interpretation.

Evaluation of a Community-Led Program for Primordial and Primary Prevention of Rheumatic Fever in Remote Northern Australia.

Environmental factors including household crowding and inadequate washing facilities underpin recurrent streptococcal infections in childhood that cause acute rheumatic fever (ARF) and subsequent rheumatic heart disease (RHD). No community-based 'primordial'-level interventions to reduce streptococcal infection and ARF rates have been reported from Australia previously. We conducted a study at three Australian Aboriginal communities aiming to reduce infections including skin sores and sore throats, usually caused by Group A Streptococci, and ARF. Data were collected for primary care diagnoses consistent with likely or potential streptococcal infection, relating to ARF or RHD or related to environmental living conditions. Rates of these diagnoses during a one-year Baseline Phase were compared with a three-year Activity Phase. Participants were children or adults receiving penicillin prophylaxis for ARF. Aboriginal community members were trained and employed to share knowledge about ARF prevention, support reporting and repairs of faulty health-hardware including showers and provide healthcare navigation for families focusing on skin sores, sore throat and ARF. We hypothesized that infection-related diagnoses would increase through greater recognition, then decrease. We enrolled 29 participants and their families. Overall infection-related diagnosis rates increased from Baseline (mean rate per-person-year 1.69 [95% CI 1.10-2.28]) to Year One (2.12 [95% CI 1.17-3.07]) then decreased (Year Three: 0.72 [95% CI 0.29-1.15]) but this was not statistically significant (p = 0.064). Annual numbers of first-known ARF decreased, but numbers were small: there were six cases of first-known ARF during Baseline, then five, 1, 0 over the next three years respectively. There was a relationship between household occupancy and numbers (p = 0.018), but not rates (p = 0.447) of infections. This first Australian ARF primordial prevention study provides a feasible model with encouraging findings.

Maternal and fetal outcomes of COVID-19 infection in pregnant women with chronic rheumatic heart disease in a South Asian population: A case series.

Rheumatic heart disease (RHD) is associated with an increased risk of adverse maternal, fetal, and neonatal outcomes, particularly in developing countries. The current COVID-19 pandemic has also affected pregnant women, probably increasing the adverse effects. It is speculated that COVID-19 infection in pregnant women would further increase the risk of complications. However, factual data is still lacking, especially from resource-constrained countries. We conducted a case series of 20 pregnant women with RHD and COVID-19 infection and compared their outcomes with 40 with RHD but without COVDI-19. We observed a high risk of adverse cardiac and pregnancy effects across the whole cohort of 60 patients. However, the comparative study between the two groups failed to show any incremental risk of complications due to COVID-19 infection. Although the sample size was limited; the results are encouraging, particularly for developing countries.

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease.

BACKGROUND: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown. METHODS: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years. RESULTS: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis). CONCLUSIONS: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Effect of postoperative high load long duration inspiratory muscle training on pulmonary function and functional capacity after mitral valve replacement surgery: A randomized controlled trial with follow-up.

OBJECTIVES: Although, pre-operative inspiratory muscle training has been investigated and reported to be an effective strategy to reduce postoperative pulmonary complications, the efficacy of postoperative inspiratory muscle training as well as the proper load, frequency, and duration necessary to reduce the postoperative pulmonary complications has not been fully investigated. This study was designed to investigate the effect of postoperative high-load long-duration inspiratory muscle training on pulmonary function, inspiratory muscle strength, and functional capacity after mitral valve replacement surgeries. DESIGN: Prospective randomized controlled trial. METHODS: A total of one hundred patients (mean age 38.3±3.29years) underwent mitral valve replacement surgery were randomized into experimental (n = 50) and control (n = 50) groups. The control group received conventional physiotherapy care, while experimental group received conventional care in addition to inspiratory muscle training, with 40% of the baseline maximal inspiratory pressure targeting a load of 80% by the end of the 8 weeks intervention protocol. Inspiratory muscle training started on the patient's first day in the inpatient ward. Lung functions, inspiratory muscle strength, and functional capacity were evaluated using a computer-based spirometry system, maximal inspiratory pressure measurement and 6MWT respectively at 5 time points and a follow-up assessment was performed 6 months after surgery. Repeated measure ANOVA and post-hoc analyses were used (p <0.05). RESULTS: Group-time interactions were detected for all the studied variables (p<0.001). Between-group analysis revealed statistically significant postoperative improvements in all studied variables in the experimental group compared to the control group (p <0.001) with large effect size of η2 ˃0.14. Within-group analysis indicated substantial improvements in lung function, inspiratory pressure and functional capacity in the experimental group (p <0.05) over time, and these improvements were maintained at follow-up. CONCLUSION: High intensity, long-duration postoperative inspiratory muscle training is highly effective in improving lung function, inspiratory muscle strength, and functional capacity after mitral valve replacement surgeries.

Hypomagnesaemia causing functional hypoparathyroidism in rheumatic mitral stenosis leading to sudden cardiac arrest in a young woman.

A 23-year-old young woman with a known history of valvular heart disease of rheumatic origin, post balloon mitral valvotomy 5 years ago, presented with fever, palpitations and breathlessness. ECG showed atrial fibrillation with fast ventricular rate. A 2D transthoracic echocardiography showed severe restenosis of mitral valve and moderate left ventricular dysfunction. She was admitted for evaluation of fever and control of the ventricular rate. She sustained cardiac arrest due to unknown cause and was resuscitated. When the patient sustained another cardiac arrest, torsades de pointes was detected on the monitor. Blood parameters showed hypomagnesaemia, hypocalcaemia and hypokalaemia, causing functional hypoparathyroidism which was treated with intravenous magnesium, oral calcium and vitamin D supplements. Timely detection of a tachyarrhythmia due to a ventricular origin was life saving, which is rarely seen in patients with rheumatic heart disease and mitral stenosis.

United in earnest: first pilot sites for increased surgical capacity for rheumatic heart disease announced by cardiac surgery intersociety alliance.

OBJECTIVES: Rheumatic heart disease (RHD) affects >33 000 000 individuals, mostly from low- and middle-income countries. The Cape Town Declaration on Access to Cardiac Surgery in the Developing World was published in August 2018, signalling the commitment of the global cardiac surgery and cardiology communities to improving care for patients with RHD. METHODS: As the Cape Town Declaration formed the basis for which the Cardiac Surgery Intersociety Alliance (CSIA) was formed, the purpose of this article is to describe the history of the CSIA, its formation, ongoing activities and future directions, including the announcement of selected pilot sites. RESULTS: The CSIA is an international alliance consisting of representatives from major cardiothoracic surgical societies and the World Heart Federation. Activities have included meetings at annual conferences, exhibit hall participation for advertisement and recruitment and publication of selection criteria for cardiac surgery centres to apply for CSIA support. Criteria focused on local operating capacity, local championing, governmental and facility support, appropriate identification of a specific gap in care and desire to engage in future research. Eleven applications were received for which 3 finalist sites were selected and site visits conducted. The 2 selected sites were Hospital Central Maputo (Mozambique) and King Faisal Hospital Kigali (Rwanda). CONCLUSIONS: Substantial progress has been made since the passing of the Cape Town Declaration and the formation of the CSIA, but ongoing efforts with collaboration of all committed parties-cardiac surgery, cardiology, industry and government-will be necessary to improve access to life-saving cardiac surgery for patients with RHD.

Lockdown and non-COVID-19 deaths: Cause-specific mortality during the first wave of the 2020 pandemic in Norway. A population-based register study (preprint)

ObjectiveTo explore the potential impact of the first wave of COVID-19 pandemic on all cause and cause-specific mortality in Norway. DesignPopulation based register study. SettingThe Norwegian cause of Death Registry and the National Population Register of Norway. ParticipantsAll recorded deaths in Norway during March to May from 2010 to 2020. Main outcome measuresRate (per 100 000) of all-cause mortality and causes of death in the EU Shortlist for Causes of Death March to May 2020. The rates were age-standardised and adjusted to a 100% register coverage and compared with a 95% prediction interval (PI) based on corresponding rates for 2010-2019. Results113 710 deaths were included, of which 10 226 from 2020. We did not observe any deviation from predicted total mortality. There were fewer than predicted deaths from chronic lower respiratory diseases excluding asthma (11.4, 95% PI 11.8 to 15.2) and from other non-ischemic, non-rheumatic heart diseases (13.9, 95% PI 14.5 to 20.2). The death rates were higher than predicted for Alzheimers disease (7.3, 95% PI 5.5 to 7.3) and diabetes mellitus (4.1, 95% PI 2.1 to 3.4). ConclusionsThere was no significant difference in the frequency of the major causes of death in the first wave of the 2020 COVID-19 pandemic in Norway. An increase in diabetes mellitus deaths and reduced mortality due to some heart and lung conditions may be linked to infection control measures.

Analysis on Diagnosis of Family Clustering Infection of SARS-CoV-2 (preprint)

Background: Novel coronavirus (nCoV, SARS-CoV-2) infection has complicated and diversified symptoms, but no special treatment. In this study, diagnosis and treatment of family clustering nCoV infection were analyzed. Methods: The Sichuan Suining Central Hospital received 11 patients with confirmed nCoV virus infection from 4 families during January 23rd, 2020 to February 20th, 2020. Their clinical symptoms, treatment conditions and changes of disease state were reviewed in the present study. Results: In all 4 families, there were 1-2 members in each family who had contact with epidemic disease. Clinical manifestations were: 3 cases had debilitation only, 1 case had cough only, 1 case had diarrhea, 5 cases had fever and cough, and 1 case had blood-stained sputum. According to image changes, no image change was observed in 1 child patient. Multiple focal ground-glass opacities were detected from 2 patients and multiple patchy shadows were observed from 8 patients, especially in lung periphery. Complications: there were hypertension in 3 cases, diabetes in 2 cases, depression in 1 cases and hypertension and diabetes in 1 case. Moreover, there’s one patient who had rheumatic heart disease and received mitral and aortic valve replacement 2 years ago. All 11 cases divided into mild type (1 child patient), moderate type (8 patients), severe type (1 patient) and critical type (1 patient). Treatment: 11 patients were treated with intravenous drip of ribavirin injection (adult 0.5g/time; child15mg/kg.time,twice per day) and lopinavir/ritonavior (adult: 2 tablets/ time; child: 1/2 tablets/times, twice per day) for 6-12 days, accompanied with appropriate amount of intravenous drip of antibiotics. Discharge: After treatment, 11 patients met the discharge criteria and were allowed to discharge. Adverse reactions: 4 patients had loose stools and abdominal discomfort, and another 2 cases had diarrhea. Conclusions: SARS-CoV-2 infection have complicated and diversified symptoms, which shall be identified according to epidemic history and novel coronavirus nucleic acid test. In particular, the whole family in which there’s a patient with confirmed SARS-CoV-2 shall be isolated for screening in addition to the patient. The lopinavir/ritonavior administration combined with ribavirin or recombinant Human Interferon (RHI) α2b is effective, accompanied with mild adverse reaction.

Analysis on Diagnosis of Family Clustering Infection of SARS-CoV-2 (preprint)

Objective: Novel coronavirus (nCoV, SARS-CoV-2) infection becomes a world-wide epidemic which has complicated and diversified symptoms, but no special treatment. In this study, diagnosis and treatment of family clustering nCoV infection were analyzed.Methods: The Sichuan Suining Central Hospital received 11 patients with confirmed nCoV virus infection from 4 families during January 23rd, 2020 to February 20th, 2020. Their clinical symptoms, treatment conditions and changes of disease state were reviewed in the present study.Results: In all 4 families, there were 1-2 members in each family who had contact with epidemic disease. Clinical manifestations were: 3 cases had debilitation only, 1 case had cough only, 1 case had diarrhea (a child patient of four years old), 5 cases had fever and cough, and 1 case had blood-stained sputum. According to image changes, no image change was observed in 1 child patient. Multiple focal ground-glass opacities were detected from 2 patients and multiple patchy shadows were observed from 8 patients, especially in lung periphery. Complications with basic diseases: there were hypertension in 3 cases, diabetes in 2 cases, and hypertension and diabetes in 1 case. Moreover, there’s one patient who had rheumatic heart disease and received mitral and aortic valve replacement 2 years ago. There’s another one who had depression and suicidal tendency. All 11 cases divided into mild type (1 child patient), moderate type (8 patients), severe type (1 patient) and critical type (1 patient). Treatment: the mild child patient (4 years old) was administrated with 2.75ml lopinavir / ritonavir oral liquid (twice per day) and intravenous drip of 0.17g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h for one week. Meanwhile, the child was asked to take azithromycin orally. 7 moderate patients were treated with intravenous drip of 0.5g ribavirin injection (1ml: 0.1g*10pcs/box) every 12h (twice per day) and two pieces of lopinavir/ritonavior (twice per day) for 7-10 days. In the same time, patients were given with reasonable amount of antibiotics by oral or intravenous drip. 1 severe patient and 1 critical patent were treated with 5,000,000 U recombinant human interferon α2b injection (3,000,000 U/pc) and aerosol inhalation of 2ml sterile water for injection (5ml*50 pcs/ box), twice per day. Besides, they took 2 pieces of lopinavir/ritonavior, twice per day. The whole treatment program lasted for 6-12 days, accompanied with appropriate amount of intravenous drip of antibiotics. The critical patient was also provided with mechanical ventilation. During the treatment, severe and critical patients were treated by resochin for 4-5 days for evident respiratory symptoms. One moderate patient was treated with 2 pieces of lopinavir/ritonavior, twice per day. In the same time, it was administrated by intravenous drip of antibiotics. However, resochin treatment was applied for positive novel coronavirus nucleic acid of respiratory sputum specimen after 11 days of treatment. Discharge: After treatment, patients with body temperatures of all patients recovered to normal level, and respiratory symptoms and digestive tract symptoms relieved significantly, significant coefficient of exudative lesion at lung according to chest CT and negative novel coronavirus nucleic acid of continuous two respiratory sputum specimens (sampling interval was at least 1 day) were allowed to be discharged. Adverse reactions: 4 patients had loose stools and abdominal discomfort, and another 2 cases had diarrhea.Conclusions: SARS-CoV-2 infection have complicated and diversified symptoms, which shall be identified according to epidemic history and novel coronavirus nucleic acid test. In particular, the whole family in which there’s a patient with confirmed SARS-CoV-2 shall be isolated for screening in addition to the patient. The lopinavir/ritonavior administration combined with ribavirin or recombinant Human Interferon (RHI) α2b is effective, accompanied with mild adverse reaction. If lopinavir/ritonavior administration and / or combined with ribavirin and RHI α2b is invalid, adding resochin might be effective.