A study of determinants and prevalence of Rheumatic Heart Disease in Cape Town

Includes abstract.Includes bibliographical references.Rheumatic Heart Disease (RHD) is a post-infectious immune disease ascribed to an interaction between a rheumatogenic strain of group A streptococcus, a susceptible host who lives in poor social conditions with limited access to medical facilities. The disease process begins with repeated group A streptococcal (GAS) infections, which, subsequently result in acute rheumatic fever (ARF). In the absence of intervention, repeated bouts of ARF in turn, may result in progression to RHD, particularly in those ARF patients with cardiac involvement. The prevalence of ARF and RHD in developed countries has shown considerable decline during the last century, largely attributed to improved living conditions and access to healthcare. Epidemiological data from developing countries, while scant, indicate a continued high prevalence of GAS-positive pharyngitis and RHD. Furthermore, while much is known about the social factors and the microbial agent that predispose individuals to ARF, little progress has been made in elucidating genetic susceptibility factors that are reproducible in different populations. This thesis aimed to establish determinants of RHD as well as to document the prevalence of RHD in South African school children. The specific objectives of each study component were as follows: To derive quantitative estimates of the size of the genetic contribution to the risk of developing ARF/RHD. To determine the prevalence of GAS carriage and emm strains of GAS isolates among asymptomatic children enrolled in primary and secondary school. To describe the epidemiology of GAS among 3- to 15-year old children with pharyngitis attending primary health care facilities. To develop a clinical prediction rule for diagnosis of GAS throat infection that is valid for children aged 5-15 years in the primary care setting within the South African context. To determine the prevalence of echocardiographically-proven rheumatic heart disease in school children

Rationale and design of the African group A streptococcal infection registry: the AFROStrep study

Introduction: Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, also known as Streptococcus pyogenes, causes pyoderma, pharyngitis and invasive disease. Repeated GAS infections may lead to autoimmune diseases such as acute post-streptococcal glomerulonephritis, acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Invasive GAS (iGAS) disease is an important cause of mortality and morbidity worldwide. The burden of GAS infections is, however, unknown in Africa because of lack of surveillance systems. Methods and analysis: The African group A streptococcal infection registry (the AFROStrep study) is a collaborative multicentre study of clinical, microbiological, epidemiological and molecular characteristics for GAS infection in Africa. The AFROStrep registry comprises two components: (1) active surveillance of GAS pharyngitis cases from sentinel primary care centres (non-iGAS) and (2) passive surveillance of iGAS disease from microbiology laboratories. Isolates will also be subjected to DNA isolation to allow for characterisation by molecular methods and cryopreservation for long-term storage. The AFROStrep study seeks to collect comprehensive data on GAS isolates in Africa. The biorepository will serve as a platform for vaccine development in Africa. Ethics and dissemination: Ethics approval for the AFROStrep registry has been obtained from the Human Research Ethics Committee at the University of Cape Town (HREC/REF: R006/2015). Each recruiting site will seek ethics approval from their local ethics’ committee. All participants will be required to provide consent for inclusion into the registry as well as for the storage of isolates and molecular investigations to be conducted thereon. Strict confidentiality will be applied throughout. Findings and updates will be disseminated to collaborators, researchers, health planners and colleagues through peer-reviewed journal articles, conference publications and proceedings

Clinical and epidemiological aspects of streptococcus pyogenes pharyngitis and carriage in Africa

Infection with Group A β-haemolytic Streptococcus, also known as Streptococcus pyogenes, results in various mucosal and skin diseases including pharyngitis. An exaggerated immune response to a single or repeated group A streptococcal (GAS) infection subsequently results in acute rheumatic fever (ARF) and, in the absence of intervention, repeated bouts of ARF may in turn result in progression to RHD, particularly in those ARF patients with cardiac involvement. Addressing GAS pharyngitis through appropriate primary prevention measures and treating all symptomatic GAS sore throats with a course of oral or parenteral penicillin presents an opportunity for the primary intervention of RHD. Failure to eradicate streptococci from the pharynx occurs in about one third of non-treated cases, giving rise to carrier status in those individuals harbouring intracellular GAS and thus representing a potential source of the acquisition of infections for other children and adults. Improved living conditions and access to healthcare during the last century are credited for the considerable decline in the prevalence of ARF and RHD in developed countries. However, a few studies have been reported from within Africa, and in these GAS carriage ranged around 9.0%. In South African studies GAS carriage isolation rates, which range from 1.62% to16.8%, were reported. As regards the prevalence of GAS pharyngitis, it is generally higher in developing countries and impoverished communities withinindustrialised nations. The most-up-to-date data from South Africa was collected more than 30 years ago with rates then ranging from 23.2% to 45.5%. There are no incidence data on GAS pharyngitis in Africa. This review found that there is a need to document the epidemiology of GAS carriage and GAS pharyngitis in school children of all ages within Africa. Molecular characterisation of strains harboured in the pharynx of carriers and of those isolated during bouts of pharyngitis, will help to identify risk factors associated with carriage in school-aged children and infl uence the planning and evaluation of management programmes in the screening of pharyngeal carriers and treatment of GAS pharyngitis

Rheumatic fever and rheumatic heart disease: Where are we now in South Africa?

South Africa continues to face unacceptably high rates of rheumatic fever (RF) and rheumatic heart disease (RHD), despite readily available and inexpensive preventive measures. However, in the past several years, key players in South Africa’s healthcare and political realms in addition to key players from many African nations have come together to acknowledge the persistent health burden attributable to RF/RHD and have agreed to a pledge of action to reduce it. The plan of action is a comprehensive RF/RHD prevention and treatment programme known as ASAP. The ASAP programme targets efforts to raise Awareness, establish Surveillance systems, Advocate for increased resources for treatment, and to promote Prevention strategies. South Africa currently has a demonstration site where activities in all of these key areas are currently underway. Efforts in the area of surveillance include a RHD prevalence study that aims to screen 4 000 school-aged children through the use of a mobile echo-surveillance unit. In addition to local efforts, South Africa will join an international initiative to create a global RHD registry that will aid in all aspects of prevention and treatment to further reduce the burden of disease attributable to RF/RHD

Burden of pneumocystis pneumonia in HIV-infected adults in sub-Saharan Africa: protocol for a systematic review

BACKGROUND: Reports from Africa have suggested that pneumocystis pneumonia (PCP) is a less important cause of morbidity than in the developed world. However, more recent studies have shown high seroprevalence rates of P. jirovecii in healthy individuals with HIV as well as high rates of clinical disease in African children. This suggests that PCP may be more common in Africa than was previously recognised. Understanding the contribution of PCP to disease in HIV-infected individuals in sub-Saharan Africa (SSA) has important implications for diagnosis, management and resource allocation. We therefore propose to conduct a systematic review and meta-analysis in order to investigate the burden of PCP in this population.METHODS AND DESIGN:We plan to search electronic databases and reference lists of relevant articles published from 1995 to May 2013 using broad terms for pneumocystis, HIV/AIDS and sub-Saharan Africa. Studies will be included if they provide clear diagnostic criteria for PCP and well-defined study populations or mortality data (denominator). A novel quality score assessment tool has been developed to ensure fidelity to inclusion criteria, minimise risk of selection bias between reviewers and to assess quality of outcome ascertainment. This will be applied to eligible full-text articles. We will extract data using a standardised form and perform descriptive and quantitative analysis to assess PCP prevalence, mortality and case fatality, as well as the quality of included studies. This review protocol has been published in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42013005530.DISCUSSION:Our planned review will contribute to the diagnosis and management of community-acquired pneumonia in HIV-infected individuals in SSA by systematically assessing the burden of PCP in this population. We also describe a novel quality assessment tool that may be applied to other prevalence reviews

The burden of antenatal heart disease in South Africa: a systematic review

<p>Abstract</p> <p>Background</p> <p>Maternal mortality in South Africa is rising, and heart conditions currently account for 41 per cent of indirect causes of deaths. Little is known about the burden of heart disease in pregnant South Africans.</p> <p>Methods</p> <p>We systematically reviewed the contemporary epidemiology and peripartum outcomes of heart disease in South African women attending antenatal care. Searches were performed in PubMed, ISI Web of Science, the EBSCO Africa-Wide database, the South African Union Catalogue, and the Current and Completed Research database (South Africa). References of included articles were also hand-searched. Studies reporting epidemiologic data on antenatal heart disease in South Africa were included. Data on morbidity and mortality were also collected.</p> <p>Results</p> <p>Seven studies were included in the systematic review. The prevalence of heart disease ranged from 123 to 943 per 100,000 deliveries, with a median prevalence of 616 per 100,000. Rheumatic valvular lesions were the commonest abnormalities, although cardiomyopathies were disproportionately high in comparison with other developing countries. Peripartum case-fatality rates were as high as 9.5 per cent in areas with limited access to care. The most frequent complications were pulmonary oedema, thromboembolism, and major bleeding with warfarin use. Perinatal mortality ranged from 8.9 to 23.8 per cent, whilst mitral lesions were associated with low birth weight. Meta-analysis could not be performed due to clinical and statistical heterogeneity of the included studies.</p> <p>Conclusion</p> <p>Approximately 0.6 per cent of pregnant South Africans have pre-existing cardiac abnormalities, with rheumatic lesions being the commonest. Maternal and perinatal morbidity and mortality continue to be very high. We conclude this review by summarising limitations of the current literature and recommending standard reporting criteria for future reports.</p

The Effects of Angiotensin Converting Enzyme Inhibitors (ACE-I) on Human N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Levels: A Systematic Review and Meta-Analysis

BACKGROUND: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues. Objective To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues. METHODS: We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO. RESULTS: Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I 2 = 44%). CONCLUSION: ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis

A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis

Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children depends on prompt and effective diagnosis and treatment of pharyngitis at the primary level of care. Cost-effectiveness modeling shows that the most cost-effective strategy for primary prevention in South Africa (SA) is to use a simple symptomatic clinical decision rule (CDR) to diagnose pharyngitis in children presenting at the primary level of care and then to treat them with a single dose of intramuscular penicillin. Treat All and CDR2+ strategies are affordable and simple and miss few cases of streptococcal pharyngitis at the primary level of care. The CDR2+ strategy is the most cost-effective for primary prevention of ARF and RHD in urban SA and should complement primordial and secondary prevention efforts

Effect of distance to health facility on the maintenance of INR therapeutic ranges in rheumatic heart disease patients from Cape Town: No evidence for an association

Background: Lack of adherence to international normalised ratio (INR) monitoring in rheumatic heart disease (RHD) patients is a contributor to cardio-embolic complications. This population-based observational study investigated whether the distance between home and an INR clinic affects the maintenance of therapeutic INR in RHD patients on warfarin. Methods: Residential addresses, INR clinics, and INR results of patients with RHD were extracted from the Cape Town component of the Global Rheumatic Heart Disease Registry (REMEDY) database. Addresses of homes and INR clinics were converted to geographical coordinates and verified in ArcGIS 10®. ArcGIS 10® and Google Maps® were used for spatial mapping and obtaining shortest road distances respectively. The travel distance between the home and INR clinic was correlated with time within therapeutic range (TTR) using the Rosendaal linear interpolation method, and with the fraction of INR within range, based on an average of three INR readings of patients and compared with recommended therapeutic ranges. Results: RHD patients (n=133) resided between 0.2 km and 50.8 km (median distance, 3.60 km) from one of 33 INR clinics. There was no significant difference in the achievement of the therapeutic INR between patients who travelled a shorter distance compared to those who travelled a longer distance (in range = 3.50 km versus out of range = 3.75 km, p=0.78). This finding was the same for patients with mechanical valve replacement (n=105) (3.50 km versus 3.90 km, p=0.81), and native valves (3.45 km versus 2.75 km, p=0.84). Conclusions: There is no association between the maintenance of INR within therapeutic range amongst RHD patients in Cape Town and distance from patients’ residence to the INR clinic

HST/WFC3 Observations of an Off-Nuclear Superbubble in Arp 220

We present a high spatial resolution optical and infrared study of the circumnuclear region in Arp 220, a late-stage galaxy merger. Narrowband imaging using HST/WFC3 has resolved the previously observed peak in H$\alpha$+[NII] emission into a bubble-shaped feature. This feature measures 1.6" in diameter, or 600 pc, and is only 1" northwest of the western nucleus. The bubble is aligned with the western nucleus and the large-scale outflow axis seen in X-rays. We explore several possibilities for the bubble origin, including a jet or outflow from a hidden active galactic nucleus (AGN), outflows from high levels of star formation within the few hundred pc nuclear gas disk, or an ultraluminous X-ray source. An obscured AGN or high levels of star formation within the inner $\sim$100 pc of the nuclei are favored based on the alignment of the bubble and energetics arguments.Comment: Accepted for publication in ApJ. 12 pages, 10 figure