Browsing by Author "Mayosi, Bongani M"
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- ItemOpen AccessA proposal for the eradication of rheumatic fever in our lifetime(2006) Mayosi, Bongani MThe Pan African Society of Cardiology (PASCAR) convened the 1st All Africa Workshop on Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD) on 15 - 16 October 2005 at the Champagne Sports Resort, Drakensberg, South Africa. The purpose of the Workshop was to formulate an action plan for the prevention of RF and RHD in Africa. The gathering was a response to the new guideline on the control of RF and RHD by the World Health Organization (WHO) in 2004.1 The meeting (and this supplement) was made possible by the generous sponsorship of the national Department of Health of South Africa, the Medical Research Council of South Africa, the WHO Regional Office for Africa (WHO-AFRO) and the World Heart Federation, and endorsed by the Heart Foundation of South Africa, the Paediatric Cardiac Society of South Africa, and the South African Heart Association. The other organisations represented at the meeting included the Africa Heart Network, the Nigerian Heart Foundation, and academics from the universities of Alexandria, Cape Town, Ghana, Ibadan, KwaZulu-Natal, Libreville, Limpopo, Nairobi, Pretoria, and Eduardo Mondlane University.
- ItemRestrictedAbnormal diastolic and systolic septal motion following pericardiectomy demonstrated by cine DENSE MRI(Clinics Cardive, 2008) Spottiswoode, Bruce; Russell, James B; Moosa, Sulaiman; Meintjes, Ernesta M; Epstein, Frederick H; Mayosi, Bongani MConstrictive pericarditis can lead to paradoxical interventricular septal motion. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) provides a method for quantifying myocardial motion and strain. A case of constrictive pericarditis is presented and the diastolic ‘septal bounce’ is clearly evident in both anatomical and DENSE ciné MRI images. (See video link to full-text electronic article). The postoperative systolic septal wall-motion abnormality of cardiac surgery is portrayed with greater precision by DENSE than anatomical ciné MRI images.
- ItemOpen AccessAfrican researchers' perceptions and expectations of the benefits of genomics research in Africa : a qualitative study(2016) Munung, Nchangwi Syntia; de Vries, Jantina; Mayosi, Bongani MIntroduction: Genomics research raises a number of ethical, legal and social issues (ELSI), one of which is the concept of benefit sharing. While benefits and benefit sharing are difficult to discuss because of questions on what needs to be shared, with whom and by whom, it cannot be pushed to the side-lines especially as it is a way of promoting justice in health research and of ensuring that research is of social value to study communities. In this study, we explored the perceptions and expectations of African genomics scientists on the benefits of genomics research to Africa. Method: This was a qualitative study and we adopted a grounded theory approach. I conducted 17 in-depth interviews with genomics researchers in Africa to explore their perceptions of benefits and benefit sharing in genomics research in Africa. Transcripts of interviews were imported into QSR-NVivo 10 for thematic analysis. A thematic analysis of informed consent documents used in 13 genomics studies in Africa was also done to explore how research benefits are documented. Results: Research collaboration, research capacity building and access to genomics medicine were perceived to be the main benefits of African genomics science (AGS). In terms of research collaboration, there were perceived fears of exploitation of African researchers and research participants, and the non-sustainability of AGS. To address the problem of exploitation, African researchers expressed the need for fairness in AGS through transparency and equity in research collaborations, enhancing research oversight, African ownership and leadership of AGS, community engagement and research capacity building. In terms of genomics medicine, African genomics researchers perceived that AGS would have an impact on healthcare in Africa in the area of diagnosis, pharmacogenomics and public health. However, there were concerns around access to genomics medicine by African populations, lack of capacity for genomics medicine in Africa and the need for AGS to focus on Africa's healthcare priorities. There was however limited awareness of the concept of benefit sharing among African genomics researchers though they perceived it is as an important concept for AGS. Interviewees suggested that benefit sharing could be in the form of research capacity building, feedback of study findings, science education, community projects and the sharing of profits.
- ItemOpen AccessAFROStrep (SA): a surveillance system for group A streptococcal infection in South Africa(2018) Barth, Dylan Dominic; Engel, Mark E; Mayosi, Bongani MBACKGROUND AND AIMS OF THE THESIS: Group A β-haemolytic Streptococcus (GAS) also known as Streptococcus pyogenes, is responsible for a wide range of invasive and non-invasive GAS diseases. Prevalence and incidence data on GAS from developing countries are largely lacking when compared with industrialised nations. This thesis sought to (1) establish the South African arm of the AFROStrep biorepository and clinical database for patients with invasive and non-invasive GAS infection, (2) identify and summarize all published studies of laboratory-confirmed GAS infection in Africa, (3) describe, from national laboratory data, the incidence of invasive and non-invasive GAS in South Africa and, (4) conduct a prospective, surveillance study in order to determine the molecular epidemiology of GAS in Cape Town, South Africa over a 12-month period. METHODS: A systematic review was conducted on population-based studies reporting on the prevalence of laboratory-confirmed GAS infection among patients living in Africa (Study 1). A retrospective study of the incidence of GAS infection was conducted on data obtained from the National Health Laboratory Service between 2003 – 2015 (Study 2). The AFROStrep registry and biorepository (based in Cape Town) was established and through passive surveillance, laboratory confirmed invasive and non-invasive GAS cases were collected over a 12-month period. The molecular analysis of invasive and non-invasive infection was determined using emm type sequencing to provide insight into vaccine development (Study 3). RESULTS AND DISCUSSION: The pooled prevalence of GAS pharyngitis in Africa was determined to be 21% (95% CI, 17% to 26%). The incidence rates of laboratory-confirmed non-invasive GAS infection in the South African public sector appears to have declined over the last 13 years. Given the possibility that the lower incidence of invasive and non-invasive GAS infection found in our study is due to infrequent submission of specimens for microbiological culture by health practitioners, our findings may be an underestimate of the true burden of disease in South Africa. In our prospective surveillance study, 46 different emm types were identified. The most prevalent emm types were M76 (16% of isolates), M81 (10%), M80 (6%), M43 (6%), and M183 (6%) and were almost evenly distributed between invasive and non-invasive GAS isolates. When compared against the putative 30-valent vaccine under development, four of our most prevalent emm types are not included; vaccine coverage (i.e. vaccine type and non-vaccine type-killing) for non-invasive and invasive GAS infection in our setting was 60% and 59% respectively, notably lower than coverage in developed countries. CONCLUSION: This work provides evidence for a significantly high prevalence of GAS pharyngitis in Africa. While GAS surveillance in South Africa indicates a declining incidence of GAS disease in parts of the country over the last thirteen years, the findings may be an underestimate of the true burden of disease, demonstrating the need for accurate and comprehensive surveillance of GAS in South Africa. Finally, this research showed a low potential vaccine coverage in our setting and thus, emphasises the need for a reworking of the potential vaccine formulation to improve coverage in areas where the burden of disease is high.
- ItemOpen AccessAnalysis of genetic variations associated with arrhythmogenic right ventricular cardiomyopathy(2016) Fish, Maryam; Mayosi, Bongani M; Shaboodien, GasnatCardiomyopathy accounts for 20-30% of acute heart failure cases in adult Africans. Several types of cardiomyopathy have been identified; this study focused primarily on the genetic causes of arrhythmogenic right ventricular cardiomyopathy (ARVC). Many genes are implicated in ARVC pathogenesis, but many remain to be identified. We investigated a South African family (ACM2) with autosomal dominant ARVC, for whom the genetic cause of disease was unknown. Extensive genetic analysis was previously performed using genome-wide linkage analysis, but no disease-causing genetic variant was identified. We subsequently performed candidate gene screening of the phospholamban (PLN) gene, genome-wide copy number variant (CNV) analysis and whole exome sequencing to identify the causal genetic variant. The ACM2 family harboured no disease-causing PLN variants. However, on screening all cardiomyopathy cases in our registry (ARVC, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy and peripartum cardiomyopathy), we identified a known pathogenic PLN variant (c.25C>T; p.R9C) in a DCM family of European descent. This variant was reported in an American DCM family of European descent. Haplotype analysis revealed independent variant origins in these families. CNV analysis revealed no disease-causing variants in the ACM2 family. Whole exome sequencing of two affected ACM2 family members revealed 38 variants shared by these individuals. Variants were verified in family members and population controls by high resolution melt analysis and Sanger sequencing, and by bioinformatics analysis to predict variant pathogenicity. A novel N-cadherin (CDH2) c.686A>C (p.Q229P) variant segregated with ARVC in the ACM2 family and was bioinformatically predicted to be deleterious. An additional pathogenic CDH2 variant (c.1219G>A (p.D407N)) was identified in another individual with ARVC after screening 85 cases. These CDH2 variants were absent in normal population controls. Furthermore, alterations in Cdh2 are known to cause cardiomyopathy in rodent models. Taken together, these findings support the causal role of N-cadherin gene variants in human cardiomyopathy.
- ItemOpen AccessAssessing scimitar syndrome - use of MRI and MRA(2007) Dahya, Vijay; Mayosi, Bongani MA 36-year-old woman was assessed as a live-related kidney donor. Her chest radiograph showed unsuspected dextroposition of the heart, diminished volumes of the right middle and lower lobes, and a scimitar-shaped shadow extending from the right hilum to the region of the inferior vena cava (a scimitar is a short sword with a curved blade originally used in Eastern countries).
- ItemOpen AccessA candidate gene analysis of arrhythmogenic right ventricular cardiomyopathy (ARVC)(2006) Du Preez, Janine; Mayosi, Bongani MHeart failure is a major public health problem throughout the world. In South Africa 17% of mortality is attributed to cardiovascular disease (CVD). Heart failure may be either ischemic or non-ischemic in origin. A significant proportion of non-ischemic heart failur is due to cardiomyopathy. There are currently five types of cardiomyopathy recognised, of which arrhythmogenic right ventricular cardiomyopathy (ARVC) is one. ARVC is familial in 30 to 50% of cases and it is inherited in an autosomal dominant or an autosomal recessive manner. Twelve chromosomal loci have been linked to ARVC and six genes have been identified. In 2004 Asano and colleagues reported a mouse model of ARVC that established LAMRI and CBX5 as candidate genes for the human form of ARVC.
- ItemRestrictedCardiac involvement in HIV-infected people living in Africa: A review(2003) Magula, Nombulelo P; Mayosi, Bongani MThe primary objective of this study was to review and summarise the literature on the spectrum and management of cardiac disease in HIV-infected people living in Africa. We searched MEDLINE (January 1980 to February 2003), reference lists of papers, and reviews on the subject, and contacted experts working in the field for information on relevant references. The review was limited to papers that were published in peer-reviewed journals and indexed on MEDLINE. Seventeen of the 21 studies identified met the inclusion criteria for analysis.
The studies confirmed that cardiac abnormalities are more common in HIV-infected people, compared to normal controls, and that about half of hospitalised patients and a significant proportion of patients followed up over several years develop cardiac abnormalities. The commonest HIV-related cardiac abnormalities were cardiomyopathy and pericardial disease. Tuberculosis was the major cause of large pericardial effusion in Africa. Myocarditis was the commonest pathological abnormality in HIV-associated cardiomyopathy, and non-viral opportunistic infections such as toxoplasmosis and cryptococcosis may account for up to 50% of cases of HIV-associated cardiomyopathy in Africa.
Echocardiography is indicated in HIV-positive patients with cardiac symptoms or signs. If cardiomyopathy or pericardial disease is identified, further investigation must be considered to exclude potentially treatable opportunistic infections. Further research in large numbers of patients is needed to determine the value of endomyocardial biopsy in the management of patients with HIV-associated cardiomyopathy, and to establish the place of adjuvant steroids in the treatment of HIV-associated tuberculous pericarditis. - ItemRestrictedCardiomyopathy in Africa: heredity versus environment(2007) Mayosi, Bongani M; Somers, KrishnaUnlike other parts of the world in which cardiomyopathy is rare, heart muscle disease is endemic in Africa. The major forms of cardiomyopathy in Africa are dilated cardiomyopathy (DCM) and endomyocardial fibrosis (EMF). Whereas DCM is a major cause of heart failure throughout the continent, EMF is restricted to the tropical regions of East, Central, and West Africa. Although epidemiological studies are lacking, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy seem to have characteristics similar to those of other populations elsewhere in the world. Recent advances in the genetic analysis of DCM in other parts of the world indicate that it is a genetically heterogeneous disorder in which some cases have a Mendelian cause and others have a non-genetic or multifactorial cause. This heterogeneous pattern of inheritance has been confirmed in small studies that have been conducted so far in Africa. The advent of human immunodeficiency virus infection and its association with cardiomyopathy has emphasised the role of inflammatory agents in the pathogenesis of DCM. By contrast with DCM in which some cases have major genetic contributions, there is scanty evidence for the role of genetic factors in the aetiology of EMF. Although the pathogenesis of EMF is not fully understood, it appears that the conditioning factor may be geography (in its widest sense, to include climate and socio-economic status), the triggering factor may be an as yet unidentified infective agent, and the perpetuating factor may be eosinophilia. There is a need for renewed effort to identify genetic and non-genetic factors in EMF and other forms of heart muscle disease that are prevalent on the continent of Africa.
- ItemOpen AccessChromosome 16q22 variants in a region associated with cardiovascular phenotypes correlate with ZFHX3 expression in a transcript-specific manner(BioMed Central, 2014-12-24) Martin, Ruairidh I R; Owens, W A; Cunnington, Michael S; Mayosi, Bongani M; Koref, Mauro S; Keavney, Bernard DBackground: The ZFHX3 gene, located in Chromosome 16q22.3, codes for a transcription factor which is widely expressed in human tissues. Genome-wide studies have identified associations between variants within the gene and Kawasaki disease and atrial fibrillation. ZFHX3 has two main transcripts that utilise different transcription start sites. We examined the association between genetic variants in the 16q22.3 region and expression of ZFHX3 to identify variants that regulate gene expression. Results: We genotyped 65 single-nucleotide polymorphisms to tag genetic variation at the ZFHX3 locus in two cohorts, 451 British individuals recruited in the North East of England and 310 mixed-ancestry individuals recruited in South Africa. Allelic expression analysis revealed that the minor (A) allele of rs8060701, a variant in the first intron of ZFHX3, was associated with a 1.16-fold decrease in allelic expression of both transcripts together, (p = 4.87e-06). The minor (C) allele of a transcribed variant, rs10852515, in the second exon of ZFHX3 isoform A was independently associated with a 1.36-fold decrease in allelic expression of ZFHX3 A (p = 7.06e-31), but not overall ZFHX3 expression. However, analysis of total gene expression of ZFHX3 failed to detect an association with genotype at any variant. Differences in linkage disequilibrium between the two populations allowed fine-mapping of the locus to a 7 kb region overlapping exon 2 of ZFHX3 A. We did not find any association between ZFHX3 expression and any of the variants identified by genome wide association studies. Conclusions: ZFHX3 transcription is regulated in a transcript-specific fashion by independent cis-acting transcribed polymorphisms. Our results demonstrate the power of allelic expression analysis and trans-ethnic fine mapping to identify transcript-specific cis-acting regulatory elements.
- ItemOpen AccessChromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression(Public Library of Science, 2010) Cunnington, Michael S; Koref, Mauro Santibanez; Mayosi, Bongani M; Burn, John; Keavney, BernardAuthor Summary Genetic variants on chromosome 9p21 have been associated with several important diseases including coronary artery disease, diabetes, and multiple cancers. Most of the risk variants in this region do not alter any protein sequence and are therefore likely to act by influencing the expression of nearby genes. We investigated whether chromosome 9p21 variants are correlated with expression of the three nearest genes ( CDKN2A , CDKN2B , and ANRIL ) which might mediate the association with disease. Using two different techniques to study effects on expression in blood from two separate populations of healthy volunteers, we show that variants associated with disease are all correlated with ANRIL expression, but associations with the other two genes are weaker and less consistent. Multiple genetic variants are independently associated with expression of all three genes. Although total expression levels of CDKN2A , CDKN2B , and ANRIL are positively correlated, individual genetic variants influence ANRIL and CDKN2B expression in opposite directions, suggesting a possible role of ANRIL in CDKN2B regulation. Our study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases.
- ItemOpen AccessClinical characteristics, causes, adherence to heart failure treatment guidelines and mortality of patients with acute heart failure: the Groote Schuur Hospital experience(2016) Szymanski, Patryk Zygmunt; Mayosi, Bongani MBackground: There is limited information on acute heart failure (AHF) and the treatment thereof in sub-Saharan Africa. Therefore, the aim of this study was to describe the clinical characteristics, causes, adherence to heart failure (HF) treatment guidelines and mortality of patients presenting to Groote Schuur Hospital with acute heart failure (AHF). Methods: This is a sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUSHF). This sub-study is a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to Groote Schuur Hospital entered into the existing registry, following the publication of the primary paper of THESUS-HF in 2012. The patients were classified into prevalent (or existing) or incident (or new) cases of heart failure. Results: Of the 119 patients included, 69 (58%) were female and the mean (SD) age was 49.9 (16.3) years. Prevalent cases were mostly of mixed ancestry (63.3%) with more hypertension (70%), diabetes mellitus (36.7%), hyperlipidaemia (33.3%) and ischaemic heart disease (36.7%) than incident cases. The main causes of heart failure were cardiomyopathy (20.2%), ischaemic heart disease (IHD) (19.3%) and rheumatic valvular heart disease (RHD) (18.5%). Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of β-blocker, aldosterone antagonist and digoxin use. Rehospitalisation at 180 days occurred in 25.2%. In-hospital mortality was 8.4 % and the case fatality rate at six months was 26.1%. Conclusion: In Cape Town the main causes of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is a serious under-use of β-blockers, aldosterone antagonists and digoxin. An emphasis on the rigorous application of treatment guidelines is needed in order to reduce re-admission and mortality.
- ItemOpen AccessCommon variation neighbouring micro-RNA 22 is associated with increased left ventricular mass(Public Library of Science, 2013) Harper, Andrew R; Mayosi, Bongani M; Rodriguez, Antony; Rahman, Thahira; Hall, Darroch; Mamasoula, Chrysovalanto; Avery, Peter J; Keavney, Bernard DAIMS: Previous genome-wide linkage analysis has suggested that chromosomal region 17p13.3 may harbour genes influencing left ventricular mass (LVM) in man. To date, the genetic factors accounting for LVM variability remain largely unknown but a non-coding RNA gene within this region, micro-RNA 22 (miR-22) , has been implicated in cardiac hypertrophy and heart failure in animal models. We thus investigated the relationship between common genetic polymorphisms surrounding miR-22 and left ventricular mass in a family-based association study. Methods and RESULTS: We studied a cohort of 255 families comprising 1,425 individuals ascertained via a hypertensive proband. Ten single nucleotide polymorphisms which together tagged common genetic variation surrounding the miR-22 gene were genotyped. There was evidence of association between the rs7223247 polymorphism, which lies within the 3′UTR of a gene of unknown function, TLCD2, immediately downstream from miR-22, and left ventricular mass determined by Sokolow-Lyon voltage (Bonferroni corrected p- value = 0.038). The T allele at rs7223247 was associated with an 0.272 standard deviation higher Sokolow-Lyon voltage. Genotype was responsible for ∼1% of the population variability in LVM. CONCLUSIONS: Genotype at the rs7223247 polymorphism affects left ventricular mass determined by Sokolow-Lyon voltage. The neighbouring genes miR-22 and TLCD2 are strong candidates to account for this observation.
- ItemOpen AccessA Cost-Effectiveness Analysis of a Program to Control Rheumatic Fever and Rheumatic Heart Disease in Pinar del Rio, Cuba(Public Library of Science, 2015) Watkins, David A; Mvundura, Mercy; Nordet, Porfirio; Mayosi, Bongani MBACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) persist in many low- and middle-income countries. To date, the cost-effectiveness of population-based, combined primary and secondary prevention strategies has not been assessed. In the Pinar del Rio province of Cuba, a comprehensive ARF/RHD control program was undertaken over 1986 - 1996. The present study analyzes the cost-effectiveness of this Cuban program. Methods and FINDINGS: We developed a decision tree model based on the natural history of ARF/RHD, comparing the costs and effectiveness of the 10-year Cuban program to a “do nothing” approach. Our population of interest was the cohort of children aged 5 - 24 years resident in Pinar del Rio in 1986. We assessed costs and health outcomes over a lifetime horizon, and we took the healthcare system perspective on costs but did not apply a discount rate. We used epidemiologic, clinical, and direct medical cost inputs that were previously collected for publications on the Cuban program. We estimated health gains as disability-adjusted life years (DALYs) averted using standard approaches developed for the Global Burden of Disease studies. Cost-effectiveness acceptability thresholds were defined by one and three times per capita gross domestic product per DALY averted. We also conducted an uncertainty analysis using Monte Carlo simulations and several scenario analyses exploring the impact of alternative assumptions about the program’s effects and costs. We found that, compared to doing nothing, the Cuban program averted 5051 DALYs (1844 per 100,000 school-aged children) and saved $7,848,590 (2010 USD) despite a total program cost of $202,890 over 10 years. In the scenario analyses, the program remained cost saving when a lower level of effectiveness and a reduction in averted years of life lost were assumed. In a worst-case scenario including 20-fold higher costs, the program still had a 100% of being cost-effective and an 85% chance of being cost saving. CONCLUSIONS: A 10-year program to control ARF/RHD in Pinar del Rio, Cuba dramatically reduced morbidity and premature mortality in children and young adults and was cost saving. The results of our analysis were robust to higher program costs and more conservative assumptions about the program’s effectiveness. It is possible that the program’s effectiveness resulted from synergies between primary and secondary prevention strategies. The findings of this study have implications for non-communicable disease policymaking in other resource-limited settings.
- ItemOpen AccessDeveloping the African national health research systems barometer(BioMed Central, 2016-07-22) Kirigia, Joses M; Ota, Martin O; Senkubuge, Flavia; Wiysonge, Charles S; Mayosi, Bongani MBackground: A functional national health research system (NHRS) is crucial in strengthening a country’s health system to promote, restore and maintain the health status of its population. Progress towards the goal of universal health coverage in the post-2015 sustainable development agenda will be difficult for African countries without strengthening of their NHRS to yield the required evidence for decision-making. This study aims to develop a barometer to facilitate monitoring of the development and performance of NHRSs in the African Region of WHO. Methods: The African national health research systems barometer algorithm was developed in response to a recommendation of the African Advisory Committee for Health Research and Development of WHO. Survey data collected from all the 47 Member States in the WHO African Region using a questionnaire were entered into an Excel spreadsheet and analysed. The barometer scores for each country were calculated and the performance interpreted according to a set of values ranging from 0% to 100%. Results: The overall NHRS barometer score for the African Region was 42%, which is below the average of 50%. Among the 47 countries, the average NHRS performance was less than 20% in 10 countries, 20–40% in 11 countries, 41–60% in 16 countries, 61–80% in nine countries, and over 80% in one country. The performance of NHRSs in 30 (64%) countries was below 50%. Conclusion: An African NHRS barometer with four functions and 17 sub-functions was developed to identify the gaps in and facilitate monitoring of NHRS development and performance. The NHRS scores for the individual sub-functions can guide policymakers to locate sources of poor performance and to design interventions to address them.
- ItemRestrictedDextrocardia with anterior myocardial infarction: images in cardiology(2003) Cocciante, Adriano G; Mayosi, Bongani M; Stevens, John EA 56-year-old female smoker presented to hospital with the sudden onset of chest tightness and dyspnoea, lasting for 4 hours. Clinical and radiological examination revealed dextrocardia and situs inversus. The admission ECG, performed with the electrodes in the conventional position, showed features of dextrocardia (rS complexes and poor QRS amplitude progression from lead V1 to V6, the tall R wave in lead aVR, and P wave and QRS axes directed at +120°) and widespread changes suggestive of myocardial ischaemia/injury (ST segment elevation of 1–2 mm in aVR, ST segment depression inferiorly, and Q waves in aVR, aVL, V1 and V2) (Fig. 1).
- ItemOpen AccessDiagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study(2014-06-18) Pandie, Shaheen; Peter, Jonathan G; Kerbelker, Zita S; Meldau, Richard; Theron, Grant; Govender, Ureshnie; Ntsekhe, Mpiko; Dheda, Keertan; Mayosi, Bongani MBackground: Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP. Methods: From October 2009 through September 2012, 151 consecutive patients with suspected TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium tuberculosis culture and/or pericardial histology served as the reference standard for definite TBP. Receiver-operating-characteristic curve analysis was used for selection of ADA and uIFNγ cut-points. Results: Of the participants, 49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. A total of 105 (74%) participants were human immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100% (85.6% to 100%), respectively. Concentration of pericardial fluid by centrifugation and using standard sample processing did not improve Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44 pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10). However, the specificity and positive likelihood ratio of uIFNγ was higher than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of TB of 30%. The sensitivity and negative predictive value of both uIFNγ and ADA were higher than Xpert-MT/RIF (P < 0.001). Conclusions: uIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test.
- ItemOpen AccessEffect 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(BioMed Central, 2015-06-01) Barth, Dylan Dominic; Zühlke, Liesl; Joachim, Alexia; Hoegger, Tyler; Mayosi, Bongani M; Engel, Mark EBackground: 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.
- ItemOpen AccessThe 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(Public Library of Science, 2015) Mnguni, Ayanda Trevor; Engel, Mark E; Borkum, Megan S; Mayosi, Bongani MBACKGROUND: 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.
- ItemOpen AccessThe effects of angiotensin converting enzyme inhibitors (ACEI) on human N-acetylseryl-aspartyl-lysyl-proline (AcSDKP) levels : a systematic review(2015) Mnguni, Ayanda Trevor; Engel, Mark E; Mayosi, Bongani MBackground: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4-8% of cases. N-acetyl-seryl-aspartyl-lysylproline (Ac-SDKP) is a ubiquitous tetrapeptide with antifibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin converting enzyme inhibitors (ACEI), which increase Ac-SDKP levels with antifibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on AcSDKP and fibrosis in human tissues. Objective: To systematically review the effects of ACEIs on Ac-SDKP levels in human tissues. Methods: We searched five electronic databases (1996-2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO.
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