Molecular Epidemiology of Noninvasive and Invasive Group A Streptococcal Infections in Cape Town.

Group A streptococcus (GAS) is responsible for a wide range of noninvasive group A streptococcal (non-iGAS) and invasive group A streptococcal (iGAS) infections. Information about the emm type variants of the M protein causing GAS disease is important to assess potential vaccine coverage of a 30-valent vaccine under development, particularly with respect to how they compare and contrast with non-iGAS isolates, especially in regions with a high burden of GAS. We conducted a prospective passive surveillance study of samples from patients attending public health facilities in Cape Town, South Africa. We documented demographic data and clinical presentation. emm typing was conducted using CDC protocols. GAS was commonly isolated from pus swabs, blood, deep tissue, and aspirates. Clinical presentations included wound infections (20%), bacteremia (15%), abscesses (9%), and septic arthritis (8%). Forty-six different emm types were identified, including M76 (16%), M81 (10%), M80 (6%), M43 (6%), and M183 (6%), and the emm types were almost evenly distributed between non-iGAS and iGAS isolates. There was a statistically significant association with M80 in patients presenting with noninvasive abscesses. Compared to the 30-valent vaccine under development, the levels of potential vaccine coverage for non-iGAS and iGAS infection were 60% and 58%, respectively, notably lower than the coverage in developed countries; five of the most prevalent emm types, M76, M81, M80, M43, and M183, were not included. The emm types from GAS isolated from patients with invasive disease did not differ significantly from those from noninvasive disease cases. There is low coverage of the multivalent M protein vaccine in our setting, emphasizing the need to reformulate the vaccine to improve coverage in areas where the burden of disease is high.IMPORTANCE The development of a vaccine for group A streptococcus (GAS) is of paramount importance given that GAS infections cause more than 500,000 deaths annually across the world. This prospective passive surveillance laboratory study evaluated the potential coverage of the M protein-based vaccine currently under development. While a number of GAS strains isolated from this sub-Sahara African study were included in the current vaccine formulation, we nevertheless report that potential vaccine coverage for GAS infection in our setting was approximately 60%, with four of the most prevalent strains not included. This research emphasizes the need to reformulate the vaccine to improve coverage in areas where the burden of disease is high.

Mutations of FAM111B gene are not associated with Systemic Sclerosis.

Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence similarity 111, member B (FAM111B) gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis, a multisystem fibrotic condition with clinical similarities to SSc. This observation has established FAM111B as a candidate gene for SSc. PATIENTS AND METHODS: Demographic and clinical characteristics of consenting adults with definite SSc were recorded. Blood DNA analysis was performed using the High-Resolution Melt technique, and samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Ethnically-matched controls from the general South African population were used to verify the frequency of variants in FAM111B. Public databases such as 1000 Genomes and ExAC were also used to verify the frequency of variants in FAM111B. RESULTS: Of 131 patients, 118 (90.1%) were female, and 78 (59.5%) were black Africans. Genetic analysis revealed two FAM111B genetic variants. The c.917 A > G variant (rs200497516) was found in one SSc patients, and one control, and was classified as a missense variant of unknown significance. The c.988 C > T variant (rs35732637) occurred in three SSc patients and 42/243 (17.3%) of healthy controls, and is a known polymorphism. CONCLUSION: One rare variant was found in a patient with SSc but has no functional or structural impact on the FAM111B gene. In this cohort, FAM111B gene mutations are not associated with SSc.

Genomics research in Africa and its impact on global health: insights from African researchers.

Africa may be heading for an era of genomics medicine. There are also expectations that genomics may play a role in reducing global health inequities. However, the near lack of genomics studies on African populations has led to concerns that genomics may widen, rather than close, the global health inequity gap. To prevent a possible genomics divide, the genomics 'revolution' has been extended to Africa. This is motivated, in part, by Africa's rich genetic diversity and high disease burden. What remains unclear, however, are the prospects of using genomics technology for healthcare in Africa. In this qualitative study, we explored the views of 17 genomics researchers in Africa on the prospects and challenges of genomics medicine in Africa. Interviewees were researchers in Africa who were involved in genomics research projects in Africa. Analysis of in-depth interviews suggest that genomics medicine may have an impact on disease surveillance, diagnosis, treatment and prevention. However, Africa's capacity for genomics medicine, current research priorities in genomics and the translation of research findings will be key defining factors impacting on the ability of genomics medicine to improve healthcare in Africa.

Incidence of myocardial injury after non-cardiac surgery: Experience at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a newly recognised entity identified as an independent risk factor associated with increased 30-day all-cause mortality. MINS increases the risk of death in the perioperative period by ~10-fold. More than 80% of patients with MINS are asymptomatic, so the majority of diagnoses are missed. Awareness of MINS is therefore important for perioperative physicians. OBJECTIVES: To investigate the incidence of MINS after elective elevated-risk non-cardiac surgery at Groote Schuur Hospital, Cape Town, South Africa (SA). METHODS: Patients aged ≥45 years undergoing elective elevated-risk non-cardiac surgery were enrolled via convenience sampling. The new fifth-generation high-sensitivity cardiac troponin T blood test was used postoperatively to identify MINS. Preoperative troponin levels were not measured. RESULTS: Among 244 patients included in the study, the incidence of MINS was 4.9% (95% confidence interval (CI) 2.8 - 8.5), which was not significantly different from that in a major international prospective observational study (VISION) (8.0% (95% CI 7.5 - 8.4)); p=0.080. CONCLUSIONS: Our SA cohort had a lower cardiovascular risk profile but a similar incidence of MINS to that described in international literature. The impact of MINS on morbidity and mortality is therefore likely to be proportionally higher in SA than in published international studies. The limited sample size and lower event rate weaken our conclusions. Larger studies are required to establish patient and surgical risk factors for MINS, allowing for revision of cardiovascular risk prediction models in SA.

Status of cardiac arrhythmia services in Africa in 2018: a PASCAR Sudden Cardiac Death Task Force report.

BACKGROUND: There is limited information on the availability of health services to treat cardiac arrhythmias in Africa. METHODS: The Pan-African Society of Cardiology (PASCAR) Sudden Cardiac Death Task Force conducted a survey of the burden of cardiac arrhythmias and related services over two months (15 October to 15 December) in 2017. An electronic questionnaire was completed by general cardiologists and electrophysiologists working in African countries. The questionnaire focused on availability of human resources, diagnostic tools and treatment modalities in each country. RESULTS: We received responses from physicians in 33 out of 55 (60%) African countries. Limited use of basic cardiovascular drugs such as anti-arrhythmics and anticoagulants prevails. Non-vitamin K-dependent oral anticoagulants (NOACs) are not widely used on the continent, even in North Africa. Six (18%) of the sub-Saharan African (SSA) countries do not have a registered cardiologist and about one-third do not have pacemaker services. The median pacemaker implantation rate was 2.66 per million population per country, which is 200-fold lower than in Europe. The density of pacemaker facilities and operators in Africa is quite low, with a median of 0.14 (0.03-6.36) centres and 0.10 (0.05-9.49) operators per million population. Less than half of the African countries have a functional catheter laboratory with only South Africa providing the full complement of services for cardiac arrhythmia in SSA. Overall, countries in North Africa have better coverage, leaving more than 110 million people in SSA without access to effective basic treatment for cardiac conduction disturbances. CONCLUSION: The lack of diagnostic and treatment services for cardiac arrhythmias is a common scenario in the majority of SSA countries, resulting in sub-optimal care and a subsequent high burden of premature cardiac death. There is a need to improve the standard of care by providing essential services such as cardiac pacemaker implantation.

Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY).

BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LIMCs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. AIM: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. RESULTS: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and more frequent INR monitoring and contraceptive counselling. CONCLUSION: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers' knowledge and efficiency in caring for RHD patients.

Clinical characteristics and causes of heart failure, adherence to treatment guidelines, and mortality of patients with acute heart failure: Experience at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: There is limited information on acute heart failure (AHF) and its treatment in sub-Saharan Africa. OBJECTIVE: To describe the clinical characteristics and causes of heart failure (HF), adherence to HF treatment guidelines, and mortality of patients with AHF presenting to Groote Schuur Hospital (GSH), Cape Town, South Africa. METHODS: This sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUS-HF) was a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to GSH and entered into the existing registry after publication of the primary THESUS-HF article in 2012. The patients were classified into prevalent (existing) or incident (new) cases of HF. RESULTS: Of the 119 patients included, 69 (58.0%) were female and the mean (standard deviation) age was 49.9 (16.3) years. The majority of prevalent cases were patients of mixed ancestry (63.3%), and prevalent cases had more hypertension (70.0%), diabetes mellitus (36.7%), hyperlipidaemia (33.3%) and ischaemic heart disease (IHD) (36.7%) than incident cases. The top five causes of HF were cardiomyopathy (20.2%), IHD (19.3%), rheumatic valvular heart disease (RHD) (18.5%), cor pulmonale (11.8%) and hypertension (10.1%), with the remaining 20.1% consisting of miscellaneous causes including pericarditis, toxins and congenital heart disease. Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of beta-blocker, aldosterone antagonist and digoxin use. Rehospitalisation within 180 days occurred in 25.2% of cases. In-hospital mortality was 8.4% and the case fatality rate at 6 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 serious under-use of beta-blockers, aldosterone antagonists and digoxin. Emphasis on the rigorous application of treatment guidelines is needed to reduce readmission and mortality.

An approach to the patient with suspected pericardial disease.

Diseases of the pericardium commonly manifest in one of three ways: acute pericarditis, pericardial effusion and constrictive pericarditis. In the developed world, the most common cause of acute pericarditis is viral or idiopathic disease, while in the developing world tuberculous aetiology, particularly in sub-Saharan Africa, is commonplace owing to the high prevalence of HIV. This article provides an approach to the diagnosis, investigation and management of these patients.

The intercalated BSc (Med) Honours/MB ChB and integrated MB ChB/PhD tracks at the University of Cape Town: models for a national medical student research training programme.

The Faculty of Health Sciences at the University of Cape Town is addressing the shortage of clinician-scientists in South Africa by introducing two research training tracks in parallel with the professional MB ChB programme, namely the intercalated BSc (Med) Hons/MB ChB track and the integrated MB ChB/PhD track. The BSc (Med) Hons/MB ChB track is available to MB ChB students who have completed the first two years of study. The track comprises a course in Molecular Medicine given concurrently with the MB ChB third-year curriculum, followed by a BSc (Med) Hons as a 'year out' of MB ChB. Subsequently students may enroll into the integrated MB ChB/PhD track that enables them to undertake a PhD concurrently with MB ChB studies, which will be spread over additional years, or alternatively to undertake a PhD after completion of the MB ChB. These tracks, which were launched in 2011, represent an opportunity to train a new cadre of young African clinician-scientists at the undergraduate level.

Peripartum cardiomyopathy and familial dilated Cardiomyopathy: a tale of two cases.

Peripartum cardiomyopathy (PPCM) is a form of pregnancyrelated heart failure that is associated with considerable morbidity and mortality. Most patients present with acute postpartal heart failure that otherwise resembles the clinical presentation of dilated cardiomyopathy (DCM). There is increasing recognition that PPCM may be due to genetic factors in a significant proportion of cases. There is evidence that at least 7% of cases of PPCM may be part of the spectrum of familial DCM. We report on two cases of PPCM, with relatives demonstrating familial DCM, both patients displaying autosomal dominant patterns of inheritance, and showing severe cardiomyopathy among proband and affected relatives. Family screening for familial DCM should be indicated in all cases of unexplained PPCM.

Medical inpatient mortality at Groote Schuur Hospital, Cape Town, South Africa, 2002-2009.

BACKGROUND: Despite the challenges facing healthcare in South Africa, empirical insights into the performance of healthcare services over time are scarce. METHODS: We analysed first admissions of adult medical inpatients to Groote Schuur Hospital, Cape Town, from January 2002 to July 2009. Data included age, sex, medical specialty, and date of admission and discharge. We used population group and hospital billing codes as proxy measures for socio-economic status (SES). We calculated the duration of stay in days from the date of admission to discharge, and inpatient mortality rates per 1 000 patient days. Poisson regression was used to estimate mortality rate ratios (MRR) in unadjusted analysis and after adjusting for potential confounders. RESULTS: There were 42 582 first admissions. Patient demographics shifted towards a lower SES. Median age decreased from 52 years in 2002 to 49 years in 2009, while patients aged 20 - 39 years increased in proportion from 26% to 31%. The unadjusted proportion of admissions which resulted in in-hospital deaths increased from 12% in 2002 to 17% in 2009. Corresponding mortality rates per 1 000 patient days were 17.0 (95% confidence interval (CI) 15.9 - 18.3) and 23.4 (95% CI 21.6 - 25.4), respectively (unadjusted MRR 1.37; 95% CI 1.23 - 1.53). Annual increases in mortality rates were highest during the first 2 days following admission (increasing from 30.1 to 50.3 deaths per 1 000), and were associated with increasing age, non-paying patient status, black population group and male sex, and were greatest in the emergency ward (adjusted MRR 1.73, comparing 2009 with 2002; 95% CI 1.49 - 2.01). DISCUSSION: Increasing medical inpatient mortality rates at a large South African academic hospital were most marked during the first 2 days after admission and appeared greatest among emergency medical inpatients.

The promise of computer-assisted auscultation in screening for structural heart disease and clinical teaching.

Cardiac auscultation has been the central clinical tool for the diagnosis of valvular and other structural heart diseases for over a century. Physicians acquire competence in this technique through considerable training and experience. In Africa, however, we face a shortage of physicians and have the lowest health personnel-to-population ratio in the world. One of the proposed solutions for tackling this crisis is the adoption of health technologies and product innovations to support different cadres of health workers as part of task shifting. Computer-assisted auscultation (CAA) uses a digital stethoscope combined with acoustic neural networking to provide a visual display of heart sounds and murmurs, and analyses the recordings to distinguish between innocent and pathological murmurs. In so doing, CAA may serve as an objective tool for the screening of structural heart disease and facilitate the teaching of cardiac auscultation. This article reviews potential clinical applications of CAA.

The 2011 United Nations high-level meeting on non-communicable diseases: the Africa agenda calls for a 5-by-5 approach.

The High Level Meeting of the 66th Session of the United Nations General Assembly was held in September 2011. The Political Declaration issued at the meeting focused the attention of world leaders and the global health community on the prevention and control of noncommunicable diseases (NCDs). The four major NCDs (cardiovascular diseases, cancer, diabetes and chronic respiratory diseases) and their four risk factors (tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol) constitute the target of the '4-by-4' approach, which is also supported by national and international health organisations. We argue that while preventing these eight NCDs and risk factors is also important in Africa, it will not be enough. A '5-by-5' strategy is needed, addressing neuropsychiatric disorders as the fifth NCD; and transmissible agents that underlie the neglected tropical diseases and other NCDs as the fifth risk factor. These phenomena cause substantial preventable death and disability, and must therefore be prioritised.

A lower body mass index is associated with cardiomyopathy in people with HIV infection: evidence from a case comparison study.

UNLABELLED: The cause of cardiomyopathy in patients infected with the human immunodeficiency virus (HIV) remains largely unknown, although a number of predisposing factors have been identified. Malnutrition has been postulated to be a contributory factor, but the association of anthropometric measures of nutritional status with HIV-associated cardiomyopathy has not been established. METHOD: We investigated the association between anthropometric measures of nutritional status and cardiomyopathy in HIV-positive individuals in a cross-sectional case comparison study. RESULTS: Seventeen cases of HIV-associated cardiomyopathy and a comparison group of 18 HIV-positive individuals without cardiomyopathy were studied. There was no significant difference between the two groups in age, gender, CD4 cell count, HIV RNA viral load or World Health Organization (WHO) clinical stage of HIV disease. Patients with HIV-associated cardiomyopathy had evidence of undernutrition compared with HIV-infected people without cardiomyopathy, as evidenced by a significantly lower body mass index (BMI) (20.9 kg/m2 v. 27.0 kg/m2, p = 0.02), mid-upper arm circumference (26.2 cm v. 27.3 cm, p = 0.02), and bone-free arm muscle area (26.7 cm2 v. 32.8 cm2, p = 0.02). However, in a multivariate stepwise logistic regression model, a lower BMI was the only independent anthropometric risk factor for cardiomyopathy (odds ratio 0.76, 95% confidence interval 0.64 - 0.97, p = 0.02). CONCLUSION: A lower BMI is associated with cardiomyopathy in people who are living with HIV.

Cardiac findings in the precompetition medical assessment of football players participating in the 2009 African Under-17 Championships in Algeria.

OBJECTIVES: To screen all players registered for the 8th CAF African Under-17 Championship for risk factors of sudden cardiac death. DESIGN: Standardised cardiac evaluation prior to the start of the competition. STUDY POPULATION: 155 male football players from all eight qualified teams; mean age 16.4 (SD 0.68) years (range 14 to 17). METHODS: The cardiac evaluation consisted of a medical history, clinical examination, 12-lead resting electrocardiogram (ECG) and echocardiography, and was performed by three experienced cardiologists using established guidelines. RESULTS: Nine (5.8%) players reported cardiac symptoms, and the clinical examination was abnormal in only two players with elevated blood pressure. A total of 40 players (25.8%) showed abnormal ECG patterns. None of the players with a positive ECG showed correlating echocardiographic findings. The echocardiogram of one player appeared highly suspicious for early-stage hypertrophic cardiomyopathy, and in another player the myocardium was suspicious for non-compaction cardiomyopathy, but both had normal ECGs. Thirteen (8.4%) players showed echocardiographic findings that needed further follow-up. The percentage of players with pathological ECG patterns and some abnormal echocardiographic measurements varied substantially between different ethnic groups. CONCLUSION: Cardiological screening for risk factors of sudden cardiac death of football players prior to an international competition proved feasible, and conduction by independent experts allowed high-quality standards and a consistent protocol for the examinations. Differences observed between ethnic groups indicate that guidelines for the analysis of ECGs and echocardiography might be adjusted to the target population.