PhD Candidate, University of Cape Town
To inform a vaccine development to prevent premature deaths caused by rheumatic heart disease.
My PhD focus is on establishment of the Group A Streptococcus (GAS) registry in Africa (the AFROStrep Registry). GAS is responsible for >20% of sore throats in Africa and plays a role in the development of more serious diseases such a rheumatic heart disease.
This work represents an important milestone in rheumatic fever and rheumatic heart disease programs within Africa, given that GAS plays an initiating role in the development of this disease which results in the mortality of many of Africa’s children. Globally, rheumatic heart disease is responsible for more than 300,000 deaths per annum with the majority of cases in developing and low-middle income countries.
There is no registry of this kind at present, unlike in the north-western countries, and thus, this work will serve to provide a strong evidence base for future research endeavors, including informing vaccine initiatives.
To date, we have collected >600 GAS isolates in Cape Town, over a 12-month period within my PhD project. This is the largest biorepository on the continent with both invasive and non-invasive infections.
My research describing the epidemiology and strains circulating in our setting has been accepted for an oral platform presentation at the prestigious Lancefield conference which takes place once every four years.
Attending this meeting will provide an opportunity to engage and network with leaders in the field of streptococcal and rheumatic heart disease research. I will also have the opportunity to share and describe, with an international arena, the prevalent GAS strains circulating in our setting so as to inform a vaccine that is currently under development. Africa carries the highest burden of rheumatic heart disease and it is imperative that our strains are considered in the vaccine formulation to prevent diseases of this nature on the African continent.
Abstract: Group A streptococcus (GAS) or Streptococcus pyogenes has been recognised as an important human pathogen since early days of modern microbiology, and it remains among the top ten causes of mortality from an infectious disease. Clinical manifestations attributable to this organism are perhaps the most diverse of any single human pathogen. These encompass invasive GAS infections, with high mortality rates despite effective antimicrobials, toxin-mediated diseases including scarlet fever and streptococcal toxic shock syndrome, the autoimmune sequelae of rheumatic fever and glomerulonephritis with potential for long-term disability, and nuisance manifestations of superficial skin and pharyngeal infection, which continue to consume a sizable proportion of healthcare resources. Although an historical perspective indicates major overall reductions in GAS infection rates in the modern era, chiefly as a result of widespread improvements in socioeconomic circumstances, this pathogen remains as a leading infectious cause of global morbidity and mortality. More than 18 million people globally are estimated to suffer from serious GAS disease. This burden disproportionally affects least affluent populations, and is a major cause of illness and death among children and young adults, including pregnant women, in low-resource settings. We review GAS transmission characteristics and prevention strategies, historical and geographical trends and report on the estimated global burden disease attributable to GAS. The lack of systematic reporting makes accurate estimation of rates difficult. This highlights the need to support improved surveillance and epidemiological research in low-resource settings, in order to enable better assessment of national and global disease burdens, target control strategies appropriately and assess the success of control interventions.
Pub.: 18 Dec '12, Pinned: 29 Aug '17
Abstract: The greatest burden of group A streptococcal (GAS) disease worldwide is due to acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Safe, effective and affordable vaccines designed to prevent GAS infections that trigger ARF could reduce the overall global morbidity and mortality from RHD. The current study evaluated the potential coverage of a new 30-valent M protein-based vaccine using GAS isolates from school children in Bamako, Mali, a population at high risk for the development of RHD.The bactericidal activity of rabbit antisera against the 30-valent vaccine was assessed using a collection of GAS isolates recovered during a study of the epidemiology of pharyngitis in Bamako.Single isolates representing 42 of 67 emm-types, accounting for 85% of the GAS infections during the study, were evaluated. All (14/14) of the vaccine emm-types in the collection were opsonized (bactericidal killing >50%) and 26/28 non-vaccine types were opsonized. Bactericidal activity was observed against 60% of the total emm-types recovered in Bamako, which accounted for 81% of all infections.Multivalent vaccines comprised of N-terminal M peptides elicit bactericidal antibodies against a broad range of GAS serotypes, indicating that their efficacy may extend beyond the emm-types included in the vaccine.
Pub.: 05 Feb '13, Pinned: 29 Aug '17
Abstract: The true burden of group A streptococcal (GAS) disease in Africa is not known. GAS is a significant cause of mortality and morbidity on the global scale and in developing countries. According to Carapetis et al, the prevalence of severe GAS disease is at least 18.1 million cases with an incidence of at least 1.78 million cases per year.We aim to provide a systematic review of studies measuring the prevalence of GAS infection among people in North and Sub-Saharan African countries. A comprehensive literature search of a number of databases will be undertaken, using an African search filter, to identify GAS prevalence studies that have been published. Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against predefined criteria. Statistical analysis will include two steps: (1) identification of data sources and documenting of estimates, and (2) the application of the random-effects and fixed-effects meta-analysis model to aggregate prevalence estimates, and to account for between study variability in calculating the overall pooled estimates and 95% CI for GAS prevalence. Heterogeneity will be evaluated using the I(2) statistic to determine the extent of variation in effect estimates that is due to heterogeneity rather than chance. This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P) 2015 Statement. This review will provide updated evidence of a review published in 2009. Our data will have implications for the development of a GAS vaccine.Ethics approval is not required for this study given that this is a protocol for a systematic review of published studies. The results of this study will be disseminated through a peer-reviewed publication and conference presentation.PROSPERO CRD4201401290 0. (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014012900).
Pub.: 01 Sep '15, Pinned: 29 Aug '17
Abstract: Existing clinical decision rules (CDR) to diagnose group A streptococcal (GAS) pharyngitis have not been validated in sub-Saharan Africa. We developed a locally applicable CDR while evaluating existing CDRs for diagnosing GAS pharyngitis in South African children.We conducted a prospective cohort study and enrolled 997 children aged 3-15 years presenting to primary care clinics with a complaint of sore throat, and whose parents provided consent. Main outcome measures were signs and symptoms of pharyngitis, and a positive GAS culture from a throat swab. Bivariate and multivariate analyses were used to develop the clinical decision rule. In addition, the diagnostic effectiveness of six existing rules for predicting a positive culture in our cohort was assessed.206 of 982 children (21%) had a positive GAS culture. Tonsillar swelling, tonsillar exudates, tender or enlarged anterior cervical lymph nodes, absence of cough and absence of rhinorrhea were associated with positive cultures in bivariate and multivariate analyses. Four variables (tonsillar swelling and one of tonsillar exudate, no rhinorrhea, no cough), when used in a cumulative score, showed 83.7% sensitivity and 32.2% specificity for GAS pharyngitis. Of existing rules tested, the McIsaac rule had the highest positive predictive value (28%), but missed 49% of the culture-positive children who should have been treated.The new four-variable clinical decision rule for GAS pharyngitis (i.e., tonsillar swelling and one of tonsillar exudate, no rhinorrhea, no cough) outperformed existing rules for GAS pharyngitis diagnosis in children with symptomatic sore throat in Cape Town.
Pub.: 22 Nov '16, Pinned: 29 Aug '17
Abstract: emm sequence typing is the most widely used method for defining group A streptococcal (GAS) strains, and has been applied to isolates in all regions of the world. We did a systematic review of the global distribution of GAS emm types. 102 articles and reports were included (38 081 isolates). Epidemiological data from high-income countries were predominant, with sparse data from low-income countries. The epidemiology of GAS disease in Africa and the Pacific region seems to be different from that in other regions, particularly high-income countries. In Africa and the Pacific, there were no dominant emm types, a higher diversity of emm types, and many of the common emm types in other parts of the world were less common (including emm 1, 4, 6, and 12). Our data have implications for the development of GAS vaccines. On the basis of the available data, the current formulation of the experimental multivalent emm vaccine would provide good coverage in high-income countries, particularly USA, Canada, and Europe, but poor coverage in Africa and the Pacific, and only average coverage in Asia and the Middle East.
Pub.: 26 Sep '09, Pinned: 29 Aug '17
Abstract: 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.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 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.
Pub.: 27 Feb '16, Pinned: 29 Aug '17