Browsing by Author "Hawkridge, Anthony"

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    Open Access
    Advances in childhood immunisation in South Africa: where to now? Programme managers' views and evidence from systematic reviews
    (BioMed Central Ltd, 2012) Wiysonge, Charles; Ngcobo, Nthombenhle; Jeena, Prakash; Madhi, Shabir; Schoub, Barry; Hawkridge, Anthony; Shey, Muki; Hussey, Gregory
    BACKGROUND: The Expanded Programme on Immunisation (EPI) is one of the most powerful and cost-effective public health programmes to improve child survival. We assessed challenges and enablers for the programme in South Africa, as we approach the 2015 deadline for the Millennium Development Goals. METHODS: Between September 2009 and September 2010 we requested national and provincial EPI managers in South Africa to identify key challenges facing EPI, and to propose appropriate solutions. We collated their responses and searched for systematic reviews on the effectiveness of the proposed solutions; in the Health Systems Evidence, Cochrane Library, and PubMed electronic databases. We screened the search outputs, selected systematic reviews, extracted data, and assessed the quality of included reviews (using AMSTAR) and the quality of the evidence (using GRADE) in duplicate; resolving disagreements by discussion and consensus. RESULTS: Challenges identified by EPI managers were linked to healthcare workers (insufficient knowledge of vaccines and immunisation), the public (anti-immunisation rumours and reluctance from parents), and health system (insufficient financial and human resources). Strategies proposed by managers to overcome the challenges include training, supervision, and audit and feedback; strengthening advocacy and social mobilisation; and sustainable EPI funding schemes, respectively. The findings from reliable systematic reviews indicate that interactive educational meetings, audit and feedback, and supportive supervision improve healthcare worker performance. Structured and interactive communication tools probably increase parents' understanding of immunisation; and reminders and recall, use of community health workers, conditional cash transfers, and mass media interventions probably increase immunisation coverage. Finally, a national social health insurance scheme is a potential EPI financing mechanism; however, given the absence of high-quality evidence of effects, its implementation should be pilot-tested and the impacts and costs rigorously monitored. CONCLUSION: In line with the Millennium Development Goals, we have to ensure that our children's right to health, development and survival is respected, protected and promoted. EPI is central to this vision. We found numerous promising strategies for improving EPI performance in South Africa. However, their implementation would need to be tailored to local circumstances and accompanied by high-quality monitoring and evaluation. The strength of our approach comes from having a strong framework for interventions before looking for systematic reviews. Without a framework, we would have been driven by what reviews have been done and what is easily researchable; rather than the values and preferences of key immunisation stakeholders.
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    Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants
    (Public Library of Science, 2011) Randhawa, April Kaur; Shey, Muki S; Keyser, Alana; Peixoto, Blas; Wells, Richard D; de Kock, Marwou; Lerumo, Lesedi; Hughes, Jane; Hussey, Gregory; Hawkridge, Anthony; Kaplan, Gilla; Hanekom, Willem A; Hawn, Thomas R
    The development of effective immunoprophylaxis against tuberculosis (TB) remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG) vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR) variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S) was associated with increased BCG-induced IFN-γ in both discovery (n = 240) and validation (n = 240) cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S) and TLR6_G1083C (synonymous) were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2). After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the development of adaptive immune responses after in vivo vaccination against a bacterial pathogen in humans. These findings could potentially guide novel adjuvant vaccine strategies as well as have implications for IFN-γ-based diagnostic testing for TB.
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    Can health workers capture data using a generic mobile phone with sufficient accuracy for Capture at Source to be used for clinical research purposes?
    (2014) Workman, Michael; Marsden, Gary; Hawkridge, Anthony
    Objective: To determine the accuracy, measured by error rate, with which Clinical Research Workers (CRWs), with minimal experience in data entry, could capture data on a feature phone during an interview using two different mobile phone applications, compared to the accuracy with which they could record data on paper Case Report Forms (CRFs). Design: A comparative study was performed where 10 participating CRWs performed 90 mock interviews using either paper CRFs or one of two mobile phone applications. The phone applications were a commonly used open source application and an application custom built for this study that followed a simplified, less flexible user interface paradigm. The answers to the interview questions were randomly generated and provided to the interviewees in sealed envelopes prior to the scheduling of the mock interview. Error rates of the captured data were calculated relative to the randomly generated expected answers. Results and Conclusion: The study aimed to show that error rates of clinical research data captured using a mobile phone application would not be inferior to data recorded on paper CRFs. For the custom application, this desired result was not found unequivocally. An error in judgment when designing the custom phone application resulted in dates being captured in a manner unfamiliar to the study participants, leading to high error rates for this type of data. If this error is condoned by excluding the date type from the results for the custom application, the custom application is shown to be non-inferior, at the 95 confidence level, to standard paper forms when capturing data for clinical research.
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    Childhood mortality in the Boland Overberg region
    (2007) Moyo, Sizulu; Mahomed, Hassan; Groenewald, Pam; Hawkridge, Anthony
    The aim of this thesis is to characterise the profile of infant, childhood and adolescent mortality in three adjancent district municipalities in the Boland region of the Western Cape Province of South Africa.
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    A quantitative evaluation of the quality of informed consent in a developing country setting
    (2005) Minnies, Deon; Ehrlich, Rodney; Hawkridge, Anthony
    Informed consent is an ethical and legal requirement for research involving human participants. However, there have been few studies that have evaluated the process, particularly in an African setting. In addition, standardized methods for assessing the quality of informed consent are not available in the literature. The aim of the study was to evaluate the quality of consent in a large tuberculosis vaccine immunology study and to identify factors associated with the quality of consent.