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Includes abstract. / Includes bibliographical references. / The Expanded Programme on Immunisation has the potential to substantially reduce child mortality and contribute to achieving the Millennium Development Goals. We assessed the programme’s performance in Africa, the reasons for poor performance, and effective interventions for improving its performance on the continent. We used a combination of methods including systematic reviews, bibliometric analyses, generalised linear models, and grading of the quality of evidence. We found that African countries have made extraordinary advances since childhood immunisation programmes began in 1974. However, there exist wide inter-country and intra-country differences, and the quality of immunisation data is poor. Besides, vaccines are administered well after the recommended ages in many countries; leaving children exposed to deadly vaccine-preventable diseases for long periods. In addition, Africa’s contribution to the global immunisation research output is minimal. There is no association between research productivity and immunisation coverage in Africa, which may signal lack of interactive communication between policymakers and researchers. Furthermore, individual and contextual factors (defined at community and country levels) are independently associated with low immunisation coverage; suggesting that immunisation system strengthening should address people and the communities and societies in which they live. Lastly, we found moderate-to-high quality evidence that interactive educational meetings, audit and feedback, supportive supervision; and use of community health workers, parent reminders, home visits, interactive communication, mass media, and material incentives have the potential to improve childhood immunisation coverage in Africa.

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Includes bibliographical references. / The clinical success of cisplatin and its derivatives for the treatment of different cancers has had a profound effect on the use of metal-containing agents in medicine. Despite the successes, the drawbacks of platinum-based therapy, such as drug resistance, toxicity and the emergence of unwanted side effects, have bred a need for effective and novel anticancer agents. Hence, the design and study of bioorganometallic complexes as potential therapeutic agents may eventually lead to the identification of new drug candidates. The purpose of this study was to synthesize and characterize a series of polynuclear transition-metal-containing complexes based on a (poly)propyleneimine dendritic scaffold, and investigate the in vitro antiproliferative activity of these complexes.

Includes abstract. / Includes bibliographical references. / The aim of this study was to evaluate the importance of CD28 in initiating protective Th2 immunity against both primary and secondary infections with N. brasiliensis. Our findings demonstrate that CD28 is required for initiation of protective Th2 immunity against primary infection with N. brasiliensis. Furthermore, the absence of CD28 impairs development of memory CD4⁺ T cell responses resulting in failure to clear adult N. brasiliensis worms during secondary infection. Failure to resolve infection was associated with reduced production of Th2 cytokines particularly IL-13 and IL-4, abrogated humoral immunity and failure to expand CXCR5⁺ TFH cells.

A body's axial temperature distribution at death was experimentally demonstrated by the author to predict the postmortem temperature plateau (PMTP), which is known to affect the measured core temperature value and hence death-time estimation. Yet today's methods of death-time estimation apply only a single-point approximation of a body's core temperature in life as well as a single-point measurement of a body's core temperature after death. Four studies were carried out to understand the relationship between a body's axial temperature distribution and the PMTP. The first study numerically approximated antemortem temperature distribution in an MRI-built, high-definition, anatomicallys egmented 3D computational human phantom consisting of several hundred tissues. Metabolic heat generation (QQmm) and blood perfusion (wwbb) parameters were applied to all thermogenic tissue using the Pennes BioHeat Model. The study demonstrated that the antemortem axial temperature distribution was nonlinear, that tissue temperature distribution was inhomogeneous, and that the position and size of the antemortem central isotherm was predicted by the size, shape and location of the most thermogenic internal organ in a given axial plane. Numerical approximation of a body’s antemortem axial temperature distribution using this study’s materials and methods was proposed for death-time estimation. The second study examined postmortem axial heat transfer. The approximated antemortem axial temperature distribution constituted the initial condition. QQmm and wwbb were set to zero to simulate death. Postmortem cooling was simulated in still air, on a cold concrete floor and on a heated floor. The antemortem central isotherm that single-point core thermometry detects was the PMTP. Its size at death, body radius, axial thermometry-depth and length of the postmortem interval (PMI) all predicted PMTP length. The cold concrete floor shifted the central isotherm away from the floor, while the heated floor shifted it towards the floor. Ground temperature and material properties, along with the aforementioned PMTP predictors, result in variation in measured single-point core thermometry values, yet today’s death-time estimation methods do not measure, approximate or standardise them. This is a source of uncertainty. This study demonstrated that a body’s postmortem axial thermal profile was very specific to the PMI at which it exists, including during the PMTP that single-point core thermometry detects. This study proposed a body’s measured postmortem axial thermal profile for death-time estimation to reduce PMTP uncertainties. The study also proposed numerical modelling of the ground, its temperature and material properties. The third study proposed a multipoint axial thermometry (MAT) device to measure a body’s postmortem axial thermal profile. The author designed the device prototype. Its fabrication was outsourced. Empiric and numerical MAT studies were conducted on a cooling dummy and 3D human phantom, respectively. MAT curves indicated a parabolic shape. The fourth study proposed a numerical protocol for death-time estimation that iteratively tested a MAT profile measured at an unknown PMI from a decedent using the proposed MAT device against MAT profiles predicted by numerical simulations of sequentially longer candidate PMIs. A candidate PMI whose MAT profile matched was considered the PMI estimated by the protocol. The proposed protocol applied the exact historical meteorological temperatures that existed during the final estimated PMI. Application of the protocol was demonstrated using a fictitious scenario in which a candidate PMI within 120s of the final estimated PMI was excluded. Potential sources of uncertainty of the proposed protocol were discussed and concluding remarks on future research were made.

Background: Language discordance, a challenge of miscommunication between health professionals and service users, is a concern for occupational therapy, a profession that foregrounds a client-centred partnership. Occupational therapy literature highlights language discordance as one of the biggest challenges encountered when working in the rural public health sector. Language discordance affects the quality of health services which results in misdiagnosis, informed consent violations, decreased service user satisfaction and safety risks, among others. Occupational therapy is not immune to these negative consequences. In a country as linguistically diverse as South Africa, the need to find effective ways to navigate language discordance in occupational therapy health care, is crucial. However, there is limited literature on language discordance and the strategies used to resolve the issue. Aim: The aim of this study was to describe strategies that occupational therapists working in the public health sector in KwaZulu-Natal use to navigate language discordance and to understand the subsequent role that language discordance has on the quality of occupational therapy care. Methodology: The study adopted a qualitative descriptive design using semi-structured interviews with eight participants recruited using purposive and snowball sampling. Thematic analysis was used to analyse data. Findings: Four themes emerged, namely; using various communication strategies concurrently, language definitely impacts that therapy process, factors perpetuating language discordance and I'm doing everything that I can, what more can I do? Conclusion: The impact of language discordance on the quality of occupational therapy care is undeniable. However, the participants showed agency in navigating language discordance using personal and institutional resources amidst the complexities of applying various strategies concurrently in order to provide the best care that they could.

Comparative genomic analyses have identified an altered capacity for cobalamin biosynthesis as a critical step in the evolution of the pathogenic Mycobacterium tuberculosis Complex strains from a common environmental ancestor. However, resolving the full gene complement involved in the complex, multi-step pathway for de novo cobalamin biosynthesis, assimilation, and salvage in different mycobacterial species is challenging. A genome-scale approach was adopted to yield detailed genetic maps of de novo cobalamin biosynthesis in M. smegmatis, a non-pathogenic saprophyte. To this end, a combination of whole-genome transposon (Tn) mutagenesis and next generation sequencing (TnSeq) was applied in M. smegmatis ΔmetE, a gene-deletion mutant in which the cobalamin-independent methionine synthase is inactivated, rendering the cobalamin-dependent isoform, MetH, essential for viability. Following growth of the metE mutant in rich medium, genomic DNA was extracted, amplified by PCR, and subjected to high-throughput sequencing to quantify all Tn junctions. Thereafter, the library was cultivated in defined minimal medium to enable identification of all conditionally essential genes – including those required for de novo cobalamin biosynthesis. A ∆metE library comprising 400,000 individual Tn insertion mutants (cfu/ml) was generated. Of the predicted 6,716 genes in the M. smegmatis genome, 213 genes were identified as essential for growth on rich agar while 356, 301, and 337 genes were identified as essential in unsupplemented, cyanocobalamin (CNCbl; vitamin B12)-supplemented and cobalt-supplemented Sauton's minimal medium, respectively. A total of 424 genes were identified as essential across all conditions tested with only 10, 13 and 24 genes (ES plus GD) uniquely required for growth in unsupplemented, CNCbl-supplemented and cobalt supplemented Sauton's minimal medium, respectively. On average, predicted cobalamin pathway genes were underrepresented in number of Tn insertions and read counts, indicating the likely essentiality of these genes during growth of the metE mutant in minimal medium. Notably, elucidation of cobalamin biosynthetic and assimilatory genes required the analysis of libraries exposed to CNCbl-unsupplemented minimal media for extended durations, probably reflecting the need to exhaust the organism's capacity for co-factor storage and recycling. Utilizing targeted silencing of individual genes by CRISPR interference, candidate cobalamin biosynthesis genes were validated, providing functional evidence of their essentiality for metE survival in minimal medium, in turn supporting the validity of the cobalamin biosynthetic pathway constructed from the TnSeq results. In addition, the results add further evidence in support of the functionality of the cobalamin riboswitch upstream of metE. This is an important observation as it suggests the potential to apply an analogous approach in M. tuberculosis, a major human pathogen whose ability to synthesize cobalamins remains unresolved. Moreover, elucidating the genetic requirements for optimal growth under specific conditions can inform our basic understanding of mycobacterial physiology and pathogenicity, identifying potential vulnerabilities for novel anti-tuberculosis therapeutics.