Browsing by Author "Kehoe, Kathleen"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Open Access
    Burden and causes of ongoing paediatric infectious disease morbidity and mortality in the Western Cape Province of South Africa
    (2025) Kehoe, Kathleen; Davies, Mary-Ann; Eley Brian
    Under-five mortality has significantly decreased globally over the past 28 years, halving to 39 deaths per 1,000 live births in 2018, yet remains high, necessitating further progress to meet the Sustainable Development Goal of reducing it to below 25 deaths per 1,000 live births by 2030. Improvements in healthcare access, nutrition, vaccinations, and socioeconomic conditions have been key drivers of this observed reduction, but infectious diseases such as lower respiratory tract infections (LRTIs) including pneumonia, diarrhoea, and malaria continue to cause substantial childhood mortality. In South Africa, LRTIs, diarrhoea, meningitis, and tuberculous meningitis (TBM) remain leading causes of childhood morbidity and mortality. The Western Cape continues to bear a substantial burden from these infectious diseases, but the available data is outdated and lacks granularity. Therefore, the aim of this thesis was to explore the morbidity and mortality of LRTIs, diarrhoea, meningitis and TBM among children younger than five years in the public sector in the Western Cape. After a brief background chapter which lays out the key issues and overview of the South African healthcare system, Chapter 2 provides a comprehensive literature review discussing the morbidity and mortality of LRTIs, diarrhoea and meningitis (including TBM where appropriate) in children under five years globally and in South Africa with a focus on the Western Cape. Chapter 3 provides a detailed description of the data management required to develop the de-duplicated dataset that was used for each of the results chapters (Chapter 4-7). Chapter 4 explores causes of death using various death data sources, including routinely collected and detailed audits, and found that routine hospital information systems had accurate causes of death relying on International Classification of Diseases 10th Revision codes, particularly for LRTIs and diarrhoea. Chapters 5 and 6 explore the impact of COVID-19 public health and social measures (PHSM) on LRTI and diarrhoea admissions. COVID-19 surges and their associated measures, including PHSM, were linked to declining LRTI admissions and in- facility deaths, likely driven by a combination of reduced infectious disease transmission and reduced use of healthcare services. Lastly, Chapter 7 identified associations with repeat infectious disease admissions (LRTIs, diarrhoea and meningitis) among children who were first admitted for an infectious disease in the first six months of life. Male children with lower birthweight, whose first admission was due to LRTI or diarrhoea (versus meningitis), experienced a longer length of stay during their initial admission, and were living with HIV were more likely to be re-admitted for an infectious disease. Both individual- and population level interventions are needed to reduce the prevalence and impact of factors associated with infectious disease re-admissions and reduce infectious disease morbidity. This thesis concludes that infectious disease morbidity and mortality persist among children under five years in the Western Cape by presenting up-to-date and comprehensive data. It highlights the need to address existing gaps to improve data quality and comprehensiveness, as well as healthcare and health outcomes for these children.
  • Thumbnail Image
    Item
    Open Access
    Long-term virologic responses to responses to antiretroviral therapy among patients entering adherence clubs in Khayelitsha, Cape Town South Africa
    (2018) Kehoe, Kathleen; Cornell, Morna
    Introduction: In 2017, approximately 36.9 million people were living with HIV and 58.1% were accessing antiretroviral therapy (ART) worldwide. In South Africa, ART coverage was 48.6% in 2015, and has since increased due to the implementation of universal Test and Treat. Given the need for lifelong care for millions of individuals, differentiated models of care for ART services are required. One such model, adherence clubs (ACs) for stable ART patients, has been successfully scaled-up in the Cape Metro Health District. In this study, we describe long-term virologic outcomes of patients who have ever entered ACs. Methods: Adult patients enrolled in ACs in Khayelitsha between January 2011 and June 2017 were eligible for inclusion. Time to, and risk factors for, an elevated viral load (first viral load >1000 copies/mL) and confirmed virologic failure (two consecutive viral loads >1000 copies/mL two to nine months apart) were estimated using the Kaplan-Meier estimator and Cox proportional hazards models. Viral load completeness was assessed at 4, 16, 28, 40 and 52 months of follow up. Results: Of 11 830 patients, 74% were female and 45% were aged 35-44 years at AC enrolment. The median time on ART at enrolment was 4.7 years (interquartile range (IQR) 2.7-7.1). An elevated viral load was observed in 517 patients (4%), 141 (27%) of whom subsequently experienced confirmed virologic failure. The median time from an elevated viral load to confirmed virologic failure was 137 days (IQR 112-168). Risk of an elevated viral load and confirmed virologic failure was higher among patients with a longer duration on ART and lower among older patients. The proportion of completed viral load tests ranged from 79% at 4 months to 75% at 52 months. Over 90% of patients with viral load assessments remained virologically suppressed (<400 copies/mL). Conclusion: This study demonstrates low rates of confirmed virologic failure among patients who entered ACs. The majority of patients remained stable despite the rapid growth of ACs, supporting the continued expansion of the model, particularly for men. Monitoring was generally consistent, but suboptimal among those who experienced an elevated viral load. Patients referred to ACs, younger patients and those with longer duration of ART should be prioritised to ensure they remain stable on lifelong ART.
  • Thumbnail Image
    Item
    Open Access
    Separation and purification of mucins and tenascin-C in breast milk of patients and the investigation of the role of mucins and tenascin-C in the inhibition of HIV-1
    (2017) Kehoe, Kathleen; Mall, Anwar Suleman
    An estimated 36.7 million people were living with HIV in 2015, with 2.1 million newly infected people with HIV in 2015 worldwide. The highest prevalence of HIV in 2015 was in the Eastern and Southern African regions. This highlights the importance for research in this field to further prevent the number of new HIV cases. Mother-to-child transmission of HIV is due to either cell-associated or cell-free virus present in the breast milk of an HIV positive mother. Most often, HIV positive mothers choose to breastfeed their infants due to the nutritional and immunological benefits outweighing that of the risk of HIV transmission. Importantly, approximately 85% of infants do not acquire HIV through daily exposure to breast milk from their HIV positive mothers who are not on ART suggesting that human breast milk has antiviral properties. Previously in our laboratory, MUC1 and MUC4 has been implicated in the inhibition of HIV-1 in an in vitro assay. Furthermore, crude breast milk was tested in this assay showing strong HIV-1 neutralisation. Pasteurisation (80°C for 10 minutes) of both HIV positive and negative breast milk indicated good neutralisation of HIV-1 in our laboratory. Another breast milk protein, tenascin-C (TNC), was recently shown to strongly neutralise HIV-1 in a study performed by another group. Therefore, with this knowledge, this study was employed to firstly compare the antiviral properties of MUC1, MUC4 and TNC. Furthermore, the HIV-1 neutralisation ability of crude breast milk was sought to be investigated along with the investigation of two different pasteurisation methods including 80°C for 10 minutes and 62.5°C for 30 minutes (Holder pasteurisation). Human breast milk was separated into milk fat and skim milk using caesium chloride density gradient ultracentrifugation. MUC1 was purified from the milk fat using gel extraction from a 4-20% sodium dodecyl sulphate polyacrylamide gel. The skim milk was chromatographed on a Sepharose 2B-CL column from which the void volume was collected to purify TNC using gel extraction from a 4-20% sodium dodecyl sulphate polyacrylamide gel. During this purification, a band consisting of MUC1 which adhered to TNC was used to co-purify the MUC1/TNC glycoprotein using gel extraction. MUC1 and TNC were individually purified using gel extraction. MUC4 was not successfully purified and from ELISA data it was concluded that the concentration of MUC4 was below the detectable limit of the ELISA kit. The average concentration of MUC1 was determined to be 307.85 ng/ml, while the concentration of TNC could not be determined due to the majority of absorbance values (450 nm) lying above the upper limit of the curve. The HIV neutralisation of each of the samples was tested in an in vitro HIV-1 assay. This assay utilises a luciferase reporter gene in modified TZM-bl/JC cells using Du422.1 virus derived from clad C of HIV-1. These assays are being performed to assess the antiviral properties of crude and heat treated breast milk and purified MUC1 and TNC separately as well as co-eluted and co-purified MUC1/TNC. The two pasteurisation methods increased the HIV-1 neutralisation when compared to crude breast milk. The HIV-1 neutralisation of these groups were compared with a Kruskal Wallis test and a statistically significant difference was detected among the crude and 62.5°C heat treated breast milk cohorts (Mann-Whitney U, p-value = 0.0021). Furthermore, a statistically significant difference in the HIV-1 neutralization was detected among the 80°C and 62.5°C heat treated breast milk cohorts (Mann-Whitney, p-value = 0.0033). From the data, and the range of IC₅₀ values (50% inhibitory concentration), the HIV-1 potency was deemed the strongest in the 62.5°C heat treated breast milk. This pasteurisation method could potentially be promoted in lower resource settings to decrease mother-to-child transmission of HIV-1. Purified MUC1 and TNC, as well as co-eluted and co-purified MUC1/TNC, was tested in the same neutralization assay in order to compare the HIV-1 potency of these glycoproteins. The difference in HIV-1 neutralisation was not statistically significant among all three groups (Kruskal Wallis, p-value = 0.13). From the range of IC₅₀ values, it was suggested that TNC has a stronger HIV-1 potency when compared to MUC1. Overall, the co-eluted and co-purified MUC1/TNC showed a lower HIV-1 potency when compared to the single, purified glycoprotein. MUC1 and TNC could be purified and cloned to aid in the protection against contracting HIV-1, especially in mother-to-child transmission of HIV-1. Histochemistry and immunohistochemistry was performed on breast tissue sections to investigate the morphology of the cells and the presence of MUC1, MUC4 and TNC respectively. The lactating breast tissue was confirmed to have wide, dilated lumina and vacuolated cytoplasm with neutral and sialomucins. The presence of MUC1, MUC4 (β subunit) and TNC were confirmed in the lactating breast tissue using immunohistochemistry.