Faculty of Health Sciences (ETDs)

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    The usefulness of monocyte fluorescence as a biomarker of Tuberculosis infection at Chris Hani Baragwanath Academic Hospital
    (University of the Witwatersrand, Johannesburg, 2023-11) Moosa, Aamina Yunus; Vaughan, Jenifer; Hodkinson, Katherine
    Introduction: South Africa has the 5th highest burden of Tuberculosis (TB) as well as coinfection with Human immunodeficiency virus (HIV) worldwide. Routine laboratory methods have varying sensitivity and specificity. The Xpert MTB/RIF (GXPU) (Cepheid, Sunnyvale, CA), has lower sensitivity in sputum smear negative cases and poor quality sputum samples. A robust, non-sputum based, inexpensive biomarker of TB would be of value in such cases. Monocytes are the major leucocyte involved in the immune response to TB. The Sysmex haematology analysers (Sysmex, Kobe, Japan) measure monocyte activation via monocyte fluorescence (MO-Y). This study aimed to evaluate the MO-Y and other Sysmex extended differential parameters (EDPs) as biomarkers of TB infection in the local setting. Methods: The MO-Y and EDPs were retrieved from the analyser for 121 adult cases (56 with TB, 65 controls). Further information was obtained from the laboratory information system, including patient demographics and other laboratory results; TB culture, SARS-CoV-2 results, C-reactive protein level, HIV status, bone marrow biopsies and the cycle threshold (CT) values on positive GXPU analysis. The MO-Y, EDPs and full blood count (FBC) values were compared among patients with and without TB (HIV positive and negative). Statistical significance was assessed (P-value of <0.05). Results: The MO-Y did not show utility in identifying patients with TB. A sub-population of patients living with HIV (PLWH) with a CD4 <100 cells/ul showed significantly higher MO-Y levels, due to other opportunistic infections affecting monocytes. Neutrophil surface fluorescence (a marker of neutrophil activation), was significantly higher in PLWH and with concomitant TB infection, possibly due to immune activation, worse illness, or increased bacterial infection. Among the PLWH, those with TB had significantly lower CD4 counts, absolute lymphocyte counts and mean cell volume (MCV) values. The MCV (cut-off value 87 fL) showed the strongest diagnostic utility for discriminating PLWH with and without TB (AUC 0.79). Conclusion: The MO-Y is not a useful biomarker of TB, but is significantly elevated in PLWH with low CD4 counts. The MCV showed adequate discriminatory power for differentiating patients with and without TB, at a cut-off level of 87fL.
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    Patterns of liver injury in HIV-positive patients in the medical admissions ward at Chris Hani Baragwanath Academic Hospital (CHBAH)
    (University of the Witwatersrand, Johannesburg, 2024) Ndwambi, Rudzani Wendy; Ally , Reidwaan; Chopdat, Nazeer
    Background Human immunodeficiency virus (HIV) infection is a major global public health concern, with approximately 37.9 million people living with HIV and acquired immunodeficiency syn- drome (AIDS) as of 2018. There has been an increase in HIV prevalence globally, with the African sub-Saharan region carrying a disproportionate burden, accounting for more than 70% of this burden. In 2018 South Africa had 7.52 million people living with HIV/AIDS (PLWHA), with approximately 115167 AIDS-related illnesses. In PLWHA, liver disease and failure contribute to more significant morbidity, mortality and higher cost of care. Aim And objectives To recognise and categorise the patterns of liver injury in people living with HIV and AIDS (PLWHA). To ascribe an etiology to the pattern of liver injury in PLWHA. Method This was a retrospective cohort, conducted at CHBAH medical admissions ward in Soweto Gauteng province, of patients living with HIV and AIDS with liver injury. All patients admitted to the medical admissions ward were selected and their hospital numbers retrieved from the admission register. Each hospital number was entered into the NHLS labtrack system to retrieve the LFT results. Any patient with abnormal LFT was checked for their HIV status. The two variables (abnormal LFT and HIV test) were matched and confirmed. After ethics approval was obtained, files were recorded and analysed. A data collection sheet was populated with all serological, histological and radio logical investigations documented. Results This study included 208 patients (PLWHA) admitted to the medical admissions ward at CHBAH, with abnormal liver enzymes between January 2019 and March 2020, aged above 18 years. One hundred and five, 50.5% were males with a mean of 43.7 years, and 49.5% (n=103) were females with a mean of 39.9 years. One hundred and forty-three, 81.3% were taking antiretroviral therapy (ART), with the majority, 88.4% (n=107), on the first-line regimen. The most common pattern of liver injury was infiltrative, accounting for 67.8% (n=141), followed by mixed at 22.1% (n=46), hepatocellular at 7.7% (n=16), and lastly was cholestatic with 2.4% (n=5). Irrespective of the pattern of the liver injury, 36.1% (n=75) of the patients had Mycobacterium tuberculosis (MTB) infection, and 22.5% (n=40) of them were on antituberculosis treatment (ATT), 6.3% (n=13) had hepatitis B viral (HBV) infection, 0.5% (n=1 ) had hepatitis C ( HCV) infection, while lymphomas (Hodgkin and non-Hodgkin lymphomas) contributed 1,9%(n=4) and 6,3% (n=13) respectively. Twelve, 5.7% (n=12) had drug induced liver Injury (DILI), and retroviral disease (RVD) cholan giopathy contributed 1.4% (n=3). A significant number of patients, 34.1% (n=71), contributed to at least one-third of patients in the study, wherein the diagnosis was either unknown or not directly related to the liver injury. Those were, Other opportunistic infections accounting for 7.7% (n=16), other diagnoses made up 13% (n=27), and no diagnosis at 13.4% (n=28). Of the infiltrative pattern, 33.13% (n=47) had MTB infection, 5.6% (n=8) had HBV, 0.3% (n=1) had HCV infection, 7.8% (n=11) had non-Hodgkin lymphoma, with Hodgkin lym- phoma, and DILI both accounting for 1,4%(n=2). Only 5.7% (n=12) of PLWHA had liver biopsies done. Conclusion Liver injury is common in PLWHA. The most common pattern of liver injury is an infiltrative pattern, and the most common etiology was MTB infection in this study.
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    Exploring healthcare user perspectives on utilisation of prevention of mother to child transmission (PMTCT) services in a high-mobility context in Johannesburg, South Africa
    (2024) Bisnauth, Melanie Ann
    Included in this thesis are four original papers. The first of four papers explored the impact of the Option B+ Prevention of Mother to Child Transmission (PMTCT) of human immunodeficiency virus (HIV) programme on the work of healthcare professionals and, investigated pregnant women living with HIV (WLWH) experiences with antiretroviral therapy (ART) for life, to gain insights in ways to better manage the programme. The first paper (Chapter 6) explored the views of both healthcare providers and user experiences with ART for life at the time the SA’s National Department of Health (NDoH) adopted World Health Organisation (WHO) 2013 guidelines on ARVs for HIV treatment and prevention in 2015. This included changes to PMTCT through Option B+ (now known as lifelong treatment). In 2015, little was known about the impact of these guidelines on the work of healthcare workers (HCWs) and no research at the time had focused on how these changes have affected adherence for the patients. Semistructured interviews were conducted with participants and revealed that work had become difficult to manage for all HCWs because of the need to strengthen indicators for tracking patients to decrease the PMTCT loss to follow-up (LTFU); there was inconsistency in delivery of counselling and support services and a need for communication across clinical departments of the hospital that both offered PMTCT services and had to provide care to the mothers and; a lack of compassion and understanding was existent amongst service providers. The overburdened healthcare environment had affected the overall views and experiences of pregnant WLWH going on ART for life. All patient participants (n=55) responded that they chose the fixed dose combination (FDC) pill for life to protect the health of the baby and felt ART for life could be stopped after giving birth, unaware of the long-term benefits for the mother. Although SA national women were interviewed at the time, RMMCH had provided PMTCT care to many migrants and their experiences needed to be heard. Further research was needed on how to strengthen the programme for long term scalability and sustainability for highly mobile WLWH to better adapt PMTCT programming within the healthcare system. Observations of the population of women accessing PMTCT at RMMCH indicated that many migrant WLWH were utilising the services and called for further investigation and lead into the next two phases of the research study. In addition, Paper 2 (Chapter 7) and Paper 3 (Chapter 8) data collection occurred during the COVID19 pandemic. Paper 2 (Chapter 7) investigated HCWs and their experiences in the provision of PMTCT services to WLWH, specifically migrants that were utilising services during the SARS-CoV-2 (COVID-19) pandemic in SA, to provide further insights on the programme. The COVID-19 pandemic resulted in SA taking preventative and precautionary measures to control the spread of infection, this inevitably proposed challenges to WLWH, especially migrant women by limiting population mobility with border closures and lockdown restrictions. Semi-structured interviews (n=12) conducted with healthcare iii providers across city, provincial, and national levels explored how COVID-19 impacted the healthcare system and affected highly mobile patients’ adherence and utilisation of PMTCT services. Findings revealed; a need for multi-month dispensing (MMD); fear of contracting COVID-19 leading to the disruption in the continuum of care; added stress to the already existent overburdened clinical environment; mistreatment and xenophobic attitudes towards the migrant HIV population and; three key areas for strengthening PMTCT programme sustainability for migrants. Paper 3 (Chapter 8) investigated the insights of migrant WLWH. Migrant typologies were not predetermined a priori. This research allowed for the different mobility typologies of migrant women utilising PMTCT services in a high mobility context of Johannesburg to first surface from the data. By analysing these experiences, it explored further into how belonging to a specific typology may have affected the health care received and their overall experience during the COVID-19 pandemic. Interviews with cross-border migrants (n=22) (individuals who move from one country to another) and internal migrants (n=18) (individuals who transcend borders within a country) revealed that women in cross-border migration patterns compared to interprovincial/intraregional mobility; expressed more fear to utilise services due to xenophobic attitudes from HCWs; were unable to receive ART interrupting adherence due to border closures and; relied on short message service (SMS) reminders to adhere to ART during the pandemic. All 40 women struggled to understand the importance of adherence due to the lack of infrastructure to properly educate them following social distancing protocols. COVID-19 amplified existing challenges for cross-border migrant women to utilise PMTCT services. Future pandemic preparedness should be addressed with differentiated service delivery (DSD) including MMD of ARVs, virtual educational care, and language sensitive information, responsive to the needs of mobile women and to assist in alleviating the burden on the healthcare system. The pandemics’ impact on the study timeline, key lessons learnt and, take away messages when conducting research during this unpredictable time are provided in Chapter 4 (Methods) and Chapter 9 (Discussion). It is important to include these reflections because of the impact it had on all participants and the entire PhD process. Paper 4 will be a future policy piece, drawn from Chapter 9, addressing the need for responsiveness from the SA government and NDoH. Chapter 9 brought together collectively the previous papers 1,2, and 3 and drew overall conclusions, recommendations, and a way forward for both policy and programme implementation. This chapter provided the principal findings of the overall thesis and in relation to other studies in the field, as well as implication for policy practice and research. Chapter 9 concludes with the recommendations for future research on WLWH, mobility typologies, service provision of PMTCT and future pandemic preparedness, and the vision for the South African PMTCT programme.