Browsing by Author "Jacobs, Ashley"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Open Access
    Early report on tuberculosis and fungal infections in lung transplant recipients from an African Centre
    (2026) Jacobs, Ashley; Calligaro, Gregory
    Background: Lung transplantation (LT) is an established therapy for patients with end-stage lung disease. However, infections remain a leading cause of morbidity and mortality post- transplant. This is the first report of LT related infections from an African setting, where the burden of pathogens such as tuberculosis (TB) and endemic fungi may differ from global trends and thus pose a unique challenge to successful transplantation. Objectives: To describe the incidence, timing, and microbiology of endemic infections such as TB and fungi in lung transplant recipients (LTRs) at Groote Schuur Hospital (GSH), Cape Town, South Africa. Methods: We conducted a retrospective cohort study of all LTRs from 2018 to 2024. Microbiological data from blood and bronchoalveolar lavage (BAL) samples were reviewed. Organisms were categorized by donor or recipient status, site, and time from transplantation. All LT recipients received isoniazid (INH) preventive therapy (IPT) to prevent TB. Results: Among 44 patients (median age 48 years, 46.7% male), one-year survival was 65.8%. Despite high regional TB incidence, no cases of post-transplant TB were detected. Donor-derived TB occurred in 1 case, 1 case of TB was diagnosed on histology of explant lungs, and 4 patients developed transient nucleic acid amplification test positivity in the absence of clinical disease. Fungal infections occurred in 11% of patients, with non-albicans Candida identified in 2 out of 3 cases of candidaemia. Non-fumigatus Aspergillus species were not uncommon and accounted for ~1/3 of cases. CMV pneumonitis occurred in 1 patient (2.3%). Conclusions: This is the first early report of post-LT endemic infections from South Africa. Although we anticipated a significant burden of TB, IPT and intensive surveillance appears to mitigate the risk of immunosuppression. A wide variety of fungal pathogens were identified which raises further questions regarding the diversity of fungi and antifungal prophylaxis in this region.
  • No Thumbnail Available
    Item
    Open Access
    The role of antibodies in tuberculosis
    (2024) Jacobs, Ashley; Wilkinson, Robert
    The role of antibodies in tuberculosis (TB) has been debated for over a century. Antibodies against Mycobacterium tuberculosis (M.tb) are detectable in persons who appear to resist M.tb infection, and yet humoral immune activation is a consistent biomarker of TB disease progression. Antibody responses to TB could therefore be a dual-edged sword, whereby antibodies promote TB pathogenesis, but some people produce antibodies that contribute to immunity against M.tb. In this thesis, I have therefore investigated the role of antibodies in TB in multiple clinical cohorts. Firstly, I generated fully human monoclonal antibodies (mAbs) against M.tb from patients with ATB. I identify the antigen of one mAb as the secreted antigen GlnA1, and then show that this mAb promotes in vitro production of TNF-α, IL-6, and IL-1β in the absence of mycobacterial killing. Secondly, I investigated antibody responses against M.tb in persons who live with HIV (PLWH). PLWH fail to mount a significant increase in IgG levels against M.tb in ATB. M.tb-specific IgG responses are also detectable in different cohorts of PLWH with negative interferon gamma release assay (IGRA) tests. However, greater levels of M.tb-specific IgG associates with IGRA conversion. Thirdly, I showed the development of flow cytometric assays to study opsonization and antibody dependant cellular phagocytosis (ADCP) of live mycobacteria in BCG vaccinated adults. These methods show that BCG vaccination induces ADCP 28 days post-vaccination. Fourthly, I tested whether unswitched memory B cells, and specifically the marginal zone B cells (MZB) subset, are impacted by ATB. MZB respond to capsular pathogens and could thus recognize the M.tb cell wall. MZB are found to be depleted in ATB but are not enriched at the site of disease in PLWH with pericardial TB. The depletion of unswitched memory B cells in TB observed in this study resembles that reported in autoimmune disease. Taken together, I provide support to the notion that at least some antibodies against M.tb could contribute to immunopathology in TB. The fact that PLWH are at greater risk of disseminated TB, and mount less of an antibody response, however, supports a role for antibodies in preventing disseminated disease that remains to be studied.