Browsing by Author "Butters, Claire"

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    The clinical features and estimated incidence of MIS-C in Cape Town, South Africa
    (2022-05-02) Butters, Claire; Abraham, Deepthi R; Stander, Raphaella; Facey-Thomas, Heidi; Abrahams, Debbie; Faleye, Ayodele; Allie, Nazneen; Soni, Khushbu; Rabie, Helena; Scott, Christiaan; Zühlke, Liesl; Webb, Kate
    Background Multisystem inflammatory syndrome is a severe manifestation of SARS-CoV-2 in children. The incidence of MIS-C after infection is poorly understood. There are very few cohorts describing MIS-C in Africa despite MIS-C being more common in Black children worldwide. Methods A cohort of children with MIS-C and healthy children was recruited from May 2020 until May 2021 from the two main paediatric hospitals in Cape Town, South Africa. Clinical and demographic data were collected, and serum was tested for SARS-CoV-2 antibodies. The incidence of MIS-C was calculated using an estimation of population exposure from seroprevalence in the healthy group. Summary data, non-parametric comparisons and logistic regression analyses were performed. Results Sixty eight children with MIS-C were recruited with a median age of 7 years (3.6, 9.9). Ninety seven healthy children were recruited with a 30% seroprevalence. The estimated incidence of MIS-C was 22/100 000 exposures in the city in this time. Black children were over-represented in the MIS-C group (62% vs 37%, p = 0.002). The most common clinical features in MIS-C were fever (100%), tachycardia (98.5%), rash (85.3%), conjunctivitis (77.9%), abdominal pain (60.3%) and hypotension (60.3%). The median haemoglobin, sodium, neutrophil count, white cell count, CRP, ferritin, cardiac (pro-BNP, trop-T) and coagulation markers (D-dimer and fibrinogen) were markedly deranged in MIS-C. Cardiac, pulmonary, central nervous and renal organ systems were involved in 71%, 29.4%, 27.9% and 27.9% respectively. Ninety four percent received intravenous immune globulin, 64.7% received methylprednisolone and 61.7% received both. Forty percent required ICU admission, 38.2% required inotropic support, 38.2% required oxygen therapy, 11.8% required invasive ventilation and 6% required peritoneal dialysis. Older age was an independent predictor for the requirement for ionotropic support (OR = 1.523, CI 1.074, 2.16, p = 0.018). The median hospital stay duration was 7 days with no deaths. Conclusion The lack of reports from Southern Africa does not reflect a lack of cases of MIS-C. MIS-C poses a significant burden to children in the region as long as the pandemic continues. MIS-C disproportionately affects black children. The clinical manifestations and outcomes of MIS-C in this region highlight the need for improved surveillance, reporting and data to inform diagnosis and treatment.
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    Regulation of HPV infection and cervical cancer development following a helminth infection
    (2025) Butters, Claire; Horsnell, William; Schafer Georgia
    Soil-transmi,ed helminth (STH) infec7ons elicit systemic immune responses and have the ability to alter suscep7bility to other infec7ons in sites uncolonized by the STH. Recent work published by our group demonstrated that hookworm infec7on increased pathology in the female genital tract (FGT) following infec7on with the commonly sexually transmi,ed herpes simplex virus (HSV)-2. Although epidemiological studies have linked helminth infec7on with an increased prevalence of the most common sexually transmi,ed infec7on, human papillomavirus (HPV), studies in our lab have demonstrated that exposure to helminth products can decrease HPV pseudovirion uptake in vitro. Persistent infec7ons with high-risk types of HPV can result in cervical cancer, the leading cause of cancer related deaths in women in South Africa. Li,le is known about the associa7on between these two diseases. In this thesis, I inves7gated how HPV pseudovirion (PsV) infec7on can be altered by an STH infec7on both in vitro and in vivo. In vitro experiments demonstrated exposure to soma7c helminth an7gens from Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri decreased HPV PsV infec7on in two cervical cancer cell lines and one primary kera7nocyte cell line (the target cell of HPV). Similarly, exposure to the excretory-secretory (ES) an7gens from H. polygyrus decreased HPV PsV infec7on in two cell lines, and increased HPV PsV infec7on in the other cervical cancer cell line. When the soma7c an7gens were heat inac7vated, the protec7on against HPV PsV infec7on was abrogated, sugges7ng the molecule involved in this protec7on is a heat unstable protein. In contrast, when H. polygyrus ES an7gen was heat inac7vated, the previously observed increase in infec7on was reversed and instead decreased HPV PsV infec7on. Addi7onally, western blot analysis revealed that exposure to N. brasiliensis soma7c an7gen resulted in increased expression of vimen7n, a molecule known to inhibit HPV infec7on. These results were then validated in vivo, through the development of a physiological murine model for HPV infec7on, u7lising a luminescent HPV PsV and in vivo imaging system (IVIS). Following op7misa7on, I found that HPV PsV infec7on was significantly reduced following intravaginal exposure to N. brasiliensis L3 an7gen and at day 9 post-infec7on with N. brasiliensis. This was associated with a significant increase in eosinophil accumula7on in the female genital tract (FGT) and iliac lymph node (iLN), the draining lymph node of the FGT. Coinfected mice demonstrated a popula7on of eosinophils expressing lower levels of Ly6C and higher levels of CD11b, a recruitment marker. When eosinophil recruitment was blocked, the helminth-dependent reduc7on in HPV infec7on is lost, sugges7ng these immune cells may contribute to this observed protec7on. Addi7onally, western blot analysis revealed that N. brasiliensis infec7on increased the expression of an HPV receptor, glypican. These data suggest that coinfec7on with N. brasiliensis has a protec7ve effect against the ini7al infec7on of HPV. Finally, to inves7gate how STH infec7on may influence the development and growth of HPVrelated cervical cancer, I developed a cervical cancer xenograY model using nude mice. Here, my data suggest that engraYed nude mice infected with N. brasiliensis displayed reduced growth of cervical cancer tumours compared to naïve mice, with no change to tumour immune cell infiltrates but rather an increase in tumour cell p53 expression and altered epithelial to mesenchymal transi7on (EMT) marker expression. Together, these findings show that helminth infec7on can protect against distal viral infec7on and suppress the growth and cancer cell behaviour of HPV associated cervical cancer.