Antibody and T-cell responses in rotavirus vaccinated Zambian infants: impact of human cytomegalovirus infection

Oral rotavirus vaccines (ORV) demonstrate lower seroconversion rates in low-income compared to high-income settings, a phenomenon that is not fully understood. There is also limited knowledge on the T-cell immune responses in vaccinated infants creating a gap in understanding rotavirus immunology. I used plasma and peripheral blood mononuclear cells collected from infants under a rotavirus vaccine trial in Zambia to measure the rotavirus specific immunoglobulin IgA (RV-IgA) antibody responses comparing two and three doses of an ORV (Rotarix) and the T cell responses associated with vaccination. I also investigated the influence of human cytomegalovirus immunoglobulin M (HCMV-IgM) seropositivity on vaccine immunogenicity. To contribute to coronavirus research, post the COVID-19 pandemic, I explored antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common cold coronaviruses among this mother-infant rotavirus trial study cohort. A low seroconversion rate of 27.8% was observed one month after two dose ORV administration and there was no significant boosting of RV-IgA three months after a third ORV dose administered at 9 months (p=0.223). HCMV-IgM seropositivity did not affect RV-IgA responses among overall infants but significantly reduced RV-IgA responses by 63% in HIVexposed-uninfected infants (p=0.008). Limited and very low frequency rotavirus VP6-specific T-cell responses were detected in vaccinated infants but enriched rotavirus VP6-specific CD4+ T-cell responses were observed among vaccine seroconverters. Overall, the thesis provided evidence that a booster ORV dose at 9 months did not improve vaccine immunogenicity by 12 months suggesting alternate rotavirus vaccine strategies or formulations may be necessary to improve vaccine immunogenicity in Zambia, and that HCMV-IgM seropositive HIV-exposed-uninfected infants were sub-populations vulnerable to reduced rotavirus immunity. The limited rotavirus-specific T-cell responses suggested that infants mount short-lived memory T-cell responses to ORV but also showed evidence of VP6-targeted CD4 T-cell dependent antibody response to rotavirus vaccination

Measuring the health impact of human rights violations related to Australian asylum policies and practices: A mixed methods study

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Johnston et al.BACKGROUND: Human rights violations have adverse consequences for health. However, to date, there remains little empirical evidence documenting this association, beyond the obvious physical and psychological effects of torture. The primary aim of this study was to investigate whether Australian asylum policies and practices, which arguably violate human rights, are associated with adverse health outcomes. METHODS: We designed a mixed methods study to address the study aim. A cross-sectional survey was conducted with 71 Iraqi Temporary Protection Visa (TPV) refugees and 60 Iraqi Permanent Humanitarian Visa (PHV) refugees, residing in Melbourne, Australia. Prior to a recent policy amendment, TPV refugees were only given temporary residency status and had restricted access to a range of government funded benefits and services that permanent refugees are automatically entitled to. The quantitative results were triangulated with semi-structured interviews with TPV refugees and service providers. The main outcome measures were self-reported physical and psychological health. Standardised self-report instruments, validated in an Arabic population, were used to measure health and wellbeing outcomes. RESULTS: Forty-six percent of TPV refugees compared with 25% of PHV refugees reported symptoms consistent with a diagnosis of clinical depression (p = 0.003). After controlling for the effects of age, gender and marital status, TPV status made a statistically significant contribution to psychological distress (B = 0.5, 95% CI 0.3 to 0.71, p </= 0.001) amongst Iraqi refugees. Qualitative data revealed that TPV refugees generally felt socially isolated and lacking in control over their life circumstances, because of their experiences in detention and on a temporary visa. This sense of powerlessness and, for some, an implicit awareness they were being denied basic human rights, culminated in a strong sense of injustice. CONCLUSION: Government asylum policies and practices violating human rights norms are associated with demonstrable psychological health impacts. This link between policy, rights violations and health outcomes offers a framework for addressing the impact of socio-political structures on health.This research was supported by an Australian National and Medical Research Council PhD Scholarship (N. 251782) and a Victorian Health Promotion Foundation research grant (No. 2002-0280)

The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care