An exploration of the concerns and motivations of community caregivers working with children in adversity.

Thesis (M.Soc.Sci.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.The deadly HIV/AIDS pandemic is one of the major developmental challenges facing our nation. Community caregivers (CCGs) play a significant role in addressing the psychosocial needs of orphan and vulnerable children (OVC); however, little attention has been paid to the work and experiences of CCGs. In an endeavour to increase our understanding of their lived experiences, this research qualitatively explored the concerns and motivations experienced by CCGs who work on a daily basis with children in circumstances of extreme adversity, specifically those affected by HIV/AIDS in South Africa. This study draws on the ecological theory of Bronfrenbrenner (1979) to provide a conceptual framework in which to consider the working circumstances of CCGs. Methodologically, focus group discussions were used as the primary source of data collection. Focus groups were conducted with CCGs from three different non-governmental organisations (NGOs) who provide psychosocial support to children affected by HIV/AIDS. The research found that CCGs are passionate about providing holistic care to the children, families and communities in which they work and they experience a variety of concerns about the way in which services are provided and how funding agendas drive the nature of the work and the manner of monitoring and evaluation. They also experience joy and satisfaction in what they do. Limitations and suggestions for future studies are noted, with the aim being for NGOs to acknowledge the concerns and motives and to develop and implement programmes to support staff, and maintain the resilience needed for CCGs to be even more effective in contributing towards providing meaningful services in the difficult circumstance in which they work

A roadmap to develop dementia research capacity and capability in Pakistan: a model for low- and middle-income countries

Objective To produce a strategic roadmap for supporting the development of dementia research in Pakistan. Background While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan. Methods We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a “research question” priority survey, and consultations with Key Opinion Leaders. Results We agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life. Conclusion This roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures

Elevated IP-10 at the Protein and Gene Level Associates With Pulmonary TB

There is an urgent need for accurate and sensitive diagnostic tools that can overcome the current challenge to distinguish individuals with latent tuberculosis infection (LTBI) from individuals with active tuberculosis (TB). Recent literature has suggested that a group of cytokines may serve as biomarkers of TB disease progression. Using a multiplex ELISA, we quantified 27 circulatory markers present within the unstimulated plasma of individuals in Durban, South Africa who were healthy (n=20), LTBI (n=13), or had active TB (n=30). RT-qPCR was performed to measure gene expression of the cytokines of interest, using RNA isolated from healthy (n=20), LTBI (n=20), or active TB (n=30). We found that at the protein level, IL-1RA, IL-6, and IP-10 were significantly more abundant in participants with active TB (p< 0.05) compared to those with LTBI individuals. IP-10 also showed the strongest association with active TB compared to healthy and LTBI at mRNA level. Our data shows that these proteins may serve as biomarkers of TB at both the protein and gene level

Similar Antibody Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 in Individuals Living Without and With Human Immunodeficiency Virus on Antiretroviral Therapy During the First South African Infection Wave

BACKGROUND: There is limited understanding of SARS-CoV-2 pathogenesis in African populations with a high burden of infectious disease comorbidities such as HIV. The kinetics, magnitude and duration of virus-specific antibodies and the underlying B cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized. METHODS: We longitudinally followed SARS-CoV-2 infected individuals in Durban, KwaZulu-Natal, South Africa and characterized SARS-CoV-2 receptor binding domain-specific IgM, IgG and IgA antibodies weekly for a month, and then at 3 months post diagnosis. 7/30 (41.7%) were PLWH, 83% (25/30) of which were on ART and with full HIV suppression. Potency of convalescent plasma neutralization was determined using a live virus neutralization assay and antibody secreting cell population frequencies were determined by flow cytometry. RESULTS: Similar seroconversion rates, time to peak antibody titer, peak magnitude and durability of anti-SARS-CoV-2 IgM, IgG, IgA, were observed in HIV uninfected and PLWH with complete HIV suppression on ART. In addition, similar neutralization potency against an isolate of SARS-CoV-2, circulating at the time of sampling in the first wave of SARS-CoV-2 infections in South Africa was observed in both groups. Loss of IgA was significantly associated with age (p=0.023) and a previous diagnosis of TB (p=0.018). CONCLUSIONS: Similar antibody response kinetics and neutralization potency in HIV negative and PLWH on stable ART in an African setting suggests that COVID-19 natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART

Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses

Introduction: The rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both acute infection and over a longer term, potentially driven by aspects of the immune response. Identifying patients likely to have persistent hyperglycemia following TB treatment would enable closer monitoring and care, and an improved understanding of underlying immunometabolic dysregulation. // Methods: We measured the relationship of plasma cytokine levels, T cell phenotypes and functional responses with the change in hemoglobin A1c (HbA1c) before and after treatment of pulmonary TB in a prospective observational cohort in Durban, South Africa. Participants were stratified based on stable/increased HbA1c (n = 16) versus decreased HbA1c (n = 46) levels from treatment initiation to 12 month follow-up. // Results: CD62 P-selectin was up- (1.5-fold) and IL-10 downregulated (0.85-fold) in plasma among individuals whose HbA1c remained stable/increased during TB treatment. This was accompanied by increased pro-inflammatory TB-specific IL-17 production (Th17). In addition, Th1 responses were upregulated in this group, including TNF-α production and CX3CR1 expression, with decreased IL-4 and IL-13 production. Finally, the TNF-α+ IFNγ+ CD8+ T cells were associated with stable/increased HbA1c. These changes were all significantly different in the stable/increased HbA1c relative to the decreased HbA1c group. // Discussion: Overall, these data suggest that patients with stable/increased HbA1c had an increased pro-inflammatory state. Persistent inflammation and elevated T cell activity in individuals with unresolved dysglycemia following TB treatment may indicate failure to fully resolve infection or may promote persistent dysglycemia in these individuals, and further studies are needed to explore potential mechanisms

Effects of a reduced dose of Stavudine on the incidence and severity of peripheral neuropathy in HIV-infected adults in South Africa.

BACKGROUND—Although recent WHO guidelines recommend withdrawing stavudine (d4T) from first-line ART therapy, it remains commonly used in resource-constrained settings. In 2006, WHO recommended decreasing the dose of d4T from 40mg to 30mg to mitigate toxicities. We compared the incidence and severity of peripheral neuropathy (PN) by d4T dose in a retrospective cohort study. METHODS—Patients’ charts from an ART-naïve population at a rural clinic in KZN, South Africa were retrospectively reviewed for signs and symptoms of incident PN and were graded for severity using the DAIDs scale. Patients enrolled prior to the WHO guideline change were enrolled if they were on d4T 40mg for at least 6 months. After the guideline change all patients were initiated on d4T 30mg. RESULTS—A total of 475 patients were analyzed; 235 in the 40mg cohort (152.7 person-years [py]) and 240 in the 30mg cohort (244.7py). Incidence of peripheral neuropathy was 90.4/100 py (95% CI:75.9–106.8) in the 40mg cohort versus 40.5/100py (95% CI:32.9–49.3) in the 30mg group (incidence rate ratio [IRR]=0.45, p<0.0001). There was no difference in proportion of severe peripheral neuropathy cases (grade 3/4) between the cohorts; 8.3% in the 40mg group and 8.9% in the 30mg group (p=1.0). In a multivariate analysis risk of peripheral neuropathy was associated with increasing age (HR=1.65 95% CI:1.24–2.19), 40 mg dose (HR=2.1, 95% CI:1.61–2.74) and concurrent tuberculosis therapy (HR= 1.41 95% CI:1.06–1.87). CONCLUSION—Incidence of peripheral neuropathy in the 40mg cohort was extremely high and though lower in the 30mg cohort, the rate was nonetheless unacceptably high

Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Ad26.CoV2.S Vaccination in People Living With Human Immunodeficiency Virus (HIV)

BACKGROUND: People living with HIV (PLWH) have been reported to have a higher risk of more severe Covid-19 disease and death. We assessed the ability of the Ad26.CoV2.S vaccine to elicit neutralizing activity against the Delta variant in PLWH relative to HIV-negative individuals. We also examined effects of HIV status and suppression on Delta neutralization response in SARS-CoV-2 infected unvaccinated participants. METHODS: We enrolled participants who vaccinated through the SISONKE South African clinical trial of the Ad26.CoV2.S vaccine in health care workers (HCW). PLWH in this group had well controlled HIV infection. We also enrolled unvaccinated participants previously infected with SARS-CoV-2. Neutralization capacity was assessed by a live virus neutralization assay of the Delta variant. RESULTS: Majority of Ad26.CoV2.S vaccinated HCW were previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared to the infected only group and 26-fold higher relative to the vaccinated only group. No decrease in Delta variant neutralization was observed in PLWH relative to HIV-negative participants. In contrast, SARS-CoV-2 infected, unvaccinated PLWH showed 7-fold lower neutralization and a higher frequency of non-responders, with the highest frequency of non-responders in people with HIV viremia. Vaccinated only participants showed low neutralization capacity. CONCLUSIONS: The neutralization response of the Delta variant following Ad26.CoV2.S vaccination in PLWH with well controlled HIV was not inferior to HIV-negative participants, irrespective of past SARS-CoV-2 infection. In SARS-CoV-2 infected and non-vaccinated participants, HIV infection reduced the neutralization response to SARS-CoV-2, with the strongest reduction in HIV viremic individuals

Chapter 15 Matching Brain–Machine Interface Performance to Space Applications

A brain-machine interface (BMI) is a particular class of human-machine interface (HMI). BMIs have so far been studied mostly as a communication means for people who have little or no voluntary control of muscle activity. For able-bodied users, such as astronauts, a BMI would only be practical if conceived as an augmenting interface. A method is presented for pointing out effective combinations of HMIs and applications of robotics and automation to space. Latency and throughput are selected as performance measures for a hybrid bionic system (HBS), that is, the combination of a user, a device, and a HMI. We classify and briefly describe HMIs and space applications and then compare the performance of classes of interfaces with the requirements of classes of applications, both in terms of latency and throughput. Regions of overlap correspond to effective combinations. Devices requiring simpler control, such as a rover, a robotic camera, or environmental controls are suitable to be driven by means of BMI technology. Free flyers and other devices with six degrees of freedom can be controlled, but only at low-interactivity levels. More demanding applications require conventional interfaces, although they could be controlled by BMIs once the same levels of performance as currently recorded in animal experiments are attained. Robotic arms and manipulators could be the next frontier for noninvasive BMIs. Integrating smart controllers in HBSs could improve interactivity and boost the use of BMI technology in space applications. © 2009 Elsevier Inc. All rights reserved

Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy

Innate lymphoid cells (ILCs) are important for response to infection and for immune development in early life. HIV infection in adults depletes circulating ILCs, but the impact on children infected from birth remains unknown. We study vertically HIV-infected children from birth to adulthood and find severe and persistent depletion of all circulating ILCs that, unlike CD4+ T cells, are not restored by long-term antiretroviral therapy unless initiated at birth. Remaining ILCs upregulate genes associated with cellular activation and metabolic perturbation. Unlike HIV-infected adults, ILCs are also profoundly depleted in tonsils of vertically infected children. Transcriptional profiling of remaining ILCs reveals ongoing cell-type-specific activity despite antiretroviral therapy. Collectively, these data suggest an important and ongoing role for ILCs in lymphoid tissue of HIV-infected children from birth, where persistent depletion and sustained transcriptional activity are likely to have long-term immune consequences that merit further investigation