Rapid identification of bovine MHCI haplotypes in genetically divergent cattle populations Using Next-Generation Sequencing

The major histocompatibility complex (MHC) region contains many genes that are key regulators of both innate and adaptive immunity including the polymorphic MHCI and MHCII genes. Consequently, the characterisation of the repertoire of MHC genes is critical to understanding the variation that determines the nature of immune responses. Our current knowledge of the bovine MHCI repertoire is limited with only the Holstein-Friesian breed having been studied in any depth. Traditional methods of MHCI genotyping are of low resolution and laborious and this has been a major impediment to a more comprehensive analysis of the MHCI repertoire of other cattle breeds. Next-generation sequencing (NGS) technologies have been used to enable high throughput and much higher resolution MHCI typing in a number of species. In this study we have developed a MiSeq platform approach and requisite bioinformatics pipeline to facilitate typing of bovine MHCI repertoires. The method was validated initially on a cohort of Holstein-Friesian animals and then demonstrated to enable characterisation of MHCI repertoires in African cattle breeds, for which there was limited or no available data. During the course of these studies we identified >140 novel classical MHCI genes and defined 62 novel MHCI haplotypes, dramatically expanding the known bovine MHCI repertoire

Understanding the barriers and facilitators of COVID-19 risk mitigation strategy adoption and COVID-19 vaccination in refugee settlements in Uganda: a qualitative study

Abstract Background Perspectives on COVID-19 risk and the willingness and ability of persons living in refugee settlements to adopt COVID-19 prevention strategies have not been rigorously evaluated. The realities of living conditions in Ugandan refugee settlements may limit the extent to which refugees can uptake strategies to mitigate COVID-19 risk. Methods In-depth qualitative interviews were conducted between April 2021 and April 2022 to assess COVID-19 knowledge, risk perception, prevention strategy adoption including COVID-19 vaccination, and COVID-19 impact on living conditions in refugee settlements in Uganda. Interview participants included 28 purposively selected refugees who called into “Dial-COVID”, a free telephone COVID-19 information collection and dissemination platform that was advertised in refugee settlements by community health workers. Interviews were analyzed using a combination of deductive and inductive content analysis. Emerging themes were mapped onto the Theoretical Domains Framework to identify domains influencing prevention behavior. Results were synthesized to provide intervention and policy recommendations for risk mitigation in refugee settlements for COVID-19 and future infectious disease outbreaks. Results The COVID-19 pandemic detrimentally impacted economic and food security as well as social interactions in refugee settlements. Youth were considered especially impacted, and participants reported incidents of child marriage and teenage pregnancy following school closures. Participants displayed general knowledge of COVID-19 and expressed willingness to protect themselves and others from contracting COVID-19. Risk mitigation strategy uptake including COVID-19 vaccination was influenced by COVID-19 knowledge, emotions surrounding COVID-19, the environmental context and resources, personal goals, beliefs about the consequences of (non)adoption, social influences, and behavior reinforcement. Resource constraints, housing conditions, and competing survival needs challenged the adoption of prevention strategies and compliance decreased over time. Conclusions Contextual challenges impact the feasibility of COVID-19 risk mitigation strategy uptake in refugee settlements. Pre-existing hardships in this setting were amplified by the COVID-19 pandemic and related lockdowns. Targeted dispelling of myths, alignment of information across communication mediums, supporting survival needs and leveraging of respected role models are strategies that may hold potential to mitigate risk of infectious diseases in this setting. Registration details World Pandemic Research Network – 490,652

Understanding the barriers and facilitators of COVID-19 risk mitigation strategy adoption and COVID-19 vaccination in refugee settlements in Uganda: a qualitative study.

Acknowledgements: We are grateful to the refugee study participants who were willing to share their time, perspectives and lived experiences. We appreciate the hard work and dedication of the Medical Teams International Village Health Teams without whose continuous efforts recruitment for the Dial-COVID study would not have been possible. For their support of this research, we thank collaborators from the Office of the Prime Minister of Uganda and the United Nations High Commissioner for Refugees.BACKGROUND: Perspectives on COVID-19 risk and the willingness and ability of persons living in refugee settlements to adopt COVID-19 prevention strategies have not been rigorously evaluated. The realities of living conditions in Ugandan refugee settlements may limit the extent to which refugees can uptake strategies to mitigate COVID-19 risk. METHODS: In-depth qualitative interviews were conducted between April 2021 and April 2022 to assess COVID-19 knowledge, risk perception, prevention strategy adoption including COVID-19 vaccination, and COVID-19 impact on living conditions in refugee settlements in Uganda. Interview participants included 28 purposively selected refugees who called into "Dial-COVID", a free telephone COVID-19 information collection and dissemination platform that was advertised in refugee settlements by community health workers. Interviews were analyzed using a combination of deductive and inductive content analysis. Emerging themes were mapped onto the Theoretical Domains Framework to identify domains influencing prevention behavior. Results were synthesized to provide intervention and policy recommendations for risk mitigation in refugee settlements for COVID-19 and future infectious disease outbreaks. RESULTS: The COVID-19 pandemic detrimentally impacted economic and food security as well as social interactions in refugee settlements. Youth were considered especially impacted, and participants reported incidents of child marriage and teenage pregnancy following school closures. Participants displayed general knowledge of COVID-19 and expressed willingness to protect themselves and others from contracting COVID-19. Risk mitigation strategy uptake including COVID-19 vaccination was influenced by COVID-19 knowledge, emotions surrounding COVID-19, the environmental context and resources, personal goals, beliefs about the consequences of (non)adoption, social influences, and behavior reinforcement. Resource constraints, housing conditions, and competing survival needs challenged the adoption of prevention strategies and compliance decreased over time. CONCLUSIONS: Contextual challenges impact the feasibility of COVID-19 risk mitigation strategy uptake in refugee settlements. Pre-existing hardships in this setting were amplified by the COVID-19 pandemic and related lockdowns. Targeted dispelling of myths, alignment of information across communication mediums, supporting survival needs and leveraging of respected role models are strategies that may hold potential to mitigate risk of infectious diseases in this setting. REGISTRATION DETAILS: World Pandemic Research Network - 490,652

Leveraging interactive voice response technology to mitigate COVID-19 risk in refugee settlements in Uganda: Lessons learned implementing "Dial-COVID" a toll-free mobile phone symptom surveillance and information dissemination tool.

Funder: UK ForeignFunder: UK National Institute for Health ResearchFunder: Wellcome TrustFunder: Commonwealth and Development OfficeFunder: Population Health Initiative at the University of WashingtonBACKGROUND: Persons living in refugee settlements in sub-Saharan Africa may be at increased risk for COVID-19 and experience barriers to accessing COVID-19 information. We aimed to evaluate the implementation of "Dial-COVID" a multi-lingual, toll free, telephone platform that uses interactive voice response (IVR) to track COVID-19 symptoms/exposure and disseminate COVID-19 health information in refugee settlements in Uganda. We hypothesized that IVR could provide an alternative way to screen for COVID-19 and communicate public health information to humanitarian populations when physical access and testing capacity were limited. METHODS: The Dial-COVID IVR platform was created in ten languages and advertised by community health workers in refugee settlements for participants to call into toll free. In a recorded IVR symptom survey, participants were screened for COVID-19 symptoms/exposures and based on their responses, received tailored public health messages about COVID-19 risk mitigation in accordance with Uganda Ministry of Health guidelines. Here we report the challenges and lessons learned implementing this research during the pandemic. RESULTS: Between February 2021 and March 2022, 15,465 calls were received by the Dial-COVID platform from all 31 refugee settlements in Uganda through which 6,913 symptom surveys were completed and 10,411 public health messages were disseminated in all study languages. Uptake of Dial-COVID fluctuated with the national COVID-19 caseload and was impacted by phone ownership and connectivity in refugee settlements. Intensified advertising efforts promoted Dial-COVID uptake. Flexibility to adapt IVR messages was contingent on translation capacity. CONCLUSION: Refugees living in refugee settlements across Uganda accessed Dial-COVID to share and obtain COVID-19 information suggesting that IVR holds potential for rapid information dissemination and screening of humanitarian populations during future infectious disease outbreaks and may be a valuable tool for routine public health programs. IVR adaptation flexibility and reach are influenced by language constraints and by contextual factors related to platform access. REGISTRATION DETAILS: World Pandemic Research Network- 490652

Knowledge and barriers of PrEP delivery among diverse groups of potential PrEP users in Central Uganda.

BackgroundScale-up of oral pre-exposure prophylaxis (PrEP) for HIV prevention in Uganda began with serodiscordant couples (SDC) and has expanded to other most at-risk populations (MARPs). We explored knowledge, acceptability, barriers and facilitators of PrEP use among potential PrEP users in four MARPs (SDC; men who have sex with men [MSM]; female sex workers [FSW], and fisher folk).MethodsWe administered quantitative surveys to potential PrEP users in multiple settings in Central Uganda at baseline and approximately 9 months after healthcare worker (HCW) training on PrEP.ResultsThe survey was completed by 250 potential PrEP users at baseline and 125 after HCW training; 55 completed both surveys. For these 250 participants, mean age was 28.5 years (SD 6.9), 47% were male and 6% were transgender women, with approximately even distribution across MARPs and recruitment locations (urban, peri-urban, and rural). Most (65%) had not heard about PrEP. After HCW training, 24% of those sampled were aware of PrEP, and the proportion of those who accurately described PrEP as "antiretrovirals to be used before HIV exposure" increased from 54% in the baseline survey to 74% in the second survey (pConclusionsInitial awareness of PrEP was low, but PrEP knowledge and interest increased among diverse MARPs after HCW training. Demand creation and HCW training will be critical for increasing PrEP awareness among key populations, with support to overcome barriers to PrEP use. These findings should encourage the acceleration of PrEP rollout in Uganda

Integrated delivery of antiretroviral treatment and pre‐exposure prophylaxis to HIV‐1 serodiscordant couples in East Africa: a qualitative evaluation study in Uganda

Abstract Introduction: Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time‐limited, oral pre‐exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long‐term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success. Methods: Data collection consisted of 274 in‐depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples’ experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain “why the integrated strategy worked.” Results: Couples found “couples‐focused” services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for “getting help” to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a “couples orientation” to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission. Conclusions: Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples’ experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out

How PrEP delivery was integrated into public ART clinics in central Uganda: A qualitative analysis of implementation processes.

Tailored delivery strategies are important for optimizing the benefit and overall reach of PrEP in sub-Saharan Africa. An integrated approach of delivering time-limited PrEP in combination with ART to serodifferent couples encourages PrEP use in the HIV-negative partner as a bridge to sustained ART use. Although PrEP has been delivered in ART clinics for many years, the processes involved in integrating PrEP into ART services are not well understood. The Partners PrEP Program was a stepped-wedge cluster randomized trial of integrated PrEP and ART delivery for HIV serodifferent couples in 12 public health facilities in central Uganda (Clinicaltrials.gov NCT03586128). Using qualitative data, we identified and characterized key implementation processes that explain how PrEP delivery was integrated into existing ART services in the Partners PrEP Program. In-depth interviews were conducted with a purposefully-selected sub-sample of 83 members of 42 participating serodifferent couples, and with 36 health care providers implementing integrated delivery. High quality training, technical supervision, and teamwork were identified as key processes supporting providers to implement PrEP delivery. Interest in the PrEP program was promoted through the numerous ways health care providers made integrated ART and PrEP meaningful for serodifferent couples, including tailored counseling messages, efforts to build confidence in integrated delivery, and strategies to create demand for PrEP. Couples in the qualitative sample responded positively to providers' efforts to promote the integrated strategy. HIV-negative partners initiated PrEP to preserve their relationships, which inspired their partners living with HIV to recommit to ART adherence. Lack of disclosure among couples and poor retention on PrEP were identified as barriers to implementation of the PrEP program. A greater emphasis on understanding the meaning of PrEP for users and its contribution to implementation promises to strengthen future research on PrEP scale up in sub-Saharan Africa

HIV-1-neutralizing IgA detected in genital secretions of highly HIV-1-exposed seronegative women on oral preexposure prophylaxis

Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals

Additional file 1 of Understanding the barriers and facilitators of COVID-19 risk mitigation strategy adoption and COVID-19 vaccination in refugee settlements in Uganda: a qualitative study

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