Structural validity of a computerized neurocognitive battery for youth affected by human immunodeficiency virus in Botswana.

Children born to mothers infected with the human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common among youth, but standardized cognitive screening is limited. The Penn Computerized Neurocognitive Battery (PennCNB), a tool that streamlines evaluation of neurocognitive functioning, was culturally adapted for use among youth in this high-burden, low-resource setting. The present study examined the structural validity of the culturally adapted PennCNB. A cohort of 7-17-year-old children living with HIV (HIV +) and HIV-exposed-uninfected (HEU) children were enrolled from the Botswana-Baylor Children's Clinical Centre of Excellence in Gaborone, Botswana. Confirmatory and exploratory factor analyses were performed on speed, accuracy, and efficiency measures for 13 PennCNB tests. Fit of the confirmatory factor analysis was acceptable, which supports the design of the battery measuring four neurocognitive domains: Executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. However, the model revealed high interfactor correlation. Exploratory factor analysis suggested that tests assessing executive functioning and sensorimotor/processing speed clustered together rather than forming differentiable factors. Overall, this research provides valuable insight into the structural validity of a neurocognitive battery adapted for use in a non-Western setting, suggesting that the PennCNB could serve as a useful tool for the assessment of neurocognitive function in Botswana and, potentially, other resource-limited settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Medical stakeholder perspectives on implementing a computerized battery to identify neurocognitive impairments among youth in Botswana.

HIV infection and in utero exposure, common in Sub-Saharan Africa, are associated with pediatric neurocognitive impairment. Cognitive screening can identify impairments, but it is rarely used in this setting. The Penn Computerized Neurocognitive Battery (PennCNB), an evidence-based cognitive screening tool, was adapted for use in Botswana. To facilitate future implementation, 20 semi-structured interviews were conducted to elicit key stakeholders' perspectives on factors likely to be related to successful uptake of the PennCNB in clinical settings. An integrated analytic approach combining constructs from the Consolidated Framework for Implementation Research and modified grounded theory was used. Results underscore the need for cognitive screening in Botswana and the acceptability of the PennCNB. Implementation barriers include limited time and resources, whereas facilitators include standard procedures for introducing new tools into medical settings and for training implementers. Recommended implementation strategies include integrating screening into the existing workflow, implementing the tool in the medical and educational sectors, and targeting selection of children for assessment. This research addresses the research-to-practice gap by engaging in pre-implementation inquiry and designing for implementation. Results will inform the development of strategies to maximize the likelihood of successful implementation of the PennCNB to identify neurocognitive impairment in children in this high-need setting.

Evaluation of COVID-19 Testing Strategies for Repopulating College and University Campuses: A Decision Tree Analysis.

PURPOSE: The optimal approach to identify SARS-CoV-2 infection among college students returning to campus is unknown. Recommendations vary from no testing to two tests per student. This research determined the strategy that optimizes the number of true positives and negatives detected and reverse transcription polymerase chain reaction (RT-PCR) tests needed. METHODS: A decision tree analysis evaluated five strategies: (1) classifying students with symptoms as having COVID-19, (2) RT-PCR testing for symptomatic students, (3) RT-PCR testing for all students, (4) RT-PCR testing for all students and retesting symptomatic students with a negative first test, and (5) RT-PCR testing for all students and retesting all students with a negative first test. The number of true positives, true negatives, RT-PCR tests, and RT-PCR tests per true positive (TTP) was calculated. RESULTS: Strategy 5 detected the most true positives but also required the most tests. The percentage of correctly identified infections was 40.6%, 29.0%, 53.7%, 72.5%, and 86.9% for Strategies 1-5, respectively. All RT-PCR strategies detected more true negatives than the symptom-only strategy. Analysis of TTP demonstrated that the repeat RT-PCR strategies weakly dominated the single RT-PCR strategy and that the thresholds for more intensive RT-PCR testing decreased as the prevalence of infection increased. CONCLUSION: Based on TTP, the single RT-PCR strategy is never preferred. If the cost of RT-PCR testing is of concern, a staged approach involving initial testing of all returning students followed by a repeat testing decision based on the measured prevalence of infection might be considered.

Development of a computerised neurocognitive battery for children and adolescents with HIV in Botswana: study design and protocol for the Ntemoga study.

INTRODUCTION: Neurodevelopmental delays and cognitive impairments are common in youth living with HIV. Unfortunately, in resource-limited settings, where HIV infection impacts millions of children, cognitive and neurodevelopmental disorders commonly go undetected because of a lack of appropriate assessment instruments and local expertise. Here, we present a protocol to culturally adapt and validate the Penn Computerized Neurocognitive Battery (PennCNB) and examine its validity for detecting both advanced and subtle neurodevelopmental problems among school-aged children affected by HIV in resource-limited settings. METHODS AND ANALYSIS: This is a prospective, observational cohort study. The venue for this study is Gaborone, Botswana, a resource-limited setting with high rates of perinatal exposure to HIV and limited neurocognitive assessment tools and expertise. We aim to validate the PennCNB in this setting by culturally adapting and then administering the adapted version of the battery to 200 HIV-infected, 200 HIV-exposed uninfected and 240 HIV-unexposed uninfected children. A series of analyses will be conducted to examine the reliability and construct validity of the PennCNB in these populations. ETHICS AND DISSEMINATION: This project received ethical approval from local and university Institutional Review Boards and involved extensive input from local stakeholders. If successful, the proposed tools will provide practical screening and streamlined, comprehensive assessments that could be implemented in resource-limited settings to identify children with cognitive deficits within programmes focused on the care and treatment of children affected by HIV. The utility of such assessments could also extend beyond children affected by HIV, increasing general access to paediatric cognitive assessments in resource-limited settings.

A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR) of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity and protective efficacy of adenoviral based malaria vaccines.