Exploring the complexity of the implementation determinants of human papillomavirus vaccination in Africa through a systems thinking lens: A rapid review.

A rapid review was conducted to explore the implementation determinants of human papillomavirus (HPV) vaccination in the World Health Organization African Region and describe their dynamic relationship. PubMed and Google Scholar were searched in October 2023 to find relevant literature. A total of 64 published studies that reported factors affecting HPV vaccination were identified. Analysis of identified factors yielded 74 implementation determinants of HPV vaccination across the five domains of the Consolidated Framework for Implementation Research (CFIR): two (2.70%) were in the innovation domain, seven (9.46%) were in the outer setting domain, 14 (18.92%) were in the inner setting domain, 37 (50%) were in the individual domain and 14 (18.92%) were in the implementation process domain. A causal loop diagram of these implementation determinants revealed four balancing and seven reinforcing loops. Applying systems lens promoted a more holistic understanding of the implementation determinants of HPV vaccination, exposing leverage points for interventions.

Human papillomavirus (HPV) trials: A cross-sectional analysis of clinical trials registries.

Every clinical trial must be registered in a publicly accessible trial registry before enrollment of the first participant. Prospectively registering clinical trials before enrolling participants helps to prevent unethical research misconduct from occurring, duplication of research and increases transparency in research. The aim of this study was to provide cross-sectional survey analysis of planned, ongoing and completed human papillomavirus (HPV) clinical trials conducted worldwide. We searched the International Clinical Trials Registry Platform (ICTR) for registered HPV trials on 5 March 2023. Two authors independently extracted data including name of the clinical trial registry, location of the trial, recruitment status of the trial, gender of participants, phase of the trial, and type of trial sponsor. We used Microsoft Excel to perform descriptive analysis. The search yielded 1632 trials registered between 1999 and 2023. Most of the trials were registered in ClinicalTrials.gov and were registered retrospectively. We also found that most trials were conducted in North America, in recruiting stage, and indicated "not applicable" under the phase of the trial field. Finally, most trials were sponsored by hospitals. Our study found that there are many HPV clinical trials registered in different clinical trial primary registries around the world. However, many of the trials were registered retrospectively instead of the required prospectively and some had missing fields. Therefore, there is a need for registries to promote prospective trial registration and completion of all fields during the registration process.

Prevalence of chronic kidney disease and associated risk factors among people living with HIV in a rural population of Limpopo Province, South Africa.

Background: Limited evidence informs on the prevalence of chronic kidney disease (CKD) in people living with HIV (PLWH) in South Africa. Thus, this study aimed to determine the prevalence of CKD and its associated risk factors among PLWH within the rural province of Limpopo, South Africa. Methods: We conducted a cross-sectional study of 143 participants, subdivided into groups of PLWH (n = 103) and individuals without HIV (n = 43). Structured questionnaires were used to collect and capture sociodemographic information including age, sex, alcohol intake, smoking status, and educational status. Basic measurements taken included levels of cluster of differentiation 4 (CD4+) count, body mass index (BMI), blood pressure, plasma cystatin C, and fasting serum glucose levels. Plasma cystatin C-based estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) estimator to determine the prevalence of CKD. Results: The prevalence of CKD was approximately 7% in PLWH. Multivariate logistic regression analysis showed that it was only diabetes mellitus (odds ratio of 5.795, 95% confidence interval, p = 0.034) and age (odds ratio of 1.078, 95% confidence interval, p = 0.039) that were significantly associated with CKD in PLWH. Conclusion: Chronic kidney disease was prevalent in PLWH, and it was further associated with cardiovascular risk factors, diabetes, and ageing. As PLWH age, the burden of CKD may be increased with the increase in cardiovascular-related comorbidities such as diabetes.

A systematic review assessing the potential use of cystatin c as a biomarker for kidney disease in people living with HIV on antiretroviral therapy.

The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.

Sustainable financing for vaccination towards advancing universal health coverage in the WHO African region: The strategic role of national health insurance.

There is a growing political interest in health reforms in Africa, and many countries are choosing national health insurance as their main financing mechanism for universal health coverage. Although vaccination is an essential health service that can influence progress toward universal health coverage, it is not often prioritized by these national health insurance systems. This paper highlights the potential gains of integrating vaccination into the package of health services that is provided through national health insurance and recommends practical policy actions that can enable countries to harness these benefits at population level.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Sarcopenia in a type 2 diabetic state: Reviewing literature on the pathological consequences of oxidative stress and inflammation beyond the neutralizing effect of intracellular antioxidants.

Sarcopenia remains one of the major pathological features of type 2 diabetes (T2D), especially in older individuals. This condition describes gradual loss of muscle mass, strength, and function that reduces the overall vitality and fitness, leading to increased hospitalizations and even fatalities to those affected. Preclinical evidence indicates that dysregulated mitochondrial dynamics, together with impaired activity of the NADPH oxidase system, are the major sources of oxidative stress that drive skeletal muscle damage in T2D. While patients with T2D also display relatively higher levels of circulating inflammatory markers in the serum, including high sensitivity-C-reactive protein, interleukin-6, and tumor necrosis factor-α that are independently linked with the deterioration of muscle function and sarcopenia in T2D. In fact, beyond reporting on the pathological consequences of both oxidative stress and inflammation, the current review highlights the importance of strengthening intracellular antioxidant systems to preserve muscle mass, strength, and function in individuals with T2D.

Hospital acquired COVID-19 infections amongst patients before the rollout of COVID-19 vaccinations, a scoping review.

BACKGROUND: Hospital settings are at increased risk of spreading Coronavirus Disease 2019 (COVID-19) infections, hence non-pharmaceutical prevention interventions (NPPIs) and prioritized vaccination of healthcare workers and resident patients are critical. The status of COVID-19 hospital acquired infections (HAIs) in low-income settings is unclear. We aimed to identify and summarize the existing evidence on COVID-19 HAIs amongst patients, prior to the rollout of vaccines in countries worldwide. METHODS: We conducted a scoping review of English peer-reviewed literature in PubMed, Web of Science and Scopus using a combination of selected search terms. Full texts articles presenting results on COVID-19 HAIs in hospitalised patients before the rollout of vaccines in countries worldwide were eligible. Data extracted from eligible articles included estimates of COVID-19 HAIs, country, and type of hospital setting, and was summarized narratively. Quality assessment of included articles was not possible. RESULTS: Literature searches generated a total of 5920 articles, and 45 were eligible for analysis. Eligible articles were from Europe, North America, Asia, and Brazil and none were from low-income countries. The proportion of COVID-19 HAIs ranged from 0% when strict NPPIs were applied, to 65% otherwise. The estimates of COVID-19 HAIs did not differ by country but were lower in studies conducted after implementation of NPPIs and in specialized hospital settings for operative surgery. Studies conducted before the implementation of NPPIs or in long-term care and psychiatric wards often reported high estimates of HAI. Although there was no clear trend in general wards, those situated in academic hospitals managed to reduce HAI rates under strict NPPI protocols. Operative surgery settings, unlike psychiatric settings, effectively prevented COVID-19 HAI using tailored NPPIs. CONCLUSION: The available evidence shows a high risk of COVID-19 HAIs, the feasibility of preventing HAIs in different healthcare settings and the importance of appropriately tailored NPPIs. There were no data from low-income settings, therefore, it is unclear whether the reported NPPI approaches could be equally effective elsewhere. We recommend routine monitoring of COVID-19 HAIs in countries with low vaccination coverage, to identify and close gaps in NPPIs and understand gains made from vaccinating healthcare workers and hospitalized patients.

Contextualised strategies to increase childhood and adolescent vaccination coverage in South Africa: a mixed-methods study.

INTRODUCTION: Despite the unparalleled success of immunisation in the control of vaccine preventable diseases, immunisation coverage in South Africa remains suboptimal. While many evidence-based interventions have successfully improved vaccination coverage in other countries, they are not necessarily appropriate to the immunisation needs, barriers and facilitators of South Africa. The aim of this research is to investigate barriers and facilitators to optimal vaccination uptake, and develop contextualised strategies and implementation plans to increase childhood and adolescent vaccination coverage in South Africa. METHODS: The study will employ a mixed-methods research design. It will be conducted over three iterative phases and use the Adopt, Contextualise or Adapt (ACA) model as an overarching conceptual framework. Phase 1 will identify, and develop a sampling frame of, immunisation stakeholders involved in the design, planning and implementation of childhood and human papillomavirus immunisation programmes in South Africa. Phase 2 will identify the main barriers and facilitators to, and solutions for, increasing vaccination coverage. This phase will comprise exploratory qualitative research with stakeholders and a review of existing systematic reviews on interventions for improving vaccination coverage. Using the findings from Phase 2 and the ACA model, Phase 3 will develop a set of proposed interventions and implementation action plans for improving immunisation coverage in South Africa. These plans will be discussed, revised and finalised through a series of participatory stakeholder workshops and an online questionnaire, conducted as part of Phase 3. ETHICS: Ethical approval was obtained from the South African Medical Research Council (EC018-11/2018). No risks to participants are expected. Various steps will be taken to ensure the anonymity and confidentiality of participants. DISSEMINATION: The study findings will be shared at stakeholder workshops, the website of Cochrane South Africa and academic publications and conferences.

Cochrane corner: universal screening for SARS-CoV-2 infection.

INTRODUCTION: coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with non-specific symptoms, although a few becoming critically ill with septic shock and multiple organ failure. There is an unknown proportion of infected individuals who remain asymptomatic and infectious. Universal screening for COVID-19 infections to detect individuals who are infected before they present clinically could therefore be an important measure to contain the spread of the disease. We highlight a Cochrane rapid review which assessed the effectiveness and accuracy of universal screening for COVID-19 infection. METHODS: the authors of the Cochrane review searched multiple electronic databases to identify studies reporting on the effectiveness of universal screening and reporting on screening test accuracy. Eligible participants for the review included people who had not sought care for potential COVID-19 symptoms. RESULTS: the authors included 22 publications, with none of them conducted in Africa. Two modelling studies reported on the beneficial and negative effects of screening; and 20 studies (cohort and modelling) reported data on the accuracy of screening tests. The included studies had wide variability in the baseline prevalence of COVID-19 infection as well as study settings and methods. All cohort studies compared screening strategies to reverse transcriptase-polymerase chain reaction (RT-PCR) as the gold standard. The rapid review suggests that there is low certainty of evidence that screening at travel hubs may slow the importation of infected cases. Furthermore, the review highlights the uncertainty and variation in the accuracy of screening. CONCLUSION: given the low accuracy of the tests included in this review, a high proportion of COVID-19 infected individuals may be missed and go on to infect others. In addition, some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals.

Social media and HPV vaccination: Unsolicited public comments on a Facebook post by the Western Cape Department of Health provide insights into determinants of vaccine hesitancy in South Africa.

On the 4 February 2019, the Western Cape Department of Health's Facebook page announced the implementation of a school-based vaccination campaign aimed to administer the first doses of human papillomavirus (HPV) vaccine in public schools to Grade 4 girls who are nine years old. This announcement was met with a flurry of social media responses posted on the campaign's Facebook page. This study identifies determinants of vaccine hesitancy amongst responses provided by social media users to this post. On 8 March 2019, we conducted a qualitative study including all 157 comments to the Facebook post. The post had 659 'emotion' reactions: 574 "likes", 62 "loves", 21 "angry faces", 2 "laughs", 2 "wows" and 1 "sad face". An overwhelming majority (636/659 i.e. 97%) of reactions were favourable to the HPV vaccination campaign. Out of the 157 comments, we judged 52 (33%) of them to be 'hesitant', suggesting that people with negative reactions though few in number, were more likely to be vocal deniers. Concern around the safety of HPV vaccines including effects on reproductive health was the most common theme identified. Other emerging themes included: risk of cervical cancer perceived as being low, issues around consent, concerns that girls are being used for research, questionable vaccine effectiveness, use of the school-based strategy for the campaign, risk-benefits calculations of HPV vaccination and constraints such as stock-outs. Knowing someone who had been affected or being at risk of cervical cancer, having knowledge about the causes of cervical cancer, confidence in the effectiveness and safety of the vaccine, knowing the vaccine was being used in high income settings, and having strong recommendations from the World Health Organisation and key actors seemed to increase the willingness to accept the vaccine. The magnitude and causes of HPV vaccine hesitancy need to be investigated to ensure the success of this programme.

Naringin protects against HIV-1 protease inhibitors-induced pancreatic ß-cell dysfunction and apoptosis.

INTRODUCTION: The protective effects of grapefruit-derived naringin against HIV-1 Protease Inhibitors (PIs)-associated oxidative damage to pancreatic ß-cells and apoptosis were investigated in RIN-5F cells in culture. METHODS: Cells in culture medium were challenged with 11-25 mM glucose with or without nelfinavir (1-10 µM), saquinavir (1-10 µM) and atazanavir (5-20 µM), respectively for 24 h to determine insulin secretion. The cells were further treated with nelfinavir (10 µM), saquinavir (10 µM), atazanavir (20 µM) with and without naringin or glibenclamide (10 µM) for 24 h to determine insulin secretion, lipid peroxidation, Superoxide Dismutase (SOD) activity, glutathione (GSH) levels, ATP production and caspase-3 and-9 activities, respectively. RESULTS: Glucose-dependent insulin secretion was significantly reduced by PIs in a concentration-dependent manner. Treatment with either naringin or glibenclamide significantly reduced lipid peroxidation, Superoxide Dismutase (SOD) activities and also increased glutathione (GSH) and ATP levels in the cells that were treated with PIs. Furthermore, naringin or glibenclamide significantly reduced caspase-3 and caspase-9 activities in cells that were treated with PIs. CONCLUSIONS: PIs impair ß-cell functions by increasing oxidative stress and apoptosis. Treatment with naringin protected RIN-5F cells from PI-induced oxidative damage and apoptosis. Our results therefore suggest that nutritional supplements with naringin could prevent pancreatic ß-cell dysfunction and the attendant metabolic complications caused by PIs in patients on antiretroviral therapy.