Vaccine hesitancy, which embodies the unwillingness to receive vaccines when vaccination services are available and accessible, is one of the greatest threats to global health. Although vaccine ...hesitancy has existed among a small percentage of people for centuries, its harmful effects are likely to be more pronounced during the COVID-19 pandemic than ever before. COVID-19 vaccine hesitancy will pose substantial risks for both people who delay or refuse to be vaccinated and the wider community. It will make communities unable to reach thresholds of coverage necessary for herd immunity against COVID-19, thus unnecessarily perpetuating the pandemic and resulting in untold suffering and deaths. Vaccine hesitancy is pervasive, misinformed, contagious, and is not limited to COVID-19 vaccination. Our work shows that vaccine hesitancy is a complex and dynamic social process that reflects multiple webs of influence, meaning, and logic. People's vaccination views and practices usually comprise an ongoing engagement that is contingent on unfolding personal and social circumstances, which can potentially change over time. Therefore, as COVID-19 vaccination rolls out globally, scientists and decision-makers need to investigate the scale and determinants of vaccine hesitancy in each setting; so that tailored and targeted strategies can be developed to address it.
Abstract
Background
Rotavirus is a primary infectious virus causing childhood diarrhoea and is associated with significant mortality in children. Three African countries (Nigeria, the Democratic ...Republic of Congo, and Angola) are among the five countries that account for 50% of all diarrheal-related deaths worldwide. This indicates that much needs to be done to reduce this burden. The World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) is a global repository for primary registries reporting on clinical trials. This study aimed to identify and describe planned, ongoing, and completed rotavirus vaccine trials conducted globally.
Methods
We searched WHO-ICTRP on 17 June 2021 and conducted a cross-sectional analysis of rotavirus studies listed in the database. Data extraction included trial location, participant age, source of the trial record, trial phase, sponsor, and availability of results. We used the Microsoft Excel 365 package to generate descriptive summary statistics.
Results
We identified 242 rotavirus vaccine trials registered from 2004 to 2020. Most of these trials were registered retrospectively, with only 26% of the rotavirus vaccine trials reporting the availability of results in their registries. Most of the trials are studying children aged less than 5 years. The recruitment status for these trials is currently shown in the WHO-ICTRP as “not recruiting” for 80.17% of trials, “recruiting” for 11.57% of trials recruiting, and unknown for 6.61% of trials. The continents in which these rotavirus vaccine trials have recruitment sites in Asia (41%) and North America (20%), with the maximum number of trials in the clinical trial registries coming from India (21%) and the USA (11%) with most being sponsored by the pharmaceutical industry. Our analysis shows that only 26% of the rotavirus vaccine trials report the availability of results in their registries.
Conclusions
Mapping rotavirus vaccine clinical trial activity using data from the WHO ICTRP beneficial provides valuable information on planned, ongoing, or completed trials for researchers, funders, and healthcare decision-makers. Despite the high rotavirus disease burden in low- and middle-income countries, including Africa, there is minimal clinical trial activity related to the condition on the continent. The clinical trial registries as a valuable tool to share interim results of the trials.
Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV ...(fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger.
In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ2 test of homogeneity and quantified it using the I2 statistic. We assessed risk of bias using the Cochrane risk of bias tool, and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The study is registered with PROSPERO, CRD42018092647.
860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51–0·72), at two doses was 0·90 (0·82–1·00), and at three doses was 0·95 (0·91–1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: −0·51 (95% CI −0·87 to −0·14) at one dose, −0·49 (−0·70 to −0·28) at two doses, and −0·98 (−1·46 to −0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I2=0%), whereas heterogeneity was observed in the two-dose (p<0·00001; I2=88%) and one-dose (p=0·0004; I2=74%) comparisons. Heterogeneity was observed in meta-analyses of GMTs for one-dose (p<0·00001; I2=92%), two-dose (p=0·002; I2=80%), and three-dose (p<0·00001; I2=93%) comparisons. Findings for types 1 and 3 were similar to those for type 2. The certainty of the evidence was high for the three-dose comparisons and moderate for the rest of the comparisons.
There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination.
South African Medical Research Council and the National Research Foundation of South Africa.
Since the outbreak of COVID-19, many lives have been impacted especially on the African continent which is already fighting the burden of multiple diseases of poverty. However, clinical research has ...offered hope for treatment and prevention options for this infectious disease. Despite many COVID-19 clinical trials conducted globally, three countries in Africa account for more than 80% of all trials from the continent registered trials in clinical trial registries. This indicates geographic disparity among COVID-19 research in Africa. From the perspective of clinical trial registration, transparency in clinical research and the availability of data became important for making informed decisions to manage the pandemic. Registries serve as a source of planned, ongoing, and completed trials while allowing efficient funding allocation for research that would not duplicate efforts. Additionally, research gaps can be identified, which provide opportunities for collaboration among researchers. Therefore, a critical lesson learnt during this pandemic is that clinical trial registration is important in facilitating the process of tracking changes made to protocols and minimizing publication bias, thereby promoting and advocating for clinical research transparency. Moreover, registration in a clinical trial registry is a condition for publication and allows for trial summary results to be publicly available. Adhering to the principle of results sharing is especially important for the rapidly growing clinical research activities racing to find evidence-based interventions to end the COVID-19 pandemic.
Safe and efficacious COVID-19 vaccines exist, but their success against the disease depends on public willingness to receive them. Vaccine hesitancy is one major obstacle to the achievement of herd ...immunity. On 25 June 2021, about 2000 supporters of the Economic Freedom Fighters (EFF) (the third biggest political party in South Africa) marched to the offices of the national regulatory authority (NRA) supporting COVID-19 vaccination and demanding approval of two additional vaccines (Sputnik V and Sinovac) in South Africa. The march was led by EFF leader, Julius Malema. By then, only three COVID-19 vaccines had received emergency use authorization in the country-the Janssen, AstraZeneca and Pfizer-BioNtech vaccines. It is worth noting that NRAs should only approve a vaccine if they are satisfied that its benefits outweigh any potential risks and not through political pressure. Nevertheless, we believe that this march might have increased COVID-19 vaccine acceptance and uptake among EFF supporters. The endorsement of COVID-19 vaccines by Malema, an influential political figure in South Africa, probably convinced some vaccine hesitant South Africans that COVID-19 vaccination is important. Therefore, we suggest vaccine endorsement by influential individuals in South Africa as one of the strategies to increase COVID-19 vaccine uptake.
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.
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.
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.
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.
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 = 0.10‑1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76‑1.63, 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.
In Mycobacterium tuberculosis (Mtb), damage-induced mutagenesis is dependent on the C-family DNA polymerase, DnaE2. Included with dnaE2 in the Mtb SOS regulon is a putative operon comprising Rv3395c, ...which encodes a protein of unknown function restricted primarily to actinomycetes, and Rv3394c, which is predicted to encode a Y-family DNA polymerase. These genes were previously identified as components of an imuA-imuB-dnaE2–type mutagenic cassette widespread among bacterial genomes. Here, we confirm that Rv3395c (designated imuA') and Rv3394c (imuB) are individually essential for induced mutagenesis and damage tolerance. Yeast two-hybrid analyses indicate that ImuB interacts with both ImuA' and DnaE2, as well as with the β-clamp. Moreover, disruption of the ImuB-β clamp interaction significantly reduces induced mutagenesis and damage tolerance, phenocopying imuA', imuB, and dnaE2 gene deletion mutants. Despite retaining structural features characteristic of Y-family members, ImuB homologs lack conserved active-site amino acids required for polymerase activity. In contrast, replacement of DnaE2 catalytic residues reproduces the dnaE2 gene deletion phenotype, strongly implying a direct role for the α-subunit in mutagenic lesion bypass. These data implicate differential protein interactions in specialist polymerase function and identify the split imuA'-imuB/dnaE2 cassette as a compelling target for compounds designed to limit mutagenesis in a pathogen increasingly associated with drug resistance.
The protective effects of grapefruit-derived naringin against HIV-1 Protease Inhibitors (PIs)-associated oxidative damage to pancreatic β-cells and apoptosis were investigated in RIN-5F cells in ...culture.
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.
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.
PIs impair β-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 β-cell dysfunction and the attendant metabolic complications caused by PIs in patients on antiretroviral therapy.
•This study investigated deleterious effects of HIV-1 protease inhibitors on pancreatic β-cell function and apoptosis using RIN-5F cells in vitro.•The results indicate that grapefruit-derived flavonoid, naringin protects the cells from PI-induced impairment of insulin secretion and apoptosis.•These effects on naringin appear to be mediated by its antioxidant effects.•These results therefore suggest that as nutritional supplement, naringin could prevent impairment of pancreatic β-cell function in patients treated with HIV-1 protease inhibitors.
Universal health coverage is defined as ensuring that all people have access to needed health services of sufficient quality to be effective while ensuring that these services do not expose the user ...the financial hardship. Universal health coverage includes three related objectives: equity in access to health services (everyone who needs services should get them, not only those who can pay for them); the quality of health services should be good enough to improve the health of those receiving services; and people should be protected against financial risk, ensuring that the cost of using services does not put people at risk of financial harm. Africa still has a long way to go to achieve these objectives. Many barriers limit the progress of the African Region towards building the robust health systems needed for universal health coverage. Such barriers include poor infrastructure, high out-of-pocket payments and catastrophic health expenditures, shortages and inequitable distribution of qualified healthcare workers, poor quality of care delivery, high cost of quality medicines, and lack of innovative technologies appropriate to the range of settings where care is delivered, health financing and governance. This paper aims to propose innovative strategies that could be applied to improve health systems in the Africa Region, which progress towards the continent attaining universal health coverage.
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