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.

Sulforaphane: A nutraceutical against diabetes-related complications.

There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.

Potential Benefits of Coffee Consumption on Improving Biomarkers of Oxidative Stress and Inflammation in Healthy Individuals and Those at Increased Risk of Cardiovascular Disease.

Cardiovascular diseases (CVDs) are considered the predominant cause of death globally. An abnormal increase in biomarkers of oxidative stress and inflammation are consistently linked with the development and even progression of metabolic diseases, including enhanced CVD risk. Coffee is considered one of the most consumed beverages in the world, while reviewed evidence regarding its capacity to modulate biomarkers of oxidative stress and inflammation remains limited. The current study made use of prominent electronic databases, including PubMed, Google Scholar, and Scopus to retrieve information from randomized controlled trials reporting on any association between coffee consumption and modulation of biomarkers of oxidative stress and inflammation in healthy individuals or those at increased risk of developing CVD. In fact, summarized evidence indicates that coffee consumption, mainly due to its abundant antioxidant properties, can reduce biomarkers of oxidative stress and inflammation, which can be essential in alleviating the CVD risk in healthy individuals. However, more evidence suggests that regular/prolonged use or long term (>4 weeks) consumption of coffee appeared to be more beneficial in comparison with short-term intake (<4 weeks). These positive effects are also observed in individuals already presenting with increased CVD risk, although such evidence is very limited. The current analysis of data highlights the importance of understanding how coffee consumption can be beneficial in strengthening intracellular antioxidants to alleviate pathological features of oxidative stress and inflammation to reduce CVD risk within the general population. Also covered within the review is essential information on the metabolism and bioavailability profile of coffee, especially caffeine as one of its major bioactive compounds.

Bioactive Properties, Bioavailability Profiles, and Clinical Evidence of the Potential Benefits of Black Pepper (Piper nigrum) and Red Pepper (Capsicum annum) against Diverse Metabolic Complications.

The consumption of food-derived products, including the regular intake of pepper, is increasingly evaluated for its potential benefits in protecting against diverse metabolic complications. The current study made use of prominent electronic databases including PubMed, Google Scholar, and Scopus to retrieve clinical evidence linking the intake of black and red pepper with the amelioration of metabolic complications. The findings summarize evidence supporting the beneficial effects of black pepper (Piper nigrum L.), including its active ingredient, piperine, in improving blood lipid profiles, including reducing circulating levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in overweight and obese individuals. The intake of piperine was also linked with enhanced antioxidant and anti-inflammatory properties by increasing serum levels of superoxide dismutase while reducing those of malonaldehyde and C-reactive protein in individuals with metabolic syndrome. Evidence summarized in the current review also indicates that red pepper (Capsicum annum), together with its active ingredient, capsaicin, could promote energy expenditure, including limiting energy intake, which is likely to contribute to reduced fat mass in overweight and obese individuals. Emerging clinical evidence also indicates that pepper may be beneficial in alleviating complications linked with other chronic conditions, including osteoarthritis, oropharyngeal dysphagia, digestion, hemodialysis, and neuromuscular fatigue. Notably, the beneficial effects of pepper or its active ingredients appear to be more pronounced when used in combination with other bioactive compounds. The current review also covers essential information on the metabolism and bioavailability profiles of both pepper species and their main active ingredients, which are all necessary to understand their potential beneficial effects against metabolic diseases.

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.

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

BACKGROUND: Rotavirus is a common cause of diarrhoea, diarrhoea-related hospital admissions, and diarrhoea-related deaths worldwide. Rotavirus vaccines prequalified by the World Health Organization (WHO) include Rotarix (GlaxoSmithKline), RotaTeq (Merck), and, more recently, Rotasiil (Serum Institute of India Ltd.), and Rotavac (Bharat Biotech Ltd.). OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO for their efficacy and safety in children. SEARCH METHODS: On 30 November 2020, we searched PubMed, the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, Conference Proceedings Citation Index-Social Science & Humanities. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies, and relevant systematic reviews. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) conducted in children that compared rotavirus vaccines prequalified for use by the WHO with either placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and assessed risk of bias. One author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analyses by under-five country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS: Sixty trials met the inclusion criteria and enrolled a total of 228,233 participants. Thirty-six trials (119,114 participants) assessed Rotarix, 15 trials RotaTeq (88,934 participants), five trials Rotasiil (11,753 participants), and four trials Rotavac (8432 participants). Rotarix Infants vaccinated and followed up for the first year of life In low-mortality countries, Rotarix prevented 93% of severe rotavirus diarrhoea cases (14,976 participants, 4 trials; high-certainty evidence), and 52% of severe all-cause diarrhoea cases (3874 participants, 1 trial; moderate-certainty evidence).  In medium-mortality countries, Rotarix prevented 79% of severe rotavirus diarrhoea cases (31,671 participants, 4 trials; high-certainty evidence), and 36% of severe all-cause diarrhoea cases (26,479 participants, 2 trials; high-certainty evidence).  In high-mortality countries, Rotarix prevented 58% of severe rotavirus diarrhoea cases (15,882 participants, 4 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, Rotarix prevented 90% of severe rotavirus diarrhoea cases (18,145 participants, 6 trials; high-certainty evidence), and 51% of severe all-cause diarrhoea episodes (6269 participants, 2 trials; moderate-certainty evidence).   In medium-mortality countries, Rotarix prevented 77% of severe rotavirus diarrhoea cases (28,834 participants, 3 trials; high-certainty evidence), and 26% of severe all-cause diarrhoea cases (23,317 participants, 2 trials; moderate-certainty evidence).  In high-mortality countries, Rotarix prevented 35% of severe rotavirus diarrhoea cases (13,768 participants, 2 trials; moderate-certainty evidence), and 17% of severe all-cause diarrhoea cases (2764 participants, 1 trial; high-certainty evidence). RotaTeq Infants vaccinated and followed up for the first year of life In low-mortality countries, RotaTeq prevented 97% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence).  In medium-mortality countries, RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence).  In high-mortality countries, RotaTeq prevented 57% of severe rotavirus diarrhoea cases (6775 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (1 trial, 4085 participants; moderate-certainty evidence).  Children vaccinated and followed up for two years In low-mortality countries, RotaTeq prevented 96% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence).  In medium-mortality countries, RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence).  In high-mortality countries, RotaTeq prevented 44% of severe rotavirus diarrhoea cases (6744 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (5977 participants, 2 trials; high-certainty evidence).  We did not identify RotaTeq studies reporting on severe all-cause diarrhoea in low- or medium-mortality countries. Rotasiil Rotasiil has not been assessed in any RCT in countries with low or medium child mortality. Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotasiil prevented 48% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In high-mortality countries, Rotasiil prevented 44% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence). Rotavac Rotavac has not been assessed in any RCT in countries with low or medium child mortality.  Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotavac prevented 57% of severe rotavirus diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence). Children vaccinated and followed up for two years In high-mortality countries, Rotavac prevented 54% of severe rotavirus diarrhoea cases (6541 participants, 1 trial; moderate-certainty evidence); no Rotavac studies have reported on severe all-cause diarrhoea at two-years follow-up. Safety No increased risk of serious adverse events (SAEs) was detected with Rotarix (103,714 participants, 31 trials; high-certainty evidence), RotaTeq (82,502 participants, 14 trials; moderate to high-certainty evidence), Rotasiil (11,646 participants, 3 trials; high-certainty evidence), or Rotavac (8210 participants, 3 trials; moderate-certainty evidence). Deaths were infrequent and the analysis had insufficient evidence to show an effect on all-cause mortality. Intussusception was rare.  AUTHORS' CONCLUSIONS: Rotarix, RotaTeq, Rotasiil, and Rotavac prevent episodes of rotavirus diarrhoea. The relative effect estimate is smaller in high-mortality than in low-mortality countries, but more episodes are prevented in high-mortality settings as the baseline risk is higher. In high-mortality countries some results suggest lower efficacy in the second year. We found no increased risk of serious adverse events, including intussusception, from any of the prequalified rotavirus vaccines.

Assessing the Implementation Determinants of Pilot Malaria Vaccination Programs in Ghana, Kenya, and Malawi through a Complexity Lens: A Rapid Review Using a Consolidated Framework for Implementation Research.

In 2019, national immunization programs in Ghana, Kenya, and Malawi commenced the implementation of RTS,S/AS01 vaccination in large-scale pilot schemes. Understanding the implementation context of this malaria vaccination in the pilot countries can provide useful insights for enhancing implementation outcomes in new countries. There has not yet been a proper synthesis of the implementation determinants of malaria vaccination programs. A rapid review was conducted to identify the implementation determinants of the pilot malaria vaccination programs in Ghana, Kenya, and Malawi, and describe the mechanism by which these determinants interact with each other. A literature search was conducted in November 2023 in PubMed and Google Scholar to identify those studies that described the factors affecting malaria vaccine implementation in Ghana, Kenya, and Malawi. Thirteen studies conducted between 2021 and 2023 were included. A total of 62 implementation determinants of malaria vaccination across all five domains of the consolidated framework for implementation research (CFIR) were identified. A causal loop diagram showed that these factors are interconnected and interrelated, identifying nine reinforcing loops and two balancing loops. As additional countries in Africa prepare for a malaria vaccine roll-out, it is pertinent to ensure that they have access to adequate information about the implementation context of countries that are already implementing malaria vaccination programs so that they understand the potential barriers and facilitators. This information can be used to inform context-specific systems enhancement to maximize implementation success. Going forward, primary implementation studies that incorporate the causal loop diagram should be integrated into the malaria vaccine implementation program to enable immunization program managers and other key stakeholders to identify and respond to emerging implementation barriers in a timely and systematic manner, to improve overall implementation performance.

Positioning implementation science in national immunization programmes to improve coverage equity and advance progress toward Immunization Agenda 2030: An urgent global health imperative.

Despite the availability of effective vaccines for preventing common childhood infectious diseases, there is still significant disparities in access and utilization across many low- and middle-income countries (LMIC). The factors that drive these disparities are often multilevel, originating from individuals, health facilities, health systems and communities, and also multifaceted. Implementation science has emerged as a field to help address "know-do" gaps in health systems, and can play a significant role in strengthening immunization systems to understand and solve implementation barriers that limit access and uptake within their contexts. This article presents a reflexive perspective on how to position implementation research in immunization programmes to improve coverage equity. Furthermore, key points of synergy between implementation research and vaccination are highlighted, and some potential practice changes that can be applied within specific contexts were proposed. Using a human rights lens, it was concluded that the cost that is associated with implementation failure in immunization programmes is significant and unjust, and future directions for implementation research to optimize its application in practice settings have been recommended.

Informal health sector and routine immunization: making the case for harnessing the potentials of patent medicine vendors for the big catch-up to reduce zero-dose children in sub-Saharan Africa.

The COVID-19 pandemic caused a surge in the number of unimmunized and under-immunized children in Africa. The majority of unimmunized (or zero-dose) children live in hard-to-reach rural areas, urban slums, and communities affected by conflict where health facilities are usually unavailable or difficult to access. In these settings, people mostly rely on the informal health sector for essential health services. Therefore, to reduce zero-dose children, it is critical to expand immunization services beyond health facilities to the informal health sector to meet the immunization needs of children in underserved places. In this perspective article, we propose a framework for the expansion of immunization services through the informal health sector as one of the pillars for the big catch-up plan to improve coverage and equity. In African countries like Nigeria, Ethiopia, Tanzania, and the Democratic Republic of Congo, patent medicine vendors serve as an important informal health sector provider group, and thus, they can be engaged to provide immunization services. A hub-and-spoke model can be used to integrate patent medicine vendors into the immunization system. A hub-and-spoke model is a framework for organization design where services that are provided by a central facility (hub) are complimented by secondary sites (spokes) to optimize access to care. Systems thinking approach should guide the design, implementation, and evaluation of this model.

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.

Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.

The impact of DNA methylation as a factor of Adverse Pregnancy and Birth Outcomes (APBOs): a systematic review protocol.

BACKGROUND: Deoxyribonucleic acid (DNA) methylation is one of the epigenetic modifications that has gained a lot of interest as a factor influencing fetal programming and as a biomarker for adverse pregnancy and birth outcomes (APBOs). Epidemiological studies have demonstrated that DNA methylation can result in adverse pregnancy and birth outcomes (APBOs) including miscarriage, intrauterine growth restriction (IUGR), low birth weight (LBW), sepsis, and preterm birth (PTB), which may later result in diseases in adulthood. However, the mechanism by which DNA methylation influences these APBOs remains unclear. The systematic review will assess the association between global and gene-specific DNA methylation with adverse pregnancy outcomes. METHOD: The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 checklist will be followed when conducting this systematic review. To develop the search strategy the PI(E)COS (population, intervention/exposure, comparator/control, outcome, and study designs) framework will be followed. Thus far, the research team has retrieved 4721 from Cochrane Library, PubMed, Web of Sciences, and MEDLINE. Out of these, 584 studies have been screened for eligibility, and approximately 124 studies meet the inclusion criteria. Pending the search results identified from the grey literature. For identification of unpublished studies in journals indexed in electronic databases, Google Scholar will be used. I.M and A.S will separately extract data from the articles and screen them, if there are any disagreements between I.M and A.S, then the L.M will resolve them. The methodological quality and bias risk of the included studies will be evaluated using the Critical Appraisal Skill Programme CASP) checklist. [Formula: see text] and [Formula: see text] alpha = 0.10 statistic will be used for assessing statistical heterogeneity between studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess and grade the overall quality of extracted data. ETHICS AND DISSEMINATION: Ethical approval is not required. The systematic review will assess available literature on possible associations between DNA methylation with adverse pregnancy and birth outcomes (APBOs) including LBW, IUGR, miscarriage, sepsis, and PTB. The findings could help guide future research assessing DNA methylation and other APBOs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRCRD42022370647.

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.

Socio-Demographic Factors Influencing Malaria Vaccine Acceptance for Under-Five Children in a Malaria-Endemic Region: A Community-Based Study in the Democratic Republic of Congo.

Two novel vaccines against malaria are proposed as a complementary control tool to prevent and reduce Plasmodium falciparum related disease and death in under-five children from moderate to high malaria transmission regions. The Democratic Republic of Congo (DRC) has committed to eradicate malaria by 2030, and significant efforts have been deployed to strengthen control and elimination measures. We aimed to understand factors influencing the malaria vaccine acceptability among the general population in eastern DRC. We conducted a survey among adult Congolese in Bukavu in March 2022. The questionnaire was adapted from the Behavioral and Social Drivers of vaccine uptake (BeSD) framework and was administered online and physically. Multivariate logistic regressions were built, and estimates were represented as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95%CI). Out of 1612 adults (median age: 39 years, 46.15% female) surveyed, only 7.26% were aware of the malaria vaccine. However, 46.53% expressed willingness to vaccinate themselves, and 52.60% were open to vaccinating their under-five children. Adjusting for confounding factors, non-student/non-healthcare worker professions (aOR = 0.58, 95%CI [0.42-0.78]) and middle-income status (aOR = 1.87, 95%CI [1.25-2.80]) were significantly associated with self-vaccination acceptance. Age played a role in under-five child vaccination acceptability, with 25 to over 64 years showing increased acceptability compared to the 18-24 age group. Additionally, non-student/non-healthcare worker professions (aOR = 1.88, 95%CI [1.37-2.59]), medium education levels (aOR = 2.64, 95%CI [1.29-5.79]), and residing in semi-rural areas (aOR = 1.63, 95%CI [1.27-2.10]) were predictors of under-five child vaccination acceptance. The acceptability of the malaria vaccine for self and for under-five children was suboptimal for effective malaria control in this community in the DRC. Our study constitutes a call for the Expanded Program on Immunization to closely work with various stakeholders to strengthen risk communication for community engagement prior to and during the introduction of this novel and lifesaving tool, malaria vaccination.

COVID-19 Vaccine Hesitancy and Associated Oral Cholera Vaccine Hesitancy in a Cholera-Endemic Country: A Community-Based Cross-Sectional Study in the Democratic Republic of Congo.

COVID-19 vaccine hesitancy and its enablers shape community uptake of non-covid vaccines such as the oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera-endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included demographics, intention to take OCV and COVID-19 vaccines, reasons for COVID-19 hesitancy, and thoughts and feelings about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude prevalence ratio, [cPR] = 1.12, 95%CI [1.03-1.21]). Independent predictors of OCV hesitancy were living in a semi-urban area (adjusted prevalence ratio [aPR] = 1.10, 95%CI [1.03-1.12]), religious refusal of vaccines (aPR = 1.06, 95%CI [1.02-1.12]), concerns about vaccine safety (aPR = 1.05, 95%CI [1.01-1.11]) and adverse effects (aPR = 1.06, 95%CI [1.01-1.12]), as well as poor vaccine literacy (aPR = 1.07, 95%CI [1.01-1.14]). Interestingly, the belief in COVID-19 vaccine effectiveness reduced OCV hesitancy by 24% (aPR = 0.76, 95%CI [0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibited a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy and trust-building interventions would likely improve the introduction of novel non-COVID-19 vaccines in the post-COVID-19 era.

Essential roles for imuA'- and imuB-encoded accessory factors in DnaE2-dependent mutagenesis in Mycobacterium tuberculosis.

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 beta-clamp. Moreover, disruption of the ImuB-beta 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 alpha-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.

Cholera vaccine clinical trials: A cross-sectional analysis of clinical trials registries.

Cholera has been one of the world's biggest public health challenges for centuries. The presence of this disease brings into focus the social determinants of health in different parts of the world. Research and development efforts to find safe and effective Cholera vaccines are critical to decreasing the disease burden from Vibrio cholerae. We searched the International Clinical Trials Registry Platform (ICTRP) and Cochrane Central Register of Controlled Trials (CENTRAL) on 5 March 2023. We included all registered randomized trials studying Cholera vaccines. We used Microsoft Excel to perform a descriptive analysis of the source registry, geographic distribution, recruitment status, phase of trials, and type of trial sponsor and presented the findings using tables and graphs. The search of ICTRP yielded 84 trials, and 315 trials were identified from CENTRAL. Seventy-four trials were included in the analysis. Most of the trials (66%, n = 49) were registered in ClinicalTrials.gov, followed by Clinical Trials Registry - India (9%, n = 7) and the Cuban Public Registry of Clinical Trials (8%, n = 6). The geographical distribution of the trials indicates that 48% (n = 36) of the trials were conducted in Asia, followed by 23% (n = 17) in North America, 15% (n = 11) in Africa, and 11% (n = 8) in Europe. Results further indicate that 81% (n = 60) of trials have a recruitment status "Not recruiting," followed by 12% (n = 9) with a status "recruiting." With the recent surge in Cholera cases and the limited supply of Cholera vaccines, research indicates the need for Cholera vaccine trials to ensure the availability of vaccines, especially in populations affected.