Perceptions toward Ebola vaccination and correlates of vaccine uptake among high-risk community members in North Kivu, Democratic Republic of the Congo.

The tenth Ebola Virus Disease (EVD) outbreak (2018-2020, North Kivu, Ituri, South Kivu) in the Democratic Republic of the Congo (DRC) was the second-largest EVD outbreak in history. During this outbreak, Ebola vaccination was an integral part of the EVD response. We evaluated community perceptions toward Ebola vaccination and identified correlates of Ebola vaccine uptake among high-risk community members in North Kivu, DRC. In March 2021, a cross-sectional survey among adults was implemented in three health zones. We employed a sampling approach mimicking ring vaccination, targeting EVD survivors, their household members, and their neighbors. Outbreak experiences and perceptions toward the Ebola vaccine were assessed, and modified Poisson regression was used to identify correlates of Ebola vaccine uptake among those offered vaccination. Among the 631 individuals surveyed, most (90.2%) reported a high perceived risk of EVD and 71.6% believed that the vaccine could reduce EVD severity; however, 63.7% believed the vaccine had serious side effects. Among the 474 individuals who had been offered vaccination, 397 (83.8%) received the vaccine, 180 (45.3%) of those vaccinated received the vaccine after two or more offers. Correlates positively associated with vaccine uptake included having heard positive information about the vaccine (RR 1.30, 95% CI 1.06-1.60), the belief that the vaccine could prevent EVD (RR 1.23, 95% CI 1.09-1.39), and reporting that religion influenced all decisions (RR 1.13, 95% CI 1.02-1.25). Ebola vaccine uptake was high in this population, although mixed attitudes and vaccine delays were common. Communicating positive vaccine information, emphasizing the efficacy of the Ebola vaccine, and engaging religious leaders to promote vaccination may aid in increasing Ebola vaccine uptake during future outbreaks.

Ebola vaccine uptake and attitudes among healthcare workers in North Kivu, Democratic Republic of the Congo, 2021.

Introduction: During the 2018-2020 Ebola virus disease (EVD) outbreak in the eastern part of the Democratic Republic of the Congo (DRC), prevention and control measures, such as Ebola vaccination were challenging by community mistrust. We aimed to understand perceptions regarding Ebola vaccination and identify determinants of Ebola vaccine uptake among HCWs. Methods: In March 2021, we conducted a cross-sectional survey among 438 HCWs from 100 randomly selected health facilities in three health zones (Butembo, Beni, Mabalako) affected by the 10th EVD outbreak in North Kivu, DRC. HCWs were eligible if they were ≥ 18 years and were working in a health facility during the outbreak. We used survey logistic regression to assess correlates of first-offer uptake (i.e., having received the vaccine the first time it was offered vs. after subsequent offers). Results: Of the 438 HCWs enrolled in the study, 420 (95.8%) reported that they were eligible and offered an Ebola vaccine. Among those offered vaccination, self-reported uptake of the Ebola vaccine was 99.0% (95% confidence interval (CI) [98.5-99.4]), but first-offer uptake was 70.2% (95% CI [67.1, 73.5]). Nearly all HCWs (94.3%; 95% CI [92.7-95.5]) perceived themselves to be at risk of contracting EVD. The most common concern was that the vaccine would cause side effects (65.7%; 95% CI [61.4-69.7]). In the multivariable analysis, mistrust of the vaccine source or how the vaccine was produced decreased the odds of first-time uptake. Discussion: Overall uptake of the Ebola vaccine was high among HCWs, but uptake at the first offer was substantially lower, which was associated with mistrust of the vaccine source. Future Ebola vaccination efforts should plan to make repeated vaccination offers to HCWs and address their underlying mistrust in the vaccines, which can, in turn, improve community uptake.

COVID-19 Vaccine Perceptions among Ebola-Affected Communities in North Kivu, Democratic Republic of the Congo, 2021.

Populations affected by humanitarian crises and emerging infectious disease outbreaks may have unique concerns and experiences that influence their perceptions toward vaccines. In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated with vaccine intention among 631 community members (CMs) and 438 healthcare workers (HCWs) affected by the 2018-2020 Ebola Virus Disease outbreak in North Kivu, Democratic Republic of the Congo. A multivariable logistic regression was used to identify correlates of vaccine intention. Most HCWs (81.7%) and 53.6% of CMs felt at risk of contracting COVID-19; however, vaccine intention was low (27.6% CMs; 39.7% HCWs). In both groups, the perceived risk of contracting COVID-19, general vaccine confidence, and male sex were associated with the intention to get vaccinated, with security concerns preventing vaccine access being negatively associated. Among CMs, getting the Ebola vaccine was associated with the intention to get vaccinated (RR 1.43, 95% CI 1.05-1.94). Among HCWs, concerns about new vaccines' safety and side effects (OR 0.72, 95% CI 0.57-0.91), religion's influence on health decisions (OR 0.45, 95% CI 0.34-0.61), security concerns (OR 0.52, 95% CI 0.37-0.74), and governmental distrust (OR 0.50, 95% CI 0.35-0.70) were negatively associated with vaccine perceptions. Enhanced community engagement and communication that address this population's concerns could help improve vaccine perceptions and vaccination decisions. These findings could facilitate the success of vaccine campaigns in North Kivu and similar settings.

Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer.

We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r = 0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy.

Genes with aberrant expression in murine preneoplastic intestine show epigenetic and expression changes in normal mucosa of colon cancer patients.

An understanding of early genetic/epigenetic changes in colorectal cancer would aid in diagnosis and prognosis. To identify these changes in human preneoplastic tissue, we first studied our mouse model in which Mthfr⁺/⁻ BALB/c mice fed folate-deficient diets develop intestinal tumors in contrast to Mthfr⁺/⁺ BALB/c mice fed control diets. Transcriptome profiling was performed in normal intestine from mice with low or high tumor susceptibility. We identified 12 upregulated and 51 downregulated genes in tumor-prone mice. Affected pathways included retinoid acid synthesis, lipid and glucose metabolism, apoptosis and inflammation. We compared murine candidates from this microarray analysis, and murine candidates from an earlier strain-based comparison, with a set of human genes that we had identified in previous methylome profiling of normal human colonic mucosa, from colorectal cancer patients and controls. From the extensive list of human methylome candidates, our approach uncovered five orthologous genes that had shown changes in murine expression profiles (PDK4, SPRR1A, SPRR2A, NR1H4, and PYCARD). The human orthologs were assayed by bisulfite-pyrosequencing for methylation at 14 CpGs. All CpGs exhibited significant methylation differences in normal mucosa between colorectal cancer patients and controls; expression differences for these genes were also observed. PYCARD and NR1H4 methylation differences showed promise as markers for presence of polyps in controls. We conclude that common pathways are disturbed in preneoplastic intestine in our animal model and morphologically normal mucosa of patients with colorectal cancer, and present an initial version of a DNA methylation-based signature for human preneoplastic colon.

Epigenetic differences in normal colon mucosa of cancer patients suggest altered dietary metabolic pathways.

We have compared DNA methylation in normal colon mucosa between patients with colon cancer and patients without cancer. We identified significant differences in methylation between the two groups at 114 to 874 genes. The majority of the differences are in pathways involved in the metabolism of carbohydrates, lipids, and amino acids. We also compared transcript levels of genes in the insulin signaling pathway. We found that the mucosa of patients with cancer had significantly higher transcript levels of several hormones regulating glucose metabolism and significantly lower transcript levels of a glycolytic enzyme and a key regulator of glucose and lipid homeostasis. These differences suggest that the normal colon mucosa of patients with cancer metabolizes dietary components differently than the colon mucosa of controls. Because the differences identified are present in morphologically normal tissue, they may be diagnostic of colon cancer and/or prognostic of colon cancer susceptibility.

DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy.

We identified potential epigenetic biomarkers for chronic kidney disease progression by comparing site-specific DNA methylation levels in more than 14,000 genes between African American and Hispanic diabetes patients with end stage renal disease (ESRD) and diabetes patients without nephropathy. We identified 187 genes that are differentially methylated between the two groups on at least two CpG sites in each gene in DNA extracted from saliva. Of the 187 genes whose mean methylation levels differed between the two groups, 39 genes, or closely related gene family members, have been reported to be involved in kidney development or diabetic nephropathy, per se, or have been associated with dialysis-induced changes in gene expression in peripheral blood cells. The fact that such a substantial fraction (21%) of the 187 candidate genes have been implicated previously through genome association or transcription profiling studies suggests strongly that the DNA methylation differences we observe are associated with disease predisposition and/or treatment. The fact that these nephropathy and/or dialysis-associated differences between patients were identified in DNA extracted from saliva offers proof-of-principle that inter-individual epigenetic differences may prove useful as predictive biomarkers of disease susceptibility.