Hepatitis B Virus Prevalence and Transmission in the Households of Pregnant Women in Kinshasa, Democratic Republic of Congo.

Background: The World Health Organization Africa region has high regional hepatitis B virus (HBV) prevalence, and evidence suggests more frequent horizontal HBV transmission than other regions. Context-specific epidemiological studies are needed to inform additional HBV prevention measures. Methods: In the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care in high-volume maternity clinics in Kinshasa, Democratic Republic of Congo. We recruited households of pregnant women ("index mothers") who were HBsAg-positive and HBsAg-negative, defining households as index-positive and index-negative, respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1006 participants from 200 households (100 index-positive, 100 index-negative) across Kinshasa. HBsAg-positivity prevalence was more than twice as high in index-positive households (5.0% [95% confidence interval {CI}, 2.8%-7.1%]) as in index-negative households (1.9% [95% CI, .6%-3.2%]). HBsAg-positivity prevalence was 3.3 (95% CI, .9-11.8) times as high among direct offspring in index-positive versus index-negative households. Factors associated with HBsAg positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among offspring in index-positive households. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

Hepatitis B virus prevalence and transmission in the households of pregnant women in Kinshasa, Democratic Republic of Congo.

Background: Despite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC's capital, Kinshasa, to inform additional prevention efforts. Methods: We introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as "exposed" and "unexposed," respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

Metagenomic Detection of Divergent Insect- and Bat-Associated Viruses in Plasma from Two African Individuals Enrolled in Blood-Borne Surveillance.

Metagenomic next-generation sequencing (mNGS) has enabled the high-throughput multiplexed identification of sequences from microbes of potential medical relevance. This approach has become indispensable for viral pathogen discovery and broad-based surveillance of emerging or re-emerging pathogens. From 2015 to 2019, plasma was collected from 9586 individuals in Cameroon and the Democratic Republic of the Congo enrolled in a combined hepatitis virus and retrovirus surveillance program. A subset (n = 726) of the patient specimens was analyzed by mNGS to identify viral co-infections. While co-infections from known blood-borne viruses were detected, divergent sequences from nine poorly characterized or previously uncharacterized viruses were also identified in two individuals. These were assigned to the following groups by genomic and phylogenetic analyses: densovirus, nodavirus, jingmenvirus, bastrovirus, dicistrovirus, picornavirus, and cyclovirus. Although of unclear pathogenicity, these viruses were found circulating at high enough concentrations in plasma for genomes to be assembled and were most closely related to those previously associated with bird or bat excrement. Phylogenetic analyses and in silico host predictions suggested that these are invertebrate viruses likely transmitted through feces containing consumed insects or through contaminated shellfish. This study highlights the power of metagenomics and in silico host prediction in characterizing novel viral infections in susceptible individuals, including those who are immunocompromised from hepatitis viruses and retroviruses, or potentially exposed to zoonotic viruses from animal reservoir species.

Purifying selection decreases the potential for Bangui orthobunyavirus outbreaks in humans.

Pathogens carried by insects, such as bunyaviruses, are frequently transmitted into human populations and cause diseases. Knowing which spillover events represent a public health threat remains a challenge. Metagenomic next-generation sequencing (mNGS) can support infectious disease diagnostics by enabling the detection of any pathogen from clinical specimens. mNGS was performed on blood samples to identify potential viral coinfections in human immunodeficiency virus (HIV)-positive individuals from Kinshasa, the Democratic Republic of the Congo (DRC), participating in an HIV diversity cohort study. Time-resolved phylogenetics and molecular assay development assisted in viral characterization. The nearly complete genome of a novel orthobunyavirus related to Nyangole virus, a virus previously identified in neighboring Uganda, was assembled from a hepatitis B virus-positive patient. A quantitative polymerase chain reaction assay was designed and used to screen >2,500 plasma samples from Cameroon, the DRC, and Uganda, failing to identify any additional cases. The recent sequencing of a US Center for Disease Control Arbovirus Reference Collection revealed that this same virus, now named Bangui virus, was first isolated in 1970 from an individual in the Central African Republic. Time-scaled phylogenetic analyses of Bangui with the related Anopheles and Tanga serogroup complexes indicate that this virus emerged nearly 10,000 years ago. Pervasive and episodic models further suggest that this virus is under purifying selection and that only distant common ancestors were subject to positive selection events. This study represents only the second identification of a Bangui virus infection in over 50 years. The presumed rarity of Bangui virus infections in humans can be explained by its constraint to an avian host and insect vector, precluding efficient transmission into the human population. Our results demonstrate that molecular phylogenetic analyses can provide insights into the threat posed by novel or re-emergent viruses identified by mNGS.

Changes in hepatitis B vaccine perception in response to the COVID-19 pandemic: Development of the Shift in vaccine confidence (SVC) survey tool.

The COVID-19 pandemic has disrupted access to, adherence to, and perceptions of routine vaccinations. We developed the Shift in Vaccine Confidence (SVC) survey tool to assess the impact of the pandemic on routine vaccinations, with a focus on the HBV vaccine, in Kinshasa, Democratic Republic of Congo (DRC). This study describes the content validation steps we conducted to ensure the survey tool is meaningful to measure changes in vaccine confidence to regular immunization (HBV vaccine) due to the pandemic. Three rounds of stakeholder feedback from a DRC-based study team, content and measurement experts, and study participants allowed us to produce a measure with improved readability and clarity.

Food insecurity in baccalaureate nursing students: A cross-sectional survey.

BACKGROUND: Food insecurity, the limited or uncertain availability of food, is reported in college students, but little is known about its prevalence in nursing students. Nursing students have extensive required clinical hours limiting their ability to work and spend money on academic and living expenses before spending on food. PURPOSE: To estimate the prevalence of food insecurity and characterize its relationship to social support and first-generation status among nursing students at a public university. METHODS: A cross-sectional survey study design was used to assess food security and social support in full-time nursing students (n=55). RESULTS: The prevalence of food insecurity reported by the survey respondents was 60%. Statistically significant correlations between food security and social support scores were found; as food security worsened, so did social support. Food-insecure students had lower grade point averages, and first-generation students (p=.001) reported food insecurity more frequently than did other participants. CONCLUSIONS: Findings support that food insecurity is negatively associated with academic performance, and level of social support may impact food insecurity in nursing students. Nursing programs should consider early assessments of cohorts to increase the potential for early intervention with food-insecure students. Collaboration with university-based food pantries and student engagement in hunger initiatives through the Student Nurses Association can support early interventions.

A high prevalence of potential HIV elite controllers identified over 30 years in Democratic Republic of Congo.

BACKGROUND: In-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates. METHODS: 10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting. FINDINGS: Our data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends. INTERPRETATION: Viral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression. FUNDING: Abbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

Nursing student's attitudes toward teams in an undergraduate interprofessional mass casualty simulation.

BACKGROUND: Interprofessional education (IPE) aims to prepare future nurses for collaboration with healthcare professionals. Army style lane training may be an effective pedagogical technique for delivering emergency care and mass casualty training while incorporating IPE. PURPOSE: This study sought to determine attitudes toward IPE and teamwork in pre-licensure, undergraduate nursing students following a lane training simulation. METHOD: Pre- and postsimulation surveys containing sociodemographic, reflection, and KidSIM Attitude Toward Teamwork in Training Undergoing Designed Educational Simulation (KidSIM) items (Sigalet et al., 2012) were conducted. RESULTS: The KidSIM tool was deemed reliable (α = .98). Paired sample t tests resulted in significant increases for the KiDSIM and its subscales, with the exception of communication. However, communication, along with situation assessment and teamwork were reported to be most enhanced by students. CONCLUSION: Results support using the Army lane training model in an IPE environment for teaching emergency care, triage, and mass casualty procedures.

Nursing Student Differences in Transcultural Self-Efficacy by Culture Curriculum: A Longitudinal Study.

INTRODUCTION: Longitudinal studies regarding educational strategies to help nursing students gain transcultural self-efficacy skills are limited. This study aimed to compare the long-term effects of an entry-level nursing culture course (ELNCC) on transcultural self-efficacy (TSE) in beginning nursing students with a graduating class who did not have the ELNCC. METHOD: Using a longitudinal, quasi-experimental time-series design, data were collected using Jeffreys's Transcultural Self-Efficacy Tool (TSET) from the experimental group (n = 106) pre- and post-ELNCC, end of second semester, and program exit. A control group of 62 senior nursing students who did not take the ELNCC were administered the TSET once, at graduation. RESULTS: All posttest scores were significantly higher than pretest scores in overall TSE, cognitive, practical, and affective dimensions. At graduation, the experimental group's scores were significantly higher than those of the control group in all dimensions except the affective. DISCUSSION: This study supports the early introduction of a separate culture course with field components to teach TSE to nursing students.

Cultivating Cultural Competence Through Academic Community Engagement and Clinical Reflection.

INTRODUCTION: Nursing curriculum must include unique ways to enhance students' cultural sensitivity to ensure the provision of culturally competent care to our diverse populations. Academic community engagement (ACE) is a pedagogy used to teach course concepts through service. METHODOLOGY: This was a qualitative study analyzing nursing students' written reflective journals following their service at a Native American powwow using Lincoln and Guba's model. The purpose was to examine if the ACE experience influenced their development of cultural sensitivity. RESULTS: Reflective journals of 34 first-semester nursing students, enrolled in a nursing specific culture course, were analyzed. Three themes were identified: (a) engagement, (b) cultural sensitivity, and (c) humility and altruism. DISCUSSION: The development of self-awareness and the revelation by students of the importance of culturally sensitive care was a key finding supporting the use of ACE as a reliable teaching strategy in nursing education.

Increased HIV in Greater Kinshasa Urban Health Zones: Democratic Republic of Congo (2017-2018).

BACKGROUND: Diagnosis of people living with HIV (PLHIV) is the first step toward achieving the new Fast Track Strategy to end AIDS by 2030: 95-95-95. However, reaching PLHIV is especially difficult in resource-limited settings such as the Democratic Republic of Congo (DRC), where reliable prevalence data is lacking. This study evaluated the prevalence of HIV in patients in the urban Kinshasa area. METHODS: Individuals seeking healthcare were tested for HIV between February 2017 and July 2018 at existing Kinshasa urban clinics. The study was conducted in two phases. Case finding was optimized in a pilot study phase using a modified cell phone-based Open\Data Kit (ODK) collection system. HIV prevalence was then determined from data obtained between March-July of 2018 from 8320 individuals over the age of 18 years receiving care at one of 47 clinics in Kinshasa. RESULTS: The prevalence of HIV in our study was 11.0% (95% CI 10.3-11.6%) overall and 8.14% in the subset of N = 1240 participants who were healthy mothers seeking prenatal care. These results are in sharp contrast to President's Emergency Plan for AIDS Relief (PEPFAR) estimates of 2.86%, but are consistent with data from surrounding countries. CONCLUSION: While this data is sub-national and reflects an urban healthcare setting, given the large population of Kinshasa and rapidly changing age demographics, the results suggest that HIV prevalence in the DRC is substantially higher than previously reported.

Comparison of Two Methods of Teaching Culture to Bachelor of Science in Nursing Students.

BACKGROUND: The nursing literature examining effective methods to teach transcultural self-efficacy demonstrates inconsistent findings. This study evaluated the effectiveness of a nursing stand-alone culture course with concurrent field experiences compared with the standard integrated culture content in the curriculum in increasing transcultural self-efficacy in nursing students. METHOD: This quasi-experimental, static-group comparison used the Transcultural Self-Efficacy Tool to measure outcomes. The treatment group consisted of first-semester nursing students (n = 53) enrolled in a pilot 2-credit culture course. The control group consisted of graduating senior nursing students (n = 19) who had culture integrated throughout the curriculum. RESULTS: The posttest of the first-semester students in the treatment group scored higher than either their pretest or the graduating senior students (control group). CONCLUSION: The stand-alone culture course had a greater positive effect than the integrated culture content on students' transcultural self-efficacy. [J Nurs Educ. 2018;57(10):609-613.].

Development of a fluorescence polarization bead-based coupled assay to target different activity/conformation states of a protein kinase.

Most of the protein kinase inhibitors being developed are directed toward the adenosine triphosphate (ATP) binding site that is highly conserved in many kinases. A major issue with these inhibitors is the specificity for a given kinase. Structure determination of several kinases has shown that protein kinases adopt distinct conformations in their inactive state, in contrast to their strikingly similar conformations in their active states. Hence, alternative assay formats that can identify compounds targeting the inactive form of a protein kinase are desirable. The authors describe the development and optimization of an Immobilized Metal Assay for Phosphochemicals (IMAP)-based couple d assay using PDK1 and inactive Akt-2 enzymes. PDK1 phosphorylates Akt-2 at Thr 309 in the catalytic domain, leading to enzymatic activation. Activation of Akt by PDK1 is measured by quantitating the phosphorylation of Akt-specific substrate peptide using the IMAP assay format. This IMAP-coupled assay has been formatted in a 384-well microplate format with a Z' of 0.73 suitable for high-throughput screening. This assay was evaluated by screening the biologically active sample set LOPAC trade mark and validated with the protein kinase C inhibitor staurosporine. The IC(50) value generated was comparable to the value obtained by the radioactive (33)P-gamma-ATP flashplate transfer assay. This coupled assay has the potential to identify compounds that target the inactive form of Akt and prevent its activation by PDK1, in addition to finding inhibitors of PDK1 and activated Akt enzymes.

Exploring the role of bromine at C(10) of (+)-4-[2-[4-(8-chloro-3,10-dibromo- 6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-piperidinyl]-2- oxoethyl]-1-piperidinecarboxamide (Sch-66336): the discovery of indolocycloheptapyridine inhibitors of farnesyl protein transferase.

The 10-bromobenzocycloheptapyridyl farnesyl transferase inhibitor (FTI) Sch-66336 (1) is currently under clinical evaluation for the treatment of human cancers. During structure-activity relationship development leading to 1, 10-bromobenzocycloheptapyridyl FTIs were found to be more potent than analogous compounds lacking the 10-Br substituent. This potency enhancement was believed to be due, in part, to an increase in conformational rigidity as the 10-bromo substituent could restrict the conformation of the appended C(11) piperidyl substituent in an axial orientation. A novel and potent class of FTIs, represented by indolocycloheptapyridine Sch-207758 [(+)-10a], have been designed based on this principle. Although structural and thermodynamic results suggest that entropy plays a crucial role in the increased potency observed with (+)-10a through conformational constraints and solvation effects, the results also indicate that the indolocycloheptapyridine moiety in (+)-10a provides increased hydrophobic interactions with the protein through the addition of the indole group. This report details the X-ray structure and the thermodynamic and pharmacokinetic profiles of (+)-10a, as well as the synthesis of indolocycloheptapyridine FTIs and their potencies in biochemical and biological assays.