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Abstract Background Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. Methods Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13–18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. Results The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. Conclusion Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

Summary: Background: Canadian Arctic communities have experienced sustained syphilis transmission, with diagnoses rates 18-times higher than the national average. Remoteness from laboratory facilities leads to delays between syphilis screening and treatment, contributing to onward transmission. Rapid diagnostic tests can eliminate treatment delays via testing at the point-of-care. This study aims to describe syphilis diagnostic gaps and to estimate the impact of introducing rapid diagnostic tests at the point-of-care on syphilis transmission. Methods: To assess the population-level impact of deploying rapid diagnostic tests, an individual-based model was developed using detailed surveillance data, population surveys, and a prospective diagnostic accuracy field study. The model was calibrated to syphilis diagnoses (2017–2022) from a community of approximately 1,050 sexually active individuals. The impacts of implementing rapid diagnostic tests using whole blood (sensitivity: 92% for infectious and 81% for non-infectious syphilis; specificity: 99%) from 2023 onward was calculated using the annual median fraction of cumulative new syphilis infections averted over 2023–2032. Findings: The median modeled syphilis incidence among sexually active individuals was 44 per 1,000 in 2023. Males aged 16–30 years exhibited a 51% lower testing rate than that of their female counterparts. Maintaining all interventions constant at their 2022 levels, implementing rapid diagnostic tests could avert a cumulative 33% (90% credible intervals: 18–43%) and 37% (21–46%) of new syphilis infections over 5 and 10 years, respectively. Increasing testing rates and contact tracing may enhance the effect of rapid diagnostic tests. Interpretation: Implementing rapid diagnostic tests for syphilis in Arctic communities could reduce infections and enhance control of epidemics. Such effective diagnostic tools could enable rapid outbreak responses by providing same-day testing and treatment at the point-of-care. Funding: Canadian Institutes of Health Research.

Haemophilus influenzae serotype a (Hia) has recently emerged as an important cause of invasive disease in the North American Arctic and Sub-Arctic regions, mainly affecting young Indigenous children. In this study, we addressed the question of whether the prevalence of Hia and all H. influenzae in the nasopharynx differed between paediatric populations from regions with high versus low incidence of invasive Hia disease. Nasopharyngeal specimens from children with acute respiratory tract infections (ARTI) collected for routine diagnostic detection of respiratory viruses were analysed with molecular-genetic methods to identify and serotype H. influenzae. In Nunavut, a region with a high incidence of invasive Hia disease, all H. influenzae and particularly Hia were found in the nasopharynx of 60.6% and 3.0% children. In Southern Ontario (Hamilton region), where Hia invasive disease is rare, the frequencies of all H. influenzae and Hia detection were 38.5% and 0.6%, respectively. In both cohorts, non-typeable H. influenzae was prevalent (57.0% and 37.9%, respectively). Considering that Hia is an important cause of severe invasive disease in Nunavut children, 3% prevalence of Hia among children with ARTI can reflect continuing circulation of the pathogen in the Northern communities that may result in invasive disease outbreaks.

Abstract Background and objectives Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). Methods We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults

Objectives . Preterm infants are at risk of hypothermia. This study described the available infant warming devices (IWDs) and explored the barriers and facilitators to their implementation in neonates in Malawi. Methods . A qualitative descriptive study was conducted among 19 health care workers in Malawi from January to March 2020. All interviews were digitally recorded, transcribed, and managed using NVivo and analyzed using a thematic approach. Results . The warming devices included radiant warmers, Blantyre hot-cots, wall-mounted heaters, portable warmers, and incubators. Inadequate equipment and infrastructure and gaps in staff knowledge and capacity were reported as the main challenges to optimal IWD implementation. Caregiver acceptance was described as the main facilitator. Strategies to optimize implementation of IWD included continuous practical training and adequate availability of equipment and spare parts. Conclusion . Implementation of warming devices for the management of neonatal hypothermia is effective when there are adequate human and material resources.

The aim of this study was to examine the factors associated with mental health outcomes in school staff during the second year of the COVID-19 pandemic. Adapting the Transactional Model of Stress and Coping, we tested whether school staff who lived with others and adopted healthier behaviours (e.g., diet, physical activity) would be more likely to manage pandemic stressors, altering mental health outcomes. The current study included 2,343 school staff (60% teachers) from the greater Vancouver area in British Columbia, Canada, who completed the online questionnaire between February 3 and June 18, 2021 as part of a longitudinal study of COVID-19 impacts on schools. Results showed that participants’ perceived risk of getting COVID-19 was associated with poorer mental health among both male and female school staff. Furthermore, when perceived risk of COVID-19 was low, living with others reduced the negative impact of pandemic stressors on anxiety symptoms and dispositional optimism among female school staff. We detected no influence of health behaviours on the associations between stressors and mental health. Favorable health behaviours were also associated with lower anxiety and psychological distress among female school staff. These findings underlie the importance of proactive prevention and intervention strategies to address the mental health of school staff.

Abstract As part of the COVID-19 pandemic, clinical laboratories have been faced with massive increases in testing, resulting in sample collection systems, reagent, and staff shortages. We utilized self-collected saline gargle samples to optimize high throughput SARS-CoV-2 multiplex polymerase chain reaction (PCR) testing in order to minimize cost and technologist time. This was achieved through elimination of nucleic acid extraction and automation of sample handling on a widely available robotic liquid handler, Hamilton STARlet. A customized barcode scanning script for reading the sample ID by the Hamilton STARlet’s software system was developed to allow primary tube sampling. Use of pre-frozen SARS-CoV-2 assay reaction mixtures reduced assay setup time. In both validation and live testing, the assay produced no false positive or false negative results. Of the 1060 samples tested during validation, 3.6% (39/1060) of samples required retesting as they were either single gene positive, had internal control failure or liquid aspiration error. Although the overall turnaround time was only slightly faster in the automated workflow (185 min vs 200 min), there was a 76% reduction in hands-on time, potentially reducing staff fatigue and burnout. This described process from sample self-collection to automated direct PCR testing significantly reduces the total burden on healthcare systems in terms of human resources and reagent requirements.

Summary: Background: The COVID-19 pandemic has perturbed the seasonality of respiratory syncytial virus (RSV) infections. However, we lack data on how this impacted the severity of paediatric RSV cases. The objective of this study was to describe the clinical severity of RSV cases before, during and after pandemic measures in British Columbia (BC), Canada. Methods: Retrospective study of RSV cases from September 1st, 2017 to May 15th, 2023, with a review of RSV outcomes in children below 18 years old at BC's paediatric hospital. Temporal changes in RSV cases and hospitalisations were quantified using interrupted time series. Findings: BC experienced only 11 RSV cases (from 95,266 tests) between September 2020 and August 2021. This was followed by a resurgence of 9,529 RSV cases (219,566 tests [4.3% positive tests]) in 2021–22 and 8,215 cases (124,449 tests [6.6% positive tests]) in 2022–23, increased compared to 1,750 cases (48,664 tests [3.6% positive tests]) per corresponding yearly period in 2017–20. From September 2017 to May 2023, the median age of children with RSV at BC Children's Hospital increased from 8.7 [IQR: 2.0–26.0] to 19.6 [3.9–43.7] months per yearly period. More children were hospitalised in 2022–23 (n = 360), compared to 2017–20 (n = 168 per period) and 2021–22 (n = 172). However, we detected no increase in hospitalisations or ICU admissions in children born prematurely or with chronic cardiorespiratory conditions. Interpretation: The increased detection of symptomatic RSV cases in older children in 2021–22 and increased RSV-related hospitalisations in 2022–23 suggest a gradual increase in the pool of immunologically vulnerable children due to a prolonged lack of viral exposure. Funding: Government of Canada via its COVID-19 Immunity Task Force.

Background: Increasing the interval between the first and second SARS-CoV-2 vaccine doses enhances vaccine immunogenicity, however the optimal timing of the third vaccine is unknown. In this study, we investigated how the time interval between the first and second (V1–V2), or second and third (V2–V3) doses affects immunogenicity after three doses of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine. Methods: This is an observational cohort consisting of 360 participants enrolled in the COVID-19 Occupational Risks, Seroprevalence, and Immunity among Paramedics in Canada (CORSIP) study. Immune responses to BA.1 and other variants were measured from serum using an ACE2 competitive binding assay for surrogate SARS-CoV-2 neutralization. We fit a multiple linear regression model to estimate the independent association between both the V1–V2 and V2–V3 intervals and serum SARS-CoV-2 neutralization, while adjusting for age, sex, and the V3-to-blood collection interval. We examined vaccine dosing intervals as continuous variables and categorized them into quartiles. Results: The mean age was 40 years, 45% were female sex (at birth), and the median BA.1 surrogate neutralization was 61% (IQR 38–77%). The multivariate analysis indicated that longer V1–V2 (β = 0.1292, 95% CI: 0.04807–0.2104) and V2–V3 (β = 0.2653, 95% CI: 0.2291–0.3015) intervals were associated with increased surrogate neutralization of BA.1. These results were consistent when examining responses against Spike from other SARS-CoV-2 strains. When categorized into V2–V3 quartiles, the first (56–231 days), and second (231–266 days) quartiles demonstrated decreased BA.1 surrogate neutralization compared to the longest V2–V3 quartile (282–329 days). There was no significant difference in surrogate neutralization between the long (266–282 days) and longest (282–329 days) V2–V3 intervals. Conclusion: Longer intervals between first, second and third doses are independently associated with increased immunogenicity for all tested SARS-CoV-2 strains. Increasing the intervals between the second and third vaccine doses up to 8.9 months provided additive benefits increasing the immunogenicity of BNT162b2 vaccine schedules.

ABSTRACT The World Health Organization recommends untargeted iron supplementation for women of reproductive age (WRA) in countries where anemia prevalence is greater than 40%, such as Cambodia. Iron supplements, however, often have poor bioavailability, so the majority remains unabsorbed in the colon. The gut houses many iron-dependent bacterial enteropathogens; thus, providing iron to individuals may be more harmful than helpful. We examined the effects of two oral iron supplements with differing bioavailability on the gut microbiomes in Cambodian WRA. This study is a secondary analysis of a double-blind, randomized controlled trial of oral iron supplementation in Cambodian WRA. For 12 weeks, participants received ferrous sulfate, ferrous bisglycinate, or placebo. Participants provided stool samples at baseline and 12 weeks. A subset of stool samples (n = 172), representing the three groups, were randomly selected for gut microbial analysis by 16S rRNA gene sequencing and targeted real-time PCR (qPCR). At baseline, 1% of women had iron-deficiency anemia. The most abundant gut phyla were Bacteroidota (45.7%) and Firmicutes (42.1%). Iron supplementation did not alter gut microbial diversity. Ferrous bisglycinate increased the relative abundance of Enterobacteriaceae, and there was a trend towards an increase in the relative abundance of Escherichia-Shigella. qPCR detected an increase in the enteropathogenic Escherichia coli (EPEC) virulence gene, bfpA, in the group that received ferrous sulfate. Thus, iron supplementation did not affect overall gut bacterial diversity in predominantly iron-replete Cambodian WRA, however, evidence does suggest an increase in relative abundance within the broad family Enterobacteriaceae associated with ferrous bisglycinate use. IMPORTANCE To the best of our knowledge, this is the first published study to characterize the effects of oral iron supplementation on the gut microbiomes of Cambodian WRA. Our study found that iron supplementation with ferrous bisglycinate increases the relative abundance of Enterobacteriaceae, which is a family of bacteria that includes many Gram-negative enteric pathogens like Salmonella, Shigella, and Escherichia coli. Using qPCR for additional analysis, we were able to detect genes associated with enteropathogenic E. coli, a type of diarrheagenic E. coli known to be present around the world, including water systems in Cambodia. The current WHO guidelines recommend blanket (untargeted) iron supplementation for Cambodian WRA despite a lack of studies in this population examining iron’s effect on the gut microbiome. This study can facilitate future research that may inform evidence-based global practice and policy.

Abstract Background Severe neonatal jaundice can result in long term morbidities and mortality when left untreated. Phototherapy is the main-stay intervention for treating moderate jaundice and for prevention of the development of severe jaundice. However, in resource-limited health care settings, phototherapy has been inconsistently used. The objective of this study is to evaluate barriers and facilitators for phototherapy to treat neonatal jaundice at Malawian hospitals. Methods We conducted a convergent mixed-method study comprised of a facility assessment and qualitative interviews with healthcare workers and caregivers in southern Malawi. The facility assessment was conducted at three secondary-level hospitals in rural districts. In-depth interviews following a semi-structured topic guide were conducted at a district hospital and a tertiary-level hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). Results The facility assessment found critical gaps in initiating and monitoring phototherapy in all facilities. Based on a total of 31 interviews, participants identified key challenges in diagnosing neonatal jaundice, counselling caregivers, and availability of infrastructure. Participants emphasized the need for transcutaneous bilirubinometers to guide treatment decisions. Caregivers were sometimes fearful of potential harmful effects of phototherapy, which required adequate explanation to mothers and family members in non-medical language. Task shifting and engaging peer support for caregivers with concerns about phototherapy was recommended. Conclusion Implementation of a therapeutic intervention is limited if accurate diagnostic tests are unavailable. The scale up of therapeutic interventions, such as phototherapy for neonatal jaundice, requires careful holistic attention to infrastructural needs, supportive services such as laboratory integration as well as trained human resources.

Abstract Background Human milk insufficiency is a significant barrier to implementing breastfeeding, and it is identified as a prevalent concern in 60–90% of mothers in low-and-middle-income countries. Breastmilk insufficiency can lead to hypoglycemia, hypernatremia, nutritional deficiencies, and failure to thrive in newborns and infants. Studies investigating the impact of breastfeeding interventions to improve milk production highlight inconsistencies between healthcare workers and mothers perceived support, as well as gaps in practical knowledge and training. The aim of this study was to determine perceptions surrounding human milk insufficiency from Malawian healthcare workers. Methods This study is a secondary analysis of 39 interviews with healthcare workers from one tertiary and three district hospitals in Malawi employing content analysis. Interviewed healthcare workers included nurses, clinical officers, midwives, and medical doctors. An inclusive coding framework was developed to identify themes related to human milk insufficiency, which were analyzed using an iterative process with NVivo12 software. Researchers focused on themes emerging from perceptions and reasons given by healthcare workers for human milk insufficiency. Results Inability to produce adequate breastmilk was identified as a prevalent obstacle mothers face in the early postpartum period in both district and tertiary facilities in Malawi. The main reasons given by participants for human milk insufficiency were mothers’ perceived normalcy of milk insufficiency, maternal stress, maternal malnutrition, and traditional beliefs around food and eating. Three focused solutions were offered by participants to improve mother’s milk production – improving education for mothers and training for healthcare providers on interventions to improve mother’s milk production, increasing breastfeeding frequency, and ensuring adequate maternal nutrition pre- and post-partum. Conclusion Health care workers perspectives shed light on the complexity of causes and solutions for human milk insufficiency in Malawi. This research highlights that a respectful professional relationship between health care workers and mothers is an essential bridge to improving communication, detecting human milk insufficiency early, and implementing appropriate interventions. The results of this study may help to inform research, clinical practice, and education in Malawi to improve human milk production.

Abstract Introduction Infections due to extended spectrum beta-lactamase producing organisms (ESBL) have emerged as the leading cause of sepsis among hospitalized neonates in Botswana and much of sub-Saharan Africa and south Asia. Yet, ESBL reservoirs and transmission dynamics within the neonatal intensive care unit (NICU) environment are not well-understood. This study aimed to assess the efficiency and feasibility of a chromogenic-culture-media-based environmental sampling approach to characterize the ESBL bioburden within a NICU. Methods A series of four point-prevalence surveys were conducted at a 36-bed NICU at a public tertiary referral hospital in Botswana from January-June 2021. Samples were collected on 4 occasions under semi-sterile technique using 1) flocked swabs & templates (flat surfaces); 2) sterile syringe & tubing (water aspiration); and 3) structured swabbing techniques (hands & equipment). Swabs were transported in physiological saline-containing tubes, vortexed, and 10 µL was inoculated onto chromogenic-agar that was selective and differential for ESBL (CHROMagar™ ESBL, Paris, France), and streaking plates to isolate individual colonies. Bacterial colonies were quantified and phenotypically characterized using biochemical identification tests. Results In total, 567 samples were collected, 248 (44%) of which grew ESBL. Dense and consistent ESBL contamination was detected in and around sinks and certain high-touch surfaces, while transient contamination was demonstrated on medical equipment, caregivers/healthcare worker hands, insects, and feeding stations (including formula powder). Results were available within 24–72 h of collection. To collect, plate, and analyse 50 samples, we estimated a total expenditure of $269.40 USD for materials and 13.5 cumulative work hours among all personnel. Conclusions Using basic environmental sampling and laboratory techniques aided by chromogenic culture media, we identified ESBL reservoirs (sinks) and plausible transmission vehicles (medical equipment, infant formula, hands of caregivers/healthcare workers, & insects) in this NICU environment. This strategy was a simple and cost-efficient method to assess ESBL bioburden and may be feasible for use in other settings to support ongoing infection control assessments and outbreak investigations.

With the growth of qualitative health research in low- and middle-income countries, local health professionals are increasingly involved in facilitating interviews with their fellow health workers. Understanding the methodological implications of such situations is required to ensure high-quality study findings and to build capacity and skills for interviewers with clinical backgrounds working with limited resources. This article reports a qualitative process evaluation of a study that assessed barriers and enablers of implementing bubble continuous positive airway pressure in Malawi. Findings were summarized through an iterative process of reflection on what worked, what did not work, areas for improvement, structural challenges, negotiating dual roles as nurses and researchers and the professional hierarchy within the health care system. Comprehensive practical training was critical to conducting qualitative research in a health setting. Interviewers were health workers themselves and required skills in reflexivity to effectively probe and navigate interviewing other health professionals, including senior staff. The main challenge in conducting interviews in a resource-limited healthcare setting was time constraints, which were compounded by staffing shortages. Lessons from this qualitative evaluation highlight the importance of training in reflexivity, engaging interviewers as collaborators and reserving adequate time to accommodate healthcare workers’ multiple roles and responsibilities.

Introduction: This study assessed the relationship between intention to receive a COVID-19 vaccine and intention to receive a seasonal influenza vaccine, as well as how intention to receive a COVID-19 vaccine has changed during the pandemic. Methods: Residents of British Columbia aged 25–69 years were invited to complete an online cross-sectional survey from August 2020 - March 2021. Mixed-effects logistic regression models assessed the relationship between intention to receive a COVID-19 vaccine and intention to receive the seasonal influenza vaccine. A generalized additive mixed model was used to investigate changes in COVID-19 vaccine intention during the pandemic (August 2020–March 2021). The relationship between intention to receive a COVID-19 vaccine and retrospective overall perceived value of vaccines prior to and during the pandemic was also considered. Results: Of 6,333 participants, 80.2 % of participants were ‘somewhat or very likely’ to receive a COVID-19 vaccine and 69 % of participants reported intending to receive a seasonal influenza vaccine. In multivariable modeling, intention to receive a COVID-19 vaccine was strongly associated with intention to receive a seasonal influenza vaccine (aOR = 4.25, 95 %CI 3.33–5.43). Intention to receive a COVID-19 vaccine increased over the study period (p

Abstract Background Exclusive breastfeeding is widely accepted as a key intervention with proven efficacy for improving newborn survival. Despite international commitments and targets to support and promote breastfeeding, there are still gaps in meeting and maintain coverage in many sub-Saharan African countries. This paper aimed to triangulate the perspectives of health workers, mothers, and their family members with facility assessments to identify gaps to improve breastfeeding support in in Malawi. Methods The study on breastfeeding barriers and facilitators was conducted in 2019 at one tertiary hospital and three secondary-level hospitals in Malawi. We conducted 61 semi-structured interviews with health workers, postnatal mothers, grandmothers, aunts, and fathers. In 2017, we carried out a neonatal care facility assessment using the World Health Organization (WHO) Integrated Maternal, Neonatal, and Child Quality of Care Assessment and Improvement Tool. Qualitative data were analysed using a thematic analysis approach within the Systems Framework for Health Policy. Results The district-level hospitals rated high with an average score of 4.8 out of 5 across the three facilities indicating that only minor improvements are needed to meet standards of care for early and exclusive breastfeeding. However, the score fell to an average of 3.5 out of 5 for feeding needs with sick neonates indicating that several improvements are needed in this area. The qualitative data demonstrated that breastfeeding was normalized as part of routine newborn care. However, the focus on routine practice and reliance on breastfeeding knowledge from prenatal counselling highlights inequities and neglect in specialized care and counselling among vulnerable mothers and newborns. Revitalisation of breastfeeding in Malawian facilities will require a systems approach that reinforces policies and guidelines; contextualises knowledge; engagement and empowerment of other relatives to the baby and task-sharing among health workers. Conclusions Breastfeeding is accepted as a social norm among health workers, mothers, grandmothers, aunts, and fathers in Malawi, yet vulnerable groups are underserved. Neglect in breastfeeding support among vulnerable populations exacerbates health inequities. Health systems strengthening related to breastfeeding requires a concerted effort among health workers, mothers, grandmothers, aunts, and fathers while remaining grounded in contexts to support family-centered hospital care.

ABSTRACT SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher’s Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.

The SARS-CoV-2 belongs to the coronavirus family, which also includes common endemic coronaviruses (HCoVs). We hypothesized that immunity to HCoVs would be associated with stronger immunogenicity from SARS-CoV-2 vaccines. The study included samples from the COSRIP observational cohort study of adult paramedics in Canada. Participants provided blood samples, questionnaire data, and results of COVID-19 testing. Samples were tested for anti-spike IgG against SARS-CoV-2, HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 antigens. We first compared samples from vaccinated and unvaccinated participants, to determine which HCoV antibodies were affected by vaccination. We created scatter plots and performed correlation analysis to estimate the extent of the linear relationship between HCoVs and SARS-CoV-2 anti-spike antibodies. Further, using adjusted log-log multiple regression, we modeled the association between each strain of HCoV and SARS-CoV-2 antibodies. Of 1510 participants (mean age of 39 years), 94 (6.2%) had a history of COVID-19. There were significant differences between vaccinated and unvaccinated participant in anti-spike antibodies to HCoV-HKU1, and HCoV-OC43; however, levels for HCoV-229E and HCoV-NL63 were similar (suggesting that vaccination did not affect these baseline values). Among vaccinated individuals without prior COVID-19 infection, SARS-COV-2 anti-spike IgG demonstrated a weak positive relationship between both HCoV-229E (r = 0.11) and HCoV-NL63 (r = 0.12). From the adjusted log-log multiple regression model, higher HCoV-229E and HCoV-NL63 anti-spike IgG antibodies were associated with increased SARS-COV-2 anti-spike IgG antibodies. Vaccination appears to result in measurable increases in HCoV-HKU1, and HCoV-OC43 IgG levels. Anti-HCoV-229E and HCoV-NL63 antibodies were unaffected by vaccination, and higher levels were associated with significantly higher COVID-19 vaccine-induced SARS-COV-2 antibodies.

The Canadian Arctic has a long history with diarrheal disease, including outbreaks of campylobacteriosis, giardiasis, and salmonellosis. Due to climate change, the Canadian Arctic is experiencing rapid environmental transformation, which not only threatens the livelihood of local Indigenous Peoples, but also supports the spread, frequency, and intensity of enteric pathogen outbreaks. Advances in diagnostic testing and detection have brought to attention the current burden of disease due to Cryptosporidium, Campylobacter, and Helicobacter pylori. As climate change is known to influence pathogen transmission (e.g., food and water), Arctic communities need support in developing prevention and surveillance strategies that are culturally appropriate. This review aims to provide an overview of how climate change is currently and is expected to impact enteric pathogens in the Canadian Arctic.

Abstract Objectives The “Integrating a neonatal healthcare package for Malawi” (IMCHA#108030) project conducted mixed-methods to understand facility-based implementation factors for newborn health innovations in low-resourced health settings. The objective of the two datasets was to evaluate: (a) capacity of quality newborn care in three districts in southern Malawi, and (b) barriers and facilitators the scale up of bubble continuous positive airway pressure (CPAP), a newborn health innovation to support babies with respiratory distress. Data description The Integrated Maternal, Neonatal and Child Quality of Care Assessment and Improvement Tool (version April-2014) is a standardized facility assessment tool developed by the World Health Organization (WHO) that examines quality as well as quantity and availability. The facility survey is complemented by a qualitative dataset of illustrative quotes from health service providers and supervisors on bubble CPAP implementation factors. Research was conducted in one primary health centre (facility assessment only), three district-level hospitals (both) and a tertiary hospital (qualitative only) in southern Malawi. These datasets may be used by other researchers for insights into health systems of low-income countries and implementation factors for the roll-out of neonatal health innovations as well as to frame future research questions or preliminary exploratory research on similar topics.

Abstract Introduction Kangaroo mother care is known to help save the lives of preterm and low birthweight infants, particularly in resource-limited health settings, yet barriers to implementation have been documented. Mothers and their families are very involved in the process of providing kangaroo mother care and the impact on their well-being has not been well explored. The objective of this research was to investigate the perspectives and experiences of a mother’s quality of life while delivering facility-based kangaroo mother care. Methods This study is a secondary analysis of the qualitative data collected within the “Integrating a neonatal healthcare package for Malawi” project. Twenty-seven health workers and 24 caregivers engaged with kangaroo mother care at four hospitals in southern Malawi were interviewed between May–August 2019. All interviews were face-to-face and followed a topic guide. Content analysis was conducted on NVivo 12 (QSR International, Melbourne, Australia) based on the six World Health Organization Quality of Life domains (physical, psychological, level of independence, social relationships, environment, spirituality). Results Fifty-one interviews were conducted with 24 caregivers and 14 health workers. Mothers experienced multidimensional challenges to their quality of life while delivering facility-based KMC. Though kangaroo mother care was considered a simple intervention, participants highlighted that continuous kangaroo mother care was difficult to practice. Kangaroo mother care was an exhausting experience for mothers due to being in one position for prolonged periods, compromised sleep, restricted movement, boredom, and isolation during their stay at the hospital as well as poor support for daily living needs such as food. Discussion A heavy burden is placed on mothers who become the key person responsible for care during kangaroo mother care, especially in resource-limited health settings. More focus is needed on supporting caregivers during the delivery of kangaroo mother care through staff support, family inclusion, and conducive infrastructure.

Sapoviruses are an important cause of acute viral gastroenteritis in children. The objective of this study was to determine the burden and genetic diversity of sapoviruses in children hospitalized with acute gastroenteritis in Botswana between 2016 and 2018. Samples were screened using the BioFire® Filmarray® GI Panel assay and for positive sapovirus samples, conventional RT-PCR was used to amplify the partial VP1 gene. Strain characterization was performed using both the Human Calicivirus Typing tool and the NCBI GenBank BLAST. Phylogenetic and evolutionary analysis was inferred using BEAST V1.10.4. General time-reversible was used as a nucleotide substitution model. Sapovirus was detected in 6.5% of participants and two different sapovirus genotypes GI.1 (5/7) and GI.6 (2/7) were identified from the seven samples. This study provides the first data on sapovirus infections and their genetic diversity in a clinical setting in Botswana, contributing to the global knowledge of this virus.

ABSTRACT We prospectively studied SARS-CoV-2 transmission at schools in an era of variants of concern, offering all close contacts serial viral asymptomatic testing up to 14 days. From the 69 primary cases detected in schools, 392 close contacts were identified and offered asymptomatic testing. A total of 229 (58%) were close school contacts, and of these, 3 tested positive (1.3%), 2 of which were detected through asymptomatic testing. This is in contrast to the 117 household contacts, where 43 (37%) went on to become secondary cases. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission. IMPORTANCE There is concern that schools may be a setting where asymptomatic infections might result in significant “silent” transmission of SARS-CoV-2, particularly after the emergence of more transmissible variants of concern. After the programmatic implementation of a strategy of asymptomatic testing of close COVID-19 contacts as part of contact tracing in the school setting, the majority of the secondary cases were still found to have occurred in home or social contacts. However, for the 6.2% of secondary cases that occurred in close school contacts, the majority were detected through asymptomatic testing. The potential added yield of this approach needs to be considered within the overall setting, including consideration of the local epidemiology, ongoing goals of case and contact management, additional costs, logistical challenges for families, and possible health impacts of asymptomatic transmission.

Abstract Background Kangaroo mother care (KMC) is an effective intervention for preterm and low birth weight infants. Effective implementation of KMC relies on a multidisciplinary team centering on the newborn’s caregiver, who delivers care with support from health care workers. This study explored the experiences of caregivers on the implementation of KMC. Methods We conducted a descriptive qualitative study in the phenomenological tradition, an interpretative approach to describe the caregivers’ lived experience with KMC at four health facilities in Malawi from April and June 2019 through 10 non-participatory observations and 24 face-to-face interviews. We drew a purposive sample of 14 mothers, six fathers, three grandmothers, and one grandfather of infants receiving KMC in three secondary and one tertiary level hospitals. Data were analyzed following a thematic approach. Results Caregivers had limited information on KMC before admission with most of the information learned from peers rather than medical professionals. Stories of positive outcomes following KMC contributed to a shift in perceptions of premature babies and acceptability of KMC as an effective intervention. Unintended consequences resulting from admission due to KMC disrupts responsibilities around the home and disrupts economic activities. Gender division of roles exists with the implementation of KMC and a mother’s support networks are crucial. Conclusion Kangaroo mother care is feasible and acceptable among caregivers. KMC babies are described more positively with the potential to grow into strong and healthy children. KMC remains focused on the mother, which undervalues the important roles of her support network. A change in the nomenclature from kangaroo mother care to kangaroo care would include fathers and others delivering care.

BackgroundThe purpose of this study was to explore factors associated with COVID-19 vaccine intentions among school staff as high vaccine uptake is essential to ensure schools return to normal activities.MethodsStaff (e.g., teachers, administrators, student support workers) from three urban school districts in the Greater Vancouver Area of British Columbia, Canada completed a survey between February and June 2021 (n = 2,393) on COVID-19 vaccine intentions and perceptions (i.e., acceptance of routine vaccines, benefits and risks of vaccination, susceptibility to, and severity of COVID-19, recommendation by authority figures, information mistrust and conspiracy beliefs) as part of a COVID-19 seroprevalence study. Confirmatory factor analysis followed by multiple logistic regression models adjusting for relevant covariates were used to identify vaccine perceptions uniquely associated with (a) intention to get the COVID-19 vaccine (intention), and (b) intention to get vaccinated right away (urgency).ResultsIn total, 95.4% of participants of the seroprevalence study completed the vaccine questionnaire, corresponding to 17.7% of the target population. Vaccine intention was associated with staff who valued expert recommendations (AOR = 10.5, 95% CI = 7.39–14.90) accepted routine vaccines (AOR = 1.94, 95% CI = 1.26–2.98) and perceived higher benefits (AOR = 1.29, 95% CI = 1.01–1.65) and lower safety risks of vaccination (AOR = 0.40, 95% CI = 0.29–0.54). Comparable associations were found with vaccine urgency. Perceived susceptibility to the COVID-19 virus was uniquely associated with vaccine urgency (AOR = 1.30, 95% CI = 1.05–1.61). A significant interaction effect (p = 0.01) revealed that staff who expressed mistrust in COVID-19 information intended to get vaccinated only if they also perceived high benefits of vaccination.ConclusionsEducation about the risks and benefits of COVID-19 vaccines from a trusted source had the strongest relationship with vaccine intentions among this occupational group. Notably, those who expressed mistrust in information still intended to get vaccinated if they also perceived strong benefits of the vaccine.

ABSTRACT We investigate the diagnostic accuracy and predictive value of finger prick capillary dried blood spot (DBS) samples tested by a quantitative multiplex anti-immunoglobulin G (IgG) assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies after infection or vaccination. This cross-sectional study involved participants (n = 6,841) from several serological surveys conducted in nonhospitalized children and adults throughout 2020 and 2021 in British Columbia (BC), Canada. Analysis used paired DBS and serum samples from a subset of participants (n = 642) prior to vaccination to establish signal thresholds and calculate diagnostic accuracy by logistic regression. Discrimination of the logistic regression model was assessed by receiver operator curve (ROC) analysis in an n = 2,000 bootstrap of the paired sample (n = 642). The model was cross-validated in a subset of vaccinated persons (n = 90). Unpaired DBS samples (n = 6,723) were used to evaluate anti-IgG signal distributions. In comparison to paired serum, DBS samples from an unvaccinated population possessed a sensitivity of 79% (95% confidence interval [95% CI]: 58 to 91%) and specificity of 97% (95% CI: 95 to 98%). ROC analysis found that DBS samples accurately classify SARS-CoV-2 seroconversion at an 88% percent rate (area under the curve [AUC] = 88% [95% CI: 80 to 95%]). In coronavirus disease 2019 (COVID-19) vaccine dose one or two recipients, the sensitivity of DBS testing increased to 97% (95% CI: 83 to 99%) and 100% (95% CI: 88 to 100%). Modeling found that DBS testing possesses a high positive predictive value (98% [95% CI: 97 to 98%]) in a population with 75% seroprevalence. We demonstrate that DBS testing should be considered to reliably detect SARS-CoV-2 seropositivity from natural infection or vaccination. IMPORTANCE Dried blood spot samples have comparable diagnostic accuracy to serum collected by venipuncture when tested by an electrochemiluminescent assay for antibodies and should be considered to reliably detect seropositivity following SARS-CoV-2 infection and/or vaccination.

ABSTRACT While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher (P

Abstract Background While Malawi has achieved success in reducing overall under-five mortality, reduction of neonatal mortality remains a persistent challenge. There has, therefore, been a push to strengthen the capacity for quality newborn care at district hospitals through the implementation of innovative neonatal technologies such as bubble continuous positive airway pressure (CPAP). This study investigates tertiary- versus secondary-level hospital differences in capacities for bubble CPAP use and implications for implementation policies. Methods A secondary analysis of interviews was conducted with 46 health workers at one tertiary hospital and three secondary hospitals in rural Southern Malawi. Grounded theory was utilized to explore the emerging themes according to health worker cadres (nurse, clinician, district health management) and facility level (tertiary- and secondary-level facilities), which were managed using NVivo 12 (QSR International, Melbourne, Australia). Results We identified frequent CPAP use and the availability of neonatal nurses, physicians, and reliable electricity as facilitators for CPAP use at the tertiary hospital. Barriers at the tertiary hospital included initiation eligibility disagreements between clinicians and nurses and insufficient availability of the CPAP machines. At secondary-level hospitals, the use was supported by decision-making and initiation by nurses, involving caretakers to assist in monitoring and reliable availability of CPAP machines. Bubble CPAP was hindered by unreliable electricity, staffing shortages and rotation policies, and poor systems of accountability. Conclusion While this study looked at the implementation of bubble CPAP in Malawi, the findings may be applicable for scaling up other novel neonatal technologies in low-resource settings. Implementation policies must consider staffing and management structures at different health services levels for effective scale-up.

Abstract Background Bubble continuous positive airway pressure (CPAP) has been shown to be effective in supporting breathing in newborns with respiratory distress. The factors that influence implementation in resource-constrained settings remain unclear. The objective of this review is to evaluate the barriers and facilitators of CPAP implementation for newborn care at sub-Saharan African health facilities and how different facility levels and types of bubble CPAP systems may impact utilization. Methods A systematic search (database inception to July 2019) was performed on MEDLINE Ovid, EMBASE, CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the WHO Regional Database for Africa, African Index Medicus (AIM), African Journals Online, grey literature and the references of relevant articles. Studies that met the inclusion criteria (primary research, bubble CPAP implementation with neonates ≤ 28 days old at a health facility in sub-Saharan Africa) were included in the review and assessed with National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) quality assessment tools. The review protocol was published to PROSPERO (CRD42018116082). Results Seventeen studies were included in the review. Reliable availability of equipment, effectively informing and engaging caregivers and staffing shortages were frequently mentioned barriers to the implementation of bubble CPAP. Understaffed neonatal units and high turnover of nurses and doctors compromised effective training. Provider-to-provider clinical mentorship models as well as affordability and cost-effectiveness of innovative bubble CPAP systems were identified as frequently mentioned facilitators of implementation. Conclusions With a strong recommendation by the World Health Organization for its use with premature infants with respiratory distress, it is important to understand the barriers and facilitators that can inform the implementation of bubble CPAP. More research is needed into health system factors that can support or impede the use of this potentially promising intervention.

Abstract Background Severe respiratory distress is a leading cause of mortality among neonates in Malawi. Despite evidence on the safety, cost effectiveness and efficacy of bubble continuous positive airway pressure (CPAP) in managing the condition, its use in Malawian health facilities is limited and little is known about caregivers’ engagement with perspectives of bubble CPAP. The purpose of this study was to explore caregiver perspectives for bubble CPAP at both central and district hospitals and key factors that enable effective caregiver engagement in Malawi. Methods This was a descriptive qualitative study employing secondary analysis of 46 health care worker in-depth interviews. We interviewed the health workers about their thoughts on caregiver perspectives regarding use of bubble CPAP. We implemented the study at a tertiary facility and three district hospitals in southern Malawi. This was a part of a larger study to understand barriers and facilitators to implementing neonatal innovations in resource-constrained hospitals. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). Health workers were purposively selected to include nurses, clinicians and district health management involved in the use of bubble CPAP. Results Emerging issues included caregiver fears around bubble CPAP equipment as potentially harmful to their new-borns and how inadequate information provided to caregivers exacerbated knowledge gaps and was associated with refusal of care. However, good communication between health care providers and caregivers was associated with acceptance of care. Caregivers’ decision-making was influenced by relatives and peer advocates were helpful in supporting caregivers and alleviating fears or misconceptions about bubble CPAP. Conclusions Since caregivers turn to relatives and peers for support, there is need to ensure that both relatives and peers are counselled on bubble CPAP for improved understanding and uptake. Health workers need to provide simplified, accurate, up-to-date information on the intervention as per caregivers’ level of understanding. Notably, contextualised comprehensible information will help alleviate caregivers’ fear and anxieties about bubble CPAP.

Abstract Background Malawi is celebrated as one of the few countries in sub-Saharan Africa to meet the Millennium Development Goal of reducing under-5 mortality by two-thirds between 1990 and 2015. However, within this age range neonatal mortality rates are the slowest to decline, even though rates of facility births are increasing. Examining the quality of neonatal care at district-level facilities where most deliveries occur is warranted. Objective The objective of this paper is to evaluate the quality of neonatal care in three district hospitals and one primary health centre in southern Malawi as well as to report the limitations and lessons learned on using the WHO integrated quality of care assessment tool. Methods These facility assessments were part of the “Integrating a neonatal healthcare package for Malawi” project, a part of the Innovating for Maternal and Child Health in Africa (IMCHA) initiative. The WHO integrated quality of care assessment tool was used to assess quality of care and availability and quantity of supplies and resources. The modules on infrastructure, neonatal care and labour and delivery were included. Facility assessments were administered in November 2017 and aspects of care were scored on a Likert scale from one to five (a score of 5 indicating compliance with WHO standards of care; one as lowest indicating inadequate care). Results The continuum of labour, delivery and neonatal care were assessed to identify areas that required improvements to meet standards of care. Critical areas for improvements included infection control (mean score 2.9), equipment, supplies and setup for newborn care in the labor ward (2.3), in the surgical theater (3.3), and nursery (3.4 nursery facilities, 3.0 supplies and equipment), as well as for management of sick newborns (3.2), monitoring and follow-up (3.6). Only one of the 12 domains, laboratory, met the standards of care with only minor improvements needed (4.0). Conclusion The WHO integrated quality of care assessment tool is a validated tool that can shed light on the complex quality of care challenges faced by district-level health facilities. The results reveal that the quality of care needs improvement, particularly for sick and vulnerable newborns.

ABSTRACT SARS-CoV-2 seroprevalence studies may be complicated by vaccination efforts. It is important to characterize the ability of serology methods to correctly distinguish prior infection from postvaccination seroreactivity. We report the performance of the Meso Scale Discovery (MSD) V-PLEX COVID-19 Coronavirus Panel 2 IgG assay. Using serum samples from a prospective cohort of paramedics, we calculated the performance of the V-PLEX nucleocapsid (“N”) assay to classify prior SARS-CoV-2 infections, defined as a (i) history of a positive SARS-CoV-2 PCR test or (ii) positive serology results using the Roche Elecsys total nucleocapsid anti-SARS-Cov-2 assay. We calculated sensitivity and specificity at the optimal threshold (defined by the highest Youden index). We compared subgroups based on vaccination status, and between models that excluded prior infections 3 to 12 months before sample collection. Of 1119 participants, 914 (81.7%) were vaccinated and 60 (5.4%) had evidence of a preceding SARS-CoV-2 infection. Overall and within vaccinated and unvaccinated subgroups, the optimal thresholds were 828 AU/mL, 827 AU/mL, and 1324 AU/mL; with sensitivities of 0.95 (95% CI: 0.94 to 0.96), 0.95 (0.94 to 0.96), 0.94 (0.92 to 0.96) and specificities of 0.88 (0.86 to 0.90), 0.87 (0.85 to 0.89), and 0.94 (0.89 to 0.98), respectively. N-assay specificity was significantly better in unvaccinated (versus vaccinated) individuals (P = 0.005). Overall optimal thresholds based on the AUC values were higher for samples from unvaccinated participants, especially when examining infections within the preceding 9 months (5855 versus 1704 AU/mL). Overall, V-PLEX nucleocapsid assay cutoff values were higher among unvaccinated individuals. Specificity was also significantly higher among unvaccinated individuals. Different thresholds were required to achieve optimal test performance, especially for detecting SARS-CoV-2 infections within the preceding 9 months. IMPORTANCE Among a cohort of adult paramedics in Canada, we investigated the performance of nucleocapsid (N) antibody detection (measured with a V-PLEX assay) to identify previous COVID-19 infections and compared differences among vaccinated and unvaccinated. Our data indicate that vaccinated and unvaccinated groups require different thresholds to achieve optimal test performance, especially for detecting COVID-19 within the preceding 9 months. Overall, specificity was significantly higher among unvaccinated, compared to vaccinated individuals.

Improving breastfeeding practices is key to reducing child mortality globally. Sub-optimal exclusive breastfeeding rates may be associated with inadequate hospital-based postpartum breastfeeding support, particularly in resource-limited health settings such as Malawi. While almost all children in Malawi are breastfed, it is a concern that exclusive breastfeeding rates in Malawi are declining. The objective of this study is to understand postpartum breastfeeding support after delivery at Malawian hospitals from the perspectives of health workers and caregivers. We conducted a secondary analysis of a descriptive qualitative study on health worker and caregiver experiences of breastfeeding support at health facilities in southern Malawi as part of the Innovating for Maternal and Child Health in Africa Initiative. In-depth interviews following a semi-structured topic guide were conducted at three secondary-level district hospitals and one tertiary-level central hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). We interviewed a total of 61 participants, including 30 caregivers and 31 health care workers. Participants shared the following themes: 1) a focus on early initiation of breastfeeding, 2) inadequate follow-up on breastfeeding practice, and 3) feasibility challenges and local solutions. There was an emphasis on early initiation of breastfeeding, which was challenged by maternal exhaustion after delivery. Study participants reported poor follow-up on breastfeeding practice after initial counselling and reacting to adverse outcomes in lieu of adequate monitoring, with a reliance on caregivers to follow-up on challenges. There was poor support for facility-based breastfeeding after initial counselling post-delivery, which revealed an overall neglect in hospital postpartum care for those considered to be in good health after initial assessment. We recommend the development of indicators to track continued facility-based breastfeeding, identify vulnerable infants at-risk of feeding problems, and strengthening care in postnatal wards, which is currently as neglected component of maternity care.

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. Results: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14–56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45–3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = −0.24 [95%CI: −1.2-(−0.12)]). A positive association was found between COVID-19 vaccination and endemic human β-coronavirus IgG titer 14–56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45–3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. Conclusions: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.

Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada.Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0–5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators.Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46–5.64), otitis media (aOR:1.83, 95%CI:1.05–3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09–2.77), compared to non-carriers.Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps.

Abstract Background There are scant data on the prevalence and clinical course of pertussis disease among infants with pneumonia in low- and middle-income countries. While pertussis vaccination coverage is high (≥90%) among infants in Botswana, human immunodeficiency virus (HIV) infection affects nearly one-third of pregnancies. We aimed to evaluate the prevalence and clinical course of pertussis disease in a cohort of HIV-unexposed uninfected (HUU), HIV-exposed uninfected (HEU), and HIV-infected infants with pneumonia in Botswana. Methods We recruited children 1–23 months of age with clinical pneumonia at a tertiary care hospital in Gaborone, Botswana between April 2012 and June 2016. We obtained nasopharyngeal swab specimens at enrollment and tested these samples using a previously validated in-house real-time PCR assay that detects a unique sequence of the porin gene of Bordetella pertussis. Results B. pertussis was identified in 1/248 (0.4%) HUU, 3/110 (2.7%) HEU, and 0/33 (0.0%) HIV-infected children. All pertussis-associated pneumonia cases occurred in infants 1–5 months of age (prevalence, 1.0% [1/103] in HUU and 4.8% [3/62] in HEU infants). No HEU infants with pertussis-associated pneumonia were taking cotrimoxazole prophylaxis at the time of hospital presentation. One HUU infant with pertussis-associated pneumonia required intensive care unit admission for mechanical ventilation, but there were no deaths. Conclusions The prevalence of pertussis was low among infants and young children with pneumonia in Botswana. Although vaccination against pertussis in pregnancy is designed to prevent classical pertussis disease, reduction of pertussis-associated pneumonia might be an important additional benefit.

Preexisting cross-reactivity to SARS-CoV-2 occurs in the absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that about 0.6% of nontriaged adults from the greater Vancouver, Canada, area between May 17 and June 19, 2020, showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determined that more than 90% of uninfected adults showed antibody reactivity against the spike protein, receptor-binding domain (RBD), N-terminal domain (NTD), or the nucleocapsid (N) protein from SARS-CoV-2. This seroreactivity was evenly distributed across age and sex, correlated with circulating coronaviruses’ reactivity, and was partially outcompeted by soluble circulating coronaviruses’ spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike and to conserved nonstructural viral proteins. We conclude that most adults display preexisting antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.

Abstract Background Norovirus is a leading cause of viral gastroenteritis worldwide with a peak of disease seen in children. The epidemiological analysis regarding the virus strains in Africa is limited. The first report of norovirus in Botswana was in 2010 and currently, the prevalence and circulating genotypes of norovirus are unknown, as the country has no systems to report the norovirus cases. This study investigated the prevalence, patterns and molecular characteristics of norovirus infections among children ≤5 years of age admitted with acute gastroenteritis at four hospitals in Botswana. Methods A total of 484 faecal samples were collected from children who were admitted with acute gastroenteritis during the rotavirus vaccine impact survey between July 2013 and December 2015. Norovirus was detected using real-time RT-PCR. Positive samples were genotyped using conventional RT-PCR followed by partial sequencing of the capsid and RdRp genes. Norovirus strains were determined by nucleotide sequence analysis using the online Norovirus Genotyping Tool Version 1.0, and confirmed using maximum likelihood tree construction as implemented in MEGA 6.0. Results The prevalence of norovirus was 9.3% (95% CI 6.7–11.9). The genotype diversity was dominated by the GII.4 strain at 69.7%. This was followed by GII.2, GII.12 each at 9.1%, GI.9 at 6.6% and GII.6, GII.10 each at 3.0%. The most common combined RdRp/Capsid genotype was the GII.Pe/GII.4 Sydney 2012. Norovirus was detected during most part of the year; however, there was a preponderance of cases in the wet season (December to March). Conclusion The study showed a possible decline of norovirus infections in the last 10 years since the first report. An upward trend seen between 2013 and 2015 may be attributable to the success of rotavirus vaccine introductions in 2012. Knowledge of circulating genotypes, seasonal trends and overall prevalence is critical for prevention programming and possible future vaccine design implications.

Background. We sought to develop diagnostic test guidance definitions for pediatric enteric infections to facilitate the interpretation of positive test results in the era of multianalyte molecular diagnostic test platforms. Methods. We employed a systematic, two-phase, modified Delphi consensus process consisting of three web-based surveys and an expert panel face-to-face meeting. In phase 1, we surveyed an advisory panel of North American experts to select pathogens requiring diagnostic test guidance definition development. In phase 2, we convened a 14-member expert panel to develop, refine, and select the final definitions through two web-based questionnaires interspersed with a face-to-face meeting. Both questionnaires asked panelists to rate the degree to which they agreed that if the definition is met the pathogen is likely to be causative of clinical illness. Results. The advisory panel survey identified 19 pathogens requiring definitions. In the expert panel premeeting survey, 13 of the 19 definitions evaluated were rated as being highly likely (“agree” or “strongly agree”) to be responsible for acute gastroenteritis symptoms by ≥67% of respondent panel members. The definitions for the remaining six pathogens (Aeromonas, Clostridium difficile, Edwardsiella, nonenteric adenovirus, astrovirus, and Entamoeba histolytica) were indeterminate. After the expert panel meeting, only two of the modified definitions, C. difficile and E. histolytica/dispar, failed to achieve the a priori specified threshold of ≥67% agreement. Conclusions. We developed diagnostic test guidance definitions to assist healthcare providers for 17 enteric pathogens. We identified two pathogens that require further research and definition development.

Background: Although the prevalences of infection with the protozoan parasites Cryptosporidium spp. and Giardia duodenalis in humans appear to be relatively high in the Canadian North, their transmission patterns are poorly understood. Objective: To determine the detection rate and the molecular characteristics of Cryptosporidium spp. and Giardia duodenalis in diarrhoeic patients in the Qikiqtani (Baffin Island) Region of Nunavut, Canada, in order to better understand the burden of illness and the potential mechanisms of transmission. Study design/methods: Diarrhoeal stool specimens (n=108) submitted to the Qikiqtani General Hospital for clinical testing were also tested for the presence of Cryptosporidium spp. and Giardia duodenalis using epifluorescence microscopy and polymerase chain reaction (PCR). DNA sequencing and restriction fragment length polymorphism (RFLP) analyses were performed on PCR-positive specimens to determine the species, genotypes and sub-genotypes of the parasites. Results: Cryptosporidium was detected in 15.7% of the diarrhoeic patients, while Giardia was detected in 4.6%. DNA sequencing of a fragment of the small subunit rRNA gene indicated that all of the Cryptosporidium amplicons had a 100% homology to C. parvum, and a gp60 assay showed that all aligned with C. parvum sub-genotype IIa. Microsatellite analysis revealed 3 cases of sub-genotype IIaA15G2R1, 2 of IIaA15G1R and 1 case each of sub-genotypes IIaA16G1R1 and IIaA15R1. For Giardia, results based on the amplification of both the 16S rRNA gene and the gdh gene were generally in agreement, and both DNA sequencing and RFLP demonstrated the presence of the G. duodenalis Assemblage B genotype. Conclusions: Both C. parvum and G. duodenalis Assemblage B were present in human diarrhoeal stool specimens from Nunavut, which was suggestive of zoonotic transmission, although human-to-human transmission cannot be ruled out. To fully understand the public health significance of the different Cryptosporidium and Giardia species and genotypes in diarrhoeic patients, it will be imperative to establish the extent of genetic diversity within these parasites through comprehensive studies of the molecular epidemiology of cryptosporidiosis and giardiasis in the Nunavut region.

Background. Little is known about the microbiology of diarrhoeal disease in Canada's Arctic regions. There are a number of limitations of conventional microbiology testing techniques for diarrhoeal pathogens, and these may be further compromised in the Arctic, given the often long distances for specimen transport. Objective. To develop a novel multiple-target nanolitre real-time reverse transcriptase (RT)-PCR platform to simultaneously test diarrhoeal specimens collected from residents of the Qikiqtani (Baffin Island) Region of Nunavut, Canada, for a wide range of bacterial, parasitic and viral agents. Study design/methods. Diarrhoeal stool samples submitted for bacterial culture to Qikiqtani General Hospital in Nunavut over an 18-month period were tested with a multiple-target nanolitre real-time PCR panel for major diarrhoeal pathogens including 8 bacterial, 6 viral and 2 parasitic targets. Results. Among 86 stool specimens tested by PCR, a total of 50 pathogens were detected with 1 or more pathogens found in 40 (46.5%) stool specimens. The organisms detected comprised 17 Cryptosporidium spp., 5 Clostridium difficile with toxin B, 6 Campylobacter spp., 6 Salmonella spp., 4 astroviruses, 3 noroviruses, 1 rotavirus, 1 Shigella spp. and 1 Giardia spp. The frequency of detection by PCR and bacterial culture was similar for Salmonella spp., but discrepant for Campylobacter spp., as Campylobacter was detected by culture from only 1/86 specimens. Similarly, Cryptosporidium spp. was detected in multiple samples by PCR but was not detected by microscopy or enzyme immunoassay. Conclusions. Cryptosporidium spp., Campylobacter spp. and Clostridium difficile may be relatively common but possibly under-recognised pathogens in this region. Further study is needed to determine the regional epidemiology and clinical significance of these organisms. This method appears to be a useful tool for gastrointestinal pathogen research and may also be helpful for clinical diagnostics and outbreak investigation in remote regions where the yield of routine testing may be compromised.