Characterization of vaccine confidence among teachers in British Columbia, Canada: A population-based survey.

OBJECTIVES: Teachers are an important occupational group to consider when addressing vaccine confidence and uptake for school-aged children due to their proximate role within school-based immunization programs. The objectives of this study were to characterize and identify sociodemographic factors associated with vaccine confidence and describe teachers' knowledge of and perceived role in the school-based immunization program, with the aim of informing public health policy and identifying opportunities for supporting teachers in their role in school-based immunization programs. METHODS: A cross-sectional survey of elementary and secondary public-school teachers in British Columbia was completed from August to November 2020. Respondents provided sociodemographic information, as well as past vaccination experience, vaccine knowledge, and perceived role in the school-based immunization program. Vaccine confidence was measured using the Vaccine Hesitancy Scale (VHS). Characteristics associated with the VHS sub-scales 'lack of confidence in vaccines' and 'perceived risk of vaccines', were explored using ANOVA. Descriptive analysis was completed for teachers' perceived role in the immunization program. RESULTS: 5,095 surveys were included in this analysis. Overall vaccine confidence was high, with vaccine hesitancy being related to the perceived risk of vaccines rather than a lack of confidence in the effectiveness of vaccines. ANOVA found significant differences for both VHS-sub-scales based on sociodemographic factors, however, the strength of the association was generally small. High general vaccine knowledge and never having delayed or refused a vaccine in the past were associated with higher vaccine confidence. Overall, teachers reported a lack of clarity in their role within the school-based immunization program. CONCLUSIONS: This large population-based observational study of teachers highlights a number of key engagement opportunities between public health and the education sector. Using a validated scale, we found that overall, teachers are highly accepting of vaccines, and well situated as potential partners with public health to address vaccine hesitancy.

Barriers to evidence use for sustainability: Insights from pesticide policy and practice.

Calls for supporting sustainability through more and better research rest on an incomplete understanding of scientific evidence use. We argue that a variety of barriers to a transformative impact of evidence arises from diverse actor motivations within different stages of evidence use. We abductively specify this variety in policy and practice arenas for three actor motivations (truth-seeking, sense-making, and utility-maximizing) and five stages (evidence production, uptake, influence on decisions, effects on sustainability outcomes, and feedback from outcome evaluations). Our interdisciplinary synthesis focuses on the sustainability challenge of reducing environmental and human health risks of agricultural pesticides. It identifies barriers resulting from (1) truth-seekers' desire to reduce uncertainty that is complicated by evidence gaps, (2) sense-makers' evidence needs that differ from the type of evidence available, and (3) utility-maximizers' interests that guide strategic evidence use. We outline context-specific research-policy-practice measures to increase evidence use for sustainable transformation in pesticides and beyond.

Collection of human and environmental data on pesticide use in Europe and Argentina: Field study protocol for the SPRINT project.

Current farm systems rely on the use of Plant Protection Products (PPP) to secure high productivity and control threats to the quality of the crops. However, PPP use may have considerable impacts on human health and the environment. A study protocol is presented aiming to determine the occurrence and levels of PPP residues in plants (crops), animals (livestock), humans and other non-target species (ecosystem representatives) for exposure modelling and impact assessment. To achieve this, we designed a cross-sectional study to compare conventional and organic farm systems across Europe. Environmental and biological samples were/are being/will be collected during the 2021 growing season, at 10 case study sites in Europe covering a range of climate zones and crops. An additional study site in Argentina will inform the impact of PPP use on growing soybean which is an important European protein-source in animal feed. We will study the impact of PPP mixtures using an integrated risk assessment methodology. The fate of PPP in environmental media (soil, water and air) and in the homes of farmers will be monitored. This will be complemented by biomonitoring to estimate PPP uptake by humans and farm animals (cow, goat, sheep and chicken), and by collection of samples from non-target species (earthworms, fish, aquatic and terrestrial macroinvertebrates, bats, and farm cats). We will use data on PPP residues in environmental and biological matrices to estimate exposures by modelling. These exposure estimates together with health and toxicity data will be used to predict the impact of PPP use on environment, plant, animal and human health. The outcome of this study will then be integrated with socio-economic information leading to an overall assessment used to identify transition pathways towards more sustainable plant protection and inform decision makers, practitioners and other stakeholders regarding farming practices and land use policy.

Areas of global importance for conserving terrestrial biodiversity, carbon and water.

To meet the ambitious objectives of biodiversity and climate conventions, the international community requires clarity on how these objectives can be operationalized spatially and how multiple targets can be pursued concurrently. To support goal setting and the implementation of international strategies and action plans, spatial guidance is needed to identify which land areas have the potential to generate the greatest synergies between conserving biodiversity and nature's contributions to people. Here we present results from a joint optimization that minimizes the number of threatened species, maximizes carbon retention and water quality regulation, and ranks terrestrial conservation priorities globally. We found that selecting the top-ranked 30% and 50% of terrestrial land area would conserve respectively 60.7% and 85.3% of the estimated total carbon stock and 66% and 89.8% of all clean water, in addition to meeting conservation targets for 57.9% and 79% of all species considered. Our data and prioritization further suggest that adequately conserving all species considered (vertebrates and plants) would require giving conservation attention to ~70% of the terrestrial land surface. If priority was given to biodiversity only, managing 30% of optimally located land area for conservation may be sufficient to meet conservation targets for 81.3% of the terrestrial plant and vertebrate species considered. Our results provide a global assessment of where land could be optimally managed for conservation. We discuss how such a spatial prioritization framework can support the implementation of the biodiversity and climate conventions.

Intentions of public school teachers in British Columbia, Canada to receive a COVID-19 vaccine.

BACKGROUND: To control the COVID-19 pandemic high vaccine acceptability and uptake will be needed. Teachers represent a priority population to minimize social disruption and ensure continuity in education, which is vital for the well-being and healthy development of youth during the pandemic. The objective of this analysis was to measure public school teachers' intentions to receive a COVID-19 vaccine in British Columbia (BC), Canada. METHODS: A population-wide cross-sectional online survey from August to November 2020 asked all BC public school teachers with an available email address how likely they were to receive a COVID-19 vaccine. Two multivariable logistic regression models explored separately sociodemographic and vaccine hesitancy predictors for intention to receive a COVID-19 vaccine. RESULTS: A total of 5,076 teachers participated. The majority, 89.7%, reported they were likely or very likely to accept a COVID-19 vaccine. In multivariable regression, sociodemographic predictors of intention to be vaccinated included being male, having an educational background in science or engineering, and using reliable information sources on vaccination such as public health and health care providers. Teachers who reported lower levels of vaccine hesitancy, higher general vaccine knowledge, and belief that COVID-19 was a serious illness were more likely to intend to receive a COVID-19 vaccine. CONCLUSION: A high proportion of public-school teachers in BC intend to receive a COVID-19 vaccine. Continued monitoring of vaccine intentions will be important to inform public health vaccine implementation.

Reaching hard-to-reach men through home-based couple HIV testing among pregnant women and their male partners in western Kenya: a qualitative study.

BACKGROUND: Globally only 79% of adults living with HIV (human immunodeficiency virus) know their status and men in sub-Saharan Africa are considered a particularly hard-to-reach population for HIV testing. Home-based HIV couple testing during the antenatal period is a safe and effective method that has been used to test male partners of pregnant women. The goal of this qualitative study was to identify elements that made couple testing successful and describe important characteristics of this home-based intervention from couples' perspectives. METHODS: Couples who received scheduled home-based couple testing during pregnancy in Kisumu, Kenya, were purposively sampled based on HIV status from January to May 2015. An interviewer administered all of the in-depth interviews and two coders were directly involved in the data analysis and reconciled codes several times in the process. RESULTS: Twenty-one couples were enrolled: 9 concordant HIV-negative couples, 8 HIV discordant couples, 3 HIV concordant HIV-positive couples, and 1 whose concordance status was unknown. Median age at the time of home-based couple testing was 24 and 28 years for women and men, respectively. Median relationship duration was 3 years and couples had a median of two pregnancies. The major themes that emerged were that home-based couple testing 1) removed the female burden of requesting couple testing, 2) overcame logistical barriers associated with clinic-based testing, 3) encouraged participants to overcome their fear of testing and disclosure, 4) provided privacy in the home, and 5) provided quality time with the health advisors. Importantly, some women appreciated individual testing at the clinic before couple testing and some couples preferred skilled, anonymous health advisors delivering the intervention rather than known community health workers. CONCLUSIONS: The results of this qualitative study suggest that home-based couple testing during pregnancy overcame many of the barriers that limit men's access to and uptake of clinic-based testing. It encouraged participants to overcome their fear of testing and disclosure through a setting that afforded privacy and quality time with skilled health advisors. These qualitative results may help design effective partner and couple HIV testing programs in the antenatal setting and alongside or within other assisted partner notification services. TRIAL REGISTRATION: Clinicaltrials.gov registry: NCT01784783. Registered prospectively on June 15, 2012.

Male Partner Linkage to Clinic-Based Services for Sexually Transmitted Infections and Human Immunodeficiency Virus Services Following Couple Home-Based Education and Testing.

BACKGROUND: Home-based human immunodeficiency virus (HIV) testing and education has increased HIV test uptake and access to health services among men. We studied how a home-based antenatal intervention influenced male partner utilization of clinic-based HIV and sexually transmitted infection (STI) services, linkage to HIV care and medical circumcision. METHODS: We conducted a secondary analysis within a randomized controlled trial of pregnant women attending antenatal care in Kenya. Women and their male partners received either a home-based couple intervention or an invitation letter for clinic-based couple HIV testing. The home-based intervention included education on STI symptoms, STI and HIV treatment and male circumcision for HIV prevention. Male self-reported outcomes were compared using relative risks at 6 months postpartum. RESULTS: Among 525 women, we reached 487 (93%) of their male partners; 247 men in the intervention arm and 240 men in the control arm. Men who received the intervention were more likely to report an STI consultation (n = 47 vs. 16; relative risk, 1.59; 95% confidence interval, 1.33-1.89). Among 23 men with newly diagnosed HIV, linkage to HIV care was reported by 4 of 15 in the intervention (3 men had missing linkage data) and 3 of 5 men in the control arms (relative risk, 0.66; 95% confidence interval, 0.34-1.29). Although the intervention identified 3 times more men with new HIV infection, the study lacked power to find significant differences in linkage to HIV care. Few eligible men sought medical circumcision (4 of 72 intervention and 2 of 88 control). CONCLUSIONS: Home-based couple education and testing increased STI consultations among male partners of pregnant women, but appeared insufficient to overcome the barriers involved in linkage to HIV care and medical circumcision.

C-terminal truncation of IFN-γ inhibits proinflammatory macrophage responses and is deficient in autoimmune disease.

Controlled macrophage differentiation and activation in the initiation and resolution of inflammation is crucial for averting progression to chronic inflammatory and autoimmune diseases. Here we show a negative feedback mechanism for proinflammatory IFN-γ activation of macrophages driven by macrophage-associated matrix metalloproteinase 12 (MMP12). Through C-terminal truncation of IFN-γ at 135Glu↓Leu136 the IFN-γ receptor-binding site was efficiently removed thereby reducing JAK-STAT1 signaling and IFN-γ activation of proinflammatory macrophages. In acute peritonitis this signature was absent in Mmp12 -/- mice and recapitulated in Mmp12 +/+ mice treated with a MMP12-specific inhibitor. Similarly, loss-of-MMP12 increases IFN-γ-dependent proinflammatory markers and iNOS+/MHC class II+ macrophage accumulation with worse lymphadenopathy, arthritic synovitis and lupus glomerulonephritis. In active human systemic lupus erythematosus, MMP12 levels were lower and IFN-γ higher compared to treated patients or healthy individuals. Hence, macrophage proteolytic truncation of IFN-γ attenuates classical activation of macrophages as a prelude for resolving inflammation.

Uptake of Home-Based Syphilis and Human Immunodeficiency Virus Testing Among Male Partners of Pregnant Women in Western Kenya.

BACKGROUND: Few men are tested for syphilis or human immunodeficiency virus (HIV) during their partner's pregnancy, a high-risk period for HIV and syphilis transmission. Offering home-based rapid testing of syphilis to couples during pregnancy can support prevention efforts to reduce transmission of sexually transmitted diseases and adverse pregnancy outcomes. METHODS: We assessed men's uptake of paired (separate tests, single blood draw) point-of-care syphilis and HIV tests within a randomized controlled trial of pregnant women who received clinic or home partner HIV testing. We evaluated acceptance of paired HIV-syphilis testing during pregnancy or at 6 months postpartum, and evaluated whether addition of syphilis testing affected the uptake of HIV testing among men. RESULTS: Of 601 women, we were unable to meet 101 male partners, and 180 tested before syphilis tests were available. Paired syphilis and HIV testing was offered at home to 80 men during pregnancy and to 230 men postpartum. For syphilis, 93% of men agreed to test during pregnancy and 98% agreed postpartum. For paired syphilis and HIV testing, 91% of men tested for both during pregnancy and 96% tested postpartum. Before syphilis test introduction, 96% of men accepted HIV testing, compared with 95% of men who accepted HIV testing when paired testing was offered. CONCLUSIONS: Uptake of syphilis and HIV testing was high among male partners offered couple testing at home. Introducing syphilis testing did not adversely affect HIV testing among men. Point-of-care diagnostics outside facilities can increase testing of male partners who rarely accompany women to antenatal clinics.

TAILS N-Terminomics and Proteomics Show Protein Degradation Dominates over Proteolytic Processing by Cathepsins in Pancreatic Tumors.

Deregulated cathepsin proteolysis occurs across numerous cancers, but in vivo substrates mediating tumorigenesis remain ill-defined. Applying 8-plex iTRAQ terminal amine isotopic labeling of substrates (TAILS), a systems-level N-terminome degradomics approach, we identified cathepsin B, H, L, S, and Z in vivo substrates and cleavage sites with the use of six different cathepsin knockout genotypes in the Rip1-Tag2 mouse model of pancreatic neuroendocrine tumorigenesis. Among 1,935 proteins and 1,114 N termini identified by TAILS, stable proteolytic products were identified in wild-type tumors compared with one or more different cathepsin knockouts (17%-44% of 139 cleavages). This suggests a lack of compensation at the substrate level by other cathepsins. The majority of neo-N termini (56%-83%) for all cathepsins was consistent with protein degradation. We validated substrates, including the glycolytic enzyme pyruvate kinase M2 associated with the Warburg effect, the ER chaperone GRP78, and the oncoprotein prothymosin-alpha. Thus, the identification of cathepsin substrates in tumorigenesis improves the understanding of cathepsin functions in normal physiology and cancer.

Home-Based HIV Testing Among Pregnant Couples Increases Partner Testing and Identification of Serodiscordant Partnerships.

INTRODUCTION: Male partner HIV testing has been recognized as an important component of prevention of mother-to-child HIV transmission. Scheduled home-based couple HIV testing may be an effective strategy to reach men. METHODS: Women attending their first antenatal visit at Kisumu County Hospital in Kenya were randomized to home-based education and HIV testing within 2 weeks of enrollment (HOPE) or to written invitations for male partners to attend clinic (INVITE). Male partner HIV testing and maternal child health outcomes were compared at 6 months postpartum. RESULTS: Of 1101 women screened, 620 were eligible and 601 were randomized to HOPE (n = 306) or INVITE (n = 295). At 6 months postpartum, male partners were more than twice as likely [relative risk (RR) = 2.10; 95% CI (CI): 1.81 to 2.42] to have been HIV tested in the HOPE arm [233 (87%)] compared with the INVITE arm [108 (39%)]. Couples in the HOPE arm [192 (77%)] were 3 times as likely (RR = 3.17; 95% CI: 2.53 to 3.98) to have been tested as a couple as the INVITE arm [62 (24%)] and women in the HOPE arm [217 (88%)] were also twice as likely (RR = 2.27; 95% CI: 1.93 to 2.67) to know their partner's HIV status as the INVITE arm [98 (39%)]. More serodiscordant couples were identified in the HOPE arm [33 (13%)] than in the INVITE arm [10 (4%)] (RR = 3.38; 95% CI: 1.70 to 6.71). Maternal child health outcomes of facility delivery, postpartum family planning, and exclusive breastfeeding did not vary by arm. CONCLUSIONS: Home-based HIV testing for pregnant couples resulted in higher uptake of male partner and couple testing, as well as higher rates of HIV status disclosure and identification of serodiscordant couples. However, the intervention did not result in higher uptake of maternal child health outcomes, because facility delivery and postpartum family planning were high in both arms, whereas exclusive breastfeeding was low. The HOPE intervention was successful at its primary aim to increase HIV testing and disclosure among pregnant couples and was able to find more serodiscordant couples compared with the invitation-only strategy. TRIAL REGISTRATION: Clinicaltrials.gov registry: NCT01784783.

Modeling the Cost-Effectiveness of Home-Based HIV Testing and Education (HOPE) for Pregnant Women and Their Male Partners in Nyanza Province, Kenya.

INTRODUCTION: Women in sub-Saharan Africa face a 2-fold higher risk of HIV acquisition during pregnancy and postpartum and the majority do not know the HIV status of their male partner. Home-based couple HIV testing for pregnant women can reduce HIV transmission to women and infants while increasing antiretroviral therapy (ART) coverage in men. However, the cost-effectiveness of this program has not been evaluated. METHODS: We modeled the health and economic impact of implementing a home-based partner education and HIV testing (HOPE) intervention for pregnant women and their male partners in a region of Western Kenya (formally Nyanza Province). We used data from the HOPE randomized clinical trial conducted in Kisumu, Kenya, to parameterize a mathematical model of HIV transmission. We conducted an in-country microcosting of the HOPE intervention (payer perspective) to estimate program costs as well as a lower cost scenario of task-shifting to community health workers. RESULTS: The incremental cost of adding the HOPE intervention to standard antenatal care was $31-37 and $14-16 USD per couple tested with program and task-shifting costs, respectively. At 60% coverage of male partners, HOPE was projected to avert 6987 HIV infections and 2603 deaths in Nyanza province over 10 years with an incremental cost-effectiveness ratio (ICER) of $886 and $615 per disability-adjusted life year averted for the program and task-shifting scenario, respectively. ICERs were robust to changes in intervention coverage, effectiveness, and ART initiation and dropout rates. CONCLUSIONS: The HOPE intervention can moderately decrease HIV-associated morbidity and mortality by increasing ART coverage in male partners of pregnant women. ICERs fall below Kenya's per capita gross domestic product ($1358) and are therefore considered cost-effective. Task-shifting to community health workers can increase intervention affordability and feasibility.

Quality of Sexually Transmitted Infection Case Management Services in Gauteng Province, South Africa: An Evaluation of Health Providers' Knowledge, Attitudes, and Practices.

BACKGROUND: The sexually transmitted infection (STI) clinical encounter is an opportunity to identify current and prevent new HIV and STI infections. We examined knowledge, attitudes, and practices regarding STIs and HIV among public and private providers in a large province in South Africa with a high disease burden. METHODS: From November 2008 to March 2009, 611 doctors and nurses from 120 public and 52 private clinics serving patients with STIs in Gauteng Province completed an anonymous, self-administered survey. Responses were compared by clinic location, provider type, and level of training. RESULTS: Most respondents were nurses (91%) and female (89%), were from public clinics (91%), and had received formal STI training (67%). Most (88%) correctly identified all of the common STI syndromes (i.e., genital ulcer syndrome, urethral discharge syndrome, and vaginal discharge syndrome). However, almost none correctly identified the most common etiologies for all 3 of these syndromes (0.8%), or the recommended first or alternative treatment regimens for all syndromes (0.8%). Very few (6%) providers correctly answered the 14 basic STI knowledge questions. Providers reporting formal STI training were more likely to identify correctly all 3 STI syndromes (P = 0.034) as well as answer correctly all 14 general STI knowledge questions (P = 0.016) compared with those not reporting STI training. In addition, several providers reported negative attitudes about patients with STI that may have affected their ability to practice optimal STI management. CONCLUSIONS: Sexually transmitted infection general knowledge was suboptimal, particularly among providers without STI training. Provider training and brief refresher courses on specific aspects of diagnosis and management may benefit HIV/STI clinical care and prevention in Gauteng Province.

Elimination of mother-to-child transmission of HIV and syphilis: A dual approach in the African Region to improve quality of antenatal care and integrated disease control.

The World Health Organization's (WHO) Strategic Framework for the Elimination of New HIV Infections among Children in Africa by 2015 identifies important synergies for the elimination of mother-to-child transmission of HIV and syphilis in terms of prevention interventions, implementation logistics and service delivery, monitoring and evaluation systems, and need for sustained political commitment. The WHO advocates the use of an integrated, rights-based dual approach with partnerships and collaboration to make the best use of available resources. Through a consultative approach, six countries in the African Region committed to dual elimination and developed and implemented action plans for this purpose. Where interest and commitment are high, this may also be possible and effective in other African countries.

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. METHODS: PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. FINDINGS: Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). CONCLUSION: Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.

A road map for the global elimination of congenital syphilis.

Congenital syphilis is the oldest recognized congenital infection, and continues to account for extensive global perinatal morbidity and mortality today. Serious adverse pregnancy outcomes caused by maternal syphilis infection are prevented with screening early in pregnancy and prompt treatment of women testing positive. Intramuscular penicillin, an inexpensive antibiotic on the essential medicine list of nations all over the world, effectively cures infection and prevents congenital syphilis. In fact, at a cost of $11-15 per disability adjusted life year (DALY) averted, maternal syphilis screening and treatment is among the most cost-effective public health interventions in existence. Yet implementation of this basic public health intervention is sporadic in countries with highest congenital syphilis burden. We discuss the global burden of this devastating disease, current progress and ongoing challenges for its elimination in countries with highest prevalence, and next steps in ensuring a world free of preventable perinatal deaths caused by syphilis.

Risk factors and algorithms to identify hepatitis C, hepatitis B, and HIV among Georgian tuberculosis patients.

OBJECTIVES: To determine prevalence, risk factors, and simple identification algorithms for HIV, hepatitis B, and hepatitis C co-infection; factors that may predispose for anti-tuberculosis therapy-induced hepatotoxicity. METHODS: We recruited 300 individuals at in-patient tuberculosis hospitals in three cities in Georgia, administered a behavioral questionnaire, and tested for antibody to HIV, hepatitis C (HCV), hepatitis B core antigen (anti-HBc), and the hepatitis B surface antigen (HBsAg). RESULTS: Of the individuals tested, 0.7% were HIV positive, 4.3% were HBsAg positive, 8.7% were anti-HBc positive, and 12.0% were HCV positive. In multivariable analysis, a history of blood transfusion, injection drug use, and prison were significant independent risk factors for HCV, while a history of blood transfusion, injection drug use, younger age at sexual debut, and a high number of sex partners were significant risk factors for HBV. Three-questionnaire item algorithms predicted HCV serostatus 74.1% of the time and HBV serostatus 85.2% of the time. CONCLUSIONS: Treatment of tuberculosis patients in resource-limited countries with concurrent epidemics of HCV, HBV, and HIV may be associated with significant hepatotoxicity. Serologic screening of tuberculosis patients for HBV, HCV, and HIV or using behavioral algorithms to identify patients in need of intensive monitoring during anti-tuberculosis therapy may reduce this risk.