Public health emergency preparedness for infectious disease emergencies: a scoping review of recent evidence.

BACKGROUND: The COVID-19 pandemic continues to demonstrate the risks and profound health impacts that result from infectious disease emergencies. Emergency preparedness has been defined as the knowledge, capacity and organizational systems that governments, response and recovery organizations, communities and individuals develop to anticipate, respond to, or recover from emergencies. This scoping review explored recent literature on priority areas and indicators for public health emergency preparedness (PHEP) with a focus on infectious disease emergencies. METHODS: Using scoping review methodology, a comprehensive search was conducted for indexed and grey literature with a focus on records published from 2017 to 2020 onward, respectively. Records were included if they: (a) described PHEP, (b) focused on an infectious emergency, and (c) were published in an Organization for Economic Co-operation and Development country. An evidence-based all-hazards Resilience Framework for PHEP consisting of 11 elements was used as a reference point to identify additional areas of preparedness that have emerged in recent publications. The findings were analyzed deductively and summarized thematically. RESULTS: The included publications largely aligned with the 11 elements of the all-hazards Resilience Framework for PHEP. In particular, the elements related to collaborative networks, community engagement, risk analysis and communication were frequently observed across the publications included in this review. Ten emergent themes were identified that expand on the Resilience Framework for PHEP specific to infectious diseases. Planning to mitigate inequities was a key finding of this review, it was the most frequently identified emergent theme. Additional emergent themes were: research and evidence-informed decision making, building vaccination capacity, building laboratory and diagnostic system capacity, building infection prevention and control capacity, financial investment in infrastructure, health system capacity, climate and environmental health, public health legislation and phases of preparedness. CONCLUSION: The themes from this review contribute to the evolving understanding of critical public health emergency preparedness actions. The themes expand on the 11 elements outlined in the Resilience Framework for PHEP, specifically relevant to pandemics and infectious disease emergencies. Further research will be important to validate these findings, and expand understanding of how refinements to PHEP frameworks and indicators can support public health practice.

Rising through the pandemic: a scoping review of quality improvement in public health during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic generated a growing interest in and need for evidence-based tools to facilitate the implementation of emergency management strategies within public health practice. Quality improvement (QI) is a key framework and philosophy to guide organizational emergency response efforts; however, the nature and extent to which it has been used in public health settings during the COVID-19 pandemic remains unclear. METHODS: We conducted a scoping review of literature published January 2020 - February 2021 and focused on the topic of QI at public health agencies during the COVID-19 pandemic. The search was conducted using four bibliographic databases, in addition to a supplementary grey literature search through custom Google search engines and targeted website search methods. Of the 1,878 peer-reviewed articles assessed, 15 records met the inclusion criteria. An additional 11 relevant records were identified during the grey literature search, for a total of 26 records included in the scoping review. RESULTS: Records were organized into five topics: 1) collaborative problem solving and analysis with stakeholders; 2) supporting learning and capacity building in QI; 3) learning from past emergencies; 4) implementing QI methods during COVID-19; and 5) evaluating performance using frameworks/indicators. CONCLUSIONS: The literature indicates that QI-oriented activities are occurring at the organizational and program levels to enhance COVID-19 response. To optimize the benefits that QI approaches and methodologies may offer, it is important for public health agencies to focus on both widespread integration of QI as part of an organization's management philosophy and culture, as well as project level activities at all stages of the emergency management cycle.

Review of sexualized drug use associated with sexually transmitted and blood-borne infections in gay, bisexual and other men who have sex with men.

PURPOSE: The aim of the present study was to quantify associations between sexualized drug use (SDU) and sexually-transmitted and blood-borne infection (STBBI) diagnoses in gay, bisexual and other men who have sex with men (GBMSM) with defined temporal proximity between SDU exposure and STBBI diagnoses. METHODS: In May 2018 and June 2019, we searched the literature for primary studies that quantified the association between STBBI and SDU among GBMSM. A random-effects model was used to meta-analyze the data and estimate the association between SDU and STBBIs. RESULTS: Nineteen studies met the inclusion criteria and fourteen studies were included in the meta-analyses. SDU was associated with higher odds of bacterial STI diagnoses, higher odds of HCV diagnoses, and higher odds of HIV diagnoses. Associations between SDU and diagnoses of bacterial STIs or HCV remained after adjustment for behavioral and sociodemographic factors. CONCLUSIONS: Robust and consistent associations between SDU and STBBI identified in this review add to the evidence suggesting SDU is a potential contributor to bacterial STIs and HCV or a proxy indicator for other risk factors.

HCV core antigen as an alternative to HCV RNA testing in the era of direct-acting antivirals: retrospective screening and diagnostic cohort studies.

BACKGROUND: Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR). METHODS: In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945-74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed. FINDINGS: From 10 006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86-98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94-100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2 000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29-3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results. INTERPRETATION: These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries. FUNDING: Abbott Diagnostics and Toronto Centre for Liver Disease.

Waning of measles maternal antibody in infants in measles elimination settings - A systematic literature review.

INTRODUCTION: Most infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination. METHODS: We conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool. RESULTS: We identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3-7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune. CONCLUSION: Although limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.

Population-based estimate of hepatitis C virus prevalence in Ontario, Canada.

BACKGROUND: Hepatitis C virus (HCV) is the most burdensome infectious illness in Canada. Current screening strategies miss a significant proportion of cases, leaving many undiagnosed. Elevated HCV prevalence in those born between 1945 and 1965 has prompted calls for birth-cohort screening in this group. However, Canada lacks population-level data to support this recommendation. We performed a serosurvey to obtain population-based HCV prevalence estimates in Ontario residents born between 1945-1974, to generate evidence for birth-cohort screening recommendations. METHODS: We tested anonymized residual sera in five-year age-sex bands from Ontario for anti-HCV antibody. We performed descriptive epidemiological analysis and used a logistic regression model to determine HCV risk-factors. RESULTS: Of 10,006 sera analyzed, 155 (1.55%, 95% confidence interval (CI) 1.32, 1.81) were positive for HCV antibody. Individuals born between 1950-1964 had a significantly higher combined prevalence of 1.92% (95% CI 1.56, 2.34) compared to 1.14% (95% CI 0.69, 1.77) (p = 0.04) for those born between 1970-1974. For males, comprising 107/155 (69.03%) of positive samples, the highest prevalence was 3.00% (95% CI 1.95, 4.39) for the 1960-1964 birth-cohort. For females, the highest prevalence was 1.56% (95% CI 0.83, 2.65) for those born between 1955-1959. Male sex was significantly associated with positive HCV serostatus. INTERPRETATION: HCV prevalence in Ontario is highest among those in this birth cohort, and higher than previous estimates. The prevalence estimates presented in our study provide important data to underpin birth-cohort screening recommendations.

The basic reproduction number (R0) of measles: a systematic review.

The basic reproduction number, R nought (R0), is defined as the average number of secondary cases of an infectious disease arising from a typical case in a totally susceptible population, and can be estimated in populations if pre-existing immunity can be accounted for in the calculation. R0 determines the herd immunity threshold and therefore the immunisation coverage required to achieve elimination of an infectious disease. As R0 increases, higher immunisation coverage is required to achieve herd immunity. In July, 2010, a panel of experts convened by WHO concluded that measles can and should be eradicated. Despite the existence of an effective vaccine, regions have had varying success in measles control, in part because measles is one of the most contagious infections. For measles, R0 is often cited to be 12-18, which means that each person with measles would, on average, infect 12-18 other people in a totally susceptible population. We did a systematic review to find studies reporting rigorous estimates and determinants of measles R0. Studies were included if they were a primary source of R0, addressed pre-existing immunity, and accounted for pre-existing immunity in their calculation of R0. A search of key databases was done in January, 2015, and repeated in November, 2016, and yielded 10 883 unique citations. After screening for relevancy and quality, 18 studies met inclusion criteria, providing 58 R0 estimates. We calculated median measles R0 values stratified by key covariates. We found that R0 estimates vary more than the often cited range of 12-18. Our results highlight the importance of countries calculating R0 using locally derived data or, if this is not possible, using parameter estimates from similar settings. Additional data and agreed review methods are needed to strengthen the evidence base for measles elimination modelling.

Double Trouble: Prevalence and Factors Associated with Tuberculosis and Diabetes Comorbidity in Bangladesh.

BACKGROUND: Diabetes among tuberculosis patients increases the risk of tuberculosis treatment failure, death, and development of multidrug-resistant tuberculosis. Yet, there is no data is available in Bangladesh on the prevalence of diabetes among tuberculosis patients. The objective of the current study was to estimate prevalence and identify factors associated with tuberculosis-diabetes co-morbidity among TB patients enrolled in the Directly Observed Treatment, Short course program. METHODS: A community based cross-sectional quantitative study was conducted among 1910 tuberculosis patients living in six urban and eleven rural areas among whom Oral Glucose Tolerance Test (those who fasted) and Random Blood Sugar test (those who did not fast) were performed. Besides glucose levels, data on socio-demographic information, family history of diabetes and anthropometric measurements (height and weight) were also collected. RESULT: Among the 1910 TB patients who participated in screening for diabetes, 245 (12.8%) were found to have diabetes and 296 (15.5%) to have pre-diabetes. Out of those who had diabetes, 34.7% were newly diagnosed through the current study and 65.3% already knew their status. Among those who were found to have prediabetes, 27 (9.1%) had impaired Fasting Blood Glucose (FBG), 230 (77.7%) had Impaired Glucose Tolerance (IGT), and 39 (13.2%) had both Impaired FBG and IGT. Older age, higher BMI, higher education (secondary level and above), being married, participation in less active work, and family history of diabetes are associated with higher prevalence of diabetes. CONCLUSION: We observed a higher prevalence of diabetes and pre-diabetes in TB patients than reported previously in Bangladesh among the general population which may challenge TB and diabetes control in Bangladesh. Diabetes diagnosis, treatment and care should be integrated in the National TB Program.

Early impact of Ontario's human papillomavirus (HPV) vaccination program on anogenital warts (AGWs): A population-based assessment.

INTRODUCTION: This study aimed to evaluate the early population impact of Ontario's school-based human papillomavirus (HPV) vaccination program, implemented in September 2007 for grade 8 females, by comparing anogenital wart (AGW) health care utilization before and after vaccine program implementation, in program-eligible and program-ineligible cohorts, focusing on 15-26year olds. METHODS: Using a retrospective longitudinal population-based study design, health administrative data were used to identify incident AGWs and total health service utilization (HSU) for AGWs for Ontario residents 15years and older between April 1 2004 and March 31 2014. The study period was divided into two eras: the pre-vaccine program era and the vaccine program era. Negative binomial models were generated to analyze trends across time by age group and sex. We adjusted female rates for routine Papanicolaou (Pap) testing to address spillover effects of Pap smear policy changes on AGW diagnosis. RESULTS: Between fiscal years 2004 and 2013, AGW incidence decreased 2.6% on average per year in 15-17year old females, and total HSU for AGWs decreased an average of 4.8% and 2.2% per year in 15-17 and 18-20year old females. Comparing the vaccine era to the pre-vaccine era, AGW incidence decreased 6.5% in 18-20year old females, and AGW HSU decreased 13.8%, 11.1%, and 10.0% in 15-17, 18-20, and 21-23year old females respectively. In contrast, male AGW incidence rates increased an average of 4.1%, 2.8%, and 0.9% per year in 15-17, 21-23, and 24-26year old males respectively. AGW incidence rates increased 12.2% in 15-17year old males from the pre-vaccine to vaccine era. CONCLUSION: The decline in AGW incidence and HSU in program-eligible females suggests the school-based HPV vaccination program has had an early population impact in Ontario. The increasing AGW incidence in males suggests no early evidence of herd effects in males.

Health service utilisation for anogenital warts in Ontario, Canada prior to the human papillomavirus (HPV) vaccine programme introduction: a retrospective longitudinal population-based study.

OBJECTIVE: Trends in occurrence of anogenital warts (AGWs) can provide early evidence of human papillomavirus (HPV) vaccination programme impact on preventing HPV infection and HPV-induced lesions. The objective of this study was to provide a baseline of AGW epidemiology in Ontario prior to the introduction of the publicly-funded school-based HPV vaccination programme in September 2007. SETTING AND PARTICIPANTS: As a retrospective longitudinal population-based study, we used health administrative data as a proxy to estimate incident AGWs and total health service utilisation (HSU) for AGWs for all Ontario residents 15 years and older with valid health cards between 1 April 2003 and 31 March 2007. OUTCOME MEASURES: The outcome of interest was AGW healthcare utilisation identified using the International Classification of Diseases, 10th revision (ICD-10) diagnostic code for AGWs, as well as an algorithm for identifying AGW physician office visits in a database with a unique system of diagnostic and procedural codes. An AGW case was considered incident if preceded by 12 months without HSU for AGWs. Time trends by age group and sex were analysed. RESULTS: Between fiscal years 2003 and 2006, we identified 123,247 health service visits for AGWs by 51,436 Ontario residents 15 years and older. Incident AGWs peaked in females and males in the 21-23 year age group, at 3.74 per 1000 and 2.81 per 1000, respectively. HSU for AGWs peaked in females and males within the 21-23 year age group, at 9.34 per 1000 and 7.22 per 1000, respectively. CONCLUSIONS: To the best of our knowledge, this is the first population-based study of AGW incidence and HSU in Ontario. The sex and age distribution of individuals with incident and prevalent AGWs in Ontario was similar to that of other provinces before HPV vaccine programme implementation in Canada.

Prevalence of knowledge and use of the female condom in South Africa.

Male condoms remain a key tool in preventing the spread of HIV and the female condom (FC) holds similar potential. Using data collected through a national cross-sectional population survey that was conducted in 2008, this report investigated the national prevalence of FC knowledge and use by sexually active males and females (n = 7,727) over the age of 15 years in South Africa, followed by a closer examination of the sexually active female population alone. Though knowledge of the FC among sexually active females over the age of 15 years (n = 4,551) was relatively high at 77.75 %, use was low at 7.16 %. The present study found statistically significant associations between knowledge or use of the FC and several demographic variables for females in South Africa. Having heard of the FC was consistently associated with locality, province, age, education level, marital status, and employment status. Use of the FC, however, was only associated with province and age group. Many demographic groups exhibited a high prevalence of knowledge but a low level of use; or conversely, a low prevalence of knowledge but a high level of use compared to their counterparts. Our findings support the need for a rigorous campaign to promote the use of FCs by women and also to increase their availability in public health sector facilities such as government clinics and hospitals in order to improve the chance of women using the FC, a cost-effective device that has the potential to protect both their rights and lives.

Homeodomain-interacting protein kinase (HIPK)-1 is required for splenic B cell homeostasis and optimal T-independent type 2 humoral response.

The homeodomain-interacting protein kinase (HIPK) family is comprised of four highly related serine/threonine kinases originally identified as co-repressors for various homeodomain-containing transcription factors. The HIPKs have been shown to be involved in growth regulation and apoptosis, with numerous studies highlighting HIPK regulation of the tumor suppressor p53. In this study, we have discovered a B cell homeostatic defect in HIPK1-deficient (HIPK1(-/-)) mice. Lymphopoietic populations within the thymus and bone marrow of HIPK1(-/-) mice appeared normal based upon FACS analysis; however, the spleen exhibited a reduced number of total B cells with a significant loss of transitional-1 and follicular B cell populations. Interestingly, the marginal zone B cell population was expanded in HIPK1(-/-) mice, yielding an increased frequency of these cells. HIPK1(-/-) B cells exhibited impaired cell division in response to B cell receptor cross-linking in vitro based upon thymidine incorporation or CFSE dilution; however, the addition of CD40L rescued HIPK1(-/-) proliferation to wild-type levels. Despite the expanded MZ B cell population in the HIPK1(-/-) mice, the T-independent type 2 humoral response was impaired. These data identify HIPK1 as a novel kinase required for optimal B cell function in mice.

Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins.

The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orchestrate the inflammatory response. The operation of feedback control mechanisms that regulate the duration and the amplitude of antigenic and cytokine receptor signaling is therefore required to prevent hyper-activation of the immune system that could lead to tissue destruction or autoimmunity. Suppressor of cytokine signaling (SOCS) proteins have been identified as a negative feedback loop to cytokine signaling. Recently, the generation of genetically engineered mouse models permitted the evaluation of their function in different processes of the immune responses. In this article, we review new insights into the modular structure of SOCS proteins and the function of SOCS1 and SOCS3 to negatively regulate activation and/or differentiation pathways in macrophages, dendritic cells, and T lymphocytes. Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses.