WHO's Investigations and Studies, Unity Studies: A global initiative creating equitable opportunities for enhanced surveillance, operational research, capacity building, and global knowledge sharing.

The World Health Organization's Unity Studies global initiative provides a generic preparedness and readiness framework for conducting detailed investigations and epidemiological studies critical for the early and ongoing assessment of emerging respiratory pathogens of pandemic potential. During the COVID-19 pandemic, the initiative produced standardized investigation protocols and supported Member States to generate robust and comparable data to inform public health decision making. The subsequent iteration of the initiative is being implemented to develop revised and new investigation protocols, implementation toolkits and work to build a sustainable global network of sites, enabling the global community to be better prepared for the next emerging respiratory pathogen with epidemic or pandemic potential.

Primary series COVID-19 vaccine effectiveness among healthcare workers in Albania, February-December 2021.

Background: Healthcare workers have experienced high rates of morbidity and mortality from coronavirus disease 2019 (COVID-19). Methods: A prospective cohort study was conducted in three Albanian hospitals between 19 February and 14 December 2021. All participants underwent polymerase chain reaction (PCR) and serological testing at enrolment, regular serology throughout, and PCR testing when symptomatic.Vaccine effectiveness (VE) against COVID-19 and against all severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections (symptomatic or asymptomatic) was estimated. VE was estimated using a Cox regression model, with vaccination status as a time-varying variable. Findings: In total, 1504 HCWs were enrolled in this study; 70% had evidence of prior SARS-CoV-2 infection. VE was 65.1% [95% confidence interval (CI) 37.7-80.5] against COVID-19, 58.2% (95% CI 15.7-79.3) among participants without prior SARS-CoV-2 infection, and 73.6% (95% CI 24.3-90.8) among participants with prior SARS-CoV-2 infection. For BNT162b2 alone, VE was 69.5% (95% CI 44.5-83.2). During the period when the Delta variant was predominant, VE was 67.1% (95% CI 38.3-82.5). VE against SARS-CoV-2 infection for the full study period was 36.9% (95% CI 15.8-52.7). Interpretation: This study found moderate primary series VE against COVID-19 among healthcare workers in Albania. These results support the continued promotion of COVID-19 vaccination in Albania, and highlight the benefits of vaccination in populations with high levels of prior infection.

Hair glucocorticoids are not a historical marker of stress - Exploring the time-scale of corticosterone incorporation into hairs in a rat model.

Hair glucocorticoids are increasingly popular biomarkers, used across numerous research fields, and studied species, as a measure of stress. Although they are suggested to be a proxy of the average HPA axis activity spanning a period of weeks or months into the past, this theory has never been tested. In the present study, adrenalectomized rats with no endogenous (adrenal) glucocorticoid production were used to study how circulating glucocorticoid levels would be reflected in the glucocorticoid levels found in hair samples. By dosing the animals daily with high levels of corticosterone for seven days, while sampling hairs before, during, and after treatments, a timeline for glucocorticoid uptake into hairs was constructed. This kinetic profile was compared to two hypothetical models, and the theory that hair glucocorticoids are a record of historical stress had to be rejected. Corticosterone concentrations in hairs were found to increase within three hours of the first injection, the highest concentrations were found on the seventh day of treatments, and the decrease in concentrations post-treatment suggests rapid elimination. We speculate that hair glucocorticoid levels can only be used to characterize a stress-response for a few days following a postulated stressor. An updated model, where glucocorticoids diffuse into, along, and out of hairs needs to be adopted to reconcile the experimentally obtained data. The inescapable consequence of this updated model is that hair glucocorticoids become a marker of - and can only be used to study - recent, or ongoing, stress, as opposed to historical events, weeks or months in the past.

De Novo Whole-Genome Sequencing of Two Pathogenic Pasteurella multocida Type D:6 Strains Isolated from Pigs.

Here, we report the complete genome sequences of Pasteurella multocida strains P504190 and P504188/1, which were isolated from the diseased lungs of a sow and her piglet, respectively. Despite the unusual clinical presentation, whole-genome sequence typing revealed both strains to be capsular type D and lipopolysaccharide (LPS) group 6, commonly found in pigs.

Factors associated with receipt of COVID-19 vaccination and SARS-CoV-2 seropositivity among healthcare workers in Albania (February 2021-June 2022): secondary analysis of a prospective cohort study.

Background: Healthcare workers (HCWs) have been disproportionally affected by COVID-19. We investigated factors associated with two- and three-dose COVID-19 vaccine uptake and SARS-CoV-2 seropositivity among 1504 HCWs enrolled (19 February-7 May 2021) in a prospective COVID-19 vaccine effectiveness cohort in Albania through a secondary analysis. Methods: We collected sociodemographic, occupational, health, prior SARS-CoV-2 infection, and COVID-19 vaccination data from all HCWs at enrollment. Vaccination status was assessed weekly through June 2022. A serum sample was collected from all participants at enrollment and tested for anti-spike SARS-CoV-2 antibodies. We analyzed HCWs characteristics and outcomes using multivariable logistic regression. Findings: By 11 June 2022, 1337 (88.9%) HCWs had received two COVID-19 vaccine doses, of whom 255 (19.1%) received a booster. Factors significantly associated with receiving three doses (adjusted odds ratio (aOR), 95% CIs) were being ≥35 years (35-44 years: 1.76 (1.05-2.97); 45-54 years: 3.11 (1.92-5.05); ≥55 years: 3.38 (2.04-5.59)) and vaccinated against influenza (1.78; 1.20-2.64). Booster dose receipt was lower among females (0.58; 0.41-0.81), previously infected (0.67; 0.48-0.93), nurses and midwives (0.31; 0.22-0.45), and support staff (0.19; 0.11-0.32). Overall 1076 (72%) were SARS-CoV-2 seropositive at enrollment. Nurses and midwifes (1.45; 1.05-2.02), support staff (1.57; 1.03-2.41), and HCWs performing aerosol-generating procedures (AGPs) (1.40; 1.01-1.94) had higher odds of being seropositive, while smokers had reduced odds (0.55; 0.40-0.75). Interpretation: In a large cohort of Albanian HCWs, COVID-19 vaccine booster dose uptake was very low, particularly among younger, female, and non-physician HCWs, despite evidence demonstrating the added benefit of boosters in preventing infection and severe disease. Reasons behind these disparities should be explored to develop targeted strategies in order to promote uptake in this critical population. SARS-CoV-2 seroprevalence was higher among non-physicians and HCWs performing APGs. A better understanding of the factors contributing to these differences is needed to inform interventions that could reduce infections in the future. Funding: This study was funded by the Task Force for Global Health (US Centers for Disease Control (CDC) cooperative agreement # NU51IP000873) and the World Health Organization, Regional Office for Europe.

Effects of Transdermal Fentanyl Treatment on Acute Pain and Inflammation in Rats with Adjuvant-induced Monoarthritis.

Eliminating unnecessary pain is an important requirement of performing animal experimentation, including reducing and controlling pain of animals used in pain research. The goal of this study was to refine an adjuvant-induced monoarthritis model in rats by providing analgesia with a transdermal fentanyl solution (TFS). Male and female Sprague-Dawley rats, single- or pair-housed, were injected with 20 µL of complete Freund adjuvant (CFA) into the left ankle joint. CFA-injected rats treated with a single dose of transdermal fentanyl solution (0.33 or 1 mg/kg) were compared with an untreated CFA-injected group and sham groups that received either no treatment or TFS treatment (1 mg/kg) during 72 h. At the tested doses, TFS reduced mechanical hyperalgesia and improved the mobility, stance, rearing, and lameness scores at 6 h after CFA injection. Joint circumferences were not reduced by TFS treatment, and no significant differences were detected between the 2 doses of TFS, or between single- and pair-housed rats. Treatment with TFS did not appear to interfere with model development and characteristics. However, overall, the analgesic effect was transient, and several opioid-related side effects were observed.

Sociodemographic and Occupational Factors Associated with Low Early Uptake of COVID-19 Vaccine in Hospital-Based Healthcare Workers, Georgia, March-July 2021.

In Georgia, an upper-middle income European country, the COVID-19 vaccine rollout began on 15 March 2021 with health workers (HWs), a priority group for vaccination. We assessed the factors associated with COVID-19 vaccination among HWs at six large hospitals in the early stages of the vaccine rollout (March−July 2021). Among 1533 HWs, 274 (17.9%) had received one dose of the COVID-19 vaccine. Strong independent predictors of early vaccine uptake were age > 40 years, especially 50−59 years old (aOR 2.40, 95% CI 1.50−3.88), considering the vaccine as "somewhat effective" or "very effective" rather than "not effective" (aOR 6.33, 95% CI 2.29−26.3 and aOR 10.9, 95% CI 3.88−45.70, respectively), and previous vaccination against seasonal influenza (aOR 2.98, 95% CI 2.19−4.08). Previous SARS-CoV-2 infection was negatively associated with receiving the vaccine (aOR 0.6, 95% CI 0.40−0.80). Compared to physicians, nurses/midwives (aOR 0.22, 95% CI 0.15−0.32), administrative staff (aOR 0.36, 95% CI 0.22−0.56), and ancillary staff (aOR 0.07, 95% CI 0.04−0.15) were less likely to have received the COVID-19 vaccine. Tailoring the COVID-19 vaccine communications campaign to younger and non-physician HWs, and emphasizing the benefits of the COVID-19 vaccine, could help further increase vaccine coverage among HWs in Georgia.

Turoctocog alfa pegol (N8-GP) in severe hemophilia A: Long-term safety and efficacy in previously treated patients of all ages in the pathfinder8 study.

Background: N8-GP (turoctocog alfa pegol; Esperoct) is a glycoPEGylated human recombinant factor VIII (FVIII). Objectives: Pathfinder8 (NCT01480180) was a phase 3, multinational, open-label, nonrandomized trial to investigate the long-term safety and efficacy of N8-GP in people of all ages with severe hemophilia A previously treated with N8-GP. Patients/Method: Patients were recruited from the completed phase 3 pathfinder2 and pathfinder5 trials to receive intravenous N8-GP prophylaxis for up to 104 weeks, administered every 7 days, twice weekly, or three times weekly. Primary and secondary end points were the number of adverse events (AEs) reported and efficacy of treatment, respectively. Results: Overall, 160 patients were exposed to N8-GP for a mean of 179 exposure days and 681 calendar days (≈1.9 years) per patient. In total, 119 patients experienced 510 AEs, corresponding to a rate of 1.71 AEs per patient-year of exposure; 97.5% of AEs were mild or moderate in severity, and no AEs led to withdrawal. No patients developed FVIII inhibitors during the trial. The Poisson estimate of mean annualized bleeding rate for all bleeds (excluding surgery) and across all regimens was 1.10 (median, 0.00), and for spontaneous bleeds was 0.61 (median, 0.00). Most (55.6%) patients experienced no bleeds that required FVIII treatment (excluding perioperative bleeds). The estimated hemostatic success rate for the treatment of 322 bleeding episodes (excluding surgery) was 95.8%, including missing values as failure. Conclusions: Long-term prophylactic use of N8-GP appeared safe and efficacious across all age groups in people with severe hemophilia A previously treated with N8-GP.

COVID-19 vaccine effectiveness among healthcare workers in Albania (COVE-AL): protocol for a prospective cohort study and cohort baseline data.

INTRODUCTION: Critical questions remain about COVID-19 vaccine effectiveness (VE) in real-world settings, particularly in middle-income countries. We describe a study protocol to evaluate COVID-19 VE in preventing laboratory-confirmed SARS-CoV-2 infection in health workers (HWs) in Albania, an upper-middle-income country. METHODS AND ANALYSIS: In this 12-month prospective cohort study, we enrolled HWs at three hospitals in Albania. HWs are vaccinated through the routine COVID-19 vaccine campaign. Participants completed a baseline survey about demographics, clinical comorbidities, and infection risk behaviours. Baseline serology samples were also collected and tested against the SARS-CoV-2 spike protein, and respiratory swabs were collected and tested for SARS-CoV-2 by RT-PCR. Participants complete weekly symptom questionnaires and symptomatic participants have a respiratory swab collected, which is tested for SARS-CoV-2. At 3, 6, 9 months and 12 months of the study, serology will be collected and tested for antibodies against the SARS-CoV-2 nucleocapsid protein and spike protein. VE will be estimated using a piecewise proportional hazards model (VE=1-HR). BASELINE DATA: From February to May 2021, 1504 HWs were enrolled. The median age was 44 (range: 22-71) and 78% were female. At enrolment, 72% of participants were seropositive for SARS-CoV-2. 56% of participants were vaccinated with one dose, of whom 98% received their first shot within 4 days of enrolment. All HWs received the Pfizer BNT162b2 mRNA COVID-19 vaccine. ETHICS AND DISSEMINATION: The study protocol and procedures were reviewed and approved by the WHO Ethical Review Board, reference number CERC.0097A, and the Albanian Institute of Public Health Ethical Review Board, reference number 156. All participants have provided written informed consent to participate in this study. The primary results of this study will be published in a peer-reviewed journal at the time of completion. TRIAL REGISTRATION NUMBER: NCT04811391.

Early epidemiological investigations: World Health Organization UNITY protocols provide a standardized and timely international investigation framework during the COVID-19 pandemic.

BACKGROUND: The declaration of Coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. METHODS: The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID-19, branded the 'UNITY studies' and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low- and middle-income countries (LMIC). RESULTS: WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. CONCLUSION: The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision-making to prevent and control the pandemic.

Transmission of SARS-CoV-2 in standardised first few X cases and household transmission investigations: A systematic review and meta-analysis.

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2 = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

Household transmission of SARS-CoV-2: a prospective observational study in Bosnia and Herzegovina, August-December 2020.

BACKGROUND: The secondary attack rate (SAR) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was estimated, and the risk factors for infection among members of households with a coronavirus disease 2019 (COVID-19) index case were identified to inform preventive measures. METHODS: Between 3 August and 19 December 2020, a household transmission study was implemented based on a standardized World Health Organization protocol. Laboratory-confirmed cases of SARS-CoV-2 infection were recruited through the federal COVID-19 database. Trained contact tracers interviewed index cases and household members to collect information on demographic, clinical and behavioural factors. Contacts were followed up for 28 days to identify secondary infections. SAR was estimated and odds ratios (OR) were calculated for risk factors for transmission. RESULTS: In total, 383 households and 793 contacts were included in this study. The overall SAR was 17% [95% confidence interval (CI) 14-21]. Contacts had higher risk for infection if the primary case had both cough and runny nose (OR 4.31, 95% CI 1.60-11.63), if the contact was aged 18-49 years (OR 4.67, 95% CI 1.83-11.93), if the contact kissed the primary case (OR 3.16, 95% CI 1.19-8.43), or if the contact shared a meal with the primary case (OR 3.10, 95% CI 1.17-8.27). CONCLUSIONS: These results add to the global literature by providing evidence from a middle-income setting. Standard preventive measures in households with positive cases remain critical to reduce transmission.

Health Information Systems in the COVID-19 Pandemic: A Short Survey of Experiences and Lessons Learned From the European Region.

Introduction: The COVID-19 crisis provides an opportunity to reflect on what worked during the pandemic, what could have been done differently, and what innovations should become part of an enhanced health information system in the future. Methods: An online qualitative survey was designed and administered online in November 2020 to all the 37 Member States that are part of the WHO European Health Information Initiative and the WHO Central Asian Republics Information Network. Results: Nineteen countries responded to the survey (Austria, Belgium, Croatia, Czech Republic, Finland, Greece, Iceland, Ireland, Israel, Italy, Kazakhstan, Latvia, Lithuania, Romania, Russian Federation, Sweden, Turkey, United Kingdom, and Uzbekistan). The COVID-19 pandemic required health information systems (HIS) to rapidly adapt to identify, collect, store, manage, and transmit accurate and timely COVID-19 related data. HIS stakeholders have been put to the test, and valuable experience has been gained. Despite critical gaps such as under-resourced public health services, obsolete health information technologies, and lack of interoperability, most countries believed that their information systems had worked reasonably well in addressing the needs arising during the COVID-19 pandemic. Conclusion: Strong enabling environments and advanced and digitized health information systems are vital to controlling epidemics. Sustainable finance and government support are required for the continued implementation and enhancement of HIS. It is important to promote digital solutions beyond the COVID-19 pandemic. Now is the time to discuss potential solutions to obtain timely, accurate, and reliable health information and steer policy-making while protecting privacy rights and meeting the highest ethical standards.

First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020.

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.

Transcranial pulsed electromagnetic fields for treatment-resistant depression: A multicenter 8-week single-arm cohort study.

BACKGROUND: The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression. METHODS: A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group. RESULTS: In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4. CONCLUSIONS: The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.

La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.

How close are countries of the WHO European Region to achieving the goal of vaccinating 75% of key risk groups against influenza? Results from national surveys on seasonal influenza vaccination programmes, 2008/2009 to 2014/2015.

BACKGROUND: Influenza vaccination is recommended especially for persons at risk of complications. In 2003, the World Health Assembly urged Member States (MS) to increase vaccination coverage to 75% among older persons by 2010. OBJECTIVE: To assess progress towards the 2010 vaccination goal and describe seasonal influenza vaccination recommendations in the World Health Organization (WHO) European Region. METHODS: Data on seasonal influenza vaccine recommendations, dose distribution, and target group coverage were obtained from two sources: European Union and European Economic Area MS data were extracted from influenza vaccination surveys covering seven seasons (2008/2009-2014/2015) published by the Vaccine European New Integrated Collaboration Effort and European Centre for Disease Prevention and Control. For the remaining WHO European MS, a separate survey on policies and uptake for all seasons (2008/2009-2014/2015) was distributed to national immunization programmes in 2015. RESULTS: Data was available from 49 of 53 MS. All but two had a national influenza vaccination policy. High-income countries distributed considerably higher number of vaccines per capita (median; 139.2 per 1000 population) compared to lower-middle-income countries (median; 6.1 per 1000 population). Most countries recommended vaccination for older persons, individuals with chronic disease, healthcare workers, and pregnant women. Children were included in < 50% of national policies. Only one country reached 75% coverage in older persons (2014/2015), while a number of countries reported declining vaccination uptake. Coverage of target groups was overall low, but with large variations between countries. Vaccination coverage was not monitored for several groups. CONCLUSIONS: Despite policy recommendations, influenza vaccination uptake remains suboptimal. Low levels of vaccination is not only a missed opportunity for preventing influenza in vulnerable groups, but could negatively affect pandemic preparedness. Improved understanding of barriers to influenza vaccination is needed to increase uptake and reverse negative trends. Furthermore, implementation of vaccination coverage monitoring is critical for assessing performance and impact of the programmes.

A global review of national influenza immunization policies: Analysis of the 2014 WHO/UNICEF Joint Reporting Form on immunization.

INTRODUCTION: The WHO recommends annual influenza vaccination to prevent influenza illness in high-risk groups. Little is known about national influenza immunization policies globally. MATERIAL AND METHODS: The 2014 WHO/UNICEF Joint Reporting Form (JRF) on Immunization was adapted to capture data on influenza immunization policies. We combined this dataset with additional JRF information on new vaccine introductions and strength of immunization programmes, as well as publicly available data on country economic status. Data from countries that did not complete the JRF were sought through additional sources. We described data on country influenza immunization policies and used bivariate analyses to identify factors associated with having such policies. RESULTS: Of 194 WHO Member States, 115 (59%) reported having a national influenza immunization policy in 2014. Among countries with a national policy, programmes target specific WHO-defined risk groups, including pregnant women (42%), young children (28%), adults with chronic illnesses (46%), the elderly (45%), and health care workers (47%). The Americas, Europe, and Western Pacific were the WHO regions that had the highest percentages of countries reporting that they had national influenza immunization policies. Compared to countries without policies, countries with policies were significantly more likely to have the following characteristics: to be high or upper middle income (p<0.0001); to have introduced birth dose hepatitis B virus vaccine (p<0.0001), pneumococcal conjugate vaccine (p=0.032), or human papilloma virus vaccine (p=0.002); to have achieved global goals for diphtheria-tetanus-pertussis vaccine coverage (p<0.0001); and to have a functioning National Immunization Technical Advisory Group (p<0.0001). CONCLUSIONS: The 2014 revision of the JRF permitted a global assessment of national influenza immunization policies. The 59% of countries reporting that they had policies are wealthier, use more new or under-utilized vaccines, and have stronger immunization systems. Addressing disparities in public health resources and strengthening immunization systems may facilitate influenza vaccine introduction and use.

Associations between Meteorological Parameters and Influenza Activity in Berlin (Germany), Ljubljana (Slovenia), Castile and León (Spain) and Israeli Districts.

BACKGROUND: Studies in the literature have indicated that the timing of seasonal influenza epidemic varies across latitude, suggesting the involvement of meteorological and environmental conditions in the transmission of influenza. In this study, we investigated the link between meteorological parameters and influenza activity in 9 sub-national areas with temperate and subtropical climates: Berlin (Germany), Ljubljana (Slovenia), Castile and León (Spain) and all 6 districts in Israel. METHODS: We estimated weekly influenza-associated influenza-like-illness (ILI) or Acute Respiratory Infection (ARI) incidence to represent influenza activity using data from each country's sentinel surveillance during 2000-2011 (Spain) and 2006-2011 (all others). Meteorological data was obtained from ground stations, satellite and assimilated data. Two generalized additive models (GAM) were developed, with one using specific humidity as a covariate and another using minimum temperature. Precipitation and solar radiation were included as additional covariates in both models. The models were adjusted for previous weeks' influenza activity, and were trained separately for each study location. RESULTS: Influenza activity was inversely associated (p<0.05) with specific humidity in all locations. Minimum temperature was inversely associated with influenza in all 3 temperate locations, but not in all subtropical locations. Inverse associations between influenza and solar radiation were found in most locations. Associations with precipitation were location-dependent and inconclusive. We used the models to estimate influenza activity a week ahead for the 2010/2011 period which was not used in training the models. With exception of Ljubljana and Israel's Haifa District, the models could closely follow the observed data especially during the start and the end of epidemic period. In these locations, correlation coefficients between the observed and estimated ranged between 0.55 to 0.91and the model-estimated influenza peaks were within 3 weeks from the observations. CONCLUSION: Our study demonstrated the significant link between specific humidity and influenza activity across temperate and subtropical climates, and that inclusion of meteorological parameters in the surveillance system may further our understanding of influenza transmission patterns.