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Background: Mass gatherings can not only trigger major outbreaks on-site but also facilitate global spread of infectious pathogens. Hajj is one of the largest mass gathering events worldwide where over two million pilgrims from all over the world gather annually creating intense congestion., Methods: We developed a meta-population model to represent the transmission dynamics of Neisseria meningitidis and the impact of Hajj pilgrimage on the risk of invasive meningococcal disease (IMD) for pilgrims population, local population at the Hajj site and country of origin of Hajj pilgrims. This model was calibrated using data on IMD over 17 years (1995-2011) and further used to simulate potential changes in vaccine policy and endemic conditions., Results: The effect of increased density of contacts during Hajj was estimated to generate a 78-fold increase in disease transmission that impacts not only pilgrims but also the local population. Quadrivalent ACWY vaccination was found to be very effective in reducing the risk of outbreak during Hajj. Hajj has more limited impact on IMD transmission and exportation in the pilgrim countries of origin, although not negligible given the size of the population considered., Conclusion: The analysis performed highlighted the amplifying effect of mass gathering on N. meningitidis transmission and confirm vaccination as a very effective preventive measure to mitigate outbreak risks., (© 2022. The Author(s).)

Background: A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years., Methods: The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2-4 years) and PedsQL™4.0 infant scales (0-2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions., Results: Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children., Conclusion: RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care., (© 2021. The Author(s).)

Background: Despite World Health Organization recommendations, in many countries young children are not targeted for influenza vaccination. To help inform influenza vaccination policy, we examined the occurrence and burden of influenza in healthy children aged 6 to 35 months using data from a recent phase III placebo-controlled influenza vaccine trial conducted in countries in the Northern and Southern Hemispheres., Methods: This was an analysis of data from participants included in the placebo arm of a phase III clinical trial in healthy children aged 6 to 35 months (EudraCT no. 2013-001231-51). Included children had never been vaccinated for influenza and were observed for one influenza season. Outcome measures included the occurrence of influenza-like illness (ILI), laboratory-confirmed influenza, virus types/subtypes, severe symptoms and complications of confirmed influenza, and healthcare use associated with confirmed influenza., Results: Data from 2210 participants were analysed. ILI was reported for 811 participants (36.7%). Of these, 255 participants (31.4%) had 263 virologically confirmed episodes of influenza. The overall influenza attack rate was 11.5%. The most common influenza virus detected was A(H3N2) (40.7%), followed by B/Yamagata (23.6%), A(H1N1) (18.6%), and B/Victoria (8.0%). Grade 3 fever was reported in 24.3% of confirmed episodes, acute lower respiratory infection in 8.7%, acute otitis media in 6.1%, and pneumonia in 1.9%. In most influenza episodes (93.2%), antipyretics, analgesics, or non-steroidal anti-inflammatory drugs were taken. Antibiotics were prescribed for 41.4% of influenza episodes. More than half of the influenza episodes (57.0%) resulted in outpatient visits. Influenza resulted in overnight hospitalisation in 1.1% of episodes., Conclusions: Influenza is associated with a significant burden of disease in healthy children. This analysis also revealed that antibiotics continue to be frequently used for young children with influenza., Trial Registration: EudraCT no. 2013-001231-51 .

Background: To improve national influenza vaccination recommendations, additional data on influenza A and B virus circulation are needed. Here, we describe the circulation of influenza A and B in the Czech Republic during 16 seasons., Methods: This was a retrospective analysis of data collected from the 2000-2001 to 2015-2016 influenza seasons by the Czech Republic national influenza surveillance network. Influenza was confirmed and viral isolates subtyped by virological assays followed by antigen detection or by reverse transcriptase-polymerase chain reaction., Results: Of 16,940 samples collected, 5144 (30.4%) were influenza-positive. Influenza A represented 78.6% of positive cases overall and accounted for more than 55.0% of all influenza cases in every season, except for 2005-2006 (6.0%). Both A/H1N1 and A/H3N2 were detected in most seasons, except for 2001-2002 and 2003-2004 (only A/H3N2), and 2007-2008 and 2009-2010 (only A/H1N1). Influenza B represented 21.4% of positive cases overall (range, 0.0-94.0% per season). Both influenza B lineages were detected in three seasons, a single B lineage in 11, and no B strain in two. For the 11 seasons where influenza B accounted for ≥20% of positive cases, the dominant lineage was Yamagata in six and Victoria in four. In the remaining season, the two lineages co-circulated. For two seasons (2005-2006 and 2007-2008), the B lineage in the trivalent influenza vaccine did not match the dominant circulating B lineage., Conclusions: In the Czech Republic, during the 2000-2001 to 2015-2016 influenza seasons, influenza virus circulation varied considerably. Although influenza A accounted for the most cases in almost all seasons, influenza B made a substantial, sometimes dominant, contribution to influenza disease.

Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain., Methods: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation., Results: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay., Conclusions: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.

Background: Many administrative data sources are available to study the epidemiology of infectious diseases, including Clostridium difficile infection (CDI), but few publications have compared CDI event rates across databases using similar methodology. We used comparable methods with multiple administrative databases to compare the incidence of CDI in older and younger persons in the United States., Methods: We performed a retrospective study using three longitudinal data sources (Medicare, OptumInsight LabRx, and Healthcare Cost and Utilization Project State Inpatient Database (SID)), and two hospital encounter-level data sources (Nationwide Inpatient Sample (NIS) and Premier Perspective database) to identify CDI in adults aged 18 and older with calculation of CDI incidence rates/100,000 person-years of observation (pyo) and CDI categorization (onset and association)., Results: The incidence of CDI ranged from 66/100,000 in persons under 65 years (LabRx), 383/100,000 in elderly persons (SID), and 677/100,000 in elderly persons (Medicare). Ninety percent of CDI episodes in the LabRx population were characterized as community-onset compared to 41 % in the Medicare population. The majority of CDI episodes in the Medicare and LabRx databases were identified based on only a CDI diagnosis, whereas almost ¾ of encounters coded for CDI in the Premier hospital data were confirmed with a positive test result plus treatment with metronidazole or oral vancomycin. Using only the Medicare inpatient data to calculate encounter-level CDI events resulted in 553 CDI events/100,000 persons, virtually the same as the encounter proportion calculated using the NIS (544/100,000 persons)., Conclusions: We found that the incidence of CDI was 35 % higher in the Medicare data and fewer episodes were attributed to hospital acquisition when all medical claims were used to identify CDI, compared to only inpatient data lacking information on diagnosis and treatment in the outpatient setting. The incidence of CDI was 10-fold lower and the proportion of community-onset CDI was much higher in the privately insured younger LabRx population compared to the elderly Medicare population. The methods we developed to identify incident CDI can be used by other investigators to study the incidence of other infectious diseases and adverse events using large generalizable administrative datasets.