Modelling disease mitigation at mass gatherings: A case study of COVID-19 at the 2022 FIFA World Cup.

The 2022 FIFA World Cup was the first major multi-continental sporting Mass Gathering Event (MGE) of the post COVID-19 era to allow foreign spectators. Such large-scale MGEs can potentially lead to outbreaks of infectious disease and contribute to the global dissemination of such pathogens. Here we adapt previous work and create a generalisable model framework for assessing the use of disease control strategies at such events, in terms of reducing infections and hospitalisations. This framework utilises a combination of meta-populations based on clusters of people and their vaccination status, Ordinary Differential Equation integration between fixed time events, and Latin Hypercube sampling. We use the FIFA 2022 World Cup as a case study for this framework (modelling each match as independent 7 day MGEs). Pre-travel screenings of visitors were found to have little effect in reducing COVID-19 infections and hospitalisations. With pre-match screenings of spectators and match staff being more effective. Rapid Antigen (RA) screenings 0.5 days before match day performed similarly to RT-PCR screenings 1.5 days before match day. Combinations of pre-travel and pre-match testing led to improvements. However, a policy of ensuring that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure proved to be much more efficacious. The State of Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. Given our findings and the spike in cases, we suggest a policy requiring visitors to have had a recent COVID-19 vaccination should have been in place to reduce cases and hospitalisations.

Effect of Phone Text Message Reminders on Compliance with Rabies Post-Exposure Prophylaxis following Dog Bites in Rural Kenya.

The prompt administration of post-exposure prophylaxis (PEP) is one of the key strategies for ending human deaths from rabies. A delay in seeking the first dose of rabies PEP, or failure to complete the recommended dosage, may result in clinical rabies and death. We assessed the efficacy of short message system (SMS) phone texts in improving the adherence to scheduled PEP doses among bite patients in rural eastern Kenya. We conducted a single-arm, before-after field trial that compared adherence among bite patients presenting at Makueni Referral Hospital between October and December 2018 (control) and between January and March 2019 (intervention). Data on their demographics, socio-economic status, circumstances surrounding the bite, and expenditures related to the bite were collected. A total of 186 bite patients were enrolled, with 82 (44%) in the intervention group, and 104 (56%) in the control group. The odds of PEP completion were three times (OR 3.37, 95% CI 1.28, 10.20) more likely among patients who received the SMS reminder, compared to the control. The intervention group had better compliance on the scheduled doses 2 to 5, with a mean deviation of 0.18 days compared to 0.79 days for the control group (p = 0.004). The main reasons for non-compliance included lack of funds (30%), and forgetfulness (23%) on days for follow-up treatment, among others. Nearly all (96%, n = 179) the bite patients incurred indirect transport costs, at an average of USD 4 (USD 0-45) per visit. This study suggests that the integration of SMS reminders into healthcare service delivery increases compliance with PEP, and may strengthen rabies control and elimination strategies.

A multicenter analysis of inpatient antibiotic use during the 2015-2019 influenza seasons in the United States: Untapped opportunities for antimicrobial stewardship.

Outpatient antibiotic use increases during winter months, but information on temporal changes in inpatient antibiotic use in US hospitals is limited. The use of certain inpatient antibiotics, including extended-spectrum cephalosporins, macrolides, and tetracyclines, was strongly associated with influenza activity during the 2015-2019 viral respiratory seasons.

Estimating social contacts in mass gatherings for disease outbreak prevention and management: case of Hajj pilgrimage.

BACKGROUND: Most mass gathering events have been suspended due to the SARS-CoV-2 pandemic. However, with vaccination rollout, whether and how to organize some of these mass gathering events arises as part of the pandemic recovery discussions, and this calls for decision support tools. The Hajj, one of the world's largest religious gatherings, was substantively scaled down in 2020 and 2021 and it is still unclear how it will take place in 2022 and subsequent years. Simulating disease transmission dynamics during the Hajj season under different conditions can provide some insights for better decision-making. Most disease risk assessment models require data on the number and nature of possible close contacts between individuals. METHODS: We sought to use integrated agent-based modeling and discrete events simulation techniques to capture risky contacts among the pilgrims and assess different scenarios in one of the Hajj major sites, namely Masjid-Al-Haram. RESULTS: The simulation results showed that a plethora of risky contacts may occur during the rituals. Also, as the total number of pilgrims increases at each site, the number of risky contacts increases, and physical distancing measures may be challenging to maintain beyond a certain number of pilgrims in the site. CONCLUSIONS: This study presented a simulation tool that can be relevant for the risk assessment of a variety of (respiratory) infectious diseases, in addition to COVID-19 in the Hajj season. This tool can be expanded to include other contributing elements of disease transmission to quantify the risk of the mass gathering events.

Antibiotic Resistance Patterns and Association With the Influenza Season in the United States: A Multicenter Evaluation Reveals Surprising Associations Between Influenza Season and Resistance in Gram-Negative Pathogens.

BACKGROUND: Viral infections are often treated with empiric antibiotics due to suspected bacterial coinfections, leading to antibiotic overuse. We aimed to describe antibiotic resistance (ABR) trends and their association with the influenza season in ambulatory and inpatient settings in the United States. METHODS: We used the BD Insights Research Database to evaluate antibiotic susceptibility profiles in 30-day nonduplicate bacterial isolates collected from patients >17 years old at 257 US healthcare institutions from 2011 to 2019. We investigated ABR in Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) and Gram-negative (Enterobacterales [ENT], Pseudomonas aeruginosa [PSA], and Acinetobacter baumannii spp [ACB]) bacteria expressed as the proportion of isolates not susceptible ([NS], intermediate or resistant) and resistance per 100 admissions (inpatients only). Antibiotics included carbapenems (Carb), fluoroquinolones (FQ), macrolides, penicillin, extended-spectrum cephalosporins (ESC), and methicillin. Generalized estimating equations models were used to evaluate monthly trends in ABR outcomes and associations with community influenza rates. RESULTS: We identified 8 250 860 nonduplicate pathogens, including 154 841 Gram-negative Carb-NS, 1 502 796 Gram-negative FQ-NS, 498 012 methicillin-resistant S aureus (MRSA), and 44 131 NS S pneumoniae. All S pneumoniae rates per 100 admissions (macrolide-, penicillin-, and ESC-NS) were associated with influenza rates. Respiratory, but not nonrespiratory, MRSA was also associated with influenza. For Gram-negative pathogens, influenza rates were associated with the percentage of FQ-NS ENT, FQ-NS PSA, and Carb-NS ACB. CONCLUSIONS: Our study showed expected increases in rates of ABR Gram-positive and identified small but surprising increases in ABR Gram-negative pathogens associated with influenza activity. These insights may help inform antimicrobial stewardship initiatives.

Disease transmission and mass gatherings: a case study on meningococcal infection during Hajj.

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.

Risk Factors for Contracting Invasive Meningococcal Disease and Related Mortality: A Systematic Literature Review and Meta-analysis.

OBJECTIVES: To describe risk factors (RFs) and quantify their effects in invasive meningococcal disease (IMD) and associated mortality across all age groups based on the available published literature. METHODS: A systematic literature review (SLR) was conducted via MEDLINE® and Embase. Study selection, data extraction, and quality assessment were performed by two independent reviewers. Associations between RFs and outcomes were quantified via a meta-analysis (MA). RESULTS: Seventy-four studies (date range 1950 - 2018) were included in the SLR. Statistically significant RFs for contracting IMD identified from the SLR (within-study) included previous IMD infection and young age (0 - 4 years). MA indicated that significant RFs for contracting IMD (11 studies) were: HIV-positive status, passive smoke exposure, and crowded living space. In the MA for IMD-related mortality risk (11 studies), age 25 - 45 years (vs. 0 - 5 years) and serogroup C (vs. serogroup B) were significantly associated with increased risk. CONCLUSIONS: Previous findings of higher risk for IMD contraction with smoke exposure and crowded living conditions in children/adolescents have been extended by this SLR/MA to all age groups. We provide strong evidence for higher risk of IMD in HIV-positive individuals, and confirm previous findings of higher IMD-related mortality risk in adults aged 25 - 45.

A Systematic Review of Influenza Epidemiology and Surveillance in the Eastern Mediterranean and North African Region.

Seasonal influenza represents a huge health burden, resulting in significant mortality and morbidity. Following the 2009 H1N1 pandemic, focus has been directed on the burden of influenza globally. Country and regional disease burden estimates play important roles in helping inform decisions on national influenza intervention programmes. Despite improvements in influenza surveillance following the 2009 pandemic, many opportunities remain unexplored in the Eastern Mediterranean and North African (EMNA) region, which has a high prevalence of patients with chronic disease and thus a population at high risk of influenza complications. We conducted a systematic literature review of Embase, Medline, Scopus and the Cochrane Database of Systematic Reviews from 1 January 1998 to 31 January 2020 covering the EMNA region with the aim to describe the epidemiology of influenza in the region and assess the influenza epidemiological surveillance research landscape. Relevant data on study characteristics, population, clinical/virology characteristics and epidemiology were extracted and summarised descriptively. Of the 112 studies identified for inclusion, 90 were conducted in the Eastern Mediterranean region, 19 in North Africa and three across the EMNA region. Data were reported on 314,058 laboratory-confirmed influenza cases, 96 of which were derived from surveillance systems. Amongst the surveillance studies, the percentage of positive cases reported ranged from 1% to 100%. The predominantly identified influenza strain was strain A; H1N1 was the most prominent circulating subtype. Typing was performed in approximately 75% and subtyping in 50% of studies, respectively. Data on those considered most at risk for influenza complications were collected in 21% of studies, highlighting a regional gap for these data. Our review reveals existing gaps in regional estimates of influenza health and economic burden, hospitalisation rates and duration, and highlights the need for robust and high-quality epidemiology data to help inform public health interventions.

Implementation of a prospective study for enhancing surveillance of invasive bacterial infections in North Africa.

OBJECTIVES: We implemented a project named MENINGSTOP in three countries of North Africa (Algeria, Morocco and Tunisia). The main objective was to use real-time PCR to detect, identify and type the three main agents (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) responsible for invasive bacterial infections (IBI). METHODS: The protocol of WHO and US CDC for real-time PCR was used to detect and type the three bacterial agents in clinical samples. We also designated two quality exercises using an external interlaboratory study and cross-testing of 10% of randomly selected samples. RESULTS: Among the 752 samples tested, 18% were positive for one of the three agents. N. meningitidis was the most frequent globally reaching 9% of all samples (7% to 17% range) followed by S. pneumoniae 8% of all samples (6% to 15%). Group B meningococci was the most frequent (74% of all positive samples for meningococci and ranging from 50% to 90%). Quality assurance showed >85% correlation scores. CONCLUSIONS: Real-time PCR can help improving epidemiological surveillance. Data confirm the prevalence of meningococci B. Our project adds a reliable tool to enhance surveillance and to help decision making in vaccination strategies against IBI.

Systematic review of invasive meningococcal disease epidemiology in the Eastern Mediterranean and North Africa region.

BACKGROUND: Invasive meningococcal disease (IMD) represents a global health burden. However, its epidemiology in the Eastern Mediterranean (EM) and North Africa (NA) regions is currently not well understood. This review had four key objectives: to describe asymptomatic meningococcal carriage, IMD epidemiology (e.g. serogroup prevalence, case-fatality rates [CFRs]), IMD presentation and management (e.g. clinical diagnosis, antibiotic treatments) and economic impact and evaluation (including health technology assessment [HTA] recommendations) in EM and NA. METHODS: A systematic literature search (MEDLINE and EMBASE) was conducted (January 2000 to February 2021). Search strings included meningococcal disease and the regions/countries of interest. Identified publications were screened sequentially by title/abstract, followed by screening of the full-text article; articles were also assessed on methodological quality. Literature reviews, genetic sequencing or diagnostic accuracy studies, or other non-pertinent publication type were excluded. An additional grey literature search (non-peer-reviewed sources; start date January 2000) was conducted to the end of April 2019. RESULTS: Of the 1745 publications identified, 79 were eligible for the final analysis (n = 61 for EM and n = 19 for NA; one study was relevant to both). Asymptomatic meningococcal carriage rates were 0-33% in risk groups (e.g. military personnel, pilgrims) in EM (no data in NA). In terms of epidemiology, serogroups A, B and W were most prevalent in EM compared with serogroups B and C in NA. IMD incidence was 0-20.5/100,000 in EM and 0.1-3.75/100,000 in NA (reported by 7/15 countries in EM and 3/5 countries in NA). CFRs were heterogenous across the EM, ranging from 0 to 57.9%, but were generally lower than 50%. Limited NA data showed a CFR of 0-50%. Data were also limited in terms of IMD presentation and management, particularly relating to clinical diagnosis/antibiotic treatment. No economic evaluation or HTA studies were found. CONCLUSIONS: High-risk groups remain a significant reservoir of asymptomatic meningococcal carriage. It is probable that inadequacies in national surveillance systems have contributed to the gaps identified. There is consequently a pressing need to improve national surveillance systems in order to estimate the true burden of IMD and guide appropriate prevention and control programmes in these regions.

Cost Utility of Switching From Trivalent to Quadrivalent Influenza Vaccine in Turkey.

OBJECTIVES: Trivalent influenza vaccines (TIVs) are widely used but protect against only 1 of the 2 co-circulating influenza B virus lineages. Quadrivalent influenza vaccines (QIVs) include a B strain from each lineage to overcome mismatches. The main objective of this study was to determine the cost-utility and budget impact of switching from vaccination with TIV to QIV in the population recommended for influenza vaccination in Turkey. METHODS: A static cohort cost-effectiveness model was developed to predict influenza-related costs and outcomes under a QIV versus a TIV program during an influenza season. The model was informed by data from Turkey on influenza strain distribution, influenza-attributable outcomes, and associated costs over the seasons 2010/2011 to 2016/2017. The effectiveness of each strategy was measured through quality-adjusted life-years (QALYs), and comparisons were based on the incremental cost-effectiveness ratio. RESULTS: In an average influenza season, the model showed that switching from TIV to QIV would prevent an additional 15 092 cases of influenza, 6311 general practitioner visits, 94 hospitalizations, 13 deaths, and gain 440 QALYs. From the societal perspective, this amounted to total cost savings of international dollars (I$) 1102 710 (US$388 643). The incremental cost-effectiveness ratio when using QIV over TIV was I$55 248/QALY gained. Switching to QIV is mostly cost-effective among older adults with I$36 413.38/QALY. Sensitivity analysis showed that vaccine effectiveness, B strain mismatch, and influenza visits highly impact the cost-effectiveness results. CONCLUSION: Switching from TIV to QIV is likely to be cost-effective in Turkey, yet highly dependent on the severity of the influenza season, B strain epidemiology, and vaccine effectiveness.

The epidemiology of meningococcal meningitis: multicenter, hospital-based surveillance of meningococcal meningitis in Iraq.

Objectives: Outbreaks of Neisseria meningitidis have reached alarming levels due to the pathogen's ability to cause severe complications, presenting as meningitis or septicemia. Our study reports the results of the first wide-scale surveillance of meningococcal meningitis in Iraq. Methods: The study included all consecutive cases of clinically suspected meningitis between June 2018 and May 2020 at 18 major hospitals around Iraq (n = 2314). Laboratory analysis of biological samples and real-time polymerase chain reaction tests were conducted to confirm bacterial etiology. Demographical and medical data were collected for statistical analysis. Results: In total, 370 patients were confirmed to have bacterial meningitis (215 had N. meningitidis, 154 had Streptococcus pneumoniae, and one case had Haemophilus influenzae type b). The most common N. meningitidis serogroup was B (77.7%), followed by W (18.1%) and X (4.2%). The annual incidence rate of N. meningitidis per 100 000 population was 0.86, with the highest being in Karbala (1.52 per 100 000 population). Cases of meningococcal meningitis were more likely to occur in children younger than 15 (OR = 3.526), and in the winter (OR = 1.474). Conclusions: Continuous surveillance of N. meningitidis is necessary in Iraq, and can only be achieved through improved detection methods. The incidence of meningococcal meningitis in Iraq warrants improved vaccination programs.