National Surveillance Network Research Articles

Systems Policy Analysis for Antimicrobial Resistance Targeted Action (SPAARTA): A Research Protocol

Background The majority of countries (64%) have an Antimicrobial Resistance (AMR) National Action Plan (NAP V.1.0), but many remain unimplemented, and lack funding for interventions. Intervention selection requires a systematic approach to explain and predict progress. Looking beyond AMR is important to ensure the capture of systemic factors at the country level, which can impede or accelerate success. Aim To provide innovative policy analysis to allow country comparison and refine targeted action, while developing and implementing NAPs (V.2.0). Methods Mixed-method multi-country case study of policies and implementation strategies to address AMR across One Health. Starting with 17 countries, the sample includes each WHO region and emerging economies. This investigation of structures, processes, and outcomes has three components: a. Textual analysis of peer-reviewed literature, policy documents, global and national progress reports, validated by global and in-country experts. An all-language article search conducted for 2000-2024, using broad search terms: ‘Antimicrobial resistance policies’, ‘national action plan’, ‘surveillance’, ‘AMR systems’ supplemented by hand searches. Deductive analysis using multi-disciplinary frameworks including the Expert Consensus for Implementation Research (ERIC). b. Longitudinal quantitative analysis assessing country contextual determinants and Antimicrobial Use (AMU) and AMR outcomes. Data from global health indicator repositories and international and national AMU and AMR surveillance networks are analysed using econometrics and machine learning approaches. c. Interactive Tableau dashboard development to display insights from a & b to allow visualisation and comparison of case-country AMR intervention context and components. Discussion This protocol provides a systematic, transparent approach for countries to benchmark their own AMR strategies. The interactive dashboard will allow comparisons between country clusters by geography or economy, and enable rapid knowledge mobilisation among strategic and operational stakeholders including policy makers and planners. This protocol facilitates others to perform this structured assessment and nominate their country for the next wave of analysis.

Implementation and Evaluation of Automated, Online Study Recruitment from Computerised Medical Records in a Primary Care Sentinel Surveillance Network.

Infectious intestinal disease (IID) is a syndrome consisting of diarrhoea and vomiting symptoms linked to a causative pathogen. The Third Study of IID (IID3) will report its incidence in the community within the UK and assess how it has changed since the second IID study (IID2) in 2012. We implemented an automated, online patient recruitment process within a national sentinel surveillance network and compared its performance versus IID2 in terms of: Patient recruitment rates and demographic characteristics of recruited participants. We utilised a text messaging system (TMS) running off a computerised medical record systems (CMR) application programme interface (API). Demographic analysis showed that the majority of those recruited to IID3/IID2 studies were >65 years and female. However, the recruitment of participants of non-white ethnicity was statistically significantly different between IID3/IID2. Further work is required to improve recruitment in the younger patient demographic and in ethnic minority populations.

Epidemiology of ESKAPEE Complex at Veracruz Children’s Hospital during 2023

Abstract Introduction The ESKAPEE complex comprises bacterial species known for their propensity to develop multiple mechanisms of resistance against antibiotics. The elevated rates of mortality and morbidity associated with these microorganisms, along with the challenges posed by their treatment, have transformed them into a significant concern in global public health. However, in Mexico, the prevalence of the ESKAPEE complex in pediatric patients within tertiary care hospitals remains understudied compared to adults. Materials and methods A cross-sectional, retrospective, and descriptive study was conducted, encompassing 179 bacteria belonging to the ESKAPEE complex. These bacteria were isolated from pediatric patients between January and December 2023 at Veracruz Children’s Hospital. Laboratory samples were processed using the VITEK 2.0 system, and descriptive statistical analyses were performed using SPSS v22 software. Results A total of 179 antibiograms were analyzed, with 55.1% corresponding to male patients. The most prevalent age group among pediatric patients was school children (5 to 11 years old), comprising 20.2% of the sample. Blood culture was the most frequently sampled site, representing 35.4% of cases. Klebsiella pneumoniae emerged as the most common bacterium, accounting for 22.5% of isolates. The Pediatric Emergency Department was the primary area from which samples were obtained, constituting 18.5% of the total. Conclusions Klebsiella pneumoniae was the most frequently isolated bacteria inside de hospital in 2023, especially among school-aged patients, followed by E. coli, which coincides with reports in the literature from various countries around the world. Key messages • Establishing a national surveillance network within public health institutions is imperative, where ESKAPEE complex microorganisms are reported. • Knowing the epidemiological profile of the ESKAPEE complex will favor the diagnosis and intentional search for infections with greater etiological certainty.

Homicide-Suicides in Pakistan: An analysis of Newspaper reports of two years.

Our understanding of homicide-suicide (H-S), a rare yet tragic event, is sparse. While the phenomenon has been studied in the West for many years, only limited literature is available from Asia and none to our knowledge from Pakistan. There is evidence of complexity of the interaction between cultural, societal, and psychological mechanisms underlying this phenomenon; therefore, research findings from the Western countries cannot be directly applied in non-Western societies. Our objective was to study homicide-suicides in Pakistan, describe the characteristics of offenders and victims, determine the types of H-S, and examine possible motives and any events prior to the offense. In the absence of any official data on homicide-suicides, we used newspaper surveillance approach of four most widely circulated Pakistani newspapers (one Urdu and three English Daily) for two years (1st January 2019 to 31st December 2020). Each case was categorized using the modified Marzuk et al., Tardiff, and Hirsch's classification of homicide-suicides. Descriptive statistics were used to analyze the data that was then compared with published literature. There were 114 H-S incidents with 198 victims of homicide during the study period, reported in the newspapers. Familial H-S particularly filicide-suicide were predominant, followed by spousal/ consortial H-S. Forty-one (36%) H-S involved multiple victims. The perpetrators across all categories of H-S were predominantly male (67%); the victims were predominantly women and children. Firearms were used in most incidents. The primary motive for the majority of H-S cases was familial, financial, and social stressors. The study highlights several unique patterns (predominance of familicide, multiple victims including high proportion of children) and a series of vulnerabilities (incidents related mostly to familial/ financial and social stressors) that overlap each other and ultimately lead to this tragic end. There is need to increase our understanding and develop effective evidence-based prevention strategies for H-S in Pakistan. It is also very important to have a national surveillance network and national violent death reporting system in the country for studying H-S cases, and for evaluating the impact of prevention programs.

Toscana Virus in Wild-Caught Sand Flies in Portugal, Findings from the National Vector Surveillance Network, 2023.

Phlebotomine sand flies play a crucial role in both human and veterinary medicine, acting as vectors for Leishmania parasites and most known phleboviruses. In Portugal, the REVIVE program, a comprehensive national surveillance network under the Ministry of Health, has included sand fly surveys since 2016. REVIVE aims to identify existing sand fly species in the country, determine which pathogens are circulating among them, and provide actionable insights for prevention and control measures when necessary. In this way, annually, from May to October, health technicians collect sand flies across mainland Portugal with CDC light traps. The collected sand flies are sent to the Centre for Vectors and Infectious Diseases Research for species identification and molecular screening of pathogens. On 21 September 2023, Toscana virus (TOSV), a well-known phlebovirus in the Mediterranean region due to its capacity to cause neurological disease, was detected in a pool of 30 sand flies collected in Algarve, the southernmost region of Portugal. A 668 bp partial sequence of the nucleoprotein gene shows similarity with TOSV strains from Spain. To our knowledge, this is the first detection of TOSV in its vector in this country, having previously only been reported in vertebrate hosts. These findings highlight the important role of ongoing surveillance efforts in monitoring and understanding the dynamics of sand fly-borne diseases in Portugal.

Assessing infection prevention and control structures in German hospitals after the COVID-19 pandemic using the WHO infection prevention and control assessment framework (IPCAF): results from 660 hospitals and comparison with a pre-pandemic survey

BackgroundThe WHO Infection Prevention and Control Assessment Framework (IPCAF) is a standardized tool to assess infection prevention and control (IPC) structures in healthcare facilities. The IPCAF reflects the eight WHO core components (CC) of IPC. Besides facility self-assessment, the IPCAF can be used for national surveys, and repeated usage can aid in describing trends concerning IPC structures. A previous survey in over 700 German hospitals conducted in 2018, yielded an overall high IPC level in participating hospitals, albeit with potentials for improvement. In 2023, the survey was repeated to describe once again the state of IPC implementation in German hospitals and compare findings to data from 2018.MethodsThe German National Reference Center for the Surveillance of Nosocomial Infections (NRC) invited 1,530 German acute care hospitals participating in the national surveillance network “KISS”, to complete a translated online version of the IPCAF between October 2023 and January 2024. The questionnaire-like nature of the IPCAF, where each answer corresponds to a number of points, allows for calculating an overall IPC score. Based on the overall score, hospitals were allocated to four different IPC levels: inadequate (0–200), basic (201–400), intermediate (401–600), and advanced (601–800). Aggregated scores were calculated and compared with results from 2018.ResultsComplete datasets from 660 hospitals were received and analyzed. The median overall IPCAF score was 692.5 (interquartile range: 642.5–737.5), with 572 hospitals (86.6%) classified as advanced, and 87 hospitals (13.2%) as intermediate. One hospital (0.2%) fell into the basic category. The overall median score was virtually unchanged when compared to 2018 (690; data from 736 hospitals). The median score for the CC on workload, staffing and bed occupancy was markedly higher (85 vs. 75), whereas the median score for the CC on multimodal strategies was slightly lower than in 2018 (75 vs. 80).ConclusionsRepeated assessments of IPC structures at the national level with the IPCAF are feasible and a means to gain insights into the evolution of IPC structures. When comparing aggregated scores, a stable and high level of IPC key aspects in Germany was observed, with improvements over time in IPC indicators related to workload and staffing.

Two Peaks of Seasonal Influenza Epidemics - China, 2023.

Influenza is a communicable respiratory disease that causes annual epidemics and occasional unpredictable pandemics. This study examines the occurrence of two unexpected influenza peaks within the year 2023. Influenza-like illness (ILI) data were reported, and specimens of ILI were collected by designated surveillance hospitals. Positive cases were confirmed using real-time reverse transcription polymerase chain reaction (rRT-PCR) testing conducted at national surveillance network laboratories. The data were then submitted to the Chinese Influenza Surveillance Information System. From December 2022 to January 2023, influenza activity was minimal until a spring epidemic began in February, peaking in late March. The outbreak spread from the north to the south, with A(H1N1)pdm09 being the predominant strain and A(H3N2) also circulating concurrently. The positivity rate in northern and southern provincial-level administrative divisions (PLADs) reached 60.0% (week 10) and 60.2% (week 13), respectively, before dropping to below 5% from May to August. Subsequently, rates surged starting in week 41 in the south and week 44 in the north, peaking at 54.4% (week 50) and 44.0% (week 49), respectively, and remained high until the end of 2023. A(H3N2) became the prevailing strain, with a notable increase in B/Victoria lineage viruses from December, resulting in two peaks during the 2023 influenza season. The pattern of the influenza epidemic shifted due to the coronavirus disease 2019 (COVID-19) outbreak and is gradually returning to its usual seasonal and intensity patterns. It is, therefore, crucial to continuously strengthen influenza surveillance, enhance the influenza surveillance network, and lay the groundwork for advancing integrated surveillance of multiple pathogens in China.

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008–2019

ObjectivesVirulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates. MethodsSymptomatic infants aged <6 months with a positive B. pertussis culture from 2008–2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 109/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph. ResultsWe included 361 infants with pertussis (median age 63 days [interquartile range, 39–86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76–7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06–16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02–19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02–13.83). DiscussionPRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.

Investigation of acute encephalitis syndrome with implementation of metagenomic next generation sequencing in Nepal

BackgroundThe causative agents of Acute Encephalitis Syndrome remain unknown in 68–75% of the cases. In Nepal, the cases are tested only for Japanese encephalitis, which constitutes only about 15% of the cases. However, there could be several organisms, including vaccine-preventable etiologies that cause acute encephalitis, when identified could direct public health efforts for prevention, including addressing gaps in vaccine coverage.ObjectivesThis study employs metagenomic next-generation-sequencing in the investigation of underlying causative etiologies contributing to acute encephalitis syndrome in Nepal.MethodsIn this study, we investigated 90, Japanese-encephalitis-negative, banked cerebrospinal fluid samples that were collected as part of a national surveillance network in 2016 and 2017. Randomization was done to include three age groups (< 5-years; 5-14-years; >15-years). Only some metadata (age and gender) were available. The investigation was performed in two batches which included total nucleic-acid extraction, followed by individual library preparation (DNA and RNA) and sequencing on Illumina iSeq100. The genomic data were interpreted using Chan Zuckerberg-ID and confirmed with polymerase-chain-reaction.ResultsHuman-alphaherpes-virus 2 and Enterovirus-B were seen in two samples. These hits were confirmed by qPCR and semi-nested PCR respectively. Most of the other samples were marred by low abundance of pathogen, possible freeze-thaw cycles, lack of process controls and associated clinical metadata.ConclusionFrom this study, two documented causative agents were revealed through metagenomic next-generation-sequencing. Insufficiency of clinical metadata, process controls, low pathogen abundance and absence of standard procedures to collect and store samples in nucleic-acid protectants could have impeded the study and incorporated ambiguity while correlating the identified hits to infection. Therefore, there is need of standardized procedures for sample collection, inclusion of process controls and clinical metadata. Despite challenging conditions, this study highlights the usefulness of mNGS to investigate diseases with unknown etiologies and guide development of adequate clinical-management-algorithms and outbreak investigations in Nepal.

Marked increase in cryptosporidiosis cases, Spain, 2023.

BackgroundBy mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched.AimWe aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years.MethodsWe analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022.ResultsIn 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. Cryptosporidium hominis was the most common species in the characterised samples (115/122), and the C. hominis IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples.ConclusionsA substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of Cryptosporidium is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.

Watching the guards: A data-driven method to trigger warnings in national wastewater surveillance networks

ABSTRACT Surveillance networks have been established in many countries worldwide to monitor SARS-CoV-2 in sewage and to estimate the communal prevalence of COVID-19 cases. Despite their popularity, gaining a rapid understanding of how infectious diseases spread across the territory covered by a network is difficult because of the many factors involved. To improve the detection of warning signals within the territory, we propose to apply principal component analysis (PCA) to screen time-series data generated from wastewater treatment plants (WWTPs) under surveillance. Our analysis allows us to identify single WWTPs deviating from the normal behavior as well as deviations of a cluster of WWTPs (indicative of an intermunicipal outbreak). Our approach is illustrated through the analysis of the dataset generated by the Catalan Surveillance Network of SARS-CoV-2 in Sewage (SARSAIGUA). Using 10 principal components, we captured 78.6% of the variance in the original dataset of 51 variables (WWTPs). Our analysis identified exceedance of the Q-statistic threshold as evidence of anomalous performance of a single WWTP, and exceedance of the T2-statistic as a sign of an intermunicipal outbreak. Our approach provides a comprehensive picture of the spread of the COVID-19 pandemic, enabling decision-makers to make informed decisions and better manage future pandemics.

Surveillance for Emerging and Reemerging Pathogens Using Pathogen Agnostic Metagenomic Sequencing in the United States: A Critical Role for Federal Government Agencies.

The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies.

Antimicrobial resistance of clinical bacterial isolates in China: current status and trends.

Antimicrobial resistance surveillance systems have been established in China. Two representative national surveillance networks are the China Antimicrobial Surveillance Network (CHINET) and China Antimicrobial Resistance Surveillance System (CARSS), both of which were established in 2005. For all clinical isolates collected in both of these surveillance networks, the ratio of Gram-negative bacilli to Gram-positive cocci was approximately 7:3 during the past 18 years. Generally, Gram-negative bacilli have a higher antimicrobial resistance profile in China. The prevalence of ESBLs in Escherichia coli is as high as approximately 50%. Acinetobacter baumannii-calcoaceticus complex (ABC) has a high antimicrobial resistance profile, with a carbapenem resistance rate of approximately 66%. However, the prevalence of carbapenem-resistant ABC has also shown a decreasing trend from 2018 to 2022. The prevalence of vancomycin-resistant Enterococcus was low, and the prevalence of MRSA and carbapenem-resistant Pseudomonas aeruginosa showed decreasing trends from 2005 to 2022. CHINET surveillance data demonstrated that the prevalence of carbapenem-resistant Klebsiella pneumoniae showed a remarkable increasing trend from 2.9% (imipenem resistance) in 2005 to 25.0% in 2018, and then slightly decreased to 22.6% in 2022. The decreasing trends may reflect the antimicrobial stewardship efforts in China: a professional consensus on the rational clinical use of carbapenems was issued by the National Health Commission of China and was well implemented nationally; after that, the clinical use of carbapenems decreased slightly in China.

Concurrent Clade I and Clade II Monkeypox Virus Circulation, Cameroon, 1979-2022.

During 1979-2022, Cameroon recorded 32 laboratory-confirmed mpox cases among 137 suspected mpox cases identified by the national surveillance network. The highest positivity rate occurred in 2022, indicating potential mpox re-emergence in Cameroon. Both clade I (n = 12) and clade II (n = 18) monkeypox virus (MPXV) were reported, a unique feature of mpox in Cameroon. The overall case-fatality ratio of 2.2% was associated with clade II. We found mpox occurred only in the forested southern part of the country, and MPXV phylogeographic structure revealed a clear geographic separation among concurrent circulating clades. Clade I originated from eastern regions close to neighboring mpox-endemic countries in Central Africa; clade II was prevalent in western regions close to West Africa. Our findings suggest that MPXV re-emerged after a 30-year lapse and might arise from different viral reservoirs unique to ecosystems in eastern and western rainforests of Cameroon.

Spatial multi-criteria decision analysis for the selection of sentinel regions in tick-borne disease surveillance

BackgroundThe implementation of cost-effective surveillance systems is essential for tracking the emerging risk of tick-borne diseases. In Canada, where Lyme disease is a growing public health concern, a national sentinel surveillance network was designed to follow the epidemiological portrait of this tick-borne disease across the country. The surveillance network consists of sentinel regions, with active drag sampling carried out annually in all regions to assess the density of Ixodes spp. ticks and prevalence of various tick-borne pathogens in the tick population. The aim of the present study was to prioritize sentinel regions by integrating different spatial criteria relevant to the surveillance goals.MethodsWe used spatially-explicit multi-criteria decision analyses (MCDA) to map priority areas for surveillance across Canada, and to evaluate different scenarios using sensitivity analyses. Results were shared with stakeholders to support their decision making for the selection of priority areas to survey during active surveillance activities.ResultsWeights attributed to criteria by decision-makers were overall consistent. Sensitivity analyses showed that the population criterion had the most impact on rankings. Thirty-seven sentinel regions were identified across Canada using this systematic and transparent approach.ConclusionThis novel application of spatial MCDA to surveillance network design favors inclusivity of nationwide partners. We propose that such an approach can support the standardized planning of spatial design of sentinel surveillance not only for vector-borne disease BDs, but more broadly for infectious disease surveillance where spatial design is an important component.

Genomic surveillance of SARS-CoV-2 reveals highest severity and mortality of delta over other variants: evidence from Cameroon

While the SARS-CoV-2 dynamic has been described globally, there is a lack of data from Sub-Saharan Africa. We herein report the dynamics of SARS-CoV-2 lineages from March 2020 to March 2022 in Cameroon. Of the 760 whole-genome sequences successfully generated by the national genomic surveillance network, 74% were viral sub-lineages of origin and non-variants of concern, 15% Delta, 6% Omicron, 3% Alpha and 2% Beta variants. The pandemic was driven by SARS-CoV-2 lineages of origin in wave 1 (16 weeks, 2.3% CFR), the Alpha and Beta variants in wave 2 (21 weeks, 1.6% CFR), Delta variants in wave 3 (11 weeks, 2.0% CFR), and omicron variants in wave 4 (8 weeks, 0.73% CFR), with a declining trend over time (p = 0.01208). Even though SARS-CoV-2 heterogeneity did not seemingly contribute to the breadth of transmission, the viral lineages of origin and especially the Delta variants appeared as drivers of COVID-19 severity in Cameroon.

Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network.

In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM). We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression. We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (-0.12%/month, 95% CI: -0.17 to -0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (-0.43%/month, 95% CI: -0.53 to -0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (-0.9%/month, 95% CI: -1.6 to -0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3-0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017. PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France.

Validation of the Medical Research Council prion disease rating scale in France.

The development of assessment tools other than survival time is necessary to conduct therapeutic trials in prion diseases (also known as subacute transmissible encephalopathies). The Medical Research Council Prion Disease Rating Scale published by Thompson et al. (The Medical Research Council prion disease rating scale: A new outcome measure for prion disease therapeutic trials developed and validated using systematic observational studies. Brain. 2013; 136: 1116-27.) is the first attempt at a specific evaluation of prion diseases to avoid the floor effect seen in other scales. Validation of this scale in other countries is essential because, given the rarity of these diseases, therapeutic trials are likely to be multi-centre and international. After translation into French, we assessed by phone 173 cases classified as sporadic Creutzfeldt-Jakob disease out of 852 patients notified to the French national surveillance network between November 2014 and May 2021. Data showed that the natural history of the disease is similar in the UK and France. Patients who have a heterozygous genotype at codon 129 of the prion protein gene have a slower decline than homozygous patients. In rapidly progressing patients, death occurs shortly after reaching a low score or after a 'pre-terminal plateau' at a very low score. The similarities of disease progression profile observed in France and the UK with somewhat different surveillance systems and by distinct procedures highlight the robustness of the Medical Research Council Prion Disease Rating Scale that can be thus used to define primary endpoints of future trials at the international level.

Genetic Comparison of H3N2 Influenza Virus in Indonesia with WHO Recommended Strains During the Period 2004 – 2021

Influenza caused by A/H3N2 virus is one commonly found infections in tropical countries. Vaccination policy against A/H3N2 virus is already established for Northern and Southern hemisphere, however, no specified policy is established for tropical countries such as Indonesia. World Health Organization (WHO) has recommended Indonesia to use vaccine formulation designated for Northern hemisphere. Some studies, however, have shown that there were mismatches between recommended vaccine and circulating strains present in Asian countries, which might have caused regional outbreaks. This study was aimed to compare the genetic makeup of WHO recommended vaccine strain with H3N2 virus circulating in Indonesia. A total of 147 HA and 148 NA complete nucleotide sequences from Indonesian population, as well as 14 HA and 14 NA WHO-recommended nucleotide sequences, were downloaded from GISAID. These sequences were subjected to phylogenetic analysis using MEGA 11. Furthermore, antigenicity of these isolates was analyzed using Kolaskar and Tangonkar Prediction method accessible through IEDB website and Vaxijen 2.0. This study revealed that WHO-recommended vaccine strain for southern hemisphere in 2010 were compatible with Indonesian strains circulating in 2009. Furthermore, there were no recommended vaccine strain that matched strain in circulation between 2010 to 2012 and 2019. Kolaskar and Tongaonkar antigenicity prediction analysis had simulated that several mutations rendered some antigenic epitopes of HA and NA protein to be non-antigenic. These findings highlighted the importance of reliable national surveillance network of influenza to prevent regional epidemic and the development of local influenza vaccine to better accommodate Indonesian population.

Evaluation of whole and core genome multilocus sequence typing allele schemes for Salmonella enterica outbreak detection in a national surveillance network, PulseNet USA.

Salmonella enterica is a leading cause of bacterial foodborne and zoonotic illnesses in the United States. For this study, we applied four different whole genome sequencing (WGS)-based subtyping methods: high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multilocus sequence typing using either all loci [wgMLST (all loci)] and only chromosome-associated loci [wgMLST (chrom)], and core genome multilocus sequence typing (cgMLST) to a dataset of isolate sequences from 9 well-characterized Salmonella outbreaks. For each outbreak, we evaluated the genomic and epidemiologic concordance between hqSNP and allele-based methods. We first compared pairwise genomic differences using all four methods. We observed discrepancies in allele difference ranges when using wgMLST (all loci), likely caused by inflated genetic variation due to loci found on plasmids and/or other mobile genetic elements in the accessory genome. Therefore, we excluded wgMLST (all loci) results from any further comparisons in the study. Then, we created linear regression models and phylogenetic tanglegrams using the remaining three methods. K-means analysis using the silhouette method was applied to compare the ability of the three methods to partition outbreak and sporadic isolate sequences. Our results showed that pairwise hqSNP differences had high concordance with cgMLST and wgMLST (chrom) allele differences. The slopes of the regressions for hqSNP vs. allele pairwise differences were 0.58 (cgMLST) and 0.74 [wgMLST (chrom)], and the slope of the regression was 0.77 for cgMLST vs. wgMLST (chrom) pairwise differences. Tanglegrams showed high clustering concordance between methods using two statistical measures, the Baker's gamma index (BGI) and cophenetic correlation coefficient (CCC), where 9/9 (100%) of outbreaks yielded BGI values ≥ 0.60 and CCCs were ≥ 0.97 across all nine outbreaks and all three methods. K-means analysis showed separation of outbreak and sporadic isolate groups with average silhouette widths ≥ 0.87 for outbreak groups and ≥ 0.16 for sporadic groups. This study demonstrates that Salmonella isolates clustered in concordance with epidemiologic data using three WGS-based subtyping methods and supports using cgMLST as the primary method for national surveillance of Salmonella outbreak clusters.