Public perspectives on COVID-19 public health and social measures in Japan and the United Kingdom: a qualitative study.

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2, was one of the greatest modern public health crises that the world has faced. Countries undertook sweeping public health and social measures (PHSM); including environmental actions such as disinfection and ventilation; surveillance and response, such as contact tracing and quarantine; physical, such as crowd control; and restrictions on travel. This study focuses on the public perceptions of PHSM in two countries, Japan and the United Kingdom (UK) as examples of high-income countries that adopted different measures over the course of the pandemic. METHODS: This study was conducted between November 2021 and February 2022, a period in which the Omicron variant of SARS-CoV-2 was predominant. Fourteen online focus group discussions were conducted in each country. Overall, 106 total participants (50 from the UK and 56 from Japan) participated in 23 focus groups (11 in the UK and 12 in Japan) with an average of three to six participants per group. Both countries were compared using a thematic analysis method. RESULTS: Both countries' participants agreed that vaccination was an effective measure. However, they did not favor mandatory vaccination policies. Working from home was well accepted by both sides, but they reported that schools should have continued to be opened as before COVID-19. Both sides of participants expressed that temperature testing alone in indoor facilities was ineffective as a COVID-19 control measure. There were contrasting views on face covering rules in public spaces, international and domestic movement restrictions. High acceptance of mask-wearing was reflective of Japanese customs, while it was accepted as a strong recommendation for participants in the UK. Japanese participants favored quarantine for international travel, while the UK participants supported banning non-essential travel. CONCLUSION: Similar and contrasting views on PHSM against COVID-19 between Japan and the UK demonstrated how policies in controlling an epidemic should be tailored by country with respect to its norms, cultures, economic and disease burden. Our findings may guide how policy makers can engage with the public through effective health communication and consider regulations that are aligned with the public's views and capacities in changing their behavior for future pandemic preparedness.

Activity-stability trade-off observed in variants at position 315 of the GH10 xylanase XynR.

XynR is a thermostable alkaline GH10 xylanase, for which we have previously examined the effects of saturation mutagenesis at position 315 on enzyme alkaliphily, and found that at pH 10, the activities of variants could be ordered as follows: T315Q > T315S = T315N > T315H = wild-type XynR (WT) > 15 other variants. In this study, we sought to elucidate the mechanisms underlying the variable activity of these different variants. Crystallographic analysis revealed that the Ca2+ ion near position 315 in WT was absent in the T315Q variant. We accordingly hypothesized that the enhancement of alkaliphily in T315Q, and probably also in the T315H, T315N, and T315S variants, could be ascribed to an activity-stability trade-off associated with a reduction in stability due to the lack of this Ca2+ ion. Consistent with expectations, the alkaline resistance of T315H, T315N, T315Q, and T315S, evaluated through the pH-dependence of stability at 0 mM CaCl2 under alkaline conditions, was found to be lower than that of WT: the residual activity at pH 11 of WT was 78% while those of T315H, T315N, T315Q, and T315S were 0, 9, 0, and 43%, respectively. In addition, the thermostabilities of these four variants, as assessed using the denaturing temperatures (Tm) at 0 mM CaCl2 based on ellipticity at 222 nm in circular dichroism measurements, were lower than that of WT by 2-8 °C. Furthermore, the Tm values of WT and variants at 5 mM CaCl2 were higher than those at 0 mM CaCl2 by 6-11 °C. Collectively, our findings in this study indicate that mutation of the T residue at position 315 of XynR to H, N, Q, and S causes an increase in the alkaliphily of this enzyme, thereby reducing its stability.

Rotavirus genotypes in children under five years hospitalized with diarrhea in low and middle-income countries: Results from the WHO-coordinated Global Rotavirus Surveillance Network.

Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network. Data from a convenience sample of children under five years of age hospitalized with acute watery diarrhea who tested positive for rotavirus were included. Country results were weighted by their estimated rotavirus disease burden to estimate regional genotype distributions. Globally, the most frequent genotypes identified after weighting were G1P[8] (31%), G1P[6] (8%) and G3P[8] (8%). Genotypes varied across WHO Regions and between countries that had and had not introduced rotavirus vaccine. G1P[8] was less frequent among African (36 vs 20%) and European (33 vs 8%) countries that had introduced rotavirus vaccines as compared to countries that had not introduced. Our results describe differences in the distribution of the most common rotavirus genotypes in children with diarrhea in low- and middle-income countries. G1P[8] was less frequent in countries that had introduced the rotavirus vaccine while different strains are emerging or re-emerging in different regions.

How to increase and maintain high immunization coverage: Vaccination Demand Resilience (VDR) framework.

BACKGROUND: Resilience in vaccination demand is ever more critical as the COVID-19 pandemic has increased our understanding of the importance of vaccines on health and well-being. Yet timid demand for COVID-19 vaccines where available and reduced uptake of routine immunizations globally further raise the urgent need to build vaccination resilience. We demonstrate the complexity of vaccination demand and resilience in a framework where relevant dimensions are intertwined, fluid, and contextual. METHODS: We developed the Vaccination Demand Resilience (VDR) framework based on a literature review on vaccination demand and expert consultation. The matrix framework builds on three main axes: 1) vaccination attitudes and beliefs; 2) vaccination seeking behavior; and 3) vaccination status. The matrix generated eight quadrants, which can help explain people's levels of vaccination demand and resilience. We selected four scenarios as examples to demonstrate different interventions that could move people across quadrants and build vaccination resilience. RESULTS: Incongruence between individuals' attitudes and beliefs, vaccination behavior, and vaccination status can arise. For example, an individual can be vaccinated due to mandates but reject vaccination benefits and otherwise avoid seeking vaccination. Such incongruence could be altered by interventions to build resilience in vaccination demand. These interventions include information, education and communication to change individuals' vaccination attitudes and beliefs, incentive programs and reminder-recalls to facilitate vaccination seeking, or by strengthening healthcare provider communications to reduce missed opportunities. CONCLUSIONS: Vaccination decision-making is complex. Individuals can be vaccinated without necessarily accepting the benefits of vaccination or seeking vaccination, threatening resilience in vaccination demand. The VDR framework can provide a useful lens for program managers and policy makers considering interventions and policies to improve vaccination resilience. This would help build and sustain confidence and demand for vaccinations, and help to continue to prevent disease, disability, and death from vaccine-preventable diseases.

Evaluation of Laboratories Supporting Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance in the World Health Organization African Region, through the Performance of Coordinated External Quality Assessment.

(1) Background: Laboratories supporting the invasive bacteria preventable disease (IB-VPD) network are expected to demonstrate the capacity to identify the main etiological agents of pediatric bacterial meningitis (PBM) (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) on Gram stains and in phenotypic identification. Individual reports of sentinel site (SSL), national (NL) and regional reference (RRL) laboratories participating in the World Health Organization (WHO)-coordinated external quality assessment, distributed by the United Kingdom National External Quality Assessment (EQA) Services (UK NEQAS) for Microbiology between 2014 and 2019 were analyzed. (2) Methods: The panels consisted of (1) unstained bacterial smears for Gram staining, (2) viable isolates for identification and serotyping/serogrouping (ST/SG) and (3) simulated cerebral spinal fluid (CSF) samples for species detection and ST/SG using polymerase chain reaction (PCR). SSLs and NLs tested for Gram staining and species identification (partial panel). RRLs, plus any SSLs and NLs (optionally) also analyzed the simulated CSF samples (full panel). The passing score was ≥75% for NLs and SSLs, and ≥90% for RRLs and NLs/SSLs testing the full panel. (3) Results: Overall, 63% (5/8) of the SSLs and NLs were able to correctly identify the targeted pathogens, in 2019; but there were challenges to identify Haemophilus influenzae either on Gram stains (35% of the labs failed 2014), or in culture. Individual performance showed inconsistent capacity, with only 39% (13/33) of the SSLs/NLs passing the EQA exercise throughout all surveys in which they participated. RRLs performed well over the study period, but one of the two failed to reach the minimal passing score in 2016 and 2018; while the SSLs/NLs that optionally tested the full panel scored between 75% and 90% (intermediate pass category). (4) Conclusions: We identified a need for implementing a robust quality management system for timely identification of the gaps and then implementing corrective and preventive actions, in addition to continuous refresher training in the SSLs and NLs supporting the IB-VPD surveillance in the World Health Organization, Regional Office for Africa (WHO AFRO).

Continuous low serum levels of advanced glycation end products and low risk of cardiovascular disease in patients with poorly controlled type 2 diabetes.

BACKGROUND: Type 2 diabetes is associated with an increased risk of developing cardiovascular events. Previous studies have reported that advanced glycation end products (AGEs) were related to cardiovascular events in type 2 diabetes. However, data on associations between long-term AGEs and cardiovascular events in type 2 diabetes are lacking. This study aimed to determine whether a long-time shift in the levels of serum AGEs is associated with cardiovascular events in patients with poorly controlled type 2 diabetes. METHODS: Two-time serum methyl-glyoxal-hydroimidazoline (MG-H1) levels were measured in 138 patients with type 2 diabetes whose mean glycated hemoglobin level was 10.1%. We categorized patients whose serum MG-H1 levels were < 2.8 µg/mL at both times as the continuous low MG-H1 group. The primary endpoints of this study were combined cardiovascular events, which were defined as heart disease, peripheral arterial disease, stroke, and all-cause death. Hazard ratios (HRs) for combined cardiovascular events with 95% confidence intervals (CIs) were calculated using the Cox proportional hazard models to compare the outcomes between the continuous low MG-H1 group and others. RESULTS: The continuous low MG-H1 group was associated with a significantly lower risk than others in combined cardiovascular events after adjusting for possible confounders (HR: 0.50; 95% CI, 0.28-0.87; P = 0.02). Furthermore, the same relationship was observed in patients without a history of cardiovascular events. CONCLUSIONS: Continuous low serum MG-H1 levels are associated with a low frequency of diabetes-related complications in patients with poorly controlled type 2 diabetes.

Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants.

We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.

Evaluation of the World Health Organization Global Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network's Laboratory External Quality Assessment Programme, 2014-2019.

Introduction. In 2009, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine Preventable Disease (IB-VPD) Surveillance Network (GISN) to monitor the global burden and aetiology of bacterial meningitis, pneumonia and sepsis caused by Haemophilus influenzae (Hi), Neisseria meningitidis (Nm) and Streptococcus pneumoniae (Sp).Hypothesis/Gap Statement. The GISN established an external quality assessment (EQA) programme for the characterization of Hi, Nm and Sp by culture and diagnostic PCR.Aim. To assess the performance of sentinel site laboratories (SSLs), national laboratories (NLs) and regional reference laboratories (RRLs) between 2014 and 2019 in the EQA programme.Methodology. Test samples consisted of bacterial smears for Gram-staining, viable isolates for identification and serotyping or serogrouping (ST/SG), plus simulated cerebrospinal fluid (CSF) samples for species detection and ST/SG by PCR. SSLs and NLs were only required to analyse the slides for Gram staining and identify the species of the live isolates. RRLs, and any SLs and NLs that had the additional laboratory capacity, were also required to ST/SG the viable isolates and analyse the simulated CSF samples.Results. Across the period, 69-112 SS/NL labs and eight or nine RRLs participated in the EQA exercise. Most participants correctly identified Nm and Sp in Gram-stained smears but were less successful with Hi and other species. SSLs/NLs identified the Hi, Nm and Sp cultures well and also submitted up to 56 % of Hi, 62 % of Nm and 33 % of Sp optional ST/SG results each year. There was an increasing trend in the proportion of correct results submitted over the 6 years for Nm and Sp. Some SSLs/NLs also performed the optional detection and ST/SG of the three organisms by PCR in simulated CSF from 2015 onwards; 89-100 % of the CSF samples were correctly identified and 76-93 % of Hi-, 90-100 % of Nm- and 75-100 % of Sp-positive samples were also correctly ST/SG across the distributions. The RRLs performed all parts of the EQA to a very high standard, with very few errors across all aspects of the EQA.Conclusion. The EQA has been an important tool in maintaining high standards of laboratory testing and building of laboratory capacity in the GISN.

Risk Factors for Mortality Among Children Younger Than Age 5 Years With Severe Diarrhea in Low- and Middle-income Countries: Findings From the World Health Organization-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children younger than 5 years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low- and middle-income countries. METHODS: Data from the World Health Organization (WHO)-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children <5 years of age who were hospitalized with diarrhea between 2008 and 2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis comprises 234 781 cases, including 1219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI], 2.81-4.50), female sex (OR = 1.18; 95% CI, 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01-3.25), no vomiting (OR = 1.13; 95% CI, .98-1.30), severe dehydration (OR = 3.79; 95% CI, 3.01-4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO regions (OR = 130.62 comparing the African Region with the European Region; 95% CI, 55.72-422.73), whereas cases from the European Region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections.

Preferential Selection of Low-Frequency, Lipopolysaccharide-Modified, Colistin-Resistant Mutants with a Combination of Antimicrobials in Acinetobacter baumannii.

Colistin, which targets lipopolysaccharide (LPS), is used as a last-resort drug against severe infections caused by drug-resistant Acinetobacter baumannii. However, A. baumannii possesses two colistin-resistance mechanisms. LPS modification caused by mutations in pmrAB genes is often observed in clinical isolates of multidrug-resistant Gram-negative pathogens. In addition to LPS modification, A. baumannii has a unique colistin resistance mechanism, a complete loss of LPS due to mutations in the lpxACD genes, which are involved in LPS biosynthesis. This study aimed to elucidate the detailed mechanism of the emergence of colistin-resistant A. baumannii using strains with the same genetic background. Various colistin-resistant strains were generated experimentally using colistin alone and in combination with other antimicrobials, such as meropenem and ciprofloxacin, and the mutation spectrum was analyzed. In vitro selection of A. baumannii in the presence of colistin led to the emergence of strains harboring mutations in lpxACD genes, resulting in LPS-deficient colistin-resistant strains. However, combination of colistin with other antimicrobials led to the selection of pmrAB mutant strains, resulting in strains with modified LPS (LPS-modified strains). Further, the LPS-deficient strains showed decreased fitness and increased susceptibility to many antibiotics and disinfectants. As LPS-deficient strains have a higher biological cost than LPS-modified strains, our findings suggested that pmrAB mutants are more likely to be isolated in clinical settings. We provide novel insights into the mechanisms of resistance to colistin and provide substantial solutions along with precautions for facilitating current research and treatment of colistin-resistant A. baumannii infections. IMPORTANCE Acinetobacter baumannii has developed resistance to various antimicrobial drugs, and its drug-resistant strains cause nosocomial infections. Controlling these infections has become a global clinical challenge. Carbapenem antibiotics are the frontline treatment drugs for infectious diseases caused by A. baumannii. For patients with infections caused by carbapenem-resistant A. baumannii, colistin-based therapy is often the only treatment option. However, A. baumannii readily acquires resistance to colistin. Many patients infected with colistin-resistant A. baumannii undergo colistin treatment before isolation of the colistin-resistant strain, and it is hypothesized that colistin resistance predominantly emerges under selective pressure during colistin therapy. Although the concomitant use of colistin and carbapenems has been reported to have a synergistic effect in vitro against carbapenem-resistant A. baumannii strains, our observations strongly suggest the need for attention to the emergence of strains with a modified lipopolysaccharide during treatment.

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

A global comprehensive vaccine-preventable disease surveillance strategy for the immunization Agenda 2030.

As part of the Immunization Agenda 2030, a global strategy for comprehensive vaccine-preventable disease (VPD) surveillance was developed. The strategy provides guidance on the establishment of high-quality surveillance systems that are 1) comprehensive, encompassing all VPD threats faced by a country, in all geographic areas and populations, using all laboratory and other methodologies required for timely and reliable disease detection; 2) integrated, wherever possible, taking advantage of shared infrastructure for specific components of surveillance such as data management and laboratory systems; 3) inclusive of all relevant data needed to guide immunization program management actions. Such surveillance systems should generate data useful to strengthen national immunization programs, inform vaccine introduction decision-making, and reinforce timely and effective detection and response. All stakeholders in countries and globally should work to achieve this vision.

Kaposi's sarcoma-associated herpesvirus ubiquitin ligases downregulate cell surface expression of l-selectin.

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic etiological factor for Kaposi's sarcoma and primary effusion lymphoma in immunocompromised patients. KSHV utilizes two immune evasion E3 ubiquitin ligases, namely K3 and K5, to downregulate the expression of antigen-presenting molecules and ligands of natural killer (NK) cells in the host cells through an ubiquitin-dependent endocytic mechanism. This allows the infected cells to evade surveillance and elimination by cytotoxic lymphocytes and NK cells. The number of host cell molecular substrates reported for these ubiquitin ligases is limited. The identification of novel substrates for these ligases will aid in elucidating the mechanism underlying immune evasion of KSHV. This study demonstrated that K5 downregulated the cell surface expression of l-selectin, a C-type lectin-like adhesion receptor expressed in the lymphocytes. Tryptophan residue located at the centre of the E2-binding site in the K5 RINGv domain was essential to downregulate l-selectin expression. Additionally, the lysine residues located at the cytoplasmic tail of l-selectin were required for the K5-mediated downregulation of l-selectin. K5 promoted the degradation of l-selectin through polyubiquitination. These results suggest that K5 downregulates l-selectin expression on the cell surface by promoting polyubiquitination and ubiquitin-dependent endocytosis, which indicated that l-selectin is a novel substrate for K5. Additionally, K3 downregulated l-selectin expression. The findings of this study will aid in the elucidation of a novel immune evasion mechanism in KSHV.

Characterization of Phosphorylation Status and Kinase Activity of Src Family Kinases Expressed in Cell-Based and Cell-Free Protein Expression Systems.

The production of heterologous proteins is an important procedure for biologists in basic and applied sciences. A variety of cell-based and cell-free protein expression systems are available to achieve this. The expression system must be selected carefully, especially for target proteins that require post-translational modifications. In this study, human Src family kinases were prepared using six different protein expression systems: 293 human embryonic kidney cells, Escherichia coli, and cell-free expression systems derived from rabbit reticulocytes, wheat germ, insect cells, or Escherichia coli. The phosphorylation status of each kinase was analyzed by Phos-tag SDS-PAGE. The kinase activities were also investigated. In the eukaryotic systems, multiple phosphorylated forms of the expressed kinases were observed. In the rabbit reticulocyte lysate system and 293 cells, differences in phosphorylation status between the wild-type and kinase-dead mutants were observed. Whether the expressed kinase was active depended on the properties of both the kinase and each expression system. In the prokaryotic systems, Src and Hck were expressed in autophosphorylated active forms. Clear differences in post-translational phosphorylation among the protein expression systems were revealed. These results provide useful information for preparing functional proteins regulated by phosphorylation.

The Global Landscape of Pediatric Bacterial Meningitis Data Reported to the World Health Organization-Coordinated Invasive Bacterial Vaccine-Preventable Disease Surveillance Network, 2014-2019.

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

Pneumococcal Meningitis Outbreaks in Africa, 2000-2018: Systematic Literature Review and Meningitis Surveillance Database Analyses.

BACKGROUND: The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. METHODS: Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. RESULTS: A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. CONCLUSIONS: Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.

Global Rotavirus and Pneumococcal Conjugate Vaccine Introductions and the Association With Country Disease Surveillance, 2006-2018.

BACKGROUND: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction. METHODS: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018. RESULTS: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction. CONCLUSIONS: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks.

Feasibility of balloon endoscope-assisted endoscopic retrograde cholangiopancreatography for the elderly.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) for patients with surgically altered anatomy is challenging. Recently, balloon endoscopy has been shown to facilitate ERCP for this population with a high technical success rate, but adverse events (AEs) are not uncommon. Compared to non-elderly patients, elderly patients may be at higher risk of AEs due to underlying comorbidities. The current study aimed to evaluate the feasibility of balloon endoscope-assisted ERCP (BE-ERCP) for the elderly. Patients and methods We retrospectively identified patients who underwent BE-ERCP between January 2010 and September 2019. For patients who underwent multiple procedures during the study period, the first session was analyzed. Early AEs associated with BE-ERCP were compared between elderly (≥ 75 years) and non-elderly patients. Results A total of 1,363 BE-ERCP procedures were performed, and 568 patients (211 elderly and 357 non-elderly) were included for the analyses. Technical success rates were high in both the elderly and non-elderly groups (80 % vs. 80 %, respectively). The rates of early AEs were similar between the groups (12 % vs. 9.0 % in the elderly and non-elderly group, respectively; P  = 0.31). The mltivariable-adjusted odds ratio for early AEs comparing elderly to non-elderly patients was 1.36 (95 % confidence interval, 0.74-2.51; P  = 0.32). Specifically, we did not observe between-group differences in rates of gastrointestinal perforation (2.4 % vs. 2.8 % in elderly and non-elderly groups, respectively; P  = 0.99) and aspiration pneumonia (1.9 % vs. 0.6 %, P  = 0.20). Conclusions BE-ERCP is a feasible procedure for elderly individuals with surgically altered anatomy.

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist: A case report.

RATIONALE: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. PATIENT CONCERNS: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. DIAGNOSIS: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. INTERVENTIONS: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. OUTCOMES: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. LESSONS: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.