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Background: Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates.Methods: Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model.Results: 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66-3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient-days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13-2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups.Conclusions: Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community. [ABSTRACT FROM AUTHOR]

Background: Meningococcal disease continues to be a global public health concern due to its epidemic potential, severity, and sequelae. The global epidemiological data on circulating meningococcal serogroups have never been reviewed concurrently with the laboratory capacity for meningococcal surveillance at the national level. We, therefore, aimed to conduct a country-level review of meningococcal surveillance, serogroup distribution, and vaccine use.Methods: We conducted a systematic literature review across six databases to identify studies (published January 1, 2010 to October 16, 2017) and grey literature reporting meningococcal serogroup data for the years 2010-2016. We performed independent random effects meta-analyses for serogroups A, B, C, W, X, Y, and other. We developed and circulated a questionnaire-based survey to surveillance focal points in countries (N = 95) with known regional bacterial meningitis surveillance programs to assess their surveillance capacity and summarized using descriptive methods.Results: We included 173 studies from 59 countries in the final analysis. The distribution of meningococcal serogroups differed markedly between countries and regions. Meningococcal serogroups C and W accounted for substantial proportions of meningococcal disease in most of Africa and Latin America. Serogroup B was the predominant cause of meningococcal disease in many locations in Europe, the Americas, and the Western Pacific. Serogroup Y also caused many cases of meningococcal disease in these regions, particularly in Nordic countries. Survey responses were received from 51 countries. All countries reported the ability to confirm the pathogen in-country, while approximately 30% either relied on reference laboratories for serogrouping (N = 10) or did not serogroup specimens (N = 5). Approximately half of countries did not utilize active laboratory-based surveillance system (N = 22). Nationwide use of a meningococcal vaccine varied, but most countries (N = 36) utilized a meningococcal vaccine at least for certain high-risk population groups, in private care, or during outbreaks.Conclusions: Due to the large geographical variations in circulating meningococcal serogroups, each country should continue to be monitored for changes in major disease-causing serogroups in order to inform vaccine and control policies. Similarly, laboratory capacity should be appropriately scaled up to more accurately understand local epidemiology and disease burden, as well as the impact of vaccination programs. [ABSTRACT FROM AUTHOR]

Background: Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI.Methods: We conducted a review of systematic reviews and meta-analyses on risk factors for CDI and rCDI published between 1990 and October 2016.Results: 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta-analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host-related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta-analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis.Conclusion: Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta-analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non-selective NSAID, and some co-morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted-CDI clinical management procedures, prevention, and research. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile is the leading cause of health care-associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance.Methods: We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI-targeted IPC recommendations and describe the assessment of evidence in available guidelines.Results: We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long-term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported "strong" recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality.Conclusion: Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations. [ABSTRACT FROM AUTHOR]

Background Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in children and young adults worldwide. The disease burden associated with N. meningitidis infections has not been systematically assessed in China. Therefore, we undertook this study to determine the burden of meningococcal disease in China. Method We performed a systematic review and meta-analysis of articles on N. meningitidis incidence, carriage, seroprevalence and mortality rates in China by searching the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed for publications from January 2005 to Aug 2015. Results In total, 50 articles were included in our analysis. The overall incidence of meningococcal disease and associated mortality were estimated to be 1.84 (95% confidence interval (CI) 0.91-3.37) per 100 000 persons per year and 0.33 (95% CI 0.12-0.86) per 100 000 persons per year, respectively. N. meningitidis carriage rate among the healthy population was estimated to be 2.7% (95% CI 2.0-3.5%). Prevalence of antibodies against N. meningitidis serogroup A and C were estimated to be 77.3% (95% CI 72.4%-81.6%) and 33.5% (95% CI 27.0%-40.8%), respectively. No studies were found for serogroup specific disease burden. Conclusions The overall incidence of meningococcal disease in China is low. The lower seroprevalence of serogroup C within the population suggests that it may pose a greater risk for meningococcal disease outbreak than serogroup A. The lack of data on serogroup disease burden by age groups suggests the implementation of laboratory based meningococcal surveillance systems are urgently needed in China. [ABSTRACT FROM AUTHOR]

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

Background. High attack rates among vaccinated young adults reported during the 2006 mumps outbreak in the United States heightened concerns regarding mumps vaccine failure. Methods. Serum specimens from university students and staff were tested for mumps immunoglobulin (Ig) G by enzyme immunoassay (EIA). A subset of participants vaccinated for ⩽5 years and ⩾15 years were tested by neutralizing antibody (NA) assay. Persons seronegative by EIA were offered a third dose of measles-mumps-rubella vaccine (MMR3), and serum specimens were obtained 7-10 days and 2-3 months after its administration. Results. Overall, 94% (95% confidence interval [CI], 91%-96%) of the 440 participants were seropositive. No differences existed in seropositivity rates by sex, age, age at receipt of the second dose of MMR vaccine (MMR2), or time since receipt of MMR2 (P = .568). The geometric mean titer (GMT) of NA among persons vaccinated with MMR2 during the previous 1-5 years was 97 (95% CI, 64-148), whereas, among those vaccinated ⩾15 years before blood collection, the GMT was 58 (95% CI, 44-76) (P = .065). After MMR3, 82% (14/17) and 91% (10/11) seroconverted in 7-10 days and 2-3 months, respectively. Conclusions. Lower levels of NA observed among persons who received MMR2 ⩾15 years ago demonstrates antibody decay over time. MMR3 vaccination of most seronegative persons marked the capacity to mount an anamnestic response. [ABSTRACT FROM AUTHOR]

Background. Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. Methods. This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. Results. Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were ~5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). Conclusions. Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants. [ABSTRACT FROM AUTHOR]

Penicillin resistance of Pneumococci is a problem in several European countries. Therefore, we examined 510 invasive pneumococcal isolates, collected between 1992 and 1999 via a national network of diagnostic laboratories covering the entire population of Scotland, for penicillin susceptibility, in order to determine the prevalence, site of infection and serogroup/type distribution of penicillin-resistant Pneumococci in the elderly (≥ 65 y). Of the 510 isolates, 91.6% (n = 467) were from blood, 4.7% (n = 24) from other sterile sites and 3.7% (n = 19) from cerebrospinal fluid. The prevalence of penicillin non-susceptible isolates during the study period was 9%. An increase in the proportion of Pneumococci non-susceptible to penicillin was detected from 1996 onwards, from 10.8% in 1996 to 14.3% in 1999. There were 2 isolates with high-level penicillin resistance, both of which were of serotype 14, accounting for 4.3% (2/46) of all non-susceptible isolates. Penicillin non-susceptible isolates belonged to the following serogroups: 14 (32.6%); 9 (30.4%); 6 (19.6%); 23 (10.9%); and 19 (6.5%). The leading non-susceptible serotype/group varied according to the specimen type: serotype 14 for blood and serogroup 9 for all other sterile sites. Current polysaccharide and new 7-, 9- and 11-valent conjugate vaccine formulations included the serogroups responsible for all the penicillin non-susceptible isolates detected. Therefore vaccination represents the most effective strategy for decreasing the burden of drug resistance. Constant surveillance of the patterns of antibiotic non-susceptible isolates, the site of infection and the serogroup/type are necessary in order to select antibiotic therapy and establish vaccination policy for the prevention of invasive pneumococcal disease. [ABSTRACT FROM AUTHOR]

The EMPRISE study evaluates the effectiveness and safety of empagliflozin (EMPA) in a broader population of patients with T2D in routine clinical care across countries. The study included 67,140 pairs of 1:1 propensity score matched (PSM) patients ≥18 years with T2D newly initiating EMPA or any DPP-4i from large databases/registers in Israel, Finland, Germany, Spain, Sweden, South Korea, Taiwan and Japan. Mostly, PSM used 100+ baseline covariates (Table), and pooled HR with 95% CI were computed using random-effects meta-analysis models. EMPA compared to DPP-4i (Table), was associated with 27-47% lower risk of hospitalization for heart failure (HHF), stroke, all-cause mortality (ACM), and two composite outcomes: HHF & ACM; and myocardial infarction, stroke & ACM. Safety analyses associated EMPA with 46% lower risk of acute kidney injury requiring dialysis. EMPRISE study results showed that EMPA is associated with reduced risk of cardiovascular (CV) disease, incl HHF, in patients with T2D in routine clinical care settings in Israel, Europe and East Asia. These results complement the results from clinical trial EMPA-REG OUTCOME®, and are in line with the ADA/EASD 2019 consensus update to prescribe SGLT-2i for patients with T2D and high-risk, vascular or chronic kidney disease or heart failure to reduce HHF and major adverse CV events/deaths. Disclosure: A. Karasik: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S. S. Lanzinger: None. E. C. H. Tan: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. Yabe: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MDS Co., Ltd., Novo Nordisk Pharma Ltd. D. Kim: None. W. Sheu: None. C. Melzer Cohen: None. R. W. Holl: None. K. Ha: None. T. Nystrom: Board Member; Self; Abbott, Lilly Diabetes, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker's Bureau; Self; AstraZeneca. L. K. Niskanen: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk. Stock/Shareholder; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Linnemann Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. M. H. Kyaw: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Nunez: Advisory Panel; Self; Novo Nordisk Pharma Ltd. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]

A correction notice was issued for a study on severe COVID-19 outcomes in five Latin American countries in the post-vaccination era, addressing an error in reported hospitalized cases in Brazil. The study analyzed clinical profiles, hospitalization rates, mortality rates, and vaccination status of confirmed COVID-19 cases, highlighting differences in outcomes between males and age groups, as well as the impact of comorbidities and COVID-19 variants on hospitalization rates. Detailed data on COVID-19 cases, mortality rates, ICU admissions, comorbidities, and vaccination status by age group is provided for Brazil, Mexico, Colombia, Argentina, and Chile, offering insights into the pandemic's impact in different regions. The authors have made corrections to ensure the scientific accuracy of their conclusions. [Extracted from the article]

Background & Aims Guidelines recommend withholding clopidogrel 7 days before polypectomy to decrease bleeding risk, but these were written based on limited evidence. We investigated whether uninterrupted clopidogrel therapy increases the risk of delayed postpolypectomy bleeding in patients undergoing colonoscopy. Methods We identified patients receiving clopidogrel for cardiovascular disease undergoing elective colonoscopies in Hong Kong from February 28, 2012 through April 11, 2018. Eligible patients were instructed to stop taking clopidogrel 7 days before colonoscopy. Then, they were randomly assigned to groups given clopidogrel (75 mg) or placebo daily until the morning of colonoscopy. All patients resumed their usual prescriptions of clopidogrel after colonoscopy. The primary end point was delayed postpolypectomy bleeding that required hospitalization or intervention up to 30 days after colonoscopy. Secondary end points were immediate postpolypectomy bleeding and serious cardio-thrombotic events for as long as 6 months after colonoscopy, according to Antithrombotic Trialists' criteria. All events were adjudicated by an independent masked committee. Results In total, 387 patients underwent colonoscopy and 216 required polypectomies (106 patients in the clopidogrel group and 110 patients in the placebo group). The cumulative incidence of delayed postpolypectomy bleeding was 3.8% (95% confidence interval 1.4–9.7) in the clopidogrel group and 3.6% (95% confidence interval 1.4–9.4) in the placebo group (P =.945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; P =.380) and cardio-thrombotic events (1.5% vs 2%; P =.713). Conclusions In a randomized controlled trial of clopidogrel users undergoing colonoscopy, a slightly larger proportion of patients continuing clopidogrel developed delayed and immediate postpolypectomy bleeding, although this difference was not statistically significant. ClinicalTrials.gov , number NCT01806090. [ABSTRACT FROM AUTHOR]

We conducted a multicountry retrospective study using data from COVID-19 national surveillance databases to analyze clinical profiles, hospitalization rates, intensive care unit (ICU) admissions, utilization of ventilatory support, and mortality rates in five Latin American countries in the context of COVID-19 vaccination implementation. We analyzed the sociodemographic characteristics, comorbidities, clinical outcomes, and vaccination status of laboratory-confirmed COVID-19 cases from January 2021 to December 2022. We calculated the yearly and quarterly hospitalization rates per 1000 confirmed COVID-19 cases and ICU admissions, use of mechanical ventilators, and mortality rates per 1000 hospitalized cases, with their corresponding 95% confidence interval (CI) of 38,852,831 confirmed COVID-19 cases. Rates of hospitalization, ICU admission, ventilatory support, and death were higher among males than among females (38.2 vs. 32.4, 148.4 vs. 117.7, 282.9 vs. 236.2, and 346.9 vs. 320.1 per 1000, respectively); higher in 2021 than in 2022 (50.7 vs. 19.9, 207.8 vs. 58.2, 441.5 vs. 114.9, and 352.5 vs. 285.2 per 1000, respectively); and in the >50 age group (range: 5.7–18.6, 20.1–71.5, 12.2–67.9, and 353.1–577.4, per 1000) than the <50 age group (range: 2.2–9.3, 5.4–33.2, 41.4–135.8, and 22–243.5 per 1000). Hypertension and diabetes mellitus were the most common comorbidities in Mexico and Colombia. Prevention and treatment strategies for these case profiles could bring benefits from a public health perspective. [ABSTRACT FROM AUTHOR]

Background & Aims There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. Methods We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 μg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. Results Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%–42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%–18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%–35.3%; P =.026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05–1.36; P =.035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1–85] to 2 [range, 0–25]) than in the placebo group (from 7 [range, 1–29] to 4 [range, 0–19] (P =.005). Conclusions In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776. Graphical abstract [ABSTRACT FROM AUTHOR]

Due to low susceptibility of coronavirus disease of 2019 (COVID-19) in children, limited studies are available regarding COVID-19 in the pediatric population in Tunisia. The current study evaluated the incidence, clinical characteristics, and outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection among children hospitalized at Béchir Hamza Children's Hospital. A retrospective cohort analysis was conducted using the hospital database between March 2020 and February 2022 with children aged ≤15 years with SARS-CoV-2 infection (confirmed by RT-PCR). A total of 327 COVID-19 hospitalized patients with a mean age of 3.3 years were included; the majority were male. Neurological disease (20%) was the most common comorbidity, while fever (95.3%) followed by cough (43.7%) and dyspnea (39.6%) were the most frequent symptoms reported. Severe disease with oxygen requirement occurred in 30% of the patients; 13% were admitted in the Intensive Care Unit. The overall incidence rate of COVID-19 hospitalization (in Tunis governorates) was 77.02 per 100,000 while the inpatient case fatality rate was 5% in the study population. The most prevalent circulating variant during our study period was Delta (48.8%), followed by Omicron (26%). More than 45% of the study population were <6 months and one-fourth (n = 25, 26.5%) had at least one comorbidity. Thus, the study findings highlight the high disease burden of COVID-19 in infants. [ABSTRACT FROM AUTHOR]

• In Luanda, 20% of young infants with possible severe infection died in hospital. • Forty percent of deaths occurred within 48 h of admission. • In multivariate analyses, tachycardia and seizures predicted death. Yearly, about two million infants die during the first 28 days of life. Most of these deaths occur in sub-Saharan Africa and a third of those are caused by severe infections. The early identification of infants at risk of death is important when trying to prevent poor outcomes. The aim of this study was to identify risk factors for death among young infants with possible serious bacterial infection (pSBI) at hospital admission. This prospective, observational, single-site, descriptive study forms part of a larger study on bacterial meningitis in infants <90 days of age admitted to the Pediatric Hospital of Luanda, the capital of Angola, from February 1, 2016 to October 23, 2017. Infants with pSBI, a known outcome, and a final diagnosis were included. Of 574 young infants with pSBI, 115 (20%) died in hospital. An altered level of consciousness, absence of spontaneous movements, dyspnea, CSF that is not clear, low CSF glucose, high CSF protein, heart rate over the median, and seizures were identified as risk factors for death in the univariate analysis. In the multivariate analysis, only heart rate over the median and seizures were independent predictors of death. Easily recognizable clinical signs – tachycardia and seizures – may guide clinicians to identify infants at high risk of death due to severe bacterial infections in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

• In Luanda, meningitis was identified in 23% of infants <90 days old and with spinal tap. • The most common agents were Klebsiella spp, Streptococcus pneumoniae , and Streptococcus agalactiae. • Of pneumococcal strains, 21% showed reduced susceptibility to penicillin. • Gram-negative bacteria showed high rates of resistance to commonly used antibiotics. Despite effective antibiotics and vaccines, bacterial meningitis (BM) remains one of the leading causes of morbidity and mortality in young infants worldwide. Data from Africa on the aetiology and antibiotic susceptibility are scarce. To describe the aetiology of BM in Angolan infants <90 days of age. A prospective, observational, single-site study was conducted from February 2016 to October 2017 in the Paediatric Hospital of Luanda. All cerebrospinal fluid samples (CSF) from infants aged <90 days with suspected BM or neonatal sepsis were assessed. The local laboratory performed microscopy, chemistry, culture, and susceptibility testing. PCR for vaccine-preventable pathogens was performed in Johannesburg, South Africa. Of the 1287 infants, 299 (23%) had confirmed or probable BM. Of the 212 (16%) identified bacterial isolates from CSF, the most common were Klebsiella spp (30 cases), Streptococcus pneumoniae (29 cases), Streptococcus agalactiae (20 cases), Escherichia coli (17 cases), and Staphylococcus aureus (11 cases). A fifth of pneumococci (3/14; 21%) showed decreased susceptibility to penicillin, whereas methicillin-resistant S. aureus (MRSA) was encountered in 4/11 cases (36%). Of the gram-negative isolates, 6/45 (13%) were resistant to gentamicin and 20/58 (34%) were resistant to third-generation cephalosporins. Twenty-four percent (33/135) of the BM cases were fatal, but this is likely an underestimation. BM was common among infants <90 days of age in Luanda. Gram-negative bacteria were predominant and were often resistant to commonly used antibiotics. Continued surveillance of the antibiogram is pivotal to detect potential changes without delay. [ABSTRACT FROM AUTHOR]

Background The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes. Methods We identified consecutive annual (July–June) cohorts of Tennessee Medicaid–enrolled children (2006–2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)–era (2006–2010) and PCV13-era (2011–2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts. Results We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013–2014 cohort compared with the 2009–2010 cohort (aHRs [95% confidence interval], 0.92 [.91–.93] and 0.76 [.72–.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM. Conclusions The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes. [ABSTRACT FROM AUTHOR]

• Neisseria meningitidis carriage is estimated at 10% in the general population. • In military academy applicants in the Russian Federation carriage was 16.2% at Day 1. • Serogroup composition was diverse at Day 1, by Day 60 serogroup W was predominant. • These results suggest higher exposure and transmission patterns in crowded settings. To determine the carriage and the serogroup distribution of Neisseria meningitidis in military academy applicants in the Russian Federation. This was a prospective, observational study of adults aged >18 years from a military academy; applicants who had samples taken on arrival (Day 1), and applicants who had samples taken after passing exams (Day 30) and 60 days after arrival. N. meningitidis serogrouping was determined by slide agglutination tests of isolates and real-time PCR. Samples were provided by 671 applicants on Day 1 and 261 applicants on Day 30, with 232 of these also providing samples on Day 60. N. meningitidis was detected in 16.2% of samples from Day 1, 7.7% of samples from Day 30 and 15.9% of samples from Day 60. Serogroup composition was most diverse at Day 1, with serogroups B and W dominant (40% [17/43 isolates] and 9% [4/43], respectively; 30% [13/43] ungroupable); by Day 60, there was a low diversity, with 58% (14/24 isolates) serogroup W. While carriage of N. meningitidis in this study appeared stable, there was an increase in carriers of serogroup W in this population. Given recent increases in outbreaks attributed to serogroup W, further monitoring may be considered. [ABSTRACT FROM AUTHOR]

Background Historically, semi-closed populations have had high rates of meningococcal carriage and have experienced recurrent outbreaks. As such, these high-risk groups are recommended for targeted vaccination in many countries. Methods A systematic review of eight databases and Google Scholar forward citations was conducted to characterize serogroup-specific meningococcal carriage in university students, military personnel, and Hajj pilgrims from 2007 to 2016. Results A total of 7014 records were identified and 22 studies were included. Overall carriage ranged from 0.0% to 27.4% in Hajj pilgrims, from 1.5% to 71.1% in university students, and from 4.2% to 15.2% in military personnel. Among serogroups A, B, C, W, X, and Y, serogroup B was most prevalent in Hajj pilgrims, B and Y in university students, and B, C, and Y in military personnel. ‘Other’ serogroups were more prevalent in university students than Hajj pilgrims or military personnel. Risk factors for carriage varied by setting. Among Hajj pilgrims, a high endemicity in the country of origin increased the risk of carriage, while smoking, male sex, and frequently attending parties increased the carriage risk for university students. Similarly, smoking increased the carriage risk for professional soldiers. Data gaps remain for many regions. Conclusions Preventative vaccination policies for high-risk groups should be based on current disease data in individual countries, supplemented by carriage data. Meningococcal carriage studies and disease surveillance are critical for determining the local epidemiology, populations responsible for disease transmission, and the need for targeted vaccination. [ABSTRACT FROM AUTHOR]

Background: Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding.Methods: For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660.Findings: Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study.Interpretation: In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety.Funding: The Research Grant Council of Hong Kong. [ABSTRACT FROM AUTHOR]

Influenza viruses cause 3-5 million severe cases and 300,000-600,000 deaths worldwide. Most of the disease burden is in Low- and Middle-Income Countries (LMICs) owing to factors such as high population density, infrastructure challenges, poor quality healthcare, lack of consistent recommendations, less prioritization of all high-risk groups, and prevalent use of trivalent influenza vaccines. Although influenza vaccines are effective in reducing the annual influenza disease burden, existing vaccines have several limitations. In this narrative review, we address the unmet needs of existing influenza vaccines in LMICs in Africa, Asia Pacific, Latin America and the Middle East and discuss the characteristics of novel vaccines in clinical development. We also describe features of a successful vaccination program that LMICs could emulate to improve their current vaccination coverage and reduce the public health burden of influenza., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Background: Antivirals are effective in reducing hospitalisation and death in mild-to-moderate coronavirus 2019 (COVID-19) patients. We estimated the antiviral uptake of nirmatrelvir/ritonavir and molnupiravir in adult patients with a syndrome coronavirus 2 (SARS-CoV-2) infection during the Emergency Use Authorization (EUA) period in Taiwan., Methods: A retrospective cohort study was conducted in Taiwan between January 2022 and December 2022. Patients aged ≥18 years with a SARS-CoV-2 infection were included from the Taipei Medical University Clinical Research Database (TMUCRD) and stratified in three risk groups according to World Health Organization criteria., Results: In total, 96 398 COVID-19 patients (mean age 46.7 ± 17.7 years, 45.8% male) were included. Of these patients 69.8% were classified as low risk, 29.8% as moderate risk, and 0.4% as high risk for progression to severe COVID-19. Nirmatrelvir/ritonavir was prescribed in 5.1% of the COVID-19 patients (low risk = 1.0%, moderate risk = 14.3%, high risk = 17.6%). Molnupiravir was prescribed in 1.9% of the COVID-19 patients (low risk = 0.1%, moderate risk = 5.8%, high risk = 6.9%)., Conclusions: Nirmatrelvir/ritonavir and molnupiravir were poorly used in the treatment of adult COVID-19 patients in Taiwan during the pandemic in 2022, especially in moderate-to-high risk groups for progression to severe COVID-19., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: JCH received research funding from Pfizer Inc. MHK, FH, BT, JS, and DL are employees of Pfizer Inc., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Influenza is a contagious respiratory illness responsible for seasonal epidemics and with potential to cause pandemics. The decline in influenza-related studies published since 2018 resulted in data gaps, particularly in emerging markets. Methods: This systematic review searched for studies in six databases and gray literature sources to define the clinical burden of influenza and influenza-like illness (ILIs) and their associated sequelae among humans across emerging markets. Eligible studies were published in English, Spanish, or Chinese between January 2018 and September 2023 and conducted in Asia, the Middle East, Africa, and Latin America. Results: In total, 256 articles were included, mostly on lab-confirmed influenza infections (n = 218). Incidences of lab-confirmed influenza cases in Asia (range 540-1279 cases/100,000 persons) and Sub-Saharan Africa (range 34,100-47,800 cases/100,000 persons) were higher compared to Latin America (range 0.7-112 cases/100,000 persons) and the Middle East and North Africa (range 0.1-10 cases/100,000 persons). Proportions of lab-confirmed influenza cases and influenza-associated outcomes (i.e., hospitalization, ICU admission and death) varied widely across regions. Temporal variation in influenza trend was observed before and during the COVID-19 pandemic. Conclusions: In conclusion, influenza causes significant disease burden in emerging markets. Robust large real-world studies using a similar methodology are needed to have more accurate estimates and compare studies within age groups and regions. Continuous monitoring of influenza epidemiology is important to inform vaccine programs in emerging markets with heavy influenza disease burden.

Objective: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age., Methods: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated., Results: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days)., Conclusion: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference., Trial Registration Number: ClinicalTrials.gov number, NCT05403307 (https://classic., Clinicaltrials: gov/ct2/show/NCT05403307)., Competing Interests: Declaration of competing interest Rodrigues, Maltempi de Souza, Manfio, de Souza, Araujo, Cohen, Barbosa, Romeiro Silva, Sganzerla, Dias da Silva, Ferreira, Kunkel, Camargo, Sarturi, Guilhem, Oliveira, Lopes, Widmar, Barufi, Nunes da Silva, Gradia, Brandalize, Royer, Luiz, Baura, Abreu, and Poitevin report honoraria fee for working in this study from Hospital Moinhos de Vento. Rosa reports honoraria fee related to investigator activities from Pfizer, and research grants from Pfizer, MSD and Brazilian Ministry of Health. Falavigna reports honoraria fee related to investigator activities from Pfizer and MSD, consulting fees from Sanofi, Ultragenyx, Novartis, Alnylam, PTC and JCR, and honoraria for lectures from Janssen, Abbvie, Sanofi, Roche, Pfizer and Novartis.Valluri, Srivastava, Julião, Melone, Allen, Kyaw, Spinardi, Castillo, and McLaughlin are Pfizer empolyees. Kucharski, and Pedrotti have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The COVID-19 pandemic triggered one of the largest global health and economic crises in recent history. COVID-19 vaccination (CV) has been the central tool for global health and macroeconomic recovery, yet estimates of CV's global health and macroeconomic value remain scarce., Methods: We used regression analyses to measure the impact of CV on gross domestic product (GDP), infections and deaths. We combined regression estimates of vaccine-averted infections and deaths with estimates of quality-adjusted life years (QALY) losses, and direct and indirect costs, to estimate three broad value components: (i) QALY gains, (ii) direct and indirect costs averted and (iii) GDP impacts. The global value is the sum of components over 148 countries between January 2020 and December 2021 for CV generally and for Pfizer-BioNTech specifically., Results: CV's global value was US$5.2 (95% CI US$4.1 to US$6.2) trillion, with Pfizer-BioNTech's vaccines contributing over US$1.9 (95% CI US$1.5 to US$2.3) trillion. Varying key parameters results in values 10%-20% higher or lower than the base-case value. The largest value component was GDP impacts, followed by QALY gains, then direct and indirect costs averted. CV provided US$740 of value per dose, while Pfizer-BioNTech specifically provided >US$1600 per dose. We estimated conservative benefit-cost ratios of 13.9 and 30.8 for CV and Pfizer-BioNTech, respectively., Conclusions: We provide the first estimates of the broad value of CV incorporating GDP, QALY and direct and indirect cost impacts. Through December 2021, CV produced significant health and economic value, represented strong value for money and produced significant macroeconomic benefits that should be considered in vaccine evaluation., Competing Interests: Competing interests: JPS, DB and JSK are employees of Data for Decisions (DfD) and worked on this study in that capacity. JPS and DB have worked on other studies funded by grants from Pfizer Inc. to DfD. DEB is an external consultant to DfD and in that capacity has worked on this and other studies funded by grants from Pfizer Inc. to DfD. JPS and DEB in their personal capacities have received compensation from Pfizer Inc. for providing consulting services and for speaking and participating in meetings and advisory boards. MDF, MK, JLN and JY are employees of Pfizer Inc. and each held Pfizer stock or stock options at the time of the study. Pfizer Inc. employs MDF, MK, JLN and JY, but otherwise played no role in study design, data collection and analysis, decision to publish or preparation of the article., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)