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Background Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. Methods In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post–COVID-19 condition (PCC) was assessed in SARS-CoV-2–positive participating children after 90 days' follow-up. Results A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2–positive and –negative index children was 10.6% (19/179; 95% CI: 6.5%–16.1%) and 2.0% (13/663; 95% CI: 1.0%–3.3%), respectively (relative risk = 5.4; 95% CI: 2.7–10.7). In households with a SARS-CoV-2–positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2–infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%–16.2%) reported PCC. Conclusions Asymptomatic SARS-CoV-2–infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2–infected children may develop PCC. [ABSTRACT FROM AUTHOR]

As the world's population grows older, vaccination is becoming a key strategy for promoting healthy aging. Despite scientific progress in adult vaccine development, obstacles such as immunosenescence and vaccine hesitancy remain. To unlock the potential of adult vaccines fully, we must enhance immunization programs, dispel misinformation, and invest in research that deepens our understanding of aging and immunity. [ABSTRACT FROM AUTHOR]

Bloodstream infections in low- and middle-income countries (LMICs) are most frequently attributed to invasive Salmonella disease caused by four primary serovars of Salmonella enterica: Typhi, Paratyphi A, Typhimurium, and Enteritidis. We showed previously that a bivalent vaccine targeting S. Typhi and S. Paratyphi A using a Multiple Antigen-Presenting System (MAPS) induced functional antibodies against S. Typhi and S. Paratyphi. In the current study, we describe the preclinical development of a first candidate quadrivalent combination Salmonella vaccine with the potential to cover all four leading invasive Salmonella serotypes. We showed that the quadrivalent Salmonella MAPS vaccine, containing Vi from S. Typhi, O-specific Polysaccharide (OSP) from S. Paratyphi A, S. Enteritidis and S. Typhimurium, combined with the Salmonella-specific protein SseB, elicits robust and functional antibody responses to each of the components of the vaccine. Our data indicates that the application of MAPS technology to the development of vaccines targeting invasive forms of Salmonella is practical and merits additional consideration. [ABSTRACT FROM AUTHOR]

Background To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected children and determined if SARS-CoV-2 test result status modified the associations. Methods We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90–28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89–33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12–18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06–3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34–7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31–6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative. [ABSTRACT FROM AUTHOR]

Despite the introduction of effective pneumococcal conjugate vaccines (PCV), Streptococcus pneumoniae remains a major cause of acute otitis media (AOM) worldwide. New, higher valency vaccines that offer broader serotype coverage have been recently developed and others are in development. However, given the capsular serotypes expressed by pneumococci causing AOM, it is unclear to what extent differing or higher valency PCVs will provide additional protection. We conducted a systematic literature search of the MEDLINE database to identify articles published from January 2016 to September 2021 in 4 low and middle income and 10 high-income countries. We searched PubMed with terms: (Streptococcus pneumoniae) OR pneumococcal AND serotype AND (conjugate vaccine). We evaluated serotype distribution and the actual or projected coverage of pneumococcal serotypes by PCV10 (GlaxoSmithKline), PCV13 (Pfizer), PCV10SII (Serum Institute of India) PCV15 (Merck) and PCV20 (Pfizer). Our review highlights the important epidemiological differences in serotype distribution and coverage by existing and higher valency vaccines to protect against AOM in children. These data provide support for further evaluation of serotype-independent vaccines for optimal control of pneumococcal AOM disease worldwide. [ABSTRACT FROM AUTHOR]

Infections by Salmonella Typhi and Paratyphi A strain are still a major cause of morbidity and mortality in developing countries. Generation of antibodies against the Vi capsular polysaccharide of S. Typhi via either pure polysaccharide or protein–polysaccharide conjugate is a very effective way to protect against S. Typhi. To date, there is no commercially available vaccine against S. Paratyphi A. The O-specific polysaccharide (OSP) has been generally considered a good vaccine target for Paratyphi A. Here, a bivalent vaccine against Vi and OSP was generated using the Multiple Antigen Presenting System (MAPS). Three different protein constructs, including CRM197, rEPA of Pseudomonas, and a pneumococcal fusion protein SP1500-SP0785, were fused to Rhizavidin (Rhavi) and evaluated their impact on immunogenicity when incorporated as fusion proteins affinity-bound to the two polysaccharides. We compared the antibody responses, antibody avidity, and cidal activity of sera post-immunization with monovalent vs. combination vaccines. We also wished to evaluate the generation of Vi-specific memory B cells in mice. We found little interference when combination vaccine was compared to monovalent vaccines with respect to antibody concentration and cidal activity of sera. Significant affinity maturation was noted for both Vi and OSP antigens. Thus, our preclinical results with a combination Vi- and OSP-MAPS vaccine strongly support the feasibility of this approach and its application of this approach to other important salmonella and Shigella species. [ABSTRACT FROM AUTHOR]

Despite the remarkable success of SARS-CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen-Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS-CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS-CoV-2 challenge. The SARS-CoV-2 MAPS vaccine generated robust neutralizing antibodies as well as Th1, Th17 and cytotoxic CD8 T-cell responses in NHPs. Furthermore, MAPS-immunized NHPs had significantly lower viral loads in the nasopharynx and lung compared to control animals. Taken together, these findings support the use of the MAPS platform to make a SARS-CoV-2 vaccine. The nature of the platform also could enable its use for the inclusion of different variants in a single vaccine. [ABSTRACT FROM AUTHOR]

The human bacterial pathogen Streptococcuspneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide ([H.sub.2][O.sub.2]), not LytA, and that the gene responsible for [H.sub.2][O.sub.2] production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating [H.sub.2][O.sub.2] in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing [DELTA]spxB mutants that do not produce [H.sub.2][O.sub.2]. Likewise, addition of [H.sub.2][O.sub.2] to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While [DELTA]lytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by [H.sub.2][O.sub.2] has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the [DELTA]spxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization.

The bactericidal activity of Streptococcus pneumoniae toward Staphylococcus aureus is mediated by hydrogen peroxide. Catalase eliminated this activity. Pneumococci grown anaerobically or genetically lacking pyruvate oxidase (SpxB) were not bactericidal, nor were nonpneumococcal streptococci. These results provide a possible mechanistic explanation for the interspecies interference observed in epidemiologic studies.

Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend on the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated whole-cell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD[4.sup.+] T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD[8.sup.+] T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD[4.sup.+] T cells at the time of challenge. Streptococcus pneumoniae | cell-mediated immunity | vaccine

Background: Household transmission contributes to SARS-CoV-2 spread, but the role of children in transmission is unclear. We conducted a study that included symptomatic and asymptomatic children and adults exposed to SARS-CoV-2 in their households with the objective of determining how SARS-CoV-2 is transmitted within households. Methods: In this case-ascertained antibody-surveillance study, we enrolled households in Ottawa, Ontario, in which at least 1 household member had tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction testing. The enrolment period was September 2020 to March 2021. Potentially eligible participants were identified if they had tested positive for SARS-CoV-2 at an academic emergency department or affiliated testing centre; people who learned about the study through the media could also self-identify for participation. At least 2 participants were required for a household to be eligible for study participation, and at least 1 enrolled participant per household had to be a child (age < 18 yr). Enzyme-linked immunosorbent assays were used to evaluate SARS-CoV-2-specific IgA, IgM and IgG against the spike-trimer and nucleocapsid protein. The primary outcome was household secondary attack rate, defined as the proportion of household contacts positive for SARS-CoV-2 antibody among the total number of household contacts participating in the study. We performed descriptive statistics at both the individual and household levels. To estimate and compare outcomes between patient subgroups, and to examine predictors of household transmission, we fitted a series of multivariable logistic regression with robust standard errors to account for clustering of individuals within households. Results: We enrolled 695 participants from 180 households: 180 index participants (74 children, 106 adults) and 515 of their household contacts (266 children, 249 adults). A total of 487 household contacts (94.6%) (246 children, 241 adults) had SARS-CoV-2 antibody testing, of whom 239 had a positive result (secondary attack rate 49.1%, 95% confidence interval [CI] 42.9%–55.3%). Eighty-eight (36.8%, 95% CI 29.3%–43.2%) of the 239 were asymptomatic; asymptomatic rates were similar for children (51/130 [39.2%, 95% CI 30.7%–48.5%]) and adults (37/115 [32.2%, 95% CI 24.2%–41.4%]) (odds ratio [OR] 1.3, 95% CI 0.8–2.1). Adults were more likely than children to transmit SARS-CoV-2 (OR 2.2, 95% CI 1.3–3.6). The odds of transmission from asymptomatic (OR 0.6, 95% CI 0.2–1.4) versus symptomatic (OR 0.9, 95% CI 0.6–1.4) index participants to household contacts was uncertain. Predictors of household transmission included household density (number of people per bedroom), relationship to index participant and number of cases in the household. Interpretation: The rate of SARS-CoV-2 transmission within households was nearly 50% during the study period, and children were an important source of spread. The findings suggest that children are an important driver of the COVID-19 pandemic; this should inform public health policy. [ABSTRACT FROM AUTHOR]

Context. Children with meningitis are routinely admitted to the hospital and administered broad-spectrum antibiotics pending culture results because distinguishing bacterial meningitis from aseptic meningitis is often difficult. Objective. To develop and validate a simple multivariable model to distinguish bacterial meningitis from aseptic meningitis in children using objective parameters available at the time of patient presentation. Design. Retrospective cohort study of all children with meningitis admitted to 1 urban children&apos;s hospital from July 1992 through June 2000, randomly divided into derivation (66%) and validation sets (34%). Patients. Six hundred ninety-six previously healthy children aged 29 days to 19 years, of whom 125 (18%) had bacterial meningitis and 571 (82%) had aseptic meningitis. Intervention. Multivariable logistic regression and recursive partitioning analyses identified the following predictors of bacterial meningitis from the derivation set: Gram stain of cerebrospinal fluid (CSF) showing bacteria, CSF protein [greater than or equal to] 80 mg/dL, peripheral absolute neutrophil count [greater than or equal to] 10 000 cells/[mm.sup.3], seizure before or at time of presentation, and CSF absolute neutrophil count [greater than or equal to] 1000 cells/[mm.sup.3]. A Bacterial Meningitis Score (BMS) was developed on the derivation set by attributing 2 points for a positive Gram stain and 1 point for each of the other variables. Main Outcome Measure. The accuracy of the BMS when applied to the validation set. Results. A BMS of 0 accurately identified patients with aseptic meningitis without misclassifying any child with bacterial meningitis in the validation set. The negative predictive value of a score of 0 for bacterial meningitis was 100% (95% confidence interval: 97%-100%). A BMS [greater than or equal to] 2 predicted bacterial meningitis with a sensitivity of 87% (95% confidence interval: 72%-96%). Conclusions. The BMS accurately identifies children at low (BMS = 0) or high (BMS [greater than or equal to] 2) risk of bacterial meningitis. Outpatient management may be considered for children in the low-risk group. Pediatrics 2002;110: 712-719; prediction model bacterial meningitis, aseptic meningitis., ABBREVIATIONS. CSF, cerebrospinal fluid; WBC, white blood cell count; Hib, Haemophilus influenzae type b; ANC, absolute neutrophil count; RBC, red blood cells; ROC, receiver operating characteristic; BMS, Bacterial Meningitis Score; [...]

Low partial pressures of arterial carbon dioxide and elevated blood urea nitrogen are risk factors for cerebral edema in children with diabetic acidosis. Cerebral edema is a swelling of the brain that can be fatal. Treatment with bicarbonate was also a risk factor for cerebral edema in a study of 416 children with diabetic acidosis.