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The article discusses the challenges in diagnosing and managing neonatal sepsis, particularly in resource-limited settings, and highlights the discovery of a rarely detected bacterial organism, Paenibacillus, as a cause of severe disease in Ugandan neonates. It mentions the importance of advanced molecular technologies for diagnosis that may not be readily available in such settings and the need for improved strategies to address neonatal sepsis in low- and middle-income countries.

Background: We hypothesized that nationwide social distancing and other preventive measures for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with reduced detection of other respiratory viruses in South Korea.Methods: We analyzed national surveillance data to compare incidence of respiratory viruses during 2016-2019 vs 2020. Results of multiplex reverse-transcription polymerase chain reaction assays for 8 respiratory viruses were included: adenovirus (ADV), parainfluenza virus (PIV), respiratory syncytial virus (RSV), influenza virus (IFV), human coronavirus (HCoV; non-SARS-CoV-2), human rhinovirus (HRV), human bocavirus (HBoV), and human metapneumovirus (HMPV).Results: During 2016-2019, rates of detection of respiratory viruses were relatively stable: ADV, 3.7%-9.2%; PIV, 1.4%-17.0%; RSV, 0.3%-15.3%; IFV, 0.4%-35.6%; HCoV, 1.5%-8.4%; HRV, 7.0%-25.1%; HBoV, 0.6%-6.3%; and HMPV, 0.7%-14.5%. Following implementation of social distancing in February 2020, rates of detection of enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) were significantly reduced by up to 100%. However, nonenveloped viruses (ADV, HRV, and HBoV) persisted throughout 2020, and HRV rates in hospitalized patients significantly increased.Conclusions: After implementation of social distancing for SARS-CoV-2 in South Korea, rates of detection of enveloped respiratory viruses decreased significantly, whereas nonenveloped viruses persisted, suggesting that enhanced infection prevention strategies are required to mitigate spread of these viruses. [ABSTRACT FROM AUTHOR]

Background. The clinical and virologic characteristics of Ebola virus disease (EVD) in children have not been thoroughly documented. Methods. Consecutive children aged <18 years with real-time polymerase chain reaction (RT-PCR)-confirmed EVD were enrolled retrospectively in 5 Ebola treatment units in Liberia and Sierra Leone in 2014/2015. Data collection and medical management were based on standardized International Medical Corps protocols. We performed descriptive statistics, multivariate logistic regression, and Kaplan-Meier survival analyses. Results. Of 122 children enrolled, the median age was 7 years and one-third were aged <5 years. The female-to-male ratio was 1.3. The most common clinical features at triage and during hospitalization were fever, weakness, anorexia, and diarrhea, although 21% of patients were initially afebrile and 6 patients remained afebrile. Bleeding was rare at presentation (5%) and manifested subsequently in fewer than 50%. The overall case fatality rate was 57%. Factors associated with death in bivariate analyses were age <5 years, bleeding at any time during hospitalization, and high viral load. After adjustment with logistic regression modeling, the odds of death were 14.8-fold higher if patients were aged <5 years, 5-fold higher if the patient had any evidence of bleeding, and 5.2-fold higher if EVD RT-PCR cycle threshold value was ≤20. Plasmodium parasitemia had no impact on EVD outcomes. Conclusions. Age <5 years, bleeding, and high viral loads were poor prognostic indicators of children with EVD. Research to understand mechanisms of these risk factors and the impact of dehydration and electrolyte imbalance will improve health outcomes. [ABSTRACT FROM AUTHOR]

• The incidence of Japanese encephalitis (JE) in South Korea increased dramatically since 2010. • The JE virus circulation increased in Artiodactyla species in 2008-2009. • JE virus activity in certain animals portends the disease in humans. The annual incidence of Japanese encephalitis (JE) has increased markedly in South Korea since 2010. We hypothesized that this increase was associated with higher frequencies of JE virus in animals. We analyzed 5201 serum samples collected from even-toed hoofed mammals (Artiodactyla species) across South Korea from 2008 to 2012 using a stratified two-stage probability approach. The highest annual incidence of human JE cases and deaths occurred in 2010. Cases increased from six (no deaths) in 2008-2009 to 26 cases (seven deaths) in 2010. The JE virus seroprevalence in deer and elk fawns increased from 2.4% in 2008 to 24.1% in 2009, and in wild boars, it increased from 19.3% to 55.0% in the same period, which preceded the surge of human cases. Furthermore, the seroprevalence in calves increased from 15.3% in 2008 to 35.8% in 2010, and that in lambs and goat kids, increased from 8.5% in 2009 to 26.2% in 2010, which coincided with the surge in humans. Our findings show that the increased incidence of human JE in South Korea was temporally associated with an increasing seroprevalence in the Artiodactyla species. Surveillance of sentinel animals may be useful to predict the emergence of JE in humans. [ABSTRACT FROM AUTHOR]

Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetyiglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/ MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/ MBL chimeric proteins should be considered as potential novel therapeutics. [ABSTRACT FROM AUTHOR]

The article discusses the necessity of conducting research studies and humanitarian assistance programs related to the control, treatment and eradication of congenial syphilis in Brazil. Topics addressed include the result of a World Health Organization (WHO)-led strategy to eliminate mother-to-child transmission of HIV and congenital syphilis, the importance of prenatal care for pregnant women and the use of penicillin G as standard antimicrobial agent for preventing transmission.

The article presents a case study of an 11 month old boy who was admitted to a hospital because of fevers and pulmonary infiltrates. A discussion of diagnostic tests which were performed on the patient, and of a diagnosis of bilateral nodular pulmonary consolidation which was given to him, is presented. The patient's treatment and recovery are discussed.

Objectives. The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. Methods. Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. Results. One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months (range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (≥ 38.4°C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4-3.5) and the presence of... [ABSTRACT FROM AUTHOR]

A prospective study of 154 consecutive high-risk hospitalized children with lower respiratory infections was conducted to determine the clinical utility of a pneumolysin-based polymerase chain reaction (PCR) assay compared with blood and pleural fluid cultures and serological and urinary antigen tests to determine the incidence of Streptococcus pneumoniae. Whole blood, buffy coat, or plasma samples from 67 children (44%) tested positive by PCR. Sensitivity was 100% among 11 promptly tested culture-confirmed children and specificity was 95% among control subjects. Age, prior oral antibiotic therapy, and pneumococcal nasopha-ryngeal colonization did not influence PCR results, whereas several surrogates of disease severity were associated with positive tests. Although serological and urinary antigen tests had comparable sensitivity, specificity varied among infected children, and statistical agreement among all assays was limited. These findings support the use of PCR tests to evaluate the protective efficacy of pneumococcal conjugate vaccines and to identify promptly children with pretreated or nonbacteremic pneumococcal lower respiratory infections. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study of asthma and neonatal airway colonization that was published in the October 2007 issue.

Background Refugees to the United States frequently have parasitic infections. If untreated, parasites can cause severe complications. The purpose of this study was to investigate the incidence, management, and outcomes of eosinophilia as a biomarker for parasites. Methods We conducted a retrospective longitudinal chart review of consecutive refugees attending 3 refugee clinics in Rhode Island that manage the health care of all pediatric and adult refugees. Results Among 812 refugees who met inclusion criteria, 147 (18.1%) had eosinophilia upon arrival and almost half had ≥1 symptom. The rates and severity of eosinophilia in those with predeparture presumptive treatment records who did (112/115, 97.4%) or did not (488/498, 98.0%) receive predeparture antiparasitic treatment were similar. All refugees with eosinophilia had ≥1 parasitic test in the United States. The most common attributable parasites were Schistosoma and Strongyloides stercoralis. Overall, parasites were detected in 63 (42.9%) of 147 refugees with eosinophilia by either stool testing, serology, or blood smear, but testing was inconsistent and likely underestimated true incidence. Only some of the identified parasites typically cause eosinophilia. Forty-five (30.6%) refugees with eosinophilia received antiparasitics in the United States. Of 81 (55.1%) individuals who had repeat blood tests, eosinophilia had resolved in 52 (64.2%). Five individuals (3.4%) had alternative diagnoses, including eczema, myelofibrosis, and drug allergy. Conclusions Our findings support Centers for Disease Control and Prevention recommendations to screen for eosinophilia in newly arrived refugees. Follow-up after 3–6 months is critical to confirm resolution of residual eosinophilia, which frequently occurs after effective predeparture treatment or if eosinophilia persists, to diagnose active parasitic infections. [ABSTRACT FROM AUTHOR]

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate–severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation. [ABSTRACT FROM AUTHOR]

In the context of the coronavirus disease 2019 pandemic, we aimed to systematically address the global seasonal patterns of human coronavirus (HCoV) infections. We identified relevant articles from MEDLINE, EMBASE, and CINAHL Plus as of May 11, 2020. The main outcomes were the peak months of HCoV infections each year and the months during which more than 5% of positive respiratory specimen tests were attributable to HCoV. Of 707 articles reviewed, 22 met the inclusion criteria. The annual percentage of HCoV infections reached a peak in February globally. We found a higher HCoV positivity rate among studies that tested only children (median: 5.9%, range: 0.9%–18.4%), compared with other studies of adults alone (median: 5.2%, range: 3.3%–7.1%) or the entire population (median: 1.9%, range: 0.2%–8.1%). We found the largest global peak of HCoV during the winter season, with the highest rate of positivity among children. [ABSTRACT FROM AUTHOR]

Background Although multiple prognostic models exist for Ebola virus disease mortality, few incorporate biomarkers, and none has used longitudinal point-of-care serum testing throughout Ebola treatment center care. Methods This retrospective study evaluated adult patients with Ebola virus disease during the 10th outbreak in the Democratic Republic of Congo. Ebola virus cycle threshold (Ct; based on reverse transcriptase polymerase chain reaction) and point-of-care serum biomarker values were collected throughout Ebola treatment center care. Four iterative machine learning models were created for prognosis of mortality. The base model used age and admission Ct as predictors. Ct and biomarkers from treatment days 1 and 2, days 3 and 4, and days 5 and 6 associated with mortality were iteratively added to the model to yield mortality risk estimates. Receiver operating characteristic curves for each iteration provided period-specific areas under curve with 95% CIs. Results Of 310 cases positive for Ebola virus disease, mortality occurred in 46.5%. Biomarkers predictive of mortality were elevated creatinine kinase, aspartate aminotransferase, blood urea nitrogen (BUN), alanine aminotransferase, and potassium; low albumin during days 1 and 2; elevated C-reactive protein, BUN, and potassium during days 3 and 4; and elevated C-reactive protein and BUN during days 5 and 6. The area under curve substantially improved with each iteration: base model, 0.74 (95% CI,.69–.80); days 1 and 2, 0.84 (95% CI,.73–.94); days 3 and 4, 0.94 (95% CI,.88–1.0); and days 5 and 6, 0.96 (95% CI,.90–1.0). Conclusions This is the first study to utilize iterative point-of-care biomarkers to derive dynamic prognostic mortality models. This novel approach demonstrates that utilizing biomarkers drastically improved prognostication up to 6 days into patient care. [ABSTRACT FROM AUTHOR]

Background: Antigametocyte-specific immune responses may regulate Plasmodium falciparum gametocyte density, providing the rationale for pursuing transmission-blocking vaccines (TBVs) that target gametocytes in the human host.Methods: To identify novel antigametocyte TBV antigens, we interrogated the gametocyte proteome with our whole proteome differential screening method using plasma from a treatment-reinfection study conducted in western Kenya. At the start of the high-transmission season, 144 males (12-35 years) were enrolled and treated with quinine and doxycycline, peripheral venous blood samples were obtained, volunteers were observed, and weekly blood films were obtained for 18 weeks to quantify gametocytemia. Using plasma pooled from individuals with low versus high gametocyte carriage, we differentially screened a P falciparum gametocyte stage complementary deoxyribonucleic acid expression library.Results: We identified 8 parasite genes uniquely recognized by gametocyte-resistant but not by gametocyte-susceptible individuals. Antibodies to one of these antigens, PfsEGXP, predicted lower gametocytemia measured over the 18-week transmission season (P = .021). When analyzed dichotomously, anti-PfsEGXP responders had 31% lower gametocyte density over 18 weeks of follow-up, compared with nonresponders (P = .04).Conclusions: PfsEGXP is one of the first reported gametocyte-specific target of antibodies that predict decreased gametocyte density in humans and supports our novel TBV antigen discovery platform. [ABSTRACT FROM AUTHOR]

We share the work of the ACGME Pediatric Infectious Diseases Working Group in creating the Pediatric Infectious Diseases-Specific Milestones and discuss key considerations that lead to the reformation of competencies to better assess learners in Pediatric Infectious Diseases. [ABSTRACT FROM AUTHOR]

Anogenital herpes simplex virus (HSV) is most commonly acquired via sexual transmission, although other nonsexual modes of transmission have been proposed. When a child presents with a first-time outbreak of anogenital HSV, providers must consider sexual abuse. There are currently no evidence-based consensus guidelines to inform management of these patients. The purpose of this study was to describe how child abuse pediatricians (CAPs) evaluate children with anogenital HSV infection and determine whether any consistent practice patterns are followed. The patients included in this study were children between the ages of 0 and 12 years with a first-time outbreak of anogenital HSV who were medically evaluated by a CAP. Patient charts were retroactively reviewed for the period of January 1 2004 to May 1 2020. Twenty-two cases were referred for evaluation by a CAP in the chosen time frame. Fifteen were seen in person. Ten of these patients were interviewed, 15 had an anogenital exam with colposcopy, and 14 were tested for at least one other sexually transmitted infection. A diagnosis of sexual abuse was made for 1 patient. This study demonstrates that although nonsexual transmission of anogenital HSV may be possible, providers must still consider sexual abuse. Children with a first-time outbreak of anogenital HSV should have a comprehensive evaluation for sexual abuse, including interview, physical exam, and testing for sexually transmitted infections. Evidence-based concerns for sexual abuse should be reported to child protective services. [ABSTRACT FROM AUTHOR]

Presents a response by Ian C. Michelow and George H. McCracken, Jr. to a letter to the editor about their article "Epidemiology and Clinical Characteristics of Community-Acquired Pneumonia in Hospitalized Children" in a 2004 issue.

Background: Identification of infants with Treponema pallidum infection of the central nervous system remains challenging. Methods: We used rabbit-infectivity testing of the cerebrospinal fluid to detect T. pallidum infection of the central nervous system in infants born to mothers with syphilis. The results were compared with those of clinical, radiographic, and conventional laboratory evaluations; IgM immunoblotting of serum and cerebrospinal fluid; polymerase-chain-reaction (PCR) assay testing of serum or blood and cerebrospinal fluid; and rabbit-infectivity testing of serum or blood. Results: Spirochetes were detected in the cerebrospinal fluid of 19 of 148 infants by rabbit-infectivity testing. Exposure of the infant to antibiotics before cerebrospinal fluid was obtained for rabbit-infectivity testing was associated with a negative test result (P=0.001). Spirochetes were detected in the cerebrospinal fluid in 17 of 76 infants (22 percent) who had no prior antibiotic exposure. These 17 infants included 41 percent (16 of 39) of those with some abnormality on clinical, laboratory, or radiographic evaluation; 60 percent (15 of 25) of those with abnormal findings on physical examination that were consistent with congenital syphilis; and 41 percent (17 of 41) of those with a positive result on IgM immunoblotting or PCR testing of serum, blood, or cerebrospinal fluid, or a positive result on rabbit-infectivity testing of serum or blood. Only one infant who had normal findings on clinical evaluation had a positive cerebrospinal fluid rabbit-infectivity test. Overall, central nervous system infection was best predicted by IgM immunoblotting of serum or PCR assay of serum or blood. Conclusions: Most infants with T. pallidum infection of the central nervous system can be identified by physical examination, conventional laboratory tests, and radiographic studies. However, the identification of all such infants requires the use of additional tests, including IgM immunoblotting and PCR assay. (N Engl J Med 2002;346:1792-8.) [ABSTRACT FROM AUTHOR]

• Comparative effectiveness analyses of different COVID-19 vaccines were performed. • Analyses were adjusted for public health and virological data from 41 countries. • Messenger RNA and adenovirus vaccines had significantly fewer cases and deaths over 6 months. • Inactivated virus vaccines had significantly more cases and deaths over the same period. To compare messenger RNA (mRNA)–based and adenovirus-vectored vaccines (ADVVs) with inactivated virus vaccines (IVVs) using real-world aggregate data. We performed longitudinal analyses of publicly accessible epidemiological, clinical, virological, vaccine-related, and other public health data from 41 eligible countries during the first half of 2021. The relationships between vaccination coverage and clinical outcomes were analyzed using repeated measures correlation analyses and mixed-effects modeling to adjust for potential mediating and confounding factors. Countries that used mRNA and/or ADVV (n = 31) vs IVV, among other vaccine types (n = 10), had different distributions of age (42.4 vs 33.9 years, respectively; P -value = 0.0006), gross domestic product per capita ($ 38,606 vs $ 20,422, respectively; P <0.0001), and population sizes (8,655,541 vs 5,139,162, respectively; P -value = 0.36). After adjustment for country differences, the stringency of nonpharmaceutical interventions, and dominant SARS-CoV-2 variant types, populations that received mRNA and/or ADVV had significantly lower rates of cases and deaths over time (P <0.001 for each analysis). Populations vaccinated with IVV, among others, had significantly higher rates of cases and deaths over time (P <0.05 for each analysis). The real-world effectiveness of IVV may be inferior to mRNA and/or ADVV, and prospective comparative studies are needed to critically evaluate the role of IVV in the context of contemporary SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: Ebola Virus Disease (EVD) causes high case fatality rates (CFRs) in young children, yet there are limited data focusing on predicting mortality in pediatric patients. Here we present machine learning-derived prognostic models to predict clinical outcomes in children infected with Ebola virus. Methods: Using retrospective data from the Ebola Data Platform, we investigated children with EVD from the West African EVD outbreak in 2014–2016. Elastic net regularization was used to create a prognostic model for EVD mortality. In addition to external validation with data from the 2018–2020 EVD epidemic in the Democratic Republic of the Congo (DRC), we updated the model using selected serum biomarkers. Findings: Pediatric EVD mortality was significantly associated with younger age, lower PCR cycle threshold (Ct) values, unexplained bleeding, respiratory distress, bone/muscle pain, anorexia, dysphagia, and diarrhea. These variables were combined to develop the newly described EVD Prognosis in Children (EPiC) predictive model. The area under the receiver operating characteristic curve (AUC) for EPiC was 0.77 (95% CI: 0.74–0.81) in the West Africa derivation dataset and 0.76 (95% CI: 0.64–0.88) in the DRC validation dataset. Updating the model with peak aspartate aminotransferase (AST) or creatinine kinase (CK) measured within the first 48 hours after admission increased the AUC to 0.90 (0.77–1.00) and 0.87 (0.74–1.00), respectively. Conclusion: The novel EPiC prognostic model that incorporates clinical information and commonly used biochemical tests, such as AST and CK, can be used to predict mortality in children with EVD. Author summary: Although case fatality rates remain high, there are limited data on predicting mortality in children with Ebola Virus Disease (EVD). Furthermore, challenges in predicting EVD outcomes using clinical and laboratory data highlight the need for the development and validation of pediatric predictive models. The novel EVD Prognosis in Children (EPiC) model uses clinical and biochemical information, such as AST and CK, to predict mortality in infected children. While few prognostic models or scoring systems have been developed to predict clinical outcomes of EVD, the majority of them were limited in geographical and temporal scope having been derived using data from one location. As such, the EPiC model is the first externally validated model for the prognosis of pediatric EVD using diverse datasets from geographically and temporally separate outbreaks. This model can be easily applied by bedside clinicians to assess pediatric patients at risk for death and help to allocate resources accordingly. [ABSTRACT FROM AUTHOR]

The article discusses a study by O'Connor and colleagues, published in the issue which highlighted the challenges with the management of syphilis in people of all ages, not just mothers and infants, namely the lack of accurate modern diagnostic tests and provider knowledge on the interpretation of the available assays. Topics include information on traditional syphillis screening and algorithm for evaluation and treatment of neonates born to mothers with reactive serologic tests for syphilis.

Background: We hypothesized that oxidative stress in Ugandan children with severe malaria is associated with mortality.Methods: We evaluated biomarkers of oxidative stress in children with cerebral malaria (CM, n = 77) or severe malarial anemia (SMA, n = 79), who were enrolled in a randomized clinical trial of immediate vs delayed iron therapy, compared with community children (CC, n = 83). Associations between admission biomarkers and risk of death during hospitalization or risk of readmission within 6 months were analyzed.Results: Nine children with CM and none with SMA died during hospitalization. Children with CM or SMA had higher levels of heme oxygenase-1 (HO-1) (P < .001) and lower superoxide dismutase (SOD) activity than CC (P < .02). Children with CM had a higher risk of death with increasing HO-1 concentration (odds ratio [OR], 6.07 [95% confidence interval {CI}, 1.17-31.31]; P = .03) but a lower risk of death with increasing SOD activity (OR, 0.02 [95% CI, .001-.70]; P = .03). There were no associations between oxidative stress biomarkers on admission and risk of readmission within 6 months of enrollment.Conclusions: Children with CM or SMA develop oxidative stress in response to severe malaria. Oxidative stress is associated with higher mortality in children with CM but not with SMA.Clinical Trials Registration: NCT01093989. [ABSTRACT FROM AUTHOR]

Rapid diagnostic tools for children with Ebola virus disease (EVD) are needed to expedite isolation and treatment. To evaluate a predictive diagnostic tool, we examined retrospective data (2014-2015) from the International Medical Corps Ebola Treatment Centers in West Africa. We incorporated statistically derived candidate predictors into a 7-point Pediatric Ebola Risk Score. Evidence of bleeding or having known or no known Ebola contacts was positively associated with an EVD diagnosis, whereas abdominal pain was negatively associated. Model discrimination using area under the curve (AUC) was 0.87, which outperforms the World Health Organization criteria (AUC 0.56). External validation, performed by using data from International Medical Corps Ebola Treatment Centers in the Democratic Republic of the Congo during 2018-2019, showed an AUC of 0.70. External validation showed that discrimination achieved by using World Health Organization criteria was similar; however, the Pediatric Ebola Risk Score is simpler to use. [ABSTRACT FROM AUTHOR]

Mannan-binding lectin (MBL) is a soluble, collagen-like C-type lectin that shows the ability to bind certain N-glycosylated carbohydrates through calcium-dependent CRDs. It is composed of three identical polypeptides that form a helical homotrimer further arranged in octadecameric and larger oligomers with a very complex quaternary structure. Several studies have revealed that this protein modulates the immune response, being able to mediate phagocytosis. Unsuitable for industrial-scale production, due to the costs and the difficulties inherent in its extremely complex quaternary structure, its potential for use in successful anti-infective therapy is limited. To produce better, less expensive therapeutic agents, less complex chimeric fusion proteins with similar ligand recognition and enhanced effector functions have been developed. In a previous study, recombinant human MBL (rhMBL) and three L-ficolin ( L-FCN) variants containing the MBL carbohydrate recognition domain and varying lengths of the collagenous domain with potential clinical application against glycosylated enveloped viruses such as Ebola and Marburg were produced. It was also demonstrated that one of these chimeras - L-FCN/MBL76 - had superior effector activity that appeared to be mediated by greater structural flexibility. In this work we have used an NMR-based approach to study, at the atomic level, the mannose-binding activities both of rhMBL and of the chimeric molecule L-FCN/MBL76. Our findings indicate that the analysis of the binding dynamics of immune effector molecules could be useful for the design and optimization of new therapeutic proteins. [ABSTRACT FROM AUTHOR]

The innate immune system is comprised of a sophisticated network of recognition and effector molecules that act together to protect the host in the first minutes or hours of exposure to an infectious challenge. The mannose-binding lectin (MBL) is an evolutionary conserved circulating host defense protein that acts as a broad-spectrum recognition molecule against a wide variety of infectious agents. Target binding triggers the MBL pathway of complement activation. MBL can be considered conceptually as an ‘ante-antibody’ because it has a role in mammals during the lag period that is required to develop an antibody response against infectious agents. Additionally, there are MBL-like homologues in animals that lack adaptive immunity that activate a primitive complement system, and under these circumstances these MBL-like molecules play an analogous role to antibodies in higher animals. These molecules might be considered to be functional antecedents of antibodies. Recent work also indicates that MBL recognizes altered self-antigens, and as such MBL has a role that extends beyond a traditional role in first line host defense as it appears to play a role as a modulator of inflammation. [Copyright &y& Elsevier]

• Few validated methods exist for teaching clinical skills and diagnostic reasoning • This Perspective addresses gaps in clinical education pedagogy • A refined educational model is proposed, focusing on infectious diseases • The new approach enhances the one-minute preceptor microskills method • Diagnosis, Evidence, Feedback, Teaching (DEFT) is a helpful reminder of the steps Few validated methods that are grounded in educational theory exist to effectively teach medical knowledge, clinical skills, and diagnostic reasoning to learners at different stages of medical training. The goal of this Perspective was to address potential gaps in clinical education pedagogy by modeling new concepts for teaching in the field of infectious diseases. Our approach involved synthesizing the relevant literature, identifying proven approaches, and enhancing an existing educational microskills model — the one-minute preceptor. Our strategy was to emphasize the essential core elements of the one-minute preceptor using a descriptive acronym — DEFT (Diagnosis, Evidence, Feedback, Teaching), meaning skillful — as a potentially helpful reminder to improve the quality of interactions between learners and preceptors. The need for learners to discuss risk factors, mechanisms of disease, and potential complications, and for preceptors to model analytical and diagnostic skills, was further illustrated using a practical example of a teacher–learner interaction about a child with a respiratory infection. The one-minute preceptor/DEFT approach is experiential, adaptable, case-driven, and skills-focused, and also applicable to clinical training in other specialties. [ABSTRACT FROM AUTHOR]

Coxiella burnetii is a Gram-negative bacterium that causes the zoonotic disease Q fever. Wild boars serve as reservoirs for C. burnetii. This study aimed to identify the risk factors associated with C. burnetii infection in wild boars. We analyzed the data from 975 wild boar samples collected from June to November 2021 in South Korea. We utilized the indirect ELISA to detect antibodies against C. burnetii. A sample optical density to positive-control optical density value exceeding 50% was classified as positive. We gathered data on the forestation, terrain, weather, agriculture, and animal density of the region where the samples were collected. Continuous variables were categorized into tertiles. We performed a univariate logistic regression analysis and included variables with a p-value < 0.2 in the final multivariable logistic regression model. In our multivariable logistic regression analysis to identify risk factors for C. burnetii infection in wild boars, we used a forward selection method to enter variables based on the order of their significance. We performed the final multivariable logistic regression analyses using either continuous variables or variables categorized into tertiles. The prevalence of C. burnetii was 14.6% (n=142). Locations with the highest maximum wind speeds (3.92–8.24 m/s) showed a 59% increase in infection odds compared to locations with the lowest speeds (1.45–3.25 m/s)(p=0.044). For each 1 m/s increase in maximum wind speed, infection odds increased by 24.1% (p=0.037). Regions with the highest percentage of paddy fields per area (8.3–45%) showed a 76% increase in infection odds compared to regions with the lowest percentage (0–1.5%)(p=0.011). For each 1% increase in the proportion of paddy fields per area, infection odds increased by 3.3% (p=0.003). High maximum wind speed and a high percentage of paddy field were identified as significant risk factors for C. burnetii infection in wild boars. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the co-seasonality and co-detection of respiratory viral infections and bacteraemia in children since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Children <18 years old were eligible for inclusion if they had a respiratory infection and a positive PCR-based assay for respiratory viruses as well as a positive blood culture between 2010 and 2018 at a single referral centre in the United States, regardless of their underlying medical condition or antibiotic treatment history. Monthly incidence rates of respiratory viruses and bacteraemia were analysed with a seasonal-trend decomposition procedure based on loess (STL) and cross-correlation functions using time series regression modelling. We identified 7415 unique positive respiratory virus tests, including 2278 respiratory syncytial virus (RSV) (31%), 1825 influenza viruses (24%), 1036 parainfluenza viruses (14%), 1017 human metapneumovirus (hMPV) (14%), 677 seasonal coronaviruses (9%), and 582 adenoviruses (8%), together with a total of 11 827 episodes of bacteraemia. Significant co-seasonality was found between all-cause bacteraemia and RSV (OR = 1.76, 95%CI 1.50–2.06, p < 0.001), influenza viruses (OR = 1.38, 95%CI 1.13–1.68, p 0.002), and seasonal coronaviruses (OR = 1.18, 95%CI 1.09–1.28, p < 0.001), respectively. Analysis of linked viral–bacterial infections in individual children indicated that the rate ratio (RR) of bacteraemia associated with hMPV (RR = 2.73, 95%CI 1.12–6.85, p 0.019) and influenza (RR = 2.61, 95%CI 1.21–6.11, p 0.013) were more than double that of RSV. Staphylococcus aureus and Streptococcus pneumoniae were the most commonly identified pathogens causing bacteraemia. There is a significant association between hMPV and influenza viruses and bacteraemia of all causes in hospitalized children at a single paediatric centre in the United States. Large multicentre studies are needed to confirm these findings and to elucidate the mechanisms by which hMPV potentiates the virulence and invasive capacity of diverse bacteria. [ABSTRACT FROM AUTHOR]

Background Clinicians cannot reliably predict complications of acute hematogenous osteomyelitis (AHO). Methods Consecutive cases of AHO from 2 pediatric centers in the United States were analyzed retrospectively to develop clinical tools from data obtained within 96 hours of hospitalization to predict acute and chronic complications of AHO. Two novel composite prediction scores derived from multivariable logistic regression modeling were compared with a previously published severity of illness (SOI) score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using area under the receiver operating characteristic curve analyses. Results The causative organisms were identified in 73% of 261 cases. Bacteremia (45%), abscesses (38%), and associated suppurative arthritis (23%) were relatively common. Acute or chronic complications occurred in 24% and 11% of patients, respectively. Multivariable logistic regression identified bone abscess (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0–5.2]), fever > 48 hours (OR, 2.7 [95% CI, 1.2–6.0]), suppurative arthritis (OR, 3.2 [95% CI, 1.3–7.5]), disseminated disease (OR, 4.6 [95% CI, 1.5–14.3]), and delayed source control (OR, 5.1 [95% CI, 1.4–19.0]) as strong predictors of acute complications. In a separate model, CRP ≥ 100 mg/L at 2–4 days after antibiotics (OR, 2.7 [95% CI, 1.0–7.3]), disseminated disease (OR, 3.3 [95% CI, 1.1–10.0]), and requirement for bone debridement (OR, 6.7 [95% CI, 2.1–21.0]) strongly predicted chronic morbidity. These variables were combined to create weighted composite prediction scores for acute (A-SCORE) and chronic (C-SCORE) osteomyelitis, which were superior to SOI, CRP, and ESR and had negative predictive values > 90%. Conclusions Two novel composite clinical scores were superior to existing tools to predict complications of pediatric AHO. [ABSTRACT FROM AUTHOR]

Background: Our objective was to quantify the risk of acquiring malaria among progeny of women with malaria during pregnancy.Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for eligible prospective studies. The primary predictor was malaria during pregnancy defined as placental malaria, parasitemia, clinical malaria, or pregnancy-associated malaria. Primary outcomes were parasitemia or clinically defined malaria of young children. We performed meta-analyses to pool adjusted risk estimates using a random-effects model.Results: Nineteen of 2053 eligible studies met inclusion criteria for the systemic review. Eleven of these studies were quantitative and were included in the meta-analyses. The pooled adjusted odds ratio (aOR) or adjusted hazard ratio (aHR) of malaria during pregnancy for detection of parasitemia in young children were 1.94 (95% confidence interval [CI], 0.93-4.07; P = .08) and 1.46 (95% CI, 1.07-2.00; P < .001), respectively. The pooled aOR or aHR for clinically defined malaria in young children were 2.82 (95% CI, 1.82-4.38; P < .001) and 1.31 (95% CI, 0.96-1.79; P = .09), respectively.Conclusions: Our results confirmed that malaria during pregnancy significantly increased the overall risk of malaria in young children via indeterminate mechanisms and emphasize the urgent need to implement safe and highly effective strategies to prevent malaria during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials. The purpose of this project was to develop CTPs and response criteria for PFAPA. Methods: The CARRA PFAPA Working Group is composed of pediatric rheumatologists, infectious disease specialists, allergists/immunologists and otolaryngologists. An extensive literature review was conducted followed by a survey to assess physician practice patterns. This was followed by virtual and in-person meetings between 2014 and 2018. Nominal group technique (NGT) was employed to develop CTPs, as well as inclusion criteria for entry into future treatment studies, and response criteria. Consensus required 80% agreement. Results: The PFAPA working group developed CTPs resulting in 4 different treatment arms: 1. Antipyretic, 2. Abortive (corticosteroids), 3. Prophylaxis (colchicine or cimetidine) and 4. Surgical (tonsillectomy). Consensus was obtained among CARRA members for those defining patient characteristics who qualify for participation in the CTP PFAPA study. Conclusion: The goal is for the CTPs developed by our group to lead to future comparative effectiveness studies that will generate evidence-driven therapeutic guidelines for this periodic inflammatory disease. [ABSTRACT FROM AUTHOR]

Cryptococcus albidus , synonymous with Naganishia albida, rarely causes opportunistic infection in immunocompromised individuals. Its clinical features, particularly in children, are not well defined. Here, we report a case of C albidus fungemia in an immunosuppressed child; we also present results of a systematic review, for which we searched PubMed, Embase, and Web of Science using the keywords "cryptococcus" and "albidus." Our goal was to describe the spectrum of disease, diagnostic approaches, therapies, and outcomes. We identified 20 cases of invasive infection, only 2 of which involved children, and 7 cases of noninvasive infection. The reports originated in the Americas, Europe, and Asia. Of those with invasive infection, 16 (80%) patients had an underlying chronic disorder or had received immunosuppressive therapy, 8 (40%) had fungemia, and 6 (30%) had a central nervous system infection. The attributable case fatality rate was 40%. C albidus is an opportunistic yeast that can rarely cause life-threatening fungemia and central nervous system infection in individuals of any age, especially those who are immunocompromised. [ABSTRACT FROM AUTHOR]

Background In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive. Methods We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, measured antibodies to Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), and related these antibodies to the risk of severe malaria in the first year of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborns' resistance to malaria. Results Children with high cord-blood anti–PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti–PfSEA-1 levels over 12 months of follow-up (P =.03). In 3 trials, pups born to PbSEA-1–vaccinated dams had significantly lower parasitemia and longer survival following a P. berghei challenge compared to pups born to control dams. Conclusions We demonstrate that maternally-derived, cord-blood anti–PfSEA-1 antibodies predict decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei challenge. These results identify, for the first time, a parasite-specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring. [ABSTRACT FROM AUTHOR]

Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-lA (rPfSEA-lA) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-lA had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion. [ABSTRACT FROM AUTHOR]

Hyle EP, Shu B, Lindstrom S, Klimov A, Hancock K, Ferraro MJ, Traum AZ, Michelow IC. A severely immunocompromised child with uncomplicated oseltamivir-resistant 2009 H1N1 pandemic influenza infection. Abstract: 2009 H1N1 pandemic influenza was associated with increased risk for severe disease in children and the immunosuppressed. We report a case of uncomplicated pneumonia because of infection with oseltamivir-resistant 2009 H1N1 virus in an immunosuppressed pediatric renal transplant patient. Innate immunity and/or altered viral fitness may be responsible for the mild clinical phenotype of the case. [ABSTRACT FROM AUTHOR]

Abstract: MBL structurally contains a type II-like collagenous domain and a carbohydrate recognition domain (CRD). We have recently generated three novel recombinant chimeric lectins (RCL), in which varying length of collagenous domain of mannose-binding lectin (MBL) is replaced with that of L-ficolin (L-FCN). CRD of MBL is used for target recognition because it has a broad spectrum in pathogen recognition compared with L-FCN. Results of our study demonstrate that these RCLs are potent inhibitors of influenza A virus (IAV). RCLs, against IAV, show dose-dependent activation of the lectin complement pathway, which is significantly higher than that of recombinant human MBL (rMBL). This activity is observed even without MBL-associated serine proteases (MASPs, provided by MBL deficient mouse sera), which have been thought to mediate complement activation. These observations suggest that RCLs are more efficient in associating with MASP-2, which predominantly mediates the activity. Yet, additional serum further increases the activity while RCL-mediated coagulation-like enzyme activities are diminished compared with rMBL, suggesting reduced association with MASP-1, which has been shown to mediate coagulation-like activity. These data suggest that RCLs may interfere less with host coagulation, which is advantageous to be a therapeutic drug. Importantly, these RCLs have surpassed rMBL for anti-viral activities, such as viral aggregation, reduction of viral hemagglutination (HA) and inhibition of virus-mediated HA and neuraminidase (NA) activities. These results are encouraging that novel RCLs could be used as anti-IAV agents with less side effect and that RCLs would be suitable candidates in developing a new anti-IAV therapy. [ABSTRACT FROM AUTHOR]

Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ≥7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To compare 2 days of antibiotic therapy (AT) to 4 days of AT in neonates with pneumonia and to assess the usefulness of neutrophil values (NV), C-reactive protein (CRP), and procalcitonin (PCT) in this population. DESIGN: The study population consisted of consecutive, eligible term neonates begun on AT for suspected pneumonia. Of 51 neonates, 26 qualified for randomization (14, 2-day group; 12, 4-day group). NV were obtained with the initial evaluation and 12 and 24 hours later. CRP and PCT were obtained 12 and 48 hours after the initial evaluation. RESULTS: None of the 12 neonates in the 4-day group developed recurrent respiratory symptoms. Three of the 14 neonates randomized to the 2-day group had recurrence of symptoms, resulting in study termination. NV, CRP, and PCT were similar in the 2- and 4-day groups. In the three neonates who developed respiratory symptoms, all absolute total neutrophil values and five out of nine absolute total immature neutrophil values were abnormal. However, all immature:total neutrophil values were normal, and CRP was strikingly elevated in only one neonate; only one of six PCT values was abnormal. In a secondary analysis of all 51 study neonates, CRP and PCT did not provide additional benefit over NV in differentiating neonates with pneumonia. CONCLUSIONS: Four days of AT appears to be adequate for selected term neonates with pneumonia; however, 2 days of AT appears to be inadequate for this population. Relative to NV, CRP and PCT appear to have a limited role. [ABSTRACT FROM AUTHOR]

The article looks at a study related to the previously vaccinated healthy children of Rhode Island with the pneumococcal conjugate vaccine (PCV-7) for the invasive pneumococcal disease (IPD). Topics discussed include children with bacteremic pneumonia were treated initially with either ampicillin or amoxicillin, blood cultures was isolated in each case and the aim of the study was to raise awareness of possible breakthrough pneumococcal infections despite vaccination.