Risk factors associated with Coxiella burnetii in wild boars: A study in South Korea.

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.

Derivation and Internal Validation of a Mortality Prognostication Machine Learning Model in Ebola Virus Disease Based on Iterative Point-of-Care Biomarkers.

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.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

Pediatric Infectious Diseases Milestones: A Step in the Right Direction to Evaluate Subspecialty Learners.

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.

The Mortality of Congenital Syphilis.

OBJECTIVES: To document the case-fatality rate (CFR) of congenital syphilis diagnosed by molecular tools and rabbit infectivity testing (RIT) of clinical specimens in addition to standard evaluation and to compare that with the CFR using the Centers for Disease Control and Prevention (CDC) surveillance case definition. STUDY DESIGN: Prospective, single site, cohort study of all cases of syphilis among mothers and their infants from 1984 to 2002. The diagnosis of congenital syphilis was determined using IgM immunoblotting, polymerase chain reaction, and RIT of fetal or infant specimens in addition to clinical, laboratory, and radiographic criteria. Data were retrospectively reviewed to ascertain fetal and neonatal mortality. RESULTS: During the 18-year study, there were 191 cases of congenital syphilis confirmed by abnormalities on clinical, laboratory, or radiographic evaluation and/or positive serum IgM immunoblot, blood polymerase chain reaction, or blood/cerebrospinal fluid RIT. Of the 191 cases, 59 died for a CFR of 31%. Of the 59 deaths, 53 (90%) were stillborn and 6 (10%) died in the neonatal period. The majority (74%, 39/53) of stillbirths occurred in the third trimester. The CDC surveillance case definition correctly identified all infants with congenital syphilis, but the CDC CFR was 10% which underestimated the CFR by more than 300%. CONCLUSIONS: Our findings corroborate the high sensitivity of the CDC surveillance definition for congenital syphilis but highlight its poor estimation of its associated mortality. The CFR among infected progeny of pregnant women with syphilis was 31%, due mostly to demise in the third trimester and as such highlights the need for detection and appropriate treatment of syphilis during pregnancy.

Changes in the epidemiology of pediatric sinogenic and otogenic intracranial infections during the COVID-19 pandemic: a single-institution study.

OBJECTIVE: Focal intracranial infections (epidural abscesses, subdural empyemas, and intraparenchymal abscesses) are uncommon complications of sinusitis and otitis media but can be associated with significant morbidity. Treatment typically requires neurosurgical and otolaryngological interventions in combination with antibiotic treatment. Historically, children have presented to the authors' pediatric referral center with sinusitis- or otitis media-related intracranial infections in low numbers. However, since the onset of the COVID-19 pandemic, the incidence of intracranial pyogenic complications has increased at this center. The objective of this study was to compare the epidemiology, severity, microbial causes, and management of pediatric sinusitis- and otitis-related intracranial infections in the periods before and during the COVID-19 pandemic. METHODS: All patients 21 years of age or younger who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's from January 2012 to December 2022 were retrospectively reviewed. Demographic, clinical, laboratory, and radiological data were systematically collated, and variables before and during COVID-19 were compared statistically. RESULTS: Overall, 18 patients were treated for sinusitis-related (n = 16) or otitis media-related (n = 2) intracranial infections during the study period. Ten patients (56%) presented from January 2012 to February 2020, none from March 2020 to June 2021, and 8 (44%) from July 2021 to December 2022. There were no significant demographic differences between the pre-COVID-19 and COVID-19 cohorts. The 10 patients in the pre-COVID-19 cohort underwent a total of 15 neurosurgical and 10 otolaryngological procedures, while the 8 patients in the COVID-19 cohort underwent a total of 12 neurosurgical and 10 otolaryngological procedures. Surgically obtained wound cultures yielded a variety of organisms; Streptococcus constellatus/S. anginosus/S. intermedius were more prevalent in the COVID-19 cohort (87.5% vs 0%, p < 0.001) as was Parvimonas micra (62.5% vs 0%, p = 0.007). CONCLUSIONS: At an institutional level, there has been an approximately threefold increase in cases of sinusitis- and otitis media-related intracranial infections during the COVID-19 pandemic. Multicenter studies are needed to confirm this observation and to investigate whether the mechanisms of infection are related directly to SARS-CoV-2, changes in the respiratory flora, or delayed care. The next steps will include expansion of this study to other pediatric centers throughout the United States and Canada.

Increasing seroprevalence of Japanese encephalitis virus in even-toed hoofed mammals (Artiodactyla species) associated with an upsurge of human cases in South Korea.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Anogenital HSV in Children: Should Providers Be Concerned for Sexual Abuse?

OBJECTIVE: 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. PARTICIPANTS AND SETTING: 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. METHODS: Patient charts were retroactively reviewed for the period of January 1 2004 to May 1 2020. RESULTS: 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. CONCLUSION: 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.

Constructing, validating, and updating machine learning models to predict survival in children with Ebola Virus Disease.

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.

A global epidemiological analysis of COVID-19 vaccine types and clinical outcomes.

OBJECTIVES: To compare messenger RNA (mRNA)-based and adenovirus-vectored vaccines (ADVVs) with inactivated virus vaccines (IVVs) using real-world aggregate data. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Detection of Parechovirus and Enterovirus Among Infants Evaluated for Late-onset Sepsis in the Neonatal Intensive Care Unit: The Viral Respiratory Infections in the Neonatal Intensive Care Unit-Parechovirus-Enterovirus Study.

In a prospective cohort study of 65 inborn infants who were evaluated for late-onset sepsis at >72 hours of age in 2 academic neonatal intensive care units, none had parechovirus or enterovirus RNA detected by polymerase chain reaction performed on nasopharyngeal specimens during the first or subsequent sepsis evaluations (n = 80).

Impact of Oxidative Stress on Risk of Death and Readmission in African Children With Severe Malaria: A Prospective Observational Study.

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.

Risk Prediction Score for Pediatric Patients with Suspected Ebola Virus Disease.

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.

Trends in clinical presentation of children with COVID-19: a systematic review of individual participant data.

BACKGROUND: There are sparse patient-level data available for children with novel coronavirus disease (COVID-19). Therefore, there is an urgent need for an updated systematic literature review that analyzes individual children rather than aggregated data in broad age groups. METHODS: Six databases (MEDLINE, Scopus, Web of Science, CINAHL, Google Scholar, medRxiv) were searched for studies indexed from January 1 to May 15, 2020, with MeSH terms: children, pediatrics, COVID-19, SARS-CoV-2. 1241 records were identified, of which only unique papers in English with individual patient information and documented COVID-19 testing were included. This review of 22 eligible studies followed Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines. RESULTS: A total of 123 patients from five countries were identified. 46% were females. The median age was 5 years (IQR = 8). At presentation, 62% had a fever, 32% had a cough, 58% had a single symptom, and 21% were asymptomatic. Abnormal chest imaging was seen in 62% (65/105) of imaged and 76.9% (20/26) of asymptomatic children. A minority of children had elevated platelets, CRP, lactate dehydrogenase, and D-dimer. CONCLUSION: Data from this independent participant data systematic review revealed that the majority of children with COVID-19 presented with either no symptoms or a single, non-respiratory symptom. IMPACT: This systematic review revealed that the majority of children with COVID-19 presented with either no symptoms or a single, non-respiratory symptom. By using an independent participant data approach, this analysis underscores the challenge of diagnosing COVID-19 in pediatric patients due to the wide variety of symptoms and seemingly poor correlation of imaging findings with symptomatic disease. The data presented from individual patients from case series or cohort studies add more granularity to the current description of pediatric COVID-19.

Enhancing the one-minute preceptor method for clinical teaching with a DEFT approach.

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.

A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies.

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.