Genetic Diversity of the Human Adenovirus C Isolated from Hospitalized Children in Russia (2019-2022).

The human adenovirus (HAdV) is a common pathogen in children that can cause acute respiratory virus infection (ARVI). However, the molecular epidemiological and clinical information relating to HAdV among hospitalized children with ARVI is rarely reported in Russia. A 4-year longitudinal (2019-2022) study among hospitalized children (0-17 years old) with ARVI in Novosibirsk, Russia, was conducted to evaluate the epidemiological and molecular characteristics of HAdV. Statistically significant differences in the detection rates of epidemiological and virological data of all positive viral detections of HAdV were analyzed using a two-tailed Chi-square test. The incidence of HAdV and other respiratory viruses such as human influenza A and B viruses, respiratory syncytial virus, coronavirus, parainfluenza virus, metapneumovirus, rhinovirus, bocavirus, and SARS-CoV-2 was investigated among 3190 hospitalized children using real-time polymerase chain reaction. At least one of these respiratory viruses was detected in 74.4% of hospitalized cases, among which HAdV accounted for 4%. A total of 1.3% co-infections with HAdV were also registered. We obtained full-genome sequences of 12 HAdVs, which were isolated in cell cultures. Genetic analysis revealed the circulation of adenovirus of genotypes C1, C2, C5, C89, and 108 among hospitalized children in the period from 2019-2022.

Osteoprotegerin in infection-induced acute inflammatory states in children.

Background and aims: Osteoprotegerin (OPG) is a tumor necrosis factor receptor superfamily member which increases in chronic inflammation and is associated with altered bone turnover and cardiovascular complications. In this study, we investigated whether OPG increases during acute inflammatory states induced by infections in children and correlated its levels with other biomarkers. Materials and methods: This is a prospective study that included 59 patients with documented bacterial infections, 20 with viral infections and 20 healthy controls. OPG, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cells (WBC) were measured. Results: OPG serum levels were significantly increased during inflammation induced by a bacterial infection, compared to viral infection and controls (4.17 pmol/l (2.40-12.12) vs 3.2 (1.66-5.33) and 3 pmol/l (2.13-4.76), respectively, p < 0.001). In addition, OPG correlated well with CRP (rho = 0.428, p = 0.0011), ESR (rho = 0.3, p = 0.026), and WBC (rho = 0.266, p = 0.05) only in the group with bacterial infection. The sensitivity of CRP in detecting a bacterial infection was superior to OPG (67.3% vs 38.3%). Conclusion: This study provides proof of concept that OPG increases differentially in bacterial infections, although with a lower sensitivity than CRP. Further studies are needed to define the role of OPG during the inflammatory states of infection in pediatric infections.

Great Plasticity in a Great Pathogen: Capsular Types, Virulence Factors and Biofilm Formation in ESBL-Producing Klebsiella pneumoniae from Pediatric Infections in Uruguay.

Klebsiella pneumoniae is widely recognized as an opportunistic hospital and community pathogen. It is one of the priority microorganisms included in the ESKAPE group, and its antibiotic resistance related to extended-spectrum ß-lactamases (ESBL) is a global public health concern. The multi-drug resistance (MDR) phenotype, in combination with pathogenicity factors, could enhance the ability of this pathogen to cause clinical infections. The aim of this study was to characterize pathogenicity factors and biofilm formation in ESBL-producing K. pneumoniae from pediatric clinical infections. Capsular types, virulence factors, and sequence types were characterized by PCR. Biofilm formation was determined by a semiquantitative microtiter technique. MDR phenotype and statistical analysis were performed. The K24 capsular type (27%), virulence factors related to iron uptake fyuA (35%) and kfuBC (27%), and sequence types ST14 (18%) and ST45 (18%) were the most frequently detected. Most of the strains were biofilm producers: weak (22%), moderate (22%), or strong (12%). In 62% of the strains, an MDR phenotype was detected. Strains with K24 capsular type showed an association with ST45 and the presence of fyuA; strains with kfuBC showed an association with moderate or strong biofilm production and belonging to ST14. Weak or no biofilm producers were associated with the absence of kfuBC. The MDR phenotype was associated with the main ESBL gene, blaCTX-M-15. The high plasticity of K. pneumoniae to acquire an MDR phenotype, in combination with the factors exposed in this report, could make it even more difficult to achieve a good clinical outcome with the available therapeutics.

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Kinetics and Role of Pancreatic Stone Protein and Midregional Proadrenomedullin as Predictors of Sepsis and Bacteremia in Children with Hematological Malignancies.

Background: To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with hematological malignancies. Material and methods: We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. CRP, PSP, and MR-proADM levels were measured at the onset of the febrile episode (day 1), day 3, and day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as an area under a receiver operating characteristic (ROC) curve. ROC curves were used for each biomarker to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis. Results: During the 2-year study period, 70 febrile neutropenia episodes in 70 children with hematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%), a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers on day 1 differed significantly between patients with and without sepsis. PSP, MR-proADM, and CRP specificity were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM, and CRP were 0.84, 0.74, and 0.88, respectively. Conclusions: PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with hematological malignancies. However, PSP has a higher sensitivity and specificity.

Pentraxin-3 and neonatal sepsis: a systematic review and meta-analysis.

Aim: The potential bond between pentraxin-3 levels and neonatal sepsis has been the center of research in many primary studies. The aim of the current meta-analysis is to examine whether there are differences among pentraxin-3 levels in septic and in healthy neonates.Materials and Methods: Our search strategy included the systematic search of the following databases: MEDLINE, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, using a structured algorithm. Statistical analysis of the overall outcome was done using Revman 5.4 software while leave-one-out and meta-regression analysis were done using the R software. Quality assessment of the included studies was done using the Newcastle-Ottawa scale.Results: Pentraxin-3 levels were found to be higher in newborns affected by sepsis than in healthy neonates with an MD = 7.66 [95% CI 0.89, 14.42 (p = .03, I2 = 99%)]. Subgroup analysis, based on the country of origin of the included study, led to I2 = 0 with an MD = 1.25 with 95% CI [0.82, 1.69], p < 10-5. Publication bias was assessed using the trim and fill method together with visual inspection of the funnel plots, showcasing no missing studies.Conclusion: The results of our study show that pentraxin-3 is elevated in neonates with sepsis making it a potential biomarker that needs to be assessed for its diagnostic accuracy in future cohort studies.

Antimicrobial susceptibility and serotype replacement of Streptococcus pneumoniae in children before and after PCV13 introduction in Taiwan.

BACKGROUND: Since 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections. METHODS: Children with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration. RESULTS: In total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p < 0.001). The prevalence of serotype 19 A had increased gradually since 2010 but declined rapidly after 2013. Serotypes 15 A and 23 A were the most common serotypes after 2015. The non-susceptibility of the S. pneumoniae isolates to penicillin, cefotaxime, and ceftriaxone decreased. Based on meningitis breakpoints, the non-susceptibility to cefotaxime and ceftriaxone gradually decreased, but increased in 2020. CONCLUSION: PCV13 was considerably effective in reducing the incidence of IPD in children; however, the prevalence of serotypes 15 A and 23 A increased. The increase in antimicrobial non-susceptibility caused by non-vaccine serotypes must be continuously monitored.

Caracterización clínico-epidemiológica de endocarditis infecciosa en pediatría

La endocarditis infecciosa es un proceso inflamatorio infeccioso causado por distintos microorganismos afectando el endocardio. Es una entidad poco frecuente en niños previamente sanos; no obstante, no es rara su ocurrencia en niños con ciertas cardiopatías congénitas; encontrándose un aumento en la incidencia en los extremos de las edades pediátricas. Objetivo: Describir las características clínicas y epidemiológicas de los pacientes pediátricos hospitalizados en el Hospital Universitario de Caracas, durante el período comprendido entre enero 2001 a diciembre 2020. Metodología: Estudio descriptivo y retrospectivo, utilizando como criterio de inclusión todo paciente pediátrico entre 0-12 años que ingresa con el diagnóstico de endocarditis infecciosa. Se recolectaron datos como edad, sexo, nivel socioeconómico, comorbilidades, factores predisponentes, hallazgos clínicos, paraclínicos, ecocardiográficos y terapéutica indicada; analizándose con estadística descriptiva, con el fin de establecer tablas de distribución de frecuencias. Resultados: Se incluyeron 17 pacientes en el estudio; el género masculino, los recién nacidos y preescolares fueron los que desarrollaron mayormente esta patología, observándose una supervivencia del 70,8 %. El principal factor predisponente para su desarrollo fue la presencia de catéter venoso central. En el 42,9 % de los hemocultivos se aisló Candida spp. Conclusión: En endocarditis infecciosa, a pesar de su baja incidencia, las complicaciones y mortalidad pueden ser altas; por lo cual ante todo paciente portador de catéter venoso central, con clínica de fiebre, taquicardia y soplo cardíaco, con hallazgos paraclínicos de leucocitosis, anemia y elevación de reactantes de fase aguda se sugiere el descarte de la misma.

Infective endocarditis is an infectious inflammatory process caused by different microorganisms affecting the endocardium. It is a rare entity in previously healthy children; however, its occurrence in children with certain congenital heart diseases is not uncommon; finding an increase in incidence at the extremes of pediatric ages. Objective: To describe the clinical and epidemiological characteristics of pediatric patients hospitalized at the Hospital Universitario de Caracas, during the period from January 2001 to December 2020. Method: Descriptive and retrospective study, using as inclusion criteria all pediatric patients between 0-12 years of age who are admitted with the diagnosis of infective endocarditis. Data such as age, sex, socioeconomic level, comorbidities, predisposing factors, clinical, paraclinical, echocardiographic findings, and indicated therapy were collected; being analyzed with descriptive statistics, in order to establish frequency distribution tables. Results: 17 patients were included in the study, the male gender, the newborns and preschoolers were the ones who developed this pathology with survival of 70.8 %. The main predisposing factor for its development was the presence of central venous catheter. Candida spp was isolated in 42.9 % of blood cultures. Conclusion: In infective endocarditis, despite having low incidence, complications and mortality can be high; therefore, in all patients with a central venous catheter, with symptoms of fever, tachycardia and heart murmur, with paraclinical findings of leukocytosis, anemia and elevation of acute phase reactants, it is suggested to discard it.

Impact of COVID-19 Countermeasures on Pediatric Infections.

(1) Background: General infection control measures have been implemented at the societal level against COVID-19 since the middle of 2020, namely, hand hygiene, universal masking, and social distancing. The suppressive effect of the social implementation of general infection control measures on pediatric infections has not been systematically assessed. (2) Methods: We addressed this issue based on publicly available data on 11 pediatric infections reported weekly by sentinel sites in Osaka and Iwate prefectures in Japan since 2010. We obtained the 5-year average for 2015-2019 and compared it to the weekly report for 2020-2021. (3) Results: The rate of 6 of the 11 pediatric infections decreased significantly during 2020-2021, regardless of the magnitude of the prevalence of COVID-19 in both areas. However, only RSV infection, one of the six infections, was endemic in 2021. Exanthem subitum was not as affected by COVID-19 countermeasures as other diseases. (4) Conclusions: The social implementation of infectious disease control measures was effective in controling certain infectious diseases in younger age groups, where compliance with the countermeasures should not be as high as that of adults.

Detection of subgenomic mRNA from endemic human coronavirus OC43 and NL63 compared to viral genomic loads, single virus detection and clinical manifestations in children with respiratory tract infections.

BACKGROUND: The importance of endemic human coronavirus (HCoV) in children has been insufficiently elucidated upon. Our aims were to develop subgenomic (sg) mRNA tests for HCoV species OC43 and NL63, and to evaluate the relationships to HCoV genomic loads, single HCoV detections and clinical manifestations. METHODS: We have used an 11-yearlong cohort study of children admitted with respiratory tract infection (RTI) and hospital controls. Nasopharyngeal aspirates were analyzed for HCoV subtypes OC43 and NL63 with in-house diagnostic PCR. Positive samples were tested with newly developed real-time PCRs targeting sg mRNA coding for the nucleocapsid protein. RESULTS: OC43 sg mRNA was detected in 86% (105/122) of available OC43-positive samples in the RTI group, and in 63% (12/19) of control samples. NL63 sg mRNA was detected in 72% (71/98) and 71% (12/17) of available NL63-positive patient and control samples, respectively. In RTI samples, sg mRNA detection was strongly associated with a Ct value <32 in both diagnostic PCR tests (OC43: OR = 54, 95% CI [6.8-428]; NL63: OR = 42, 95% CI [9.0-198]) and single NL63 detections (OR = 6.9, 95% CI [1.5-32]). Comparing RTI and controls, only OC43 was associated with RTI when adjusted for age (aOR = 3.2, 95% CI [1.1-9.4]). CONCLUSION: We found strong associations between OC43 and NL63 sg mRNA and high viral genomic loads. sg mRNA for OC43 was associated with RTI. The association between sg mRNA and clinical manifestations needs further evaluation.

The Gram-Negative Bacilli Isolated from Caves-Sphingomonas paucimobilis and Hafnia alvei and a Review of Their Involvement in Human Infections.

The opportunistic infections with Gram-negative bacilli are frequently reported. The clinical studies are focused on the course of human infectious and very often the source of infection remain unclear. We aim to see if the Gram-negative bacilli isolated from a non-contaminated environment-the caves-are reported in human infections. Eleven samples were collected from six Romanian caves. We used the standard procedure used in our clinical laboratory for bacterial identification and for antibiotic susceptibility testing of the cave isolates. Out of the 14 bacterial strains, three isolates are Gram-negative bacilli-one isolate belong to Hafnia alvei and two strains belong to Sphingomonas paucimobilis. We screened for the published studies-full-text original articles or review articles-that reported human infections with S. paucimobilis and H. alvei. Data sources-PubMed and Cochrane library. We retrieved 447 cases from 49 references-262 cases (58.61%) are S. paucimobilis infections and 185 cases (41.39%) are H. alvei infections. The types of infections are diverse but there are some infections more frequent; there are 116 cases (44.27%) and many infections of the bloodstream with S. paucimobilius (116 cases) and 121 cases (65.41%) are urinary tract infections with H. alvei. The acquired source of the bloodstream infections is reported for 93 of S. paucimobilis bloodstream infections-50 cases (43%) are hospital-acquired, and 40 cases (37%) are community-acquired. Most of the infections are reported in patients with different underlying conditions. There are 80 cases (17.9%) are reported of previously healthy persons. Out of the 72 cases of pediatric infections, 62 cases (86.11%) are caused by S. paucimobilis. There are ten death casualties-three are H. alvei infections, and seven are S. paucimobilis infections.

Human adenovirus infections in pediatric population - An update on clinico-pathologic correlation.

Human adenoviruses can cause infections at any age but most commonly in pediatric population, especially in young children and infants. By the time of 10 years old, most children have had at least one episode of adenovirus infection. Adenoviruses can cause many symptoms similar to common cold, including rhinorrhea, fever, cough, and sore throat. Lower respiratory infections such as bronchitis, bronchiolitis, and pneumonia can be severe and even fatal. Other diseases such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, and meningoencephalitis can also be associated with adenovirus infections. A variety of recent advancement of structural and molecular biology methods have revamped the taxonomy of adenoviruses and furthered our understanding of the diversity of related clinical diseases. Because of the wide spectrum and complexity of diseases associated with human adenovirus infections, the scope of this review is limited to basic virology and epidemiology of adenoviruses with a main focus on the clinico-pathologic correlation. Clinical manifestations and pathology of any infectious disease are always related; therefore, it is logical to review clinico-pathologic correlation within the specific disease entity caused by adenoviruses to better understand this common viral infection in pediatric population.

Ultrasound diagnosis of pyogenic flexor tenosynovitis in a 9-month-old infant: a rare case report.

Pyogenic flexor tenosynovitis (PFT) is an aggressive infection of the flexor tendon sheath, requiring prompt intervention to minimize adverse outcomes. The diagnosis of pediatric PFT is often delayed due to the variable presence of Kanavel's signs in children and communication difficulties. A 9-month-old male presented to the emergency department with one of four Kanavel signs. The diagnosis of PFT was delayed until ultrasound was used to identify a fluid collection within the flexor tendon sheath. He was successfully treated with surgical debridement and antibiotic therapy, achieving full recovery by 6-month follow-up. This represents the youngest reported case of PFT. Difficulties with communication and physical exam as well as the variability of Kanavel's signs in young children can delay the diagnosis of pediatric PFT. Ultrasound can be a useful adjunct when clinical history and exam are equivocal, especially in children who present prior to language acquisition.

Pediatric Non-COVID-19 Community-Acquired Pneumonia in COVID-19 Pandemic.

INTRODUCTION: The COVID-19 lockdown strategies were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmissions. Social distancing and other lockdown strategies effectively slowed down the spread of common respiratory viral diseases and decreased the need for hospitalization among children. Thus, a decline in the incidence of respiratory viral diseases had been reported following the COVID-19 outbreak. However, the trend of non-COVID-19 pneumonia in children remains uncertain. This study aimed to assess the impact of the COVID-19 pandemic on the incidence of non-COVID-19 community-acquired pneumonia in children. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients (age ≤18 years) presenting with pulmonary infection from January 2019 to December 2020 in a tertiary-level teaching hospital. We compared the number of pediatric patients admitted to our hospital with community-acquired pneumonia from January to December 2020 to those from the same period in 2019. RESULTS: A total of 65 patients were diagnosed with community-acquired pneumonia in 2019 and 18 in 2020. The number of patients with community-acquired pneumonia in 2020 was lower than that in 2019 by 47 cases in 2020. The most age distribution of pediatric patients with community-acquired pneumonia was 2-5 years in 2019, indicating the decreasing number of community-acquired pneumonia patients from 36 patients in 2019 to 3 in 2020. CONCLUSION: The number of pediatric with community-acquired pneumonia was lower than in the same period in 2019, which markedly decreased (-72.3%) in 2020. These interventions applied to control the COVID-19 pandemic were effective not only in substantial changes in the seasonal influenza activity but also in decreasing cases of pediatric community-acquired pneumonia.

Study of the Etiology of Acute Respiratory Infections in Children Under 5 Years at the Dr. Agostinho Neto Hospital, Praia, Santiago Island, Cabo Verde.

Background: Acute respiratory infections are one of the major causes of morbidity and mortality in children under 5 years in developing countries and are a challenge for the health system of these countries. In Cabo Verde, despite the lack of recent studies, data indicate that it affects thousands of children, being the fourth leading cause of infant mortality in 2013. The aim of this study was to identify and describe the etiological agents associated with acute respiratory tract infections in children under 5 years old, and their associated risk factors, such as clinical symptoms or socio-demographic characteristics. Methods: Naso-pharyngeal samples were collected from children under 5 years attending at Dr. Agostinho Neto Hospital (Praia, Santiago Island, Cabo Verde) with suspected ARI at different time-points during 2019. Samples were analyzed using FilmArray® Respiratory Panel v. 2.0 Plus to identify etiological agents of ARI. A questionnaire with socio-demographic information was also collected for each participant. Data analyses were carried out using the IBM SPSS version 25 (IBM Corporation, Armonk, NY) and R 3.5.1 statistical software. Results: A total of 129 naso-pharyngeal samples were included in the study. Seventeen different etiologic agents of respiratory infections were identified. HRV/EV was the most frequent agent detected, followed by FluA H3 and RSV. Coinfection with two or more pathogens was detected in up to 20% of positive samples. The results were analyzed in terms of age-group, sex, period of the year and other social and demographic factors. Conclusion: Viruses are the main causative agents of ARI in children <5 years attending at the pediatrics service at the Dr. Agostinho Neto Hospital in Praia city, Santiago Island, Cabo Verde. Some factors are described in this study as statistically associated with the presence of an infectious agent, such as having one or more children sharing the bedroom with an adult and the presence of some clinical symptoms. The data addresses the need for studies on respiratory tract infections in Cabo Verde.

SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19.

Background: Previously, we conducted a systematic review and analyzed the respiratory kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Chen et al., 2021). How age, sex, and coronavirus disease 2019 (COVID-19) severity interplay to influence the shedding dynamics of SARS-CoV-2, however, remains poorly understood. Methods: We updated our systematic dataset, collected individual case characteristics, and conducted stratified analyses of SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) across COVID-19 severity, sex, and age groups (aged 0-17 years, 18-59 years, and 60 years or older). Results: The systematic dataset included 1266 adults and 136 children with COVID-19. Our analyses indicated that high, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. Severe cases tended to show slightly higher URT shedding post-symptom onset, but similar rates of viral clearance, when compared to nonsevere infections. After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of respiratory shedding. The estimated accuracy for using LRT shedding as a prognostic indicator for COVID-19 severity was up to 81%, whereas it was up to 65% for URT shedding. Conclusions: Virological factors, especially in the LRT, facilitate the pathogenesis of severe COVID-19. Disease severity, rather than sex or age, predicts SARS-CoV-2 kinetics. LRT viral load may prognosticate COVID-19 severity in patients before the timing of deterioration and should do so more accurately than URT viral load. Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, NSERC Senior Industrial Research Chair, and the Toronto COVID-19 Action Fund.

Invasive Mycobacterium abscessus Outbreak at a Pediatric Dental Clinic.

BACKGROUND: Mycobacterium species, specifically M. abscessus and M. chelonae (MABs), are known to contaminate water systems and are uncommon causes of health care-associated infection, but morbidity can be significant and treatment complex. METHODS: Odontogenic MAB infections occurred in patients following pulpotomy procedures at dental clinic A from 1 January to 6 September 2016. We identified confirmed and probable cases using culture data, imaging, pathology results, and surgical findings. Epidemiologic and clinical data including demographics, symptoms, laboratory findings, treatment regimens, and outcomes were extracted. RESULTS: Of 1082 at-risk patients, 71 case patients (22 confirmed; 49 probable) were identified. Median age was 6 years. Median symptom onset was 85 days postpulpotomy. Pain and/or swelling on admission occurred in 79%. On imaging, 49 of 70 had abnormalities of the mandible or maxilla, 13 of 70 had lymphadenopathy, and 19 of 68 had pulmonary nodules. Seventy were hospitalized (average of 8.5 days). Intravenous antibiotics were administered to 32 cases for a median length of 137 days. Clofazimine was administered to 29 patients as part of their multidrug regimen. Antibiotic treatment was associated with many adverse effects. Treated children showed evidence of jaw healing with resolved/improving pulmonary nodules at 1-year follow-up. CONCLUSIONS: This is the largest outbreak of invasive MAB infections associated with a pediatric dental practice. While infections were indolent, patients suffered medical and surgical consequences of treatment, including permanent tooth loss. Identification of this outbreak led to a change in water standards for pediatric dental procedures in California. Enhanced national dental water quality standards are needed to prevent future outbreaks.

Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child.

BACKGROUND: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. CASE PRESENTATION: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. CONCLUSION: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

Using the COVID-19 to influenza ratio to estimate early pandemic spread in Wuhan, China and Seattle, US.

BACKGROUND: Pandemic SARS-CoV-2 was first reported in Wuhan, China on December 31, 2019. Twenty-one days later, the US identified its first case--a man who had traveled from Wuhan to the state of Washington. Recent studies in the Wuhan and Seattle metropolitan areas retrospectively tested samples taken from patients with COVID-like symptoms. In the Wuhan study, there were 4 SARS-CoV-2 positives and 7 influenza positives out of 26 adults outpatients who sought care for influenza-like-illness at two central hospitals prior to January 12, 2020. The Seattle study reported 25 SARS-CoV-2 positives and 442 influenza positives out of 2353 children and adults who reported acute respiratory illness prior to March 9, 2020. Here, we use these findings to extrapolate the early prevalence of symptomatic COVID-19 in Wuhan and Seattle. METHODS: For each city, we estimate the ratio of COVID-19 to influenza infections from the retrospective testing data and estimate the age-specific prevalence of influenza from surveillance reports during the same time period. Combining these, we approximate the total number of symptomatic COVID-19 infections. FINDINGS: In Wuhan, there were an estimated 1386 [95% CrI: 420-3793] symptomatic cases over 30 of COVID-19 between December 30, 2019 and January 12, 2020. In Seattle, we estimate that 2268 [95% CrI: 498, 6069] children under 18 and 4367 [95% CrI: 2776, 6526] adults were symptomatically infected between February 24 and March 9, 2020. We also find that the initial pandemic wave in Wuhan likely originated with a single infected case who developed symptoms sometime between October 26 and December 13, 2019; in Seattle, the seeding likely occurred between December 25, 2019 and January 15, 2020. INTERPRETATION: The spread of COVID-19 in Wuhan and Seattle was far more extensive than initially reported. The virus likely spread for months in Wuhan before the lockdown. Given that COVID-19 appears to be overwhelmingly mild in children, our high estimate for symptomatic pediatric cases in Seattle suggests that there may have been thousands more mild cases at the time.

Seven-Year Case-Control Study in California of Risk Factors for Infant Botulism.

OBJECTIVE: To ascertain possible risk factors for infant botulism, the intestinal infectious form of human botulism, in the years immediately following its initial recognition in California in 1976. STUDY DESIGN: Parents of 159 California laboratory-confirmed cases of infant botulism from 1976 to 1983 and 318 healthy controls were interviewed using a comprehensive (>300 factors) questionnaire. "Neighborhood controls" (n = 184) were matched on date of birth, sex, race/ethnicity, and neighborhood of residence. "County controls" (n = 134) were matched only on date of birth, sex, and county of residence. Age-stratified bivariate and multivariate conditional logistic regression analyses were performed using SAS. RESULTS: All cases required hospitalization. Bivariate analyses identified several risk factors that in multivariate analyses were not significant. In multivariate analyses, risk factors differed with stratification by age. For the ≤2 month-old neighborhood controls comparison, birth order >1, cesarean delivery, ≤1 bowel movements (BMs) per day, and windy residence area were associated with illness hospitalization, and for the county controls comparison, only pacifier use was associated. For the <2 month-old neighborhood controls comparison, <1 bowel movements (BMs) per day, cesarean delivery, birth order >1, and windy residence area were associated with illness hospitalization, and for the county controls comparison, pets in the home was an additional risk factor. CONCLUSIONS: With the exception of the ≤2-month-old county controls group, slower intestinal transit time (≤1 BM/d) was associated with illness. Otherwise, our case-control investigation identified few physiologic, environmental, and maternal factors associated with infant botulism hospitalization in California.