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ImportanceChildren are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established.ObjectiveTo identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection.DesignCohort study, enrollment from February 1, 2020 until May 31, 2021Setting15 children’s hospitals in Canada, Iran, and Costa RicaParticipantsPatients ExposuresVariables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings.Main Outcomes and MeasuresThe primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of ≥6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease.ResultsWe identified 403 hospitalizations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, pConclusions and RelevancePediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.Key pointsQuestionWhat are the risk factors for severe disease in children hospitalized for PCR-positive SARS-CoV-2 infection?FindingsIn this multinational cohort study of 403 children, multiple comorbidities, obesity, neurological disorder, anemia, and/or hemoglobinopathy, shortness of breath, bacterial and/or viral coinfections, chest imaging compatible with COVID-19, neutrophilia, and MIS-C diagnosis were independent risk factors for severity. The risk profile and presence of comorbidities differed between pediatric age groups, but age itself was not associated with severe outcomes.MeaningThese results can inform targeted treatment approaches and vaccine programs that focus on patient groups with the highest risk of severe outcomes.

BACKGROUNDSARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We investigated risk factors for severe disease and explored changes in severity over time.METHODSChildren up to 17 years of age admitted March 1, 2020 through March 7th, 2021 to 15 hospitals in Canada, Iran and Costa Rica with confirmed or probable MIS-C were included. Descriptive analysis and comparison by diagnostic criteria, country, and admission date was performed. Adjusted absolute average risks (AR) and risk differences (RD) were estimated for characteristics associated with ICU admission or cardiac involvement.RESULTSOf 232 cases (106 confirmed) with median age 5.8 years, 56% were male, and 22% had comorbidities. ICU admission occurred in 73 (31%) but none died. Median length of stay was 6 days (inter-quartile range 4-9). Children 6 to 12 years old had the highest AR for ICU admission (44%; 95% confidence interval [CI] 34-53). Initial ferritin greater than 500 mcg/L was associated with ICU admission. When comparing cases admitted up to October 31, 2020 to those admitted later, the AR for ICU admission increased from 25% (CI 17-33) to 37% (CI 29-46) and for cardiac involvement from 44% (CI 35-53) to 75% (CI 66-84). Risk estimates for ICU admission in the Canadian cohort demonstrated a higher risk in December 2020-March 2021 compared to March-May 2020 (RD 25%; 95%CI 7-44).INTERPRETATIONMIS-C occurred primarily in previously well children. Illness severity appeared to increase over time. Despite a high ICU admission incidence, most children were discharged within one week.

BackgroundA cohort study was conducted to describe and compare the characteristics of SARS-CoV-2 infection in hospitalized children in three countries.MethodsThis was a retrospective cohort of consecutive children admitted to 15 hospitals (13 in Canada and one each in Iran and Costa Rica) up to November 16, 2020. Cases were included if they had SARS-CoV-2 infection or multi-system inflammatory syndrome in children (MIS-C) with molecular detection of SARS-CoV-2 or positive SARS-CoV-2 serology.ResultsOf 211 included cases (Canada N=95; Costa Rica N=84; Iran N=32), 103 (49%) had a presumptive diagnosis of COVID-19 or MIS-C at admission while 108 (51%) were admitted with other diagnoses. Twenty-one (10%) of 211 met criteria for MIS-C. Eighty-seven (41%) had comorbidities. Children admitted in Canada were older than those admitted to non-Canadian sites (median 4.1 versus 2.2 years; pConclusionsApproximately half of hospitalized children with confirmed SARS-CoV-2 infection or MIS-C were admitted with other suspected diagnoses. Disease severity was higher at non-Canadian sites. Neonates, children with comorbidities and those with chest radiographs compatible with COVID-19 were at increased risk for severe or critical COVID-19.Main pointsApproximately half of hospitalized children with laboratory confirmed MIS-C or SARS-CoV-2 infection were admitted with another primary diagnoses. The severity of disease was higher in the middle income countries (Costa Rica and Iran) than in Canada.

Background: Knowledge about neurological manifestations of SARS-CoV-2 in children is limited. We describe neurological manifestations in an international cohort of hospitalized pediatric patients. Methods: This is a multi-national observational study involving tertiary healthcare institutions in Canada, Costa Rica and Iran. We included patients 1 day-18 years admitted for any medical reason February 1, 2020-January 31, 2021 with laboratory evidence of SARS-CoV-2 infection by RT-PCR or serological testing. Descriptive analyses and logistic regression were performed where appropriate using JASP version 0⋅13. Findings: 298 hospitalized children with confirmed SARS-CoV-2 infection (median age 3⋅9 years [IQR 0⋅6-10⋅1]) from Canada (n=152), Costa Rica (n=115) and Iran (n=31) were included. Fifty-one (17%) had neurological manifestations, of which headache (73%), seizures (23%) and altered mental status (6%) were most frequently seen. Children with neurological symptoms had equivalent rates of comorbidities overall but were more likely to have underlying chronic neurological conditions. Additionally, those with neurological symptoms were more likely to be admitted to the ICU (15/51 [29%] vs. 32/247 [13%]; p =0⋅0033) and had longer length of hospital stay (6 days [IQR 3-8] vs. 4 days [IQR 2-7]; p =0⋅0060). Abnormalities were found in all children with neurological manifestations who received neuroimaging (n=6). Neurological manifestations were seen in 19% of the Iranian cohort, 23% of the Costa Rican cohort, and 12% of the Canadian cohort. Country of residence Costa Rica (adjusted OR: 2⋅520, 95% CI: 1⋅325-4⋅791, p =0⋅005), ICU admission (adjusted OR: 2⋅678, 95% CI: 1⋅307-5⋅486, p =0⋅007) and number of acute SARS-CoV-2 infection symptoms (adjusted OR: 1⋅355, 95% CI: 1⋅232-1⋅491, p

Antimicrobial resistance (AMR) is a global threat that affects not only human health, but also animal, agricultural and environmental health. In the United States, antibiotic resistance–the most om...

Secondary bacterial infections following Viperidae snakebite envenomation in children are common. Among 75 patients admitted because of snakebites at the only pediatric hospital in Costa Rica, 16 (21.3%) had a culture-confirmed secondary bacterial infection. Morganella morganii (37.5%), Aeromonas hydrophila (31.2%), and Providencia rettgeri (18.7%) were the most common pathogens. Empiric prophylaxis is still recommended and should be based on local etiological agents and antimicrobial susceptibilities.

To describe the impact following a 1-dose Varicella vaccination schedule introduced in Costa Rica in September 2007. Areas covered: This is a retrospective review using epidemiologic surveillance national databases of varicella cases and hospitalizations, period 2000-2015. We analyzed age-related varicella incidence cases and hospitalization trends before and after the vaccine introduction. Expert commentary: Varicella vaccine coverage among children 16 months age increased from 76% in 2008 to 95% in 2015. During this period Costa Rica reached a 73.8% reduction of Varicella reported cases and 85.9% reduction of hospitalizations in the general population. Among children under 5 years of age, that reduction was 79.1% and 87%, respectively. Varicella complications in hospitalized patients decreased 98%, from n = 53 in 2008 to n = 1 in 2014. After 8-years post implementation of a 1-dose schedule of universal varicella vaccination, a dramatic overall disease reduction in incidence, hospitalizations and complicated cases has been observed in all age groups.

ObjectivesAlthough devastating acute effects associated with snake envenoming are well described, the long-term sequelae resulting from these envenomings have not been adequately addressed, especially in the paediatric population. The aim of our study is to describe the clinical characteristics among paediatric patients in Costa Rica who developed long-term sequelae secondary to snakebite envenoming.DesignRetrospective descriptive study of paediatric patients under 13 years who were admitted with a history of a recent snakebite at the National Children’s Hospital in Costa Rica from January 2001 to December 2014.ResultsWe enrolled 74 patients admitted to our centre due to envenoming, and separated those who did not develop sequelae (50 patients) from those who did (24 patients). Of those who presented acute complications during hospitalisation, local wound infection and clinically diagnosed compartmental syndrome were significantly higher in the group that developed sequelae thereafter. Hypertrophic scars (66.7%), functional limitation of affected limb (37.5%) and the need of skin graft (37.5%) were the most common sequelae. The median follow-up of patients with long-term sequelae after discharge was 25.4 months (5.6–59.4). No deaths were reported during this time period.ConclusionsGiven the high economic, personal and healthcare burden that entails follow-up of these patients, efforts should be carried out to prevent the factors associated with sequelae among the affected population.

Background: Introduced in June 2017 by the World Health Organization (WHO) as a Neglected Tropical Diseases, snakebite envenoming is a global health problem. In Costa Rica, an incidence of 15 per 100,000 inhabitants and a mortality rate of 0·15 per 100,000 inhabitants per year were reported from 2005-2012. Children are also affected and prone to complications. Methods: Retrospective descriptive 14-year study of children with envenomings by Viperidae snakebites managed at the tertiary pediatric hospital in Costa Rica. Findings: 80 patients (pts) were included and classified as having mild (17 pts, 29·3%), moderate (58 pts, 72·5%) or severe (5 pts, 6·2%) envenoming. 52/80 (65%) patients received treatment within the first four hours, three (3·75%) between 5-8 hours, three between 9-12 hours, four (4%) between 13-16 hours, two (2·5%) between 17-20 hours, and seven (8·75%) after 20 hours. Edema was documented in 76/80 (95%), pain in 58 (72·5%), local bleeding in 23 (28·8%), emesis in 10 (12·5%), bullae formation in 8 (10%), and tissue necrosis in three (3·8%) pts. Complications presented according with degree of envenoming, being more common in severe cases: wound infection occurred in 14/58 (24·1%) with moderate envenoming and 5/5 pts with severe envenoming (p

Background Costa Rica (CR) has local transmission of Zika Virus (ZIKV) Infection since February 2016. Perinatal exposure (PE) and infection (PI) cases have been documented. Following a national protocol, reporting and follow-up of patients is mandatory. 2018 data of CR reported 272 women with confirmed ZIKV infection during pregnancy. Even though neurological sequelae are described in PI, including microcephaly, affected patients can develop symptoms within months after birth with development, language, and behavior alterations. Methods Retrospective descriptive study of patients born from August 1, 2016 until July 31, 2018, with laboratory confirmed PE. Follow-up was performed at referral hospital. Results 101 patients were enrolled (37% of all national confirmed perinatal ZIKV exposure during study period). Median age of first evaluation was 5 months (range: 0.6–21). 86/101 (86%) were classified as adequate term infants. 34/101 (33.7%) mothers got infected at first trimester, 55 (54.4%) at second, and 11 (10.8%) at third trimester. No data available in one. 8/101 (8%) patients had microcephaly at birth, with only 3/101 (3%) with persistence at follow-up, and 3/101 (3%) developed it later (after 9 months). 3/101 (3%) had confirmed congenital ZIKV syndrome (laboratory confirmation in symptomatic children), and 2 (2%) congenital ZIKV infection (laboratory confirmation in asymptomatic child). 6/101 (6%) had tone abnormalities and global development delay. 9 (9%) had central nervous system (CNS) ultrasound abnormalities, and 3 (3%) developed seizures. 2 (2%) had visual abnormalities, 1 (1%) had hearing impairment, 4 (4%) developed eating abnormalities, 6 (6%) developed language delay, and 4 (4%) had hyperactive behavior. All findings were divided according to maternal trimester of infection. Conclusion PI is a health problem in CR. Microcephaly at is infrequent, with international data showing it affects less than 1% of newborns. Most motor and development delay were documented in patients infected early during pregnancy, but specific language and behavior abnormalities also affected patients with later PE. Mortality was not documented, but significant CNS abnormalities were evident in congenital ZIKV syndrome patients. Disclosures All authors: No reported disclosures.

A combined meeting of the American Society of Microbiology and the Infectious Diseases Society of America was held recently in Washington, DC, USA, which gathered worldwide experts in the fields of infectious diseases, microbiology and the pharmaceutical industry, among others. Owing to its huge attendance and being among the largest conferences in the world during the year for infectious disease specialists, we focus only in the most relevant issues related to pediatric vaccines. Among others, we mention dengue, rotavirus, HIV, influenza virus, Streptococcus pneumoniae, Neisseria meningitidis, pertussis, measles and mumps. The case with mumps and measles illustrates the negative impact that vaccine refusal, fears and low coverage rates have on the resurgence of outbreaks produced by these two viruses. However, even with full vaccination schedules, other factors, such as waning immunity, influence the resurgence of these old diseases: pertussis, measles and mumps. This illustrates the importance of contin...

Evaluation of: Snape MD, Perrett KP, Ford KJ et al. Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial. JAMA 299(2), 173–184 (2008).Despite the advances in pediatric vaccinology during the last few decades, Neisseria meningitidis continues to be a threat to young infants, children and adolescents, in whom meningitis and septicemia are responsible for serious disease, mortality and long-term sequelae. Pure polysaccharides vaccines are poorly immunogenic in infants and children, and conjugation with protein carriers offer the best means for reaching protective antibody levels in these populations. However, no effective conjugate vaccines containing the five most common serogroups (A, B, C, W-135 and Y) are available and the best options reached at this moment, which contain more than one serogroup, are the tetravalent vaccines for older children and adolescents. The paper under evaluation describes the results of a multicenter prospective clinical ...

Introducción: La ataxia cerebelosa aguda posvaricela (ACAPV) y la meningoencefalitis son las complicaciones neurológicas agudas más comunes de la varicela. El objetivo del estudio es describir la presentación clínica, el tratamiento médico y el pronóstico de la ACAPV en niños costarricenses hospitalizados en el único hospital pediátrico de nuestro país, donde la vacunación contra la varicela aún no es sistemática. Métodos: Estudio descriptivo retrospectivo; se incluyeron pacientes de entre 1 y 12 años de edad, egresados del Hospital de Nacional Niños de Costa Rica entre enero de 1997 y junio de 2004, con el diagnóstico de ACAPV. Resultados: De los 441 pacientes inmunocompetentes que fueron hospitalizados por presentar complicaciones asociadas a virus varicela zóster durante este período, 37 pacientes (8,4 %) tuvieron ACAPV, y 24/37 (64,9 %) fueron varones. La edad media (rango) fue de 5 años (1-10 años). La media (rango) de aparición de la ataxia tras el inicio del brote fue de 2 días (1-30). El análisis del líquido cefalorraquídeo (LCR) se realizó en 22 pacientes (59,5 %) y en todos fue normal. La tomografía computarizada (TC) mostró edema cerebral en 6/18 pacientes (33,3 %). Un total 23 niños de 37 recibieron aciclovir intravenoso, aunque no se observaron diferencias significativas (p > 0,05) entre ambos grupos en cuanto a beneficio con la terapia. La duración media (rango) de la ataxia fue de 4 días (1-10) y 7 pacientes (19 %) fueron dados de alta atáxicos. La estancia hospitalaria media (rango) fue de 4,4 días (2-11). Se documentaron secuelas menores en 13/24 pacientes (54,2 %) durante las visitas de seguimiento y contactos telefónicos. Conclusiones: La ACAPV usualmente se asocia con un pronóstico favorable; sin embargo, pueden producirse secuelas neurológicas. La utilidad real del aciclovir y de realizar estudios de imágenes cerebrales en estos niños es controvertida. : Introduction: Postvaricella cerebellar ataxia (PVCA) and meningoencephalitis are the most common acute neurological complications of chickenpox. The objective of this study was to describe the clinical presentation, management, and outcome of children hospitalized with PVCA in the only pediatric hospital of this developing country, where routine varicella immunization is not yet available. Methods: We performed a retrospective chart review of children aged 1-12 years old admitted to the National Children's Hospital of Costa Rica from January 1997 to June 2004 with a diagnosis of PVCA. Results: Among the 441 immunocompetent patients admitted for varicella zoster virus-associated complications during this period, 37 (8.4 %) had PVCA. Twenty-four of the 37 (64.9 %) patients were boys. The mean (range) age was 5 (1-10) years. The median (range) interval from rash onset to admission was 2 (1-3) days. Cerebrospinal fluid analysis was available in 22 (59.5 %) patients and was normal in all. Head computed tomography showed cerebral edema in six out of 18 patients (33.3 %). Intravenous acyclovir was administered to 23 patients but no significant differences in clinical manifestations or outcomes were observed in treated versus untreated patients. The mean (range) length of ataxia was 4 (1-10) days, and seven (19 %) patients were still ataxic on discharge. The mean (range) length of hospital stay was 4.4 (2-11) days. Minor sequelae were documented in 13 out of 24 (54.2 %) patients during follow-up visits and telephone contacts. Conclusions: PVCA is usually associated with a favorable prognosis; however, neurological sequelae can occur. The real utility of acyclovir treatment and brain imaging studies in these children remains controversial.

Background Dengue virus infection has been rising in tropical countries. Clinical manifestations range from fever and general malaise to hemorrhagic manifestations and death. The role of endothelial damage and cytokines has not been well established for dengue infection. Objective Determine the profile of the pro-inflammatory cytokines and several markers of coagulopathy of dengue infection. Methods Patients admitted between September 2000 and April 2001, who met the WHO dengue diagnosis criteria, were enrolled. Blood samples were collected at 0, 6, 12, 24, 48, 72 h and 5 and 7 days after hospitalization. Profile of pro-inflammatory cytokines, markers of coagulopathy, protein C, protein S, d-dimer, prothrombin time, activated partial thromboplastin time, fibrinogen and activated protein C levels were determined. Results Thirty-three patients were enrolled. Median (range) age was 31 (13–70) years; 51.5% (17/33) were female. Ten of 33 (30%) presented with hemorrhagic manifestations. Patients were classified: Grade 1: 23/33 (70%), Grade II: 10/33 (30%). At study entry IL-6 was the most elevated, followed by IL-8 and TNFα. IL-10 was not elevated. No significant differences (p Conclusion The systemic host inflammatory and coagulation activation response occurs early in patients with dengue viral infection in the absence of severe hemorrhagic manifestations, and provides the basis for considering future clinical study in the use of recombinant human activated protein C to treat patients with severe sepsis from dengue infection.

The skin rash of Kawasaki syndrome is usually erythematous. A 23-month-old Costa Rican boy was admitted with a clinical picture compatible with Kawasaki syndrome, except for his skin lesions. He had diffuse, confluent, multiple sterile whitish pustular lesions on his chest, abdomen, neck, genitals, and thighs.

The immunopathogenesis of respiratory syncytial virus (RSV) and human rhinovirus lower respiratory tract infections in children remains to be defined. We measured nasal wash concentrations of 29 cytokines in infants with RSV or human rhinovirus lower respiratory tract infections. Concentrations of interferon-γ in RSV and innate immunity cytokines in both infections inversely correlated with disease severity.

BACKGROUND: The trends in hospitalization rates and risk factors for severe bronchiolitis have not been recently described, especially after the routine implementation of prophylaxis for respiratory syncytial virus (RSV) infections. OBJECTIVES: To define the burden of hospitalizations related to RSV and non-RSV bronchiolitis in a tertiary-care children's hospital from 2002 to 2007 and to identify the risk factors associated with severe disease. METHODS: Medical records of patients hospitalized for bronchiolitis were reviewed for demographic, clinical, microbiologic, and radiologic characteristics as well as the presence of underlying medical conditions. Differences were evaluated between children with RSV and non-RSV bronchiolitis, and multivariable logistic regression analyses were performed to identify independent risk factors for severe disease. RESULTS: Bronchiolitis hospitalizations in children younger than 2 years old (n = 4800) significantly increased from 536 (3.3%) in 2002 to 1241 (5.5%) in 2007, mainly because of RSV infections. Patients with RSV bronchiolitis (n = 2840 [66%]) were younger at hospitalization and had a lower percentage of underlying medical conditions than children hospitalized with non-RSV bronchiolitis (27 vs 37.5%; P < .001). However, disease severity defined by length of hospitalization and requirement of supplemental oxygen, intensive care, and mechanical ventilation was significantly worse in children with RSV bronchiolitis. RSV infection and prematurity, regardless of the etiology, were identified as independent risk factors for severe bronchiolitis. CONCLUSIONS: There was a significant increase in hospitalizations for RSV bronchiolitis from 2002 to 2007. A majority of the children with RSV bronchiolitis were previously healthy, but their disease severity was worse compared with those hospitalized with non-RSV bronchiolitis.