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Background: Respiratory Syncytial Virus (RSV) is a common cause of lower respiratory tract infections (LRTI) and hospitalization worldwide. The impact of RSV in Latin America and the Caribbean (LAC) including expensive treatment options, such as palivizumab, have been extensively discussed. However, publications on the impact of RSV disease burden in the region are scarce. This systematic review aimed to determine the incidence and prevalence of RSV in LAC by age and RSV subtype., Methods: We conducted a systematic review following Cochrane methods to evaluate the disease burden of RSV in LAC countries. We searched studies from January 2012 to January 2023 in literature databases and grey literature without language restrictions. We included guidelines, observational, economic, and surveillance studies from LAC countries. Pairs of reviewers independently selected, and extracted data from included studies. The risk of bias was assessed using the Study Quality Assessment Tools (NHLBI) and AGREE-II. We performed proportion meta-analyses using methods to stabilize the variance. The protocol was registered in PROSPERO (CRD42023393731)., Results: We included 156 studies, mainly from Brazil (25%), Colombia (14.5%), and Argentina (13.8%), as well as four clinical practice guidelines. Most studies were cross-sectional (76.9%) and were classified as low risk of bias (52.6%). The majority included inpatients (85.6%), pediatric (73.7%), and normal-risk patients (67.1%). The highest pooled prevalence was estimated in patients <1 year old (58%), with type A and B prevalence of 52 and 34%, respectively. The RSV-LRTI incidence was 15/100 symptomatic infants aged <2 years old, and the ICU admission was 42%. The RSV-LRTI lethality was 0.6, 3% in patients aged <2 and 0-5 years old, respectively, and 23% among >65 years old high-risk patients. The identified guidelines lack methodological rigor and have limitations in their applicability. The seasonality was more evident in South America than in Central America and The Caribbean, with a clear gap during the pandemic., Conclusion: This is the most exhaustive and updated body of evidence describing a significant burden of RSV in LAC, particularly at the extremes of life, and its seasonality patterns. Our findings could contribute could contribute facilitating effective prevention and treatment strategies for this significant public health problem., Systematic Review Registration: PROSPERO CRD UK (registration number: CRD42023393731)., Competing Interests: JL works for Vaccine Medical, Pfizer SAS, Bogotá, Colombia and RA works for Pfizer Inc., New York, New York, United States. RU-G has participated recently in scientific events sponsored by Pfizer and AstraZeneca, received honoraria as a speaker by Pfizer, and in advisory boards by MSD, all related to RSV prevention and treatment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ciapponi, Palermo, Sandoval, Baumeister, Ruvinsky, Ulloa-Gutierrez, Stegelmann, Ruesjas, Cantos, LaRotta, de Almeida and Bardach.)

This Systematic Review assesses the economic impact of Respiratory Syncytial Virus (RSV) in Latin America and the Caribbean (LAC) in relation to healthcare resource utilization and associated costs. We searched online databases from January 2012 to November 2022 to identify eligible publications. We identified 12 publications that reported direct costs, indirect costs, and resources associated with RSV and its complications. The primary direct medical resources reported were medical services, diagnostics tests and procedures, and length of stay (LOS). Direct total costs per patient ranged widely from $563 to $19,076. Direct costs are, on average, 98% higher than indirect costs. Brazil reported a higher total cost per patient than Colombia, El Salvador, México, Panamá, and Puerto Rico, while for indirect costs per patient, El Salvador and Panamá had higher costs than Brazil, Colombia, and Mexico. The mean LOS in the general ward due to RSV was 6.9 days (range 4 to 20 days) and the mean Intensive Care Unit LOS was 9.1 days (range 4 to 16 days). In many countries of the LAC region, RSV represents a considerable economic burden on health systems, but significant evidence gaps were identified in the region. More rigorous health economic studies are essential to better understand this burden and to promote effective healthcare through an informed decision-making process. Vaccination against RSV plays a critical role in mitigating this burden and should be a priority in public health strategies.

3-indoxyl sulfate (3-IS) results from a hepatic transformation of indole, a tryptophan degradation product produced by commensal gut bacteria. The metabolite has shown promise as a biomarker of dysbiosis and clinical outcomes following hematopoietic stem cell transplant (HSCT) in adults. Nonetheless, there is a paucity of data regarding microbiome health and outcomes in the pediatric HSCT setting. We developed and thoroughly validated an affordable high-performance liquid chromatography/fluorescence detector (HPLC-FLD) method to quantify 3-IS in urine for use in the pediatric setting. Chromatographic separation was achieved on a C18 column (250 × 4.6 mm × 5 μm) with a mobile phase consisting of pH 4.0 acetic acid-triethylamine buffer and acetonitrile (88:12, v / v ), eluted isocratically at 1 mL/min. 3-IS fluorescence detection was set at excitation/emission of 280 and 375, respectively. The method was fully validated according to FDA-specified limits including selectivity, linearity (0.10 to 10.00 mg/L, r 2 > 0.997), intra- and inter-day accuracy, and precision. 3-IS stability was confirmed after three freeze-thaw cycles, for short- and medium-term on a benchtop and at 4 °C and for long-term up to 60 days at -20 °C. The validated method was used to quantify 3-IS in urine samples from HSCT pediatric patients.

Background: Invasive pneumococcal diseases (IPD) are associated with high morbidity, mortality, and health costs worldwide, particularly in Latin America and the Caribbean (LAC). Surveillance about the distribution of serotypes causing IPD and the impact of pneumococcal vaccination is an important epidemiological tool to monitor disease activity trends, inform public health decision-making, and implement relevant prevention and control measures., Objectives: To estimate the serotype distribution for IPD and the related disease burden in LAC before, during, and after implementing the pneumococcal vaccine immunization program in LAC., Methods: Systematic literature review following Cochrane methods of studies from LAC. We evaluated the impact of the pneumococcal vaccine on hospitalization and death during or after hospitalizations due to pneumococcal disease and serotype-specific disease over time. We also analyzed the incidence of serotyped IPD in pneumococcal conjugate vaccine PCV10 and PCV13. The protocol was registered in PROSPERO (ID: CRD42023392097)., Results: 155 epidemiological studies were screened and provided epidemiological data on IPD. Meta-analysis of invasive diseases in children <5 years old found that 57%-65% of causative serotypes were included in PCV10 and 66%-84% in PCV13. After PCV introduction, vaccine serotypes declined in IPD, and the emergence of non-vaccine serotypes varied by country., Conclusions: Pneumococcal conjugate vaccines significantly reduced IPD and shifted serotype distribution in Latin America and the Caribbean. PCV10/PCV13 covered 57-84% of serotypes in children under 5, with marked decline in PCV serotypes post-vaccination. Continuous surveillance remains crucial for monitoring evolving serotypes and informing public health action., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bardach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease., Objectives: To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC)., Methods: Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097)., Results: We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum., Conclusion: The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Brizuela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed., Methods: We conducted a systematic review to evaluate the frequency of antimicrobial resistance of Streptococcus pneumoniae from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097)., Results: From 8,600 records identified, 103 studies were included, with 49,660 positive samples of S. pneumoniae for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7-25.0, I 2 : 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2-6.9, I 2 : 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2-36.4, I 2 : 87.7], and 9.7% [95%IC 5.9-15.6, I 2 : 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime., Conclusion: Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sandoval, Ruvinsky, Palermo, Alconada, Brizuela, Wierzbicki, Cantos, Bardach, Ciapponi and Gagetti.)

Simulation training is an educational tool that provides technical and cognitive proficiency in a risk-free environment. Several models have recently been presented in Latin America and the Caribbean (LAC). However, many of them were presented in non-indexed literature and not included in international reviews. This scoping review aims to describe the simulation models developed in LAC for neurosurgery training. Specifically, it focuses on assessing the models developed in LAC, the simulated neurosurgical procedures, the model's manufacturing costs, and the translational outcomes. Simulation models developed in LAC were considered, with no language or time restriction. Cadaveric, ex vivo, animal, synthetic, and virtual/augmented reality models were included for cranial and spinal procedures. We conducted a review according to the PRISMA-ScR, including international and regional reports from indexed and non-indexed literature. Two independent reviewers screened articles. Conflicts were resolved by a third reviewer using Covidence software. We collected data regarding the country of origin, recreated procedure, type of model, model validity, and manufacturing costs. Upon screening 917 studies, 69 models were developed in LAC. Most of them were developed in Brazil (49.28%). The most common procedures were related to general neurosurgery (20.29%), spine (17.39%), and ventricular neuroendoscopy and cerebrovascular (15.94% both). Synthetic models were the most frequent ones (38.98%). The manufacturing cost ranged from 4.00 to 2005.00 US Dollars. To our knowledge, this is the first scoping review about simulation models in LAC, setting the basis for future research studies. It depicts an increasing number of simulation models in the region, allowing a wide range of neurosurgical training in a resource-limited setting., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

SARS-CoV-2 dynamics across different COVID-19 waves has been unclear in immunocompromised children. We aimed to compare the dynamics of SARS-CoV-2 RNA viral load (VL) during the first and third waves of COVID-19 in immunocompromised children. A retrospective and longitudinal cohort study was conducted in a pediatric referral hospital of Argentina. The study included 28 admitted immunocompromised children with laboratory confirmed SARS-CoV-2 infection. Thirteen acquired the infection during COVID-19 first wave (May to August 2020, group 1 (G1)) and fifteen in the third wave (January to March 2022, group 2 (G2)). RNA viral load measure and its dynamic reconstruction were performed in nasopharyngeal swabs by validated quantitative, real time RT-PCR, and linear mixed-effects model, respectively. Of the 28 children included, 54% were girls, most of them had hemato-oncological pathology (57%), and the median age was 8 years (interquartile range (IQR): 3-13). The dynamic of VL was similar in both groups (P = 0.148), starting from a level of 5.34 log 10 copies/mL (95% confidence interval (CI): 4.47-6.21) in G1 and 5.79 log 10 copies/mL (95% CI: 4.93-6.65) in G2. Then, VL decayed with a rate of 0.059 (95% CI: 0.038-0.080) and 0.088 (95% CI: 0.058-0.118) log 10 copies/mL per day since diagnosis and fell below the limit of quantification at days 51 and 39 after diagnosis in G1 and G2, respectively. Our results evidenced a longer viral RNA persistence in immunocompromised pediatric patients and no difference in VL dynamic between COVID-19 first wave-attributed to ancestral infections-and third wave-attributed to Omicron infections., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Pediatric hepatic steatosis is a global public health concern, as an increasing number of children are affected by this condition. Liver biopsy is the gold standard diagnostic method; however, this procedure is invasive. Magnetic resonance imaging (MRI)-derived proton density fat fraction has been accepted as an alternative to biopsy. However, this method is limited by cost and availability. Ultrasound (US) attenuation imaging is an upcoming tool for noninvasive quantitative assessment of hepatic steatosis in children. A limited number of publications have focused on US attenuation imaging and the stages of hepatic steatosis in children., Objective: To analyze the usefulness of ultrasound attenuation imaging for the diagnosis and quantification of hepatic steatosis in children., Material and Methods: Between July and November 2021, 174 patients were included and divided into two groups: group 1, patients with risk factors for steatosis (n = 147), and group 2, patients without risk factors for steatosis (n = 27). In all cases, age, sex, weight, body mass index (BMI), and BMI percentile were determined. B-mode US (two observers) and US attenuation imaging with attenuation coefficient acquisition (two independent sessions, two different observers) were performed in both groups. Steatosis was classified into four grades (0: absent, 1: mild, 2: moderate and 3: severe) using B-mode US. Attenuation coefficient acquisition was correlated with steatosis score according to Spearman's correlation. Attenuation coefficient acquisition measurements' interobserver agreement was assessed using intraclass correlation coefficients (ICC)., Results: All attenuation coefficient acquisition measurements were satisfactory without technical failures. The median values for group 1 for the first session were 0.64 (0.57-0.69) dB/cm/MHz and 0.64 (0.60-0.70) dB/cm/MHz for the second session. The median values for group 2 for the first session were 0.54 (0.51-0.56) dB/cm/MHz and 0.54 (0.51-0.56) dB/cm/MHz for the second. The average attenuation coefficient acquisition was 0.65 (0.59-0.69) dB/cm/MHz for group 1 and 0.54 (0.52-0.56) dB/cm/MHz for group 2. There was excellent interobserver agreement at 0.94 (95% CI 0.92-0.96). There was substantial agreement between both observers (κ = 0.77, with a P < 0.001). There was a positive correlation between ultrasound attenuation imaging and B-mode scores for both observers (r = 0.87, P < 0.001 for observer 1; r = 0.86, P < 0.001 for observer 2). Attenuation coefficient acquisition median values were significantly different for each steatosis grade (P < 0.001). In the assessment of steatosis by B-mode US, the agreement between the two observers was moderate (κ = 0.49 and κ = 0.55, respectively, with a P < 0.001 in both cases)., Conclusion: US attenuation imaging is a promising tool for the diagnosis and follow-up of pediatric steatosis, which provides a more repeatable form of classification, especially at low levels of steatosis detectable in B-mode US., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Proctored on site simulation-based surgical education has been integrated in our residents curricula since 2012. Due to COVID-19 pandemic and social distance protocols, we developed a Tele-assisted Essential Skills Training Module (T-ESTM). The aim of this study is to evaluate comparative effectiveness between Telesimulation (T) versus Standard Simulation (S) for minimally invasive surgery (MIS) essential skills training., Methods: ESTM includes academic lectures, tutorials for ergonomics and 7 hands-on tasks scheduled into 2 sessions of 3 hours. Initial and final assessment scoring (adapted from GOALS) as well as timing for 3 of the tasks were registered. Telesimulation (T) group accessed the content online and completed their Hands-On practice through a digital communication platform. Standard Simulation (S) group attended conferences and Hands-On practice at the simulation center. Both groups were proctored by the same educators with summative and formative feedback and debriefing. Data was analyzed with the R-studio software program., Results: Each group had 20 participants with a mean age of 28 ± 5 years. 67.5% were surgeons in training, 47.5% had performed low complexity procedures and 40% had previous experience with simulation training. We observed a significant improvement in scoring and time reduction for all assessed tasks in S and T groups (p < 0.001), with no statistically significant differences when comparing both groups. Similar performance could be achieved with both strategies., Conclusion: Telesimulation is a reproducible and effective educational tool for remote MIS essential skills training, and should be considered as an alternative to on-site simulation programs., Level of Evidence: Level II., Type of Study: Clinical Research., (Copyright © 2022 Elsevier Inc. All rights reserved.)

At present, different reports have shown that children reach similar SARS-CoV-2 viral load (VL) levels compared to adults; however, the impact of VL on children remains ambiguous when asymptomatic versus symptomatic cases are compared. Thus, the aim of this study was to assess VL at the time of diagnosis in asymptomatic and symptomatic SARS-CoV-2 infected children. VL analysis was retrospectively carried out from nasopharyngeal swabs on 82 SARS-CoV-2 infected children, from March to October 2020. Of the 82 children, 31 were asymptomatic. Symptomatic patients had significantly higher VL values compared to asymptomatic ones (median=7.41 vs 4.35log10 copies/ml, respectively). Notwithstanding, 8 out of 31 asymptomatic children had high VL levels, overlapping levels observed above the first quartile in the symptomatic group. Analysis of different age groups revealed that median VL values were higher in the symptomatic groups, although there was only a significant difference in children younger than 5 years of age. On the other hand, there was no significant difference between the VL values from the 82 SARS-CoV-2 infected children according to age, sex, underlying disease, symptoms or severity of COVID-19 related disease. This study emphasizes the importance of VL analysis in SARS-CoV-2 infected children, who could contribute to viral spread in the community. This concern could be extended to healthcare workers, who are in contact with children., (Copyright © 2022 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Inborn errors of immunity, previously named primary immunodeficiency are a heterogeneous group of genetic defects of different components of the immune system. Patients present high susceptibility to an only or several microorganisms, developing recurrent infections; the severity is related to the specific genetic type of immunity defect. The main strategy on the management of these illness is the prevention of infections. These consensus guidelines made by the Pediatric Immunology Work Group of Sociedad Argentina de Pediatría, givese main approaches of infection prevention in order to provide a useful tool for all practitioners who are involved in the management of these patients, based on scientific evidence and broad consensus of a specialized panel expert.., (Sociedad Argentina de Pediatría.)

Introduction: Central venous catheter (CVC)- related bacteremias are common in pediatric patients following surgery for complex congenital heart disease admitted to a pediatric cardiac intensive care unit (PCICU) and have a high morbidity and mortality., Objective: To analyze the effectiveness of an interdisciplinary program for the prevention of CVC-related bacteremias in the PCICU., Material and Methods: Quasi-experimental, before and after implementation study without a control group. Study period: 01-01-2008 to 12- 31-2018. Population: PCICU staff who care for patients following surgery for complex heart disease at a hospital. Pre-intervention period: 01- 01-2008 to 12-31-2008; intervention period: 01-01- 2009 to 01-01-2018. Intervention: implementation of an ongoing improvement program. The rate of CVC-related bacteremias/1000 days and CVC use/100 days, RACHS score, standardized infection ratio (SIR), relative risk (RR), and 95% confidence interval (CI) were analyzed and a p value < 0.05 was considered statistically significant. The reference rate was estimated as the average for the 2008-2009 period and the annual and reference rates were compared., Results: The bacteremia reference rate for 2008- 2009 was 10.6/1000 days of CVC to analyze the SIR. A RACHS score over 3 was similar across all studied periods. The annual comparison showed a statistically significant reduction (p < 0.05) in the SIR. The comparison between the baseline bacteremia rate/1000 days of CVC (11.9) and the final rate (3.8) showed a significant reduction (RR: 0.16; 95 % CI: 0.07-0.35; p < 0.001)., Conclusions: The program was effective; the rate of CVC-related bacteremias in the PCICU showed a progressive, significant reduction., Competing Interests: None., (Sociedad Argentina de Pediatría.)

Background: Antibiotic-resistant gram-negative bloodstream infections (BSI) remain a leading cause morbidity and mortality in pediatric patients with a high impact on the public health system. Data in resource-limited countries, including those in Latin America and the Caribbean region, are scarce. The aim of the study was to identify risk factors for acquiring carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in children and to assess the use of resources., Methods: A retrospective case-control study was conducted to analyze demographic, epidemiological, clinical, microbiological, and outcome data as well as the use of resources between 2014 and 2019. Univariate and logistic regression analysis was performed in order to identify risk factors associated with CRE-BSI. The R software version 4.1.2 was used., Results: A total of 46 cases with CRE-BSI and 92 controls with gram-negative non-CRE-BSI were included. No statistical difference was observed regarding: median age (36 months; IQR, 11.2-117 vs. 48 months, IQR 13-119), male sex (50 vs. 60%), and underlying disease (98 vs. 91%) in cases vs. controls, respectively. The most frequent mechanism of CRE bacteremia were: KPC in 74%, OXA in 15%, and NDM in 6.5%. A total of 54.3% of cases vs. 32.6 % ( p = 0.016) of controls were admitted to the pediatric intensive care unit (PICU), and 48 vs. 21% ( p = 0.001) required mechanical ventilation. Bacteremia secondary to intra-abdominal infection was observed in 56.5% of cases vs. 35% of controls ( p = 0.032). Previous colonization with CRE was detected in 76% of cases vs. 8% of controls. Combination antimicrobial treatment was most frequent in cases vs. control (100 vs. 56.5%). No difference was observed in median length of hospital stay (22 days; IQR, 19-31 in cases vs. 17.5 days; IQR, 10-31 in controls; p = 0.8). Overall case fatality ratio was 13 vs. 5.5%, respectively. The most statistically significant risk factors included previous PICU stay (OR, 4; 95%CI, 2-8), invasive procedures/surgery (OR, 3; 95%CI, 1-7), central venous catheter placement (OR, 6.5; 95%CI, 2-19), urinary catheter placement (OR, 9; 95%CI 4-20), mechanical ventilation (OR, 4; 95%CI, 2-10), liver transplantation (OR, 8; 95%CI, 2-26), meropenem treatment (OR, 8.4; 3.5-22.6) in univariate analysis. The logistic regression model used for multivariate analysis yielded significant differences for previous meropenem treatment (OR, 13; 95%CI, 3-77; p = 0.001), liver transplantation (OR, 13; 95%CI, 2.5-100; p = 0.006), and urinary catheter placement (OR, 9; 95%CI, 1.4-94; p = 0.03)., Conclusion: CRE-BSI affects hospitalized children with underlying disease, mainly after liver transplantation, with previous urinary catheter use and receiving broad-spectrum antibiotics, leading to high PICU requirement and mortality. These risk factors will have to be taken into account in our region in order to establish adequate health policies and programs to improve antimicrobial stewardship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruvinsky, Voto, Roel, Deschutter, Ferraro, Aquino, Reijtman, Galvan, Motto, García, Sarkis and Bologna.)

Objective: The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.

Background: With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide; however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries., Methods: A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed., Results: Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6-7.4 years); 60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection; 59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9-10) and PICU stay 5.75 (IQR, 5-6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%., Conclusion: Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruvinsky, Voto, Roel, Fustiñana, Veliz, Brizuela, Rodriguez, Ulloa-Gutierrez and Bardach.)

Coronavirus 2 infection has spread rapidly throughout the world. Most of the current publications describe different behavior between an adult and pediatric population, this last one is associated with less clinical severity. The purpose of this study was to analyze the process of care, the epidemiological and clinical features, the evolution and the use of resources in pediatric patients with SARS-Cov-2 infection, treated during the first pandemic wave, at the beginning of 2020. An observational and retrospective study was carried out in the pediatric population with SARS-CoV-2 infection, treated in a highly complex pediatric hospital from April 1 to August 31, 2020. A total of 333 patients were included, 175 (53%) residents of the Metropolitan area of Buenos Aires (AMBA). The median age was 5.47 years (IQR 1.1-10.9) and 177 (53%) were women. A total of 209 (63%) patients required hospitalization and 152 (46%) had an underlying disease. Most of the patients (n 295, 89%) had mild/asymptomatic disease and the main symptom was fever (N169, 65%). In the univariate analysis, neurological disease (OR 4.5, IC95% 1.9-11, p 0.002), chronic respiratory disease (OR 3.9, IC95% 1.5-10.3, p 0.002) and genetics (OR 11, IC95%3.4-34.4, p < 0.001), as well as neurological symptoms (OR 2.8, IC95%1.1-6.6, p 0.035) and respiratory (OR 20.2, IC95%8.5-48.2, p 0.001) were associated with more severe disease. Active surveillance of pediatric patients with underlying diseases should continue to define the pandemic's impact on this specific population.

Objectives/hypothesis: To identify factors associated to increased risk of extra-laryngeal spread in pediatric patients with recurrent respiratory papillomatosis (RRP)., Study Design: Retrospective chart review., Methods: A retrospective study was conducted evaluating the clinical charts of patients younger than 16 years with histopathologically confirmed RRP treated between January 2014 and December 2018. Characteristics of patients with and without extra-laryngeal disease dissemination were compared. Odds ratios were calculated and multivariate logistic regression analysis was performed., Results: Data from 82 patients were analyzed. Mean age at symptom onset was 42 months. Fifteen (18.29%) patients had extra-laryngeal spread (ELS) at time of diagnosis and in four, the disease continued to spread to other sites. Of 67 patients with disease restricted to the larynx, 17 (25.37%) developed ELS during the disease course. Human papilloma virus (HPV) typing was performed in 49 (59.8%) patients; in 28 (57.1%) HPV subtype 6 was identified and in 21 (42.9%) HPV subtype 11. ELS was found in 11 patients with serotype 11 (52.38%) and in seven patients with serotype 6 (25%) (P = .048). Statistically significant differences for ELS were also found for age at diagnosis younger than 5 years (P = .045), presence of tracheostomy (P = .031), and need for adjuvant therapy (P = .010)., Conclusions: Age at diagnosis of RRP younger than 5 years and presence of tracheostomy were factors related to ELS. A statistically significant association between infection with HPV subtype 11 and ELS were also observed. Adjuvant medication might be considered a protective factor against ELS. Laryngoscope, 131:1652-1656, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Background: Vancomycin has been considered the treatment of choice especially for methicillin-resistant Staphylococcus aureus (MRSA) infections; but its poor tissue penetration, renal toxicity, and requiring of dosages monitoring, raises the need for new treatment alternatives such as daptomycin., Aims: To analyze the safety and effectiveness of daptomycin in children., Methods: Children with microbiologically documented infections treated with daptomycin were retrospectively included., Results: The most frequent infections were endocarditis in 9 (32%), sepsis in 4 (14%), bacteremia in 7 (associated with catheter in 3) (25%), osteomyelitis in 3 (10%), peritonitis associated with dialysis in 3 (10%) and suppurative thrombophlebitis in 2 patients (p) (7%). Methicillin-resistant Staphylococcus aureus was the most common pathogen in 18 patients (64%). The indications for daptomycin were due to the failure of conventional treatment in 17 (61%), and the toxicity or intolerance to vancomycin in 11 patients (39%). The average duration of treatment was 19 days (95% ICR 7-42 days). Four patients (14%) completed outpatient treatment, 22 patients had a favorable response (79%). Adverse events were reported in 3 patients (2 creatinine-phosfo-kinase increase) and in one severe skin rash., Conclusions: Daptomycin demonstrated a favorable efficacy and safety in this pediatric population.

This study sought to describe experiences, barriers and facilitators to the implementation of interventions for controlling Aedes aegypti in Latin America and the Caribbean. A qualitative approach with semi-structured in-depth interviews with program implementation experts (19 participants in nine countries) was carried out. We used a software to codify the data and created matrices to compare them. Based on our findings, we developed a graphic representation of the theoretical dimensions that encompass the barriers and facilitators to the implementation of interventions. At the global level, the natural and built environment contributed to the mosquito's reproduction. In the health system, the lack of priority given to the problem and the scarcity of material and human resources are the most important obstacles. Sectors other than health must take responsibility for actions directed at improving social determinants of health. There are transversal barriers related to governance, lack of coordination between central and local levels, lack of continuity in terms of interventions and technical groups. The community faces problems such as lack of information, poverty or resistance to recommendations. Public opinion can have a positive or negative impact, indirectly influencing political decisions. This study proposes a framework of analytical dimensions based on our findings; describes factors that influence policy implementation, which can guide future actions from an integrated perspective.

Objective: To determine the effectiveness and degree of implementation of interventions for the control of Aedes aegypti in Latin America and the Caribbean (LAC) as reported in scientific literature., Methods: We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, and LILACS, for experimental and observational studies, economic assessments and qualitative experiences carried out in LAC from 2000 to 2016. We assessed incidence and morbimortality of Aedes aegypti-related diseases and entomological indices: Breteau (containers), House, and Pupae per Person. We used GRADE methodology for assessing quality of evidence., Results: Of 1826 records retrieved, 75 were included and 9 cluster randomised clinical trials could be meta-analysed. We did not identify any intervention supported by a high certainty of evidence. In consistency with qualitative evidence, health education and community engagement probably reduces the entomological indices, as do the use of insecticide-treated materials, indoor residual spraying and the management of containers. There is low certainty of evidence supporting the use of ovitraps or larvitraps, and the integrated epidemiological surveillance strategy to improve indices and reduce the incidence of dengue. The reported degree of implementation of these vector control interventions was variable and most did not extend to whole cities and were not sustained beyond 2 years., Conclusions: We found a general lack of evidence on effectiveness of vector control in the region, despite a few interventions that showed moderate to low certainty of evidence. It is important to engage and educate the community, apart from achieving the implementation of integrated actions between the health and other sectors at national and regional level., (© 2019 John Wiley & Sons Ltd.)

Hydatidosis is a parasitic infection caused by the Echinococcus granulosus larvae, transmitted by the ingestion of infected food, characterized by the formation of cysts in vital organs. In Argentina, the disease is spread throughout the territory, constituting an important public health issue. The disease usually affects the liver and lungs. The affection of other organs is rare, and even more uncommon the affection of the heart. We present the case of a disseminated hydatidosis in a pediatric patient, whose initial clinical manifestation was an acute arterial embolism of the right limb caused by the rupture of a hydatidic cardiac cyst., (Sociedad Argentina de Pediatría.)

Introduction: Catheter-related infections (CRIs) cause a high level of morbidity and mortality with the increasing use of hospital resources., Objective: To describe the outcomes of a program implemented to reduce the rate of CRIs in pediatric intensive care units in Argentina., Population and Methods: Collaborative, multi center, clinical-epidemiological, quasiexperimental, before-and-after intervention study. Children who had a central venous catheter during hospitalization in 9 pediatric intensive care units in the Autonomous City of Buenos Aires, Greater Buenos Aires, and other provinces between June 2011 and April 2012 were included. A bundle of measures based on health care staff training on catheter insertion, hand hygiene, and checklists was put into practice and implemented measures were monitored. The number and annual rate of CRIs and the rate of central venous catheter use before and after the program implementation were compared (Stata 8.0)., Results: The total number of CRIs was 117 and 74 before and after the intervention, respectively. The rate of CRIs was 8.6/1000 days of central venous catheter use and 5.8/1000 days before and after the intervention, respectively; RR: 0.82 (95% confidence interval: 0.68-0.98), p= 0.015. The rate of central venous catheter use decreased from 54% to 49%, a non-significant difference., Conclusions: The program achieved a significant reduction in CRI rates. Based on the program, CRI surveillance was implemented in all participating pediatric intensive care units. Training and continuous surveillance are necessary to maintain and improve the outcomes accomplished with the program., (Sociedad Argentina de Pediatría.)

Introduction: The association between enterovirus D68 and acute flaccid myelitis was first described in the United States in 2014. Since then, sporadic cases have been reported in Canada and Europe. This study describes a series of cases of acute flaccid myelitis at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," in Buenos Aires, Argentina, during 2016., Methods: Descriptive, retrospective study. All patients with acute flaccid myelitis and lesions in the spinal cord involving the gray matter, as observed in the magnetic resonance imaging (MRI) scan, hospitalized from 04/01/2016 to 07/01/2016, were included in the study. Samples of nasopharyngeal secretions, fecal swabs and cerebrospinal fluid were collected and processed to look for the causative agent., Results: Ten patients were included. The median age was 4 years old (range from 3 months to 5 years old). Eight patients had a self-limiting febrile condition before the onset of neurological symptoms. Neurological findings were flaccid weakness in, at least, one limb, cervical paralysis (n= 2) and facial paralysis (n= 2). All patients had longitudinal lesions in the spinal cord, with gray matter involvement, mainly in the anterior horn. In all cases, a lumbar puncture (spinal tap) was performed. Pleocytosis was observed in 7 patients. In four children, enterovirus D68 was identified in nasopharyngeal secretions, and in one, it was detected in the cerebrospinal fluid. Neurological deficit persisted in all patients at the time of discharge., Conclusions: The first outbreak of acute flaccid myelitis associated to enterovirus D68 is reported in Argentina. Active epidemiological surveillance will help to determine the true incidence, epidemiology and etiology of this disease., (Sociedad Argentina de Pediatría)

Brain abscess is a focal infection that occurs with a frequency of 0.3-1.3 cases per 100,000 people/year. We describe the epidemiology, clinical and microbiology characteristics of 38 children diagnosed with brain abscess hospitalized between 4/1/2005 and 12/31/2015 at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" in Buenos Aires City. Twenty-four patients were male. The median age was 132 months. Predisposing factors were detected in 25 children. The median evolution from onset of symptoms to the visit was 7 days. There were 27 cases with single lesions. Surgical drainage was performed in 34 patients. The most frequent bacteria were anaerobes, Streptococcus viridans and Staphylococcus aureus. The median of antibiotic treatment was 56 days and the median of hospitalization was 43 days. The lethality was 3%., (Sociedad Argentina de Pediatría.)

Competing Interests: Conflicto de intereses. Ninguno declarado por los autores.

Chemotherapy regimens and clinical support advances have improved survival in children with acute lymphoblastic leukemia. The after-effects of treatment are a reason for concern, including damage to the immune system induced by immunosuppressive therapy which is reflected in the loss of antibody protection provided by prior immunizations. Our goal was to assess the presence of measles, rubella, and tetanus protective antibody titers among patients with acute lymphoblastic leukemia after completing chemotherapy. Sixty-one children with acute lymphoblastic leukemia seen at the Hospital Garrahan were included; patients had finished their chemotherapy at least 6 months earlier and had a complete immunization schedule before diagnosis. The rates of protective antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60% (CI 47-63) for rubella. These results strengthen the need to reconsider revaccination in this group of patients., (Sociedad Argentina de Pediatría.)

Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria., (Sociedad Argentina de Pediatría.)

Recurrent respiratory papillomatosis (RRP) is a rare condition characterized by recurrent growth of papilloma in the respiratory tract. RRP is caused by human papilloma virus. Its incidence is 4 per 100,000 children. Vertical transmission of the virus during gestation or during delivery is the major route of contracting the disease in children. One hundred and thirty different human papilloma virus types have been identified. Types 6 and 11 are involved in RRP and type 11 develops more aggressive disease with recurrence and progression to the respiratory tract and also nasopharyngeal surface. We present a 7 year old boy with diagnosis of RRP based on radiology and endoscopy.

Introduction: Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical., Objectives: To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness., Methods: Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed., Results: N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54). Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated that they never had the infection; and 41% (n: 44) did not recall a history of varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65); immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects were observed in relation to the different prophylaxis measures. No secondary cases were observed at 30 days., Conclusions: Implemented measures were effective to prevent secondary cases. Among healthy and immunocompromised children, prophylaxis with acyclovir was effective and well-tolerated.

Unlabelled: A common (5%) complication of cerebrospinal fluid (CSF) shunt systems is infection. CSF cytochemical findings have been used to choose the initial empirical antimicrobial treatment. The objective was to evaluate the results of cytochemical and microbiological analyses of CSF samples obtained from children with pyogenic ventriculitis associated to ventriculoperitoneal shunt systems. This was a retrospective, descriptive and analytical study. Thirty-two cases of pyogenic ventriculitis were included; Gram-positive bacteria were predominant in 26 cases (81.25%); the rest corresponded to Gram-negative bacteria. There were no statistically significant differences for the studied outcome variables (CSF cellularity, glucose and protein levels)., Conclusion: Gram-positive bacteria were widely predominant as a cause of pyogenic ventriculitis associated to the surgical procedure. CSF characteristics show a high heterogeneity and were not associated to the type of microorganism in this studied sample.

Background: Multidrug-resistant Acinetobacter baumannii (MAB) is an important nosocomial pathogen., Objectives: To analyze the risk factors for acquiring MAB, and the clinical and microbiological characteristics of MAB bacteremia (MABB) in children., Materials and Methods: Control-case study 2005-2008. Demographic and clinical data from all MABB and from non-multiresistant gram-negative bacteremias were recorded. Identification at species level, antimicrobial susceptibility tests, time-kill studies and clonally relationships were performed. Stata 8.0 was used for data analysis., Results: A total of 50 MABB and 100 controls were included. Ninety four percent of patients acquired MAB in ICU and the 88% had underlying diseases. All patients had invasive procedures previous to MABB. The median of hospitalization stay previous to MABB was different in cases than in controls (16 vs 7 days, p < 0.001). Five clones were detected among the MABB. Time-killing curves showed bactericidal activity of ampicillin/sulbactam plus gentamicin and polymixin B. Three patients with MAB died. In a multivariate analysis final predictors of MABB were: previous use of broad-spectrum antibiotics [OR: 7,0; IC 95% 1,93-25,0; p: 0,003] and mechanical ventilation [OR: 4,19; IC 95% 1,66-10,0; p: 0,002]., Conclusions: MABB were detected in patients with underlying conditions, invasive procedures and prolonged hospitalization. Predictors of MABB were mechanical previous use of broad-spectrum antibiotics and mechanical ventilation.

Background: Pneumococcal meningitis and bacteremia pose a significant disease burden in Latin America and the Caribbean (LAC)., Methods: To perform a systematic review of studies of pediatric pneumococcal meningitis and non-pneumonia, non-meningitis pneumococcal bacteremia in LAC, we conducted an exhaustive search from 2000 to 2010 in electronic databases and grey literature. Pairs of independently selected reviewers assessed the quality and extracted the studies' data. A STROBE-based checklist was used to assess the risk of bias in observational studies. Meta-analyses were performed., Results: Of 1218 retrieved studies, 39 were included. In children <5 years, the pooled 95% confidence interval (CI) percentage of pneumococcal etiology out of cases studied with cerebrospinal fluid/blood cultures was 6.0% (95% CI: 3.3-9.5) for meningitis and 8.0% (95% CI: 5.3-12.4) for bacteremia. The incidences per 100,000 children were 4.7 (95% CI: 3.2-6.1) and 3.9 (95% CI: 2.0-5.9) for pneumococcal meningitis and non-pneumonia, non-meningitis bacteremia, respectively. The mortality was 8.3 (95% CI: 0.0-21.0) and 0.5 (95% CI: 0.3.0-0.6)/100,000 for meningitis and sepsis, respectively. The case fatality ratio was 33.2% (95% CI: 21.3-46.2) for meningitis and 29.0% (95% CI: 21.9-36.8) for sepsis. The pooled serotype distribution from SIREVA surveillance data showed that 14, 5, 6B (for meningitis) and 14, 6B, 19F (for bacteremia) were the most frequent serotypes, all included in licensed vaccines., Conclusion: Pneumococcal meningitis and bacteremia are important causes of morbidity and mortality in LAC children <5 years of age. This systematic review provided evidence about the burden of pneumococcal disease and the serotype distribution to assess the impact the pneumococcal vaccines and to assist decision makers in the region.

Introduction: Inadequate antibiotic use is associated with an increased emergence of resistant microorganisms, higher morbidity and mortality rates, and an impact on public health., Objective: To assess the effectiveness of a program aimed at improving the use of antimicrobials in patients hospitalized at Hospital Garrahan., Material and Methods: Prospective, longitudinal, before and after study with no control group., Study Period: From November 1st, 2010 to June 30th, 2011. Patients receiving parenteral antibiotics were included. Newborn infants, burned patients and those receiving prophylactic antibiotics were excluded. The periods before and after implementing discussion and monitoring workshops for antibiotic prescription and distributing treatment guidelines were compared. An univariate analysis and a multiple logistic regression study were performed (STATA 8.0)., Results: In the pre-intervention period,376 patients were included; of them, 35.6% had received inadequate treatment. The multiple regression analysis showed that the endpoints for inadequate antibiotic use were acute lower respiratory tract infection (OR: 3.80; 95% CI: 1.35-3.26; p=0.04), fever without a source in hospitalized patients (OR: 5.55; 95% CI: 2.43-12.6; p < 0.01), and febrile neutropenia (OR: 0.29; 95% CI: 0.10-0.7; p < 0.01). In the post-intervention period, 357 patients were included; 21.5% had received inadequate treatment. A reduction in inadequate antibiotic prescription was observed compared to the pre-intervention period (p < 0.01). The multiple regression analysis showed that endpoints for inadequate use were skin and soft tissue infections (OR: 0.33; 95% CI: 0.13-0.93; p = 0.035), and febrile neutropenia (OR: 0.48; 95% CI: 0.220.94; p= 0.04)., Conclusion: The program was effective and allowed to improve antibiotic prescription practices in hospitalized children.

Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory infection and the most common cause of bronchiolitis in infants. The aim of this systematic review and meta-analysis was to obtain a comprehensive epidemiological picture of the data available on disease burden, surveillance, and use of resources in Latin America. Pooled estimates are useful for cross-country comparisons. Data from published studies reporting patients with probable or confirmed RSV infection in medical databases and gray literature were included from 74 studies selected from the 291 initially identified. When considering all countries, the largest pooled percentage RSV in low respiratory tract infection patients was found in the group between 0 and 11 months old, 41.5% (95% CI 32.0–51.4). In all countries, percentages were increasingly lower as older children were included in the analyses. The pooled percentage of RSV in LRTIs in the elderly people was 12.6 (95% CI 4.2–24.6). The percentage of RSV infection in hospitalized newborns was 40.9% (95% CI 28.28–54.34). The pooled case fatality ratio for RSV infection was 1.74% (95% CI 1.2–2.4) in the first 2 years of life. The average length of stay excluding intensive care unit admissions among children with risk factors for severe disease was 12.8 (95% CI 8.9–16.7) days, whereas it averaged 7.3 (95% CI 6.1/8.5) days in otherwise healthy children.We could conclude that infants in their first year of age were the most vulnerable population. To our knowledge, this is the first systematic review on RSV disease burden and use of health resources in Latin America., (© 2013 The Authors. Reviews in Medical Virology published by John Wiley & Sons, Ltd.)

Introduction: Dengue virus infection is the most common arthropod-borne disease worldwide with approximately 50 to 100 million cases of dengue infection occurring annually. Globally, dengue incidence has increased in the last 40 years, especially in Latin American and Caribbean (LAC) countries where the highest incidence is found. This systematic review aimed to present information on dengue disease burden and use of health resources in the LAC region in the last 15 years., Methods: We searched the main international and regional databases and generic and academic Internet search engines. Gray literature was retrieved mainly from regional health ministries and Pan American Health Organization. A set of inclusion criteria was defined., Results: We identified 2,041 articles of which 25 met these criteria, 13 for incidence and 12 for the use of resources and related costs. The pooled incidence of classic dengue fever was 72.1 cases per 100,000 persons-years in the 44 LAC countries analyzed (95% confidence interval 71.5-72.7), with an upward trend from 1995 up to 2010. Case-fatality ratio was highest in 1997 (0.12 [0.05-0.22]) and lowest in 2009, and the overall mortality was 0.02 per 100,000 people. More than 60% of the cases in the LAC region came from Brazil. The length of hospital stay ranged from 5 to 13 days., Conclusions: Activities to control dengue transmission in the region have been important but insufficient. The surveillance of dengue burden of disease and circulating strains help shape and evaluate the present and future health policies., (© 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Published by International Society for Pharmacoeconomics and Outcomes Research (ISPOR) All rights reserved.)

Tuberculosis is an important public health problem. It is estimated that around 5-10% of patients with tuberculosis present with central nervous system involvement; meningitis and tuberculoma being two of the most frequent manifestations. The paradoxical reaction in patients undergoing antituberculosis treatment is infrequent, nevertheless it is an important consideration in patients, who after an appropriate initial response to specific treatment, present with worsening clinical and radiological signs or the appearance of new lesions.

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.

Background: Varicella-zoster virus causes chickenpox and herpes zoster. More than 90% of varicella cases occur in childhood. The aim of this study was to gather all relevant information on epidemiology and resource use in Latin America and the Caribbean since 2000., Methods: Epidemiologic studies published since 2000 with at least 50 cases of varicella or herpes zoster, or at least 10 cases of congenital disease were included. Gray literature was also searched. Outcomes included incidence, admission rate, mortality and case-fatality ratio. Use of resources and both direct and indirect costs associated were extracted., Results: From the 495 records identified, 23 were included in the meta-analysis to report varicella-zoster virus outcomes and 3 in the herpes zoster analysis. The global pooled varicella incidence in subjects under 15 years of age was 42.9 cases per 1000 individuals per year (95% confidence interval: 26.9-58.9); children under 5 years of age were the most affected. Pooled general admission rate was 3.5 per 100,000 population (95% confidence interval: 2.9-4.1) and median hospitalization was 5-9 days. The most common varicella complications reported in studies were skin infections (3-61%), followed by respiratory infections (0-15%) and neurologic problems (1-5%). Direct costs averaged (2011/international dollar [I$]) $2040 per admission (range, I$ 298-5369) and I$70 per clinical visit (range, 11-188 I$)., Conclusions: Limited information was available on the outcomes studied. Improvements in the surveillance of ambulatory cases are required to obtain a better epidemiologic picture. As of 2011, only 2 countries introduced the vaccine in national immunization programs in Latin America and the Caribbean.

Upper respiratory tract infections are the most common source of antibiotic prescriptions. Acute pharyngitis is caused mainly by viruses, viral cases can be distinguished from acute streptococcal pharyngitis using Centor clinical epidemiological criteria, by rapid antigen tests or throat culture. Treatment of choice for streptococcal infection is penicillin V given in two daily doses. In children, acute otitis media (AOM) is the infection for which antibiotics are most often prescribed. Predominant causative pathogens include Streptococcus pneumoniae, Haemophilus influenzae non-type b and Moraxella catarrhalis. Diagnosis is based on history, physical examination and otoscopic exam. Antibiotic treatment should be initiated promptly in all children<2 years of age, and in older children presenting bilateral AOM, otorrhoea, co-morbidities or severe illness. In Argentina, amoxicillin is the drug of choice given the low penicillin resistance rates for S. pneumoniae. In children who fail amoxicillin therapy, amoxicillin/clavulanate provides better coverage against beta-lactamase producing H. influenzae and M. catarrhalis. Rhinosinusitis is caused mainly by viruses, secondary bacterial complication occurs in less than 5% of cases. Diagnosis is based on physical examination and additional studies are not usually required. Acute bacterial sinusitis is caused by the same pathogens that cause AOM and amoxicillin is the drug of choice.

Objective: Determine the reasons for inappropriate prescription of antibiotics and identify opportunities to improve prescription of these drugs in pediatric patients hospitalized in intermediate and intensive care units., Methods: A prospective, descriptive longitudinal study was conducted of pediatric patients in intermediate and intensive care units who received parenteral administration of antibiotics, with the exception of newborns, burn unit patients, and surgical prophylaxis patients. A univariate analysis and multiple logistic regression were performed., Results: A total of 376 patients with a median of age of 50 months were studied (interquartile range [IQR] 14.5-127 months). Out of the total patients studied, 75% had one or more underlying conditions. A total of 40.6% of these patients had an oncologic pathology and 33.5% had neurological conditions. The remaining 25.9% had other underlying conditions. Antibiotic treatment was inappropriate in 35.6% of the patients studied (N = 134). In 73 (54.4%) of the 134 cases, inappropriate use was due to the type of antibiotic prescribed, the dose administered, or the treatment period. The 61 (45.5%) remaining cases did not require antibiotic treatment. In the multivariate analysis, the risk factors for inappropriate use of antibiotics were: administration of ceftriaxone OR 2 (95% CI, 1.3-3.7; P = 0.02); acute lower respiratory tract infection OR 1.8 (95% CI, 1.1-3.3; P < 0.04); onset of fever of unknown origin in hospital inpatients OR 5.55 (95% CI, 2.5-12; P < 0.0001); and febrile neutropenia OR 0.3 (95% CI, 0.1-0.7; P = 0.009)., Conclusions: Inappropriate use of antibiotics was less common in the clinical conditions that were well-characterized. Prescribing practices that could be improved were identified through the preparation and circulation of guidelines for antibiotic use in hospital inpatients.

Introduction: In Argentina, pandemic influenza pH1N1 caused nearly 10,000 confirmed cases with high impact in pediatrics., Objectives: To describe clinical and epidemiological characteristics and analyse the risk factor of lethality in children hospitalized with infection pH1N1 confirmed by PCR., Population and Methods: We identifed all suspected cases (according to Ministry of health) in 34 centers and we included all the confirmed cases of 0-18 years from 1/4/09 to 31/8/09 in a retrospective cohort study. The viral diagnosis was confirmed by RT-PCR method. Data are expressed in percentages, average, median, standard deviation, and range (IQR) as appropriate; and as a measure of association, relative risk (RR), with 95% confidence interval (95%CI). Multiple logistic regression was conducted to determine the independent risk predictors., Results: Total number of suspected cases were: 2367; PCR was performed to 47.8% (n: 1131) being positive for pH1N1 65.5% (n: 741/1131); 57.2% males; 61.5% <24 months, median age: 14 months (IQR 6-46 months); 45.1% with underlying disease; more frequent clinical pictures were: pneumonia (39,7%) and bronchiolitis 25.8%; Case-fatality rate: 5.9% (44/741). Mortality risk factors were [RR (95%CI)]: neurological disease [5.00 (2.84-8.81)], genetic disease [3.67 (1.58-8.52)], malnutrition [3,07 (1.46-6.48)] and prematurity [2.28 (1.14-4.56)]. Independent mortality predictor: neurological disease [3.84 (1.81-8.14)]. No significant association between age, chronic respiratory disease, immunosuppression and viral co-infection with lethality was observed., Conclusions: Almost half of children with pH1N1 infection had underlying disease; the neurological condition was a separate CFR predictor.