Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Follow-up for 3 years of a pediatric population diagnosed in 2018 with mother-to-child transmission of HIV in 8 Latin American countries in the PLANTAIDS cohort.

INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

Risk Factors Associated with Intensive Care Admission in Children with Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome (MIS-C) in Latin America: A Multicenter Observational Study of the REKAMLATINA Network.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment.

Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network.

OBJECTIVES: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). STUDY DESIGN: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). RESULTS: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). CONCLUSION: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD.

Analysis of the social and psychosocial factors associated with adherence to antiretroviral therapy in adolescents with perinatal HIV-1 infection in Panama from a gender perspective.

Adherence is vital for an effective antiretroviral treatment. This cross-sectional study explored social and psychosocial factors associated with adherence among adolescents with perinatal human immunodeficiency virus type 1 infection in Panama from a gender perspective. A questionnaire developed for the study was applied to 38 adolescent patients (20 female, 18 male; median age, 14 years). Thirty-two patients (86%; one missing response) still depended on an adult to remember taking their medication, among whom 28 relied on a female relative. Although 18 (47%) patients reported to become ill no more than once a year, only 10 (26%) patients showed an undetectable viral load, and 4 (11%) patients showed no CD4 suppression. Seventeen (45%) patients recalled correctly their medication. During the week prior to the interview, 26 patients (68%) reported that they had missed at least one dose. When asked the reason for missing a dose, 23 out of 34 (68%; 4 missing responses) patients responded, "I forgot". Female patients gave more excuses for missing doses (mean ± SD number of excuses per female, 2.4 ± 2; per male, 1.2 ± 1; p = .02), while more male than female patients described an action plan if they ran out of medication (13 vs. 8; p = .05). Educational programs involving patients and also family members are warranted to improve adherence.

What Is the Added Benefit of Oropharyngeal Swabs Compared to Nasal Swabs Alone for Respiratory Virus Detection in Hospitalized Children Aged <10 Years?

We evaluated the added value of collecting both nasal and oropharyngeal swabs, compared with collection of nasal swabs alone, for detection of common respiratory viruses by reverse transcription-polymerase chain reaction in hospitalized children aged <10 years. Nasal swabs had equal or greater sensitivity than oropharyngeal swabs for detection of respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus, and influenza virus but not parainfluenza virus. The addition of an oropharyngeal swab, compared with use of a nasal swab alone, increased the frequency of detection of each respiratory virus by no more than 10% in children aged <10 years.

Multisystem inflammatory syndrome in children across 16 Latin American countries: A multicenter study from the REKAMLATINA Network.

Objectives: Our aim was to describe the epidemiology and outcomes of multisystem inflammatory syndrome in children (MIS-C) in Latin America. Methods: We conducted an observational, retrospective, and prospective multicenter study that gathered information from 84 participating centers across 16 Latin American countries between August 1, 2020 and June 30, 2022. Results: Of the 1239 reported children with MIS-C, 84.18% were previously healthy. The most frequent clinical manifestation in our studied population was abdominal pain (N = 804, 64.9%), followed by conjunctival injection (N = 784, 63.3%). The median duration of fever at the time of hospital admission was 5 days and a significant number of subjects required admission to an intensive care unit (N = 589, 47.5%). Most of the subjects (N = 1096, 88.7%) were treated with intravenous immunoglobulin, whereas 76.7% (N = 947) were treated with steroids, of whom 10.6% (N = 100) did not receive intravenous immunoglobulin. The death rate attributed to MIS-C was 4.88%, with a rate of 3.39% for those initially diagnosed with MIS-C and 8.85% for those whose admission diagnosis was not MIS-C (P <0.001, odds ratio 2.76, 95% confidence interval 1.6-4.6). Conclusions: One of the most significant findings from our study was the death rate, especially in those not initially diagnosed with MIS-C, in whom the rate was higher. This highlights the importance of increasing awareness and making an earlier diagnosis of MIS-C in Latin America.

Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus (RSV) infection: Safety, efficacy, and pharmacokinetic results.

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants (≥1 to ≤12 months) and neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to ≤36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. This contrasts with the findings of the previous RSV-A adult challenge study where significant antiviral activity was noted, without incidence of neutropenia. Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 (phase 2b).

Factors Associated With Hospitalization or Intensive Care Admission in Children With COVID-19 in Latin America.

Background: Limited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19. Objective: To describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America. Method: Multicenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children <18 years of age with COVID-19 confirmed by polymerase chain reaction or antigen detection from the nasopharynx were included. Children with multisystem inflammatory syndrome in children (MIS-C) were excluded. Associations were assessed using univariate and multivariable logistic regression models. Results: A total of 1063 children with COVID-19 were included; 500 (47%) hospitalized, with 419 (84%) to the pediatric wards and 81 (16%) to the ICU. In multivariable analyses, age <1 year (Odds Ratio [OR] 1.78; 95% CI 1.08-2.94), native race (OR 5.40; 95% CI 2.13-13.69) and having a co-morbid condition (OR 5.3; 95% CI 3.10-9.15), were associated with hospitalization. Children with metabolic or endocrine disorders (OR 4.22; 95% CI 1.76-10.11), immune deficiency (1.91; 95% CI 1.05-3.49), preterm birth (OR 2.52; 95% CI 1.41-4.49), anemia at presentation (OR 2.34; 95% CI 1.28-4.27), radiological peribronchial wall thickening (OR 2.59; 95% CI 1.15-5.84) and hypoxia, altered mental status, seizures, or shock were more likely to require PICU admission. The presence of pharyngitis (OR 0.34; 95% CI 0.25-0.48); myalgia (OR 0.47; 95% CI 0.28-0.79) or diarrhea (OR 0.38; 95% CI 0.21-0.67) were inversely associated with hospital admission. Conclusions: In this data analysis reported to the SLIPE research network in Latin America, infants, social inequalities, comorbidities, anemia, bronchial wall thickening and specific clinical findings on presentation were associated with higher rates of hospitalization or PICU admission. This evidence provides data for prioritization prevention and treatment strategies for children suffering from COVID-19.

Enterovirus D68 infection among hospitalized children with severe acute respiratory illness in El Salvador and Panama, 2012-2013.

We assessed EV-D68 epidemiology and phylogenetics among children aged ≤9 years hospitalized with severe acute respiratory illnesses at five sites in Panama and El Salvador during 2012-2013. Respiratory specimens positive for enterovirus or rhinovirus were tested by real-time RT-PCR for EV-D68, and partial VP1 gene sequences were determined. Of 715 enrolled children, 17 from sites in both countries were EV-D68-positive and commonly had a history of asthma or wheezing. Phylogenetically, 15 of 16 sequences fell into Clade B1, and one into Clade A2. The Central American EV-D68s were closely related genetically to contemporaneous strains from North America, South America, and the Caribbean.

[Impact of an antimicrobial stewardship program in a pediatric third level hospital in Panama]. / Impacto de un programa de optimización de uso de antimicrobianos en un hospital pediátrico de tercer nivel en Panamá.

BACKGROUND: Antimicrobial Stewardship Programs (ASP) focus in the appropriate use of antimicrobials to improve clinical results and minimize risk of adverse events. AIMS: To compare consumption and costs of antimicrobials before and after the establishment of an antimicrobial stewardship program and to describe the resistance proportion of priority bacteria. METHODS: Quasi-experimental, retrospective and prospective, descriptive and analytical study, to compare consumption and costs of antimicrobials in a pre- intervention period (2007-2010) and a post- intervention period (2011-2017). Additionally, a descriptive analysis of bacterial resistance from 2010 was performed. RESULTS: Gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem consumption decreased significantly in the post-intervention period compared to the pre-intervention period (p < 0.05) while consumption of amikacin, piperacillin/tazobactam, cefepime and levofloxacin increased significantly in the post-intervention period. The reduction in costs was not significant for gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem, meanwhile, costs increased for amikacin, piperacillin/tazobactam, cefepime and levofloxacin, but this was not significant. The isolation of Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis decreased during the post-intervention period. CONCLUSION: The ASP showed a decrease in consumption and costs of some antimicrobials.

[Multicenter retrospective study about the epidemiological, clinical and therapeutic aspects of Kawasaki disease in children from Panama]. / Estudio multicéntrico retrospectivo de los aspectos epidemiológicos, clínicos y terapéuticos de la enfermedad de Kawasaki en niños de Panamá.

BACKGROUND: Kawasaki disease (KD) is the leading cause of pediatric acquired heart disease in many countries, however, there are few published studies from Latin America (LA). AIM: To describe the epidemiology, clinical aspects, and treatment of KD in children from Panama as part of the REKAMLATINA-2 in LA. METHODS: Retrospective descriptive review of hospitalized patients diagnosed with KD, attended at three main pediatric hospitals of Panama from January-1-2009 to December-31-2013. RESULTS: 111 patients were analyzed, 61(54.9 %) were male. All children were hospitalized, and had a mean length of hospitalization of 5.8 (4-7) days. Median age at admission was 28.9 (12-38) months. Prior to KD final diagnosis, 63.9% patients received antibiotics for other presumed diagnoses. 105 (94.6%) patients received IGIV, 10 (9.5%) were resistant. On initial echocardiogram, 11.7% of cardiovascular complications were reported, of which coronary artery lesions (CALs) were detected in 3 (2.9 %) patients. CONCLUSION: The data suggest that KD in Panama has an incidence of about 2.05 x 100,000 in children under 15 years of age, and with a frequency 2.6 times higher in children under 3 years. A high rate of antibiotic misuse on outpatient prior to diagnostic confirmation was observed, suggesting KD unawareness and late recognition in Panamá.

Use of Adjunctive Therapy in Acute Kawasaki Disease in Latin America.

Objective: To characterize the use of adjunctive therapy in Kawasaki disease (KD) in Latin America. Methods: The study included 1,418 patients from the Latin American KD Network (REKAMLATINA) treated for KD between January 1, 2009, and May 31, 2017. Results: Of these patients, 1,152 received only a single dose of IVIG, and 266 received additional treatment. Age at onset was similar in both groups (median 2 vs. 2.2 years, respectively). The majority of patients were male (58 vs. 63.9%) and were hospitalized with the first 10 days of fever (85.1 vs. 84.2%). The most common adjunctive therapy administered was steroids for IVIG-resistance, followed by additional doses of IVIG. The use of biologics such as infliximab was limited. KD patients who received adjunctive therapy were more likely to have a lower platelet count and albumin level as well as a higher Z score of the coronary arteries. Conclusion: This is the first report of adjunctive therapies for KD across Latin America. IVIG continues to be the initial and resistance treatment, however, steroids are also used and to a lesser extent, biological therapy such as infliximab. Future studies should address the barriers to therapy in children with acute KD throughout Latin America.

Presentation and Outcomes of Kawasaki Disease in Latin American Infants Younger Than 6 Months of Age: A Multinational Multicenter Study of the REKAMLATINA Network.

Objective: To characterize the clinical presentation and outcomes of Kawasaki disease (KD) in infants <6 months of age as compared to those ≥6 months in Latin America. Methods: We evaluated 36 infants <6 months old and 940 infants ≥6 months old diagnosed with KD in Latin America. We compared differences in laboratory data, clinical presentation, treatment response, and coronary artery outcomes between the two cohorts. Results: The majority (78.1%) of infants and children ≥6 months of age were initially diagnosed with KD, as compared to only 38.2% of infants <6 months. Clinical features of KD were more commonly observed in the older cohort: oral changes (92 vs. 75%, P = 0.0023), extremity changes (74.6 vs. 57.1%, P = 0.029), and cervical lymphadenopathy (67.6 vs. 37.1%, P = 0.0004). Whether treated in the first 10 days of illness or after the 10th day, infants <6 months were at greater risk of developing a coronary artery aneurysm compared to KD patients ≥6 months treated at the same point in the course of illness [ ≤ 10 days (53.8 vs. 9.4%, P = 0.00012); >10 days (50 vs. 7.4%, P = 0.043)]. Conclusion: Our data show that despite treatment in the first 10 days of illness, infants <6 months of age in Latin America have a higher risk of developing a coronary artery aneurysm. Delay in the diagnosis leads to larger coronary artery aneurysms disproportionately in these infants. Thus, suspicion for KD should be high in this vulnerable population.

Costs associated with acute respiratory illness and select virus infections in hospitalized children, El Salvador and Panama, 2012-2013.

BACKGROUND AND OBJECTIVES: Although acute respiratory illness (ARI) is a leading cause of hospitalization among young children, few data are available about cost of hospitalization in middle-income countries. We estimated direct and indirect costs associated with severe ARI resulting in hospitalization among children aged <10 years in El Salvador and Panama through the societal perspective. METHODS: During 2012 and 2013, we surveyed caregivers of children hospitalized with ARI about their direct medical (i.e., outpatient consultation, medications, hospital fees), non-medical (transportation, childcare), and indirect costs (lost wages) at discharge and 7 days after discharge. We multiplied subsidized hospital bed costs derived from administrative data by hospitalization days to estimate provider costs. RESULTS: Overall, 638 children were enrolled with a median age of 12 months (IQR 6-23). Their median length of hospitalization was 4 days (IQR 3-6). In El Salvador, caregivers incurred a median of US$38 (IQR 22-72) in direct and indirect costs per illness episode, while the median government-paid hospitalization cost was US$118 (IQR 59-384) generating an overall societal cost of US$219 (IQR 101-416) per severe ARI episode. In Panama, caregivers incurred a median of US$75 (IQR 39-135) in direct and indirect costs, and the health-care system paid US$280 (IQR 150-420) per hospitalization producing an overall societal cost of US$393 (IQR 258-552). CONCLUSIONS: The cost of severe ARI to caregivers and the health care system was substantive. Our estimates will inform models to estimate national costs of severe ARI and cost-benefit of prevention and treatment strategies.

Prevalencia y patrones de resistencia adquirida a antirretrovirales en menores de 18 años en el Hospital de Especialidades Pediátricas "Omar Torrijos Herrera" / Prevalence and patterns of acquired resistance to antiretrovirals in children under 18 years of age

Introducción: La resistencia a antirretrovirales compromete la efectividad del tratamiento de pacientes con infección por VIH, llevando a falla virológica e inmunológica, deterioro clínico y comprometiendo tratamientos futuros. Los niños y adolescentes tienen mayor riesgo de desarrollo de resistencia asociados a terapias prolongadas, mala adherencia y limitadas opciones terapéuticas. Se desconoce la prevalencia y patrones de resistencia adquirida en población pediátrica panameña. Objetivos: Conocer la prevalencia y describir los patrones de resistencia adquirida en población pediátrica infectada con falla virológica en el período 2009-2019 Material y Método: Estudio descriptivo. Se incluyeron sujetos menores de 18 años de edad, con al menos un año de tratamiento, en falla virológica y que contaban con una prueba de genotipaje. Se realizó revisión de los expedientes clínicos para la obtención de los datos. Se describen las características demográficas, historial de tratamiento, resistencia a familias de antirretrovirales y mutaciones específicas Resultados y conclusiones: 13 pacientes fueron incluidos en el estudio de un total de 72 pacientes con infección de VIH atendidos en el período de estudio, para una prevalencia de resistencia del 18% de sujetos en terapia con resistencia. Se encontró 92% de resistencia a Inhibidores de la transcriptasa reversa análogo de nucleósidos, 61.5% a inhibidores de la transcriptasa reversa no análogos de nucleósidos y 23% de resistencia a Inhibidores de proteasa, las mutaciones M184V y K103N fueron las más frecuentes. Se requiere mantener la vigilancia de resistencia en niños con el fin de ajustar las recomendaciones de tratamiento.

Introduction: Antiretroviral resistance compromises the effectiveness of the treatment of patients with HIV infection, leading to virological and immunological failure, clinical deterioration and compromising future treatments. Children and adolescents are at increased risk of developing resistance associated with prolonged therapies, poor adherence, and limited therapeutic options. The prevalence and patterns of acquired resistance in the Panamanian pediatric population are unknown. Metodology Descriptive study. Subjects under 18 years of age, with at least one year of treatment, in virological failure and who had a genotyping test were included. A review of the clinical records was carried out to obtain the data. Demographic characteristics, treatment history, and at the time of genotyping, resistance to antiretroviral families and specific mutations are described. Conclusions: 13 patients were included in the study of a total of 72 patients with HIV infection attended in the study period, for a prevalence of 18% of subjects on antirretroviral therapy. It was found 92% resistance to nucleoside reverse transcriptase inhibitor, 61.5% to non- nucleoside reverse transcriptase inhibitor and 23% resistance to protease inhibitor. The M184V and K103N mutation were the most frequent. Surveillance of ARV resistance in children is required to adjust treatment recommendations.

Adherencia a la norma de profilaxis antibiótica y riesgo de infección de sitio quirúrgico en pacientes pediátricos intervenidos en el Hospital de Especialidades Pediátricas "Omar Torrijos Herrera" / Compliance to guidelines of antibiotic surgical prophylaxis and risk of surgical site infection in pediatric patients at Hospital de Especialidades Pediatricas Omar Torrijos Herrera

Introducción: El uso de profilaxis antibiótica quirúrgica adecuada es una de las medidas de prevención más importantes con evidencia de reducción de riesgo de infección del sitio operatorio (ISO). Material y Métodos: Se realizó un estudio prospectivo para evaluar la adherencia a las normas de profilaxis quirúrgica y riesgo de infección del sitio operatorio en pacientes de 30 días a 18 años de edad sometidos a intervenciones quirúrgicas en el Hospital de Especialidades Pediátricas Omar Torrijos Herrera (HEPOTH) durante agosto 2019 ­ julio 2020. Resultados: En el HEPOTH se realizaron desde agosto 2019 ­ julio 2020, 751 cirugías trazadoras. Se enrolaron 77 sujetos y se incluyeron 72 sujetos para valorar la adherencia a la norma de profilaxis. En 63 sujetos se evaluó la presencia de infección de sitio operatorio (ISO). El 72% de los sujetos se encontraban hospitalizados y 28% de los procedimientos fueron ambulatorios. La adherencia a la norma de profilaxis antibiótica fue de 31% (22/72). El 100% de las cirugías ambulatorias fue adherente a la norma comparado con una adherencia de 3.8% en las cirugías intrahospitalarias. Los pacientes que presentaron infección del sitio operatorio representaron un 5% (3/63), en ningún caso de infección del sitio operatorio se cumplió con la norma de profilaxis. Conclusiones: Se debe optimizar la adherencia a la norma de profilaxis antibiótica con el objetivo de reducir el riesgo de infección del sitio operatorio y disminuir la exposición a antibióticos en los pacientes pediátricos, lo que conlleva a mayor resistencia antibiótica futura.

Introduction: The use of adequate surgical antibiotic prophylaxis is one of the most important prevention measures with evidence of risk reduction of surgical site infections (SSI). Materials and methods: A prospective study was conducted to evaluate compliance of surgical prophylaxis standards and the risk of SSI in patients from 30 days to 18 years of age undergoing surgical interventions at the Omar Torrijos Herrera Pediatric Specialties Hospital (HEPOTH) during August 2019 - July 2020. Results: In HEPOTH, 751 tracer surgeries were performed from August 2019 - July 2020, 77 subjects were enrolled and 72 subjects were included to assess compliance to the prophylaxis guide, 63 subjects were evaluated looking for the presence of surgical site infections, 52 subjects were hospitalized (72%) and the rest were managed on an outpatient basis. Compliance to the antibiotic prophylaxis standard was 31% (22/72). In the outpatient surgeries they were 100% compliant to the guide of antibiotic prophylaxis compared with 3.8% of the inpatient surgeries. The patients presenting surgical site infections represent 5% (3/63), in no case the prophylaxis standard was met. Conclusions: Compliance to the antibiotic prophylaxis standard should be improved with the aim of reducing surgical site infections and reducing antibiotic exposure in pediatric patients. Which leads to greater future antibiotic resistance.

A randomized, double-blind, placebo-controlled trial evaluating the safety of early oseltamivir treatment among children 0-9 years of age hospitalized with influenza in El Salvador and Panama.

BACKGROUND: Oseltamivir reduces symptom duration among children with uncomplicated influenza, but few data exist on treatment efficacy and tolerability among hospitalized children, particularly among infants aged <1 year. We evaluated tolerability and efficacy of oseltamivir treatment of children aged 0-9 years hospitalized with influenza. METHODS: We conducted a double-blind, randomized, placebo-controlled trial at tertiary care hospitals in El Salvador and Panama. Primary outcomes were length of hospitalization and increased work of breathing. Children were eligible if hospitalized <7 days after symptom onset with cough or sore throat plus tachypnea. Children were randomized 1:1 to receive oseltamivir or placebo; had swabs collected at enrollment for influenza RT-PCR testing; were assessed at enrollment and every 12 h for work of breathing; and were followed for adverse events through 7 days after discharge. Analyses were intention-to-treat. RESULTS: Overall, 683 children were randomized (oseltamivir, n = 341, placebo n = 342). Fifty-three percent were aged <1 year and 30 had influenza (oseltamivir, n = 19; placebo, n = 11). The study was terminated early after enrollment of 21% of the sample size due to lower than anticipated participant accrual. Using Kaplan-Meier analysis, there was no significant difference in median length of hospitalization (3 days, IQR 2-4 vs. 5 days, IQR 3-7, p = 0.22) and increased work of breathing (36 h, IQR 24-72 vs. 96 h, IQR 13-108, p = 0.14) between oseltamivir versus placebo recipients. There was no difference in adverse events between groups. CONCLUSION: Oseltamivir treatment was well tolerated among hospitalized children, including among infants aged <1 year.

Impacto de un programa de optimización de uso de antimicrobianos en un hospital pediátrico de tercer nivel en Panamá / Impact of an antimicrobial stewardship program in a pediatric third level hospital in Panama

Resumen Introducción: Los programas de optimización de uso de antimicrobianos (PROA) se enfocan en el uso apropiado de antimicrobianos para ofrecer mejores resultados clínicos y menores riesgos de eventos adversos. Objetivos: Comparar consumo y costos de antimicrobianos antes y después de instauración de un programa de regulación de antimicrobianos y describir la proporción de resistencia de bacterias prioritarias. Métodos: Estudio cuasi-experimental, retrospectivo y prospectivo, descriptivo y analítico, que comparó el consumo y costo de antimicrobianos en un período pre- intervención (2007-2010) y un período post-intervención (2011-2017). Se realizó análisis descriptivo de resistencias bacterianas prioritarias. Resultados: El consumo de gentamicina, vancomicina, meropenem, cefotaxima, ceftazidima e imipenem disminuyó significativamente en el período post-intervención comparado con el período pre-intervención (p < 0,05), mientras que el consumo de amikacina, piperacilina/tazobactam, cefepime y levofloxacina en el período post-intervención mostró un aumento significativo. La reducción de costos no fue significativa para gentamicina, vancomicina, meropenem, cefotaxima, ceftazidima e imipenem. Para amikacina, cefepime, piperacilina/tazobactam y levofloxacina el aumento de costos no fue significativo. Los aislamientos de Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus y Enterococcus faecalis disminuyeron durante el período post-intervención. Conclusión: el PROA demostró disminución en consumo y costos de algunos antimicrobianos.

Abstract Background: Antimicrobial Stewardship Programs (ASP) focus in the appropriate use of antimicrobials to improve clinical results and minimize risk of adverse events. Aims: To compare consumption and costs of antimicrobials before and after the establishment of an antimicrobial stewardship program and to describe the resistance proportion of priority bacteria. Methods: Quasi-experimental, retrospective and prospective, descriptive and analytical study, to compare consumption and costs of antimicrobials in a pre- intervention period (2007-2010) and a post- intervention period (2011-2017). Additionally, a descriptive analysis of bacterial resistance from 2010 was performed. Results: Gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem consumption decreased significantly in the post-intervention period compared to the pre-intervention period (p < 0.05) while consumption of amikacin, piperacillin/tazobactam, cefepime and levofloxacin increased significantly in the post-intervention period. The reduction in costs was not significant for gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem, meanwhile, costs increased for amikacin, piperacillin/tazobactam, cefepime and levofloxacin, but this was not significant. The isolation of Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis decreased during the post-intervention period. Conclusion: The ASP showed a decrease in consumption and costs of some antimicrobials.

Madariaga virus infection associated with a case of acute disseminated encephalomyelitis.

We present the first report of a pediatric case of acute disseminated encephalomyelitis (ADEM) associated with Madariaga virus infection (MADV, Alphavirus, Togaviridae; formerly known as South American variants of eastern equine encephalitis virus [EEEV]) in a patient of the 2010 alphaviral epidemic reported in Panama. The patient was admitted to the Hospital del Niño in Panama City with suspected meningitis, exhibited with decreased alertness and disorientation in space and time, hemiparesis, and left Babinski sign. The patient was transferred to the intensive care unit and treated with aciclovir and methylprednisolone. The magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense lesions at T2-weighted images (T2) and fluid-attenuated inversion recovery (FLAIR) on the cortical-subcortical level. Sera samples obtained on days 6 and 12 were immunoglobulin M (IgM) positive for MADV. The findings on the clinical and cerebrospinal analyses, rapid symptom progression as well as neuroimaging, and serologic studies support our diagnosis. Our results suggest that MADV should be included in the etiologic differential diagnosis of ADEM in endemic countries.