Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Cat Scratch Disease in Pediatrics: Who Has Systemic Involvement?

BACKGROUND: Bartonella henselae is the agent responsible for cat scratch disease (CSD). Although lymphadenopathy is typically the defining symptom, some patients develop potentially severe systemic compromise. It is unknown why some patients progress to systemic disease. The objective of this study was to describe the clinical, epidemiologic and laboratory characteristics of children with CSD and to analyze the differences between systemic versus localized infections. METHODS: Patients were identified by a retrospective review of medical records at a tertiary pediatric care hospital in Buenos Aires, Argentina, from January 2012 to July 2021. A CSD case was defined as any patient who presented compatible clinical findings with a positive serologic test (IgG >1/64 or IgM immunofluorescence) for B. henselae. RESULTS: A total of 197 patients were identified, with a median age of 8 years (range: 1-17.4 years). The most frequent clinical symptoms were fever and lymphadenopathy. Systemic involvement was present in 34.5% (n = 68) of patients and the most common presentation was splenic abscess (n = 51), followed by liver abscess (n = 23), chorioretinitis (n = 9), osteomyelitis (n = 5) and pneumonitis (n = 3). Patients with invasive disease more frequently presented with fever (79.4% vs. 50.3%) (P<0.001) and had higher C-reactive protein levels (24.9 vs. 6.7 mg/L) (P<0.001). Antibiotic therapy was administered to 95.9% (n = 187) of patients and most with systemic disease (77%) used combination treatment. Most patients recovered fully, and there were no reported deaths. CONCLUSIONS: CSD must be considered a potential cause of lymphadenopathy. Patients with fever and elevated C-reactive protein should be evaluated to rule out systemic compromise.

[Meningococcal disease: always present. Serogroup changes in the Southern Cone]. / Enfermedad meningocóccica: siempre presente. Cambios en los serogrupos en el Cono Sur.

Meningococcal disease (MD) caused by Neisseria meningitidis is a condition with high mortality rates in childhood. Serogroup W135 N. meningitidis (MenW135) is usually associated with 1 to 8% of MD cases worldwide, and with a low carriage rate. During March 2000, an increase in the number of cases of MenW135 in Saudi Arabia was reported that coincided with the Hajj pilgrimage (Hajj-2000 strain). Mayer et al studied MenW135 strains from outbreaks related with this pilgrimage and found that all had been caused by the same hypervirulent clone (ST-11/complex ET-37). The circulation of this strain could also be documented in Latin America. In the last years, changes in serogroup prevalence have been observed in the region, the increase of MenW135 in the Southern Cone being the most significant. N. meningitidis infections of several serogroups including MenW135 may be prevented with chemoprophylaxis with antibiotics and quadrivalent vaccines. Better knowledge of the global epidemiology through the new molecular techniques, jointly with the availability of vaccines are the most relevant tools to control hyperendemic or epidemic periods of MD.

Distinct Immune Phenotypes and Cytokine Profiles in Children with Differing Severity of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is usually mild and self-limited in children. However, a few Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections in children may progress to severe disease with respiratory distress or can result in a multisystem inflammatory syndrome (MIS-C) associated with COVID-19. The immune mechanisms for these differential clinical outcomes are largely unknown. METHODS: A prospective cohort study was performed to analyze the laboratory parameters, antibody response, immune phenotypes and cytokine profiles of 51 children with different clinical presentations of COVID-19. RESULTS: We found that the absolute lymphocyte counts gradually decreased with disease severity. Furthermore, SARS-CoV-2 IgG levels in the acute phase and convalescence were not significantly different in patients with different disease severity. A decrease in CD3 + , CD4 + and CD8 + T cells was observed as disease severity increased. Both CD4 + and CD8 + T cells were activated in children with COVID-19, but no difference in the percentage of HLADR + -expressing cells was detected across the severity groups. In contrast, MIS-C patients exhibited augmented exhausted effector memory CD8 + T cells. Interestingly, the cytokine profile in sera of moderate/severe and MIS-C patients revealed an increase in anti-inflammatory IL-1RA and a suppression of tumor necrosis factor-α, RANTES, eotaxin and PDGF-BB. MIS-C patients also exhibited augmented IL-1ß. CONCLUSIONS: We report distinct immune profiles dependent on severity in pediatric COVID-19 patients. Further investigation in a larger population will help unravel the immune mechanisms underlying pediatric COVID-19.

Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials.

BACKGROUND: Shortages of component two of Sputnik V vaccine (rAd5) are delaying the possibility of achieving full immunisation. The immunogenic response associated with the use of alternative schemes to complete the scheme was not explored. METHODS: We did two non-inferiority randomized clinical trials with outcomes measures blinded to investigators on adults aged 21-65 years, vaccinated with a single dose of rAd26 ≥ 30 days before screening and no history of SARS-CoV-2. Participants were assigned (1:1:1:1:1) to receive either rAd5; ChAdOx1; rAd26; mRNA-1273 or BBIBP-CorV. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-spike IgG concentration at 28 days after the second dose, when comparing rAd26/rAd5 with rAd26/ChAdOx1, rAd26/rAd26, rAd26/mRNAmRNA-1273 and rAd26/BBIBP-CorV. Serum neutralizing capacity was evaluated using wild type SARS-CoV-2 reference strain 2019 B.1. The safety outcome was 28-day rate of serious adverse. The primary analysis included all participants who received ≥ 1 dose. The studies were registered with NCT04962906 and NCT05027672. Both trials were conducted in Buenos Aires, Argentina. FINDINGS: Between July 6 and August 3, 2021, 540 individuals (age 56·7 [SD 7·3]; 243 (45%) women) were randomly assigned to received rAd5 (n=150); ChAdOx1 (n=150); rAd26 (N=87); mRNAmRNA-1273 (n=87) or BBIBP-CorV (n=65). 524 participants completed the study. As compared with rAd26/rAd5 (1·00), the GMR (95%CI) at day 28 was 0·65 (0·51-0·84) among those who received ChAdOx1; 0·47 (0·34-0·66) in rAd5; 3·53 (2·68-4·65) in mRNA-1273 and 0·23 (0·16-0·33) in BBIBP-CorV. The geometric mean (IU/ml) from baseline to day 28 within each group increased significantly with ChAdOx1 (4·08 (3·07-5·43)); rAd26 (2·69 (1·76-4·11)); mRNA-1273 (21·98 (15·45-31·08)) but not in BBIBP-CorV (1·22 (0·80-1·87)). INTERPRETATION: Except for mRNA-1273 which proved superior, in all other alternatives non-inferiority was rejected. Antibody concentration increased in all non-replicating viral vector and RNA platforms. FUNDING: The trials were supported (including funding, material support in the form of vaccines and testing supplies) by the Buenos Aires City Government.

Genetic Susceptibility to Life-threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants.

BACKGROUND: Genetic background may be an important host determinant of respiratory syncytial virus (RSV) disease severity, but full characterization of susceptibility genes remains unclear. This study aimed to assess the presence of specific single-nucleotide polymorphisms (SNPs) in selected genes codifying for different components of the antiviral innate immune response, to determine their role for developing RSV life-threatening disease (LTD). METHODS: Prospective cohort study including previously healthy full-term infants hospitalized with a first RSV infection during 2017-2018. RSV detection, quantification and subgroup determination, and genotyping for SNPs in Toll-like receptor 4 (TLR4 rs4986790, rs4986791), Toll-like receptor 8 (TLR8 rs3761624), macrophage receptor with collagenous structure(MARCO rs1318645) and myxovirus resistance 1(MX1 rs469390) were performed by real-time polymerase chain reaction in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit requiring ventilatory support. RESULTS: Seventy-five patients were studied, 15 (20%) developed LTD. Infants with concurrent SNPs in MX1 and TLR8, MARCO and TLR8 or MARCO, MX1 and TLR8 had an increased risk of developing LTD. Multivariable logistic regression analysis confirmed this significant association (odds ratio [OR] = 3.75, P = 0.046; OR = 3.92, P = 0.040; OR = 5.56, P = 0.010, respectively). No differences were seen in viral load of patients with LTD compared with those with better outcome (P = 0.737). In addition, no differences in viral load were seen in patients with the described high-risk SNPs compared with those without these polymorphisms. CONCLUSIONS: Life-threatening RSV infection in previously healthy infants was significantly associated with the presence of combined SNPs in MARCO, MX1 and TLR8.

Abscesos renales: experiencia en un hospital pediátrico de referencia / Renal abscesses: Experience at a referent Pediatric Hospital

INTRODUCCIÓN: El absceso renal es infrecuente en pediatría, con clínica y laboratorio inespecíficos. Ante su sospecha, es necesario realizar imágenes para establecer diagnóstico. Objetivo: Describir las características clínico-epidemiológicas, microbiológicas, diagnósticas y terapéuticas de abscesos renales en pediatría. PACIENTES Y MÉTODOS: Estudio retrospectivo, descriptivo, de pacientes internados con absceso renal, en seguimiento por Infectología del Hospital de Niños Ricardo Gutiérrez, durante 9 años. RESULTADOS: 15 pacientes (67% varones), mediana de edad 9 años (rango [r] 0,7-17). Cuatro pacientes con comorbilidades. El síntoma más frecuente fue fiebre seguido por dolor lumbar. El recuento medio de leucocitos en sangre fue de 15.700/mm3 (r: 7.100-45.000) y la PCR de 193 mg/L (r: 1-362). Cuatro pacientes presentaron urocultivo positivo: dos Escherichia coli, uno Klebsiella pneumoniae y E. coli y otro Candida albicans y K. pneumoniae. Ningún paciente presentó bacteriemia. El diagnóstico se confirmó por ecografía. Se realizó drenaje en siete pacientes, con aislamiento de Staphylococcus aureus en dos y Pseudomonas aeruginosa en uno. El tratamiento incluyó terapia combinada en 67%. Mediana de antibioterapia intravenosa fue 16 días (r: 7-49), total de 28 (r: 14-91). Un paciente requirió terapia intensiva y dos, nefrectomía. CONCLUSIÓN: Los abscesos renales son infrecuentes, con gran morbimortalidad. Sospechar en paciente con infección del tracto urinario (ITU) de evolución tórpida que persiste febril. En nuestro estudio, la alta sensibilidad de la ecografía renal permitió su diagnóstico precoz.

BACKGROUND: Renal abscesses are infrequent in pediatrics, with nonspecific clinical and laboratory findings. When suspected, imaging is essential to establish the diagnosis. Aim: To describe the clinical-epidemiological, microbiological, diagnostic and therapeutic characteristics of renal abscesses in pediatrics. METHODS: Retrospective and descriptive study of hospitalized patients with renal abscess, followed by Infectious Diseases Department of Ricardo Gutiérrez Children's Hospital during 9 years. Statistical analysis: Epi Info 7.2.2.6. RESULTS: 15 patients (67% male), median age 9 years (range [r] 0.7-17) were included. Four patients had underlying disease. The most frequent symptom was fever, with a median duration of 10 days (r:1-36), followed by lumbar pain. The median white blood cell count was 15,700/mm3 (r: 7,100-45,000) and CRP 193mg/L (r: 1-362). Four patients presented positive urine culture: 2 Escherichia coli, 1 Klebsiella pneumoniae and E. coli and 1 Candida albicans and K. pneumoniae. No patient had bacteremia. The diagnosis of abscess was confirmed by ultrasound. Surgical drainage was performed in 7 patients, with isolation of Staphylococcus aureus in 2 and Pseudomonas aeruginosa in 1. Empirical treatment included 3rd generation cephalosporin, combined in 67% of cases. The median of intravenous antibiotic therapy was 16 days (r: 7-49) with a total of 28 days (r:14-91). One patient required transfer to intensive care unit and 2 nephrectomy. CONCLUSION: Renal abscesses are infrecuent in pediatrics, but they present significant morbidity and mortality. It should be suspected in patients with urinary tract infection (UTI)with torpid evolution that persists with fever without antibiotic response. In our study, the high sensitivity of renal ultrasound allowed early diagnosis.

The current situation of meningococcal disease in Latin America and recommendations for a new case definition from the Global Meningococcal Initiative.

The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with expertise in meningococcal disease (MD). It promotes MD prevention through education and research. Given geographic differences in disease epidemiology, prevention strategies (e.g., vaccination) should be country-specific to ensure local needs are met. However, regional policies/recommendations and standardized disease diagnostic criteria should be implemented to improve surveillance and control strategies, and allow for more robust data comparisons. Consequently, the GMI convened a meeting with Latin American representatives to discuss the burden of MD and vaccination practices/policies, and consider if the global GMI recommendations could be tailored. The group determined that as robust, uniform epidemiologic data are required to make informed health-policy decisions, it would be useful to first summarize the regional situation herein (including disease surveillance, case definitions, epidemiology, vaccination and outbreak control strategies) and then determine a consensus-based meningococcal case definition for use throughout the region.

Case characteristics and use of oseltamivir in children and household contacts.

In May 2009, the onset of pandemic influenza A (H1N1) began in Buenos Aires schools and a containment program was implemented. We report the first 191 school-aged cases. Influenza (H1N1) was a mild disease in children. Oseltamivir was well tolerated and resulted in a significantly reduced duration of symptoms in this group. Oseltamivir was also effective at preventing secondary cases.

[Nasal septal abscess]. / Absceso del septum nasal.

A nasal septal abscess (NA) is defined as a collection of pus between the cartilage or bony septum and its normally applied mucoperichondrium or mucoperiostium. It is an uncommon disease which should be suspected in a patient with acute onset of nasal obstruction and recent history of nasal trauma, periodontal infection or an inflammatory process of the rhinosinusal region. We report a case of an 8-year-old boy with bilateral NA caused by community-acquired methicillin-resistant Staphylococcus aureus(MR-CO) in order to emphasize the importance of prompt diagnosis and adequate treatment to prevent the potentially dangerous spread of infection and the development of severe functional and cosmetic sequelae.

Enfermedad meningocóccica: siempre presente. Cambios en los serogrupos en el Cono Sur / Meningococcal disease: always present. Serogroup changes in the Southern Cone

Meningococcal disease (MD) caused by Neisseria meningitidis is a condition with high mortality rates in childhood. Serogroup W135 N. meningitidis (MenW135) is usually associated with 1 to 8% of MD cases worldwide, and with a low carriage rate. During March 2000, an increase in the number of cases of MenW135 in Saudi Arabia was reported that coincided with the Hajj pilgrimage (Hajj-2000 strain). Mayer et al studied MenW135 strains from outbreaks related with this pilgrimage and found that all had been caused by the same hypervirulent clone (ST-11/complex ET-37). The circulation of this strain could also be documented in Latin America. In the last years, changes in serogroup prevalence have been observed in the region, the increase of MenW135 in the Southern Cone being the most significant. N. meningitidis infections of several serogroups including MenW135 may be prevented with chemoprophylaxis with antibiotics and quadrivalent vaccines. Better knowledge of the global epidemiology through the new molecular techniques, jointly with the availability of vaccines are the most relevant tools to control hyperendemic or epidemic periods of MD.

La enfermedad meningocóccica (EM) producida por Neisseria meningitidis es una causa de alta mortalidad en la niñez. N. meningitidis serogrupo W135 (MenW135) es habitualmente asociado en el mundo con el 1 al 8% de los casos de EM y con una baja tasa de portadores. En 2000 en Arabia Saudita se informó un aumento del MenW135 coincidente con la peregrinación a la Meca, Hajj (cepa Hajj-2000). Mayer y cols. estudiaron cepas MenW135 de brotes relacionados con la peregrinación, y hallaron que todos los casos fueron producidos por el mismo clon hipervirulento (ST-11/complejo ET-37), cepa cuya circulación también se pudo documentar en América Latina. En los últimos años en la región se han producido cambios en la prevalencia de serogrupos, siendo el más significativo el aumento de MenW135 en el Cono Sur. Para la prevención de las infecciones por N. meningitidis de los diversos serogrupos incluyendo MenW135, se dispone de la quimioprofilaxis a través del uso de antimicrobianos y de las vacunas cuadrivalentes. El mejor conocimiento de la epidemiología global a través de las nuevas técnicas de laboratorio moleculares, junto con la disponibilidad de las vacunas, son las herramientas más relevantes para controlar períodos hiperendémicos o epidémicos de EM.

Absceso del septum nasal / Nasal septal abscess

Se define como absceso del septum nasal (AN) a la colección de pus entre el cartílago o hueso del septum nasal y el mucopericondrioo mucoperiostio. Se trata de una patología poco frecuente que el pediatra debesospechar ante todo paciente que presente obstrucción nasal deinstalación aguda e historia reciente de traumatismo, infecciónperiodontal o proceso inflamatorio que involucre la regiónrinosinusal. Presentamos el caso de un paciente de 8 años con AN bilateral por Staphylococcus aureus meticilino-resistente de la comunidad (MR-CO), con el objeto de enfatizar la necesidad de un rápido diagnóstico y tratamiento para disminuir el riesgo de complicaciones infecciosas graves y posibles secuelas funcionalesy estéticas.