Serum Vitamin D Levels and Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants.

BACKGROUND: 25-hydroxyvitamin D (VD) effects on lung function and immune-modulation might affect respiratory syncytial virus (RSV) infection outcomes. We aimed to assess VD levels on admission and their association with life-threatening RSV disease (LTD). METHODS: A prospective cohort study was conducted during 2017-2019. Previously healthy infants aged <12 months, hospitalized with a first episode of RSV infection, were enrolled. LTD was defined by need for intensive care and ventilatory support. Serum VD levels <20 ng/mL were categorized as deficient, and 20-29.9 ng/mL as insufficient. RESULTS: Of 125 patients studied, 73 (58%) were male. Median age was 4 months. Twenty-two patients developed LTD. No differences in viral load were seen between cases with LTD and controls (P = .94). Patients who developed LTD had significantly lower VD levels: median 18.4 ng/mL (IQR, 15.1-26.9 ng/mL) versus 31.7 ng/mL (IQR, 23.6-42.0 ng/mL), P < .001; 59% of infants with LTD had VD deficiency compared with 12% in those with better outcome. Multivariable regression analysis confirmed VD deficiency as a risk factor (odds ratio, 11.83; 95% confidence interval, 3.89-35.9; P < .001). CONCLUSIONS: These findings provide additional evidence for the development of strategies to prevent severe RSV infections.

Antibody levels against respiratory syncytial virus fusion protein conformations and lack of association with life-threatening infection in previously healthy infants.

BACKGROUND: Humoral immune response against the pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a protective role against infection. An RSV pre-F maternal vaccine has been recently approved in several countries to protect young infants against RSV. We aimed to assess serum IgG titers against the pre-F and post-F conformations of RSV F protein and their association with life-threatening RSV disease (LTD) in previously healthy infants. METHODS: A prospective cohort study including hospitalized infants <12 months with a first RSV infection was conducted during 2017-2019. Patients with LTD required intensive care and mechanical respiratory assistance. RSV pre-F exclusive and post-F antibody responses were determined by post-F competition and non-competition immunoassays, respectively, and neutralizing activity was measured by plaque reduction neutralization test. RESULTS: Fifty-eight patients were included; the median age was 3.5 months and 41 % were females. Fifteen patients developed LTD. RSV F-specific antibody titers positively correlated with neutralizing antibody titers in acute and convalescent phases but, importantly, they did not associate with LTD. Acute RSV pre-F exclusive and post-F IgG titers negatively correlated with patient age (P = 0.0007 and P < 0.0001), while a positive correlation was observed between the fold changes in RSV F-specific antibody titers between convalescent and acute phase and patient age (P = 0.0014 and P < 0.0001). Infants ≤2 months exhibited significantly lower fold-changes in RSV F-specific and neutralizing antibody titers between convalescence and acute phase than older infants. Additionally, acute RSV antibody titers showed no correlation with nasal RSV load and, furthermore, nasal viral load was not associated with the development of LTD. CONCLUSIONS: This study highlights that protection against life-threatening RSV disease is not necessarily antibody-dependent. Further characterization of the immune response against RSV and its role in protection against severe disease is important for the development of the safest possible preventive strategies.

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.

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.

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.

Peripheral tuberculous lymphadenitis in pediatrics: 16 years of experience in a tertiary care pediatric hospital of Buenos Aires, Argentina. / Tuberculosis ganglionar periférica en pediatría: 16 años de experiencia en un centro pediátrico de tercer nivel de Buenos Aires, Argentina.

Extrapulmonary tuberculosis accounts for 15-20 % of all clinical presentations of tuberculosis. Peripheral tuberculous lymphadenitis is the second most common presentation of extrapulmonary tuberculosis in children, after pleural tuberculosis, in Argentina. We analyzed 92 patients with peripheral tuberculous lymphadenitis seen at the Department of Tisiology of Hospital de Niños "Dr. Ricardo Gutiérrez" between August 2000 and September 2015. The patients' mean age was 8.7 ± 5 years. Nodal sites corresponded to single peripheral (31.5 %), multiple peripheral (20.6 %), and peripheral associated with deep nodes (47.8 %). Cervical lymph nodes were the most common site of involvement (80 %). In 80 % of patients previous antibiotic therapy had been administered, without response. The tuberculosis source was known in 56 %; 69 % had a positive tuberculin skin test; and 54 %, a pathological chest X-ray. Tuberculosis treatment was started on all patients based on clinical criteria, exposure and/or positive tuberculin skin test, prior to microbiological or histological confirmation. The clinical course was either healing (81.5 %), referral to a facility near home (8.7 %) or dropout (8.7 %). One patient died.

La tuberculosis extrapulmonar representa el 1520 % de todas las formas de presentación. La tuberculosis ganglionar periférica es la segunda forma extrapulmonar más frecuente en niños de Argentina, luego de la pleural. En el Servicio de Tisiología del Hospital de Niños "Dr. Ricardo Gutiérrez", se analizaron en forma retrospectiva 92 casos de tuberculosis ganglionar periférica asistidos entre agosto, 2000-septiembre, 2015. La edad media fue 8,7 ± 5 años. Las adenopatías fueron periféricas únicas (31,5 %), periféricas múltiples (20,6 %) y periféricas asociadas a profundas (47,8 %). Predominó la localización cervical (80 %). El 80 % recibió antibioticoterapia previa, sin respuesta. El 56 % tenía foco de contagio conocido; 69 %, prueba cutánea de tuberculina positiva y 54 %, radiografía de tórax patológica. Todos iniciaron tratamiento antifímico por clínica compatible, exposición y/o prueba cutánea de tuberculina positiva, antes de la confirmación microbiológica o histológica. La evolución fue curación (81,5 %), derivación cercana al domicilio (8,7 %), abandono (8,7 %). Un paciente falleció.

Tuberculosis ganglionar periférica en pediatría: 16 años de experiencia en un centro pediátrico de tercer nivel de Buenos Aires, Argentina / Peripheral tuberculous lymphadenitis in pediatrics: 16 years of experience in a tertiary care pediatric hospital of Buenos Aires, Argentina

La tuberculosis extrapulmonar representa el 1520 % de todas las formas de presentación. La tuberculosis ganglionar periférica es la segunda forma extrapulmonar más frecuente en niños de Argentina, luego de la pleural. En el Servicio de Tisiología del Hospital de Niños "Dr. Ricardo Gutiérrez", se analizaron en forma retrospectiva 92 casos de tuberculosis ganglionar periférica asistidos entre agosto, 2000-septiembre, 2015. La edad media fue 8,7 ± 5 años. Las adenopatías fueron periféricas únicas (31,5 %), periféricas múltiples (20,6 %) y periféricas asociadas a profundas (47,8 %). Predominó la localización cervical (80 %). El 80 % recibió antibioticoterapia previa, sin respuesta. El 56 % tenía foco de contagio conocido; 69 %, prueba cutánea de tuberculina positiva y 54 %, radiografía de tórax patológica. Todos iniciaron tratamiento antifímico por clínica compatible, exposición y/o prueba cutánea de tuberculina positiva, antes de la confirmación microbiológica o histológica. La evolución fue curación (81,5 %), derivación cercana al domicilio (8,7 %), abandono (8,7 %). Un paciente falleció.

Extrapulmonary tuberculosis accounts for 15-20 % of all clinical presentations of tuberculosis. Peripheral tuberculous lymphadenitis is the second most common presentation of extrapulmonary tuberculosis in children, after pleural tuberculosis, in Argentina. We analyzed 92 patients with peripheral tuberculous lymphadenitis seen at the Department of Tisiology of Hospital de Niños "Dr. Ricardo Gutiérrez" between August 2000 and September 2015. The patients' mean age was 8.7 ± 5 years. Nodal sites corresponded to single peripheral (31.5 %), multiple peripheral (20.6 %), and peripheral associated with deep nodes (47.8 %). Cervical lymph nodes were the most common site of involvement (80 %). In 80 % of patients previous antibiotic therapy had been administered, without response. The tuberculosis source was known in 56 %; 69 % had a positive tuberculin skin test; and 54 %, a pathological chest X-ray. Tuberculosis treatment was started on all patients based on clinical criteria, exposure and/or positive tuberculin skin test, prior to microbiological or histological confirmation. The clinical course was either healing (81.5 %), referral to a facility near home (8.7 %) or dropout (8.7 %). One patient died.