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.

Image evaluation of HIV encephalopathy: a multimodal approach using quantitative MR techniques.

INTRODUCTION: A multimodal approach of the human immunodeficiency virus (HIV) encephalopathy using quantitative magnetic resonance (MR) techniques can demonstrate brain changes not detectable only with conventional magnetic resonance imaging (MRI). The aim of this study was to compare conventional MRI and MR quantitative techniques, such as magnetic resonance spectroscopy (MRS) and relaxometry and to determine whether quantitative techniques are more sensitive than conventional imaging for brain changes caused by HIV infection. METHODS: We studied prospectively nine HIV positive children (mean age 6 years, from 5 to 8 years old) and nine controls (mean age 7.3 years; from 3 to 10 years), using MRS and relaxometry. Examinations were carried on 1.5-T equipment. RESULTS: HIV-positive patients presented with only minor findings and all control patients had normal conventional MR findings. MRS findings showed an increase in choline to creatine (CHO/CRE) ratios bilaterally in both frontal gray and white matter, in the left parietal white matter, and in total CHO/CRE ratio. In contrast, N-acetylaspartate to creatine (NAA/CRE) ratios did not present with any significant difference between both groups. Relaxometry showed significant bilateral abnormalities, with lengthening of the relaxation time in HIV positive in many regions. CONCLUSION: Conventional MRI is not sensitive for early brain changes caused by HIV infection. Quantitative techniques such as MRS and relaxometry appear as valuable tools in the diagnosis of these early changes. Therefore, a multimodal quantitative study can be useful in demonstrating and understanding the physiopathology of the disease.

Pneumococcal nasopharyngeal carriage among infants born to human immunodeficiency virus-infected mothers immunized with pneumococcal polysaccharide vaccine during gestation.

BACKGROUND: We have previously shown that 23-valent pneumococcal polysaccharide vaccine (PPV) is immunogenic in human immunodeficiency virus (HIV)-infected mothers and provides vaccine-induced antibodies to the infant. We compared the nasopharyngeal pneumococcal colonization (NPC) rates in <6-month-old infants born to HIV-infected mothers, according to immunization with PPV during pregnancy. METHODS: NPC was evaluated in 45 term infants born to vaccinated women (PPV+) and in 60 infants in a control group (PPV-), at 2 months (±30 days), 4 months (±30 days), and 6 months (±30 days) of age. RESULTS: A total of 82 infants completed the study (at least 2 of 3 evaluations), 35 (77%) in the PPV+ and 47 (78.3%) in the PPV- groups, respectively. Infant gender, HIV infection status, number of adults, children, and smokers in the household, day-care attendance, occurrence of respiratory signs, and cotrimoxazole use were similar in both groups. NPC rates increased equally with age in both groups (2 months = 26.7% vs. 25.6%; 4 months = 34.5% vs. 38.6%; 6 months = 38.7% vs. 56.3%, in PPV+ and PPV-, respectively). After controlling for potential confounders, we found no association between maternal vaccination and infant pneumococcal carriage (adjusted odds ratio = 0.70; 95% confidence interval: 0.23, 2.21) CONCLUSIONS: Vaccination of HIV-infected mothers with PPV did not protect infants younger than 6 months of age from nasopharyngeal pneumococcal carriage.

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency.

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children's growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling.

Nasopharyngeal colonization with Streptococcus pneumoniae in children infected with human immunodeficiency virus.

OBJECTIVES: To determine the prevalence of pneumococcus colonization among HIV-infected outpatients aged 0 to 18 years. To determine the resistance to penicillin of the microorganisms observed, to identify their serotypes, and to determine whether there are associations between known risk factors and colonization in this group. MATERIAL AND METHOD: This was an observational and cross-sectional study in which nasopharynx swabs were collected from 112 children on the occasion of their monthly appointments and a questionnaire applied to the mothers. The material collected was processed at the microbiology laboratory of the hospital in accordance with National Committee for Clinical Laboratory Standards (NCCLS) regulations and serotyping was performed at the Centers for Diseases Control and Prevention (CDC). Data were analyzed statistically using the chi-square test and with univariate and multivariate analysis with multiple logistic regression. RESULTS: The prevalence rate of nasopharyngeal colonization by pneumococci was 28.6%, with a 15.6% rate of resistance to penicillin (6.2% intermediate resistance and 9.4% full resistance). The serotypes identified were 6A, 6B, 7C, 9V, 11A, 13, 14, 15A, 16F, 18C, 19B, 19F, 23B, 23F, and 34. In this population there were no associations between pneumococcal colonization and the risk factors studied. CONCLUSIONS: The prevalence of pneumococcal colonization among HIV-infected children at our service was not higher than prevalence rates observed in healthy children and reported in the literature.

Nasopharyngeal colonization with Streptococcus pneumoniae in children infected with human immunodeficiency virus

OBJECTIVE: To determine the prevalence of pneumococcus colonization among HIV-infected outpatients aged 0 to 18 years. To determine the resistance to penicillin of the microorganisms observed, to identify their serotypes, and to determine whether there are associations between known risk factors and colonization in this group. MATERIAL AND METHOD: This was an observational and cross-sectional study in which nasopharynx swabs were collected from 112 children on the occasion of their monthly appointments and a questionnaire applied to the mothers. The material collected was processed at the microbiology laboratory of the hospital in accordance with National Committee for Clinical Laboratory Standards (NCCLS) regulations and serotyping was performed at the Centers for Diseases Control and Prevention (CDC). Data were analyzed statistically using the chi-square test and with univariate and multivariate analysis with multiple logistic regression. RESULTS: The prevalence rate of nasopharyngeal colonization by pneumococci was 28.6%, with a 15.6% rate of resistance to penicillin (6.2% intermediate resistance and 9.4% full resistance). The serotypes identified were 6A, 6B, 7C, 9V, 11A, 13, 14, 15A, 16F, 18C, 19B, 19F, 23B, 23F, and 34. In this population there were no associations between pneumococcal colonization and the risk factors studied. CONCLUSIONS: The prevalence of pneumococcal colonization among HIV-infected children at our service was not higher than prevalence rates observed in healthy children and reported in the literature.