Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study.

OBJECTIVES: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. METHODS: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. RESULTS: Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. CONCLUSIONS: In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.

Reinfection or relapse? A case study of whole genome sequencing guided genomic characterization of Mycobacterium abscessus chronic infection in a cystic fibrosis patient.

A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declining pulmonary function was diagnosed with clarithromycin resistant Mycobacterium abscessus infection. Treatment was initiated with clofazimine, linezolid and cefoxitin; she responded well to therapy and achieved microbiological clearance after completion of 12-month treatment. One year later, she had re-emergence of worsening symptoms and her sputum culture again grew clarithromycin resistant M. abscessus. Using a laboratory developed whole genome sequencing (WGS) test, the bacterium was determined to be the same strain with the same resistance mechanisms, indicating a relapse. This was deemed a critical element of clinical information, as the isolation of a genetically distinct organism would have indicated a new infection and would have served as evidence that a 12-month regimen was likely sufficient to achieve eradication. The confirmation of a relapse prompted the prolongation of the therapy plan to a goal of 24 months. Reinfection and relapse are great challenges in patients with cystic fibrosis who may acquire new strain of M. abscessus from the environment, may harbor multiple subpopulations of bacteria, or may have persistent infections but intermittent bacteria shedding that could not be eradicated. WGS has emerged as a powerful molecular tool to accurately differentiate re-infection from relapse thus solving this conundrum.

Unique Case of Disseminated Plague With Multifocal Osteomyelitis.

Plague is a disease caused by Yersinia pestis. Septicemic and pneumonic plague have a high mortality rate if untreated. Here we describe the challenges of accurately diagnosing a nonfatal pediatric case of septicemic plague with involvement of multiple organs; to our knowledge, the first documented case of multifocal plague osteomyelitis.

Herpes Zoster Meningitis Presenting With a Cerebrospinal Fluid Leukemoid Reaction in an Adolescent With preB-ALL in Remission.

A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia.

Pediatric HIV-1-specific cytotoxic T-lymphocyte responses suggesting ongoing viral replication despite combination antiretroviral therapy.

Human immunodeficiency virus-1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses are common in infected adults and usually exhibit rapid decay after combination antiretroviral therapy (ART). CTLs develop later in the first year of life, and the fate of HIV-1-specific responses in perinatally infected children after ART is less well described. HIV-1-specific CTL responses were measured in 17 perinatally infected children and adolescents (ages 3-20 y) receiving combination ART. Seven had prolonged viral suppression (<400 copies/mL) for 2.5-5.3 y and 10 had persistent viremia (median, 77,550 copies/mL). HIV-1-specific CTL responses were tested by interferon (IFN)-gamma enzyme-linked immunospot (ELIS-pot) assays using 53 overlapping peptide pools spanning the entire HIV-1 proteome. HIV-1-specific CTL responses were detected in 14 of 17 individuals. Responses to one to four viral proteins were found in eight of 10 individuals with persistent viremia and six of seven with prolonged viral suppression. The magnitude and breadth of CTL responses were similar between groups. HIV-1-specific CTL responses were present in the majority of perinatally infected subjects, irrespective of viremia at evaluation. Because ART-treated infected adults usually have rapid decay of responses, these data suggest viral replication below the limits of detection is more persistent in combination ART-treated perinatally infected pediatric subjects. The long-term clinical implications of these findings remain to be determined.

HIV-1 vaccine induced immune responses in newborns of HIV-1 infected mothers.

OBJECTIVE: Breast milk transmission continues to account for a large proportion of cases of mother-to-child transmission of HIV-1 worldwide. An effective HIV-1 vaccine coupled with either passive immunization or short-term antiretroviral prophylaxis represents a potential strategy to prevent breast milk transmission. This study evaluated the safety and immunogenicity of ALVAC HIV-1 vaccine with and without a subunit envelope boost in infants born to HIV-1-infected women. DESIGN: : Placebo-controlled, double-blinded study. METHODS: Infants born to HIV-1-infected mothers in the US were immunized with a prime-boost regimen using a canarypox virus HIV-1 vaccine (vCP1452) and a recombinant glycoprotein subunit vaccine (rgp120). Infants (n = 30) were randomized to receive: vCP1452 alone, vCP1452 + rgp120, or corresponding placebos. RESULTS: Local reactions were mild or moderate and no significant systemic toxicities occurred. Subjects receiving both vaccines had gp120-specific binding serum antibodies that were distinguishable from maternal antibody. Repeated gp160-specific lymphoproliferative responses were observed in 75%. Neutralizing activity to HIV-1 homologous to the vaccine strain was observed in 50% of the vCP1452 + rgp120 subjects who had lost maternal antibody by week 24. In some infants HIV-1-specific proliferative and antibody responses persisted until week 104. HIV-1-specific cytotoxic T lymphocyte responses were detected in two subjects in each treatment group; the frequency of HIV-1 specific cytotoxic T lymphocyte responses did not differ between vaccine and placebo recipients. CONCLUSION: The demonstration of vaccine-induced immune responses in early infancy supports further study of HIV-1 vaccination as a strategy to reduce breast milk transmission.

Nocardia asteroides brain abscesses and meningitis in an immunocompromized 10-year-old child.

Nocardiosis is an uncommon pediatric infection. We describe the successful treatment of Nocardia brain abscesses and meningitis in an immunocompromized boy with a history of both liver and bone marrow transplants.

Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution.

The purpose of this study was to determine the incidence of fungal infections in pediatric hematology and oncology (PHO) patients and to describe variations regarding site of infection, organisms, and mortality. The records of 1,052 patients presenting to the UCLA PHO service with various malignancies from 1991 to 2001 were retrospectively reviewed. No patient received invasive antifungal prophylaxis. Transplant patients were excluded. The 11-year incidence of fungal infections in this pediatric oncology cohort was 4.9%. There was a linear increase in the incidence of fungal infections from 2.9% to 7.8% between 1996 and 2001 (P = 0.001). Patients with acute leukemia represented 36% of the population but had a disproportionate incidence (67%) of fungal infections. Adolescents had twice the expected incidence of infection (P < 0.0001). Overall, Candida sp. was the major pathogen. Over time, a trend of fewer infections caused by Candida and more due to Aspergillus was noted. Blood-borne infections decreased over time, while those in the urinary and respiratory tracts increased (P = 0.04). Sixty-two percent of infections occurred in neutropenic patients. PHO patients had an overall mortality of 21%, but those with fungal infections experienced a 2.6-fold higher mortality that was not attributable to infections alone. Empiric antifungal therapy had no effect on mortality rates. Concurrent nonfungal infections did not increase mortality rates. The incidence of fungal infections increased over time, possibly as a result of advances in antibacterial and chemotherapeutic regimens. Adolescents and patients with leukemia were especially at risk. Fungal infections are a poor prognostic factor, independent of fungal-related mortality. New diagnostic methods allowing for early detection and treatment as well as more effective therapies are needed.

Factores de riesgo para infección por Virus de Hepatitis B en personal hospitalario / Risk factors for Virus B Hepatitis infection in hospital personnel

La hepatitis viral es una de las principales causas de enfermedad en el mundo. En Latinoamérica es un importante problema de salud. Se realizó un estudio caso-control buscando factores de riesgo para infección por virus de hepatitis B. Encontramos 0.41% de frecuencia de HBsAg y 8.13% de Anti-HBs entre las 492 personas muestreadas. Se confirmó que el contacto con sangre es un factor de riesgo para infección por Virus de hepatitis B; el lavado de agujas hipodérmicas usadas fue edentificado como un importante factor de riesgo. Entre los servicios del hospital se encontró que el personal de la sala de esterilización se hallaba en elevado riesgo de infección. El personal auxiliar de enfermería también fue identificado como en alto riesgo. Sugerimos que debe erradicarse el lavado de agujas y se debe eliminar el sistema de rotaciones del personal auxiliar de enfermería