Pediatric Infectious Disease Journal最新文献

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.

Using the Data Evaluation and Preparation for HIV-Exposed Uninfected Child Cohorts project's standardized child HIV exposure definitions, 64%, 64% and 90% of children exposed to HIV in utero could be classified as HIV-uninfected with moderate or high certainty at the ages of 1 and 3 years and at the time of first infectious disease hospitalization, respectively. These definitions can be applied retrospectively to routine datasets with linked mother-child data.

Background: Associations between ganciclovir and severe nephrotoxicity are incompletely defined. Studies incorporating the time-varying nature of medication exposures and those that address confounding by indication are particularly scarce in children undergoing hematopoietic cell transplantation.

Methods: We identified children undergoing hematopoietic cell transplantation in the Pediatric Health Information System database and tracked them for 1 year following transplantation. The primary exposure of interest was the use of ganciclovir, which was treated as a time-varying variable. Secondary exposures of interest included cidofovir, foscarnet, amphotericin B, aminoglycosides, vancomycin and calcineurin inhibitors. The primary outcome of interest was renal replacement therapy, which was assessed using marginal structural Cox proportional hazards regression model incorporating time-varying variables and inverse-probability-of-treatment weight.

Results: Of 17,924 children who underwent hematopoietic cell transplantation during the study period, 3078 (17.2%) had exposure to ganciclovir. In marginal structural Cox proportional hazards regression model incorporating time-varying variables and inverse-probability-of-treatment weight, ganciclovir was associated with an increased hazard of renal replacement therapy (adjusted hazard ratio: 1.84, 95% confidence interval: 1.22-2.76). Some of secondary exposures of interest, including cidofovir, amphotericin B and vancomycin, also were associated with renal replacement therapy.

Conclusions: Intravenously administered ganciclovir is associated with renal dysfunction severe enough to require renal replacement therapy in pediatric hematopoietic cell transplant recipients. Ganciclovir should be used with caution and close monitoring. Approaches to mitigate the risks of nephrotoxicity should be investigated.

Background: Pretreatment of HIV drug resistance among children living with HIV (CLHIV) can compromise antiretroviral therapy (ART) effectiveness. Resistance may be transmitted directly from mothers or acquired following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis.

Methods: We performed resistance testing in children aged <3 years, newly diagnosed with HIV in Western Cape, South Africa (2021-2022), who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/or (2) were exposed to protease inhibitors or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as testing HIV-polymerase chain reaction positive at age >28 days, after previously testing negative. We used surveillance drug-resistance mutation lists to define mutations.

Results: We included 135 CLHIV. Most mothers started ART prepregnancy (73%). Overall, 57% (77/135) of children had resistance mutations detected. Nonnucleoside reverse transcriptase inhibitor-associated, nucleoside reverse transcriptase inhibitor-associated, protease inhibitor-associated and INSTI-associated mutations were found in 55% (74/135), 10% (13/135), <1% (1/135) and <1% (1/122) of children tested, respectively. One child with breastfeeding transmission had high-level INSTI resistance detected at HIV diagnosis, aged 18 months (E138K and G118R mutations).

Conclusions: Although not clinically relevant, nonnucleoside reverse transcriptase inhibitor-associated mutations were common. Dolutegravir is currently the preferred first-line treatment for adults and CLHIV age ≥4 weeks, and although very low INSTI resistance levels have been observed in adults, limited data exist on genotyping the integrase region in children. Pretreatment INSTI resistance in children is likely to be unusual, but future surveillance, including longitudinal studies with paired mother-child resistance testing, is needed.

Japan experienced a large outbreak of wild poliovirus in the 1960s. The government made an exceptional decision to import oral polio vaccines (OPVs) from the Soviet Union and Canada while bypassing the usual approval process for medical products. Mass vaccination and subsequent, routine immunization successfully contained the wild poliovirus; the last case in Japan was reported in 1980. Domestic OPV had been used to sustain Japan's polio-free state. In 2012, the world's first inactivated polio vaccine developed from the Sabin vaccine replaced OPVs. Domestic vaccines combined with Sabin-derived inactivated polio vaccine are currently used in Japan. When the World Health Assembly announced the Global Polio Eradication Initiative in 1988, the Japanese government made a commitment to support endemic countries. The Japan International Cooperation Agency supported the establishment of microbiological laboratories, surveillance, distribution of polio vaccines and capacity building. Vaccine-derived poliovirus emerged as a new, international risk in the early 2000s. Vaccine-derived poliovirus was also detected in several Asian countries and required an outbreak response with additional vaccinations and strengthened surveillance. Genetically stable, novel, oral polio vaccine type 2 became available for use in outbreak responses and was used in Indonesia. Japan maintains its commitment to work toward the eradication of the poliovirus.

Background: The spectrum and incidence of influenza-associated neuropsychiatric complications are not well-characterized. The objective of this study was to define the incidence of specific neurologic and psychiatric complications associated with influenza in children and adolescents.

Methods: We assembled a retrospective cohort of children 5-17 years of age with an outpatient or emergency department International Classification of Diseases, 10th revision influenza diagnosis and enrolled in Tennessee Medicaid from 2016 to 2020. Serious neurologic or psychiatric complications requiring hospitalization were identified using a validated algorithm. Incidence rates of complications were expressed per 100,000 person-weeks of influenza and 95% confidence intervals (CIs) were reported.

Results: A total of 156,661 influenza encounters (median age of 9.3 years) were included. The overall incidence of neurologic complications was 30.5 (95% CI: 24.0-38.6) per 100,000 person-weeks of influenza and 1880.9 (95% CI: 971.9-3285.5) among children with an underlying neurologic comorbidity. The distribution of antiviral treatment was similar among those with and without neurologic or psychiatric complications. The overall incidence of psychiatric complications was 20.2 (95% CI: 15.1-27.0) per 100,000 person-weeks of influenza and 111.8 (95% CI: 77.9-155.5) among children with an underlying psychiatric comorbidity. Seizures (17.5, 95% CI: 12.8-23.9) were the most common neurologic complications whereas encephalitis (0.5, 95% CI: 0.02-2.5) was rare. Mood disorders (17.5, 95% CI: 12.8-23.9) were the most frequent psychiatric complications and self-harm events (0.9, 95% CI: 0.3-3.3) were the least common.

Discussion: Our findings reveal that the incidence of neuropsychiatric complications of influenza is overall low; however, the incidence among children with underlying neurologic or psychiatric condition is significantly higher than among children without these conditions.

We investigated if children with Long Covid (n=14) have activated platelets compared with healthy controls (n=14). Platelet activation and secretion markers were investigated by flow cytometry using MoAbs directed against P-selectin, CD63, and PAC-1 in quiescent platelets and in platelets stimulated with 10-µM adenosine diphosphate and 25-µM protease activated receptor 1-activating peptide. Circulating platelets of patients with Long Covid had significantly increased expression of the activation marker cytometry using MoAbs directed against P-selectin (P = 0.019).