Anti-NMDAR Encephalitis After Neonatal HSV-1 Infection in a Child With Low TLR-3 Function.

Neonatal herpes simplex virus encephalitis (HSVE) often results in long-lasting neuro-disability in affected children. In addition to primary HSVE and HSVE relapses, children with herpes simplex virus are at increased risk of developing anti-N-methyl-d-aspartate receptor encephalitis (NMDARe), an autoimmune encephalitis. In this study, we describe a patient with neonatal disseminated herpes infection, who developed HSVE after discontinuation of 2 years of acyclovir suppressive therapy. After resolution of HSVE, the patient rapidly deteriorated with significant behavioral and neurologic changes including emotional outbursts, fearfulness, involuntary movements, and focal seizures. The patient was diagnosed with anti-NMDARe and was later found to have low toll-like receptor-3 function. In this study, we review published pediatric cases of anti-NMDARe after HSVE as well as previous literature and primary data examining the presentation, predisposing risk factors, predictive outcomes, future directions, and the role of immunodeficiency in HSVE-mediated anti-NMDARe. The neonatal immune system and developing brain are disproportionately vulnerable to early viral exposure; therefore, it is important to recognize the value of early immunodeficiency screening in patients with neonatal herpes simplex virus. By understanding the immune landscape within this patient population, we can mitigate long-term neurologic disability and improve the quality of life of affected children.

Long-term follow-up of post-cardiac surgery Mycobacterium chimaera infections: A 5-center case series.

OBJECTIVES: In multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3-7 years of follow-up for survivors. METHODS: Identified at five hospitals in the United States 2010-2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. RESULTS: Of 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). CONCLUSIONS: Given poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

Clostridium septicum gas gangrene in a previously healthy 8-year-old female with survival.

We present the only reported case of an immunocompetent pediatric patient in the literature to have fulminate gas gangrene of the lower extremity and concomitant gastrointestinal tract infection due to Clostridium septicum coinfected with Clostridium difficile colitis respectively. The patient survived with aggressive medical and surgical treatment.

Residual NADPH oxidase activity and isolated lung involvement in x-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is characterized by inherited immune defects resulting from mutations in the NADPH oxidase complex genes. The X-linked type of CGD is caused by defects in the CYBB gene that encodes gp91-phox, a fundamental component of the NADPH oxidase complex. This mutation originates the most common and severe form of CGD, which typically has absence of NADPH oxidase function and aggressive multisystemic infections. We present the case of a 9-year-old child with a rare CYBB mutation that preserves some NADPH oxidase activity, resulting in an atypical mild form of X-linked CGD with isolated lung involvement. Although the clinical picture and partially preserved oxidase function suggested an autosomal recessive form of CGD, genetic testing demonstrated a mutation in the exon 3 of CYBB gene (c.252 G>A, p.Ala84Ala), an uncommon X-linked CGD variant that affects splicing. Atypical presentation and diagnostic difficulties are discussed. This case highlights that the diagnosis of mild forms of X-linked CGD caused by rare CYBB mutations and partially preserved NADPH function should be considered early in the evaluation of atypical and recurrent lung infections.

Directly observed therapy (DOT) for nonadherent HIV-infected youth: lessons learned, challenges ahead.

Adherence to medications is critical to optimizing HIV care and is a major challenge in youth. The utility of directly observed therapy (DOT) to improve adherence in youth with HIV remains undefined and prompted this pilot study. Four U.S. sites were selected for this 24-week cooperative group study to assess feasibility and to identify the logistics of providing DOT to HIV-infected youth with demonstrated adherence problems. Once-a-day DOT was provided by DOT facilitators at the participant's choice of a community-based location and DOT tapered over 12 weeks to self-administered therapy based on ongoing adherence assessments. Twenty participants, median age 21 years and median CD4 227 cells/microl, were enrolled. Participants chose their homes for 82% of DOT visits. Compliance with recommended DOT visits was (median) 91%, 91%, and 83% at weeks 4, 8, and 12, respectively. Six participants completed >90% of the study-specified DOT visits and successfully progressed to self-administered therapy (DOT success); only half sustained >90% medication adherence 12 weeks after discontinuing DOT. Participants considered DOT successes were more likely to have higher baseline depression scores (p = 0.046). Via exit surveys participants reported that meeting with the facilitator was easy, DOT increased their motivation to take medications, they felt sad when DOT ended, and 100% would recommend DOT to a friend. In conclusion, this study shows that while community-based DOT is safe, feasible, and as per participant feedback, acceptable to youth, DOT is not for all and the benefits appear short-lived. Depressed youth appear to be one subgroup that would benefit from this intervention. Study findings should help inform the design of larger community-based DOT intervention studies in youth.

Malignancy in perinatally human immunodeficiency virus-infected children in the United States.

OBJECTIVES: To determine the incidence of and factors associated with malignancy in perinatally human immunodeficiency virus (HIV)-infected children in the United States. METHODS: Included were 2969 children followed in the Pediatric AIDS Clinical Trials Group (PACTG) 219/219C cohort from 1993 through 2003. Cancer incidence by sex, race, age, histology and highly active antiretroviral therapy (HAART) era (pre-HAART, 1993-1997; HAART, 1998-2003) was estimated, and the standardized incidence ratio contrasting infected and uninfected children was determined. Poisson regression was used to further investigate the relation between HAART use (> or =3 drugs of > or =2 classes, 1 of which was a protease inhibitor), CD4% and cancer. RESULTS: There were 37 cancers (17 prevalent and 20 incident) diagnosed in 2969 children for a prevalence of 0.6% [95% confidence interval (CI), 0.3, 0.9] and an incidence of 1.56/1000 person-years (95% CI 0.95, 2.41). Compared with uninfected children, the standardized incidence ratio was 10.08 (95% CI 5.87, 16.14). Incidence did not significantly differ by sex, race, age or HAART era. Of the cases, 35% were immunocompetent (CD4 > or =25%), 25% were moderately immunosuppressed (15%< or = CD4 < or =24%) and 40% were severely immunosuppressed (CD4 <15%) at diagnosis. In multivariate regression, the cancer rate was 3.09 (95% CI 1.22, 7.85) times higher in children with < or =2 years of HAART use than in children with >2 years of HAART and 3.20 (95% CI 1.32, 7.76) times higher in children with CD4 <15% at cohort enrollment than in children with CD4 > or =15%. CONCLUSION: Cancer incidence in this U.S. pediatric cohort was lower than that of European cohorts but was markedly higher than that of HIV-uninfected children. Cancer incidence was highest in children who were severely immunosuppressed and in children who received HAART for < or =2 years.