La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Analysis of Clinical/Neurobehavioral Outcomes and Predictors of Disease Severity.

BACKGROUND: La Crosse virus (LACV) is the most common neuroinvasive arboviral infection in children in the United States. However, data regarding predictors of disease severity and neurologic outcome are limited. Additionally, long-term neurologic and neurobehavioral outcomes remain relatively sparse. METHODS: This was a single-center, retrospective cohort study, followed by recruitment for a cross-sectional analysis of long-term neurobehavioral outcomes, among children aged 0-18 years with proven or probable LACV neuroinvasive disease (LACV-ND) between January 2009 and December 2018. Case ascertainment was assured by International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes cross-referenced with laboratory results detecting LACV. Demographics, diagnostics, radiographs, and outcomes were evaluated. Recruitment of patients with prior diagnosis of LACV-ND occurred from January 2020 to March 2020, with assessment performed by validated pediatric questionnaires. RESULTS: One-hundred fifty-two children (83 males; median age, 8 years [interquartile range, 5-11.5 years]) were diagnosed with proven (n = 61 [47%]) and probable (n = 91 [60%]) LACV-ND. Sixty-five patients (43%) had severe disease. Altered mental status (AMS) (odds ratio [OR], 6.36 [95% confidence interval {CI}, 2.03-19.95]; P = .0002) and seizures at presentation (OR, 10.31 [95% CI, 3.45-30.86]; P = .0001) were independent predictors of severe disease. Epileptiform discharges on electroencephalogram (EEG) were independently associated with epilepsy diagnosis at follow-up (OR, 13.45 [95% CI, 1.4-128.77]; P = .024). Fifty-four patients were recruited for long-term neurobehavioral follow-up, with frequent abnormal assessments identified (19%-54%) irrespective of disease severity. CONCLUSIONS: Severe disease was observed frequently among children with LACV-ND. Seizures and AMS at presentation were independent predictors of severe disease. EEG may help determine long-term epilepsy risk. Long-term neurobehavioral issues are frequent and likely underrecognized among children with LACV-ND.

EVALI versus MIS-C, one more overlapping diagnosis to consider.

We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased D-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities. SARS-CoV-2 polymerase chain reaction and serologies were negative. All patients reported a history of vaping, prompting E-cigarette, or vaping, product use-associated lung injury (EVALI) diagnosis. MIS-C has overlapping clinical and laboratory features highlighting the added challenge of diagnosing EVALI during the COVID-19 pandemic. Keywords COVID-19 pandemic, EVALI, MIS-C.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection.

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Completion of therapy for latent tuberculosis in children of different nationalities.

We performed a retrospective review of prospectively stored data on 545 children from 54 different birth countries with latent tuberculosis cared for in a pediatric tuberculosis clinic between August 1, 2005 and July 31, 2006. For analysis, patients were grouped into 6 geographic regions. The overall rate of completion of therapy was 54.4%. There were no significant differences among regions in the rate of completion of therapy by age, duration in the United States, or exposure to active tuberculosis. However, no children from Eastern Europe completed therapy compared with 67.9% from Central and South America. Of those children who did not complete therapy, parental refusal to start medication accounted for 54% and 80% of Eastern European and Asian children compared with <10% of children from Sub-Saharan Africa, Central and South America, and the United States.

Immunotherapy to reconstitute immunity to DNA viruses.

Defects in cytotoxic T-lymphocyte (CTL) function after hemopoietic stem cell transplantation (HSCT) are associated with an increased frequency and severity of viral diseases. Initial investigations of viral infections in immunosuppressed mice and subsequent clinical studies of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in human stem cell transplant patients have suggested that adoptive transfer of virus-specific T cells may restore protective immunity and control established infections. Current efforts focus on optimizing adoptive immunotherapy approaches and developing strategies for generating T cells specific for multiple viruses to provide broader protection.