Genetic Variants and Immune Responses in a Cohort of Patients With Varicella Zoster Virus Encephalitis.

BACKGROUND: Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in which otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection. METHODS: We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were evaluated. Data were analyzed by Mann-Whitney U test. RESULTS: We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients. CONCLUSIONS: This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.

Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus.

Varicella-zoster virus (VZV) is a common cause of viral central nervous system (CNS) infection, and patients may suffer from severe neurological sequelae. The biomarker neurofilament light chain (NFL) is used for assessment of neuronal damage and is normally measured in cerebrospinal fluid (CSF). Novel methods have given the possibility to measure NFL in serum instead, which could be a convenient tool to estimate severity of disease and prognosis in VZV CNS infections. Here, we investigate the correlation of serum and CSF NFL in patients with VZV CNS infection and the association of NFL levels in serum and CSF with different VZV CNS entities. NFL in serum and CSF was measured in 61 patients who were retrospectively identified with neurological symptoms and VZV DNA in CSF detected by PCR. Thirty-three herpes zoster patients and 40 healthy blood donors served as control groups. NFL levels in serum and CSF correlated strongly in the patients with VZV CNS infection. Encephalitis was associated with significantly higher levels of NFL in both serum and CSF compared with meningitis and Ramsay Hunt syndrome. Surprisingly, herpes zoster controls had very high serum NFL levels, comparable with those shown in encephalitis patients. We show that analysis of serum NFL can be used instead of CSF NFL for estimation of neuronal injury in patients with VZV CNS infection. However, high levels of serum NFL also in patients with herpes zoster, without signs of CNS involvement, may complicate the interpretation.

Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections.

In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from breakthrough infections was identified. Our results indicate that a high risk of onward transmission is limited to naïve infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.

Infant outcome at four years of age after intrapartum sampling of scalp blood lactate for fetal assessment. A cohort study.

OBJECTIVE: To correlate the value of lactate in fetal scalp blood at delivery and the outcomes of the offspring at four years of age. METHODS: Cases where scalp blood lactate was taken within sixty minutes before delivery were identified from the randomized trial "Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress". Data were grouped according to the generally accepted cutoffs for normality, pre-acidemia, acidemia and concentrations above mean +2 SD during the second stage. The outcome measures included gross-/fine motor function, vision, hearing, speaking and cognitive disorders, signs of central motor damage and referral to specialized pediatric services. RESULTS: 307 cases were available for final analyse. With normal scalp lactate concentration, the number of children with a diagnosed disorder was lower compared to the pre-acidemic/acidemic groups, although the findings were only significant for fine motor dysfunction (p = 0.036). Elevated lactate values were significantly associated with increased risk for a poorer capacity of attention and understanding of instructions (OR 1.37, 95% CI 1.07-1.74), and for fine motor dysfunction (OR 1.22, 95% CI 1.00-1.49) at the age of four. CONCLUSION: Higher levels of lactate in fetal scalp blood seems to be associated with increased risk of an aberrant developmental outcome at four years of age in some areas.