Influenza A (H3) illness and viral aerosol shedding from symptomatic naturally infected and experimentally infected cases.

BACKGROUND: It has long been known that nasal inoculation with influenza A virus produces asymptomatic to febrile infections. Uncertainty persists about whether these infections are sufficiently similar to natural infections for studying human-to-human transmission. METHODS: We compared influenza A viral aerosol shedding from volunteers nasally inoculated with A/Wisconsin/2005 (H3N2) and college community adults naturally infected with influenza A/H3N2 (2012-2013), selected for influenza-like illness with objectively measured fever or a positive Quidel QuickVue A&B test. Propensity scores were used to control for differences in symptom presentation observed between experimentally and naturally infected groups. RESULTS: Eleven (28%) experimental and 71 (86%) natural cases shed into fine particle aerosols (P < .001). The geometric mean (geometric standard deviation) for viral positive fine aerosol samples from experimental and natural cases was 5.1E + 3 (4.72) and 3.9E + 4 (15.12) RNA copies/half hour, respectively. The 95th percentile shedding rate was 2.4 log10 greater for naturally infected cases (1.4E + 07 vs 7.4E + 04). Certain influenza-like illness-related symptoms were associated with viral aerosol shedding. The almost complete lack of symptom severity distributional overlap between groups did not support propensity score-adjusted shedding comparisons. CONCLUSIONS: Due to selection bias, the natural and experimental infections had limited symptom severity distributional overlap precluding valid, propensity score-adjusted comparison. Relative to the symptomatic naturally infected cases, where high aerosol shedders were found, experimental cases did not produce high aerosol shedders. Studying the frequency of aerosol shedding at the highest observed levels in natural infections without selection on symptoms or fever would support helpful comparisons.

Minimal transmission in an influenza A (H3N2) human challenge-transmission model within a controlled exposure environment.

Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer 'Donors' (n = 52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). 'Recipients' randomized to Intervention (IR, n = 40) or Control (CR, n = 35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p = 0.47 for group difference), and 1.3% overall, significantly less than 16% (p<0.001) expected based on a proof-of-concept study secondary attack rate and considering that there were twice as many Donors and days of exposure. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols.

Blood Epstein-Barr virus DNA does not predict outcome in advanced HIV-associated Hodgkin lymphoma.

In HIV-seronegative patients with advanced Hodgkin lymphoma (HL), Epstein-Barr virus (EBV) viraemia at diagnosis predicts a worse progression-free survival (PFS), independent of the International Prognostic Score. However, its role in HIV-associated HL is uncharacterised. We collected clinico-pathologic and treatment data from a prospective series of 44 HIV-associated HLs from 2000 to 2016. We evaluated circulating EBV DNA as a prognostic factor on uni- and multivariable analyses in relationship to the International Prognostic Index criteria. In 44 patients with HIV-associated HL, EBV was detected by in situ hybridisation in all diagnostic biopsies. Blood EBV DNA was detectable in 26 patients (59%) with a median of 600 copies/mL (range 0-161,000). EBV DNA was independent of CD4 cell count (p = 0.9) or HIV viral load (p = 0.6) and did not predict PFS (HR 1.6, 95% CI 0.39-6.7, p = 0.49). EBV DNA is not a prognostic trait in HIV-associated HL. Prognostication in HIV-associated HL should be solely based on the International Prognostic Index criteria.

Neuroglian and FasciclinII can promote neurite outgrowth via the FGF receptor Heartless.

To further investigate the role of the Drosophila cell adhesion molecules (CAMs), we have developed an in vitro assay that allows us to test the contribution individual CAMs make to promote outgrowth of specific Drosophila neurons. The extension of primary cultured neurons on a substrate of purified recombinant CAM is measured. We show that both FasciclinII and Neuroglian are able to promote outgrowth of FasciclinII or Neuroglian expressing neurons, respectively. Furthermore, this growth promotion activity is provided when the CAMs are presented both in a substrate bound or soluble form. We also show that the signal provided by the CAMs acts via the Heartless fibroblast growth factor receptor (FGFR) as outgrowth is reduced to basal levels in the presence of an FGFR inhibitor or if Heartless function is missing from the neurons.