Oseltamivir treatment of influenza A and B infections in infants

BackgroundOseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group.MethodsIn a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017‐June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re‐examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms <48 hours received oseltamivir treatment. The parents filled out daily symptom diaries.ResultsAmong 23 infants with influenza A, the mean total duration of illness in oseltamivir recipients was 82.1 hours, compared with 253.5 hours in infants without treatment (P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir‐treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1‐2 days after the initiation of oseltamivir treatment.ConclusionsOseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections.     

Intratonsillar detection of 27 distinct viruses: A cross-sectional study

Palatine tonsils have been observed to harbor several distinct respiratory and herpesviruses in separate studies. In this study, the presence of these viruses in palatine tonsils was comprehensively studied in both children and adults. A cross-sectional analysis of 181 patients (median age 22 years; range, 2.6-66) operated for a benign tonsillar disease was conducted. Real-time polymerase chain reaction was performed to detect 27 distinct viruses in all: eight human herpesviruses, 16 respiratory viruses, parvo B19, and polyoma BK/JC viruses. Clinical characteristics of the patients and underlying conditions were evaluated. In total, 92% of patients had virus detected in tonsils (Epstein-Barr virus 72%, human herpesvirus 7, and 6B 54% and 16%, respectively, enterovirus 18%, parvovirus B19 7% and the rest <4%). No herpes simplex virus 2, varicella zoster virus, polyoma JC virus, parainfluenza-, metapneumo-, or coronaviruses were found. Enterovirus was more common in children and was frequently observed in the presence of HHV6B. None of the viruses showed a positive association to the tonsillar disease. Respiratory symptoms were not associated with the prevalence of viruses. This study comprehensively reports a cross-sectional view of intratonsillar virus infections in elective tonsillectomy patients in a wide age range cohort. Tonsils are a major virus reservoir for distinct herpes and respiratory viruses without a positive association with tonsillar disease or respiratory symptoms.     

The In Vitro Replication,Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1

Herpes simplex virus type 1 (HSV-1) is the only FDA- and EMA- approved oncolytic virus, and accordingly, many potential oncolytic HSVs (oHSV) are in clinical development. The utilized oHSV parental strains are, however, mostly based on laboratory reference strains, which may possess a compromised cytolytic capacity in contrast to circulating strains of HSV-1. Here, we assess the phenotype of thirty-six circulating HSV-1 strains from Finland to uncover their potential as oHSV backbones. First, we determined their capacity for cell-to-cell versus extracellular spread, to find strains with replication profiles favorable for each application. Second, to unfold the differences, we studied the genetic diversity of two relevant viral glycoproteins (gB/UL27, gI/US7). Third, we examined the oncolytic potential of the strains in cells representing glioma, lymphoma, and colorectal adenocarcinoma. Our results suggest that the phenotype of a circulating isolate, including the oncolytic potential, is highly related to the host cell type. Nevertheless, we identified isolates with increased oncolytic potential in comparison with the reference viruses across many or all of the studied cancer cell types. Our research emphasizes the need for careful selection of the backbone virus in early vector design, and it highlights the potential of clinical isolates as backbones in oHSV development.     

L-cysteine augments the vasorelaxation induced by sodium nitrite and SIN-1 but not that due to acetylcholine.

The effects of 1 mM L-cysteine on sodium nitrite-, 3-morpholinosydnonimine (SIN-1)- and acetylcholine-induced relaxation and cyclic GMP accumulation were studied in isolated noradrenaline-precontracted rat mesenteric arterial rings. L-Cysteine augmented the relaxation and cyclic GMP increase induced by sodium nitrate and SIN-1 but not those induced by acetylcholine. The effects of L-cysteine on relaxation were independent of the presence of intact endothelium. The results suggest that L-cysteine protects exogenously released nitric oxide.     

Early selegiline therapy reduces levodopa dose requirement in Parkinson's disease

In an earlier report of our placebo-controlled selegiline trial on de novo parkinsonian patients, we have shown that the need to start additional levodopa therapy is significantly postponed by using selegiline monotherapy. Now we report the two-year interim results of the double-blind continuation of the trial in 44 patients after the introduction of levodopa to the earlier therapy with placebo or selegiline (21 and 23 patients, respectively). The clinical disability was assessed by three rating scales. The daily dose of levodopa needed to maintain an optimal condition had to be increased progressively up to a 52% higher level in the placebo group than in the selegiline group (543 ± 150 and 358 ± 117 mg, respectively, p<0.001). The number of daily doses of levopoda was also statistically significantly higher in the placebo group during the 24 months' observation period (p<0.01). The ratio of levodopa doses that was expected to stay the same contrarily significantly increased suggesting that selegiline would, besides having the levodopa potentiating effect, also have a beneficial influence on the progression of the basic cerebral dopamine deficiency. The combination of selegiline and levodopa was well tolerated, and the adverse event profiles did not differ from each other. In conclusion, early selegiline therapy allows a significant saving in the subsequent levodopa dosage. This saving seems to become even stronger along with the treatment time.     

Polyomaviruses BK,JC, KI,WU, MC,and TS in children with allogeneic hematopoietic stem cell transplantation

Timely and reliable detection of viruses is of key importance in early diagnosis of infection(s) following allogeneic HSCT. Among the immunocompetent, infections with BKPyV and JCPyV are mostly subclinical, while post‐HSCT, the former may cause HC and the latter PML. The epidemiology and clinical impact of the newly identified KIPyV, WUPyV, MCPyV, and TSPyV in this context remain to be defined. To assess the incidence and clinical impact of BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, and TSPyV infections, we performed longitudinal molecular surveillance for DNAemias of these HPyVs among 53 pediatric HSCT recipients. Surveillance pre‐HSCT and for three months post‐HSCT revealed BKPyV DNAemia in 20 (38%) patients. Our data demonstrate frequent BKPyV DNAemia among pediatric patients with HSCT and the confinement of clinical symptoms to high copy numbers alone. MCPyV and JCPyV viremias occurred at low and TSPyV viremia at very low prevalences. KIPyV or WUPyV viremias were not demonstrable in this group of immunocompromised patients.