Does CETP rs5882, rs708272, SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, VEGFA rs833068, IL6 rs1800795 polymorphisms play a role in optic neuritis development?

Objectives: Optic neuritis (ON) is defined as inflammation of the optic nerve, which is mostly idiopathic. However, it can be associated with various causes (demyelinating lesions, autoimmune disorders, infectious and inflammatory conditions). Inflammatory demyelinating disorder of the optic nerve can be associated with multiple sclerosis. It is thought that CETP, SIRT1, FGFR2, STAT3, VEGFA and IL6 genes play a key role in this autoimmune inflammatory disease. The aim of our study was to determine if the frequency of the CETP, SIRT1, FGFR2, STAT3, VEGFA and IL6 gene polymorphisms have an influence on the development of acute ON.

Methods: The study enrolled patients with ON and a random sample of healthy population. The genotyping test of the CETPrs5882,rs708272, SIRT1rs12778366, FGFR2rs2981582, STAT3rs744166, VEGFArs833068, IL6rs1800795 polymorphisms was carried out using the RT-PCR method.

Results: Our study determined that the G/A genotype of CETPrs708272 was associated with two-fold-decreased odds of ON development under the codominant (OR = 0.495;95%CI:0.256–0.959) and overdominant (OR = 0.501;95%CI:0.280–0.895) models. Also, each allele C at VEGFArs833068 was associated with 1.7-fold increased odds of ON development under the additive model (OR = 1.733;95%CI:1.148–2.615). Furthermore, IL6 rs1800795 G/G genotype was associated with increased odds of ON development under the codominant (OR = 2.869;95%CI:1.280–6.434) and recessive (OR = 2.315;95%CI:1.251–4.285) models.

Conclusions: We revealed that the genotypes of CETPrs708272 G/A, IL6rs1800795 G/G, and each allele C at VEGFArs833068 were associated with ON. CETPrs708272 G/G genotype was associated with decreased by 62% odds of ON with MS development under the recessive (OR = 0.379;95%CI:0.155–0.929; p = .034) model.     

Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children

Background

There were increased reports of fevers and febrile reactions in young children (particularly children aged <5?years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis

BackgroundSerotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease.MethodsWe performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data.ResultsTwo published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2–75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7–76.9%]). No heterogeneity was observed.ConclusionsCurrently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.     

Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-α. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups.