Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Evaluation of muco-adhesive properties and in vivo activity of ophthalmic vehicles based on hyaluronic acid

A series of prospective ophthalmic vehicles based on hyaluronic acid (HA) and on polyacrylic acid (PAA) (solutions, gels, matrices prepared by compression and by casting) containing pilocarpine (Pi) or tropicamide (Tr) was evaluated for muco-adhesion, for ocular retention and for biological activity (miosis, mydriasis) in rabbits. The muco-adhesive properties were investigated in vitro using a tensile apparatus with mucin-coated surfaces, while the ocular behviour was estimated visually, using vehicles containing a fluorescent marker. Good to excellent muco-adhesive properties were detected in the HA preparations. The bioavailability-enhancing effect, however, was not very satisfactory with Pi, probably on account of the high solubility and diffusivity of the drug. The effect was more evident with the less soluble drug Tr. The validity of the method used for evaluating bioadhesion, and the relevance of the physicochemical characteristics of the drug to a muco-adhesive ocular delivery system are discussed

Evaluation of high- and low-molecular weight fractions of sodium hyaluronate and an ionic complex as adjuvants for topical ophthalmic vehicles containing pilocarpine

Two low-molecular-weight fractions of sodium hyaluronate (Na-HA), denominated Hyalastin® and Hyalectin®, were investigated as potential adjuvants for ophthalmic vehicles containing pilocarpine nitrate (PiN). Tests were also performed on an ionic complex (HA/PiB) prepared from hyaluronic acid (derived from Hyalastin®) and pilocarpine base. The performance of the vehicles under study was verified by miosis and ocular retention tests carried out on albino rabbits, against a series of reference vehicles, three of which contained a high-molecular-weight fraction of Na-HA (Healon®). The group of 14 reference and test preparations exhibited Newtonian or pseudoplastic flow characteristics and encompassed a wide range of apparent viscosities (1 to 1054 mPa s). The results indicate that the HA/PiB salt and the high-MW Na-HA can significantly increase the bioavailability of pilocarpine with respect to reference vehicles of comparable viscosity: an effect that can be reasonably attributed to muco-adhesive effects. Conversely, in the present rabbit tests, the low-MW fractions of Na-HA performed poorly as adjuvants for the PiN solutions

Mucoadhesive liquid ophthalmic vehicles - Evaluation of macromolecular ionic complexes of pilocarpine

Pilocarpine (Pi), a widely used anti-glaucoma drug, is characterized by a very low bioavailability, due to poor corneal penetration and extensive precorneal loss. Purpose of the present study was the preparation and 'in vivo' evaluation of a series of liquid formulations containing salts (or ionic complexes) of Pi with soluble polyanionic polymers of natural, synthetic or semi-synthetic origin. It was speculated that since to some of the polymers have been attributed muco-adhesive properties, they might favour the preocular retention of the ionically bound drug, and enhance its bioavailability. The polymers submitted to investigation were a) hyaluronic acid (HA); b) poly-(galacturonic acid) (PGA); c) Mesoglycan (MG, a complex mixture of mucopolysaccharides); d) Carboxymethylchitin (CMCh) and e) two poly(acrylic acids) of different molecular weight (PAA1 and PAA2). Aqueous solutions of the Pi polymer salts, each containing 1.53% w/w Pi base (equivalent to 2.0% Pi nitrate) were tested for miotic activity in albino rabbits, using as reference an aqueous, 2% solution of Pi nitrate, either as such or viscosized with 1.5 and 5.0% poly(vinyl alcohol), (PVA). All polymeric solutions enhanced, in some cases to a statistically significant extent, the bioavailability of the drug with respect to the reference solutions. The relevance of viscosity effects, and of possible muco-adhesive phenomena to the bioavailability of Pi from the salt-vehicles are discussed