In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens.

INTRODUCTION: Recent virus epidemics and rising antibiotic resistance highlight the importance of hygiene measures to prevent and control outbreaks. We investigated the in vitro bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7% gargle/mouthwash at defined dilution against oral and respiratory tract pathogens. METHODS: PVP-I was tested against Klebsiella pneumoniae and Streptococcus pneumoniae according to bactericidal quantitative suspension test EN13727 and against severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV), rotavirus strain Wa and influenza virus A subtype H1N1 according to virucidal quantitative suspension test EN14476. PVP-I 7% gargle/mouthwash was diluted 1:30 with water to a concentration of 0.23% (the recommended concentration for "real-life" use in Japan) and tested at room temperature under clean conditions [0.3 g/l bovine serum albumin (BSA), viruses only] and dirty conditions (3.0 g/l BSA + 3.0 ml/l erythrocytes) as an interfering substance for defined contact times (minimum 15 s). Rotavirus was tested without protein load. A ≥ 5 log10 (99.999%) decrease of bacteria and ≥ 4 log10 (99.99%) reduction in viral titre represented effective bactericidal and virucidal activity, respectively, per European standards. RESULTS: PVP-I gargle/mouthwash diluted 1:30 (equivalent to a concentration of 0.23% PVP-I) showed effective bactericidal activity against Klebsiella pneumoniae and Streptococcus pneumoniae and rapidly inactivated SARS-CoV, MERS-CoV, influenza virus A (H1N1) and rotavirus after 15 s of exposure. CONCLUSION: PVP-I 7% gargle/mouthwash showed rapid bactericidal activity and virucidal efficacy in vitro at a concentration of 0.23% PVP-I and may provide a protective oropharyngeal hygiene measure for individuals at high risk of exposure to oral and respiratory pathogens. FUNDING: Mundipharma Research GmbH & Co. KG (MRG).

Rapid and Effective Virucidal Activity of Povidone-Iodine Products Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA).

INTRODUCTION: Since the first case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was reported in 2012, the virus has infected more than 1300 individuals in 26 countries, and caused more than 480 deaths. Human-to-human transmission requires close contact, and has typically occurred in the healthcare setting. Improved global awareness, together with improved hygiene practices in healthcare facilities, has been highlighted as key strategies in controlling the spread of MERS-CoV. This study tested the in vitro efficacy of three formulations of povidone iodine (PVP-I: 4% PVP-I skin cleanser, 7.5% PVP-I surgical scrub, and 1% PVP-I gargle/mouthwash) against a reference virus (Modified vaccinia virus Ankara, MVA) and MERS-CoV. METHODS: According to EN14476, a standard suspension test was used to assess virucidal activity against MVA and large volume plating was used for MERS-CoV. All products were tested under clean (0.3 g/L bovine serum albumin, BSA) and dirty conditions (3.0 g/L BSA + 3.0 mL/L erythrocytes), with application times of 15, 30, and 60 s for MVA, and 15 s for MERS-CoV. The products were tested undiluted, 1:10 and 1:100 diluted against MVA, and undiluted against MERS-CoV. RESULTS: A reduction in virus titer of ≥4 log10 (corresponding to an inactivation of ≥99.99%) was regarded as evidence of virucidal activity. This was achieved versus MVA and MERS-CoV, under both clean and dirty conditions, within 15 s of application of each undiluted PVP-I product. CONCLUSION: These data indicate that PVP-I-based hand wash products for potentially contaminated skin, and PVP-I gargle/mouthwash for reduction of viral load in the oral cavity and the oropharynx, may help to support hygiene measures to prevent transmission of MERS-CoV. FUNDING: Mundipharma Research GmbH & Co.

Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses.

BACKGROUND: The recent Ebola virus (EBOV) epidemic highlights the need for efficacious virucidal products to help prevent infection and limit the spread of Ebola virus disease. However, there is limited data on the efficacy of virucidal products against EBOV, because the virus has a high biosafety level and is only available in a few laboratories worldwide. The virucidal efficacy of antiseptics and disinfectants can be determined using the European Standard EN14476:2013/FprA1:2015. Modified vaccinia virus Ankara (MVA) was introduced in 2014 as a reference virus for the claim 'virucidal active against enveloped viruses for hygienic hand rub and hand wash'. For EBOV, also an enveloped virus, the suitability of MVA as a surrogate needs to be proven. The aim of this study was to test the in vitro efficacy of four povidone iodine (PVP-I) formulations against EBOV: 4% PVP-I skin cleanser; 7.5% PVP-I surgical scrub; 10% PVP-I solution; and 3.2% PVP-I and 78% alcohol solution. The formulations were tested with MVA to define the test conditions, and as a secondary objective the suitability of MVA as a surrogate for enveloped viruses like EBOV was assessed. METHODS: According to EN14476, a standard suspension test was used for MVA. Large-volume plating was used for EBOV to increase test sensitivity and exclude potential after-effects. All products were tested under clean (0.3 g/L BSA) and dirty (3.0 g/L BSA + 3.0 mL/L erythrocytes) conditions with MVA for 15, 30, and 60 s. The concentration-contact time values obtained with MVA were verified for EBOV. RESULTS: Viral titres of MVA and EBOV were reduced by >99.99% to >99.999% under clean and dirty conditions after application of the test products for 15 seconds. CONCLUSIONS: All products showed excellent virucidal efficacy against EBOV, demonstrating the important role PVP-I can play in helping to prevent and limit the spread of Ebola virus disease. The efficacy against both test viruses after 15 s is helpful information for the implementation of guidance for people potentially exposed to EBOV, and confirms the excellent virucidal efficacy of PVP-I against enveloped viruses. MVA was found to be a suitable surrogate for enveloped viruses like EBOV.

Safety of MF59 adjuvant.

The need to enhance the immunogenicity of purified subunit antigens has prompted the development of new adjuvants. The adjuvant emulsion MF59 has been tested in animals in combination with different antigens and finally evaluated in humans. It was licensed after the successful outcome of preclinical and clinical testing. This paper summarizes the main characteristics of the MF59 adjuvant, including animal testing, clinical experience with various vaccines, and information from current postmarketing surveillance data. This review supports the hypothesis that MF59 is a safe adjuvant for human use.