Investigation on virucidal activity of chlorine dioxide. Experimental data on Feline calicivirus, HAV and Coxsackie B5

Introduction. The aim of this study was to evaluate the efficacy of ClO2 with regard to viruses which show a particular resistance to oxidizing agent such as HAV and Norwalk and Norwalk-like viruses, and which play an important role in the epidemiology of viral foodborne diseases. In the food industry, disinfection of processing systems and equipment is a very important instrument to prevent secondary contamination and to guarantee food safety. Among disinfectants, chlorine dioxide (ClO2) presents a good efficacy at wide range of pH values, its action is rapid and generates few reaction byproducts if compared to hypoclorite. Experimental studies have highlighted that ClO2 shows a good bactericidal activity and it is also active towards viruses. Furthermore, the low concentrations and low contact times required to obtain microbial load reduction are favourable elements for the application of this compound in the industrial sanitizing practices. Methods. As it is impossible to cultivate the Norwalk virus in vitro, we tested the resistance of Feline calicivirus (F9 strain) vs. ClO2, in comparison with HAV (strain HM-175) and CoxsackieB5. Chlorine dioxide was used at concentrations ranging from 0.2 to 0.8 mg/l in water solution, at pH 7 and at +20 °C. Viral suspensions were added to disinfecting solution and, at pre-set times, were sampled to undergo to titration after blocking the disinfectant action with thiosulphate 0.05 M. On the basis of the data obtained, for each virus and in relation to different concentrations, mean reduction times were calculated for 99%, 99.9% and 99.99% using the regression analysis model. Results. As regards Feline calicivirus, at a concentration of 0.8 mg/l of ClO2, we obtained the complete elimination of the viral titre in 2 min while 30 min were required at concentrations of 0.2 mg/l. Coxackie B5 showed a similar behaviour, being completely inactivated in 4 min with 0.4 mg/l of ClO2 and after 30 min at a concentration of 0.2 mg/l. Inactivation was quicker for HAV, which was eliminated after only 30 sec at a concentration of 0.8 mg/l and after 5 min at 0.4 mg/l. Conclusion. Our data show that for complete inactivation of HAV and Feline calicivirus, concentrations ? 0.6 mg/l are required. This observation is true for Coxsackie B5 too, but this virus has shown a good sensitivity at all concentration tested according to regression analysis results. For Feline calicivirus and HAV, at low concentrations of disinfectant, prolonged contact times were needed to obtain a 99.99% reduction of viral titres (about 16 and 20 minutes respectively)

[strategies For Integration Of Health Care Practices And Sanitary Surveillance In The Context Of The Implementation Of Rede Cegonha - A Brazilian Mother And Infant Health Care Network].

Mother and infant mortality has been the scope of analysis throughout the history of public health in Brazil and various strategies to tackle the issue have been proposed to date. The Ministry of Health has been working on this and the Rede Cegonha strategy is the most recent policy in this context. Given the principle of comprehensive health care and the structure of the Unified Health System in care networks, it is necessary to ensure the integration of health care practices, among which are the sanitary surveillance actions (SSA). Considering that the integration of health care practices and SSA can contribute to reduce mother and infant mortality rates, this article is a result of qualitative research that analyzed the integration of these actions in four cities in the State of São Paulo/Brazil: Campinas, Indaiatuba, Jaguariúna and Santa Bárbara D'Oeste. The research was conducted through interviews with SSA and maternal health managers, and the data were evaluated using thematic analysis. The results converge with other studies, identifying the isolation of health care practices and SSA. The insertion of SSA in collectively-managed areas appears to be a potential strategy for health planning and implementation of actions in the context under scrutiny.194457-6

Use of Miltefosine in a Patient With Mucosal Leishmaniasis and HIV-coinfection: A Challenge in Long-Term Management

The management of mucosal leishmaniasis in immunocompromised patients is not standardized and limited data are available on the use of miltefosine for treatment and secondary prophylaxis. We describe a case of mucosal leishmaniasis in an HIV-coinfected patient treated with miltefosine due to a severe allergic reaction to liposomal amphotericin B

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

INVESTIGATION ON VIRUCIDAL ACTIVITY OF CHLORINE DIOXIDE. EXPERIMENTAL DATA ON FELINE CALICIVIRUS, HAV AND COXSACKIE B5

Introduction. The aim of this study was to evaluate the efficacy of ClO2 with regard to viruses which show a particular resistance to oxidizing agent such as HAV and Norwalk and Norwalk-like viruses, and which play an important role in the epidemiology of viral foodborne diseases. In the food industry, disinfection of processing systems and equipment is a very important instrument to prevent secondary contamination and to guarantee food safety. Among disinfectants, chlorine dioxide (ClO2) presents a good efficacy at wide range of pH values, its action is rapid and generates few reaction byproducts if compared to hypoclorite. Experimental studies have highlighted that ClO2 shows a good bactericidal activity and it is also active towards viruses. Furthermore, the low concentrations and low contact times required to obtain microbial load reduction are favourable elements for the application of this compound in the industrial sanitizing practices. Methods. As it is impossible to cultivate the Norwalk virus in vitro, we tested the resistance of Feline calicivirus (F9 strain) vs. ClO2, in comparison with HAV (strain HM-175) and CoxsackieB5. Chlorine dioxide was used at concentrations ranging from 0.2 to 0.8 mg/l in water solution, at pH 7 and at +20 °C. Viral suspensions were added to disinfecting solution and, at pre-set times, were sampled to undergo to titration after blocking the disinfectant action with thiosulphate 0.05 M. On the basis of the data obtained, for each virus and in relation to different concentrations, mean reduction times were calculated for 99%, 99.9% and 99.99% using the regression analysis model. Results. As regards Feline calicivirus, at a concentration of 0.8 mg/l of ClO2, we obtained the complete elimination of the viral titre in 2 min while 30 min were required at concentrations of 0.2 mg/l. Coxackie B5 showed a similar behaviour, being completely inactivated in 4 min with 0.4 mg/l of ClO2 and after 30 min at a concentration of 0.2 mg/l. Inactivation was quicker for HAV, which was eliminated after only 30 sec at a concentration of 0.8 mg/l and after 5 min at 0.4 mg/l. Conclusion. Our data show that for complete inactivation of HAV and Feline calicivirus, concentrations ≥ 0.6 mg/l are required. This observation is true for Coxsackie B5 too, but this virus has shown a good sensitivity at all concentration tested according to regression analysis results. For Feline calicivirus and HAV, at low concentrations of disinfectant, prolonged contact times were needed to obtain a 99.99% reduction of viral titres (about 16 and 20 minutes respectively)

Integration of health surveillance actions and health care practices in the brazilian policy for maternal and child health : the search for comprehensiveness

Orientador: Maria Filomena de Gouveia VilelaDissertação (mestrado profissional) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: As mortalidades materna e infantil têm sido objeto de análise ao longo da história da saúde coletiva no Brasil e diversos têm sido as estratégias de enfrentamento propostas. O Ministério da Saúde tem trabalhado neste sentido, sendo a estratégia da Rede Cegonha a mais recente política neste contexto. Tendo em vista o princípio da integralidade e a conformação do Sistema Único de Saúde (SUS) em redes de atenção faz-se necessário efetivar a integração de práticas em saúde desenvolvidas, dentre as quais estão as ações de vigilância sanitária (Visa). Considerando que a integração de práticas assistenciais e de Visa pode contribuir para reduzir as taxas de mortalidade citadas, o presente estudo é decorrente de uma pesquisa qualitativa que analisou a integração destas ações em quatro municípios do Estado de São Paulo: Campinas, Indaiatuba, Jaguariúna e Santa Bárbara D¿Oeste. A pesquisa foi realizada através de entrevistas com gestores de Visa e de saúde materna e os dados foram analisados a partir da técnica de análise de conteúdo. Os resultados convergem com outros estudos, identificando o isolamento de práticas assistenciais e de Visa. A inserção da Visa nos espaços coletivos de gestão mostra-se estratégia em potencial para o planejamento e execução das ações de saúde no contexto estudadoAbstract: Maternal and child mortality have been object of analysis throughout the history of public health in Brazil and several coping strategies have been proposed so far. The Health Ministry has been working in this direction , with the strategy of "Rede Cegonha", the latest policy in this context. Given the principle of comprehensive health care and the conformation of the Brazilian Públic Health System (SUS) in attention networks, it is necessary to carry out the integration of health practices developed, among which are the sanitary surveillance actions (SSA).Whereas the integration of care practices and SSA in the context of "Rede Cegonha" can contribute to improvements in mortality rates, this article is a result of a qualitative research aimed to analyze the integration of these actions in four cities of the State of São Paulo: Campinas , Indaiatuba, Jaguariúna and Santa Bárbara D'Oeste. The survey was conducted through interviews with SSA and maternal health managers, and the data were analyzed through thematic analysis . The results converge with other studies , identifying the isolation of care practices and SSA. The insertion of SSA in collective management strategies proves a potential strategy for planning and implementation of health actions in the studied contextMestradoPolítica, Planejamento e Gestão em SaúdeMestra em Saúde Coletiv

Recovery tests of cytopathogenic viruses from artificiallycontaminated food samples

Abstract The artificial contamination tests were carried out by using a Coxsackie B5 virus of known titration to contaminate vegetable food products (lettuce and berries). The experimental protocol was divided basically into two phases: elution with alkaline pH buffer solution and following concentration of viral particles recovered by using PEG8000 (polyethylene glycol). A third phase of purification with chloroform was introduced between these two steps in order to assess its effect on the yield of the final recovery, and tests were performed in parallel with both the protocols to compare them in terms of recovery efficiency. Elution phase proved to be the most critical, since the viral recovery from food samples during this phase resulted moderate (2.95% and 2.16% respectively in tests without and with chloroform purification phase), data already observed in previous studies. The final concentration phase with PEG8000 recorded average recoveries equalling 0.29% in tests without chloroform and equalling 3.97% in tests with purification phase, thus showing a significant improvement with a lesser interference by the organic material