RESUMO
BACKGROUND: People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. METHODS: A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. RESULTS: Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. CONCLUSIONS: The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID.
Assuntos
Botulismo/prevenção & controle , Surtos de Doenças/prevenção & controle , Redução do Dano , Dependência de Heroína/epidemiologia , Infecção dos Ferimentos/prevenção & controle , Adulto , Analgésicos Opioides/química , Botulismo/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Contaminação de Medicamentos , Feminino , Heroína/química , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Gestão de Riscos , Escócia/epidemiologia , Infecção dos Ferimentos/epidemiologia , Adulto JovemRESUMO
In this study, a risk assessment of proteolytic Clostridium botulinum in canned foie gras was performed, the number of illnesses per year in France due to C. botulinum in foie gras was estimated. Data on initial level in raw materials were collected at manufacturers and analysed using a Negative Binomial distribution. The effect of the usual foie gras heat treatment (equivalent time at 121 °C: F0=0.5 min) was considered at two levels: first, it led to an inactivation (estimated to 2.3 log); second it led to a spore injury and then to a spore inhibition. This latter effect was assessed by analysing data from a challenge test study carried out with Clostridium sporogenes spores in the foie gras product. The probability of spore recovering after thermal inhibition was estimated to 9.5×10(-8) (corresponding to 7.0 log). The data on the consumption pattern were collected on the French market. The Quantitative Microbiological Risk Assessment (QMRA) model and all the assumptions are reported in detail in the study. The initial contamination of raw materials, effect of thermal treatment on microbial inactivation and spore inhibition were handled mathematically using a probabilistic framework, considering only the variability dimension. The model was implemented in Excel and run through Monte Carlo simulation, using @Risk software. In parallel, epidemiological data collected from the French Institute for Public Health Surveillance during the period 2001-2012 were used to estimate an Appropriate Level Of Protection (ALOP) and then a Food Safety Objective (FSO): ALOP equalled to 2.5×10(-3) illnesses per million inhabitant per year, FSO equalled to 1.4×10(-9) foie gras portions containing C. botulinum spore (expressed in decimal logarithm, FSO=-8.9). The QMRA model output values were smaller, but on the same order of magnitude as these two figures: 8.0×10(-4) illnesses per million inhabitants per year, and, 4.5×10(-10) (-9.3 log) foie gras portions containing C. botulinum spores able to recover. It was then possible to conclude that the current practices regarding thermal treatment of canned foie gras are sufficient to control the risk of C. botulinum in foie gras in France.
Assuntos
Botulismo/epidemiologia , Manipulação de Alimentos/normas , Microbiologia de Alimentos , Botulismo/prevenção & controle , Clostridium/isolamento & purificação , Clostridium/fisiologia , Clostridium botulinum/isolamento & purificação , Clostridium botulinum/fisiologia , França/epidemiologia , Temperatura Alta , Humanos , Viabilidade Microbiana , Modelos Estatísticos , Medição de Risco , Esporos Bacterianos/isolamento & purificaçãoRESUMO
Orange Flame is an Israeli preparedness build-up project, conducted by the Ministry of Health, that is aimed at improving national readiness and preparedness for unusual biological events. The project is intended for both medical and nonmedical organizations, and, since 2011, the exercise has also included operational units outside the medical corps. This has provided valuable insights into the consequences of bioterror or naturally occurring outbreaks for operative functionality and for the unique medical, logistical, and administrative efforts required from the armed forces in such an event. The 2-day drill reported on here executed a notional scenario in which category A bioterror agents were dispersed, causing civil and military casualties. Military personnel observed and assessed the performances of all participating organizations and observed the employment of emergency protocols during the drill. Military sustainment and operative capabilities were significantly affected by the occurrence of an unusual biological event. Comprehensive actions to be executed during such a scenario included quarantining military bases, considering postponement of military operations, and transferring on-call missions to other bases. Logistic consequences included the need for manpower and equipment reinforcement, as well as food and water supplies in cases of suspected source contamination. The project unveiled many operational and logistic quandaries and exposed various potential effects of a bioterror attack in the military. Lessons learned were used to revise preevent national and military doctrine for unusual biological events.
Assuntos
Derramamento de Material Biológico , Bioterrorismo , Defesa Civil/organização & administração , Planejamento em Desastres/organização & administração , Controle de Infecções/organização & administração , Militares , Antraz/diagnóstico , Antraz/epidemiologia , Antraz/prevenção & controle , Toxinas Botulínicas , Botulismo/diagnóstico , Botulismo/epidemiologia , Botulismo/prevenção & controle , Fortalecimento Institucional , Atenção à Saúde/organização & administração , Emergências , Contaminação de Alimentos , Humanos , Israel , Incidentes com Feridos em MassaRESUMO
Tetanus is caused by the tetanus neurotoxin (TeNT), a 150 kDa single polypeptide molecule which is cleaved into an active two-chain molecule composed of a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chains. Recently, extensive effort has focused on characterization of TeNT binding receptors and toxin neutralization by monoclonal antibodies (mAbs). Toxin binding inhibition and neutralization is routinely assessed either in vitro by the ganglioside GT1b binding inhibition assay or in vivo using an animal model. These two assay systems have never been compared. In the present study, we report characterization of eleven mAbs against different parts of TeNT. The toxin inhibitory and neutralization activity of the mAbs was assessed in vitro and in vivo respectively. Our data demonstrated that seven mAbs bind to fragment C of the heavy chain, two mAbs react with the light chain, one mAb recognizes both chains and one mAb reacts with neither light chain nor fragment C. Six fragment C specific mAbs were able to inhibit TeNT binding to GT1b ganglioside in vitro but three failed to neutralize the toxin in vivo. One in vitro inhibitory mAb (1F3E3) was found to synergize with the in vivo neutralizing mAbs to reduce toxin lethal activity in vivo. Sequencing of the immunoglobulin heavy and light chain variable region genes revealed that the three in vivo neutralizing mAbs were derived from a common origin. Altogether, our data suggests that fragment C specific mAbs contribute to toxin neutralization in both systems, though some of the GT1b binding inhibitory mAbs may not be able to neutralize TeNT in vivo.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Botulismo/prevenção & controle , Toxina Tetânica/antagonistas & inibidores , Animais , Gangliosídeos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Testes de Neutralização , Ligação Proteica , Análise de SobrevidaRESUMO
A recombinant botulinum vaccine (rBV A/B) is being developed to protect adults 18-55 years of age from fatal botulism caused by inhalational intoxication with botulinum neurotoxin complex (BoNT) serotype A, subtype A1 (BoNT/A1) and BoNT serotype B, subtype B1 (BoNT/B1). Fundamental to the advanced development process is an initial demonstration of product safety in animals. A comprehensive series of studies was conducted to evaluate the general toxicity, neurobehavioral toxicity and local reactogenicity of the rBV A/B vaccine prior to first use in humans. Toxicity was evaluated in CD-1 mice vaccinated with control material and three dosages of rBV A/B with or without Alhydrogel(®) by intramuscular (IM) injection on Study Days 0, 28, 56 and 70 in a volume of 100µL. Total immunizing protein given in each dose was either 0, 2, 4 or 8 µg/animal. Local reactogenicity was evaluated in mice at the dosages given and in New Zealand white (NZW) rabbits using the same injection volume (0.5 mL) and formulations (10, 20 and 40 g/mL total antigen with 0.2% (w/v) Alhydrogel(®)) intended for human use. The rBV A/B vaccine produced no apparent systemic or neurobehavioral toxicity and only transient mild inflammation at the injection site. Together these results indicated a favorable safety profile for rBV A/B and supported its use in a Phase 1 clinical trial.
Assuntos
Vacinas Bacterianas/toxicidade , Toxinas Botulínicas/toxicidade , Botulismo/prevenção & controle , Animais , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos , Coelhos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/toxicidadeRESUMO
UNLABELLED: Consumer demand for food safety and quality improvements, combined with new regulations, requires determining the processor's confidence level that processes lowering safety risks while retaining quality will meet consumer expectations and regulatory requirements. Monte Carlo calculation procedures incorporate input data variability to obtain the statistical distribution of the output of prediction models. This advantage was used to analyze the survival risk of Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) and Clostridium botulinum spores in high-temperature short-time (HTST) milk and canned mushrooms, respectively. The results showed an estimated 68.4% probability that the 15 sec HTST process would not achieve at least 5 decimal reductions in M. paratuberculosis counts. Although estimates of the raw milk load of this pathogen are not available to estimate the probability of finding it in pasteurized milk, the wide range of the estimated decimal reductions, reflecting the variability of the experimental data available, should be a concern to dairy processors. Knowledge of the C. botulinum initial load and decimal thermal time variability was used to estimate an 8.5 min thermal process time at 110 °C for canned mushrooms reducing the risk to 10â»9 spores/container with a 95% confidence. This value was substantially higher than the one estimated using average values (6.0 min) with an unacceptable 68.6% probability of missing the desired processing objective. Finally, the benefit of reducing the variability in initial load and decimal thermal time was confirmed, achieving a 26.3% reduction in processing time when standard deviation values were lowered by 90%. PRACTICAL APPLICATION: In spite of novel technologies, commercialized or under development, thermal processing continues to be the most reliable and cost-effective alternative to deliver safe foods. However, the severity of the process should be assessed to avoid under- and over-processing and determine opportunities for improvement. This should include a systematic approach to consider variability in the parameters for the models used by food process engineers when designing a thermal process. The Monte Carlo procedure here presented is a tool to facilitate this task for the determination of process time at a constant lethal temperature.
Assuntos
Agaricales , Clostridium botulinum tipo B/crescimento & desenvolvimento , Alimentos em Conserva/microbiologia , Leite/microbiologia , Modelos Biológicos , Mycobacterium avium subsp. paratuberculosis/crescimento & desenvolvimento , Pasteurização/métodos , Animais , Carga Bacteriana , Botulismo/prevenção & controle , Clostridium botulinum tipo B/isolamento & purificação , Clostridium botulinum tipo B/fisiologia , Armazenamento de Alimentos , Carpóforos , Temperatura Alta/efeitos adversos , Cinética , Viabilidade Microbiana , Método de Monte Carlo , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Mycobacterium avium subsp. paratuberculosis/fisiologia , Paratuberculose/prevenção & controle , Controle de Qualidade , Reprodutibilidade dos Testes , Esporos Bacterianos/crescimento & desenvolvimento , Esporos Bacterianos/isolamento & purificação , Esporos Bacterianos/fisiologiaAssuntos
Contaminação de Alimentos/prevenção & controle , Doenças Transmitidas por Alimentos/prevenção & controle , Distúrbios Nutricionais/prevenção & controle , Fenômenos Fisiológicos da Nutrição , Adolescente , Adulto , Botulismo/prevenção & controle , Criança , Pré-Escolar , Dieta , Inspeção de Alimentos , Alimentos Fortificados , Promoção da Saúde , Serviços de Saúde/normas , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estado Nutricional , Serviços Preventivos de Saúde , Saúde Pública , Federação RussaRESUMO
Recombinant botulinum neurotoxin serotype A binding domain [BoNT/A(Hc)], expressed in Pichia pastoris, was developed as a vaccine candidate for preventing botulinum neurotoxin type A (BoNT/A) intoxication. After fermentation and cell disruption, BoNT/A(Hc) was purified by using a three-step chromatographic process consisting of expanded-bed chromatography, Mono S cation-exchange chromatography, and hydrophobic interaction chromatography. Two pools of immunogenic product were separated on the Mono S column and processed individually. Both products were more than 95% pure and indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Each protein was assayed for potency in mice at immunogen doses ranging from 2.4 ng to 10 microg, followed by challenge with 1,000 mouse intraperitoneal 50% lethal doses (i.p. LD50) of BoNT/A. The calculated 50% effective dose for both peaks was approximately 0.1 microg/mouse. Peak 1 was evaluated further in a mouse efficacy assay. Mice were injected either once, twice, or three times at five different doses and subsequently challenged with 100,000 mouse i.p. LD50 of BoNT/A. In general, multiple injections protected better than one, with complete or nearly complete protection realized at doses of >/=0.5 microg/mouse. Serum neutralization and ELISA titers were also determined. Tellingly, 82 of 83 mice with antibody titers of >/=1, 600, as measured by ELISA, survived, but only 6 of 42 mice with titers of =100 survived. This work shows that the purified BoNT/A(Hc) produced was a highly effective immunogen, able to protect against a high challenge dose of neurotoxin.
Assuntos
Vacinas Bacterianas/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Botulismo/prevenção & controle , Vacinas Sintéticas/uso terapêutico , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/economia , Sítios de Ligação , Toxinas Botulínicas Tipo A/biossíntese , Toxinas Botulínicas Tipo A/genética , Toxinas Botulínicas Tipo A/toxicidade , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Estudos de Avaliação como Assunto , Expressão Gênica , Genes Sintéticos , Esquemas de Imunização , Dose Letal Mediana , Camundongos , Testes de Neutralização , Pichia/genética , Vacinas Sintéticas/economiaRESUMO
Morbidity and mortality from infectious diseases clearly remain high. Economic assessments should not be based soley on the costs of existing disease but should incorporate costs saved by preventive efforts as well as savings likely to be attained within several years by improved preventive measures. These factors can be used to assess the relative needs for research for specific infections and to compare the economic importance of infections with that of other health problems. Preventive activities for individuals and for larger groups are outlined, and the relation of research to prevention and control of infections is presented.