Evaluation of switching low-dose inhaled corticosteroid to pranlukast for step-down therapy in well-controlled patients with mild persistent asthma.

OBJECTIVE: Treatment guidelines for asthma recommend step-down therapy for well-controlled asthma patients. However, the precise strategy for step-down therapy has not been well defined. We investigated whether well-controlled patients with mild persistent asthma can tolerate a step-down therapy of either a reduced dose of inhaled corticosteroid (ICS) or a switch to a leukotriene receptor antagonist (LTRA), pranlukast hydrate. METHODS: We recruited 40 adult patients with mild persistent asthma who were well-controlled for at least 3 months with a low-dose ICS therapy. The patients were randomly assigned to either an ICS dose reduction or a switch to pranlukast for 6 months. RESULTS: FeNO levels in the pranlukast group were significantly increased over that in the ICS group. There were no significant differences between the two groups for lung function, FOT, at the endpoint. The percentage of patients with controlled asthma was 72.2% in the pranlukast group and 90% in the ICS group. No statistically significant difference between the two groups in the percentages of patients with treatment failure was observed. CONCLUSIONS: Patients with mild persistent asthma that is well-controlled by a low dose of ICS can be switched to pranlukast safely for at least 6 months. However, 27.8% of the pranlukast group failed to maintain well-control, and FeNO levels increased with the switch to pranlukast at 6 months. This study was been limited by the small sample size and should therefore be considered preliminary. Further studies are needed to investigate the therapeutic efficacy of LTRA monotherapy as a step-down therapy.

World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: A Data Synthesis.

BACKGROUND: Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food. METHODS AND FINDINGS: Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4-79.0 million) and 59,724 (95% UI 48,017-83,616) deaths annually resulting in 8.78 million (95% UI 7.62-12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2-38.1 million) cases and 45,927 (95% UI 34,763-59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61-8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29-22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40-14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14-3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65-2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000-1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi). CONCLUSIONS: Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations.

Estimating the burden of foodborne diseases in Japan.

OBJECTIVE: To assess the burden posed by foodborne diseases in Japan using methods developed by the World Health Organization's Foodborne Disease Burden Epidemiology Reference Group (FERG). METHODS: Expert consultation and statistics on food poisoning during 2011 were used to identify three common causes of foodborne disease in Japan: Campylobacter and Salmonella species and enterohaemorrhagic Escherichia coli (EHEC). We conducted systematic reviews of English and Japanese literature on the complications caused by these pathogens, by searching Embase, the Japan medical society abstract database and Medline. We estimated the annual incidence of acute gastroenteritis from reported surveillance data, based on estimated probabilities that an affected person would visit a physician and have gastroenteritis confirmed. We then calculated disability-adjusted life-years (DALYs) lost in 2011, using the incidence estimates along with disability weights derived from published studies. FINDINGS: In 2011, foodborne disease caused by Campylobacter species, Salmonella species and EHEC led to an estimated loss of 6099, 3145 and 463 DALYs in Japan, respectively. These estimated burdens are based on the pyramid reconstruction method; are largely due to morbidity rather than mortality; and are much higher than those indicated by routine surveillance data. CONCLUSION: Routine surveillance data may indicate foodborne disease burdens that are much lower than the true values. Most of the burden posed by foodborne disease in Japan comes from secondary complications. The tools developed by FERG appear useful in estimating disease burdens and setting priorities in the field of food safety.

Science as a common language for contribution to sustainability and peace.

There are many reasons and background factors for conflict including differences in political and social beliefs and values. Wars have also been a threat to the environment and sustainability. Inequality and disparity are more apparent in the world due to COVID-19. Now, we also need to consider environmental changes caused by human activities as climate extremes might cause new conflicts. More studies are needed for a comprehensive understanding of holistic views on challenges at the interfaces of peace and sustainability that inherently involve inter- and trans-disciplinary collaboration among cohorts of communities of practice. Collaborative scientific research on these interfaces is being conducted under the Future Earth Programme, and many others. In this commentary, I posit that science offers an effective pathway and a common platform for engagement and interactions aimed at the nexus of sustainability and peace under global changes.

Are we ignoring a black elephant in the Anthropocene? Climate change and global pandemic as the crisis in health and equality.

Climate change and coronavirus pandemic are the twin crises in the Anthropocene, the era in which unsustainable growth of human activities has led to a significant change in the global environment. The two crises have also exposed a chronic social illness of our time-a deep, widespread inequality in society. Whilst the circumstances are unfortunate, the pandemic can provide an opportunity for sustainability scientists to focus more on human society and its inequalities, rather than a sole focus on the natural environment. It opens the way for a new normative commitment of science in a time of crises. We suggest three agendas for future climate and sustainability research after the pandemic: (1) focus on health and well-being, (2) moral engagement through empathy, and (3) science of loss for managing grief.

Quantitative risk assessment of Vibrio parahaemolyticus in finfish: a model of raw horse mackerel consumption in Japan.

The aim of this study was to evaluate the effects of implemented control measures to reduce illness induced by Vibrio parahaemolyticus (V. parahaemolyticus) in horse mackerel (Trachurus japonicus), seafood that is commonly consumed raw in Japan. On the basis of currently available experimental and survey data, we constructed a quantitative risk model of V. parahaemolyticus in horse mackerel from harvest to consumption. In particular, the following factors were evaluated: bacterial growth at all stages, effects of washing the fish body and storage water, and bacterial transfer from the fish surface, gills, and intestine to fillets during preparation. New parameters of the beta-Poisson dose-response model were determined from all human feeding trials, some of which have been used for risk assessment by the U.S. Food and Drug Administration (USFDA). The probability of illness caused by V. parahaemolyticus was estimated using both the USFDA dose-response parameters and our parameters for each selected pathway of scenario alternatives: washing whole fish at landing, storage in contaminated water, high temperature during transportation, and washing fish during preparation. The last scenario (washing fish during preparation) was the most effective for reducing the risk of illness by about a factor of 10 compared to no washing at this stage. Risk of illness increased by 50% by exposure to increased temperature during transportation, according to our assumptions of duration and temperature. The other two scenarios did not significantly affect risk. The choice of dose-response parameters was not critical for evaluation of control measures.

Quantitative modeling for risk assessment of Vibrio parahaemolyticus in bloody clams in southern Thailand.

A risk assessment of Vibrio parahaemolyticus in bloody clams (Anadara granosa) consumed in southern Thailand was conducted. This study estimated the prevalence and concentration of pathogenic V. parahaemolyticus in bloody clams at harvest and retail stages; and during this process, methods to detect the total and pathogenic V. parahaemolyticus were investigated. Consumption of bloody clams and cooking efficiency were studied using interviews and on-site observation of consumers. A beta-Poisson dose-response model was used to estimate probability of illness applying estimation methods for the most likely parameter values presented by USFDA. Microbial and behavioral data were analyzed by developing a stochastic model and the simulation gave a mean number of times a person would get ill with V. parahaemolyticus by consuming bloody clams at 5.6 x 10(-4)/person/year. Sensitivity analysis demonstrated the fraction of people who did not boil the clams properly was the primary factor in increasing risk. This study serves as an example of how a microbiological risk assessment with limited data collection and international cooperation leads to valuable local insight.

Simulating the BSE epidemic and multiplication factor in dairy herds in Japan.

With the objective of evaluating the effectiveness of an administrative guidance on the use of ruminant meat-and-bone meal in ruminant feed, effective from April 1996 to September 2001, we developed a model to simulate the evolution of the BSE epidemic and to estimate the BSE multiplication factor (K) in the Japanese dairy population. The output that provided the best fit to the number of BSE cases both observed and predicted to date suggest that the probability that bovine MBM was fed back to cattle was 14.2-75.2% and 0.129-0.570% during the periods from 1992 to April 1996 and from April 1996 to October 2001, respectively. Given these estimates, the value of K would have peaked in 1995 at 40-48 and then declined to 0.32-0.67 between 1997 and 2001. These results suggest that the administrative guidance was effective in reducing the amount of MBM fed to cattle by a factor of 104-141 and was perhaps enough to drive the epidemic towards extinction.

The human health burden of foodborne infections caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus in Miyagi Prefecture, Japan.

To estimate the human health burden of foodborne infections caused by Campylobacter, Salmonella, and Vibrio parahaemolyticus in Japan, an epidemiological study was conducted in Miyagi Prefecture. Laboratory-confirmed infections among patients with diarrhea caused by the three pathogens were ascertained from two clinical laboratories in the prefecture from April 2005 to March 2006. To estimate the number of ill persons who were not laboratory-confirmed, we estimated physician-consultation rates for patients with acute diarrhea by analyzing foodborne outbreak investigation data for each pathogen and the frequency at which stool specimens were submitted from a physician survey. Each factor was added to a Monte-Carlo simulation model as a probability distribution, and the number of laboratory-confirmed cases was extrapolated to estimate the total number of ill persons. The estimated incidence of foodborne infections per 100,000 per year in this region estimated by this model was 237 cases for Campylobacter, 32 cases for Salmonella, and 15 cases for V. parahaemolyticus. Simulated results indicate a significant difference between our estimated incidence and the reported cases of food poisoning in this region. An enhanced surveillance system is needed to complement the present passive surveillance on foodborne illnesses in Japan to identify food safety issues more precisely, and to monitor the effectiveness of risk management options.

Assessment of the impact of cattle testing strategies on human exposure to BSE agents in Japan.

In Japan, cattle screening tests for BSE are conducted at slaughterhouses for surveillance purposes and as a meat safety measure, but the public health impacts of such testing and the subsequent removal of positive animals from the food chain have not been quantitatively assessed. We evaluated the influence of removing specified risk materials and the alternation of age limits for testing cattle at the slaughterhouse on human exposure to the BSE agent in Japan by constructing a probabilistic risk model. A stochastic model using Monte Carlo simulation was constructed in order to estimate the BSE infectivity destined for the food chain from a single BSE-infected animal at slaughter. The impact of different testing strategies and risk material removal were then compared. Murine intra-cerebral ID50 (m.i.c. ID50) units were used as units for BSE infectivity. Sensitivity analysis was conducted for key input variables by changing values within plausible ranges. The expected fraction of BSE-infected cattle presented for slaughter that would be detected by screening tests was 20%, even if all slaughtered cattle were tested. The removal of risk materials reduced the median value estimate of infectivity destined for human consumption by 95%. Cattle screening tests reduced the infectivity further, but reduction efficacy did not differ among the various testing strategies. Sensitivity analysis indicated that the characteristics of BSE infectivity accumulation during the incubation period, extension of the incubation period, and lowering the detection limit of screening tests had no significant impact on relative infectivity reduction, which remained stable irrespective of testing strategy or changes in these parameters. This study suggests that the impact of changing the age limit for testing cattle on beef safety is small, provided that the removal of risk materials is conducted properly.

Current Measures on Radioactive Contamination in Japan: A Policy Situation Analysis.

BACKGROUND: The Great East Japan Earthquake on 11th March 2011 and the subsequent Fukushima Dai-ichi nuclear power plant disaster caused radioactive contamination in the surrounding environment. In the immediate aftermath of the accident the Government of Japan placed strict measures on radio-contamination of food, and enhanced radio-contamination monitoring activities. Japan is a pilot country in the WHO Foodborne Disease Burden Epidemiology Reference Group (FERG), and through this initiative has an opportunity to report on policy affecting chemicals and toxins in the food distribution network. Nuclear accidents are extremely rare, and a policy situation analysis of the Japanese government's response to the Fukushima Dai-ichi nuclear accident is a responsibility of Japanese scientists. This study aims to assess Japan government policies to reduce radio-contamination risk and to identify strategies to strengthen food policies to ensure the best possible response to possible future radiation accidents. METHODS AND FINDINGS: We conducted a hand search of all publicly available policy documents issued by the Cabinet Office, the Food Safety Commission, the Ministry of Health, Labor and Welfare (MHLW), the Ministry of Agriculture, Forestry and Fishery (MAFF) and prefectural governments concerning food safety standards and changes to radiation and contamination standards since March 11th, 2011. We extracted information on food shipment and sales restrictions, allowable radio-contamination limits, monitoring activities and monitoring results. The standard for allowable radioactive cesium (Cs-134 and Cs-137) of 100 Bq/Kg in general food, 50 Bq/Kg in infant formula and all milk products, and 10 Bq/Kg in drinking water was enforced from April 2012 under the Food Sanitation Law, although a provisional standard on radio-contamination had been applied since the nuclear accident. Restrictions on the commercial sale and distribution of specific meat, vegetable and fish products were released for areas at risk of radioactive contamination. Monitoring of radioactive materials in food products in the prefectures has been mainly conducted before shipment to restrict the distribution of radio-contaminated foods. Between March 2011 and March 2012, 133,832 tests of non-commercial and commercial products were conducted, and 1,204 tests (0.9%) were found to violate the provisional standards. Since April 2012, 278,275 tests were conducted, and 2,372 tests (0.9%) were found to violate the revised standards. MHLW assessment of representative market baskets of foodstuffs at 15 locations throughout Japan between February and March 2014 found very low estimated dietary intake of radioactive cesium (0.0007-0.019 mSv/year), as did assessments of the contents of an average day's food. Monitoring of fisheries products in coastal areas affected by the nuclear accident found very limited and declining radio-contamination of live fish outside of Fukushima prefecture. Fisheries monitoring is of limited geographical scope and covers only certain fishes. CONCLUSIONS: Area-specific bans on production and distribution have been effective in preventing radioactive contamination in the Japanese food market. Currently there is no major concern about radioactive cesium concentrations in retail foodstuffs in Japan, and very low levels of contamination at the production and wholesale stage. However, because the residue limits and food safety policies were revised on an ad hoc, emergency basis after the nuclear accident, the monitoring procedure needs to be reviewed based on objective and scientifically rational criteria. A transparent and objective scientific framework is needed for prioritizing foodstuffs for inspection and revising Prefecture-specific restrictions. Monitoring of fishes and other seafood products in the wild should be regularized and the information made more publicly accessible, and monitoring activities expanded to identify foodstuffs that are no longer a food safety risk. Consultation with producers and consumers should be more formalized to ensure their concerns are incorporated into regular policy reviews in an appropriate and transparent manner. However, despite the limited available knowledge on best practice in food control and enforcement of provisional radio-contamination limits after the accident, current Japanese policy is sufficient to protect the Japanese public from major risk of radio-contamination from the commercial food market.

Future Earth Health Knowledge-Action Network.

Future Earth is an international research platform providing the knowledge and support to accelerate our transformations to a sustainable world. Future Earth 2025 Vision identified eight key focal challenges, and challenge #6 is to "Improve human health by elucidating, and finding responses to, the complex interactions amongst environmental change, pollution, pathogens, disease vectors, ecosystem services, and people's livelihoods, nutrition and well-being." Several studies, including the Rockefeller Foundation/Lancet Planetary Health Commission Report of 2015, the World Health Organization/Convention on Biological Diversity report and those by oneHEALTH (former ecoHEALTH), have been conducted over the last 30 years. Knowledge-Action Networks (KANs) are the frameworks to apply Future Earth principles of research to related activities that respond to societal challenges. Future Earth Health Knowledge-Action Network will connect health researchers with other natural and social scientists, health and environmental policy professionals and leaders in government, the private sector and civil society to provide research-based solutions based on better, integrated understanding of the complex interactions between a changing global environment and human health. It will build regional capacity to enhance resilience, protect the environment and avert serious threats to health and will also contribute to achieving Sustainable Development Goals. In addition to the initial partners, Future Earth Health Knowledge-Action Network will further nourish collaboration with other on-going, leading research programmes outside Future Earth, by encouraging them in active participation.

Dose response modelling of Escherichia coli O157 incorporating data from foodborne and environmental outbreaks.

A human dose response model for Escherichia coli O157 would enable prediction of risk of infection to humans following exposure from either foodborne or environmental pathways. However, due to the severe nature of the disease, volunteer human dose response studies cannot be carried out. Surrogate models from Shigella fed to humans and E. coli O157 to rabbits have been utilised but are significantly different to one another. In addition data obtained by animal exposure may not be representative for human beings. An alternative approach to generating and validating a dose response model is to use quantitative data obtained from actual human outbreaks. This work collates outbreak data obtained from global sources and these are fitted using exponential and beta-Poisson models. The best fitting model was found to be the beta-Poisson model using a beta-binomial likelihood and the authors favour the exact version of this model. The confidence levels in this model encompass a previously published Shigella dose response model. The potential incorporation of this model into QMRAs is discussed together with applications of the model to help explain foodborne outbreaks.

Prolonged incubation period of salmonellosis associated with low bacterial doses.

In gastroenteritis outbreaks caused by Salmonella-contaminated lunches at elementary, junior high, and nursery schools. outbreaks with long median incubation periods (i.e., 60 to 120 h) were observed frequently between 1990 and 1999 in Japan. We analyzed epidemiological data on 185 outbreaks of Salmonella Enteritidis infection to study the factors underlying the long incubation period. These survey results showed that the median incubation period for Salmonella Enteritidis infection from contaminated school and nursery school lunches was significantly longer than that from other types of cooking facilities. In addition, we analyzed the relationship between the median incubation period and the bacterial dose ingested per person in nine outbreaks of Salmonella Enteritidis infection; the bacterial dose was estimated with reference to the bacterial concentration in the causative foods. A significant negative correlation between the bacterial dose ingested per person and the median incubation period is clearly shown. The time elapsed from the start of the cooking process to the consumption of school and nursery school lunches was significantly shorter than at other cooking facilities, suggesting limited bacterial growth, which in turn is thought to lead to a long incubation period.

Ribotyping and a study of transmission of Staphylococcus aureus collected from food preparation facilities.

Food poisoning from Staphylococcus aureus is sometimes caused by improper handling of food items in food preparation facilities. Prevention of contamination by employees is particularly important in facilities where a significant amount of food preparation is performed by hand. Some experiments have been performed to describe bacterial cross-contamination in the food preparation process, but there have been few studies of cross-contamination in actual food preparation facilities. Aiming to shed light on the transmission of S. aureus in food preparation facilities, this study collected samples of 66 strains of this bacterium from the fingers of food preparation staff, foodstuffs, prepared foods, cooking utensils, and cooking equipment and typed them with the ribotyping method. S. aureus from the same ribogroup was detected on the hands of a study participant, a faucet, knife, frying pan, and a salad, indicating that bacteria found on the hands of the study participant was transmitted to cooking utensils and prepared foods. Transmission (from a faucet to a frying pan handle) of bacteria by another person, a third party, was also detected.

Archiving of food samples from restaurants and caterers--quantitative profiling of outbreaks of foodborne salmonellosis in Japan.

The Ministry of Health, Labor and Welfare (former MHW) of Japan issued a Directive in 1997 advising restaurants and caterers to freeze portions of both raw food and cooked dishes for at least 2 weeks. This system has been useful for determining vehicle foods at outbreaks. Enumeration of bacteria in samples of stored food provide data about pathogen concentrations in the implicated food. Data on Salmonella concentrations in vehicle foods associated with salmonellosis outbreaks were collected in Japan between 1989 and 1998. The 39 outbreaks that occurred during this period were categorized by the settings where the outbreaks took place, and epidemiological data from each outbreak were summarized. Characteristics of outbreak groups were analyzed and compared. The effect of new food-storage system on determination of bacterial concentration was evaluated. Freezing and nonfreezing conditions prior to microbial examination were compared in the dose-response relationship. Data from outbreaks in which implicated foods had been kept frozen suggested apparent correlation between the Salmonella dose ingested and the disease rate. Combined with results of epidemiological investigation, quantitative data from the ingested pathogen could provide complete dose-response data sets.

[Safety information project on drug, food and chemicals. Division of Safety Information on Drug, Food and Chemicals. National Institute of Health Sciences].

Recent issues on BSE(Bovine Spongiform Encephalopathy) and health hazards caused by adverse reactions of medical drugs, have strongly emphasized the necessity for safety measures to secure public health. These issues have been attributed to the delay to obtain overseas information on safety and regulation, and the lack of an adequate system for acquirement and assessment of such information. In order to develop a system where domestic and international safety information is collected, analyzed, assessed and presented both scientifically and systematically, the Division of Chem-Bio Informatics of the National Institute of Health Sciences was reorganized to the Division of Safety Information on Drug, Food and Chemicals in April, 2003. Collection and evaluation of safety information on medical drugs, food and chemical substances is now centralized at the Division, which consists of 5 sections, the first, second and third sections being newly established. The first section assesses information on medical drugs, the second section deals with food microorganisms, and the third section focuses on chemicals in food. The fourth and fifth sections retain their previous functions, namely, chemical safety information research and information network infrastructure support within the institute, respectively. The purpose of this paper is to describe how we will manage safety information on drug, food and chemicals, focusing on the role of the three new sections.

[Trends of plant toxin food poisonings during the past 50 years in Japan].

In the present study, we reviewed food poisoning data published by the Ministry of Health, Labour and Welfare of Japan from 1961 to 2010 in Japan to analyze the trends of plant toxin food poisonings (PTFPs). The annual number of incidents of PTFPs has gradually increased since 1995. PTFPs were predominantly caused by Datura spp., Veratrum spp. and Aconitum spp. Although PTFPs frequently occurred in April and May, poisonings caused by some plants occurred in all seasons, e.g. Datura spp. The major location of PTFPs was "at home", and most of the patients had accidentally harvested poisonous plants. During the past decade, the numbers of incidents of PTFPs caused by Veratrum spp., Narcissus spp., Solanum tuberosum and Alocasia odora were especially increased. Consumer advice to prevent PTFPs associated with certain plants that are cultivated in gardens and contain toxic substances is needed, because PTFPs caused by such plants are increasing. In addition, education of elementary school teachers and children about the potential risks of natural toxins in plants, particularly Solanum tuberosum, is desirable.

The global burden of foodborne parasitic diseases: an update.

Foodborne diseases (FBDs) are a major cause of morbidity and mortality in the human population. Accurate information on the burden of FBDs is needed to inform policy makers and allocate appropriate resources for food safety control and intervention. Consequently, in 2006 the WHO launched an initiative to estimate the global burden of FBDs in terms of Disability Adjusted Life Years (DALYs). This review gives an update of the progress on evaluating the burden of foodborne parasitic diseases that has been generated by this study. Results to date indicate that parasitic diseases that can be transmitted through food make a substantial contribution to the global burden of disease.

Providencia alcalifaciens causes barrier dysfunction and apoptosis in tissue cell culture: potent role of lipopolysaccharides on diarrheagenicity.

Providencia alcalifaciens is a member of the Enterobacteriaceae family that occasionally causes diarrheagenic illness in humans via the intake of contaminated foods. Despite the epidemiological importance of P. alcalifaciens, little is known about its pathobiology. Here we report that P. alcalifaciens causes barrier dysfunction in Caco-2 cell monolayers and induces apoptosis in calf pulmonary artery endothelial cells. P. alcalifaciens infection caused a 30% reduction in transepithelial resistance in Caco-2 cell monolayers, which was greater than that for cells infected with Shigella flexneri or non-pathogenic Escherichia coli. As with viable bacteria, bacterial lysates treated with heat, benzonase or proteinase, but not with polymixin B, were also involved in the cellular response. TLR4 antibody neutralisation significantly restored the P. alcalifaciens-induced transepithelial resistance reduction in Caco-2 cells, suggesting that lipopolysaccharides (LPSs) might play a central role in this cellular response. Western blotting further indicated that P. alcalifaciens LPSs reduced occludin levels, whereas LPSs from Shigella or E. coli did not. Although the viability of Caco-2 cells was not altered significantly, the calf pulmonary artery endothelial cell line was highly sensitive to P. alcalifaciens infection. This sensitivity was indeed dependent on LPS, which induced rapid apoptosis. Together, these data show that P. alcalifaciens LPSs participate in epithelial barrier dysfunction and endothelial apoptosis. The findings give insight into the LPS-dependent cell signal events affecting diarrheagenicity during infection with P. alcalifaciens.