Shiga Toxin-Producing Escherichia coli Infections Associated With Romaine Lettuce-United States, 2018.

BACKGROUND: Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation. METHODS: A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination. RESULTS: We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157. CONCLUSIONS: We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.

A scoping review of waterborne and water-related disease in the Florida environment from 1999 to 2022.

Florida's environments are suitable reservoirs for many disease-causing agents. Pathogens and toxins in Florida waterways have the potential to infect mosquito vectors, animals, and human hosts. Through a scoping review of the scientific literature published between 1999 and 2022, we examined the presence of water-related pathogens, toxins, and toxin-producers in the Florida environment and the potential risk factors for human exposure. Nineteen databases were searched using keywords relating to the waterborne, water-based toxins, and water-related vector-borne diseases which are reportable to the Florida Department of Health. Of the 10,439 results, 84 titles were included in the final qualitative analysis. The resulting titles included environmental samples of water, mosquitoes, algae, sand, soil/sediment, air, food, biofilm, and other media. Many of the waterborne, water-related vector-borne, and water-based toxins and toxin-producers of public health and veterinary importance from our search were found to be present in Florida environments. Interactions with Florida waterways can expose humans and animals to disease and toxins due to nearby human and/or animal activity, proximal animal or human waste, failing or inadequate water and/or sanitation, weather patterns, environmental events, and seasonality, contaminated food items, preference of agent for environmental media, high-risk populations, urban development and population movement, and unregulated and unsafe environmental activities. A One Health approach will be imperative to maintaining healthy waterways and shared environments throughout the state to protect the health of humans, animals, and our ecosystems.

Review article: Impact of pandemics on rural emergency departments: A scoping review.

Pandemics can cause much distress to communities and present a major burden to the resources and functioning of hospitals. This scoping review aimed to identify, evaluate and summarise current literature regarding how pandemics impact rural EDs in terms of staff wellbeing, structure, function and resources. A systematic search of six databases using search terms including pandemic, ED and rural and remote was undertaken. Articles were included if they were peer-reviewed, written in English, original research, published between January 2010 and October 2021 and discussed the impact of pandemics on rural EDs. Articles were critically appraised using the Mixed Methods Appraisal Tool (MMAT). Three articles, one from Canada and two from the United States, met the inclusion criteria. The articles included were quantitative in design and fulfilled most of the MMAT critical analysis criteria. Pandemics reported on included H1N1 and COVID-19. These pandemics impacted rural EDs in terms of functioning and resourcing; no description of staff wellbeing or structure was identified. Rural ED functioning was affected in terms of input; with an increase in patient presentations and time to physician assessment during H1N1, but a decrease in patient presentations and transfers during COVID-19. Rural ED resources were impacted in regard to staffing, difficulty in obtaining stocks of personal protective equipment and medication, and community response. Further research to understand and address the short- and long-term impacts pandemics may have on rural EDs is required.

A Systematic Review of Zoonotic Enteric Parasites Carried by Flies, Cockroaches, and Dung Beetles.

Filth flies, cockroaches, and dung beetles have been close neighbors with humans and animals throughout our joint histories. However, these insects can also serve as vectors for many zoonotic enteric parasites (ZEPs). Zoonoses by ZEPs remain a paramount public health threat due to our close contact with animals, combined with poor water, sanitation, and hygiene access, services, and behaviors in many global regions. Our objective in this systematic review was to determine which ZEPs have been documented in these vectors, to identify risk factors associated with their transmission, and to provide effectual One Health recommendations for curbing their spread. Using PRISMA guidelines, a total of 85 articles published from 1926 to 2021 were reviewed and included in this study. Qualitative analysis revealed that the most common parasites associated with these insects included, but were not limited to: Ascaris spp., Trichuris spp., Entamoeba spp., and Cryptosporidium spp. Additionally, prominent risk factors discovered in the review, such as poor household and community WASH services, unsafe food handling, and exposure to domestic animals and wildlife, significantly increase parasitic transmission and zoonoses. The risk of insect vector transmission in our shared environments makes it critically important to implement a One Health approach in reducing ZEP transmission.

A systematic review of waterborne and water-related disease in animal populations of Florida from 1999-2019.

BACKGROUND: Florida's waters are a reservoir for a host of pathogens and toxins. Many of these microorganisms cause water-related diseases in people that are reportable to the Florida Department of Health. Our objective in this review was to ascertain which water-related pathogens and toxins of public health importance have been found in animal populations in Florida over the last twenty years. METHODS: Nineteen databases were searched, including PubMed and Web of Science Core Collection, using keywords and search terms for the waterborne diseases, water-related vector-borne diseases, and water-based toxins reportable to the Florida Department of Health. For inclusion, peer-reviewed journal articles were to be written in English, published between January 1, 1999 and December 31, 2019, and contain primary research findings documenting at least one of the water-related pathogens or toxins of interest in an animal population within Florida during this same time frame. RESULTS: Of over eight thousand initial search results, 65 studies were included for final analysis. The most common animal types implicated in the diseases of interest included marine mammals, fish and shellfish, wild birds, and livestock. Toxins or pathogens most often associated with these animals included toxin-producer Karenia brevis, vibriosis, Escherichia coli, and Salmonellosis. DISCUSSION/CONCLUSION: Findings from this review elucidate the water-related disease-causing pathogens and toxins which have been reported within animal populations in recent Florida history. As most of these diseases are zoonotic, our results suggest a One Health approach is necessary to support and maintain healthy water systems throughout the state of Florida for the protection of both human and animal populations.

Twenty years of waterborne and related disease reports in Florida, USA.

Florida represents a unique challenge for preventing and responding to infectious disease associated with water. This study cataloged the prevalence of reportable waterborne and water-related disease within Florida residents over the last twenty years and identified relationships between confirmed cases by location and additional risk factors. Data was collected through FLHealthCHARTS for confirmed cases between January 1, 1999 and December 31, 2019. Case records were compiled and analyzed by year, county, pathogen name and disease category, patient age, and where the infection was acquired. During this time, 218,707 cases of water-related disease were recorded with 214,745 due to waterborne disease, 3255 cases of water-related vector-borne disease, and 707 cases caused by a water-based toxin. Children aged 0-4 and the elderly demonstrated a higher proportion of waterborne disease while 45-49 year olds had increased rates of water-based toxins and water-related vector-borne disease. Most cases were reported in the southeast region. Across the state, opportunities for water contact have led to high rates of water-related infectious disease. Public health initiatives and response efforts should target the pathogens of greatest impact for each region, largely zoonotic waterborne diseases, using a One Health approach.

Zoonotic enteric parasites in Mongolian people, animals, and the environment: Using One Health to address shared pathogens.

BACKGROUND: Cryptosporidium spp. and Giardia duodenalis are important zoonotic enteric pathogens of One Health concern for humans, animals, and the environment. For this study, we investigated parasite prevalence and risk factors among rural, peri-urban, and urban households and environments of Mongolia. METHODS: This cross-sectional study implemented a household risk factor survey at 250 home sites along with sample collection from humans, animals, flies, and drinking water. Multiplex real-time PCR analysis was conducted to look for Cryptosporidium spp. and/or Giardia duodenalis within household samples. RESULTS: Lab analysis found one or both zoonotic parasites at 20% of the participating households (51/250). Human samples had a parasite prevalence of 6.4% (27/419), domestic animals at 3.3% (19/570), pooled filth flies at 14.8% (17/115), and drinking water samples at 2% (5/250). Parasite presence at the household was significantly associated with a household's use of an improved drinking water source (OR 0.27; CI 0.12-0.61; p = < 0.01), having an indoor handwashing site (OR 0.41; CI 0.19-0.92; p = 0.03), domestic animal ownership (OR 2.40; CI 1.02-5.65; p = 0.05), and rural location (OR 0.50; CI 0.25-0.98; p = 0.04). Household use of an improved drinking water source remained significant in the multivariate model (OR 0.16; CI 0.04-0.68; p = 0.01). CONCLUSION: In Mongolia, public and veterinary health are intertwined, particularly for rural herding households. Increased access to safe water, sanitation and hygiene infrastructure could help prevent further transmission of zoonotic enteric parasites. Public health interventions, policy and messaging should utilize a One Health framework employing joint leadership from local human and animal health sectors.

A Series of Papaya-Associated Salmonella Illness Outbreak Investigations in 2017 and 2019: A Focus on Traceback, Laboratory, and Collaborative Efforts.

ABSTRACT: In 2017 and 2019, five outbreaks of infections from multiple strains of Salmonella linked to the consumption of whole, fresh Maradol papayas were reported in the United States, resulting in 325 ill persons. Traceback, laboratory, and epidemiologic evidence indicated papayas as the likely vehicle for each of these outbreaks and identified the source of papayas. State and U.S. Food and Drug Administration (FDA) laboratories recovered Salmonella from papaya samples from various points of distribution, including at import entry, and conducted serotyping, pulsed-field gel electrophoresis, and phylogenetic analyses of whole genome sequencing data. Federal and state partners led traceback investigations to determine the source of papayas. Four different suppliers of papayas were linked by traceback and laboratory results to five separate outbreaks of Salmonella infections associated with papayas. In 2017, multiple states tested papaya samples collected at retail, and Maryland and Virginia investigators recovered strains of Salmonella associated with one outbreak. FDA collected 183 papaya samples in 2017, and 11 samples yielded 62 isolates of Salmonella. Eleven serotypes of Salmonella were recovered from FDA papaya samples, and nine serotypes were closely related genetically by pulsed-field gel electrophoresis and whole genome sequencing to clinical isolates of four outbreaks, including the outbreak associated with positive state sample results. Four farms in Mexico were identified, and their names were released to the general public, retailers, and foreign authorities. In 2019, FDA collected 119 papaya samples, three of which yielded Salmonella; none yielded the 2019 outbreak strain. Investigators determined that papayas of interest had been sourced from a single farm in Campeche, Mexico, through traceback. This information was used to protect public health through public guidance, recalls, and import alerts and helped FDA collaborate with Mexican regulatory partners to enhance the food safety requirements for papayas imported from Mexico.

Feline-Human Zoonosis Transmission in North Africa: A Systematic Review.

Throughout human history, domestic animal species have represented a unique zoonotic disease risk for the transmission of pathogens ranging from viral, bacterial, parasitic, and fungal. In North Africa, cats have a particularly long record and occupy a specialized niche within many communities. This systematic review was conducted to analyze the current and historical literature documenting the breadth and variety of zoonoses in North Africa, specifically relating to the domesticated feline. Multiple electronic databases were searched on January 16, 2019, for published reports on feline zoonoses in North Africa. A total of 76 studies met the inclusion criteria for a full assessment. Articles selected for the review ranged in publication dates from 1939 to 2019 and included a case study, cross-sectional surveys, genomic analyses, and a book chapter. The most commonly studied pathogen was Toxoplasma gondii (n = 17) followed by a variety of helminths (n = 10). Of the countries in the target region, most publications were of studies conducted in Egypt (n = 53) followed by Tunisia (n = 12), Algeria (n = 11), Morocco (n = 5), and Libya (n = 3). The results of this review identify a variety of viral, bacterial, fungal, and parasitic zoonotic diseases associated with cats in North Africa, ranging from historically endemic diseases in both human and animal populations in the region, to emerging infections with recent confirmatory diagnoses. This review describes reported feline zoonoses in North Africa and provides recommendations for their prevention and control. In addition to vaccination campaigns for domesticated felines and postexposure prophylaxis for humans, prompt veterinary and medical care of exposure risks and subsequent infections are essential in limiting the zoonotic disease burden in North African communities of humans and cats.

Lay Summaries of Clinical Study Results: An Overview.

The European Union Clinical Trials Regulation (EU CTR) 536/2014 includes a requirement for the submission of lay summaries. Study participants, advocacy groups, and, to a lesser extent, the general public have called for greater transparency in their quest for information on clinical studies. As a complement to other forms of clinical study disclosure such as registry postings and scientific publications, lay summaries may aid in the transparency of a sponsor's clinical study results, thereby promoting trust, partnership, and patient engagement throughout the clinical study process. The data transparency field is changing rapidly; therefore, data owners should strive to stay abreast of the changes and deliver meaningful tools to their study participants and the public. Points to consider when developing lay summaries of clinical study results include regulatory drivers, the target audience, communication of complex data in a lay manner, and efficient processes for the development of lay summaries within one's company.

There is a rule in Europe that clinical studies (experiments in humans) must have a summary written in plain language. Summaries written in plain language help people who are not scientists or doctors understand complex medical information. People who participate in clinical studies, and others, may want to know information about clinical study results. Lay summaries are a way to share clinical study results, but they do not replace other ways that information is shared. Lay summary writers must think about how they can help readers understand the information. It is hard to describe the results of clinical studies in a way that everyone can understand. This article gives some ideas to think about when writing lay summaries.

Overview of Leafy Greens-Related Food Safety Incidents with a California Link: 1996 to 2016.

An increase in the number of foodborne illness outbreaks associated with produce has been noted in the literature, and leafy greens have been the most common produce category associated with these outbreaks. California is the largest leafy greens producer in the United States, and many related foodborne illness incidents were traced to this state. A systematic overview of leafy greens incidents linked to California was conducted by the California Department of Public Health, Food and Drug Branch through analysis of complaints, routine surveillance sampling, disease outbreaks, and investigations covering 1996 to 2016. The goal was to develop a risk assessment tool to modernize emergency response efforts to foodborne illnesses related to leafy greens. A database including environmental, epidemiologic, and laboratory information for each incident was developed, and descriptive analysis was performed to identify trends. In the 21-year period analyzed, 134 incidents were identified, the majority of which were surveillance related. Approximately 2,240 U.S. cases of confirmed illness were reported (298 California cases resulting in 50 hospitalizations). Romaine lettuce and spinach were the most commonly implicated vehicles. The most prevalent hazard type was microbiological, in particular bacterial, specifically associated with pathogenic strains of Escherichia coli. In California, the overview provided the Food and Drug Branch with a platform to (i) enhance its Food Safety Program, Emergency Response Unit, and California Food Emergency Response Team; (ii) assist in more efficient investigation, response, control, and prevention of California-linked foodborne illness incidents; and (iii) identify knowledge gaps and develop effective definitions, procedures, training, guidelines, and policies that will be used to help prevent future outbreaks. Outcomes provide insight into the situation in the largest leafy greens-producing state and may be used to prioritize limited national food safety resources and aid in future leafy greens-related research and foodborne incident investigations.

A case series of fatal meningoencephalitis in Mongolia: epidemiological and molecular characteristics of tick-borne encephalitis virus.

In Mongolia, the incidence and fatality rates of tick-borne encephalitis (TBE) have been increasing. We aimed to identify the epidemiological and molecular characteristics of tick-borne encephalitis virus (TBEV) associated with fatal meningoencephalitis in Mongolia. We conducted a descriptive study of 14 fatal cases of TBE that occurred between 2008 and 2017 in Mongolia. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect viral RNA in brain tissue. RT-PCR products from six patients who died from TBE between 2013 and 2017 were directly sequenced and analysed phylogenetically. Ticks collected from Selenge and Bulgan provinces were also tested for TBEV by RT-PCR. Between 2008 and 2017, there were 14 fatal TBE cases in hospitals in Mongolia. The 14 patients who died reported receiving tick bites in Bulgan or Selenge province; 71.4% of deaths resulted from tick bites in Bulgan province. The TBE case fatality rate was 28.6% for patients in Bulgan province and 2.7% for those in Selenge province. All of the fatalities were men; the median age was 45 ± 12.6 years. Tick bites occurred between April and June in forested areas. In 2013, a 388 base pair fragment of the envelope (E) gene was obtained from a hospitalized patient. The closest relatives of this virus are Far-Eastern TBEV isolates. The case fatality rate differed between two provinces where tick bites occurred. A higher number of TBE cases and the virulent Far-Eastern subtype occurred in patients in Bulgan province. This province should increase vaccination coverage, training, education and investigations.

The association between domestic animal presence and ownership and household drinking water contamination among peri-urban communities of Kisumu, Kenya.

INTRODUCTION: Household drinking water can be contaminated by diarrheagenic enteropathogens at numerous points between the source and actual consumption. Interventions to prevent this contamination have focused on preventing exposure to human waste through interventions to improve drinking water, sanitation and hygiene (WASH). In many cases though, the infectious agent may be of zoonotic rather than human origin suggesting that unsafely managed animal waste may contribute to the contamination of household drinking water and the associated diarrheal disease burden. METHODS: A cross-sectional household survey of 800 households was conducted across three informal peri-urban neighborhoods of Kisumu, Kenya, collecting stored drinking water samples, administering a household survey including water, sanitation and hygiene infrastructure and behaviors, and recording domestic animal presence and ownership. We used multivariate logistic regression to assess the association of traditional WASH factors and domestic animal presence and ownership on microbial contamination of household drinking water. RESULTS: The majority of households sampled had fecally contaminated drinking water (67%), defined by the presence of any colony forming units of the fecal indicator bacteria enterococci. After adjustment for potential confounders, including socio-economic status and water and sanitation access, both household animal ownership (aOR 1.31; CI 1.00-1.73, p = 0.05) and the presence of animal waste in the household compound (aOR 1.38; CI 1.01, 1.89, p = 0.04) were found to be significantly associated with household drinking water contamination. None of the conventional WASH variables were found to be significantly associated with household drinking water contamination in the study population. CONCLUSIONS: Water, sanitation, and hygiene strategies to reduce diarrheal disease should consider the promotion of safe animal contact alongside more traditional interventions focusing on the management of human waste. Future research on fecal contamination of unsafe household drinking water should utilize host-specific markers to determine whether the source is human or animal to prepare targeted public health messages.

A systematic review of zoonotic enteric parasitic diseases among nomadic and pastoral people.

INTRODUCTION: Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water, sanitation, and hygiene practices and diet. While most communities are now sedentary, nomadic and pastoral populations still exist and experience unique exposure risks for acquiring zoonotic enteric parasites. Through this systematic review we sought to summarize published research regarding pathogens present in nomadic populations and to identify the risk factors for their infection. METHODS: Using systematic review guidelines set forth by PRISMA, research articles were identified, screened and summarized based on exclusion criteria for the documented presence of zoonotic enteric parasites within nomadic or pastoral human populations. A total of 54 articles published between 1956 and 2016 were reviewed to determine the pathogens and exposure risks associated with the global transhumance lifestyle. RESULTS: The included articles reported more than twenty different zoonotic enteric parasite species and illustrated several risk factors for nomadic and pastoralist populations to acquire infection including; a) animal contact, b) food preparation and diet, and c) household characteristics. The most common parasite studied was Echinococcosis spp. and contact with dogs was recognized as a leading risk factor for zoonotic enteric parasites followed by contact with livestock and/or wildlife, water, sanitation, and hygiene barriers, home slaughter of animals, environmental water exposures, household member age and sex, and consumption of unwashed produce or raw, unprocessed, or undercooked milk or meat. CONCLUSION: Nomadic and pastoral communities are at risk of infection with a variety of zoonotic enteric parasites due to their living environment, cultural and dietary traditions, and close relationship to animals. Global health efforts aimed at reducing the transmission of these animal-to-human pathogens must incorporate a One Health approach to support water, sanitation, and hygiene development, provide education on safe food handling and preparation, and improve the health of domestic animals associated with these groups, particularly dogs.

Reverse zoonotic disease transmission (zooanthroponosis): a systematic review of seldom-documented human biological threats to animals.

BACKGROUND: Research regarding zoonotic diseases often focuses on infectious diseases animals have given to humans. However, an increasing number of reports indicate that humans are transmitting pathogens to animals. Recent examples include methicillin-resistant Staphylococcus aureus, influenza A virus, Cryptosporidium parvum, and Ascaris lumbricoides. The aim of this review was to provide an overview of published literature regarding reverse zoonoses and highlight the need for future work in this area. METHODS: An initial broad literature review yielded 4763 titles, of which 4704 were excluded as not meeting inclusion criteria. After careful screening, 56 articles (from 56 countries over three decades) with documented human-to-animal disease transmission were included in this report. FINDINGS: In these publications, 21 (38%) pathogens studied were bacterial, 16 (29%) were viral, 12 (21%) were parasitic, and 7 (13%) were fungal, other, or involved multiple pathogens. Effected animals included wildlife (n = 28, 50%), livestock (n = 24, 43%), companion animals (n = 13, 23%), and various other animals or animals not explicitly mentioned (n = 2, 4%). Published reports of reverse zoonoses transmission occurred in every continent except Antarctica therefore indicating a worldwide disease threat. INTERPRETATION: As we see a global increase in industrial animal production, the rapid movement of humans and animals, and the habitats of humans and wild animals intertwining with great complexity, the future promises more opportunities for humans to cause reverse zoonoses. Scientific research must be conducted in this area to provide a richer understanding of emerging and reemerging disease threats. As a result, multidisciplinary approaches such as One Health will be needed to mitigate these problems.

Serological evidence of ongoing transmission of dengue virus in permanent residents of Key West, Florida.

INTRODUCTION: Dengue fever is the most important mosquito-borne viral disease in the world, with 40% of the global population at risk of infection. Dengue virus is responsible for infections in over 100 countries, including the Americas and Caribbean Basin; however, it has been largely eradicated from the United States through the implementation of effective vector control programs. However, between 2009 and 2010, 27 permanent residents of Key West, Florida, were reported to have locally acquired infections, marking the first autochthonous cases detected in Florida since 1934. Despite this recent and unusual transmission, and the potential risk of serious illness associated with sequential infections, no active surveillance had been conducted since. MATERIALS AND METHODS: A serosurvey of permanent residents of Key West, Florida, was conducted in March of 2012. After informed consent, enrolled participants (n=173) were given a dengue virus rapid diagnostic test and completed a corresponding questionnaire. RESULTS: The presence of immunoglobulin G (IgG) antibodies was indicated in 12 participants (6.9%), all of whom reported travel to endemic countries within the past 2 years. Surprisingly, six participants (3.5%) without any recent travel outside the state of Florida gave positive results for IgM antibodies. The presence of birdbaths and bromeliads on the property and sleeping outdoors emerged as significant factors related to previous exposure, whereas home air conditioning without the use of open windows and the use of mosquito repellent were protective. CONCLUSIONS: These findings suggest local transmission occurred in Key West in early 2012, indicating that transmission may not have subsided in 2010.

Cyclooxygenase inhibition and hyperthermia for the potentiation of the cytotoxic response in ovarian cancer cells.

OBJECTIVES: The progression of chemotherapy-resistant cancer confers poor prognosis and decreases overall survival in ovarian cancer patients. Adjuvants to traditional chemotherapy regimens have become attractive modalities for the clinical treatment of refractory or resistant ovarian cancer. We evaluated whether the addition of NSAID to hyperthermic chemotherapy would increase cytotoxicity in cisplatin- and taxane-treated ovarian cancer cells. METHODS: Western blot analysis was utilized to determine COX-2 protein expression levels in the 2008, cisplatin-sensitive, and C13*, cisplatin-resistant, cell lines. PGE2 levels were determined and analyzed as a function of cyclooxygenase activity by LC/MS/MS. Cells were treated with cisplatin, docetaxel or paclitaxel in combination with either NS-398 or sulindac sulfide at 37 degrees C, 41 degrees C or 43 degrees C. Cell viability was determined by a MTS cell proliferation assay. RESULTS: Both cell lines expressed COX-2 protein, and NS-398 and sulindac sulfide effectively blocked PGE2 production. The addition of a NSAID to cisplatin treatment in 2008 and C13* cells offered enhanced cytotoxicity and this effect was further enhanced at 41 degrees C. In docetaxel-treated 2008 cells, both NS-398 and sulindac sulfide offered enhanced cell kill; however, this result was not observed in paclitaxel-treated cells. Hyperthermia appeared to play no additional role in taxane cytotoxicity enhancement, however no antagonism was detected. CONCLUSIONS: Our results suggest that the combination treatment (cisplatin or docetaxel in combination with NSAID) cause a dose-dependent enhancement of cytotoxicity. Hyperthermia may improve the results of intraperitoneal cisplatin therapy, thus warranting further evaluation in clinical studies.