Quantitative microbial risk assessment of haemolytic uremic syndrome associated with Argentinean kosher beef consumption in Israel.

The aim of this study was to perform a quantitative microbial risk assessment (QMRA) of Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) linked to the consumption of Kosher beef produced in Argentina and consumed in Israel in children under 14 years. A probabilistic risk assessment model was developed to characterize STEC prevalence and contamination levels in the beef supply chain (cattle primary production, cattle transport, processing and storage in the abattoir, for export and at retail, and home preparation and consumption). The model was implemented in Microsoft Excel 2016 with the @Risk add-on package. Results of 302 surveys with data collected in Israel were as follows: 92.3% of people consumed beef, mostly at home, and 98.2% preferred levels of cooking that ensured STEC removal from the surface of beef cuts. The preferred degree of ground beef doneness was "well-done" (48.2%). Cooking preference ranged from red to "medium-well done" (51.8%). Median HUS probability from Argentinean beef cut and ground beef consumption in children under 14 years old was <10-15 and 8.57x10-10, respectively. The expected average annual number of HUS cases and deaths due to beef cut and ground beef consumption was zero. Risk of infection and HUS probability correlated with salting effect on E. coli count, processing raw beef before vegetables, ways of storage and refrigeration temperature at home, joint consumption of salad and beef cuts, degree of beef doneness and cutting board washing with detergent after each use with beef and vegetables. The STEC-HUS risk in Israel from consumption of bovine beef produced in Argentina was negligible. The current QMRA results were similar to those of previous beef cut consumption QMRA in Argentina and lower than any of the QMRA performed worldwide in other STEC-HUS linked to ground beef consumption. This study confirms the importance of QMRA to estimate and manage the risk of STEC-HUS from beef consumption. The impact variables identified in the sensitivity analysis allowed us to optimize resources and time management, to focus on accurate actions and to avoid taking measures that would not have an impact on the risk of STEC-HUS.

Incidence and cost of haemolytic uraemic syndrome in urban China: a national population-based analysis.

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a severe syndrome that causes a substantial burden for patients and their families and is the leading cause of acute kidney injury in children. However, data on the epidemiology and disease burden of HUS in Asia, including China, are limited. We aimed to estimate the incidence and cost of HUS in China.  METHODS: Data about HUS from 2012 to 2016 were extracted from the Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) databases. All cases were identified by ICD code and Chinese diagnostic terms. The 2016 national incidence rates were estimated and stratified by sex, age and season. The associated medical costs were also calculated. RESULTS: The crude incidence of HUS was 0.66 per 100,000 person-years (95% CI: 0.35 to 1.06), and the standardized incidence was 0.57 (0.19 to 1.18). The incidence of HUS in males was slightly higher than that in females. The age group with the highest incidence of HUS was patients < 1 year old (5.08, 95% CI: 0.23 to 24.87), and the season with the highest incidence was autumn, followed by winter. The average cost of HUS was 2.15 thousand US dollars per patient, which was higher than the national average cost for all inpatients in the same period. CONCLUSIONS: This is the first population-based study on the incidence of HUS in urban China. The age and seasonal distributions of HUS in urban China are different from those in most developed countries, suggesting a difference in aetiology.

Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010-2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19-2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10-1.75) and hospitalisation (OR 1.71, 95% CI 1.36-2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16-2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40-2.27; OR 1.85, 95% CI 1.35-2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22-2.70; soil contact, OR 1.52, 95% CI 2.13-1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Paediatric HUS Cases Related to the Consumption of Raw Milk Sold by Vending Machines in Italy: Quantitative Risk Assessment Based on Escherichia coli O157 Official Controls over 7 years.

A quantitative risk assessment (RA) was developed to estimate haemolytic-uremic syndrome (HUS) cases in paediatric population associated with the consumption of raw milk sold in vending machines in Italy. The historical national evolution of raw milk consumption phenomenon since 2008, when consumer interest started to grow, and after 7 years of marketing adjustment, is outlined. Exposure assessment was based on the official Shiga toxin-producing Escherichia coli O157:H7 (STEC) microbiological records of raw milk samples from vending machines monitored by the regional Veterinary Authorities from 2008 to 2014, microbial growth during storage, consumption frequency of raw milk, serving size, consumption preference and age of consumers. The differential risk considered milk handled under regulation conditions (4°C throughout all phases) and the worst time-temperature field handling conditions detected. In case of boiling milk before consumption, we assumed that the risk of HUS is fixed at zero. The model estimates clearly show that the public health significance of HUS cases due to raw milk STEC contamination depends on the current variability surrounding the risk profile of the food and the consumer behaviour has more impact than milk storage scenario. The estimated HUS cases predicted by our model are roughly in line with the effective STEC O157-associated HUS cases notified in Italy only when the proportion of consumers not boiling milk before consumption is assumed to be 1%. Raw milk consumption remains a source of E. coli O157:H7 for humans, but its overall relevance is likely to have subsided and significant caution should be exerted for temporal, geographical and consumers behaviour analysis. Health education programmes and regulatory actions are required to educate people, primarily children, on other STEC sources.

[After the crisis is before the crisis: Coping-strategies for public health emergency situations on different levels--experiences of the German E. coli outbreak 2011]. / Nach der Krise ist vor der Krise. Allgemeine Strategien für die erfolgreiche Bewältigung medizinischer Krisensituationen basierend auf den Erfahrungen des EHEC-Ausbruchs 2011.

The German E. coli crisis in 2011 posed multifaceted challenges to the actors of the German health care system. This paper analyzes the outbreak from a multidisciplinary perspective. It offers best practices and general recommendations for future public health emergencies for hospitals as well as at the federal and local level, addressing medical practitioners as well as health care managers.

Modeling uncertainty of estimated illnesses attributed to non-O157:H7 Shiga toxin-producing escherichia coli and its impact on illness cost.

Because of numerous reported foodborne illness cases due to non-O157:H7 Shiga toxin-producing Escherichia coli (STEC) bacteria in the United States and elsewhere, interest in requiring better control of these pathogens in the food supply has increased. Successfully putting forth regulations depends upon cost-benefit analyses. Policy decisions often depend upon an evaluation of the uncertainty of the estimates used in such an analysis. This article presents an approach for estimating the uncertainties of estimated expected cost per illness and total annual costs of non-O157 STEC-related illnesses due to uncertainties associated with (i) recent FoodNet data and (ii) methodology proposed by Scallan et al. in 2011. The FoodNet data categorize illnesses regarding hospitalization and death. We obtained the illness-category costs from the foodborne illness cost calculator of the U.S. Department of Agriculture, Economic Research Service. Our approach for estimating attendant uncertainties differs from that of Scallan et al. because we used a classical bootstrap procedure for estimating uncertainty of an estimated parameter value (e.g., mean value), reflecting the design of the FoodNet database, whereas the other approach results in an uncertainty distribution that includes an extraneous contribution due to the underlying variability of the distribution of illnesses among different sites. For data covering 2005 through 2010, we estimate that the average cost per illness was about $450, with a 98% credible interval of $230 to $1,000. This estimate and range are based on estimations of about one death and 100 hospitalizations per 34,000 illnesses. Our estimate of the total annual cost is about $51 million, with a 98% credible interval of $19 million to $122 million. The uncertainty distribution for total annual cost is approximated well by a lognormal distribution, with mean and standard deviations for the log-transformed costs of 10.765 and 0.390, respectively.

[Risk communication of the Federal Institute for Risk Assessment during a food-related outbreak]. / Risikokommunikation des Bundesinstituts für Risikobewertung bei einem lebensmittelbedingten Ausbruch.

Information about and explanation of risks as well as the initiation of behavioral changes and preventive actions are core tasks of risk communication. During the EHEC/HUS outbreak in spring 2011, the governmental agencies responsible for risk communication mainly focused on these tasks. In general, risk communication is understood as a continuous, long-term process that aims at an adequate handling of risks. In contrast, crisis communication is focused rather on an acute event and aims at timely information and behavioral measures. During the EHEC/HUS outbreak, risk communication partly changed over to crisis communication. The risk communication activities of the Federal Institute for Risk Assessment (Bundesinstitüt für Risikobewertung, BfR) during the EHEC/HUS outbreak are presented here. The results of a representative survey that was conducted in Germany shortly after the outbreak show details of the success of these risk communication activities. Finally, the necessity of communication about scientific uncertainty is addressed and new ways in risk communication with regard to new media are highlighted.

Quantitative risk assessment of verocytotoxin-producing Escherichia coli O157 and Campylobacter jejuni related to consumption of raw milk in a province in Northern Italy.

A quantitative risk assessment was developed to describe the risk of campylobacteriosis and hemolytic uremic syndrome (HUS) linked to consumption of raw milk sold in vending machines in Northern Italy. Exposure assessment considered the microbiological status of dairy farms, expected milk contamination, storage conditions from bulk tank to home storage, microbial growth during storage, destruction experiments, consumption frequency of raw milk, age of consumers, serving size, and consumption preference. The differential risk between milk handled under regulation conditions (4°C throughout all phases) and the worst field handling conditions was considered. The probability of Campylobacter jejuni infection was modeled with a single-hit dose-response beta-Poisson model, whereas for HUS an exponential dose-response model was chosen and two probabilities were used to model the higher susceptibility of children younger than 5 years old. For every 10,000 to 20,000 consumers each year, the models predicted for the best and worst storage conditions, respectively, 2.12 and 1.14 campylobacteriosis cases and 0.02 and 0.09 HUS cases in the 0- to 5-year age group and 0.1 and 0.5 HUS cases in the >5-year age group. The expected pediatric HUS cases do not differ considerably from those reported in Italy by the Minister of Health. The model developed may be a useful tool for extending the assessment of the risk of campylobacteriosis and HUS due to raw milk consumption at the national level in Italy. Considering the epidemiological implications of this study, the risk of illness linked to raw milk consumption should not be ignored and could be reduced by the use of simple measures. Boiling milk before consumption and strict control of temperatures by farmers during raw milk distribution have significant effects on campylobacteriosis and HUS and are essential measures for risk management.

Cost of illness and disease burden in The Netherlands due to infections with Shiga toxin-producing Escherichia coli O157.

Infections with Shiga toxin-producing Escherichia coli O157 (STEC O157) are associated with hemorrhagic colitis, hemolytic uremic syndrome (HUS), and end-stage renal disease (ESRD). In the present study, we extend previous estimates of the burden of disease associated with STEC O157 with estimates of the associated cost of illness in The Netherlands. A second-order stochastic simulation model was used to calculate disease burden as disability-adjusted life years (DALYs) and cost of illness (including direct health care costs and indirect non-health care costs). Future burden and costs are presented undiscounted and discounted at annual percentages of 1.5 and 4%, respectively. Annually, approximately 2.100 persons per year experience symptoms of gastroenteritis, leading to 22 cases of HUS and 3 cases of ESRD. The disease burden at the population level was estimated at 133 DALYs (87 DALYs discounted) per year. Total annual undiscounted and discounted costs of illness due to STEC O157 infection for the Dutch society were estimated at €9.1 million and €4.5 million, respectively. Average lifetime undiscounted and discounted costs per case were both €126 for diarrheal illness, both €25,713 for HUS, and €2.76 million and €1.22 million, respectively, for ESRD. The undiscounted and discounted costs per case of diarrheal disease including sequelae were €4,132 and €2,131, respectively. Compared with other foodborne pathogens, STEC O157 infections result in relatively low burden and low annual costs at the societal level, but the burden and costs per case are high.

Diagnóstico de situación y evaluación de un programa de educación comunitaria para la prevención del Síndrome Urémico Hemolítico / Situation Diagnosis and Evaluation of a Community Education Program for the Prevention of Hemolytic Uremic Syndrome

Se conocen los puntos precisos de intervención en la cadena epidemiológica para prevenir el Síndrome Urémico Hemolítico, pero las condiciones pueden variar entre distintas localidades. OBJETIVOS: Con este estudio se pretende mostrar la utilidad de un modelo de diagnóstico de situación que permite optimizar la implementación de un programa preventivo de educación comunitaria de tipo “formación de formadores” en dos municipios de la provincia de Buenos Aires, y una evaluación de procesos. MÉTODO: El diagnóstico incluyó el relevamiento de la situación socio-sanitaria, hábitos y costumbres alimentarios y detección de los problemas en la cadena de producción, comercialización y consumo de alimentos. La evaluación del proceso fue cuali-cuantitativa: número de talleres y de participantes, e indagación de fortalezas y debilidades del proceso. RESULTADOS: Los principales problemas encontrados fueron la carencia de agua potable y de manejo de las excretas en un gran porcentaje de la población y los deficientes controles bromatológicos y de mantenimiento de la cadena de frío en la provisión de carne y leche. Este diagnóstico permitió adaptar el programa a las condiciones específicas locales, elemento necesario para lograr una intervención eficaz. Se realizaron en total 26 talleres con la participación de 588 agentes. El material gráfico fue de gran utilidad para la comprensión de los contenidos docentes y todos los participantes de los talleres respondieron con gran motivación. Se logró el apoyo de las autoridades locales, lo que facilitó la ejecución del programa

The precise points of intervention in the epidemiological chain to prevent Hemolytic Uremic Syndromeare well known, although conditions may vary between different localities. OBJECTIVES: This study aims to show the usefulness of a situation diagnostic model to optimize the implementation of a preventive community education program type “training the trainers” in two municipalities in the province of Buenos Aires, and the evaluation of the process. METHODS: The diagnosis included a survey of the socio-sanitary conditions, food habits and identifying problem sin the chain of production, marketing and consumption of food. Process assessment was qualitative and quantitative: number of workshops and participants, and determination of strengths and weaknesses of the process. RESULTS: The main concerns were: lack of safe water and excreta management in a large percentage of the population, weak bromatological controls and maintenance of cold chainin providing meat and milk. This diagnosis allowed to adaptthe program to specific local conditions, which is necessary to achieve effective intervention. A total of 26 workshops involving 588 agents were carried out. The artwork was useful for the understanding of educational contents and all workshop participants responded with great motivation. The support from local authorities facilitated the implementation of the program

[Hamburger consumption patterns and exposure assessment for verocytotoxigenic Escherichia coli (VTEC): simulation model]. / Hábitos de consumo de hamburguesas y riesgo de exposición a Escherichia coli verotoxigénica (VTEC): modelo de simulación.

A quantitative risk assessment was developed for verocytotoxigenic Escherichia coli (VTEC) associated with hamburger consumption. The assessment (simulation model) considers the distribution, storage and consumption patterns of hamburgers. The prevalence and concentration of VTEC were modelled at various stages along the agri-food beef production system using input derived from Argentinean data, whenever possible. The model predicted an infection risk of 4.45 x 10(-4) per meal for adults. The risk values obtained for children were 2.6 x 10(-4), 1.38 x 10(-5) and 4.54 x 10(-7) for infection, Hemolytic Uremic Syndrome (HUS) and mortality, respectively. The risk of infection and HUS was positively correlated with bacterial concentration in meat (r = 0.664). There was a negative association between homemade hamburgers (r = -0.116) and the risk of illness; however this association has been considered due to differences between retail and domiciliary storage systems (r = -0.567) and not because of the intrinsic characteristics of the product. The most sensitive points of the production system were identified through the risk assessment, therefore, these can be utilized as a basis to apply different risk management policies in public health.

Hábitos de consumo de hamburguesas y riesgo de exposición a Escherichia coli verotoxigénica (VTEC): modelo de simulación / Hamburger consumption patterns and exposure assessment for verocytotoxigenic Escherichia coli (VTEC): simulation model

El objetivo del trabajo fue evaluar cuantitativamente el riesgo para la salud pública debido a la infección por VTEC derivado del consumo de hamburguesas. Mediante un modelo de simulación, se analizaron procesos de distribución, almacenamiento y venta, así como hábitos de consumo. La prevalencia y concentración de VTEC fue incluida en el modelo sobre la base de información científica publicada acerca de la enfermedad. Las distribuciones de probabilidad que mejor describieron cada paso del proceso fueron incorporadas en el programa @RiskR, y se realizaron múltiples simulaciones empleando el análisis Monte Carlo. El riesgo estimado de padecer la infección por VTEC en los adultos fue de 4,45 x 10-4; mientras que en los niños, los riesgos de adquirir la infección, de padecer Síndrome Urémico Hemolítico (SUH) y de mortalidad fueron de 2,6 x 10-4, 1,38 x 10-5 y 4,54 x 10-7, respectivamente. El riesgo de adquirir la infección y sus secuelas estuvo correlacionado con la concentración bacteriana en la carne (r = 0,664). El consumo de hamburguesas de elaboración propia (r = -0,203) estuvo asociado con el riesgo de enfermar dadas las características del almacenamiento (r = -0,567), que forman parte de los hábitos de consumo de la población. La información generada debería considerarse durante el diseño de estrategias de gestión y comunicación del riesgo del SUH, con énfasis en la importancia que estos factores tienen en la trasmisión de la enfermedad.

A quantitative risk assessment was developed for verocytotoxigenic Escherichia coli (VTEC) associated with hamburger consumption. The assessment (simulation model) considers the distribution, storage and consumption patterns of hamburgers. The prevalence and concentration of VTEC were modelled at various stages along the agri-food beef production system using input derived from Argentinean data, whenever possible. The model predicted an infection risk of 4.45 x 10-4 per meal for adults. The risk values obtained for children were 2.6 x 10-4, 1.38 x 10-5 and 4.54 x10-7 for infection, Hemolytic Uremic Syndrome (HUS) and mortality, respectively. The risk of infection and HUS was positively correlated with bacterial concentration in meat (r = 0.664). There was a negative association between homemade hamburgers (r = -0.116) and the risk of illness; however this association has been considered due to differences between retail and domiciliary storage systems (r = -0.567) and not because of the intrinsic characteristics of the product. The most sensitive points of the production system were identified through the risk assessment, therefore, these can be utilized as a basis to apply different risk management policies in public health.

Quantitative risk assessment for verocytotoxigenic Escherichia coli in ground beef hamburgers in Argentina.

A quantitative risk assessment was developed for verocytotoxigenic Escherichia coli (E. coli VTEC) following hamburger consumption. The assessment considers initial contamination levels, cross-contamination and decontamination events during the cattle slaughter process and the distribution, storage and consumption patterns in Argentina and in similar countries in Latin-American. The model predicted an infection risk of 8.12x10(-7), a probability of Hemolytic Uremic Syndrome (HUS) of 4.6x10(-8) and a probability of mortality of 5.9x10(-9) per meal for adults. For children, the estimates per meal were 3.23x10(-7), 1.8x10(-8) and 6.31x10(-10) for infection, HUS and mortality, respectively. The risk of infection and HUS, were sensitive to the type of storage at home (r=-0.416), slaughterhouse storage temperature (r=0.240) and bacterial concentration in the cattle hide (r=0.239). There was an association between home preparation of hamburgers (r=-0.116) and the risk of illness, although this was a result of the type of storage at retail (r=-0.110) and at home and not their intrinsic characteristics. The most sensitive stages of the process were identified through the risk assessment and these can be used as a basis for measures of risk management.

Quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef patties consumed by young children in French households.

A quantitative risk assessment for Escherichia coli O157:H7 in frozen ground beef patties consumed by children under 10 years of age in French households was conducted by a national study group describing an outbreak which occurred in France in 2005. Our exposure assessment model incorporates results from French surveys on consumption frequency of ground beef patties, serving size and consumption preference, microbial destruction experiments and microbial counts on patties sampled from the industrial batch which were responsible for the outbreak. Two different exposure models were proposed, respectively for children under the age of 5 and for children between 5 and 10 years. For each of these two age groups, a single-hit dose-response model was proposed to describe the probability of hemolytic and uremic syndrome (HUS) as a function of the ingested dose. For each group, the single parameter of this model was estimated by Bayesian inference, using the results of the exposure assessment and the epidemiological data collected during the outbreak. Results show that children under 5 years of age are roughly 5 times more susceptible to the pathogen than children over 5 years. Exposure and dose-response models were used in a scenario analysis in order to validate the use of the model and to propose appropriate guidelines in order to prevent new outbreaks. The impact of the cooking preference was evaluated, showing that only a well-done cooking notably reduces the HUS risk, without annulling it. For each age group, a relation between the mean individual HUS risk per serving and the contamination level in a ground beef batch was proposed, as a tool to help French risk managers.

Public health implications of a case of haemolytic-uraemic syndrome associated with a concomitant outbreak of mild gastroenteritis in a small rural community.

The concomitant occurrence of a case of haemolytic-uraemic syndrome (HUS) and 62 cases of mild gastroenteritis in schools of a small rural community in southern Italy induced the health authorities to suspect a foodborne outbreak of shiga-toxin-producing Escherichia coli (STEC) infection. The schools were closed and the catering service involved was investigated. However, STEC were not isolated from the HUS case or from the 56 cases of gastroenteritis examined, and the HUS case and the outbreak of gastroenteritis were probably just coincidental. A retrospective cohort study failed to show any correlation with consumption of school meals and suggested that the outbreak probably started outside the school setting and then spread within the schools by person-to-person transmission. All the cases examined were negative for common enteric pathogens and the responsible agent for the cases of gastroenteritis was not identified. The concern raised in the small community by the occurrence of a severe case of HUS and the lack of a rapid epidemiological assessment excluding the occurrence of a STEC outbreak, turned an epidemic episode of mild gastroenteritis into a public health emergency with relevant socioeconomic consequences. Prompt intervention in outbreaks following timely and effective risk communication are crucial for taking the most appropriate control measures and avoiding the spread of fear and panic in the community.

Economic cost of illness due to Escherichia coli O157 infections in the United States.

The Centers for Disease Control and Prevention (CDC) has estimated that Shiga toxin-producing Escherichia coli O157 (0157 STEC) infections cause 73,000 illnesses annually in the United States, resulting in more than 2,000 hospitalizations and 60 deaths. In this study, the economic cost of illness due to O157 STEC infections transmitted by food or other means was estimated based on the CDC estimate of annual cases and newly available data from the Foodborne Diseases Active Surveillance Network (FoodNet) of the CDC Emerging Infections Program. The annual cost of illness due to O157 STEC was $405 million (in 2003 dollars), including $370 million for premature deaths, $30 million for medical care, and $5 million in lost productivity. The average cost per case varied greatly by severity of illness, ranging from $26 for an individual who did not obtain medical care to $6.2 million for a patient who died from hemolytic uremic syndrome. The high cost of illness due to O157 STEC infections suggests that additional efforts to control this pathogen might be warranted.

Thrombotic microangiopathy after renal transplantation in the United States.

BACKGROUND: Analysis of the incidence, time to event, and risk factors for thrombotic microangiopathy (TMA) after renal transplantation (RT), has not been reported in a national population. METHODS: This is a historical cohort study of 15,870 RT recipients in the United States Renal Data System (USRDS) with Medicare as their primary payer between January 1, 1998, and July 31, 2000, followed until December 31, 2000. Patients with Medicare claims with a diagnosis of TMA (International Classification of Diseases, 9th Revision, codes 283.11x or 446.6x) after RT were assessed by Cox regression. RESULTS: Among patients with end-stage renal disease owing to hemolytic uremic syndrome (HUS), 29.2% later had TMA versus 0.8% of patients with ESRD owing to other causes. The incidence of TMA in RT recipients was 5.6 episodes per 1,000 person-years (PY; 189/1,000 PY; for recurrent TMA versus 4.9/1,000 PY for de novo TMA). The risk of TMA was highest for the first 3 months after transplant. Risk factors for de novo TMA included younger recipient age, older donor age, female recipient, and initial use of sirolimus. Patient survival rate after TMA was approximately 50% at 3 years. CONCLUSION: De novo TMA is uncommon and may occur later after RT than previously reported. Risk factors for de novo TMA were also identified.