Review

J Med Discov (2021); 6(1):jmd20058; DOI:10.24262/jmd.6.1.20058; 
Received August 03rd, 2020, Revised September 25th, 2020, Accepted November 21st, 2020, Published February 2rd, 2021.

Population-based Study of Septicaemia and Intestinal Infection Diseases Deaths in America and Twenty Major Developed Countries 2013-15: Indicative of Poor Food Production and Handling?  

Colin Pritchard¹,Lars Hansen², Stefan Kleidpoedszus¹

¹Faculty of Health & Social Sciences, Bournemouth University,

²School of Medicine, University of Southampton.

* Correspondence:Colin Pritchard, Royal London House, Christchurch Rd; Bournemouth BH13LT.E-mail: cpritchard@bournemouth.ac.uk

Introduction: American research produced evidence that USA food production and handling, and, the misuse of anti-biotics is linked to increased cases of septicaemia and food-poisoning. This led to this comparison of the extremes of this problem examining current Intestinal Infection Disease Deaths (IIDD) and Septicaemia mortality rates in the USA compared to the twenty Major Developed Countries (MDC) 2013-2015.

Methods & Material: WHO mortality data analysed for Septicaemia and IIDD mortality Age-Standardised-Deaths -Rates (ASDR) controlling for age, gender and population. In addition, Adult (55-74) and Infant (>1) death rates per million (pm) compares MDC and USA latest mortality. Odds Ratios calculated between MDC to USA to determine any substantial difference taken as >1:1.50.

Results: USA had highest Combined IDD and Sepsis.  Septicaemia – USA 211pm was highest Adult rate, MDC averaged 67pm, (minus USA) yielding an MDC: USA ratio of 1:3.15, America is substantially higher than 19 MDC. USA 43pm second highest Infant, MDC averaging 17pm, a MDC: USA ratio of 1:2.53. USA is substantially higher than 17 MDC.

Intestinal Disease Deaths- USA Adult joint highest at 38pm, MDC averaged 10pm, an MDC: USA ratio 1:3.80, America double 18 MDC rates. USA 59pm highest Infant, MDC averaging 6pm, a MDC: USA ratio 1:9.83, USA double all the MDC.

Conclusions: Had USA matched MDC averages there would have been 14,448 fewer American deaths. Both USA sepsis and IIDD adult and infant rates double most MDCC suggesting worse anti-biotic misuse and poor food production, perhaps indicating the WHO warning about possible future epidemic?

Keywords: intestinal infection sepsis deaths USA international

There has been criticism by American researchers of USA food production, food handling and medical misuse of anti-biotics, which has led to increases in cases of food-poisoning and septicaemia, which has also inadvertently led to the development of Multi-Drug-Resistant (MDR) bacteria and micro-organisms (Hoyle 2004, Ogutta, 2008; Bonnet, 2009, Aperce 2016, Roth, 2017, Afema et al, 2017; Cummings et al, 2017; Doyle et al, 2017; Roth 2017; Gast et al, 2018; Hamilton et al, 2018.). Though this problem has also been found in other Major Developed Countries (MDC) (Folgori, 2014, Pandic, 2015; Cai 2018, Alcamo, 2019, Ballo 2019, Giradli, 2019, Suzuki, 2019) but it may be a greater problem in the USA?

In regard to issues of food production via animal welfare, this is related to cattle, pigs, poultry and is linked with food-poisoning in the USA (Hoyle et al, 2004; Ogutta et al, 2008;  Bonnett et al, 2009; Aperce et al, 2016; Roth et al, 2017; Self et al, 2017).

Moreover, a number of USA researchers have highlighted the link with growing MDR anti-microbial resistance, evolving from poor anti-biotic use in medical treatment and, animal and avian welfare practices leading to food-born infections (Hoyle, 2004, Ogutta, 2008; Bonnet, 2009, Aperce 2016, Roth, 2017, Afema et al, 2017; Cummings et al, 2017; Doyle et al, 2017; Gast et al, 2018; Hamilton et al, 2018).

Of greater concern however is the growing link between cases of septicaemia and the development of MDR bacteria, attributed to human and animal-welfare misuse of anti-biotics, which has been noted for more than a decade (Angus, 2001, Dombrovisky, 2007, Zilberg, 2016, Barrasa-Villar, 2017, Rhee, 2017, Paoli, 2018, Giraldi, 2019). Indeed, the WHO has recently warned that the development of MDR micro-organisms is a serious threat to the foundation of modern medicine, especially surgery and should have the highest prioritisation (Rello, 2019). Furthermore, sepsis and its link with MDR bacteria has been found across a specialisms for both for child and adult patients (Thacker, 2014, Zilkberberg, 2016, Mader 2018, Alcamo, 2019; Ballo, 2019). An international study on rising septicaemia levels in low-and-middle-income countries asked whether this might also affect developed countries such as America and the UK as it reported that deaths are running into the hundreds of thousands world-wide. Indeed, in a Global Burden of Disease study, covering 195 countries, it was noted that dialarhoea-related-deaths accounted for eighth highest cause of death for all ages and fifth for children under-five (0-4), especially infants aged <1year (Troeger et al, 2018). As would be expected, there was a marked variation between developed and developing countries and in the latter there was a range of causal pathogens, mainly rotavirus, which in Western countries are mainly related to infections acquired along the food production and processing stages, though the youngest children in all countries are at relatively higher risk (Havelaar et al, 2015; Hald et al, 2016; Food Standards Agency, 2017; Troeger et al, 2018). Other research of 95 countries, which included the USA, found that the source of intestinal infections often came from contaminated eggs, poultry and cattle due to poor animal-welfare practices (Hoyle, 2004; Bonnet 20009, Roth, 2017, Eaton et al, 2019). Whilst an American study of mortality from infectious diseases found that whilst there have been major reductions over the past twenty years, dialarhoea diseases, related to food poisoning had increased over the period (El Bacheraouil, 2018).  Perhaps unexpectedly, research on salmonella infections in New York found there has been virtually no improvement over the past twenty years, which suggests a degree of complacency (Firestone & Hedberg, 2018). Crucially, the sources of such infections start very much at the beginning of the production with animal welfare (El Bacheraouli 2018; Firestone & Hedberg, 2018; Gast et al, 2018; Appling et al, 2019). This includes food-safety handling (Firestone & Hedberg, 2018; Hernandez-Patlan et, 2018; Guo et al, 2019), managing salmonella risks (Manning, 20917; Self et al, 2017; Firestone & Hedberg, 2018) and prevention of infections in different food sources, pigs, pork, shrimps, chickens etc (Painter et al, 2013; Manning, 2017; Hamilton et al, 2018; Lomonoaco, et al, 2018; Appling et al, 2019). However, there are likely to be other factors, such as life-styles and social factors patterns of disease that make people more vulnerable to infections (Painter et al, 2013; Doyle et al, 2017)? Yet as American and British research indicates most food poisonings are largely avoidable (Hald et al, 2016; FSA, 2017; Jones et al, 2017; Troeger et al, 2018).

The above studies led us to examine the extremes of cases of Sepsis and Intestinal Disease Deaths (IDD), that is mortality rates, as indicators of under-lying poor food production and handling, and misuse of anti-biotics in medicine and animal welfare to compare these mortality rates of the USA with the other twenty Major Developed Countries (MDC). As, with the exception of a comparison between Germany and the Netherlands concerning salmonella outbreaks (van Assett et al, 2017) and comparative managements of norovirus reporting in Europe (Kroneman et al, 2008), we could not find any direct comparative international research in developed countries related to intestinal infections and sepsis mortality.

The Septicaemia and IIDD and mortality rates per million (pm) population of the USA and the twenty MDC are based upon the latest available WHO data (WHO, 2020).

Sepsis and IDD rates are analysed for total rates based upon Age-Standardised-Death-Rates (ASDR) and Adults, people aged 55-74, which is below the life-expectancy of all countries under-review, and, the most vulnerable, Infants <1years (Bula-Rudas et al, 2015; Alcamo et al, 2019; Eaton et al, 2019).

There is one working null hypothesis, that there will be no substantial differences, odds ratios of >1.1.50 or <1:0.50) between USA and the other twenty Major Developed Countries sepsis and IID mortality rates.

Methods

All mortality data is drawn from the WHO (2020), updated May 2018, controlled for population, which allows comparison to be made between countries of different sizes. Total Age-Standardised-Deaths-Rates (ASDR) for IDD and Septicaemia were analysed which controls for age, gender and population. It was recognised that these rates might not be relatively to high to other mortalies. In order to gain a sense of relative seriousness, we identify any American ASDR mortality category that may be lower than the combined infectious deaths from perusing the WHO data base (2020). The main comparison was examining mortality rates for Adults aged 55-74, which is below the life-expectancy of all countries reviewed and for Infants (<1year) who are especially vulnerable (Havelaar et al, 2015; Hald et al, 2016; Food Standards Agency, 2017; Troeger et al, 2018; WHO,2020). Adult and Infant rates are determined by dividing the numbers of deaths by the age-band’s population to provide a rate per million (pm) population per country. The MDC countries are Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Japan, Netherlands, New Zealand, Norway, Portugal, Spain, Sweden, Switzerland and the UK. Which it is assumed broadly shares the same medical and scientific systems though it is known that there are different configurations of the countries health care systems and expenditure on health (Harding & Pritchard 2016). Whilst deaths rates are controlled for population and age to provide a firm comparative parameter, little can be said about levels of incidence and prevalence of the disorders that does not lead to a death. So classically, such deaths can be considered the `tip of the iceberg’.

The rates are based on the average of the WHO latest three years 2013-2015, though four MDC earlier index years 2011-13 and 2012-14, which are indicated in the tables.

The 10^th edition of the International Classification of Diseases reported in the WHO 2020, codes Septicaemia deaths as A40-A41 and sometimes reported as sepsis. Intestinal Infection Diseases Deaths are coded as A00 to A09, which includes the following. Cholera A00, typhoid & paratyphoid fevers A01, other salmonella poisonings A02, Shigellosis dysentery A03, other bacterial infections A04, other bacterial food bourn infections A05, Amoebiasis A06, other protozoal diseases A07, viral intestinal infections A08 and diarrhoea & gastroenteritis A09. We can only report deaths from the whole category but those from the developed world it would be assumed the largest single diagnostic category would be the salmonella and food bourn infections (Havelaar et al,  2015; Hald et al, 2016; FSA, 2017: Firestone & Hedberg, 2018; Appling et al, 2019).^.

To determine any substantial difference between the USA and each of the MDC, a series of specific MDC to USA odds ratios will be calculated for each country’s two age-band mortalities and substantial differences are considered when the ratio is beyond >1:1.50.

Table [1] is the current Age-Standardised-Death-Rates (ASDR) per million (pm) for IDD and Sepsis deaths. Septicaemia was higher than IDD in every country. The highest combined IDD and Sepsis rates were in the USA at 88pm, Greece 70pm and Germany 61pm, down to lows in Finland 10pm, Austria 12pm and Switzerland 16pm, averaging 30pm, minus the USA, producing a MDC: USA ratio of 1;2.93. To put these infectious disease deaths in context these USA rates were higher than the current American mortality rates for the anaemias, HIV, meningitis, pneumonia, TB., and higher than bladder, cervix, leukaemia, lymphomas, lip, melanoma, pancreas, oesophagus, ovary and stomach cancers.

Table [1] Intestinal Infections Deaths Total ASDR rates per million in USA and Major Developed Countries 2013-15. Ranked by Highest Combined ASDR.

IDD and Septicaemia Rho=+0.3706 p<0.05.

Table [2] lists from highest to lowest the Adult (55-74) Septicaemia mortality rates per million (pm).  Headed by the USA at 2211pm, followed by Belgium 116pm and Germany and the Netherlands 114pm down to lows of Austria 16pm, Finland 21m and New Zealand 26pm.

The MDC average was 670pm yielding a MDC : USA ratio of 1:3.15.

The USA had substantially (>1:1.50) higher deaths than 20 MDC and more than treble the rates of eleven other countries.

Table [3] lists the Infant (<1year) Septicaemia deaths led by Greece 78pm then America 43pm and Italy 36pm, with seven countries having rates of less than 10pm and no sepsis deaths were recorded in Denmark and Switzerland. The other nations average 16pm leading to a MDC to USA 1:2.69 ratio, with America having substantial higher rates than 18 other countries. Though it should be noted that compared to the other MDC Greece was the outlier, relative to the USA.

Table [4] presents Adult (55-74) IIDD rates, the highest being in the USA and Germany at 38pm, to the lowest in Greece at 1pm and Finland and Italy 6pm, averaging  10pm, with a MDC to USA ratio of 1:3.80 with the USA having more than treble the rates of  ten other countries.

Table [2] Septicaemia Mortality Adults 55-7 rates per million USA v Major Developed Countries  MDC to USA Odds Ratios. 2013-15

Table [3] Septicaemia Mortality rates per million Infant {<1). USA v Major Developed Countries MDC to USA Ratios.  2013-15

Table [4] Intestinal Infection Deaths (IID)  55-74+ rates per million USA v Major Developed Countries.  MDC to USA Ratios 

Table [5] shows IDD in infants (<1), the highest was the USA at 59pm, New Zealand 21pm and Australia and Austria 13pm. Nine countries had rates of less than 1pm, averaging 6pm, yielding a MDC to USA ratio of 1:9.82

Table [5] Infant IDD <1year rates per million in USA v Major Developed Countries. MDC to USA Ratios 2013-15.

Correlating Adult & Infant Septicaemia Rho= + 0.5091 p<0.01.

Adult IDD & Septicaemia Rho =+0.4567 p<0.025

Adult & Infant Septicaemia Rho =+0.2604 n.sig

Infant IDD & Septicaemia Rh= +0.1573 n.sig

The main limitation to the study is that we can know anything about people with pre-existing conditions to make them more vulnerable to dying from infections. Also the IDD category covers a wide range of separate conditions, from the statistically very rare cholera in Western countries to the relatively common salmonella. Furthermore, while we do have studies reporting the numbers of infected people in the USA and the UK (Painter et al, 2013; Jones et al, 2017) we do not know the severity of their illness. Furthermore, there are different configurations of health provision amongst the countries, but this does not have appeared to influence the `infectious disease’ results as America spends by far the highest percentage of its GDP on health care (Harding & Pritchard, 2016) yet has substantially poorer results than most MDC. The one exception was Greece having the highest rate for infant sepsis mortality, which may be linked to reducing its GDP on health following the 2008 crash (Harding& Pritchard,2016). Only country-specific research can explain individual national results.

It has been claimed that the negative media comments about American animal welfare and food standards were both inaccurate and unfair (Johnson, 2019) but these results appear to refute such a claim.

This suggests that perhaps the influence of poor food production and handling, with possible links to MDR bacteria, which can underlay sepsis, is a greater problem in the USA than most Western countries. Nonetheless, it may be thought that the highest combined death rate 88pmn in the USA, is not of serious concern yet it is higher than ten major cancer sites, so it is not insignificant.

In one sense these results are counter-intuitive when the richest and one of the most scientifically developed nations in the world has worse infectious mortality outcomes. Consequently, we reject the null hypothesis, that there will be no substantial differences between the MDC and the USA in regard to food poisoning and sepsis deaths.

We have known for some time that infections and the development of MDR microorganism occurs via the misuse of anti-biotics in treating patients and the poor animal-welfare and food management ( Hoyle et al, 2004; Ogutta et al, 2008; Jimenez-Belenguer et al, 2016; Troeger et al, 2018; Rello et al, 20919; Suzuki et al, 2019). Indeed, it is reported that there had been little change in New York salmonella over the past twenty years or increased (El Bacherouli et al, 2018; Firestone & Hedberg, 2018). It is noteworthy that most of the recent research expressing concern about animal welfare and food processing and its links to food-poisoning are mainly from the USA. Though there are growing concerns about sepsis and the growth of MDR resistant micro-organisms, linked to anti-biotic misuse in humans and animals in other developed as well as developing countries (Angus, 2001, Dombrovisky, 2007, Rhee 2017, Cia, 2018, Paoli 2018, Alcamo, 2019, Giradli, 2019, Rello, 2019).

This study sought to explore whether Sepsis and Intestinal Disease Death rates in America would be as good or better than the other major developed countries. It appears that the USA have failed that test. If the USA had matched the other nations mortality averages in 2015 there would have been 14,448 fewer American deaths. In parenthesis, in terms of incidence of food-poisoning, it was reported that there were nine million cases in the USA (Self et al, 2017) and 525,000 infections in the UK (Jones et al, 2017). Based upon their two populations this means that one in thirty-five Americans had an infection (assuming just one person per infection) and one in more than 120 British people

Whether these results do infer a link with poor animal welfare and food production and handling, related to poorer use of anti-biotics in the USA, is still open to debate but these results provide evidence that the question is a valid one. Without wishing to be too extreme, the WHO has warned about rising MDR bacteria (Rello, 2019) and if the trend continues it could put surgery back into the 19^th century and the current covid-19 pandemic should make us take seriously the increasing concern expressed by the WHO.

Whilst more country-specific and detailed research is needed, it appreciated that these results might be considered surprising, probably unwelcome. However, unless we speak truth to power, little will change, with the danger that current complacency will continue.

The authors have no vested or conflict of interest in the study. External Funding: None, there was no external funding for the project.

No humans or animals were involved in the study so ethical approval was unnecessary.

All authors contributed to the development, design of the study and to its final write-up.

None

1. Alcamo AM, Alessi LJ, Vehovic SN, Bansal N, Bond GJ, Carcillo JA, et al. Severe Sepsis    in Pediatric Liver Transplant Patients: The Emergence of Multidrug-Resistant Organisms.Pediatr Crit Care Med. 2019 Jul;20(7):e326-e332. doi: 10.1097/PCC.0000000000001983.
2. Afema JA, Mather AE, Sischo WM. Antimicrobial Resistance Profiles and Diversity in Salmonella from Humans and Cattle, 2004-2011.Zoonoses Pub Health. 2017; 62:506-517.
3. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care. Crit Care Med. 2001. 29:1303-1310.
4. Angulo FJ, Nargund VN, Chiller TC. Evidence of an association between use of anti-microbial agents in food animals and anti-microbial resistance among bacteria isolated from humans and the human health consequences of such resistance.J Vet Med B Infect Dis Vet Public Health. 2004; 51:374-379.
5. Aperce CC, Amachawadi R, Van Bibber-Krueger CL, Nagaraja TG, Scott HM, Vinasco-Torre J et al.Effects of Menthol Supplementation in Feedlot Cattle Diets on the Fecal Prevalence of Antimicrobial-Resistant Escherichia coli. PLoS One. 2016 Dec 28;11(12):e0168983. doi: 10.1371/journal.pone.0168983. eCollection 2016.
6. Appling XS, Lee P, Hedberg CW. Understanding the Relation between Establishment Food Safety Management and Salmonella Risk Factor Violations Cited during Routine Inspections.J Food Prot. 2019; 82:339-343.
7. Ballo O, Tarazzit I, Stratmann J, Reinheimer C, Hogardt M, Wichelhaus TA et al. Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukaemia undergoing intensive induction chemotherapy.PLoS One. 2019 Jan 23;14(1):e0210991. doi: 10.1371/journal.pone. 0210991. eCollection 2019.
8. Barrasa-Villar JI, Aibar-Remón C, Prieto-Andrés P, Mareca-Doñate R, Moliner-Lahoz J. Impact on Morbidity, Mortality, and Length of Stay of Hospital-Acquired Infections by Resistant Microorganisms.Clin Infect Dis. 2017. 65:644-652.
9. Bonnet C, Diarrassouba F, Brousseau R, Masson L, Topp E, Diarra MS.Pathotype and antibiotic resistance gene distributions of Escherichia coli isolates from broiler chickens raised on antimicrobial-supplemented diets. Appl Environ Microbiol. 2009.75:6955-62.
10. Bula-Rudas FJ, Rathore MH, Maraqa NF. Salmonella Infections in Childhood. Adv Pediatr.2015; 62:29-58.
11. Cai G, Ye J, Wen M. Relationship Between Sepsis-induced immunosuppression and multi-drugs resistant bacteria. Zhonghua Wei Zhong Bing. 2018. 30:1095-1098
12. Cipolla D, Giuffrè M, Mammina C, Corsello G. Prevention of nosocomial infections and surveillance of emerging resistances in NICU.J Matern Fetal Neonatal Med. 2011. Suppl 1:23-26.
13. Cummings KJ, Rodriguez-Rivera LD, Norman KN, Ohta N, Scott HM. Identification of a Plasmid-Mediated Quinolone Resistance Gene in Salmonella Isolates from Texas Dairy Farm Environmental Samples.Zoonoses Pub Health. 2017; 64:305-307.
14. Davidson VJ, Ravel A, Nguyen TN, Fazil A, Ruzante JM. Food-specific attribution of selected gastrointestinal illnesses: estimates from a Canadian expert elicitation survey.Foodborne Pathog Dis. 2011; 8:983-95.
15. Dombrovskiy VY, Martin AA, Sunderram J, Rapid increase in hospitalisation and mortality rates for severe sepsis in the United States: A trend analysis from 1993-2003. Crit Care Med. 2007. 35:1244-1250.
16. Doyle CJ, O’Toole PW, Cotter PD. Metagenome-based surveillance and diagnostic approaches to studying the microbial ecology of food production and processing environments.Environ Microbiol. 2017;19:4382-4391.
17. Eaton JC, Rothpletz-Puglia P, Dreker MR, Iannotti L, Lutter C, Kaganda J et al. Effectiveness of provision of animal-source foods for supporting optimal growth and development in children 6 to 59 months of age.Cochrane Database Syst Rev. 2019 Feb 19;2:CD012818. doi: 10.1002/14651858.CD012818.pub2.
18. El Bacherouli C, Mokdad AH, Dwyer-Lindgren L, Bertozzi-Villa A, Stubbs RW, Morozoff C et al. Trends and patterns of differences in infectious disease mortality among US counties, 1980–2014. JAMA. 2018. 319:1248-1260.
19. Folgori L, Livadiotti S, Carletti M, Bielicki J, Pontrelli G, et al. Epidemiology and clinical outcomes of multidrug-resistant, gram-negative bloodstream infections in a European tertiary paediatric hospital during a 12-month period.Pediatr Infect Dis J. 2014. 33:929-32.
20. Food Standards Agency (2017). Foodborne Disease Strategy 2010–15.  London, FSA.
21. Firestone MJ& Hedberg CW. Restaurant Inspection Letter Grades and Salmonella Infections, New York, New York, USA. Emerg Infect Dis. 2018; 24:2164-2168.
22. Gast RK, Regmi P, Guraya R, Jones DR, Anderson KE, Karcher DM. Colonization of internal organs by Salmonella Enteritidis in experimentally infected laying hens of four commercial genetic lines in conventional cages and enriched colony housing.Poult Sci. 2019 Dec 11. doi: 10.3382/ps/pey541. [Epub ahead of print]
23. Giraldi G, Montesano M, Napoli C, Frati P, La Russa R, Santurro A et al. Healthcare-Associated Infections Due to Multidrug-Resistant Organisms: a Surveillance Study on Extra Hospital Stay and Direct Costs.Curr Pharm Biotechnol. 2019;20:643-652.
24. Guo R, Li Z, Zhou X, Huang C. Induction of arthritis in chickens by infection with novel virulent Salmonella Pullorum strains.Vet Microbiol. 2019; 228:165-172.
25. Hald T, Aspinall W, Devleesschauwer B, et al. World Health Organization Estimates of the Relative Contributions of Food to the Burden of Disease Due to Selected Foodborne Hazards: A Structured Expert Elicitation. PLoS One.2016 Jan 19;11(1):e0145839. doi: 10.1371/journal.pone. 0145839. eCollection 2016.
26. Hamilton KA, Chen A, de-Graft Johnson E. Salmonella risks due to consumption of aquaculture-produced shrimp.Microb Risk Anal. 9:22-32.
27. Harding AJE & Pritchard C (2016) UK and Twenty Comparable Countries GDP Expenditure –      on-Health 1980-2013: The Historic and Continued Low Priority of UK Health Related   Expenditure. International Journal of Health Policy & Management. 5, (9) 519-523.
28. Havelaar AH, Kirk MD, Torgerson PR.  World Health Organization Foodborne Disease Burden Epidemiology Reference Group. World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010. PLoS Med.2015 Dec 3;12(12):e1001923. doi: 10.1371/ journal. pmed.1001923. eCollection 2015 Dec.
29. Hernandez-Patlan D, Solis-Cruz B, Adhikari B. Evaluation of the antimicrobial and intestinal integrity properties of boric acid in broiler chickens infected with Salmonella enteritidis: Proof of concept.Res Vet Sci. 2018;123:7-13.
30. Heudorf U, Gustav C, Mischler D, Schulze J. Healthcare associated infections (HAI), antibiotic use and prevalence of multidrug-resistant bacteria (MDRO) in residents of long-term care facilities: the Frankfurt HALT plus MDRO project 2012].Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2014.57:414-422.
31. Hoyle DV, Knight HI, Shaw DJ, Hillman K, Pearce MC.Acquisition and epidemiology of antibiotic-resistant Escherichia coli in a cohort of newborn calves. J Antimicrob Chemother. 2004; 53:867-871.
32. Jiménez-Belenguer A, Doménech E, Villagrá A, Fenollar A, Ferrús MA.Antimicrobial resistance of Escherichia coli isolated in newly-hatched chickens and effect of amoxicillin treatment during their growth. Avian Pathol. 2016;45:501-507.
33. Johnson W. `The World Today’ Interview. BBC Radio 4. 6/03.2019.    https:// inews.co.uk/news/uk/food-poisoning-us-ambassador-woody-johnson…
34. Jones AK, Cross P, Burton M, Millman C, O’Brien SJ, Rigby D. Estimating the prevalence of food risk increasing behaviours in UK kitchens.PLoS One. 2017 Jun 28;12(6):e0175816. doi: 10.1371/journal.pone.0175816. eCollection 2017.
35. Kroneman A, Harris J, Vennema H. Data quality of 5 years of central norovirus outbreak reporting in the European Network for food-borne viruses.J Public Health (Oxf). 2008; 30:82-90.
36. Lundin JI, Dargatz DA, Wagner BA, Lombard JE, Hill AE, et al. Antimicrobial drug resistance of faecal Escherichia coli and Salmonella spp. isolates from United States dairy cows.Foodborne Pathog Dis. 2008; 5:7-19.
37. Lomonaco S, Magossi G, Sanchez Leon M. Draft Genome Sequences of 57 Salmonella enterica Strains from Selected U.S. Swine Feed Mills.Microbiol Resour Announc. 2018 Nov 1;7(17). pii: e01191-18. doi: 10.1128/MRA.01191-18. eCollection 2018 Nov.
38. Mader MM, Grensemann J, Kluge S, Westphal M, Czorlich P. Rate and impact of multidrug-resistant organisms in patients with aneurysmal subarachnoid haemorrhage.Acta Neurochir (Wien). 2018;160:2049-2054.
39. Manning L. Categorizing food-related illness: Have we got it right? Crit Rev Food Sci Nutr.2017; 57:1938-1949.
40. Martin-Loeches I, Torres A, Rinaudo M, Terraneo S, de Rosa F. Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification of multidrug resistant organisms.J Infect. 2015;70:213-222.
41. Oguttu JW, Veary CM, Picard JA. Antimicrobial drug resistance of Escherichia coli isolated from poultry abattoir workers at risk and broilers on antimicrobials.J S Afr Vet Assoc. 2008;79:161-166.
42. Painter JA, Hoekstra RM, Ayers T, Tauxe RV, Braden CR Attribution of foodborne illnesses, hospitalizations, and deaths to food commodities by using outbreak data, United States, 1998-2008.Emerg Infect Dis. 2013; 19:407-415.
43. Padkin A, Goldfrad C, Brady AM, Young D, Black N, Rowan K. Epidemiology of severe sepsis occurring in the first 24s ICU in England, Wales and Northern Ireland. Crit Care Med. 2015. 43:282-287.
44. Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Croiuser E. Epidemiology and costs of Sepsis in the United States.  An analysis based on timing of diagnosis and severity level. Crit Care Med. 2018. 46:1889-1897.
45. Rello J, Kalwaje Eshwara J,  Lagunes L, Alves J, Wunderink RG. A global priority list of the top ten  resistant microorganisms (TOTEM) study at intensive care: a prioritization exercise based upon multi-criteria decision analysis. Eur J Clin Microbiol Infect Dis. 2019. 38: 319- 323.
46. Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW,CDC Prevention Epicenter Program. Incidence and Trends of Sepsis in US Hospitals Using Clinical vrs Claims Data. JAMA. 2017. 318:1241-1249
47. Roth N, Mayrhofer S, Gierus M, Weingut C, Schwarz C.Effect of an organic acids based feed additive and enrofloxacin on the prevalence of antibiotic-resistant E. coli in cecum of broilers. Poult Sci. 2017. 96:4053-4060.
48. Schuhbech A (2018) Deutscher Kuchenbuch. Berlin, Phaedion.
49. Self JL, Luna-Gierke RE, Fothergill A, Holt KG, Vieira AR. Outbreaks attributed to pork in the United States, 1998-2015.Epidemiol Infect. 2017; 145:2980-2990.
50. Suzuki K, Yossapol M, Sugiyama M, Asai T.Effects of Antimicrobial Administration on the Prevalence of Antimicrobial-Resistant Escherichia coli in Broiler Flocks. Jpn J Infect Dis. 2019;72:179-184.
51. Thacker N, Pereira N, Banavali SD, Narula G, Vora T. Alarming prevalence of community-acquired multidrug-resistant organisms colonization in children with cancer and implications for therapy: A prospective study.Indian J Cancer. 2014;51:442-446.
52. Troeger C, Reiner B, Hay SI, Mokdad A, Murray JL, Naghavi M( 2018) GBD 2016 Diarrhoeal Disease Collaborators. Estimates of the  global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Infectious Diseases. 19 September 2018. doi:10.1016/S1473-3099(18)30424-9. Retovirus.
53. van Asselt ED, van der Fels-Klerx HJ, Breuer O, Helsloot I. Food Safety Crisis Management-A Comparison between Germany and the Netherlands.J Food Sci. 2017; 82:477-483.
54. van Lier EA, Havelaar AH, Nanda A. The burden of infectious diseases in Europe: a pilot study.Euro Surveill. 2007; 12:E3-4. WHO. Annual Statistics. www.who.int/healthinfo/statistics/mortality/whodpms

© This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/