O104:H4: A New Disease with Old Preventions
Opinion
"I watched my friends get sick, just melt away, and die in hours." A senior, returning to our college from Nepal in 1968, after participating in a 5 year program allowing students a year abroad. His education included what we now would describe as post traumatic stress. Many readers will recognize the disease course of cholera, the toxin-mediated imbalanced loss of electrolytes causing massive fluid loss. This was a few years prior to the physiological demonstration of co-transport of salts with sugars and the widespread acceptance of oral rehydration therapy (ORT) as a primary response. A decade later most cholera patients' lives could be saved for a fraction of a penny. Cholera is preventable by clean drinking water sources, usually achieved by both sanitation and water treatment. It can be food borne or water borne but in epidemic outbreaks water borne transmission dominates the outbreak course.
Bill Marler has described the usual course and cost of treatment for HUS in O157:H7 cases in several postings [1, 2 ]. He focuses on renal damage and its consequences, which at the extreme of failure requires either kidney transplantation or lifelong dialysis; when advanced medical treatment is available. O104:H4 has a more virulent course than O157:H7 and the prior non-O157:H7 STEC E. coli that have caused outbreaks. This is shown by: an unknown number sickened, 4,000 with some form of hospital admission, presumably with bloody diarrhea, approximately 400 with HUS, 100 with kidney failure, nearly 40 deaths. Hospital staff have also been troubled by a higher level of neurological symptoms, starting with patients presenting with a listless affect and proceeding to severe symptoms, that may be subsequent to kidney stress and damage, or involve a neurotoxin, or both.
Staff, even at HUS specializing centers, are reported to be overwhelmed and stressed.
The German hospitals' finances are also stressed. If the United States, at least for now, has a more advanced epidemiology and investigation system, which itself is under threat from cutbacks, it may not have even adequate healthcare coverage for patients if an outbreak occurred here, even if our medical infrastructure and training are at least equal to Germany. Bloodbanks also are stressed in Germany, where initial treatment of serious cases may start with complete transfusions. In wealthy countries with advanced medical systems, just keeping patients alive, much less treating them for a lifetime, can cost millions of dollars, not fractions of a penny.
The fact that the course of disease progression is so much worse is one grounds for treating O104:H4 as a new disease.
In the U.S. the focus is on the Shiga toxins that are critical for the development of prior outbreaks like O157:H7; therefore "STEC" strains. In Europe they focus on the larger family of verotoxins that are similar to Shiga toxins and the consequence of their effective deployment in pathogenic (disease causing) strains so they use EHEC (enterohaemorrhagic E. coli). Because O104:H4 has variants of the stx-2 gene for its toxin, and because screening for STEC toxins are effective for identifying both prior outbreak strains and this new strain, the STEC nomenclature is useful in the U.S.
The preliminary genomics of two outbreak isolates show a combination of genetics from both STEC (EHEC) E. coli and EAEC (enteroaggregative E. coli), repeatedly described as an unusual combination. This is the second reason for treating O104:H4 as a new disease.
EAEC's are associated with diarrhea in both children and adults [3]. STEC E. coli can be transmitted by food, water and, to a lesser extent, person-to-person but seem more associated with food borne transmission. EAEC is similar, more associated with food borne disease, can be water borne, but also has been shown to be associated with transmission to food from food handlers in some cases (example, [4]).
Bacteria can exchange cassettes of genetic functionalities for pathogenicity (ability to cause disease) and virulence (extent of damage to the host or person) rather promiscuously, through a variety of mechanisms; examples include when the Stx genes moved from Shigella to E. coli to create STEC strains, acid tolerance, and multiple antibiotic (drug) resistance.
This is a third reason for treating the outbreak as a new disease; the functionality, borrowed from multiple places, and organized for disease and virulence, is crucial to the damage done.
If the world is very lucky then the O104:H4 outbreak may be an unusual incident, resulting from an atypica contaminated lot of legumes (beans, soy beans, etc.) grown and sold for seed, food, or feed; multiplied under the favorable conditions of sprout production, and eaten raw in our peculiar industrialized cuisine. As a food borne disease, it would be bad enough. As a water transmitted disease, its impact world wide could be much worse.
One usually thinks of O157:H7 as a food-borne disease, but it has been involved in repeated outbreaks from water sources, although much less prominent than food-borne outbreaks. These could be classified as (probably) due to water contaminated by cattle, contaminated by humans, and either due to both or ambiguous.
A major North American example was the Walkerton Ontario outbreak, May-June 2000. This involved the contamination of a municipal well that was accessible to contamination by flooding, and the failure to adequately monitor or treat water from that well [5]. It called into question the adequacy of routine groundwater treatment. The Public Health Agency of Can- ada estimated over 2,000 total cases and found the outbreak strain in cattle farms whose runoff or leaching could have reached the well. 65 were hospitalized, 27 developed HUS and 6 people died. Most cases were due to drinking municipal water, but 39 out of 1,346 reported cases were due to secondary transmission.
The Walkerton case may give a rough estimate of the human-human transmission component to expect in the O104:H4 outbreak if it acts like O157:H7: without further contaminated sources, under 3% additional cases (100 - 120 persons). But if O104:H4 acts more like some EAEC cases and has food handling as a transmission mechanism, for example, one might expect more cases.
There has not been much press attention to the steps that have been taken in Germany to prevent secondary infections, while even early in the outbreak they were segregating ill children and decontaminating classrooms, for example.
Industrialized countries are protected from water borne diseases, including STEC E. coli, primarily by the public health infrastructure.
In other countries both public health infrastucture and medical infrastructure are lacking. As Mintz and Guerrant wrote in the New England Journal of Medicine [6]:
"Inexcusably, the completely preventable ancient scourge of cholera rages among poverty-stricken and displaced people today, with as many as one in five persons with severe illness dying for lack of safe drinking water and sanitation and a simple therapy consisting of salt, sugar, and water."
There is a common pathway to prevent multiple kinds of enteric pathogens including cholera, STEC E. coli, O104:H4, and shigella dysentery: potable water, sanitary systems, and sanitation in food handling and hygiene. Because O104:H4 is a new phenomena, that could be treated as a new disease, no one know how it will evolve both as a pathogen and a disease. Its potential impacts on different lives in different countries, however, could be worse than the outbreak in Germany.
Ideally, OH104:H4 would be an idiosyncratic outbreak, possible only under specialized circumstances, and perhaps containable. That may be a low probability hope. In the absence of knowledge, steps that are common to the prevention of all enteric diseases may be the most practical.
Daniel B. Cohen
Maccabee Seed Company
Davis, California*
[1] German E. coli O104:H4 Outbreak - $2.84 Billion in Human Damage and Rising. Marlerblog June 08, 2011,
[2] Hemolytic Uremic Syndrome (HUS). Marlerblog August 13 2010
[3] James P. Natarro, Theodore Steiner, Richard L. Guerrant "Enteroaggregative Escherichia coli." Emerging Infectious Diseases Vol 4, No. 2 April- June 1998.
[4] Oundo, J. O., Kariuki, S. M., Boga, H. I., Muli, F. W. and Iijima, Y. (2008), High Incidence of Enteroaggregative Escherichia coli Among Food Handlers in Three Areas of Kenya: A Possible Transmission Route of Travelers' Diarrhea. Journal of Travel Medicine, 15: 31-38. doi: 10.1111/j.1708-8305.2007.00174.x
[5] WATERBORNE OUTBREAK OF GASTROENTERITIS ASSOCIATED WITH A CONTAMINATED MUNICIPAL WATER SUPPLY, WALKERTON, ONTARIO, MAY-JUNE 2000. Canada Communicable Disease Report Vol. 26-20, 15 October 2000.
[6] A Lion in Our Village -- The Unconscionable Tragedy of Cholera in Africa. Eric D. Mintz M.D. and Richard l. Guerant, M.D. New England Journal of Medicine, 360:11 1060 - 1063. March 12, 2009.
*This is an essay, not a research review, written by a plant breeder, not an epidemiologist.
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