As I mentioned yesterday, the epidemiology of hemolytic uremic syndrome (HUS) was murky for several decades after it was first defined in the literature in 1955. In the ensuing decades, HUS was associated with a number of infectious agents, leading to the general belief that it was a "multifactorial disease"--one that had components of genetics and environment, much like we think of multiple sclerosis today, for example.
Several HUS outbreaks made people think twice about that assumption, and look deeper into a potential infectious cause. A 1966 paper documented the first identified outbreak of HUS, which occurred in Wales. The researchers examined a number of possible environmental factors the patients may have had in common--including food, water, and various toxins--but came up empty. They sum up:
Since it is almost invariably preceded by a gastrointestinal or respiratory illness, it seems probable that it represents a response to an infection. Although Gianantonio et al. (1964) have identified one possible causative virus, it may be that various infective agents can initiate the syndrome.
This idea held throughout the next 20-odd years, as numerous studies looked at both environmental and genetic effects that may be leading to HUS. A 1975 paper examined HUS in families, suggesting that there may be two types of HUS (which we now know to be true--the genetic form is less often associated with diarrhea, and tends to have a worse prognosis as I mentioned yesterday). But still, no definitive cause for either.
There were also a number of studies testing individuals for many different types of pathogens. A 1974 paper enrolled patients in the Netherlands between 1965 and 1970, but one of the inclusion criteria was a "history of a prodromal illness in which gastrointestinal or respiratory tract symptoms were present." The respiratory tract symptoms are mentioned in a number of papers, and were probably a red herring that sent people in search of the wrong pathogens for awhile. In this particular paper, they examined children for infection with a number of viral and bacterial pathogens, using either culture or serological methods (looking for antibodies which may suggest a recent infection). In that portion of the paper, they note a possible association with adenoviruses, but state that the data don't support a bacterial infection--a viral etiology was deemed more likely. Regarding basic epidemiology, they did note a few small clusters of cases in families or villages, as well as a peak in cases in spring/summer--as well as an increasing number of cases from the first year of their study to the last. The epidemiology of HUS was starting to become clearer, and the syndrome appeared to be on the rise.
Even as additional case reports occasionally targeted foods as a precursor to HUS outbreaks, it wasn't until the late 1970s and early 1980s that HUS really started to come into focus. In 1977, a paper was published identifying the "Vero toxin"--a product of E. coli that caused cytotoxicity in Vero cells (a line of African green monkey kidney cells, commonly used in research). Researchers were closing in.
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I appreciate your article. My son had HUS in 1974 (5 yrs old). We were on vacation at the time and he got violently ill. No one had a clue as to what it was. After 14 days he wound up in Children's in L.A. when he became jaundiced. His liver and speen were enlarged. Childrens identified it as HUS and gave him packed platelets. They did not understand E-Coli connection, I believe, at the time. Doctors said it was only the third case seen in the US at time in a child over 3 yrs and that it was primarily seen in South America. I believe Childrens said that there were only 32 recorded cases at the time. This may or may not be true.
Im finding it very interesting with the outbreak in Germany to hear HUS mentioned frequently now, as my wife and I first knew of this with our son in 1974...most people we talked to then thought we were crazy!
Thanks! Ed
My husband's 90-year-old grandmother recently recovered from a bout of E. coli that developed into HUS. She doesn't remember most of her illness and recovery; she was very very sick. This is an interesting post because of that.
I had hus in 1977 as an infant. No one seemed to know what was happening to me either. I became extremely ill over time and it was not until I was transported to Rainbow Babies and Children, one of the best children's hospitals in the United States...or maybe the world, that I was treated and began to recover. Unfortunately I was near death by this time and the previous hospital I was taken to and "treated" at hadn't a clue what was wrong with me. I am now 34 years old and truly thankful that I was able to survive.