I know it should not matter so much but whenever I see incidence and prevalence figures for aHUS in articles etc, it often “does my head in”. Quite some confusion exists when seeking how many aHUS patients there are.
Why is that the case? I have written many articles about estimates of incidence and prevalence of aHUS on this website to clarify what they mean and what answers they produce.
The only truth is that no one knows what the incidence and prevalence of aHUS is. There are no accurate records to say what they are. Not in the USA nor in the rest of world.
But estimates of the number of aHUS patients are made for various reasons. Particularly in the Rare Disease World – e.g. does aHUS prevalence meet the criteria to be a rare disease and go through rare disease health technology appraisals for treatment access . How many patients need treatment now and will in the future?
So a quick definition of the incidence and prevalence of a disease is :
The proportion of the population that has a disease at a point in time (prevalence) and the rate of occurrence of new disease during a period of time (incidence)
Prevalence is a number in the population living with aHUS “at a point in time”
Incidence is the number of new disease happening “during a period of time”
Take a “point in time” as 31st December and “a period of time” as 1 January to 31st December there will be two different figures for aHUS numbers.
But how are they are going to be calculated/estimated if there are no exact records being kept.
Well usually the “population” needs to come into the equation. And to get to a “proportion” and “ rate” , someone has to estimate them as a percentage or number per part of the population. Usually they are expressed as “x per million”. The “x per million” can then be applied to the population to produce the figures.
It would be a surprise if viewers of this article have not seen a prevalence rate of aHUS as 2 per million of the population, as well as seeing an incidence rate of 2 per million.
But think about it , it cannot be both. In a global population of 8 billion at those rates it would mean that 16,000 aHUS patients incidents will have occurred in the year ending 31 December 2022. But at 31 December 2022 only 16000 of those who have ever had aHUS will still be alive ( prevalence) . Does that “do your head in” or what?
Someone will have got their incidence or prevalence rates mixed up at some point. And it happens a lot.
Where did the 2 per million rate come from and is it incidence or prevalence? What is more is it correct?
I have found that the 2 per million rate has been around for 20 years or so and has been cited for both incidence and prevalence.
Again just think about it and switch to the USA population. In 2004 the US population was 293 million and by 2022 the population had risen to an estimated 328 million.
So keeping prevalence of aHUS to 2 per million there would have been 586 patients in 2004 and 656 in 2022.
Treatments for aHUS in 2002 were limited, most patients died or ended up on dialysis. By 2022 eculizumab and ravulizumab have been available for more than 10 years and after spending billions of dollars on those treatments the prevalent aHUS population would have only grown by only 70!
That is not believable.
In any case, if the incidence of aHUS had been 2 per million per year in each of those 20 years there would have been on average patient incidence of 621 each year for 18 years. that would have been 12 420 new USA aHUS patients over that period.
That is not believable either.
It is that confusion which makes the head ache.
So can the 2 per million incidence or prevalence now be seen as plainly wrong? If so what could replace them?
But firstly how did the “much cited” 2 per million rate come about.
When quoting aHUS patient numbers in a clinical articles, authors would have to cite a source for them.
Here is an example from a 2017 article. “aHUS is considered a rare disease, but its incidence is not known precisely. The annual incidence of aHUS is estimated to be two cases per million in the USA ,”
The reference “22” article is one by the Constatinescu group published in 2004 . This is the source article which started this all off. This is a link to that article so that viewers can see for themselves on page HERE
The article was about “Nondiarrheal or Streptococcus pneumoniae-related hemolytic uremic syndrome (HUS) “ which the authors call “enteropathic HUS “ one of the precursor names for aHUS i.e. not typical HUS caused by Shiga toxin/ e.coli. I will refer to it as “aHUS”
The article had a number of objectives. One of which was to estimate the incidence of such “aHUS” compared with the incidence of HUS/
In the article the incident patients over a four year period 1997 to 2001 were participants in a clinical trial for an anti e coli drug. They were from 26 hospitals in the US and Canada. Or to be more exact the “aHUS” patients were the ones who were excluded from the trial because they did not show symptoms of diarrhoea in the 7 days before a diagnosis of HUS was made. Those who were included in the trial were. There was little or no screening for e.coli or genetic testing. The “ aHUS “ patient group group just did not have diarrhoea. ( Note in the aHUS patient cohort included in the aHUS Diagnosis Process articles produced by Global Action , 33% of patients reported diarrhoea as a symptom)
27 of the 247 incident patients over that four year period were deemed to have “aHUS”.
You might ask how does that result in incidence of aHUS is 2 per million?
The first thing to note is that study only estimated the INCIDENCE and NOT the PREVALENCE of “aHUS”. So forget all about the 2 per million prevalence rate.
Furthermore the conclusion of the study is based only on the incidence for childhood “aHUS”. The group did not use the childhood population of the catchment areas of the city hospitals in the trials to work out an incidence per million children there.
The 2 per million was derived from an HUS incidence rate calculated by some other researchers , Corrigan and Boineau. They estimated HUS incidence at between 1 and 3 per 100,000 each year.
That would be 10 to 30 per million*.
The Constantinescu group had found that their 27 “aHUS” patients represented 11% of the total 247 incidents over the fours years.
Some of “aHUS” group were S. Pneumonia HUS patients. The remainder were regarded as “aHUS” .
So Constantinescu’s group took 10% of Corrigan and Boineau’s higher end incident rate of 30 per million incidents per year i.e. 3 per million and split it between S. Pneumonia HUS with an incidence of 1 per million per year and “aHUS” with a 2 per million incidence rate,
And that is how the 2 per million incidence rate came about and it is that which has been quoted down the years.
It depended both on how the Constantinescu Group defined their “aHUS” and the accuracy of Corrigan and Boineau’s HUS incidence rate ( their article is not available on line to check).
Twenty years ago the population of the USA was 285 million and therefore by Corrigan and Boineau’s estimated rate of incidence of HUS there would have between 2850 to 8550 incident cases of HUS in the USA.
An article about the incidence of HUS in New York in 2004 found the incidence to be between 1 and 2 per million based on reports of ecoli and D+HUS that had been collected from 1994.
Now here is modern statistic about HUS “ Anyone can get HUS. HUS is a rare disease but is more common in children than adults, especially children less than five years of age. HUS is the leading cause of acute kidney failure in children. About 200-300 cases of HUS are reported in the United States each year.”
200 to 300 incidents of HUS each year. Less than 1 per million of the current population of the USA. The bottom end of what Corrigan and his partner estimated would be for a 100,000 population but close to the New York article estimate.
Hygiene practices and awareness of E. coli have increased substantially since the turn of the century mitigating possible E. coli infections. If calculating an aHUS incidence rate today relative to an HUS incidence rate the result of Constantiescu’s “relative incidence” calculation would be a different percentage.
So something has to give. E.coli HUS incidence is down but nothing would have altered the incidence of aHUS.
In a Constantinescu like study today the total number of HUS incidents over four years would be fewer. So the relationship between HUS and “ aHUS” would not be 10 to 1 but more like 2 to 1 of a smaller overall HUS incidence rate of 1 per million say. That would mean an estimated incidence rate for aHUS of about 0.3 per million.
That is quite a drop in aHUS incidence per million from 2. It is an alternative rate but is it right?
Since the UK has had an expert centre in Newcastle upon Tyne nearly 10 years ago, the number of aHUS patients diagnosed and treated with eculizumab in England has been between 20 and 30 per year. Say on average 25.
The average population in that time has been about 55 million . The USA population is six times higher. The population characteristic mix of the two countries are similar so there would six times more aHUS incidents or 150 new patients each year in the USA. Roughly 0.45 per million of the population.
A recalculated incidence rate of 0.3 per million still depends on the relative frequency of HUS and aHUS each year, but as can be seen it is not far removed from an incidence found in annual “all age” aHUS diagnosis practice in England.
My head would hurt less if the “all age” INCIDENCE rate for aHUS in the USA ( or any where) was seen as say 0.5 per million of the population instead of the 2 per million of the past. That would be a 2 million to one chance of someone onseting with aHUS in 2023.
The 2 per million never was an estimate of aHUS prevalence and that statistic should be discarded as such.
To be replaced by what? Well that is another question.
Global Action believes aHUS prevalence is between 6 and 9 per million in the USA. It is likely to be lower in countries which do not have access to the same level of health care as USA aHUS patients can have.
See a previous article on USA aHUS patient prevalence and why Global Action thinks that..
Article No. 362 27 July 2020 Ask Google ” how many aHUS patients are there in the USA?” and you will not get an exact answer. Understandable really, as there…
Article No 568