Again, just how many aHUS patients are there?

Article  No. 369
12 August 2020

Recently when preparing an article about USA aHUS patient numbers ( see Article 362 ) an article appeared in a Google search that had recently been published. Its title is
Epidemiology of atypical Hemolytic Uremic Syndrome- A Systematic Literature Review
It was written by an investigator group from British Columbia, Canada, led by Kevin Yan. The article can viewed by clicking on the title above.
The group’s research takes the form of a “literature review” of articles about the incidence and prevalence estimates of aHUS globally. This is something that aHUS alliance Global Action has been interested in for some time. The topic is embedded in the Global aHUS Patients’ Research Agenda- “How many aHUS patients are there in my local area, my country and the world and how do they differ?”
The Yan Group undertook a database trawl of aHUS articles to find articles which addressed the subject of incidence and prevalence estimates of aHUS  in a systematic way. From a starting list of 2960 aHUS articles, only eight articles met the criteria for further study.
No wonder this is a question that is difficult to answer!
The main reason for excluding articles from the study was a lack of clear definition that the patient  cohort in the article was just aHUS patients. Other statistical reasons about the data also came into the exclusion decision.
The eight studies that remained were carried out in Europe , Australia or New Zealand. They varied in scope , four looked at pediatric patients only, one was about adults  and three addressed all ages. The studies were mostly retrospective , looking back at records over several years  but registries  and prospective  methods were also used.

Four research studies looked at incidence and six looked at prevalence. All showed results “per million of the population” apart from one which used “per 100,000”. The incidence and prevalence  rates derived were expressed at continental level as well as Regional. Five of the studies produced incidence rates which were country specific including  France(2), Norway Australia and Italy. A country prevalence rate was also calculated for Italy. A full analysis of the scope of the studies can be found in Table 1 of the article.
Figures 1 and 2 in the published article give a graphical representaion of the incidence and prevalence rates found in the studies and these are summarised for ease of reference in the Table A below.
Table A

*Austria, Denmark, Spain, Finland, France, Greece, Netherlands, Norway, Romania, Sweden, Scotland
**Austria, Germany, Czechia, Hungary, Switzerland, United Kingdom, Italy, Turkey,
All rates reported are from developed world countries.
Incidence rates vary with the age group studied, most in the 0.24 to 0.44 per million range with outliers for child aHUS incidence at 0.76 and 1.00 from Italy and Norway respectively. But the highest 1.9 is reported by  the Bayer Group and is for all ages in France. This french study is also the latest to be published.
Similarly prevalence vary with age groups mostly in the 2 to 5 per million range often cited. One stands out though that from the Ardissino Group in Italy with a prevalence of 9 per million in children.
Where a study has produced both incidence and prevalence rates it is noticeable that the latter lies most often between 10 to 12 times the corresponding incidence rate.
The investigators made no attempt to pool the rates to arrive at  overall  global estimate rates. Producing such rates would have been  of limited use in a global context because the  USA, in particular, would have been excluded, as would all of the developing world countries.
The results from Italy, although confined to pediatric aHUS  patients, were of particular interest to Global Action  because they were close to what we had found when trying to estimate a current USA aHUS population.
The aHUS incidence rate 1.9 per million reported by the Bayer group stands out. The group found it in a study of all TMAs in a hospital cluster in Tours, France . Their publication also provides a novel insight into where aHUS stands among the prevalence of all TMA patients, no matter what the cause. More on that to come.
The aHUS Patients Research Agenda topic question is going to be hard to answer. There are certainly many barriers to overcome and much time would be needed. For now the Yan group’s answer is all there is. But aHUS Global Action will continue to search again.
 
Note: the featured image is one that the aHUS alliance has used for a long time. Global Action accepts that the “2 per million statistic”  is looking to be an understatement in post eculizumab times. But even some thing higher would still make aHUS appear as just a leaf in a forest!