Subject: reply- caruaru's main messages
Subject: Caruaru- a dialysis tragedy in Brazil
ORIGINAL MESSAGE FROM JRCRocha
April 27, 1996
To All : In Caruaru, a city on the northeast of Brazil, state of
Pernambuco, 126 pts. on HD were intoxicated, several weeks ago.
Investigations suggested the cause to be Microcystin LR, a toxic product
from Microcystis sp. blue alga ( cyanobacteria ). Yesterday, died the 43rd.
patient, of toxic hepatitis.
Sad Clinical Facts :
Apparently all pts. suffered a severe form of toxic hepatitis
Pts. continued to die many weeks after stopping dialysing in the
original unit and after being removed to the state capital.
The blue algae were found in the < dam > that serves water to the
city. There are no reports of non-uremic persons suffering from this
Mycrocystin LR is a cyclic heptapeptide and a potent hepatotoxic.
Anatoxin-a is another common toxin in blue algae, but it is neurotoxic.
The dialysis unit in focus used deionization as water treatment.
That region of Brazil is often under severe drought and many
hospitals have to rely on water brought by < tank-trucks >, as it was
the case here. This water is treated in the truck with chlorine and
analysis of the water involved indeed showed large amounts of chlorine.
Hard Biological facts :
Cases of hepatotoxic poisoning have been found in < every corner of the
world > The toxin is released only if the cell breaks or becomes old
and leaky, mainly during . Substances added to water to
impede blooming causes death of cells and release of toxins.Microcystin
has been implicated in liver cancer in some parts of China.These
hepatotoxins act in a time-scale, from hours to days, by inhibiting
protein phosphatases in the hepatocytes.
Anatoxin-a is an alkaloid that mimics acetylcholine, binding and
opening the ion channel. It cannot however be deactivated by
acetylcholinesterase, so the ion channel remains open, the muscle cell
continues to contract until it fails from exhaustion. Anatoxin-a is the
only natural organophosphate known. (1)
Removal of Microcystin LR and Anatoxin-a can be difficult :
Chlorination is not recommended since it does not removes Ana-a and is
efective against Microcystin only at low pH or long residence times in
water systems ( over 22 Hrs. ) if pH is 7-9.
Other ways of removing it are: GAC and PAC ( ?? ), ozonization,
potassium permanganate and high dose UV-irradiation.(2)
Microcystin has been found, for instance, in the water supply of major
cities such as Winnipeg, Canada. Removal of Microcystin can be
achieved with activated charcoal.(3)
Questions and comments :
Given the ubiquitous presence of these algae, we can expect other
catastrophic intoxications in the future, mainly in cities where water
treatment is poor or the water used comes from dams or .
I could not found refs. to reverse osmosis x toxins. Ref # 2
mentions as effective for Microcystin but not for
One can argue that chlorination in Caruaru was not effective due to pH
problems, and the charcoal ( activated ? ) in the filters either could
not impede passage or became saturated. Another possibility is that
algae died in the sand-charcoal trap, releasing enormous amounts of
toxin, directly into the reservoir.
From all the above, it would be interesting if Nephrol pursue this issue
further, consulting experts ( maybe Kim could contact site # 3, since it states
< Health Canada will recommend guidelines for M-LR next meeting of
Federal-Provincial Subcommitte on Drinking Water > ) to find out how can we
impede another tragedy, not only in Brazil, but all over the world.
jose roberto c. rocha
3- http://www.src.sk.caSubject: Philip Orr comments - Caruaru
DR. CARMICHAEL'S FIRST REPLY ( APRIL 4, 1996 )
Below is a reply sent to me from Prof Wayne Carmichael reagrding the
>Ben: Since we are involved in the analysis of microcystins for the human
>poisonings in Caruraru, Brazil i can provide some clarification as we
>currently understand it:
>1) Most of the details as Dr. Daugiradas provides it are correct. HD
>suffered most because they received the water i.v. While there are other
>reports of gastroenteritis from persons using the water for drinking non
>of these persons report acute toxicity or are they hospitalized.
>2) Initial reports using HPLC did find microcystin in the water source and
>in the clinics (there are two involved) including the carbon filters for
>the inhouse water system. The reference to microcystin-LR is due to the fact
>that it was the only standard available and hence by co-elution on HPLC was
>the toxin identified--others are certainly present as well.
>3) Our analysis of liver and serum from persons who had died and/or been
>hospitalized (only serum from patients still alive) using ELISA and PPIA
>confirm microcystins at levels which we associate with acute or lethal
>4) Much remains to be done however. Since the source water couold have
>toxic orgainics including pesticides it is to soon to conlude that
>were the prime toxins involved. Since we have not data base of human
>we cannot make direct comparisons with the symptoms found in these
>and microcystin acute/lethal symptoms. Therefore at this point we can sa=
>microcysins are present and are certainly a factor but perhaps not the
>factor. Both our lab, CDC in Atlanta and the Brazilian labs are still
>analyzing. If it is microcystin that is the prime toxin involved it will
>be a first-a very significant first.
>Dept. Biol. Sci.
>Wright State Univ.
>Dayton, Ohio 45435
PHILIP ORR'S COMMENTS ( APRIL 30, 1996 ):
The original post is both tragic and potentially very significant. If
microcystin is shown rather than just implicated it will be the first
confirmed human fatalites from microcystin poisoning.
Was microcystin actually measured in the water or just implicated?
Were Post Mortems carried out on the victims to determine if liver
and internal haemhorraging had occurred?
If microcystinis the cause, it is likely that the chlorination process
killed the cells, releasing the toxins into the water. Chlorination may
have not been sufficiently strong to deactivate the toxin (oxidation of the
diene in the ADDA residue). If the dialysis did not size exclude
microcystin, then direct entry into the bloodstream would almost certainly
enhance its uptake into the liver compared to its normal route through
ingestion via the bile transport pathway.
Microcystin has accute (death by liver damage) and chronic (as a tumor
promoter but NOT a carcinogen) effects. Accute effects occur at much
higher dose levels. The chronic effects are observed through exposure to very
low doses for lengthy periods of time.
In Australia, safe recommeded levels of microcystin-LR in drinking water is
1nM (~1=microg/L). Microcystin-LR has a mouse I.P. injection LD100 of
Philip Orr E-mail firstname.lastname@example.org
CSIRO Division of Water Resources, FINGER for PGP Public Key
Locked Bag No3. Phone +61 69 62 5604 (Home)
Griffith NSW 2680 Phone +61 69 60 1555 (Work)
Australia FAX +61 69 60 1600 (Work)
*** There is no greater fury than a vested ***
*** interest masquerading as a moral principle ***
(C) Copyright 1996.
FALCONER,HUMPAGE'S COMMENTS ( MAY 1, 1996 )
Comments on the deaths of dialysis patients in Brazil reported by Dr. Jose
This case shows a similarity to the report from Dr. Filomena Araujo of
Evora, Portugal, on deaths of dialysis patients in which the water supply to
the unit was drawn from a river heavily contaminated with Microcystis
A perfectly functioning reverse osmosis filter will not allow
microcysins to cross, however filter defects happen. The alkaloid toxins from
cyanobacteria are more likely to cross the filter than the cyclic peptides.
Activated carbon filters become saturated. Adding chlorine to a water tanker
of cyanobacterial bloom can be expected to liberate toxins very effectively
into the water.
A number of questions can usefully be answered before any conclusions
- What species of cyanobacterium was present?
- Was it toxic?
- Were any samples taken for chemical or other toxin tests?
- Was the remaining renal function of the patients further damaged?
- Was the post mortem histopathology of the liver examined?
If we can be of any assistance, we can easily be contacted at the following
Ian Falconer, Andrew Humpage.
Dept. of Clinical and Experimental Pharmacology,
University of Adelaide Medical School,
PROF. CARMICHAEL'S 2ND REPLY (MAY 2, 1996 )
Dear Dr. Carmichael :
Last saturday I posted on Nephrol ( a Net list for nephrologist )the
Caruaru tragedy, mainly to inform all colleagues of what happened and to
collect impressions and suggestions to avoid further tragedies in the dialysis
Dr. Daugirdas then promplty forwarded my message to Mr Long who in
turn informed you and also kindly sent me some informations on microcystins
as well as your address.
Mr Long now forwards me your message on the studies you are doing
on Caruaru pts. and I would like to request your permission to post your
response to Nephrol.
While much is still unknown -you have my permission to post the summary of my
response. I Will be in Brazil next week and hopefully have more information
upon my return. We nephrologist are both scared and curious about microcystins,
a subject we literally know nothing. We became painfully aware of these
cyanobacterias only after Caruaru.
Many dialysis units exist around the world where water could well be
contaminated by cyanobact and we don't really know what to do to avoid
intoxications. As you point out in your poster, this may well be the first
known severe intoxication in man, and possibly only the first one....
We need your help to dismiss our fears, and at this moment I would like
to ask you some of the questions that go thru my mind :
Many of the following questions are answered in a resource manual
that I helped publish by the American Water works Research Foundation-
titled--"Cyanobacterial (blue-green algal) Toxins: A resource Guide".
1995---American Water Works Association--Denver, Colorado--contact
- Are microcystins a contaminant of treated city waters?
- The usual treatment of municipal water is enough to kill the
bacteria or to neutralize the toxin ?
- Charcoal-sand ( deionization ) filters utilized in thousands of
dialysis units around the world are safe enough if there is no
massive contamination ?
- Does reverse osmosis treatment impede the passage of the toxins ?
- Is culturing and identification of the organism a very difficult
- Pts. on dialysis often show unexplained alterations in liver enzymes,
that cannot be attributed to known viruses. Could this be the result
of chronic, low level microcystin intoxication ?
As you can see, we have so many questions that I feel somewhat
ashamed of my ignorance. Unfortunately, however, this is now another
important point to be clarified, for the safety of our pts. and we all
would like to have your opinions on this matter.
Again, if you agree, I would like to spread your comments to the
Thank you very much
jose roberto c. rocha,md
*****I hope this helps--Wayne Carmichael, Professor.
SECOND MESSAGE May 4 1996 FROM JRCRocha
To all :
After my message on "Caruaru, a dialysis tragedy" I received
several private mails, besides the ones posted here. I'll try to summarize
things for you. Many thanks to Drs. Solez and Daugirdas and to Mr. Ben Long
who helped a lot :
1- The 3 doctors who owned the unit were indicted by the state gov. for
2- A parlament comission indicated the doctors, the state health and the
municipal health secretaries as responsible for the events.
3- The message was posted at a CYANO-TOX discussion group
4- Philip Orr, Div. of Water Resources, Au wanted to know if microcystins were
really involved. If so
5- Prof. Wayne Carmichael, Dayton, Ohio (Biol. Sc.) is actually studying this
tragedy.He authorized me to post this : < HPLC did find microcystin in the
water source and the in the clinics, including the carbon filter....Other
microcystins, besides LR are certainly involved... Analys is of liver and serum
from pts. ( dead or alive ) with ELISA and PPIA confirm micro at levels we
associate with acute or lethal toxicities...It is too soon to conclude Micro
were the prime toxins since the water could have others...including pesticides.
Our lab, CDC and brazilian labs are working on it... If microcystin is the
prime toxin, it will be a first- a very significant first... >
6- From Adelaide Med. School, Falconer and Humpage comment: < similarity with
report from Dr. Filomena Araujo, Evora, Portugal, on deaths of HD pts.
in wich water supply to the unit, from a river, was heavily contaminated with
Microcystis aeruginosa... A perfectly functioning RO filter will not allow
Micro to cross, however filter defects happens...Activated carbon
filters become saturated. Adding chlorine to water tanker of cyanobact.
bloom can be expected to liberate toxins very effectively into the water.>
7- Dr. Carmichael will be back in Brasil next week to look for more
Those that wish to have the full text of any of these messages
please feel free to contact me ( email@example.com )
Do you feel this should be posted further or should we stop here ??