Thursday, December 12, 2013

The long and winding road (Musings on 30 years of transfusion-associated AIDS)

Updated: 13 Dec. 2013
AABB's Transfusion for October 2013 is a themed issue.
Since few transfusion professional will probably read, let alone scan, all 238 pages, this blog will review the two items (among several gems) that I found most interesting, a commentary and a letter to the editor from authors in Brazil.    
  • Dubin C, Francis D. Closing the circle: a thirty-year retrospective on the AIDS/blood epidemic. Transfusion 2013 Oct;53(10 Pt 2):2359-64. (Commentary)   
  • Salles NA, Levi JE, Barreto CC, Sampaio LP, Romano CM, Sabino EC, Júnior AM. Human immunodeficiency virus transfusion transmission despite nucleic acid testing. Transfusion 2013 Oct;53(10 Pt 2):2593-5. (Letter)  
The blog's title derives from a 1970 Beatles tune. But why blog about an old transfusion issue like HIV/AIDS? I can see some of you yawning. After all, our blood supply in developed nations is the safest it's ever been.

We in the transfusion medicine community can congratulate ourselves on how safe we have made blood from viruses like HIV, HBV, HCV, and WNV. Fact is, we often do. 

Now the main threats for fortunate us exist elsewhere. As but two examples, transfusing an incorrect blood group (due to patient misidentification) and transfusing the wrong blood product (perhaps due to clinician lack of knowledge or communication errors between hospital departments).

Why blog on HIV/AIDS?

1. Because AIDS was in the news 30 years ago, it follows that health professionals age 45 or younger were children at the time and unlikely to be aware of HIV and AIDS.

2. We're told by transfusion experts that the era of transfusion transmitted infections is all but over due to these reasons:

  • Better pre-donation screening
  • Almost foolproof donor testing for infectious diseases
  • Manufacturing processes such as viral inactivation and filtration
But it's not. Besides the situation in the 'third world' in which governments cannot afford expensive tests and do not have the infrastructure to support them, human and systemic errors happen, infectious disease tests are not 100% sensitive, and donors may lie about risky behavior on predonation screening questions.

3. Significant historical events should be acknowledged as a sign of respect.

4. George Santayana got it right: Those who cannot remember the past are condemned to repeat it.

DISCLOSURE: Be aware, what follows is not always politically correct. I mean no disrespect but will call 'em as I see 'em (or recall 'em). Also, the content is highly selective based on my biases. Lastly, there's more than a few 'tacky' aspects to the so-called tainted blood tragedy. Have barf bags handy.

For interest, the Transfusion special issue features 6 papers on HIV (from China, Hong Kong, Germany, South Africa, Zimbabwe, and the International NAT study Group). Also included are 7 papers on hepatitis, 4 on NAT, and 4 on other viruses.

A brief trip down memory lane... My early days at Canadian Red Cross were pre-AIDS. Then we screened blood donors only for syphilis and later the hepatitis B surface antigen (HBsAg). The 'good old days' of farcical government regulation, no SOPs. Training was sort of like the long-standing medical school model:

  •  See one, Do one, Teach one.
Early infectious disease tests were far from perfect. For example, I have fond memories (nightmares at the time) of trying to visualize the white precipitin lines of positive HBsAg reactions between donor serum and anti-HBs wells after counterimmunoelectropheresis (CIEP). CIEP was a  'second generation' test that was the first test used to mass screen blood donors for hepatitis. To say such tests were subjective is an understatement.

A few historical highlights / lowlights:

1981: Then came AIDS, first reported as 'gay-related immune deficiency' (GRID) in 1981, and soon identified in sex workers, Haitians in the USA, and IV drug users. Cause unknown.

1982: The term AIDS first appeared when it was used by the CDC to describe a disease affecting the immune system. Cause unknown.

1982: Evidence for a blood-borne pathogen transmitted by transfusion emerged when reports of AIDS were reported in 3 hemophilia A patients who were heterosexual, had no other known risk factors, and were frequently transfused with Factor VIII concentrate. Cause unknown.

1984: The US government held a press conference to announce that Robert Gallo, a National Cancer Institute scientist, had discovered the cause of AIDS, which he named HTLV-III, and had invented a screening test worth mega-bucks.

1983: In truth the French research team of Luc Montagnier (who later delved into quackery) discovered HIV a year earlier and had sent Gallo a sample to investigate. They called it lymphadenopathy-associated virus (LAV). 

1984: Gaëtan Dugas dies. He was a French Canadian flight attendant linked by CDC to 40 of the first 248 reported cases of AIDS in USA, purported to be 'patient zero', a claim later disputed.

1985: Once it became known that Ryan White, a hemophiliac, had contracted AIDS from a blood transfusion, school officials banned him from classes. Ryan died of AIDS at age 18 in 1990.

1985: US President Reagan, he of 'win one for the Gipper' fame, first used the word AIDS, expressing skepticism in allowing children with AIDS to continue in school although he supported their right to do so.

1985: Blood donor tests for HIV began in USA, Canada and elsewhere.

1985: The Pasteur Institute filed a lawsuit against the National Cancer Institute to claim a share of the royalties from the NCI's patented AIDS test.

1986: HIV is adopted as name of the virus that causes AIDS.

1994: The battle for patent rights to the HIV test lasted for more than a decade and ultimately favored the French claim, although all decided to play nicey-nicey in the end.

2008: Montagnier and Françoise Barré-Sinoussi shared the 2008 Nobel Prize in Medicine and Physiology for the discovery of HIV (along with  Harald zur Hausen, who discovered that human papilloma viruses can cause cervical cancer). Gallo was frozen out.

See amfAR for an interesting review of AIDS, 1981-2011.


My take on this commentary, written from a USA perspective, but applicable everywhere:

Dubin C, Francis D. Closing the circle: a thirty-year retrospective on the AIDS/blood epidemic. Transfusion 2013 Oct;53(10 Pt 2):2359-64.  (Commentary) 

I love that AABB included a commentary by Cory Dubin and Dr. Donald Francis. Kudos!

A few selected excerpts from Closing the circle: a thirty-year retrospective on the AIDS/blood epidemic (which I've condensed):
AIDS devastated 4 generations of families with hemophilia. But the real story predates HIV/AIDS. Pharmaceutical firms are required to manufacture safe biologics, yet the blood community remained indifferent to the presence of hepatitis in the blood supply for decades.

That indifference set the stage for the HIV/AIDS catastrophe. It was as if a 'collective denial' spread through the blood community. Despite warning signals, the system allowed dangerous practices such as collecting plasma from prisoners and importing plasma from undeveloped countries. Plasma collection in prisons did not end until 1993. 
In hemophilia, factor concentrates were the 'Golden Goose' that revolutionized treatment. Concentrates brought independence from hospitals and convenient treatment. 
Widespread denial blinded the entire blood system. The CDC warned the blood community, but inertia prevailed. What followed was one of the worst medical disasters in history.
Authors' take home message
In 2013, 30 years after transfusion-associated HIV/AIDS was confirmed, we must not become complacent due to improved regulations and scientific gains. We must resist the influence of conflict of interest while rejecting the scientific and medical arrogance that contributed to the AIDS/blood epidemic. We must never forget the human cost. We must prepare for the unexpected and unforeseen.


* Because Factor VIII concentrates were a god-send to patients with hemophilia, physicians kept transfusing the product, even realizing the danger, because they

(1) Thought most hemophiliacs were already infected (2) Believed the alternative was patients potentially bleeding to death
* Physicians were in denial about HIV / AIDS in the blood system, illustrated in this interview with Dr. Noel Buskard of Canadian Red Cross (Sorry about the short ads). Quote: Physicians and hemophiliacs must weight the cost benefit ratio in every therapy - If I give you an aspirin there is a risk...

* Canada's Krever Report makes it clear that transfusion experts, however well motivated, screwed up, big time.

The slowness in taking appropriate measures to prevent the contamination of the blood supply was largely due to experts rejecting, or at least not accepting, an important tenet of the precautionary principle.
When there was reasonable evidence that serious infectious diseases could be transmitted by blood, the principal actors in the blood supply system in Canada refrained from taking essential preventive measures until causation had been proved with scientific certainty. The result was a national public health disaster.
Best line from the Dubin and Francis commentary:
We must resist the influence of conflict of interest while rejecting the scientific and medical arrogance that contributed to the AIDS/blood epidemic.

Now to the themed issue's letter to the editor in Transfusion:

* Salles NA, Levi JE, Barreto CC, Sampaio LP, Romano CM, Sabino EC, Júnior AM. Human immunodeficiency virus transfusion transmission despite nucleic acid testing. Transfusion 2013 Oct;53(10 Pt 2):2593-5.     

Key facts:
* The risk of HIV transmission by blood transfusion in a blood center in São Paulo, Brazil was estimated to be 0.68 per 100,000 donations [6.8/million] using nucleic acid testing (NAT) on minipools of six donations. 
[For reference, in Canada the residual risk of HIV is 1 per 8 million donations, where residual risk is estimated as the incidence multiplied by the window period.]
* In November 2012, a leukemia patient became HIV-positive after 47 transfusions of RBCs and platelets. Upon follow-up, one donor was found to be HIV positive, with a pattern that suggested he likely donated a few days after becoming infected.

* The donor had denied all risk factors in the interview when donating and continued to deny high-risk behavior in 3 subsequent visits to the blood bank, even after his HIV status was disclosed to him. He also did not self-defer by confidential unit exclusion before the implicated donation.

* The literature has several reports of transfusion-transmitted HIV in the NAT-negative window period, although this case may have the lowest documented viral load.

* This case shows that even individual NAT (not pools of 6 donors) by the most sensitive methods available might not detect HIV. Thus, we must to continue to understand motivations for blood donation and publicize the risk of donating shortly after risky behaviors.

Blood donors lie and infectious disease screening test are not perfect. HIV windows of negativity still exist no matter how short. Transfusion-associated HIV is extremely rare. But if it's you or a loved one who becomes infected, you don't care how rare it is.

Transfusion professionals must resist becoming blasé
 about how protected the blood supply in developed countries is from HIV and other infectious agents. Unfortunately, many are blasé.

For example, in Canada we have Health Canada and the CEO of CBS saying that paid plasma donation is no big deal because infectious disease screening tests and manufacturing processes used to produce plasma derivatives like IVIg are foolproof.

As an aside, on a related issue in 2013 Health Canada decided to allow men to donate blood if they haven't had sex with a man in the last five years

For years the gay community has campaigned to drop the permanent ban on blood donation for MSM donors on the grounds the ban is unscientific and discriminates. 

CBS's Public Affairs put out an interview with Dr. Dana Devine, Vice President, Medical, Scientific & Research Affairs on the changed MSM policy.  She noted that it will take years to gather valid data set to evaluate impact of changed policy on blood safety as incidence of HIV+ donors is extremely low. 

The geek in me wants to suggest it's a matter of statistical power: The ability of a study to detect a real difference, if one exists. Power is affected by how big the difference is and sample size. If a difference is big, it's easier to detect. And large sample sizes make a real difference easier to detect .
I'll end on a personal note with a newspaper article that appeared in the Toronto Star, Feb. 18, 2006 but is no longer online. I hope the Star doesn't mind that I've reproduced it. 
When I worked at Canadian Red Cross in Winnipeg, Barry and Ed Kubin would drop by periodically to pick up cryoprecipitate and, later, Factor VIII concentrate.

Admittedly, it's hard to say 'for fun' on an issue that has devastated so many. But please enjoy this 1970 ditty by The Beatles, the last one released shortly after they broke up and while all 4 were alive. 

* The Long and winding road (Paul McCartney and The Beatles)

As always, comments are welcome.