Correspondence
Transmission of Human Herpesvirus 8 by Blood Transfusion
N Engl J Med 2007; 356:87-89January 4, 2007
- Article
To the Editor:
Hladik and colleagues (Sept. 28 issue)1 provide evidence of human herpesvirus 8 (HHV-8) transmission by blood transfusion. They suggest that HHV-8 blood screening for immunocompromised patients may be warranted. However, their statement that nucleic acid testing would not be effective for blood-bank screening is debatable. The viral load is an important marker of disease activity for a number of viruses, including the human immunodeficiency virus (HIV), cytomegalovirus, and HHV-8. By contrast, the clinical significance of seroreactivity to HHV-8 antigens is not clear.2 Reliable techniques to detect HHV-8 DNA have been developed.2 One would expect patients with HHV-8 DNA that is detectable in blood to be at the highest risk for spreading the infection.
2 ReferencesSaverio Giuseppe Parisi, M.D.
University of Padua, 35121 Padua, Italy
saverio.parisi@unipd. it Mario Cruciani, M.D.
Center of Preventive Medicine, 37135 Verona, ItalyGiorgio Palù, M.D.
University of Padua, 35121 Padua, Italy1
Hladik W ,Dollard SC ,Mermin J , et al. Transmission of human herpesvirus 8 by blood transfusion. N Engl J Med 2006;355:1331-1338
Full Text | Web of Science | Medline2
Tedeschi R ,Enbom M ,Bidoli E ,Linde A ,De Paoli P ,Dillner J . Viral load of human herpesvirus 8 in peripheral blood of human immunodeficiency virus-infected patients with Kaposi's sarcoma. J Clin Microbiol 2001;39:4269-4273
CrossRef | Web of Science | Medline
To the Editor:
In their Perspective article on transfusion-transmitted infections (Sept. 28 issue),1 Blajchman and Vamvakas say that there are no “reports of an association between transfusion and the development of Kaposi's sarcoma” — supporting a wait-and-watch approach to blood screening. In fact, a number of studies show that transfusion and parental exposure are risk factors for Kaposi's sarcoma.2-5
In the same issue, Hladik et al. show that HHV-8, also known as Kaposi's sarcoma–associated herpesvirus, is transmitted through blood transfusion. Although the use of highly active antiretroviral therapy has reduced the public health urgency for controlling this virus among patients with HIV and AIDS in the United States, Kaposi's sarcoma is one of the most common tumors in sub-Saharan Africa. Among immunosuppressed patients and patients who have undergone organ transplantation, Kaposi's sarcoma remains a major cause of cancer-related deaths. Disease rates as high as 25 to 64% have been reported among patients who have been infected during transplantation.
There is no HHV-8 screening test approved by the Food and Drug Administration. Developing such a test is a critical step in controlling HHV-8 transmission. Consideration of screening for HHV-8 during both blood transfusion and organ transplantation should be made a priority by clinicians, blood banks, and regulatory agencies.
Patrick S. Moore, M.D., M.P.H.
Yuan Chang, M.D.
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15217
psm9@pitt.edu Harold W. Jaffe, M.D.
University of Oxford, Oxford OX3 7LF, United KingdomDrs. Moore and Chang report being inventors of serologic tests for the detection of Kaposi's sarcoma–associated herpesvirus infection that are licensed by Epiphany Biosciences and being on the scientific advisory board for and receiving stock options in Epiphany Biosciences.
5 References1
Blajchman MA ,Vamvakas EC . The continuing risk of transfusion-transmitted infections. N Engl J Med 2006;355:1303-1305
Full Text | Web of Science | Medline2
Bendsoe N ,Dictor M ,Blomberg J ,Agren S ,Merk K . Increased incidence of Kaposi sarcoma in Sweden before the AIDS epidemic. Eur J Cancer 1990;26:699-702
CrossRef | Web of Science | Medline3
Padilla S ,Rivera-Perlman Z ,Solomon L . Kaposi's sarcoma in transfusion-associated acquired immunodeficiency syndrome: a case report and review of the literature. Arch Pathol Lab Med 1990;114:40-42
Web of Science | Medline4
Aboulafia D ,Mathisen G ,Mitsuyasu R . Aggressive Kaposi's sarcoma and campylobacter bacteremia in a female with transfusion associated AIDS. Am J Med Sci 1991;301:256-258
CrossRef | Web of Science | Medline5
Velez-Garcia E ,Robles-Cardona N ,Fradera J . Kaposi's sarcoma in transfusion-associated AIDS. N Engl J Med 1985;312:648-648
Web of Science | Medline
To the Editor:
Blajchman and Vamvakas describe the transmission of various infections, including HHV-8, through the transfusion of blood and blood products. They discuss the reduction of these risks by screening donors and blood components. We think that the easiest way to reduce transfusion-related infections is not to give transfusions.
For example, in the intensive care setting, much work has been done to assess hemoglobin transfusion triggers and the mortality and morbidity associated with transfusions. In the Transfusion Requirements in Critical Care Trial, Hébert and colleagues showed that a restrictive transfusion policy could reduce 30-day mortality.1 The CRIT Study showed that the number of transfused units was an independent predictor of both morbidity (according to length of stay in the intensive care unit and in the hospital) and mortality. Mortality was 25% among patients who received 6 or more units of blood, as compared with 10% among those who did not receive blood.2
In the treatment of patients with cancer, iron supplementation and erythropoietin are increasingly used instead of blood transfusion.3 Several techniques also facilitate the use of autologous blood in surgical practice.4
In some patients, transfusion is absolutely indicated. In others, we should be as sure as possible that transfusion will be of benefit and should use a restrictive transfusion policy.
4 ReferencesHeather J. Black, F.R.C.A.
Andy M. Johnston, M.R.C.P.
University Hospital Birmingham, Birmingham B15 2TH, United Kingdom1
Hebert PC ,Wells G ,Blajchman MA , et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-417[Erratum, N Engl J Med 1999;340:1056.]
Full Text | Web of Science | Medline2
Corwin HL ,Gettinger A ,Pearl RG , et al. The CRIT Study: anemia and blood transfusion in the critically ill -- current clinical practice in the United States. Crit Care Med 2004;32:39-52
CrossRef | Web of Science | Medline3
Rizzo JD ,Lichtin AE ,Woolf SH , et al. Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 2002;20:4083-4107
CrossRef | Web of Science | Medline4
Carless PA ,Henry DA ,Moxey AJ ,O'Connell DL ,Fergusson DA . Cell salvage for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2003;4:CD001888-CD001888
Medline
Author/Editor Response
We agree with Parisi et al. that seroreactivity to HHV-8 may not predict the infectiousness of a blood unit, but polymerase chain reaction (PCR) tests could be even less predictive. Martró et al.1 showed that HHV-8–infected persons have viral loads that can be very low and not consistently detectable by means of current, sensitive PCR methods, but they may be high enough to cause infection with the volumes of blood ordinarily transfused. This finding is consistent with the absence of detectable HHV-8 DNA in most of the seropositive donors who were linked to seroconversion in the transfusion recipients in our study in Uganda, according to PCR testing of donor blood performed by the laboratory there (unpublished data). The use of donor pools to make nucleic acid testing more cost-effective would further lower PCR sensitivity for detecting HHV-8. PCR screening should remain under consideration, but proof is required that such an expensive intervention is effective.
1 ReferencesSheila Dollard, Ph.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333
sgd5@cdc.gov Philip Pellett, Ph.D.
Cleveland Clinic Foundation, Cleveland, OH 44195Wolfgang Hladik, M.D.
Centers for Disease Control and Prevention, Entebbe, Uganda1
Martro E ,Cannon MJ ,Dollard SC , et al. Evidence for both lytic replication and tightly regulated human herpesvirus 8 latency in circulating mononuclear cells, with virus loads frequently below common thresholds of detection. J Virol 2004;78:11707-11714
CrossRef | Web of Science | Medline
Author/Editor Response
We agree with Black and Johnston that transfusions should be administered only when clinically indicated, by adhering to evidence-based, restrictive transfusion policies, by using alternatives to blood-product transfusions (preoperative autologous donation, perioperative blood recovery, and the use of erythropoietin), and by using single-donor platelets (apheresis) rather than pooled (whole-blood–derived) platelets that expose recipients to four to six donors. A reduction in the number of donor exposures is the only safe way currently available to reduce both the risk posed by emerging (not yet identified) transfusion-transmitted pathogens and the residual risk associated with known transfusion-transmitted pathogens (e.g., pathologic prions) for which we do not yet have totally effective screening methods or proven pathogen-reduction techniques.
Moore and colleagues cite several case reports or case series that predated the 1994 discovery of HHV-8 and its association with Kaposi's sarcoma. These reports described the development of Kaposi's sarcoma in patients who received transfusions and were not infected with HIV1 or patients with transfusion-associated AIDS.2,3 Even though such reports suggest the possibility of transfusion-transmitted HHV-8 as a cause of Kaposi's sarcoma, we are not aware of any well-documented reports of Kaposi's sarcoma that occurred in patients after they had contracted HHV-8 infection from transfusions. Also, as we state in our Perspective article, the possibility of the development of Kaposi's sarcoma in patients who have contracted HHV-8 infection from transfusions has not yet been adequately investigated. Nonetheless, we think that given the strong evidence of the transfusion-related transmission of HHV-8 reported by Hladik et al., it is necessary to determine the best approaches to the prevention of this form of transmission, particularly in transfusions of blood products given to immunocompromised patients.
We therefore agree with Moore and colleagues that appropriate measures should be established and implemented to protect the blood supply from HHV-8. Such measures could include donor screening for HHV-8, universal leukoreduction, and pathogen-reduction techniques applied to either all components or components intended for transfusion to immunocompromised patients. However, before such measures are introduced, their efficacy in preventing the transmission of HHV-8 should be established.
3 ReferencesMorris A. Blajchman, M.D.
McMaster University, Hamilton, ON L8N 3Z5, CanadaEleftherios C. Vamvakas, M.D., Ph.D.
University of Ottawa, Ottawa, ON K1G 4J4, Canada1
Bendsoe N ,Dictor M ,Blomberg J ,Agren S ,Merk K . Increased incidence of Kaposi sarcoma in Sweden before the AIDS epidemic. Eur J Cancer 1990;26:699-702
CrossRef | Web of Science | Medline2
Padilla S ,Rivera-Perlman Z ,Solomon L . Kaposi's sarcoma in transfusion-associated acquired immunodeficiency syndrome: a case report and review of the literature. Arch Pathol Lab Med 1990;114:40-42
Web of Science | Medline3
Aboulafia D ,Mathisen G ,Mitsuyasu R . Aggressive Kaposi's sarcoma and campylobacter bacteremia in a female with transfusion associated AIDS. Am J Med Sci 1991;301:256-258
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Vivian Kourí, Pedro Ariel Martínez, Orestes Blanco, Virginia Capó, María Elena Rodríguez, María del Carmen Dovigny, Lidia Cardellá, Angela Gala, Narciso A. Jiménez, Caridad Luzardo, Consuelo Correa, Yoan Alemán, Lissette Pérez, Alina Álvarez, Ulrich Hengge. (2010) Kaposi’s sarcoma-associated herpesvirus load in asymptomatic contacts of Cuban epidemic KS patients. Archives of Virology 155:12, 1971-1976
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