hacked by p@3t_b@y for turks

Authors: Tonnetti, Laura; Eder, Anne F.; Dy, Beth; Kennedy, Jean; Pisciotto, Patricia; Benjamin, Richard J.; Leiby, David A.

Source: Transfusion, Volume 49, Number 12, December 2009 , pp. 2557-2563(7)

Publisher: Blackwell Publishing
Abstract:

BACKGROUND:

Babesia microti, the primary cause of human babesiosis in the United States, is an intraerythrocytic parasite endemic to the Northeast and upper Midwest. Published studies indicate that B. microti increasingly poses a blood safety risk. The American Red Cross Hemovigilance Program herein describes the donor and recipient characteristics of suspected transfusion-transmitted B. microti cases reported between 2005 and 2007.

STUDY DESIGN AND METHODS:

Suspected transfusion-transmitted Babesia infections were reported by transfusion services or were discovered through recipient-tracing investigations of prior donations from donors with a positive test for B. microti in a serologic study. Follow-up samples from involved donors were tested by Babesia-specific immunofluorescence assay, Western blot, and/or real-time polymerase chain reaction analysis.

RESULTS:

Eighteen definite or probable B. microti infections, including five fatalities, were identified in transfusion recipients, 16 from hospital-reported cases and two through serologic lookback studies. Thirteen recipients were 61 to 84 years old and two were 2 years old or younger. Two recipients had sickle cell disease and four were known to be asplenic, including one with sickle cell disease. Seventeen antibody-positive donors were implicated; 11 (65%) were residents in Babesia-endemic areas, while four (24%) nonresident donors had a history of travel to endemic areas.

CONCLUSIONS:

Transfusion-transmitted B. microti can be a significant cause of transfusion-related morbidity and mortality, especially in infant, elderly, and asplenic blood recipients. These data demonstrate the need for interventions, in both endemic and nonendemic areas of the United States, to reduce patient risk.
Document Type: Research article

DOI: 10.1111/j.1537-2995.2009.02317.x

http://www.ingentaconnect.com/content/bsc/trf/2009/00000049/00000012/art00005;jsessionid=2o5n96fb2rqh5.alexandra

Yong Zhao, Kenneth R. Love, Scott W. Hall, and Frank V. Beardell
From the Department of Pathology and the Department of Medicine, Christiana Care Health System, Newark, Delaware.
Correspondence to  Yong Zhao, MD, Department of Pathology, Christiana Care Health Services, 4755 Ogletown-Stanton Road, Newark, DE 19718; e-mail: yzhao@christianacare.org.
Copyright © 2009 AABB

ABSTRACT
BACKGROUND: Most cases of human babesiosis in North America are caused by Babesia microti, which is endemic in the northeastern and upper midwestern United States. Although the disease is usually transmitted by a tick bite, there has been an increase in the number of transfusion-transmitted cases reported. We describe a fatal case of transfusion-transmitted babesiosis in a nonendemic state, Delaware.

CASE REPORT: The patient was a 43-year-old Caucasian woman with history of transfusion-dependent Diamond-Blackfan syndrome, hepatitis C, and splenectomy. She was admitted initially for presumptive pneumonia. The next day, a routine examination of the peripheral blood smears revealed numerous intraerythrocytic ring forms, consistent with Babesia. The parasitemia was approximately 5% to 6%. The diagnosis was confirmed by positive polymerase chain reaction (PCR) for B. microti DNA and high titer of antibody to B. microti (1:2048). Despite aggressive therapy including clindamycin and quinine antibiotics, the patient expired 3 days after admission. Subsequently, 13 blood donors were tested for B. microti. All tested donors were negative by PCR. However, one donor living in New Jersey had a significant elevated B. microti antibody titer (1:1024).

CONCLUSIONS: We believe that this is the first reported case of transfusion-transmitted babesiosis in Delaware, a nonendemic state. Our case illustrates that clinicians should consider babesiosis in the differential diagnosis of immunocompromised patients who have fever and recent transfusion history, even in areas where babesiosis is not endemic. It also demonstrates the need for better preventive strategies including more sensitive, specific, and rapid blood donor screening tests to prevent transfusion-transmitted babesiosis.
——————————————————————————–

Received for publication May 8, 2009; revision received August 17, 2009, and accepted August 23, 2009.

DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1537-2995.2009.02454.x

http://www3.interscience.wiley.com/journal/122680319/abstract?CRETRY=1&SRETRY=0

Contact: Nancy Cawley Jean
njean@lifespan.org
Lifespan

Research finds dramatic increase in number of transfusion-transmitted babesiosis cases
Babesiosis is a potentially dangerous parasitic disease transmitted by ticks and is common in the Northeast and the upper Midwest.

Babesia lives inside of red blood cells, meaning it can also be transmitted through a blood transfusion from an infected but otherwise asymptomatic blood donor.

Now a new study led by researchers at Rhode Island and The Miriam hospitals finds a dramatic increase in the number of transfusion-transmitted babesiosis cases (TTB), leading the investigators to call for a better screening test in blood donors living in areas of the country where babesiosis is prevalent. Their paper is published in an upcoming edition of the journal Transfusion, and is now available online in advance of print.

Infectious diseases specialist Leonard Mermel, DO, is the medical director of infection control for Rhode Island Hospital and corresponding author of the paper. He and his colleagues, Shadaba Asad, MD, a hospitalist at The Miriam Hospital (sister hospital to Rhode Island and also a Lifespan partner), and Joseph Sweeney, MD, director of transfusion services at Rhode Island and The Miriam hospitals, observed an increase in the number of TTB cases, and initiated a retrospective study to gauge the extent of TTB in Rhode Island.

Babesiosis became a reportable disease in Rhode Island in 1994. For the purpose of this study, cases of babesiosis reported to the Rhode Island Department of Health (RIDOH) between January 1999 and December 2007 were reviewed, along with information on blood donors from the Rhode Island Blood Center.

People who are infected with the parasite may go undiagnosed as symptoms may not occur. In others, however, the disease can cause severe illness that may include fever, fatigue, jaundice, and anemia. Mermel, who is also a professor of medicine at The Warren Alpert Medical School of Brown University and a member of the University Medicine Foundation, says, “At present, the only means of screening blood donors is a questionnaire that includes a query regarding a known history of babesiosis. Because many babesiosis cases are minimally symptomatic or asymptomatic in otherwise healthy people, the questionnaire may not effectively exclude all donors who may transmit the disease by donating blood.”

Mermel and his colleagues found that a total of 346 cases of babesiosis were reported to the RIDOH between 1999 and 2007. Of these, 21 cases appear to have been transmitted by blood transfusion rather than from a tick. During this time period, the number of TTB cases per number of units of blood transfused increased annually. On average, there was at least one case of TTB per 15,000 units of red blood cells transfused during the entire period. However, from 2005 to 2007, the incidence approached one case per 9,000 units. In 2007, TTB accounted for 10 percent of the total babesiosis cases reported in Rhode Island.

Based on their findings, Mermel suggests, “The diagnosis of babesiosis in winter and early spring in northern latitudes, when deer ticks are less prevalent, should raise suspicion of Babesia transmission due to a blood transfusion.”
###

Mermel is a past president of the Society for Healthcare Epidemiology of America. Sweeney is a professor of pathology and laboratory medicine and Asad is a clinical assistant professor of medicine at Brown University. Asad is also a physician with University Medicine Foundation (http://www.umfmed.org), a non-profit, multi-specialty medical group practice employing many of the full-time faculty of the department of medicine of Alpert Medical School.

http://www.eurekalert.org/pub_releases/2009-10/l-bbs102009.php

Transfusion. 2009 Oct 10. [Epub ahead of print]
Johnson ST, Cable RG, Tonnetti L, Spencer B, Rios J, Leiby DA.
From the Transmissible Diseases Department, Jerome H. Holland Laboratory, and Biomedical Services, American Red Cross, Farmington, Connecticut; the Transmissible Diseases Department, Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland; and Biomedical Services, American Red Cross, Dedham, Massachusetts.

BACKGROUND: Current estimates of 70 cases of transfusion-transmitted Babesia microti, with 12 associated deaths, suggest that Babesia is a growing blood safety concern. The extent of Babesia infections among blood donors has not been well defined. To determine how common exposure to B. microti is among blood donors, a seroprevalence study was undertaken in the American Red Cross Northeast Division.

STUDY DESIGN AND METHODS: Blood donations at selected blood drives in Connecticut and Massachusetts (2000 through 2007) were tested for the presence of immunoglobulin (Ig)G antibodies to B. microti using immunofluorescence assay. Geographic and temporal trends of B. microti seroprevalence were estimated for donor’s zip code of residence.

RESULTS: Overall, a 1.1% seroprevalence was identified in Connecticut, with the highest levels found in two Southeastern counties (Middlesex and New London). Observed seroprevalence for offshore islands of Massachusetts was 1.4%. Seropositive donations were identified from donors residing in all eight counties in Connecticut and three counties in Massachusetts. Although a seasonal peak was found between July and September, seropositive donations were identified in every month of the year.

CONCLUSIONS: Foci of statistically higher B. microti seroprevalence among blood donors were observed; however, B. microti transfusion transmission risk exists for blood collected throughout Connecticut and portions of Massachusetts. Similarly, a seasonal peak was identified; nevertheless, seropositive donations were found year-round. Thus, geographic and/or seasonal exclusion methods are insufficient to fully safeguard the blood supply from Babesia transmission. Steps should be taken to reduce risk of transfusion-transmitted B. microti, perhaps through implementation of year-round, regional testing.

PMID: 19821951 [PubMed - as supplied by publisher]

Posted : Tue, 04 Aug 2009 12:15:42 GMT
Author : Aphios Corporation 
Category : Press Release 
News Alerts by Email ( click here ) 
 
Aphios Corporation today announced that it has been awarded a Phase I Small Business Innovative Research (SBIR) grant from the National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH) to develop CFI as a generally-applicable virus and pathogen inactivation technology for human plasma, plasma products and biologics.

The recent outbreaks of potentially pandemic strains of influenza such as the H1N1 swine flu and the H5N1 bird flu, the worldwide AIDS epidemic, the emergence of West Nile virus and Babesia spp, and the periodic emergence of Ebola and SARS as well as the bioterrorism potential have highlighted a persistent concern in the health care community — the need for effective sterilization techniques for human blood plasma, plasma products and biologics. The causes of the more rapid emergence and spread of these potential “killer” pathogens are not entirely known, but are thought to be caused by some combination of deforestation with urbanization of wild virus habitats, evolutionary mutations and rapid travel between countries around the globe.

Current approaches such as heating or pasteurization; solvent-detergent (SD) technique; Ultra Violet (UV) irradiation; chemical inactivation and filtration are not always effective against a wide spectrum of human and animal viruses, are sometimes encumbered by process-specific deficiencies, and often result in denaturation of the biologics that they are designed to protect. Some of the commercially available methods such as SD are effective in inactivating enveloped viruses, such as HIV, but are not very effective against non-enveloped viruses such as Hepatitis A (HAV) and parvovirus B19.

Aphios’ CFI (critical fluid inactivation) technology works, in part, by first permeating and inflating the virus and pathogen particles with a selected SuperFluids™ gas under pressure. The overfilled particles are then decompressed, and the dense-phase fluid rapidly changes into a gaseous state rupturing the virus and pathogen particles at their weakest points — very much like the embolic disruption of the ear drums of a scuba diver who surfaces too rapidly. The virus and pathogen particles are thus rendered inactive. The CFI process is purely physical and does not involve the use of heat, chemicals or irradiation that could damage sensitive enzymes and proteins.

According to Dr. Trevor P. Castor, the primary inventor of the Aphios CFI technology: “In addition to its direct applicability to human plasma and plasma proteins, CFI has the capability to clear viruses and pathogens from biotechnology drugs and monoclonal antibodies. It also has the potential for the rapid manufacturing of antiviral human and animal vaccines since protein integrity and antigenicity are retained during the purely physical virus inactivation step.”

The number of the Phase I SBIR grant from NHLBI, NIH is 1R43HL090192-01A2. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of NHLBI and the National Institutes of Health.

Aphios Corporation is a biotechnology company that is developing enabling technology platforms to improve drug discovery, manufacturing delivery and safety as well as enhanced therapeutic products for health maintenance, disease prevention and the treatment of certain cancers, infectious diseases and CNS disorders.

http://www.earthtimes.org/articles/show/aphios-awarded-nih-grant-for,914378.shtml

Posted on: Monday, 19 January 2009, 10:33 CST

The U.S. Food and Drug Administration has received nine reports of deaths since 2005 caused by blood transfusion due to a parasitic infection known as babesiosis.

Babesiosis, stemmed from the parasite Babesia, can be transmitted through a tick bite, the same tick that causes lime disease. However, transmission via blood transfusion has been reported to be a cause as well. This disease is hardest on the elderly and people with weak immune systems.

Dr. Diane M. Gubernot at the FDA in Rockville, Maryland, and colleagues advise that doctors should consider babesiosis in immunocompromised patients fever with a history of recent transfusion.

Gubernot and colleagues ask the FDA for safety surveillance systems for trends in babesiosis reporting since 1997.  They uncovered nine deaths between 2005 and 2008, and the patients ranged from 43 to 88 years of age.

Those patients showed signs of altered mental status, developed kidney failure, or respiratory distress, with symptoms appearing anywhere from 2.5 to 7 weeks following blood transfusion. When the symptoms developed, death followed within 5 to 17 days.  The blood donations were identified, and all donors tested positive for the infection.

The number of reports of potential transfusion-transmitted Babesia infection and post-donation babesiosis rose from zero in 1999 to 25 in 2007.

Babesia species can survive blood banking procedures, including freezing, according to Gubernot and her associates.

http://www.redorbit.com/news/health/1625118/babesiosis_causes_death_in_transfusion_cases/

Nashua Telegraph, Dave Brooks

Published: Wednesday, January 14, 2009

Let’s see: The global economy is collapsing, climate change is accelerating, my TV will become useless next month and I’ve got a hangnail.

Hoo, boy; let’s talk about something fun for a change. How about disease-carrying deer ticks!

Actually, it isn’t the ticks or the disease they transmit (babesiosis, in this case, not Lyme disease) that interests me. Rather, it’s the way the Red Cross is using the vast volunteer army of blood donors to hunt down an elusive ailment and see how much of a problem it is.

In buzzword terms, you could call this the crowdsourcing of epidemiology.

I encountered this the last time our family gave blood, when the paperwork for donors included an announcement it would be tested for a protozoan parasite called babesia, which cause a disease called babesiosis.

(Pause for public service announcement: If you’re a healthy adult and don’t donate blood at least once a year, shame on you. It’s easy, just painful enough to make you feel virtuous and serves a real need. Call the Red Cross right now and find the nearest blood drive; no excuses.)

My wife, a veterinarian who deals with tick-borne diseases all the time, noticed the notice and wanted to know more.

So I talked to David Leiby, head of the transmissible disease department for the American Red Cross, who designed the study.

Babesiosis, it turns out, isn’t too dangerous, although it can produce harmful, malaria-like symptoms in the young, the old and those with weak immune systems. Most people who get infected show no signs at all.

Babesiosis has long been endemic in Connecticut, Rhode Island and Long Island, and there are anecdotes about it creeping north past Cape Cod into New Hampshire, particularly near the coast.

But most people who are infected don’t show any symptoms, so it’s hard to say for sure where it is.

“If I go to the (Centers for Disease Control & Prevention) and say, ‘Where is babesia and how often does it occur in New Hampshire?’ they don’t really know,” Leiby said. “Sometimes, with emerging diseases like this, the only recourse is to do the study ourselves.”

Why does the Red Cross care? Because, Leiby explained, “sometimes this agent (the parasite) gets transmitted by blood transmission.”

(Surprisingly, a lot of diseases can’t be passed on via blood transmission – including Lyme disease.)

If the babesia parasite is common, then the Red Cross will have to start screening all blood supplies for the protozoa, adding it to the seven or eight other things it screens for.

Screening is time-consuming and expensive, however, and first they need to see if it’s a real problem. So, they’re using blood donors to conduct a study of how many people are infected or who have antibodies showing they were infected in the past.

You could hardly ask for a better medical survey. Instead of getting people to answer a questionnaire, the highly suspect basis for much of public health’s decision-making, you get actual medical data from people’s blood.

It isn’t a random population sample, but it’s pretty darn close, and while it has issues (if I have antibodies in my blood, was I exposed in New Hampshire or when I visited Nantucket?), it’s still pretty darn good.

“A lot of our studies start out as epidemiology, to determine the extent, transmission, spread of disease. Then we assess that data, determine if it is a threat to blood supply,” Leiby said.

A similar survey process in the past led the Red Cross to screen all blood donations for Charga’s disease.

Leiby said the Red Cross has been doing babesia surveys around Connecticut for several years, but the possibility of a spread has moved the issue up on the priority list.

The study only just began in New Hampshire.

“We don’t know what we’re going to find,” he said, so it isn’t clear what action the Red Cross will take. One possibility is that blood supplies would be screened for babesiosis only in the Northeast, the nation’s “epicenter” for the disease. If so, that would be the first time the Red Cross does blood screening regionally, rather than nationally.

It will probably take at least a year before any conclusions are reached, but in the meantime, we all have a chance to add a little bit to the nation’s knowledge of its health-care picture.

In other words: Go donate some blood, will you?

http://www.nashuatelegraph.com/apps/pbcs.dll/article?AID=/20090114/COLUMNISTS03/301149932/-1/news

JAMA. 2008;300(23):2718-2720.

MMWR. 2008;57:1145-1148

1 table omitted

Anaplasma phagocytophilum, a gram-negative, obligate intracellular bacterium of neutrophils, causes human anaplasmosis, a tickborne rickettsial disease formerly known as human granulocytic ehrlichiosis.1 In November 2007, the Minnesota Department of Health was contacted about A. phagocytophilum infection in a hospitalized Minnesota resident who had recently undergone multiple blood transfusions. Subsequent investigation indicated the infection likely was acquired through a transfusion of red blood cells. This report describes the patient’s clinical history and the epidemiologic and laboratory investigations. Although a previous case of transfusion-transmitted anaplasmosis was reported,2 this is the first published report in which transfusion transmission of A. phagocytophilum was confirmed by testing of the recipient and a donor. Although polymerase chain reaction (PCR) assays provided reliable evidence of transmission in this case, no cost-effective method for screening blood donors for A. phagocytophilum exists. Screening donors for a recent history of tick bite is not likely to be sensitive or specific because such exposures are common and often not recalled by persons with anaplasmosis.3 Physicians should consider the possibility of anaplasmosis in patients who develop posttransfusion acute thrombocytopenia, especially if accompanied by fever, and should report suspected transfusion-associated cases to health authorities.

Case Report  

The patient, a male aged 68 years with a medical history of chronic renal insufficiency, psoriatic arthritis, ankylosing spondylitis, and corticosteroid therapy, underwent elective knee arthroplasty and synovectomy on October 12, 2007. Three weeks before his hospitalization, the patient had traveled to an area where blacklegged ticks (Ixodes spp.) were endemic, but he did not spend time outdoors and had no known tick bites. Several hours after the procedure, the patient developed bleeding at the surgical site and associated coagulopathy, indicated by elevated international normalized ratio (INR) and partial thromboplastin time (PTT) and by decreased fibrinogen and platelet counts. The extensive hemorrhage required two surgical evacuations of hematoma from the knee, popliteal artery embolization, and transfusion of multiple blood components. During October 12-21, the patient received 34 units of nonleukoreduced red blood cells (RBC), 4 units of leukocyte-reduced apheresis platelets, 14 units of fresh frozen plasma (FFP), and 7 units of cryoprecipitate. The components came from 59 individual blood donors; all donations were collected by Memorial Blood Centers (St. Paul, Minnesota). On October 19, the patient developed sepsis and multisystem failure. He was treated empirically with antibiotics (cefazolin, piperacillin/tazobactam, vancomycin, and levofloxacin). Blood cultures were negative on October 18, 20, and 31, and urine cultures were negative on October 19 and 25.

On October 31, the patient was found to have worsening thrombocytopenia. His platelet count declined from 178,000/mm3 on October 31 to 54,000/mm3 on November 5. On November 1, he developed hypotension and fever attributed to urinary tract infection. He was treated with levofloxacin and sulfamethoxazole/trimethoprim and was afebrile by November 3. On November 3, 22 days after admission, a peripheral blood smear from the patient demonstrated inclusions compatible with A. phagocytophilum morulae in neutrophils. Retrospective review of an October 15 blood smear from the patient showed no evidence of intracellular morulae. Whole blood specimens from November 3-5 were positive for A. phagocytophilum DNA by PCR assays conducted at the Mayo Medical Laboratory, Minnesota Department of Health, and CDC. Serum from November 3-5 was tested at CDC and found to be weakly positive by indirect immunofluorescence assay (IFA) (titer 1:64) for immunoglobulin G (IgG) antibodies to A. phagocytophilum. Doxycycline treatment was begun on November 5. The patient’s platelet count steadily improved and returned to a normal level of 163,000/mm3 on November 10. Pretransfusion blood samples and serum from the patient’s convalescence period were not available for further testing. The patient improved clinically and was transferred to a rehabilitation unit on November 13. After rehabilitation, the patient was discharged on December 3, 2007.

Epidemiologic and Laboratory Investigation 

In early November, Memorial Blood Centers began an investigation to identify whether any of the 59 blood donors associated with the 34 RBC, 4 platelet, 14 FFP, and 7 cryoprecipitate units had evidence of A. phagocytophilum infection. Paired whole blood specimens from the original donations had been retained from all 34 RBC donors and eight of 14 FFP donors and were available for PCR testing. During November 2007–March 2008, Memorial Blood Centers also collected postdonation blood samples for serologic testing and information on recent illness history and potential tick exposure from 53 of the 59 donors. In addition, plasma components from two FFP donors and two cryoprecipitate donors who donated again during December 2007–January 2008 were retained for serologic testing. The whole blood specimens retained from initial donation were tested by PCR, followed by sequencing of the PCR amplicons at CDC. Serum and plasma specimens were tested by IFA for IgG antibodies to A. phagocytophilum.

PCR and IFA tests on samples from a female RBC donor aged 64 years were positive for A. phagocytophilum infection. A. phagocytophilum DNA was found in an RBC product donated by this woman on September 28 and transfused to the patient on October 13. IgG IFA titers to A. phagocytophilum were 1:512 and 1:256, respectively, in subsequent sera collected November 17 and December 18. The donor did not recall being bitten by a tick, but had spent time in wooded areas of northeast Minnesota where anaplasmosis is endemic within the month before her donation. She reported no history of fever during the month before or after her donation. No other patients received blood components from her donation.

No whole blood samples from other tested donors were PCR positive for A. phagocytophilum. Sera from two RBC donors were weakly positive by IFA (titer 1:64), but their respective whole blood samples from the original transfused units were PCR negative. These two donors did not live on wooded property and reported they had no tick exposure or illness during the 2 months before donation. Available postdonation serum samples from other donors were negative for A. phagocytophilum by IFA (titer <1:32).

Reported by: 

M Kemperman, MPH, D Neitzel, MS, Minnesota Dept of Health; K Jensen, J Gorlin, MD, E Perry, MD, Memorial Blood Centers, Saint Paul; T Myers, MD, T Miley, MD, Park Nicollet Methodist Hospital, Saint Louis Park, Minnesota. J McQuiston, DVM, ME Eremeeva, MD, PhD, ScD, W Nicholson, PhD, J Singleton, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; J Adjemian, PhD, EIS Officer, CDC.
CDC Editorial Note: 

A. phagocytophilum, the causative agent of anaplasmosis, typically is transmitted to humans by infected Ixodes spp. ticks. In wooded areas of the United States, A. phagocytophilum is transmitted by the blacklegged tick (Ixodes scapularis) in the Northeast and upper Midwest and by the western blacklegged tick (Ixodes pacificus) on the West Coast. In infected persons who are symptomatic, illness onset occurs 5-21 days after a bite from an infected tick. Initial presentation typically includes sudden onset of fever, headache, malaise, and myalgia, often accompanied by thrombocytopenia, leukopenia, and elevated liver transaminases. Severe infections can include prolonged fever, shock, confusion, seizures, pneumonitis, renal failure, hemorrhages, opportunistic infections, and death.1 Anaplasmosis and other tickborne diseases, including human ehrlichiosis, Rocky Mountain spotted fever, and babesiosis, caused by Ehrlichia chaffeensis or Ehrlichia ewingii, Rickettsia rickettsii, and Babesia spp., respectively, represent a potential risk for transmission via blood transfusion in the United States.2-6

The case described in this report provides strong presumptive evidence that A. phagocytophilum infection in this patient was acquired through blood transfusion. Pretransfusion blood samples and convalescent serum from the transfusion recipient were not available for PCR or serologic testing to demonstrate conclusively that the patient was free of A. phagocytophilum infection before his hospitalization on October 12. However, the patient reported limited outdoor exposure that might include potential tick contact during the 3 weeks before hospitalization, and a blood smear collected 3 days after hospital admission showed no evidence of intracellular morulae. The timing of events and the expected incubation period for anaplasmosis (5-21 days) suggest that the patient’s exposure most likely occurred during hospitalization. A. phagocytophilum DNA was found in a retained sample from the implicated RBC product that was transfused to the recipient, providing strong evidence that this was the likely route of disease transmission to the blood transfusion recipient.

Some blood transfusion recipients (i.e., those who are immune compromised) likely are at increased risk for developing severe complications associated with tickborne diseases. Both A. phagocytophilum and E. chaffeensis can survive in refrigerated RBCs, and possible transfusion-transmission cases have been reported for anaplasmosis (Minnesota Department of Health, unpublished data, 1998).2-3,5-6 However, because of the rarity of transfusion-associated cases, concerns regarding the specificity of available tests, (none of which are approved by the Food and Drug Administration), and the economic costs associated with implementation, the U.S. blood supply is not routinely screened for tickborne disease using laboratory methods.7

As a method to reduce the risk for certain pathogens in blood products, blood banks often defer donations if the potential donor is ill at the time of donation. However, persons infected with tickborne disease might experience mild illness or have asymptomatic infection, as was the case with the implicated donor in this report.1, 3 Screening donors for a recent history of tick bite is unlikely to identify high-risk donors, because this type of exposure frequently is not recalled by persons with anaplasmosis.3 In this case, the implicated donor did not recall a tick bite, although she did report contact with wooded habitat in an anaplasmosis-endemic area. Nearly 75% of the other blood donors in this investigation reported similar outdoor contact, making the screening of blood donors for tick-related exposures poorly predictive for possible infection. Because Ehrlichia and Anaplasma are associated with white blood cells, leukoreduction techniques would be expected to reduce the risk for Ehrlichia and Anaplasma transfusion-transmission through RBC components.5, 8 In the absence of effective screening tools to identify donors or products infected with the organisms, physicians should weigh the benefits of using leukoreduced blood components, to potentially reduce the risk for Ehrlichia and Anaplasma transmissions.

Although transfusion-associated transmission of A. phagocytophilum appears to be rare, reported incidences of anaplasmosis and other tickborne diseases are increasing in the United States.1 A record 322 cases of anaplasmosis were reported in Minnesota in 2007 (6.2 cases per 100,000 population).9 As the incidence of tickborne diseases increases, physician vigilance for possible transmission of these agents via transfusions also should increase. In addition to other more common etiologies, physicians should suspect possible rickettsial infection if transfusion recipients develop acute thrombocytopenia posttransfusion, especially if accompanied by fever. Such signs should lead to rapid assessment for rickettsial agents and empiric treatment with doxycycline.1 Although insensitive, blood smear can provide timely support for a presumptive diagnosis of anaplasmosis, followed by IFA or PCR to confirm the diagnosis.1 Similarly, babesiosis should be suspected in patients who develop hemolytic anemia and fever posttransfusion.3-4

Anaplasmosis and ehrliciosis are nationally notifiable diseases. Suspected cases of tickborne rickettsial diseases should be reported promptly to the state or local health department, and suspected transfusion-associated transmission should be reported to the supplying blood center and appropriate public health authorities.
Acknowledgments 

The findings in this report are based, in part, on contributions by G Liu, PhD, and K Smith, DVM, PhD, Minnesota Dept of Health; M Kuehnert, MD, National Center for Preparedness, Detection, and Control of Infectious Diseases, and S Holzbauer, DVM, Coordinating Office for Terrorism Preparedness and Emergency Response, CDC.

REFERENCES 

1. CDC. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis—United States. MMWR. 2006;55(No.RR-4). 
2. Eastlund T, Persing D, Mathiesen D; et al. Human granulocytic ehrlichiosis after red cell transfusion. Transfusion. 1999;39:117S. 
3. McQuiston JH, Childs JE, Chamberland ME, Tabor E. Transmission of tickborne agents of disease by blood transfusion: a review of known and potential risks in the United States. Transfusion. 2000;40(3):274-284. FULL TEXT | ISI | PUBMED 
4. Herwaldt BL, Neitzel DF, Gorlin JB; et al. Transmission of Babesia microti in Minnesota through four blood donations from the same donor over a 6-month period. Transfusion. 2002;42(9):1154-1158. PUBMED 
5. McKechnie DB, Slater KS, Childs JE, Massung RF, Paddock CD. Survial of Ehrlichia chaffeensis in refrigerated, ADSOL-treated RBCs. Transfusion. 2000;40(9):1041-1047. FULL TEXT | PUBMED 
6. Kalantarpour F, Chowdhury I, Wormser GP, Aguero-Rosenfeld ME. Survival of the human granulocytic ehrlichiosis agent under refrigeration conditions. J Clin Microbiol. 2000;38(6):2398-2399. FREE FULL TEXT 
7. AuBuchon JP. Meeting transfusion safety expectations. Ann Intern Med. 2005;143(7):537-538. FREE FULL TEXT 
8. Mettille FC, Salata KF, Belanger KJ, Casleton BG, Kelly DJ. Reducing the risk of transfusion-transmitted rickettsial disease by WBC filtration, using Orientia tsutsugamushi in a model system. Transfusion. 2000;40(3):290-296. FULL TEXT | PUBMED 
9. CDC. Final 2007 reports of nationally notifiable infectious diseases. MMWR. 2008;57:901, 903-13.

http://jama.ama-assn.org/cgi/content/full/300/23/2718

HemOnc Today, November 3, 2008
Bacteria causes the tickborne rickettsial disease human anaplasmosis.

In the first confirmed case of its kind, an elective knee arthroplasty and synovectomy patient in Minnesota who received a blood transfusion developed symptoms of human anaplasmosis and was confirmed to carry the bacteria Anaplasma phagocytophilum. Epidemiologic and laboratory analyses traced the bacteria to a specific donor. The case was reported in the CDC’s Morbidity and Mortality Weekly Report.

A. phagocytophilum is a gram-negative, obligate intracellular bacterium that attacks neutrophils. Typically it is transmitted to humans via bites from ticks in the Ixodes genus, including the blacklegged tick in the Northeast and upper Midwest United States and the western blacklegged tick on the West Coast. Anaplasmosis onset generally occurs between five and 21 days after a tick bite. Initial symptoms include sudden onset of fever, headache and myalgia, along with thrombocytopenia, leukopenia and elevated liver transaminases. Severe or untreated infections can lead to seizures, renal failure, hemorrhages and death.

Case details
 
Although the authors report that one previous case of transfusion-transmitted anaplasmosis exists, it did not include confirmed tests of both the blood donor and recipient. In this case, a 68-year-old man underwent elective knee arthroplasty and synovectomy on Oct. 12, 2007. Soon after the procedure, bleeding at the surgical site and coagulopathy required transfusion of multiple blood components. Over the course of nine days, he received 34 units of nonleukoreduced red blood cells, four units of leukocyte-reduced apheresis platelets, 14 units of fresh frozen plasma and seven units of cryoprecipitate; donations came from 59 different donors.

Seven days following the initial procedure, the patient developed sepsis and multisystem failure. Eleven days after that, physicians found he had worsening thrombocytopenia. On October 31 his platelet count was 178,000/mm3, and by November 5 it had declined to 54,000/mm3. He also developed hypotension and fever, and a blood smear on November 3 indicated the possibility of A. phagocytophilum infection. A review of a previous smear, from three days after the initial procedure, showed no evidence of the bacteria.

The patient received doxycycline treatment, resulting in steadily improving platelet count until a return to normal on November 10. Following rehabilitation, he was discharged on Dec. 3, 2007.

One infected donor

Polymerase chain reaction (PCR) and immunofluorescence assay tests on blood samples from all 34 red blood cell samples and eight of 14 fresh frozen plasma samples received by the patient showed that one woman donor tested positive for A. phagocytophilum infection. According to the report, “the donor did not recall being bitten by a tick, but had spent time in wooded areas of northeast Minnesota where anaplasmosis is endemic within the month before her donation. She reported no history of fever during the month before or after her donation.” No whole blood samples from other donors had evidence of the bacteria, although two red blood cell donors’ sera tested weakly positive by immunofluorescence assay (IgG titers 1:64, vs. 1:512 for the PCR-positive donor, where 1:32 and above was considered positive). Neither donor tested positive by PCR and neither reported any exposure to ticks or illness in the period prior to blood donation.

“The case described in this report provides strong presumptive evidence that A. phagocytophilum infection in this patient was acquired through blood transfusion,” the authors wrote. There was no conclusive evidence that the patient’s blood was free of the infection prior to blood transfusion, but he reported limited outdoor exposure that might involve tick contact. Furthermore, the suspected incubation period for anaplasmosis of five to 21 days strongly suggests that the infection was transmitted during the patient’s hospital stay.

Looking forward

This case and other unpublished reports suggest that some patients — such as those who are immunocompromised — might be at risk for some tickborne diseases, which can often survive in refrigerated red blood cell samples. The rarity of transfusion-related cases, however, makes specific tests or screening of blood donors — especially in areas of high tick concentration — cost ineffective. The authors noted that patients with anaplasmosis often do not recall specific tick bites or even possible tick exposure.

Notably, the reported incidence of anaplasmosis and other tickborne illnesses has risen in recent years. In 2007 in Minnesota, 322 cases of anaplasmosis were reported. “As the incidence of tickborne diseases increases, physician vigilance for possible transmission of these agents via transfusions also should increase,” the investigators wrote. “In addition to more common etiologies, physicians should suspect possible rickettsial infections if transfusion recipients develop acute thrombocytopenia posttransfusion, especially if accompanied by fever. Such signs should lead to rapid assessment for rickettsial agents and empiric treatment with doxycycline.” – by Dave Levitan
 
 
Perspective

This interesting case reinforces the teaching that any organism that has infected a blood donor can potentially be transmitted to a recipient. Although viral infections and bacterial infections (particularly from platelet concentrates) are of greater concern in the U.S. blood supply, other infectious agents including parasites and rickettsia can cause transfusion transmitted disease. These infections can be commonplace in endemic areas as with malaria or unusual as seen in the current case. The finding of an unusual infectious agent in the blood of a patient should prompt the clinician to review recent transfusions and report to the transfusion service if a transfusion transmission is suspected. If a cluster of cases occurs, blood collection agencies can consider screening donors by history or laboratory testing to prevent further transmissions; in the current case, it is not likely that donor questions or testing would be effective or cost-effective and false positive answers to screening questions would result in loss of many potential donors.

Since it will never be possible to prevent the transmission of all infectious agents by transfusion using questions and laboratory tests, many transfusion authorities are hoping that pathogen reduction technologies will become available in the near future. There are systems available in Europe to reduce pathogens in platelets but they are not licensed in the United States; pathogen reduction systems for red cells are under development by several companies and may become available in the future if safety and efficacy can be established.
– Paul M. Ness, MD

HemOnc Today Editorial Board member

http://www.hemonctoday.com/article.aspx?rid=32409

Last Updated: Thursday, October 30, 2008 | 2:49 PM ET Comments4Recommend7CBC News

A nurse inserts a needle into a donor at a Canadian Blood Services clinic in Victoria, BC. (Don Denton/Canadian Press)

Blood transfusion — the process of transferring blood or blood components from one person into another — treats massive blood loss due to trauma or replaces blood lost during surgery. It’s also used to treat people suffering from conditions such as severe anemia caused by a blood disease, such as hemophilia, sickle-cell anemia and thalassemia.

The early history of blood transfusion was dominated by trial and error. Mostly error.

So many people died after receiving the earliest recorded transfusions in the mid-17th century that the practice was banned in several European countries. Back then, doctors often used small quantities of the blood of animals, believing there was some benefit to inter-species blood exchange. Several of those early human patients survived, probably because the small quantity of blood used kept any reactions to a minimum.

Transfusion remained a risky proposition until the early 20th century, when scientists discovered that people had different blood types and mixing some types could lead to a fatal reaction. Another discovery — that refrigerated blood treated with special preservatives could be stored and used days later — made transfusion a viable treatment method.

Today, most blood transfusions do not involve whole blood but one or several of the components that make up blood. Blood is a mixture of cells and liquid, and each component performs specific tasks.

Red blood cells carry oxygen to the body’s tissues. They remove carbon dioxide. These cells comprise up to 45 per cent of your blood.
White blood cells are the immune system’s main defence against infection. They make up less than one per cent of your blood.
Platelets are cell fragments that clot, which helps to prevent and control bleeding. Platelets make up five per cent of your blood.
Plasma is a straw-coloured liquid that is 90 per cent water. It is vital to your survival. It provides the transportation system for blood cells. Without plasma, the cells would not be able to do their work. Besides water, plasma also contains dissolved salts and minerals like calcium, sodium, magnesium, and potassium. Plasma also carries microbe-fighting antibodies that fight disease, and makes up about 55 per cent of our blood.

The average adult carries about five litres of blood. The average unit of donated blood is half a litre.

Blood cells are produced by bone marrow. Some cancer patients may need transfusions to build up red blood cell counts that have been reduced by chemotherapy, which can interfere with the ability of bone marrow to produce red blood cells. People suffering from hemophilia, a disease that affects their blood’s ability to clot, may require plasma or the clotting factors contained in plasma to help their blood clot and prevent internal bleeding.

While the science of blood transfusion has advanced, there remain risks to the procedure. They include:

Fever, which can be caused by a reaction between the recipient’s immune system and immune cells in the donor blood.
Allergic reactions like hives or itching sometimes happen because of a reaction between the recipient’s immune system and proteins in the donated blood. These are usually mild but can be severe enough to force doctors to stop the transfusion.
Hemolytic reaction, or the destruction of red blood cells, occurs when the donated blood and the patient’s blood are not a match. This can be life-threatening. It’s also extremely rare as health-care professionals go to great lengths to make sure that blood types are compatible before the transfusion.

There are other risks, like the transmission of certain diseases, including HIV, hepatitis A, hepatitis B, hepatitis C and Lyme disease. (For a complete list, go to the Public Health Agency of Canada.)

Since November 1985, all blood collected in Canada has been screened for HIV and other communicable diseases. It’s estimated that the risk of contracting HIV from donated blood is now 1 in 2.1 million. In the mid-1980s, that risk was 1 in 16,000. The risk of contracting hepatitis C is estimated at 1 in 1.9 million.

Canadian Blood Services (CBS) and Héma-Québec are responsible for collecting blood and administering the blood supply in Canada. The two agencies supply hospitals with well over 1.2 million units of blood a year. They strive to maintain a six-day supply of blood but periodically they fall below that.

On Oct. 29, 2008, CBS issued an urgent appeal for donors, saying the blood supply had fallen to just a two-day supply. Dr. Graham Sher, an official with the CBS national office in Ottawa, said donations had dropped 40 per cent over the previous two months.

“Demand for blood continues to outstrip our ability to collect it and if that continues, we’re going to get into a very difficult situation where there just isn’t going to be enough blood for all the procedures that patients need.”

While the agencies do appeal for more blood donors from time to time, an October appeal is uncommon. Normally, the blood supply drops off during the summer, when people take holidays and donors are scarce.

CBS and Héma-Québec have established basic criteria that blood donors must meet before they can give blood. They include that you must:

Be between 17 and 71 years old to be a regular donor (17 to 61 to be a first-time donor).
Weigh at least 50 kg (110 pounds).
Be in general good health and feeling well when you donate.
Complete a screening questionnaire.

Certain people are not allowed to donate at all. They include:

People who lived in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, Gabon, Niger and Nigeria who may have been exposed to a new strain of HIV.
People who received a blood transfusion while visiting those countries or who have had sex with someone who lived there.
People who spent three months or more in Britain or France between 1980 and 1996. They may have been exposed to variant Creutzfeldt-Jakob disease.
All men who have had sex with another man, even once, since 1977. CBS argues that statistics show men who have sex with men are at greater risk for HIV/AIDS infection than other people. Anyone who has taken illegal drugs intravenously.
Diabetics who are treated with insulin.

If you’ve recently had part of your body tattooed or pierced, you’re also excluded as a blood or bone marrow donor, but for only six months. If you’ve given blood and want to donate again, you have to wait at least 56 days.

According to the World Health Organization, at least 65 countries do not test all donated blood for HIV, hepatitis B, hepatitis C and syphilis. Tainted blood still accounts for as much as five per cent of HIV infections in Africa. The WHO estimates that six million tests that should be done for infections in donated blood are not carried out.

International blood factoids

Over 80 million units of blood are donated every year around the world.
Only 38% is collected in developing countries where 82% of the global population live.
More than half a million women die every year from complications related to pregnancy and childbirth worldwide — 99% of them are in developing countries. Hemorrhage, which accounts for 25% of the complications, is the most common cause of maternal death.
Up to 70% of all blood transfusions in Africa are given to children with severe anemia due to malaria, which accounts for about one in five of all childhood deaths in Africa.

Blood types

The eight major types of blood (and the percentage of the population that have them) are:

O positive (about 38%)
O negative (about 7%)
A positive (about 34%)
A negative (about 6%)
B positive (about 9%)
B negative (about 2%)
AB positive (about 3%)
AB negative (about 1%)
People who are O negative can donate blood to anyone. People who are AB positive can receive blood from anyone.

http://www.cbc.ca/health/story/2008/10/30/f-blood-donation.html