Blood Products Advisory Committee Meeting

December 13-14, 2001

Gaithersburg, MD

 

Title: Topic I.  Potential concerns for Simian Foamy virus (SFV) transmission by Blood and Blood Products

 

Issue:  FDA seeks advice on its approach to assessing the possible transfusion risk from SFV.

 

Background:

Foamy viruses (FV), or Spumaviruses, belong to retroviridae family. The FV genome encodes the canonical retroviral gag, pol, and env genes, as well as at least two additional genes termed tas (bel-1) and bet. FV was first described in 1954 when it was found to contaminate primary monkey kidney cell cultures. Soon thereafter, FV was isolated from a wide variety of nonhuman primate species (1).  The prevalence of FV infection in naturally infected animals is generally high and varies widely depending on the species and environmental condition (1). The seroprevalence is generally high in animals housed in captivity compared to animals in the wild. In 1971 a putative human FV was isolated from nasopharyngeal carcinoma (NPC) from a Kenyan patient (2). However, further analysis of the so calledso-called human FV clone by several investigators revealed that it is a variant strain of chimpanzee FV.   Nonetheless, this demonstrated human infection from SFV, and raised the question of disease association.  The precise mode of transmission of FV is not well understood. So foar the studies indicate that transmission can occur through saliva.

 

The mMechanism of FV infection pathogenesis has and disease potential have been studied in several animal models such as rabbits and mice (3, 4). Virus has been recovered from various organs from such animals. No pathology was noted in any FV-infected animals. A wide variety of diseases such as thyroiditis de Quervain, Graves disease, multiple sclerosis, Myasthenia Gravis have been tenuously associated with FV infection of humans (1). However, studies using use of combination of multiple assays (western blot, RIPA, IFA and PCR) in combination for the detection of the virus, have failed to confirm either endemic human infection or the association of disease with FV in humans. Because of no definite FV pathogenesis in man or animals, this virus has been dubbed as “ a virus in search of a disease” (5).

 

Studies have also focused on determining whether specific human population is at risk to be infected by FV. The outcome of several studies over a period of time has shown that a significant number of people living in East and central Africa are seropositive by more than one assay. Recent studies with nonhuman primate handlers such as veterinarians and zookeepers have also indicated a small but significant number (1.8- 3.0%) are seropositive (6, 7). There was neither any evidence of diseases nor sexual transmission of SFV in one of the studyies (7).

 

[Add a brief summary (or reference) to the lookback study done by CDC and Atlanta Red Cross.]In addition, in a lookback study done by CDC and Atlanta Red Cross, they  identifiedthey identified a blood donor who has beenwas confirmed to have been infected with SFV since at least 1981.  Between 1992 and 1997 this person, unaware of his infection, had donated blood 6 times.  Recipients of 7 components transfused between 3 and 35 days aferafter donation were identified.  Two recipients had died of unrelated causes.  One recipient was alive but not available for testing. Four recipients tested negative for SFV 1.5 to 7 years after transfusion.  

 

In conclusion at present there is not enough evidence for to implicate FV pathogenesis as a cause of disease in humans, and  or transmission by blood transfusion has not been shown.

 

 

IssueCurrent Concerns:

On June 29, 2001 In May of this year, Health Canada researchers conducted an anonymous, unlinked SFV surveillance study of individuals who work with non-human primates. Indicative of SFV zoonosis, of the 46 participants tested, one serum sample reacted strongly while another serum sample reacted weakly to SFV proteins (western blot analysis).  The purpose of this study was to determine the risk of SFV infection in animal handlers and to determine the impact, if any, on risk to the Canadian Blood supply. Based on these findings, tThere also was a discussion by Health Canada whether the employees handling nonhuman primates should defer from donating blood, tissue or organs until more is known about the pathogenesis of SFV. Subsequently, we had a teleconference with scientists from Health Canada and CDC to discuss the issue of SFV transmission from nonhuman primates to humans. As is evident from the literature survey, summarized above, there is no definite proof of SFV pathogenesis in humans nor is there evidence of as well as SFV transmission by blood. However, laboratory studies have shown the presence of SFV in blood cells.  Hira:  is this true?]SFV has been isolated from human peripheral blood lymphocytes exposed to nonhuman primates (7, 8). At present it appears that there is insufficient data to exclude the risk of SFV transmission by transfusion.  Therefore, FDA in consultation with CDC and Health Canada Canada decided it would discuss the issue of SFV pathogenesis in humans and transmission by blood to seeks advice from itsthe  Blood Products Advisory Committee members to seek their input. In addition, both

 

CDC and FDA will present the outline of future studies in both monkeys and humans to address the question of possible SFV transmission by blood transfusion. Based on the outcome of these studies, FDA in future will present the data to BPAC members and at that time will seek their opinion about possible blood donor deferral of nonhuman primate handlers.intends to reexamine the question of appropriate blood safety precautions at a future time.

 

Following are the specific questions we plan to seek opinion from ask the BPAC members.

 

Questions:

 

Q1a: Does the committee agree that the currently available data are insufficient to assess if determine whether SFV can cause adverse health effects in humans?

 

Q21b: Does the committee agree that currently available data are insufficient to determine whether SFV can be transmitted by blood transfusion?

 

 

 

 

3: Please comment on the adequacy of Are the proposed studies adequate to evaluate SFV transmission by blood ?transfusion.


References:

 

 

 

 

1.         Meiering CD, Linial ML. (2001) Historical perspective of foamy virus epidemiology and infection. Clin Microbiol Rev. 14: 165-176.

2.         Achong BG, Mansell PW, Epstein MA, Clifford P. (1971) An unusual virus in cultures from a human nasopharyngeal carcinoma. J Natl Cancer Inst. 46: 299-307.

3.         Schmidt M, Niewiesk S, Heeney J, Aguzzi A, Rethwilm A. (1997) Mouse model to study the replication of primate foamy viruses. J Gen Virol. 78: 1929-1933.

4.         Swack NS, Hsiung GD. (1975) Pathogenesis of simian foamy virus infection in natural and experimental hosts. Infect Immun. 12: 470-474.

5.         Weiss RA. (1988) Foamy retroviruses. A virus in search of a disease. Nature. 333: 497-498.

6.         Sandstrom PA, Phan KO, Switzer WM, Fredeking T, Chapman L, Heneine W, Folks TM. (2000) Simian foamy virus infection among zookeepers. Lancet. 355: 551-552.

7.         Heneine W, Switzer WM, Sandstrom P, Brown J, Vedapuri S, Schable CA, Khan AS, Lerche NW, Schweizer M, Neumann-Haefelin D, Chapman LE, Folks TM. (1998) Identification of a human population infected with simian foamy viruses. Nat Med. 4: 403-407.

8.         Schweizer M, Falcone V, Gange J, Turek R, Neumann-Haefelin D. (1997) Simian foamy virus isolated from an accidentally infected human individual. J Virol. 71: 4821-4824.