Preliminary Risk Assessment on Simian Foamy Virus (SFV) and Deferral Policy for Blood and CTO Donation

October 20, 2004

Blood Safety Surveillance and Health Care Acquired Infections Division
Centre for Infectious Disease Prevention and Control
Public Health Agency of Canada

• Issue
• Purpose/Objective
• Background
• Epidemiological Data
• International Policies for Protection of Blood Supplies
• Simian Foamy Virus and the Canadian Blood Supply
• Conclusion and Recommendations

ISSUE

The prevention of Simian Foamy Virus (SFV) transmission through the transfusion of blood and blood components and/or transplants of cells, tissues and organs.

PURPOSE/OBJECTIVE

To review the available literature and current research to assess the potential risk to blood and tissue recipients from SFV, and to provide recommendations around the issue of blood and tissue donor referral based on potential exposure to SFV infection.

BACKGROUND

The known human retroviruses, HIV-1, HIV-2, HTLV I and HTLV II emerged through cross species transmission from non-human primates. It has been well established that non-human primates harbour additional retroviruses that have been shown to be transmissible to humans. Among these viruses, SFV has been found to be the most readily transmissible to humans. Because of the ease of cross species transmission and the availability of well characterized assays, SFV is considered an indicator of settings in which non-human primate (NHP) retroviruses may be introduced into humans. SFV was first described in 1954, when the virus was found to contaminate primary monkey kidney cell cultures. Shortly afterwards, SFV was found to widely infect a number of non-human primate (NHP) species. Although the prevalence of SFV infection in NHP is high, no pathology has been noted among those infected. (There exist conflicting data in the scientific literature regarding the pathology of SFV in experimental animal models.)

The virus is present in both peripheral blood lymphocytes and saliva. In addition, the virus has a number of different genetic profiles generally specific to each NHP host. The only suspected human Foamy Virus (FV) was isolated in 1971 from an individual in Kenya. However, research performed between 1978 and 1980 consistently found that this FV was phylogenetically similar to the SFV isolated from a chimpanzee. This suggested that human FV was a variant strain of the SFV type 6.

In 2001-02, Health Canada considered deferral measures in the blood donation system based on SFV status. At that time, no measures were implemented. This decision was based on a paucity of evidence on a number of fronts. There was insufficient information related to the capacity of SFV to be transmitted through blood transfusion. There was also a lack of association between SFV and disease in humans. Finally, there was a lack of data concerning the pathways to infection in humans. In light of these gaps in understanding, it was deemed unnecessary to risk the loss of donors by initiating deferral when the shortage of blood and blood products that may have resulted was a more relevant and immediate threat. In the interim, additional scientific information on the issue of cross species transmission of simian retroviruses in general and SFV in particular has emerged resulting in a request from Health Canada to the Public Health Agency of Canada for an assessment of the risk of SFV to the Canadian blood supply. Recently, scientists at the Public Health Agency of Canada have completed a new research study into this issue, adding to the body of knowledge on SFV. Using an experimental model, these scientists have demonstrated that SFV can be transmitted between non-human primates by blood transfusion and thus there is a theoretical possibility of transmission in humans of SFV through blood transfusion.

EPIDEMIOLOGICAL DATA

Overall, the body of knowledge on SFV and its potential for transmission from NHP to humans is not large. In the available literature, it is generally agreed that the prevalence of SFV in NHP born in captivity is between 70 and 90 percent. In the wild, this prevalence drops to approximately 44 percent, though this estimate is based on a relatively small sample size.

As recently as 2000, researchers were largely of the opinion that human infection with SFV was an end-point infection (there is no onward transmission) that was not pathogenic. Since that time, there have been a small number of studies performed which examine the relationship between humans and non-human primates and its effect on the transmission of SFV. These studies generally found similar results and are summarized.

Among individuals working in close proximity with non-human primates, evidence of past or current infection with SFV has been reported to be between 1.8 and 4.3 percent. The vast majority of these individuals report some sort of direct percutaneous contact with NHP, such as bites, scratches, or other percutaneous exposures such as needlesticks or cuts. In spite of the relatively high prevalence in this population, there is no evidence of human disease related to SFV over the 2-20 years the individuals have been followed. However, current data on health effects of SFV infection in humans is limited for a number of reasons. Long-term follow-up of SFV infected humans is biased toward healthy volunteers. Selection for follow-up in the current studies would exclude deceased individuals, and may exclude individuals with ill health. Data on long-term follow-up is available on fewer than 25 SFV infected individuals. Furthermore, collection of additional data on SFV infection in humans may be complicated by prolonged latency, and possible low incidence of pathogenicity that is characteristic of some human retroviral infections.

Given that SFV is present in peripheral blood lymphocytes, it was considered theoretically possible that the virus could be transmitted between humans through blood and tissue transplant. As a result, there have been a number of studies performed which attempt to assess this possibility. While the studies found that SFV infected individuals have donated blood, there is little available data on the resulting blood products and the consequences of their use. None of the three recipients of blood donated by a SFV infected veterinarian were found to have evidence of SFV infection.

In addition, available information does not indicate that transmission of SFV occurs between infected individuals and their spouses, shedding no light on the possibility of sexual transmission or transmission through other routes of close personal contact, including exposure to saliva.

Recently, data has been published which adds another dimension to the role SFV might play in human disease scenarios. It has been shown in vitro that SFV, while not producing pathogenicity on its own, may alter the infectivity of other viruses. The implication being that if an individual is exposed to both SFV and some other enveloped virus, the infection with this second enveloped virus may be more likely. Viruses for which SFV could theoretically enhance infectivity include Human Immunodeficiency Virus (HIV), Human Papilloma Virus, human cytomegalovirus and others.

It should be noted that data on SFV infected humans comes almost exclusively from people infected by African Old World Primates. Currently, the vast majority of NHP used in biomedical research are Asian Old World Primates such as the Cynomologous macaques. Consequently, the predominant type of SFV to which people are exposed in occupational settings is the least well characterized in terms of human infections. There is no indication that SFV from New World Primates, which are the primary type of primates kept as pets, can be transmitted to humans.

Further to this, recent research performed by scientists at the Public Health Agency of Canada (unpublished) shows that SFV is transmissible through blood transfusion in an animal model. The particulars of this research are not yet available for discussion, as the research is pending publication and has been deemed confidential.

INTERNATIONAL POLICIES FOR PROTECTION OF BLOOD SUPPLIES

In 2002, researchers associated with the Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta (CDC) and the American Red Cross determined that there was no evidence found to indicate that a SFV antibody positive blood donor had transmitted the virus to recipients of his blood components. However, in spite of the paucity of the evidence, they determined that it would be prudent to recommend self deferral of those who had been confirmed infected with SFV. These recommendations do not represent the official position of the Food and Drug Administration's (FDA), Center for Biologics Evaluation and Research (CBER).

In an effort to clarify the issue in the United States, the Blood Products Advisory Committee (BPAC) of the FDA has scheduled a meeting for October 21, 2004. The agenda for this meeting includes a review of the available information on SFV.

There is no indication that other industrialized nations have any policy in place that provides guidance or recommendations in the venue of blood donor deferral in response to SFV infection.

SIMIAN FOAMY VIRUS AND THE CANADIAN BLOOD SUPPLY

Currently, there is no mandatory deferral policy for SFV infected individuals in Canada. However, in light of the various studies finding a high seroprevalence of SFV in human handlers of NHP, recent research implicating SFV in the disease course of other viral agents, and the demonstration in animal models of the transmissibility of SFV through blood transfusion, Health Canada has requested this risk assessment.

There is now experimental data, from an animal model, that demonstrates that SFV is transmissible by blood transfusion using whole blood, while data on the health effects of SFV infection in humans remain insufficient to exclude SFV pathogenicity.

CONCLUSION AND RECOMMENDATIONS

Between 2-4% of Canadians who work with non-human primates are likely infected with SFV. There are 21 institutions (excluding zoos) in Canada that have non-human primates registered with the Canadian Council of Animal Care as being used in research. At present, these primate workers are not excluded from blood donation. Animal evidence demonstrates that SFV can be transmitted through whole blood transfusion. Pathogenic effect of simian retrovirus infection in humans is unknown and uncertainty will likely remain for a considerable time due to the difficulties in obtaining sufficient data.

Having considered the emerging scientific evidence on SFV and other simian retroviruses, it is the position of the Public Health Agency of Canada that any potential for the introduction of a novel simian retrovirus into the Canadian blood supply or its transmission by cells, organs and tissues needs to be prevented. Although there are no known health risks from human SFV infection, the prudent course is to take measures to prevent SFV and other simian retroviruses from entering the Canadian blood supply or being transmitted through transplantation. Thus, using the precautionary principle, Health Canada should give consideration as to what risk mitigation strategies are required to protect the Canadian blood supply and transplantation recipients from this threat.

Based on available studies, the Public Health Agency of Canada recommends that deferral of blood transfusion and cell, organ and tissue donation be considered for those individuals who work directly with NHP in institutions such as zoos, public or private biomedical research institutions, and animal sanctuaries. As available data does not allow us to define the mechanism of transmission or the specific risk factors associated with retrovirus infection within these groups, we would recommend that deferral be considered for these groups as a whole.

The concern regarding SFV raises the question of the risk of SFV infection for NHP pet owners. Currently, there are no studies available by which to assess the risk of simian retroviral transmission from NHP maintained as pets. Most NHP pets are New World Primates which are thought to be at low risk of transmission of retrovirus to humans because of biological differences. In the absence of scientific information at this time, we can neither conclusively say that this group be included or excluded from any risk mitigation measures put in place for protecting the blood supply.

This document will be reviewed once more following the release of data presented at the BPAC meeting on October 21, 2004.