[Table of Contents]

Volume: 27S3 • September 2001

Viral Hepatitis and Emerging Bloodborne Pathogens in Canada

Cytomegalovirus, Herpesvirus 6, 7, and 8, and Parvovirus B19 in Canada

Zhiyong Hong, Shimian Zou, Antonio Giulivi

A large number of microbes (bacteria, rickettsiae, chlamydiae, viruses, fungi, parasites) have been identified within the last 20 years⁽¹⁾. Human herpesvirus 6 (HHV-6), HHV-7, HHV-8, parvovirus B19, and cytomegalovirus (CMV) are examples of such new or re-emerging etiologic agents. Changes in human behaviour, industrial and economic development, travel and mass movement, civil unrest and war, medical treatment (especially transplantation and the widespread use of anti-microbial agents), and microbial change and adaptation result in their emergence or re-emergence. Surveillance and research activities are being carried out in Canada to monitor and study these pathogens⁽²⁾. A recent expert working group meeting summarized the findings on HHV-6 and HHV-7 from Canada and other countries⁽³⁾.

Cytomegalovirus

Human CMV was first isolated in the 1950s⁽⁴⁾. The importance of human CMV as a pathogen has increased over the past 20 years as immunosuppressive states resulting either from post-transplantation therapies or AIDS and other immunodeficiency states have come to the forefront in medicine. These conditions predispose individuals to primary CMV infection or to reactivation of latent infection. CMV is transmitted by blood transfusion, and a large reservoir of seropositive individuals remains an important source of virus in many settings. Embil et al provided the first case report of cytomegalic inclusion disease in Canada in 1965⁽⁵⁾. During the 1960s and 1970s, a series of epidemiologic investigations were conducted on the prevalence of CMV infection in the normal population in Nova Scotia⁽⁶⁾, Montreal⁽⁷⁾, Hamilton⁽⁸⁾, and the Northwest Territories⁽⁹⁾. In Nova Scotia, for example, 34% of infants possessed antibodies to CMV, presumably of maternal origin. There followed a decline until 2 years of age (4% with antibodies to CMV), and then a gradual increase up to 16% by age 20, and to 50% by age 40. Dene and Inuit women had a significantly higher prevalence of CMV antibodies than Edmonton women at all ages. The lower socio-economic status of the population was presumed to be a contributing factor in the higher CMV prevalence.

Ernst et al described the symbiosis of Pneumocystis carinii and cytomegalovirus in 1983⁽¹⁰⁾, and CMV as an opportunistic pathogen in AIDS was investigated in 1983-1984⁽¹¹⁾. Other studies have included CMV infection and survival in patients who have undergone liver transplantation⁽¹²⁾, lung transplantation⁽¹³⁾, and bone marrow transplantation⁽¹⁴⁾. Table 1 summarizes the relationship between CMV infection and transplantation in Canada from 1989 to the present. The data show that CMV infection among recipients has resulted in higher mortality.

Strategies have been developed to combat CMV infection⁽¹⁶⁾. Long-term ganciclovir prophylaxis may have the greatest benefit for lung transplant recipients, CMV-positive marrow transplant recipients, and any CMV-negative recipients of a CMV-positive donor; CMV-negative blood products are suitable for CMV-negative recipients of a CMV-negative donor. Pre-emptive ganciclovir therapy guided by detection of CMV or use of anti-lymphocyte antibody therapy may be best suited for CMV-positive patients receiving a renal, liver, or heart transplant.

Table 1 Cytomegalovirus infection and transplantation in Canada (1989-2000)
Type of transplantation	No.	Follow-up time	CMV incidence	Survival rate
Children
Liver transplantation(12)	18	2 years	30% (4/12) infection 25% (3/12) CMV disease	New CMV infection: 25% Pretransplant immunity or CMV(-): 75%
Adults
Lung transplantation(13)	95	1-5 years	24%-26% CMV disease	55%-61% for 5 years (3 CMV-related deaths)
Bone marrow transplantation(14)	103	1 year	3%	CMV(-): 76% for 1 year CMV(+): 52% for 1 year
Liver transplantation(15)	97	12 weeks	62.9% infection 21.6% CMV disease	Acute rejection: 47.6% in CMV disease 22.4% in no CMV disease

Human herpesvirus 6

HHV-6 was identified as a causal agent for Exanthema subitum in 1988⁽¹⁷⁾. The basic epidemiology of HHV-6, with particular reference to its role in diseases in normal children and immuno-compromised patients, has been associated with the development of febrile syndrome, hepatitis, pneumonitis, and encephalitis after transplantation⁽¹⁸⁾. Acott et al observed a significant correlation between renal allograft and HHV-6 infection at a children’s hospital in Halifax, Nova Scotia, during a 30-month period from February 1993 to August 1995⁽¹⁹⁾. Humar et al⁽²⁰⁾ observed the coexistence of HHV-6 and CMV in liver transplant recipients at The Toronto General Hospital. Additional Canadian data can be found in the recent summary by the expert working group⁽³⁾.

Human herpesvirus 7

HHV-7 was discovered in 1990, when Frenkel and coworkers observed a cytopathic effect in culture of peripheral blood lymphocytes from healthy adults⁽²¹⁾. HHV-7 is highly prevalent worldwide and is typically acquired during childhood. Infectious HHV-7 can easily be detected in the saliva of 75% of healthy adults⁽²²⁾ and in the peripheral blood of 83% of healthy adults⁽²³⁾. HHV-7 has also been detected in cervical swabs of pregnant women⁽²⁴⁾, raising the possibility of perinatal or congenital transmission. More details can be found in the recent expert working group report⁽³⁾.

Human herpesvirus 8

HHV-8 was discovered in tissues from Kaposi’s sarcoma lesions in 1994⁽²⁵⁾. The prevalence of antibodies to HHV-8 varies internationally. It is lower in Northern Europe and the U.S. (0% to 10%), higher in Mediterranean countries such as Greece and Italy (4% to 35%), and highest in parts of Africa (10% to 60%). In the U.S. and Northern Europe, HHV-8 was found with highest frequency in homosexuals infected with AIDS, and sexual transmission is strongly indicated⁽²⁶⁾.

The general properties of the recently discovered herpesviruses (HHV-6, 7, and 8) are summarized by Dollard and Pellett⁽²⁷⁾ in Table 2.

Table 2 General properties of the recently discovered herpesviruses*
Virus	Mode of transmission			Seroprevalence		Principal clinical syndromes
	Casual contact	Intimate contact	Organ transplant	Young children	Healthy adults
HHV-6A	Possible	Unlikely	Possible	?	> 50%	Febrile illness
HHV-6B	Yes	Possible	Possible	> 90%	99%	Roseola post-transplant disease
HHV-7	Yes	Unlikely	Possible	70%	80%-95%	Roseola post-transplant disease
HHV-8	Possible	Yes	Yes	?	0%-10%†	KS, MCD, PEL
* Source: Dollard and Pellett(27) KS: Kaposi’s sarcoma; MCD: multicentric Castleman’s disease; PEL: primary effusion lymphoma. † Does not include KS endemic regions or population at high risk for KS.

Parvovirus B19

Parvovirus B19 was discovered in 1974, while healthy blood donors were being screened for hepatitis B⁽²⁸⁾. The first disease associated with parvovirus B19 was aplastic crisis in patients with sickle-cell disease⁽²⁹⁾. Rodis et al investigated the management of parvovirus infection during pregnancy in the U.S. and Canada in 1997. They observed that approximately one-third of the cases of parvovirus-produced nonimmune hydrops resolved spontaneously, whereas 83.5% of hydropic fetuses transfused survived⁽³⁰⁾.

Many questions about parvovirus B19 infection remain unanswered: the normal route of transmission, the spread of the virus from the port of entry to the site of replication in the bone marrow, and the role of B19 in chronic arthritis, myocarditis, vasculitis, and neurologic diseases.

Prevention

The Centers for Disease Control and Prevention (CDC) in the U.S. have developed a plan to address emerging infectious disease threats⁽³¹⁾. The plan has four major goals: (a) surveillance and response, including detection, prompt investigation, and monitoring of emerging pathogens, the diseases they cause, and the factors that influence their emergence; (b) applied research, including integrated research of laboratory science and epidemiology to optimize public health practice; (c) prevention and control, such as enhanced communication of public health information about emerging diseases and prompt implementation of prevention strategies; (d) infrastructure, such as strengthened local, state, and federal public health infrastructure to support surveillance and implementation of prevention and control programs. Canada is also setting up surveillance for these agents, especially with regard to the safety of the blood supply, as described by Giulivi⁽²⁾.

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