Prevalence of human T cell lymphotropic virus 1 infection in Canada
Authors: Laetitia Amar, Michelle Le, Feras M. Ghazawi, Elham Rahme, Amanda Segal, Elena Netchiporouk, Gizelle Popradi, Linda Moreau, Osama Roshdy, Denis Sasseville, and Ivan Litvinov
Human T cell lymphotropic virus 1 (htlv-1) is a bloodborne retrovirus that infects at least 5-20 million people around the world1. The virus is known to be endemic in Central and West Africa, the Caribbean, East Asia, and Central and South America, and in intravenous drug users in the United States2. Active surveillance and targeted programs to decrease the vertical transmission of htlv-1 are in place in Japan3, but in the United States and Canada, the virus remains mostly neglected by medical regulatory authorities and does not appear on the list of notifiable bloodborne pathogens. However, in 1990, Canada began screening the blood supply for htlv-1 serology to minimize the risk of transmission from blood donors. That initiative resulted in a decline in the htlv-1 rate from 9.35 per 100,000 donations in 1990 to 1.1 per 100,000 donations in 20104. The htlv-1 and -2 retroviruses are transmitted mainly during prolonged breastfeeding, through sexual contact, or parenterally, including through blood transfusions and intravenous drug use. Although the htlv-1 virus confers a lifelong chronic infection, most people with it typically remain asymptomatic. However, the virus can also be associated with potentially devastating diseases. It was shown that up to 5% of people infected with the virus develop adult T cell leukemia/lymphoma (atll)5, a subtype of cutaneous T cell lymphoma recognized by the World Health Organization6. On average, it takes approximately 20-30 years for symptoms of atll to appear5. Importantly, based on current knowledge, atll does not occur in uninfected individuals. Also, htlv-1-associated myelopathy/tropical spastic paraparesis, a devastating demyelinating neurologic condition, can occur in affected patients. Infective dermatitis, htlv-1-associated uveitis, arthropathy, and opportunistic infections, including Strongyloides stercoralis hyperinfection have also been reported in people with htlv-1 infection 1. Notably, even in healthy htlv-1 carriers, an impaired immune response against the Epstein-Barr virus has been observed8. One way in which htlv-1 leads to immunodeficiency is by impairing thymic function, as demonstrated by the low percentage of naïve T cells in htlv-1 carriers. In Canada, htlv-1 is known to be prevalent in native populations (that is, First Nations) and in immigrants from the endemic regions mentioned earlier. Importantly, a number of molecular studies in the First Nations communities of British Columbia and Nunavut documented the appearance of the virus in Canada during the pre-Columbian era (more than 1500 years ago) and the fact that the virus in Canada shares an ancestral source with the htlv-1 that is endemic in Japan and Eastern Asia. Phylogenetic findings show that the virus was not introduced into native communities from a single source at some point after the Columbian expeditions. Unfortunately, there are no reliable estimates of the overall burden of this infection in Canada. Furthermore, the Canadian government, the media, and previous studies that tried to estimate rates of infection have sent conflicting messages about the commonality of the virus in Canada and in First Nations communities specifically. We recently used the Canadian Cancer Registry, the Registre québécois du cancer, and the Canadian Vital Statistics (mortality) database to analyze the incidence and mortality rates for cutaneous T cell lymphoma and its variants in Canada16,17. That work established that, in Canada from 1992 to 2010, approximately 200 cases of atll were diagnosed (40% in women, 60% in men), resulting in 75 reported deaths. Given that up to 5% of patients infected with htlv-1 will progress to atll (lifetime cumulative risk of 4.0% in men and 4.2% in women, if infected during childhood5), the number of htlv-1-infected individuals can be extrapolated to be approximately 4000-5000 [200 cases of atll during the 19 years of the study (1992-2010) divided by the approximately 4%-5% lifetime risk for atll after htlv-1 infection]. Considering that the average lifespan in Canada is approximately 80.8 years, which is 4.25 times the surveillance period (19 years) of the study, the foregoing result would have to be multiplied by 4.25, which equates to approximately 17,000- 21,250 htlv-1-infected people in total (or 54.71-67.55 per 100,000 population). We also used the same methodology described in our earlier report16 to estimate the age-specific incidence of atll across Canada.
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