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 patients7. 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 carriers9.
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 Asia4,10–15. Phylogenetic findings show that the virus was not introduced into native communities from a single source at some point after the Columbian expeditions14,15.
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 specifically4,10–13.
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 deaths16,17.
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 (Table I).
TABLE I.
Estimated incidence of adult T cell leukemia/lymphoma (ATLL), by age group
| Age group | Diagnosed ATLL casesa (n) | Population at riskb | Incidence per year (per 100,000)a |
|---|---|---|---|
| 0–29 Years | 25 | 12,247,000 | 0.011 |
| 30–59 Years | 80 | 13,470,000 | 0.031 |
| ≥60 Years | 95 | 5,320,000 | 0.094 |
Randomly rounded (up or down) to the nearest 5 per the rules of the Canadian Cancer Registry or the Registre québécois du cancer. Cases of ATLL were defined based on the International Classification of Diseases for Oncology, 3rd edition (code 9827).
Estimates rounded to nearest thousand.
Using the same calculation and methodology, we also extrapolated data for the Canadian provinces and territories (Table II). It is notable that, based on a conservative estimate of a 5% lifetime risk of atll in htlv-1–positive individuals, Quebec has the highest estimated number of infected people (approximately 8100 or 108.78 per 100,000 population) and the highest prevalence of htlv-1 infection of all Canadian provinces. Quebec is home to many francophone immigrants from Africa and the Caribbean, including Haiti.
TABLE II.
Incidence of adult T cell leukemia/lymphoma (ATLL) and corresponding extrapolated prevalence of HTLV-1 infection in Canada based on 2007 life expectancy at birth
| Geographic area | Incidencea | Estimates of ... | ||||
|---|---|---|---|---|---|---|
| Populationb | Average life expectancy (years)c | HTLV-1– infected individualsd | Annualized HTLV-1 prevalence per 100,000 individuals | |||
| Value | 95% CI | |||||
| Atlantic Canadae | 10 | 2,356,000 | 79.72 | 840 | 35.65 | 33.24 to 38.06 |
| Quebec | 95 | 7,446,000 | 81.0 | 8100 | 108.78 | 106.41 to 111.15 |
| Ontario | 70 | 11,868,000 | 81.2 | 5980 | 50.39 | 49.11 to 51.66 |
| Manitoba, Saskatchewan, Nunavut | 10 | 2,196,000 | 79.24 | 835 | 38.02 | 35.44 to 40.60 |
| Alberta | 10 | 3,109,000 | 80.5 | 845 | 27.18 | 25.35 to 29.01 |
| British Columbia | 10 | 4,040,000 | 81.4 | 855 | 21.16 | 19.74 to 22.58 |
| Canada | 200 | 31,087,000 | 80.8 | 17,010 | 54.71 | 53.90 to 55.54 |
Randomly rounded (up or down) to the nearest 5 per the rules of the Canadian Cancer Registry or the Registre québécois du cancer. Cases of ATLL were defined based on the International Classification of Diseases for Oncology, 3rd edition (code 9827).
Rounded to nearest thousand.
Based on data obtained from the 2007–2009 Statistics Canada report. Rate estimates are extrapolated. The confidence interval calculations are approximate and do not account for the full variation of the extrapolated estimate.
Using the conservative assumption that 5% of individuals infected with HTLV-1 are at risk of developing ATLL.
Newfoundland and Labrador, New Brunswick, Nova Scotia, and Prince Edward Island.
CI = confidence interval.
Based on our earlier studies16,17, confirmed by public reports in the media10,11,13, 3 cases of atll have been reported in Nunavut, which would suggest that at least about 60 individuals in that territory are affected by htlv-1, within an estimated population of 30,000 (that is, a rate of approximately 200 per 100,000). As described in the original study16, we were also able to obtain atll mortality results from the Canadian Vital Statistics database, which are presented here for completeness (Table III).
TABLE III.
Mortality in adult T cell leukemia/lymphoma (ATLL) based on 2007 life expectancy at birth
| Geographic area | ATLL-related deathsa (n) | Estimates of ... | ||
|---|---|---|---|---|
| Populationb | Annualized ATLL mortality rate per million individuals | |||
| Value | 95% CI | |||
| Atlantic Canadac | 5 | 2,356,000 | 0.11 | 0.013 to 0.21 |
| Quebec | 20 | 7,446,000 | 0.14 | 0.080 to 0.20 |
| Ontario | 25 | 11,868,000 | 0.11 | 0.067 to 0.15 |
| Alberta, Manitoba, Saskatchewan, Nunavut | 15 | 5,305,000 | 0.15 | 0.073 to 0.22 |
| British Columbia | 10 | 4,040,000 | 0.13 | 0.050 to 0.21 |
| Canada | 75 | 31,087,000 | 0.13 | 0.98 to 0.16 |
Randomly rounded (up or down) to the nearest 5 per the rules of the Canadian Cancer Registry or the Registre québécois du cancer. Cases of ATLL were defined based on the International Classification of Diseases for Oncology, 3rd edition (code 9827).
Rounded to nearest thousand.
Newfoundland and Labrador, New Brunswick, Nova Scotia, and Prince Edward Island.
CI = confidence interval.
We also highlight the report in a previous study that, based on the 1990–2010 records of blood donation, the prevalence of htlv-1 positivity is approximately 1 per 10,000 first-time blood donors3. Hence, our finding of 54.71 htlv-1–positive people per 100,000 population (or approximately 5 per 10,000) appears to be a reasonable estimate, considering that people likely to volunteer to donate blood constitute a select group, and that group might include fewer newly settled immigrants, intravenous drug users, or individuals residing in northern communities.
The analysis presented here has a number of important limitations. Considering that atll is a rare disease that can mimic certain variants of cutaneous T cell lymphoma, accurately diagnosing and surveying its incidence causes difficulties. Because of the requirements set out by the Canadian Cancer Registry and the Registre québécois du cancer to round the number of cases or deaths to a multiple of 5 and to group jurisdictions so that the combined number of cases reaches a minimum of 5 for presentation, we were not able to describe in detail the mortality incidence in each province or territory. Also, because we could not reliably determine the occurrence of htlv-1 infection in the studied individuals in early childhood, we were not able to make use of some of the available calculation models that link htlv-1 infection rates with the atll incidence5. Finally, because the databases we used do not collect data about race or ethnicity (as described in our earlier work16,17), we are not able to comment on the race or ethnicity of htlv-1– infected individuals in Canada.
In summary, based on our findings, htlv-1 remains a rare infection in Canada, even considering that the virus is endemic in First Nations communities. This report for the first time estimates the rate of htlv-1 infection across the country and highlights Quebec as the province with the largest number of atll cases. Hence, a significant number of htlv-1–positive people likely reside in Quebec (that is, more than 8000). Combining those results suggests that it might be important to raise awareness of htlv-1–associated health risks in select provinces and territories and to consider implementing programs to decrease htlv-1 transmission, as are currently in place in Japan3.
ACKNOWLEDGMENTS
This work was supported by a Cole Foundation Grant to IVL, Canadian Dermatology Foundation research grants to DS and IVL, and a Fonds de la recherche en santé du Québec grants (nos. 34753 and 36769) to IVL.
Footnotes
CONFLICT OF INTEREST DISCLOSURES
We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.
REFERENCES
- 1.Carneiro-Proietti AB, Catalan-Soares BC, Castro-Costa CM, et al. htlv in the Americas: challenges and perspectives. Rev Panam Salud Publica. 2006;19:44–53. doi: 10.1590/S1020-49892006000100007. [DOI] [PubMed] [Google Scholar]
- 2.Goncalves DU, Proietti FA, Ribas JG, et al. Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1–associated diseases. Clin Microbiol Rev. 2010;23:577–89. doi: 10.1128/CMR.00063-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Satake M, Yamaguchi K, Tadokoro K. Current prevalence of htlv-1 in Japan as determined by screening of blood donors. J Med Virol. 2012;84:327–35. doi: 10.1002/jmv.23181. [DOI] [PubMed] [Google Scholar]
- 4.O’Brien SF, Goldman M, Scalia V, et al. The epidemiology of human T-cell lymphotropic virus types I and II in Canadian blood donors. Transfus Med. 2013;23:358–66. doi: 10.1111/tme.12057. [DOI] [PubMed] [Google Scholar]
- 5.Murphy EL, Hanchard B, Figueroa JP, et al. Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I. Int J Cancer. 1989;43:250–3. doi: 10.1002/ijc.2910430214. [DOI] [PubMed] [Google Scholar]
- 6.Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90. doi: 10.1182/blood-2016-01-643569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kaplan JE, Osame M, Kubota H, et al. The risk of development of htlv-I–associated myelopathy/tropical spastic paraparesis among persons infected with htlv-I. J Acquir Immune Defic Syndr. 1990;3:1096–101. [PubMed] [Google Scholar]
- 8.Katsuki T, Yamaguchi K, Matsuoka Y, Hinuma Y. Impairment of T-cell control of Epstein–Barr virus infected B-cells in patients with adult T-cell leukemia. AIDS Res. 1986;2(suppl 1):S125–30. [PubMed] [Google Scholar]
- 9.Yasunaga J, Sakai T, Nosaka K, et al. Impaired production of naive T lymphocytes in human T-cell leukemia virus type I– infected individuals: its implications in the immunodeficient state. Blood. 2001;97:3177–83. doi: 10.1182/blood.V97.10.3177. [DOI] [PubMed] [Google Scholar]
- 10.Sobol I, Palacios C, Osborne G, et al. Initial management of an outbreak of the htlv-1 virus in Nunavut, Canada. Alaska Med. 2007;49(suppl):204–6. [PubMed] [Google Scholar]
- 11.CBC News. Rare blood virus found in almost 4 in 1, 000 in Nunavut [Web news article] Toronto, ON: CBC News; 2007. [Available at: https://www.cbc.ca/news/canada/north/rare-bloodvirus-found-in-almost-4-in-1-000-in-nunavut-1.664291; cited 18 December 2018] [Google Scholar]
- 12.Martin JD, Mathias RG, Sarin C, Byrne SE. Human T-lymphotropic virus type I and II infections in First Nations alcohol and drug treatment centres in British Columbia, Canada, 1992–2000. Int J Circumpolar Health. 2002;61:98–103. doi: 10.3402/ijch.v61i2.17411. [DOI] [PubMed] [Google Scholar]
- 13.Sibbald B. htlv-1 virus detected in Nunavut. CMAJ. 2006;174:150–1. doi: 10.1503/cmaj.051581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Picard FJ, Coulthart MB, Oger J, et al. Human T-lymphotropic virus type 1 in coastal natives of British Columbia: phylogenetic affinities and possible origins. J Virol. 1995;69:7248–56. doi: 10.1128/jvi.69.11.7248-7256.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis. 2007;7:266–81. doi: 10.1016/S1473-3099(07)70081-6. [DOI] [PubMed] [Google Scholar]
- 16.Ghazawi FM, Netchiporouk E, Rahme E, et al. Comprehensive analysis of cutaneous T-cell lymphoma (ctcl) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy. Cancer. 2017;123:3550–67. doi: 10.1002/cncr.30758. [DOI] [PubMed] [Google Scholar]
- 17.Ghazawi FM, Netchiporouk E, Rahme E, et al. Distribution and clustering of cutaneous T-cell lymphoma (ctcl) cases in Canada during 1992 to 2010. J Cutan Med Surg. 2018;22:154–65. doi: 10.1177/1203475417745825. [DOI] [PubMed] [Google Scholar]