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Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): Implications for blood transfusion safetyL’infection par le virus human T-lymphotropic types-1 et -2 (HTLV-1 et -2) : implications pour la sécurité de la transfusion sanguine

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Abstract

Many countries currently perform antibody screening for HTLV-1 infection in blood donors, and this intervention is likely cost-effective in preventing HTLV-1 related diseases in high prevalence countries. However, a number of high-income countries with low prevalence of HTLV-1 infection also perform universal HTLV-1 screening and debate has arisen regarding the cost-effectiveness of these strategies. Filter-based leukoreduction is likely to substantially reduce HTLV-1 transmission by removing infected lymphocytes, but actual laboratory data on its efficacy is currently lacking. Similarly, cost-effectiveness research on HTLV-1 prevention strategies is limited by poor data on prevalence, transmission efficacy and the cost of treating HTLV1 diseases.

Résumé

De nombreux pays effectuent actuellement le dépistage des anticorps anti-HTLV-1 chez les donneurs de sang. Cette mesure a un bon rapport coût-efficacité dans la prévention des pathologies liées à ce virus dans les pays à forte prévalence. Cependant, un certain nombre de pays à revenu élevé et à faible prévalence de l’infection réalisent aussi un dépistage universel des anti-HTLV-1. Cette politique sécuritaire soulève la question du bénéfice de cette stratégie en termes de coût-efficacité au regard de l’existence parallèle et systématique de mesures de déleucocytation susceptible de réduire la transmission virale par la suppression des lymphocytes infectés. Toutefois, les données de l’efficacité de cette procédure de filtration des produits sanguins obtenues en laboratoire font actuellement défaut. De même, la recherche de la rentabilité des stratégies de prévention HTLV-1 est limitée par les données sur la prévalence, l’efficacité de la transmission et le coût de traitement des maladies du HTLV-1.

Introduction

Human T lymphotropic virus types-1 and -2 (HTLV-1 and -2) were discovered in the early 1980s and cause chronic infection of humans. Soon after their discovery, it was realized that blood transfusion was associated with high rates of transmission due to the infusion of infected lymphocytes. Transfusion-transmitted HTLV-1 was also associated with the accelerated onset of HTLV associated myelopathy (HAM), a debilitating spinal cord condition and with case reports of adult T-cell leukemia/lymphoma (ATL). Antibody screening for HTLVs was therefore introduced in many countries and remains in place today. In addition to its primary purpose of preventing transfusion transmission, such screening also provides a public health resource in allowing estimation of population prevalence of HTLV infection.

Paradoxically, most countries performing HTLV screening of blood donors have very low prevalence and incidence, while certain countries in Africa with probable high HTLV-1 prevalence in their donors do not currently perform antibody screening due to cost concerns. By analogy to cytomegalovirus, it is likely that filter leukoreduction of blood products reduces the transfusion risk of HTLV, although there are only suggestive data to support this hypothesis and leukoreduction is similarly impractical in many high prevalence countries.

My late colleague Jean Jacques Lefrere was an avid scholar of all threats to transfusion safety. Unbeknownst to me until I researched this article, he had published several articles on HTLV-1 infection, including an early comparison of donor prevalence between endemic Guadeloupe and the non-endemic Paris region and a comprehensive review of HTLV-1 and transfusion safety [1], [2]. Our community of scientists will be diminished by the absence of his keen intellect and energy, but we shall also miss him as a faithful and cultivated friend.

Section snippets

Early epidemiologic studies of transfusion transmission

Soon after HTLV-1 was discovered and prior to the introduction of HTLV antibody screening, several studies were able to quantify the risk of transfusion-transmitted HTLV-1 infection. In Japan, Okochi et al. were the first to demonstrate transfusion transmission of HTLV-1 [3]. Of the 41 patients who received cellular blood products from HTLV-1 positive donors, 26 (63%) seroconverted to HTLV-1. None of 14 recipients of HTLV-1 positive plasma transfusions seroconverted. Blood products stored less

Case reports of transfusion-transmitted HTLV-1 infection

Since HTLV infection is often asymptomatic, clinically recognized reports of patients infected via blood transfusion are rare. However, several case reports document the potential for adverse consequences of infection. A French patient who received a heart transplant and required large volumes of transfused red cells, platelets and plasma developed symptoms and signs of HAM within 4 to 5 months and was found to have seroconverted for HTLV-1 in a blood sample drawn at 14 weeks post transfusion

Prevalence of infection - HTLV-1

HTLV-1 is widely disseminated and between 5 and 10 million people worldwide are estimated to be infected [11]. Studies of HTLV-1 prevalence among blood donors underestimate prevalence in the general population but are still useful in comparing between nations (Table 1). Endemic clusters of HTLV-1 seropositivity or infection are present in southern Japan, the islands of the Ryukyu Chain (including Okinawa), and some isolated villages in the north of Japan among aboriginal Ainu populations; rates

Prevalence of infection–HTLV-2

HTLV-2 has a more restricted distribution than HTLV-1 and occurs primarily in the Americas and among pygmy tribes in Africa. Amerindians residing in North, Central, and South America show various rates of positivity for HTLV-2 (5 to 30%). Pockets of infection are present among the Seminoles in southern Florida and the Pueblo and Navajo in New Mexico but not among various tribes in Alaska. In Central America, the Guaymi Indians residing in northeastern Panama near the Costa Rican border have

HTLV-1 and -2 incidence and residual risk

The blood donation setting is valuable for studies of HTLV-1 and HTLV-2 incidence since a single donor can be tracked prospectively across his or her donations to observe seroconversions. In the United States, several studies have documented HTLV-1/2 incidence ranging from 1–2 per 105 person years in the 1990s [37], [38] to 0.2 per 105 person-years in 2007–2008 (Table 2) [39]. With knowledge of the estimated window period between infection – estimated at 51 days from the transmission studies

Current testing and cost effectiveness, by country

Unfortunately, the World Health Organization global database on blood safety does not include HTLV testing as one of its data collected from countries around the world. According to another recent review and supplementary information [41], the following countries test all blood donations for HTLV-1 and -2 antibody: Argentina (endemic regions), Australia, Brazil, Canada, USA, Canada, China (some regions) [14], Colombia, French West Indies, Iran, Israel, Jamaica, Japan, New Zealand, Saudi Arabia,

Gaps in knowledge and controversies

At present, the main gaps in knowledge regarding transfusion-transmitted HTLV-1 can be ascribed to inadequate prevalence data in some regions of Africa and Asia, uncertainty regarding the effectiveness of leukoreduction, and the cost effectiveness of less-than-universal antibody screening. Cassar and Gessain made a comprehensive survey of HTLV-1 prevalence across the globe but noted that their global estimate of 5 million to 10 million cases was substantially limited by inadequate data on

Conclusions and future directions

In conclusion, there is currently a mismatch of prevention strategies for transfusion transmission of HTLV-1 across the world, with high-income countries performing expensive testing in very low prevalence and incidence settings. In contrast, many low and middle-income countries with much higher endemicity of HTLV-1 are currently performing no or ineffective HTLV-1 screening. A shift in global priorities and resources would seem to be in order, with the potential adoption of less costly

Disclosure of interest

The author declares that he has no competing interest.

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