Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) belong to the family Retroviridae, subfamily Orthoretrovirinae, and genus Deltaretrovirus (1), and both were isolated in the early 1980s (2, 3). HTLV-1/2 is characterized by the ability to cause a persistent and silent infection, and its forms of transmission are contact with contaminated organic fluids through sexual intercourse, syringe and needle sharing and breastfeeding (4, 5).

Although most individuals infected with the virus show no symptoms, HTLV-1 is associated with serious diseases, such as HTLV-1-associated myelopathy (HAM) and adult T-cell leukemia/lymphoma (ATL), pathologies that may occur in ~2–3% of people living with HTLV (PLHTLV) (2, 6, 7). HTLV-1 is also associated with other diseases, such as uveitis, infectious dermatitis, bronchitis, bronchiectasis, arthropathies, myositis, urinary dysfunction, and strongyloidiasis (8–10). For HTLV-2, there are reports that correlate it to cases of neurological disorders similar to HAM; however, there are no precise indications of the clinical manifestations of these disorders (11, 12).

The diagnosis of infection is initially performed using an enzyme-linked immunosorbent assay (ELISA) as a screening method for the detection of anti-HTLV-1/2 antibodies. Positive cases are referred for infection confirmation by Western blot, INNO-LIA and/or conventional (PCR) or real-time (qPCR) polymerase chain reaction assays (13). The first two tests are used for the detection of specific antibodies to different virus proteins, and PCR is used for the detection of proviral DNA, to differentiate between viral types and subtypes, and to quantify the proviral load (13–15).

Globally, it is estimated that 5 to 10 million individuals are infected with HTLV, with the distribution varying based on ethnic group, behavioral risk factors for infection and geographic location; southwestern Japan, sub-Saharan Africa and South America have the highest endemicity of the virus (16). In Brazil, there are an estimated 2.5 million PLHTLV (17), and Brazil is considered the country with the highest absolute number of HTLV-1/2 seropositive individuals in the world (18). The infection is endemic, being heterogeneously distributed among the different Brazilian regions and states, with Bahia, Maranhão and Pará recording the highest prevalence rates in Brazil (6, 17, 18).

Previous studies conducted in the state of Pará have reported high prevalence rates of HTLV infection in specific groups, such as blood donors (18, 19), pregnant women (20), indigenous populations (21), the Quilombola people (22) and people living with human immunodeficiency virus (PLHIV) (23). The prevalence of the virus in the metropolitan region of Belém, the most population-dense area in the state of Pará, is still unknown because of a lack of the early diagnosis of infection and diseases associated with HTLV (24), reinforcing the fact that the epidemiology of this viral agent should be better described for the capital of Pará.

It is of paramount importance the counseling of asymptomatic HTLV-1-infected subjects, to perform a clinical follow-up of the individual aiming to detect early the symptoms of diseases associated with the virus. Additionally, the lack of public policies for the active identification of cases of infection and subsequent counseling and screening for intrafamilial transmission results in a loss of productivity for those affected and their families. In addition, the absence of policies for preventing new infections and for providing adequate care for those living with HTLV-1 contributes to the increase in socioeconomic disparity between and within countries (25). Given this, the Laboratory of Virology of the Institute of Biological Sciences of Federal University of Pará (Universidade Federal do Pará—UFPA), with support from the Brazilian National Council for Scientific and Technological Development (CNPq, acronym in Portuguese) and the Pan American Health Organization (PAHO), implemented a public HTLV-1/2 serological screening and confirmation service for the general population of the city of Belém (metropolis of the Brazilian Amazon) and, if necessary, provided counseling and follow-up by a nurse and a referral for care by various health professionals (nurse, occupational therapist and doctor). In the present study, we aimed to describe the main results after the first year of service implementation.

Investigations of the prevalence of HTLV-1/2 infection in the state of Pará have been conducted in specific population groups, such as blood donors, indigenous populations, the Quilombola people, PLHIV and Japanese immigrants (22, 28–30). The present study provides seroepidemiological information on the prevalence of HTLV-1 and HTLV-2 in the general population of Belém, the capital of the state of Pará.

A study by Silva et al. (24), conducted between 2014 and 2015, showed a 2% prevalence of HTLV infection (1.4% for HTLV-1 and 0.5% for HTLV-2) in a sample from the city of Belém, classifying this location as an area of moderate endemicity. The prevalence found in the present study of 0.38% was well below that described by Silva et al. (24); this difference may be due to (i) a possible reduction in prevalence over the 6 years separating the studies; (ii) the fact that Silva et al. (24) sampled adult individuals who were passing public places such as the Ver-o-Peso Complex, a location with a high circulation of people from other municipalities of the metropolitan region of Belém, which differs from the present study, which evaluated only people residing in Belém; (iii) sample size; or (iv) differences in the sensitivity of the different ELISAs used in the two studies. Currently, we are collecting seroepidemiological information from neighboring municipalities that compose the metropolitan region of Belém, for example, Ananindeua, Marituba and Benevides, with the objective of separately evaluating prevalence and thus identifying the overall occurrence of infection in the region. Our results did not differ from those observed by Maneschy et al. (31) in a study conducted between 2015 and 2019 in a blood center in the state of Pará; the results indicated an HTLV prevalence of 0.3% (1476/453,626) among blood donors, among whom most positive individuals were from the metropolitan region of Belém. In another study conducted with pregnant women, the estimated prevalence of HTLV was 0.6% (32).

During the screening and confirmation analyses, two individuals were identified by INNO-LIA with a serological profile of HTLV, and qPCR molecular analysis confirmed the presence of HTLV-1 proviral DNA in one individual and HTLV-2 proviral DNA the other. Another individual was positive for HTLV-1 based on INNO-LIA diagnostic criteria, but proviral DNA was not detected by qPCR. These serological (INNO-LIA) and molecular (qPCR) methods have been used and endorsed for the confirmatory and differential diagnosis of HTLV-1 and HTLV-2 infections (13). Differences in results between serological and molecular methods are frequent and result from differences in the sensitivity and specificity of the tests (26). Furthermore, Caterino-de-Araújo and Rodrigues Campos (33) described difficulties in the laboratory diagnosis of the infection, including the presence of incomplete HTLV viral particles (characterized by the absence of a viral gene, such as the tax gene), low quality of extracted DNA, mutations and a low proviral load, which can potentially lead to the absence of gene amplification and thus result in a false-negative diagnosis for infection. Therefore, the use of a single laboratory method to confirm and differentiate HTLV-1/2 infection is not recommended; it is necessary to adopt complementary confirmatory assays to minimize diagnostic and prevalence estimate errors.

In addition to an accurate laboratory diagnosis that allows identifying the prevalence of infection in a given geographic area, it is necessary to implement a counseling and follow-up service for PLHTLV to provide efficient clinical, laboratory and psychological monitoring. Rosadas et al. (34) emphasize the importance of including the multiprofessional screening of HTLV in the routine care provided in services for people infected with HIV and other STIs. For this reason, all individuals diagnosed in our study were referred to initial counseling with a nurse, at which time they were informed about HTLV, its modes of transmission and prevention, associated diseases and supportive therapies for infection-related symptoms. Subsequently, those individuals who, in counseling, complained of neurological changes were referred to a neurologist. Of the six individuals with confirmed cases of infection, four individuals were asymptomatic. Interestingly, the two individuals who presented complaints suggestive of neurological disorders were infected with HTLV-2. Although there is some rare evidence in the literature associating this viral type with neurological diseases similar to HAM (11, 12), the initial evaluation by the neurologist did not identify the presence of clinical changes that confirmed a diagnosis of HAM.

The results presented here are part of the first year of a screening, confirmation, counseling and multiprofessional follow-up service for PLHTLV offered through the Laboratory of Virology of the Federal University of Pará and implemented as part of a National Network of laboratories, funded by the Ministry of Health and PAHO. The main limitation of the study can be considered the difficulty of convincing the seropositive individual to perform a new blood collection in order to carry out the confirmatory tests. On the other hand, the main strength of the study is to contribute with the prevention and control measures for HTLV infection to reduce transmission and to identify the main risk factors associated with infection, characterizing the individuals or groups that may be more vulnerable to HTLV, and thus provide information that will support the development of public health policy strategies to combat the spread of this virus in Brazil.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Human Research Ethics Committee of the Health Sciences Institute of the Federal University of Pará and by the National Research Ethics Committee (CAAE No. 27290619.2.0000.0018). The patients/participants provided their written informed consent to participate in this study.

AV and IC conceived and designed the study. FL, MV, AL, and FF performed the laboratory experiments. FL, RS, JC, MV, AL, RF, AR, and LM performed the fieldwork. CA-A and EM performed clinical follow-ups. FL and AV wrote the manuscript. All authors read and approved the final version of the manuscript.

This study received financial support from the National Council of Science and Technology (CNPq # 442522/2019-3 and CNPQ # 302935/2021-5) and the Ministry of Health of Brazil and the Pan American Health Organization (#SCON2021-00310).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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