Background

Human T-cell lymphotropic virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered [1]. Currently, there are three other known members of the HTLV family of viruses: HTLV-2, HTLV-3 and HTLV-4 [2]–[4]. HTLV-1 is associated with adult T-cell leukemia/lymphoma and with myelopathy/tropical spastic paraparesis [5]–[7]. HTLV-1 is also associated with tuberculosis, uveitis, infective dermatitis, and strongyloidiasis [8]–[11]. HTLV-2 infection produces less disease than HTLV-1, but has been associated with recurrent pneumonia and neuropathy [12]. It is not known if HTLV-3 or -4 are associated with disease in humans.

HTLV-1 and -2 infections are transmitted via breastfeeding, sexual contact, and parenteral transmission via blood transfusion and intravenous drug use [5], [12]. HTLV is estimated to infect 10 to 20 million people worldwide and is endemic in Japan, the Melanesian islands, the Middle East, sub-Saharan Africa, South America and the Caribbean [13]–[16]. In South America and the Caribbean, specifically in Jamaica, Martinique, Guyana, French Guyana, Colombia, and the north of Brazil, HTLV-1 infection is frequent among people of African descent, whereas in Peru and northern Argentina it is more prevalent among indigenous people [17]–[21].

In Peru, most HTLV infections have been reported in indigenous people from the Andean Region (Quechua and Aymara ethnicities), and among African-Peruvian and mestizo populations (a mix of Spanish and Andean indigenous blood) [15], [20], [22], [23]. In contrast, there is limited information about HTLV infection in Amazonian ethnic groups, with limited reports of HTLV infection in Shipibo-Konibo, Kechwa-Lamas, Wampis, and Harakmbut villages [19], [21], [24]. HTLV has also been reported in populations at high risk for sexually transmitted infections, such as female sex workers (FSW) and men who have sex with men (MSM) [25]–[27].

As part of a previous study conducted among ten indigenous groups in the Peruvian Amazon, we found 18 HTLV infections restricted to the Shipibo-Konibo people, one of the largest Peruvian Amazonian ethnic groups residing along the Ucayali river [24]. However the sample size for that study limited the exploration of risk factors for the infection. Therefore, the objective of our study was to conduct a population-based study in the Shipibo-Konibo ethnic group to determine the prevalence and risk factors for HTLV-1 and HTLV-2 infections among women 15 to 39 years of age.

Methods

Results

Between July and December 2010, we approached leaders of 21 Shipibo-Konibo communities and 19 consented participation of their communities. Two communities were located in Lima, and 17 were Amazon jungle communities located near the city of Pucallpa. In these communities we approached 1,460 women, of whom 58 refused to participate. Of the 1,402 consenting women 149 were excluded because they did not belong to the Shipibo-Konibo ethnic group. All the remaining 1,253 eligible women could speak Spanish. Of these women, 74 (5.9%) tested positive for HTLV-1, 47 (3.8%) for HTLV-2 infection, and four (0.3%) had indeterminate results. Participants with indeterminate results were excluded from further analysis. The combined HTLV-1/2 prevalence was 9.7%. There were no dual infections. HTLV infected participants were born in seven out of 10 districts included in the Ucayali region and in 4 out of 11 districts included in the Loreto region. The distribution of HTLV within communities did not follow a clear geographical pattern. Figure 1 shows the frequency of HTLV-1 and -2 positive individuals per community in the Ucayali Region. To protect the identity of the communities participating, only their relative locations are shown and the two easily identifiable communities in Lima were excluded. This is in response to the request of the IRB which agreed with the communities to never report HTLV prevalence by community.

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Figure 1. Frequency of HTLV-1 and -2 infections per community in the Ucayali region.

https://doi.org/10.1371/journal.pone.0073978.g001

HTLV-1 infected women were more likely than HTLV-negative participants to be older (There was a 4% increase in HTLV-1 prevalence for each additional year of age), less educated, married or cohabiting, to have a last sexual partner either younger or of the same age than HTLV negative women, to live with current sex partner, to not use a condom in their last sexual intercourse, to have a last sex partner who worked at a logging camp and to self-report a history of tuberculosis (Table 1).

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Table 1. Factors associated with human T cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections among women from the Shipibo-Konibo ethnic group.

https://doi.org/10.1371/journal.pone.0073978.t001

HTLV-2 infected women were more likely to be older and not living in the community where they were born. They were also more likely to be sexually active, to have a last sexual partner younger or of the same age than HTLV negative women, to report a history of bleeding during a dental procedure and a history of crusted scabies (Table 1).

We did not find an association between having had a partner who used intravenous drug use, having tattoos, piercing or surgery and HTLV-1 or -2 infection (data not shown). We were not able to evaluate duration of breastfeeding as a risk factor for HTLV-1 or -2 infection, since 850 (68.1%) of participants did not recall this information. When analyzing women who knew the duration of breastfeeding, the mean duration of breastfeeding was similar for both HTLV seropositive and seronegative participants (15.3 months vs. 15.1 months, p = 0.85).

Overall, 15.0% (17) participants who reported they were pregnant at the time of the interview were infected with HTLV, 10 with HTLV-1 and 7 with HTLV-2. The mean number of sexual partners during the last 12 months among HTLV negative, HTLV-1 and HTLV-2 positive participants was similar (1.0 vs. 1.0 vs. 1.2 partners). Among sexually active participants, the combined HTLV-1 and -2 prevalence was 10.2%, whereas among participants reporting not having initiated sexual activity the prevalence was 4.2%, suggesting vertical transmission is a common cause of HTLV-1 and -2 infection.

In the multivariate analysis, factors associated with HTLV-1 infection were age, having primary education or less, having the most recent sex partner either younger or of the same age, and having the most recent sex partner who worked at a logging camp. The only factor independently associated with HTLV-2 infection was age (Table 2).

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Table 2. Multivariate analysis of factors associated with human T cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections in women from the Shipibo-Konibo ethnic group.

https://doi.org/10.1371/journal.pone.0073978.t002

Discussion

To our knowledge, this is the largest population-based study to assess the prevalence of HTLV-1 and -2 infections in indigenous populations in Latin America. We found a combined HTLV-1 and -2 prevalence of 9.7% among Shipibo-Konibo women, the highest prevalence described in an indigenous group in Peru.

In the multivariate analysis, older age was associated with both HTLV-1 and -2 infections. Other studies that have assessed risk factors for HTLV infection have reported that seroprevalence increases with age, suggesting that sexual intercourse plays an important role in the transmission of this virus [28], [29], or suggesting a cohort effect for an infection that is diminishing. The detection of HTLV infection among women reporting not having initiated sexual activity, suggests that mother-to-child transmission is also present. The high prevalence found in this study along with the long duration of breastfeeding reported (mean = 15 months) could explain high rates of vertical transmission.

We also found that lower education level was associated with HTLV-1 infection. In a study in Salvador, Brazil, formal education of less than 7 years was associated with HTLV-1 infection in females [30]. A study in Iran also found a higher prevalence of HTLV-1 infection observed among illiterate people compared to participants with higher levels of education [31]. As many of the traditional practices that may have perpetuated the persistence of HTLV-1 infection within this ethnic group (shared breastfeeding, tattoos, polygyny) have decreased with westernization and with increasing access to education.

In our study, having a most recent sex partner who was younger or of the same age, and having a most recent sex partner who worked at a logging camp were both associated with HTLV-1 infection. While the first finding is intriguing, a previous study that assessed risk factors for STI among men from 10 indigenous groups in the Peruvian Amazon found that illegal logging camps were venues where heterosexual males were often exposed to unprotected sex with FSW and MSM, and therefore at higher risk for acquiring HTLV and other STI [32]. Other studies have reported the prevalence of HTLV-1 infection among women increased with a younger initiation of sexual activity, higher number of sex partners, history of an STI and higher number of different men fathering a child by the woman [33]–[35]. In our study, the age of sexual initiation and the number of partners in the past year were similar for HTLV-1 positive and negative women but partner characteristics, such as age and previous work at a logging camp, were different.

HTLV-2 infection was associated with a self-reported history of crusted scabies and HTLV-1 infection was associated with a history of tuberculosis. Crusted scabies is a rare but severe infection caused by massive infestation with Sarcoptes scabiei var. hominis [36], [37]. In a hospital study in Brazil, all patients presenting with crusted scabies tested positive for HTLV-1 [38]; we have not identified previous reports of crusted scabies in patients with HTLV-2 infection. Regarding the association between HTLV-1 and tuberculosis, a case control study in Brazil reported a statistically significant increase in the risk of tuberculosis in subjects infected with HTLV-1 [39]. HTLV-1 has also been associated with worse outcome of tuberculosis and with a mortality rate of 25% among those infected with HTLV-1, compared with 8% in those without HTLV-1 infection [40].

Although we included non-sexually active women of reproductive age, one limitation of our study is the exclusion of participants under 15 years of age that would have provided valuable data regarding vertical transmission.

In conclusion, HTLV infection is endemic among Shipibo-Konibo women, particularly among older and less educated women. Remarkably, two characteristics of the sexual partner (younger age and labor history) were associated with infection in women. These results suggest the need for implementation of both HTLV screening during the antenatal healthcare visits of Shipibo-Konibo women, as well as counseling about the risk of HTLV transmission through prolonged breastfeeding in women infected with the virus. We also suggest the implementation of programs oriented towards preventing sexual transmission of this virus through educational interventions that cover safe-sex behavior and condom use. Additionally, we suggest clinical follow-up of HTLV infected people in order to provide early diagnosis and treatment of HTLV-associated diseases. For an intervention to be successful and tailored to this indigenous community, researchers should integrate input from the Shipibo-Konibo community into the development of evidence-based interventions.

Acknowledgments

We would like to thank the indigenous health program and the regional organizations (ORAU and FECONAU) of the Interethnic Association for the Development of the Peruvian Rainforest (AIDESEP) for their support in the development of this study. We also want to thank the indigenous leaders who helped us conduct this study, and the personnel of this project, especially Yolanda Nunta, Jeiser Suarez, Greti Trigoso, Neylar Morales, Rosario Trujillo, Janet Soto, and Maybee Terrones. We also want to thank Monica Nieto and Ada Romero for performing the HTLV testing.

Disclaimer: The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, the U.S. Government, nor Merck.

Dr. Silvia Montano is an employee of the U.S. Government. This work was prepared as part of her official duties. Title 17 U.S.C. § 105 provides that ‘Copyright protection under this title is not available for any work of the United States Government’. Title 17 U.S.C. § 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties.