Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring

Paiva, Afonso; Assone, Tatiane; Haziot, Michel E.; Smid, Jerusa; Fonseca, Luiz Augusto Marcondes; Luiz, Olinda do Carmo; Oliveira, Augusto César Penalva de; Casseb, Jorge

doi:10.1038/s41598-018-25939-y

Cited by 55 publications

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References 36 publications

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“…After the adoption of mandatory national blood screening tests in 1993 and the observed behavioral change from intravenous to inhalation drug abuse, parental exposure to HTLV-1/2 dropped [4][5][6]. However, our group has documented rates of 40% of sexual transmission [6] and of 13% of vertical transmission [7,8].…”

Section: Introductionmentioning

confidence: 83%

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

et al. 2019

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Background: Despite its relatively low incidence of associated diseases, Human T-cell Leukemia Virus-1 (HTLV-1) infection was reported to carry a significant risk of mortality in several endemic areas. HTLV-1-associated diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP), as well as frequent coinfections with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and Strongyloides stercoralis were associated to increased morbidity and mortality of HTLV-1 infection. Objective: To determine the mortality rate and its associated variables from an open cohort started in July 1997 at the HTLV Clinic, Emilio Ribas Institute (IIER), a major infectious disease hospital in São Paulo, Brazil. Methods: Since inception up to September 2018, we admitted 727 HTLV-1-infected individuals, with a rate of 30–50 new admissions per year. All patient data, including clinical and laboratory data, were regularly updated throughout the 21-year period, using a dedicated REDCap database. The Ethical Board of IIER approved the protocol. Results: During 21 years of clinical care to people living with HTLV-1 in the São Paulo region, we recruited 479 asymptomatic HTLV-1-infected individuals and 248 HAM/TSP patients, of which 632 remained under active follow-up. During a total of 3800 person-years of follow-up (maximum follow-up 21.5 years, mean follow-up 6.0 years), 27 individuals died (median age of 51.5 years), of which 12 were asymptomatic, one ATLL patient and 14 HAM/TSP patients. HAM/TSP diagnosis (but neither age nor gender) was a significant predictor of increased mortality by univariate and multivariate (hazard ratio (HR) 5.03, 95% CI [1.96–12.91], p = 0.001) Cox regression models. Coinfection with HIV/HCV was an independent predictor of increased mortality (HR 15.08; 95% CI [5.50–41.32]; p < 0.001), with AIDS-related infections as a more frequent cause of death in asymptomatics (6/13; p = 0.033). HIV/HCV-negative fatal HAM/TSP cases were all female, with urinary tract infection and decubitus ulcer-associated sepsis as the main cause of death (8/14, p = 0.002). Conclusions: All-cause mortality among people living with HTLV-1 in São Paulo differs between asymptomatic (2.9%) and HAM/TSP patients (7.3%), independent of age and gender. We observe a dichotomy in fatal cases, with HAM/TSP and HIV/HCV coinfection as independent risk factors for death. Our findings reveal an urgent need for public health actions, as the major causes of death, infections secondary to decubitus ulcers, and immune deficiency syndrome (AIDS)-related infections, can be targeted by preventive measures.

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Section: Introductionmentioning

confidence: 83%

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

et al. 2019

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“…HTLV is an ancient infection in humans and alternates between persistence and productive cycles, which favors an effective mechanism involving vertical and horizontal transmission. According to the geographical environment and behavioral risk factors, the increased risk of transmission of the virus increases the prevalence and incidence of infection and disease [6,[28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil

Ishak

Vallinoto

2020

Retrovirology

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HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in the Amazon region of the country. Presently, HTLV spreads mainly by the sexual route and from mother to child, and virus persistence is an active biological factor aiding its transmission. Recently, the use of illicit drugs has been shown to be an additional risk factor, showing the influence of new habits on the epidemiology of HTLV in the region. Despite the detection of the virus in several different populations in the Amazon region of Brazil for almost 30 years, the exact prevalence of HTLV-1/2 is not well defined. The original biases in sampling and the selection of epidemiologically unsuitable populations were commonly repeated in most prevalence studies, generating unreliable and conflicting figures that do not represent the actual prevalence of HTLV. The improvements in clinical and laboratory facilities have resulted in the description of several clinical manifestations that were previously unknown in the region. The extent of the spread of the virus must be defined in this region, which is the largest geographical area of the country. As prophylaxis advances toward the use of vaccines against HTLV-1, it is important to determine who is at risk of being infected and developing a disease to successfully implement preventive measures, particularly as proposals are made to eradicate the virus among humans.

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“…After the adoption of mandatory national blood screening tests in 1993 and the observed behavioral change from intravenous to inhalation drug abuse, parental exposure to HTLV dropped [4][5][6]. However, our group has documented rates of 40 percent of sexual transmission [7] and of 13 percent of vertical transmission [8,9].…”

Section: Introductionmentioning

confidence: 83%

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

Marcusso¹,

Weyenbergh²,

Moura³

et al. 2019

Preprint

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BACKGROUND: During the natural history, the incidence HTLV-1 related diseases were 0.5% until 10% after decades of infection. Despite relative low lethality, previous study observed that HTLV-1 infection is associated with significantly increased mortality. For example, the incidence of ATLL and HAM/TSP, co-infections with HIV and HCV, parasitic co-infection with Strongyloides stercoralis may increase morbidity and mortality. OBJECTIVE: Determine the mortality rate and its major variables as possible risk factors, analyzing the HTLV Clinic at Emilio Ribas Institute, a continuous open cohort of HTLV patients since 1997. METHODS: This cohort open cohort possesses new patients added at a rate of approximately 50 patients/year. There were 1100 HTLV-infected subjects identified by September 30th 2018. All clinical data including clinical and laboratory data, which have been updated on a regular basis over the last 22 years, were entered into a specific REDCap database. The Ethical Board of the IIER approved the protocol. RESULTS: Along 22 years of clinical care in the HTLV-out clinic, 727 HTLV-1-infected subjects and 248 HAM/TSP cases. Four-hundred sixty-eight patients of whom remaining under active follow up. The mean follow-up time of the cohort was 12 years. Twenty-seven patients died (median age of 51,5 years old). From this total, 13 was asymptomatic carriers and 14 HAM/TSP subjects, 12 of asymptomatic and seven HAM/TSP possess co-infected with HIV or/and HCV. Other seven presented HAM/TSP without co-infection, and all was female, and sepsis was the majority cases the majority of cases of sepsis were related to infection of the urinary tract (p=0.058) and to ulcers of decubitus (p=0.021), and it was associated with risk factors for mortality. CONCLUSIONS: Overall, the mortality rate for HAM-TSP patients was six percent. The mean life expectancy in Brazil is about 78 years in 2018, twenty-two years higher than HAM/TSP patients without any other coinfection. This study highlights the possibility of higher death risk among HTLV-1-infected patients and HAM/TSP subjects in Brazil, and identified some risk factors for this outcome. Also, these patients may possess higher risk for morbidity, usually urinary tract infections and decubitus scars, which could increase risk for death.

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Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring

Cited by 55 publications

References 36 publications

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

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Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring

Cited by 55 publications

References 36 publications

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in S&atilde;o Paulo, Brazil

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Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil