Louise de Souza Canto Ferreira

Familial Transmission of Human T-cell Lymphotrophic Virus: Silent Dissemination of an Emerging but Neglected Infection

Background HTLV-1 is a retrovirus that causes lymphoproliferative disorders and inflammatory and degenerative diseases of the central nervous system in humans. The prevalence of this infection is high in parts of Brazil and there is a general lack of public health care programs. As a consequence, official data on the transmission routes of this virus are scarce. Objective To demonstrate familial aggregation of HTLV infections in the metropolitan region of Belém, Pará, Brazil. Method A cross-sectional study involving 85 HTLV carriers treated at an outpatient clinic and other family members. The subjects were tested by ELISA and molecular methods between February 2007 and December 2010. Results The prevalence of HTLV was 43.5% (37/85) for families and 25.6% (58/227) for the family members tested (95% CI: 1.33 to 3.79, P = 0.0033). Sexual and vertical transmission was likely in 38.3% (23/60) and 20.4% (29/142) of pairs, respectively (95% CI: 1.25 to 4.69, P = 0.0130). Positivity was 51.3% (20/39) and 14.3% (3/21) in wives and husbands, respectively (95% CI: 0.04 to 0.63, P = 0.0057). By age group, seropositivity was 8.0% (7/88) in subjects <30 years of age and 36.7% (51/139) in those of over 30 years (95% CI: 0.06 to 0.34, P<0.0001). Positivity was 24.1% (7/29) in the children of patients infected with HTLV-2, as against only 5.8% (4/69) of those infected with HTLV-1 (95% CI: 0.05 to 0.72, P = 0.0143). Conclusion The results of this study indicate the existence of familial aggregations of HTLV characterized by a higher prevalence of infection among wives and subjects older than 30 years. Horizontal transmission between spouses was more frequent than vertical transmission. The higher rate of infection in children of HTLV-2 carriers suggests an increase in the prevalence of this virus type in the metropolitan region of Belém.

Occurrence of strongyloidiasis among patients with HTLV-1/2 seen at the outpatient clinic of the Núcleo de Medicina Tropical, Belém, State of Pará, Brazil

INTRODUCTION This study investigated the occurrence of Strongyloides stercoralis infestation and coinfection with HTLV-1/2 in Belém, Brazil. METHODS S. stercoralis was investigated in stool samples obtained from individuals infected with HTLV-1/2 and their uninfected relatives. RESULTS The frequency of S. stercoralis was 9% (9/100), including six patients infected with HTLV-1 (14.3%), two patients infected with HTLV-2 (11.1%), and one uninfected relative. Two cases of hyperinfestation by S. stercoralis were characterized as HTLV-1. CONCLUSIONS These results support the need for the routine investigation of S. stercoralis in patients with HTLV-1, in an attempt to prevent the development of severe forms of strongyloidiasis.

Moderada endemicidade da infecção pelo vírus linfotrópico-T humano na região metropolitana de Belém, Pará, Brasil

INTRODUCTION The spread of the HTLV infection in families living in the metropolitan area of Belém, Pará, Brazil, and the lack of studies in the general population requires studies to better understand its prevalence in the region. METHODS An anti-HTLV-1/HTLV-2 antibodies test was carried out on random adults in public places in Belém between November 2014 and November 2015. A proviral DNA test detected if the person was infected, and then a clinical evaluation and an intrafamilial investigation were carried out. RESULTS Of the 1059 individuals being investigated, 21 (2.0%) had seroreagent samples, 15 (1.4%) had HTLV-1, 5 (0.5%) had HTLV-2, and proviral DNA was undetectable in one case. The mean age of the infected people (57.2) was higher than that of those that were uninfected (46.2) (p = 0.0010). The prevalence of infection increased with age, especially in individuals with a family income equal to or less than a minimum wage. Intrafamilial transmission seems to have occurred in all of the families being studied. Among the patients with HTLV-1, 30% (3/10) already had some symptom related to the infection. DISCUSSION The increase in prevalence rates according to age may be due to late seroconversion of a previously acquired infection, or the cumulative risk of new infections, especially in women. CONCLUSION There was a moderate prevalence of the HTLV infection among adult individuals from the metropolitan area of Belém, with a predominance of HTLV-1. This infection was associated with low income and increasingly older women. It also presented intrafamily spread and negligence in the diagnosis of associated diseases.RESUMO: Introducao: A disseminacao da infeccao pelo virus linfotropico-T humano (HTLV) em familias da area metropolitana de Belem, Para, Brasil, e a ausencia de estudos na populacao em geral requisitam investigacoes que esclarecam melhor a sua prevalencia na regiao. Metodologia: Foi realizada pesquisa de anticorpos anti-HTLV-1/HTLV-2 em individuos adultos transeuntes de logradouros publicos de Belem, entre novembro de 2014 e novembro de 2015. A infeccao foi confirmada por pesquisa de DNA proviral e foi realizada avaliacao clinica e investigacao intrafamiliar dos infectados. Resultados: Dos 1.059 individuos investigados, 21 (2,0%) apresentaram amostras sororeagentes, 15 (1,4%) confirmados para HTLV-1, 5 (0,5%) para HTLV-2 e o DNA proviral foi indetectavel em 1 caso. A media de idade dos infectados (57,2) foi maior que a dos nao infectados (46,2) (p = 0,0010). A infeccao aumentou com a idade e se destacou nos individuos com renda familiar menor ou igual a um salario minimo. A transmissao intrafamiliar parece ter ocorrido em todas as familias investigadas. Dentre os portadores de HTLV-1, 30% (3/10) ja apresentavam algum sintoma relacionado a infeccao. Discussao: O aumento da infeccao de acordo com a idade pode ocorrer por soroconversao tardia de infeccao pre-adquirida ou pelo risco cumulativo de novas infeccoes, sobretudo em mulheres. Conclusao: A infeccao por HTLV demonstrou moderada prevalencia na populacao estudada, com predominio do HTLV-1. Essa mostrou-se associada a baixa renda e ao aumento da idade das mulheres. Tambem apresentou disseminacao intrafamiliar e negligencia no diagnostico das doencas associadas.

Low genetic diversity of the Human T-cell Lymphotropic Virus (HTLV-1) in an endemic area of the Brazilian Amazon basin

The Human T-cell Lymphotropic Virus (HTLV-1) is a Deltaretrovírus that was first isolated in the 1970s, and associated with Adult T-cell Leucemia-Lymphoma (ATLL), and subsequently to Tropical Spastic Paraparesis-Myelopathy (TSP/HAM). The genetic diversity of the virus varies among geographic regions, although its mutation rate is very low (approximately 1% per thousand years) in comparison with other viruses. The present study determined the genetic diversity of HTLV-1 in the metropolitan region of Belém, in northern Brazil. Blood samples were obtained from patients at the UFPA Tropical Medicine Nucleus between January 2010 and December 2013. The DNA was extracted and the PX region of the HTLV was amplified using nested PCR. The positive samples were then digested using the Taq1 enzyme for the identification and differentiation of the HTLV-1 and HTLV-2. The 5’LTR region of the positive HTLV-1 samples were amplified by nested PCR, and then sequenced genetically. The phylogenetic analysis of the samples was based on the maximum likelihood method and the evolutionary profile was analyzed by the Bayesian approach. Overall, 78 samples tested positive for HTLV-1, and 44 were analyzed here. The aA (cosmopolitan-transcontinental) subtype was recorded in all the samples. The following evolutionary rates were recorded for the different subtypes–a: 2.10−3, b: 2.69. 10−2, c: 6.23. 10−2, d: 3.08. 10−2, e: 6. 10−2, f: 1.78. 10−3, g: 2.2. 10−2 mutations per site per year. The positive HTLV-1 samples tested in the present study were characterized by their low genetic diversity and high degree of stability.