Anna Bárbara Carneiro-Proietti

Global epidemiology of HTLV-I infection and associated diseases.

Epidemiologic aspects of human T-lymphotropic virus type I (HTLV-I) infection have been thoroughly studied over the course of approximately 25 years since its first description. The geographic distribution of the virus has been defined, with Japan, Africa, Caribbean islands and South America emerging as the areas of highest prevalence. The reasons for HTLV-I clustering, such as the high ubiquity in southwestern Japan but low prevalence in neighboring regions of Korea, China and eastern Russia are still unknown. The major modes of transmission are well understood, although better quantitative data on the incidence of transmission, and on promoting/inhibiting factors, are needed. Epidemiologic proof has been obtained for HTLV-Is causative role in major disease associations: adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-associated uveitis and infective dermatitis. However, more and better studies are needed for other apparent disease outcomes such as rheumatologic, psychiatric and infectious diseases. Since curative treatment of ATL and HAM/TSP is lacking and a vaccine is unavailable, the social and financial cost for the individual, his/her family and the health system is immense. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of paramount importance.

Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases

SUMMARY Human T-cell leukemia virus type 1 (HTLV-1), the first human retrovirus to be discovered, is present in diverse regions of the world, where its infection is usually neglected in health care settings and by public health authorities. Since it is usually asymptomatic in the beginning of the infection and disease typically manifests later in life, silent transmission occurs, which is associated with sexual relations, breastfeeding, and blood transfusions. There are no prospects of vaccines, and screening of blood banks and in prenatal care settings is not universal. Therefore, its transmission is active in many areas such as parts of Africa, South and Central America, the Caribbean region, Asia, and Melanesia. It causes serious diseases in humans, including adult T-cell leukemia/lymphoma (ATL) and an incapacitating neurological disease (HTLV-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) besides other afflictions such as uveitis, rheumatic syndromes, and predisposition to helminthic and bacterial infections, among others. These diseases are not curable as yet, and current treatments as well as new perspectives are discussed in the present review.

Heterogeneous geographic distribution of human T-cell lymphotropic viruses I and II (HTLV-I/II): serological screening prevalence rates in blood donors from large urban areas in Brazil

Brazil may have the highest absolute number of HTLV-I/II seropositive individuals in the world. Screening potential blood donors for HTLV-I/II is mandatory in Brazil. The public blood center network accounts for about 80.0% of all blood collected. We conducted a cross-sectional study to assess the geographic distribution of HTLV-I/II serological screening prevalence rates in blood donors from 27 large urban areas in the various States of Brazil, from 1995 to 2000. Enzyme immunoassay (EIA) was used to test for HTLV-I/II. The mean prevalence rates ranged from 0.4/1,000 in Florianopolis, capital of Santa Catarina State, in the South, to 10.0/1,000 in São Luiz, Maranhão State, in the Northeast. EIA prevalence rates are lower in the South and higher in the North and Northeast. The reasons for such heterogeneity may be multiple and need further studies.

Infecção e doença pelos vírus linfotrópicos humanos de células T (HTLV-I/II) no Brasil

HTLV-I/II infection is present in all regions of Brazil, but its prevalence varies according to the geographical area, being higher in Bahia, Pernambuco and Pará. It has been estimated that Brazil has the highest absolute number of infected individuals in the world. Blood donors screening and research conducted with special groups (indigenous population of Brazil, IV drug users and pregnant women) are the major sources of information about these viruses in our Country. HTLV-I causes adult T cell leukemia/lymphoma (ATLL), HTLV associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV associated uveitis (HAU), dermatological and immunological abnormalities. HTLV-II is not consistently associated with any disease. Diagnosis is established using screening (enzymatic assays, agglutination) and confirmatory (Western blot, PCR) tests. The viruses are transmitted by blood and contaminated needles, by sexual relations and from mother to child, especially by breast feeding. Prevention efforts should focus on education of positive blood donors, infected mothers and IV drug users.

HTLV in the Americas: challenges and perspectives

The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.

Ten-Year Incidence of Chagas Cardiomyopathy Among Asymptomatic Trypanosoma cruzi–Seropositive Former Blood Donors

Background— Very few studies have measured disease penetrance and prognostic factors of Chagas cardiomyopathy among asymptomatic Trypanosoma cruzi–infected persons. Methods and Results— We performed a retrospective cohort study among initially healthy blood donors with an index T cruzi–seropositive donation and age-, sex-, and period-matched seronegatives in 1996 to 2002 in the Brazilian cities of São Paulo and Montes Claros. In 2008 to 2010, all subjects underwent medical history, physical examination, ECGs, and echocardiograms. ECG and echocardiogram results were classified by blinded core laboratories, and records with abnormal results were reviewed by a blinded panel of 3 cardiologists who adjudicated the outcome of Chagas cardiomyopathy. Associations with Chagas cardiomyopathy were tested with multivariate logistic regression. Mean follow-up time between index donation and outcome assessment was 10.5 years for the seropositives and 11.1 years for the seronegatives. Among 499 T cruzi seropositives, 120 (24%) had definite Chagas cardiomyopathy, and among 488 T cruzi seronegatives, 24 (5%) had cardiomyopathy, for an incidence difference of 1.85 per 100 person-years attributable to T cruzi infection. Of the 120 seropositives classified as having Chagas cardiomyopathy, only 31 (26%) presented with ejection fraction <50%, and only 11 (9%) were classified as New York Heart Association class II or higher. Chagas cardiomyopathy was associated (P<0.01) with male sex, a history of abnormal ECG, and the presence of an S3 heart sound. Conclusions— There is a substantial annual incidence of Chagas cardiomyopathy among initially asymptomatic T cruzi–seropositive blood donors, although disease was mild at diagnosis.

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS‐II study, 2007 to 2008

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics.

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Inflammatory Network

HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) is a systemic immune-mediated inflammatory disease and tissues other than nervous can be damaged, mainly ocular, rheumatic and dermatologic. Over 90% of HTLV-1-infected individuals remain lifelong asymptomatic and this retrovirus persists indefinitely in their CD4+ T-lymphocytes. The infection is maintained due to the proliferation of lymphocytes that harbor a provirus and express HTLV-1 proteins, particularly Tax, promoting an active and selective expansion of infected T cells. High proviral load is related to disease progression, which is correlated to disequilibrium between host and virus. Cytotoxic T lymphocytes are abundant and chronically activated in asymptomatic carriers and in HAM/TSP patients. The asymptomatic carriers were shown to have a high frequency of pro-inflammatory monocytes and anti-inflammatory IL-10+CD4+ and IL-10+CD8+ T-cells, as an immunoregulatory mechanism to counterbalance the monocyte-derived TNF-alpha. A putative immunomodulatory event would be the key to control their overall immunological status. In HAM/TSP, a pro-inflammatory microenvironment is the hallmark of the immunological profile. Enhanced frequency of activated CD8+ T-cells (HLA-DR+) in combination with high CD18 surface expression has been seen. In blood and cerebrospinal fluid, increased levels of Type-1 cytokines, as interferon-(IFN)-gamma, Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-2, and pro-inflammatory IL-6, can be found. Concerning the progression, HLA polymorphisms may influence HAM/TSP and the allele HLA-A*2 has been associated with protection. The authors showed that HAM/TSP is strongly associated with a decreased percentage of B-cells, with enhanced T/B-cell ratio and activated CD8+ T-cells. These immunological parameters have been proposed as a prognostic biomarker for HAM/TSP.

Human immunodeficiency virus prevalence, incidence, and residual risk of transmission by transfusions at Retrovirus Epidemiology Donor Study-II blood centers in Brazil

BACKGROUND: In Brazil nationally representative donor data are limited on human immunodeficiency virus (HIV) prevalence, incidence, and residual transfusion risk. The objective of this study was to analyze HIV data obtained over 24 months by the Retrovirus Epidemiology Donor Study‐II program in Brazil.

Os vírus linfotrópicos de células T humanos (HTLV) na última década (1990-2000): aspectos epidemiológicos

Vinte anos apos o isolamento do virus linfotropico humano tipo I, muitos aspectos epidemiologicos, patogenicos e filogeneticos ja estao esclarecidos. Sabe-se que em regioes endemicas a prevalencia aumenta com a idade e e maior no sexo feminino. Tres patologias estao claramente relacionadas a ele: paraparesia espastica tropical / mielopatia associada ao HTLV, leucemia de celulas T do adulto e uveite. Os modos de infeccao, semelhantes aos dos outros retrovirus, sao: transfusao de sangue, relacoes sexuais nao protegidas, transplacentaria e durante o aleitamento materno. A historia natural das doencas relacionadas ao HTLV-I ainda nao esta bem estabelecida. O risco de portadores da infeccao desenvolverem patologias depende de mais estudos de incidencia para serem corretamente estimados. Menos se conhece sobre o HTLV-II. A despeito do alto grau de homologia entre os dois tipos, os virus interagem de forma bem diversa com os infectados, nao havendo uma associacao clara de doenca com o HTLV-II. Relatos recentes tem apontado sua participacao em casos de mielopatia cronica semelhante a TSP/HAM. As implicacoes incertas do prognostico para pessoas infectadas pelo virus linfotropico humano (HTLV-I/II) e suas formas de transmissao constituem um problema de saude publica, principalmente em areas consideradas endemicas para esse virus.