Impact of HIV co-infection on immunological biomarker profile of HTLV-1 infected patients.

The impact of HIV co-infection on the plasma immunological biomarker profile of HTLV-1 infected patients was evaluated. The plasma levels of leukotrienes and chemokines/cytokines were quantified by ELISA and Cytometric Bead Array. A total of 138 volunteers were enrolled and divided into two subgroups ("HTLV-1(+)HIV(-)" and "HTLV-1(+)(HIV(+)"), which were categorized according to the HTLV-1-associated neurological disease (AS, pHAM and HAM). Reference controls were BD and HIV mono-infected patients. HAM(+) exhibited higher CD4+ T-cell counts as compared to HIV+ mono-infected patients and lower HTLV-1 proviral load as compared to mono-infected HAM(-) patients. AS(+) exhibited higher levels of CysLT, CXCL8/IL-8 and lower levels of CCL5/RANTES as compared to AS(-). Increased levels of IL-6 and TNF with reduced levels of CXCL10/IP10 and CCL5/RANTES were observed in co-infected pHAM(+) as compared to mono-infected pHAM(-). HAM(+) patients revealed an increase in CXCL8/IL-8, CCL2/MCP-1, CXCL-10/IP-10, TNF and a decrease in IL-2 as compared to HAM(-) subgroup.

Schistosoma mansoni granulomas in the skeletal striated muscles in the murine model of neuroschistosomiasis: histological findings.

Schistosomiasis mansoni presents many clinical manifestations during migration of schistosomes in their hosts, including diarrhea, hepatomegaly, splenomegaly, liver abscesses, skinlesions, brain tumors and myeloradiculopathy. No lesions have been reported in skeletal striated muscles due to schistosomiasis mansoni in the literature. This short communication reports the histopathological findings on skeletal musculature in a murine model of neuroeschistosomiasis mansoni. Lesions were found in the tongue, masseter muscle, buccinator muscle, digastric muscle and temporalis muscle. Worm recovery was carried out to confirm the infection. We describe here, for the first time in the literature, injuries in the skeletal musculature due to Schistosoma mansoni nfection.

Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation may reveal subclinical alterations in human T-cell lymphotropic virus type 1-associated myelopathy.

BACKGROUND: Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) evaluates the motor spinal cord and identifies subclinical myelopathies. We used galvanic-VEMP to compare spinal cord function in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) from asymptomatic status to HTLV-1-associated myelopathy (HAM). METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study with 122 individuals included 26 HTLV-1-asymptomatic carriers, 26 individuals with possible HAM, 25 individuals with HAM, and 45 HTLV-1-seronegative individuals (controls). The groups were similar regarding gender, age, and height. Galvanic stimuli (duration: 400 ms; intensity: 2 mA) were applied bilaterally to the mastoid processes and VEMP was recorded from the gastrocnemius muscle. The electromyographic parameters investigated were the latency and amplitude of the short-latency (SL) and medium-latency (ML) responses. While SL and ML amplitudes were similar between groups, SL and ML latencies were delayed in the HTLV-1 groups compared to the control group (p<0.001). Using neurological examination as the gold standard, ROC curve showed an area under the curve of 0.83 (p<0.001) for SL and 0.86 (p<0.001) for ML to detect spinal cord injury. Sensibility and specificity were, respectively, 76% and 86% for SL and 79% and 85% for ML. Galvanic-VEMP disclosed alterations that were progressive in HTLV-1-neurological disease, ranging from SL delayed latency in HTLV-1-asymptomatic carriers, SL and ML delayed latency in possible HAM group, to absence of VEMP response in HAM group. CONCLUSIONS/SIGNIFICANCE: The worse the galvanic-VEMP response, the more severe the myelopathy. Galvanic-VEMP alteration followed a pattern of alteration and may be a prognostic marker of progression from HTLV-1-asymptomatic carrier to HAM.

Thrombocytopenia as a marker of liver steatosis in a low-endemic area for schistosomiasis mansoni / Trombocitopenia como marcador de esteatose hepática em áreas de baixa endemicidade de esquistossomose mansoni

Summary Introduction: Thrombocytopenia is commonly found in patients living in highly endemic areas for Schistosoma mansoni. Recently, different degrees of liver steatosis have also been associated with low platelet counts worldwide. We investigated the association of platelet counts with hepatosplenic schistosomiasis and with liver steatosis in an area of low prevalence of schistosomiasis in Brazil. Method: Pains, a city in the state of Minas Gerais, Brazil, had a population of 8,307 inhabitants and a schistosomiasis prevalence of 8%. Four micro-areas comprising 1,045 inhabitants were selected for this study. Blood sample was collected and a complete blood count (CBC) was performed. Eighty-seven (87) patients had low platelet counts (group 1 - 8.3%) and 94 volunteers presenting normal CBC were randomized (group 2 - 8.9%). They underwent clinical and ultrasound examinations. Liver steatosis was determined as either present or absent using abdominal ultrasound. A spleen > 12 cm in length, measured by ultrasound (US), was considered to be increased. Data collected were analyzed using SPSS software version 19.0. Results: Twenty-two patients (22/25.3%) in group 1 had liver steatosis compared with 11 volunteers (11.7%) in group 2 (p=0.02). Hepatosplenic schistosomiasis was diagnosed in two patients (p>0.05). Conclusion: Thrombocytopenia was not a good marker of hepatosplenic schistosomiasis mansoni in a low prevalence area in Brazil. Liver steatosis was associated with thrombocytopenia in our study.

Resumo Introdução: Trombocitopenia é um achado comum em pacientes que residem em áreas com alta endemicidade de esquistossomose mansônica. Recentemente, diferentes graus de esteatose hepática também têm sido associados a níveis baixos de plaquetas em todo o mundo. Investigamos a associação de níveis séricos de plaquetas com a forma grave da esquistossomose e com esteatose hepática em área de baixa prevalência de esquistossomose no Brasil. Método: Pains, cidade localizada no estado de Minas Gerais/Brasil, tem população de 8.307 habitantes e prevalência de esquistossomose de 8%. Em quatro microáreas dessa região, 1.045 habitantes foram avaliados para o estudo. Amostra de sangue foi coletada para realização do hemograma. Oitenta e sete (87) pessoas com níveis baixos de plaquetas formaram o grupo 1 (8,3%), e 94 voluntários com hemograma normal foram randomizados para compor o grupo 2 (8,9%). Todos os participantes dos grupos 1 e 2 foram submetidos a exame clínico e ultrassonografia (US) abdominal. Esteatose hepática foi caracterizada como presente ou ausente pela ultrassonografia (US) abdominal. Baços com mais de 12 cm de comprimento à US foram considerados aumentados. Os dados coletados foram analisados pelo programa de estatística SPSS 19.0. Resultados: Vinte e dois (22) indivíduos do grupo 1 (25,3%) e 11 do grupo 2 apresentaram esteatose hepática (11,7%) (p=0,02). Esquistossomose hepatoesplênica foi diagnosticada em dois pacientes (p>0,05). Conclusão: Trombocitopenia não foi um bom marcador de esquistossomose mansônica hepatoesplênica em área de baixa prevalência da esquistossomose no Brasil. Esteatose hepática foi associada com trombocitopenia no presente estudo.

Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil

Abstract INTRODUCTION: The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil. METHODS: Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis. RESULTS: The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%). CONCLUSIONS: Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.

Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni.

BACKGROUND: Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. METHODOLOGY/PRINCIPAL FINDINGS: Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. CONCLUSIONS/SIGNIFICANCE: S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.

Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity.

This study aimed at establishing the immunological signature and an algorithm for clinical management of the different clinical stages of the HTLV-1-infection based on serum biomarkers. A panel of serum biomarkers was evaluated by four sets of innovative/non-conventional data analysis approaches in samples from 87 HTLV-1 patients: asymptomatic carriers (AC), putative HTLV-1 associated myelopathy/tropical spastic paraparesis (pHAM/TSP) and HAM/TSP. The analysis of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-α/IFN-γ, counterbalanced by IL-4/IL-10. The analysis of biomarker networks showed that AC presented a strongly intertwined pro-inflammatory/regulatory net with IL-4/IL-10 playing a central role, while HAM/TSP exhibited overall immune response toward a predominant pro-inflammatory profile. At last, the classification and regression trees proposed for clinical practice allowed for the construction of an algorithm to discriminate AC, pHAM and HAM/TSP patients with the elected biomarkers: IFN-γ, TNF-α, IL-10, IL-6, IL-4 and CysLT. These findings reveal a complex interaction among chemokine/leukotriene/cytokine in HTLV-1 infection and suggest the use of the selected but combined biomarkers for the follow-up/diagnosis of disease morbidity of HTLV-1-infected individuals.

Fatal outcome o infection by dengue 4 in a patent with thrombocytopenic purpuura as a comorbid condition in Brazil / Óbito por dengue 4 no Brasil em paciente com púrpura trombocitopênica idiopática

Dengue is currently a major public-health problem. Dengue virus (DENV) is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions.

Dengue é atualmente um importante problema de saúde pública. O vírus da dengue (DENV) é classificado em quatro sorotipos distintos, DENV 1-4. Após 28 anos de ausência, o DENV-4 foi detectado novamente no Brasil em 2010 no Estado de Roraima, e um ano depois, o vírus foi identificado em outros estados do norte do país, Amazonas e Pará, seguido pelos estados do Rio de Janeiro e São Paulo. Em Minas Gerais, o primeiro caso confirmado de DENV-4 ocorreu no município de Frutal em 2011 e, desde então, o sorotipo foi isolado em um número crescente de pacientes. Apesar do DENV-2 estar associado a um maior risco de formas graves e morte, o DENV-4 também tem sido associado a casos graves e a risco aumentado de manifestações hemorrágicas. Neste relato, descrevemos o primeiro caso fatal confirmado por DENV-4 no Brasil. A paciente era uma menina de 11 anos do município de Montes Claros, no norte de Minas Gerais, Brasil. Apresentava púrpura trombocitopênica idiopática e evoluiu de forma fulminante durante a infecção por dengue, com óbito associado a complicações hemorrágicas. O diagnóstico foi confirmado pela detecção de anticorpos IgM específicos para dengue, por método imunoenzimático, e por semi-nested RT-PCR. Médicos e outros profissionais de saúde devem estar cientes que infecções por DENV-4 também podem resultar em formas graves da doença com complicações hemorrágicas e óbito, principalmente em pacientes com comorbidades.

Brain schistosomiasis in mice experimentally infected with Schistosoma mansoni.

INTRODUCTION: Human neuroschistosomiasis has been reported in the literature, but the possibility of modeling neuroschistosomiasis in mice is controversial. METHODS: In two research laboratories in Brazil that maintain the Schistosoma mansoni life cycle in rodents, two mice developed signs of brain disease (hemiplegia and spinning), and both were autopsied. RESULTS: S. mansoni eggs, both with and without granuloma formation, were observed in the brain and meninges of both mice by optical microscopy. CONCLUSIONS: This is the first description of eggs in the brains of symptomatic mice that were experimentally infected with S. mansoni. An investigation of experimental neuroschistosomiasis is now feasible.

Revisiting the concept of hepatosplenic schistosomiasis and its challenges using traditional and new tools

Different aspects of hepatosplenic schistosomiasis are revisited here. Manson's schistosomiasis causes periportal fibrosis and portal hypertension in approximately 6% of infected subjects, usually with preservation of their hepatic function. The assessment of liver involvement is of major importance in determining the prognosis and risk of complications from schistosomiasis, such as upper digestive bleeding secondary to variceal rupture. For many years, the diagnosis of hepatosplenic schistosomiasis and liver fibrosis was made by abdominal palpation and the finding of liver and/or spleen enlargement. However, there is no consensus regarding the clinical parameters of the liver and spleen to be considered in this physical evaluation. For the last three decades, abdominal ultrasound (US) has become the best imaging technique to evaluate liver fibrosis caused by schistosomiasis mansoni. However, US is a subjective procedure and is therefore examiner-dependent. Magnetic resonance imaging (MRI) findings have provided valuable information in addition to ultrasound and clinical examination. The combination of a comprehensive history and physical examination, basic laboratory tests (a stool examination for Schistosoma mansoni eggs and a blood cell count), biomarkers for liver fibrosis/portal hypertension and imaging methods seem to offer the best approach for evaluating patients with this disease. In situations where research is involved or in patients with severe disease, MRI may be considered.

Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for Schistosomiasis mansoni

Introduction This study aimed to evaluate whether a low platelet count is a good surrogate marker of hepatosplenic schistosomiasis (HSS) in a rural area of Brazil. A small district in southeastern Brazil, with a population of 1,543 individuals and a 23% prevalence of schistosomiasis, was selected for this investigation. Methods In July 2012, 384 volunteers were subjected to clinical, ultrasonography (US), and laboratory examinations, including stool sample analysis. The HSS patients were classified into four groups: Group 1 consisted of patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of patients with a spleen >13cm measured by US; and Group 4 consisted of patients with a palpable spleen. Results Eight patients were in Group 1 (2.1%), twenty-one were in Group 2 (5.5%), eight were in Group 3 (2.1%), and eighteen were in Group 4 (4.7%). A significant difference in the mean platelet counts was observed between the patients with and without HSS (p<0.01). Based on the receiver operating characteristic (ROC) curve (platelet count <143,000/mm3), the sensitivity was greater than 92% in all groups, and the specificity varied from 44.4% to 75%. Conclusions We concluded that in endemic areas, thrombocytopenia demonstrates good sensitivity for detecting HSS and may be used as a screening tool to identify patients with HSS. .

Brain schistosomiasis in mice experimentally infected with Schistosoma mansoni

Introduction Human neuroschistosomiasis has been reported in the literature, but the possibility of modeling neuroschistosomiasis in mice is controversial. Methods In two research laboratories in Brazil that maintain the Schistosoma mansoni life cycle in rodents, two mice developed signs of brain disease (hemiplegia and spinning), and both were autopsied. Results S. mansoni eggs, both with and without granuloma formation, were observed in the brain and meninges of both mice by optical microscopy. Conclusions This is the first description of eggs in the brains of symptomatic mice that were experimentally infected with S. mansoni. An investigation of experimental neuroschistosomiasis is now feasible. .

Association of Schistosoma mansoni-specific IgG and IgE antibody production and clinical schistosomiasis status in a rural area of Minas Gerais, Brazil.

BACKGROUND: Studies in murine models and human populations have indicated that the collagen-rich granulomatous response against parasite eggs trapped in the liver is associated with the development of severe hepatosplenic schistosomiasis, characterized by periportal fibrosis and portal hypertension. The role of the humoral response in parasite susceptibility has been well established, but its participation in disease severity remains poorly understood. In this work, we evaluated the relationship between parasite-reactive IgE and IgG levels and schistosomiasis morbidity in infected patients with similar parasite burdens. METHODOLOGY/PRINCIPAL FINDINGS: Ninety-seven Schistosoma mansoni-infected individuals were subjected to clinical examination and abdominal ultrasound analysis. IgG reactivity and IgE concentration against Schistosoma mansoni soluble egg antigens (SEA) and adult worm antigen preparation (SWAP) were evaluated by ELISA assay. Multivariable linear regression models were used to evaluate the relationship between parasite-reactive antibodies and the co-variables investigated. The study population showed low parasite burden (median 30 eggs/g feces), constant re-infection, and signs of fibrosis was detected in more than 30% of individuals. Most infected individuals showed IgG reactivity, and the median concentrations of IgE anti-SEA and anti-SWAP antibodies were 1,870 and 1,375 ng/mL, respectively. There was no association between parasite burden and antibody response or any parameter of disease severity. However, IgG anti-SWAP level was positively associated with morbidity parameters, such as spleen size and thickness of portal vein at the entrance and secondary branch. In contrast, the data also revealed independent inverse correlations between concentration of parasite-reactive IgE and gallbladder wall thickness, a marker of fibrosis in schistosomiasis. CONCLUSIONS/SIGNIFICANCE: The data indicate that IgG anti-SWAP is positively associated with severe schistosomiasis, independently of parasite burden, while high production of parasite-specific IgE is associated with mild disease in the human population. Antibody profiles are good correlates for schistosomiasis severity and could be tested as biomarkers of disease severity.

Acute schistosomiasis diagnosis: a new tool for the diagnosis of schistosomiasis in a group of travelers recently infected in a new focus of Schistosoma mansoni

Introduction The diagnosis of schistosomiasis mansoni on early stages of infection is important to prevent late morbidity. A simple, cheap, sensitive and specific assay for routine diagnosis of schistosome infection based on the detection of specific IgG for schistosomula tegument antigens (ELISA-SmTeg) was developed by our group. Methods We describe here an acute outbreak involving a travel group of 80 individuals from a non-endemic area of the State of Minas Gerais, Brazil. These individuals were in contact with a freshwater pool where Biomphalaria glabrata was found. Results obtained from our new methodology were compared to IgG antibody titers against soluble worm antigenic preparation (SWAP) by ELISA and, also to parasitological examination, nuclear magnetic resonance and clinical findings. Results ELISA-SmTeg was capable of detecting 64 positive cases among the 80 individuals participating at the survey with a positivity ratio of 80% and a higher sensitivity than ELISA-SWAP that was only sensitive for 56% of positive cases. Besides, a significant correlation was found for the severity of the infection and the specific IgG titers against SmTeg. Conclusions Our data showed that ELISA-SmTeg might serve as the initial diagnostic tool for acute stages of the infection in community-based helminth control programs or for the surveillance of individuals from non-endemic areas. .

An outbreak of acute Schistosoma mansoni Schistosomiasis in a nonendemic area of Brazil: a report on 50 cases, including 5 with severe clinical manifestations.

BACKGROUND: Acute schistosomiasis is a systemic hypersensitivity reaction against the migrating schistosomula and eggs. In this report, we describe an atypical outbreak of the disease with severe cases. Transmission occurred in a nonendemic area of Brazil, which became a new focus of transmission due to the in-migration of infected workers. METHODS: From December 2009 to March 2010, the 50 patients with acute schistosomiasis (group 1) bathed in a swimming pool supplied by a brook on a country estate in the outskirts of São João del Rei, Brazil. Thirty other subjects (group 2) living in the same area, who denied having contact with the swimming pool, volunteered to participate in the study. All participants were submitted to clinical, laboratory, and ultrasound examinations. RESULTS: Five of 50 (10%) patients were admitted to the hospital: 1 with myeloradiculopathy, 1 with diffuse pulmonary micronodules, and 3 with diarrhea and dehydration. All 5 had hypereosinophilia and prolonged fever. Group 1 patients more frequently had cercarial dermatitis (P = .01), blood in the stool (P = .04), and intra-abdominal lymph nodes (P = .001). All group 1 patients were treated with praziquantel; 1 patient with myeloradiculopathy also received oral prednisone (60 mg/day) for 6 months with complete recovery. CONCLUSIONS: This report describes the first time that patients from an outbreak of acute schistosomiasis have been compared to controls. Five subjects (10%) had severe manifestations of schistosomiasis. Diagnosis of the disease and its severity was delayed because physicians did not consider that an epidemic of schistosomiasis might emerge in a nonendemic area.

Proviral load and the balance of serum cytokines in HTLV-1-asymptomatic infection and in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

This study compared the proviral load and the plasma cytokine profiles (interleukin-IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) in 87 HTLV-1-infected individuals, including 28 with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 32 with possible pHAM/TSP and 27 asymptomatic carriers (AC). The control group was composed by 21 HTLV-1-seronegative individuals. Our finding demonstrated that HAM/TSP group presented higher proviral load as compared to all other HTLV-1 groups (p<0.0001). The HAM/TSP group showed higher serum concentration of IL-6 (p=0.0009) as compared to all other groups. Moreover, higher serum concentration of IFN-γ (p=0.0118) and IL-4 (p=0.0166) were observed in HAM/TSP group as compared to the healthy controls. Additionally, the HAM/TSP group also showed higher serum concentration of TNF-α (p=0.0239) and IFN-γ (p=0.0118) as compared to AC. No differences in the serum concentration of IL-2 and IL-10 were observed among the groups. The analysis of cytokine balance demonstrated that HAM/TSP presented higher pro-inflammatory profile with enhanced IFN-γ/IL-10 and IFN-γ/IL-4 ratio as compared to AC and pHAM/TSP. Further analysis pointed out to a positive correlation between the IFN-γ response and the proviral load in AC. Conversely, a negative association between TNF-α and IL-2 with the proviral load was the hallmark of HAM/TSP group. These findings suggested that the proviral load and the pro-inflammatory cytokine profile may be independent events in the peripheral blood of HAM/TSP individuals. The knowledge about the existence of individual virological/immunological behavior upon HTLV-1 infection, may guide to the establishment of more effective therapeutic interventions.