Mycobacterium tuberculosis y virus linfotrópico humano, una co-infección fatal / Mycobacterium tuberculosis and human lymphotropic virus, a fatal co-infection

La tuberculosis es una infección de alta incidencia en Latinoamérica. Su presentación como infección activa está determinada por factores de riesgo del hospedero. Comunicamos el caso clínico de una mujer joven que presentó una forma grave de tuberculosis pulmonar. Al explorar sus factores de riesgo se confirmó un estado de inmunosupresión profundo, causado por un linfoma de células T, asociada a una co-infección por virus linfotrópico T humano tipo 1. Se destacan los aspectos microbiológicos y de pronóstico de la co-infección de Mycobacterium tuberculosis y HTLV-1

Tuberculosis is a high-incidence infection in Latin America. Its presentation as an active infection is determined by risk factors in the host. We report the case of a young woman who presented a severe form of pulmonary tuberculosis. When exploring her risk factors, a profound state of immunosuppression was found, caused by T-cell lymphoma, associated with co-infection with human lymphotropic virus. Microbiological and prognostic aspects of Mycobacterium tuberculosis and HTLV-1 co-infection are highlighted.

Computed tomography with 6-year follow-up demonstrates the evolution of HTLV-1 related lung injuries: A cohort study.

Previous observational studies have demonstrated the development of pulmonary impairments in human T-lymphotropic virus type 1 (HTLV-1) infected individuals. The main observed lesions due to chronic inflammation of viral infection in situ are bronchiectasis and lung-scarring injuries. This lung inflammation may be the causal agent of restrictive and obstructive lung diseases, primarily in tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) patients. We conducted a prospective cohort study to compare spirometry and high-resolution computed tomography (HRCT) findings among 28 HTLV-1-carrier patients over the course of 6 years (2014-2019) (male/female: 7/21; mean age: 54.7 ± 9.5, range: 41-68 years). Chest HRCT exams revealed the development and evolution of lung lesions related to TSP-HAM: including centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. Spirometry exams showed maintenance of respiratory function, with few alterations in parameters suggestive of obstructive and restrictive disorders primarily in individuals with lung lesions and TSP-HAM. The findings of the present study indicate that pulmonary disease related to HTLV-1 is a progressive disease, with development of new lung lesions, mainly in individuals with TSP-HAM. To improve clinical management of these individuals, we recommend that individuals diagnosed with PET-MAH undergo pulmonary evaluation.

Prevalence of infection by human T Cell lymphotropic viruses (HTLV-1/2) in adult population in Vitoria-ES

ABSTRACT Introduction: Brazil has a high number of HTLV-1/2 infections which are unequally distributed in the country. Most prevalence studies have focused on specific populations, such as blood donors and pregnant women. Some areas, for example the state of Bahia, have robust information about HTLV-1/2 infection, however there is no information available about this infection in the general population of Vitoria, Espírito Santo, Brazil. Objective: To determine the prevalence of HTLV-1/2 infection in adults from the municipality of Vitoria, ES. Methods: A cross sectional study was performed from September 2010 to December 2011, in individuals of both sexes, aged 18 or older living in Vitoria-ES. Venous blood samples were collected and tested for anti-HTLV-1/2 antibodies by chemiluminescent immunoassay (CMIA). Individuals with CMIA reactive results were submitted to a new blood collection for retesting by CMIA, followed by PCR to confirm infection and discriminate the viral type. Results: From 1502 tested samples, eight were reactive in CMIA and all were confirmed by PCR. Therefore, the prevalence of HTLV-1/2 was 0.53% (8/1502, 95% CI: 0.2-1.0%). The infection rate was 0.7% in men (5/711, 95% CI: 0.17-1.51%), and 0.38% in women (3/791, 95% CI: 0 -0.81%). Conclusions: The prevalence of HTLV-1/2 infection was 0.53% (8/1502; 95% CI: 0.2 -0.9%). Confirmatory test using real-time PCR (qPCR) identified seven individuals positive for HTLV-1 and one for HTLV-2. Considering the risk of infected individuals to develop high morbidity and mortality diseases, it would be important to implement public health policies aimed at stopping transmission of these viruses in this municipality. 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

HTLV-I induces lesions in the pulmonary system: A systematic review.

This study analyzed the relationship between infection by human T-cell lymphotropic virus type 1 (HTLV-1) and changes in the pulmonary system. Cohort and case-control study models that analyzed a causal association between HTLV-1 and changes in the pulmonary system were considered. There were no restrictions on language and publication period. The study was registered in the PROSPERO systematic analysis database (Protocol No. CRD42017078236) and was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The following databases were used: PubMed, BVS Regional Portal, Embase, CINAHL and Web of Science. We utilized the Newcastle-Ottawa Scale to assess the methodological quality of published studies and the Kappa coefficient to assess the agreement level between two reviewers. Of the total 1156 studies retrieved by the search strategy, 28 were considered potentially eligible (Kappa test = 0.928). Of the 28 studies, three fully met the inclusion criteria. These indicated that pulmonary lesions, such as bronchiectasis and bronchitis/bronchiolitis, were observed in patients with HTLV-1, with high-resolution computed tomography of the chest being the main method of diagnostic investigation. The analyzed cohort and case-control studies indicated an etiological relationship between HTLV-1 infection and the presence of lung lesions, with emphasis on bronchiectasis in the presence of high viral loads, as well as a higher mortality in these individuals compared with the general population.

CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.

The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

Increased expression of HBZ and Foxp3 mRNA in bronchoalveolar lavage cells taken from human T-lymphotropic virus type 1-associated lung disorder patients.

OBJECTIVE: Human T-lymphotropic virus type 1 (HTLV-I) causes adult T-cell leukemia/lymphoma (ATLL), and is associated with chronic inflammatory diseases, including inflammatory pulmonary diseases. HTLV-I bZIP factor (HBZ), which is expressed in all adult T-cell leukemia cells, plays a critical role in the development of lymphoma and systemic inflammation. HTLV-I is harbored by CD4(+) T cells that express forkhead box P3 (Foxp3), and HBZ interacts with Foxp3. This study investigated the chest computed tomography (CT) findings and expression of HBZ and Foxp3 in the bronchoalveolar lavage (BAL) cells from patients with HTLV-I-associated lung disorders. METHODS: CT scans obtained from 37 patients (10 men and 27 women, aged 37-77 years) with HTLV-I-associated lung disorders were retrospectively evaluated. The expression levels of HBZ and Foxp3 mRNA in BAL cells and the levels of inflammatory cytokines in the BAL fluid (BALF) from patients were compared with those in control subjects. RESULTS: CT scans frequently revealed a diffuse panbronchiolitis (DPB)-like pattern, along with a nonspecific interstitial pneumonia (NSIP) pattern. An analysis of the BALF revealed lymphocytosis and increased expression of HBZ mRNA in patients with HTLV-I-associated lung disorders. The expression of Foxp3 mRNA positively correlated with the percentages of lymphocytes present in the BALF. The inflammatory cytokine and IL-10 levels were significantly increased in the BALF from patients with HTLV-I-associated lung disorders. CONCLUSION: The NSIP pattern may be a manifestation of pulmonary involvement in HTLV-I-infected patients, as is the DPB-like pattern. HBZ and Foxp3 likely have a role in the development of lung inflammation.

Pulmonary CT findings in 320 carriers of human T-lymphotropic virus type 1.

PURPOSE: To retrospectively evaluate pulmonary computed tomographic (CT) findings in human T-lymphotropic virus type 1 (HTLV-1) carriers, who were characterized by means of polyclonal integration of proviral DNA. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. Chest CT scans obtained between January 1996 and October 2004 in 320 (154 men, 166 women; age range, 31-86 years; mean, 64 years) patients with HTLV-1 were retrospectively evaluated by three chest radiologists. Parenchymal abnormalities (ground-glass opacity, consolidation, centrilobular nodules, thickening of bronchovascular bundles, interlobular septal thickening, and bronchiectasis) were evaluated, along with enlarged lymph nodes and pleural effusion. In 58 patients who underwent surgical biopsy or transbronchial biopsy, comparison of CT images with the actual specimens was performed by a pathologist and three chest radiologists. RESULTS: On CT scans, abnormal findings were seen in 98 (30.1%) patients and consisted of centrilobular nodules (n = 95), thickening of bronchovascular bundles (n = 55), ground-glass opacity (n = 51), bronchiectasis (n = 50), interlobular septal thickening (n = 28), and consolidation (n = 5). These abnormalities were predominantly seen in the peripheral lung parenchyma (n = 70). Pathologically, these findings corresponded to lymphocytic infiltration along respiratory bronchioles and bronchovascular bundles. Pleural effusion and enlarged lymph nodes were found in two and five patients, respectively. CONCLUSION: CT findings in patients with HTLV-1 consisted mainly of centrilobular nodules, ground-glass opacity, and thickening of the bronchovascular bundles in the peripheral lung. These CT findings are considered suggestive of thoracic involvement in patients with HTLV-1.

Treatment for HTLV-I associated arthropathy: a case study and synovial tissue culture analysis.

OBJECTIVE: There are few reports regarding the treatment of HTLV-I associated arthropathy (HAAP). This is a case study describing the treatment of a patient diagnosed with HAAP. We also analyzed the effects of various agents on cultured synovial tissue explants from the patient. METHODS: Arthroscopic synovectomy of the left knee was performed. We investigated the effects of pirarubicin (THP), bestatin, betamethasone, and hyaluronic acid (HA) in synovial tissue culture to evaluate the efficacy of these medications. RESULTS: Swelling and pain of the left knee was transiently diminished after synovectomy. However, bilateral swelling of the knees and C reactive protein (CRP) concentrations were increased. In the explant culture experiments, CD8+ cells decreased with the addition of bestatin, betamethasone, and HA. The structure of synovial cells was preserved by the addition of HA. However, the addition of THP induced fibrosis of synovial tissues, increased cells without nuclei, and diminished fascin-expressing cells. CONCLUSION: THP inhibited, but HA preserved the structure of hypertrophic synovial cells. Scopic synovectomy effectively improved joint effusion and pain; however, the effect was transient, and additional treatment with predonisolone was required. Therefore, it is important to develop a more effective treatment for HAAP.

HTLV-1-associated bronchopneumonopathy (HAB): CT-pathological correlation.

We describe the thin-section CT appearances of HTLV-1-associated bronchopneumonopathy, with histopathological correlation, in two biopsy proven cases.

Primary adult T cell leukemia of bone: two patients with primary bone lesion showing monoclonal integration of HTLV-I proviral DNA.

Adult T cell leukemia (ATL), a neoplasm of mature helper T lymphocytes is etiologically associated with human T lymphotropic virus type-I (HTLV-I). ATL cells infiltrate various organs, the lung, skin, central nervous system, gastrointestinal tract, and bone, causing various clinical manifestations. Two unusual cases of ATL, in which lytic bone lesion was the primary site of ATL, are described. One patient had multiple lytic lesions in bones without any involvement of other organs, and the other patient had a bone lesion in the right radius, which disappeared after chemotherapy. In both cases, monoclonal integration of HTLV-I provirus was demonstrated in the genomic DNA from each bone lesion. Although their clinical courses and pathological findings were different, ATL in both patients began as a bone lesion, showing that primary lymphoma of bone can be manifested in ATL cases.

Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies.

We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 men and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific.

Primary T-cell lymphoma with myelopathy associated with HTLV-1.

The case of a patient who had myelopathy associated with human T-cell lymphotropic virus Type 1 (HTLV-1) for 10 years and developed a T-cell lymphoma in the cerebellum is reported. The relationship between myelopathy associated with HTLV-1 and primary T-cell lymphoma is discussed.