High Human T-Cell Leukemia Virus Type 1c Proviral Loads Are Associated With Diabetes and Chronic Kidney Disease: Results of a Cross-Sectional Community Survey in Central Australia.

BACKGROUND: A link between chronic inflammation and several noncommunicable diseases (NCDs) has been established. Although chronic infection with the human T-cell leukemia virus type 1 (HTLV-1) is the recognized cause of several inflammatory diseases and these are associated with a high number of HTLV-1-infected cells in peripheral blood (proviral load [PVL]), possible interactions between PVL and NCDs have not been studied at a community level. METHODS: Adult Aboriginal residents of 7 remote communities were invited to complete a health survey between 25 August 2014 and 30 June 2018. Blood was drawn for HTLV-1 serology and PVL, and relevant medical conditions were obtained from health records. Associations between HTLV-1 PVL and diabetes, chronic kidney disease (CKD), and coronary artery disease (CAD) were determined using logistic regression, adjusting for available confounders. RESULTS: Among 510 participants (56% of the estimated adult resident population, 922), 197 (38.6%) were HTLV-1-infected. A high HTLV-1 PVL was associated with a 2-fold increase in the odds of diabetes and CKD (diabetes, adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.61; P = .033 and CKD: aOR, 2.00; 95% CI, 1.03-3.8; P = .041). A nonsignificant association between high PVL and CAD (aOR, 7.08; 95% CI, 1.00-50.18; P = .05) was found for participants aged <50 years at the time of angiography. CONCLUSIONS: In a community-based study in central Australia, people with HTLV-1 who had high HTLV-1 PVL were more likely to have diabetes and CKD. These findings have potential clinical implications.

Strongyloides hyperinfection following hematopoietic stem cell transplant in a patient with HTLV-1-associated T-cell leukemia.

Strongyloides stercoralis has the potential to cause accelerated autoinfection in immunocompromised hosts. Screening tests for strongyloidiasis may be falsely negative in the setting of immunosuppression. We report a case of Strongyloides hyperinfection syndrome in a patient with human T-lymphotropic virus type 1-associated T-cell leukemia early after hematopoietic stem cell transplant. The diagnosis was made by stool ova and parasite examination, despite a negative screening enzyme-linked immunosorbent assay. Because of anticipated prolonged neutropenia, an extended course of treatment was utilized.

Cutaneous histoplasmosis with prominent parasitization of epidermal keratinocytes: report of a case.

Disseminated histoplasmosis most commonly occurs in immunosuppressed individuals and involves the skin in approximately 6% of patients. Cutaneous histoplasmosis with an intraepithelial-predominant distribution has not been described. A 47-year-old man was admitted to our institution with fever and vancomycin-resistant enterococcal bacteremia. He had been diagnosed with T-cell prolymphocytic leukemia 4 years earlier and had undergone matched-unrelated-donor stem cell transplant 2 years earlier; on admission, he had relapsed disease. His medical history was significant for disseminated histoplasmosis 6 months before admission, controlled with multiple antifungal regimens. During this final hospitalization, the patient developed multiple 2-5 mm erythematous papules, a hemorrhagic crust across the chest, shoulders, forearms, dorsal aspect of the fingers, abdomen and thighs. Skin biopsy revealed clusters of oval yeast forms mostly confined to the cytoplasm of keratinocytes and within the stratum corneum; scattered organisms were present in the underlying superficial dermis without any significant associated inflammatory infiltrate. Special stains and immunohistochemical studies confirmed these to be Histoplasma organisms. We highlight this previously unrecognized pattern of cutaneous histoplasmosis to ensure its prompt recognition and appropriate antifungal therapy.

Elderly people with human T-cell leukemia virus type 1-associated myelopathy present an early impairment in cognitive skills.

BACKGROUND: Cerebral changes occur in individuals with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) and seem to predominate in subcortical areas. Little is known about the cognitive decline in the elderly living with HTLV-1. OBJECTIVE: To evaluate the cognitive aging of individuals infected with HTLV-1 aged ≥ 50 years. METHODS: This is a cross-sectional study of former blood donors infected with HTLV-1 who have been followed in the cohort of the Interdisciplinary Research Group on HTLV-1 since 1997. The groups of study consisted of 79 HTLV-1 infected individuals aged ≥ 50 years, with 41 of them presenting symptomatic HAM and 38 being asymptomatic carriers, and 59 seronegative individuals (controls) aged ≥ 60 years. All were submitted to the P300 electrophysiological test and neuropsychological tests. RESULTS: Individuals with HAM presented delayed P300 latency in relation to the other groups, and this latency delay increased progressively with aging. The performance of this group in the neuropsychological tests was also the worst. The HTLV-1- asymptomatic group performance was similar to that of the control group. CONCLUSIONS: Individuals with HAM presented cognitive decline that progressed with aging and, although HTLV-1-asymptomatic carriers appear to present cognitive aging similar to that of healthy elderly people, concern about a subclinical cognitive impairment is warranted in this population.

ANTECEDENTES: Alterações cerebrais ocorrem em indivíduos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1 (HTLV-1) (HAM) e parecem predominar em áreas subcorticais. Pouco se sabe sobre o declínio cognitivo em idosos vivendo com HTLV-1. OBJETIVO: Avaliar o envelhecimento cognitivo de indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos. MéTODOS: Trata-se de um estudo transversal com ex-doadores de sangue infectados pelo HTLV-1 acompanhados na coorte do Grupo Interdisciplinar de Pesquisa em HTLV-1 há 20 anos. Os grupos de estudo foram compostos por 79 indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos, sendo que 41 apresentavam HAM e 38 eram portadores assintomáticos, e 59 indivíduos soronegativos (controles) com idade ≥ 60 anos. Todos foram submetidos ao teste eletrofisiológico P300 e testes neuropsicológicos. RESULTADOS: Indivíduos com HAM apresentaram atraso na latência do P300 em relação aos demais grupos, e esse atraso de latência aumentou progressivamente com o envelhecimento. O desempenho desse grupo nos testes neuropsicológicos também foi o pior. O desempenho do grupo HTLV-1- assintomático foi semelhante ao do grupo controle. CONCLUSãO: Indivíduos com HAM apresentaram declínio cognitivo que progrediu com o envelhecimento e, embora os portadores assintomáticos do HTLV-1 pareçam apresentar envelhecimento cognitivo semelhante ao dos idosos saudáveis, justifica-se a preocupação com um comprometimento cognitivo subclínico nessa população.

Human T-cell Leukemia Virus Type 1 (HTLV-1)-induced Uveitis.

Human T-cell leukemia virus type 1 (HTLV-1) is a human retrovirus that causes T-cell malignant diseases (adult T-cell leukemia/lymphoma) and HTLV-1-related non-malignant inflammatory diseases, such as HTLV-1 uveitis. Although the symptoms and signs of HTLV-1 uveitis are nonspecific, intermediate uveitis with various degrees of vitreous opacity is the most common clinical presentation. It can occur in one or both eyes and its onset is acute or subacute. Intraocular inflammation can be managed with topical and/or systemic corticosteroids; however, recurrence of uveitis is common. The visual prognosis is generally favorable, but a certain proportion of patients have a poor visual prognosis. Systemic complications of patients with HTLV-1 uveitis include Graves' disease and HTLV-1-associated myelopathy/tropical spastic paraparesis. This review describes the clinical characteristics, diagnosis, ocular manifestations, management, and immunopathogenic mechanisms of HTLV-1 uveitis.

The Association between Diabetes and Human T-Cell Leukaemia Virus Type-1 (HTLV-1) with Strongyloides stercoralis: Results of a Community-Based, Cross-Sectional Survey in Central Australia.

In central Australia, an area that is endemic for the human T-cell leukaemia virus type-1 (HTLV-1), the prevalence of Strongyloides stercoralis and its association with other health conditions are unknown. A cross-sectional community-based survey was conducted in seven remote Aboriginal communities in central Australia, from 2014 to 2018. All residents aged ≥10 years were invited to complete a health survey and to provide blood for Strongyloides serology, HTLV-1 serology and HTLV-1 proviral load (PVL). Risk factors for Strongyloides seropositivity and associations with specific health conditions including diabetes and HTLV-1 were determined using logistic regression. Overall Strongyloides seroprevalence was 27% (156/576) (children, 22% (9/40); adults (≥15 years), 27% (147/536), varied widely between communities (5-42%) and was not associated with an increased risk of gastrointestinal, respiratory or dermatological symptoms. Increasing age, lower HTLV-1 PVL (<1000 copies per 105 peripheral blood leucocytes) compared to the HTLV-1 uninfected group and community of residence were significant risk factors for Strongyloides seropositivity in an adjusted model. A modest reduction in the odds of diabetes among Strongyloides seropositive participants was found (aOR 0.58, 95% CI 0.35, 1.00; p = 0.049); however, this was lost when body mass index was included in the adjusted model (aOR 0.48, 95% CI 0.48, 1.47; p = 0.542). Strongyloides seropositivity had no relationship with anaemia. Exploring social and environmental practices in communities with low Strongyloides seroprevalence may provide useful lessons for similar settings.

Work ability and associated factors in people living with human T-cell leukemia virus type 1.

BACKGROUND: Infection with the human T-lymphotropic virus type 1 (HTLV-1) affects an estimated 10-15 million people worldwide. However, knowledge of the impact of HTLV-1 infection on work ability is lacking. This study aimed to measure the frequency and identify factors associated with poor work ability in patients living with HTLV-1. METHODS: This cross-sectional study included 207 individuals infected with HTLV-1 who attended the University Hospital in Salvador, Bahia, Brazil. HTLV-1 antibodies were detected in the participants' blood by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blotting. Participants answered a questionnaire on sociodemographic data, personal habits, clinical data, health-related quality of life, and work ability, evaluated using the work ability index questionnaire. A Poisson regression model with a robust variance estimate was used to identify the factors associated with the prevalence of poor work ability. RESULTS: Patients mean age was 55.2, ranging from 19 to 84 years, 73.0% were females, 100% had monthly family income less than US$ 394, and 33.8% presented HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). No individual was classified as having excellent work ability. Poor work ability prevalence was strongly associated (prevalence ratio; 95% confidence interval [CI]) with sedentarism (1.30; 1.03-1.65), neurological symptoms (1.25; 1.02-1.52), and low physical (0.95; 0.94-0.96) and mental (0.98; 0.97-0.99) component summaries of health-related quality of life. CONCLUSIONS: Poor work ability among people living with HTLV-1 is associated with sedentarism, neurologic symptoms, and low health-related quality of life.

Human T-Cell Leukemia Virus Type 1-Related Diseases May Constitute a Threat to the Elimination of Human Immunodeficiency Virus, by 2030, in Gabon, Central Africa.

The Joint United Nations Program on HIV/AIDS (UNAIDS) has adopted the Sustainable Development Goals (SDGs) to end the HIV/AIDS epidemic by 2030. Several factors related to the non-suppression of HIV, including interruptions of antiretroviral therapy (ART) and opportunistic infections could affect and delay this projected epidemic goal. Human T-Cell leukemia virus type 1 (HTLV-1) appears to be consistently associated with a high risk of opportunistic infections, an early onset of HTLV-1 and its associated pathologies, as well as a fast progression to the AIDS phase in co-infected individuals, when compared to HIV-1 or HTLV-1 mono-infected individuals. In Gabon, the prevalence of these two retroviruses is very high and little is known about HTLV-1 and the associated pathologies, leaving most of them underdiagnosed. Hence, HTLV-1/HIV-1 co-infections could simultaneously imply a non-diagnosis of HIV-1 positive individuals having developed pathologies associated with HTLV-1, but also a high mortality rate among the co-infected individuals. All of these constitute potential obstacles to pursue targeted objectives. A systematic review was conducted to assess the negative impacts of HTLV-1/HIV-1 co-infections and related factors on the elimination of HIV/AIDS by 2030 in Gabon.

Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.

Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34+ BM precursor cells using gammaretroviral vectors. While 9 of 10 patients were successfully treated, 4 of the 9 developed T cell leukemia 31-68 months after gene therapy. In 2 of these cases, blast cells contained activating vector insertions near the LIM domain-only 2 (LMO2) proto-oncogene. Here, we report data on the 2 most recent adverse events, which occurred in patients 7 and 10. In patient 10, blast cells contained an integrated vector near LMO2 and a second integrated vector near the proto-oncogene BMI1. In patient 7, blast cells contained an integrated vector near a third proto-oncogene,CCND2. Additional genetic abnormalities in the patients' blast cells included chromosomal translocations, gain-of-function mutations activating NOTCH1, and copy number changes, including deletion of tumor suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement. These findings functionally specify a genetic network that controls growth in T cell progenitors. Chemotherapy led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth. Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer.

Acute cardiac tamponade: presenting sign of acute leukaemia.

Cardiac tamponade is a life-threatening emergency that has to be promptly recognised. We report the case of a young adult patient with an acute cardiac tamponade as a rare presenting symptom of T-cell acute leukaemia. An emergency pericardiocentesis was performed with immediate relief of the symptoms. The aetiology was diagnosed on the basis of the serological hyperleucocytosis and the anatomopathological analysis of the pericardial fluid. The patient was subsequently referred for chemotherapy. Acute leukaemia presenting with pericardial tamponade as a first sign is rare, and described only in a few case reports. Furthermore, we discuss the diagnostic and therapeutic measures of haemodynamic unstable cardiac tamponade.

Critical illness polyneuropathy: a rare but serious adverse event in pediatric oncology.

Critical illness polyneuropathy (CIP) may aggravate sepsis and multiorgan dysfunction in pediatric oncology patients characterized by quadriparesis and difficult weaning from mechanical ventilation. Here, we report on an adolescent patient with acute lymphoblastic T-cell leukemia who developed critical illness neuropathy after an episode of sepsis with need for mechanical ventilation and intravenous catecholamines. Differential diagnoses like vincristine-induced polyneuropathy, anterior lumbosacral radiculopathy (ALR), Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy - all occurring in pediatric patients with acute leukemia - are discussed.

Fulminant Hepatitis due to de novo Hepatitis B after Cord Blood Transplantation Rescued by Medical Treatment.

A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.

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.

Severe and recurrent episodes of bronchiolitis obliterans organising pneumonia associated with indolent CD4+ CD8+ T-cell leukaemia.

The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs. Clinical and pathological characteristics revealed bronchiolitis obliterans with organising pneumonia (BOOP) that responded dramatically to prednisone. BOOP is characterised by inflammation of the bronchioles and surrounding tissue in the lungs. It can mimic infectious pneumonia but diagnosis is suspected when there is no response to multiple antibiotic treatment, and blood and sputum cultures are negative for microorganisms. A high proportion of double-positive (DP)-T-cells was detected in peripheral blood and in bronchoalveolar lavage, expressing CD4 and CD8alphabeta heterodimer with memory phenotype. These DP-T-lymphocytes expressed specific homing molecules that could explain their tropism to lung tissue, giving rise to the clinical symptoms. The patient did not present organomegaly, lymphadenopathy, lymphocytosis or other features of malignancy. However, T-cell receptor Vbeta chain analysis indicated clonal rearrangement, and cytogenetic studies displayed chromosomic alterations that were similar to clonal proliferation observed in ataxia-telangiectasia and T-prolymphocytic leukaemia. The findings suggest a smouldering form of lymphoproliferation, the first sign of which was bronchiolitis obliterans organising pneumonia requiring constant corticoid treatment.

Anemia and survival in childhood acute lymphoblastic leukemia.

BACKGROUND: Several studies have demonstrated that patients with childhood acute lymphoblastic leukemia presenting with mild anemia at diagnosis have an increased risk of poor outcome compared to patients with more severe anemia. However, it has not been reported whether there is any correlation between degree of anemia and leukemia subtype. DESIGN AND METHODS: In a cohort of 1162 patients with childhood acute lymphoblastic leukemia we analyzed whether there was a correlation between degree of anemia and leukemia subtype. We also studied the association between degree of anemia and event-free survival within the subtypes. RESULTS: Hemoglobin levels at diagnosis were distributed in a non-random pattern. The degree of anemia was significantly different for three distinct groups of patients compared to the remaining patients (mean hemoglobin; T-cell leukemia: 106 g/L versus 76 g/L (precursor B-cell acute lymphoblastic leukemia); within precursor B-cell ALL: TEL-AML1 positive: 68 g/L versus 79 g/L; BCR-ABL positive: 93 g/L versus 76 g/L; each p<0.05). Furthermore, in contrast to the entire study group, patients with T-cell leukemia, TEL-AML1(+), and BCR-ABL(+) precursor B-cell leukemia had a more favorable prognosis if presenting with a higher hemoglobin level (>/=80 g/L). CONCLUSIONS: These observations indicate that the formerly reported direct correlation between severity of anemia and survival in childhood acute lymphoblastic leukemia mainly reflects differences in the degree of anemia between distinct biological subgroups with different treatment outcomes. On the other hand, the inverse relationship between severity of anemia and survival found within specific subgroups suggests that very low hemoglobin levels at diagnosis are associated with more advanced disease in these subgroups.

What is your diagnosis? Pancytopenia in a dog.

A 4-year-old male, castrated, mixed-breed dog was presented to the Colorado State University Veterinary Teaching Hospital with a 1-week history of polyuria, polydipsia, lethargy, fever, inappetence, weight loss, and soft mucoid stool. The dog was depressed and had pale, icteric mucous membranes. Results of a CBC included normocytic, normochromic, nonregenerative anemia, neutropenia, and thrombocytopenia, with 43% blast cells (200/microL), many of which contained fine azurophilic granules. Cytologic evaluation of the bone marrow aspirates revealed mild granulocytic hyperplasia that appeared to be left-shifted in an apparent maturation arrest. A large population of blast cells comprised 35% of nucleated cells; the blasts had high nuclear to cytoplasmic ratios, deeply basophilic cytoplasm with vacuoles, and prominent nucleoli. Most cells also contained many fine azurophilic granules clustered in the paranuclear region. At necropsy, neoplastic cells were abundant in the bone marrow. Immunohistochemically the cells expressed CD3epsilon, and an oligoclonal T-cell rearrangement was found. The diagnosis was proliferative disorder of CD3(+) granular lymphocytes, with associated pancytopenia. Because the blast cells were morphologically similar to myeloblasts and immunohistochemistry was required to confirm the diagnosis, T-cell lymphoproliferative disease should be considered in dogs with pancytopenia presenting with similar clinical features.

A 61-Year-Old Caribbean Man With Thrush and Acute Respiratory Failure.

CASE PRESENTATION: A 61-year-old Caribbean man presented to the ED with dyspnea that had progressed over the previous week with associated cough and high fevers. Four days prior to admission, his primary care physician noted oral thrush and obtained a chest radiograph that revealed a right middle lobe infiltrate. He was prescribed levofloxacin and clotrimazole. Despite therapy, his symptoms progressed. He had an 11 pack-year smoking history and hypertension but had been in good health. He denied recent travel, alcohol or illicit drug use, or high-risk sexual behaviors, and his only previous medicine was amlodipine. Institutional review board approval was not obtained for this case report, as all patient data are anonymous and obtained during routine patient care activities.

Cryptococcal immune reconstitution inflammatory syndrome following alemtuzumab therapy.

Alemtuzumab is a lymphocyte ablative agent that may cause susceptibility to severe opportunistic infections similar to those seen in AIDS. Pathogen-specific immune reconstitution syndromes can complicate antiretroviral therapy and immune recovery in HIV-infected patients. We present the first reported case of immune reconstitution syndrome associated with T lymphocyte recovery after alemtuzumab therapy.