Evidence of New Endemic Clusters of Human T-Cell Leukemia Virus (HTLV) Infection in Bahia, Brazil

BackgroundSalvador, Bahia (northeastern Brazil), has been identified as the epicenter of Human T-cell leukemia virus Human T-cell leukemia virus (HTLV) type 1 infection in the country. This study aims to estimate the rate of HTLV infection and the geographical distribution of this virus in this state.MethodsAll HTLV tests (chemiluminescence/ELISA assays/Western Blotting) performed in the Central Laboratory of Public Health of Bahia (LACEN) from 2004 to 2013 were included. Data was extracted from LACEN’s database using high volume extract, transformation and load throughput. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants considering municipalities grouped in microregions and/or mesoregions as the unit of analysis.ResultsA total of 233,876 individuals were evaluated. Individuals were from 394 out of 417 municipalities of Bahia (94.5%). HTLV chemiluminescence/ELISA assay was found to be reactive for 3,138 individuals from whom 2,323 had WB results (1,978 positives, 62 negative and 282 indeterminate). Out of 1978 reactive samples, 1,813 (91.7%) were positive for HTLV-1, 58 (2.9%) for HTLV-2 and 107 (5.4%) were for both HTLV-1 and HTLV-2. The cumulative mean rate of HTLV-positive cases in Bahia was 14.4 per 100,000 inhabitants. Three microregions presented rates >20 HTLV-positive cases/100,000 inhabitants: Barreiras (24.83 cases per 100,000 inhabitants), Salvador (22.90 cases per 100,000 inhabitants), and Ilhéus-Itabuna (22.60 cases per 100,000 inhabitants).ConclusionHTLV infection is disseminated in the state of Bahia, with an overall moderate rate of infection. Further studies should be conducted to characterize the epidemiological and clinical profile of HTLV-infected individuals better and to propose effective prevention measures

Impacto da mielopatia associada ao HTLV/paraparesia espástica tropical (TSP/HAM) nas atividades de vida diária (AVD) em pacientes infectados pelo HTLV-1

Objetivo: Descrever o desempenho nas atividades de vida diária (AVD) em pacientes infectados pelo HTLV-1 com TSP/HAM e medir o impacto da doença sobre a qualidade de vida dos pacientes. Método: Trata-se de um estudo descritivo, de corte transversal. Um total de setenta e três pacientes com TSP/HAM acompanhados no Centro de HTLV da Escola Baiana de Medicina e Saúde Pública, Salvador, Bahia, Brasil foram selecionados. O índice de independência funcional foi calculada usando o Health Assessment Questionnaire (HAQ). A qualidade de vida foi avaliada incluindo a capacidade funcional, dor e aspecto físico, utilizando do Short-Form Health Survey (SF-36). Resultados: Um total de setenta e três pacientes com TSP/HAM foram avaliados: a idade média foi de 48,9 ± 11,4 anos, e 57 (78,1%) eram mulheres. A duração da doença TSP/HAM foi de 10 a 37 anos em 50,7% dos pacientes. Trinta e seis pacientes (49,3%) necessitavam de ajuda de suportes para andar. As pontuações mais baixas no desempenho das AVD foram observadas entre as mulheres e se referiam à locomoção e à mobilidade / (98,2%), ao vestuário (73,7%) e ao autocuidado (57,9%). O escore de qualidade de vida para o aspecto físico foi 24,2 e o da capacidade funcional foi 27,1. A média de dor foi 41,7. Conclusão: A TSP/HAM afeta negativamente a qualidade de vida e o desempenho nas AVD dos pacientes. Dispositivos de tecnologia assistiva devem ser usados para melhorar a capacidade funcional e a qualidade de vida desses pacientes.Aim: To describe the performance of activities of daily living (ADL) of HTLV-1 infected patients with HAM/TSP and to measure the impact of the disease on the patients’ quality of life. Methods: This study is a de-scriptive, cross-sectional study. A total of seventy-three HAM/TSP pa-tients were enrolled at the HTLV Center of the Bahia School of Medicine and Public Health, Salvador, Bahia, Brazil. The index of functional inde-pendence was calculated using the Health Assessment Questionnaire HAQ. The quality of life, including functional capacity, pain, and physi-cal appearance was assessed using the Short-Form Health Survey (SF-36).Results: A total of seventy-three HAM/TSP patients were enrolled with a mean age of 48.9 ± 11.4 years, 57 of whom were (78.1%) women. The duration of HAM/TSP disease was 10 to 37 years (in 50.7% of the patients). Thirty-six patients (49.3%) had a need for walking supports. The lowest ADL performance scores were observed among women and referred to mobility/locomotion (98.2%), dressing (73.7%), and self-care (57.9%) aspects. The quality of life score for the physical aspect was 24.2, and the functional capacity was 27.1. The average for pain was 41.7. Conclusion: HAM/TSP has a negative impact the on the ADL performance of the patients and their quality of life. Assistive technol-ogy devices should be used to improve functional capacity and quality of life for these patients

C7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive disease that occurs in individuals infected with the human T lymphotropic virus type 1 (HTLV-1). Patients with aggressive ATLL have a poor prognosis because the leukemic cells are resistant to conventional chemotherapy. We have investigated the therapeutic efficacy of a biphosphinic cyclopalladated complex {Pd2 [S(−)C2, N-dmpa]2 (μ-dppe)Cl2}, termed C7a, in a patient-derived xenograft model of ATLL, and investigated the mechanism of C7a action in HTLV-1-positive and negative transformed T cell lines in vitro. In vivo survival studies in immunocompromised mice inoculated with human RV-ATL cells and intraperitoneally treated with C7a led to significantly increased survival of the treated mice. We investigated the mechanism of C7a activity in vitro and found that it induced mitochondrial release of cytochrome c, caspase activation, nuclear condensation and DNA degradation. These results suggest that C7a triggers apoptotic cell death in both HTLV-1 infected and uninfected human transformed T-cell lines. Significantly, C7a was not cytotoxic to peripheral blood mononuclear cells (PBMC) from healthy donors and HTLV-1-infected individuals. C7a inhibited more than 60% of the ex vivo spontaneous proliferation of PBMC from HTLV-1-infected individuals. These results support a potential therapeutic role for C7a in both ATLL and HTLV-1-negative T-cell lymphomas

Evaluación de la infección por Strongyloides stercoralis en pacientes con HTLV-1

Introduction: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis (S. stercoralis) infection with low therapeutic response. Objective: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1, who were seen at a Reference Center for HTLV-1 (CHTLV), in Salvador, Bahia, Brazil. Materials and methods: This was a cross-sectional study conducted with 178 HTLV-1-infected individuals, treated at the HTLV specialized center between January 2014 and December 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed by an in house Enzyme Lynked-Immunosorbent Assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot. Results: The frequency of S. stercoralis infection was 3.4% (6/178). Moreover, individuals infected with S. stercoralis from rural area (50.0%; 3/6), also showed S. stercoralis hyperinfection (> 3,000 larvae/gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). Conclusions: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.Introducción. Los individuos infectados por el virus linfotrópico T humano tipo 1 (HTLV-1) pueden presentar formas graves y diseminadas de infección por Strongyloides stercoralis (S. stercoralis) con baja respuesta terapéutica. Objetivo. Investigar la infección por S. stercoralis y la seroprevalencia de IgG anti-S. stercoralis en individuos infectados por HTLV-1, que fueron atendidos en un Centro de Referencia para HTLV-1 (CHTLV), en Salvador, Bahía, Brasil. Materiales y métodos. Estudio transversal realizado con 178 individuos infectados por HTLV-1, atendidos en el centro especializado de HTLV entre enero de 2014 y diciembre de 2018. El diagnóstico parasitológico de S. stercoralis se realizó mediante métodos de Hoffman, Pons y Janer, cultivo en placa de agar y Baermann-Morais. La detección de IgG anti-S. stercoralis se realizó mediante un ensayo de inmunoabsorción enzimática (ELISA) casero. La infección por HTLV-1 se diagnosticó usando un ELISA comercial y se confirmó mediante transferencia Western. Resultados. La frecuencia de infección por S. stercoralis fue del 3,4% (6/178). Además, los individuos infectados por S. stercoralis de la zona rural (50,0%; 3/6) también mostraron hiperinfección por S. stercoralis (> 3.000 larvas / gramo de heces). La frecuencia de anticuerpos IgG anti-S. stercoralis fue del 20,8% (37/178). Conclusiones. las personas infectadas por HTLV-1 que viven en condiciones sanitarias precarias son más propensas a desarrollar formas graves de infección por S. stercoralis. Teniendo en cuenta la alta susceptibilidad y el resultado desfavorable de la infección en estos individuos, se debe considerar el diagnóstico serológico de S. stercoralis para administrar el tratamiento

Protocol for evaluating the in vitro effect of violet light-emitting diodes (LEDs) 410 nm ± 10 nm on yeast cultures

BACKGROUND: Candida spp and Malassezia spp cause superficial infections that may be resistant to conventional treatments. Violet light-emitting diodes (LEDs) therapy is a therapeutic alternative. PURPOSE: To describe the protocol for evaluating the antifungal effect of violet LEDs 410 nm ± 10 nm on Candida spp and Malassezia spp in vitro. PROTOCOL: LEDs 410 nm ± 10 nm are applied to a fungal suspension at fluences of 61.13 J/cm2, 91.70 J/cm2, and 183.39 J/cm2. The isolates are cultured for 48 to 72 hours. Colony forming units (CFUs) are quantified by visual counting and percent culture plate occupancy by digital analysis. Morphology is assessed by light microscopy and Gram staining, and yeast metabolism/function by transmission electron microscopy, assessment of reactive oxygen species, and DNA fragmentation. DATA ANALYSIS: the percentage of LEDs inhibition is calculated considering the growth of the negative control condition and the percentage of plate occupancy by yeasts by dividing the number of pixels classified as colonies by the total number of pixels on the plate. The morphological and functional aspects are described for the intervention and negative control. The ANOVA test is used to compare the mean percentages of growth inhibition and plate occupancy between the three fluences of LEDs 410 nm ± 10 nm and the negative control. ESTIMATED RESULTS: We intend to determine the antifungal effect of the different fluences of LEDs 410 nm ± 10 nm on Candida spp and Malassezia spp. The evaluation of other fungal species by this protocol should be investigated

Clinical Outcomes of Thirteen Patients with Acute Chagas Disease Acquired through Oral Transmission from Two Urban Outbreaks in Northeastern Brazil

Chagas disease is caused by a parasitic protozoan transmitted to humans by the contaminated feces of blood-feeding assassin bugs from the Triatominae subfamily. It may also be transmitted from mother to baby during pregnancy, by breastfeeding, blood transfusion or organ transplant. In rare cases, the disease can also be caused by accidental ingestion of contaminated food (sugar cane or açaí juice, drinking water, etc.). Acute Chagas disease often presents itself as a mononucleosis-like syndrome, with symptoms including fever, lymph node enlargement and muscle pain. The mortality rate of acute Chagas disease is high, mainly due to heart failure as a consequence of cardiac fiber lesions. There are few studies describing clinical outcomes and the disease progression of patients who receive therapeutic treatment, especially with regard to cardiac exam findings. In this report, the authors describe clinical findings from two micro-outbreaks occurring in impoverished towns in northeastern Brazil. Prior to receiving treatment, patient mortality rate was 28.6% in one of the outbreaks, and one pregnant woman experienced a spontaneous abortion due to the disease in the other outbreak. Most patients complained of fever, dyspnea, myalgia and periorbital edema. After receiving a two-month course of treatment, clinical symptoms improved and the number of abnormalities in cardiac exams decreased

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection