Maria Fernanda Rios Grassi

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

Background Outbreaks of orally transmitted Trypanosoma cruzi continue to be reported in Brazil and are associated with a high mortality rate, mainly due to myocarditis. Methods This study is a detailed report on the disease progression of acute Chagas disease in 13 patients who were infected during two micro-outbreaks in two northeastern Brazilian towns. Clinical outcomes as well as EKG and ECHO results are described, both before and after benznidazole treatment. Results Fever and dyspnea were the most frequent symptoms observed. Other clinical findings included myalgia, periorbital edema, headache and systolic murmur. Two patients died of cardiac failure before receiving benznidazole treatment. EKG and ECHO findings frequently showed a disturbance in ventricular repolarization and pericardial effusion. Ventricular dysfunction (ejection fraction <55%) was present in 27.3% of patients. After treatment, EKG readings normalized in 91.7% of patients. Ventricular repolarization abnormalities persisted in 50% of the patients, while sinus bradycardia was observed in 18%. The systolic ejection fraction normalized in two out of three patients with initially depressed ventricular function, while pericardial effusion disappeared. Conclusions Myocarditis is frequently found and potentially severe in patients with acute Chagas disease. Benznidazole treatment may improve clinical symptoms, as well as EKG and ECHO findings.

Systemic lupus erythematosus, human papillomavirus infection, cervical pre-malignant and malignant lesions: a systematic review.

The purpose of this study was to review and evaluate systematically the scientific evidence on the relationship between systemic lupus erythematosus (SLE), human papillomavirus (HPV) infection, pre-cancerous cervical abnormalities, and cervical cancer. Establishing strict inclusion and exclusion criteria, we performed an extensive search for studies in MEDLINE and BIREME databases to assess the studies that evaluated the frequency of HPV infection, pre-cancerous cervical abnormalities, and cervical cancer in women with SLE. Secondary references were additionally obtained from the included articles. Thirty-three articles met the criteria previously established. Fifteen out of 18 studies that performed cytological analysis showed a higher frequency of squamous intraepithelial lesions in SLE patients compared with normal women. Moreover, three studies found a higher frequency of high-grade squamous intraepithelial lesions. Additionally, it was observed that women with SLE had a higher frequency of HPV infection, confirmed by molecular biology techniques. Curiously, despite the above findings, no increased frequency of cervical cancer was observed in the majority of the studies which addressed this issue. Five studies observed a relationship between cervical abnormalities and previous use of immunosuppressive drugs. This review suggests that SLE patients seem not to be at increased risk for developing cervical cancer; however, they should be considered at higher risk for HPV infection and cervical dysplasia than the general population. Thus, gynecological visits at shorter intervals seem to be a reasonable approach for those patients.

Human T cell lymphotropic virus type 1 (HTLV‐1) proviral load of HTLV‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients according to new diagnostic criteria of HAM/TSP

A high human T‐cell lymphotropic virus type 1 (HTLV‐1) proviral load is described in HTLV‐1‐associated diseases, especially HAM/TSP. However, the cut‐off value to define high levels of HTLV‐1 proviral load is not well established. 281 HTLV‐1‐infected patients from the HTLV reference center in Salvador, Brazil, were followed from 2005 to 2008. Patients were classified as asymptomatic, possible‐, probable‐, and definite‐HAM/TSP, in accordance with diagnostic criteria proposed by De Castro‐Costa et al. (2006): AIDS Res Hum Retroviruses 22:931–935. HTLV‐1 proviral load was determined using real‐time PCR. A receiver operator characteristic (ROC) curve was constructed using only asymptomatic individuals and definite‐HAM/TSP patients. The ROC curve was used to predict the proviral load level that differentiates these two groups. Out of 281 patients, 189 were asymptomatic and 92 were diagnosed with HAM/TSP (22 possible, 23 probable, 47 definite). The mean HTLV‐1 proviral load was higher in possible‐ (89,104 ± 93,006 copies/106 PBMC), ‐probable (175,854 ± 128,083 copies/106 PBMC), and definite‐HAM/TSP patients (150,667 ± 122,320 copies/106 PBMC), when compared to asymptomatic individuals (27,178 ± 41,155 copies/106 PBMC) (P < 0.0001). A comparison of all HAM/TSP groups showed the highest proviral loads in probable‐HAM/TSP patients, yet the differences in mean values were not statistically significant. The ROC curve suggested a value of 49,865 copies/106 PBMC, with 87% sensitivity (95% CI = 74–95) and 81% specificity (95% CI = 75–86), as the best proviral load cut‐off point to differentiate definite HAM/TSP patients from asymptomatic individuals. HTLV‐1 proviral loads are higher in groups of infected patients with neurological symptoms and may represent a relevant biological marker of disease progression. J. Med. Virol. 83:1269–1274, 2011.

Prevalence and Risk Factors for Bacterial Vaginosis and Other Vulvovaginitis in a Population of Sexually Active Adolescents from Salvador, Bahia, Brazil

Bacterial vaginosis, trichomoniasis, and genital candidiasis are considered the main etiologies of vulvovaginitis. Few studies estimate the prevalence of vulvovaginitis among adolescents, especially in Brazil. This study aimed to determine the prevalence and main risk factors associated with bacterial vaginosis and genital infection by C. albicans and Trichomonas vaginalis among a group of adolescents from Salvador, Bahia, Brazil. One hundred sexually active adolescents followed at an adolescent gynecology clinic were included. Endocervical and vaginal samples were obtained during gynecological examination. Nugent criteria were applied for the diagnosis of bacterial vaginosis. For Candida albicans and Trichomonas vaginalis detection, culture in Sabouraud agar plates and Papanicolaou cytology were used, respectively. The mean age of participants was 16.6 ± 1.6 years. The prevalence of bacterial vaginosis was 20% (95% CI 12–28) and of genital infection by Candida was 22% (95% CI 14–30). Vaginal cytology detected Trichomonas vaginalis in one patient. Alcohol, tobacco, and illegal drug use (P = 0.02) and multiple lifetime partners were statistically related to bacterial vaginosis (P = 0.01). The prevalence of bacterial vaginosis and genital candidiasis was similar to other studies carried out among adolescents worldwide.

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.

Leishmaniasis as a Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-Infected Patients: A Literature Review.

Introduction: After the onset of highly active antiretroviral therapy (HAART), some HIV-infected patients present a severe inflammation in response to a latent or a previously treated opportunistic pathogen termed immune reconstitution inflammatory syndrome (IRIS). Few reports of tegumentary and visceral leishmaniasis have been described in association with IRIS. Methods:  A systematic literature review of IRIS in association with leishmaniasis identified 34 reported cases. Results and Discussion: The majority of these occurred in males 4 months following the onset of HAART. The mean CD4 count before HAART was 94 ± 77 cells/mm3, increasing to 5 times the initial value between the onset of HAART and IRIS presentation. Visceral leishmaniasis and post–kala-azar dermal leishmaniasis were the most commonly reported clinical manifestations, followed by tegumentary leishmaniasis and uveitis. Conclusions: Commonly found characteristics included cutaneous involvement, regardless of Leishmania species; appearance of lesions unrelated to time of probable Leishmania infection; rapid recovery of CD4 count following HAART; and rapid progression.

Impact of depression on quality of life in people living with human T cell lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

PurposeA previous study found the prevalence of depression in HTLV-1-infected patients to be approximately 30%, but few studies have attempted to correlate depression with quality of life (QOL) in these patients. The present study investigates the association between depression and QOL in people living with HTLV-1.MethodsA clinical-epidemiological questionnaire, the Mini International Neuropsychiatric Interview and the WHOQOL-Bref were applied to 88 HTLV-1-infected patients (32 with TSP/HAM) at the HTLV Center of the Bahiana School of Medicine and Public Health, Salvador, Brazil.ResultsThe prevalence of depression among people living with HTLV-1 was 34.1%. Depression was significantly associated with a poor QOL in the physical, psychological, social relationship and environment domains, when controlling for other variables, such as gender, age, time of knowledge of serological diagnosis and presence of tropical spastic paraparesis/HTLV-1associated myelopathy (TSP/HAM). Moreover, patients with TSP/HAM experienced a reduction in their QOL in the physical, psychological and environment domains.ConclusionOur results showed that depression negatively affects the quality of life of people living with HTLV-1, regardless of the presence of TSP/HAM. Since it is possible to improve a patient’s QOL by treating depression, psychological evaluations are strongly recommended as a measure to integrate the treatment protocols of HTLV-1 intervention programs.

Evolution of HTLV-1 proviral load in patients from Salvador, Brazil

INTRODUCTION Variations in human T cell lymphotropic virus type 1 (HTLV-1) proviral load (PVL) in infected individuals over time are not well understood. OBJECTIVE To evaluate the evolution of proviral load in asymptomatic individuals and HAM/TSP patients in order to help determine periodicity for measuring proviral load. METHODS A group of 104 HTLV-1 infected patients, followed at the HTLV reference center in Salvador, Brazil, were included in the study (70 asymptomatic and 34 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients). HTLV-1 PVL was measured using real-time polymerase chain reaction (PCR) at baseline and again at another point, either ≤ 12 months, between 12-24 months, or ≥ 24 months. RESULTS HAM/TSP patients had higher PVL (ranging from 11,041 to 317,009 copies/10(6) PBMC) when compared to asymptomatic individuals (ranging from 0 to 68,228 copies/10(6) PBMC). No statistically significant differences were observed in the medians of PVL in HAM/TSP patients or asymptomatic individuals over time. However, in asymptomatic individuals with a PVL below 50,000 copies/10(6) PBMC, a statistically significant two-fold increase was observed over time. CONCLUSION HTLV-1-PVL remained stable in both asymptomatic individuals and HAM/TSP patients over time. Frequent monitoring of asymptomatic individuals with low PVLs is recommended and further studies should be conducted to assess the course of PVL in these patients over extended periods of time.

Candida species isolated from the vaginal mucosa of HIV-infected women in Salvador, Bahia, Brazil

BACKGROUND Vulvovaginal candidiasis (VVC) is the second most common vaginal infection. HIV-infection is a risk factor for this infection. OBJECTIVE To determine the frequency of VVC and to describe the main Candida species isolated and their susceptibility to antifungal drugs in HIV-infected patients, compared to HIV-uninfected women in Salvador, Brazil. METHODS Cross-sectional study including a group of 64 HIV-infected women and 76 uninfected women, followed up at the AIDS reference center and at the Gynecological Clinic of Escola Bahiana de Medicina e Saúde Pública (Salvador, Bahia, Brazil). RESULTS Frequency of Candida spp. was higher in HIV-infected women (29.7%) than in HIV-uninfected controls (14.5%) (p = 0.02). The odds ratio value for vulvovaginal candidiasis in HIV-infected patients was 2.6 (95% CI: 1.07 - 6.32 p = 0.03). Candida albicans was the most commonly isolated species in both HIV-infected (52.3%) and uninfected women (85.7%), followed by C. parapsolis in 17.6% and 14.3%, respectively. In HIV-infected women, C. glabrata, C. parapsilosis, and a coinfection of C. albicans and C. glabrata were also identified. There was no significant difference between Candida species isolated from the vaginal mucosa of women with VVC and colonization of the vaginal mucosa of HIV-infected and HIV-uninfected women. One C. glabrata isolate from an HIV-infected patient was resistant to fluconazole and other two isolates exhibited a dose-dependent susceptibility. CONCLUSION Our results confirm a higher frequency of Candida spp. isolated from the vaginal mucosa of HIV-infected women and a broader spectrum of species involved. Only Candida glabrata isolates showed decreased susceptibility to fluconazole.

An Evaluation of the Spontaneous Proliferation of Peripheral Blood Mononuclear Cells in HTLV-1-Infected Individuals Using Flow Cytometry.

The spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) is a hallmark of the human T-lymphotropic virus (HTLV) type-1. Cell proliferation is usually measured using a [3H]thymidine incorporation assay. This study aims to quantify the spontaneous proliferation of PBMCs using flow cytometry. PBMCs were cultured for 24 to 120 hours in the presence of 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE). For comparison, PBMCs were also cultured with [3H]thymidine. The cutoff values for spontaneous proliferation were >0.06 for the division index and >5.8% for the percentage of divided cells. Sixty-two percent of HTLV-1-infected individuals presented spontaneous proliferation of PBMCs, which was detected in the first 24 hours. Moreover, proliferation was detected in CD4+ and CD8+ T-lymphocyte subsets. A positive correlation was found between the division index and [3H]thymidine incorporation. This method may prove useful to better understand the phenomenon of spontaneous proliferation of PBMC of patients infected with HTLV-1.