Predictors of chronic joint pain after Chikungunya virus infection in the INOVACHIK prospective cohort study.

BACKGROUND: Chikungunya can cause persistent chronic joint pain. Knowledge of the risk factors for disease progression is important for preventing and controlling complications. This study aimed to identify factors associated with chronic joint pain. METHODS: This prospective cohort study was conducted at a reference center in Rio de Janeiro. Men and women (aged ≥ 18 years) in the acute phase of Chikungunya were included. Clinical data and samples were collected over three months. Risk factors were evaluated using multivariate and logistic regression analyses. RESULTS: A total of 107 patients were followed up. The incidence rate of joint tenderness was 61.7 %. Female sex (adjusted odds ratio [AOR] 3.24, 95 % confidence interval [CI]:1.07-9.77), diarrhea (AOR 5.08, 95 % CI:1.55-16.67), severe joint pain (AOR 4.26, 95 % CI:1.06-17.06), and CHIKV real-time reverse transcription polymerase chain reaction positivity up to 5 days after the onset of symptoms in urine or saliva (AOR 4.56, 95 % CI:1.41-14.77) were identified as predictors of persistent chronic pain. CONCLUSIONS: In a predominantly female population, musculoskeletal symptoms are not the sole determinant of chronic pain, and careful evaluation of CHIKV detection in alternative body fluids (such as saliva and urine) during the early phase of the disease is warranted.

Two-dimensional strain derived parameters provide independent predictors of progression to Chagas cardiomyopathy and mortality in patients with Chagas disease.

BACKGROUND: Patients with chronic Chagas disease (CD) cardiomyopathy have a high mortality. We evaluated if two-dimensional (2D) strain (ε) parameters provide independent predictors of progression to CD cardiomyopathy and all-cause mortality. METHODS: A total of 408 patients with chronic CD (58.6% women; 53 ± 11 years; clinical forms: indeterminate 34.1%, cardiac 57.6%, digestive 1.2%, cardiodigestive 7.1%) were consecutively included in this single-center prospective longitudinal study. Echocardiographic evaluation included left atrial and left ventricular (LV) function on ε analyses. Primary end-point was a composite of all-cause mortality or heart transplant. Secondary end-point was CD progression defined as the occurrence of changes typical of CD in electrocardiogram, sustained ventricular tachycardia, wall motion abnormalities, or heart failure among patients with the indeterminate form at baseline. Multivariable Cox-proportional-hazards regression analyses were performed to test if 2D ε parameters were associated with the studied end-points. P values < 0.05 were considered significant. RESULTS: The primary end-point occurred in 91 patients after a follow-up of 6.5 ± 2.7 years. CD progression occurred in 26 out of 144 patients without cardiac form at baseline (2.88 cases/100 patient-years). Peak LV circumferential (HR 1.09, 95% CI 1.01-1.18, P = .02) and radial (HR 0.97, 95% CI 0.95-0.99, P = .007) ε, and LV torsion (HR 0.51, 95% CI 0.35-0.74, P = .0004) were independent predictors of the primary end-point. Peak LV radial ε (HR 0.96, 95% CI 0.93-0.99, P = .03) was an independent predictor of CD progression. CONCLUSIONS: Therefore, 2D ε derived parameters can be useful for CD progression and mortality prediction.

Bone sporotrichosis: 41 cases from a reference hospital in Rio de Janeiro, Brazil.

BACKGROUND: Bone sporotrichosis is rare. The metropolitan region of Rio de Janeiro is hyperendemic for zoonotic sporotrichosis and the bone presentations are increasing. METHODS: We studied a retrospective cohort of 41 cases of bone sporotrichosis, diagnosed from 1999-2016. The inclusion criteria was fungal culture isolation from any clinical specimen associated to bone involvement (radiography and/or computed tomography) compatible with fungal osteomyelitis or histopathological findings of bone material compatible with sporotrichosis. Molecular identification was performed when possible. RESULTS: Male patients represented 58.5% of the cases, with a cohort median age of 43 years. Immunosuppressive conditions were present in 68.3% of the patients, mostly HIV coinfection (51.2%). Multifocal bone involvement (more than one anatomical segment) was diagnosed in 61% of the patients, while 39% presented unifocal involvement. The bones of the hands were the most affected (58.5%), followed by the feet (41.5%) and tibia (26.8%). Multifocal group was characterized by a higher proportion of males (p = 0.0045) with immunosuppressive conditions (p = 0.0014). Amphotericin B followed by oral itraconazole was the main treatment, with a median time of 16.7 months (1.5 to 99.2 months), and cure of 53.7% of the patients (84.6% of immunocompetent and 39.3% of immunocompromised patients). Sequelae occurred in 12.2% of the patients-amputations (7.3%) and ankylosis (4.9%), while 22% died in the course of the disease. Sporothrix brasiliensis was the causative agent in all the 9 (22%) performed cases. CONCLUSIONS: Bone sporotrichosis is a chronic, challenging condition with prolonged treatment, often with poor results and sequelae.

Comparative evaluation of the quality of Papanicolaou staining at different intervals of fixation times using 96% ethyl alcohol / Avaliação comparativa da qualidade da coloração de Papanicolaou em diferentes tempos de fixação em álcool etílico a 96%

ABSTRACT Introduction: Fixation of cytological smears consists of immediate immersion in appropriate fixative, in order to preserve cellular morphological characteristics, it is essential for the microscopic examination and diagnostic interpretation. Objective: To evaluate the influence of fixation times on the morphological and staining characteristics of samples fixed in ethanol and stained by the Papanicolaou method. Method: Experimental, quantitative and qualitative research was carried out on 99 samples of the jugal mucosa scrapings from 33 participants, fixed in 96% ethyl alcohol in three different times. Group A: 15 minutes; group B: 30 minutes; group C: seven days. The quality of staining was categorized in Optimal, Good, Regular and Poor, with subsequent recategorization at optimal and non-optimal. To verify the association among the groups and the categories, Fisher's exact test was performed, with significance level of 0.05. Results: From the 99 stained slides, 19 were discarded due to acellularity, remaining 80 slides. From these, 28 in group A, 26 in group B and 26 in group C were evaluated. In Group A, optimal quality was found in 60.7% (n = 17), good in 28.6% (n = 8), regular in 10.7% (n = 3) and poor in 0% (n = 0). In group B optimal was found in 61.5% (n = 16), good in 30.8% (n = 8), regular in 7.7% (n = 2) and poor in 0% (n = 0). In group C, optimal was found in 92.3% (n = 24), good in 7.7% (n = 2), regular in 0% (n = 0) and poor in 0% (n = 0). In the three groups, there was no representation of the Poor category. Conclusion: The results suggest that there is a significant difference in the staining quality (p-value = 0.01) according to the fixation time.

RESUMEN Introducción: La fijación de extensiones citológicas consiste en la inmersión inmediata en fijador adecuado para preservar la morfología celular, siendo esencial para el análisis microscópico y la interpretación diagnóstica. Objetivo: Evaluar la influencia de los tiempos de fijación en las características morfológicasy de tinción de muestras fijadas con metanoly tenidas con el método de Papanicolaou. Método: Se realizó una investigación experimental, cuantitativa y cualitativa de 99 muestras de raspado de la mucosa yugal de 33 participantes, fijadas con etanol al 96% en tres tiempos distintos. Grupo A: 15 minutos; grupo B: 30 minutos; grupo C: 7 días. La calidad de la tinción fue categorizada en óptima, buena, regular y mala, con posterior reclasificación en óptima y no óptima. Para determinar la asociación entre los grupos y las categorias, se realizó la prueba exacta de Fisher, con un nivel de significación del 0,05. Resultado: De las 99 muestras tenidas, 19 fueron desechadas por acelularidad, quedando 80 para ser analizadas. De estas muestras, 28 fueron evaluadas en el grupo A, 26 en el grupo B y 26 en el grupo C. En el grupo A, hemos encontrado calidad óptima - 60,7% (n =17); buena - 28,6% (n = 8); regular -10,7% (n = 3) y mala - 0% (n = 0). En el grupo B, óptima - 61,5% (n = 16); buena - 30,8% (n = 8); regular - 7,7% (n = 2); y mala - 0% (n = 0). En el grupo C, óptima - 92,3% (n = 24); buena - 7,7% (n = 2); regular - 0% (n = 0) y mala - 0% (n = 0). En los tres grupos no hubo representación en la categoria mala. Conclusión: Los resultados sugieren que hay diferencia significativa en la calidad de la tinción (p = 0,01) de acuerdo con el tiempo de fijación.

RESUMO Introdução: A fixação dos esfregaços citológicos consiste na imersão imediata em fixador adequado para preservar as características morfológicas celulares, sendo essencial para a análise microscópica e a interpretação diagnóstica. Objetivo: Avaliar a influência dos tempos de fixação nas características morfológicas e tintoriais de amostras fixadas em álcool etílico e coradas pelo método de Papanicolaou. Método: Realizou-se pesquisa experimental, quantitativa e qualitativa de 99 amostras de raspado da mucosa jugal de 33participantes, fixadas em álcool etílico 96% em três tempos diferentes. Grupo A: 15 minutos; grupo B: 30 minutos; grupo C: sete dias. A qualidade da coloração foi categorizada em ótima, boa, regular e ruim, com posterior recategorização em ótimo e não ótimo. Para verificar a associação entre os grupos e as categorias, realizou-se teste exato de Fisher, com nível de significância de 0,05. Resultado: Das 99 lâminas coradas, 19 foram desprezadas por acelularidade, restando 80 lâminas para serem analisadas. Destas, foram avaliadas 28 no grupo A, 26 no grupo B e 26 no grupo C. No grupo A, foi encontrada qualidade ótima - 60,7% (n = 17); boa - 28,6% (n = 8); regular - 10,7% (n = 3) e ruim - 0% (n = 0). No grupo B, ótima - 61,5% (n = 16); boa - 30,8% (n = 8); regular - 7,7% (n = 2); e ruim - 0% (n = 0). E no Grupo C, ótima - 92,3% (n = 24); boa - 7,7% (n = 2); regular - 0% (n = 0); e ruim - 0% (n = 0). Nos três grupos não houve representação na categoria ruim. Conclusão: Os resultados sugerem que há diferença significativa na qualidade da coloração (p = 0,01) de acordo com o tempo de fixação.

Quality of life and associated factors in patients with chronic Chagas disease.

OBJECTIVES: To evaluate the quality of life (QoL) of patients with Chagas disease (CD) and the association between QoL domains and several clinical, socioeconomic and lifestyle characteristics of this population. METHODS: Cross-sectional observational study conducted from March 2014 to March 2017 including a total of 361 outpatients followed at Evandro Chagas National Institute of Infectious Disease, Brazil. QoL was assessed using the Portuguese shorter version of the original WHO Quality of Life questionnaire (WHOQOL-BREF). Information about clinical CD presentation, presence of comorbidities, functional class, previous benznidazole treatment, socioeconomic profile and lifestyle was also obtained. RESULTS: Environment and physical domains presented the worst QoL scores, while the social relationship domain presented the highest score. Multivariate regression analysis demonstrated that variables independently associated with QoL were functional class, sex, clinical presentation of CD, sleep duration, schooling, physical activity level, smoking, income per capita and residents by domicile. CONCLUSIONS: The low socioeconomic status and the physical limitations imposed by the disease presented an important impact on the QoL reduction among CD patients, especially on environment and physical domains. Strategies to improve QoL among CD patients should be tailored and consider many different variables to maximise improvements not only of patients' physical but also of their mental health.

ABCB1 gene polymorphism associated with clinical factors can predict drug-resistant tuberculosis.

Polymorphism in the ABCB1 gene encoding P-glycoprotein, a transmembrane drug efflux pump, contributes to drug resistance and has been widely studied. However, their association with rifampicin and ethambutol resistance in tuberculosis (TB) patients is still unclear. Genotype/allele/haplotype frequencies in c.1236C > T (rs1128503), c.2677G > T/A (rs2032582), and c.3435C > T (rs1045642) were obtained from 218 patients. Of these, 80 patients with rifampicin and/or ethambutol resistance were selected as the case group and 138 patients were selected for the control group through the results of their culture and drug-sensitive tests. Patients aged <18 years and HIV-positive serologic tests were excluded. ABCB1 polymorphisms were determined using a PCR direct-sequencing approach, and restriction fragment length polymorphism (RFLP). A nomogram was constructed to simulate a combined prediction of the probability of anti-TB drug resistance, with factors including genotype c.1236C > T (rs1128503) (P=0.02), clinical form (P=0.03), previous treatment (P=0.01), and skin color (P=0.03), contributing up to 90% chance of developing anti-TB drug resistance. Considering genotype analyses, CT (rs1128503) demonstrated an increased chance of anti-TB drug resistance (odds ratio (OR): 2.34, P=0.02), while the analyses for ethambutol resistance revealed an association with a rare A allele (rs2032582) (OR: 12.91, P=0.01), the haplotype TTC (OR: 5.83, P=0.05), and any haplotype containing the rare A allele (OR: 7.17, P=0.04). ABCB1 gene polymorphisms in association with others risk factors contribute to anti-TB drug resistance, mainly ethambutol. The use of the nomogram described in the present study could contribute to clinical decision-making prior to starting TB treatment.

Mortality in HIV-infected women, heterosexual men, and men who have sex with men in Rio de Janeiro, Brazil: an observational cohort study.

BACKGROUND: Mortality in HIV-infected individuals might differ by sex and mode of HIV acquisition. We aimed to study mortality in HIV-infected women, heterosexual men, and men who have sex with men (MSM) in a cohort from Rio de Janeiro, Brazil. METHODS: In this observational cohort study, we included HIV-infected women, heterosexual men, and MSM (aged ≥18 years) from the Instituto Nacional de Infectologia Evandro Chagas database who were enrolled between Jan 1, 2000, and Oct 30, 2011, and who had at least 60 days of follow-up. Causes of deaths, defined with the Coding of Death in HIV protocol, were documented. Cox proportional hazards models accounting for competing risks were used to explore risk factors for AIDS-related and non-AIDS-related deaths. FINDINGS: We had 10 142 person-years of follow-up from 2224 individuals: 817 (37%) women, 554 (25%) heterosexual men, and 853 (38%) MSM. Of 103 deaths occurred, 64 were AIDS related, 31 were non-AIDS related, and eight were of unknown causes. In unadjusted analyses, compared with women, the hazard of AIDS-related deaths was higher for heterosexual men (hazard ratio [HR] 3·52, 95% CI 1·30-9·08; p=0·009) and for MSM (2·30, 0·89-5·94; p=0·084). After adjustment for age, CD4 cell counts, last HIV viral load, antiretroviral therapy use, and AIDS-defining infection, AIDS-defining malignant disease, and hospital admission during follow-up, the excess risk of AIDS-related death decreased for heterosexual men (adjusted HR 1·99, 0·75-5·25; p=0·163) but was unchanged for MSM (2·24, 0·82-6·11; p=0·114). Non-AIDS-related mortality did not differ by group. INTERPRETATION: Compared with women, increased risk of AIDS-related death in heterosexual men was partly mitigated by risk factors for AIDS mortality, whereas the excess risk in MSM was unchanged. Further study of reasons for disparity in AIDS-related mortality by mode of transmission is needed. FUNDING: US National Institutes of Health, Brazilian National Council of Technological and Scientific Development (CNPq), and Research Funding Agency of the State of Rio de Janeiro (FAPERJ).

Association of itraconazole and potassium iodide in the treatment of feline sporotrichosis: a prospective study.

Feline sporotrichosis is an endemic disease in Rio de Janeiro, Brazil, where zoonotic transmission of Sporothrix spp. has been reported since 1998. Itraconazole (ITZ) remains the first choice for treating this disease in cats. However, there have been reports of therapeutic failure and a long-term endeavor. Potassium iodide (KI), considered in the past as a drug with variable effectiveness in cats with sporotrichosis, arises as an important option in the treatment of cats from the endemic area of Rio de Janeiro. In order to evaluate the effectiveness of the association of ITZ and KI in naive cats with sporotrichosis, a prospective cohort study was conducted on 30 cats receiving ITZ 100 mg/day and KI 2.5 mg-20 mg/kg/day. Clinical and laboratory adverse effects were assessed once a month according to the standard care protocol. The cure rate was 96.15% within a median of 14 weeks of treatment. Adverse effects were observed in 50% of cats and were managed with a temporary drug suspension and/or a hepatoprotective therapy. The association of ITZ and KI emerges as an effective option for the treatment of feline sporotrichosis.

The role of cigarette smoking and liver enzymes polymorphisms in anti-tuberculosis drug-induced hepatotoxicity in Brazilian patients.

Tuberculosis (TB) is still a major health concern and side-effects related to the treatment, especially drug-induced hepatotoxicity (DIH), should be better investigated. In the present study, a possible association between anti-TB DIH and cigarette smoking, N-acetyltransferase 2 (NAT2), Cytochrome P450 2E1 (CYP2E1) and Cytochrome P450 3A4 (CYP3A4) genotypes was studied in 131 TB Brazilian patients. The NAT2 and CYP3A4 genetic polymorphisms were determined using a polymerase chain reaction (PCR) direct sequencing approach and genetic polymorphisms of CYP2E1 gene were determined by restriction fragment length polymorphism (RFLP). The risk of anti-TB DIH was lower in rapid/intermediate acetylators when compared to slow acetylators (OR: 0.34, CI 95: 0.16-0.71; p < 0.01). A decreased risk of developing anti-TB DIH was also observed in active smokers when compared to non-smokers (OR: 0.28, 95 CI: 0.11-0.64; p < 0.01). Significant association between CYP3A4 genotypes and hepatotoxicity was not observed, as well as between CYP2E1 genotype and hepatotoxicity, whose frequency of patients with wild homozygous was more prevalent. The anti-TB drugs interactions with smoking on hepatotoxicity, as well as the NAT2 phenotype, may require to adjust therapeutic regimen dosages or alarm in case of adverse event developments.