Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Aim: Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy. Methods: Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6-12 months after treatment, and intention-to-treat analysis was used. Results: We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60-0.97) vs. 66% (95% CI 0.40-0.86), p = 0.47, at 6 months and 68% (95% CI 0.43-0.87) vs. 72% (95% CI 0.46-0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group. Conclusion: G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02154269].

Prevalent tuberculosis at HIV diagnosis in Rio de Janeiro, Brazil: the TB/HIV in Rio (THRio) Cohort.

BACKGROUND: Although Brazil has model HIV care programs, many patients continue to present late to care. We studied the frequency of tuberculosis (TB) diagnosed at HIV diagnosis in Rio de Janeiro, Brazil, to quantify missed opportunities for TB prevention. METHODS: People living with HIV (PLHIV) and enrolled in the TB/HIV in Rio study between September 1, 2005, and August 31, 2009, were included. Prevalent TB was defined as TB diagnosed within 60 days of HIV diagnosis or HIV diagnosis during TB therapy. Survival was measured from HIV diagnosis. We conducted Kaplan-Meier survival plots and Cox regression analyses. RESULTS: Four thousand five hundred forty-eight newly diagnosed PLHIV were enrolled: 476 (10.5%) with prevalent TB. Individuals with prevalent TB were older, had lower CD4 counts, and higher viral loads than did those without TB. Median time to receiving highly active antiretroviral therapy (HAART) in those with prevalent TB was 99 days (interquartile range = 58-191) vs. 126 days (interquartile range = 63-301) in those without TB (P = 0.021). Among those with prevalent TB, 17% died during follow-up compared with 8% among those without TB (P < 0.001). After adjustment for sex, age, baseline CD4, and baseline viral load, the risk of occurrence of death remained significantly higher among those with prevalent TB [adjusted hazard ratio = 1.72 (confidence interval 95% 1.19 to 2.48)]. CONCLUSIONS: More than 10% of new PLHIV in our study presented to care with concurrent active TB disease and thus missed the opportunity for undergoing TB preventive therapy. Despite initiating HAART more quickly, these individuals were at a significantly greater risk of death. Earlier HIV diagnosis is necessary to provide earlier initiation of HAART and TB preventive therapy to reduce morbidity and mortality in PLHIV.

The functional assessment of patients with pulmonary multidrug-resistant tuberculosis.

BACKGROUND: Tuberculosis (TB) remains an important public health problem worldwide, as its residual lesions result in functional and quality of life impairments. Few studies have investigated multiple-drug-resistant pulmonary TB (MDR-TB), and the literature regarding the functional parameters of this group of patients is scarce. Functional characterization may point to the need for post-treatment intervention measures that optimize the quality of life in patients with MDR-TB. Thus, this study sought to analyze the respiratory function, functional capacity, and quality of life of patients who were treated for MDR pulmonary TB. METHODS: This study investigated a cross-sectional cohort of MDR-TB patients who underwent drug treatment for at least 18 months. Patients who had associated diseases (human immunodeficiency virus [HIV], severe heart disease, and hypertension) or disabilities that prevented them from walking were excluded. The subjects underwent the following assessments: forced spirometry, a chest radiograph, the 6-min walk test, a bioelectrical impedance analysis, maximal inspiratory and expiratory pressures, and a health-related quality of life questionnaire. RESULTS: Eighteen patients who met the eligibility criteria were enrolled. Spirometric evaluation showed that 78% of the subjects had abnormal patterns. The maximal respiratory pressures were significantly decreased in all subjects, despite the fact that their nutritional status was within the normal range. The distance completed in the 6-min walk test was less than expected in 72% of the subjects. All of the subjects who were evaluated had residual lesions, and 78% reported a worsening in their quality of life. CONCLUSIONS: In conclusion MDR-TB cured subjects exhibit impaired respiratory function and a mildly reduced functional capacity and quality of life, suggesting that a portion of these patients may require a pulmonary rehabilitation approach.

Multilocus variable-number tandem repeat analysis distinguishes outbreak and sporadic Escherichia coli O157:H7 isolates.

Escherichia coli O157:H7 is a major cause of food-borne illness in the United States. Outbreak detection involves traditional epidemiological methods and routine molecular subtyping by pulsed-field gel electrophoresis (PFGE). PFGE is labor-intensive, and the results are difficult to analyze and not easily transferable between laboratories. Multilocus variable-number tandem repeat (VNTR) analysis (MLVA) is a fast, portable method that analyzes multiple VNTR loci, which are areas of the bacterial genome that evolve quickly. Eighty isolates, including 21 isolates from five epidemiologically well-characterized outbreaks from Pennsylvania and Minnesota, were analyzed by PFGE and MLVA. Strains in PFGE clusters were defined as strains that differed by less than or equal to one band by using XbaI and the confirmatory enzyme SpeI. MLVA was performed by comparing the number of tandem repeats at seven loci. From 6 to 30 alleles were found at the seven loci, resulting in 64 MLVA types among the 80 isolates. MLVA correctly identified the isolates from all five outbreaks if only a single-locus variant was allowed. MLVA differentiated strains with unique PFGE types. Additionally, MLVA discriminated strains within PFGE-defined clusters that were not known to be part of an outbreak. In addition to being a simple and validated method for E. coli O157:H7 outbreak detection, MLVA appears to have a sensitivity equal to that of PFGE and a specificity superior to that of PFGE.