Source investigation of two outbreaks of skin and soft tissue infection by Mycobacterium abscessus subsp. abscessus in Venezuela.

Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela.

Pharmacokinetics of anti-tuberculosis drugs in Venezuelan children younger than 16 years of age: supportive evidence for the implementation of revised WHO dosing recommendations.

OBJECTIVES: The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dose recommendations for children, with dose increases proposed for each drug. No pharmacokinetic data are available from South American children. We examined the need for implementation of these revised guidelines in Venezuela. METHODS: Plasma isoniazid, rifampicin, pyrazinamide and ethambutol concentrations were assessed prior to and at 2, 4 and 8 h after intake of TB drugs by 30 TB patients aged 1-15 years. The effects of dose in mg/kg, age, sex, body weight, malnutrition and acetylator phenotype on maximum plasma drug concentrations (Cmax) and exposure (AUC0-24) were determined. RESULTS: 25 patients (83%) had an isoniazid Cmax below 3 mg/l and 23 patients (77%) had a rifampicin Cmax below 8 mg/l. One patient (3%) had a pyrazinamide Cmax below 20 mg/l. The low number of patients on ethambutol (n = 5) precluded firm conclusions. Cmax and AUC0-24 of all four drugs were significantly and positively correlated with age and body weight. Patients aged 1-4 years had significantly lower Cmax and AUC0-24 values for isoniazid and rifampicin and a trend to lower values for pyrazinamide compared to those aged 5-15 years. The geometric mean AUC0-24 for isoniazid was much lower in fast acetylators than in slow acetylators (5.2 vs. 12.0, P < 0.01). CONCLUSION: We provide supportive evidence for the implementation of the revised WHO pediatric TB drug dose recommendations in Venezuela. Follow-up studies are needed to describe the corresponding plasma levels that are achieved by the recommended increased doses of TB drugs.

Helminths and skewed cytokine profiles increase tuberculin skin test positivity in Warao Amerindians.

The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in Venezuela. Pediatric household contacts of sputum smear-positive tuberculosis (TB) cases were enrolled for TST, chest radiograph, plasma cytokine analyses, QuantiFERON-TB Gold In-Tube (QFT-GIT) testing and stool examinations. Factors associated with TST positivity were studied using generalized estimation equations logistic regression models. Of the 141 asymptomatic contacts, 39% was TST-positive. After adjusting for age, gender and nutritional status, TST positivity was associated with Trichuris trichiura infections (OR 3.5, 95% CI 1.1-11.6) and low circulating levels of T helper 1 (Th1) cytokines (OR 0.51, 95% CI 0.33-0.79). Ascaris lumbricoides infections in interaction with Th2- and interleukin (IL)-10-dominated cytokine profiles were positively associated with TST positivity (OR 3.1, 95% CI 1.1-8.9 and OR 2.4, 95% CI 1.04-5.7, respectively). A negative correlation of QFT-GIT mitogen responses with Th1 and Th2 levels and a positive correlation with age were observed (all p < 0.01). We conclude that helminth infections and low Th1 cytokine plasma levels are significantly associated with TST positivity in indigenous Venezuelan pediatric TB contacts.

Carriage and invasive isolates of Streptococcus pneumoniae in Caracas, Venezuela: the relative invasiveness of serotypes and vaccine coverage.

The introduction of a pneumococcal conjugate vaccine in Venezuela needs previous studies to assess vaccine efficiency. We conducted a survey of nasopharyngeal pneumococcal carriage in urban children in Caracas and studied the distribution of serotypes. We compared these data with survey data available for invasive strains isolated in the same area and in the same time period. An overall pneumococcal carriage rate of 27% was observed. The most predominant capsular serotypes among carriage isolates were 6B (29%), 19A (13.8%), 23F (10%), 14 (8.3%), 6A (8.3%) and 15B/C (3.3%) and among invasive isolates 6B (25%), 14 (15%), and 19A, 6A, 7F, and 18 (7.5% each). The serotypes/groups 1, 5, 7F and 18, jointly covering 30% of the invasive strains, represented less than 0.7% of the carrier strains. The theoretical coverage of the pneumococcal conjugate vaccine PCV13 for carriage and invasive strains was calculated to be 74% and 90%, respectively. Our study demonstrates important differences for the serotype distribution in disease and carriage isolates and provides a key baseline for future studies addressing the prevalence and replacement of invasive and carriage serotypes after the introduction of the PCV 13 vaccine in Venezuela in the year 2010.

[Pneumococcal carriage in mothers and children of the Panare Amerindians from the State of Bolivar, Venezuela]. / Estado de portador nasofaríngeo de Streptococcus pneumoniae en madres e hijos de la población indígena Panare del estado Bolívar, Venezuela.

In North America, the indigenous groups have been identified as a population with increased risk of pneumococcal colonization and pneumococcal invasive disease. However, little information is available from South American natives. In the present study we evaluated the nasopharyngeal carriage and serotype distribution of Streptococcus pneumoniae in mothers and children of the Panare people from Venezuela. In May 2008, in 8 distinct geographically isolated communities, 148 nasopharyngeal samples were obtained from 64 healthy mothers and 84 healthy Panare children under 5 years of age. S. pneumoniae was isolated and identified by standard techniques. Strains were typified by multiplex PCR and resistance patterns were determined by the disk diffusion method. A total of 65 strains were isolated; 11% of the mothers and 69% of the children carried S. pneumoniae. Serotypes 6B (48%), 33F (21,5%), 6A (6%), 19A (3,1%) and 23F (1,5%) were the most predominant. Of the 6 colonized mother-child pairs, 3 pairs (2 with 6B), were colonized with the same serotype. All strains were sensitive to penicillin and 13,7% were resistant to macrolides. The high colonization rates in the Panare people suggest that the children are at increased risk of pneumococcal invasive disease and could benefit from vaccination. Four conjugate vaccine serotypes (6B, 6A, 19A and 23F) representing 58 % of all strains were present in the population at the moment of sampling. Resistance to antibiotics is (still) not a problem.

The molecular epidemiology of tuberculosis in Caracas, Venezuela, with IS6110 DNA fingerprinting.

In this retrospective study we asses the molecular epidemiological situation of Tuberculosis of the city of Caracas, Venezuela in the year 1994, applying IS6110 DNA Fingerprinting of clinical isolates. Fingerprinting of Mycobacterium tuberculosis strains of sixty-four patients TB patients from all the 5 districts of the city revealed fifty-one distinct IS6110 patterns. Isolates from 20 patients (30%) had fingerprints that were shared with at least one other patient. Based on this sampling we conclude that at least a third of the tuberculosis cases in Caracas in the year 1994 were the result of recent and ongoing transmission, indicating micro-epidemics in the town.

The glucose permease of the phosphotransferase system of Bacillus subtilis: evidence for IIGlc and IIIGlc domains.

Glucose is taken up in Bacillus subtilis via the phosphoenolpyruvate:glucose phosphotransferase system (glucose PTS). Two genes, orfG and ptsX, have been implied in the glucose-specific part of this PTS, encoding an Enzyme IIGlc and an Enzyme IIIGlc, respectively. We now show that the glucose permease consists of a single, membrane-bound, polypeptide with an apparent molecular weight of 80,000, encoded by a single gene which will be designated ptsG. The glucose permease contains domains that are 40-50% identical to the IIGlc and IIIGlc proteins of Escherichia coli. The B. subtilis IIIGlc domain can replace IIIGlc in E. coli crr mutants in supporting growth on glucose and transport of methyl alpha-glucoside. Mutations in the IIGlc and IIIGlc domains of the B. subtilis ptsG gene impaired growth on glucose and in some cases on sucrose. ptsG mutants lost all methyl alpha-glucoside transport but retained part of the glucose-transport capacity. Residual growth on glucose and transport of glucose in these ptsG mutants suggested that yet another uptake system for glucose existed, which is either another PT system or regulated by the PTS. The glucose PTS did not seem to be involved in the regulation of the uptake or metabolism of non-PTS compounds like glycerol. In contrast to ptsl mutants in members of the Enterobacteriaceae, the defective growth of B. subtilis ptsl mutants on glycerol was not restored by an insertion in the ptsG gene which eliminated IIGlc. Growth of B. subtilis ptsG mutants, lacking IIGlc, was not impaired on glycerol. From this we concluded that neither non-phosphorylated nor phosphorylated IIGlc was acting as an inhibitor or an activator, respectively, of glycerol uptake and metabolism.