High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.

Complicaciones neurológicas asociadas a infección por virus Influenza / Neurological complications associated to Influenza virus infection

Objetivos. Revisar las complicaciones neurológicas por virus Influenza y las características clínico-epidemiológicas. Material y métodos. Estudio descriptivo, observacional, retrospectivo mediante revisión de historias clínicas de niños ingresados con complicaciones neurológicas por virus Influenza entre enero de 2013 y febrero de 2019. Resultados. Se incluyeron 14 pacientes (11 varones), el 85,7% con infección por Influenza A. La mediana de edad fue 2 años (3 meses-11 años). Tenían antecedentes neurológicos 3 (convulsiones febriles). El 64,3% asociaba fiebre, con una duración media de 2,15±2,3 días. Los síntomas neurológicos se presentaron el primer día de fiebre en 7 pacientes. La clínica neurológica fue: convulsión (11/14): 8 febriles y 3 afebriles, encefalopatía (1), cefalea (1) y meningismo (1). En cuanto a las convulsiones febriles, la mediana de edad fue de 3 años. Cuatro tenían más de 6 años. En el 75% la convulsión febril se produjo el primer día de fiebre y en 5 recurrieron en 24 horas. Se aisló Influenza A en el 82% de pacientes con convulsiones. Recibieron tratamiento con oseltamivir 6 pacientes. Ninguno ha presentado secuelas. Conclusiones. En nuestra muestra, el virus más frecuente fue el virus Influenza A, produciendo este la mayoría de las complicaciones a nivel neurológico, especialmente en varones en edad escolar. La complicación más frecuente fue la convulsión, la mayoría convulsiones febriles, aunque hasta en un 28% se presentó a una edad atípica. Al igual que en otras series, el virus Influenza se puede asociar a complicaciones graves como rombencefalitis. En la mayoría de los pacientes los exámenes complementarios fueron normales (AU)

Objectives. To review neurological complications due to influenza virus and clinical-epidemiological characteristics. Material and methods. Descriptive, observational, retrospective study by reviewing clinical records of children admitted with neurological complications due to influenza virus between January 2013-February 2019. Results. Fourteen patients were included (11 males), 85.7% with infection by Influenza A. Median age was 2 years (3 months-11 years). They had neurological history 3 (febrile seizures). The 64.3% associated fever, with a mean duration of 2.15±2.3 days. Neurological symptoms occurred on the first day of fever in 7 patients. The neurological clinic was: seizure (11/14): 8 febrile and 3 afebrile, encephalopathy (1), headache (1) and meningism (1). As for febrile seizures, the median age was 3 years. Four were older than 6 years old. In 75% the febrile seizure occurred on the first day of fever and in 5 they recurred within 24 hours. Influenza A was isolated in 82% of patients with seizures. Six patients were treated with oseltamivir. None of them presented sequelae. Conclusions. In our sample, the most frequent virus was the Influenza A virus, producing most of the neurological complications, especially in school-age males. The most frequent complication was the seizure, mostly febrile seizures; although up to 28% presented at an atypical age. As in other series, the Influenza virus can be associated to serious complications such as rhombencephalitis. In most of the patients, the complementary exams were normal (AU)

Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment.

Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST.

Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay.

OBJECTIVE: To establish breakpoint concentrations for the fluoroquinolones (moxifloxacin [MFX] and ofloxacin [OFX]) and injectable second-line drugs (amikacin [AMK], kanamycin [KM] and capreomycin [CPM]) using the microscopic observation drug susceptibility (MODS) assay. SETTING: A multinational study conducted between February 2011 and August 2012 in Peru, India, Moldova and South Africa. DESIGN: In the first phase, breakpoints for the fluoroquinolones and injectable second-line drugs (n = 58) were determined. In the second phase, MODS second-line drug susceptibility testing (DST) as an indirect test was compared to MGIT™ DST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS second-line DST directly from sputum. RESULTS: Breakpoints for MFX (0.5 µg/ml), OFX (1 µg/ml), AMK (2 µg/ml), KM (5 µg/ml) and CPM (2.5 µg/ml) were determined. In all phases, MODS results were highly concordant with MGIT DST. The few discrepancies suggest that the MODS breakpoint concentrations for some drugs may be too low. CONCLUSION: MODS second-line DST yielded comparable results to MGIT second-line DST, and is thus a promising alternative. Further studies are needed to confirm the accuracy of the drug breakpoints and the reliability of MODS second-line DST as a direct test.

Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. The Tuberculosis Working Group in Peru.

Inexpensive, rapid, and reliable methods of detecting infection by and drug susceptibility of Mycobacterium tuberculosis (MTB) are crucial to the control of tuberculosis. The novel microscopic observation broth-drug susceptibility assay (MODS) detects early growth of MTB in liquid medium, allowing more timely diagnosis and drug susceptibility testing. Sputum samples from hospitalized patients in Peru were analyzed by using stains, culture, and PCR. Sensitivity of MODS (92%) compared favorably with the most sensitive of the other culture methods (93%). Sputum samples positive for tuberculosis were tested for susceptibility to isoniazid and rifampin with the microwell alamar blue assay (MABA) and MODS. In 89% of cases, there was concordance between MODS and MABA. Of the diagnostic and susceptibility testing methods used, MODS yielded results most rapidly (median, 9.0 and 9.5 days, respectively). MODS is a rapid, inexpensive, sensitive, and specific method for MTB detection and susceptibility testing; it is particularly appropriate for use in developing countries burdened by significant infection rates and increasing numbers of multiple-drug-resistant cases.

Hospital control and multidrug-resistant pulmonary tuberculosis in female patients, Lima, Peru.

We examined the prevalence of tuberculosis (TB), rate of multidrug-resistant (MDR) TB, and characteristics of TB on a female general medicine ward in Peru. Of 250 patients, 40 (16%) were positive by sputum culture and 27 (11%) by smear, and 8 (3%) had MDRTB. Thirteen (33%) of 40 culture-positive patients had not been suspected of having TB on admission. Six (46%) of 13 patients whose TB was unsuspected on admission had MDRTB, compared with 2 (7%) of 27 suspected cases (p = 0.009). Five (63%) of 8 MDRTB patients were smear positive and therefore highly infective. In developing countries, hospital control, a simple method of reducing the spread of MDRTB, is neglected.