There is an urgent need for new tools to improve our ability to diagnose tuberculosis (TB) and multidrugresistant TB (MDR-TB) in resource-poor settings. In a retrospective analysis undertaken in a region with a high incidence of TB, we evaluated the performance of the microscopic observation drug susceptibility assay (MODS), a novel assay developed in Perú which uses an inverted light microscope and culture in Middlebrook 7H9 broth to detect mycobacterial growth. MODS detected 94.0% of 1,908 positive sputum cultures, whereas Löwenstein-Jensen (LJ) culture detected only 86.9% (P < 0.001). The median time to culture positivity was 8 days (compared to 16 days for the same 208 samples by LJ culture; P < 0.001, Wilcoxon signed rank test). The results obtained by direct susceptibility testing using MODS demonstrated excellent concordance for isoniazid and rifampin and the detection of multidrug resistance with those obtained by indirect colorimetric methods: the microplate Alamar Blue assay (MABA) and the tetrazolium microplate assay (TEMA) (agreement, 95, 98, and 94%; kappa values, 0.8, 0.7, and 0.7, respectively). The concordance of the susceptibility testing results for ethambutol and streptomycin was poor. MODS is a novel assay which can detect the organisms responsible for TB and MDR-TB directly from sputum inexpensively, rapidly, and effectively. A comprehensive prospective evaluation of MODS is under way in Perú, and independent validation in nonresearch laboratories should be undertaken at the earliest opportunity.Every single day at least 6,000 people die of tuberculosis (TB), a curable respiratory disease. The diagnosis of TB by sputum smear microscopy is an integral feature of the World Health Organization DOTS (direct observation of treatmentshort-course chemotherapy) strategy for global TB control (25). Low cost, simplicity, and inherent detection of the most infectious cases are the three principal advantages of microscopy for acid-fast bacilli. However, the sensitivity of microscopy for the detection of all cases is low, even when the optimum sensitivity of microscopy is achieved (approximately half of all culture-positive cases are smear negative), and the performance of microscopy is highly variable. Furthermore, the contribution of transmission of infection by smear-negative culture-positive patients (which, by definition, pass undetected when the sole mode of diagnosis is sputum smear) is not inconsiderable (2), and the potential impact of the detection and treatment of these patients is significant (19). Moreover, in this era of emerging drug resistance (9), the lack of information on drug susceptibility threatens the continuing role of the sputum smear as the sole tool for the diagnosis of the majority of cases of TB worldwide. The development of new, low-cost diagnostic tools offers the possibility of future TB control on the basis of culture-based diagnosis and more widespread, targeted susceptibility testing.The simple microscopic observation drug susceptibility assay (MODS) (5), developed in o...
A link between acute infections and the development of acute coronary syndromes (ACS) has been proposed. We used retrospective cohort and self-controlled case series analyses to define the closeness of the association between acute bacterial pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae and ACS. For the retrospective cohort analysis we included a control group of patients with admission diagnoses other than pneumonia or ACS. For the self-controlled case series analysis, we made within-person comparisons of the risk for ACS during the 15 days after admission for pneumonia with that of 365 days before and after that event. In 206 pneumonia patients (144 S. pneumoniae, 62 H. influenzae) we identified 22 (10.7%) cases of ACS, which compared to 6 (1.5%) among 395 controls resulted in an odds ratio (OR) of 7.8 (95% confidence interval [CI], 3.1-19.4). With multivariate logistic regression analysis, the OR for ACS in the pneumonia group remained elevated (OR, 8.5; 95% CI, 3.4-22.2). By the self-controlled case series method, the risk of ACS remarkably increased during the first 15 days after the diagnosis of pneumonia (incidence rate ratio, 47.6; 95% CI, 24.5-92.5). The characteristics and strength of these associations suggest a causal role for the acute infection in this relationship.
Our data suggest that obesity may exert a protective effect against 30-day mortality from community-acquired bacterial pneumonia.
Neurocysticercosis (NCC) includes a wide spectrum of illnesses. Newer neurosurgical approaches are being applied to NCC. Although clinical trials are leading to a consensus on medical management, fewer data address neurosurgical approaches. We reviewed all neurocysticercosis patients evaluated by neurosurgery at Ben Taub General Hospital, Houston, Texas, between August 1997 and December 2005. From 31 patients that had a neurosurgical evaluation, 16 patients were treated with shunts (5 had shunt failure requiring revision), 13 by surgical resection of cysts (9 underwent craniotomy and 4 endoscopy), and 2 by medical therapy. A fifth endoscopy was performed in one patient with shunt failure. None of the endoscopic patients needed another intervention. Despite the availability of anti-parasitic and anti-inflammatory therapies, neurosurgery continues to play an important role in the management of selected cases of NCC. In contrast to the high rate of shunt failure, neuroendoscopy seems to be associated with higher success rate than any other neurosurgical approach.
Neurocysticercosis, one of the most common parasitic infections of the human nervous system, has emerged as an important infection in the United States. Neurocysticercosis causes significant morbidity associated with acute seizures, chronic epilepsy, and hydrocephalus.We retrospectively identified patients with definitive or probable neurocysticercosis seen at Ben Taub General Hospital, the largest public teaching hospital in Houston, Texas, from September 1997 through December 2005. We collected demographic, clinical, therapeutic, and outcome variables. Neurocysticercosis was classified according to the location of cysts in imaging studies. We compared cases with parenchymal and extraparenchymal disease.We included 111 patients (48 had definitive and 63 probable neurocysticercosis). The mean age was 28.6 years (standard deviation, 13.6 yr), and the male to female ratio was 2:1. Most patients (93%) were Hispanic immigrants. Sixty (54%) patients had parenchymal disease, 22 (20%) intraventricular, 13 (12%) subarachnoid disease, and 13 (12%) had calcifications only. Additionally, 2 patients had hydrocephalus only, and 1 had ocular cysticercosis. Thirteen (40%) of 32 patients with parenchymal disease and 3 (30%) of 10 patients with calcifications had relapsed seizures at follow-up. Extraparenchymal disease was associated with longer duration of hospitalization compared with parenchymal disease. No deaths were identified in our series during a median follow-up of 1 year.Neurocysticercosis has emerged as an important parasitic infection in developed countries as a result of increased migration. With current management, mortality is limited, but there continues to be significant morbidity. Further studies of the epidemiology and pathophysiology of the infection are urgently needed to develop better preventive and therapeutic strategies.
Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current studies examined the hypothesis that SP mediates seizures in NCC. We demonstrated by immunostaining that 5 of 5 brain biopsies from NCC patients contained substance P (SP)-positive (+) cells adjacent to but not distant from degenerating worms; no SP+ cells were detected in uninfected brains. In a rodent model of NCC, seizures were induced after intrahippocampal injection of SP alone or after injection of extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice. Seizure activity correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal pre-injection of SP receptor antagonist. Furthermore, extracts of granulomas from WT mice caused seizures when injected into the hippocampus of WT mice, but not when injected into SP receptor (NK1R) deficient mice. These findings indicate that SP causes seizures in NCC, and, suggests that seizures in NCC in humans may be prevented and/or treated with SP-receptor antagonists.
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