To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60).
View Article and Find Full Text PDFTwo rapid dual color fluorescence in situ hybridization (FISH) assays were evaluated for detecting M. tuberculosis and related pathogens in cultures. The MN Genus-MTBC FISH assay uses an orange fluorescent probe specific for the Mycobacterium tuberculosis complex (MTBC) and a green fluorescent probe specific for the Mycobacterium and Nocardia genera (MN Genus) to detect and distinguish MTBC from other Mycobacteria and Nocardia.
View Article and Find Full Text PDFBackground: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load.
View Article and Find Full Text PDFBackground: Pyrazinamide (PZA) is the most important drug against the latent stage of tuberculosis (TB) and is used in both first and second line treatment regimens. The continued increase in multi-drug resistant TB and the prevalence of PZA resistance makes the development of alternative assays for prompt identification of PZA resistance all the more important.
Methods: We standardized and evaluated a quantitative variant of the Wayne assay (QW) for determining PZA resistance in Mycobacterium tuberculosis strains.
Introduction: Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients.
View Article and Find Full Text PDFBackground: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss.
View Article and Find Full Text PDFIn this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB).
View Article and Find Full Text PDFObjectives: To implement a system for remote diagnosis of tuberculosis and multidrug resistance (MDR) using the Microscopic-Observation Drug Susceptibility Assay (MODS) method in the Mycobacteria Laboratory, Trujillo Center of Excellence in Tuberculosis (CENEX-Trujillo). The system included a variant of an algorithm for recognition of Mycobacterium tuberculosis recently reported from digital images of MODS cultures of sputum samples.
Materials And Methods: The recognition algorithm was optimized using a retraining statistical model based on digital images of MODS cultures from CENEX-Trujillo.
Background: Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid.
View Article and Find Full Text PDFTuberculosis control efforts are hampered by a mismatch in diagnostic technology: modern optimal diagnostic tests are least available in poor areas where they are needed most. Lack of adequate early diagnostics and MDR detection is a critical problem in control efforts. The Microscopic Observation Drug Susceptibility (MODS) assay uses visual recognition of cording patterns from Mycobacterium tuberculosis (MTB) to diagnose tuberculosis infection and drug susceptibility directly from a sputum sample in 7-10 days with a low cost.
View Article and Find Full Text PDFBeijing family strains of Mycobacterium tuberculosis have attracted worldwide attention because of their wide geographical distribution and global emergence. Peru, which has a historical relationship with East Asia, is considered to be a hotspot for Beijing family strains in South America. We aimed to unveil the genetic diversity and transmission characteristics of the Beijing strains in Peru.
View Article and Find Full Text PDFTuberculosis (TB) is a leading cause of morbidity and mortality and is frequently complicated by emergence of drug-resistant strains. Diagnosis of TB in developing countries is often based on the relatively insensitive acid-fast staining that does not enable susceptibility profiling. Microscopic observation drug susceptibility assay (MODS) is an inexpensive, simple method that enables rapid TB culture coupled with susceptibility testing.
View Article and Find Full Text PDFBackground: Bleach-sedimentation may improve microscopy for diagnosing tuberculosis by sterilising sputum and concentrating Mycobacterium tuberculosis. We studied gravity bleach-sedimentation effects on safety, sensitivity, speed and reliability of smear-microscopy.
Methods: This blinded, controlled study used sputum specimens (n = 72) from tuberculosis patients.
Background: The diagnosis of pulmonary tuberculosis presents challenges in children because symptoms are non-specific, specimens are difficult to obtain, and cultures and smears of Mycobacterium tuberculosis are often negative. We assessed new diagnostic approaches for tuberculosis in children in a resource-poor country.
Methods: Children with symptoms suggestive of pulmonary tuberculosis (cases) were enrolled from August, 2002, to January, 2007, at two hospitals in Lima, Peru.
Background: Effective tuberculosis control is compromised by a lack of clarity about the timeframe of viable Mycobacterium tuberculosis shedding after treatment initiation under programmatic conditions. This study quantifies time to conversion from smear and culture positivity to negativity in unselected tuberculosis patients receiving standardized therapy in a directly observed therapy short-course (DOTS) program.
Methods: Longitudinal cohort study following up 93 adults initiating tuberculosis therapy in Lima, Peru.
Pulmonary tuberculosis diagnosis is difficult when patients cannot produce sputum. Most sputum is swallowed, and tuberculosis DNA can survive intestinal transit. We therefore evaluated molecular testing of stool specimens for detecting tuberculosis originating from the lungs.
View Article and Find Full Text PDFTissue destruction characterizes infection with Mycobacterium tuberculosis (Mtb). Type I collagen provides the lung's tensile strength, is extremely resistant to degradation, but is cleaved by matrix metalloproteinase (MMP)-1. Fibroblasts potentially secrete quantitatively more MMP-1 than other lung cells.
View Article and Find Full Text PDFObjectives: In a pilot implementation project of the microscopic-observation drug-susceptibility methodology, we conducted a process evaluation to identify health system and logistic challenges that need to be addressed in order to harness the benefits of rolling out promising new diagnostic tools for multidrug-resistant tuberculosis (MDRTB).
Methods: Regional data relating to health system practices and performance related to the MDRTB diagnostic algorithm were collected at health center, local, and regional laboratories.
Results: Parallel implementation of a new test and an existing method creates demands on funds, personnel, sample transport, and information systems in addition to new test startup costs.
Pyrazinamide is a first-line drug for treating tuberculosis, but pyrazinamide resistance testing is usually too slow to guide initial therapy, so some patients receive inappropriate therapy. We therefore aimed to optimize and evaluate a rapid molecular test for tuberculosis drug resistance to pyrazinamide. Tuberculosis PCR-single-strand conformational polymorphism (PCR-SSCP) was optimized to test for mutations causing pyrazinamide resistance directly from sputum samples and Mycobacterium tuberculosis isolates.
View Article and Find Full Text PDFBackground: The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.
Methods And Findings: All air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof.
The intersample and intrasample variability of the results obtained with the microplate Alamar blue assay for the indirect drug susceptibility testing of Mycobacterium tuberculosis was investigated. Between 1.2 and 8.
View Article and Find Full Text PDFTests for pleural tuberculosis are insensitive and expensive. We compared nonproprietary microscopic-observation drug-susceptibility (MODS) culture with Löwenstein-Jensen culture for evaluation of pleural specimens. MODS culture was associated with greatly increased diagnostic sensitivity and shorter time to diagnosis, compared with Löwenstein-Jensen culture (sensitivity of culture of biopsy specimens, 81% vs.
View Article and Find Full Text PDFThe antiproliferative bioassay-guided fractionation of five Peruvian plants, Doliocarpus dentatus, Picramnia sellowii, Strychnos mitscherlichii, Iryanthera juruensis, and Croton alnifolius, led to the isolation and identification of their different major cytotoxic constituents, betulinic acid (1), nataloe-emodin (2), bisnordihydrotoxyferine (4), 2',4'-dihydroxy-6'-methoxy-3,4-methylenedioxydihydrochalcone (5), and 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone (6) and 12-O-tetradecanoylphorbol-13-acetate (7), respectively. Eight human tumor cell lines and two nontumorigenic cell lines were used in this investigation. Their in vitro activity against Mycobacterium tuberculosis is also reported.
View Article and Find Full Text PDFBackground: Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures.
Methods: An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru.