The infectiousness of tuberculosis patients coinfected with HIV

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, Peru, 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

Determination of pulsation periods and other parameters of 2875 stars classified as MIRA in the All Sky Automated Survey (ASAS)

We have developed an interactive PYTHON code and derived crucial ephemeris data of 99.4% of all stars classified as 'Mira' in the ASAS data base, referring to pulsation periods, mean maximum magnitudes and, whenever possible, the amplitudes among others. We present a statistical comparison between our results and those given by the AAVSO International Variable Star Index (VSX), as well as those determined with the machine learning automatic procedure of Richards et al. 2012. Our periods are in good agreement with those of the VSX in more than 95% of the stars. However, when comparing our periods with those of Richards et al, the coincidence rate is only 76% and most of the remaining cases refer to aliases. We conclude that automatic codes require still more refinements in order to provide reliable period values. Period distributions of the target stars show three local maxima around 215, 275 and 330 d, apparently of universal validity, their relative strength seems to depend on galactic longitude. Our visual amplitude distribution turns out to be bimodal, however 1/3 of the targets have rather small amplitudes (A $<$ 2.5$^{m}$) and could refer to semi-regular variables (SR). We estimate that about 20% of our targets belong to the SR class. We also provide a list of 63 candidates for period variations and a sample of 35 multiperiodic stars which seem to confirm the universal validity of typical sequences in the double period and in the Petersen diagramsComment: 14 pages, 14 figures, and 8 tables. Accepted to The Astrophysical Journal Supplement Series, September 201

The detection of airborne transmission of tuberculosis from HIV-infected patients, using an in vivo air sampling model

Background. 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. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. Results. Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%–53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV‐positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV‐negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0–44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. Conclusions. HIV‐positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection

Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: 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. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

Protocol for studying cough frequency in people with pulmonary tuberculosis.

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. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution. METHODS: This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed

The Symbiosis Interactome: a computational approach reveals novel components, functional interactions and modules in Sinorhizobium meliloti

<p>Abstract</p> <p>Background</p> <p><it>Rhizobium</it>-Legume symbiosis is an attractive biological process that has been studied for decades because of its importance in agriculture. However, this system has undergone extensive study and although many of the major factors underpinning the process have been discovered using traditional methods, much remains to be discovered.</p> <p>Results</p> <p>Here we present an analysis of the 'Symbiosis Interactome' using novel computational methods in order to address the complex dynamic interactions between proteins involved in the symbiosis of the model bacteria <it>Sinorhizobium meliloti </it>with its plant hosts. Our study constitutes the first large-scale analysis attempting to reconstruct this complex biological process, and to identify novel proteins involved in establishing symbiosis. We identified 263 novel proteins potentially associated with the Symbiosis Interactome. The topology of the Symbiosis Interactome was used to guide experimental techniques attempting to validate novel proteins involved in different stages of symbiosis. The contribution of a set of novel proteins was tested analyzing the symbiotic properties of several <it>S. meliloti </it>mutants. We found mutants with altered symbiotic phenotypes suggesting novel proteins that provide key complementary roles for symbiosis.</p> <p>Conclusion</p> <p>Our 'systems-based model' represents a novel framework for studying host-microbe interactions, provides a theoretical basis for further experimental validations, and can also be applied to the study of other complex processes such as diseases.</p

New occurrence records of Eleutherodactylus syristes in Guerrero and Oaxaca, Mexico

AbstractThe Sierra Madre del Sur (SMS) of southern Mexico is known for its exceptionally high levels of amphibian endemism, but knowledge of species’ ranges in the region is incomplete. Here, we report new locality records for Eleutherodactylus syristes (Hoyt, 1965) from the states of Oaxaca and Guerrero. Previously, this species was known only from the Pacific slopes of the Sierra de Miahuatlán and Mixteca Alta in Oaxaca. These new occurrence records extend the known range of this species by approximately 335km from the type locality and increase the elevational range, indicating it is more widespread in the SMS. Eleutherodactylus syristes is currently listed as endangered by the IUCN based on its limited distribution and ongoing threats to its persistence

Desarrollo de bioherramientas para la remediación de agua y suelos contaminados con cobre

Motivación: La contaminación por cobre es uno de los principales problemas mediambientales en Andalucía. Diversos estudios señalan el estuario conjunto de los ríos Tinto y Odiel como uno de los ecosistemas más contaminados del mundo (Sáinz et al., 2004). El objetivo de este trabajo es diseñar bioherramientas útiles para la descontaminación de suelos y aguas residuales contaminadas con cobre. Métodos: Se ha caracterizado un operón copABCD de resistencia a cobre de la cepa Pseudomonas sp. Az13 , aislada de la rizosfera de leguminosas que crecían de forma espontánea en la zona de Aznalcóllar afectada por el vertido tóxico de 1998 (Dary et al., 2010). Diversos genes de dicho operón se han transferido a rizobios y a plantas, con el propósito de aumentar su resistencia y/o capacidad de acumulación de Cu. Resultados: Con el objetivo de mejorar la respuesta de la simbiosis Sinorhizobium medicae-Medicago truncatula en suelos contaminados con Cu (lo que permitiría su enriquecimiento en nitrógeno), se obtuvo una cepa de S. medicae modificada genéticamente que expresaba parte del operón resistencia a Cu (genes copAB). Las plantas inoculadas con esta bacteria tienen parámetros de crecimiento y nodulación similares en sustratos contaminados con 300 µM de Cu y sin contaminar. El microsimbionte obtenido por ingeniería genética parece dirigir la acumulación de Cu de forma preferente al nódulo. Por otro lado, el gen copC (cuyo producto es capaz de unir dos átomos de Cu) se introdujo en plantas de Arabidopsis thaliana y en raíces pilosas de tabaco. En plantas transgénicas que expresaban dicho gen se incrementó hasta 5 veces su capacidad de acumulación de Cu, si bien su tolerancia al metal disminuía (Rodríguez-Llorente et al., 2012). Por su parte, las raíces transgénicas que expresan el mismo gen se han mostrado como el sistema vivo capaz de acumular los niveles de Cu más altos descritos hasta la fecha, alcanzando valores de 30.000 ppm, sin mostrar síntomas aparentes de toxicidad. Conclusiones: La cepa de S. medicae que expresa los genes copAB tiene un gran potencial como herramienta para la fitoestabilización de Cu utilizando plantas del género Medicago. La expresión de copC tanto en plantas como en raíces permite aumentar su capacidad de acumulación de Cu, haciendo esta herramienta útil en biorremediación de suelos y aguas contaminadas por Cu