M. tuberculosis

The present investigation was carried out to determine the possible bioactive components of tuber of Ruellia tuberosa L. (Acanthaceae) using GC-MS analysis. Twenty five compounds were identified. The prevailing compounds in the ethanol extract of tuber of R. tuberosa were Lupeol (68.14%), Stigmasterol (8.89%), á-Sitosterol (3.99%), Sucrose (2.24%), Cholest-5-ene, 3-bromo-, (3á- (2.24%), Octadecane, 2-methyl- (2.10%), Nonadecane, 2-methyl- (1.93%), Eicosane, 2-methyl- (1.79%) Heptacosane (1.43%) and Heptacosane (1.29%).

La presentación de estos dos casos de tuberculosis, hospitalizados muy recientemente en nuestro servicio de medicina interna, tiene como objetivos familiarizar al estudiante con una entidad que seguirá encontrando bajo muchas manifestaciones radiológicas y diversas formas clínicas a lo largo del ejercicio profesional en su país y a la vez sensibilizarlo socialmente con una dolorosa realidad para la que hasta ahora no ha existido, al igual que para muchas otras, una verdadera voluntad política.

No hay duda de que la desorganización de los sistemas de salud, la deficiente aplicación de la estrategia DOTS, la ausencia de métodos diagnósticos más sensibles para su detención, la presencia del SIDA, el descuido de su importancia por parte de los docentes, los grupos violentos con sus cultivos de coca y hasta el mismo ciclo epidémico de la tuberculosis, responden, pero solo en forma parcial, por la vergonzosa incidencia de esta entidad en nuestro país; la otra parte de la responsabilidad tenemos que asumirla los 40 millones de colombianos que con nuestro silencio cómplice nos negamos a exigir la voluntad política necesaria para cambiar esa realidad... al igual que muchas otras. REC 2014:20:44-48.

This essay suggests that there is great value to be gained from looking at the history of the major threats to health that humans have endured throughout human (and even hominin) history.  The possibilities for multi-disciplinary work in the field of global health history have never been richer.  Work in genetics, paleopathology, and traditional forms of documentary History can now be combined to reconstruct the histories of the oldest global diseases (tuberculosis and leprosy) to the newest (HIV/AIDS).  All these narratives show the need to think systematically about the manifold forces that create and sustain diseases throughout the world. http://www.ashgate.com/isbn/9781409409243

Impacts • Tuberculosis is a serious re-emerging disease worldwide. The problem of antibiotic resistance is becoming increasingly common. The rate of childhood TB increases annually. • Mycobacterium bovis is responsible for great economic losses and represents a severe threat to public health. • The purpose of this review was to highlight the seriousness of M. bovis for both humans and animals, and to focus on the importance of molecular epidemiological studies of M. bovis and the recent tools used in such studies. Summary Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), is a serious re-emerging disease in both animals and humans. The evolution of the Multi-and Extensively drug-resistant M. bovis strains (MDR-TB and XDR-TB) represents a global threat to public health. Worldwide, the disease is responsible for great economic losses in the veterinary field, serious threat to the ecosystem, and about 3.1% of human TB cases, up to 16% in Tanzania. Only thorough investigation to understand the pathogen's epidemiology can help in controlling the disease and minimizing its threat. For this purpose, various tools have been developed for use in advanced molecular epidemiological studies of bTB, either alone or in combination with standard conventional epidemiological approaches. These techniques enable the analysis of the intra-and inter-species transmission dynamics of bTB. The delivered data can reveal detailed insights into the source of infection, correlations among human and bovine isolates, strain diversity and evolution, spread, geographical localization, host preference, tracing of certain virulence factors such as antibiotic resistance genes, and finally the risk factors for the maintenance and spread of M. bovis. They also allow for the determination of epidemic and endemic strains. This, in turn, has a significant diagnostic impact and helps in vaccine development for bTB eradication programs. The present review discusses many topics including the aetiology, epidemiology and importance of M. bovis, the prevalence of bTB in humans and animals in various countries , the molecular epidemiology of M. bovis, and finally applied molecular epidemiological techniques.

Background: Various primers have been used for detection of Mycobacterium tuberculosis complex (MTBC) DNA using Polymerase chain reaction (PCR). The MPB64 gene has been demonstrated to be a highly specific target for MTBC detection.
Aims & Objectives: To detect MTBC DNA using MPB64 primers in clinical specimens of Nepalese patients suspected to have tuberculosis (TB). Materials and Methods: DNA was extracted from 44 clinical specimens of patients suspected of having TB and MPB64 targeted PCR was performed.
Results: Bands comprising 240 base pair (bp) of MPB64 sequence were present in 15 of the 44 clinical samples, of which 4 were pulmonary and the remainders were extra-pulmonary samples. The overall positivity of MPB64 targeted PCR was 34.1%.
Conclusion: PCR targeting the MPB64 fragment has a potential of detecting the MTBC DNA and has potentially valuable clinical applications in early detection of TB in Nepal.
Key Words: MPB64; Tuberculosis; Extra- Pulmonary Tuberculosis; Polymerase Chain Reaction

Tuberculosis (TB) is a chronic inflammatory and zoonotic disease caused by Mycobacterium tuberculosis complex (MTBC) members, which affects various domestic animals, wildlife, and humans. Some wild animals serve as reservoir hosts in the transmission and epidemiology of the disease. Therefore, the monitoring and surveillance of both wild and domestic hosts are critical for prevention and control strategies. For TB diagnosis, the single intradermal tuberculin test or the single comparative intradermal tuberculin test, and the gamma-interferon test, which is regarded as an ancillary test, are used. Postmortem examination can identify granulomatous lesions compatible with a diagnosis of TB . In contrast, smears of the lesions can be stained for acid-fast bacilli, and samples of the affected organs can be subjected to histopathological analyses. Culture is the gold standard test for isolating mycobacterial bacilli because it has high sensitivity and specificity compared with other metho...

Actualización de la bacteriología clínica moderna, se describen las bacterias que producen patología infecciosas y se estudia cada género bacteriano de importancia médica desde la perspectiva de su reciente ubicación taxonómica.
ISBN: 958-683-052-7

La tuberculosis es una de las enfermedades infecciosas más prevalentes en el mundo y una de las principales causas de mortalidad por infección. La Organización Mundial de la Salud (OMS) estimó en el año 2011, 8.7 millones de casos de tuberculosis, de éstos el 13% presentaba coinfección por el Virus de Inmunodeficiencia Humana (VIH). Dos billones de personas presentan infección tuberculosa latente, lo que correspondería a un tercio de la población mundial, lo que se convierte en un serio problema de salud pública, por ello la OMS la declaró como emergencia mundial. Tradicionalmente, el diagnóstico de la tuberculosis en pediatría requiere la presencia de varios criterios que incluyen el epidemiológico, clínico, radiológico, tuberculínico y microbiológico, este último consta de métodos convencionales como el cultivo, que es el estándar de oro y métodos de biología molecular para la amplificación de ácidos nucleicos, que tienen mayor auge por la posibilidad de un diagnóstico preciso y más rápido, ya que el bacilo tuberculoso es un microorganismo de crecimiento lento y requiere un número mínimo de 104 bacilos en la muestra para ser cultivado, esto dificulta su aislamiento en pacientes paucibacilares e impide el diagnóstico precoz. Las nuevas técnicas de biología molecular se han convertido en una buena opción para el diagnóstico y tratamiento de las infec¬ciones producidas por el complejo de micobacterias tuberculosas y no tuberculosas, dada la rapidez en los resultados, su alta sensibilidad y especificidad y la capacidad para detectar la resistencia a fármacos antituberculosos.

Context: According to a report by the World Health Organization (WHO), there were 1.4 million deaths worldwide in 2015 from tuberculosis (TB), with 3.9% being new cases and 21% being previously treated cases of multidrug-resistant tuberculosis (MDR-TB).

Aims: To review the literature concerning the costing analysis situation of MDR-TB treatment.

Methods: The study was conducted as a systematic review, with a modified checklist being used as the vital instrument. A search was performed of three databases (PubMed, Cochrane, and Scopus) using the terms (cost OR economic, socioeconomic, expenditure, burden, fee, charge, budget impact) AND (resistance OR multidrug resistance, MDR) AND (tuberculosis OR TB, Mycobacterium tuberculosis) in order to identify relevant articles published from 2006 to the present.

Results: A total of 1238 abstracts were identified, and 12 papers were ultimately included in the study. The quantity of the published articles was found to increase during in the period 2008 to 2016. Almost all the studies were based on patients’ and healthcare systems’ perceptions. The main data sources used were medical establishments and the reports of various relevant organizations. Primary data were used twice as much as secondary data. All the costing types, including direct costs and indirect costs, were mentioned, albeit not with the same frequency.

Conclusions: Africa owns one-third of the articles included. Further, it was found that MDR-TB should be treated using ambulatory care rather than hospital-based models. Future research studies should focus on Asia, where drug resistance has proved to be a challenging issue.

A chest x-ray screening system for pulmonary pathologies such as tuberculosis (TB) is of paramount importance due to the increasing mortality rate of patients with undiagnosed TB, especially in densely-populated developing countries. As a first step toward developing such screening systems, this paper presents a novel computer vision module that automatically segments the lungs from posteroanterior digital chest x-ray images. The segmentation task is non-trivial, due to poor image contrast and occlusion of the lung region by ribs, clavicle, heart, and by non-TB abnormalities associated with pulmonary diseases. In the proposed procedure, we first compute a lung shape model by employing a level set based technique for registration up to a homography. Next, we use this computed mean lung shape to initialize the level set that is based on a best fit measure obtained in a heuristically estimated search space for the projective transform parameters. Once the level set is initialized, a suite of customized lower level image features and higher level shape features up to a homography evolve the level set function at a lower resolution in order to achieve a coarse segmentation of the lungs. Finally, a fine segmentation step is performed by adding additional shape variation constraints and evolving the level set in a higher resolution. We processed the standard Japanese Society of Radiological Technology (JSRT) dataset, comprised of 247 images, using this scheme. The promising results (92% accuracy) demonstrate the viability and efficacy of the proposed approach. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Managing drug-resistant Mycobacterium tuberculosis requires drug susceptibility testing, yet conventional drug susceptibility
testing is slow, and molecular testing does not yield results for all antituberculous drugs. We addressed these challenges by utilizing
real-time PCR of mycobacteriophage D29 DNA to evaluate the drug resistance of clinical M. tuberculosis isolates. Mycobacteriophages infect and replicate in viable bacterial cells faster than bacterial cells replicate and have been used for detection and drug resistance testing for M. tuberculosis either by using reporter cells or phages with engineered reporter constructs. Our primary protocol involved culturing M. tuberculosis isolates for 48 h with and without drugs at critical concentrations, followed by incubation with 103 PFU/ml of D29 mycobacteriophage for 24 h and then real-time PCR. Many drugs could be incubated instantly with M. tuberculosis and phage for 24 h alone. The change in phage DNA real-time PCR cycle threshold (CT) between control M. tuberculosis and M. tuberculosis treated with drugs was calculated and correlated with conventional agar proportion drug susceptibility results. Specifically, 9 susceptible clinical isolates, 22 multidrug-resistant (MDR), and 1 extensively drugresistant (XDR) M. tuberculosis strains were used and CT control-CT drug cutoffs of between
0.3 and6.0 yielded 422/429 (98%) accurate results for isoniazid, rifampin, streptomycin, ethambutol, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide, para-aminosalicylic acid, cycloserine, and linezolid. Moreover, the CT values correlated with isolate MIC for most agents. This D29 quantitative PCR assay offers a rapid, accurate, 1- to 3-day phenotypic drug susceptibility test for
first- and second-line drugs and may suggest an approximate MIC.

Tuberculosis is one of the most widespread bacterial diseases on the planet. It is an infection that has plagued humans for over millennia. One line of bioarchaeological research is concerned with the origins and spread of the disease (phylogeography). A new research study within this field indicates that the origin of the disease in the South American continent is attributable to transmission from seals and sea lions, rather than from people.

Background: Even though the proportion of previously treated TB patients’ (retreatment cases) is increasing at
alarming rate, there is scarcity of data regarding their magnitude and treatment outcomes. Therefore, this study is
meant to assess TB retreatment case rate and their treatment outcomes at Adama hospital medical college (AHMC)
in Ethiopia.
Methods: The study employed a retrospective cross-sectional survey where a total of 732 registered TB patients’
data were reviewed between Aprils to May 2014. Data analysis was done using SPSS version 20.0.
Results: In this study, 147 (20%) of 732 TB cases were registered as retreatment cases. Of these, 16 (11%)
relapse, 13 (9%) return after defaulted (RAD), 23 (16%) failure and 95 (64%) were categorized as ‘other’ among
which 61 (64.9%) had sputum smear-negative pulmonary TB (PTB) and 34 (35.1%) had extra PTB (EPTB).
Retreatment case is more likely to occur in HIV positive 48 (59%) individuals. Regarding their treatment outcomes,
treatment success rate (cure plus treatment completed) of 65 (63.7%) was obtained. Whereas 13 (12.8%) registered
as died, 10 (9.8%) as failure, 9 (8.8%) as defaulters and 5 (4.9%) as transferred out cases to other health facility.
HIV positive individuals are more likely (54%) to have poor treatment outcomes.
Conclusion: The prevalence of TB retreatment cases obtained in this study was higher as compared to similar
studies. Similarly, their treatment success rate (TSR) was lower as compared to the national figure. Therefore, more
attention should be given to the prevention and treatment of TB retreatment cases to avoid social and economic
burden of tuberculosis in Ethiopia.

Aims: The purpose of this study was to determine the prevalence of paragonimiasis and aspergillosis in patients suspected of pulmonary tuberculosis in Yaounde.
Study Design: Cross sectional study.
Place and Duration of Study: Participants were recruited between March and June 2014 using the tuberculosis treatment centers of the University Hospital Center and Jamot Hospital Center of Yaounde
Methodology: Two sputum samples were collected from participants and analysed using standard microbiological methods.
Results: A total of 260 patients were enrolled, 131 (50.4%) females and 129 (49.6%) males. Of the 260 samples collected, Mycobacterium tuberculosis was detected in 44 (16.92%) [CI: 12.33–21.51], Aspergillus spp. in 42 (16.15%) [CI: 11.65–20.66] and Paragonimus africanus in 7 (2.69%) [CI: 0.7 – 4.67]. Aspergillosis was more prevalent in the age group 41-60years 29 (44.62%) (P = .000) and among builders 19 (45%) (P = .013). Isolates of Aspergillus included A. fumigatus 20 (47.62%), A. flavus 10 (24%) and A. niger 10 (24%). Other pathogens isolated included Candida albicans 80 (39.8%) and Histoplasma capsulatum var duboisii 21 (8.1%). Nine (3.46%) and 20 (7.69%) of patients with tuberculosis were coinfected with Aspergillus spp., and Candida albicans respectively. No coinfection was observed between Mycobacterium tuberculosis and Paragonimus africanus. Gram staining revealed that 20 (7.7%) were positive for fungal elements, 80 (30.8%) for yeast, 5 (1.9%) for yeast and Gram positive rods, 40 (15.4%) for Gram negative rods and 30 (11.5%) for Gram positive cocci.
Conclusion: This study demonstrates varying prevalence of Aspergillus spp., Paragonimus africanus in patients suspected of tuberculosis in Yaounde. Other potential pathogens isolated included Candida albicans, and Histoplasma capsulatum var duboisii. Further studies will be required to shed more light on the biology and transmission of Paragonimus africanus in Yaounde.

Tuberculosis (TB), an ongoing public health threat, is worsened by the emergence of drug resistance. With an estimated 630000 cases per year of multidrug resistant (MDR)-TB, and 9% of those being extensively drug resistant (XDR)-TB, there is an urgent need for new and more effective anti-TB drugs. New TB treatment regimens should be able to shorten the duration of therapy that currently takes at least six months. The non-compliance with this long treatment duration is one of the reasons for the development of drug resistance. In spite of the difficulties and alleged lack of interest from the pharmaceutical industry for the discovery and development of new antibiotics, several new or repurposed drugs are being evaluated in clinical trials. This review article summarizes the information available and presents an update on the drugs currently in clinical trials for TB and briefly introduces some new compounds in pre-clinical development.

Tuberculosis (TB) has been one of the most important infectious diseases affecting mankind and still represents a plague on a global scale. In this narrative review the origins of tuberculosis are outlined, according to the evidence of paleopathology. In particular the first cases of human TB in ancient skeletal remains are presented, together with the most recent discoveries resulting from the paleomicrobiology of the tubercle bacillus, which provide innovative information on the history of TB. The paleo-pathological evidence of TB attests the presence of the disease starting from Neolithic times. Traditionally, it was thought that TB has a zoonotic origin, being acquired by humans from cattle during the Neolithic revolution. However, the biomolecular studies proposed a new evolutionary scenario demonstrating that human TB has a human origin. The researches show that the disease was present in the early human populations of Africa at least 70000 years ago and that it expanded following the migrations of Homo sapiens out of Africa, adapting to the different human groups. The demographic success of TB during the Neolithic period was due to the growth of density and size of the human host population, and not the zoonotic transfer from cattle, as previously hypothesized. These data demonstrate a long coevolution of the disease and its human host. Understanding the changes of TB through time thanks to the advances in the field of paleopathology can help to solve the present problems and understand the future evolution of TB.

This Research Paper deals with the following constellation of issues: Tuberculosis and Poverty; Tuberculosis and Human Rights violations apropos the following rights: Right to Non-Discrimination and Equality, Right to Life, Right to the Highest Attainable Standard of Physical and Mental Health, Right to Bodily Integrity, Right to Freedom of Movement, Right to Freedom from Arbitrary Arrest and Detention, Right to Fair Trial, Right of All Persons Deprived of their Liberty to be treated with Humanity, Right to Freedom from Torture or Cruel, Inhuman or Degrading Treatment or Punishment, Right to Privacy, Right to Freedom of Expression and Right to Information, Right to Freedom of Assembly and Association, Right to Enjoy the Benefits of Scientific Progress and its Application; Tuberculosis and Key Vulnerable Groups (Women, Children, Migrants, Refugees and Prisoners). This paper argues that, fight against Tuberculosis via the social mobilization approach is the best way forward. Lastly, author concludes with the following finding of fact: ‘Recognizing TB as a social, economic and political disease, and not just a medical problem, will prompt the need to explore new avenues through which efforts to ensure TB prevention and access to TB cure will be strengthened.’

This review focusses on the current ongoing research in the field of tuberculosis comprising the resistant strains.
It specifies a proper data analysiswith results in concise form fromareas gripping in: diagnostic nanotechnology,
vaccine nanotechnology and the prime field of interest i.e., therapeutic nanotechnology. Primarily, therapeutic
area recollects the research findings from advanced drug delivery (primary era) to the targeted drug delivery
(modern era). The vaccine-based area derives the immune-specific targetingwith enhancedemphasis on vaccine
extraction and preparation of nanoparticles. Finally, the diagnostic area signifies the imaging techniques that may
be employed in the diagnosis of TB. Not only that, there are some researches that emphasized on finding the
comparable diagnostic differences between normal and resistant strains. With the advent of carbon nanotubes,
metallic NPs, a newer hope has emerged out in diagnostic research, which may extend to therapeutic research
applications too. Modifications of natural polymers, least or no use of organic solvents, size controlled NPs, optimized
methodology, etc., are fields that need more effort to bypass toxicity. If above desired possibilities get the
priority during research, it may lead to shift in the timeline towards much more oriented research.

Rationale. Therapeutic drug monitoring (TDM) is a
process of adjusting drug dosages on the basis of serum
drug concentrations for the purpose of optimizing drug
therapy. This study introduces the use of TDM in the
management of mycobacterial infections. Pyrazinamide
(PZA) has been marketed as tablet in other countries.
It is only in the Philippines wherein pyrazinamide is
available both in tablet and suspension forms. No study
has been done on pyrazinamide suspension use for the
treatment of tuberculosis to this date.
Objectives. To examine the serum concentration of
pyrazinamide suspension in children with tuberculosis
Design. Descriptive study
Methods. Thirty pediatric patients who were taking
pyrazinamide suspension for at least 1 week as part of
chemotherapy for tuberculosis were included in this study.
Blood was taken prior to the dose then 2, 4, 8 hours after
administration of PZA suspensiongfor thefirst 4 patients.
Specimens were submitted to the Pharmacology
Department Laboratory of the University of the
Philippines – College of Medicine and were analyzed
using High Performance Liquid Chromatography
technique. The samples from the first 4 patients were
used to determine the time when the drug reaches its
maximum concentration (Tmax). For subsequent
patients, 2 determinations were taken at the time when
the drug reaches its maximum concentration and trough
level.
Results. At at a Tmax of 2 hours, the mean serum
concentration of PZA suspension is at 34.6+ 11.86 ug/
ml. The mean serum trough level is 4.55+ 4.63 ug/ml.
There were no significant differences in serum
concentration of PZA suspension among 3 brand names
of PZA (p-value: 0.506).
Keywords. Pyrazinamide, antituberculosis, therapeutic drug monitoring, pharmacokinetics,
tuberculosis
*Department of Pediatrics, UP-PGH
Conclusion. Mean serum concentration of PZA
suspension falls within the established therapeutic range
for pyrazinamide. But 2 subjects failed to reach the
therapeutic levels. No subject reached toxic levels

Authors: Djalma S Lima-Junior, Diego L Costa, Vanessa Carregaro, Larissa D Cunha, Alexandre L N Silva, Tiago W P Mineo, Fredy R S Gutierrez, Maria Bellio, Karina R Bortoluci, Richard A Flavell, Marcelo T Bozza, João S Silva & Dario S Zamboni

Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study we show that the Nlrp3 inflammasome is activated in response to Leishmania infection and is important for the restriction of parasite replication both in macrophages and in vivo as demonstrated through the infection of inflammasome-deficient mice with Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum chagasi. Inflammasome-driven interleukin-1β (IL-1β) production facilitated host resistance to infection, as signaling through IL-1 receptor (IL-1R) and MyD88 was necessary and sufficient to trigger inducible nitric oxide synthase (NOS2)-mediated production of NO. In this manuscript we identify a major signaling platform for host resistance to Leishmania spp. infection and describe the molecular mechanisms underlying Leishmania-induced NO production.