New diagnostics in Tuberculosis control

Background: Antigen specific release of IP-10 is an established marker for infection with M.tuberculosis. Compared to IFN-c, IP-10 is released in 100-fold higher concentrations enabling the development of novel assays for detection. Dried blood spots are a convenient sample for high throughput newborn screening.

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%).

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.

The challenge of tuberculosis (TB) remains in diagnosing the disease particularly in the young age group children. Clinical manifestations of TB in children are usually subtle and are not similar to the adult counterpart because of the pathogenesis of TB itself. The paucibacillary phase, which is common in children with TB and manifested as latent tuberculosis infection (LTBI), have several immunologic properties. The release of interferon (IFN)-g by blood mononuclear cells in LTBI have been observed and have been clinically applied as main principle for tuberculin skin test (TST). The test, however, is not specific for Mycobacterium tuberculosis since it was derived from the proteins of M. bovis. Antigen complex of early secretory antigen target (ESAT)-6 and culture filtrate protein (CFP)-10 are secretory protein expressed from gene locus of region of difference (RD)-1 specifically from M. tuberculosis and are interacting with circulatory T-cells which in turn would stimulate the release of IFN-g The laboratory test of enzyme-linked immunosorbent spot (ELISPOT) or TSPOT.TB and QuantiFERON®-TB (QTF) are using the principle of IFN-g release assay (IGRA) and are more specific and more sensitive than TST for diagnosing LTBI and active TB.

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.

The aim of this study was to study the diagnostic parameters in
brain tuberculosis (meningeal and parenchymal)
Material and Methods: This study was conducted in the
department of Neurosurgery and Neurology SKIMS for a period
of two years. A total of 61 patients presenting with brain
tuberculosis admitted at skims during these two years were
included in the study.
Results: The most presenting symptom in our study was headache
found in 95.10% followed by vomiting found in 86.90% of
subjects, fever in 78.70%, altered sensorium in 49.20%, seizures in
19.70% and diplopia in18%. Out of 61 patients cranial nerve
involment was found in 34(55.73%) with 11 having more than two
cranial nerves involved. The most common cranial nerve involved
were 3rd and 6th. ADA was positive in 36 of 53 patients of TBM
with a sensitivity of 67.9% and a specificity of 75%. PCR proved
to be highly specific CT scan of head was abnormal in 56 out of
61 patients (91.8%). 12 (19.70%) were in stage I (meningeal
involvement only), 29 (47.50%) were in stage II (parenchymal
involvement only) and 15 (24.60%) were in stage III (both
parenchymal and meningeal invlolvement). The most common
finding in CT head was meningeal enhancement in 43 patients,
hydrocephalus in 37 patients and tuberculomas in 14 patients. The
most common sites of tuberculomas were frontal lobe (n=6;
42.8%), parietal lobe (n=4; 28.5%), followed by cerebellum in 2
patients and occipital in two. Nine patients had single and five
multiple tuberculomas. Of the 14 patients with tuberculomas,
hydrocephalus on CT was seen in 6 patients.
Conclusion: CT scan is a useful diagnostic tool even in very early
stages of TBM. Abnormalities reported on CT scan done are
hydrocephalus, infarcts, basal enhancement, and tuberculomas.
Normal study is reported in up to 20% of the cases.

Tuberculosis is an airborne disease that affects many organs in the body especially lungs. This disease is caused by a bacteria known as Mycobacterium Tuberculosis. When the bacteria becomes active it affects the body. If the disease is not treated properly a loss of life may occur. A robotic detection of tuberculosis is presented in this paper with the help of patient chest x ray(CXR).The input image is then filtered by Gaussian filter to remove noise and then the lung region gets segmented by using graph cut segmentation. The segmented lung region is partitioned into four lobes. The infected region is then segmented for that region the feature values are calculated. With these values it is classified as normal or abnormal by using Ada boost classifier.

BackgroundThe performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.Methodology/Principal Findings161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67–81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p=0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p=0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p=0.03). Low CD4 cell count (<300 cells/µl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81–92%) and did not differ between HIV-negative and HIV–positive patients (88 vs. 83%, p=0.39).Conclusions/SignificanceSensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.

Objectives: India has the largest burden of MDR-TB worldwide, with an annual incidence of 1,30 000 patients. Multidrug-resistant tuberculosis (MDR-TB) carries a poor prognosis, a high mortality rate, and treatment success rates as low as 65%. The mortality in India is estimated to be about 480,000 per year. The aim of the study was to evaluate Rifampicin-resistant Tuberculosis and its distribution by GeneXpert in a tertiary care hospital. Methods: A total of 2864 samples were processed from the patients attending outpatient departments and indoor wards as per the pediatrician's request. Acid-fast bacilli (AFB) smear microscopy was done on all samples by Acid-fast staining for early diagnosis followed by GeneXpert MTB/RIF (CBNAAT) testing. Specimens were transported and stored at 2-8 °C prior to processing for CBNAAT. Results were read and reported within 2 hours. Results: A total of 2864 samples were tested for TB using CBNAAT (including 645 [22.5%] extra-pulmonary and 2219 [77.5%] pulmonary samples). The test results were positive in a total of 346 (12%) samples by CBNAAT. The positivity is highest in the age group >10 years and in sputum samples (37.28%) followed by pus samples (23.26%) in pulmonary and extrapulmonary distribution. Out ZN staining was positive in 244 (8.5%) specimens. There were 102 (29.5%) CBNAAT positive specimens which showed negative results for Acid-fast bacilli (70.52% Sensitivity). Among 346 TB-positive patients, 10.46% samples were pulmonary and 17.67% were extrapulmonary. It was observed that in positive CBNAAT patients, the prevalence of Rifampicin resistance was 12.72% i.e. 44 samples which include 31(13.36%) and 13(11.40%) pulmonary and extra-pulmonary samples respectively. Among the Rifampicin resistant samples, there were 29.55% samples that were extrapulmonary. Conclusion: GeneXpert MTB/RIF is a very rapid diagnostic assay that provides information regarding the mutation pattern of RIF resistance in MTB isolates.

The aim of this work is the application of optimal control for the system of ordinary differential equations modeling a tuberculosis disease with exogenous reinfection. Seeking to reduce the infectious group by the reduction of the contact between infectious and exposed individuals, we use control representing the prevention of exogenous reinfection. The Pontryagin&#x27;s maximum principle is used to characterize the optimal control. The optimality system is derived and solved numerically.

Spiro acenapthene derivatives are structurally diverse group of compounds that show the wide range of antituberculosis activity. The computational evaluation of spiro acenapthene derivatives as rpoB protein from Mycobacterium tuberculosis inhibitor has been performed. The gene rpoB encodes the β–subunit of RNA polymerase. Since no crystal structure was available for the rpoB protein, the three–dimensional structure of rpoB protein from Mycobacterium tuberculosis has been modeled to see the drug interactions,thus allowing us to predict the mutations D435V, H445Y, S450L in the modeled structure. The docking analysis was performed by PyRx software using Autodock 4. The study provides the base for further in vitro and in vivo study of the spiro acenapthene derivatives as rpoB protein inhibitor