An Ancient Harappan Genome Lacks Ancestry from Steppe Pastoralists or Iranian Farmers.

We report an ancient genome from the Indus Valley Civilization (IVC). The individual we sequenced fits as a mixture of people related to ancient Iranians (the largest component) and Southeast Asian hunter-gatherers, a unique profile that matches ancient DNA from 11 genetic outliers from sites in Iran and Turkmenistan in cultural communication with the IVC. These individuals had little if any Steppe pastoralist-derived ancestry, showing that it was not ubiquitous in northwest South Asia during the IVC as it is today. The Iranian-related ancestry in the IVC derives from a lineage leading to early Iranian farmers, herders, and hunter-gatherers before their ancestors separated, contradicting the hypothesis that the shared ancestry between early Iranians and South Asians reflects a large-scale spread of western Iranian farmers east. Instead, sampled ancient genomes from the Iranian plateau and IVC descend from different groups of hunter-gatherers who began farming without being connected by substantial movement of people.

Protective effect of Achyranthes aspera against compound 48/80, histamine and ovalbumin-induced allergic disorders in murine model.

BACKGROUND: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed. METHODS AND RESULTS: Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200 mg/kg BW. AaAq 400 (400 mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-ß and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000 mg/kg BW. CONCLUSIONS: Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.

Efficacy of Long-Acting Bedaquiline Regimens in a Mouse Model of Tuberculosis Preventive Therapy.

Rationale: Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy. Objectives: The objectives of this study were to 1) determine the total duration of activity after an injection of long-acting bedaquiline and 2) evaluate the activity of regimens comprised of long-acting bedaquiline plus short (2-4 wk) oral companion courses of bedaquiline, with or without rifapentine, using the validated mouse model of tuberculosis preventive therapy. Methods: After the establishment of a stable Mycobacterium tuberculosis lung infection in bacillus Calmette-Guérin (BCG)-immunized BALB/c mice, treatment was initiated with 1 of 12 randomly assigned regimens. In addition to positive and negative controls, six regimens included one or two injections of long-acting bedaquiline (alone or with oral bedaquiline with or without rifapentine), and four comparator regimens consisted of oral agents only. Lung bacterial burden was measured monthly for up to 28 weeks. Measurements and Main Results: One injection of long-acting bedaquiline at 160 mg/kg exerted antituberculosis activity for 12 weeks. Compared with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bactericidal activity (including two all-oral comparator regimens), and two regimens had superior sterilizing activity: one injection with 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bedaquiline. Conclusions: Long-acting injectable bedaquiline has significant potential for shortening tuberculosis preventive therapy.

2D-DIGE based urinary proteomics and functional enrichment studies to reveal novel Mycobacterium tuberculosis and human protein biomarker candidates for pulmonary tuberculosis.

In the absence of a sensitive and specific diagnostic modality capable of detecting all forms of tuberculosis (TB), proteomics may identify specific Mycobacterium tuberculosis (M.tb) proteins in urine, with a potential as biomarkers. To identify candidate biomarkers for TB, proteome profile of urine from pulmonary TB patients was compared with non-disease controls (NDC) and disease controls (DC, Streptococcus pneumonia infected patients) using a combination of two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LCMS/MS). Eleven differentially expressed host proteins and Eighteen high abundant M.tb proteins were identified. Protein-protein interactome (PPI) and functional enrichment analyses like Gene Ontologies, Reactome pathway etc. demonstrated that the human proteins mainly belong to extracellular space and show physiological pathways for immune response and hematological disorders. Whereas, M.tb proteins belong to the cell periphery, plasma membrane and cell wall, and demonstrated catalytic, nucleotide binding and ATPase activities along with other functional processes. The study findings provide valuable inputs about the biomarkers of TB and shed light on the probable disease consequences as an outcome of the bacterial pathogenicity.

In Vitro Activity of Bedaquiline and Imipenem against Actively Growing, Nutrient-Starved, and Intracellular Mycobacterium abscessus.

Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria. Currently, the standard of care is a multidrug regimen with at least 3 active drugs, preferably including a ß-lactam (imipenem or cefoxitin). These regimens are lengthy and toxic and have limited efficacy. The search for more efficacious regimens led us to evaluate bedaquiline, a diarylquinoline licensed for treatment of multidrug-resistant tuberculosis. We performed in vitro time-kill experiments to evaluate the activity of bedaquiline alone and in combination with the first-line drug imipenem against M. abscessus under various conditions. Against actively growing bacteria, bedaquiline was largely bacteriostatic and antagonized the bactericidal activity of imipenem. Contrarily, against nutrient-starved persisters, bedaquiline was bactericidal, while imipenem was not, and bedaquiline drove the activity of the combination. In an intracellular infection model, bedaquiline and imipenem had additive bactericidal effects. Correlations between ATP levels and the bactericidal activity of imipenem and its antagonism by bedaquiline were observed. Interestingly, the presence of Tween 80 in the media affected the activity of both drugs, enhancing the activity of imipenem and reducing that of bedaquiline. Overall, these results show that bedaquiline and imipenem interact differently depending on culture conditions. Previously reported antagonistic effects of bedaquiline on imipenem were limited to conditions with actively multiplying bacteria and/or the presence of Tween 80, whereas the combination was additive or indifferent against nutrient-starved and intracellular M. abscessus, where promising bactericidal activity of the combination suggests it may have a role in future treatment regimens.

New ß-Lactamase Inhibitors Nacubactam and Zidebactam Improve the In Vitro Activity of ß-Lactam Antibiotics against Mycobacterium abscessus Complex Clinical Isolates.

The new diazabicyclooctane-based ß-lactamase inhibitors avibactam and relebactam improve the in vitro activity of ß-lactam antibiotics against bacteria of the Mycobacterium abscessus complex (MABC). Here, we evaluated the in vitro activities of two newer diazabicyclooctane-based ß-lactamase inhibitors in clinical development, nacubactam and zidebactam, with ß-lactams against clinical isolates of MABC. Both inhibitors lowered the MICs of their partner ß-lactams, meropenem (8-fold) and cefepime (2-fold), respectively, and those of other ß-lactams, similar to prior results with avibactam and relebactam.

In Vitro Activity of New Tetracycline Analogs Omadacycline and Eravacycline against Drug-Resistant Clinical Isolates of Mycobacterium abscessus.

Tigecycline is used in multidrug regimens for salvage therapy of Mycobacterium abscessus infections but is often poorly tolerated and has no oral formulation. Here, we report similar in vitro activity of two newly approved tetracycline analogs, omadacycline and eravacycline, against 28 drug-resistant clinical isolates of M. abscessus complex. Since omadacycline and eravacycline appear to be better tolerated than tigecycline and since omadacycline is also formulated for oral dosing, these tetracycline analogs may represent new treatment options for M. abscessus infections.

Activity of a Long-Acting Injectable Bedaquiline Formulation in a Paucibacillary Mouse Model of Latent Tuberculosis Infection.

The potent antituberculosis activity and long half-life of bedaquiline make it an attractive candidate for use in long-acting/extended-release formulations for the treatment of latent tuberculosis infection (LTBI). Our objective was to evaluate a long-acting injectable (LAI) bedaquiline formulation in a validated paucibacillary mouse model of LTBI. Following immunization with Mycobacterium bovis rBCG30, BALB/c mice were challenged by aerosol infection with M. tuberculosis H37Rv. Treatment began 13 weeks after challenge infection with one of the following regimens: an untreated negative-control regimen; positive-control regimens of daily rifampin (10 mg/kg of body weight), once-weekly rifapentine (15 mg/kg) and isoniazid (50 mg/kg), or daily bedaquiline (25 mg/kg); test regimens of one, two, or three monthly doses of LAI bedaquiline at 160 mg/dose (BLAI-160); and test regimens of daily bedaquiline at 2.67 mg/kg (B2.67), 5.33 mg/kg (B5.33), or 8 mg/kg (B8) to deliver the same total amount of bedaquiline as one, two, or three doses of BLAI-160, respectively. All drugs were administered orally, except for BLAI-160 (intramuscular injection). The primary outcome was the decline in M. tuberculosis lung CFU counts during 12 weeks of treatment. The negative- and positive-control regimens performed as expected. One, two, and three doses of BLAI-160 resulted in decreases of 2.9, 3.2, and 3.5 log10 CFU/lung, respectively, by week 12. Daily oral dosing with B2.67, B5.33, and B8 decreased lung CFU counts by 1.6, 2.8, and 4.1 log10, respectively. One dose of BLAI-160 exhibited activity for at least 12 weeks. The sustained activity of BLAI-160 indicates that it shows promise as a short-course LTBI treatment requiring few patient encounters to ensure treatment completion.

In Vitro Activity of the New ß-Lactamase Inhibitors Relebactam and Vaborbactam in Combination with ß-Lactams against Mycobacterium abscessus Complex Clinical Isolates.

Pulmonary disease due to infection with Mycobacterium abscessus complex (MABC) is notoriously difficult to treat, in large part due to the intrinsic resistance of MABC strains to most antibiotics, including ß-lactams. MABC organisms express a broad-spectrum ß-lactamase that is resistant to traditional ß-lactam-based ß-lactamase inhibitors but inhibited by a newer non-ß-lactam-based ß-lactamase inhibitor, avibactam. Consequently, the susceptibility of MABC members to some ß-lactams is increased in the presence of avibactam. Therefore, we hypothesized that two new non-ß-lactam-based ß-lactamase inhibitors, relebactam and vaborbactam, would also increase the susceptibility of MABC organisms to ß-lactams. The objective of the present study was to evaluate the in vitro activity of various marketed ß-lactams alone and in combination with either relebactam or vaborbactam against multidrug-resistant MABC clinical isolates. Our data demonstrate that both ß-lactamase inhibitors significantly improved the anti-MABC activity of many carbapenems (including imipenem and meropenem) and cephalosporins (including cefepime, ceftaroline, and cefuroxime). As a meropenem-vaborbactam combination is now marketed and an imipenem-relebactam combination is currently in phase III trials, these fixed combinations may become the ß-lactams of choice for the treatment of MABC infections. Furthermore, given the evolving interest in dual ß-lactam regimens, our results identify select cephalosporins, such as cefuroxime, with superior activity in the presence of a ß-lactamase inhibitor that are deserving of further evaluation in combination with these carbapenem-ß-lactamase inhibitor products.

Non-classical transpeptidases yield insight into new antibacterials.

Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the ß-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of ß-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for ß-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria. We have characterized the molecular mechanisms responsible for inhibition of L,D-transpeptidases of Mycobacterium tuberculosis and a range of bacteria including ESKAPE pathogens, and used this information to design, synthesize and test simplified carbapenems with potent antibacterial activity.

Mutation in an Unannotated Protein Confers Carbapenem Resistance in Mycobacterium tuberculosis.

ß-Lactams are the most widely used antibacterials. Among ß-lactams, carbapenems are considered the last line of defense against recalcitrant infections. As recent developments have prompted consideration of carbapenems for treatment of drug-resistant tuberculosis, it is only a matter of time before Mycobacterium tuberculosis strains resistant to these drugs will emerge. In the present study, we investigated the genetic basis that confers such resistance. To our surprise, instead of mutations in the known ß-lactam targets, a single nucleotide polymorphism in the Rv2421c-Rv2422 intergenic region was common among M. tuberculosis mutants selected with meropenem or biapenem. We present data supporting the hypothesis that this locus harbors a previously unidentified gene that encodes a protein. This protein binds to ß-lactams, slowly hydrolyzes the chromogenic ß-lactam nitrocefin, and is inhibited by select penicillins and carbapenems and the ß-lactamase inhibitor clavulanate. The mutation results in a W62R substitution that reduces the protein's nitrocefin-hydrolyzing activity and binding affinities for carbapenems.

In vitro and in vivo activity of biapenem against drug-susceptible and rifampicin-resistant Mycobacterium tuberculosis.

Background: Biapenem, a carbapenem antibiotic, has been shown to have synergistic bactericidal anti-TB activity when combined with rifampicin both in vitro and in the mouse model of TB chemotherapy. We hypothesized that this synergy would result in biapenem/rifampicin activity against rifampicin-resistant Mycobacterium tuberculosis . Objectives: Our objective was to evaluate the synergy of biapenem/rifampicin against both low- and high-level rifampicin-resistant strains of M. tuberculosis , in vitro and in the mouse model. Methods: Biapenem/rifampicin activity was evaluated using three strains of M. tuberculosis : strain 115R (low-level rifampicin resistance); strain 124R (high-level rifampicin resistance); and the drug-susceptible H37Rv parent strain. Biapenem/rifampicin synergy was evaluated in vitro by chequerboard titration. In vivo , we first conducted a dose-ranging experiment with biapenem against H37Rv in the mouse model. We then evaluated biapenem/rifampicin activity in mice infected with each M. tuberculosis strain. Results: In vitro , synergy was observed between biapenem and rifampicin against H37Rv and strain 115R. In vivo , biapenem exhibited clear dose-dependent activity against H37Rv, with all biapenem doses as active or more active than rifampicin alone. Biapenem and rifampicin had synergistic bactericidal activity against H37Rv in the mouse model; no synergy was observed in mice infected with either of the rifampicin-resistant strains. Biapenem alone was active against all three strains. Conclusions: Our preclinical experiments indicate that biapenem has potential for use as an anti-TB drug, including for use against rifampicin-resistant TB. Thus, biapenem has promise for repurposing as a 'new' - and desperately needed - drug for the treatment of drug-resistant TB.

An evolved oxazolidinone with selective potency against Mycobacterium tuberculosis and gram positive bacteria.

Innovation of new antibacterials that are effective against strains that have developed resistance to existing drugs would strengthen our ability to treat and subsequently control spread of pathogenic bacteria. Increasing incidence of infections with drug resistant bacteria has become a common occurrence in recent times. We have developed an evolved oxazolidinone, T145, which inhibits growth of Enterococcus faecalis, Staphylococcus aureus and Mycobacterium tuberculosis (Mtb) with sub µg/ml potencies that are potentially therapeutically valuable. The oxazolidinone is bactericidal against Mtb but bacteriostatic against E. faecalis and S. aureus. In addition to therapeutically valuable potency and bactericidal activity against Mtb, T145 minimizes selection of spontaneous resistant mutants, a trait that prolongs longevity of a drug in clinical use.

Carbapenems and Rifampin Exhibit Synergy against Mycobacterium tuberculosis and Mycobacterium abscessus.

An effective regimen for treatment of tuberculosis (TB) is comprised of multiple drugs that inhibit a range of essential cellular activities in Mycobacterium tuberculosis. The effectiveness of a regimen is further enhanced if constituent drugs act with synergy. Here, we report that faropenem (a penem) or biapenem, doripenem, or meropenem (carbapenems), which belong to the ß-lactam class of antibiotics, and rifampin, one of the drugs that forms the backbone of TB treatment, act with synergy when combined. One of the reasons (carba)penems are seldom used for treatment of TB is the high dosage levels required, often at the therapeutic limits. The synergistic combination of rifampin and these (carba)penems indicates that (carba)penems can be administered at dosages that are therapeutically relevant. The combination of faropenem and rifampin also limits the frequency of resistant mutants, as we were unable to obtain spontaneous mutants in the presence of these two drugs. The combinations of rifampin and (carba)penems were effective not only against drug-sensitive Mycobacterium tuberculosis but also against drug-resistant clinical isolates that are otherwise resistant to rifampin. A combination of doripenem or biapenem and rifampin also exhibited synergistic activity against Mycobacterium abscessus. Although the MICs of these three drugs alone against M. abscessus are too high to be of clinical relevance, their concentrations in combinations are therapeutically relevant; therefore, they warrant further evaluation for clinical utility to treat Mycobacterium abscessus infection, especially in cystic fibrosis patients.

Green biotechnology, nanotechnology and bio-fortification: perspectives on novel environment-friendly crop improvement strategies.

Food insecurity and malnutrition are prominent issues for this century. As the world's population continues to increase, ensuring that the earth has enough food that is nutritious too will be a difficult task. Today one billion people of the world are undernourished and more than a third are malnourished. Moreover, the looming threat of climate change is exasperating the situation even further. At the same time, the total acreage of arable land that could support agricultural use is already near its limits, and may even decrease over the next few years due to salination and desertification patterns resulting from climate change. Clearly, changing the way we think about crop production must take place on multiple levels. New varieties of crops must be developed which can produce higher crop yields with less water and fewer agricultural inputs. Besides this, the crops themselves must have improved nutritional qualities or become biofortified in order to reduce the chances of 'hidden hunger' resulting from malnourishment. It is difficult to envision the optimum way to increase crop production using a single uniform strategy. Instead, a variety of approaches must be employed and tailored for any particular agricultural setting. New high-impact technologies such as green biotechnology, biofortification, and nanotechnology offer opportunities for boosting agricultural productivity and enhancing food quality and nutritional value with eco-friendly manner. These agricultural technologies currently under development will renovate our world to one that can comfortably address the new directions, our planet will take as a result of climate change.

Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models.

A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations. The objective of this pilot study was to evaluate the impact of co-administration of hyaluronidase on the drug release kinetics, pharmacokinetic profiles, and injection site histopathology of the long-acting injectable paliperidone palmitate for up to four weeks following intramuscular injection in mouse and rat models. In both species, co-administration of hyaluronidase increased paliperidone plasma exposures the first week after injection but did not negate the overall long-acting release nature of the formulation. Hyaluronidase-associated modification of the injection site depot was observed in mice but not in rats. These findings suggest that further investigation of hyaluronidase with long-acting injectable agents is warranted.

Apolipoprotein A1 as a potential biomarker in the ascitic fluid for the differentiation of advanced ovarian cancers.

CONTEXT: Primary ovarian cancer and ovarian metastasis from non-ovarian cancers in advanced stage are closely mimicking conditions whose therapeutics and prognosis are different. OBJECTIVE: To identify biomarkers that can differentiate the two variants of advanced ovarian cancers. METHODS: Gel-based proteomics and antibody-based assays were used to study the differentially expressed proteins in the ascitic fluid of fourteen patients with advanced ovarian cancers. RESULTS: Programmed Cell Death 1-Ligand 2, apolipoprotein A1, apolipoprotein A4 and anti-human fas antibody are differentially expressed proteins. CONCLUSIONS: Apolipoprotein A1 with a 61.8 ng/ml cut-off is a potential biomarker with the best differentiating statistical parameters.

Enhanced Anti-Proliferative Effect of Carboplatin in Ovarian Cancer Cells Exploiting Chitosan-Poly (Lactic Glycolic Acid) Nanoparticles.

OBJECTIVE: The present article aimed to enhance the therapeutic efficacy of carboplatin (CP) using the formulation of chitosan-poly (lactic glycolic acid) nanoparticles (CS-PLGA NPs). METHODS: Nanoparticles were synthesized by an ionic gelation method and were characterized for their morphology, particle size, and surface potential measurements by TEM and zeta sizer. This study was highlighted for the evaluation of drug entrapment, loading and in vitro drug release capabilities of the prepared nanoparticles by spectrophotometric analysis. The stability study was also conducted after 3 months for their particle size, zeta potential, drug loading and encapsulation efficiencies. Further, ovarian cancer cell line PEO1 was used to evaluate the toxicity and efficacy of nano-formulation by MTT assay. Additionally, the study was evaluated for apoptosis using flow cytometric analysis. RESULTS: The CS-PLGA-CP NPs were uniform and spherical in shape. The particle size and zeta potential of CS-PLGA-CP NPs were measured to be 156 ±6.8 nm and +52 ±2.4 mV, respectively. High encapsulation (87.4 ± 4.5%) and controlled retention capacities confirmed the efficiency of the prepared nanoparticles in a time and dose-dependent manner. The cytotoxicity assay results also showed that CS-PLGA-CP NPs have a high efficiency on PEO1 cells compared to the free drug. The flow cytometric result showed 64.25% of the PEO1 cells were apoptotic, and 8.42% were necrotic when treated with CS-PLGA-CP NPs. CONCLUSION: Chitosan-PLGA combinational polymeric nanoparticles were not only steady but also non-toxic. Our experiments revealed that the chitosan-PLGA nanoparticles could be used as a challenging vehicle candidate for drug delivery for the therapeutic treatment of ovarian cancer.

The second wave of COVID-19 wreaked havoc: A look at clinical and laboratory parameters of survivors and non-survivors admitted to Intensive Care Unit, a single-centered retrospective study.

Background: The second wave of COVID-19 was disastrous and claimed many lives in India and abroad. The most challenging task was to provide the required treatment as per the patient's condition, within a limited span of time. The lack of prognostic predictors at the time of admission led to failure in prioritizing the patient's need for intensive care. Aim: This study was conducted to find out the clinical and laboratory parameters at the time of admission to ICU as predictors of outcomes in COVID-19 patients, which can help in judicious utilization of the available resources for better patient care. Subjects and Methods: Study comprises of 161 ICU admitted patients. Study of clinical traits, comorbidities, test results, and demographic variables were carried out among survivors and non-survivor. Result: Maximum death were patients of age group 21-30 years and male gender. Mortality in hypertensives, diabetics, and patients with sepsis were found to be statistically significant. Patients who developed ARDS and pneumonia or needed ventilation died invariably. High levels of laboratory parameters like IL-6, LDH, PT, INR, aPTT, ferritin, WBC count, and D-dimer were significantly associated with poor outcomes and at a particular cutoff had optimum sensitivity and specificity to predict mortality in ICU admitted COVID-19 patients. At the same time, low lymphocyte count and PaO2/FiO2 ratio was significantly associated with bad prognosis (P < 0.05). Conclusion: This paper will help in prioritizing patients in ICU who need special attention especially at the time of meager supply of resources.

Diagnostic potential of 16 kDa (HspX, α-crystalline) antigen for serodiagnosis of tuberculosis.

BACKGROUND & OBJECTIVES: Tuberculosis (TB) is a public health problem worldwide. Rapid and accurate diagnosis of tuberculosis is crucial to facilitate early treatment of infectious cases and to reduce its spread. The present study was aimed to evaluation of 16 kDa antigen as a serodiagnostic tool in pulmonary and extra-pulmonary tuberculosis patients in an effort to improve diagnostic algorithm for tuberculosis. METHODS: In this study, 200 serum samples were collected from smear positive and culture confirmed pulmonary tuberculosis patients, 30 tubercular pleural effusions and 21 tubercular meningitis (TBM) patients. Serum samples from 36 healthy, age matched controls (hospital staff), along with 60 patients with non-tubercular respiratory diseases were also collected and evaluated. Humoral response (both IgG and IgA) was looked for 16 kDa antigen using indirect ELISA. RESULTS: Sensitivity of detection in various categories of pulmonary TB patients ranged between 73.8 and 81.2 per cent. While in the extra-pulmonary TB samples the sensitivity was 42.8 per cent (TBM) and 63.3 per cent (tubercular pleural effusion). The test specificity in both the groups was high (94.7%). All of the non-disease controls were negative. Among non-tubercular disease controls, five patients gave a positive humoral response against 16 kDa. INTERPRETATION & CONCLUSIONS: Serodiagnostic tests for TB have always had drawbacks of suboptimal sensitivity and specificity. The antigen used in this study gave encouraging results in pulmonary TB only, while in extra-pulmonary TB (tubercular meningitis and tubercular pleural effusion), this has shown a limited role in terms of sensitivity. Further work is required to validate its role in serodiagnosis of TB especially extra-pulmonary TB.