Containment Of Tuberculosis Research Articles

A robust ensemble deep learning framework for accurate diagnoses of tuberculosis from chest radiographs.

Tuberculosis (TB) stands as a paramount global health concern, contributing significantly to worldwide mortality rates. Effective containment of TB requires deployment of cost-efficient screening method with limited resources. To enhance the precision of resource allocation in the global fight against TB, this research proposed chest X-ray radiography (CXR) based machine learning screening algorithms with optimization, benchmarking and tuning for the best TB subclassification tasks for clinical application. This investigation delves into the development and evaluation of a robust ensemble deep learning framework, comprising 43 distinct models, tailored for the identification of active TB cases and the categorization of their clinical subtypes. The proposed framework is essentially an ensemble model with multiple feature extractors and one of three fusion strategies-voting, attention-based, or concatenation methods-in the fusion stage before a final classification. The comprised de-identified dataset contains records of 915 active TB patients alongside 1,276 healthy controls with subtype-specific information. Thus, the realizations of our framework are capable for diagnosis with subclass identification. The subclass tags include: secondary tuberculosis/tuberculous pleurisy; non-cavity/cavity; secondary tuberculosis only/secondary tuberculosis and tuberculous pleurisy; tuberculous pleurisy only/secondary tuberculosis and tuberculous pleurisy. Based on the dataset and model selection and tuning, ensemble models show their capability with self-correction capability of subclass identification with rendering robust clinical predictions. The best double-CNN-extractor model with concatenation/attention fusion strategies may potentially be the successful model for subclass tasks in real application. With visualization techniques, in-depth analysis of the ensemble model's performance across different fusion strategies are verified. The findings underscore the potential of such ensemble approaches in augmenting TB diagnostics with subclassification. Even with limited dataset, the self-correction within the ensemble models still guarantees the accuracies to some level for potential clinical decision-making processes in TB management. Ultimately, this study shows a direction for better TB screening in the future TB response strategy.

Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study.

The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

Management and Marketing of Circulation of First-Line Antituberculosis Medicines: Use of Innovative Research Technologies

The management and marketing of first-line antituberculosis medicines are paramount for the effective containment and treatment of tuberculosis, a global health challenge. Ensuring the optimal circulation of these medicines requires a seamless integration of supply chain management, demand forecasting, and strategic marketing. The introduction of innovative research technologies has transformed the landscape, offering enhanced methods for drug distribution, patient adherence, and efficacy tracking. Digital platforms harness data analytics to predict medicine demand more accurately, ensuring timely production and distribution, minimizing wastage, and optimizing resource allocation. Furthermore, innovative technologies such as blockchain can fortify the drug supply chain against counterfeits, ensuring that only genuine products reach end-users. On the marketing front, artificial intelligence-driven tools enable targeted awareness campaigns, providing personalized patient information and improving adherence to drug regimens. As tuberculosis treatment necessitates prolonged medication courses, ensuring patient compliance is crucial. Advanced research technologies assist in real-time monitoring of patient's drug intake, identifying potential drop-offs, and intervening timely. The main principles of pharmacotherapy of tuberculosis were presented in the article. Pharmaceutical marketing of anti-tuberculosis drugs was experimentally researched. The most promising manufacturers in terms of availability, quality, and demand for doctors, pharmacists, and patients were highlighted. In summary, innovative research technologies are indispensable in the modern management and marketing strategies of first-line antituberculosis medicines, fostering improved treatment outcomes, patient safety, and global tuberculosis containment efforts.

Immune Regulatory Effect of Osteopontin Gene Therapy in a Murine Model of Multidrug Resistant Pulmonary Tuberculosis.

Tuberculosis (TB) has been for many years a major public health problem since treatment is long and sometimes ineffective favoring the increase of multidrug-resistant mycobacteria (MDR-TB). Gene therapy is a novel and effective tool to regulate immune responses. In this study we evaluated the therapeutic effect of an adenoviral vector codifying osteopontin (AdOPN), a molecule known for their roles to favor Th1 and Th17 type-cytokine expression which are crucial in TB containment. A single dose of AdOPN administration in BALB/c mice suffering late progressive pulmonary MDR-TB produced significant lower bacterial load and pneumonia, due to higher expression of IFN-γ, IL-12, and IL-17 in coexistence with increase of granulomas in number and size, resulting in higher survival, in contrast with mice treated with the control adenovirus that codify the green fluorescent protein (AdGFP). Combined therapy of AdOPN with a regimen of second line antibiotics produced a better control of bacterial load in lung during the first days of treatment, suggesting that AdOPN can shorten chemotherapy. Taken together, gene therapy with AdOPN leads to higher immune responses against TB infection, resulting in a new potential treatment against pulmonary TB that can co-adjuvant chemotherapy.

A New CpG ODN Induces a Fine-Tuning of Innate Response Resulting in Mycobacterium tuberculosis Containment

Synthetic oligodeoxynucleotides containing bacterial CpG motifs trigger an immunomodulatory response that correlates with both the CpG hhhexamers and their flanking regions. In this study, four new phosphodiester backbone CpG ODNs were studied in the contest of the innate immune response to Mycobacterium tuberculosis (MTB) infection. Two out of the four CpG ODNs (CpG2 and CpG3) displayed significant and opposite immunomodulatory effects: CpG2 enhanced MTB containment by human Monocyte-Derived-Macrophages (MDM), while CpG3 promoted an increased pathogen growth, higher ROS and Labile Iron Pool (LIP) levels. Accordingly, for iron homeostasis genes transcription, CpG2 and CpG3 induced, respectively, an iron retention and iron release phenotype. Moreover, CpG2 induced NLRC4 and TRAF6 gene expression and repressed IKK alpha and TREM1 while CpG3 induced PPBP and IL-36 RN and repressed TRAF6, IL-1B, IL-1R2 and NF-kB2. After MTB infection, CpG2 increased the release of soluble TREM1 protein among many others as compared with fewer innate response-associated proteins induced by CpG3. We suggest that CpG2 helps the containment of MTB infection, by inducing an early tight balance of MDM activation players, including LIP, chemokines, ROS and TREM1 receptors. Oppositely, CpG3 induces in MDM an excessive and unregulated inflammatory response unable to contain MTB infection.

Immunologic goalposts for TB vaccine development

A limiting factor in identifying effective tuberculosis (TB) vaccines is our incomplete understanding of correlates of protection. In this issue of Cell Host & Microbe, Esaulova et al. reveal cell types associated with TB containment and disease progression in non-human primates, which may provide immunologic goalposts for vaccine design.

Detailed epidemiological analysis as a strategy for evaluating the actual behavior of tuberculosis in an apparently low-incidence region

ABSTRACT Tuberculosis control in developing regions with apparent low incidence, like the low-income Mexican state of Michoacán, with mean annual incidence rates below 10/100,000 inhabitants, requires knowledge of the actual behavior of the disease. This can be determined using an epidemiological profile at sub-regional level, allowing disclosure of the clinical and social factors that may be hampering efforts to control tuberculosis. In this work, a detailed epidemiological profile was outlined using data of all new monthly cases registered in the National System of Epidemiological Surveillance Database for Michoacán municipalities from 2000 to 2012. Cases were grouped by gender and age, and sociodemographic data were obtained both from the National Institute of Statistics and Geography and from the United Nations Development Programme. Correlations were calculated by Chi-square, Mann-Whitney U, and Kruskal-Wallis H tests. We observed no statistically significant differences between notification rates for the years 2000, 2005 and 2010 (χ2 = 0.222, p = 0.895). The percentage of cases is similar between all age groups older than 15, while some regions had low notification rates but high proportions of pediatric cases. Higher proportions of cases of extrapulmonary tuberculosis were observed in municipalities in northern Michoacán. No correlation was found between municipal Human Development Index values and municipal notification rates. Michoacán is undergoing an epidemiological transition with three regions having different epidemiological profiles and particular needs for effective prevention and containment of tuberculosis. Our work shows the importance of the spatial scale of epidemiological profiles for determining specific regional needs of surveillance and containment.

Tuberculosis Knowledge:A Survey among Students of a Medical College from Coastal Karnataka, India

Background: Tuberculosis (TB) is one of the most common diseases, and globally, it ranks second, first being AIDS. It has been said that one-third of the global population is already infected with M. tuberculosis. By 2020, an estimated 200 million of these people would contract TB. A very crucial step for containment of TB is to make sure that there is understanding of its risk factors, mode of transmission, and diagnosis. Aims and Objectives: This study aimed to assess the knowledge and understanding of MBBS students at coastal Karnataka, India Medical College, about Tuberculosis. Methodology: An online survey was conducted addressing areas of general factors, risk and transmission factors, diagnosis factors, treatment, and prevention factors. A total of 31 statements were given in the online survey. Results: The respondents showed overall good knowledge about Tuberculosis. The females had a better understanding than males, and the interns scored better on the study than the other MBBS students. Conclusion: This study has shown that the students have high essential awareness about TB. However, section by section analysis shows that knowledge about a few topics needs to be strengthened.

Prevalence of Malaria and TB Coinfection at a National Tuberculosis Treatment Centre in Uganda.

The prevalence of malaria and tuberculosis (TB) coinfection is not well established in countries that are highly burdened for both diseases. Malaria could impair TB containment and increase mortality of TB patients. The objective of this study was to determine the prevalence of malaria/TB coinfection among bacteriologically confirmed adult TB patients at a national TB treatment centre in Uganda. Using a cross-sectional study design we enrolled 363 bacteriologically confirmed adult TB patients, and data on demographics and medical history was collected. Blood samples were tested for malaria blood smear, rapid malaria diagnostic test (RDT), complete blood count, haematological film analysis, HIV serology, and CD4+ and CD8+ cell counts. Malaria was defined as either a positive blood smear or RDT. The study participants were mostly male (61.4%), with a median age of 31 (interquartile range, IQR: 25-39) years, and 35.8% were HIV positive. The prevalence of malaria was 2.2% (8/363) on the overall and 5% (3/58) among participants with rifampicin resistance. A triple infection of HIV, malaria, and rifampicin resistant TB was observed in 3 participants. The prevalence of malaria among TB patients is low, and further evaluation of the epidemiological, clinical, and immunological interaction of the two diseases is warranted.

CD4 T Cell Count in Newly diagnosed PTB Patients With Reference to their HIV Sero status

Introduction: CD4 and CD8 T cells facilitate the containment of tuberculosis (TB) and has been postulated that there will be changes in their level in patients with TB. This study was carried out to analyze the CD4 cell counts in pulmonary tuberculosis (PTB) patients with reference to their HIV status.Methods: A cross-sectional study was conducted at the Department of Microbiology of a tertiary care hospital of eastern Nepal from May 2012 to April 2013. A total of 160 individuals, 40 each in the PTB, PTB/HIV, HIV and healthy population were included after obtaining informed consent. PTB and HIV diagnosis was made according to national guidelines. CD4 T cells were analyzed using a BD FACS Count Cytometer. Data were entered in Microsoft Excel 2007 and analyzed using SPSS version 11.7.Results: The mean absolute CD4 cells in PTB patient were 562.20 ± 197.3 cells/ul, which was a clear reduction (p &lt; 0.001) when compared to the healthy population of this area (786.30 ± 239.17 cells/ul). There was significant decrease in the CD4 level among the HIV/TB patient (123.70 ± 99.4 cells/ul) as compared to PTB patient without HIV (p &lt; 0.001). The study also noted that the mean CD4 cell level among HIV infected population (249.68 cells/ul) was higher compared to the HIV/TB co-infected population (p &lt; 0.05).Conclusion: CD4 cell count can reflect the degree of immunosuppression in PTB patient irrespective of their HIV status but it cannot predict the disease severity in PTB patient.

Serum Vitamin D Level as a Risk Factor for Female Genital Tuberculosis (FGTB).

Vitamin D is now known to be essential to Mycobacterium tuberculosis containment and killing through activation of 25-hydroxyvitamin-D receptors (VDRs) present on all immune cells or obtained from dietary food stuffs as either vitamin D3 or vegetable vitamin D2 (also known as ergocalciferol). To evaluate the association of serum vitamin D level between the Female Genital Tuberculosis (FGTB) cases and healthy controls. Total 120 cases and 120 controls enrolled for the study following inclusion and exclusion criteria. Detailed clinical history was taken from each subjects. Total of 3 ml of the blood was collected in EDTA vial from each subject (case and control). Quantification of serum vitamin D level was measured by active human vitamin D ELISA kit using an ELISA reader. Statistical analysis was done using Statistical Package for Social Science (SPSS) version 21.0. A p-value <0.05 was considered as significant. A total of 120 confirmed FGTB cases and 120 healthy control enrolled for study. Out of 120 women 97.5%, 10.0%, 3.3%, 3.3% were detected positive for M. tuberculosis respectively. Comparing the mean demographic value of age and BMI were (29.03±3.127, 28.03±3.00) and (22.92±3.33, 24.15±3.97) respectively with the p=0.012* and p=0.010* found to be significant among cases and controls. The mean serum vitamin D level was 14.96±8.81 in cases and 23.00±8.83 in controls with p-value<0.001. There was a significant positive association found in low serum vitamin D level among FGTB cases than controls. Vitamin D is important for normal immune cell function, as well as regression of FGTB disease. FGTB may be controlled by regulating the serum vitamin D level concentration. This study suggests that, vitamin D deficiency and BMI is strongly associated with the progression of active FGTB disease which alters the expression of antimicrobial peptide and lead to the persistence of TB infection. Therefore, serum vitamin D level may play an important role in treatment of FGTB.

Vitamin D deficiency and TB disease phenotype

BackgroundExtrapulmonary TB is increasingly common, yet the determinants of the wide clinical spectrum of TB are poorly understood.MethodsWe examined surveillance data (Birmingham, UK: 1980–2009 and USA Centers for Disease Control:...

Suppress for Success: A JAK Inhibitor for Adjunct Therapy of Tuberculosis

Standard chemotherapy of tuberculosis (TB), which is caused by infection with Mycobacterium tuberculosis (Mtb) and which primarily affects the lung, consists of a combination of antimicrobial drugs (isoniazid, rifampin, ethambutol and pyrazinamide). Concomitant administration of these antimicrobials helps eradicate active infection and prevents disease relapse (Zumla et al., 2015). In most patients suffering from drug-susceptible TB, strong adherence to treatment for at least 6 months leads to cure of TB disease. However, poor compliance with the prolonged treatment regime facilitates spread of infection, as active TB patients expectorate bacteria. Prolonged treatment also promotes the development of drug-resistant Mtb. Multidrug-resistant (MDR)-TB is clinically difficult to manage and accounted for 3.5% of the 9 million new TB cases in 2013 and about 20.5% of previously treated TB patients (WHO, 2014). Shortening the length of TB chemotherapy could thus limit spread of the disease and restrict emergence of drug resistance. In this issue of EBioMedicine, Maiga et al. provide pre-clinical evidence that Tofacitinib, an FDA-approved Janus kinase (JAK) inhibitor, accelerates bacterial clearance when co-administered with canonical TB chemotherapy. Recent approaches toward more efficacious interventions against TB, including shortening the length of the chemotherapy, include host-directed therapy (HDT) (Kaufmann et al., 2014). HDTs that focus on modulation of inflammation comprise strategies to release immune suppression and enhance anti-microbial mechanisms, or alternatively, reduce inflammatory responses. Corticosteroids, TNF blockers, statins, thalidomide analogues and inhibitors of phosphodiesterases, cyclooxygenases and leukotrienes have been singled out as potentially adjunctive to canonical chemotherapy (Wallis and Hafner, 2015). Reduction of inflammation promotes bacillary replication and destabilizes granulomas, thereby enhancing the tissue penetrability of drugs effective against metabolically active bacteria. The rationale for dampening inflammation has been informed by the efficacy of most anti-mycobacterial drugs against actively replicating Mtb and their limited activity against dormant bacilli. Tofacitinib inhibits JAK3- and to a lesser extent JAK-2-mediated phosphorylation of activated cytokine receptors and subsequently limits responsiveness to pro-inflammatory cytokines (Pesu et al., 2008). Tofacitinib is licensed for therapy of rheumatoid arthritis and ulcerative colitis. Moreover, similar to usage of TNF blockers, TB reactivation has been reported for this JAK inhibitor in cases of latent TB infection (Winthrop et al., 2012) and in a mouse model of chronic paucibacillary TB (Maiga et al., 2012). Pursuing observations that Tofacitinib interferes with containment of TB (Maiga et al., 2012) and based on pharmacokinetic studies, Maiga et al. evaluated efficacy of Tofacitinib as HDT for standard TB chemotherapy in different mouse models (Maiga et al., in press). The authors showed that addition of Tofacitinib to standard chemotherapy profoundly shortened time to lung sterility in a chronic TB mouse model. Importantly, treatment did not lead to isoniazid resistance and did not alter the time required to achieve relapse-free TB cure, which together are critical for the design of novel, more efficacious treatment regimens. These findings strengthen the concept that strategies promoting “awakening” of dormant Mtb are favorable for TB patients when applied concomitantly with chemotherapy. Many anti-inflammatory drugs are clinically approved, and as such are a rationale choice for accelerating the transition of preclinical findings to clinical trials. Design of novel therapies based on repurposing drugs is particularly appealing for protracted disease courses that require lengthy therapy, such as TB. Furthermore, the authors provide proof of principle for successful JAK-centered HDT of TB as an adjunct to standard TB chemotherapy. Ideal for translational work, the therapy regimen used in murine studies by Maiga et al. encompasses first-line drugs as recommended for canonical TB treatment. Advancing HDT to the arena of human clinical research requires the addition of immunomodulatory compounds to standard TB treatment. Refinement of JAK inhibitors according to enzyme specificities and pharmacological profiles could further enhance efficacy of a JAK-centered HDT in TB. Moreover, compounds with immunomodulatory activity similar to Tofacitinib could exhibit more pronounced adjunctive effects in TB therapy. Preclinical validation of Tofacitinib as adjunct to canonical chemotherapy effectively consolidates a framework of anti-inflammatory HDT for TB. Some questions remain, however. Shortening the length of treatment was observed for the Balb/c mouse model, a commonly used mouse strain for studies investigating efficiency of anti-mycobacterial drugs. Tofacitinib administration to Mtb-infected C3HeB/FeJ mice did not show therapeutic effectiveness as observed in Balb/c animals. Notably, C3HeB/FeJ mice developed lung lesions resembling human TB granulomas, including hypoxia, necrosis and caseation (Driver et al., 2012). Discrepant chemotherapeutical outcomes could reflect differences in inflammatory patterns and lung pathology in the mouse models under investigation. Future studies will clarify the mechanisms underlying divergent therapeutic outcomes. Further elaboration of disease diversity and how efficacy of medication is affected accordingly, will advance anti-TB therapy and contribute to our understanding of the complexity of TB pathophysiology.

Height-weight indices in HIV-infected children

Background: CD4 and CD8 T cells facilitate the containment of tuberculosis (TB) and has been postulated that there will be changes in their level in patients with TB. So this study was carried out to analyse the CD4 cell counts in pulmonary tuberculosis (PTB) patients with reference to their HIV status and determine the relation between the severity of PTB and CD4 count. Methods & Materials: A cross-sectional study was conducted at the CD4 laboratory, Department of Microbiology fromMay 2012 to April 2013 and was approved by IERB, BPKIHS. A total of 160 individuals, 40 each in the PTB, PTB/HIV, HIV and healthy population was included after obtaining informed consent. PTB diagnosis was made according to national tuberculosis program guidelines. HIV test was done following the VCT guidelines of Nepal. CD4 T cells were analyzed using a BD FACS Count Cytometer. Data were entered in Microsoft Excel 2007 and analyzed using SPSS version 11.7. Results: The mean absolute CD4 cells in PTB patient was 562.20±197.3 cells/ul, which was a clear reduction (p<0.001) when compared to the healthy population of this area (786.30±239.17cells/ul). Therewas significantdecrease in theCD4 level among theHIV/TBpatient (123.70±99.4 cells/ul) as compared to PTB patient without HIV(p<0.001). The study also noted that the mean CD4 cell level among HIV infected population (249.68 cells/ul)was higher compared to theHIV/TB co-infectedpopulation (p<0.05). No correlation between bacillary load and CD4 cells was observed in PTB patient, although a decreasing CD4 cellswere associated with increasing bacillary load in HIV/TB co-infected patient. Conclusion: CD4 cell count can reflect the degree of immunosuppression in PTB patient irrespective of their HIV status but it cannot predict the disease severity in PTB patient.

Phagocytosis via Complement or Fc-Gamma Receptors Is Compromised in Monocytes from Type 2 Diabetes Patients with Chronic Hyperglycemia

Type 2 diabetes patients (DM2) have a higher risk of tuberculosis (TB) that may be attributed to functional defects in their mononuclear phagocytes given the critical role of these cells in Mycobacterium tuberculosis containment. Our previous findings suggest that monocytes from DM2 have reduced association with serum-opsonized M. tuberculosis. To determine if this alteration is due to defects in phagocytosis via complement or Fc-gamma receptors (FcγRs), in this study we evaluated the uptake of sheep red blood cells coated with IgG or complement, respectively, by monocytes from individuals with and without DM2. We found that chronic hyperglycemia was significantly associated with reduced phagocytosis via either receptor by univariable and multivariable analyses. This defect was independent of host serum opsonins and flow cytometry data indicated this was not attributed to reduced expression of these phagocytic receptors on DM2 monocytes. The positive correlation between both pathways (R = 0.64; p = 0.003) indicate that monocytes from individuals with chronic hyperglycemia have a defect in the two predominant phagocytic pathways of these cells. Given that phagocytosis is linked to activation of effector mechanisms for bacterial killing, it is likely that this defect is one factor contributing to the higher susceptibility of DM2 patients to pathogens like M. tuberculosis.

Association of Receptors, Purinergic P2X7 and Tumor Necrosis Factor-alpha Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients

Introduction: The purinergic P2X7-receptors and tumor necrosis factor-alpha (TNF-α) may play important roles in the development of pulmonary tuberculosis (PTB). Genetic contribution of the host is among the most important factors that plays a significant role in the susceptibility of the disease. In this regard, both genes for P2X7 receptor and TNF-α have been identified as essential components of the host immune response in the containment of TB. However, the relationship between P2X7 and TNF-α polymorphism and TB susceptibility remains inconclusive. Objectives: This study was designed to investigate the association of P2X7 and TNF- α gene polymorphisms among Iranian PTB patients. Materials and Methods: In a case-control study, single nucleotide polymorphisms (SNPs) in P2X7 (+1513, -762) and TNF-α (at -238, -308, -244, -857 and -863) genes were assessed using PCR-RFLP and allele-specific PCR. Thereafter, haplotype and diplotype variability were compared and analyzed. Results: For the 1513 loci, the heterozygosity was higher in patients (35; 44.3%) than control subjects (12; 24%) [(P = 0.026) ORS; 2.45 CI95 % (1.13 - 5.33)]. For the -762 loci, the frequency of mutant alleles between patients and controls were not statistically significant. No statistical difference was observed in allele frequencies of TNF -308 and -857. However, the frequency of -238 A allele was more in tuberculosis (TB) cases (72.1%) (P = 0.000) [ORs: 5.85 (2.70 - 12.64)]. Data analysis showed greater frequency of haplotypes, i.e. TGGA-CA and CGGA-TA in the patient (21.5%; 14.6%) than control group (2.0%; 6.0%), respectively. Additionally, the diplotype

Advances in nanotechnology for diagnosis and treatment of tuberculosis

Tuberculosis (TB) has been a most turbulent problem prevailing for the last several decades. The emergence of multidrug-resistant strains and the dearth of anti-TB drugs are threatening the future containment of TB. Nanotechnology presents an exciting opportunity for proper identification of mycobacterial strains and to improve the potential of drugs for the treatment of TB. Nanoscience has provided humankind with several unique and comparatively more effective drug delivery carriers, encompassing liposomal-mediated drug delivery, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, nanoemulsions, nanosuspensions and other nanosystems exploiting the extraordinary properties of matter at the nanoscale. Nanoparticle-based assays have shown significant improvements in diagnosis, treatment and prevention of TB. Nanoparticles as drug carriers enable higher stability and carrier capacity along with immense improvement of drug bioavailability which further leads to reduction in dosage frequency. This review covers the prospect of using nanotechnology for the detection of mycobacterial strains and nanotechnology-based drug delivery systems for effective eradication of mycobacterial infections.

Radical Host-Specific Therapies for TB

Although proinflammatory cytokines such as TNF are critical for containment of tuberculosis, they can also exacerbate disease when produced at high levels. In this issue of Cell, Roca and Ramakrishnan demonstrate that high TNF production induces reactive oxygen species in infected macrophages, ultimately leading to macrophage necrosis and bacterial dissemination.

Association between tumor necrosis factor alpha-238G/a polymorphism and tuberculosis susceptibility: a meta-analysis study

BackgroundTumor necrosis factor alpha (TNF-α) plays a key role in the containment of tuberculosis. The relationship between the TNF -238G/A polymorphism and tuberculosis susceptibility remains inconclusive. A comprehensive meta-analysis was made to provide a more precise estimate of the relationship between them.MethodsMultiple search strategies were used. A fixed effect model was takentook to estimate pooled OR with 95% confidence interval (CI) for the association between the TNF -238G/A polymorphism and tuberculosis susceptibility. The Chi-squared-based Q-test and I-squaredI2 statistic were calculated to examine heterogeneity. Begg’s funnel plot and Egger’s test were used to assess publication bias.Results9 case-control studies were included in this meta-analysis. No significant heterogeneity was demonstrated, and no obvious publication bias was detected among the included studies. The meta-analysis indicated that there was no significant association between the TNF -238G/A polymorphism and tuberculosis susceptibility (GA+AA versus GG model: OR=1.005, 95% CI: 0.765-1.319; A versus G model: OR=1.000, 95% CI: 0.769-1.300). In the subgroup analyses by ethnicity, types of TB and human immunodeficiency virus (HIV) status, no significant association were identified.ConclusionsThe meta-analysis involving 2723 subjects did not detect any association between the TNF -238G/A polymorphism and tuberculosis susceptibility.

Inhaled Drug Delivery for Tuberculosis Therapy

One third of the world population is infected with tuberculosis (TB), and new infections occur at a rate of one per second. The recent increase in the emergence of drug-resistant strains of Mycobacterium tuberculosis and the dearth of anti-TB drugs is threatening the future containment of TB. New drugs or delivery systems that will stop the spread of TB and slow down or prevent the development of drug-resistant strains are urgently required. One of the reasons for the emergence of drug-resistant strains is the exposure of mycobacteria to sub-therapeutic levels of one or more antibiotics. Lung lesions containing large numbers of bacteria are poorly vascularized and are fortified with thick fibrous tissue; conventional therapy by the oral and parenteral routes may provide sub-therapeutic levels of anti-TB drugs to these highly sequestered organisms. Administering drugs by the pulmonary route to the lungs allows higher drug concentrations in the vicinity of these lesions. Supplementing conventional therapy with inhaled anti-TB therapy may allow therapeutic concentrations of drug to penetrate effectively into lung lesions and treat the resident mycobacteria.