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   Table of Contents - Current issue
Coverpage
April-June 2019
Volume 3 | Issue 2
Page Nos. 67-133

Online since Monday, June 17, 2019

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REVIEW ARTICLES  

The immunopathology of tuberculosis, the mode of action of the Bacillus Calmette-Guérin, of the tuberculin and of the immunotherapy Highly accessed article p. 67
Roland Maes
DOI:10.4103/bbrj.bbrj_5_19  
The outer surface of the cell membrane of Mycobacterium tuberculosis is made of carbohydrates and lipids that do not readily induce the formation of antibodies by the invaded host. The absence of antibodies against the outer cell membrane of wild strains explains the long persistence of the pathogen in the invaded host. Its immunopathology sequence proceeds in four complex steps, some generating an immunodeficiency. TB presents a pronounced phenotypic variation, with the result that strains thriving in different parts of the world differ widely immunologically. The bacterium is ubiquitous, and the claim that the infection affects a quarter of the human population is an understatement. The Bacillus Calmette–Guerin (BCG) vaccination is a primo-infection that may generate an immunodepression and favor the infection of immunodepressed hosts. The BCG vaccine elicits a vigorous cellular immune response that prevents proliferation. This explains why BCG does not protect against infection but prevents dissemination from the primary foci to other parts of the body. The mycobacterium Mycobacterium vaccae fails to elicit a cellular immune response at a par with that generated by BCG. However, it is far superior to BCG at the humoral immunity level. The boosting of the synthesis of nitric oxide is possible by food supplements, as an adjuvant to immunotherapy.
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Sputum smear microscopy in tuberculosis: It is still relevant in the era of molecular diagnosis when seen from the public health perspective p. 77
Prasanta Kumar Das, Somtirtha B Ganguly, Bodhisatya Mandal
DOI:10.4103/bbrj.bbrj_54_19  
Smear Microscopy has been the sole diagnostic support since the inception of the Revised national Tuberculosis Control Program. Treatment initiation and evaluation of prognosis both were dependant on the Smear Microscopy results. The recent commissioning of the CBNAAT machines raised questions on relevance of smear microscopy. The review explores the merits and demerits of the smear microscopy and other molecular technologies and debated on the relevance of microscopy when seen from the perspective of public health.
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ORIGINAL ARTICLES Top

Role of CXCR3+CCR5+ Th1 cells in pulmonary tuberculosis patients: At pathogenic site p. 80
Pradip K Saha, Prabhat K Sharma, Binit Kumar Singh, Chaitenya Verma
DOI:10.4103/bbrj.bbrj_78_19  
Objective: Tuberculosis (TB) still remains a major global public health problem followed by drug-resistant TB. Understanding of deeper immunopathogenesis into the pathogen–host interactions is required so that it can be translated into effective tools at a public health level. Methods: We recruited 40 pulmonary TB (PTB, sputum smear-negative) patients and studied their peripheral blood (PBL) and bronchoalveolar lavage (BAL) fluid. Of 40 patients, BAL fluid from 10 patients was collected from normal lung and diseased lung in the same patients. Immunophenotyping and intracellular cytokines were performed by flow cytometry. Results: We observed a significant increased expression of CXCR3+CCR5+T-cells (P = 0.002), CXCR3+ T-cells (P = 0.002), CCR5+ T-cells (P = 0.002), CXCR3+CD11ahigh T-cells (P = 0.002), and CCR5+CD11ahigh T-cells (P = 0.002) in BAL (n = 10) over PBL (n = 40). Increased frequency of CXCR3+CCR5+ T-cells (P = 0.02), CXCR3+ (P = 0.034), CCR5+T-cells (P = 0.039), CXCR3+CD11ahigh T-cells (P = 0.05), and CCR5+CD11ahigh T-cells (P = 0.05) was also observed in BAL of disease lung as compared to normal lung (n = 10). There was a significant decrease of inflammatory cytokine (P = 0.028) in the interferon-gamma level, whereas interleukin-4 level was significantly increased (P = 0.028) in BAL as compared to PBL. Conclusion: We conclude that in spite of significant enrichment of CXCR3+CCR5+ Th1-cells with the ability to produce inflammatory cytokines and CD11ahigh T-cells which play an important role in the recruitment of these T-cells, they are not able to control the TB infection. Therefore, our data provide insight into the functionality of effector T-cells at the disease site.
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Second-line drug susceptibilities of multidrug- and rifampicin-resistant Mycobacterium tuberculosis isolates in Delhi p. 87
Zeeshan Sidiq, M Hanif, KK Chopra, Ashwani Khanna, Indrani Jadhav, Kaushal Kumar Dwivedi
DOI:10.4103/bbrj.bbrj_53_19  
Background: Multidrug-resistant tuberculosis (MDR-TB) is a threat to the accomplishments of the World Health Organization's (WHO) End TB Strategy. The treatment of MDR-TB is less effective and more toxic; additional resistance to second-line drugs makes the treatment more difficult. India accounts for one-fourth of the global TB burden. In 2015 alone, 2.8 million cases of TB were diagnosed of which 79,000 cases had MDR/rifampicin-resistant TB (RR-TB). This study was conducted to analyze the baseline susceptibility pattern of MDR/RR-TB isolates against second-line drugs. Methods: A total of 374 culture-positive MDR and rifampicin-resistant M. tuberculosis isolates were tested for susceptibility against capreomycin (CAP), kanamycin, levofloxacin, moxifloxacin, clofazimine, and linezolid. Results: Of the total 374 isolates, 236 (63.10%) strains were susceptible to all drugs, whereas 138 (36.89%) were resistant at least to one of the second-line drugs. One hundred and sixteen (31.01%) strains were identified as preextensively drug-resistant (XDR) (MDR isolates with additional resistance to either fluoroquinolones or second-line injectables) and 22 (5.88%) of the isolates tested were identified as XDR. Conclusion: India is a signatory to the WHO's “The End TB Strategy” with the aim of ending the global TB epidemic; intensified efforts for early detection and treatment of drug-resistant cases from both public and private sectors are required to accelerate the rate at which TB incidence falls and accomplish the desired results.
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Drug resistance pattern of Mycobacterium abscessus: Change of pattern in 20-year period after the first report of human pulmonary infection in Thailand p. 92
Beuy Joob, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_35_19  
Background: Mycobacterium abscessus is a new emerging problematic mycobacterial infection seen in several countries including Thailand, a tropical country in Indochina, at present. This infection usually has the problem of antibiotic resistance. Methods: The authors hereby review and reappraise the pattern of drug resistance pattern of M. abscessus to study the change of pattern in 20-year period after the first report of human pulmonary infection in Thailand. Results: The drug resistance pattern is observable, and there are some remained nonresistant drugs. Conclusion: In our setting, drug resistance of M. abscessus has been an important problem for a long time. Nevertheless, there is still no much change of the pattern of drug resistance.
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Coinfection between human immunodeficiency virus and tuberculosis: A consideration on ritonavir-related heme Oxygenase-1 pathway p. 95
Won Sriwijitalai, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_50_19  
Background: Human immunodeficiency virus (HIV) infection is an important infection seen worldwide. HIV-infected patients usually have impaired immune function and get infected with other concurrent infections. Tuberculosis is a common concurrent infection in HIV-infected cases. The effect of coinfection and the response to the standard antiretroviral therapy in HIV-infected patients with concurrent tuberculosis infection is interesting. Methods: The aim of this study is to assess the effect of pharmacological pathway of ritonavir on tuberculosis treatment in HIV-infected patients with concurrent tuberculosis infection. The standard network pharmacology analysis is performed. Results: According to the network pharmacology analysis, the identified linkage is heme oxygenase-1. The ritonavir can result in increased expression of heme oxygenase-1 that further possible induces tuberculosis treatment failure in HIV-infected patients with concurrent tuberculosis infection. Conclusion: Ritonavir-related heme oxygenase-1 pathway is an important pathway that might affect the treatment of tuberculosis. Ritonavir dosage adjustment for tuberculosis treatment in HIV-infected patients with concurrent tuberculosis infection is necessary.
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Drug–drug interaction analysis: Antituberculosis drugs versus antiretroviral drugs p. 101
Won Sriwijitalai, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_52_19  
Background: Human immunodeficiency virus (HIV) infection is an important public health globally. An important concomitant medical disorder among HIV-infected patients is tuberculosis. The management of concurrent infection between HIV and tuberculosis is usually difficult. The concomitant use of antituberculosis drug and antiretroviral drug is required. The important clinical pharmacological concern is on the possible drug–drug interaction. Methods: Here, the authors performed an informatics study. The standard drug–drug interaction analysis was done. The possible interaction between antituberculosis drug and antiretroviral drug is accessed, and the degree of severity is also predicted using a standard bioinformatics tool, drug interaction checker. Results: Several possible drug–drug interactions can be predicted through the bioinformatics analysis tool. The different degrees of interactions can be observed for different combinations between antituberculosis drug and antiretroviral drug. Conclusion: The drug–drug interaction between antituberculosis drug and antiretroviral drug is possible and can occur at various degrees. The monitoring of the concomitant use of drugs in each specific HIV-infected individual is necessary.
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Predictive value of serum adenosine deaminase levels in prospect of tubercular infections p. 105
Trupti G Lende, Pranita Waghmare, Abhaykumar W Ambilkar, Satish Kumar
DOI:10.4103/bbrj.bbrj_51_19  
Background: Tuberculosis (TB) is well-known public health problem with one-fifth of global burden in India. Even though there are diagnostic and prognostic markers for TB, there is further need to study and understand the role of adenosine deaminase (ADA) in different forms of TB for its rapid control. The present study is conducted to ascertain the role of biochemical enzymatic marker, i.e., ADA in different forms of TB and in Bacillus Calmette–Guérin-vaccinated healthy controls. The aim is to study the role of ADA in different forms of TB compared with healthy controls. This cross-sectional study was conducted on patients attending outpatient department under a district tuberculosis center. Methods: A total 100 participants 25 in each study group and 25 in healthy control were enrolled. After taking sociodemographic profile and detailed history, serum levels of ADA were assessed and compared within study groups. Difference in level of ADA among different study groups was evaluated using the Kruskal–Wallis test. Receiver operating characteristic curve analysis was done to identify the cutoff values for ADA that has maximum sensitivity and specificity. Results: Of total 100 enrolled participants, 53 were males and 47 were females belonging to the age group range of 16–65 years. Among 75 participants who had TB, 68% had pulmonary and 32% had extrapulmonary TB. Levels of serum ADA were found to be significantly higher in relapse TB, fresh TB, and those on anti-TB treatment compared to healthy controls. Conclusions: Serum ADA levels may serve as prognostic markers in TB.
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Smear-negative pulmonary tuberculosis: Relative incidence and outcome of treatment in a drug-resistant endemic setting in Indochina p. 109
Pathum Sookaromdee, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_138_18  
Background: Pulmonary tuberculosis is an important public health problem at present. The disease is still highly prevalent in several areas including tropical Indochina. In the area between Thailand and Myanmar body, the emerging drug-resistant tuberculosis is an interesting problem in the present day. Early diagnose and management of tuberculosis patient is important. Methods: In this specific article, the authors summarize and discuss on the locally available data on smear-negative pulmonary tuberculosis in a drug-resistant endemic foci in Indochina. The relative incidence and the outcome of the treatment are specifically focused. Results: Based on the present study, the outcome of the treatment of cases with smear-negative pulmonary tuberculosis is similar to cases with smear-positive pulmonary tuberculosis. Conclusion: Since the outcome of the treatment of cases with smear-negative pulmonary tuberculosis is similar to cases with smear-positive pulmonary tuberculosis, therefore, it is recommended for therapeutic management of those cases.
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Concurrent dengue and tuberculosis: An estimated incidence in endemic tropical country and explanation for low observed incidence p. 111
Beuy Joob, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_37_19  
Background: In tropical developing countries, there are several common infectious diseases including tuberculosis and dengue. The concurrence between dengue and tuberculosis is possible. Methods: Here, the authors perform a mathematical model study to estimate the incidence of concurrent dengue and tuberculosis in Thailand, a tropical country in Indochina. The estimation is performed based on joint probability principle. Results: The estimated incidence of concurrent dengue and tuberculosis in the studied setting is equal to 0.148/100,000 population. Conclusion: There is a low incidence of concurrent dengue and tuberculosis, and this might be due to several possible reasons.
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Thai ethnopharmacological herbs for tuberculosis treatment: Pharmacoinformatics analysis for therapeutic property p. 117
Pathum Sookaromdee, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_32_19  
Background: Tuberculosis is still an important infection at present. The use of antituberculosis drug is the standard therapeutic management. Due to the emerging drug resistance, it requires the new drug search. Additional to the modern medicine, the role of complementary and alternative medicine (CAM) which has been existed in the endemic area of tuberculosis for centuries should be appraised. Methods: Here, the authors studied on the local CAM regimens in Thailand, a tropical country in Indochina, where tuberculosis is highly prevented, mentioned for the usefulness of treatment of tuberculosis. The data from famous classical Thai CAM centers are collected to find specific ethnopharmacological registered data on Thai herbs for the management of tuberculosis was further assessed. The comparative informatics appraisal with the public standard medical database is further done to verify any the existed usefulness of identified local herbs. Results: There are many identified local Thai CAM herbs, but there are onlytwo herbs that have proven for supportive evidence in the published literature for feasibility in using for treatment of tuberculosis. Conclusion: The identification of ethnopharmacological property of locally available CAM herbs might be useful for searching for a new natural product for the development of a new drug for tuberculosis treatment.
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Effect of ginseng against tuberculosis: A pathway interrelationship analysis p. 120
Won Sriwijitalai, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_55_19  
Background: The role of traditional herb in the treatment of infectious diseases is very interesting. There are many researches on the effects of herbs on infectious pathogens. The research on tuberculosis, a common public health disorder, is very interesting. Methods: In this study, the authors performed a network pharmacology analysis to assess the common biological pathway for the pharmacological effect of ginseng and the pathophysiological process of tuberculosis. Results: According to the interrelationship analysis, the authors can identify the common pathway through vimentin, showing that ginseng is useful in the treatment of tuberculosis. Conclusion: Ginseng has been found to be useful for the treatment of tuberculosis.
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Incidence of pulmonary tuberculosis and particulate matter 2.5 pollutant level: The association analysis for 2019 air pollution Crisis, Bangkok Thailand p. 126
Beuy Joob, Viroj Wiwanitkit
DOI:10.4103/bbrj.bbrj_31_19  
Background: Pulmonary tuberculosis is an important pulmonary infection that it is common in many developing countries. The poor sanitation is the basic problem relating to the occurrence of the pulmonary tuberculosis. The relationship between air pollutant and incidence of pulmonary tuberculosis becomes the new public health consideration. Here, the author-specific focus is on the effect of particulate matter (PM) 2.5 pollutant on tuberculosis. Methods: The authors hereby assessed the correlation between incidence of pulmonary tuberculosis and PM 2.5 pollutant level regarding 2019 air pollution crisis, Bangkok Thailand. Results: There is no significant relationship between incidence of pulmonary tuberculosis and PM 2.5 pollutant level regarding 2019 air pollution crisis, Bangkok Thailand (P > 0.05). Conclusion: There is a lack of relationship between incidence of pulmonary tuberculosis and PM 2.5 pollutant level.
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Genetic polymorphisms namely TLR2 Gene Arg753gln and Arg677trp polymorphisms and tuberculosis: Comparison on the effects of molecular weight alterations p. 129
Pathum Sookaromdee, Viroj Wiwanitkit, Beuy Joob
DOI:10.4103/bbrj.bbrj_19_19  
Background: Tuberculosis is an important mycobacterial infection. This problem is still the present public health problem in several countries around the world. The genetic underlying factor is usually mentioned for the effect on the natural history of tuberculosis infection. Methods: Here, the authors perform a standard assessment on the molecular change due to TLR2 gene Arg753Gln and Arg677Trp polymorphisms and further study on the effect on the corresponding phenotypic expression changes. Results: The molecular weight changes comparing to naïve molecule in cases of Arg753Gln and Arg677Trp polymorphisms are equal to –16.1% and +17.2%, respectively. Conclusion: According to the molecular structure analysis, Arg753Gln has a relationship with active tuberculosis whereas Arg677Trp polymorphism is not.
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LETTER TO EDITOR Top

Comparison of two methods for direct susceptibility testing of Salmonella typhi and Salmonella paratyphi a from blood cultures in a high-burden laboratory setting p. 131
Yusra Shafquat, Ghazala Shaheen, Farah Qamar, Sadia Shakoor
DOI:10.4103/bbrj.bbrj_70_19  
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