Tuberculosis: Current Status, Diagnosis, Treatment and Development of Novel Vaccines

Tuberculosis (TB) is an infectious disease that mainly affects the lungs and spreads to other organs of the body through the haematogenous route. It is one of the ten major causes of mortality worldwide. India has the highest incidence of new- and multidrug-resistant (MDR) - TB cases in the world. Bacille Calmette-Guerin (BCG) is the vaccine commonly available against TB. BCG does offer some protection against serious forms of TB in childhood but its protective effect wanes with age. Many new innovative strategies are being trailed for the development of effective and potent vaccines like mucosal- and epitope-based vaccines, which may replace BCG or boost BCG responses. The use of nanotechnology for diagnosis and treatment of TB is also in the pipeline along with many other vaccines, which are under clinical trials. Further, in-silico models were developed for finding new drug targets and designing drugs against Mycobacterium tuberculosis (Mtb). These models offer the benefit of computational experiments which are easy, inexpensive and give quick results. This review will focus on the available treatments and new approaches to develop potent vaccines for the treatment of TB.

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Global Threats and the Control of Multidrug-Resistant Tuberculosis

Journal of Disaster Research ◽

10.20965/jdr.2011.p0443 ◽

2011 ◽

Vol 6 (4) ◽

pp. 443-450 ◽

Cited By ~ 1

Author(s):

Kazuo Kobayashi ◽

◽

Manabu Ato ◽

Sohkichi Matsumoto ◽

Keyword(s):

Immune Deficiency Syndrome ◽

Multidrug Resistant ◽

Deficiency Syndrome ◽

Chemotherapeutic Agents ◽

Drug Resistant ◽

Injectable Drugs ◽

Resistant Tuberculosis ◽

Mdr Tb ◽

Causes Of Mortality ◽

Active Disease

About one-third of the world’s population has been infected with Mycobacterium tuberculosis. Active disease develops in about 9 million people per year, and tuberculosis is responsible for 2 million deaths per year. The disease caused by this bacterium, tuberculosis (TB), remains one of the leading causes of mortality caused by infection worldwide and is a major threat to global health. The situation of TB is recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with human immunodeficiency virus/acquired immune deficiency syndrome, which greatly increases the risk of latent M. tuberculosis infection progressing to active disease. Multidrug-resistant (MDR) tuberculosis is defined as disease caused by strains of M. tuberculosis that are at least resistant to isoniazid and rifampicin; extensively drug-resistant (XDR) tuberculosis refers to disease caused by MDR strains that are also resistant to any fluoroquinolone and any of the injectable drugs used in treatment with second-line anti-tuberculosis drugs (amikacin, capreomycin, and kanamycin). MDR- and XDR-TB are serious threats to the progress that has been made in the control of tuberculosis worldwide over the past decade. In this review, we focus on threats of MDR-TB and the research and development of improved diagnostics, new chemotherapeutic agents, and vaccine candidates for MDR-TB.

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Different profiles of body mass index evolutions among patients with multidrug-resistant tuberculosis: a retrospective cohort study.

10.21203/rs.2.16913/v1 ◽

2019 ◽

Author(s):

Alhassane Diallo ◽

Boubacar Djelo Diallo ◽

Lansana Mady Camara ◽

Lucrèce Ahouéfa Nadège Kounoudji ◽

Boubacar Bah ◽

...

Keyword(s):

Body Mass Index ◽

Treatment Outcome ◽

Body Mass ◽

Mixed Model ◽

Multidrug Resistant ◽

The Body ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background Despite the predictor role of the body weight variation on multidrug-resistant tuberculosis (MDR-TB) treatment outcome, little data are available to corroborate this finding. We aimed to study the course of weight in patients with MDR-TB, to identify subgroups of weight evolutions, and to determine factors that influence these evolutions.Methods Patients treated with a shorter MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 from three major drug-resistance TB centres in Guinea, who had rifampicin resistance, and who were cured or died were analysed. Patients were seen monthly until the end of treatment. Clinical outcome was the Body Mass Index (BMI). We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup of BMI evolutions.Results Of 232 patients treated for MDR-TB during the study period, 165 (71%) were analysed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors that associated with faster BMI progression were cured to MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205), and the absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two subgroups of BMI evolution were identified: “Rapid BMI (n = 121; 85%) and “Slow BMI evolution (n = 22; 15%). Patients in the slow increasing BMI group were mostly female (68%) without history of TB treatment (41%) with most severe clinical condition at baseline, characterized by a higher frequency of symptoms including HIV infection (59%), depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelets count, and higher liver SGOT count. These patients had also a longer time to-initial culture conversion delay (log-rank test: p = 0.0087).Conclusion The available data provide quantitative information on BMI progression of patients with MDR-TB treated with a shorter regimen, and allowed the identification of the subgroup of patients with different BMI evolutions. Furthermore, they emphasize the usefulness of BMI as biomarker to monitor MDR-TB treatment outcome.

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Value Addition on Trend of Tuberculosis Disease in India- The Current Update

International Journal of TROPICAL DISEASE & Health ◽

10.9734/ijtdh/2020/v41i930317 ◽

2020 ◽

pp. 41-54

Author(s):

Praveen Kumar Gupta ◽

Mohammed Haseeb Nawaz ◽

Shyam Shankar Mishra ◽

Roshmee Roy ◽

E. Keshamma ◽

...

Keyword(s):

Immune System ◽

Causes Of Death ◽

Close Contact ◽

Multidrug Resistant ◽

The Body ◽

Concentration Method ◽

Mdr Tb ◽

Pcr Method ◽

Tuberculosis Disease ◽

Dna Pcr

Tuberculosis (TB) is infectious diseases were the lungs are mostly affected. It is caused by the Mycobacterium tuberculosis bacteria and is spread when a person already affected with TB coughs, sneezes, spits, laughs, or talk. Even though it’s is contagious does not easily catch i.e. chances of catching TB are much higher with someone you live with or work than from a stranger. Multidrug-Resistant TB (MDR-TB) arises when the antibiotic fails to kill bacteria. MDR-TB can be treatable and curable with specific anti-TB drugs but unfortunately, these are limited in quantities or not readily available. As per WHO around 4,50,000 people developed MDR-TB in the year 2012. People with a weak immune system are at maximum risk of active TB development. For instance, HIV conquers the immune system, making it harder for the body to control TB bacteria. People infected with both HIV and TB are 20-30% more probable to develop active TB than those who do not have HIV. Besides, WHO estimates, every year 9 million people get sick with TB and 3 million with these are “missed” by health systems. Among the top 3 causes of death in women between 15- 44 TB is one the major cause. The symptoms of TB may be mild for many months and can infect 10-15 other people through close contact. This study involves a comparative evaluation of the presence of Tuberculosis concerning factors such as socioeconomic status, sex ratio, age, addiction of nicotine or alcohol, etc. All the screenings were based upon various methods of diagnosis used in pulmonary tuberculosis such as Ziehl Neelsen staining, culture on L.J media, Petroff’s concentration method, and DNA PCR method.

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Prediction of the Complication Risk in Drug-Resistant Tuberculosis After Surgery: Development and Assessment of a Novel Nomogram

Frontiers in Surgery ◽

10.3389/fsurg.2021.689742 ◽

2021 ◽

Vol 8 ◽

Author(s):

Liwei Wu ◽

Xiyong Dai ◽

Haijiang Wang ◽

Chaolin Huang ◽

Fan Xia ◽

...

Keyword(s):

Clinical Features ◽

Multidrug Resistant ◽

The Body ◽

Multivariable Logistic Regression Analysis ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Internal Validation ◽

Resistant Tuberculosis ◽

Complication Risk ◽

Mdr Tb

Background: Surgery is increasingly accepted as an adjunctive approach to treat multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB). However, a model that includes all factors to predict the risk of postoperative complications is lacking.Methods: We developed a prediction model based on 138 patients who had undergone surgery as treatment for drug-resistant tuberculosis (DR-TB) after 24 months. Clinical features on the lesion type (L), treatment history (T), physiologic status of the body (B), and surgical approach (S) were evaluated. Multivariable logistic regression analysis was conducted by clinical features selected in the least absolute shrinkage and selection operator (LASSO) to build a nomogram. The discrimination, calibration, and clinical usefulness of the nomogram were assessed using the C-Index, calibration plots, and decision curves. Internal validation was assessed using bootstrapping.Results: The nomogram contained the features L, B, T, cavitary, recurrent chest infection (RCI) and MDR-TB/XDR-TB. The model displayed good discrimination with a C-Index of 0.879 (95% CI: 0.799–0.967). A high C-Index of 0.824 was achieved in the interval validation. Decision-curve analysis showed that the nomogram was clinically useful if intervention was decided at the non-adherence possibility threshold of 4%.Conclusion: Our novel nomogram could be used conveniently to predict postoperative complication risk in DR-TB patients.

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MULTIDRUG-RESISTANT TUBERCULOSIS AMONG CHILDREN UNDER 15 YEARS OF AGE IN KHYBER PAKHTUNKHWA PROVINCE AND FEDERALLY ADMINISTERED TRIBAL AREAS PAKISTAN

Journal of Applied Pharmacy ◽

10.21065/19204159.12.82 ◽

2020 ◽

Vol 12 ◽

pp. 82

Author(s):

Umer Farooq ◽

Keyword(s):

Preventive Measures ◽

Multidrug Resistant ◽

Drug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

The World ◽

Mdr Tb ◽

Khyber Pakhtunkhwa Province ◽

New Challenges ◽

Tribal Areas

Tuberculosis is re-emerging in the form of drug resistant causing deaths of humans throughout the world. In 2015, WHO estimates, this disease developed in 10.4 million and causes death in 1.8 million human population. Moreover, new challenges like TB/HIV co-infection, MDR-TB is resisting to the preventive measures for controlling TB worldwide

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Treatment Outcomes of Patients Switching From an Injectable Drug to Bedaquiline During Short Standardized Treatment for Multidrug-resistant Tuberculosis in Mozambique

Clinical Infectious Diseases ◽

10.1093/cid/ciz196 ◽

2019 ◽

Vol 69 (10) ◽

pp. 1809-1811 ◽

Cited By ~ 1

Author(s):

Mathieu Bastard ◽

Lucas Molfino ◽

Cláudia Mutaquiha ◽

Miriam Arago Galindo ◽

Pereira Zindoga ◽

...

Keyword(s):

Multidrug Resistant ◽

World Health ◽

Injectable Drug ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

The World ◽

Standardized Treatment ◽

Mdr Tb ◽

Small Cohort ◽

Health Organization

Abstract Bedaquiline was recommended by the World Health Organization as the preferred option in treatment of multidrug-resistant tuberculosis (MDR-TB) with long regimens. However, no recommendation was given for the short MDR-TB regimen. Data from our small cohort of patients who switched from injectable drug to bedaquiline suggest that a bedaquiline-based short regimen is effective and safe.

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Multidrug-resistant tuberculosis around the world: what progress has been made?

European Respiratory Journal ◽

10.1183/09031936.00101814 ◽

2014 ◽

Vol 45 (1) ◽

pp. 150-160 ◽

Cited By ~ 68

Author(s):

Dennis Falzon ◽

Fuad Mirzayev ◽

Fraser Wares ◽

Inés Garcia Baena ◽

Matteo Zignol ◽

...

Keyword(s):

Treatment Success ◽

Multidrug Resistant ◽

Outcome Data ◽

Interquartile Range ◽

World Health ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Number Of Patients ◽

The World ◽

Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa.The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide.In 2012, a median of 14% (interquartile range 6–50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40–70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010.Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB.

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Different profiles of body mass index evolutions among patients with multidrug-resistant tuberculosis: a retrospective cohort study.

10.21203/rs.2.16913/v2 ◽

2020 ◽

Author(s):

Alhassane Diallo ◽

Boubacar Djelo Diallo ◽

Lansana Mady Camara ◽

Lucrèce Ahouéfa Nadège Kounoudji ◽

Boubacar Bah ◽

...

Keyword(s):

Body Mass Index ◽

Treatment Outcome ◽

Body Mass ◽

Mixed Model ◽

Multidrug Resistant ◽

The Body ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background: Despite the predictor role of the body weight variation on multidrug-resistant tuberculosis (MDR-TB) treatment outcome, little data are available to corroborate this finding. We aimed to study the course of weight in patients with MDR-TB, to identify subgroups of weight evolutions, and to determine factors that influence these evolutions. Methods: Patients treated with a shorter MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 from three major drug-resistance TB centers in Guinea, who had rifampicin resistance, and who were cured or died were analyzed. Patients were seen monthly until the end of treatment. Clinical outcome was the Body Mass Index (BMI). We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup of BMI evolutions. Results: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors that associated with faster BMI progression were cured to MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205), and the absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two subgroups of BMI evolution were identified: “Rapid BMI (n = 121; 85%) and “Slow BMI evolution (n = 22; 15%). Patients in the slow increasing BMI group were mostly female (68%) without history of TB treatment (41%), with positive HIV infection (59%), with most severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelets count, and higher liver SGOT count. These patients had also a longer time to-initial culture conversion delay (log-rank test: p = 0.0087). Conclusion: The available data provided quantitative information on BMI progression of patients with MDR-TB treated with a shorter regimen, and allowed the identification of the subgroup of patients with different BMI evolutions. Furthermore, they emphasized the usefulness of BMI as biomarker to monitor MDR-TB treatment outcome.

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Utilizing the Crosstalk Among Minocycline, Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized) and Vitamin D as a Potent Quadrate Therapy for treating coinfection with Multidrug-resistant TB and COVID-19 . A double-edged sword Clinical Study

10.21203/rs.3.rs-963736/v1 ◽

2021 ◽

Author(s):

Mahmoud Ramadan Elkazzaz ◽

Amr Ahmed

Keyword(s):

Vitamin D ◽

Mycobacterium Tuberculosis ◽

Retinoic Acid ◽

The Elderly ◽

Multidrug Resistant ◽

Severe Form ◽

Hospitalized Patients ◽

The Body ◽

Chicoric Acid ◽

Mdr Tb

Abstract Tuberculosis (TB) is a major infectious disease killer globally. It affected 10 million and killed 1.4 million people in 2019 alone. TB is considered a disease caused by a bacterium—Mycobacterium tuberculosis—that usually attacks the lungs, but can attack any part of the body. But TB has a worrisome connection to the novel coronavirus.. Both diseases are airborne and spread when people cough or sneeze. The predicted impact of the COVID-19 pandemic is an additional 190,000 TB deaths in 2020, and it is expected in the next 5 y that there will be up to a 20% increase in the global TB disease burden, stressing the critical need for new safe and effective drugs against Mycobacterium tuberculosis (Mtb). In addition, controlling multidrug-resistant TB (MDR-TB) presents a huge public health challenge. Recently it was showed that hospitalized patients with Tuberculosis are more susceptible to COVID-19 infection and complication. Furthermore, hospitalized patients with MDR-TB are increasingly vulnerable to COVID-19 complications than patients with non-resistant tuberculosis.. For someone with latent TB, contracting COVID-19 could activate the bacterium, potentially leading to an accelerated and more severe form of the disease WHO estimates that these COVID-19 related disruptions in access to TB care could cause an additional half a million TB deaths. Older age, especially >65 years, may be a risk factor for death from COVID-TB, consistent with previous findings indicating that the mortality rate from COVID-19 increases exponentially with age. Thus, the elderly should be the primary focus of both COVID-19 and COVID-TB mitigation efforts due to its much higher mortality risk in that group. COVID-TB patients had a much higher rate of comorbidities than COVID-19 patients At present, evidence suggests that the main transmission route of both COVID-19 and TB is via respiratory droplets, and their main target are the lungs, which can lead to a worse outcome among COVID-19 and TB coinfection patients (aptly abbreviated COVID-TB). As a result, coinfections with common viral and bacterial (COVID-TB) pathogens among hospitalized patients are a severe concern that will likely worsen patient outcomes and pose a real challenge for treating those patients.ConclusionsNew drug discovery could require several years with no guarantee but repurposing established drugs may be useful to treat confection with COVID-19 and Nonresistant Strains of Mycobacterium tuberculosis: or resistant Strains of Mycobacterium tuberculosis . Here we demonstrate that we could utilize the crosstalk among Chicoric Acid, 13-Cis Retinoic Acid, Minocycline and vitamin D as a novel quadrate therapy against Multidrug-resistant TB and COVID-19 coinfection.

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Adenosine A2A Receptor as a Potential Drug Target - Current Status and Future Perspectives

Current Pharmaceutical Design ◽

10.2174/1381612825666190716113444 ◽

2019 ◽

Vol 25 (25) ◽

pp. 2716-2740 ◽

Cited By ~ 9

Author(s):

Omar H.A. Al-Attraqchi ◽

Mahesh Attimarad ◽

Katharigatta N. Venugopala ◽

Anroop Nair ◽

Noor H.A. Al-Attraqchi

Keyword(s):

Drug Targets ◽

Therapeutic Potential ◽

Wide Distribution ◽

The Body ◽

Current Status ◽

Potential Drug ◽

Recent Advances ◽

Body Tissues ◽

A2a Receptor ◽

Adenosine A2a

Adenosine receptors (ARs) are a class of G-protein coupled receptors (GPCRs) that are activated by the endogenous substance adenosine. ARs are classified into 4 subtype receptors, namely, the A1, A2A, A2B and A3 receptors. The wide distribution and expression of the ARs in various body tissues as well as the roles they have in controlling different functions in the body make them potential drug targets for the treatment of various pathological conditions, such as cardiac diseases, cancer, Parkinson’s disease, inflammation and glaucoma. Therefore, in the past decades, there have been extensive investigations of ARs with a high number of agonists and antagonists identified that can interact with these receptors. This review shall discuss the A2A receptor (A2AAR) subtype of the ARs. The structure, properties and the recent advances in the therapeutic potential of the receptor are discussed with an overview of the recent advances in the methods of studying the receptor. Also, molecular modeling approaches utilized in the design of A2AAR ligands are highlighted with various recent examples.

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