Basalingappa, Pugazhandhi B, Nagalambika P, Gopenath T S, Gowda S, Karthikeyan M, Ashok G, and Devi: Tuberculosis – An overview


Introduction

Tuberculosis (TB) is caused by the strain Mycobacterium Tuberculosis and is known to be one of the human-known diseases which exist for a long time. TB has many forms of manifestation, of which pulmonary TB to be the most common form of manifestation. Besides pulmonary involvement, TB can also affect the central nervous system, bones (Pott’s disease), and other systems. Being a multi-system targeting organism, TB will bring out a severe complication to one’s health. It’s all beginning from aerosol droplets that contain Mycobacterium Tuberculosis strains onto the lung alveolar surface. Once get infected, it will trigger the inflammatory cell infiltration where it tries to contain the bacteria in a place, forming a primary Ghon complex where it prevents the spread of the organism to another part of the body. It can either remain latent or reactive were the primary Ghon complex rupture and give rise to secondary TB. Although it does not produce any forms of a toxin like another organism, Mycobacterium tuberculosis virulence is not simple and complex since its structural and physiological features make it virulent. Some of the structural and physiological aspects include the ability to grow intracellularly, detoxification of radicals from oxygen, cord factor, high lipid density in the cell wall, Erp surface-located protein, mycocerosic acid, and adherence such as heparin-binding hemagglutinin (HbhA) are the most probable cause. Proper investigation and management should be done to cure TB patients. The investigation includes identification of acid-fast bacilli using BACTEC System via Ziehl Neelsen stains and culture.

Source of Information

For the literature, a total number of 6146 articles related to emerging aspects of tuberculosis were retrieved. Out of these 6146 articles, most of the articles were full-length articles and only a few were abstracts. Additional publications from World Health Organization (WHO) website, Clinical Research Centre (CRC) were also included. The database that used to search for relevant materials were from BioMed Central, PubMed Central, World Health Organization (WHO), the Malaysian Journal of Medical Sciences (MJMS), the Centers for Disease Control and Prevention (CDC) and Ministry of Health of Malaysia (MOH).

Characteristics of Mycobacterium Tuberculosis

Tuberculosis is a chronic infection of Mycobacterium tuberculosis. It is spread through the air from person to person and mainly targets the lungs of an individual. Most of the infected people have latent TB, only some will develop active TB disease. Mycobacterium tuberculosis is a bacterium in the form of a nonmotile rod, also known as Koch's bacillus. It is a slow-growing bacterium that requires aerobes and is categorized as acid-fast bacteria. Middlebrook’s medium and Lowenstein-Jensen medium is used to grow Mycobacterium tuberculosis. Its cell wall contains peptidoglycan and three major lipid components like mycolic acids, cord factor and wax-D. Mycolic acids are powerful hydrophobic molecules that create a lipid shell and affect the permeability of the cell surface. The cord factor is harmful to mammalian cells and is an inhibitor of PMN migration. In the cell envelope, wax-D is found and also a major component of the Freund’s complete adjuvant. Special characteristics such as stain and dye absorption coefficient, tolerance to certain antibiotics, acid and alkaline compound resistance. Killing, resistance by complement deposition to osmotic lysis and resistance to lethal oxidation and survival of macrophage have been provided by high lipid concentrations in the Mycobacterium tuberculosis cell wall.1

Epidemiology of Tuberculosis

In 2014, According to the Global TB Survey 2015, 1.5 million people have died from TB, 0.4 million people were HIV positive among these individuals. In 2014, an estimated 9.6 million new TB cases were registered, reflecting a global average of 133 cases per 100,000 population. There were approximately 30,20,000 cases and 4 lakhs 80thousands TB deaths among women. An estimated 10,00,000 childhood TB cases and 140,000 deaths have been reported as well. An approximate 5.4 million cases of TB among men and 890,000 deaths have been reported. In the WHO South-East Asia Region and the WHO Western Pacific Region, the largest number of new cases of TB occurred in 2014, accounting for 58 percent of new cases worldwide. Of all the new activities, five nations, including India, Indonesia, China, Nigeria, and Pakistan, accounted for 54 percent. Africa, however, had the most extreme burden, with 281 cases per 100,000 inhabitants.2

Table 1

Estimated WHO Regional TB statistics for 2014

Region

TB Mortality

HIV Positive TB Mortality

Prevalence

Incidence

Population

Africa

450,000

310,000

3,200,000

2,700,000

963,361,000

Americas

17,000

6,000

350,000

280,000

981,613,000

Eastern Mediterranean

88,000

3,200

1,000,000

7,40,000

635,745,000

Europe

33,000

3,200

440,000

340,000

907,279,000

South East Asia

460,000

62,000

5,400,000

4,000,000

1,906,087,000

Western Pacific

88,000

4,900

2,100,000

1,600,000

1,845,184,000

Global Total

1,100,000

390,000

13,000,000

9,600,000

7,239,269,000

[i] (Source taken from: WHO | Global tuberculosis report 2015 (Rep.). (n.d.). Retrieved from www.who.int/tb/publications/global_report/en/)

Table 2

Statistics for TB in “High Burden” countries 2014

Country

TB Mortality

HIV Positive TB Mortality

Prevalence

Incidence

Population

Afghanistan

14,000

100

110,000

60,000

31,628,000

Bangladesh

81,000

200

640,000

360,000

159,078,000

Brazil

5,300

2,400

110,000

90,000

206,078,000

Cambodia

8,900

800

100,100

60,000

15,328,000

China

38,000

700

1,200,000

930,000

1,369,436,000

DR Congo

52,000

6,300

4,00,000

240,000

74,877,000

Ethiopia

32,000

5,500

190,000

200,000

96,959,000

India

220,000

31,000

2,500,000

2,200,000

1,295,292,000

Indonesia

100,000

22,000

1,600,000

1,000,000

254,455,000

Kenya

9,400

8,100

120,000

110,000

44,864,000

Mozambique

18,000

37,000

150,000

150,000

27,216,000

Myanmar

28,000

4,100

240,000

200,000

53,437,000

Nigeria

170,000

78,000

590,000

570,000

177,476,000

Pakistan

48,000

1,300

630,000

500,000

185,044,000

Philippines

10,000

100

410,000

290,000

99,139,000

Russian Federation

16,000

1,100

160,000

120,000

143,429,000

South Africa

24,000

72,000

380,000

450,000

53,969,000

Thailand

7,400

4,500

160,000

120,000

67,726,000

UR Tanzania

30,000

28,000

270,000

170,000

51,823,000

Uganda

4,500

6,400

60,000

61,000

37,783,000

Viet Nam

17,000

1900

180,000

130,000

92,423,000

Zimbabwe

2,300

5,200

44,000

42,000

15,246,000

Total for High Burden Countries

940,000

320,000

10,000,000

8,000,000

4,552,704,000

[i] (Source taken from: WHO | Global tuberculosis report 2015 (Rep.). (n.d.). Retrieved from www.who.int/tb/publications/global_report/en/)

Drug-resistant Tuberculosis

Drug-resistant tuberculosis is widespread, which may jeopardize global TB control and, as found in all countries surveyed, has become a major public health issue. This is due to mismanagement of care and has been transmitted from person to person via the classical tuberculosis transmission model.3 Drug-resistant tuberculosis is divided into multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. The bacteria resistant to isoniazid and rifampin are multidrug-resistant tuberculosis, while the bacteria resistant to fluoroquinolones along with isoniazid and rifampicin are extensively drug-resistant tuberculosis.4, 5, 6

Epidemiology of Drug-Resistant Tuberculosis

According to the 2015 Global TB Report, there were an estimated 4,80,000 new MDR-TB cases worldwide and 1,90,000 deaths from MDR-TB in 2014. There are also an estimated 300,000 cases of MDR-TB among patients with pulmonary TB. Globally, 123,000 MDR-TB patients have been registered, of whom about 75% live in Europe, India, South Africa, or China. Apart from that, 105 countries have registered XDR-TB. An approximate 9.7 percent of people with MDR-TB have XDR-TB, on average.2 In Malaysia, an estimated 0.4 percent of the 40,000 cases of TB with MDR-TB occurred in 2014, based on the TB country profile. Among the confirmed cases of pulmonary TB, there were an estimated 80 cases of MDR-TB.7

Figure 1

TB country profile data and graphs

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/693c6033-4608-464d-835b-29bdec8d3701/image/bee5f484-407c-477f-a80d-cd92c0b14a18-uimage.png

The Emergence of Drug-Resistant Tuberculosis

The global drug-resistant genetic diversity Mycobacterium tuberculosis suggests that drug resistance grows in regional hotspots of TB incidence on multiple occasions. As there has been continuous production of M.tuberculosis, this has allowed investigating the genetic determinants of this bacterium's drug resistance.8, 9, 10 The drug resistance acquisition in M. Tuberculosis depends primarily on the efflux processes enabling the bacteria to tolerate higher levels of medication. It does not rely on plasmid resistance and horizontal transfer of genes that play a major role in most bacterial pathogens in the selection of drug resistance.9 The concurrent selection and accumulation of mutations conferred by bacterial chromosome resistance has become a driving force for multi-antibiotic-resistant strain growth. These mutations interfere mainly with drug-target binding such as RIF-rpoB and FQ-gyrA, compromise prodrugs activation such as INH-katG and PA-824-fgd, or Over-expression of the target is induced by the promoter region, such as INH/ETH of inhA.11, 12, 13, 14, 15 Epistasis and bacterial health impact the evolutionary mechanism of drug resistance.16 Epistasis is characterized as a genetic interaction array where one mutation's phenotypic effect determines the existence of one or more mutations, while growth rate, virulence, and transmissibility are a function of bacterial fitness.17, 18 Most drug-resistance mutations have been shown to bear a fitness expense that typically includes very small fitness defects in resistant strains. As evolution is an ongoing process, resistant mutant fitness is not fixed and clinical strains typically bypass any resistance-imposed fitness costs relative to laboratory strains carrying the same mutation of drug resistance.19 It is also proven that M. tuberculosis have the capacity to induce disease and develop drug resistance strains from various lineages vary.20 The HN878 strains within Lineage 2, that is the East Asian lineage which includes the Beijing family of strains, are more mutable as compared to CDC1551 strains within Lineage 4, which is the Euro-American lineage, as they have polymorphisms in DNA replication, recombination, and repair genes.21, 22 The approaches such as whole-genome sequencing, phylogeny, molecular epidemiology, and mutation frequency analyses have been used to counter drug-resistant evolution M. tuberculosis.23, 24, 25

Conclusion

In summary, since tuberculosis remains a significant public health concern, modification of the global strategy to the unique TB treatment and prevention issues is important. It is critical for planning and vital services within a country to ensure political engagement, support, and stewardship. The implementation of a national strategic plan for the elimination of tuberculosis, integrated in national strategies for the health and social sector, and transparency for its execution should be ensured by the enhancement of central coordination under government stewardship by the setting up a national policy committee on TB. A patient-centered approach to care and service that is compassionate and sensitive to patients' needs and based on clear ethical principles is critical. Consideration should be provided to tailored training and TB awareness-raising events for medical and social care workers in touch with high-risk groups. Social initiatives need to reach beyond people already ill with TB and, through a "health-in-all-policies" approach, often focus on people and populations at risk. Without any financial burden, country-to-country cooperation and national legislation can ensure the functionality and accessibility of TB services for all migrants. In addition, it is necessary to screen for active LTBI TB in TB contacts and selected high-risk groups, and to provide adequate treatment. In short, through bilateral and multinational mechanisms, each country should support the implementation of all aspects of the global tuberculosis strategy, as the promotion of global tuberculosis advocacy could provide the visibility needed for sustained efforts to eradicate tuberculosis.

Abbreviations

Tuberculosis (TB); World Health Organisation (WHO); Clinical Research Centre (CRC); Multidrug-resistant TB (MDR-TB); Latent tuberculosis infection (LTBI); Extensively drug-resistant TB (XDR TB); Isoniazid (INH) susceptibility (katG and inhA); Rifampicin (rif); Fluoroquinolone (FQ).

Source of Funding

No targeted funding reported.

Availability of Data and Materials

All data and materials are presented with this manuscript. No additional materials are available.

Competing Interests

Authors declare no competing interest.

Acknowledgements

The KMC Manipal Health Sciences Library, Manipal Academy of Higher Education, Madhav Nagar, Manipal, Karnataka 576104.

References

1 

Tuberculosis. (n.d.). Retrieved June 24, 2016, fromhttp://textbookofbacteriology.net/tuberculosis.html

2 

WHO | Global tuberculosis report 2015 (Rep.). (n.d.). Retrieved from www.who.int/tb/publications/global_report/en/

3 

M Adhvaryu B Vakharia Drug-resistant tuberculosis: emerging treatment optionsClin Pharmacol20113516710.2147/cpaa.s11597

4 

NS Shah A Wright F Drobniewski Extreme drug-resistance in tuberculosis (‘XDR-TB’): a global survey of supranational reference laboratories for Mycobacterium tuberculosis with resistance to second-line drugsInt J Tuberc Lung Dis200591S77

5 

Centers for Disease Control and Prevention. The emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs worldwideMorb Mortal Wkly Rep2006553015

6 

GB Migliori R Loddenkemper F Blasi MC Raviglione 125 years after Robert Koch's discovery of the tubercle bacillus: the new XDR-TB threat. Is "science" enough to tackle the epidemic?Eur Respir J2007293423710.1183/09031936.00001307

7 

TB country profile (Rep.). (n.d.)https://extranet.who.int/.../Reports

8 

J Li X Gao T Luo J Wu G Sun Q Liu Association of gyrA/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosisEmerg Microbiol Infect20143e19

9 

S Borrell S Gagneux Strain diversity, epistasis and the evolution of drug resistance in Mycobacterium tuberculosisClin Microbiol Infect20111768152010.1111/j.1469-0691.2011.03556.x

10 

SH Gillespie Evolution of Drug Resistance in Mycobacterium tuberculosis: Clinical and Molecular PerspectiveAntimicrob Agents Chemother20024622677410.1128/aac.46.2.267-274.2002

11 

EA Campbell N Korzheva A Mustaev K Murakami S Nair A Goldfarb Structural Mechanism for Rifampicin Inhibition of Bacterial RNA PolymeraseCell200110469011210.1016/s0092-8674(01)00286-0

12 

FM Barnard A Maxwell Interaction between DNA Gyrase and Quinolones: Effects of Alanine Mutations at GyrA Subunit Residues Ser 83 and Asp 87Antimicrob Agents Chemother20014571994200010.1128/aac.45.7.1994-2000.2001

13 

DA Rouse JA DeVito Z Li H Byer SL Morris Site-directed mutagenesis of the katG gene of Mycobacterium tuberculosis: effects on catalase-peroxidase activities and isoniazid resistanceMol Microbiol19962235839210.1046/j.1365-2958.1996.00133.x

14 

CK Stover P Warrener DR VanDevanter DR Sherman TM Arain MH Langhorne A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosisNature20004056789962610.1038/35016103

15 

Y Zhang WW Yew Mechanisms of drug resistance in Mycobacterium tuberculosisInt J Tuberc Lung Dis200913132030

16 

DM Weinreich Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter ProteinsScience20063125770111410.1126/science.1123539

17 

B Müller S Borrell G Rose S n Gagneux The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosisTrends Genet2013293160910.1016/j.tig.2012.11.005

18 

L Fenner M Egger T Bodmer E Altpeter M Zwahlen K Jaton Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosisAntimicrob Agents Chemother201256630475310.1128/aac.06460-11

19 

S Gagneux The Competitive Cost of Antibiotic Resistance in Mycobacterium tuberculosisScience200631257821944610.1126/science.1124410

20 

R Johnson Drug-resistant tuberculosis epidemic in the Western Cape driven by a virulent Beijing genotype strainInt J Tuberc Lung Dis201014119121

21 

CA Taype JC Agapito RA Accinelli JR Espinoza S Godreuil SJ Goodman Genetic diversity, population structure and drug resistance of Mycobacterium tuberculosis in PeruInfect Genet Evol20121235778510.1016/j.meegid.2012.02.002

22 

O Mestre Phylogeny of Mycobacterium tuberculosis Beijing strains constructed from polymorphisms in genes involved in DNA replication, recombination, and repairPLoS ONE201161e1602010.1371/journal.pone.0016020

23 

MR Farhat BJ Shapiro KJ Kieser R Sultana KR Jacobson TC Victor Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosisNat Genet20134511839

24 

F Lanzas PC Karakousis JC Sacchettini TR Ioerger Multidrug-resistant tuberculosis in Panama is driven by clonal expansion of a multidrug-resistant Mycobacterium tuberculosis strain related to the KZN extensively drug-resistant M. tuberculosis strain from South AfricaJ Clin Microbiol201351327785

25 

H Zhang D Li L Zhao J Fleming N Lin T Wang Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistanceNat Genet201345125560



jats-html.xsl

© This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Article highlights
  • Article tables
  • Article images

Article History

Received : 10-05-2021

Accepted : 22-05-2021

Available online : 30-07-2021


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/10.18231/j.ijmr.2021.019


Article Metrics






Article Access statistics

Viewed: 258

PDF Downloaded: 131



Wiki in hindi