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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
Tuberculosis is an infection of the lungs caused by Mycobacterium tuberculosis and related species. It is prevalent in tropical regions and continues to occur in more than 10 million new individuals annually and despite many advances in medicine, still results in 1.3 million deaths annually.
This clinical practice handbook presents information on all topics related to the disease, including its epidemiology, microbiology, clinical features, diagnostic procedures, treatments, BCG vaccination and infection control in health facilities. Special topics such as the treatment of tuberculosis is pediatric patients, surgery, multi-drug resistance and adverse reactions to tuberculosis drugs are also covered. Information is presented in 16 simple easy-to read chapters with key figures, tables and references that help to explain relevant topics.
Tuberculosis: A Clinical Practice Guide is an ideal reference manual for medical students and healthcare personnel seeking information about tuberculosis.
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Veröffentlichungsjahr: 2020
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FOREWORD
Dr. Laniado Laborín has accumulated vast experience in various fields of Pulmonology and Public Health, specialties that he has practiced for 40 years, standing out, especially in tuberculosis and drug-resistant tuberculosis.
He has numerous publications on this topic, but, more than what is written, I would have to ponder his experience accumulated over the years treating patients with this ancient disease that science has not yet managed to control, much less eradicate. Many difficult patients have passed through the Tuberculosis Clinic of the General Hospital of Tijuana, especially those who suffer from drug-resistant forms of the disease, aggravated by the vulnerable conditions that are unfortunately so frequently associated, and to whom he has always devoted a full attention in terms of humanity and knowledge.
His teaching performance as a professor at the Autonomous University of Tijuana is nationally and internationally recognized for his knowledge and human qualities. Countless young doctors have rotated through his service, taking a clear perception of tuberculosis's reality, both from a scientific, social and human point of view.
He has published several books throughout his career, including Drug-resistant Tuberculosis, A Practical Guide, and La Tuberculosis en México.
The work to which we have been granted the honor of writing the prologue, Tuberculosis: A Clinical Practice Guide, displays throughout its 16 chapters a detailed and well-founded overview of the disease, from epidemiology, clinical aspects, diagnosis, and prevention, in addition to delving into particular aspects such as special situations and, of course, devotes several chapters to the medical treatment of sensitive and drug-resistant TB, surgical aspects and a difficult subject such as adverse reactions to anti-tuberculosis drugs. The 15 images of outstanding quality included in the chapter of radiologic diagnosis of tuberculosis are paradigmatic of various pulmonary, extrapulmonary, and disseminated TB situations. In the 24 tables of the work, various aspects are clearly and precisely summarized, such as first and second-line drugs, treatment, and retreatment schemes.
The author, showing off his proverbial modesty, directs his work to students and health personnel who are not experts in tuberculosis. After reading, which is enjoyable and shows the extensive experience of Dr. Laniado Laborín on the subject, I have concluded that the book goes beyond these objectives, as it provides throughout its 150 pages (expandable through of the excellent bibliography that proposes) a synthesis of the current state of the art on the disease, which will provide to those who assimilate them with the knowledge of an expert in tuberculosis.
So let us welcome this work for its quality and ease of reading, which will undoubtedly occupy a prominent place in the tuberculosis literature.
PREFACE
Tuberculosis has accompanied human beings since time immemorial, and without a doubt, it is the disease of infectious origin that has caused the highest number of deaths in the history of humankind.
However, despite the extraordinary technological advances achieved in the last decade, tuberculosis continues to cause more than 10 million cases and 1.3 million deaths annually.
The reasons that explain this pandemic are multiple, mainly poverty and poor medical care (95% of cases and deaths occur in low-income countries); other contributing factors include infection by the human immunodeficiency virus, substance abuse and the emergence of drug-resistant tuberculosis.
An additional contributing factor is the little attention that has been paid to the disease in the training of health personnel, where maybe a couple of hours are dedicated to the subject in the curriculum of universities. This lack of attention results in insufficient knowledge of tuberculosis, with the consequent delay in diagnosis and the prescription of inadequate treatment.
This book aims to be a reference manual for the student and health personnel who are not an expert in tuberculosis, since it contains information on all topics related to the disease, including epidemiological, microbiological, clinical, diagnostic and treatment aspects, BCG vaccination and the control of tuberculosis infection in health facilities.
I hope this work is useful for my colleagues during their everyday practice and benefits our patients that suffer from tuberculosis.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The author declares no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Declared none.
DEDICATION
Tuberculosis Global Epidemiology
Rafael Laniado-LaborínAbstract
Globally, tuberculosis is one of the top 10 overall causes of death, the leading cause of death from a single infectious agent, and the principal cause of death among subjects living with human immunodeficiency virus infection.
The United Nations and the World Health Organization (WHO) have set very ambitious goals for the period 2020-2035 that include a 95% reduction in the number of deaths and a 90% reduction in TB incidence by 2035 compared with 2015.
The WHO reported in 2018, an estimated 10 million incident cases of TB (global incidence rate: 133 cases per 105 population), and 1.2 million TB deaths, for a case fatality rate of 15.7%. Incidence rates vary widely among regions of the world; geographically, most TB cases in 2018 were in the WHO regions of South-East Asia (44%), Africa (24%) and the Western Pacific (18%).
Rifampin-resistant (RR-TB) or multidrug-resistant TB (MDR-TB) in 2018 occurred in an estimated half a million cases, and accounted for 3.4% of all new cases and 18% of previously treated cases; an estimated 230,000 persons died of either RR or MDR-TB (case fatality rate: 41%).
Almost a quarter of the world population (1.7 billion people or 23%) are estimated to have latent TB infection and therefore are at risk of developing active TB during their lifetime.
Progress toward global TB elimination during 2018 was very modest, as it has occurred in recent years, and if kept at this current pace, the global targets for the period 2020-2035 will not be accomplished.
INTRODUCTION
Tuberculosis (TB) has affected humans for most of its history and continues to do so even though we have had an effective pharmacological treatment for more than 70 years [1]. TB is a leading cause of death among adults in the most productive age groups, and even those that have been cured can be left with significant irreversible sequelae that will substantially affect their quality of life [2].
Globally, tuberculosis is one of the top 10 overall causes of death, the leading cause of death from a single infectious agent, and the principal cause of death among subjects living with human immunodeficiency virus infection, causing approximately 40% of deaths in this population group [3].
The United Nations (UN) and the World Health Organization (WHO) have set very ambitious goals for the period 2020-2035 (Table 1) that include a 95% reduction in the number of deaths and a 90% reduction in TB incidence by 2035 compared with 2015 [4, 5].
A Stop TB Partnership target is that by the year 2050, the global incidence of active TB will be less than one case per million population per year. The components of the Stop TB Strategy are:
Pursue high-quality DOTS expansion and enhancement.Address TB-HIV, MDR-TB, and the needs of poor and vulnerable populations.Contribute to health system strengthening based on primary health care.Engage all care providers.Empower people with TB, and communities through partnership.Enable and promote research.Tuberculosis Statistics
TB incidence has never been measured at a country level, since this would require long term prospective studies, including large population cohorts (hundreds of thousands) with very high costs and challenging logistics. As a proxy of real incidence, TB incidence is estimated from case reports included in routine surveillance systems. Unfortunately, in many countries, surveillance systems cannot provide an adequate measure of TB incidence because of underreporting or underdiagnosis of cases [6].
Incidence rates vary widely among regions of the world (Table 2). The lowest rates (<10 per 105) are reported from high-income countries including most countries from Western Europe, Canada, the United States, Australia, and New Zealand; most countries in the Americas (the WHO region with the lowest TB burden) have rates <50 per 105, although some countries like Haiti (181 per 105), Bolivia (111 per 105), and Peru (116 per 105) still have very high rates [7]. The countries with the highest rates are mostly located in Africa.
Geographically, most TB cases in 2018 were in the WHO regions of South-East Asia (44%), Africa (24%), and the Western Pacific (18%) [8]. Eight countries account for two-thirds of the world cases: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (5%), Nigeria (4%), Bangladesh (4%) and South Africa (3%). On the other hand, only 3% of the global cases are reported by the WHO European Region and 3% by the WHO Americas region [7, 9].
The WHO reported for the year 2018, an estimated 10 million (range 9.0-11.1 million) incident cases of TB (global rate: 133 cases per 105population), and 1.2 million TB deaths (range 1.1 to 1.3 million [8]. This represents a reduction of 1.8% and 3.9% in incident TB cases and TB deaths, respectively, in comparison with the year 2016; 920,000 (9%) of the incident cases and an estimated 300,000 deaths (case fatality rate 32.6%) occurred among persons living with HIV. Of the estimated 10 million cases, there were 5.8 million men, 3.2 million women, and 1 million children. Ninety percent of the cases are reported in adults (≥15 years), and, as mentioned, 9% occurred in people living with HIV, 72% of those living in Africa [9].
Rifampin-resistant (RR-TB) or multidrug-resistant TB (MDR-TB) occurred in an estimated half a million cases (range 417,000-556,000) in 2018, which constitutes 5.6% of all cases. RR/MDR-TB accounted for 3.4% and 18% of new and previously treated cases, respectively, in 2018; an estimated 230,000 persons died of either RR or MDR-TB (case fatality rate: 41%) [9]. Among the RR-TB cases, 78% were MDR [8]; of the MDR-TB cases, 8.5% (CI95% 6.2-11%) were estimated to have extensively drug-resistant TB, also known as XDR-TB. Three countries accounted for almost half of the world cases of RR/MDR-TB: India (24%), China (13%), and the Russian Federation (10%). Although the overall incidence of TB in the WHO European region was only 30 per 105, the proportion of TB cases with RR or MDR-TB in this region (40%) was much higher than that in all the other five regions (range: 3.6%–6.3%) [9].
Almost a quarter of the world population (1.7 billion people or 23%) are estimated to have latent TB infection (LTBI) and therefore are at risk of developing active TB during their lifetime, become infectious, and transmit the disease [10].
Achieving the targets of the End TB strategy (Table 1) for a reduction in TB cases and deaths set for 2020 and 2025 will require to accelerate the current annual decline from 1.5% per year in 2015 to 4-5% per year by 2020, and by 10% per year by 2025. The global proportion of people who die from TB (case fatality ratio) needs to be reduced from 15.7% in 2017 to 10% by 2020 and 6.5% by 2025. This reduction in rates will only be possible if all those with TB can access high-quality health services for early diagnosis and effective treatment.
Reaching the 2030 and 2035 targets will require an average acceleration of the decline rate of 17% per year. Such acceleration will depend on technological developments that could substantially reduce the risk of progression to an active disease of 1.7 billion people with LTBI through an effective post-exposure vaccine [11] or a concise, effective, and safe treatment for LTBI [1, 6].
Despite advances in treatment and prevention, tuberculosis is one of the leading causes of morbidity and mortality and the leading cause of death from an infectious disease globally.
Tuberculosis ceased to be an essential public health issue in economically developed countries as the main determinants of disease -extreme poverty, severe malnutrition, and overcrowding- gradually disappeared. Some public health experts declared that “virtual elimination of tuberculosis was in sight” [12].
Although the development of antibiotic resistance due to M. tuberculosis was reported almost immediately after the introduction of the first effective regimen in the treatment of tuberculosis in 1944 with streptomycin, the effectiveness of regimens consisting of a combination of several antimicrobials in the treatment of tuberculosis during the decades of the 50’s and 60’s, brought as a consequence, the lack of interest in the development of new anti-tuberculosis drugs; 40 years had to pass between the introduction of rifampicin in the 1960s and the development of two new drugs, bedaquiline and delamanid in the 2010s [13].
However, drug resistance is only one of the factors that favor the persistence of tuberculosis as a serious public health problem. Extreme poverty and co-infection with HIV in economically underdeveloped regions are a very significant contributing factor. Globalization has improved the mobility of the population but also the transmission of tuberculosis.
The control of tuberculosis will require a comprehensive approach to tackle the disease’s socio-cultural determinants in combination with scientific advances in diagnosis [14] and treatment [15] if the disease is to be eradicated one day.
REFERENCES
[1]MacNeil A, Glaziou P, Sismanidis C, Maloney S, Floyd K. Global epidemiology of tuberculosis and progress toward achieving global targets - 2017. MMWR Morb Mortal Wkly Rep 2019; 68(11): 263-6.[http://dx.doi.org/10.15585/mmwr.mm6811a3] [PMID: 30897077][2]Miller TL, McNabb SJ, Hilsenrath P, Pasipanodya J, Weis SE. Personal and societal health quality lost to tuberculosis. PLoS One 2009; 4(4): e5080.[http://dx.doi.org/10.1371/journal.pone.0005080] [PMID: 19352424][3]Gupta RK, Lucas SB, Fielding KL, Lawn SD. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS 2015; 29(15): 1987-2002.[http://dx.doi.org/10.1097/QAD.0000000000000802] [PMID: 26266773][4]UN United NationsSustainable development goals New York, NY: United Nations 2016. https://sustainabledevelopment.un.org[5]WHO World Health OrganizationThe end TB strategy Geneva, Switzerland: World Health Organization 2015. https://www.who.int/tb/strategy/ end-tb/en/[6]Glaziou P, Sismanidis C, Floyd K, Raviglione M, Raviglione M. Global epidemiology of tuberculosis. Cold Spring Harb Perspect Med 2014; 5(2): a017798.[http://dx.doi.org/10.1101/cshperspect.a017798] [PMID: 25359550][7]OPS. Organización Panamericana de la Salud 2018. Tuberculosis en las Américas 2018. Washington, DC: OPS, 2018. Número de documento: OPS/CDE/18-036[8]WHO. Global tuberculosis report 2019. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO.[9]WHOWorld Health Organization Global tuberculosis report 2018 2018.[10]Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 2016; 13(10): e1002152.[http://dx.doi.org/10.1371/journal] [PMID: 1002152][11]Tait DR, Hatherill M, Van Der Meeren O, et al. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis. N Engl J Med 2019; 381(25): 2429-39.[http://dx.doi.org/10.1056/NEJMoa1909953] [PMID: 31661198][12]Castro KG, LoBue P. Bridging implementation, knowledge, and ambition gaps to eliminate tuberculosis in the United States and globally. Emerg Infect Dis 2011; 17(3): 337-42.[http://dx.doi.org/10.3201/eid1703.110031] [PMID: 21392421][13]Armocida E, Martini M. Tuberculosis: a timeless challenge for medicine. J Prev Med Hyg 2020; 61(2): E143-7.[http://dx.doi.org/10.15167/2421-4248/jpmh2020.61.2.1402] [PMID: 32802997][14]WHO consolidated guidelines on tuberculosis. Module 3: diagnosis – rapid diagnostics for tuberculosis detection. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO.[15]WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO.Microbiology of Tuberculosis
Rafael Laniado-LaborínAbstract
Mycobacterium tuberculosis (MTB) is the primary etiological agent of tuberculosis in humans (since the disease may be due to other mycobacteria of the MTB complex such as M. bovis). It belongs to the order of the Actinomycetales and the Mycobacteriaceae family. It is a bacillus that lacks capsule or flagella and does not produce spores or toxins; it measures 0.5 by four microns. Its generation time is prolonged (up to 24 hours). It is an aerobic bacillus that, if necessary, can persist under anaerobic conditions.
It has a cell wall of extremely complex composition, with great strength and thickness, constituted up to 60% by lipids, generally known as mycolic acids that form complexes with polysaccharides such as arabinogalactan and peptidoglycan; these lipids determine their resistance to discoloration by alcohol-acid after they have been stained with carbol fuchsin (hence the term acid-fast bacilli acid or AFB). A distinctive feature of the MTB cell wall is its content of N-glycolimuranic acid instead of N-acetylmuramic acid found in most bacteria.
The unusual cell wall of MTB also allows it to survive initially in the macrophage. The cell wall also constitutes a robust and highly impermeable barrier to harmful compounds and drugs. MTB can sense when the local tissue conditions are inadequate for survival (low oxygen tension and nutrient depletion), as in the macrophages and granulomas, responding by the activation of a dormant state, in which the bacilli stop multiplying, down-regulates its metabolism and activates anaerobic metabolism.
INTRODUCTION
The Mycobacterium Tuberculosis Complex (MTC)
Members of the MTC are bacteria that share a genetically identical 16SrRNA sequence and a greater 99.9% nucleotide identity. The four original species of the MTC are M. tuberculosis (affects humans, known as M. tuberculosis sensu stricto), M. africanum (affects humans), M. microti (affects voles) and M. bovis (affects cattle and other bovines). Newer species of the MTC include M. pinnipedii
(affects pinnipeds: seals and sea lions), M. canettii (affects humans? it is the most ancestral recognized MTC member, although rarely isolated), the dassie bacillus (affects the rock hyraxes, [Procavia capensis]), M. caprae (affects goats), Myco bacterium orygis, (associated with various species), Mycobacterium mungi (which infects banded mongooses [Mungos mungo]), Mycobacterium suricattae (which affects meerkats [Suricata suricattae]), and M. bovis-BCG [1, 2]. The most accurate method to distinguish members of the MTC from one another are through genetic markers, single nucleotide polymorphisms (SNPs) in the 16S rDNA and gyrB genes and elsewhere in the genome, as well as extensive sequence polymorphisms referred to as regions of difference [2].
The deciphering of the Mycobacterium tuberculosis (MTB) genome that contains 4,411,529 base-pairs with high guanine-cytosine content [3] has allowed the reconstruction of the evolutionary history of MTB as an infectious agent at a global level. MTB emerged from Africa 70,000 years ago and followed human migrations and was forced to genetically evolve to be able to persist in these low-density migrant populations. The increase in human population density associated with the introduction of agriculture and overall civilization led to the selection and transmission of more virulent MTB strains, which are now known as modern MTB strains [4].
No human remains older than 11,000 years have shown the presence of tuberculosis disease, while the earliest tuberculosis case in animals has been reported in the 17,000-year-old remains of a bison [5].
Human disease by M. bovis strains is a frequent clinical finding, with transmission to the human host occurring via aerosol (in people in contact with livestock) or the consumption of infected milk. There has always been speculation that human TB originally was acquired as a zoonotic disease from cattle; the fact that animal tuberculosis preceded human tuberculosis suggests some causality with the increase in domestication of livestock. It has been hypothesized that contact of animal stocks and humans favored transmission from cattle to humans (in the past, humans shared their home with domesticated animals to protect them from the weather and predators). However, this hypothesis proved to be false when mycobacterial interspersed repetitive unit genotyping and whole-genome sequencing (WGS) provided strong evidence against such a linear explanation [5]; the accumulation of genomic deletions makes it improbable that M. bovis is the precursor of M. tuberculosis and that human TB was associated with the domestication of cattle [1].
Paleopathological studies had proven that mycobacterial disease was present in America in the pre-Columbian era [6] when Mycobacterium tuberculosis DNA was identified in a pre-Columbian Peruvian mummy [7]. It has been suggested that seals were the source of human tuberculosis in South America, predating the entrance of Mycobacterium tuberculosis L4 strains carried by the European Conquistadores. However, M. pinnipedii has been entirely replaced by the L4 lineage in the present day [8].
M. tuberculosis belongs to the order of the Actinomycetales and the Myco bacteriaceae family. It lacks capsule or flagella and does not produce spores or toxins; it stains very weakly as Gram-positive; it measures 0.5 by 4 μ. It is a preferably aerobic bacillus that, if necessary, can persist under anaerobic conditions. A distinctive feature of the M. tuberculosis cell wall is its content of N-glycolimuranic acid instead of N-acetylmuramic acid found in most bacteria. The unusual cell wall of M. tuberculosis allows it to survive inside the alveolar macrophage, a cell that usually destroys the bacteria that phagocytes.
Transmission of tuberculosis usually occurs through aerosols from one diseased host to a contact. Mycobacteria virulence will adapt to the host immunity. However, greater virulence would facilitate transmission, and it would also produce disseminated disease and some forms of TB that are nontransmissible (e.g., TB meningitis), types of disease that would rapidly kill the host stopping the chain of transmission; therefore, excessive virulence could be detrimental to mycobacteria survival. Optimal transmissibility requires enough virulence to produce a disease with a high rate of transmission (e.g., pulmonary disease through aerosols) before killing the host [1].
Mycobacterium tuberculosis is characterized by its slow growth rate (generation time in synthetic media is about 24 hours), dormancy (known clinically as latent TB infection), a sophisticated cell wall, and genetic homogeneity. The state of dormancy reflects metabolic shut down as a response to the cell-mediated immune response of the host, a response that will contain, but not sterilize the lesion. When immunity wanes (e.g., old age) or the host immune response is inadequate (e.g., due to immunosuppressive treatment or HIV co-infection), latent bacteria can reactivate, even decades after the primary infection [9].
One of the host responses to M. tuberculosis infection is the formation of a cluster of macrophages, creating a granuloma surrounding the mycobacteria. Host immune containment by granuloma formation creates a physical micro environment with nutrient limitations, a low pH, the presence of hydrolytic enzymes, and reduced oxygen tension. These granulomas are initially solid or caseous during latent infection, but when the immune pressure wanes (aging, immunosuppression by HIV infection, among others), the granuloma liquefies, allowing rapid bacterial replication and tissue damage. M. tuberculosis cultures with low oxygen tension (or anaerobic conditions) develop a thicker cell wall as an adaptation to low-oxygen conditions [10].
MTB cell wall (which stains weakly as a Gram-negative) constitutes a robust and highly impermeable barrier to harmful compounds and drugs. It includes an asymmetrical lipid bilayer made of mycolic acids on the inside and glycolipids and waxy components on the external layer. On the inside of the cell wall, there is a thin layer of peptidoglycan covalently linked to arabinogalactan and lipoarabinomannan, which in turn are bound to the mycolic acids. The mycolic acids retain the stain with carbol fuchsin or auramine when decolorized by acid alcohol, hence the term acid-fast bacilli. Two of the first-line antituberculosis drugs, isoniazid (mycolic acids), and ethambutol (arabinogalactan), target components of the cell wall.
MTB has several secretion systems, which are required for its full virulence. One of the secretion systems (ESX1) secretes among other antigens, ESAT-6 and CFP-10, antigens that are now used for the immunologic diagnosis of MTB infection in the interferon-gamma release assays (known as IGRA tests). M. bovis-BCG (an attenuated strain of wild M. bovis) has lost the ESX1 secretion system, and does not express ESAT-6 or CFP-10; therefore, IGRAs can be utilized to distinguish between M. tuberculosis infection and the immune reaction caused by BCG vaccination (unlike the tuberculin skin test).
MTB can sense when the local tissue conditions are inadequate for survival (low oxygen tension and nutrient depletion), as in the macrophages and granulomas, responding by the activation of a dormant state, in which the bacilli stop multiplying, down-regulates their metabolism and activate anaerobic metabolism. These dormant mycobacteria can persist in the host for years and revert to an active state when the conditions allow it (e.g., immunosuppression) [4].
M. tuberculosis can synthesize all the essential amino acids, vitamins, and enzyme co-factors. It can also metabolize carbohydrates, hydrocarbons, alcohols, ketones, and carboxylic acids. Under aerobic conditions, adenosine triphosphate (ATP) will be generated by oxidative phosphorylation, but mycobacteria must adapt its metabolism to the microaerophilic and anaerobic environment present at the center of a granuloma.
M. tuberculosis is naturally resistant to many antibiotics. An essential factor in this resistance capacity is due mainly to its highly hydrophobic cell wall acting as a permeable physical barrier, but many resistance determinants are encoded in its genome, including hydrolases, β-lactamases and drug-efflux systems [9].
REFERENCES
[1]Mostowy S, Behr MA. The origin and evolution of Mycobacterium tuberculosis. Clin Chest Med 2005; 26(2): 207-216, v-vi.[http://dx.doi.org/10.1016/j.ccm.2005.02.004] [PMID: 15837106][2]Clarke C, Van Helden P, Miller M, Parsons S. Animal-adapted members of the Mycobacterium tuberculosis complex endemic to the southern African subregion. J South African Vet Association 2016; 87(1) a1322.[http://dx.doi.org/10.4102/ jsava. v87i1.1322][3]Lin SY, Desmond EP. Molecular diagnosis of tuberculosis and drug resistance. Clin Lab Med 2014; 34(2): 297-314.[http://dx.doi.org/10.1016/j.cll.2014.02.005] [PMID: 24856529][4]Delogu G, Sali M, Fadda G. The biology of mycobacterium tuberculosis infection. Mediterr J Hematol Infect Dis 2013; 5(1): e2013070.[http://dx.doi.org/10.4084/mjhid.2013.070] [PMID: 24363885][5]Rothschild BM, Martin LD, Lev G, et al.Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present. Clin Infect Dis 2001; 33(3): 305-11.[http://dx.doi.org/10.1086/321886] [PMID: 11438894][6]Stead WW, Eisenach KD, Cave MD, et al. When did Mycobacterium tuberculosis infection first occur in the New World? An important question with public health implications. Am J Respir Crit Care Med 1995; 151(4): 1267-8.[http://dx.doi.org/10.1164/ajrccm.151.4.7697265] [PMID: 7697265][7]Salo WL, Aufderheide AC, Buikstra J, Holcomb TA. Identification of Mycobacterium tuberculosis DNA in a pre-Columbian Peruvian mummy. Proc Natl Acad Sci USA 1994; 91(6): 2091-4.[http://dx.doi.org/10.1073/pnas.91.6.2091] [PMID: 8134354][8]Barbier M, Wirth T. The evolutionary history, demography, and spread of the Mycobacterium tuberculosis complex. Microbiol Spectrum 2016; 4(4). [http://dx.doi.org/10.1128/microbiolspec.TBTB2-0008-2016][9]Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998; 393(6685): 537-44.[http://dx.doi.org/10.1038/31159] [PMID: 9634230][10]Rosenkrands I, Slayden RA, Crawford J, Aagaard C, Barry CE, III, Andersen P. Hypoxic response of mycobacterium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins. J Bacteriol 2002; 184(13): 3485-91.[http://dx.doi.org/10.1128/JB.184.13.3485–3491.2002]Tuberculosis: A Natural History of the Disease
Rafael Laniado-LaborínAbstract
Tuberculosis infection occurs when a subject inhales the Mycobacterium tuberculosis bacilli (MTB). An active case of pulmonary or laryngeal tuberculosis generates infectious particles called droplet nuclei of <5 microns in diameter, when coughing, sneezing or through any other forceful expiratory maneuver. The infectiousness of a patient with TB is directly related to the form of the disease (laryngeal, pulmonary), the presence of cough, cavitary lung disease and the positivity of the sputum smear/culture.
The prevalence of M. tuberculosis
