Mycobacterium Tuberculosis Complex

Members of MTB complex are rod-shaped, acrid-fast, aerobic, boring-growing intracellular pathogens that subvert phagosomal cells in order to persist and evade immune system

From: Diagnostic Pathology: Infectious Diseases , 2015

Mycobacteria

Richard A. McPherson Dr., MSc , in Henry'south Clinical Diagnosis and Management past Laboratory Methods , 2022

Mycobacterium Tuberculosis Circuitous

Four general strategies for controlling TB are described. The most of import is early identification and acceptable treatment of persons with infectious TB. This renders the infected person noncontagious within a few weeks and eventually results in cure. The second strategy entails identification and treatment of individuals with noncontagious TB: extrapulmonary disease, primary pulmonary affliction in children, bacteriologically unconfirmed pulmonary disease, and latent infection with MTBC (i.eastward., positive TST or IGRA, normal breast radiograph, no symptoms).

The third strategy involves cosmos of a safe environment in situations in which the run a risk for transmitting infection is loftier: autopsy suites, sputum induction cubicles, chest dispensary waiting areas, correctional institutions, some shelters for the homeless, and mycobacteriology laboratories. To achieve this, several issues must be addressed (Segal-Maurer & Kalkut, 1994). Rooms housing infectious patients or in which potentially infectious specimens are handled should be nether negative pressure, and air likely to be contaminated with infectious droplet nuclei should be exhausted to the outside. A unmarried-pass ventilation organisation (all-time accomplished past locating air supply outlets at the ceiling level and frazzle inlets near the flooring) and a minimum of half dozen air changes per hour (12 exchanges per hour for dissection suites) are recommended. Universal precautions must be followed when handling all specimens, and both specimens and cultures must be handled in a certified, course Ii biological safety cabinet. Moreover, a particulate respirator that filters out particles ane to v μm in bore should be worn, and personnel should be trained in a respiratory programme; the standard surgical mask is not adequate.

The fourth strategy is vaccination with the BCG vaccine, an attenuated vaccine derived from a strain ofM. bovis by Calmette and Guérin in France. This vaccine is used in many countries where the prevalence of TB is high to prevent TB meningitis and miliary TB in children simply by and large is not recommended in the United States, because the risk for infection with MTBC is low and the effectiveness of the vaccine in adults is variable. The BCG vaccine should not be given to immunocompromised persons, those likely to become immunocompromised, or pregnant women. DisseminatedYard. bovis in patients with AIDS andM. bovis lymphadenitis in symptomatic HIV-infected infants have occurred following BCG vaccination (CDC, 1985;Blanche et al., 1986). All the same, disseminated1000. bovis has not been reported in asymptomatic persons infected with HIV. In populations where the adventure for TB is high, the WHO recommends that the BCG vaccine be given to HIV-infected children at birth or before long thereafter. It should non be given to children with symptomatic HIV infection, to populations in which the risk for tuberculosis is depression, or to persons known or suspected to exist infected with HIV (WHO, 1987).

The Ascension and Fall of the Mycobacterium tuberculosis Complex

Marcel A. Behr , Sébastien Gagneux , in Genetics and Development of Infectious disease, 2011

Publisher Summary

This affiliate explains the Mycobacterium tuberculosis Complex, the Mycobacterium genus and the evolution of evolution of Mycobacterium tuberculosis. Information technology defines the organisms which are the subject of consideration and outlines nigh their role in human and veterinary disease. The current understanding of the genus mycobacterium and the situation of Chiliad. tuberculosis within this genus are discussed. This chapter also describes the species M. tuberculosis and M. bovis with examples and delves into the results of genetic studies within the M. tuberculosis circuitous and the inferences of these findings on the population biological science of this organism. Thousand. leprae is the cause of leprosy, and this organism was the 2d mycobacterium to have its genome determined. Thousand. tuberculosis was situated in a more bequeathed position, with a larger genome, while M. bovis was situated in a more derived position, with a smaller genome, and served as the parental strain for BCG vaccines that M. tuberculosis complex represented. M. tuberculosis is a strong reduction in purifying selection against nonsynonymous changes. When the authors analyzed the specific antigen regions known to collaborate with human being T cells, they found that these T jail cell epitopes were the most conserved of all genomic regions analyzed. G. bovis has a smaller genome, the reason for its ability to cause disease in a large number of hosts is yet unknown. The affiliate concludes that the challenge at hand is to harness the new data, interpret it into new insights, and employ this information to help inform the next generation of TB inquiry.

Read total chapter

URL:

https://www.sciencedirect.com/science/commodity/pii/B9780123848901000248

Antimicrobial Susceptibility Testing

Nader Rifai PhD , in Tietz Textbook of Clinical Chemistry and Molecular Diagnostics , 2018

Mycobacterium Tuberculosis Complex

Antimicrobial resistance amongst the MTBC is a meaning clinical concern. For additional word on this organism, seeAffiliate 76. Monotherapy was shown early in the days of antituberculosis chemotherapy to pb to option of genomic mutations in MTBC that conferred resistance to antimicrobials used. In contrast, data revealed that therapy with multiple drugs suppressed resistance. Today, routine prescription of multidrug regimens for the treatment of MTBC infections utilizes the backbone combination of rifampin and isoniazid, and typically pyrazinamide and ethambutol. 124 Isolates that were resistant to isoniazid and rifampin emerged throughout the 1970s and 1980s; such isolates are referred to as multidrug-resistantYard. tuberculosis (MDR-TB). Today, approximately 500,000 patients per year have a primary infection caused by MDR-TB. Unfortunately, only 0.v% of these patients receive treatment that is considered the standard of care in industrialized nations. 125 Such inadequately treated patients fueled the emergence of extensively drug-resistantYard. tuberculosis (XDR-TB), that is, strains that are resistant to not only isoniazid and rifampin, but also the fluoroquinolones and at least one second-line injectable drug (amikacin, kanamycin, or capreomycin). In 2009, totally drug-resistantM. tuberculosis (TDR-TB) was described in Iran and India, 126 which was resistant to all first- and second-line drugs used to treat MTBC infections.

AST of MTBC isolates is performed by assessing the ability of the isolate to abound on agar or in broth containing a unmarried "critical" concentration of drug. Critical concentration is divers as the concentration that inhibits 95% of WT strains that take never come into contact with the drug, just does not inhibit strains isolated from patients who failed handling. Resistance is defined as >1% of the inoculated bacterial cells growing in the presence of the "critical" concentration of the drug. Critical concentrations were beginning established in Lowenstein-Jensen medium, and equivalent (but unlike) concentrations have since been established for Middlebrook 7H10 and 7H11, and other commercial susceptibility test systems.

Mostly, the first isolate of MTBC from each patient should exist tested, and AST should be repeated if the patient fails to answer to therapy, or if cultures remain positive at three months. In order to ensure early detection of resistant MTBC, CLSI and CDC recommend reporting results of MTBC susceptibility within 15–xxx days of receipt of a specimen in the laboratory, or 7–xiv days subsequently isolation of MTBC. To help meet this goal, testing can be performed direct from the specimen if a patient is smear positive, which yields results within iii weeks in most cases. Primary antimicrobials tested include isoniazid, rifampin, ethambutol, and pyrazinamide. For isoniazid, two concentrations are tested; if an isolate is resistant to the critical concentration (0.2 mg/L) simply susceptible to the higher concentration (one.0 mg/L), it is considered to have a depression-level resistance, and the patient may even so do good from continuing isoniazid therapy. If an isolate is resistant to rifampin or any two of the other master drugs, a secondary console consisting of streptomycin, capreomycin, ethionamide, amikacin, p-aminosalicylic acid, rifabutin, cyloserine, linezolid, moxifloxacin, and levofloxacin is tested. This testing is typically performed at reference or public health laboratories.

Bacterial Diseases

Keith G. Mansfield , James 1000. Fox , in The Common Marmoset in Captivity and Biomedical Research, 2019

Etiology

The MTC consists of Mycobacterium africanum, Mycobacterium bovis, Mycobacterium canettii, Mycobacterium microti, and M. tuberculosis and contains known pathogens of humans and wild and domesticated species of mammals. They are obligate pathogens and the etiologic agents of tuberculosis, and then named considering of the nodular lesions observed in lungs, which are termed tubercles. These organisms can exist visualized using acid-fast stains such every bit the Ziehl–Neelsen, Fite, and Kinyon stains, which fail to decolorize with weak acids in mycobacteria due to the organism's waxlike cell wall. If a Gram stain is performed, bacilli may exist weakly Gram-positive or -negative. Grand. tuberculosis and Thousand. bovis are the two most common species in the MTC to be reported in One-time World primates and tin can cause desultory or epizootic disease of loftier morbidity and mortality in these species. Infection with other members of the MTC (Yard. africanum) is less commonly reported [xix].

PCR surveys of neotropical primates kept as pets or in zoological collections have detected a high rate of M. tuberculosis in buccal swabs [twenty], and mycobacterial cultures of gastric lavage have demonstrated like results [21]. However, reports of MTC-associated disease in neotropical primates are uncommon. There is a single case study documenting M. tuberculosis in a pet common marmoset with likely human-to-animal transmission [22]. In contrast, common marmosets are highly susceptible to experimental inoculation of M. tuberculosis by the aerosolized and intratracheal routes [23,24]. The reasons for this disparity are unclear, and efforts should exist made to further document the natural history of MTC infection in common marmosets and neotropical primates in general.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128118290000169

Tuberculosis : Pathogenesis and Immunity

V. Courtney Broaddus Physician , in Murray & Nadel's Textbook of Respiratory Medicine , 2022

G. Tuberculosis and theM. Tuberculosis Complex

Tuberculosis is caused by several species of the Mycobacterium tuberculosis complex (MTBC), includingM. tuberculosis,M. africanum,M. bovis, and rarely past other animate being-adapted species. The rod-shaped bacteria grow slowly, and are characterized by their acid-fastness (they retain chemical dyes after washing with solutions of strong acid in booze), which in turn is attributable to a bacterial envelope equanimous of mycolic acids with acyl chains up to 90 carbons in length, with diverse structural characteristics including cyclopropane rings, methyl branches, ketones, and methoxy groups. 1 Although1000. tuberculosis can infect and cause disease in many mammalian species, humans are the just significant reservoir and, with rare exceptions, infected humans are the source of transmission.

The genome of the MTBC consists of approximately 4.four × ten6 nucleotides in a single round chromosome and is guanine-cytosine rich (overall 65.6%). The genome of the reference strain H37Rv (isolated from a patient in 1905) encodes 4006 proteins and fifty RNA species two ; there is also experimental show for noncoding RNAs with regulatory functions. 3

Much of the MTBC genome contains genes in mutual with other bacteria, including those whose products function in metabolism, cell wall synthesis, membrane send, cell partitioning, RNA synthesis, and adaptation to environmental conditions. The MTBC genome encodes at least three distinct protein secretion systems. Of these, the type 7 secretion system, which is besides present in certain gram-positive bacteria, consists of five loci, termed Esx loci due to the initial discovery of the locus that secretesearly secreted antigenic target of 6 kD (ESAT-6). Of these, ESX-1 is responsible for secreting proteins (ESAT-vi and CFP-ten), which are important for virulence and are also targets of recognition by host immune responses (encounter afterward andFig. 52.1). ESX-iii secretes the substrate EsxH, implicated in impeding phagosome maturation and MHC class II antigen presentation, iv , 5 and essential for bacterial iron acquisition. 6 , 7 ESX-5 is required for secretion of PE and PPE proteins (described later) that contribute to regulation of virulence and immunity. The functions of ESX-ii and ESX-iv are not yet defined.

The genome of the MTBC includes several multigene families, including theproline-glutamate (pe) andproline-proline-glutamate (ppe) genes, named for proline-glutamic acid or proline-proline-glutamic acid motifs, near the amino termini of their poly peptide products. These gene families are unique to mycobacteria and are markedly expanded in pathogenic mycobacteria (due east.chiliad., 99pe and 69ppe genes inM. tuberculosis H37Rv). eight Although the functions of thepe andppe genes are poorly understood, the individual members of these gene families are under markedly different evolutionary selection pressures, indicating that they do not serve redundant functions, 9 despite their sequence and structural similarities.

The Species Concept

Ali Akbar Velayati , Parissa Farnia , in Atlas of Mycobacterium Tuberculosis, 2017

Mycobacterium tuberculosis Circuitous

Mycobacterium tuberculosis complex (MTC) constitutes a remarkably genetically homogeneous grouping. They are characterized by 99.9% similarity at the nucleotide level and identical 16S rRNA sequences (Böddinghaus et al., 1990; Sreevatsan et al., 1997), but they differ widely in terms of their host tropisms, phenotypes, and pathogenicity (Brosch et al., 2002; Rastogi and Sola,2007; Wirth et al., 2008). The MTC includes Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium microti, Mycobacterium canettii, Mycobacterium caprae, Mycobacterium pinnipedii, Mycobacterium suricattae, Mycobacterium mungi, Mycobacterium dassie, and Mycobacterium oryx. From those species, M. tuberculosis, "a pathogen of the mammalian respiratory organisation," is the most well-known member, infecting more than than ane-third of world'due south human population; it is also able to infect animals that accept contact with humans (Borgdorff, 2000; Smith, 2004; Dye, 2006; Montoro and Rodriguez, 2007; van Soolingen et al., 2007).

1000. bovis displays the broadest spectrum of host infection, affecting humans, domestic or wild bovines, and goats (Karlson and Lessel, 1970; Grange et al., 1996; Phillips et al., 2003; O'Brien, 2011). G. bovis is usually transmitted to humans past infected milk, although information technology as well spread via aerosol aerosol (Velayati et al., 2007). Thou. bovis BCG, historically known equally Calmette et Guérin, is prepared from an adulterate strain of the live bovine tuberculosis bacillus 1000. bovis (King and Park, 1929; Aronson, 1948; Andersen, 1948). K. bovis BCG is the only vaccine used in tuberculosis prevention during early childhood (Murohasi, 1948; Price, 1949; Trunz et al., 2006; WHO, 2007; Roy et al., 2014). 1000. canettii and M. africanum are closely related to K. tuberculosis. K. canettii was start reported in 1969 (Canetti), has shorter generation time than clinical isolates of M. tuberculosis, and presented a unique characteristic phenolic glycolipid and lipooligosaccharide (van Soolingen et al., 1997). Tuberculosis acquired past both Chiliad. canettii and M. africanum appears to be an emerging illness in African patients or those of African ancestry (Forrellad et al., 2013). Grand. microti is a rodent pathogen, usually isolated from voles, and information technology can likewise crusade diseases in immunocompromised human patients (Brosch et al., 2002). Grand. caprae has been recognized mainly in fundamental Europe, where it has been occasionally isolated from tuberculous lesions from cattle, pigs, red deer (Cervus elaphus), and wild boars (Sus scrofa). Its isolation from humans has also been described (García-Rodríguez et al., 2011). One thousand. pinnipedii, Chiliad. suricattae, Grand. mungi, Thou. dassie, and Yard. oryx can infect seals, meerkats, mongoose, dassie, and the Bovidae family unit (Wagner and Bokkenheuser, 1961; Van Ingen et al., 2012; Alexander et al., 2010).

Today, based on genomic analysis, it has been suggested that members of the MTC evolved from a common antecedent via successive Dna deletions/insertions resulting in the present speciation of Mycobacterium (Forrellad et al., 2013). Even so, the advent of molecular methods and the discovery of the polymorphic nature of the direct repeat (DR) locus (Groenen et al., 1993; Kamerbeek et al., 1997) with subsequent evolution of the spoligotyping method based on DR locus variability innovate more than modern concepts and tools for agreement MTC genotyping (Sola, 1999; Table 1.ix). Later, the discovery of tandem repeat loci in the MTC (Frothingham and Meeker-O'Connell, 1998; Supply et al., 2001; Bakery et al., 2004), systematic unmarried-nucleotide polymorphism genotyping (Filliol et al., 2006; Gutacker et al., 2006), and large sequence polymorphism (Mostowy and Behr, 2002; Tsolaki et al., 2005; Rastogi and Sola, 2007) was introduced. These molecular approaches favor of the being of lateral genetic transfer in the precursor of the MTC and allowed the definition of genetically unlike lineages amid M. tuberculosis species.

Table 1.9. Spoligotyping Subdivided 1000. tuberculosis Into Seven Main Lineages

The main lineages inside the M. tuberculosis species
1.

The East-African-Indian (EAI) lineage

2.

The Beijing lineage

3.

The Central-Asian (CAS) or Delhi lineage

four.

The Haarlem family

5.

The Latin American and Mediterranean (LAM) family unit

6.

The X family: The European IS6110 low banders

7.

The T families and others

The East African-Indian lineage was beginning described in Guinea-Bissau (Källenius et al., 1999) and was shown to be frequent in Southeast Asia, India, and East Africa (Kremer et al., 1999). This grouping of strains is characterized by a low number of IS6110 copies. A subgroup of these strains harboring a single re-create of IS6110 was shown to exist widespread in Malaysia, Tanzania, and Oman (Fomukong et al., 1994). These lineages are characterized by the absence of spacers 29–32, the presence of spacer 33, and the absence of spacer 34. This lineage was shown to belong to Cluster Group i or Cluster I (Filliol et al., 2006; Gutacker et al., 2006).

The Beijing genotype belongs to the principal genetic Grouping 1 of Sreevatsan, and its specific spoligotype design is the absence of spacer 1–33 and the presence of spacer 34–43 that was discovered in 1995 (van Soolingen et al., 1995). The Central-Asian (CAS) or Delhi lineage with its specific spoligotype pattern that is absence of spacers four–27 and 23–34 is shown to be endemic in Sudan, other sub-Saharan countries, and Pakistan (Brudey et al., 2006). This spoligotype-signature shows numerous variants and several subgroups such as CAS1-Kili (for Kilimanjaro) and CAS1-Dar (for Dar-es-Salaam), which take already been defined on the basis of new spoligotype-signatures that are specific for each new clonal complex (McHugh et al., 2005; Eldholm et al., 2006).

The Haarlem family was described in the Netherlands in 1999 (Kremer et al., 1999). The spoligotype is characterized by the absence of spacer 31, which is due to the presence of a second copy of IS6110 in the DR region (Groenen et al., 1993). Three chief spoligotype-signatures ascertain the variants H1 to H3 (Filliol et al., 2002). The LAM family unit is frequent in Mediterranean countries, and its presence in Latin America (Zumárraga et al. 2014) is supposed to be linked to the Lusitanian-Hispanian colonization of the New World. The family is characterized by absence of spacers 21–24 in the spoligotyping (Sola et al., 2001). The 10 family of strains is defined by 2 concomitant features: a depression number of IS6110 copies and the absence of spacer 18 in the spoligotyping (Sebban et al., 2002). The Ten family was as well the commencement grouping identified in Guadeloupe (Sola et al., 1997) and French Polynesia (Torrea et al., 1995). Specific epidemic variants of this genotype family were described in Due south Africa (Streicher et al., 2004). The T families are strains that miss spacers 33–36 and tin can hardly be classified in other groups.

Read total chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128038086000013

Overview of Leaner

Audrey Wanger , ... Amitava Dasgupta , in Microbiology and Molecular Diagnosis in Pathology, 2017

Mycobacterium tuberculosis

Mycobacterium tuberculosis complex comprises Thousand. tuberculosis, One thousand. bovis, M. bovis BCG, Mycobacterium africanum, amidst others. The organisms dissever every 12–24 hours, requiring weeks before growth is detected and are niacin and nitrate positive. Pulmonary infection is a deadening progression of chronic inflammation and caseation with the subsequent formation of cavities. When the foci rupture, there are a large number of organisms that spread to the lungs and are aerosolized. Transmission occurs via these aerosolized droplets from coughing of infected person.

Decontamination of the specimen is required to release mycobacteria trapped in cells and concentration of specimen is recommended to recover mycobacteria, also as to remove other normal flora. Straight detection of M. tuberculosis complex in respiratory specimens and identification of the presence of the rpoB factor that determines rifampicin resistance tin be made using molecular techniques. Two different interferon-gamma release assays are whole blood tests that measure a person's immune reactivity to One thousand. tuberculosis. Both T-Spot and QuantiFERON tin aid in diagnosis M. tuberculosis simply practise not differentiate latent infection from tuberculosis disease.

An important virulence factor is that of the cord factor, a glycolipid called trehalose 6,6'-dimycolate or TDM, is present in the outer envelope of all mycobacteria and protects the bacteria from the host response [34].

Organisms in the Thou. tuberculosis complex are buff colored on solid media, take a cording advent when grown in broth and cannot be differentiated from each other past DNA probe or PCR. However, Thou. tuberculosis is positive for both niacin and nitrite and M. bovis is negative. MTB is too NAP test positive, pyrazinaimidase positive, and grows on media with TCH, while M. bovis is negative for NAP and pyrazinimidase (resistant to PZA) and will non grow on media with TCH. Treatment for M. tuberculosis includes an extended regimen with pyrazinamide, isoniazid, ethambutol, and rifampicin (if not resistant).

Read full chapter

URL:

https://www.sciencedirect.com/scientific discipline/commodity/pii/B9780128053515000065

Bacterial Infections

In Diagnostic Pathology: Infectious Diseases, 2015

Infectious Agents

•

Mycobacterium tuberculosis complex comprises several species with > 99.ix% identity

○

Members pertinent for human being illness include Thou. tuberculosis, M. africanum, M. canetti, Thou. bovis, M. caprae, and Thousand. pinnipedii

•

Transmission is mainly by inhalation of contaminated droplets, though One thousand. bovis infection tin can exist transmitted from cattle via undercooked meat or unpasteurized milk

•

MTB are intracellular pathogens that subvert phagosomal cell in order to persist and evade allowed system

•

Immunomodulatory components include cell wall, which contains a unique complement of glycolipid moieties

○

Includes lipomannan, lipoarabinomannan and mycolic acids, responsible for acid-fastness of organism

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780323376778500607

Human Pathogenic Mycobacteria

C. Gutierrez , A. Somoskovi , in Reference Module in Biomedical Sciences, 2014

Global Expansion and Diversity of Chiliad. tuberculosis

After the evolutionary bottleneck, human MTBC strains have been coevolving with their host for more than than l 000 years to split into half dozen principal phylogenetic lineages (Figure 13). While their genome is highly conserved, some polymorphic regions however be, e.g., SNPs, indels, MLVA (MIRU), and CRISPRs that concordantly place these lineages. The 6 branches of human MTBC and their current geographic distribution reflect the history of Out-of-Africa migrations of modernistic humans and their successive colonization of the world, every bit it has been inferred for biogeographic patterns in Helicobacter pylori and Streptococcus mutans, which are thought to have accompanied humans when they migrated from Africa fifty 000 years ago.

Effigy 13. The global phylogeny of Mycobacterium tuberculosis complex (MTBC). Colors indicate congruent lineages.

 Adapted from Hershberg, R., Lipatov, G., Small, P.Thousand., et al., 2008. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and homo demography. PLoS Biol. 6 (12), e311.

Lineages i to 4 of human MTBC stand for to Thou. tuberculosis sensu stricto, which left Africa and spread into Eurasia, and lineages five and 6 to M. africanum, which remained in Africa. The more than 'ancient' evolutionary branches are M. africanum and lineage 1 ('East-African Indian,' expanded through the Indian Ocean countries and Philippines). Lineage 2 ('Beijing,' in East Asia mainly in China), lineage 3 ('CAS,' in Central Asia), and lineage 4 (in Europe and the Americas), which diverged at a afterwards time indicate from a mutual ancestor and are chosen 'mod' lineages, are more successful in terms of their geographical spread compared with the 'ancient' lineages. Strong and recent demographic expansion in almost all M. tuberculosis lineages coincides with the human population explosion of the last two centuries.

Different lineages of homo MTBC strains have dissimilar clinical and epidemiological consequences. For example, lineages ane and iii are associated with the power to produce exclusively extrapulmonary tuberculosis disease and lineage 2 is associated to faster development of drug resistance, whereas progress of 1000. africanum infection to agile affliction is lower than for 'modern' lineages. Studies on brute models concluded that lineages may also differ with respect to other characteristics of the biology of the diseases, such equally the pathogenicity, infectiousness, or interaction with the innate and adaptive immune systems. Inside each lineage, specific strains may also influence the grade of affliction following infection (Achtman, 2008; Portevin et al., 2011; Wirth et al., 2008).

Read total chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128012383001379

Renal Tuberculosis, Xanthogranulomatous Pyelonephritis, Renal Malakoplakia

In Diagnostic Pathology: Genitourinary (Second Edition), 2016

ETIOLOGY/PATHOGENESIS

Infectious Agents

•

RTB caused by members of Mycobacterium tuberculosis complex, mostly Mycobacterium tuberculosis, but rarely M. bovine, and occasionally by Bacille Calmette-Guérin (BCG) as complication of intravesical treatment of bladder cancer

○

Very rare cases by K. avium-intracellulare in AIDS and other immunosuppressed individuals

○

Unlike other bacterial urinary infections, TB is descending infection resulting from hematogenous spread of bacilli in corticomedullary junction: Areas of high blood perfusion and claret oxygen saturation

–

Granulomas latent for many years, with mycobacteria reactivated after immune suppression, spilling into nephrons, getting trapped in narrow loops of Henle and causing caseating papillary lesions

□

Bacilli shed into urine, spreading TB to downstream urothelium and adjacent genital organs

•

XGP and RMP: Near ofttimes, associated with gram-negative leaner

○

Escherichia coli found in nigh cases, with other gram-negative bacilli as less common pathogens

○

XGP: Consistently associated with obstruction, calculi, and recurrent urinary tract infections

○

RMP: Believed to be due to defective macrophage lysosomal digestion of phagocytosed bacteria (particularly coliforms)

–

Decreased levels of intracellular cyclic guanosine monophosphate (cGMP) might be crusade of defective phagocytosis in RMP

□

Inadequate elimination leads to accumulation of partially digested bacteria or bacterial glycolipids

□

Deposition of calcium and atomic number 26 occurs on residual bacterial glycolipid in monocytes or macrophages, forming Michaelis-Gutmann bodies

•

Patients with XGP commonly with underlying systemic illness, east.chiliad., SLE, diabetes mellitus, myotonic dystrophy, or chronic active hepatitis

Read full chapter

URL:

https://www.sciencedirect.com/science/commodity/pii/B978032337714050016X