Infection with Mycobacteria

• Mycobacteria include more than 70 species, with Tuberculosis being part of the M. tuberculosis complex, which consists of seven closely-related species, including human pathogens like M. tuberculosis and M. bovis
• Non-tuberculous mycobacteria (NTM), also known as "atypical mycobacteria" or mycobacteria other than tuberculosis (MOTT), include species like M. kansasii, M. xenopi, and M. avium-intracellulare complex (MAC)
• Characteristics of the Genus Mycobacteria:

  • Aerobic, non-spore forming, non-motile rods
  • Cell wall has high lipid content
  • Difficult to stain with commonly used dyes in the laboratory
  • Resistant to common antibacterial agents
  • Do not grow on conventional agar plates such as blood; need special media
  • Specimens containing other bacteria (e.g. sputum) require decontamination before culture to prevent overgrowth
• Virulence of M. tuberculosis:

  • Evades innate and adaptive immune responses
  • Replicates in alveolar macrophages, preventing phagosome-lysosome fusion
  • Masks antigenic areas with lipids to avoid recognition by the host innate immune system
• Primary Tuberculosis:

  • Primary TB infection is halted by surrounding granulomas formed by CD 4+ T-lymphocytes
  • In some cases, granulomas become necrotic and cavitate, enabling transmission but increasing the likelihood of host mortality (Post-primary TB)
• Epidemiology:

  • In 2019, an estimated 1.7 million people worldwide were infected by TB
  • 98% of TB deaths occur in low-to middle-income countries
  • Multi-drug resistant (MDR) TB infection is an increasing problem, with poverty, overcrowding, malnutrition/famine as major contributory factors
• Transmission of TB:

  • TB is transmitted through respiratory droplets expelled when an infectious individual coughs, sneezes, or speaks
  • Close contacts are at the highest risk of becoming infected
• Diagnosis of TB:

  • Clinical suspicion based on specific symptoms like haemoptysis, systemic symptoms, and no response to antibiotics
  • Skin tests like Mantoux or Heaf, and Interferon-gamma release assay (IGRA) blood tests are used for diagnosis
• Interferon-gamma release assay (IGRA) is a whole blood assay that detects the release of interferon gamma by sensitized cells incubated with M. tuberculosis peptides or proteins
• IGRA is not affected by the BCG vaccine and does not distinguish primary from latent/secondary TB
• Microbiological diagnosis of TB includes:

  • Specimens for pulmonary TB: sputum samples/BAL
  • Specimens for extrapulmonary TB: site-specific specimens like early morning urine (EMU), CSF, pus, tissue
  • Microscopy using ZN stain or auramine for presumptive diagnosis
• PCR NAAT provides a quick provisional diagnosis and rifampicin resistance identification, especially when microscopy is negative
• Culture methods for TB diagnosis include automated liquid culture or Lowenstein-Jensen slopes
• Radiology methods like CXR, CT, or MRI are used for suggestive diagnosis, while histology shows caseating granulomata seen with ZN stain positive on tissue
• Factors to consider when determining how infectious a TB patient may be:

  • Combination therapy with usually 4 agents for months, not days, of antibiotics
  • Most agents used are not conventional antibiotics, with drugs that penetrate intracellularly as TB likes to live in macrophages
• First-line drugs for TB treatment:

  • R: rifampicin
  • I: isoniazid
  • P: pyrazinamide
  • E: ethambutol
  • Potential toxicities associated with each drug
• Regimen for TB treatment is governed by susceptibility results, lasting at least 6 months depending on the site of infection and susceptibility
• Drug-resistant TB can be primary or secondary, with risk factors including previous exposure to TB drugs, contact with drug-resistant TB, and inadequate treatment regimen
• Multi-Drug Resistant TB (MDR-TB) is resistant to isoniazid and rifampicin plus other drugs, with outbreaks reported abroad and challenges like non-compliance and delays in testing
• Prevention of TB includes social improvements, patient isolation, contact tracing, and BCG vaccination, which is controversial and contraindicated in immunosuppressed patients
• Non-tuberculous mycobacteria are less pathogenic, found in the environment, and increasing in prevalence due to various factors like AIDS and cystic fibrosis
• Mycobacterium avium-intracellulare complex (MAC) infection typically affects elderly white women who suppress the normal cough reflex, leading to chronic infections
• Leprosy, caused by Mycobacterium leprae, historically associated with disfigurement, is diagnosed through tissue smears for acid-fast bacilli and histopathology
• Leprosy treatment involves Dapsone, rifampicin, and clofazimine for 6-12 months, with surgery for deformities and prevention focusing on early detection and treatment
• Mycobacterial diseases are globally significant, with variable clinical presentations, challenges in drug-resistant TB, and an increasing presence of other mycobacteria in specific patient populations