MYCOBACTERIA Dr.Qurat-Ul-Ain Senior Demonstrator Microbiology, KEMU, Lahore

Mycobacterial Clinical Syndromes

History TB has been known as Pthisis, King’s Evil, Pott’s disease, consumption, the White Plague. Egyptian mummies from 3500 BCE have the presence of Mycobacterium tuberculosis

Factors Contributing to the Increase in TB Cases HIV epidemic Increased immigration from high-prevalence countries Transmission of TB in congregate settings (e.g., correctional facilities, long term care) Deterioration of the public health care infrastructure 26

Persons at Risk for Developing TB Disease Persons at high risk for developing TB disease fall into 2 categories Those who have been recently infected Those with clinical conditions that increase their risk of progressing from LTBI to TB disease 27

Recent Infection as a Risk Factor Persons more likely to have been recently infected include Close contacts to persons with infectious TB Skin test converters (within past 2 years) Recent immigrants from TB-endemic areas (within 5 years of arrival to the U.S.) Children ≤ 5 years with a positive TST Residents and employees of high-risk congregate settings (e.g. correctional facilities, homeless shelters, healthcare facilities) 28

Increased Risk for Progression to TB Disease Persons more likely to progress from LTBI to TB disease include HIV infected persons Those with history of prior, untreated TB Underweight or malnourished persons Injection drug use Those receiving TNF-α antagonists for treatment of rheumatoid arthritis or Crohn’s disease Certain medical conditions 29

Virulence Mechanisms of TB 1. TB mechanism for cell entry The tubercle bacillus can bind directly to mannose receptors on macrophages via the cell wall- associated mannosylated glycolipid 2. TB can grow intracellularly Effective means of evading the immune system Once TB is phagocytosed, it can inhibit phagosome- lysosome fusion TB can remain in the phagosome or escape from the phagosome ( Either case is a protected environment for growth in macrophages)

Virulence mechanisms of TB 3. Slow generation time Immune system cannot recognize TB, or cannot be triggered to eliminate TB 4. High lipid concentration in cell wall accounts for impermeability and resistance to antimicrobial agents Accounts for resistance to killing by acidic and alkaline compounds in both the inracellular and extracelluar environment Also accounts for resistance to osmotic lysis via complement depostion and attack by lysozyme

Progression of TB

Laboratory Diagnosis of Mycobacterial Disease Nucleic acid probes Nucleic acid sequencing

PPD Tuberculosis Skin Test Criteria PPD = Purified Protein Derivative from M. tuberculosis

“The co-epidemic” HIV & TB HIV is the most powerful factor known to increase the risk of TB HIV promotes both the progression of latent TB infection to active disease and relapse of the disease in previously treated patients. TB is one of the leading causes of death in HIV-infected people.

TB/HIV Facts Up to 70% of TB patients are co-infected with HIV in some countries. One-third of the 40 million people living with HIV/AIDS worldwide are co-infected with TB. Without proper treatment, approximately 90% of those living with HIV die within months of contracting TB. HIV/AIDS is dramatically fuelling the TB epidemic in sub-Saharan Africa

TB/HIV Facts Individual infected with HIV has a 10 x increased risk in developing TB By 2000 nearly 11.5 million HIV-infected people worldwide were co-infected with M. tuberculosis

Patterns of HIV-related TB As HIV infection progresses CD4+ T-lymphocytes decline in number and function. CD4+ cells play an important role in the body’s defense against tubercle bacilli Immune system becomes less able to prevent growth and local spread of M. tuberculosis