Consequences of Listeria monocytogenes Infection Enters into Circulation Systemic Infection and Meningitis Stillbirth; Birth defects in InfantGroup of Mycobacteria Distinctive Features M. tuberculosis Complex Closely related in terms of nucleotide sequences M. tuberculosis Highest morbidity and mortality rates worldwide M. africanum Higher rates of disease than Mtb in Africa M. canettii Rare M. bovis Has broad host range—infects several mammals including humans and cattle; attenuated strain used as vaccine M. marinum Close relative of the Mtb Complex; Natural hosts are fish, frogs, Drosophilia, Slime Molds; an emerging model for studying human TB Fast doubling time (~4hr) M. ulcerans Causes Buruli ulcers M. leprae Causes leprosy M. avium complex (MAC) Widespread in nature; immunocomprimised individuals susceptible; highly drug resistant; M. avium subsp. paratuberculosis implicated in Crohn’s diseaseSalyers, and Whitt, Bacterial Pathogenesis, 2nd ed., 2002, p.299Roles and Consequences of Mycobacterial walls 1) Protects bacteria from phagolysomal components 2) Has inhibited research 3) Contributes to resistance to chemicals 4) Contributes to slow growth 5) Resistance to drying 6) Higly stimulatory to the immune systemDiagnosis 1. Skin Test--can identify most people infected with tubercle bacilli six to eight weeks after initial exposure. 2. X-ray--may show evidence of TB infection, usually in the form of cavities or lesions in the lungs. 3. Culture--a positive bacteriologic culture of M. tuberculosis is essential to confirm the diagnosis and determine which drugs will work against the strain of TB the patient carries. 4. PCR—now used. Shortens time of diagnosis from weeks to about two daysSymptoms Weight Loss Fever Night Sweats Loss of AppetiteDrug Mechanism Isoniazid Ethambutol Rifampin PyrazinamidePeople at High Risk for TB • Close contacts of people with newly diagnosed infectious TB • People whose skin test results have recently converted from negative to positive; • People with positive skin test reactions who also have special medical conditions known to increase the risk of TB • HIV-positive people or those suspected to be HIV-infected • People with positive skin test reactions who also have special medical conditions • Injection drug users who have positive skin test reactions. • Foreign-born people from countries where TB is common • People in medically underserved, low-income groups, especially African Americans, Hispanics, and Native Americans • Residents of long-term care facilities such as prisons, nursing homes, and mental institutionsReasons for Resurgence of TB • Dismantled programs • Curtailed research • Resistant Strains • The HIV/AIDS epidemic • Increased numbers of immigrants from countries with many cases of TB • Increased poverty, injection drug use, and homelessness • Poor compliance with treatment regimens, especially among disadvantaged groups • Increased numbers of residents in long-term care facilities such as nursing homesHIV AND TB q TB the leading cause of death in HIV-infected individuals. q A few years ago in the United States, an estimated 100,000 HIV-infected people also carried M. tuberculosis, according to CDC. q TB frequently occurs early in the course of HIV infection, often months to years before other opportunistic infections such as Pneumocystis carinii pneumonia. q TB may be the first indication that a person is HIV-infected, and often occurs in areas outside the lungs, particularly in the later stages of HIV disease. q In the United States, people coinfected with TB and HIV develop active TB at a rate of about 8 percent each year. By comparison, otherwise healthy individuals infected with M. tuberculosis have a 10 percent lifetime risk of developing active TB. People with HIV also are at greater risk of having a new infection progress directly to active disease.The BCG Vaccine Pros q Cheap (ten cents per dose) q Safe for Infants q Billions of Doses Given q Prevents Spread of TB in Infants (particulary TB meningitis) q Cross protection from Leprosy Cons q Does not Prevent Initial Infection or Reactivation q Effectiveness Widely variable in Adults (some cases, 70-80% effective to 0% effective q Induced Infection in Some Aids Patients q Limits Use of Skin Test because individuals become skin test positiveConsequences of Reductive Evolution in M. leprae Defects in: § Siderophore production § Part of the oxidative respiratory chain § Most of the microaerophilic and anaerobic respiratory chain § Numerous catabolic systems and their regulatory circuitsPerry, Jerome J., and James T. Staley, Microbiology: Dynamics and Diversity, Saunders College Publishing, Harcourt Brace College Publishers, New York, 1997, ISBN