Data are as reported to WHO. Estimates of TB and MDR-TB burden are produced by WHO in consultation with countries. * Ranges represent uncertainty intervals

Obligate aerobe acid-fast rods

TUBERCULOSIS OVERVIEW, CAUSE, AND PATHOGENESIS Tuberculosis, MTB, or TB (short for tubercle bacillus) common, and in many cases lethal infectious disease caused by various strains of mycobacteria usually Mycobacterium tuberculosis Mycobacterium tuberculosis, was identified and described on 24 March 1882 by Robert Koch Tuberculosis may infect any part of the body most commonly occurs in the lungs pulmonary tuberculosis

Tuberculosis holds a special place in medical history Can humble master clinicians challenge public health authorities treatable and preventable WHO (TB) data 2 million deaths occur worldwide, each year Over 8 million cases, each year In 2012, nearly 9 million people around the world became sick around 1.3 million TB-related deaths worldwide ≤ 33% of world’s population have silent latent infection

A Person with Latent TB InfectionA Person with TB Disease Has no symptoms Has symptoms that may include: a bad cough that lasts 3 weeks or longer pain in the chest coughing up blood or sputum weakness or fatigue weight loss no appetite chills fever sweating at night Does not feel sick Usually feels sick Cannot spread TB bacteria to others May spread TB bacteria to others Usually has a skin test or blood test result indicating TB infection Has a normal chest x-ray and a negative sputum smear May have an abnormal chest x-ray, or positive sputum smear or culture Needs treatment for latent TB infection to prevent TB disease Needs treatment to treat TB disease The Difference between Latent TB Infection (LTBI) and TB Disease

Tuberculosis in the United States is now largely a disease of the disadvantaged In 2006, there were 13,767 reported cases of TB in the United States cases were reported in every state drug-resistant cases co-infection with M. tuberculosis and HIV estimated 10 to 15 million persons remain latently infected A total of 9,945 TB cases were reported in the United States in 2012 Both the number of TB cases reported and the case rate decreased this represents a 5.4% and 6.1% decline, respectively, compared to 2011

Mycobacterium tuberculosis slightly curved or straight rod-shaped bacillus requires special acid-fast stains to be visualized It is closely related to M. bovis primarily pathogen of cattle and related animals M. tuberculosis is also related to M. leprae leprosy Mycobacterium tuberculosis

Tuberculosis is spread from person to person through the air by droplet nuclei 1 to 5 m in diameter that have been expulsed into the air Cough is the primary means by which tubercle bacilli are aerosolized singing, sneezing, or speaking may contribute to a lesser extent Droplet nuclei small enough to remain suspended in the air for long time The probability of transmission depends on numerous factors source case exposed contact air space shared

Usual pathogenesis of tuberculosis. About 5% of infected persons develop clinical disease within the first year of infection; another 5% develop reactivation later during their lives.

TB pathogenesis begins when a droplet containing viable tubercle bacilli is inhaled Bacilli then spread through the pulmonary lymphatics reach lymph nodes may become enlarged Efferent lymphatics then carry bacilli into the systemic circulation lungs, brain, kidneys, and bones Tubercle bacilli replicate relatively slowly dividing time within 18 to 24 hours 20 minutes for most common pathogens Thus, the process of local, lymphatic, and eventual systemic spread described above typically requires several weeks

PULMONARY TUBERCULOSIS Worldwide, tuberculosis remains the most common cause of death Pulmonary tuberculosis is the most common manifestation and the form of the disease usually responsible for its transmission The usual patient with pulmonary tuberculosis presents with a history of several weeks of a progressive illness The most important pulmonary symptom is cough Constitutional complaints coexist and may predominate fever, chills, night sweats, weight loss, appetite loss, and easy fatigability

HIV and TB HIV has greatly increasing the risk of TB Diagnosis of TB in patients with HIV can be difficult Suspicion of TB is an indication for HIV antibody testing

Laboratory diagnosis 1- Mantoux skin test (Tuberculin) 2- Chest X-ray 3- Isolation of Mycobacterium species Löwenstein–Jensen medium (L.J. medium) microscopic positive results for acid-fast bacilli 4- Identification of microbial genetic material molecular methods such as PCR

Positive skin test - tuberculosis indicates exposure to organism does not indicate active disease

The Mantoux skin test consists of an intradermal injection of one-tenth of a milliliter (ml) of PPD tuberculin.

The size of induration is measured 48–72 hours later. Erythema (redness) should not be measured.

Mantoux test injection site in a subject without chronic conditions or in a high-risk group clinically diagnosed as negative at 50 hours

Skin testing for tuberculosis, using the Mantoux test.

Chest X-ray

Microscopic Examination of Mycobacterium The Mycobacteria are aerobic acid fast, non-motile, non- spore forming rods M. tuberculosis is a non capsulated straight or slightly curved rod, measuring 1-4µm x µm The most common pathogens that cause disease to man are M. tuberculosis, M. bovis, M. africanum, and M.microti

Laboratory diagnosis M. tuberculosis acid fast bacteria – sputum TB in Sputum

M. tuberculosis is best demonstrated by using the Ziehl -Neelsen technique or a fluorescence technique. When stained by ZN, they appear as thin pink rods arranged singly or in groups. Once stained, they resist decolorization with 2% H2SO4 and alcohol or 3% HCl in 95% ethyl alcohol (Acid-fast, Alcohol fast).

Cultural Characteristics and colony morphology M. tuberculosis is strict aerobic grows very slowly (2-4 weeks) egg enriched medium Lowenstein-Jensen medium giving dry creamy colored colonies Other selective media as Middlebrook 7H10, 7H11 agar and 7H9 broth used for primary isolation antibiotic susceptibility testing

M. tuberculosis is a non chromogen does not grow on media contain p-nitrobenzoic acid these characteristics help to differentiate them from M. avium, M. intracellulare, and M. kansasii The optimum temperature for growth is at 37C The culture must be incubated up to 12 weeks M. tuberculosis produces rough, and tough colonies on glycerol and pyruvate egg media They are niacin producers and grow under aerobic conditions at 37 C

TB Culture Cultivation and culture characteristics of Tubercle bacilli on Lowenstein Jensen medium (raised dry cream colored colonies)

Tuberculosis polymerase chain amplification polymerase chain amplification rapid diagnosis rapid diagnosis

Antibotic treatment - tuberculosis extensive time periods (e.g. 9 months) extensive time periods (e.g. 9 months) organism grows slowly, or dormant organism grows slowly, or dormant two or more antibiotics two or more antibiotics e.g. rifampin and isoniazid e.g. rifampin and isoniazid resistance minimized resistance minimized

Tuberculosis and Drug resistance Multiple drug resistant (MDR) Resistant to first line drugs Extremely drug resistant (XDR) Resistant to some of the second line drugs Nearly un-treatable

Transmission - tuberculosis M. tuberculosis is carried in airborne particles, called droplet nuclei, of 1– 5 microns in diameter Depending on the environment, these tiny particles can remain suspended in the air for several hours M. tuberculosis is transmitted through the air, not by surface contact Transmission occurs when a person inhales droplet nuclei containing M. tuberculosis traverse the mouth or nasal passages, upper respiratory tract, and bronchi reach the alveoli of the lungs

Aerosol from Sneeze

Vaccination BCG vaccine – an attenuated strain of M. bovis – not effective in US, in US, – incidence is low – vaccination not practiced – immunization interferes with diagnosis

An apparatus (4-5 cm length, with nine short needles) used for BCG vaccination in Japan. Shown with ampoules of BCG and saline.

M. avium - M. intracellulare complex (M. avium) non-AIDS – infection almost never AIDS AIDS – major bacterial opportunist multiple drug-resistance multiple drug-resistance

spread from cattle infected cattle are culled infected cattle are culled – positive skin test rarely seen in US rarely seen in US M. bovis

M. leprae leprosy leprosy major disease of third world major disease of third world rare in US rare in US

A 24-year-old man from Norway, infected with leprosy, 1886.

Deformities from leprosy in India