Infectious disease pathology Lecture 2 Mays Ibrahim Arab

Infectious disease pathology Lecture 2 Mays Ibrahim, Arab board of pathology, CABP University of Al-Mustansiriyah, college of medicine

Main points in this lecture 1. 2. Tuberculosis i. Primary TB ii. Progressive primary TB iii. Secondary TB Leprosy i. ii. Tuberculoid leprosy Lepromatous leprosy

Tuberculosis: Tuberculosis is a communicable chronic granulomatous disease, in which the lungs are the prime target, although any organ may be infected. � � Etiology: 1. Mycobacterium tuberculosis hominis which is acquired by Inhalation of aerosols from expectoration of infected individuals and give rise to pulmonary disease. 2. Mycobacterium tuberculosis bovis which is acquired by the ingestion of infected milk and give rise to Oropharyngeal and intestinal tuberculosis. � Mycobacterium are aerobic rods, have a unique waxy cell wall composed of mycolic acid, which makes them acid fast.

Epidemiology � 1. 7 billion persons infected worldwide � 5%-10% progress to (active disease) Other 90% are latent (neither develop symptoms nor transmit the disease). �

Risk groups for Tuberculosis are: 1. Poverty. 2. Patient with HIV infection. 3. Old age with low immunity. 4. Chronic diseases: diabetes mellitus, chronic renal failure, chronic lung disease. 5. Malnutrition, alcoholism.

Pathogenesis: � � � Inhalation ingestion by alveolar macrophages replicate within the phagosome, and cause blocking of fusion of the phagosome and lysosome. Thus, earliest stage of primary tuberculosis (<3 weeks) in the nonsensitized individual, bacteria proliferate in the pulmonary alveolar macrophages and airspaces, resulting in bacteremia and seeding of multiple sites. Despite the bacteremia, most people at this stage are asymptomatic or have a mild flu-like illness. After 3 weeks of infection, a T-helper 1 response and secrete IFN -γ, activates macrophages to become epithelioid histiocytes that characterize the granulomatous response, and may fuse together to form LANGHANS giant cells.

Activated macrophage (epithelioid histiocytes) release many mediators. These include: ◦ Tumor necrosis factor TNF that help differentiate the other macrophages into EPITHELOID cells. ◦ Nitric oxide &free radicals that have bactericidal activity.

Ranke complex

Primary tuberculosis � is the form of disease that characterized by: Develops in a previously unexposed. About 5% of newly infected people develop clinically significant disease( primary progressive disease). While the other 95% will go into latent phase. Source of the organism is exogenous. In most people, the primary infection is controlled, but in others, primary tuberculosis is progressive.

Typically, the inhaled bacilli implant in the mid to lower zone of the lung, usually close to the pleura causing sign of infection in the area Ghon focus: is granulomatous lung lesion, located in the mid to lower zone of the sub pleural area 3 weeks after the first exposure to T. B. bacilli. Ghon complex: Is the involvement of the lung (subpleural area) by T. B granuloma (Gohn focus) +involvement of the HILAR lymph nodes. Ranke complex: is a radiologically detectable sign caused by progressive fibrosis and calcification of Ghon complex

Microscopical: caseating or noncaseating granuloma, enclosed within a fibroblastic rim punctuated by lymphocytes. Langhans giant cells also present in the granulomas. � Primary tuberculosis may progress directly to progressive primary tuberculosis in (AIDS, elderly or children with nonspecific impairment of host defense)

Caseating T. B. granuloma Non caseating T. B. granuloma

progressive primary tuberculosis � Occur AIDS. in people with severe immunosuppression, � resembles an acute bacterial pneumonia, with lower and middle lobe consolidation � Hilar lymphadenopathy, and pleural effusion � Cavitation is rare. � Lymphohematogenous dissemination may result in the development of tuberculous meningitis and miliary tuberculosis

Secondary tuberculosis � Occur in a previously sensitized host. � Most commonly it arises many years after the initial infection. � Reactivation of a latent infection or exogenous reinfection. Secondary TB is commonly caused by reactivation � Only 5% of the primary TB subsequently develop secondary TB. � � Prefer the apex of the upper lobes of one or both lungs. Cavitation. Erosion of the cavities into an airway is an important source of infection because the person now coughs sputum that contains bacteria. � Histologically: Granuloma with central caseation � �

Secondary pulmonary tuberculosis. The upper parts of both lungs are riddled with gray-white areas of caseation and multiple areas of softening and cavitation

Clinical manifestation � Usually insidious in onset. � low grade fever, anorexia and weight loss. � � Remittent low grade fever (appearing late each afternoon and then subsiding), and profuse night sweats occur. Later in disease , cough with sputum. Hemoptysis is present in about half cases. Pleuritic pain. Extrapulmonary manifestations depend on the organ involved.

Diagnosis of TB � Clinically: History, physical and radiographic findings of consolidation or cavitation in the apices of the lungs � Laboratory: 1. Sputum Acid-fast smears as a rapid test 2. Cultures and sensitivity of the sputum 3. PCR 4. Tuberculin skin test( mantoux skin test)

Tuberculin (Mantoux) skin test. Intracutaneous injection of purified protein derivative (PPD) of M. tuberculosis, induces a visible and palpable induration at least 5 mm in diameter that peaks in 48 to 72 hours. � A positive test signifies T cell–mediated immunity to mycobacterial antigens. �

False-positive 1. 2. Prior vaccination with BCG (Bacillus Calmette-Guerin) Infection by atypical mycobacteria False-negative 1. 2. 3. 4. 5. HIV with low CD 4 count Sarcoidosis Malnutrition Hodgkin lymphoma, Immunosuppression Note: due to these variability’s, IGRA( interferon gamma release assay) has a fewer false positive results from BCG vaccination than tuberculin skin test. �

Tuberculosis in HIV positive patients � is characterized by: � 1. No caseating granuloma � 2. Negative sputum smear for AFB � 3. More extrapulmonary involvement � 4. False negative PPD test

Natural history of the disease (Fate) of T. B: � 90% of cases will end up with HEALING of the primary complex (i. e lung and L. N) by fibrosis +calcification which is quite small. � 10% show progressive course , due to the highly virulent m. o or low immunity and this will lead to T. B complications.

Complications of T. B 1. Pleural effusion: in which the subpleural lesion get larger and the bacilli will get access to the pleural cavity. 2. T. B pneumonia: in which the pulmonary lesion enlarges and doesn’t heal. 3. T. B bronchopneumonia: in which there is erosion of the bronchilal wall by the hilar L. N so the bacilli can enter the bronchus. 4. Collapse of the lung: when the hilar L. Ns enlarges and obstructs the bronchus. 5. Systemic miliary tuberculosis occurs when bacteria disseminate through lymphatics (miliary pulmonary T. B) or the arterial system. Miliary tuberculosis is most prominent in the liver, bone marrow, spleen but could involve any organ. � Note: Miliary T. B is called so because the lesions are small tiny yellow white spots similar to millet seeds fed to birds.

Miliary T. B. of the spleen

Ghon complex Primary tb Secondary TB in the upper lobe Miliary TB all over lung

Leprosy(Hansen's disease) � � � is a slowly progressive infection caused by Mycobacterium leprae; an acid fast bacilli that likes cool temperatures. It infects skin and superficial nerves (in a gloves and stocking pattern), leading to loss of sensation with resultant deformities. Inhaled M. leprae are phagocytized by pulmonary macrophages and disseminated hematogenously; however, they replicate only in cooler tissues of the periphery. � Transmitted from person to person through aerosols � The incubation period is usually 3 - 5 years

� The T-helper lymphocyte response to M. leprae determines whether an individual has tuberculoid or lepromatous leprosy � Leprosy has two patterns of disease 1. Tuberculoid leprosy 2. Lepromatous leprosy

Tuberculoid leprosy � � Less severe form with The infection is limited to the skin and peripheral nerve. � Is associated with high cell mediated immunity (TH 1 response) � bacilli are almost never found, hence the name “paucibacillary” leprosy � � � Clinically, there are insidious, dry, scaly skin lesions lacking sensation, hypopigmentation , with asymmetric peripheral nerve involvement. Local anesthesia with skin and muscle atrophy increases the risk of trauma with chronic ulcers and autoamputation of digits. Histopathology: Extensive granulomatous inflammation surrounding the nerves with few bacilli.

Lepromatous leprosy � � � is associated with a low cell mediated immunity. It is widely disseminated infection affecting many systems in the body abundant bacteria will be found inside macrophages hence the name “multibacillary” leprosy with masses (“globi”) of acid-fast bacilli Clinically: there are disfiguring cutaneous thickening and nodules all over the skin giving rise to leonine “lion like “facies, . The testes are usually extensively involved, leading to sterility. Histopathology: Large collections of lipid-laden macrophages over-stuffed with bacilli (lepra cells).

Diagnosis � Skin biopsy: showing one of the following �Tuberculoid leprosy : Extensive granulomatous inflammation with few bacilli. �lepromatous leprosy: Large collections of lipid-laden macrophages over-stuffed with bacilli. � � Acid fast staining or the fite stain: The presence of acid-fast bacilli confirms the diagnosis of Hansen’s disease. PCR

TUBERCULOID LEPROSY LEPROMATOUS LEPROSY more severe with multisystemic affection. less severe form with localized lesions to skin and nerve have dry, scaly skin lesions skin thickening and nodules asymmetric involvement symmetric high cell mediated immunity low cell mediated immunity bacilli are almost never found abundant bacteria Extensive granulomatous inflammation Large collections of lipid-laden macrophages over-stuffed with bacilli