Mycobacteria & Fungal Mycobacteria & Fungal Respiratory Tract Respiratory Tract PathogensPathogens

Prof. Dr. Asem ShehabiProf. Dr. Asem Shehabi

Faculty of MedicineFaculty of Medicine

University of JordanUniversity of Jordan

Global Prevalence of Tuberculosis

The World Health Organization (WHO) estimates that approximately one-third of the global population is infected with M. tuberculosis (TB).

Around 10 million new cases of TB are being reported each year, 2-3 million deaths occur each year worldwide.. 95% in developing countries in developing countries

After emerging (HIV)/AIDS, TB is the second most common cause of death in AIDS patients due to an infectious disease.

Mycobacterium TuberculosisMycobacterium Tuberculosis

Tubercle Bacilli.. Acid-Fast Bacilli.. Widely Tubercle Bacilli.. Acid-Fast Bacilli.. Widely distributed in Human, Animals, Birds, distributed in Human, Animals, Birds, Environment.. TB bacilli grow slowly, Resistant to Environment.. TB bacilli grow slowly, Resistant to Dryness, low Acidity.. survive years in nature.. But Dryness, low Acidity.. survive years in nature.. But Susceptible to UV-light, Heat.Susceptible to UV-light, Heat.

M. tuberculosisM. tuberculosis.. Causes 95% of human TB .. Causes 95% of human TB cases.. mostly pulmonary .. Respiratory cases.. mostly pulmonary .. Respiratory infection ..Few cells.. Lung positive person may infection ..Few cells.. Lung positive person may infect hundred of susceptible person.. All ages.. infect hundred of susceptible person.. All ages.. mostly children.. with malnutrition .mostly children.. with malnutrition .

Optimal conditions for transmission include: Optimal conditions for transmission include: overcrowding, Large cities, poor conditions & Low overcrowding, Large cities, poor conditions & Low standard public hygiene.. standard public hygiene..

Acid Fast Bacilli Stained Acid Fast Bacilli Stained

by Ziehl-Neelsen (AF Stain)by Ziehl-Neelsen (AF Stain)

Infection With Mycobacteria Infection With Mycobacteria mostly through RT air mostly through RT air dropletsdroplets

Pulmonary InfectionPulmonary Infection

Primary TuberculosisPrimary Tuberculosis: 90% Pulmonary : 90% Pulmonary TB , Children, Asymptomatic, TB Bacilli TB , Children, Asymptomatic, TB Bacilli infect Alveolar macrophages.. Develop infect Alveolar macrophages.. Develop small lung lesions..Fibrosis, Calcification, small lung lesions..Fibrosis, Calcification, Hypersensitivity.. Infected person Hypersensitivity.. Infected person becomes becomes Positive for Tuberculin Skin Positive for Tuberculin Skin test. test.

Few cases Primary TB infection may Few cases Primary TB infection may spread from Lesion by direct extension to spread from Lesion by direct extension to lymphatic system, bronchi, blood, Kidneys lymphatic system, bronchi, blood, Kidneys Gastrointestinal, Meningitis (children).. Gastrointestinal, Meningitis (children).. rarely developing rarely developing Military tuberculosis. Military tuberculosis.

Post-Pulmonary Infection-2Post-Pulmonary Infection-2 Post primary tuberculosis:Post primary tuberculosis: Reactivation old Reactivation old

lesions/infection .. Common in young adults & lesions/infection .. Common in young adults & elderly persons.. Developing Large Lung elderly persons.. Developing Large Lung lesions.. Cavities , Less lymphatic involvement , lesions.. Cavities , Less lymphatic involvement , intensive intensive Granuloma & CaseationGranuloma & Caseation.. May spread .. May spread rapidly to other body part, CNS, rapidly to other body part, CNS, Gastrointestinal/Urinary Tract . Gastrointestinal/Urinary Tract .

Clinical Features Pulmonary TB:Clinical Features Pulmonary TB: Productive Productive Cough..bloody sputum, Low continuous Fever, Cough..bloody sputum, Low continuous Fever, Night- sweating , Loss weight & Appetite.. Night- sweating , Loss weight & Appetite.. General weakness, Breath shortness, Lesions/ General weakness, Breath shortness, Lesions/ Cavities can be detected easily by Cavities can be detected easily by Chest x-ray, Chest x-ray, Sputum culture , Tuberculin test positiveSputum culture , Tuberculin test positive

Tuberculin TestTuberculin Test

Symptomatic/ asymptomaticSymptomatic/ asymptomatic infected persons..infected persons.. develop positivedevelop positive Tuberculin skin test.. Reaction to Tuberculin skin test.. Reaction to TB glycerol extract ( TB glycerol extract ( Mycolic acids + lipoproteins )Mycolic acids + lipoproteins )

MantouxMantoux -Tuberculin skin test-Tuberculin skin test.. Specific TB .. Specific TB antigens produced from boiling culture of antigens produced from boiling culture of M. M. tuberculosistuberculosis. .

The test consists an intradermal injection of The test consists an intradermal injection of 5 5 tuberculin units (0.1 ml) tuberculin units (0.1 ml) of PPD in the forearm.. of PPD in the forearm.. The test is read after 48-72 hours. The test is read after 48-72 hours.

Positive tuberculinPositive tuberculin: : Indurations, Edema & Indurations, Edema & Erythematic skin > 1 cm, Interpretation Erythematic skin > 1 cm, Interpretation

Vaccination with Vaccination with BCGBCG ..Protection 30-78%..result ..Protection 30-78%..result in positive Tuberculin test.in positive Tuberculin test.

Tuberculin (PPD) Skin Tuberculin (PPD) Skin TestTest

Other Human Pathogenic Other Human Pathogenic Mycobacteria speciesMycobacteria species

M. bovisM. bovis:: common in domestic animal.. rare human.. common in domestic animal.. rare human.. Infection.. source: milk, dairy products, meat.. begins Infection.. source: milk, dairy products, meat.. begins mostly intestinal infection.. may spread to other parts.. mostly intestinal infection.. may spread to other parts.. Slow grower Slow grower

Atypical mycobacteriaAtypical mycobacteria: Widely distributed in nature.. : Widely distributed in nature.. water, soil, birds, animals , mostly slow grower (1-3 water, soil, birds, animals , mostly slow grower (1-3 weeks)weeks)

M. kansasiiM. kansasii: Soil, : Soil, Photochromogenic, Photochromogenic, Produce Produce yellow/orange color during incubation in light.. Mostly yellow/orange color during incubation in light.. Mostly Lung tuberculosis.. immuno-suppressed persons, AIDS. Lung tuberculosis.. immuno-suppressed persons, AIDS.

M. marinum :M. marinum : Water ,Fish , localized Skin, ulcers-soft Water ,Fish , localized Skin, ulcers-soft tissues, Swimming pool, tissues, Swimming pool, aquarium granulomaaquarium granuloma.. Lymph .. Lymph nodes. nodes.

M. avium complex M. avium complex : Animals, water,: Animals, water,,,Skin Lesions, Skin Lesions, rarely Pulmonary disease.. rarely Pulmonary disease..

M.ulcernasM.ulcernas: : Soil in Tropical countriesSoil in Tropical countries, , Skin lesions, Skin lesions, necrosis, More Resistant to anti-tuberculosis drugs.. necrosis, More Resistant to anti-tuberculosis drugs..

Diagnosis & Treatment-1Diagnosis & Treatment-1

Rapidly growing Mycobacteria speciesRapidly growing Mycobacteria species:: Rarely cause skin ulceration, mostly non-Rarely cause skin ulceration, mostly non-pathogens.. pathogens.. M. smegmatisM. smegmatis .. Found in on .. Found in on extragenital tract.. May contaminate urine extragenital tract.. May contaminate urine culture.culture.

Diagnosis & treatment: Diagnosis & treatment: Tuberculosis is confirmed Tuberculosis is confirmed by positive Direct AF Smear/ Culture, by positive Direct AF Smear/ Culture, PCRPCR X-ray, X-ray, Positive tuberculin Test.Positive tuberculin Test.

Clinical specimens: Clinical specimens: Sputum, Urine, CSF, Sputum, Urine, CSF, Tissues, Culture Loewenstein-Jensen Agar.. Tissues, Culture Loewenstein-Jensen Agar.. 4-8 4-8 WeeksWeeks.. No Blood Serological test... No Blood Serological test.

Treatment Multiple Antibiotics: Treatment Multiple Antibiotics: 6-24 Months.. 6-24 Months.. Rifampicin, Isonaized, PyrazinamidRifampicin, Isonaized, Pyrazinamid, Ethambutol, , Ethambutol, development of Multidrug resistant MB tuberculosis.. At development of Multidrug resistant MB tuberculosis.. At present 1-5% worldwide..present 1-5% worldwide.. Completing treatment is Completing treatment is essential for cureessential for cure

NocardiosisNocardiosis Nocardia asteroidsNocardia asteroids/ / N. barsiliensisN. barsiliensis. Aerobic . Aerobic

G+ve Pleomorphic Bacilli & Branched short G+ve Pleomorphic Bacilli & Branched short Filaments.. Slightly Acid Fast.. Common as Filaments.. Slightly Acid Fast.. Common as Environmental Saprophytes. Environmental Saprophytes.

Human Exogenous Infection.. Mostly Human Exogenous Infection.. Mostly Pulmonary Pulmonary localized abscesseslocalized abscesses.. Necrosis.. small Cavities.. .. Necrosis.. small Cavities.. spread to Brain, Kidneys.. Common in spread to Brain, Kidneys.. Common in Immunosuppressed & Lung malignancyImmunosuppressed & Lung malignancy

Chronic suppurationChronic suppuration.. Abscess.. Granulomas, .. Abscess.. Granulomas, Draining sinuses containing granules.. Muscles, Draining sinuses containing granules.. Muscles, Bones, Feet, Hands and other body parts.Bones, Feet, Hands and other body parts.

Diagnosis & TreatmentDiagnosis & Treatment: Sputum/biopsies : Sputum/biopsies culture on blood 1-4 weeks at room culture on blood 1-4 weeks at room temperature , Co-trimoxazole, Rifampicin, temperature , Co-trimoxazole, Rifampicin, Amikacin.. 4-6 Weeks.Amikacin.. 4-6 Weeks.

RespiratoryRespiratory Fungal AgentsFungal Agents Fungal respiratory diseases Fungal respiratory diseases can be divided into: can be divided into: Fungal agents ..Widely distributed in Environment.. CauseFungal agents ..Widely distributed in Environment.. Cause

mostly infection in immunocompromised individuals.. mostly infection in immunocompromised individuals.. receiving immunosuppressive therapy.. undergoing bone receiving immunosuppressive therapy.. undergoing bone marrow transplantation or solid-organ transplant .. HIV marrow transplantation or solid-organ transplant .. HIV infection. infection.

Clinical presentations : Clinical presentations : Fungal respiratory infections are Fungal respiratory infections are non-specific .. often overlap with other infectious and non-non-specific .. often overlap with other infectious and non-infectious processes..mostly without feverinfectious processes..mostly without fever

The causative agents can be opportunistic endogenous The causative agents can be opportunistic endogenous YeastYeast or exogenous or exogenous filmentous Fungi /Moldsfilmentous Fungi /Molds

Yeast Form:Yeast Form: Oral CandidiasisOral Candidiasis

Part of oral /intestinal/vaginal floraPart of oral /intestinal/vaginal flora .. causes characteristic .. causes characteristic mucosa patches of a creamy-white to grey pseudomembrane mucosa patches of a creamy-white to grey pseudomembrane composed of composed of BlastosporesBlastospores and and PseudohyphaePseudohyphae . .

Candidasis Candidasis often develop after long antibiotics treatment .often develop after long antibiotics treatment . Oral candidasis may spread.. Oral candidasis may spread.. Esophagus, Esophagus, Bronchi, Bronchi,

Lungs, Gastro-intestinal tract, or become systemic .. Lungs, Gastro-intestinal tract, or become systemic .. Candidiaemia, may results in endocarditis..meningitis.Candidiaemia, may results in endocarditis..meningitis.

Systemic Candidiasis Systemic Candidiasis is common in patients with cell-is common in patients with cell-mediated immune deficiency, receiving aggressive cancer, mediated immune deficiency, receiving aggressive cancer, immunosuppression, transplantation therapy. immunosuppression, transplantation therapy.

C. albicans, C.glabrata,C. tropicalis, C. krusei, C. albicans, C.glabrata,C. tropicalis, C. krusei,

11 - -Pseudohyhae , Blastospores, Chlamydospores Pseudohyhae , Blastospores, Chlamydospores 2- Oral Candida Trush2- Oral Candida Trush

Candida Pseudohyphae with Candida Pseudohyphae with Blastospores-Gram-stainBlastospores-Gram-stain

Predisposing Factors for the Predisposing Factors for the Development of CandidiasisDevelopment of Candidiasis

Impaired epithelial barrierImpaired epithelial barrier:: Burns, Wounds / abrasions, Burns, Wounds / abrasions, Hydration/maceration, Indwelling catheters, Foreign bodies Hydration/maceration, Indwelling catheters, Foreign bodies (Dentures, etc), Increased gastric pH, Cytotoxic/ Antibiotics (Dentures, etc), Increased gastric pH, Cytotoxic/ Antibiotics agents.. Radiationagents.. Radiation

Systemic disorders: Systemic disorders: Diabetes mellitus, Pregnancy/oral Diabetes mellitus, Pregnancy/oral contraceptives, Malnutrition, Malabsorption, Iron contraceptives, Malnutrition, Malabsorption, Iron deficiency.deficiency.

Malignancy / Haematologic disorders: Malignancy / Haematologic disorders: NeutropneaNeutropnea / / Leukemia, Lymphoma, advanced cancer, AIDS all Leukemia, Lymphoma, advanced cancer, AIDS all immunodeficiency conditions. immunodeficiency conditions.

Sytemic treatmentSytemic treatment: : fluconazole , amphotericin B, fluconazole , amphotericin B, Caspofungin. Caspofungin.

Local Ointment: Nystatin, micronazole, Local Ointment: Nystatin, micronazole, clotrimazole clotrimazole

Yeast: CryptococcosisYeast: Cryptococcosis

EncapsulatedEncapsulated C. neoformans..C. neoformans.. cause a chronic, cause a chronic, subacute -acute pulmonary.. systemic or subacute -acute pulmonary.. systemic or meningitic disease.. Meningoencephalitis..Often meningitic disease.. Meningoencephalitis..Often isolated from Pigeon & Birds excreta.isolated from Pigeon & Birds excreta.

Primary pulmonary infections: Primary pulmonary infections: Mostly pneumonia-Mostly pneumonia-like illness, with symptoms such as cough, fever, like illness, with symptoms such as cough, fever, chest pain..dissemination may include central chest pain..dissemination may include central nervous system ..Lesions in brain, skin, bones nervous system ..Lesions in brain, skin, bones and other visceral organs..Common significant and other visceral organs..Common significant opportunistic pathogens in immunodifficient opportunistic pathogens in immunodifficient humans ,AIDS patients. humans ,AIDS patients. Diagnosis: Culture + Diagnosis: Culture + Antigens detection in Serum , CSF & Biopsy.Antigens detection in Serum , CSF & Biopsy.

Cryptococcus detection byCryptococcus detection by India ink test India ink test

Molds: Aspergillosis-1Molds: Aspergillosis-1

Most common Most common Aspergillus Aspergillus speciesspecies A. fumigatus, A. flavus, A. niger. A. fumigatus, A. flavus, A. niger. AspergillusAspergillus  widely distributed in nature..   widely distributed in nature..

Survive harsh environmental conditions. Found Survive harsh environmental conditions. Found in all dead animal, plants , Grains, soil, spread in all dead animal, plants , Grains, soil, spread via small spores that are extremely light and via small spores that are extremely light and float easily in the air. float easily in the air. 

1) 1) Allergic Bronchopulmonary: Allergic Bronchopulmonary: Presence of conidia Presence of conidia or fungal filaments in lung tissues, Sinuses.. often or fungal filaments in lung tissues, Sinuses.. often associated with associated with Allergic reaction Allergic reaction ..Eosinophilia.. ..Eosinophilia.. Asthma.. Asthma..

3) 3) MycotoxicosisMycotoxicosis due to ingestion of contaminated due to ingestion of contaminated foods with fungal toxin foods with fungal toxin A. flavus A. flavus .. .. Produce Produce Aflatoxins.. Liver cirrhosis..DeathAflatoxins.. Liver cirrhosis..Death

Septated Hyphae & SporesSeptated Hyphae & Spores

Aspergillosis-2Aspergillosis-2 3) 3) Pulmonary AspergillomaPulmonary Aspergilloma ( Fungus Ball).. ( Fungus Ball)..

Invasive Aspergillosis.. Pre-existing lung cavity, Invasive Aspergillosis.. Pre-existing lung cavity, inflammatory, granulomatous, necrotizing disease of inflammatory, granulomatous, necrotizing disease of lungs..May spread to other organs.. Causing mostly lungs..May spread to other organs.. Causing mostly ThrombosisThrombosis.. .. Rhino-cerebral lesionsRhino-cerebral lesions rarely systemic rarely systemic and fatal disseminated disease. and fatal disseminated disease.

Treatment:Treatment: Fluconazole, Itraconazole, Caspofungin Fluconazole, Itraconazole, Caspofungin Amphotericin B ..Amphotericin B ..

Less common Respiratory fungi: Less common Respiratory fungi: Mucor, RhizopusMucor, Rhizopus FusariumFusarium spp.. Common Rhino-cerebral spp.. Common Rhino-cerebral mucormycosis mucormycosis

Dimorphic Fungus:Dimorphic Fungus: Histoplasmosis-1 Histoplasmosis-1

Histoplasma capsulatumHistoplasma capsulatum.. Dimorphic fungus with .. Dimorphic fungus with conidia and yeast forms at body temperature and hyphae conidia and yeast forms at body temperature and hyphae & marcoconidia in vitro culture.. Common in soil enriched & marcoconidia in vitro culture.. Common in soil enriched with excreta of birds. Endemic in southern U.S.A, Australia.. with excreta of birds. Endemic in southern U.S.A, Australia.. Less other countries.Less other countries.

The primary site of infection is usually The primary site of infection is usually LungLung.. inhalation .. inhalation dust with microconidia.. Phagocytosed by macrophages, dust with microconidia.. Phagocytosed by macrophages, obligate intracellular parasites.. Causing slight obligate intracellular parasites.. Causing slight inflammatory reaction.. Most cases of inflammatory reaction.. Most cases of histoplasmosishistoplasmosis are are asymptomatic /subclinical, benign as Flu-like syndrome.asymptomatic /subclinical, benign as Flu-like syndrome.

Few may develop chronic Few may develop chronic progressive lung diseaseprogressive lung disease.. .. Granuloma & fibrosis, chronic cutaneous or systemic Granuloma & fibrosis, chronic cutaneous or systemic disease involve any internal organ.. disease involve any internal organ.. Fatal systemic diseaseFatal systemic disease..

All infected persons become positive by histoplasmin skin All infected persons become positive by histoplasmin skin test. test.

Histoplasma capsulatumHistoplasma capsulatumin infected White Blood in infected White Blood cellscells

Coccidioidomycosis &Coccidioidomycosis &Blastomycosis-2Blastomycosis-2

Coccidioides immitisCoccidioides immitis & Blastomyces dermatitidis & Blastomyces dermatitidis.. .. soil inhabiting Dimorphic Fungussoil inhabiting Dimorphic Fungus.. Endemic in south-.. Endemic in south-western U.S.A., northern Mexico and various parts South western U.S.A., northern Mexico and various parts South America.America.

Respiratory infection.. inhalation of microconidia, Respiratory infection.. inhalation of microconidia, often resolves rapidly leaving the patient with a often resolves rapidly leaving the patient with a strong strong specific immunity to re-infectionspecific immunity to re-infection..

Some individuals the disease may progress to a Some individuals the disease may progress to a chronic pulmonary chronic pulmonary condition or a condition or a systemic systemic disease disease involving the meninges, bones, joints, involving the meninges, bones, joints, subcutaneous, cutaneous tissues.. Antigen Skin subcutaneous, cutaneous tissues.. Antigen Skin test positive.. Not significant in diagnosis.test positive.. Not significant in diagnosis.

Laboratory DiagnosisLaboratory Diagnosis

Direct microscopy and culture Direct microscopy and culture should be performed should be performed on all specimens (sputum, bronchial washings, CSF, on all specimens (sputum, bronchial washings, CSF, pleural fluid tissue biopsies from various visceral pleural fluid tissue biopsies from various visceral organs ).organs ).

wet mounts in 10% KOH with india ink.. Ovoid-wet mounts in 10% KOH with india ink.. Ovoid-budding yeast cells (b) Gram-stain smear.. budding yeast cells (b) Gram-stain smear..

Cultures on Cultures on Sabouraud dextrose agar Sabouraud dextrose agar should be should be maintained for one month at 25C.... fungal growths maintained for one month at 25C.... fungal growths & Wet Mount.. Identification ..produces hyphae-like & Wet Mount.. Identification ..produces hyphae-like conidio-phores & Spores.. Color of fungal growthconidio-phores & Spores.. Color of fungal growth

Serological tests are of limited valueSerological tests are of limited value.. not significant.. not significant Detection of Histoplasm antigen in blood & urine is Detection of Histoplasm antigen in blood & urine is significantsignificant

Pneumocystis (carinii, Rats type) Pneumocystis (carinii, Rats type)

P. jiroveci (Human type)P. jiroveci (Human type) Small Yeast like Cells ..No filaments or Capsules Small Yeast like Cells ..No filaments or Capsules PneumocystisPneumocystis infection occurs by inhalation infection occurs by inhalation

contaminated dust .. It is commonly found in contaminated dust .. It is commonly found in the lungs of healthy individuals. .without the lungs of healthy individuals. .without symptomssymptoms

Asymptomatic Infection Asymptomatic Infection mostly started in mostly started in children & increased in Adults .. Worldwide.children & increased in Adults .. Worldwide.

Clinical Disease Clinical Disease occurs only associated with occurs only associated with both decrease of cellular immunity and humoral both decrease of cellular immunity and humoral immunity, suppressed immunity .immunity, suppressed immunity .

Infectious trophic formInfectious trophic form of the organism attaches of the organism attaches to the to the lung alveolilung alveoli.. Encyst & multiple in host .. Encyst & multiple in host tissues. tissues.

Pneumocystis-2Pneumocystis-2 Clinical disease Clinical disease .. .. PneumoniaPneumonia.. Organism is usually .. Organism is usually

found in the interstitial fluid in the lungs, Lung found in the interstitial fluid in the lungs, Lung tissue.. of tissue.. of immunocompromised patientsimmunocompromised patients.. .. AIDS ..may disseminate to other internal body AIDS ..may disseminate to other internal body organs.. Associated with high mortality.organs.. Associated with high mortality.

Sputum /lung biopsy specimens are usually used for Sputum /lung biopsy specimens are usually used for PC detection. PC detection.

Silver – Giemsa-, Stain.. Immunofluorescent Silver – Giemsa-, Stain.. Immunofluorescent AntigenAntigen (IFA).. (IFA).. Treatment: Treatment: CotrimoxazoleCotrimoxazole alone or alone or with intravenous Pentamidine in sever cases.with intravenous Pentamidine in sever cases.