Viral & Fungal Pneumonia Lecture Notes PDF

VIRAL & FUNGAL PNEUMONIA LECTURE -5 RESPIRATORY MODULE 3rd YEAR MBBS  Viral Infection of LRT Pneumonia Bronchiolitis  Bronchiolitis It is acute viral infection affecting small bronchioles Occur in infancy and small children (first 2 ye...

VIRAL & FUNGAL PNEUMONIA LECTURE -5 RESPIRATORY MODULE 3rd YEAR MBBS  Viral Infection of LRT Pneumonia Bronchiolitis  Bronchiolitis It is acute viral infection affecting small bronchioles Occur in infancy and small children (first 2 years ) Human is the only source of infection Etiology : respiratory syncytial virus (RSV) Incubation period : 4: 8 days Symptoms : cough , wheezing , shortness of breath, some children suffer from difficulty in feeding Signs : Crackles and or wheezes are typical finding on listening on chest by stethoscope X-ray show typical bilateral perihilar fullness of bronchioles Treatment : Bronchodilators Antibiotic prevent secondary bacterial prevention Hospitalization is recommended in children with underlying heart or lung disease  Viral Pneumonia Viruses are recently recognized as important pathogens of community acquired pneumonia (CAP). Viral pneumonia is a serious disease especially in old and immunocompromised patients Viruses cause of up to 35% of CAP in adults and children Risk factors for viral pneumonia: 1. Elderly 2. Chronic chest diseases: e.g., asthma 3. Immunocompromised patients  Clinical presentation of viral pneumonia  Symptoms tend to be of gradual onset and less severe than bacterial pneumonia.  Symptoms of viral pneumonia begin few days after upper respiratory symptoms, as sore throat.  Secondary bacterial respiratory infection is common especially in high-risk patients  Viral Pneumonia Common organisms Influenza virus Respiratory syncytial virus (RSV) Coronaviruses Para influenza virus Adenovirus - type 7 Epstein-barr virus (EBV) Cytomegalovirus(CMV), Herpes simplex virus (HSV) Measles virus Routes of infection Inhalation  Influenza Family – Orthomyxoviridae Spherical or filamentous viruses Single-stranded segmented RNA genome Three serotypes – influenza A,B &C is based on internal and matrix protein. Hemagglutinin & neuraminidase are the two types of surface glycoprotein are attached to the envelope.  Properties of virus Frequent changes in the antigenicity of HA and NA results in epidemics and pandemics. Antigenic drift- minor antigenic changes of HA or NA resulting in epidemics (point mutations in HA and NA genes) Antigenic shift- major antigenic changes either in hemagglutinin or neuraminidase resulting in pandemics. (Change results from gene reassortment)  Clinical features After incubation period of 3 to 4 days - abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache Complications Pulmonary- secondary bacterial infection Non pulmonary- 1. Myositis 2. Encephalopathy 3. Peripheral nervous system -Guillain-barré syndrome (GBS) 4. Reye’s syndrome Lab diagnosis Demonstration of the virus antigen RT -PCR, immunofluorescence Isolation of the virus- monkey kidney cells Serology Hemagglutination inhibition test : more specific test Complement fixation test (CFT) ELISA Treatment: Amantadine and Rimantidine Oseltamivir (tamiflu) & zanamivir- block viral neuraminidase & more effective.  Prophylaxis 1. Inactivated vaccines 2. Inactivated subunit vaccine 3. Recombinant vaccine Killed vaccine induce the formation of circulating antibodies, they do not lead to local immunity. 4. Live attenuated vaccines: Stimulate production of local IgA antibodies and gives specific local immunity.  Coronaviruses Coronaviruses are a large family of viruses, some cause illness in humans, and others cause illness in animals. Coronaviruses belongs the family coronaviridae, the largest among known RNA viruses Corona represents crown-like spikes on the outer surface of the virus. Enveloped + ve sense ss RNA viruses with nucleocapsid of helical symmetry. Frequent cause of common cold Incubation period: 2 to 14 days Mortality is 11% esp. In elderly HUMAN CORONA VIRUS HAS 7 STRAINS : 1. HUMAN COV 229 E 2. HUMAN COV OC43 Mild to moderate infection: Common cold, bronchitis, bronchiolitis in infants 3. HUMAN COV NL63 & children 4. HUMAN COV HKU 1 5. SARS-COV (2003 outbreak)-transmitted from civet cats and cave-dwelling horseshoe bats to humans in China in 2002 6. MERS-COV (2012 outbreak)- from dromedary camels to humans in Saudi Arabia in 2012 7. SARS-COV-2 ( 2019-outbreak)- from ? Bat  SEVERE ACUTE RESPIRATORY SYNDROME (SARS) SARS is caused by a strain of CORONAVIRUS, the same family of viruses that causes the common cold. First outbreak – south China in 2002 In Feb 2003, there was a pandemic affecting 30 countries and over 800 death. SARS typically begins with flu-like signs and symptoms — fever of 100.5 F (380 C) or higher, chills, dry cough, shortness of breath, muscle aches and occasionally diarrhea. Complication Pneumonia. Respiratory failure. Heart & liver failure.  Severe acute respiratory syndrome (SARS) Lab diagnosis: – PCR ( sputum, blood, stool) – Detection of serum antibodies Treatment : - Respiratory support - Ribavirin, interferons - “High dose steroids”- ??? - no vaccine  Middle east respiratory syndrome coronavirus (MERS-COV) The first known cases of MERS occurred in Jordan in April 2012 and in Saudi Arabia in September 2012. People with comorbidities- diabetes; cancer; individuals with weakened immune systems and chronic lung, heart, and kidney disease may be more likely to become infected with MERS-COV or have a severe case. Transmission: spread from ill people to others through close contact  MERS-COV Incubation period- usually about 5 or 6 days but can range from 2-14 days. Symptoms: fever, cough, shortness of breath, gastrointestinal symptoms including diarrhea and nausea/vomiting. Complications : pneumonia and kidney failure.  LABORATORY DIAGNOSIS: MERS-COV Specimens: respiratory specimens, serum Investigations: Serologic testing- :Antibody detection Serum for real time RT-PCR testing Treatment: - There is no vaccine to prevent infection - There is no specific antiviral treatment recommended. - “Supportive management.”  SARS-COV -2 coronavirus disease 2019 (COVID-19) Is an infectious disease caused by SARS-COV-2 (COVID-19) ,a virus closely related to the SARS virus. It is primarily spread between people via respiratory droplets from infected individuals when they cough or sneeze ACE-2 has been identified as a functional receptor for SARS-COV and is highly expressed on the pulmonary epithelial cells.  Signs and symptoms The incubation period is between 2 and 14 days. Those infected may either be asymptomatic or develop symptoms , including fever, cough or shortness of breath. Diarrhea or upper respiratory symptoms (e.g., Sneezing, runny nose , sore throat) are less frequent. Cases can progress to pneumonia and multi-organ failure and death. Diagnosis Molecular tests (RT-PCR) Serology. Blood tests CT Chest x-ray Treatment Antiviral drugs: lopinavir, ribavirin, interferon beta-1b, Corticosteroids- dexamethasone, prednisolone. Immunomodulator- tocilizumab Prevention 1- Prevent the spread of covid-19 Wear a facemask Cover your coughs and sneezes Clean your hands often Maintain social distance Quarantine for 14 days 2- Vaccines Several different types of potential vaccines for covid-19 are in development, including: Inactivated or weakened virus vaccines Protein-based vaccines Viral vector vaccines RNA and DNA vaccines  Respiratory syncytial virus (RSV) Enveloped RNA virus (paramyxovirus) RNA genome is non-segmented Second most common cause of viral pneumonia in adults especially those with chronic lung disease, or immunocompromised. RSV is a major cause of severe pneumonia in young children. Infection starts in upper respiratory tract, then spread to cause bronchiolitis, pneumonia and acute respiratory failure  Signs: Crackles and/or wheeze are typical findings on listening to the chest with a stethoscope. Treatment - Bronchodilators- nebulization with salbutamol - Nebulized tribavirin- 20mg/ml for three days. - Antibiotics- prevents secondary infection. Hospitalization is recommended for children with underlying lung or heart disease.  PNEUMONIA Measles - giant cell pneumonia Cytomegalovirus - interstitial pneumonia in bone marrow transplanted patient. Parainfluenza virus : common cause of croup, bronchiolitis, pneumonia in infants Human metapneumovirus- bronchiolitis and pneumonia  PREVENTION Wash your hands often with soap and water for 20 seconds/ use an alcohol-based hand sanitizer. Cover your nose and mouth with a tissue when you cough or sneeze, then throw the tissue in the trash. Avoid touching your eyes, nose and mouth with unwashed hands. Avoid personal contact, such as kissing, or sharing cups or eating utensils, with sick people. Clean and disinfect frequently touched surfaces and objects, such as doorknobs. FUNGAL PNEUMONIA  INTRODUCTION Fungal pneumonia is infection of the lungs by either primary pathogenic or opportunistic fungi or both. Pathogenic fungi can infect both healthy and immunocompromised persons. Mortality in fungal pneumonia can be as high as 90% in immunocompromised patients, while persons with normal immunity generally respond well to anti-fungal therapy.  TRANSMISSION Fungal infection occurs following inhalation of spores. Pathogenic fungi: 1) Histoplasma capsulatum: histoplasmosis 2) Coccidioides immitis: coccidioidomycosis 3) Blastomyces dermatitidis: blastomycosis 4) Paracoccidioides brasiliensis: pracoccidioidomycosis  All are thermally dimorphic fungi  Pathogenic fungi can infect both healthy and immunocompromised persons.  Infection occurs at certain geographic locations around the world.  Histoplasmosis: ohio valley fever Histoplasma capsulatum – most common true pathogen; causes histoplasmosis Typically, dimorphic Distributed worldwide, most prevalent in eastern and central regions of US Grows in moist soil high in nitrogen content Soil contaminated by droppings of birds & bats is rich source of H. Capsulatum 35 Pathogenesis: Airborne spores (conidia) enter the lungs & germinate into yeast cells Yeast cells resist killing by macrophages & multiply intracellularly (like M. Tuberculosis) Inhaled conidia produce primary pulmonary infection that may progress to systemic involvement of a variety of organs and chronic lung disease.  Coccidioidomycosis: valley fever Coccidioides immitis - causes coccidioidomycosis Distinctive morphology: block-like arthrospores in the free- living stage and spherules containing endospores in the lungs Lives in alkaline soils in semiarid, hot climates and is endemic to southwestern U.S. Arthrospores inhaled from dust- spores germinate into large spherules creates nodules in the lungs Dissemination occurs to CNS (meningitis) 38  Blastomyces dermatitidis: North American blastomycosis Blastomyces dermatitidis- causes blastomycosis Blastomycosis is a potentially fatal pulmonary disease Dissemination may occur to skin (70%) & bones (30%) mostly in males causing chronic cutaneous, bone, and nervous system complications Dimorphic Free-living species (microconidia) in soil. Inhaled 10-100 conidia convert to yeasts and multiply in lungs Symptoms include cough and fever.  Paracoccidioidomycosis Paracoccidioides brasiliensis Distributed in central and south America Lung infection occurs through inhalation or inoculation of spores. From the lungs, dissemination occurs to mucosa of mouth & nose leading to painful destructive lesions Systemic disease is not common.  Primary pathogenic fungi (endemic fungi ) Disease Causative agent site of dissemination Tissue form Histoplasmosis Ohio Histoplasma Systemic involvement of a Yeast cells valley fever capsulatum variety of organs and chronic lung disease Coccidioidomycosis Coccidioides Dissemination occurs to spherule valley fever immitis CNS (meningitis) Blastomyces Blastomyces Dissemination may occur Yeast cells dermatitidis dermatitidis to skin (70%) & bones North American (30%) blastomycosis Paracoccidioidomycosis Paracoccidioides Dissemination occurs to Yeast cells brasiliensis mucosa of mouth & nose  Opportunistic fungi Pneumonia caused by opportunistic fungi is increasing due to: - Use of immunosuppressive drugs after organ transplantation - Use of cytotoxic drugs in cancer therapy - Large number of AIDS patients worldwide - Opportunistic fungi 1. Candida albicans 2. Aspergillus fumigatus 3. Cryptococcus neoformans 4. Pneumocystis carinii  Opportunistic fungi: candida species Fungal infections represent approximately 15% of nosocomial infections in intensive care units (ICU), with candida species being the most common Candidiasis is caused by candida albicans, which is normal body flora of the mouth, intestine, and birth canal C. albicans is a dimorphic fungus Systemic candidiasis is a potentially fatal infection  Opportunistic fungi candida species Infections occur when bacterial flora are eliminated by broad spectrum antibiotics, allowing overgrowth of candida albicans. Oral thrush Gram stain  Opportunistic fungi aspergillus species Aspergillus fumigatus (main species). Aspergillus fumigatus causes severe acute pneumonia in immunosuppressed individuals and patients treated with broad- spectrum antibiotics. Lung infection causes a fungus ball (aspergilloma), which is a mass of fungus filaments that can form in lung cavities (in tuberculosis, cystic fibrosis) Aspergilloma- X ray Culture -SDA  Opportunistic fungi cryptococcus neoformans Cryptococcosis is caused by cryptococcus neoformans, present in soil containing bird droppings (especially pigeons), although the birds are not affected. Most common form of cryptococcosis is pneumonia. Spread often occurs to brain and meninges, with fatal effects. Diagnosis : C. Neoformans has characteristic thick capsule that surrounds the budding yeast cell (India ink stain). Biochemical tests, serological testing Treatment : Systemic infection requires amphotericin B and fluconazole. Negative stain demonstrating encapsulated budding yeast  Pneumocystis carinii A small, unicellular fungus that causes pneumonia -pneumocystis jiroveci pneumonia (PJP)- the most prominent opportunistic infection in AIDS patients This pneumonia forms secretions in the lungs that block breathing and can be rapidly fatal if not controlled with medication. Diagnosis : Sputum- silver staining Staining with toluidine blue, silver stain, periodic acid Schiff stain No culture is available Treatment : Pentamidine and cotrimoxazole  Opportunistic fungi Causative agent Site Type of fungus Disease produced Candida albicans Normal flora on Dimorphic fungus Systemic Candidiasis skin and GIT Cryptococcus Its spore present Capsulated yeast Pneumonia , Brain neoformans in soil containing abscess , meningitis bird droppings Aspergillus species Its spore is Filamentous fungus Aspergilloma , present free in Systemic aspergillosis the environment , Allergic disease Pneumocystis carnii Infected person unicellular fungus Pneumonia  Laboratory diagnosis of fungal pneumonia Microscopic examination of sputum, BAL Culture on Sabouraud dextrose agar Molecular methods- PCR Serological investigations- ELISA Skin test