M33+Infections+of+the+Respiratory+Tract.pdf

Infections of the Respiratory TractChandra Shekhar Bakshi, Ph.D.Professor of Pathology, Microbiology and ImmunologySchool of MedicineNew York Medical CollegePh: 914-594-4814E mail: [email protected] 33 2OverviewInfections of the Respiratory TractAnatomy of the Respiratory TractPathogens of t...

Infections of the Respiratory TractChandra Shekhar Bakshi, Ph.D.Professor of Pathology, Microbiology and ImmunologySchool of MedicineNew York Medical CollegePh: 914-594-4814E mail: [email protected] 33 2OverviewInfections of the Respiratory TractAnatomy of the Respiratory TractPathogens of the Respiratory TractBacterial Infections of the Upper Respiratory Tra c tBacterial Infections of the Lower Respiratory Tra c tFungal Infections of the Respiratory TractViral Infections of the Upper Respiratory TractViral Infections of the Lower Respiratory TractNon-Infectious Respiratory Diseases 3Why study infections of the respiratory tract? 4Why study infections of the respiratory tract?•Amajorportalofentryforinfectiousorganismsmakesitthemostcommonlyinfectedsystem.•Over35millionAmericansareaffectedbysomeformofrespiratorydisease,rangingfromacutepulmonaryinfectionstoChronicObstructivePulmonaryDisease(COPD)andasthma.•Respiratoryillnessesaccountforone-thirdofthemostcommoncausesofdeathamongAmericans.•Respiratoryhealthisconnectedwithoralhealth:Pathogensinthemouthserveasriskfactorsfordevelopingarespiratorydisease.•Dentistsshouldrecognizeoralconditions:-Thatmaycauserespiratoryinfections-Tocontroltheprogressionofpotentialrespiratorydiseasedevelopment 5Association of oral and respiratory tract infectionsSpread of oral infections to respiratory tractHematogenous route-Rare occurrenceThrough aspirations•Inhealthypeoplewhilesleepingandinthosewithimpairedconsciousness•Periodontalpathogensand/orrespiratorypathogenscolonizingindentalbiofilmswhicharethenaspiratedor •Periodontalpathogenscouldfacilitatethecolonizationofrespiratorypathogenswhicharethenaspirated 6Anatomy of the Respiratory TractUpper Respiratory Tract: •Continuously exposed to potential pathogens•Infections are very common•Easy to treatLower Respiratory Tract: •Essentially a sterile environment•Infections are serious•Difficult to treathttp://www.medicinenet.com 7Pathogens of the Upper Respiratory TractBacterial Pathogens of Nose and Sinuses:Staphylococcus aureusStreptococcus pneumoniaeHaemophilus influenzaePeptostreptococcihttp://www.medicinenet.comViral Pathogens of Nose and Sinuses:RhinovirusMyxovirusAdenovirusEnterovirusMeasles virus Viral Infections of the Upper Respiratory TractRHINOVIRUS INFECTION (Common cold)There are several hundred serotypes of rhinovirus.•50% are picornaviruses•Extremely small, non-enveloped, single-stranded RNA viruses•Optimum temperature for picornavirusgrowth is 33˚C; the temperature in the nasopharynxTra n sm ission :•Droplet, hand contaminationSymptoms:•Sneezing, nasal discharge, sore throat, headache, mild cough and fever•Due to multiple Rhinoviruses, no cross protection due to antibodiesTreat m ent: Symptomatic 9Bacterial Pathogens of Pharynx:Streptococcus pyogenesCorynebacteriumdyptheriaeHemophilusinfluenzaeCandia albicansVincent’s organismshttp://www.medicinenet.comViral Pathogens of Pharynx:RhinovirusMyxovirusAdenovirusEnterovirusMeasles virusHerpes Simplex virusRespiratory SyncytialVirus (RSV)Epstein-Barr virusPathogens of the Upper Respiratory Tract 10Respiratory Syncytial virus (RSV)•Is a member of Pneumovirusgenus; does not have neuraminidase•Single stranded, negative-sense enveloped RNA virus•Two serotypes: RSV A and RSV B; no antigenic drift•RSV induces syncytiaTra n sm ission a n d Pat h olog y •Discovered in 1957 in chimpanzees•Leading cause of respiratory illness in infants and young children (64 million children infected globally, 160,000 deaths)•Can cause lower respiratory tract infections in bone marrow and lung-transplant patients•RSV is very contagious; incubation period is 4-5 days•Respiratory illness ranging from common cold to pneumonia•Always occurs in fall-winter-spring•Cause localized respiratory tract infection leading to necrosis of bronchi and bronchiolesViral Infections of the Upper Respiratory Tract Pathogenesis of RSV1234 12Symptoms in young children:•URI: Fever, cough, congestion rhinorrhea•Otitis media (ear infection)•LRI: bronchiolitis, pneumonia and apnea in infancy; wheezing in older childrenElderly hospitalized patients:•Pneumonia, COPD, congestive heart failure, asthmaDiagnosis: RT-PCR and ELISATreat m ent•Supportive treatment , Ribavirin (a guanosine analog) is effective, •Passive immunization with anti-RSV immunoglobulin (Palivizumab) is available for premature and high risk infants•No vaccine is currently availableViral Infections of the Upper Respiratory Tract 13Bacterial Pathogens of Lungs:HemophilusinfluenzaeStreptococcus pneumoniaeKlebsiella pneumoniaeMycoplasmapneumoniaeLegionellaspeciesMycobacterium tuberculosisViral Pathogens of Lungs:ParainfluenzavirusAdenovirusRespiratory SyncytialVirus (RSV)Pathogens of the Lower Respiratory Tract 14PA R A I N F LU E N Z A :Can cause both upper and lower respiratory tract infections There are four serotypes of parainfluenza virus that belongs to the paramyxovirus group-Enveloped, single-stranded RNA viruses-Contain hemagglutininand neuraminidase-Types 1, 2 and 3 cause severe lower respiratory tract infections (Laryngotracheobronchitis or Croup); type 4 cause mild upper respiratory tract infectionTra n sm ission a n d Pat h olog y Similar to influenza virus, but there are differences:-Parainfluenzavirus replicates in the cytoplasm (Influenza virus replicates in the nucleus) Parainfluenzais genetically more stable than influenza.-Very little mutation, little antigenic drift, no antigenic shiftParainfluenzais a serious problem in infants and small children.-Only a transitory immunity to re-infection-Infection becomes milder as the child ages-Croup: Results from subglottal swelling with characteristic “seal bark cough”Viral Infections of the Lower Respiratory Tract Structure of Adenoviruses•Non-enveloped, icosahedralviruses•Contain linear double stranded DNA with a terminal protein(required for DNA replication)•Capsid consists of fiber, haxonand pentonbase proteins•Fiber and pentonproteins are required for receptor binding and virus internalization•Fiber and pentonproteins are toxic to the host cellsSerotypes result from differences in penton base and fiber protein Time course of adenovirus respiratory infection Epidemiology of Adenoviruses:Non-Military:•Adenoviruses are responsible for 3-5% of acute respiratory illness in children younger than 14 years of age•Long-term care facilities•Day care facilities•Swimming pools•Tra ining ca mps•Immunocompromised patients•Males and females are equally susceptible Epidemiology of Adenoviruses:Military:•Outbreaks reported since 1950s•50-80% incidence rate•Risk factors include:-Stressful training, fatigue-Environmental factors-Exposure of susceptible young adults during conditions of crowding and stress-Caused by serotypes 4 and 7 Diagnosis•Cell Culture: A549, HEK, Hep-2 (takes up to 6 days). Enteric adenoviruses (serotype 40 and 41) do not grow readily in cell cultures.•Immunofluorescence•Serology (ELISA)•PCR and DNA probe analysis http://www.med.navy.mil/sites/nhrc/geis/Documents/FRIUpdate.pdf*FRI = Febrile Respiratory IllnessVa c c i n e s d eve l o p e d fo r a d e n ov i r u s s e ro t y p e s 4 a n d 7 , a re available only for preventing ARD among military recruits. 21Viral infections of the Lower Respiratory Tract•Influenzahttp://www.medicinenet.comZoonosis:•COVID-19•SARS (Human Coronavirus) (Bats)•Avian Influenza (Birds)•Hendra Virus (Flying Fox)•NipahVirus (Bats)Newly Recognized Causes:•Rhinoviruses 1, 2 and 3•Parainfluenza 4•Coronaviruses 1, 2, and HKU1; SARS-CoV-2•Human Metapneumovirus1, 2 and 3•Human bocavirus1, 2 and 3•Polyomaviruses KI and WU What is a Coronavirus (CoV)?Single-stranded positive-sense RNA (+ssRNA)Spike protein determines the host-specificityFirst human CoVwas identified in mid-1960sSolar corona-like appearanceCrown (Latin) Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 *Spike protein is required for attachment and entry of CoVinto the host cellsWan et al., Journal of Virology, 2020Spike (S) ProteinS1= Virus host range and cellular tropismS2= Virus-cell membrane fusionSARS-CoV-2SARS= Severe Acute Respiratory SyndromeMERS= Middle Eastern Respiratory Syndrome Tra n s m is s ion of SARS-CoV-2No evidence of vertical transmission or through breast-feedingPre-symptomatic•Infected but yet to exhibit symptomsAsymptomatic•Infected but never exhibit symptomsSymptomaticInanimate objects3-5 FeetDropletsSARS-CoV-2 Pathogenesis of COVID-19Distribution of ACE2 ReceptorBaiget al., 2020•ACE-2receptorispresentonlung,heart,brain,kidney,gastro-intestinalcellsaswellascellsofbloodvesselsandtestis•Therespiratory,cardiacandneurologicalsymptomsofCOVID-19areduetheabilityofSARS-CoV-2toreplicateinlung,heart,andbraincells Exaggerated and prolonged innate immune response contributes to the severity of COVID-19The Journal of Heart and Lung Transplantation2020 39405-407DOI: (10.1016/j.healun.2020.03.012) •Release of inflammatory signals •Recruitment of macrophages and cytokines production•Recruitment of neutrophils The Journal of Heart and Lung Transplantation2020 39405-407DOI: (10.1016/j.healun.2020.03.012) •CYTOKINE STORM: Very high levels of IL-6, TNF-α, IL-1βand other pro-inflammatory cytokines •Elevated C-reactive protein and D-dimer levels•Elevated neutrophil-lymphocyteratio Ver y hi gh l evel s of I L-6 and increased neutrophil-to-lymphocyte ratio are indicators of disease severity and poor clinical outcomesExaggerated and prolonged innate immune response contributes to the severity of COVID-19 Progression of COVID-19 Stage I (STAY HOME)•Asymptomatic or pauci-symptomatic incubation period •Virus may or may not be clinically detectableStage II (MAY REQUIRE HOSPITALIZATION)•Non-severe symptomatic illness (Shortness of breath) with detectable virus•Approximately 80% will recover in Stages I and IIStage III (ICU, VENTILATOR AND LIFE-SUPPORT) •Severe inflammatory response syndrome (SIRS)•Acute respiratory distress syndrome (ARDS)•Sepsis, respiratory and multi-organ failure Cardiovascular Disease•Heart Damage, arrythmias-Replication of virus-Cytokine stormBlood Clotting Abnormalities •Pulmonary embolism and stroke •High levels of D-dimer: Byproduct of blood clots •Blood vessel constriction: -Swollen painful digits and tissue death-Lack of gasping despite low-oxygen Renal Failure•Viral replication•Collateral damage to Kidneys:-Vent ilato rs-To x i c i t y d u e t o a n t i v i r a l s-Cytokine storm-Pre-existing conditions (diabetes)Neurological complications•Loss of sense of smell and taste•Seizures, hallucination•Stroke•Depression of the brain stem reflex that senses oxygen starvationGI Complications•Viral replication•Detection of Viral RNA in in patients’ stool samples•Diarrhea•No evidence of transmission through feces •Damage to the liver is mostly collateralSARS-CoV-2 targets multiple organs COVID-19 in childrenZimmermann, Petra; Curtis, Nigel. The Pediatric Infectious Disease Journal39(5):355-368, May 2020.Pediatric Multi-System Inflammatory Syndrome Temporally Associated with COVID-19Kawasaki-like disease caused by SARS-CoV-2 •Occur days to weeks after the COVID-19 illness in children•Abdominal pain, vomiting and diarrhea•Myocarditis and other cardiovascular changes•Inflammatory disorder associated with very high levels of C-reactive proteins, increased ESR and ferritin levels Sarkar et al., 2021; https://doi.org/10.1101/2021.12.04.21267284Spike Protein of SARS-CoV-211 Mutations37 Mutations (12)10 Mutations (2)11 Mutations (3)11 Mutations (1)Va r i a nt s o f C o n c e r n o f SA RS-CoV-2 Sarkar et al., 2021; https://doi.org/10.1101/2021.12.04.21267284Spike Protein of SARS-CoV-2Va r i a nt s o f C o n c e r n o f SA RS-CoV-211 Mutations37 Mutations (12)10 Mutations (2)11 Mutations (3)11 Mutations (1)•Increased transmissibility•More severe disease / increased hospitalizations•Reduced effectiveness of treatment, vaccines and detection Sub-lineages of the SARS-CoV-2 Omicron Varianthttps://www.nature.com/articles/s41392-022-00997-xCDC https://synbiobeta.com/timeline-shows-3-paths-to-covid-19-treatment-and-prevention-infographic/Repurposed DrugsNirmatrelvir + Ritonavir(Paxlovid)RemdesivirChloroquine/HydroxychloroquineMonoclonal antibodiesTherapy 36COVID-19 VaccinesInactivated SARS-CoV-2 Vaccine•Covaxin(developed in India)•Sinovac(developed in China)•Two-dose vaccine administered 28 days apart•Two-dose vaccine administered 21-28 days apart + 2 additional boostersNovavax: S-Protein-subunit vaccine 07/13/22 Management of Patients with Respiratory DiseasesAs a Dentist:•Consult with patient’s physician before any dental procedure•Review Patient ’s medical history for:-Disease severity-Medications-Chronic respiratory illnesses •Position patient such that the patient can breath easily and prevent any aspirations•Make sure the availability of nitrous oxide or oxygen for patients with upper respiratory infections•Allergy to antibiotics (Penicillin) •Avoid triggering of hypersensitive airways by cotton rolls or suction tips [email protected]: 914-594-4814