respiratory viruses

Respiratory VirusesTitiek DjannatunBagian Mikrobiologi Fakultas kedokteran Universitas YARSI

Viruses Associated with Respiratory Infections

Syndrome

Commonly Associated Viruses

Less Commonly Associated Viruses

Corza

Rhinoviruses, Coronaviruses

Influenza and parainfluenza viruses, enteroviruses, adenoviruses

Influenza

Influenza viruses

Parainfluenza viruses, adenoviruses

Croup

Parainfluenza viruses

Influenza virus, RSV, adenoviruses

Bronchiolitis

RSV

Influenza and parainfluenza viruses, adenoviruses

Bronchopneumonia

Influenza virus, RSV, Adenoviruses

Parainfluenza viruses, measles, VZV, CMV

INFEKSI VIRUS PADA SALURAN PERNAPASAN

Virus Penyebab yang Paling SeringSindromaGejala UtamaBayiAnak-anakDewasaFluHidung tersumbat, pilekRinoAdenoRinoAdenoRinoCoronaFaringitisSakit tenggorokanAdenoHerpes SimplexAdenoCoxackievirusAdenoCoxackievirusLaringitis, batuk dengan sesak napasSerak, batukParainfluenzaInfluenzaParainfluenzaInfluenzaParainfluenzaInfluenzaTrakeobronkitisBatukParainfluenzaInfluenzaParainfluenzaInfluenzaInfluenzaAdenoBronkiolitisBatuk, sesak napasSinsitial pernapasaParainfluenzaJarangJarangPneumoniaBatuk, nyeri dadaSinsitial pernapasanInfluenzaInfluenzaParainfluenzaInfluenzaAdeno

Common Cold (Rhinitis/Selesma)

VirusTipeReseptor pd sel hospesPenyakitRhinovirus (> 100 tipe)Beberapa tipeICAM-1Common coldCoxsackie virus A (24 tipe)Terutama A21ICAM-1Common cold, herpanginaVirus InfluenzaBeberapa tipeglikoproteinBisa menyebabkan infeksi LRTVirus Parainfluenza1, 2, 3, 4glikosidaDapat menyerang laringRSV(2 tipe)Reseptor Protein GBisa menyebabkan infeksi LRTCoronavirussemuaglikoproteinCommon cold, SARSAdenovirus (41 tipe)5 - 10Reseptor PentonFaringitis, bronchitis, conjunctivitisEchovirus (34 tipe)4, 9, 11, 20, 25-Common cold

Viral Pharingitis

Rhinovirus, CoronavirusCommon coldAdenovirus (3, 4, 7, 14, 21)Pharyngoconjunctival feverParainfluenza virus> Berat dari CCInfluenza virus, CMVTidak selalu adaCoxsackie A dan enterovirus lainHerpanginaEpstein-Barr virusGlandular feverHerpes simplex virus tipe 1Ulkus dan vesikel pada palatum

Viral Pneumonia

VirusManifestasi klinisInfluenza A dan BPneumonia primerParainfluenza (tipe 1-4)Croup, Pneumonia pada anakMeaslesPneumonia sekunderRSVBronchiolitis (bayi)AdenovirusPharyngoconjunctival fever, pharyngitis, atypical pneumoniaCMVInterstitial pneumoniaCoronavirusSARS

Influenzae VirusesAn Overview

Influenza VirusRNA virus, genome consists of 8 segmentsenveloped virus, with haemagglutinin and neuraminidase spikes3 types: A, B, and CType A undergoes antigenic shift and drift.Type B undergoes antigenic drift only and type C is relatively stable(Courtesy of Linda Stannard, University of Cape Town, S.A.)

NOMENKLATURFAMILIA ORTHOMYXOVIRIDAEGENUS INFLUENZAVIRUS A INFLUENZAVIRUS B INFLUENZAVIRUS CSIFAT-SIFAT PENTING :VIRION BULAT, PLEOMORFIK,HELIKS, 80-120 nmSS RNA, BERSEGMEN (8MOL), POLARITAS - , REPLIKASI TRANKRIPSI : NUKLEUS; MATURASI : M PLASMAMENYEBABKAN EPIDEMI DI SELURUH DUNIA

NOMENKLATUR

PERBEDAAN ORTHOMYXOVIRUS & PARAMYXOVIRUS

SIFAT-SIFATORTHOMYXOVIRUSPARAMYXOVIRUSPENYAKIT PD MANUSIAInfluenza tipe A, B, CParainfluenza 1-4, peny. Sinsitium pernafasan, gondong, campakPENGATURAN GENOMss RNA DLM 8 BAGIANss RNA DLM 1BAGIANHELIKS RIBONUKLEOPROTEINBERDIAMETER 9 nmBERDIAMETER18 nm

RNA DLM NUKLEOKAPSIDPEKA THDP RNaseRESISTEN THDP RNase

FUSI VIRUS -SELENDOSOMMEMBRAN PLASMATRANSKRIPSINUKLEUSSITOPLASMAPEMILIHAN GENETIKSERINGJARANGPERUBAHAN GENETIKTINGGIRENDAH

PERBEDAAN INFLUENZA A, B DAN C

TIPE ATIPE BTIPE C

DERAJAT PENYAKIT+++++++HEWAN RESERVOIRYATIDAKTIDAKPANDEMIK PADA MANUSIAYATIDAKTIDAK

EPIDEMIK PADA MANUSIAYAYATIDAK (SPORADIK)PERUBAHAN ANTIGENIKSHIFT, DRIFTDRIFTDRIFTGENOM BERSEGMENYAYAYAAMANTADINE, RIMANTIDINESENSITIFTIDAK BEREFEKTIDAK BEREFEKZANAMIVIRSENSITIFSENSITIFGLIKOPROTEIN PERMUKAAN221

STRUKTUR ANTIGENHA 15 SUBTIPE NA 9 SUBTIPE

STRUKTUR ANTIGEN

STRUKTUR ANTIGENHEMAGLUTININ KEMAMPUAN MENGAGLUTINASI ERITROSIT FUNGSI MEDIASI ADHESI VIRUS SEL HOSPES FASILITASI PENETRASI VIRUS

NEURAMINIDASE MERUSAK PERTAHANAN MUKOSAMEMBANTU BUDDING VIRAL & PELEPASAN VIRUS

MERUPAKAN TONJOLAN GLIKOPROTEIN (FAKTOR VIRULENSI VIRUS ) BERUBAH TIBA2/SEC GRADUAL TERHINDAR DARI KEKEBALAN MEMORI SEL VARIABILITAS TINGGI

MORFOLOGI VIRUS

Influenza A Virus

Undergoes antigenic shifts and antigenic drifts with the haemagglutinin and neuraminidase proteins.Antigenic shifts of the haemagglutinin results in pandemics. Antigenic drifts in the H and N proteins result in epidemics.

Usually causes a mild febrile illness.

Death may result from complications such as viral/bacterial pneumonia.

EpidemiologyPandemics - influenza A pandemics arise when a virus with a new haemagglutinin subtype emerges as a result of antigenic shift. As a result, the population has no immunity against the new strain. Antigenic shifts had occurred 3 times in the 20th century.

Epidemics - epidemics of influenza A and B arise through more minor antigenic drifts as a result of mutation.

Past Antigenic Shifts1918H1N1Spanish Influenza 20-40 million deaths

1957H2N2Asian Flu1-2 million deaths

1968H3N2Hong Kong Flu700,000 deaths

1977H1N1 Re-emergenceNo pandemic

At least 15 HA subtypes and 9 NA subtypes occur in nature. Up until 2007, only viruses of H1, H2, H3 and H5 and NA (N1,N2) are known to infect and cause disease in humans.

Influenzae A virusesThe Influenzae virus can subdivided into different serotypes base on Antibody response to these viruses. The serotypes that have been confirmed in humans ordered by the number of known human pandemic deaths are:H1N1 spanish fluH2N2 Asian FluH3N2 Hongkong fluH5N1 Pandemic threat in 2007-2008 flu seasonH7N7 Zoonotic potentialH1N1 endemic in human and pigsH9N2, H7N2, H7N3, H10N7

Avian InfluenzaH5N1An outbreak of Avian Influenza H5N1 occurred in Hong Kong in 1997 where 18 persons were infected of which 6 died.The source of the virus was probably from infected chickens and the outbreak was eventually controlled by a mass slaughter of chickens in the territory.All strains of the infecting virus were totally avian in origin and there was no evidence of reassortment.However, the strains involved were highly virulent for their natural avian hosts.

H9N2 Several cases of human infection with avian H9N2 virus occurred in Hong Kong and Southern China in 1999.The disease was mild and all patients made a complete recoveryAgain, there was no evidence of reassortment

VARIASI ANTIGENIKANTIGENIC DRIFT

MUTASI KONSTAN PADA GLIKOPROTEIN

SERING PADA SISI TEMPAT GLIKOPROTEINBINDING AB, JARANG PADA SISI UNTUK MELEKAT PADA SEL HOSPES

PERUBAHAN SECARA GRADUAL KOMPOSISI ASAM AMINO MENURUN KEMAMPUAN SEL MEMORI SEL HOSPES UNTUK VIRUS

VARIASI ANTIGENIKANTIGENIC SHIFT GENETIC REASSORTMENT

PERTUKARAN DARI 1 GEN (GENOM VIRUS T/D 8 GEN DIKODE SS RNA) DENGAN GEN / STRAND DARI VIRUS INFLUENZAE YANG LAIN

SEBABKAN PANDEMIK

VARIASI ANTIGENIK

Theories Behind Antigenic Shift1.Reassortment of the H and N genes between human and avian influenza viruses through a third host. There is good evidence that this occurred in the 1957 H2N2 and the 1968 H3N2 pandemics.2. Recycling of pre-existing strains this probably occurred in 1977 when H1N1 re-surfaced.3. Gradual adaptation of avian influenza viruses to human transmission. There is some evidence that this occurred in the 1918 H1N1 pandemic.

Reassortment

Avian H3

Human H2

Human H3

Reassortment

PATOGENESATRANSMISI INHALASI (KONTAK DIREK/INDIREK)

DROPLETSAEROSOLSFOMITES

MASA INKUBASI 18 72 JAMVIRUS ADA PADA SEKRESI TRACHEA/HIDUNG 24-48 JAM SETELAH GEJALAPATOGENESA RECOVERY & PROTECTION SEL HOSPES

VIRAL REPLIKASI

GEJALA DAN KOMPLIKASIINFLUENZA TANPA KOMPLIKASI:DEMAM (38 400C)MIALGIA, HEADACHEOCULAR SYMPTOM FOTOPOBIA, BERAIR, ACHEBATUK KERING, NASAL DISCHARGE

PULMONARY COMPLICATIONS, SEQUELE:CROUP (LARYNGOTRACHEOBRONCHITIS AKUT) PADA ANAK2 PRIMARY INFLUENZA VIRUS PNEUMONIAINF SEK BAKTERI S. pneumonia, S. aureus, H. influenzae

GEJALA DAN KOMPLIKASINON-PULMONARY COMPLICATIONS:

MYOSITIS JARANG, PADA ANAK STLH INF TIPE BCARDIAC COMPLICATIONSENCEPHALOPATHYSINDROM REYESINDROM GUILLAIN BARRE

DIAGNOSA DAN PENCEGAHANDIAGNOSA :ISOLASI DAN IDENTIFIKASI VIRUS 3 10 HARISROLOGI PCR, ELISA, IMMUNOFLUORESCENSI

PENCEGAHAN :VAKSINASI EFEKTIF 70 90% VIRUS MATI YANG DITUMBUHKAN PADA TET (MENGANDUNG 3 MACAM VIRUS) USIA 6 BLN

FLUMIST NASSAL VACCINE 3 STRAIN ATTENUATED VIRUS MERANGSANG KEKEBALAN MUKOSA (SECRETORY)AMAN & EFEKTIF UNTUK ORANG USIA 5 49 TAHUNTIDAK UNTUK INDIVIDU YANG IMUN RENDAH

Laboratory DiagnosisDetection of Antigen - a rapid diagnosis can be made by the detection of influenza antigen from nasopharyngeal aspirates and throat washings by IFT and ELISA

Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs.

Serology - a retrospective diagnosis may be made by serology. CFT most widely used. HAI and EIA may be used to give a type-specific diagnosis

ManagementAmantidine is effective against influenza A if given early in the illness. However, resistance to amantidine emerges rapidlyRimantidine is similar to amantidine but but fewer neurological side effects.Ribavirin is thought to be effective against both influenza A and B.Neuraminidase inhibitors are becoming available. They are highly effective and have fewer side effects than amantidine. Moreover, resistance to these agents emerge slowly

PreventionInactivated split/subunit vaccines are available against influenza A and B.The vaccine is normally trivalent, consisting of one A H3N2 strain, one A H1N1 strain, and one B strain.The strains used are reviewed by the WHO each year.The vaccine should be given to debilitated and elderly individuals who are at risk of severe influenza infection. Amantidine can be used as an prophylaxis for those who are allergic to the vaccine or during the period before the vaccine takes effect.

Parainfluenza VirusssRNA virusenveloped, pleomorphic morphology5 serotypes: 1, 2, 3, 4a and 4bNo common group antigenClosely related to Mumps virus(Linda Stannard, University of Cape Town, S.A.)

PENDAHULUANTAKSONOMI :FAMILIA PARAMYXOVIRIDAEGENUS PARAMYXOVIRUSSPESIES HUMAN PARAINFLUENZA VIRUS

AGEN PENYEBAB INFEKSI PADA SALURAN PERNAFASAN BAYI DAN ANAK KECIL USIA DI BAWAH 5 TAHUN

SIFAT-SIFAT PENTINGVIRION BULAT, PLEOMORFIK, DIAMETER 150-300 nm, NUKLEOKAPSID HELIX 18 nmGENOM SS RNA, TIDAK BERSEGMEN, LURUS, - , 16 20 KBPROTEIN 6 PROTEIN STRUKTURALENVELOPE GLIKOPROTEIN :HEMAGLUTININ (HN) KADANG MEMBAWA AKTIVITAS NEUROAMINIDASEFUSI (F) RINGKIHREPLIKASI SITOPLASMA, BERTUNAS DI M PLASMACIRI KHAS ANTIGEN STABIL, PARTIKEL LABIL JUGA SANGAT INFEKSIUS

STRUKTUR DAN KOMPOSISIMIRIP VIRUS INFLUENZA, UKURAN LEBIH BESARGENOM TIDAK BERSEGMEN STABILPROTEIN :6 PROTEIN STRUKTIRAL 3 PROTEIN BERSATU RNA-NUKLEOPROTEIN (NP/N)PROTEIN P & L AKTIVITAS POLIMERASE VIRUS DLM TRANSKRIPSI DAN REPLIKASI3 PROTEIN PEMBENTUK ENVELOPEPROTEIN MATRIX (M) MENDASARI ENVELOPEGLIKOPROTEIN HN / H AKTIVITAS HEMAGLUTININ & NEURAMINIDASEGLIKOPROTEIN F FUSI MEMBRAN & AKTIVITAS HEMOLISIN

VIRAL STRUCTURE

Viral Life Cycle (RER=Rough endoplasmic reticulum)

SPECIES PARAMYXOVIRUSPARAINFLUEZAE (TIPE 1-4) CROUPS (TIPE 1&2), PNEUMONIA PADA ANAK < 5 THNPENY SAL PERNAFASAN ATAS (SERING SUBKLINIK) PADA ANAK & DEWASATIPE 1 VIRUS SENDAICOMMOND COLD

SPECIES PARAMYXOVIRUSVirus Measles :PNEUMONIA DI NEGARA BERKEMBANG SEBABKAN GIANT CELL PNEUMONIAVIRUS REPLIKASI PADA SAL PERNAFASAN BAWAH KERUSAKAN SEL INFEKSI SEKUNDER DENGAN BAKTERI PNEUMONIAMALNUTRISI RESPON IMMUN BURUKKOPLIKS SPOT PADA MUKOSA BUCCAL

SPECIES PARAMYXOVIRUS VIRUS MUMPS : GONDONG, PAROTITIS, ORCHITIS

VIRUS SINSITIA PERNAFASAN :PNEUMONIA

INFEKSI VIRUSPATOGENESA & PATOLOGIIMUNITASDIAGNOSA LABORATORIUMEPIDEMIOLOGIPENGOBATAN DAN PENCEGAHAN

Clinical ManifestationsCroup (laryngotraheobroncitis) - most common manifestation of parainfluenza virus infection. However other viruses may induce croup e.g. influenza and RSV.Other conditions that may be caused by parainfluenza viruses include Bronchiolitis, Pneumonia, Flu-like tracheobronchitis, and Corza-like illnesses.

Laboratory DiagnosisDetection of Antigen - a rapid diagnosis can be made by the detection of parainfluenza antigen from nasopharyngeal aspirates and throat washings.

Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs.

Serology - a retrospective diagnosis may be made by serology. CFT most widely used.

ManagementNo specific antiviral chemotherapy available.Severe cases of croup should be admitted to hospital and placed in oxygen tents.No vaccine is available.

Respiratory Syncytial Virus (RSV)ssRNA eveloped virus.belong to the genus Pneumovirus of the Paramyxovirus family.Considerable strain variation exists, may be classified into subgroups A and B by monoclonal sera.Both subgroups circulate in the community at any one time.Causes a sizable epidemic each year.

Clinical ManifestationsMost common cause of severe lower respiratory tract disease in infants, responsible for 50-90% of Bronchiolitis and 5-40% of BronchopneumoniaOther manifestations include croup (10% of all cases).In older children and adults, the symptoms are much milder: it may cause a corza-like illness or bronchitis.

Infants at Risk of Severe Infection1. Infants with congenital heart disease - infants who were hospitalized within the first few days of life with congenital disease are particularly at risk. 2. Infants with underlying pulmonary disease - infants with underlying pulmonary disease, especially bronchopulmonary dysplasia, are at risk of developing prolonged infection with RSV.3. Immunocompromized infants - children who are immunosuppressed or have a congenital immunodeficiency disease may develop lower respiratory tract disease at any age.

Laboratory DiagnosisDetection of Antigen - a rapid diagnosis can be made by the detection of RSV antigen from nasopharyngeal aspirates. A rapid diagnosis is important because of the availability of therapy

Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates. However, this will take several days.


Treatment and PreventionAerosolised ribavirin can be used for infants with severe infection, and for those at risk of severe disease.

There is no vaccine available.

RSV immunoglobulin can be used to protect infants at risk of severe RSV disease.

Adenovirusds DNA virusnon-envelopedAt least 47 serotypes are knownclassified into 6 subgenera: A to F

(Linda Stannard, University of Cape Town, S.A.)

Clinical Syndromes1. Pharyngitis 1, 2, 3, 5, 7 2. Pharyngoconjunctival fever 3, 7 3. Acute respiratory disease of recruits 4, 7, 14, 21 4. Pneumonia 1, 2, 3, 7 5. Follicular conjunctivitis 3, 4, 11 6. Epidemic keratoconjunctivitis 8, 19, 37 7. Pertussis-like syndrome 5 8.Acute haemorrhaghic cystitis 11, 21 9. Acute infantile gastroenteritis 40, 41 10.Intussusception 1, 2, 511.Severe disease in AIDS and other immunocompromized patients 5, 34, 3512. Meningitis 3, 7

Laboratory DiagnosisDetection of Antigen - a rapid diagnosis can be made by the detection of adenovirus antigen from nasopharyngeal aspirates and throat washings.

Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates, throat swabs, and faeces.


Treatment and PreventionThere is no specific antiviral therapy.

A vaccine is available against Adult Respiratory Distress Syndrome. It consists live adenovirus 4, 7, and 21 in enterically coated capsules. It is given to new recruits into various arm forces around the world.

Common Cold VirusesCommon colds account for one-third to one-half of all acute respiratory infections in humans.

Rhinoviruses are responsible for 30-50% of common colds, coronaviruses 10-30%.

The rest are due to adenoviruses, enteroviruses, RSV, influenza, and parainfluenza viruses, which may cause symptoms indistinguishable to those of rhinoviruses and coronaviruses.

RhinovirusssRNA virusBelong to the picornavirus familyssRNA virusacid-labileat least 100 serotypes are knownReconstructed Image of rhinovirus particle (Institute for Molecular Virology)

CoronavirusssRNA VirusEnveloped, pleomorphic morphology2 serogroups: OC43 and 229E

Pendahuluan CoronavirusVirus RNA polaritas positif, berenvelopCoronavirus manusia menyebabkan Common cold (rhinitis, selesma) dan gastroenteritis pada bayi.Corona virus yang ditemukan tahun 2003 SARS Associated Coronavirus infeksi saluran nafas bawah.Coronavirus sulit dikultur

Sifat CoronavirusGenom terdiri atas RNA-ss tidak bersegmen, positif-senseEnvelope mempunyai tonjolan membentuk koronaReplikasi di sitoplasmaFamili CoronaviridaeGenus Coronavirus dan TotovirusHuman Coronavirus ada 2 strain 229E dan OC43

SARS Associated CoronovirusBACK

Infeksi pada ManusiaVirus mempunyai tropisme pada sel epitel saluran nafas dan pencernaan.Virus manusia biasanya terbatas pada sal nafas atas, kecuali SARS Coronavirus yang menyebabkan pneumonia berat.Manifestasi klinis:Common cold (seperti rhinovirus)Gastroenteritis partikel virus pernah ditemukan dari fesesSARS virus berasal dari non-human

ImunitasImunitas yang terbentuk sesudah infeksi tidak bersifat mutlakAb terpenting adalah Ab terhadap protein permukaan virus95% pasien SARS membentuk Ab thd Ag virus (immunofluoresens/ELISA); serum konvalesens diambil > 28 hari sesudah gejala timbul

Pemeriksaan LaboratoriumDeteksi Ag dan As. NukleatELISAMikroskop elektron, sampel dari fesesPCR, sampel dari sekret sal nafas atau fesesKultur:Sukar dilakukanSARS virus sel Vero dari sampel orofaringSerologi:Konfirmasi diagnosis dengan ELISA

EpidemiologiCoronavirus tersebar di seluruh duniaPenyebab 15-30% kasus CCSARS:Penularan dengan kontak dekatDikenal adanya super spreader (seperti pada infeksi rubella, Ebola, dan tbc) tergantung faktor hospes, virus dan lingkungan.

Terapi dan PencegahanTidak ada terapi dan vaksin spesifik untuk CoronavirusKontrol SARS efektif dengan cara:Isolasi penderitaKarantina orang yang kontak dengan penderitaPembatasan kunjungan (travel restriction)Pemakaian alat pelindung (masker, goggles, baju, sarung tangan) bagi tenaga medisBACK

Common ColdDisebabkan oleh > 200 tipe virusRhinovirus, Coronavirus, adenovirus, influenza virus, parainfluenza virus, coxsackie virus, echovirus, RSVCC bisa menjadi faktor predisposisi infeksi sekunder, e.g. bakteriFaktor virulensi adalah adhesin pada permukaan partikel virusDiagnosis Lab: umumnya tidak perluBACK

SARS VACCINEAttenuated vaccine

SARS VACCINE

Drugs Development

respiratory viruses

Documents