Diarrhoeal Viruses

Titiek Djannatun Bagian Mikrobiologi-FKUY

Viral Gastroenteritis

It is thought that viruses are responsible for up to 3/4 of all infective diarrhoeas.
Viral gastroenteritis is the second most common viral illness after upper respiratory tract infection. In developing countries, viral gastroenteritis is a major killer of infants who are undernourished. Rotaviruses are responsible for half a million deaths a year.

Many different types of viruses are found in the gut but

only some are associated with gastroenteritis.

Viruses found in the gut (1)

A. Associated with gastroenteritis

Rotaviruses Adenoviruses 40 41 Caliciviruses Norwalk like viruses or SRSV (Small Round Structured Viruses) Astroviruses SRV (Small Round Viruses) Coronaviruses Toroviruses

Viruses found in the gut (2)

B. Found in the gut, not normally associated with gastroenteritis

Polio Coxsackie A Coxsackie B Echo Enteroviruses 68-71 Hepatitis A Hepatitis E Adenoviruses 1-39 Reoviruses

C. Found in the gut as opportunistic infection

CMV HSV VZV HIV

VIRUS PENYEBAB GASTROENTERITIS AKUT PADA MANUSIA

VIRUS UKURAN (nm) EPIDEMIOLOGI KEPENTINGAN DLM MENYEBABKAN PENY
YA TIDAK TIDAK YA

ROTAVIRUS GRUP A GRUP B GRUP C ADENOVIRUS ENTERIK NORWALKVIRUS & VIRUS MIRIPNYA CALICIVIRUS ASTROVIRUS

70 70 70 70-80

PENY TPTG DIARE ENDEMIS BERAT PD BAYI & ANAK KCL DI SELURUH DUNIA WABAH DIARE PD ANAK & DEWASA DI CHINA KASUS SPORADIS & KDG WABAH DIARE PD ANAK-ANAK TERPENTING KE DUA PENYAKIT DIARE ENDEMIS PD BAYI & ANAK KCL DI SELURUH DUNIA PENY PTG WABAH MUNTAH & PENY DIARE PD ANAK YG LBH BESAR & DEWASA DI KELUARGA, KOMUNITAS, PERKANTORAN , SERING KRN PENGOLAHAN MAKANAN KASUS SPORADIS & KDG WABAH PENY DIARE PD BAYI, ANAK KCL & LANJUT USIA KASUS SPORADIS & KDG WABAH PENY DIARE PD BAYI, ANAK KCL & LANJUT USIA

27-32

TIDAK

28-40 28

TIDAK TIDAK

ROTAVIRUS

PENDAHULUAN
FAMILIA GENUS SPECIES : REOVIRIDAE : ROTAVIRUS : ROTAVIRUS

GENUS REOVIRIDAE PENTING BAGI MANUSIA YANG LAIN ORTHOREOVIRUS, COLTIVIRUS, ORBIVIRUS PENYEBAB ENTERITIS, DIARHAE DISEASES PADA BAYI MANUSIA DAN HEWAN PENYEBAB PENTING GASTROENTERITIS AKUT PADA BAYI DI SELURUH DUNIA TERUTAMA PADA ANAK PRA SEKOLAH SERING JUGA PADA ORANG DEWASA

Rotaviruses (1)

Naked double stranded RNA viruses, 80 nm in diameter. Also found in other mammals and birds, causing diarrhoea. Account for 50-80% of all cases of viral gastroenteritis.

Usually endemic, but responsible for occasional outbreaks.

Causes disease in all age groups but most severe symptoms in neonates and young children. Asymptomatic infections common in adults and older children. Symptomatic infections again common in people over 60. Up to 30% mortality rate in malnourished children, responsible for up to half a million deaths per year.

SIFAT PENTING
VIRION IKOSAHEDRAL, DIAMETER 60-80 nm, 132 KAPSOMER, BERKULIT TUNGGAL

GENOM
PROTEIN

Ds RNA, LINIER, 11 SEGMEN, 680 bp,

9 PROTEIN STRUKTURAL, CORE BERISI BEBERAPA ENZIM

ENVELOPE
REPLIKASI CIRI KHAS

TDK ADA ( TRANSIENT PSEUDOENVELOPE), TERDAPAT SELAMA MORFOGENESIS PARTIKEL

SITOPLASMA PENYUSUNAN GENETIK TERJADI MUDAH PENYEBAB UTAMA DIARE PADA BAYI

Rotavirus Particle

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

TUGAS MENGKODE GEN

STRUKTUR ANTIGEN
OUTER STRUCTURAL PROTEIN: VP4 VIRAL HEMAGLUTININ VP7 ANTIGEN SUBGRUP INNER CORE STRUCTURAL PROTEIN: VP6 ANTIGEN SUBGRUP ANTIGEN DETERMINANT PENTING VP1,2,3 GRUP A F: D, E, F TDK DITEMUKAN PD MANUSIA A DIARE RINGAN PD ANAK & DEWASA B DI CHINA DIARE PD ANAK2, DIARE RINGAN PD DEWASA

STRUKTUR ANTIGEN
15 SEROTIPE: 6 BERDASARKAN AB THDP VP7 (P TYPE) 9 BERDASARKAN VP4 (G TYPE) 9 SEROTIPE ROTAVIRUS MANUSIA 5 SEROTIPE ROTAVIRUS HEWAN ROTAVIRUS GRUP A GASTROENTERITIS PADA MANUSIA DETEKSI ELISA, IMMUNOFLUORESCENS

PATOGENESA

Rotavirus, an RNA virus, is a member of the family Reoviridae and includes seven distinct antigenic groups (A-G). Group A viruses are the major cause of rotavirus diarrhea in the U.S. and groups B and C can cause gastroenteritis in adults In developing countries, rotavirus accounts for a significant number of gastroenteritis-associated deaths. In the United States, rotavirus accounts for a 3.5 million cases of diarhea, 50,000 hospitalizations, and 20 deaths in children younger than 5 years of age.

Rotavirus is an important cause of gastroenteritis in infants and young children in both developed and developing countries (4). promote growth

Rotaviruses (2)

80% of the population have antibody against rotavirus by the age of 3.

More frequent during the winter. Faecal-oral spread. ? respiratory droplets 24-48 hr incubation period followed by an abrupt onset of vomiting and diarrhoea, a low grade fever may be present. Diagnosed by electron microscopy or by the detection rotavirus antigens in faeces by ELISA or other assays. Live attenuated vaccines now available for use in children. of

PATOGENESA
RESIKO INFEKSI: ANAK USIA 3 TH, MAX INSIDEN UMUR 6-24 BLN SERING PADA USIA 5 BLN PENURUNAN IMUNITAS DIDAPAT DARI IBU DITEMUKAN PD PETUGAS MILITER, PEKERJA RS, SEBABKAN TRAVELERS DIARRHEA WABAH NOSOKOMIAL PADA ORG DEWASA ASIMPTOMATIS, SERING TERTULAR DARI ANAK TERINFEKSI TIDAK TERJADI REINFEKSI PD ANAK DAN DEWASA PENULARAN ANTAR MANUSIA VIA FECAL ORAL, FOMITES, MAKANAN, AIR

PATOGENESA
VIRUS VILLI USUS (VP4) REPLIKASI PADA SITOPLASMA SEL USUS, MASUK DENGAN CARA ENDOSITOSIS (MERUSAK MEKANISME TRANSPORT) NSP4 (ENTEROTOKSIN, MERANGSANG SEKRESI) VIRUS + SEL USUS YANG RUSAK MASUK KE LUMEN USUS FESES EKSKRESI VIRUS BERAKHIR 2-12 HARI SEHAT BILA NUTRISI BAIK DIARE (3-8 MINGGU) KELEMAHAN ABSORPSI NATRIUM DAN GLUKOSA AKIBAT KERUSAKAN VILLI USUS

GEJALA KLINIS DAN DIAGNOSA

BAYI & ANAK FEVER, MUNTAH, DIARE, DEHIDRASI DIARE WATERY WITHOUT BLOOD OR MUCUS KASUS BERAT NEUROLOGIC SYMPTOM PD ANAK DG IMUNODEFISIENSI BERMINGGU/BERBULAN DIAGNOSA: IDENTIFIKASI VIRUS FESES/RECTAL SWAB ELISA LATEX AGGLUTINATION POLYACRYLAMIDE GEL ELECTROPHORESIS GRUP A / NON GRUP A

TERAPI
MENGGANTI CAIRAN DAN ELEKTROLIT YANG HILANG CEGAH DEHIDRASI ASI PADA BAYI 24 JAM STLH ONSET MAKANAN BERGIZI LAKTOSA BEBAS KH 24 JAM SETELAH ONSET MINUMAN MENGANDUNG RENDAH SODIUM, OSMOLARITAS TINGGI JUICE BUAH & SOFT DRINK JANGAN ANTIVIRAL

PENCEGAHAN
CEGAH INFEKSI FECAL ORAL BAYI EKSKRESI VIRUS PADA FESES 4 7 HARI STLH ONSET, PENDERITA DENGAN GANGGUAN IMUN 30 HARI ATAU LEBIH HYGIENE PERAWATAN BAYI VIRUS TAHAN PADA PERMUKAAN, TANGAN, AIR TERKONTAMINASI SELAMA BEBERAPA HARI RESISTEN DESINFEKTAN BIASA, DIINAKTIF DENGAN KLORIN CUCI TANGAN SEBELUM DAN SESUDAH MENANGANI PASIEN ATAU BAYI 1999 DIKEMBANGKAN VAKSIN DI USA (RRV-TV) LIVE TETRAVALENT RHESUS-HUMAN REASSORTANT VACCINE (ROTASHILD) HUMAN G TYPE 1, 2, 4 & SIMIAN G TYPE 3

Adenovirus Particle

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

Enteric Adenoviruses

Naked DNA viruses, 75 nm in diameter.

Fastidious enteric adenovirus types 40 and 41 are associated with gastroenteritis. Associated with cases of endemic gastroenteritis, usually in young children and neonates. Can cause occasional outbreaks. Possibly the second most common viral cause of gastroenteritis (715% of all endemic cases). Similar disease to rotaviruses

Most people have antibodies against enteric adenoviruses by the age of three.
Diagnosed by electron microscopy or by the detection of adenovirus antigens in faeces by ELISA or other assays.

Caliciviruses

Small RNA viruses, characteristic surface morphology consisting of hollows. particles 35 nm in diameter. Associated mainly with epidemic outbreaks of gastroenteritis, although occasionally responsible for endemic cases. Like Norwalk type viruses, vomiting is the prominent feature of disease. Majority of children have antibodies against caliciviruses by the age of three. Diagnosed by electron microscopy only, often difficult to diagnose because of small size.

Calicivirus Particles

(Source: ICTV database)

NORWALKVIRUS

Norwalk-like Viruses

Small RNA viruses, with ragged surface, 35 nm in diameter, now classified as caliciviruses.
Always associated with epidemic outbreaks of adults more commonly affected than children. gastroenteritis,

Associated with consumption of shellfish and other contaminated foods. Aerosol spread possible as well as faecal-oral spread.
Also named "winter vomiting disease", with vomiting being the prominent symptom, diarrhoea usually mild.

Antibodies acquired later in life, in the US, only 50% of adults are seropositive by the age of 50.
Diagnosis is made by electron microscopy and by PCR.

KLASIFIKASI
FAMILIA GENUS SPESIES : CALICIVIRIDAE : CALICIVIRUS : NORWALKVIRUS

Norwalk-like Virus Particles

(Source: ICTV database)

PENDAHULUAN
VIRUS PENYEBAB GASTROENTERITIS EPIDEMIKA MELALUI AIR, MAKANAN, KERANG BERBENTUK BULAT KECIL Ss RNA (7,6 kb), POLARITAS POSITIF, TIDAK BERENVELOPE, 27-35 nm, MEMPUNYAI PROTEIN KAPSID TUNGGAL, RAGGED SURFACE 1972 DITEMUKAN DR FESES PASIEN GASTROENTERITIS DI NORWALK, OHIO SEROTYPE HAWAII, SNOW MOUNTAIN (CO), MC (MD), TAUNTON (ENGLAND), OTOFUKE (JAPAN), SAPPORO (JAPAN) AB ROTAVIRUS AWAL MASA ANAK-ANAK AB NORWALK 50% ORANG DEWASA, NEGARA BERKEMBANG USIA 4 TAHUN

PATOGENESA

GEJALA KLINIS
ANAK-ANAK & DEWASA BISA TERTULAR MASA INKUBASI PENDEK < 24 JAM (6-96 JAM, RATARATA 24-30 JAM), ONSET CEPAT PERJALANAN KLINIS PENDEK < 3 HARI, BERAKHIR 24-48 JAM NAUSEA, VOMITING, KRAM ABDOMEN, WATERY DIARRHEA DISERTAI SAKIT KEPALA, DEMAM, MALAISIE TIDAK IMUNITAS JANGKA PANJANG, 2 TH BISA TERTULAR DG VIRUS YANG SAMA KEJADIAN INSTITUSI, KAPAL MAKANAN & MINUMAN TERKONTAMINASI PENYEBARAN FECO-ORAL, VOMITUS

DIAGNOSA & TERAPI

DIAGNOSA: IMMUNE EM SEROLOGI EPIDEMIOLOGI TERAPI: SIMTOMATIS CUCI TANGAN PENGOLAHAN MAKANAN YG BAIK PEMURNIAN AIR MINUM, AIR KOLAM RENANG

CALICIVIRUS YANG LAIN

DITEMUKAN 1976 Ss RNA, TIDAK BERENVELOPE, 30-45 nm, BULAT, IKOSAHEDRAL, PROTEIN KAPSID TUNGGAL ANTIGENIC TYPE UK 1 5, JAPAN/SAPPORO EPIDEMIOLOGI WORLWIDE DISTRIBUTION KEJADIAN PADA BAYI, ANAK-ANAK USIA SEKOLAH, TERUTAMA USIA 4 TAHUN TRANSMISI FECO-ORAL, MAKANAN KONTAMINASI (SEAFOOD)

GEJALA KLINIS & DIAGNOSA

MASA INKUBASI 12 JAM SAMPAI 4 HARI INFEKSI ASIMTOMATIS DIARE RINGAN, MUNTAH, ANOREXIA, FEVER SIMPTOM PERNAFASAN (1/3 PENDERITA) SEPERTI FLU DIAGNOSA: EM EKSKRESI VIRAL ELISA IMMUN EM

ASTROVIRUS
1975 WABAH GASTROENTERITIS Ss RNA, TIDAK BERENVELOPE, 27-32 nm, FAMILIA ASTROVIRIDAE PADA FESES BAYI, ANAK USIA SANGAT MUDA 7 SEROTIPE MANUSIA GEJALA DIARE, HEADACHE, NAUSEA, FEVER (SUHU TIDAK TERLALU TINGGI), MUNTAH EPIDEMIOLOGI WORLDWIDE, TERUTAMA ANAK USI < 7 TAHUN TRANSMISI FECAL-ORAL PENULARAN SEAFOOD/AIR TERKONTAMINASI FESES DIAGNOSA EM, IMMUNE EM, IMMUNEFLUORESCENS (SEROTIPE)

Astroviruses

Small RNA viruses, named because of star-shaped surface morphology, 28 nm in diameter. Associated with cases of endemic gastroenteritis, usually in young children and neonates. Can cause occasional outbreaks. Responsible for up to 10% of cases of gastroenteritis. Similar disease to rota and adenoviruses.

Most people have antibodies by the age of three.

Diagnosed by electron microscopy only, often difficult because of small size. very

Astrovirus Particles

(Source: ICTV database)

Other Possible Diarrhoeal Viruses

Coronaviruses

RNA viruses with a crown-like appearance Not convincing associated with gastroenteritis at present

Small Round Viruses

Small virus-like particles with a smooth surface, 22-28nm in diameter May possibly be parvoviruses, enteroviruses, or cubic bacteriophages Occasionally seen in the faeces of endemic or epidemic cases of gastroenteritis