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

ROTAVIRUS

GRUP A 70 PENY TPTG DIARE ENDEMIS BERAT PD BAYI & ANAK KCL DI SELURUH DUNIA

YA

GRUP B 70 WABAH DIARE PD ANAK & DEWASA DI CHINA TIDAK

GRUP C 70 KASUS SPORADIS & KDG WABAH DIARE PD ANAK-ANAK TIDAK

ADENOVIRUS ENTERIK

70-80 TERPENTING KE DUA PENYAKIT DIARE ENDEMIS PD BAYI & ANAK KCL DI SELURUH DUNIA

YA

NORWALKVIRUS & VIRUS MIRIPNYA

27-32 PENY PTG WABAH MUNTAH & PENY DIARE PD ANAK YG LBH BESAR & DEWASA DI KELUARGA, KOMUNITAS, PERKANTORAN , SERING KRN PENGOLAHAN MAKANAN

TIDAK

CALICIVIRUS 28-40 KASUS SPORADIS & KDG WABAH PENY DIARE PD BAYI, ANAK KCL & LANJUT USIA

TIDAK

ASTROVIRUS 28 KASUS SPORADIS & KDG WABAH PENY DIARE PD BAYI, ANAK KCL & LANJUT USIA

TIDAK

ROTAVIRUS

PENDAHULUAN

FAMILIA : REOVIRIDAE

GENUS : ROTAVIRUS

SPECIES : 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 Ds RNA, LINIER, 11 SEGMEN, 680 bp,

PROTEIN 9 PROTEIN STRUKTURAL, CORE BERISI BEBERAPA ENZIM

ENVELOPE TDK ADA ( TRANSIENT PSEUDOENVELOPE), TERDAPAT SELAMA MORFOGENESIS PARTIKEL

REPLIKASI SITOPLASMA

CIRI KHAS 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 HEMAGLUTININVP7 ANTIGEN SUBGRUP

INNER CORE STRUCTURAL PROTEIN:VP6 ANTIGEN SUBGRUP

ANTIGEN DETERMINANT PENTINGVP1,2,3

GRUP A – F:D, E, F TDK DITEMUKAN PD MANUSIAA DIARE RINGAN PD ANAK & DEWASAB 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 of

rotavirus antigens in faeces by ELISA or other assays. Live attenuated vaccines now available for use in children.

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 (7-

15% 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 gastroenteritis,

adults more commonly affected than children. 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 : CALICIVIRIDAE

GENUS : CALICIVIRUS

SPESIES : NORWALKVIRUS

Norwalk-like Virus Particles

(Source: ICTV database)

PENDAHULUAN

VIRUS PENYEBAB GASTROENTERITIS EPIDEMIKA MELALUI AIR, MAKANAN, KERANG BERBENTUK BULAT KECILSs RNA (7,6 kb), POLARITAS POSITIF, TIDAK BERENVELOPE, 27-35 nm, MEMPUNYAI PROTEIN KAPSID TUNGGAL, RAGGED SURFACE1972 DITEMUKAN DR FESES PASIEN GASTROENTERITIS DI NORWALK, OHIOSEROTYPE HAWAII, SNOW MOUNTAIN (CO), MC (MD), TAUNTON (ENGLAND), OTOFUKE (JAPAN), SAPPORO (JAPAN)AB ROTAVIRUS AWAL MASA ANAK-ANAKAB 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, RATA-RATA 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 ASTROVIRIDAEPADA FESES BAYI, ANAK USIA SANGAT MUDA7 SEROTIPE MANUSIAGEJALA DIARE, HEADACHE, NAUSEA, FEVER (SUHU TIDAK TERLALU TINGGI), MUNTAHEPIDEMIOLOGI WORLDWIDE, TERUTAMA ANAK USI < 7 TAHUNTRANSMISI FECAL-ORALPENULARAN SEAFOOD/AIR TERKONTAMINASI FESESDIAGNOSA 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 very

difficult because of small size.

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