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Bagaimana rotavirus manusia umumnya ditularkan?

Bagaimana rotavirus manusia umumnya ditularkan?


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Saya tahu rotavirus adalah virus RNA untai ganda dan saya bertanya-tanya apakah penularan pada manusia mirip dengan cara penularan melalui hewan.


Penularan fekal-oral. Referensi dari https://en.wikipedia.org/wiki/Rotavirus


Bagaimana rotavirus manusia umumnya ditularkan? - Biologi

Mekanisme Infeksi dan Penyebaran Virus Melalui Tubuh

(halaman 595-614 dalam buku Anda)

Patogenesis virus = seluruh proses dimana virus menyebabkan penyakit

Virulensi = patogenisitas = kemampuan virus untuk menyebabkan penyakit

  • Partikel besar (10 & 181m ke atas) disaring pada lapisan mukosiliar turbinat hidung. Kemudian disapu ke kerongkongan
  • Partikel intermediet (5-10 µm) biasanya terperangkap pada lapisan mukosiliar trakea dan bronkiolus. Dari sana mereka tersapu ke kerongkongan.
  • Partikel yang lebih kecil sering sampai ke alveoli paru-paru di mana mereka dapat menyebabkan infeksi atau dihancurkan oleh makrofag alveolar.
  • paru-paru dan jaringan mukosa lainnya adalah tempat sekresi imunoglobulin (IgA) yang akan memfasilitasi pembunuhan virus
  • lapisan kerongkongan yang tebal
  • antibodi sekretori (IgA)
  • bahan kimia - empedu, asam lambung, protease

C. Kulit, saluran genital, dan konjungtiva

Kulit: Lapisan luar yang keras hampir tidak dapat ditembus - masuknya melalui luka, goresan, gigitan (serangga atau hewan), iatrogenik (intervensi manusia - jarum)

Beberapa virus menghasilkan infeksi lokal di kulit (papiloma), tetapi sebagian besar bergerak melalui kulit dan ke lapisan yang lebih dalam dan akhirnya ke aliran darah (viremia).

Saluran umum: saluran genital adalah jalan masuk bagi patogen penting seperti HSV, papiloma, HIV, HTLV, Hepatitis B dan C. Aktivitas seksual dapat menyebabkan robekan kecil pada vagina dan uretra, tempat virus dapat masuk. Beberapa bervariasi tetap lokal (virus papiloma), yang lain menyebar secara sistemik (HIV, HepB dan C, HTLV)

Mata: Konjungtiva memiliki mekanisme perlindungan (lisozim dalam air mata, mencuci, menyeka kelopak mata, dll) dan biasanya bukan merupakan rute infeksi. Beberapa virus, bagaimanapun, dapat menginfeksi di sini. Biasanya infeksi melalui robekan kecil di konjungtiva dan bahkan infeksi biasanya dimulai dengan inokulasi langsung (menyentuh secara fisik sesuatu yang memiliki virus di atasnya).

A. Virus memiliki pilihan untuk membuat infeksi pada titik mereka memasuki tubuh atau memasuki aliran darah dan membuat infeksi pada titik lain.

Arah tunas sangat penting untuk bagaimana virus menyebar. Jika menyebar di permukaan apikal biasanya dilepaskan ke lumen di mana ia dapat menyebar dengan cepat pada permukaan epitel lumen, atau bahkan ditumpahkan ke bagian luar inang. Jika tunas basolateral, ia akan menghadapi gerakan lambat dan berbagai pertahanan tuan rumah. Dalam banyak kasus, tunas menentukan jenis infeksi yang terjadi.

B. Penyebaran Lokal pada Permukaan Epitel

Hal ini tidak banyak terjadi pada kulit karena virus sulit diangkut tanpa bantuan air. Papillomavirus menginfeksi lapisan basal epidermis tetapi virus tidak matang sampai sel-sel bergerak menuju permukaan luar kulit dan menjadi keratan. Pada titik ini, virus matang dan menghasilkan kutil. Beberapa virus pox, seperti molluscum contagiosum, orf dan tanapox tetap terlokalisasi di kulit, menyebar dari sel ke sel, dan menyebabkan benjolan (titik infeksi) di kulit. Poxvirus lainnya, seperti cacar, masuk ke sistem limfatik dan menyebar ke seluruh tubuh.

Dalam epitel internal permukaan dilapisi dengan air dan ini membuat penyebaran lebih mudah. Oleh karena itu infeksi ini cenderung memiliki waktu inkubasi yang lebih singkat. Dalam kasus paramyxoviruses, virus influenza, dan rotavirus jaringan epitel terinfeksi tetapi tidak ada invasi di luar lapisan ini - mungkin karena kurangnya reseptor seluler di lapisan jaringan yang lebih dalam, atau mungkin karena suhu yang lebih tinggi di jaringan seluler yang lebih dalam. . Namun, mereka masih bisa sangat parah.

C. Invasi Subepitel ion dan Penyebaran Limfatik

Sistem limfa adalah sistem saluran, pembuluh, dan kelenjar yang terletak tepat di bawah membran basal kulit. Tujuan utama dalam imunosurveilans -- mendeteksi dan menyingkirkan penyerang asing. Banyak sel imun dapat ditemukan di kelenjar getah bening dan cairan getah bening. Makrofag mungkin adalah pembela utama. Mereka memakan virus dan menggunakan bagian protein untuk mengaktifkan respon imun.

Virus menghindari sistem getah bening dengan dua cara utama. Mereka dapat langsung menginfeksi sel-sel kekebalan (yang akhirnya menemukan jalan mereka ke dalam aliran darah), atau mereka dapat melewati dengan cepat melalui sistem getah bening (menghindari makrofag) dan ke dalam aliran darah.

D. Viremia Primer dan Sekunder

Masuknya virus pertama kali ke dalam aliran darah adalah viremia primer (bisa aktif atau pasif). Viremia ini mungkin subklinis dan merupakan rute dimana virus sampai ke tempat infeksi mereka. Setelah infeksi terjadi, maka dapat terjadi viremia sekunder karena pelepasan virus dari organ yang terinfeksi. Viremia sekunder ini kemudian dapat menjadi penyebab infeksi di tempat lain di tubuh.

Virus dapat bersirkulasi secara bebas di dalam darah (hepadnavirus, togavirus, flavivirus, dan enterovirus), atau dapat berasosiasi dengan leukosit (WBC), trombosit, atau eritrosit dan disimpan olehnya (HIV, Rift Valley Fever, Colorado tick fever). Infeksi virus yang terakhir lebih sulit untuk dibersihkan dan cenderung menjadi infeksi yang lebih persisten.

Makrofag sangat berkaitan dengan jenis infeksi yang mungkin disebabkan setelah viremia primer. Faktor-faktor yang penting adalah area tubuh di mana infeksi terjadi (berbagai jenis makrofag di berbagai bagian tubuh), kerentanan makrofag terhadap infeksi, keadaan aktivasinya, dan usia serta genetik dari organisme tersebut. tuan rumah. Dalam kebanyakan kasus, makrofag adalah penghancur virus yang efisien, tetapi dalam beberapa kasus, seperti pada demam berdarah, mereka dapat berfungsi sebagai inang dan membawa virus ke berbagai bagian tubuh.

Infeksi di suatu tempat setelah viremia primer sangat berkaitan dengan sifat sel endotel vaskular di tempat itu dan jumlah aliran darah yang melalui tempat itu. Virion cenderung menempel lebih baik di daerah di mana aliran darah lebih lambat. Virus dapat menembus sel endotel dengan meremas antar sel, atau dengan menginfeksinya secara langsung dan berpindah dari sel ke sel.

Karena sistem kekebalan Anda terus-menerus melawan virus dalam aliran darah, pasti ada semacam mekanisme untuk terus-menerus mengeluarkan virus untuk mempertahankan viremia. Ini sangat penting dalam penyebaran ke bagian tubuh tertentu seperti sistem saraf pusat, di mana viremia konstan diperlukan agar virus dapat melewati sawar darah/otak. Viremia biasanya dipertahankan oleh infeksi langsung sel darah (biasanya leukosit) atau infeksi organ lain yang terus-menerus mengeluarkan virus ke dalam aliran darah.

E. Tempat infeksi sekunder.

Kulit - ini biasanya menghasilkan semacam ruam yang terdiri dari makula, papula, vesikel atau pustula.

SSP - penyebaran biasanya dari pembuluh darah di meningen dan pleksus koroid dan infeksi neuron di cairan serebrospinal, atau langsung dari pembuluh darah otak dan sumsum tulang belakang. Penyebaran biasanya baik melalui infeksi sel endotel atau transportasi langsung melalui lapisan endotel. Jarang oleh leukosit yang terinfeksi pindah ke otak.

Rute penting lainnya adalah perjalanan virus ke neuron (rabies, varicella, herpes simplex)

Meningitis adalah infeksi selaput otak dan SSP (meninges)

Ensefalitis adalah infeksi otak

Organ lain - hati (hepatitis), jantung (karditis), paru-paru (pneumonia), kelenjar ludah (gondong), testis (orkitis)

Janin - 1) efek teratogenik (CMV dan rubella) seperti ketulian, kebutaan, kelainan jantung dan otak bawaan, 2) kematian janin (cacar, parvovirus 19)

Dasar gerak tropisme

  • reseptor seluler
  • faktor transkripsi - beberapa elemen penambah hanya bekerja untuk faktor transkripsi sel tertentu (hep B di hati, papiloma 11 di keratinosit)
  • protease seluler - adanya protease seluler yang diperlukan untuk membelah protein virus untuk membuat virus dewasa - influenza HA dan tryptase Clara

Tempat masuknya sering menentukan cara penyebaran dan tingkat keparahan penyakit - Rabies.

Diperlukan untuk pemeliharaan infeksi pada populasi.

A. Sekresi respiratorik dan orofaringeal

lendir atau air liur dari batuk bersin dan berbicara - campak. cacar air, rubella. penularan langsung air liur atau lendir - virus herpes, CMV, EBV

B. Kotoran

virus enterik - sering dapat bertahan untuk jangka waktu yang lebih lama (tidak berselubung)

C. Kulit

kontak langsung yang diperlukan untuk penularan - moluskum kontagiosum, kutil, herpes genital, poxvirus.

D. Urine

Viruria adalah cara utama penumpahan pada infeksi arenavirus pada hewan pengerat. Virus gondok dan CMV pada manusia

E. Susu

CMV dalam ASI

F. Sekresi alat kelamin

HIV, HSV I, HSV II, papillomavirus, hepatitis B dan C, HTLV

G. Darah dan cairan tubuh

Hepatitis B, C, D, HIV, HTLV. Untungnya beberapa demam berdarah yang lebih fatal hanya dapat ditularkan dengan cara ini.

H. No Shedding -- cerita Kuru


Rotavirus mengalihdayakan protein seluler CK1-alpha untuk merakit pabrik virus

Mikrograf elektron transmisi partikel rotavirus utuh, bercangkang ganda Mikrograf elektron transmisi partikel rotavirus utuh, bercangkang ganda. Kredit: CDC

Rotavirus, seperti semua virus, berkembang biak di dalam sel hidup. Membuat virus baru memerlukan perakitan pabrik replikasi melalui proses yang kompleks dan sedikit diketahui yang melibatkan komponen virus dan seluler. Sebuah laporan di Prosiding National Academy of Sciences oleh tim multidisiplin yang dipimpin oleh para peneliti di Baylor College of Medicine mengungkapkan bahwa pembentukan pabrik rotavirus bergantung pada protein seluler yang disebut CK1α, yang secara kimiawi memodifikasi komponen virus NSP2, sehingga memicu lokalisasi dan perakitannya ke dalam pabrik virus, langkah penting dalam pembentukan virus baru.

“Salah satu kepentingan laboratorium kami adalah untuk lebih memahami proses perakitan pabrik rotavirus,” kata rekan penulis pertama Dr. Jeanette M. Criglar, staf ilmuwan virologi molekuler dan mikrobiologi di Baylor College of Medicine dan lulusan program .

Dalam proses penyelidikan ini, Criglar dan rekan-rekannya menemukan bahwa protein seluler yang disebut CK1α diperlukan untuk merakit pabrik rotavirus. "Ketika kami membungkam CK1α dalam sel sebelum infeksi rotavirus, kami menurunkan replikasi virus lebih dari 90 persen, menunjukkan bahwa CK1α sebagian besar mengendalikan pembentukan pabrik rotavirus," kata Criglar.

CK1α adalah enzim dengan kemampuan untuk memodifikasi protein lain dan fungsinya secara kimia dengan menambahkan gugus fosfat ke dalamnya. Para peneliti menemukan bahwa CK1α memediasi efeknya pada pembentukan pabrik replikasi rotavirus dengan menambahkan gugus fosfat ke protein rotavirus yang disebut NSP2. Modifikasi fosfat ini memicu perakitan unit oktamerik NSP2 menjadi struktur seperti kristal dan tampaknya diperlukan untuk pembentukan pabrik rotavirus.

"CK1α biasanya menangani tugas-tugas rumah tangga di dalam sel. Rotavirus mengambil keuntungan dari aktivitas protein ini, 'mengalihdayakannya' untuk merakit pabrik virus," kata penulis korespondensi Dr. Mary K. Estes, Cullen Foundation Endowed Professor Chair of Human and Molecular Virologi di Baylor College of Medicine dan direktur pendiri emeritus dari Pusat Penyakit Pencernaan Pusat Medis Texas.

Selain itu, tim menemukan bahwa protein rotavirus NSP2 dapat menambahkan gugus fosfat ke dirinya sendiri, sehingga memodifikasi aktivitasnya dan mempengaruhi protein lain yang terlibat dalam perakitan virus. Ini adalah temuan yang mengejutkan, jelas Estes, karena fungsi ini belum pernah dijelaskan sebelumnya untuk protein virus ini.

“Secara keseluruhan, temuan kami menunjukkan bahwa kaskade modifikasi kimia fosfat, yang dimediasi sebagian oleh CK1α dan NSP2, sangat penting untuk pembentukan pabrik rotavirus,” kata rekan penulis Dr. BV Venkataram Prasad, profesor dan Ketua Alvin Romansky dalam Biokimia dan Biologi Molekuler, dan anggota Pusat Kanker Komprehensif Dan L Duncan di Baylor. "Temuan ini memberikan wawasan baru yang dapat mengarah pada cara yang sebelumnya tidak terduga untuk melawan penyakit di masa depan." "Ada kemungkinan bahwa temuan kami juga dapat menjelaskan perakitan pabrik virus untuk virus lain yang juga membutuhkan CK1α, seperti hepatitis C, atau yang juga membentuk pabrik virus sitoplasma seperti West Nile dan virus dengue," kata Criglar. "Jika kita dapat memahami bagaimana virus lain merakit pabriknya, mungkin menggunakan mekanisme yang mirip dengan rotavirus, kita dapat memajukan pemahaman tentang penyakit itu juga."


Diagnosis dan Tes

Bagaimana rotavirus didiagnosis?

Jika anak Anda memiliki tanda-tanda rotavirus, hubungi penyedia layanan kesehatan Anda. Penyedia seringkali dapat mendiagnosis rotavirus berdasarkan gejala dan pemeriksaan fisik. Dalam beberapa kasus, mereka mungkin mengambil sampel tinja (kotoran) untuk mengujinya terhadap rotavirus. Tapi, langkah ini biasanya tidak diperlukan.

Jika Anda perlu mengambil sampel tinja, penyedia Anda akan memberi Anda wadah steril (bebas kuman). Anda mengumpulkan beberapa tinja anak Anda di dalam wadah. Sebuah laboratorium menganalisis tinja untuk rotavirus.


Isi

Enterovirus adalah anggota keluarga picornavirus, kelompok besar dan beragam dari virus RNA kecil yang dicirikan oleh RNA genomik untai positif tunggal. Semua enterovirus mengandung genom sekitar 7.500 basa dan diketahui memiliki tingkat mutasi yang tinggi karena replikasi dengan ketelitian yang rendah dan rekombinasi yang sering. [4] [5] Setelah infeksi sel inang, genom diterjemahkan secara cap-independen menjadi poliprotein tunggal, yang selanjutnya diproses oleh protease yang dikode virus menjadi protein kapsid struktural dan protein nonstruktural, yang terutama terlibat dalam replikasi virus. [6]

Rekombinasi RNA tampaknya menjadi kekuatan pendorong utama dalam evolusi enterovirus serta dalam pembentukan arsitektur genetik mereka. [7] [5] Mekanisme rekombinasi genom RNA kemungkinan melibatkan perpindahan untai template selama replikasi RNA, sebuah proses yang dikenal sebagai rekombinasi pilihan salinan. [7] Rekombinasi RNA dianggap sebagai adaptasi untuk menangani kerusakan genom RNA dan sumber keragaman genetik. [8] Ini juga merupakan sumber perhatian untuk strategi vaksinasi, karena strain hidup yang dilemahkan/bermutasi yang digunakan untuk vaksinasi berpotensi bergabung kembali dengan strain terkait tipe liar, seperti yang terjadi pada Vaccine Derived PolioViruses (cVDPDs) yang bersirkulasi [9] [ 10]. Wilayah kapsid dan khususnya VP1 adalah titik dingin rekombinasi, [5] dan ini adalah salah satu alasan utama untuk menggunakan wilayah ini untuk genotipe [2] .Namun, persimpangan 5'UTR - kapsid dan awal dari P2 wilayah telah diamati untuk bergabung kembali sangat sering, meskipun rekombinasi memang terjadi di sisa genom juga. [5] Menariknya, spesies enterovirus EV-A, EV-B, EV-C, EV-D belum diamati sejauh ini untuk bertukar wilayah genom di antara mereka, dengan pengecualian 5'UTR. [5] [11] [12] Sebaliknya, wilayah genomik ORF dipertukarkan di antara genotipe yang berbeda dari spesies yang sama, dengan genotipe tertentu seperti EV71 dan CVA6 dari EV-A, E30 dan E6 dari EV-B, PV1 dan PV2 dari EV-C memainkan peran kunci sebagai hub rekombinasi. [5] Selain itu, analisis rekombinasi dari

3000 genom Enterovirus mengidentifikasi banyak peristiwa rekombinasi di mana salah satu mitra rekombinasi belum diurutkan, sehingga mengungkapkan bahwa ada reservoir genetik enterovirus yang besar namun tidak terdeteksi yang dapat menyebabkan peristiwa rekombinasi baru dan munculnya galur, genotipe, dan patogen baru. [5]

Enterovirus A - L Sunting

Enterovirus adalah sekelompok virus di mana-mana yang menyebabkan sejumlah infeksi yang biasanya ringan. Genus picornavirus termasuk enterovirus dan rhinovirus. Enterovirus A termasuk coxsackievirus A2, A3, A4, A5, A6, A7, A8, A10, A12, A14, A16 dan enterovirus A71, A76 A89, A89, A90, A91, A92, A144, A119, A120, A121, A122 ( simian virus 19), A123 (simian virus 43), A124 (simian virus 46), A125 (baboon enterovirus A13). [13] Beberapa virus yang awalnya dilaporkan sebagai novel ternyata salah diidentifikasi. Jadi, coxsackievirus A23 adalah serotipe yang sama dengan echovirus 9, dan coxsackievirus A15 adalah serotipe yang sama dengan coxsackievirus A11 dan coxsackievirus A18 adalah serotipe yang sama dengan coxsackievirus A13.

Virus Coxsackie A16 menyebabkan penyakit tangan, kaki dan mulut pada manusia.

Enterovirus B termasuk coxsackievirus B1,2,3,4,5,6 coxsackievirus A9 echovirus 1-33 dan enterovirus B69-113. [13] Virus Coxsackie B ditemukan di seluruh dunia dan dapat menyebabkan miokarditis (radang jantung), perikarditis (radang kantung yang mengelilingi jantung), meningitis (radang selaput yang melapisi otak dan sumsum tulang belakang) dan pankreatitis (radang selaput otak). pankreas). Virus Coxsackie B juga dilaporkan menyebabkan kelumpuhan spastik karena degenerasi jaringan saraf dan cedera otot. Infeksi biasanya terjadi selama bulan-bulan musim panas yang hangat dengan gejala termasuk eksantema, pleurodynia, penyakit seperti flu yang terdiri dari demam, kelelahan, malaise, mialgia, mual, sakit perut dan muntah. [14] Echovirus adalah penyebab dari banyak infeksi virus nonspesifik yang dapat berkisar dari penyakit ringan hingga parah, kondisi yang berpotensi fatal seperti meningitis aseptik, ensefalitis, kelumpuhan, dan miokarditis. [15] Hal ini terutama ditemukan di usus, dan dapat menyebabkan gangguan saraf. [16] Enterovirus tipe B bertanggung jawab atas sejumlah besar infeksi ringan dan akut. Mereka telah dilaporkan tetap berada di dalam tubuh menyebabkan infeksi persisten yang berkontribusi terhadap penyakit kronis seperti diabetes tipe I. [17]

Enterovirus C terdiri dari poliovirus 1,2 dan 3 coxsackievirus A1, A11, A13, A18, A17, 20, A21, A22, A24 dan enterovirus C95, C96, C99, C102, C104, C105, C109, C113, C118. Ketiga serotipe virus polio, PV-1, PV-2, dan PV-3 masing-masing memiliki protein kapsid yang sedikit berbeda. Protein kapsid menentukan spesifisitas reseptor seluler dan antigenisitas virus. PV-1 adalah jenis yang paling umum menyebabkan infeksi pada manusia, namun ketiga bentuk ini sangat menular dan menyebar melalui kontak orang ke orang. Poliovirus menyebabkan Polio, atau Poliomyelitis, yang merupakan penyakit melumpuhkan dan mengancam jiwa yang menyebabkan paresthesia, meningitis dan kelumpuhan permanen. [18] Gejalanya dapat berupa sakit tenggorokan, demam, kelelahan, mual, sakit kepala, dan sakit perut, meskipun 72% dari mereka yang terinfeksi tidak akan menunjukkan gejala yang terlihat. [18] Ada dua jenis vaksin yang tersedia untuk mencegah polio: vaksin virus polio yang tidak aktif diberikan sebagai suntikan di kaki (IPV) atau vaksin poliovirus lengan dan oral (OPV). Vaksin polio sangat berkhasiat memberikan perlindungan pada 99 dari 100 anak yang divaksinasi. [18]

Enterovirus non-sitolitik (non-sitopatik) Sunting

Enterovirus biasanya hanya mampu menghasilkan infeksi akut yang dengan cepat dibersihkan oleh respon imun adaptif. [19] [20] Namun mutasi genom, yang dapat diperoleh serotipe enterovirus B di inang selama fase akut, dapat mengubah virus ini menjadi bentuk non-sitolitik (juga dikenal sebagai enterovirus non-sitopatik atau defek). Ini adalah quasispecies bermutasi [19] enterovirus, yang dapat menyebabkan infeksi persisten pada jaringan jantung manusia terutama pada beberapa pasien dengan miokarditis atau kardiomiopati dilatasi. [21] [19] Pada infeksi persisten RNA virus hadir hanya pada tingkat yang sangat rendah dan tidak diyakini berkontribusi pada penyakit miokard yang sedang berlangsung menjadi sisa memudar dari infeksi akut baru-baru ini [20] meskipun beberapa ilmuwan berpikir sebaliknya. [22]

Enterovirus D68 Sunting

EV-D68 pertama kali diidentifikasi di California pada tahun 1962. Dibandingkan dengan enterovirus lainnya, virus ini jarang dilaporkan di AS dalam 40 tahun terakhir. Kebanyakan orang yang terinfeksi adalah bayi, anak-anak, dan remaja. EV-D68 biasanya menyebabkan penyakit pernapasan ringan hingga berat, namun spektrum penuh penyakit EV-D68 tidak terdefinisi dengan baik. Sebagian besar dimulai dengan gejala flu biasa seperti pilek dan batuk. Beberapa, tetapi tidak semua, mungkin juga mengalami demam. Untuk kasus yang lebih parah, kesulitan bernapas, mengi, atau masalah pernapasan dapat terjadi. Pada 4 Oktober 2014, telah terjadi satu kematian di New Jersey yang terkait langsung dengan EV-D68, [23] serta satu kematian di Rhode Island [ kutipan diperlukan ] dikaitkan dengan kombinasi EV-D68 dan sepsis yang disebabkan oleh infeksi staphylococcus aureus. [24] [25]

Enterovirus A71 Sunting

Enterovirus A71 (EV-A71) terkenal sebagai salah satu agen penyebab utama penyakit tangan, kaki dan mulut (HFMD), dan kadang-kadang dikaitkan dengan penyakit sistem saraf pusat yang parah. [26] EV-A71 pertama kali diisolasi dan dicirikan dari kasus penyakit neurologis di California pada tahun 1969. [27] [28] Sampai saat ini, sedikit yang diketahui tentang mekanisme molekuler respon host terhadap infeksi EV-A71, tetapi peningkatan tingkat mRNA yang mengkode kemokin, protein yang terlibat dalam degradasi protein, protein pelengkap, dan protein proapoptotis telah terlibat. [29]

Sunting virus polio

Ada tiga serotipe virus polio, PV-1, PV-2, dan PV-3 masing-masing dengan protein kapsid yang sedikit berbeda. Protein kapsid menentukan spesifisitas reseptor seluler dan antigenisitas virus. PV-1 adalah bentuk yang paling umum ditemui di alam namun, ketiga bentuk tersebut sangat menular. [30] Virus polio dapat mempengaruhi sumsum tulang belakang dan menyebabkan poliomielitis.

virus polio sebelumnya diklasifikasikan sebagai spesies yang termasuk dalam genus Enterovirus dalam famili Picornaviridae. Spesies Poliovirus telah dieliminasi dari genus Enterovirus. Serotipe berikut, Human poliovirus 1, Human poliovirus 2, dan Human poliovirus 3, dimasukkan ke dalam spesies Human enterovirus C, dalam genus Enterovirus dalam famili Picornaviridae. Jenis spesies dari genus Enterovirus diubah dari Poliovirus menjadi Human enterovirus C. Ini telah diratifikasi pada April 2008. [31] Komite Eksekutif ke-39 (EC39) dari Komite Internasional untuk Taksonomi Virus (ICTV) bertemu di Kanada selama bulan Juni 2007 dengan proposal taksonomi baru. [32]

Dua dari proposal dengan tiga perubahan adalah:

  • Kode 2005.261V.04: Untuk menghapus spesies Poliovirus berikut dari genus Enterovirus yang ada dalam famili Picornaviridae.
  • Kode 2005.262V.04: Untuk menetapkan virus PV-1, PV-2, PV-3 ke spesies yang ada Enterovirus C manusia dalam genus Enterovirus dalam famili Picornaviridae. [33]
  • Kode 2005.263V.04 : Untuk mengubah jenis spesies Poliovirus dari genus Enterovirus yang ada dalam famili Picornaviridae menjadi jenis spesies Human enterovirus C. [34]

Proposal yang disetujui pada pertemuan (EC39) tahun 2007, dikirim ke anggota ICTV melalui email untuk diratifikasi dan telah menjadi taksonomi resmi. Ada total 215 proposal taksonomi, yang telah disetujui dan diratifikasi sejak Laporan ICTV ke-8 tahun 2005. [35]

Proses ratifikasi dilakukan melalui email. Proposal dikirim secara elektronik melalui email pada tanggal 18 Maret 2008, kepada anggota ICTV dengan permintaan untuk memilih apakah akan meratifikasi proposal taksonomi, dengan tenggat waktu 1 bulan. Berikut ini adalah dua proposal taksonomi dengan tiga perubahan yang telah diratifikasi oleh anggota ICTV pada April 2008:

  • 2005.261V.04: Untuk menghapus spesies berikut dari genus Enterovirus yang ada dalam famili Picornaviridae: Poliovirus. (Catatan: Poliovirus dengan ini kehilangan statusnya sebagai spesies virus.)
  • 2005.262V.04: Untuk menetapkan virus berikut ke spesies Human enterovirus C dalam genus Enterovirus yang ada dalam famili Picornaviridae: Human poliovirus 1, Human poliovirus 2, Human poliovirus 3. (Ini tidak sepenuhnya diperlukan sebagai proposal taksonomi karena menyangkut entitas di bawah tingkat spesies, tetapi dibiarkan untuk memperjelas reorganisasi Picornaviridae ini.)
  • 2005.263V.04: Mengubah jenis spesies dari genus Enterovirus dalam famili Picornaviridae, dari Poliovirus menjadi Human enterovirus C. [31]

Enterovirus menyebabkan berbagai gejala, dan sementara daftar panjang tanda dan gejala mereka harus menempatkan mereka pada daftar diagnosis banding dari banyak penyakit, mereka sering luput dari perhatian. Enterovirus dapat menyebabkan apa saja mulai dari ruam pada anak kecil, pilek musim panas, ensefalitis, penglihatan kabur, hingga perikarditis. Infeksi enteroviral memiliki kisaran besar dalam presentasi dan keseriusan. Enterovirus non polio menyebabkan 10-15 juta infeksi dan puluhan ribu rawat inap di AS setiap tahun. [37] Enterovirus dapat diidentifikasi melalui kultur sel atau uji PCR, dikumpulkan dari spesimen tinja atau pernapasan. [38] Di bawah ini adalah penyakit umum terkait enterovirus, termasuk poliomielitis.

    terutama melalui rute fekal-oral yang ditemukan pada anak-anak yang dites positif enterovirus 68. [39][40]
  • Penyakit demam nonspesifik adalah presentasi paling umum dari infeksi enterovirus. Selain demam, gejalanya termasuk nyeri otot, sakit tenggorokan, gangguan gastrointestinal / ketidaknyamanan perut, dan sakit kepala. [41] Namun, pada bayi baru lahir gambarannya mungkin seperti sepsis, dan bisa parah serta mengancam jiwa.
  • Enterovirus sejauh ini merupakan penyebab paling umum meningitis aseptik pada anak-anak. Di Amerika Serikat, enterovirus bertanggung jawab atas 30.000 hingga 50.000 rawat inap meningitis per tahun sebagai akibat dari 10-15 juta infeksi. [42] atau pleurodynia epidemik ditandai dengan nyeri paroksismal parah di dada dan perut, bersama dengan demam, dan kadang-kadang mual, sakit kepala, dan muntah. dan/atau miokarditis biasanya disebabkan oleh enterovirus. Gejala berupa demam disertai sesak napas dan nyeri dada. Aritmia, gagal jantung, dan infark miokard juga telah dilaporkan. dapat disebabkan oleh enterovirus. disebabkan oleh virus Coxsackie A, dan menyebabkan ruam vesikular di rongga mulut dan faring, disertai demam tinggi, sakit tenggorokan, malaise, dan sering disfagia, kehilangan nafsu makan, sakit punggung, dan sakit kepala. Ini juga membatasi diri, dengan gejala biasanya berakhir dalam 3-4 hari. adalah penyakit masa kanak-kanak yang paling sering disebabkan oleh infeksi oleh virus Coxsackie A atau EV71. adalah manifestasi infeksi enterovirus yang jarang terjadi, enterovirus yang paling sering ditemukan sebagai penyebab adalah echovirus 9. ditandai dengan peradangan pada miokardium (sel otot jantung). Selama beberapa dekade terakhir, banyak penyebab telah diidentifikasi berperan dalam patogenesis miokarditis selain enterovirus, yang pada awalnya merupakan virus yang paling sering terlibat dalam patologi ini. [43] Salah satu enterovirus paling umum yang ditemukan sebagai penyebab miokarditis adalah virus Coxsackie B3. [44]
  • Sebuah studi tahun 2007 menunjukkan bahwa infeksi pernapasan atau gastrointestinal akut yang terkait dengan enterovirus dapat menjadi faktor dalam sindrom kelelahan kronis. [45]

Penyakit yang dicurigai Sunting

Kemungkinan korelasi sedang dipelajari Sunting

Enterovirus telah berspekulasi terkait dengan diabetes tipe 1. [47] [48] [49] [50] Telah diusulkan bahwa diabetes tipe 1 adalah respons autoimun yang dipicu virus di mana sistem kekebalan menyerang sel yang terinfeksi virus bersama dengan sel beta penghasil insulin di pankreas. [51] Sebuah tim yang bekerja di University of Tampere, Finlandia telah mengidentifikasi jenis enterovirus yang mungkin terkait dengan diabetes tipe 1 (yang merupakan penyakit autoimun). [52] [53]

Kebanyakan orang yang tertular enterovirus memiliki gejala ringan yang berlangsung sekitar satu minggu. Mereka yang berisiko lebih tinggi mungkin memiliki lebih banyak komplikasi, terkadang menjadi fatal. [54] Tanda paling umum dari enterovirus adalah flu biasa. Gejala enterovirus yang lebih intens termasuk hipoksia, meningitis aseptik, konjungtivitis, penyakit tangan, kaki dan mulut, dan kelumpuhan.

Pengobatan untuk infeksi enteroviral terutama bersifat suportif. Dalam kasus pleurodynia, pengobatan terdiri dari analgesik untuk menghilangkan rasa sakit yang parah yang terjadi pada pasien dengan penyakit pada beberapa kasus yang parah, opiat mungkin diperlukan. Pengobatan untuk meningitis aseptik yang disebabkan oleh enterovirus juga sebagian besar bersifat simtomatik. Pada pasien dengan karditis enteroviral, pengobatan terdiri dari pencegahan dan pengobatan komplikasi seperti aritmia, efusi perikardial, dan gagal jantung. Perawatan lain yang telah diselidiki untuk karditis enteroviral termasuk imunoglobulin intravena. [55]


Bagaimana rotavirus manusia umumnya ditularkan? - Biologi

Di Spanyol, diare tetap menjadi penyebab utama penyakit pada bayi dan anak kecil. Untuk menentukan prevalensi genotipe rotavirus dan perbedaan temporal dan geografis dalam distribusi strain, studi surveilans terstruktur pada anak-anak yang dirawat di rumah sakit <5 tahun dengan diare dimulai di berbagai wilayah di Spanyol selama tahun 2005. Rotavirus terdeteksi sendiri dalam sampel dari 362 (55,2% ) sampel dan sebagai koinfeksi dengan virus lain di 41 sampel (6,3%). Agen bakteri enteropatogen terdeteksi pada 4,9% sampel astrovirus dan RNA norovirus terdeteksi pada masing-masing 3,2% dan 12,0% sampel dan antigen adenovirus terdeteksi pada 1,8% sampel. Termasuk infeksi campuran, tipe G yang paling dominan adalah G9 (50,6%), diikuti oleh G3 (33,0%) dan G1 (20,2%). Infeksi dengan beberapa jenis rotavirus terdeteksi pada >11,4% sampel yang diteliti selama tahun 2005.

Rotavirus grup A adalah penyebab utama diare berat pada bayi. Di negara berkembang, diare parah yang disebabkan oleh rotavirus manusia menyebabkan sekitar 500.000 hingga 608.000 kematian anak setiap tahun di seluruh dunia, menyebabkan 2 juta rawat inap (1,2).

Rotavirus termasuk dalam Reoviridae keluarga. Partikel virus tidak berselubung, dan kapsid protein berlapis tiga membungkus genom 11 segmen dsRNA. Protein utama di lapisan tengah kapsid virus adalah VP6, yang menentukan 7 kelompok rotavirus (A–G) yang berbeda. Lapisan luar kapsid virus terdiri dari 2 protein struktural, VP4 (dikodekan oleh gen 4) dan VP7 (dikodekan oleh gen 7, 8, atau 9, tergantung pada strain) (3). Kedua protein ini membawa determinan antigenik utama, yang menghasilkan antibodi penetralisir dan dianggap sebagai tipe spesifik. Rotavirus grup A tersebar luas pada manusia dan hewan dan dibagi lagi menjadi genotipe yang berbeda, G dan P (4). Studi epidemiologis infeksi rotavirus semakin menunjukkan bahwa keragaman besar strain rotavirus beredar dalam populasi manusia di seluruh dunia. Genotipe rotavirus grup A yang paling umum (≈90%), yang menyebabkan gastroenteritis dehidrasi pada bayi dan anak kecil di seluruh dunia, adalah G1P[8], G2P[4], G3P[8], dan G4P[8] G1P[8] adalah yang paling umum di seluruh dunia (5). Namun, genotipe G lainnya secara epidemiologi penting, seperti G5 di Brasil (6,7), G9 dan G10 di India (8,9), dan G8 di Malawi (10).

Di Spanyol, diare tetap menjadi penyebab penting penyakit pada bayi dan anak kecil. Sebuah penelitian yang dilakukan dari tahun 1998 hingga 2002 mendeteksi rotavirus pada 1.155 (31%) dari 3.760 spesimen yang diuji. G1 adalah genotipe dominan yang terdeteksi (53%), diikuti oleh G4 (24%), G2 (14%), G9 (6%), dan G3 (2%) (11). The distribution of genotypes indicated a genotypic shift over time: G4 strains predominated (57%) from 1998 through 2000, whereas G1 gradually increased to account for 75% from 2000 through 2002 (11). Similar studies conducted in other regions of Spain indicated similar shifts in the prevalence of rotavirus genotypes (12,13).

We conducted structured surveillance among children with diarrhea who were hospitalized in 6 hospitals in Spain our primary goals were to determine the prevalence of rotavirus diarrhea in hospitalized children, the G and P types among infecting rotavirus strains, and the temporal and geographic differences in strain distribution throughout the regions.

Bahan dan metode

Hospitals and Patients

Stool samples were collected from children attending 6 public hospitals located in different healthcare areas throughout Spain. These hospitals intentionally represented the geographic, climatic, and ethnic diversity of Spain. Their respective catchment areas are shown in Table 1. The study was conducted between January 2005 and January 2006 and included children <5years of age who were hospitalized with acute gastroenteritis and from whom a stool sample was obtained.

Acute gastroenteritis was defined as >3 looser-than-normal stools within a 24-hour period or an episode of forceful vomiting and any loose stool. To enable reporting of test results to hospitals, stool specimens were labeled with the date of collection and a unique surveillance identification number. Permission for enrollment in the study was obtained from children's legal guardians, and ethical approval was obtained from the institutional review board of the Hospital de La Ribera.

Specimen Collection and Testing

Whole stool specimens were collected and transported immediately to hospital laboratories and stored at 4°C until processing. All fecal samples were screened for enteropathogenic bacterial agents by conventional culture methods previously described (14).

Each month, specimens were sent to the reference laboratory (Viral Gastroenteritis Unit, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain). A 10% suspension in 0.1 mol/L phosphate-buffered saline (pH 7.2) was prepared and tested by reverse transcription (RT)-PCR for rotavirus, astrovirus, norovirus, and sapovirus (11,15,16) and by an immunochromatographic method for enteric adenoviruses (14).

Nucleic Acid Extraction and G/P Rotavirus Typing

Viral RNA was extracted from 250 μL of the 10% fecal suspension by using the guanidine isothiocyanate method and the Rnaid Spin Kit (BIO 101, Anachem Bioscience, Bedfordshire, UK) according to the manufacturer's instructions, with slight modifications (16). RNA was eluted in 50 μL of RNase-free distilled water and stored at –20°C. To determine the G/P type patterns present in children hospitalized from 2005 through 2006, a total of 98 rotavirus strains were P typed. G and P rotavirus genotyping were performed by using RT-PCR methods as previously reported (11,17).

DNA Sequencing and Analysis

Rotavirus amplicons were genetically characterized by nucleotide sequencing of both strands of the amplified PCR products. These products were purified by using QIAquick PCR Purification kit (Qiagen, Valencia, CA, USA) and then sequenced using an ABI PRISM BigDye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems, Foster City, CA, USA) on an ABI automated sequencer (Applied Biosystems, model 3700). Data analysis was performed by using Clustal for multiple alignments and neighbor-joining and maximum parsimony methods for phylogenetic analysis (Bionumerics, Kortrijk, Belgium). Spanish strains were submitted to GenBank under accession numbers DQ440613 through DQ440624.

Hasil

Mikrobiologi

A total of 656 hospitalized children were enrolled. Enteropathogenic bacterial strains were detected in 5.0% of samples (Table 2). Astrovirus and norovirus RNA was detected in 3.2% and 12.0% samples, respectively, and adenovirus antigen in 1.8% samples.

A total of 403 rotavirus strains were detected. Rotavirus was found alone in 362 (55.2%) samples but was found in another 41 samples (6.3%) as a coinfection with other viruses. The percentage of children with gastroenteritis caused by rotavirus as unique agent ranged from 36.7% in Leon to 68.2% in Valencia (Table 2).

Rotavirus Characterization

G typing RT-PCR for rotavirus alone was performed on 362 samples positive for rotavirus but could not be determined in 10 (2.8%) samples. The G types detected, including mixed infections with multiple rotavirus strains, are shown in Table 3. Briefly, the most predominant G type was G9 (50.6%), followed by G3 (33.0%), G1 (20.2%), and G2 (7.1%) the least common G type was G4 (0.6%). G1, previously reported as the most common G type in Spain, was found in only 20.2% of rotavirus infections. With the exceptions of Valencia and Albacete, where G1 and G3, respectively, were the predominant G types, the results from all other regions showed a predominance of G9. However, even in these 2 areas, G9 was the second most common strain detected when cases with coinfection were added (26.7% and 31.6%, respectively).

Common G/P combinations, infrequent patterns, and mixed-infection combinations were all detected (Table 4). G9P[8] (40%) and G3P[8] (31%) were the most common combinations detected, but G types in combination with P[6] and P[9] were also detected.

Using DNA sequencing and phylogenetic analysis of partial sequences of the gene encoding VP7, we compared 2 G3 strains from this study with 9 G3 strains isolated previously in Spain. All G3 strains from Spain shared >99.0% homology and were more closely related to each other than to strains isolated in Italy, United Kingdom, India, and China.

Diskusi

Genetically and antigenically diverse rotavirus strains cocirculate in humans. The prevalence of rotavirus genotypes varies according to location and time. Throughout the world, genotyping and serotyping studies have identified common cocirculating rotavirus types, and G1P[8], G2P[4], G3P[8], and G4P[8] are the predominant strains. However, from time to time, other less common genotypes, such as G9P[8], G5P[8], and G8P[6], have been predominant in various countries (5).

In Spain, previous studies have identified G1P[8] and G4P[8] as the predominant cocirculating strains from 1996 through 2004 (11,17,18) (Table 5). However, in our study, conducted in 2005 and 2006, a major shift in the predominant strains was detected. G9P[8] and G3P[8] have become the predominant genotypes cocirculating in several regions of Spain, and infection with multiple rotavirus strains was detected in 11.4% of the cases studied.

Since its widespread introduction into the human population in 1995, G9P[8] has become one of the predominant viruses worldwide. In 2 separate studies conducted in Thailand (19,20), this genotype has been reported as the predominant virus circulating from 2000 through 2002 and in Brazil from 1999 through 2002 (21). G3P[8] has recently been reported as the predominant strain circulating in the Japanese population (22).

Less common G- and P-type combinations were also detected in this study. This finding may suggest either an earlier reassortment between animal and human strains, resulting in the emergence of strains such as G2P[6] and G3P[9], or zoonotic transmission to humans of an animal strain, as possibly occurred with G9P[6]. The VP4-genotypes P[6] and P[9] are reported to be associated with infection in pigs and cats, respectively. Although animal rotavirus strains replicate poorly in humans and person-to-person transmission is rare, the relatively high frequency of multiple infections detected in this study suggests that the opportunity for dual infection of a cell, and therefore reassortments, exists (23).

The main limitations of this study are having only 1 year of data, the minimal variations in the sampling schemes in each institution (frequency of sampling, test procedures, motivations of investigators), and the small sample size collected. Although the sampling strategy enabled monitoring for rotavirus in a large number of children, future studies with hospital-based surveillance should be initiated in different areas of Spain, and even Europe, with larger samples.

Morbidity rates worldwide and morbidity and mortality rates caused by diarrhea in developing countries remain high despite efforts to improve sanitary conditions, water quality, and the healthcare infrastructure. These high rates have driven efforts to develop a safe and effective rotavirus vaccine, and the World Health Organization has recognized that developing a vaccine is a priority for reducing infant deaths in developing countries. The level and type of protection in rotavirus disease is poorly understood, although neutralizing antibody responses are thought to be type specific. Because these responses are associated with VP7 and VP4 viral proteins, establishing the G and P genotypes of strains circulating in the human population is important. Currently, 2 candidate rotavirus vaccines are undergoing clinical trials. A multivalent vaccine directed against G1, G2, G3, G4, and P[8] and a monovalent vaccine to G1P[8] have been developed (24,25). Homotypic protection has been demonstrated for both vaccines, but the degree to which they cross-protect against less common G- and P-type combinations not included in the vaccine formulations has yet to be established, and the importance of genotype-specific protection against rotavirus disease is still under discussion (26,27). Considering that G9 rotavirus type has emerged as one of the most common rotavirus genotypes in humans around the world, and it is becoming very prevalent in some countries, future rotavirus vaccine candidates will need to provide adequate protection against disease caused by G9 viruses. Therefore, surveillance of regional networks must be maintained to document rotavirus strain distribution and prevent the appearance of new strains or new variants that could escape immune protection induced by an outdated vaccine.

Dr Sánchez-Fauquier is the head of the Viral Gastroenteritis Unit, National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid. Her primary research interests are the epidemiology, immunology, pathogenesis, and molecular biology of viral gastroenteritis. She also is coordinator of the Spanish Viral Gastroenteritis Network (VIGESS-Net).


Pengelolaan

Regardless of the infecting agent, children presenting with diarrhoea are assessed for dehydration and treated accordingly. A mild case of rotavirus disease, where the child is active, shows no signs of dehydration, has had between zero and two vomiting episodes within 12 hours, has had a few loose or low output watery stools per day and has no fever or a low-grade fever, requires only observation. Symptoms can last for 1–5 days, but if they last for >1 week, medical consultation should be sought. Increasing and/or intense vomiting and repeated episodes of watery diarrhoea (for example, >1 episode per hour, especially if abundant) are the main features that indicate the need for specific treatment. In low-income countries, the goal of treatment is avoiding or rapidly treating severe dehydration and maintaining protein–calorie intake to prevent death or worsening malnutrition, whereas in middle-income and high-income countries, reducing hospitalization and the duration of diarrhoea are the main goals. Key treatment concepts including fluid and electrolyte management (including ORS and intravenous rehydration), dietary management and the use of probiotics, anti-emetics, antisecretory drugs and antiviral drugs are discussed below comprehensive reviews of acute diarrhoea management can be found elsewhere 135,136 .

Fluid and electrolyte management

One of the most important medical advancements in the past 50 years that has saved millions of infant lives was that administration of ORS resulted in glucose-coupled sodium and water absorption in the small intestine 137 . Oral rehydration therapy has been used safely and successfully to prevent and treat dehydration due to diarrhoeal pathogens, including rotavirus, in infants and young children 138 . Clinical scales that consider the presence of signs and symptoms are available to assess for dehydration 139,140 , and a thirsty, restless or fatigued child with a dry mouth should alert caretakers to ongoing dehydration. Prompt replacement of fluids and electrolytes, spoon by spoon if necessary, with hypo-osmolar ORS (containing 60–75 mmol per litre of sodium in addition to glucose, potassium, chloride and citrate) 141 is the cornerstone of treatment for children without dehydration but with intense and repeated vomiting and/or diarrhoea episodes and for children with mild to moderate dehydration. If ORS is not available, homemade solutions can be prepared using water, sugar and salt. Plain water, soda, chicken broth and apple juice should be avoided in children with dehydration, especially in infants, as they are hyperosmolar solutions and do not sufficiently restore potassium, bicarbonate and sodium levels 142 . Intravenous fluids can be used in cases of severe dehydration, hyperemesis, oral rehydration therapy failure or severe electrolyte imbalances. Importantly, most children, even those with severe dehydration, can be managed effectively with ORS to prevent severe complications, including death.

Dietary management

Dietary management is an important factor in the care of children with acute diarrhoea 143 . Breastfeeding should be encouraged and is never contraindicated. In patients with dehydration, food withdrawal is advised for only 4–6 hours after initiating rehydration therapy 136,144 . The administration of repetitive, small portions of regular undiluted milk formulas is recommended for infants and children >6 months of age. The administration of lactose-free formulas might reduce the duration of treatment and the risk of treatment failure 143 and can be considered for selected children, such as those requiring hospitalization 136 . Importantly, the maintenance of adequate protein–calorie intake during the diarrhoea episode using home-available, age-appropriate foods should be encouraged, especially in low-income settings 143 . In addition, zinc supplementation can improve the outcome of acute diarrhoea in low-income regions, in which malnutrition is common. Although the mechanisms of the efficacy of zinc supplementation are unclear, data from animal studies suggest zinc has anti-inflammatory properties 145 and antisecretory effects 146 , among others. Zinc deficiency is common in low-income countries and can occur in children with acute gastroenteritis due to intestinal fluid loss. For children living in low-income regions, the WHO recommends daily zinc supplementation for infants and children for 10–14 days, starting as soon as the diarrhoea episode has been diagnosed 147 . However, zinc supplementation can increase vomiting after the initial dose 148 .

Probiotik

Commonly used probiotics for the treatment of acute diarrhoea are lactic acid-producing bacteria, such as Lactobacillus rhamnosus, Lactobacillus plantarum, several strains of Bifidobakteri dan Enterococcus faecium (the SF68 strain), and yeast, such as Saccharomyces boulardii 149 . Most meta-analyses suggest a modest benefit of probiotics in reducing the duration of diarrhoea by ∼ 1 day and up to 2 days for rotavirus-induced diarrhoea, although studies have been performed largely in middle-income and high-income countries 3 , and some studies did not report a clear benefit 150,151 . The mechanisms underlying this have been postulated to include the activation of antigen-presenting cells, a reduction in the levels of pro-inflammatory cytokines, the modulation of effector T cell and regulatory T cell immune responses, innate immune signalling (through interactions with several TLRs) and the promotion of enterocyte proliferation and/or migration 152 . In low-income regions, treatment with probiotics has a positive immunomodulatory effect (that is, an increased anti-rotavirus IgG response in individuals who received treatment compared with individuals who received placebo), improves intestinal function in children with rotavirus infection and might decrease repeat episodes of rotavirus diarrhoea 153,154 . However, probiotics are not included in the standard of care for children with rotavirus diarrhoea globally.

Other drugs

Antiviral therapy for rotavirus infection has been studied but remains mostly in preclinical stages. One exception is nitazoxanide, a broad-spectrum antiviral drug 155 that has been reported to reduce the duration of diarrhoea and the duration of hospitalization of children with acute rotavirus diarrhoea 155–157 . Nitazoxanide inhibits the replication of rotavirus by interfering with viral morphogenesis 158 . One study in hospitalized children 5 months to 7 years of age reported a significant reduction in the median time to the resolution of all rotavirus-associated gastrointestinal symptoms from 75 hours in children who received placebo treatment to 31 hours in children who received a 3-day course of nitazoxanide treatment 156 .

Recommendations for the use of anti-emetics (such as metoclopramide, dimenhydrinate and ondansetron) for children with rotavirus disease have progressed from ‘not recommended’ to ‘possibly recommended’ owing to their effects of reducing the number of vomiting episodes and reducing the need for intravenous rehydration and hospitalization 150,159 . Indeed, one dose of ondansetron reduces the likelihood of needing intravenous rehydration, although this can increase diarrhoea output. Importantly, repeated doses do not provide an additional benefit over one dose. The largest benefit can be gained when ondansetron is used early in the clinical course of children with rotavirus infection and intense vomiting.

Other potential therapies for rotavirus gastroenteritis include racecadotril and smectite. Racecadotril (an intestinal enkephalinase inhibitor that reduces the secretion of water and electrolytes into the gut 160 ) has been shown to significantly decrease diarrhoea output at 48 hours after treatment and did not increase the frequency of adverse effects 161 . However, treatment with racecadotril did not reduce the proportion of patients with diarrhoea 5 days after treatment 161 . In addition, one meta-analysis of seven clinical trials reported that racecadotril treatment is more effective than placebo or no intervention at reducing the duration of illness and stool output in children with acute diarrhoea 162 . However, in Kenya, racecadotril did not alter the number of stools after 48 hours, the duration of hospital stay or the duration of diarrhoea in children with severe gastroenteritis who received ORS and zinc 163 and was not effective in Indian children with acute diarrhoea and vomiting 164 . Thus, racecadotril can be considered for the management of children with severe secretory diarrhoea, but the efficacy is variable. Smectite (a natural adsorbent that binds to endotoxins, exotoxins, bacteria and viral particles) has been reported to decrease the duration of acute diarrhoea by 18–29% in a meta-analysis of mostly open-label trials in children with acute diarrhoea. In addition, smectite has been shown to increase the cure rate at day 5, without any increase in the risk of adverse events and accordingly could be beneficial in some individuals with rotavirus disease 165,166 .

Combination trials evaluating the simultaneous use of several treatments are lacking 99 . Indeed, improvements in treatment strategies are needed, especially in regions where rotavirus-associated deaths occur and where vaccines are underutilized.


Rotavirus Infection

Rotavirus is a virus that infects the bowels, causing severe inflammation of the stomach and bowels (known as gastroenteritis). Rotavirus is the most common cause of severe diarrhea among infants and children throughout the world and causes the death of about 500,000 children worldwide annually. The name rotavirus comes from the characteristic wheel-like appearance of the virus when viewed by electron microscopy (the name rotavirus comes from the Latin rota, meaning "wheel").

Since 2006, vaccines have been available for rotavirus infection. Before the availability of a rotavirus vaccine, rotavirus infected almost all children by their third birthday. Repeat infections with different viral strains are possible, and most children had several episodes of rotavirus infection in the first years of life. After several infections with different strains of the virus, children acquire immunity to rotavirus. Babies and toddlers between 6-24 months of age are at the greatest risk for developing severe disease from rotavirus infection. Adults sometimes become infected, but the resulting illness is usually mild.

Worldwide, rotavirus infection is still a significant cause of death in infants and children. Rotavirus affects populations in all socioeconomic groups and is equally prevalent in industrialized and developing countries, so differences in sanitation practices or water supply are not likely to affect the incidence of the infection.

In the U.S., rotavirus infections usually peak in the fall months in the Southwest and spread to the Northeast by spring, so infections are most common during the winter months from November to May. However, infection with rotavirus can occur at any time of the year.

Rotavirus Infection

Childhood Illnesses Every Parent Should Know Slideshow

Rotavirus infection is responsible for significant morbidity and mortality in children in less developed countries where access to the rotavirus vaccine is limited. The infection causes significant fever, vomiting, and diarrhea in children. This can often lead to serious problems with dehydration, especially in very young children and infants.

What are rotavirus infection symptoms and signs?

Symptoms of the disease include fever, vomiting, and watery diarrhea. Abdominal pain may also occur, and infected children may have profuse watery diarrhea up to several times per day. Symptoms generally persist for three to nine days. Immunity from repeated infection is incomplete after a rotavirus infection, but repeated infections tend to be less severe than the original infection.

Rotavirus infection can be associated with severe dehydration in infants and children. Severe dehydration can lead to death in rare cases, so it is important to recognize and treat this complication of rotavirus infection. In addition to the symptoms of rotavirus infection discussed above, parents should be aware of the symptoms of dehydration that can occur with rotavirus infection or with other serious conditions.

Symptoms of dehydration include

  • lethargy,
  • dry, cool skin,
  • absence of tears when crying,
  • dry or sticky mouth,
  • sunken eyes or sunken fontanel (the soft spot on the head of infants), and
  • extreme thirst.

Apa penyebab rotavirus infections?

The rotavirus is a member of the Reoviridae family of viruses and contains double-stranded RNA enclosed by a double-shelled outer layer (capsid). Infection with different strains of the virus is possible, so it is common to have several separate rotavirus infections in childhood. Adults may also become infected, but the resulting illness is usually less severe than that in infants and young children.

Rotavirus vs. norovirus

Norovirus is the most common cause of gastroenteritis in the U.S. Noroviruses cause about 50%-70% of cases of gastroenteritis in adults, whereas rotavirus most typically affects young children. Like rotavirus, norovirus is highly contagious and spreads rapidly. Contaminated food and liquids can transmit noroviruses, as can touching objects contaminated with norovirus and then placing the hands or fingers in the mouth, direct contact with an infected individual, and contact with infected individuals and objects in day care centers and nursing homes.

What are risk factors for rotavirus infection?

Rotavirus most commonly infects infants and children. Since rotavirus infection is highly contagious, those who are around infected people are at high risk of infection. For this reason, children in group day care settings are at risk. However, rotavirus infects most children by 3 years of age.

Can adults get a rotavirus infection?

Yes, it is possible for anyone to develop a rotavirus infection. However, most adults who become infected have only minor symptoms, or may not have symptoms at all. Since neither vaccination nor previous infection provides full immunity, it is possible to get rotavirus infection more than once. The first infection tends to produce more severe symptoms than subsequent infections, and vaccination is very effective in infants in preventing severe symptoms (see below).

SLIDESHOW

Is rotavirus contagious? How long is rotavirus contagious?

Rotavirus infection is highly contagious. Contamination of hands or surfaces with the stool of an infected person and then touching the mouth is the main method of spread. Rotavirus infection is contagious (can be spread to other people) from the time before diarrhea develops until up to 10 days after symptoms have disappeared.

How does rotavirus spread?

The primary mode of transmission of rotavirus is the passage of the virus in stool to the mouth of another child, known as a fecal-oral route of transmission. Children can transmit the virus when they forget to wash their hands before eating or after using the toilet. Touching a surface contaminated with rotavirus and then touching the mouth area can result in infection.

There also have been cases of low levels of rotavirus in respiratory-tract secretions and other body fluids. Because the virus is stable (remains infective) in the environment, transmission can occur through ingestion of contaminated water or food and contact with contaminated surfaces. Rotavirus can survive for days on hard and dry surfaces, and it can live for hours on human hands.

What is the incubation period for rotavirus?

The time from initial infection to symptoms (incubation period) for rotavirus disease is typically around two days, but varies from one to three days.


How are human rotaviruses generally transmitted? - Biologi

Infection with a rare G3P[19] rotavirus A strain was identified in an immunosuppressed patient in Italy. The strain showed a P[19] viral protein 4 gene and a complete AU-1–like genomic constellation. Phylogenetic analyses showed high nucleotide identity between this strain and G3P[19] rotavirus A strains from Asia, indicating possible reassortment events.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children <5 years of age worldwide, causing ≈450,000 deaths annually. The RVA genome is composed of 11 double-stranded RNA segments, encoding 6 structural viral (VP) and 5 nonstructural (NS) proteins (1). The outer capsid proteins, VP7 and VP4, elicit neutralizing antibodies. The genes encoding these proteins specify at least 27 G and 37 P genotypes, which are used for RVA binary classification.

Most RVA human infections worldwide are related to 5 major genotypes: G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] (2). Genome segment reassortment between human strains or human and animal strains during co-infections can generate viruses with novel genotype combinations, possibly influencing the virus phenotype (2). Some human and animal RVA strains possess unusual genotype combinations (3,4), and some strains might partially escape vaccine-induced immune protection (5).

Since 2007, the RVA surveillance network RotaNet-Italy has confirmed circulation of common RVA genotypes among children in Italy, despite sporadic uncommon, exotic, or zoonotic genotypes (6,7). We describe infection with a rare G3P[19] RVA strain in an immunosuppressed adult patient in Italy who had severe diarrhea.

Pembelajaran

In 2012, a 35-year-old woman who was hospitalized in the Hematology Unit of Rome University Hospital “Agostino Gemelli” in Rome, Italy she experienced acute gastroenteritis after a bone marrow allotransplant. Stool samples were collected and tested for classic bacterial, viral, and parasitic enteropathogens. The study was performed in compliance with informed consent guidelines in Italy.

Viral RNA was extracted by using the Viral RNeasy MiniKit (QIAGEN/Westburg, Milan, Italy) and stored at −80°C until use. Rotavirus G- and P-genotyping were performed by reverse transcription nested PCR by using VP7 or VP4 primer mixtures described previously (8,9). Nucleotide sequencing was performed by Macrogen, Inc. (Seoul, South Korea) by using the PCR primers. After analysis in Chromas Pro 2.23 (http://www.technelysium.com.au), consensus sequences were obtained by using SeqMan II (http://www.dnastar.com/t-seqmanpro.aspx). Multiple sequence alignments were carried out, and phylogenetic trees were created by using MEGA5 software (http://www.megasoftware.net) (10), using the maximum-likelihood method and Kimura 2- (NS 4–5) or Tamura 3- (all other genes) parameter tests. Strain sequences from this study were deposited in GenBank (accession nos. KF729023–729032).

The patient had Down syndrome, acute lymphatic leukemia, and blood type A Rh+ CCDeekk phenotype a transcranial Doppler scane did not show any abnormalities . She had received a stem cell allotransplant, followed by immunosuppressive treatment. Acute gastroenteritis began 2 days after immunosuppression, on day 10 after admission to the Hematology Unit. Diarrhea was nonbloody and watery, not accompanied by vomiting and fever, and lasted 3 days, during which rehydration therapy was administered. The patient was released from the hospital in stable condition she died of systemic complications 3 months later.

Stool samples were collected at diarrhea onset and tested for bacterial and viral enteric pathogens. Results were negative for Salmonella, Shigella, Campylobacter, Yersinia, Escherichia coli, staphylococci, Giardia, norovirus, and adenovirus. Only rotavirus and Klebsiella pneumoniae were detected because the patient did not exhibit chronic/bloody diarrhea or other systemic pathologies typically related to K. pneumoniae infection, this pathogen was not investigated further.

Figure 1. Phylogenetic trees of rotavirus A (RVA) isolates based on the open reading frames of genes coding for the viral protein (VP) regions. A) VP1 (nt 73–390) B) VP2 (nt 1–425) C).

Figure 2. Phylogenetic trees of rotavirus A (RVA) isolates based on the open reading frames of genes coding for the nonstructural protein (NS) regions. A) NS1 (nt 67–1087), B) NS2 (nt 47–1012), C).

The rotavirus strain, RVA/human-wt/ITA/ROMA116/2012/G3P[19] (ROMA116), was characterized by analyzing its 11 genomic RNA segment sequences in RotaC Tool (http://rotac.regatools.be/). The strain showed the genotype constellation of G3-P[19]-I3-R3-C3-M3-A3-N3-T3-E3-H3. Phylogenetic analyses confirmed a full AU-1–like genomic constellation, associated with the P[19] VP4 gene (Figures 1, 2). The strain clustered strictly with RVA/human-tc/CHN/L621/2006/G3P[9] from China (11), sharing 98%–99% nucleotide identities for most genes except VP1 (identity 91%), and the VP4 and NS5 genes, which belonged to different genotypes (Figures 1, 2). ROMA116 also showed high nucleotide identities (98%–99%) in VP2, VP6–7, and NS1–4 genes with strain RVA/human-wt/THA/CU365-KK/2008/G3P[9] from Thailand (12).

The VP7 tree (Figure 1, panel D) revealed strict clustering of ROMA116 with G3 strains from China, Thailand, and Hong Kong, all associated with P[9] VP4. However, other G3 RVA strains from Italy reported in humans or cats grouped in the same cluster. The VP4 tree (Figure 1, panel E) shows the correlation of the ROMA116 P[19] sequence with P[19] sequences detected in human and swine strains from 1994–2010, suggesting possible human-pig reassortment at the origin of ROMA116 VP4. Further evidence of reassortment resulted from both VP1 and NS5 tree analyses. In VP1, ROMA116 showed the highest nucleotide identity (95%) with simian strain TUCH (Figure 1, panel A) in NS5, the uncommon H3 genotype of ROMA116 clustered with strains detected in or derived from animals (Figure 2, panel E).

The phylogenetic trees show the divergence of ROMA116 from the constellation 3 putative ancestor AU-1 (13), characterized during the 1980s. ROMA116 shared relatively high nucleotide sequence conservation of only the NS1 gene with AU-1, but all other genes analyzed clustered more closely with RVA strains detected in Asia. This mixed genomic pattern probably was generated by previous reassortment events between strains circulating in that area. Analysis of the VP1, VP4, and NS5 gene trees together indicates that ROMA116 may have evolved through multiple reassortment events involving RVA strains of different animal origins.

Kesimpulan

The G3P[19] RVA strain we identified represents a single sporadic detection among >7,000 human RVA strains investigated in Italy during a 7-year period, which suggests either a recent introduction or a low ability of this strain to spread among humans. However, the phylogenetic analysis shows that the overall genome of ROMA116 is more similar to those reported for human strains than for animal strains, suggesting that the strain has a lower fitness for replicating in animal hosts than in humans. A study in Thailand (14) reported an outbreak of diarrhea in piglets caused by G3P[19] RVA, but no information was available for the other genes of that strain.

The possible importation of an apparently exotic rotavirus strain such as ROMA116 into Italy is not surprising the country’s geographic position favors massive migratory flows of persons from developing countries. Although rare, similar events have been suggested previously (7). The source of this infection was not identified no additional case was reported among hospital ward patients and personnel or in the patient’s family. The patient’s parents had been cleared to assist their daughter daily after the transplant, but strict control measures for opportunistic infectious agents were otherwise enforced. The patient’s family lived in a rural area where swine, bovine, and ovine farming activities occur in close proximity to human residential settlements, which may favor the circulation and zoonotic transmission of viruses from domestic animals to a higher extent than is possible inside urban settings such as Rome. The G3P[19] RVA strain may have been transmitted by an asymptomatic but infected relative, or the patient may have been harboring the strain in the gut before hospital admission, with active viral replication and disease occurring after immunosuppressive treatment.

Because no other enteropathogens were detected among the large panel of bacteria, viruses, and parasites investigated, it is likely that rotavirus was directly involved in causing illness in the patient, whose clinical symptoms were compatible with acute watery rotavirus diarrhea. It is possible that this RVA genotype may not cause disease in immunocompetent persons and that the compromised immune status of this patient played a critical role. Even if G3P[19] RVA, as with other uncommon viral strains, does not present a direct risk for public health in Italy, it could nonetheless be a donor of atypical RVA genes that might reassort into novel epidemic strains that could escape existing herd immunity in humans. In this view, RVA surveillance of both farmed and pet animals could be of valuable support to human surveillance of severe cases in hospitals (15), particularly in the postvaccine globalized world.

Dr Ianiro works as a postdoctoral researcher in the National Center for Immunobiologicals Research and Evaluation and the Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome. His main research areas are molecular biology and epidemiology of human and animal rotaviruses.


Kesimpulan

Efforts to help alleviate the burden of rotavirus disease in sub-Saharan Africa and other developing countries have increased significantly in recent years. In this study, we evaluated the possibility of producing rotavirus VLPs using a plant expression system to produce a vaccine specifically adapted to the sub-Saharan African regions. We had partial success in demonstrating the capacity of the transient plant expression system to express specific rotavirus proteins. Despite the fact that no VLPs were observed for our fusion proteins, expression was detected for all chimeric proteins engineered, illustrating the versatility of plant-based systems. While this work is preliminary, we believe that it will serve as a solid basis for future studies on plant-made rotavirus vaccines for Africa.


Characterization of a Novel P[25],G11 Human Group A Rotavirus

ARA. 1 . Neighbor-joining phylogenetic tree based on nucleotide sequences of the VP7 encoding genes (nt 49-1026) for Dhaka6 and other established rotavirus G types. BO, bovine HU, human PO, porcine EQ, equine AV, avian. The VP7 sequences were obtained from published reports and the GenBank database. The GenBank accession numbers of the following strains are given in parentheses: Wa (KO2033), HU5 (A01028), SA11 (K02028), ST3 (X13603), OSU (X04613), NCDV (M12394), PA151 (L20881), Se584 (AJ311740), Ch2 (X56784), B37 (J04334), B223 (X57852), YM (M23194), L26 (M58290), L333 (D13549), FI23 (M61876), and Hg18 (AF237666). The VP7 sequence of WI61 was obtained from Green et al. (16). ARA. 2 . Comparison of the amino acid sequences of antigenic regions of Dhaka6 and other rotavirus G types. Dots indicate amino acids identical to the respective amino acids of Dhaka6. ARA. 3 . Neighbor-joining phylogenetic tree based on the nucleotide sequences (nt 44-762) of the VP8* fragments of the VP4 genes for Dhaka6 and other established rotavirus P types. BO, bovine HU, human PO, porcine EQ, equine SI, simian OV, ovine MU, murine RH, rhesus LA, lupine. The VP4 sequences and their GenBank accession numbers are as follows: A5 (D13395), SA11 (X14204), HCR3 (L19712), RV5 (M32559), UK ST3 (L33895), OSU (X13190), Wa (L34161), AU1 (D10970), 69 M (M60600), 116E (L94072), H2 (L04638), MDR13 (L07886), Mc35 (D14032), Lp14 (L11599), Eb (L18992), 993/83 (D16352), L338 (D13399), 4F (L10359), EHP (U08424), Hg18 (AF237665) 160/01 (AF528202), A34 (L35059), and TUCH (AY596179).


Tonton videonya: Virus part 2 of 2 Penyakit-Penyakit yang disebabkan virus (Februari 2023).