Ebolas Tansaniassa. Uusi kanta?Ebolan reservoaariisäntää etsitään.

Eilen luin uutisissa maininnan mahdollisesta uudesta ebolakannasta, joka on ilmeentynyt juuri Tansaniassa , mutta enempää ei eilinen uutinen selvittänyt.

Mutta missä Ebola väliaikoina piileskelee? Tätä tutkitaan intensiivisesti ja on päädytty erääseen lepakkolajiin ainakin yhtenä ehdokkaana (Fruit Bats)
Seuraavaa faktaa on luonnon reservoaarista:

Natural reservoir

* The natural reservoir of the Ebola virus is unknown despite extensive studies, but it seems to reside in the rain forests on the African continent and in the Western Pacific.

EBOLA-viruksen luonnonreservoaari on tuntematon laajoista tutkimuksista huolimatta, mutta tiedetään sen oleskelevan Afrikan mantereeen sademetsissä ja Läntisen Tyynen meren seuduilla.

* Although non-human primates have been a source of infection for humans, they are not thought to be the reservoir. They, like humans, are believed to be infected directly from the natural reservoir or through a chain of transmission from the natural reservoir.

Vaikka ihmisille tulee tartuntaa kädellisistä eläimistä, niitä ei kuitenkaan pidetä taudin reservoaarina. Nekin infektoituvat jostain luonnonlähteestä käsin tai jostain tartuntaketjusta käsin.

* On the African continent, Ebola infections of human cases have been linked to direct contact with gorillas, chimpanzees, monkeys, forest antelope and porcupines found dead in the rainforest. So far, the Ebola virus has been detected in the wild in carcasses of chimpanzees (in Côte-d’Ivoire and the Republic of the Congo), gorillas (Gabon and the Republic of the Congo) and duikers (the Republic of the Congo).

Afrikassa ihmiset ovat saaneet ebolatartuntaa suorasta kontaktista gorilloihin, simpansseihin, apinoihin, puikkija-antilooppeihin ja piikkisikoihin, joita löytyy kuolleina sademetsistä.

* Different hypotheses have been developed to explain the origin of Ebola outbreaks. Laboratory observation has shown that bats experimentally infected with Ebola do not die, and this has raised speculation that these mammals may play a role in maintaining the virus in the tropical forest.

On tehty oletus toisensa jälkeen ebolapurkausten selityksiksi. Laboratoriotutkimukset ovat osoittaneet, että kokeellisesti ebolalla infektoidut lepakot eivät menehdy ja tästä on arveltu, että nämä nisäkäseläimet voisivat olla virusta ylläpitäviä troppisissa metsiköissä.

* Extensive ecological studies are under way in the Republic of the Congo and Gabon to identify the Ebola's natural reservoir. (WHO)

laajoja ekologisia tutkimuksia on meneillään Kongossa ja Gabonissa, jotat löydettäisiin Ebolan luonnolloset reservoaarit. (WHO lähteestä)

YFV patofysiologiasta

Large vaccination campaigns and A aegypti control programs have decreased the incidence of yellow fever worldwide. Despite the availability of an effective live-attenuated 17D vaccine, yellow fever has reemerged across Africa and South America. The populations at highest risk for the illness are those in the poorest countries in the world that lack funding or infrastructure to support a widespread vaccination program. A aegypti mosquitoes are now present in the Americas, and there is a concern that large yellow fever outbreaks could occur.

Flaviviruses, including those that cause yellow fever, also have a potential use as a biologic weapon.³ For more information, see the article CBRNE - Viral Hemorrhagic Fevers in eMedicine’s Emergency Medicine volume.

Pathophysiology

Yellow fever virus is a positive-sense, single-stranded, RNA-enveloped flavivirus with a diameter of about 50-60 nm. The virus is transmitted via the saliva of an infected mosquito. Local replication of the virus takes place in the skin and regional lymph nodes. Viremia and dissemination follows.

The virus gains entrance through receptor-mediated endocytosis. RNA synthesis occurs in the cytoplasm and protein synthesis in the endoplasmic reticulum. Virions are released through the cell membrane. Its viral envelope contains a lipid bilayer taken from the infected cell. Virulence factors include the following:

• Capsid protein C facilitates viral binding.
• Membrane protein M is a minor glycoprotein.
• E proteins initiate infection and mediate viral entry.
• Nonstructural protein 1 (NS1) may play a role in RNA replication.
• NS2A protein is involved in RNA replication and packaging.
• NS2B and NS3 form a complex and are involved in polyprotein processing and replication of RNA.
• NS5 has a major role in RNA replication.

The E protein interacts with the cellular receptor, and virions are endocytosed into the dendritic cells. Subsequently, epidermal dendritic cells and lymph channels disseminate virions. After invasion in the host, Kupffer cells (fixed liver macrophages) are infected within 24 hours.

The infection quickly disseminates to kidneys, lymph nodes, spleen, and bone marrow. Renal failure occurs as renal tubules undergo fatty change and eosinophilic degeneration, likely due to direct viral effect, hypotension, and hepatic involvement.

Liver involvement is a late manifestation of the infection. Direct viral effects lead to apoptotic cell death of the midzonal hepatic cells. Vitamin K–depleted clotting factors and disseminated intravascular coagulation lead to coagulopathy and bleeding. Hepatic involvement is associated with higher risk of mortality.

Finally, circulatory shock develops secondary to cytokine storm, with evidence of increased levels of interleukin (IL)–6, IL-1 receptor antagonist, inferno-inducible protein-10, and tumor necrosis factor (TNF)–alpha. Viral antigens are found diffusely in kidneys, myocardium, and hepatocytes. In individuals who survive yellow fever, the recovery is complete, with no residual fibrosis.

Keltakuumeviruksen elämänsykli

http://www.bio.davidson.edu/people/sosarafova/Assets/Bio307/mepeele/page01.html

The Yellow Fever Virus

• Fagosytoituminen makrofagiin ihmiskehossa. Virus tekee makrofagin kyvyttömäski sulattamaan itseään.
  

Upon entering the host, the virus waits to be phagocytosed by a macrophage. Immediately following phagocytosis, the virus sheds its envelope and disables further digestion by the macrophage.

• Ehjä virus makrofagissa saapuu imusolmukkeeseen ja siellä virus alkaa replikoitua.
  

The macrophage continues with the healthy virus to the lymph nodes where the virus begins replication in earnest.

• Virus hajoittaa isäntäsolunsa makrofagin ja koettaa infektoida uusia makrofageja.
  

The virus lyses its host macrophage and seeks to infect other macrophages.

• Imusolmukkeesta virus päässee veren kierron mukana maksaan.
  

From the lymph node the virus is eventually carried through the blood stream to the liver.

• Maksassa YFV infektoi Kupfferin solulinjaa, joka reunustaa maksan verisuonia. Kupfferin solut ovat sellaisia makrofageja, jota maksan alueella ovat vastuussa solujätteen ja verenkierrosta tulevien vaurioituneitten verisolujen hävittämisestä.
  

Once in the liver, the virus is able to infect Kupffer cells lining bloodvessels in the liver. The Kupffer cells are macrophages residing in the liver responsible for clearing cellular debris and dead and damaged blood cells from the bloodstream.

• Kupfferin solujen infektoituminen ja kuolema vaurioittaa ympäröivät maksasolut ja johtavat hyaliinin muodostumiseen, mikä on keltakuumeelle tunnusomaista.
  

The infection and death of Kupffer cells damages surrounding hepatocytes, leading to the formation of translucent hyaline "councilman bodies," the hallmark of yellow fever.

• Maksan vaurio estää maksan tärkeää funktiota: sapen alkuaine bilirubiini ei voi muuntua biliverdiiniksi, mistä seuraa potilaan keltainen väri, "keltakuume"
  

Liver damage prevents the bile precursor bilirubin from being converted to biliverdin, leading to the most visible symptom of yellow fever; jaundice.

• Kun virus on lisääntynyt hyvin runsaasti ja maksavaurio on laaja, oireita on lievästä flunssan tapaisesta nivelkipuihin, aivotulehdukseen ja verenvuototautiin asti.
  

Once the virus has heavily replicated and liver damage is extensive symptoms ranging from flu-like symptoms, joint-pain, encephalitis, and hemorrhagic disease develop.

• Keltakuume johtaa menehtymiseen 10-30%:ssa tapauksista. kun tauti on systeeminen, hyttysen saamista veriaterioista virus aloittaa uuden elinkiertonsa.
  

Yellow fever is lethal in 10-30% of cases. Once systemic, the virus is collected from the bloodstream by mosquitos, where it begins its life cycle again.

Barnes E. Diseases and Human Evolution. Albuquerque : University of New Mexico Press, 2005.

Tesh RB, Guzman H, Travassos de Rosa APA, Bunnell JE, Zhang H, Xiao SY. 2001. Experimental Yellow Fever Virus in the Golden Hamster (Mesocricetus auratus). I. Virologic, Biochemical, and Immunologic Studies. The Journal of Infectious Diseases 183: 1435.

Keltakuumeviruksen genotyypeistä

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Yellow fever virus in Haemagogus leucocelaenus and Aedes serratus mosquitoes, southern Brazil, 2008.

Cardoso Jda C, de Almeida MA, dos Santos E, da Fonseca DF, Sallum MA, Noll CA, Monteiro HA, Cruz AC, Carvalho VL, Pinto EV, Castro FC, Nunes Neto JP, Segura MN, Vasconcelos PF.

Emerg Infect Dis. 2010 Dec;16(12):1918-24.PMID: 21122222 [PubMed - in process]Free ArticleRelated citations

2.

Molecular Epidemiology of Yellow Fever in Bolivia from 1999 to 2008.

Baronti CX, Goitia NJ, Cook S, Roca Y, Revollo J, Flores JV, de Lamballerie X.

Vector Borne Zoonotic Dis. 2010 Oct 6. [Epub ahead of print]PMID: 20925524 [PubMed - as supplied by publisher]Related citations

3.

Yellow fever virus maintenance in Trinidad and its dispersal throughout the Americas.

Auguste AJ, Lemey P, Pybus OG, Suchard MA, Salas RA, Adesiyun AA, Barrett AD, Tesh RB, Weaver SC, Carrington CV.

J Virol. 2010 Oct;84(19):9967-77. Epub 2010 Jul 14.PMID: 20631128 [PubMed - indexed for MEDLINE]Related citations

4.

Genetic relationships among populations of Aedes aegypti from Uruguay and northeastern Argentina inferred from ISSR-PCR data.

Soliani C, Rondan-Dueñas J, Chiappero MB, Martínez M, Da Rosa EG, Gardenal CN.

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5.

Genome-based polymorphic microsatellite development and validation in the mosquito Aedes aegypti and application to population genetics in Haiti.

Lovin DD, Washington KO, deBruyn B, Hemme RR, Mori A, Epstein SR, Harker BW, Streit TG, Severson DW.

BMC Genomics. 2009 Dec 9;10:590.PMID: 20003193 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

6.

Two different routes of colonization of Aedes aegypti in Argentina from neighboring countries.

Dueñas JC, Llinás GA, Panzetia-Dutari GM, Gardenal CN.

J Med Entomol. 2009 Nov;46(6):1344-54.PMID: 19960679 [PubMed - indexed for MEDLINE]Related citations

7.

Detection of a new yellow fever virus lineage within the South American genotype I in Brazil.

de Souza RP, Foster PG, Sallum MA, Coimbra TL, Maeda AY, Silveira VR, Moreno ES, da Silva FG, Rocco IM, Ferreira IB, Suzuki A, Oshiro FM, Petrella SM, Pereira LE, Katz G, Tengan CH, Siciliano MM, Dos Santos CL.

J Med Virol. 2010 Jan;82(1):175-85.PMID: 19950229 [PubMed - indexed for MEDLINE]Related citations

8.

A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

Meier KC, Gardner CL, Khoretonenko MV, Klimstra WB, Ryman KD.

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9.

Reduced levels of genetic variation in Aedes albopictus (Diptera: Culicidae) from Manaus, Amazonas State, Brazil, based on analysis of the mitochondrial DNA ND5 gene.

Maia RT, Scarpassa VM, Maciel-Litaiff LH, Tadei WP.

Genet Mol Res. 2009 Aug 18;8(3):998-1007.PMID: 19731220 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

10.

Gene flow, subspecies composition, and dengue virus-2 susceptibility among Aedes aegypti collections in Senegal.

Sylla M, Bosio C, Urdaneta-Marquez L, Ndiaye M, Black WC 4th.

PLoS Negl Trop Dis. 2009;3(4):e408. Epub 2009 Apr 14.PMID: 19365540 [PubMed - indexed for MEDLINE]Free PMC ArticleFree textRelated citations

13.

The enigma of yellow fever in East Africa.

Ellis BR, Barrett AD.

Rev Med Virol. 2008 Sep-Oct;18(5):331-46. Review.PMID: 18615782 [PubMed - indexed for MEDLINE]Related citations

14.

The Yin and Yang of linkage disequilibrium: mapping of genes and nucleotides conferring insecticide resistance in insect disease vectors.

Black WC 4th, Gorrochetegui-Escalante N, Randle NP, Donnelly MJ.

Adv Exp Med Biol. 2008;627:71-83. Review.PMID: 18510015 [PubMed - indexed for MEDLINE]Related citations

15.

Mitochondrial DNA polymorphism and heteroplasmy in populations of Aedes aegypti in Brazil.

Paduan Kdos S, Ribolla PE.

J Med Entomol. 2008 Jan;45(1):59-67.PMID: 18283943 [PubMed - indexed for MEDLINE]Related citations

16.

A mutation in the voltage-gated sodium channel gene associated with pyrethroid resistance in Latin American Aedes aegypti.

Saavedra-Rodriguez K, Urdaneta-Marquez L, Rajatileka S, Moulton M, Flores AE, Fernandez-Salas I, Bisset J, Rodriguez M, McCall PJ, Donnelly MJ, Ranson H, Hemingway J, Black WC 4th.

Insect Mol Biol. 2007 Dec;16(6):785-98.PMID: 18093007 [PubMed - indexed for MEDLINE]Related citations

17.

Yellow fever: a disease that has yet to be conquered.

Barrett AD, Higgs S.

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18.

Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad.

Cha SJ, Chadee DD, Severson DW.

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Amplified fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the yellow fever mosquito Aedes aegypti.

Zhong D, Menge DM, Temu EA, Chen H, Yan G.

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20.

Genome analysis and phylogenetic relationships between east, central and west African isolates of Yellow fever virus.

von Lindern JJ, Aroner S, Barrett ND, Wicker JA, Davis CT, Barrett AD.

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