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==Diagnosis== Yellow fever is most frequently a clinical [[diagnosis]], based on [[symptomatology]] and travel history. Mild cases of the disease can only be confirmed virologically.<ref name="who.int"/> Since mild cases of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea, and vomiting 6–10 days after leaving the affected area) is treated seriously.<ref name="who.int"/> If yellow fever is suspected, the virus cannot be confirmed until 6–10 days following the illness. A direct confirmation can be obtained by [[reverse transcription polymerase chain reaction]], where the genome of the virus is amplified.<ref name=Toll2009/> Another direct approach is the isolation of the virus and its growth in cell culture using [[blood plasma]]; this can take 1–4 weeks.<ref>{{cite journal | vauthors = Leland DS, Ginocchio CC | title = Role of cell culture for virus detection in the age of technology | journal = Clinical Microbiology Reviews | volume = 20 | issue = 1 | pages = 49–78 | date = January 2007 | pmid = 17223623 | pmc = 1797634 | doi = 10.1128/CMR.00002-06 }}</ref><ref name="pmid17304460"/> Serologically, an [[ELISA|enzyme-linked immunosorbent assay]] during the acute phase of the disease using specific [[IgM]] against yellow fever or an increase in specific [[Immunoglobulin G|IgG]] [[titer]] (compared to an earlier sample) can confirm yellow fever.<ref>{{cite journal | vauthors = Falconar AK, de Plata E, Romero-Vivas CM | title = Altered enzyme-linked immunosorbent assay immunoglobulin M (IgM)/IgG optical density ratios can correctly classify all primary or secondary dengue virus infections 1 day after the onset of symptoms, when all of the viruses can be isolated | journal = Clinical and Vaccine Immunology | volume = 13 | issue = 9 | pages = 1044–1051 | date = September 2006 | pmid = 16960117 | pmc = 1563575 | doi = 10.1128/CVI.00105-06 }}</ref> Together with clinical symptoms, the detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever. As these tests can cross-react with other flaviviruses, such as [[dengue virus]], these indirect methods cannot conclusively prove yellow fever infection.<ref>{{cite journal | vauthors = Houghton-Triviño N, Montaña D, Castellanos J | title = Dengue-yellow fever sera cross-reactivity; challenges for diagnosis | journal = Revista de Salud Publica | volume = 10 | issue = 2 | pages = 299–307 | date = March 2008 | pmid = 19039426 | doi = 10.1590/s0124-00642008000200010 | doi-access = free }}</ref> Liver [[biopsy]] can verify [[inflammation]] and [[necrosis]] of hepatocytes and detect viral [[antigen]]s. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable ''post mortem'' to confirm the cause of death.<ref>{{cite journal | vauthors = Talwani R, Gilliam BL, Howell C | title = Infectious diseases and the liver | journal = Clinics in Liver Disease | volume = 15 | issue = 1 | pages = 111–130 | date = February 2011 | pmid = 21111996 | pmc = 3660095 | doi = 10.1016/j.cld.2010.09.002 }}</ref> In a [[differential diagnosis]], infections with yellow fever must be distinguished from other feverish illnesses such as [[malaria]]. Other [[viral hemorrhagic fever]]s, such as [[Ebola virus]], [[Lassa virus]], [[Marburg virus]], and [[Junin virus]], must be excluded as the cause.<ref>{{cite journal | vauthors = Cleri DJ, Ricketti AJ, Porwancher RB, Ramos-Bonner LS, Vernaleo JR | title = Viral hemorrhagic fevers: current status of endemic disease and strategies for control | journal = Infectious Disease Clinics of North America | volume = 20 | issue = 2 | pages = 359–93, x | date = June 2006 | pmid = 16762743 | pmc = 7135140 | doi = 10.1016/j.idc.2006.02.001 }}</ref>
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