Yellow fever

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Epidemiology

Due to non-specific acute febrile illness in its early stage including substantial number of asymptomatic cases, there are limitations to define the true incidence and case fatality rate of YF.

Case definitions

• WHO suggests case definitions to survey YF with suspected case as Any person with acute onset of fever, with jaundice appearing within 14 days of onset of the first symptoms.

World Health Organization. (2022). Yellow Fever Outbreak Toolbox. https://www.who.int/emergencies/outbreak-toolkit/disease-outbreak-toolboxes/yellow-fever-outbreak-toolbox

Epidemiology according to geography

• An estimation of YF endemicity in African continent using generalized linear regression model resulted in 130,000 cases with fever and jaundice or haemorrhage (not confirmed yellow fever cases) including 78,000 deaths in the year of 2013 taking into account of YF vaccination campaign.

Garske, T., van Kerkhove, M. D., Yactayo, S., Ronveaux, O., Lewis, R. F., Staples, J. E., Perea, W., Ferguson, N. M., Burke, D., de La Hoz, F., Grenfell, B., Hansen, P. M., & Hutubessy, R. (2014). Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data. PLoS Medicine, 11(5). https://doi.org/10.1371/journal.pmed.1001638

• A systematic review found incidences of YF across African countries were quite heterogenous (I²=99.4%) as <1:100,000 in Nigeria to 10,350:100,000 in Ghana and failed in quantitative synthesis for meta-analysis.

Nwaiwu, A. U., Musekiwa, A., Tamuzi, J. L., Sambala, E. Z., & Nyasulu, P. S. (2021). The incidence and mortality of yellow fever in Africa: a systematic review and meta-analysis. BMC Infectious Diseases, 21(1), 1–11. https://doi.org/10.1186/s12879-021-06728-x

Epidemiology according to severity and Case fatality rate

• A mathematical estimation using Bayesian model showed probability of asymptomatic infection, mild disease and severe disease as 55%, 33% and 12%, respectively, as well as case fatality rate among severe disease as 47%, but the 11 studies authors collected for the study were highly heterogeneous.

Johansson, M. A., Vasconcelos, P. F. C., & Staples, J. E. (2014). The whole iceberg: Estimating the incidence of yellow fever virus infection from the number of severe cases. Transactions of the Royal Society of Tropical Medicine and Hygiene, 108(8), 482–487. https://doi.org/10.1093/trstmh/tru092

• A systematic review and meta-analysis concluded from 14 articles that case fatality rate of YF among severe disease is 39% (95%CI 31-47).

Servadio, J. L., Muñoz-Zanzi, C., & Convertino, M. (2021). Estimating case fatality risk of severe Yellow Fever cases: systematic literature review and meta-analysis. BMC Infectious Diseases, 21(1), 1–12. https://doi.org/10.1186/s12879-021-06535-4

transmission

• sylvatic cycle
• savannah cycle only in Africa
• urban cycle
• reason why YF doesn't exist in Asia is unknown

clinical features

• 3-6 days incubation
• infection phase
• remission phase
  • most patients ended with remission phase
• intoxication phase

YF vaccine

YF vaccine and Thymus disease

• Eidex RB and YF Vaccine Safety Working Group in US-CDC reported potential association between thymus diseases/thymectomy and YEL-AVD as that among reported 23 cases of YEL-AVD as of 2004 4 cases had history of thymus disease and thymectomy. The authors issued alert to Thymectomy, Thymoma, Myasthenia gravis and DiGeorge syndrome.

Eidex, R. B., & Yellow Fever Vaccine Safety Working Group. (2004). History of thymoma and yellow fever vaccination. In Lancet (Vol. 364, Issue 9438, p. 936). Elsevier B.V. https://doi.org/10.1016/S0140-6736(04)17017-7

New vaccine development

• Inactivated YF vaccine has been under development. Phase 1 trial of XRX-001 purified whole-virus, β-propiolactone-inactivated vaccine (cultured in Vero cell, adjuvanted with alumninum hydroxide) investigated 2 separated doses in 21 days apart with antigen of 4.8 μg, 0.48 μg and placebo.

Monath, T. P., Fowler, E., Johnson, C. T., Balser, J., Morin, M. J., Sisti, M., & Trent, D. W. (2011). An Inactivated Cell-Culture Vaccine against Yellow Fever. New England Journal of Medicine, 364(14), 1326–1333. https://doi.org/10.1056/NEJMoa1009303