Virology tidbits

Virology tidbits

Friday, 10 June 2016

Yellow fever virus in Africa: current situation and importance

Yellow haemorraghic fever (YF) is caused by Yellow Fever Virus (YFV), a prototype Flavivirus and as such as related to Japanese Encephalitis Virus (JEV), Dengue Virus (DENV) and Zika Virus (ZIKV). Similar to DENV and ZIKV, YFV is transmitted by Aedes agypti both in Africa and South America and clinical manifestations range from asymptomatic infections to multi organ failure and subsequent death. In the case of symptomatic infections, most cases are self-limiting with a febrile illness lasting for about four days that associated with myalgia, prostration and back pain which is accompanied with high viraemia and increased risk for mosquitoe infection during a blood meal. 15-25% of infected patients however enter a period of “intoxication” following the remission of fever, multi-organ disease involving failure of the liver and kidneys, jaundice and an unusual susceptibility haemorrhage due to coagulation defects (bleeding diathesis), resulting in the death of 20-50% of affected patients.

YF was initially confined to Africa but entered South America together with infected Ae. Agypti with the crowded conditions on slave ships supported and sustained the introduction of YFV into South America. Following the arrival in the slave port cities, the surrounding forests became the breeding ground of Ae. Agypti for centuries to come. Similar to ZIKV, YFV is an enzootic virus, maintained in sylvatic transmission cycles between monkeys and mosquitoes only causing sporadic outbreaks in human –particularly urban-populations. In both Africa and South America, mosquitoe populations reach high densities during the “wet” (rainy) season of the year and thus increase risk of human infections by either occupational or recreational exposure thus causing relative small outbreaks that are self-limiting. Larger outbreaks however become more common in areas where larger human and vector populations overlap and thus allow for human to human transmission and spread to previously uninfected areas by travel. Indeed, YFV epidemics were reported as far north as Philadelphia as late as the 18th century due to travel. Following the development and introduction of the Yellow Fever vaccine and mass mosquitoe extermination campaigns in the mid-20th century, despite a brief resurgence, epidemic YF has been almost eradicated from the Americas, with local outbreaks associated with forest exposure. However the appearance of Chikungunya Virus  (CHIKV), DENV and most recently ZIKV, suggests that the failure of sustained vector control and YFV vaccination might lead to a resurgence of YFV as well.

In contrast to the Americas, in Africa 150 YF outbreaks in 26 countries with 200000 cases annually were recorded between 1980 and 2012 by the WHO. Vaccination campaigns however resulted in a 57% decrease of cases in targeted countries.

Figure: Yellow Fever in Africa 2010 and 2011 per WHO

                                Current outbreaks

Despite a vaccination rate of 70% in 2015, Angola and neighbouring countries are currently experiencing an outbreak of YFV which originated in Angola in 2015 and is spreading into neighbouring mainly by travel.
In Angola, 2893 suspected cases with 788 confirmed cases and 325 deaths have been reported since Dec 2015. Cases in Kenya (2), Sao Tome and Principe (2), Democratic Republic of Congo (44 imported/8 locally transmitted including 2 sylvatic), China (11) and possibly Ethiopia  (22) have been linked to outbreak in Angola highlighting the contribution of travel to the spread of YFV by travel whereas the outbreak in Uganda (7 confirmed and 68 suspected cases) is not linked to Angola.

Figure: Number and distribution of cases linked to the current outbreak in Angola (excluding China)

 Of particular concern is the introduction of YFV to China since Angola is home to a large Chinese community. ZIKV was originally introduced to Asia from Africa before causing the current epidemic in the Americas and CHIKV spread from Kenya to Asia before being introduced to the Pacific, South America and the Caribbean.
Spread of YFV however might be limited since individuals with DENV immunity in DENV endemic areas might not become infected with YFV due to cross-protection which might explain the absence of YF in Asia, although other factors such as the higher dependence of YFV on a sylvatic transmission cycle and the higher mortality compared to DENV or ZIKV might contribute to the absence of YFV outside of Africa and South America.
Notwithstanding, the current outbreak in Angola is a major concern for the region.

Further reading

Wasserman S, Tambyah PA, & Lim PL (2016). Yellow fever cases in Asia: primed for an epidemic. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases PMID: 27156836

Monath, T. (2001). Yellow fever: an update The Lancet Infectious Diseases, 1 (1), 11-20 DOI: 10.1016/S1473-3099(01)00016-0 

Barrett AD (2016). Yellow Fever in Angola and Beyond - The Problem of Vaccine Supply and Demand. The New England journal of medicine PMID: 27276108 

Amanna IJ, & Slifka MK (2016). Questions regarding the safety and duration of immunity following live yellow fever vaccination. Expert review of vaccines PMID: 27267203

Tilak R, Ray S, Tilak VW, & Mukherji S (2016). Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat. Medical journal, Armed Forces India, 72 (2), 157-63 PMID: 27257326

Carrington CV, & Auguste AJ (2013). Evolutionary and ecological factors underlying the tempo and distribution of yellow fever virus activity. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 13, 198-210 PMID: 22981999 

Cathey, J., & Marr, J. (2014). Yellow fever, Asia and the East African slave trade Transactions of the Royal Society of Tropical Medicine and Hygiene, 108 (8), 519-519 DOI: 10.1093/trstmh/tru081

Bryant, J., Holmes, E., & Barrett, A. (2007). Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas PLoS Pathogens, 3 (5) DOI: 10.1371/journal.ppat.0030075 

Tabachnick, W. (1991). Evolutionary Genetics and Arthropod-borne Disease: The Yellow Fever Mosquito American Entomologist, 37 (1), 14-26 DOI: 10.1093/ae/37.1.14 

 Monath TP (1999). Facing up to re-emergence of urban yellow fever. Lancet (London, England), 353 (9164) PMID: 10334247 

Theiler M, & Anderson CR (1975). The relative resistance of dengue-immune monkeys to yellow fever virus. The American journal of tropical medicine and hygiene, 24 (1), 115-7 PMID: 1111351

Agampodi, S., & Wickramage, K. (2013). Is There a Risk of Yellow Fever Virus Transmission in South Asian Countries with Hyperendemic Dengue? BioMed Research International, 2013, 1-9 DOI: 10.1155/2013/905043

Xiao SY, Guzman H, da Rosa AP, Zhu HB, & Tesh RB (2003). Alteration of clinical outcome and histopathology of yellow fever virus infection in a hamster model by previous infection with heterologous flaviviruses. The American journal of tropical medicine and hygiene, 68 (6), 695-703 PMID: 12887029

WHO situation report accessed 10 June 2016

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