August 17, 2016

Could Yellow Fever Be The Next PHEIC?

Overshadowed amidst vast media coverage of Zika, Angola and the Democratic Republic of the Congo (DRC) have been grappling with their own mosquito-borne disease outbreak: yellow fever. For much of the United States, yellow fever is not on the radar, thought of mainly as a disease faced by our ancestors as it has been considered eradicated for over a century. For much of Africa and tropical regions of South America, however, this is not the case.  In at least 43 countries of these two regions, yellow fever is endemic or intermittently endemic. Despite the existence of a vaccine, outbreaks still occur within these endemic regions. Angola and the DRC’s most recent ongoing outbreaks shed light on the harsh reality that the existence of a vaccine alone does not prevent outbreaks.

Yellow fever is an RNA virus transmitted by both the Aedes and Haemagogus species of mosquitos, the same mosquitos that transmit the Zika virus, dengue fever, and Chikungunya.  Yellow fever infection is asymptomatic or mild in most infected humans but can develop into severe disease in about 15% of cases, characterized by fever, jaundice, bleeding, organ failure, and often death. There is no existing treatment for this disease, but a yellow fever vaccine that provides complete, life-long immunity in 99% of vaccinated individuals has been in existence for over 70 years.

For this most recent outbreak, cases were first identified in Angola in December of 2015. The WHO officially announced an outbreak within Angola’s capital, Luanda, on February 12 of 2016, followed by the DRC reporting cases to the WHO onMarch 22, directly linked to local transmission from Angola. On May 19, the WHO convened an Emergency Committee (EC) to assess the yellow fever outbreak, and the committee decided that the state of the outbreak did not constitute a Public Health Emergency of International Concern (PHEIC) at that time.  As of August 12, Angola had 3,867 suspected cases (879 of which were laboratory confirmed) and 369 deaths tied to yellow fever. Likewise, as of August 8, the DRC had 2,269 suspected cases (74 confirmed) and 95 deaths reported since the start of the outbreak. This recent outbreak raises several questions: How is the current outbreak different from past yellow fever outbreaks? Could the yellow fever outbreak spread beyond the current outbreak regions of Angola and the DRC? What regions are most at risk of outbreak spread? We asked guest contributor, Dr. Peter Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine, to weigh in:

“According to World Health Organization (WHO) estimates, approximately 2,000-3,000 reported cases of yellow fever occur annually, with most of them (approximately 90 percent) occurring in a zone that spans from West to Central Africa, but also extending into Ethiopia and elsewhere in East Africa.  Some modeling estimates indicate that the actual number of cases could be much higher, possibly as many as 200,000 cases annually, resulting in tens of thousands of deaths. 

Since the end of 2015, Angola has experienced its worse outbreak in decades.  The epidemic was first reported in Luanda, the capital, and then spread to multiple Angolan provinces, resulting in over 2,000 additional cases.  From there, yellow fever spread into the Democratic Republic of Congo (DRC) and Kenya.  Uganda has also experienced a separate yellow fever outbreak. A major concern of the 2016 yellow fever outbreak is that it struck highly populated urban areas in both Luanda and in DRC in the northern suburbs of Kinshasa.  In this sense, the spread of a highly lethal disease such as yellow fever in an urban population bears some resemblance to the entry of Ebola virus infection into Guinea, Liberia, and Sierra Leone during 2014.

Urban yellow fever has the potential to spread wherever the major vector species Aedes aegypti is present and where a high percentage of the population remains unvaccinated. Shown in Fig 1 is a geospatial map of the distribution of Ae aegypti produced by Simon Hay’s group at Oxford University and the University of Washington.  Outside of Africa, the map identifies Ae aegypti areas of the Western Arabian Peninsula, which suggests that this area could be at risk due to the annual Hajj pilgrimage beginning this September.  Currently, all Hajj travelers from yellow fever endemic countries are required to provide evidence of vaccination.  While Ae aegypti is also widely distributed in South and Southeast Asia, it’s interesting to note that yellow fever has so far not gained a foothold there.  In contrast, Brazil is at risk and has a long history of yellow fever endemicity, as do other areas of the Americas.  Is it conceivable that one day, yellow fever, dengue, Chikungunya, and Zika virus infection – each transmitted by Ae aegypti – could become co-endemic in the Latin American and Caribbean region?  

Figure 1: Map of Occurrence Points for Ae. Aegypti.

The continental United States has not experienced a yellow fever outbreak since the one in New Orleans in 1905.  But as I havepreviously pointed out, there also remains a potential risk given the presence of Ae aegypti on the Gulf Coast and in Tucson, Arizona and elsewhere, especially in poor neighborhoods of crowded urban areas.

Because a yellow fever vaccine is available, in terms of responding to the yellow fever epidemics in Angola, DRC, and elsewhere in Africa, the WHO has a capacity to respond in ways that are not currently possible for other Ae aegypti-transmitted arbovirus infections.”

As Dr. Hotez mentions, the yellow fever vaccine has provided the WHO with a unique capacity to respond to this outbreak. However, the response has not been immune to major setbacks and shortfalls. Since 1997, the WHO and international aid community have worked to maintain global stockpiles of major vaccines, such as yellow fever vaccine, and to create an International Coordinating Group (ICG) to manage these stockpiles. The ICG stocks 6 million doses of yellow fever vaccine each year for emergency outbreak response. Since the start of this most recent Angola outbreak in 2015, the WHO and its partners, working through the ICG, have sent over 18 million doses of yellow fever vaccine to Africa, consequentially depleting the global stockpile twice this year already. The yellow fever vaccine takes 12 months to produce with 4 major manufacturers worldwide, meaning these companies have been working nonstop to attempt to replenish the stockpile. As the WHO itself admits, “this has never happened before.” Alongside scaling up vaccine production, the international community has also decided to vaccinate 8.5 million people in DRC’s capital, Kinasha, at one-fifth the usual dose as an emergency measure to provide immunity for at least 12 months, if not longer.

The WHO reported in an August 6th press release that the outbreak in Angola appears to be declining as there have been no newly confirmed cases in the past 6 weeks. This announcement has been coupled with criticism, however, as the WHO and its partners recently admitted that about 1 million of the 6 million vaccines sent to Angola in a February 2016 shipment went missing, never reaching those most in need of vaccination. This represents one of many unique challenges that response groups and African health ministries have had to face with this yellow fever outbreak. The WHO and its partners appear optimistic that the outbreak in Angola and the DRC will remain contained in current outbreak regions, with further mass vaccination campaigns scheduled in both countries over the next month. As Dr. Hotez points out, however, further spread cannot be ruled out due to the widespread presence of the Ae Aegypti mosquito. The WHO has repeatedly acknowledged the need for heightened vigilance and continued mass vaccination within Angola and DRC to control the outbreak, reiterating this in their most recent yellow fever situation report. With the threat of further outbreak spread still looming, however, the question remains: could yellow fever be the next PHEIC?

Peter Hotez, MD, PhD, is Professor and Founding Dean of the National School of Tropical Medicine at Baylor College of Medicine, President and Director of the Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development. Dr. Hotez is a US Science Envoy, and he is Senior Fellow at Scowcroft Institute of International Affairs, and Baker Fellow in Disease and Poverty at Rice University. Dr. Hotez is the Editor-in-Chief of PLOS Neglected Tropical Diseases.

Kate Consavage is a Program Associate at HSP. She holds a B.S. in Biology from Emmanuel College, and she currently attends Georgetown University in pursuit of a M.S. in Global Health.