This week, Brazil’s Ministry of Health confirmed 846 cases of yellow fever, including 260 deaths, in the country since July 1, 2017. This represents an approximately 25% increase in cases from the same time last year during the same period. Most confirmed cases and deaths have been reported in the regions surrounding Brazil’s largest cities, including São Paulo and Rio de Janeiro. If the virus spreads to these cities, it would put an estimated 32.3 million urban dwellers at risk, most of whom have not previously received a yellow fever vaccine, according to Brazil’s Ministry of Health.

Brazilian health officials are currently vaccinating millions of people to prevent a full-blown yellow fever outbreak in the cities. In light of the outbreak, the US CDC issued an “alert level 2--practice enhanced precautions” travel notice in January, urging Americans to avoid traveling to the affected states without getting vaccinated first. Below we take a closer look at the yellow fever outbreak and the vaccination strategies used by Brazilian public health authorities to limit its spread.

A Tropical Threat

Yellow fever is a hemorrhagic virus endemic to many tropical regions of Central and South America and sub-Saharan Africa. The burden of yellow fever in Africa was estimated at 130,000 cases and 78,000 deaths in 2013. Symptoms of yellow fever include fever, chills, headache, vomiting, and fatigue. According to the CDC, about 15% of yellow fever cases progress to develop a more severe form of the illness. Symptoms of the severe form, which has a case fatality between 20% and 50%, include fever, bleeding, and jaundice (which gives the disease its characteristic name). There is no treatment, but the yellow fever vaccine is highly effective, providing lifelong immunity for most people when a full dose is administered.

Yellow fever is spread primarily through the bite of an infected mosquito. The virus is endemic to the Amazon rainforest which comprises the majority of Brazil’s land area; however, Brazil’s populous coastal regions are normally not at risk. This is because yellow fever has two transmission cycles in South America: “jungle” and “urban”. Typically, the virus spreads via the jungle (or sylvatic) cycle, which involves viral transmission between infected monkeys living in the rainforest and mosquitoes belonging to the Haemagogus and Sabethes genus. Humans who visit the Amazon for work or recreation can then contract the virus from infected mosquitos (humans cannot contract the virus directly from monkeys). In contrast, the urban cycle ensues when the virus is brought to cities by a human who was infected in the jungle, thus allowing for transmission between humans and Aedes aegypti mosquitoes in urban settings.

The current outbreak is concerning because if it enters Brazil’s megacities, it could enable urban transmission and cause the highest number of casualties. The Aedes aegypti mosquito (which also spreads Zika, dengue, and chikungunya) is highly prevalent in urban settings, including the slums of Brazil, where it breeds in standing pools of water and water-filled containers. Urban transmission has not been documented in Brazil since 1942; however, the virus is migrating south at more than a mile per day, and it is likely to keep spreading during Brazil’s hot and rainy summer months.

Vaccination Nation

In addition to educating the public about the need to take precautions while visiting the rainforest, Brazilian authorities are vaccinating millions of residents against the virus in the states of Rio de Janeiro, Bahia, and São Paulo to limit the outbreak’s spread. As of February 27, about 5.5 million people have been vaccinated. This represents 23.2% of the roughly 23 million people targeted for vaccination, according to the Ministry of Health.

Due to limited supply of the yellow fever vaccine in Brazil and globally, Brazilian authorities are administering smaller doses of the vaccine, known as fractional dosing. Fractional dosing has been shown to be an effective strategy to reduce viral transmission of yellow fever in other contexts, such as the Democratic Republic of the Congo. The WHO’s Strategic Advisory Group of Experts states a 5-fold fractional dose still provides immunity for at least 12 months. As such, fractional dosing is “the best way to stretch vaccine supplies and protect as many people as possible to stop the spread of yellow fever in emergency situations,” according to the WHO. It is not considered a long-term strategy or to be used for routine yellow fever vaccination.

Vaccine hesitancy has reportedly been a major challenge to inoculating Brazilian citizens against yellow fever. According to the New York Times, initial enthusiasm for the yellow fever vaccine, including long lines at clinics, diminished after anti-vaccine activists began spreading rumors about the vaccine’s safety on social media. While the vaccine is safe and effective, there is a rare chance of a serious adverse event. Approximately 1 in 100,000 patients suffer a life-threatening reaction to the vaccine, and 1 in a million dies. With Brazilian authorities aiming to vaccinate 23 million residents, this means 23 people could die, although this is far less than the projected fatality rate from a widespread yellow fever outbreak. In addition, pregnant women, people older than 60, and children between 6 and 8 months are only given the vaccine when the risk of infection is high, due to greater risk of adverse events, according to the CDC. Children under 6 months or those with a compromised immune system are not eligible for the vaccine.

Social media has amplified the voices of those who have suffered adverse events and those who are opposed to vaccination on personal grounds. A Facebook post about a teenage girl’s (unconfirmed) fatal reaction after receiving the yellow fever vaccine went viral. In recent weeks, the Ministry of Health has deployed mobile vaccination clinics to offer free vaccinations to residents of Sao Paulo and other cities, which has reportedly improved vaccine coverage. Outbreak Observatory has previously reported that targeted outreach, proactive adverse event monitoring, and enhanced risk communication can help to improve vaccine coverage during government-led mass vaccination campaigns.

A “Reemerging” Disease

Hopefully, Brazil’s mass vaccination campaign will limit the spread and impact of the yellow fever outbreak until the dry season begins in June and July. Even so, the number of yellow fever cases are expected to increase in the years ahead, and the potential for reemergence of urban yellow fever epidemics (which has not occurred in Brazil since the 1940s) is considered “major.” Climate change, deforestation, and development in the Amazon have increased the range of mosquito vectors for yellow fever, expanded the proximity of humans to monkey species which may carry the virus, and introduced other risk factors for the reemergence of yellow fever.  

Due to this increasing risk of yellow fever, studies recommend that health officials act early, such as by implementing vaccination campaigns in high risk zones, to prevent harm to millions of people living in or adjacent to regions where yellow fever is endemic. In sub-saharan Africa, for instance, recent vaccination campaigns funded by the GAVI Vaccine Alliance and other partners were estimated to have reduced the number of yellow fever cases and deaths by 27%.

In light of the global vaccine shortage — including in the US, where vaccine manufacturer Sanofi Pasteur announced a temporary total depletion of US licensed yellow fever vaccines until the end of 2018 — governments and vaccine manufacturers should increase national vaccine production as well as global vaccine stockpiles. A greater vaccine supply will reduce the need for fractional dosing and enable longer-term prevention strategies to counter the reemergence of yellow fever.

Photo: A brightly colored Sabethes cyaneus mosquito, which lives in the Amazon rainforest canopy and can transmit yellow fever.

Photo courtesy of CDC/ Prof. Woodbridge Foster; Prof. Frank H. Collins

Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.