Yellow fever has been haunting Brazilians again since late 2016. The outbreak has been recorded as the largest number of human cases since 1980, with more than 400 fatalities. The virus has also spread geographically through forest areas at unprecedented rates, and is now classified as a human and environmental tragedy. There are two transmission cycles in the Americas: urban yellow fever (UYF) and sylvatic yellow fever (SYF).

Previously, all the reported cases resulted from sylvatic transmission, involving sylvatic mosquito species, especially from the genera Haemagogus and Sabethes. In these cases, non-human primates (NHP) are the principal hosts, and humans are accidental hosts, infected in rural and sylvatic areas when not properly immunized. This raised great concern over the possibility of the outbreak including not only sylvatic transmission, but also urban transmission.

Reinaldo Martins, scientific consultant from Bio-Manguinhos/FIOCRUZ, believes that there are several reasons for the epidemic to have spread so quickly in various states. “Monkeys, mainly howler monkeys, play an important role in outbreaks and epidemics. Before human cases, cases appear in monkeys, which are infected and can either die or survive. After the outbreak, the surviving monkeys are immune to yellow fever. Over the course of the following years, new susceptible monkeys accumulate until a new outbreak occurs and the cycle repeats itself,” he explained, citing global warming, ecological disruption, and the population’s growing mobility as other determinant factors. “In Minas Gerais, an area where immunization is recommended, low vaccination coverage in adults in the rural area was the most important factor, which should serve as a warning for us,” he said.

The vaccine

The yellow fever vaccine is the most important measure to prevent and control the disease. Its efficacy ranges from 95% to 99%. Since April this year, the vaccine is recommended for individuals from nine months to 59 years of age. A single dose provides lifetime immunity. Previously, a booster dose was recommended 10 years after the first dose. The single dose guideline was issued by the World Health Organization (WHO). This means that under the current rule, persons that have already been vaccinated any time in life do not need a booster dose.

Although immunization is extremely important, it is essential to respect the risk groups in order to avoid reactions to the vaccine. These are: patients with primary or acquired immunodeficiency; weakened immune system secondary to disease or immunosuppressive or immunomodulatory therapies (chemotherapy, radiotherapy, or high-dose steroids); transplant patients or with cancer and on chemotherapy; individuals with severe hypersensitivity reaction or neurological disease after previous dose of the vaccine; persons with severe allergic reaction to egg; and previous history of thymus disorder.

“The vast majority of people either feels nothing after vaccination or merely has mild symptoms, like malaise, fatigue, and low-grade fever. Very rarely, two severe adverse events can occur: viscerotropic disease (VTD), similar to yellow fever itself, and neurologic disease, the latter usually with good evolution and without leaving sequelae,” Reinaldo explained.

The numbers are decreasing thanks to mass vaccination, but the country is still on alert. “We should make no mistake: yellow fever has reached the Atlantic Forest and tends to spread even further next summer. We need to expand vaccination to cover the entire Brazilian population before next summer, with the city of Rio de Janeiro as the top priority, given the high risk of re-urbanization there. The last great urban yellow fever epidemic in Brazil was in Rio de Janeiro, in 1928-1929, when there was still no vaccine available. It would be a pity if re-urbanization of the virus began with Rio,” he commented.

A disease studied in minute detail

Just as the Zika outbreak led to a series of projects to analyze the virus, yellow fever (although a widely known disease) has also been the focus of many research projects. Bio-Manguinhos alone has four projects under way, analyzing the disease, according to Maria de Lourdes Maia, coordinator of the Clinical Advisory Division at Bio-Manguinhos.

One such study aims to determine whether the military personnel that volunteered to receive reduced doses of YFV in 2009 are still immune. “The initial results are promising. If they are confirmed, they will support the use of fractionated doses in individuals over two years of age in emergency situations,” he explained. The study is being conducted by the Clinical Advisory Division of Bio-Manguinhos with the support of the Brazilian Army and WHO, funded by the Welcome Trust, with participation by FIOTEC.

Meanwhile, the study “Immunity to yellow fever after a single dose of the vaccine in children and adults: a cohort study in a non-endemic area” seeks to answer the problem of scarcity of data in the literature to allow estimating the duration of the vaccine’s protective immune response and thus underpin public health decisions. “It will be important to know the interference in the immune response to the yellow fever vaccine, caused by immunity to dengue, which is already quite widespread in Brazilian cities; and to Zika, which has caused major epidemics in recent years in Brazil, especially in the Northeast,” said Maria de Lourdes.

The other two studies analyze lower doses in children and genetic causes of the severe adverse events that occur rarely after yellow fever vaccination.

Elsewhere at FIOCRUZ

Other units are also involved in the fight against yellow fever. For example, the Sergio Arouca National School of Public Health (ENSP/FIOCRUZ) is leading the project entitled “Duration of immunity after two or more doses of yellow fever vaccine in adults”.

The Oswaldo Cruz Institute is leading the study on the risk of reemergence of urban yellow fever in Brazil due to invasion by the mosquito Aedes albopictus. Both studies are supported by FIOTEC.