Yellow fever, the return of an old threat

On the path that leads to Castelo Mourisco - a construction that started during Oswaldo Cruz’s time, in 1905, and is a symbol of the health work in fighting yellow fever and smallpox - the Rio de Janeiro TV Globo news team awaits to begin the interview. The camera lenses frame the current president of Fiocruz, Nísia Trindade, while reporter Mônica Sanches inquires about the currently most commented disease in Brazil. Shortly before, it was the time for the coordinator of the Center of Information on Wild Health (CISS/Fiocruz), Márcia Chame, to be approached with questions aimed at understanding the dangers of the disease’s outbreak that had 209 confirmed deaths registered until April 12. Where did it come from? Why are there so many cases? What to do? Doubts reflecting the panic of the population related to the threat of contracting the disease. At Museu da Vida, located nearby, reporters from other TV and radio stations - SBT, Band, TV Brasil and CBN - were asking the same questions, while their cameras faced the audience and awaited the beginning of the conference that would address how the researchers were monitoring the advance of the outbreak.

The disease that gathered the press, researchers and health professionals in 2017, however, was not a new, little known ill, with promises of great discoveries. The same yellow fever that mobilized public health efforts in the early 20th century is once again under the spotlight , 75 years after having its urban cycle eradicated in 1942. This acute infectious disease, an old acquainted of science, returned to cause concern after an outbreak was registered in Minas Gerais, in the region of Rio Doce and Mucuri valleys, in the east of the state, with cases confirmed or investigated also in São Paulo, Espírito Santo, Bahia and Tocantins. Until the closing of this edition, 2,422 suspicious occurrences were identified, and 623 of them were confirmed in total. Out of the 326 deaths notified, 209 were confirmed, 151 of them in Minas Gerais, according to the epidemiological report dated April 12 from the Ministry of Health. 

“We don’t have an outbreak with more than 100 cases and this lethality in over 70 years,” says Pedro Luiz Tauil, an epidemiologist specialized in infectious and parasitic diseases for the University of Brasília (UNB). The difference between yellow fever outbreaks from the beginning of the 20th century is that, on its new ressurgence, so far the disease has only been transmitted in wild regions where humans are bitten by mosquito species that live in forests. In the past, the main transmitter was the Aedes Aegypti, the same one that spreads dengue, zika and chikungunya viruses and that lives in urban environments. 

For health researchers and authorities, the major risk is the so-called yellow fever “reurbanization”, which can lead to the return of the disease in large Brazilian cities. “There is a risk; however, it is still difficult to calculate. We live with Aedes for so many years and, theoretically, it has the capacity to transmit yellow fever,” analyzes the biologist Márcia Chame. At the border between the wild and the urban, this large yellow fever outbreak also gives rise to discussions about the relation of human health and environmental degradation. In addition, the population’s search for vaccines as a protection also raises the question of which strategy should be adopted to immunize people against old and new diseases.

Wild x Urban

There has been no news about urban yellow fever for 75 years in Brazil. This form of transmission was eradicated in 1942 when the last case occurred in the city of Sena Madureira, State of Acre. Since then, all occurrences registered had wild transmission, although there is no difference between the wild and urban disease’s characteristics. “Both urban and wild yellow fever are the same disease with the same lethality. The only difference is the form of transmission,” explains the epidemiologist Pedro Luiz Tauil. In the wild cycle, transmitters are mosquitoes that live in forests, of the genera Haemagogus and Sabethes. These insects infect human beings entering forests or monkeys - the death of these animals is the first warning sign of the disease’s progress through a certain area, revealing that caution is needed. 

In the urban cycle, human beings are the main hosts and the vector disseminating the disease is an old acquainted in the fight against endemias: Aedes aegypti. What intrigues researches is the possibility of the disease to return to urban environments. This happened in Angola, Africa, as of December, 2015. According to Pedro, the high index of mosquito infestation is what led to the spread of the disease in cities of the African country. “The world did not have enough vaccine for the entire population of Angola. On the other hand, Aedes infestations in Brazil are not as intense as in Angola,” he says, although adding that the scenario is concerning (read more about Fiocruz's efforts to fight yellow fever in Africa here). According to the epidemiologist, yellow fever is different from dengue because it has a shorter period of transmission. “This is one of the reasons why we have so many cases of dengue fever and not urban yellow fever, even though there are wild cases that come to the city and can theoretically infect mosquitoes in the city,” he says.

According to Márcia Chame, the disease is defined as wild because the virus is transmitted by mosquito species that cannot be found in the urban environment. “Who gets sick with yellow fever in Brazil? Monkeys found in the wild area and people who live in the border or enter these areas to do an activity as extractivism or tourism,” she explains. Men in working age with a profile of greater exposure to forests are the ones who get sick the most. Warmer months, from December to May, are the period with the greatest occurrence of outbreaks.

In Brazil, the wild form is considered endemic and more frequently occurring in the Amazon. However, two outbreaks from 2000 to 2009 have led to the spread of yellow fever to the south and east of the country. Therefore, the Ministry of Health defined the so-called Area with Vaccine Recommendation (ACRV), a wide area covering 18 Brazilian states and the Federal District. People who live in these places should take two doses of the vaccine throughout their lives, respecting recommendations or contraindications; people traveling to these areas should also be vaccinated. “By maintaining this disease in its wild cycle, it is not possible to think about eradication, but strategies for prevention, detection and prediction of new cases,” explained the coordinator of the Technical Unit for Surveillance of Communicable Diseases of the Ministry of Health, Renato Vieira Alves, during the Panel “Yellow Fever”, held at Museu da Vida of Fiocruz (1/31) in Rio de Janeiro. 

According to the doctor of the National Institute of Infectious Diseases Evandro Chagas (INI/Fiocruz), Juliana Arruda de Matos, yellow fever causes from asymptomatic infections to severe and fatal cases. The symptoms are the same, regardless of the form of transmission. The incubation period of the disease (ranging from the mosquito bite and virus transmission to the onset of symptoms) varies from 3 to 6 days, but may extend up to 15 days. “If the person shows signs of the disease and has returned from the transmission area in the last 15 days, it is possible that he/she has yellow fever,” she said. Symptoms vary, according to the classification of cases, ranging from moderate to severe, and include fever, chills, headache, prostration, nausea, vomiting and renal and hepatic failure, which causes jaundice (yellowing of the skin, characteristic that gives name to the disease). 

It's not the monkeys' fault

The monkeys are not the villains here.  On the contrary, they are considered “sentinels” by biologists and surveillance professionals. If these animals start to die, it is time to turn the yellow warning sign on. “The occurrence of human cases is invariably preceded by primate deaths. It is a standard because the virus remains in the monkeys population,” signaled Renato. The most susceptible species are howler monkeys, marmosets and capuchin monkeys. The so-called epizootic surveillance (when the disease is spread by an animal community in a large number of cases) is a strategy adopted to detect the occurrence of the disease and death of these animals. From there, the vaccination of the population of the region begins. “This type of surveillance helps pinpointing the path of yellow fever and the need for prevention,” he said.

On the borders between wild and urban spaces, yellow fever shows the relation of human health with the environment. According to Márcia, this relation has been studied by researchers worldwide and originated a report published by the World Health Organization (WHO) and the Secretariat of the Convention on Biodiversity in 2015, which had the participation of Fiocruz. This set of studies showed that human health and welfare are being threatened by the imbalance of nature. “The loss of biodiversity may destabilize ecosystems, promote outbreaks of infectious diseases and undermine development and nutritional safety and protection against natural disasters progress,” a report excerpt says.

The loss of natural environments causes the species to be restricted to a smaller area, which promotes a greater circulation of infectious agents. “In the case of yellow fever, the mortality of monkeys is observed in places where forest fragments are very small,” says Márcia. Inside the increasingly restricted forest belt, there are less resources for survival as food and shelter, and many types of living things tend to disappear in that place. “The species that remain are the ones with capacity to adapt to environmental changes. And we have been noting that they are good keepers and transmitters of infectious agents,” she told Radis.

Factors that lead to environmental degradation include changes to the use of land, exploration of biological resources, pollution and predatory extractive activities as mining. On January 14, O Estado de S. Paulo published an articled with Márcia Chame’s declaration indicating that the outbreak of yellow fever could be related to Samarco’s environmental crime occurred in Mariana (MG), in 2015. For Radis, the researcher clarifies that there is not only a cause for the great disease outbreak. “This is a complex process that has been observed in many situations. They are impacts of many origins, including throughout history,” she explains. According to her, this situation is not new and an upsurge of the disease was already expected - the only difference was the proportion of the number of cases.

The researcher said that Brazilian studies already indicate the association of some diseases with environmental degradation. It is the case of spotted fever and Chagas' disease, for example. In the latter, the transmitting insect - the barber - prefers to settle in palm trees - common plants in areas that have suffered degradation. “The loss of biodiversity (that is, the loss of a set of wild species related in a cycle) makes a wild disease spread out of the countryside and into the urban area,” says. For Márcia, the greater the diversity of species inside natural areas, the greater the chance of maintaining environmental balance, and the natural cycle of diseases tends to remain restricted to these spaces.

The epidemiologist Pedro Luiz Tauil believes that there might be a relation between environmental changes and the disease outbreak; however, it is not proven. “We don’t know all the reasons to explain the number of cases in this year’s outbreak,” he said to Radis. For him, the only explanation is that only 50% of the population of Minas Gerais was vaccinated, when it is recommended that at least 80% of the population is vaccinated. “The cause for having so many human cases is the low vaccine coverage in the area where monkey deaths occurred,” he said. According to him, it is possible to avoid people from being infected, thus making the population living in these areas protected through vaccination, as well as those going to these regions.

After all, when should vaccination occur?

The surveillance helps showing the need for vaccines, also declared the coordinator of the Technical Unit for Surveillance of the Ministry of Health, Renato Vieira Alves. According to him, trying to identify possible cases to anticipate the virus circulation should be a priority. “If there is an extremely effective vaccination, with excellent immunity, this is a great differential of yellow fever, which allows us to invest in vigilance,” he said. According to Renato, unlike zika and dengue, other diseases also transmitted by the Aedes, when dealing with yellow fever the advantage is the existence of vaccination produced domestically, which gives the possibility of management over this input in order to ensure response to emergencies. “We can think about strategies to predict the virus circulation, since we have a tool that can prevent people from getting sick,” he said.

Vaccination against yellow fever is considered the most important measure to prevent and control the disease. It exists since 1937 and is produced in Brazil by the Immunobiological Technology Institute (Bio-Manguinhos/Fiocruz). This vaccination is prepared with live attenuated viruses from chicken eggs. A question that can be recurrent in the common sense is: why not vaccinating the entire population and make it immune to yellow fever? The infectologist Juliana Arruda de Matos warns that the vaccination is not a resource that can be indiscriminately recommended. “There are general precautions with regard to the vaccine, which need to be analyzed on a case-by-case basis, given the cost/benefit of whether or not vaccinating is worth it,” she said. Vaccination is not indicated for pregnant women, women who are breast-feeding and children under the age of six months. Avoiding the first dose for patients above 60 years is also a recommendation. “In this case, the expert needs to evaluate if vaccination is worth it or not, taking into account the risk of exposure to the disease,” completed (Read more information about the vaccine at the end of the story).

Vaccinating the entire population to prevent the disease from spreading runs into another dilemma: there is not enough vaccine in the world for this, says Pedro Luiz Tauil. “The vaccine produced has a very old production process, which has existed since 1937, and industries are not very interested in this production system,” he says. According to him, there is no need for panic and an indiscriminate search for vaccine. It is recommended to think about gradually immunizing the population in the long term. “We have been discussing the need to vaccinate the entire Brazilian population gradually for over 10 years by including the vaccination against yellow fever on the vaccination calendar of all children, not only those living in the area with recommendation,” he says. According to the researcher, two doses would be administered: one with nine months and the other at the age of 4. “Progressive vaccination would provide protection for the entire Brazilian population with smaller risks of adverse events,” Pedro says. He tells that when vaccination is done massively and hastily, motivated by an outbreak, many of the contraindications are not respected.

Renato thinks vaccination should respect the criteria established by the Ministry of Health as a priority for the population living in areas with disease outbreak. “Actions must be very precise and targeted to priority areas and populations that are in fact most exposed to the risk of getting yellow fever,” he said. The search for vaccines has been leading people to health facilities even in areas without an outbreak. “Just to have an idea, 15 thousand people were vaccinated per month in the state of Rio de Janeiro [that doesn’t have suspect outbreak]. Today, we are close to vaccinating 250 thousand,” said the undersecretary for Health Surveillance of the state of Rio de Janeiro, Alexandre Chieppe. He also advocates keeping priority criteria for areas at risk. “Discussing a public policy change at the heat of the outbreak is probably not the best idea,” he said. Even without suspect cases, the state established a belt formed by the municipalities in the border with Minas Gerais where residents should be vaccinated.

Track of changes

Researches on yellow fever mix with the history of health sciences. It was the first disease described by scientists as transmitted by a vector, still in the 19th century, tells the virologist of Oswaldo Cruz Institute (IOC/Fiocruz), Ana Bispo. “At the time, it was a reason to close ports, and it caused an impact on the economic activity. The wild form was only described in 1932 and, from 1931 to 1937, the attenuated vaccine was developed,” reports. She explains that the virus is classified by scientists as an “arbovirus” (transmitted by arthropods), and belongs to the same family as those that cause dengue, zika and West Nile fever. Goreti Rosa Freitas, an expert in vectors and also researcher of IOC/Fiocruz, tells the disease stayed in Rio de Janeiro for 61 years, from 1849 to 1910, because it was very difficult to eradicate it. Cases could only be eliminated with the work of the Oswaldo Cruz health team. “Oswaldo Cruz was not popular given the lack of faith at a time a mosquito could transmit a disease,” she also narrated during the panel “Yellow Fever” (01/31).

In new times, the yellow fever poses challenges to think about health on a global scale, and its relation with environmental factors and changes to the evolutionary pattern, said the president of Fiocruz, Nísia Trindade Lima. “In the past, Rio elites fled to Petrópolis, but we have nowhere else to go, so there is a need for interdependence of actions and systematic and permanent vigilance,” says. According to her, experts had to rethink the separation between human and animal health. “Changing the mobility pattern between urban and wild areas is crucial, alongside with changes in habits and the circulation of people and goods,” she said.

“We were not able to win the diseases from the past,” highlights the researcher Márcia Chame to Radis. According to her assessment, Brazil is a mix of large urban centers and gigantic rural areas and to provide such a large country with surveillance is a challenge. “We need a very large contingent of health workers, who must be empowered for the new challenges brought by those endemic diseases we used to call rural endemic diseases.” The qualification of professionals should take into account old aggravations and new emergencies, which include viruses that arrived in the country with the movement of people, as it was the case of zika and chikungunya. “This is one of the globalization effects: people move and so do viruses. It is a very dynamic process,” completes.

Pedro Luiz Tauil thinks municipalities are responsible for control actions, but should be supported and encouraged in this task. According to him, a strategy with mobile vaccination teams for the population of rural areas of cities with vaccine recommendation would be of great help. “It is harder for a person living in a rural area to go to the city and get vaccinated. And this population is more vulnerable, as it is closer to the woods,” he considers. In addition to surveillance of the vaccine coverage, he also advocates health education strategies for the population going to these areas. Márcia Chame thinks that what stops being a problem in the present starts being neglected and may return later, with more power. “We are a tropical and biodiverse country and the environmental monitoring has to be part of our health policy,” she states. Before being faced as things from the past, old acquaintances of science as yellow fever need to be always within priorities.

What do you need to know about vaccination?

The vaccination against yellow fever is recommended for Brazilian areas with transmission considered possible, especially for individuals that were not vaccinated and who expose themselves to wood areas. According to the Ministry of Health, immediate vaccine in the state of Minas Gerais could be especially administered preferably in people living in rural areas of the city with suspect cases and those who have never been immunized against the disease. The rest of the country has the same recommendation: every person living in Areas with Recommendation of Vaccine (ACRV) and people traveling for these regions. “Vaccinating the entire population now is not necessary, but having the population vaccinated progressively is very good,” says the epidemiologist Pedro Luiz Tauil to Radis. The doctor also reminds that the vaccine takes 10 days to immunize the person; therefore, if you are traveling tomorrow, don’t get vaccinated today. It is also worth remembering the contraindications.

This story was originally published in Portuguese by Radis Magazine. It can be read here.