BOB fm (Reino Unido)

FAPESP: Change in vaccination strategy prevented the urban yellow fever cycle in SP

Publicado em 10 novembro 2021

Yellow fever is a non-contagious viral disease with two cycles of transmission: wild and urban. Initially, the virus spreads among monkeys, and is transmitted in Brazil by mosquitoes of the same species Himagogus NS Septis. In a second, it spreads between humans, transmitted by Aedes aegypti. Brazil has not had cases of urban yellow fever since 1942, but the wild version can, by chance, infect people who live near, or frequented, forests and jungles.

This is what happened in the last wild outbreaks in São Paulo between 2016 and 2019. Article 2 published employment Scientific Reports Describing the process of spreading in the state, the disease killed people in places very close to the capital and in cities that did not have vaccine recommendations, where they never contracted the disease, such as Campinas. Scientists have now revealed that had the vaccination strategy not been adapted to the circumstances, the effects could have been much worse, leading to more deaths.

“We are in great danger of a re-emergence of urban yellow fever in the cities neighboring São Paulo. An epidemic in urban areas would have very serious effects and would be a setback,” he said. Francisco Ciravalotti NettoProfessor, Department of Epidemiology, Faculty of Public Health, University of São Paulo (FSP-USP). Work co-authored, conducted with the support FAPESP (São Paulo State Research Support Foundation).

Two waves have been identified between 2016 and 2019: one coming from west to east (2016 and 2017) and the other spreading from the Campinas region to the neighboring municipalities of Rio de Janeiro, Minas Gerais and Parana, to the coast of São Paulo (2017 to 2019). The first wave left São José do Rio Preto in April 2016 and arrived in Campinas in August 2017 at a speed of one kilometer (kilometres) per day. “At that time, due to low vaccine coverage, cases in humans increased and the disease spread towards the capital São Paulo, the coast, Valle de Paraíba and Sorocaba at the same speed, as well as to the Valle de Ribera, where it moved more slowly,” the FSP-USP professor recalls.

The vaccination strategy followed by the Ministry of Health and the State Secretariat in these cases is to vaccinate the municipalities at risk as well as the neighboring municipality. “But when the disease struck Campinas, the State Immunization Service abandoned this strategy, which involved vaccinating the entire city as well as neighboring municipalities, such as Indaiatuba and Paulínia, and decided to vaccinate cities such as Jundiaí, Jarinu and Itatiba, as it was discovered that this is where the transmission was At that time, Campinas and neighboring cities had a population of more than a million, but less than a million doses were available in the state,” summarizes Adriano Pinter, a scientific researcher at the Endemic Disease Control Authority (Sucen), a state agency. São Paulo State Department of Health, and co-author of the article.

He claims that in Mairipora, a city where 181 human cases have occurred, coverage was close to 80% when the disease arrived (unfortunately, around Christmas time, when the number of visitors increases). “If Mairipora has over a hundred deaths even with vaccination coverage above 80%, imagine if they hadn’t been vaccinated?” “People are only vaccinated when they travel.”

Scientists warn that the situation that occurred between 2016 and 2019 could be repeated. “We have to be careful, because we know the path the disease can take. Studies show that these waves of yellow fever start in the Amazon, and through forest corridors, pass through Tocantins, Goiás and Tringollo Mineiro until they reach the state of São Paulo, spreading along the coast and migrating south Today the wave reached Rio Grande do Sul and is believed to be waves that happen every five years. Campinas has never been affected by the wild cycle, it was the first time. And we describe this process well in action,” says Pinter.

Until 1999, the wild version of yellow fever was restricted to the northern and central regions of the country, with sporadic cases in the southeast. Since 2000, São Paulo has been one of the centers of the spread and circulation of the disease. Between 2016 and 2019, 648 human cases were confirmed in the state, with 230 deaths, and 850 cases in monkeys or monkey groups. Yellow fever can present with mild symptoms, which occur in most cases, but the mortality rate in severe cases is 40%.

breeding pattern

Although not a contagious disease, the pattern of spread described by scientists is called “contagion” spread, an expression referring to transmission in an area (as if parts of the forest were “infectious” to each other).

According to the first author of the article, Alec Brian LacerdaThe spread of the disease can occur through expansion, transmission, or in a hybrid manner. “Diffusion by expansion is divided into two parts: by infection, when the spread is observed due to the proximity of the area, or hierarchy, when large municipalities are generally affected. In this case, reproduction does not follow the pattern of land continuity, but takes great leaps, which can be be an indicator of an outbreak in urban areas.”

In the spread by resettlement, migratory movement is observed: the disease leaves its point of origin, where it stops growing, and moves to a more favorable point, creating a new point of origin. “This occurs, for example, when people leave areas without a vaccine recommendation and, without a vaccine, enter areas that are recommended for a vaccine. In hybrid breeding, transmission also occurs, but with the old point of origin still active. We have described the processes in this way and created maps that show Municipalities and cases that have occurred: whether cases are in monkeys or humans or both,” explains Lacerda, who began developing the work as a Scholarship holder Scientific Start-up Program at FAPESP.

According to Pinter, at the time the vaccination proposal was made, it was considered that the virus was circulating only among wild mosquitoes, and because they were not able to fly much, it was suggested that the spread would be due to territorial continuity. But there is still a question as to whether or not humans were involved in the transmission. We confirm in the article that this did not happen, and that transmission in fact occurred only between mosquitoes and non-human primates, and that this man was infected in the end, but he did not transmit, and no transmission occurred in the city. If man had been involved in the transmission process, it would have been hierarchical, that is, people would appear infected in large cities, and the transmission would take “leaps” from one place to another. And what was happening was that the virus was spreading in small towns, due to regional continuity.”

direction and speed

Lacerda explains that the group used data from the Center for Epidemiological Surveillance Professor Alexandre Franjak (CVE), of the São Paulo Health Department (cases including monkeys and human cases, according to the municipality) as well as vaccination coverage data from 2015 to 2018 from the National Immunization Program. (PNI).

“We used immunization coverage data for the population aged 0-5 years and based on this we have approximated the overall population coverage, as the data available for this age group is the most accurate record of how the health system reached the population. The Ministry of Health recommends its use in research such as ours” , he says.

With the data in hand, the scientists applied a statistical technique called kriging (Craiging) to map the spread of the virus. For each municipality, we specify a date, always the date of the first case, whether human or epidemiological, then we create a numerical sequence corresponding to the months, link the municipalities to the months in which the dissemination process began and use the kriging technique to map the phenomenon in space and time, creating curves showing the direction and speed of the progression of the spread . Once the maps were ready, we were able to compare them with the vaccination coverage map and conclude, for example, that the epidemic reached Campinas when the vaccination coverage was very low or there was no vaccination recommendation”, recalls Chiaravalloti Neto.

hot winter

The arrival of the disease in places where it was not previously affected raises several hypotheses that need to be tested. “The thing that makes the most sense to me is about the warmer winters. There should be no winged mosquitoes in the winter. There should only be eggs, because the larva does not survive the cold and dies. But what we saw is that transmission also occurred during the winter of 2017. In other words, the mosquito was flying through the winter,” says Pinter.

It is believed that it is possible that the colder winters were responsible for preventing transmission of the virus in the past, and protecting cities such as Campinas and Maipura. “But now we have less cold winters. I’m not talking about a big difference in temperature, but 2°C and 3°C. There are articles about dengue showing that temperatures around 20°C are good for mosquitoes, while 16°C is good for mosquitoes. Really harmful. The same thing happens with yellow fever. So what makes sense to me amid many hypotheses is that our winters were less cold, and the warmer they were, the faster this virus spreads.”

The main symptoms of the disease are malaise, headache, high fever, muscle aches and chills, fatigue, vomiting, nausea and diarrhea, but it can also affect the kidneys and liver. Fortunately, there is a yellow fever vaccine, produced in Brazil since 1937. Offered by the Unified Health System (SUS), it provides lifelong protection. “Our advice to residents is to get vaccinated,” the three authors say in unison.

Article An outbreak of yellow fever ring in the state of São Paulo, Brazil, also signed by scholars Leila del Castillo Saad, of CVE, and Priscilla Venâncio Ikefuti, of FSP-USP, can be accessed at