In August, Brazil launched a countrywide vaccination campaign against measles and polio in the midst of a concerning situation. In 2017, childhood immunization rates for 17 diseases – among them measles – reached their lowest levels in many years. The Brazilian Ministry of Health, as well as experts in immunology, epidemiology and public health who were consulted in the report, outlined nine reasons to explain the abrupt decline in the numbers. The reasons vary between the misperception by the general population that vaccinating is not necessary as illnesses have disappeared, to problems with the information system used to register vaccinations. All are reasonable and probable causes and they may work in combination. However, they have not yet been quantified, which would help identify and implement strategies to support vaccination campaigns and recover the higher immunization levels of years past.
One particular consequence of the reduction in the number of children vaccinated was the measles outbreak in Roraima and Amazonas. The coverage rate of MMR, which prevents the disease and reached 96% of children in 2015, dropped to 84% in 2017 and opened the way for the return of the disease in Brazil. Transmitted by air, its cause—a virus of the Morbilivirus family—causes high fever, discomfort, persistent cough, conjunctivitis, and leaves red marks on the body. It attacks the cells of the immune system and reduces the body’s line of defense for a long period of time, increasing the likelihood of secondary infections that can lead to death. The measles virus had been eliminated in Brazil in 2016, but has now returned via Venezuela. Between February and July 23rd, 822 individuals were infected with the disease—272 cases in Roraima, 519 in Amazonas, 14 in Rio de Janeiro, 13 in Rio Grande do Sul, 2 in Pará, 1 in São Paulo and 1 in Rondônia—causing 5 deaths.
The Ministry of Health recognizes the severity of the problem. Sociologist and epidemiologist Carla Domingues, general manager of the ministry’s National Immunization Program (PNI), confirmed on July 26th at an event organized by the Emílio Ribas Institute of Infectious Diseases in the city of São Paulo that the current measles outbreak “proves that our vaccination coverage is inadequate and there is an urgent need to improve it.”
In addition to the decline in the administration of MMR, which also prevents mumps and rubella, data published by the ministry in June showed a significant reduction in 2016 and 2017 in the administration of nine other vaccines recommended for the first year of life. These 10 vaccines, which are available at no cost through Brazil’s United Health System (SUS) clinics, protect against 17 illnesses caused by viruses and bacteria that, up until 40 years ago, killed thousands of Brazilians every year or left many with irreversible side effects (for how vaccines work, see sidebar “Training for battle” at the end of this piece).
After the coverage of some vaccines remained high for more than a decade, six of the vaccines plummeted 18 to 21 percentage points in 2017, in comparison with 2015 (see graphs). As a result, 23% of close to 3 million children who were born or completed their first year in 2017 did not receive complete protection from the polio virus, which can cause permanent paralysis in the legs and arms. A similar number became susceptible to the hepatitis A and B viruses, which damage the liver, and to bacteria associated with serious infections such as tetanus, diphtheria, pertussis (whooping cough) and meningitis. Only the BCG vaccine, which safeguards against bacteria that cause serious forms of tuberculosis and is applied in a single dose in maternity wards, reached the World Health Organization’s (WHO) recommended levels of immunization. The recommended coverage is 90% for BCG and the vaccine for rotavirus, which causes severe diarrhea. For the other vaccines, it is 95%.
“It’s an alarming drop,” states immunologist Jorge Kalil Filho, professor at the School of Medicine at the University of São Paulo (USP) and member of the Technical Advisory Committee on Immunizations (CTAI), a consultative body of the ministry that evaluates PNI strategies and recommends changes to the vaccination calendar. “The Brazilian program is one of the most successful in the world. It is very damaging to the country’s international image to allow the coverage rates, which were close to 95%, to drop to close to 80%,” reports pediatrician Alexander Precioso, director of clinical trials and pharmacovigilance at the Butantan Institute, one of the country’s institutions that produces vaccines, serums and other immunobiological agents.
In an interview with Pesquisa FAPESP on July 13th, Carla Domingues reported that, in addition to measles, another current concern is the risk of the return of polio. “Identification of a possible case of paralysis caused by the polio virus in Venezuela in April caused alarm,” she reports. Subsequent exams ruled out the virus, in principle, as the cause of paralysis in a young boy of 2 years and 9 months, according to the June report by the Pan-American Health Organization (PAHO).
Nevertheless, there is cause for concern. The numbers published by the ministry indicate that the number of Brazilian children immunized against polio in 2017 is the lowest since 2000: on average, 77% of them received the three doses recommended for the first year of life. “It is a national problem. The vaccination target was not reached in 22 of the 27 federative units,” states the PNI coordinator. Of even greater concern: in 312 Brazilian municipalities (44 in the state of São Paulo), less than half of the children were immunized.
These data reinforce the importance of the current campaign, which aims to immunize against polio and measles 11.2 million children between 1 and 5 years of age. “This has been the plan since 2017,” states pediatrician Helena Sato, technical director of the Immunization Division of the São Paulo State Department of Health. “Every four or five years, we rerun these campaigns to bring to zero the number of children who did not receive the routine vaccination.”
Initiated in 1980, the countrywide vaccination campaigns against polio eliminated from Brazil the most aggressive form (wild-type) of the virus—the last case of infantile paralysis caused by the polio virus was in 1989 in Paraíba. Nevertheless, the campaigns remain necessary. “The wild virus is endemic in Pakistan, Afghanistan, and Nigeria, and the movement of people across borders is high,” reports Helena.
According to Carla Domingues, when the ministry confirmed the decline in vaccinations, it took the first steps to remedy the situation by alerting municipal leaders and societies of health experts. “On June 28th, in a meeting of state and municipal representatives, we spoke of the danger of the reintroduction of polio and we charged the municipal leaders with the task of developing strategies to increase vaccination rates,” she confirms. “We also spoke with professional councils and medical societies, in particular those of pediatrics, immunology and infectology, so that they bring this problem to the attention of their associates. It is the doctors and other health professionals who should recommend the vaccine.”
These are the initial steps—albeit timid ones—that will address a recent problem with multiple causes that have not yet been fully understood. Carla Domingues and other specialists cite nine reasons for the fall in vaccination rates. However, they do not know how much each contributes to this phenomenon. “No one knows exactly,” recognizes epidemiologist Eliseu Waldman, professor at the School of Public Health (FSP) of USP.
We identify reports by physicians who counsel people to not get vaccinated, says Carla Domingues
The ministry places more weight on five of the reasons: the misperception among parents that there is no longer a need to vaccinate as illnesses have disappeared; a lack of understanding about which vaccines are part of the national vaccination calendar and are mandatory; fear that the vaccines will cause adverse side effects; concern about a high number of vaccines overwhelming the immune system; and lack of time for people to go to health clinics which only operate from 8 a.m. to 5 p.m. Monday to Friday. These reasons are the most mentioned in the surveys undertaken by Brazilian municipalities following national campaigns—in the state of São Paulo, 58,000 households were visited after the 2017 campaign. “These factors can interfere with vaccination coverage, but they are not the only factors,” confirms Domingues. “We also identify reports by physicians and other health professionals who recommend that people not vaccinate against illnesses that no longer exist in this country.”
Some specialists interpret the perception that vaccination is no longer needed as a result of the success of immunization strategies. In the last century, different strategies—routine vaccination, mass immunization, or to deal with outbreaks—eliminated yellow fever from cities in 1942 and smallpox in the 1970s. With the establishment of the PNI in 1973, the strategies became systematic and helped to bring polio to an end and reduce cases of measles, whooping cough, tetanus and serious forms of tuberculosis.
“Thanks to immunization, there are no more cases of many of these diseases and news of adverse side effects of the vaccinations is rare,” says Precioso of the Butantan Institute and member of the Permanent Advisory Commission on Immunization for the state of São Paulo. “The new generations have never seen these illnesses and are not afraid of them,” says Kalil of USP, who had colleagues with polio in the 1960s.
The origin of the problem, according to the ministry, is not a lack of vaccines, despite temporary reductions in supply of some vaccines due to production problems. “Vaccine purchases have not decreased. In Brazil, there are no resource contingencies for the purchase of vaccines,” reports Carla Domingues. “The PNI is integrated as a budget line in the budget of the ministry, which is obliged to execute it.”
In 22 years, the program’s spending for the purchase of immunobiological agents (vaccines, serums, and antibodies) has multiplied by 44: from R$94.5 million in 1995 to R$4.2 billion in 2017, which is 30% higher than in 2015. During this period, there was an increase in the number of doses acquired to supply the population, which grew from 160 million to 208 million, while diversity in the vaccines also increased. Today, the program also serves young people and adults with 28 vaccines that stimulate the body to create defenses against infectious agents, as well as 13 serums and four antibodies, that directly neutralize invasive microorganisms or toxic compounds released by them.
“The calendar became more complex. There were six childhood vaccines in the 1990s. Today, there are 14,” recounts health physician Rita Barradas Barata of the Santa Casa School of Medical Science of São Paulo. “If the pediatrician does not provide guidance, mothers will not know which their children should take,” reports the researcher who has carried out four surveys on vaccination coverage in Brazilian cities.
In 2007 and 2008, the most recent survey was carried out, with financing by the ministry, where teams led by Barradas Barata and her associates analyzed vaccination records for 17,295 children up to a year and a half in the 26 capital cities and in the Federal District. One quarter of the Brazilian population resides in these cities, where one in five children had not received all of the vaccines they should have, according to an article published in 2012 in the Journal of Epidemiology and Community Health. The proportion of children with an incomplete vaccination record was significantly higher (22.8%) among the wealthier sample than in the poorer segment (varied from 13.8% to 18.8%). This seemingly contradictory relationship—assuming parents who are considerably more informed and with greater financial means have better access to vaccines—was observed in eight capital cities, among them being the three most populated: Rio de Janeiro, São Paulo, and Belo Horizonte. “In the smaller cities with weaker public support networks, the wealthier vaccinate more because they live in neighborhoods with health centers or that have access to private clinics. In the larger cities, the public network is broader and much more structured, and the poorer population vaccinates more,” says Barradas Barata.
Vaccination levels also seem to depend on the link between families and the health service. Under the orientation of Waldman, of FSP-USP, nurse Márcia Tauil followed vaccination coverage from 2012 to 2014 of 2,612 children from Araraquara, in the interior region of São Paulo, who were served by public health clinics, private clinics, or both. This city of 226,000 inhabitants was a pioneer in the country, implementing an information system to register immunizations in the 1980s. During her doctoral studies, which she completed in 2017, Tauil verified that the children only served by public health clinics had a higher probability of having an up-to-date vaccination record than those served by private clinics or by both. Why? A higher connection with the public health clinic. “In these clinics, there is an emphasis on the training of professionals such that they encourage vaccination,” says Waldman.
We must not discount as causes of the decline in vaccination rates the influence of false news that circulates in social media and initial actions taken by groups against immunization. A report in May 2017 in the newspaper O Estado de S. Paulo identified on Facebook five Brazilian anti-vaccine groups with close to 13,000 members. “We monitor and try to respond quickly to fake news, but we believe that the anti-vaccine groups here are not yet as structured as they are in other countries,” says Carla Domingues. In Europe and in the United States, it is more common to have groups that do not believe in vaccination for reasons of untruthful news or religious and philosophical reasons. A study published in June in PLOS Medicine reports that, from 2009 to 2016, the number of US states where parents did not vaccinate their children for philosophical reasons rose from 12 to 18 states—in these states, the proportion of children protected from measles, mumps and rubella was lower than in the others.
The anti-vaccine movements gained strength after surgeon Andrew Wakefield published a study in 1998 in Lancet, a respected magazine in the medical field, insinuating that MMR (for measles, mumps, and rubella) was associated with autism. Later studies negated the connection and showed that Wakefield held stocks in a company that proposed the use of another vaccine. His medical license was revoked, but the damage was done and outbreaks of measles reappeared in Europe (see Pesquisa FAPESP issue no. 181).
Part of the drop in numbers for vaccine coverage in Brazil can also be credited to a change in the system for immunization registration, which was initiated in 2012 and expanded in the last two years. In the former system, professionals in vaccination clinics registered on paper each dose administered over a four-week period. At the end of the month, they consolidated the data and forwarded it to the management of the municipal epidemiological surveillance team who completed the Information System for SUS (DataSUS). This only required one computer, connected to the internet, in each of the 5,570 municipalities.
The Information System for the National Immunization Program (SIPNI), which substituted the former system, required the installation of computers in 36,200 vaccination clinics, as well as employee training. SIPNI registers the name and personal data of each vaccinated individual and the doses he or she receives. This information is accessible to vaccination clinics and public health clinics throughout the country (which is important in the case of adverse reactions), allowing for easy retrieval of information when an individual loses his or her vaccination booklet. It also facilitates for Brasília the registration, almost in real time, of the number of administered doses. SIPNI is installed in 24,388 vaccination clinics (67.4% of the total) in 5,257 municipalities. There are two types of systems in operation: the most recent, online, with data transmission in real time; and the former system, desktop version, where data completion is done offline and data is sent at the end of the month to DataSUS. One of the barriers is the need for constant upgrading and updating to the desktop version used by the clinics. There are also problems with file transmission in municipalities that use their own information systems, which can create discrepancies between local data and the consolidated numbers at the national level. “We don’t know how each of these systemic problems contributes to the drop in vaccination coverage, but this does not explain everything,” confirms Helena Sato, who is also a member of the CTAI.
In a letter sent by the media relations department, the Brazilian Ministry of Health confirms that “both the municipalities that use the former system and those that use SIPNI exhibit low vaccination coverage.” Carla Domingues confirms that, through the Ministry of Health in Brasília, there is no way of knowing what happened in each city throughout the country. The vaccines purchased by the ministry and sent to the states may not have arrived or, having arrived, parents did not take their children to be immunized. It is also possible that they arrived and the municipalities administered the vaccinations but did not register them, or everything was done correctly and the data was not sent to the Ministry of Health. “Each municipality must identify what happened,” advises Carla. “Right now, what is important is that there is national effort to recover the high, evenly distributed coverage.” In São Paulo, Helena Sato and her team plan to carry out a study this year to identify the individuals who have not been vaccinated and measure factors that might influence their decision for not taking a vaccine.
The impact of a vaccine on the defense system of an organism is similar to the training of a combat squad. It prepares part of this group to identify the potential invader, another to fight it and a third to recognize it, in the case that it reappears.
The defense system kicks into action when infectious agents, such as a virus or bacteria, get through the skin or the membranes of some organs and penetrate the blood or bodily tissues. The infection first activates the dendritic cells, which digest the invaders and present their parts to other cells, the T lymphocytes. The CD4 T lymphocytes activate the CD8 lymphocytes, which produce molecules to fight the invader and infected cells. Some of the lymphocytes multiply and transmit to their successors the ability to recognize and fight the invaders. The T lymphocytes communicate with the B lymphocytes, which produce specific antibodies against the agents that cause diseases or part of them.
If the organism is able to deal with the invaders itself, why take a vaccine?
One reason is that some infectious agents, which cause serious diseases that are often lethal, such as the measles virus and yellow fever, or the bacteria that causes meningitis, can reproduce much faster than the defense system’s ability to fight them. In this case, the defense system needs external help, such as antibiotics or antiviral medication. However, in some cases, these medications may not work.
The vaccine, by causing a much milder version of the infection, which should not cause any damage to the organism, prepares the immune system to act more quickly and prevent the multiplication of the invader.
The first vaccine, which was developed at the end of the eighteenth century by the British physician Edward Jenner (1749–1823), was for smallpox, a lethal and deforming infection that killed millions of people in the twentieth century. The mass vaccination campaign eliminated smallpox from the world in the 1970s.
Close to 60 vaccines have been approved for use in humans and protect against 26 serious diseases caused by viruses or bacteria. Every year, according to the World Health Organization (WHO), these formulations prevent the death of 2 million children under the age of 5. They can be produced using very weak or less aggressive versions of viruses or bacteria; others use an inactivated (killed) infectious agent or part of it. “In principle, it is possible to obtain a vaccine for any infectious agent,” confirms Brazilian immunologist Gabriel Victora, professor at Rockefeller University in the United States. “For various reasons, however, we have not yet been able to develop vaccines for many aggressive viruses and bacteria, as well as for protozoa, such as the causes of malaria.”
Vaccination coverage and factors associated with incomplete vaccination in mid-sized municipalities, state of São Paulo, Brazil (no. 14/11714-7); Grant Mechanism PhD Grant; Principal Investigator Eliseu Alves Waldman (FSP-USP); Recipient Márcia de Cantuária Tauil; Investment R$109,950.44.
BARATA, R. C. et al. Socioeconomic inequalities and vaccination coverage: Results of an immunization coverage survey in 27 Brazilian capitals, 2007–2008. Journal of Epidemiology and Community Health. Vol. 66, no. 10, pp. 934–41. Oct. 2012.
OLIVE, J. K. et al. The state of the antivaccine movement in the United States: A focused examination of nonmedical exemptions in states and counties. PLOS Medicine. Online. June 12, 2018.