Reemergence of mumps in São Paulo , Brazil – the urgent need for booster shot campaign to prevent a serious infectious disease Paulo

Introduction: Neglected infectious diseases like mumps may be opportunistic in controlled areas with low vaccine coverage, particularly in developed and emerging countries. Methods: A retrospective analysis of mumps-related data from 2001 to 2016 for São Paulo State, Brazil was conducted. Results: From 2014 to 2015, there was an increase of 82% in reported mumps cases in São Paulo, with prevalence of n=49 and 297, respectively in young adults aged 15-29 years. Conclusions: A booster-shot campaign on MMR vaccination is recommended to prevent the spread of mumps in unvaccinated children and recipients of only the first dose.

The recent mumps outbreaks in populations considered to have achieved high coverage of the vaccine, particularly in developed and emerging countries, suggest among other reasons a problem related to vaccine acceptance in these nations, which is mainly caused by a failure in booster vaccination and by individual/authorities negligence 1 .
Humans are the only natural host for MuV, although other animal species, such as hamster, mouse, chicken embryo and non-human primates can be infected.However, the infection occurs only in laboratory experiments 3 .In humans, the incubation period is between 14 and 24 days, being transmissible via saliva droplets in the air from three days before to four days after the onset of parotitis 4,5 .
MuV is responsible for mumps disease, characterized by unilateral or bilateral swelling of the parotid salivary glands, usually affecting children and young adolescents.Half of infected individuals develop the classic symptoms, while others may be asymptomatic or develop non-specific respiratory manifestations.The virus can also infect susceptible adults of any age, in whom the consequences can be more severe, leading to hearing loss, orchitis, oophoritis, pancreatitis, and meningoencephalitis 6 .As a result, an increase in the incidence rates of orchitis may be observed in populations experiencing mumps outbreaks 7 .Among women who acquire mumps during the first trimester of pregnancy, more than 25% suffer a spontaneous abortion.Less common, but equally important, unilateral or bilateral deafness, the worst consequence of the infection may also occur and the rate today is about 1/20,000 cases 8 .
The measles/mumps/rubella (MMR) vaccine contains live and attenuated strains of the measles, mumps, and rubella viruses.A single dose of vaccine is only partially effective (78-92%) against mumps virus, but a second dose can increase this effectiveness to 88-95% 9 .Globally, 290 cases per 100,000 population were reported between 1977 and 1985.With the introduction of the MMR vaccine in the late of 1960s, more than a 90% reduction in the incidence of mumps was achieved.In countries with no vaccination program against mumps, however, its incidence remains high, with epidemic peaks occurring every 2-5 years 10 .
Nevertheless, even in countries with vaccination policies, outbreaks are reported every year.Besides the probably low acceptance of vaccine campaigns in some regions, such repeated reemergence of mumps may be attributable to several factors,

Confirmed cases
Outbreaks ('000) including the low persistence of protective antibodies, the emergence of new strains capable of evading the vaccine, the difficulties in accessing hard-to-reach populations, the nonvaccination of children or adults motivated by ideological or religious reasons, as well as demographic and economic reasons.
In particular, the lack of a booster dose during childhood, the astonishing misinformation about its benefits, and the fear of adverse effects from being vaccinated are among the main reasons that compromise the vaccine coverage for mumps 11 .As an example, the vaccination denial for children across Europe resulted in 26,000 cases of measles only in 2011 5 .
Additionally, the combination of low or insufficient immunity and the continuous virus importation by travelers may contribute to the reintroduction of viruses in partially susceptible populations.
Brazil's immunization program is one of the most impressive in the world.The country makes most of its own vaccines, which are widely distributed.Since the 1970s, when the national vaccination program started, Brazil has experienced a sharp decline in infant mortality and deaths from infectious diseases 12 .Until 2013, the Brazilian vaccination schedule recommended the MMR vaccination of children at 12 months and the second dose in children from 4 to 6 years.A booster was recommended in adolescents 11-19 years of age, and a second booster after 20 years 13 .The 2016 updated schedule, however, recommends the MMR vaccine be applied at 12 months of age and a second dose at 15 months of age.Two additional boosters shots are indicated before 20 years of age, or a single dose in individuals over 20 years of age 14 .
From 2014 to 2015, there was an 82% increase in the number of reported mumps cases in São Paulo State (Figure 1), with the highest incidence in young adults between 15-29 years of age (n=49 for 2014, and n=297 for 2015).This number is also higher than recorded in the 2003 and 2007/2008 outbreaks, considered as important outbreaks in the country.Although the previous vaccination program was reasonable, the campaigns for vaccination boosters are very ineffective, and only the first dose is usually applied.
The 2016 mumps outbreak appears to be the largest ever recorded in São Paulo in the last 10 years.São Paulo is the most populous state in Brazil and is the most important site of population movement to and from the state.As a consequence, nine Brazilian states recorded mumps outbreaks in 2016.The most affected regions were the South and Southwest regions (Table 1); only Espírito Santo and Rio de Janeiro (RJ) recorded no confirmed case.Probably the outbreak which occurred in 2015 in RJ, together with the implementation of the mass vaccination program in 2015 (that reached ~150,000 individuals), had some impact on the incidence of mumps in the state in 2016.In São Paulo, most cases were reported in people between 20-49 years of age [660 (38.7%) cases] followed by young people aged  1).
Several reasons can contribute to the continuous reemergence of mumps, but a definite solution to actually reducing the incidence of this disease is to increase the measures of prevention and vaccination campaigns in young adults.The 2016 Brazilian vaccination schedule seems to be very effective in the long term, but campaigns dedicated to encouraging adolescents and adults to receive the vaccine boosters are particularly important to prevent contagion among young adults since this age group is currently suffering from the weak immunity induced by a single dose in the past 15 .A mass second dose vaccination campaign is challenging but is the only way to prevent the spread of the virus in unvaccinated children or those who received only the first dose.However, more studies are needed to determine the real reasons for the emergence of outbreaks.

TABLE 1
Brazilian states and their respective capitals with confirmed cases of mumps, divided by regions.
15 to 19 years of age [507 (29.7%) cases], thus corroborating the need for a booster dose after childhood as well as the decline in vaccine coverage in the younger population (Table