COVID-19 and long-term impact on symptoms and Health-Related Quality of Life in Costa Rica: the RESPIRA cohort study.

BACKGROUND: Evidence continues to accumulate regarding the potential long-term health consequences of COVID-19 in the population. To distinguish between COVID-19-related symptoms and health limitations from those caused by other conditions, it is essential to compare cases with community controls using prospective data ensuring case-control status. The RESPIRA study addresses this need by investigating the lasting impact of COVID-19 on Health-related Quality of Life (HRQoL) and symptomatology in a population-based cohort in Costa Rica, thereby providing a robust framework for controlling HRQoL and symptoms. METHODS: The study comprised 641 PCR-confirmed, unvaccinated cases of COVID-19 and 947 matched population-based controls. Infection was confirmed using antibody tests on enrollment serum samples and symptoms were monitored monthly for 6 months post-enrolment. Administered at the 6-month visit (occurring between 6- and 2-months post-diagnosis for cases and 6 months after enrollment for controls), HRQoL and Self-Perceived Health Change were assessed using the SF-36, while brain fog, using three items from the Mental Health Inventory (MHI). Regression models were utilized to analyze SF-36, MHI scores, and Self-Perceived Health Change, adjusted for case/control status, severity (mild case, moderate case, hospitalized) and additional independent variables. Sensitivity analyses confirmed the robustness of the findings. RESULTS: Cases showed significantly higher prevalences of joint pain, chest tightness, and skin manifestations, that stabilized at higher frequencies from the fourth month post-diagnosis onwards (2.0%, 1.2%, and 0.8% respectively) compared to controls (0.9%, 0.4%, 0.2% respectively). Cases also exhibited significantly lower HRQoL than controls across all dimensions in the fully adjusted model, with a 12.4 percentage-point difference [95%CI: 9.4-14.6], in self-reported health compared to one year prior. Cases reported 8.0% [95%CI: 4.2, 11.5] more physical limitations, 7.3% [95%CI: 3.5, 10.5] increased lack of vitality, and 6.0% [95%CI: 2.4, 9.0] more brain fog compared to controls with similar characteristics. Undiagnosed cases detected with antibody tests among controls had HRQoL comparable to antibody negative controls. Differences were more pronounced in individuals with moderate or severe disease and among women. CONCLUSIONS: PCR-confirmed unvaccinated cases experienced prolonged HRQoL reductions 6 months to 2 years after diagnosis, this was particularly the case in severe cases and among women. Mildly symptomatic cases showed no significant long-term sequelae.

Cohort profile: evaluation of immune response and household transmission of SARS-CoV-2 in Costa Rica: the RESPIRA study.

PURPOSE: The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19. PARTICIPANTS: From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence. FINDINGS TO DATE: Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up. FUTURE PLANS: RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024. TRIAL REGISTRATION NUMBER: NCT04537338.

Estimating the cumulative incidence of SARS-CoV-2 infection in Costa Rica: modelling seroprevalence data in a population-based cohort.

Background: The true incidence of SARS-CoV-2 infection in Costa Rica was likely much higher than officially reported, because infection is often associated with mild symptoms and testing was limited by official guidelines and socio-economic factors. Methods: Using serology to define natural infection, we developed a statistical model to estimate the true cumulative incidence of SARS-CoV-2 in Costa Rica early in the pandemic. We estimated seroprevalence from 2223 blood samples collected from November 2020 to October 2021 from 1976 population-based controls from the RESPIRA study. Samples were tested for antibodies against SARS-CoV-2 nucleocapsid and the receptor-binding-domain of the spike proteins. Using a generalized linear model, we estimated the ratio of true infections to officially reported cases. Applying these ratios to officially reported totals by age, sex, and geographic area, we estimated the true number of infections in the study area, where 70% of Costa Ricans reside. We adjusted the seroprevalence estimates for antibody decay over time, estimated from 1562 blood samples from 996 PCR-confirmed COVID-19 cases. Findings: The estimated total proportion infected (ETPI) was 4.0 times higher than the officially reported total proportion infected (OTPI). By December 16th, 2021, the ETPI was 47% [42-52] while the OTPI was 12%. In children and adolescents, the ETPI was 11.0 times higher than the OTPI. Interpretation: Our findings suggest that nearly half the population had been infected by the end of 2021. By the end of 2022, it is likely that a large majority of the population had been infected. Funding: This work was sponsored and funded by the National Institute of Allergy and Infectious Diseases through the National Cancer Institute, the Science, Innovation, Technology and Telecommunications Ministry of Costa Rica, and Costa Rican Biomedical Research Agency-Fundacion INCIENSA (grant N/A).

Behavioral factors and SARS-CoV-2 transmission heterogeneity within a household cohort in Costa Rica.

INTRODUCTION: Variability in household secondary attack rates and transmission risks factors of SARS-CoV-2 remain poorly understood. METHODS: We conducted a household transmission study of SARS-CoV-2 in Costa Rica, with SARS-CoV-2 index cases selected from a larger prospective cohort study and their household contacts were enrolled. A total of 719 household contacts of 304 household index cases were enrolled from November 21, 2020, through July 31, 2021. Blood specimens were collected from contacts within 30-60 days of index case diagnosis; and serum was tested for presence of spike and nucleocapsid SARS-CoV-2 IgG antibodies. Evidence of SARS-CoV-2 prior infections among household contacts was defined based on the presence of both spike and nucleocapsid antibodies. We fitted a chain binomial model to the serologic data, to account for exogenous community infection risk and potential multi-generational transmissions within the household. RESULTS: Overall seroprevalence was 53% (95% confidence interval (CI) 48-58%) among household contacts. The estimated household secondary attack rate is 34% (95% CI 5-75%). Mask wearing by the index case is associated with the household transmission risk reduction by 67% (adjusted odds ratio = 0.33 with 95% CI: 0.09-0.75) and not sharing bedroom with the index case is associated with the risk reduction of household transmission by 78% (adjusted odds ratio = 0.22 with 95% CI 0.10-0.41). The estimated distribution of household secondary attack rates is highly heterogeneous across index cases, with 30% of index cases being the source for 80% of secondary cases. CONCLUSIONS: Modeling analysis suggests that behavioral factors are important drivers of the observed SARS-CoV-2 transmission heterogeneity within the household.

When living in the same house with known SARS-CoV-2 cases, household members may change their behavior and adopt preventive measures to reduce the spread of SARS-CoV-2. To understand how behavioral factors affect SARS-CoV-2 spreading in household settings, we focused on household members of individuals with laboratory-confirmed SARS-CoV-2 infections and followed the way SARS-CoV-2 spread within the household, by looking at who had antibodies against the virus, which means they were infected. We also asked participants detailed questions about their behavior and applied mathematical modeling to evaluate its impact on SARS-CoV-2 transmission. We found that mask-wearing by the SARS-CoV-2 cases, and avoiding sharing a bedroom with the infected individuals, reduces SARS-CoV-2 transmission. However, caring for SARS-CoV-2 cases, and prolonged interaction with infected individuals facilitate SARS-CoV-2 spreading. Our study helps inform what behaviors can help reduce SARS-CoV-2 transmission within a household.

Estimating vaccine effectiveness against SARS-CoV-2 infection, hospitalization and death from ecologic data in Costa Rica.

BACKGROUND: Clinical trials and individual-level observational data in Israel demonstrated approximately 95% effectiveness of mRNA-based vaccines against symptomatic SARS-CoV-2 infection. Individual-level data are not available in many countries, particularly low- and middle- income countries. Using a novel Poisson regression model, we analyzed ecologic data in Costa Rica to estimate vaccine effectiveness and assess the usefulness of this approach. METHODS: We used national data from December 1, 2020 to May 13, 2021 to ascertain incidence, hospitalizations and deaths within ecologic units defined by 14 age groups, gender, 105 geographic areas, and day of the epidemic. Within each unit we used the proportions of the population with one and with two vaccinations, primarily tozinameran. Using a non-standard Poisson regression model that included an ecologic-unit-specific rate factor to describe rates without vaccination and a factor that depended on vaccine effectiveness parameters and proportions vaccinated, we estimated vaccine effectiveness. RESULTS: In 3.621 million persons aged 20 or older, there were 125,031 incident cases, 7716 hospitalizations, and 1929 deaths following SARS-CoV-2 diagnosis; 73% of those aged ≥ 75 years received two doses. For one dose, estimated effectiveness was 59% (95% confidence interval 53% to 64%) for SARS-CoV-2 incidence, 76% (68% to 85%) for hospitalizations, and 63% (47% to 80%) for deaths. For two doses, the respective estimates of effectiveness were 93% (90% to 96%), 100% (97% to 100%), and 100% (97% to 100%). CONCLUSIONS: These effectiveness estimates agree well with findings from clinical trials and individual-level observational studies and indicate high effectiveness in the general population of Costa Rica. This novel statistical approach is promising for countries where ecologic, but not individual-level, data are available. The method could also be adapted to monitor vaccine effectiveness over calendar time.

Behavioral factors and SARS-CoV-2 transmission heterogeneity within a household cohort in Costa Rica.

Variability in household secondary attack rates (SAR) and transmission risks factors of SARS-CoV-2 remain poorly understood. To characterize SARS-CoV-2 transmission in a household setting, we conducted a household serologic study of SARS-CoV-2 in Costa Rica, with SARS-CoV-2 index cases selected from a larger prospective cohort study and their household contacts were enrolled. A total of 719 household contacts of 304 household index cases were enrolled from November 21, 2020, through July 31, 2021. Demographic, clinical, and behavioral information was collected from the index cases and their household contacts. Blood specimens were collected from contacts within 30-60 days of index case diagnosis; and serum was tested for presence of spike and nucleocapsid SARS-CoV-2 IgG antibodies. Evidence of SARS-CoV-2 prior infections among household contacts was defined based on the presence of both spike and nucleocapsid antibodies. To avoid making strong assumptions that the index case was the sole source of infections among household contacts, we fitted a chain binomial model to the serologic data, which allowed us to account for exogenous community infection risk as well as potential multi-generational transmissions within the household. Overall seroprevalence was 53% (95% confidence interval (CI) 48% - 58%) among household contacts The estimated household secondary attack rate (SAR) was 32% (95% CI 5% - 74%) and the average community infection risk was 19% (95% CI 14% - 26%). Mask wearing by the index case was associated with the household transmission risk reduction by 67% (adjusted odds ratio = 0.33 with 95% CI: 0.09-0.75) and sleeping in a separate bedroom from the index case reduced the risk of household transmission by 78% (adjusted odds ratio = 0.22 with 95% CI 0.10-0.41). The estimated distribution of household secondary attack rates was highly heterogeneous across index cases, with 30% of index cases being the source for 80% of secondary cases. Modeling analysis suggests behavioral factors were important drivers of the observed SARS-CoV-2 transmission heterogeneity within the household.

Clinical and therapeutic features of pulmonary nontuberculous mycobacterial disease, Brazil, 1993-2011.

To identify clinical and therapeutic features of pulmonary nontuberculous mycobacterial (PNTM) disease, we conducted a retrospective analysis of patients referred to the Brazilian reference center, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, who received a diagnosis of PNTM during 1993­2011 with at least 1 respiratory culture positive for NTM. Associated conditions included bronchiectasis (21.8%), chronic obstructive pulmonary disease (20.7%), cardiovascular disease (15.5%), AIDS (9.8%), diabetes (9.8%), and hepatitis C (4.6%).Two patients had Hansen disease; 1 had Marfan syndrome. Four mycobacterial species comprised 85.6% of NTM infections: Mycobacterium kansasii, 59 cases (33.9%); M. avium complex, 53 (30.4%); M. abscessus, 23 (13.2%); and M. fortuitum, 14 (8.0%). A total of 42 (24.1%) cases were associated with rapidly growing mycobacteria. In countries with a high prevalence of tuberculosis, PNTM is likely misdiagnosed as tuberculosis, thus showing the need for improved capacity to diagnose mycobacterial disease as well as greater awareness of PNTM disease prevalence.

Molecular epidemiology of Neisseria meningitidis serogroup B in Brazil.

BACKGROUND: Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of São Paulo (1988-2006) for study (n = 372). METHODS: We performed multi-locus sequence typing (MLST) and sequence analysis of five outer membrane protein (OMP) genes, including novel vaccine targets fHbp and nadA. RESULTS: In 2004, strain B:4:P1.15,19 clonal complex ST-32/ET-5 (cc32) predominated throughout Brazil; regional variation in MLST sequence type (ST), fetA, and porB was significant but diversity was limited for nadA and fHbp. Between 1988 and 1996, the São Paulo isolates shifted from clonal complex ST-41/44/Lineage 3 (cc41/44) to cc32. OMP variation was associated with but not predicted by cc or ST. Overall, fHbp variant 1/subfamily B was present in 80% of isolates and showed little diversity. The majority of nadA were similar to reference allele 1. CONCLUSIONS: A predominant serogroup B lineage has circulated in Brazil for over a decade with significant regional and temporal diversity in ST, fetA, and porB, but not in nadA and fHbp.

Impacto da vacinação contra rubéola na ocorrência da síndrome da rubéola congênita / Impact of rubella vaccination strategy on the occurrence of congenital rubella syndrome

OBJETIVO: A vacinação rotineira contra a rubéola foi implementada na Paraíba, nordeste brasileiro, através de uma campanha de catch-up direcionada a crianças com idades entre 1 e 11 anos em 1998. Uma campanha entre as mulheres em idade reprodutiva foi realizada em 2001. Descrevemos a epidemiologia da rubéola e da síndrome da rubéola congênita (SRC) no estado da Paraíba entre 1999 e 2005. MÉTODOS: Foram analisados os dados de vigilância da rubéola e da SRC entre 1999 e 2005. Os casos suspeitos de rubéola foram confirmados por exames laboratoriais, vínculo epidemiológico ou por critério clínico. Foram utilizadas as definições internacionais padrão de SRC. RESULTADOS: Dos 5.924 casos suspeitos de rubéola entre 1999 e 2005, 1.266 (21 por cento) foram confirmados, 766 (61 por cento) deles através dos exames laboratoriais. Durante uma epidemia de rubéola em 2000 (18,8/100.000), a incidência entre os indivíduos com idades entre 14 e 19 anos (42/100.000) quadruplicou em relação a crianças com idades entre 1 e 13 anos (intervalo de confiança de 95 por cento = 3,2-5,1). A incidência geral da rubéola foi de 0,9/100.000 em 2005. Dos 177 casos suspeitos de SRC entre 1999 e 2005, 167 (94 por cento) foram testados para a presença de IgM. Dos 14 (8 por cento) casos de SRC confirmados laboratorialmente, 12 (86 por cento) haviam nascido em 2001, com uma incidência de 0,2/100.000 crianças menores de 1 ano nesse ano. CONCLUSÕES: A campanha de vacinação contra a rubéola em 1998 não foi suficiente para prevenir um surto entre adultos jovens em 2000, com uma alta incidência de SRC em 2001. Entre 2002 e 2005, as incidências de rubéola e de SRC diminuíram; entretanto, a alta cobertura da vacina e a vigilância de alta qualidade são importantes para que se atinja a erradicação da SRC até 2010.

OBJECTIVE: Routine rubella vaccination was introduced in Paraíba, northeastern Brazil, through a catch-up campaign targeting children aged 1-11 years, in 1998. A campaign among women of childbearing age was conducted in 2001. We describe the epidemiology of rubella and congenital rubella syndrome (CRS) in the state of Paraíba between 1999 and 2005. METHODS: Rubella and CRS surveillance data for the 1999-2005 period were analyzed. Suspected cases of rubella were confirmed by laboratory findings, epidemiological link, or clinical data. International standardized CRS definitions were used. RESULTS: Of 5,924 suspected cases of rubella between 1999 and 2005, 1,266 (21 percent) were confirmed, 766 (61 percent) by laboratory findings. During a rubella epidemic in 2000 (18.8/100,000), the incidence among individuals aged 14-19 years (42/100,000) had a fourfold increase relative to children aged 1-13 years (95 percent confidence interval = 3.2-5.1). The overall rubella incidence was 0.9/100,000 in 2005. Of 177 suspected cases of CRS between 1999 and 2005, 167 (94 percent) were tested for IgM. Of 14 (8 percent) laboratory confirmed cases of CRS, 12 (86 percent) were born in 2001, with an incidence of 0.2/100,000 children aged less than 1 year. CONCLUSIONS: The 1998 rubella vaccination campaign was insufficient to prevent an outbreak among young adults in 2000, with a high CRS incidence in 2001. Between 2002 and 2005 the incidence of rubella and CRS decreased; however, high routine vaccination coverage and high-quality surveillance remain critically important to achieve CRS elimination by 2010.

Impact of rubella vaccination strategy on the occurrence of congenital rubella syndrome.

OBJECTIVE: Routine rubella vaccination was introduced in Paraíba, northeastern Brazil, through a catch-up campaign targeting children aged 1-11 years, in 1998. A campaign among women of childbearing age was conducted in 2001. We describe the epidemiology of rubella and congenital rubella syndrome (CRS) in the state of Paraíba between 1999 and 2005. METHODS: Rubella and CRS surveillance data for the 1999-2005 period were analyzed. Suspected cases of rubella were confirmed by laboratory findings, epidemiological link, or clinical data. International standardized CRS definitions were used. RESULTS: Of 5,924 suspected cases of rubella between 1999 and 2005, 1,266 (21%) were confirmed, 766 (61%) by laboratory findings. During a rubella epidemic in 2000 (18.8/100,000), the incidence among individuals aged 14-19 years (42/100,000) had a fourfold increase relative to children aged 1-13 years (95% confidence interval = 3.2-5.1). The overall rubella incidence was 0.9/100,000 in 2005. Of 177 suspected cases of CRS between 1999 and 2005, 167 (94%) were tested for IgM. Of 14 (8%) laboratory confirmed cases of CRS, 12 (86%) were born in 2001, with an incidence of 0.2/100,000 children aged less than 1 year. CONCLUSIONS: The 1998 rubella vaccination campaign was insufficient to prevent an outbreak among young adults in 2000, with a high CRS incidence in 2001. Between 2002 and 2005 the incidence of rubella and CRS decreased; however, high routine vaccination coverage and high-quality surveillance remain critically important to achieve CRS elimination by 2010.

PorA variable antigenic regions VR1, VR2, and VR3 of Neisseria meningitidis serogroups B and C isolated in Brazil from 1999 to 2004.

The high genetic diversity found among the PorA regions VR1 and VR2 of 101 Neisseria meningitidis isolates from patients with meningococcal disease and healthy carriers in Brazil contrasts with the stability found in the PorA VR3 of these isolates. The presence of VR3 epitope variant 35 or 36 on the surfaces of 87% of the strains analyzed suggests that these antigens should be considered for inclusion in new formulations of vaccines against serogroup B meningococci in Brazil.

Incidence, clinical features and estimated costs of congenital rubella syndrome after a large rubella outbreak in Recife, Brazil, 1999-2000.

BACKGROUND: During 1998-2000, a large rubella outbreak was reported from Recife, the capital municipality of Pernambuco State, in northeastern Brazil. In 2002, a study was conducted to assess the burden of congenital rubella syndrome (CRS) after this outbreak. METHODS: To describe the rubella outbreak, we analyzed data available from the National Notifiable Disease System. A retrospective record review for CRS was conducted at 6 maternity hospitals where 53% of Recife's resident live births occurred during 1999-2000 and 1 tertiary health care center. Suspected CRS cases were infants with any manifestation of CRS or maternal infection during pregnancy. Standard international definitions for compatible and confirmed CRS cases were used. Direct CRS costs were based on reimbursements by the National Health System. RESULTS: From October 1998 to July 2000, Recife reported 681 confirmed rubella cases. The highest incidence of rubella was among children 5-11 years of age (5.4 per 1000 population). Forty-five suspected CRS cases were identified; 29 were clinically compatible and 2 were laboratory-confirmed. The average annual incidence of CRS was 0.9 per 1000 live births during 1999-2000. Overall costs for the first year follow-up were estimated at 61,824 US dollars in this cohort. CONCLUSIONS: High rubella vaccination coverage is required to prevent the severe congenital disabilities and high economic costs of CRS. Increased clinician awareness is critical for early CRS detection. Complete reporting is essential to evaluate the impact of vaccination programs and to document progress toward the goal of CRS elimination in the Americas by the year 2010.

Interruption of measles transmission in Brazil, 2000-2001.

In 1992, Brazil adopted the goal of measles elimination by the year 2000; however, in 1997, after a 4-year period of good control, there was a resurgence of measles in Brazil. In 1999, to achieve the elimination goal, Brazil implemented the Supplementary Emergency Measles Action plan, with one measles surveillance technician designated to each state. Of 10,007 suspected measles cases reported during 1999, 908 (9.1%) were confirmed, and of them 378 (42%) were confirmed by laboratory analysis. Of 8358 suspected measles cases reported in 2000, 36 (0.4%) were confirmed (30 [83%] by laboratory); 92% of the discarded cases were classified on the basis of laboratory testing. In 2001, only 1 of 5599 suspected measles cases was confirmed, and it was an imported case from Japan. The last outbreak occurred in February 2000, with 15 cases. Current data suggest interruption of indigenous measles transmission in Brazil.

Burden of congenital rubella syndrome after a community-wide rubella outbreak, Rio Branco, Acre, Brazil, 2000 to 2001.

BACKGROUND: During 1999 and 2000 rubella outbreaks were reported in 20 of 27 states in Brazil, many among young adults. We investigated a large rubella outbreak in Rio Branco, Acre, in northwestern Brazil, where rubella vaccination targeting children 1 to 11 years old had been introduced in April 2000. Surveillance for congenital rubella syndrome (CRS) was initiated after the outbreak. METHODS: Suspected rubella cases were detected through active and passive surveillance. Confirmed rubella cases were patients with fever, rash and rubella-specific IgM antibodies. Suspected CRS cases were infants born with CRS-compatible defects or born to mothers with a history of rubella during pregnancy. Confirmed cases were infants with CRS-compatible defects and rubella-specific IgM antibodies. RESULTS: From April 1 to December 31, 2000, 391 confirmed rubella cases were reported. The incidence among persons ages 12 to 19 years (3.3 per 1000 population) was increased 3.7-fold relative to children ages 1 to 4 years (95% confidence interval, 2.4 to 5.8). Of 21 infants with suspected CRS cases, 17 (91%) were tested for rubella-specific antibodies, of whom 7 were IgM-positive and 5 had confirmed CRS. The peak incidence of confirmed CRS (4.3 per 1000) was in March 2001, 7 months after the outbreak peak, with an annualized incidence of 0.6 per 1000. CONCLUSIONS: Vaccination among school age children was insufficient to prevent a rubella outbreak among young adults that resulted in the occurrence of at least 5 cases of CRS. To prevent further cases of CRS, outbreak vaccination of young adults was conducted in November 2000 and among women ages 12 to 39 years in 2001 as part of a national campaign, with a coverage of 98% statewide.

The risk of aseptic meningitis associated with the Leningrad-Zagreb mumps vaccine strain following mass vaccination with measles-mumps-rubella vaccine, Rio Grande do Sul, Brazil, 1997.

BACKGROUND: Few data are available on the risk of aseptic meningitis following vaccination with the Leningrad-Zagreb (L-Z) strain of mumps vaccine. In 1997 the mumps vaccine was introduced into the state of Rio Grande do Sul in Brazil through mass vaccination with mumps-measles-rubella (MMR), targeting children aged 1-11 years. Five municipalities used exclusively MMR vaccine containing the L-Z strain of mumps. An outbreak of aseptic meningitis was observed shortly after the mass campaign. METHODS: To estimate the risk of aseptic meningitis associated with this strain, we analysed vaccination and meningitis case surveillance data from the selected municipalities. A case of vaccine-associated aseptic meningitis was defined as one with a pleocytosis of 10-1,500 leukocytes/ml and occurring within 15-35 days after vaccine receipt. RESULTS: We estimated a risk of 2.9 cases per 10,000 doses of L-Z administered, equivalent to 1 case per 3,390 doses administered. The overall risk of aseptic meningitis following the campaign was increased 12.2-fold (95% CI: 6.0-24.7) compared with the same period in 1995-1996. Following the mass campaign, the incidence of mumps declined 93% during 1998-2000. CONCLUSIONS: Vaccination with the L-Z strain of mumps vaccine as part of a mass campaign was associated with a significantly increased risk of aseptic meningitis. Decisions about type of mumps vaccine and mumps vaccination strategies must consider vaccine safety issues in addition to other criteria.