Measles, rubella, mumps and Toxoplasma gondii antibodies in saliva of vaccinated students of schools and universities in São Paulo City, Brazil

ABSTRACT Introduction: Vaccines are well-established public health interventions with major impacton the prevalence of infectious diseases, but outbreaks are occurring frequently due to pri-mary and secondary failures, despite high coverage. Surveillance of efficacy and duration ofinduced immunity is a difficult task as it requires invasive blood sampling in children andteenagers. Saliva can be an acceptable alternative source of IgG to assess vaccine efficacyand toxoplasmosis incidence. We investigated IgG response for measles, mumps, rubella,and T. gondii in saliva samples of vaccinated young people. Methods: Saliva was collected from 249 public schools students from São Paulo, Brazil, aged7 to 13 years old, during an interactive exhibition on hygiene. We used S. aureus proteinA solid phase capture assay for IgG reactive to biotinylated purified proteins. Paired salivaand serum (47) were tested from young adults with serum evidence of T. gondii infectionand from negative children less than 12 month old for standardization. Reproducibility wasgreater than 98% and sensitivity and specificity of the saliva assays were greater than 95%,as well as the concordance of paired saliva and serum samples. Results: Saliva from high school students showed a prevalence of 8.5% (95% CI: 5.0-11.9%)for anti T. gondii IgG; 96.8% (94.6-99%) of anti-measles IgG; 59.1% (53-65%) of anti-rubella IgG,and 57.5% (51.3-63.6%) of anti-mumps IgG. Discussion: The prevalence of antibodies against mumps and rubella after 6-8 years of vaccination was lower than against measles among students. The findings of this study demonstrate the feasibility of saliva sampling for follow-up of vaccine immune status in teenagers. This useful approach allows for IgG detection for vaccine control or epidemio- logical studies.

Frecuencia de anticuerpos IgG a seis agentes infecciosos en los estudiantes de la carrera de Química Biológica / Frequency of IgG antibodies to six infectious agents in students of the Biological Chemistry degree

Se determinó la frecuencia de anticuerpos IgG para Toxoplasma gondii y los virus de paperas, sarampión, rubéola, varicela y hepatitis B en 90 estudiantes de la carrera de Química Biológica de la Facultad de CCQQ y Farmacia. La mayor frecuencia se encontró para rubéola y sarampión, 98.9% para cada prueba y la menor frecuencia fue para T. gondii con 23.3%. No se encontró asociación significativa entre la positividad y el género, entre la positividad a paperas, sarampión, varicela y el haber sufrido la infección o haber estado en contacto con personas infectadas y entre la positividad a T. gondii y el consumir carne roja y/o comida callejera (p > .05). Únicamente en el caso de la hepatitis B se encontró una asociación significativa entre la positividad y la edad (p = < .001), el hecho de estar vacunado (p < .001) y el ser sexualmente activo (p = .004). Los porcentajes de vacunación en la población en estudio fue alta únicamente para hepatitis B (80%), mientras que para las otras infecciones fue 35.6% para rubéola y sarampión, 22.2% para varicela y 10% para paperas. Más de 82% de los estudiantes presentaron protección a los seis agentes estudiados y se recomienda realizar encuestas sero-epidemiológicas constantes, evaluar los programas de inmunización, identificar los grupos a riesgo y que las personas que no presenten anticuerpos se vacunen.

The frequency of IgG antibodies for Toxoplasma gondii and the mumps, measles, rubella, varicella and hepa-titis B viruses was determined in 90 students of the Biological Chemistry career of the Faculty of CCQQ and Pharmacy. The highest frequency was found for Rubella and Measles, 98.9% each, and the lowest frequency was for T. gondii with 23.3%. No significant difference was found between positivity and gender, between positivity to mumps, measles, chicken pox and having suffered infection or having been in contact with infected persons and between positivity to T. gondii and consuming red meat and / or street food (p > .05). Only in the case of Hepatitis B a significant difference between positivity and age (p = .001), the fact of being vaccinated (p = .001) and being sexually active (p = .004 was found. The percentage of vaccination in the study population was high only for He-patitis B (80%), while for the other infections it was 35.6% for rubella and measles, 22.2% for varicella and 10% for mumps. More than 82% of the students presented protection to the six agents studied and it is recommended to carry out constant sero-epidemiological surveys, to evaluate the immunization programs, to identify the risk groups and that people who do not present antibodies get vaccinated.

Polyspecific antibodies without persisting antigen in multiple sclerosis, neurolupus and Guillain-Barré syndrome: immune network connectivity in chronic diseases / Anticorpos poliespecíficos sem antígeno persistente em esclerose múltipla, neurolupus e síndrome de Guillain-Barré: conectividade imunológica em doenças crônicas

ABSTRACT The polyspecific antibody synthesis in multiple sclerosis (MS) gained diagnostic relevance with the frequent combination of measles-, rubella- and varicella zoster antibodies (MRZ-antibody reaction) but their pathophysiological role remains unknown. This review connects the data for intrathecal polyspecific antibody synthesis in MS and neurolupus with observations in the blood of patients with Guillain-Barré syndrome (GBS). Simultaneously increased antibody and autoantibody titers in GBS blood samples indicate that the polyspecific antibodies are based on a general property of an immune network, supported by the deterministic day-to-day concentration variation of antibodies in normal blood. Strongly correlated measles- and rubella- antibody variations point to a particular connectivity between the MRZ antibodies. The immune network, which provides serological memory in the absence of an antigen, implements the continuous change of the MRZ pattern in blood, not followed by the earlier immigrated B cells without corresponding connectivity in the brain. This may explain the different antibody patterns in cerebrospinal fluid, aqueous humor and blood of the individual MS patient. A complexity approach must implement a different view on causation in chronic diseases and causal therapies.

RESUMO A síntese de anticorpos poliespecíficos em esclerose múltipla (EM) ganhou relevância diagnóstica com a combinação frequente de anticorpos contra sarampo, rubéola e varicela-zoster (reação de anticorpos MRZ), mas seu papel fisiopatológico permanece desconhecido. Esta revisão relaciona os dados da síntese intratecal de anticorpos poliespecíficos em EM e Neurolupus com observações no sangue de pacientes com síndrome de Guillain Barré (SGB). Simultaneamente, os títulos aumentados de anticorpos e autoanticorpos em amostras de sangue de SGB indicam que os anticorpos poliespecíficos se baseiam numa propriedade geral de uma rede imunitária, suportada pela variação determinística da concentração diária de anticorpos no sangue normal. As variações fortemente correlacionadas de anticorpos contra sarampo e rubéola apontam para uma conectividade particular entre os anticorpos MRZ. A rede imunitária, que fornece memória sorológica na ausência de um antígeno, implementa a mudança contínua do padrão MRZ no sangue, não seguida pelas células B que imigraram anteriormente sem conectividade no cérebro. Isto pode explicar os diferentes padrões de anticorpos no LCR, humor aquoso e sangue do paciente individual de EM. Uma abordagem complexa deve implementar uma visão diferente sobre a causalidade em doenças crônicas e terapias causais.

Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR) immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0) seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

Seroprevalence of mumps before inclusion of mumps vaccination in the Iranian Expanded Programme on Immunization

The current target groups for measles, mumps and rubella vaccination in the Islamic Republic of Iran are children at 12 months and 4-6 years. A study of the age-specific seroprevalence of antibodies against mumps in children aged 3-18 years in Shahrekord aimed to establish the need for booster vaccinations to cover non-immune children. Of 338 children, 19.8% were seronegative. Age-specific seronegativity was 33.3%, 20.5% and 4.6% in age groups 7-11, 12-14 and 15-18 years respectively. To obtain herd immunity, we suggest that for the next 5 years children aged 7-11 years entering guidance school are selected as the main group for vaccination

serological survey of measles, mumps and rubella immunity among school aged children in Western Saudi Arabia

To evaluate the adequacy of measles, mumps and rubella [MMR] vaccination among children and to assess risk of outbreak in Jeddah, Kingdom of Saudi Arabia [KSA]. We recruited a total of 527 children from schools located at different urban regions, and preschool children from those attending the well baby clinics in Jeddah, KSA. We tested for MMR viruses antibodies using ELISA technique. Approximately 99% of children received MMR vaccine. Overall seropositivity for measles antibodies was 71%, mumps 65% and rubella 90%, which were elevated in vaccinated versus non-vaccinated children [p<0.000]. In vaccinated children, percentage of seropositivity for MMR was higher in public school children versus private [p<0.01] or those who did not attend school [p<0.01] and in Saudi versus non-Saudi children [p<0.000]. In vaccinated children, percentage of seropositivity obtained according to age groups of 4-6 years for measles was 73.7%, for mumps 66.7% and for rubella 91.7%. As for 7-11 years age group, seropositivity for measles was 72.6%, for mumps 68.1% and for rubella 93%, while for the 12-14 years, seropositivity for measles was 66.4%, mumps 59.1% and for rubella 86.1%. The prevalence of seropositivity against the above-mentioned viruses decreased with progression of age. Measles, mumps and rubella mass vaccination program achieved high coverage rate among children, in Jeddah, KSA. However, there is still a high level of sera negative children among vaccinated ones for measles and mumps. Seropositivity decreased with age, which might raise possibility of outbreaks among adolescent. Additional doses of vaccine against measles and mumps are recommended and evaluation of new MMR protocol should be made

Frequência de anticorpos para o vírus da caxumba / Frequence of antibody to mumps virus

Introdução: A caxumba é uma infecção viral aguda que ocorre principalmente em crianças e adolescentes na idade escolar. Durante a infecção os anticorpos IgG, geralmente são detectados cerca de duas a três semanas após o inicio dos sintomas, indicando imunidade adquirida. A presença de anticorpos IgM iniciam com eleva- dos títulos até as duas primeiras semanas, com posterior redução desses níveis, possibilitando o diagnóstico de infecção aguda ou recente. Objetivo: Determinar a freqüência de anticorpos das classes G (IgG) eM (IgM) para o vírus da caxumba em indivíduos assintomáticos residentes em dois bairros da área urbana de Belém, Pará, Brasil. Método: Foram coletadas 411 amostras de soro de indivíduos assintomáticos provenientes de dois bairros de Belém, Pará (Terra Firme e Guamá) no período de setembro a novembro de 1994. Todos os espécimes colhidos foram examinados pelo método imunoenzimático (ELISA) utilizado na detecção de anticorpos IgG e IgM específicos para o vírus da caxumba. Resultados: Em 63,5 por cento (261/411) das amostras de soro testadas foram detectados anticorpos da classe IgG e, em 12,9por cento (53/411), anticorpos da classe IgM para o vírus da caxumba. o sexo masculino foi mais acometido que o feminino com 81,8por cento (153/187) e 48,2por cento (108/224), respectivamente, com diferença estatística significativa de P=0,00l. Nossos resultados demonstraram que 52,4por cento (119/227) dos indivíduos investigados com idades abaixo de 15 anos foram susceptíveis à infecção pelo vírus em questão. Conclusão: Esses resultados podem ser utilizados para que sejam intensificadas medidas profiláticas capazes de reduzir o aparecimento dessa virose na população de Belém, Pará, Brasil

Serosurvey of measles, mumps and rubella antibodies in Saudi children

A serosurvey study to evaluate the proportion of children with antibodies against diseases targeted by the Expanded Program of Immunization in the Kingdom of Saudi Arabia. Using multistage sampling techniques, we collected samples and sent them for laboratory assay from the following age groups; 100 samples at 6 months, 12 months, 18 months, 6 years, 13 years, and 17 years. We conducted the study from September 2001 to February 2002. We assayed sera for measles, rubella, and mumps antibodies in the measles-mumps-rubella reference laboratory in Germany, using enzyme immunoassay and plaque neutralization [PN] as a backup test for equivocal and negative samples. We only carried out a backup test for measles samples. The age group of 6 months had the highest proportion with negative measles antibodies. After adding the backup test [PN], the proportions of children with protective measles antibody were; 64% at 6 months, 87% at 12 months, 91% at 18 months, 75% at 6 years, 96% at 13 years, and 98% at 17 years. Rubella antibody positivity rates [>7 IU] were 28% at 6 months, 49% at 12 months, 97% at 18 months, 98% at 6 years, and 100% at 13 years. While positivity rates in mumps were 14% at 6 months, 29% at 12 months, 59% at 18 months, 64% at 6 years, and 75% at 13 years. The unexpected low proportion of children with protective level at 6 years, despite being vaccinated with 2 measle doses is an important phenomenon. This reflects the interference between the first and the second measles dose. The Ministry of Health decided to conduct a catch up campaign targeting 1st through 3rd grade primary schools, who did not catch the mass campaign conducted in 2000. Also, this supports the decision taken by the ministry to change the measles immunization schedule to MMR at 12 months and a second dose at 6 years of age

A randomized comparative trial in order to assess the reactogenicity and immunogenicity of a new measles mumps rubella (MMR) vaccine when given as a first dose at 12-24 months of age.

An open, randomized multi-center trial, involving 700 infants, was conducted in order to compare a new measles mumps rubella (MMR) vaccine, SB MMR (containing a Jeryl Lynn derived mumps strain RIT 4385) with a widely used vaccine, Merck MMR, when given to children between 12-24 months. Infants were divided between 2 groups; group 1 received SB MMR while group 2 received Merck MMR. Solicited local and general symptoms were recorded using diary cards and antibody levels were measured using ELISA assays. There was a significantly lower incidence of redness (p < 0.001) and swelling (p = 0.03) observed in group 1 compared with group 2. The incidence of all other solicited local and general symptoms were comparable between groups. In initially seronegative subjects equivalent seroconversion rates and post-vaccination GMTs were observed between groups. In conclusion, these results demonstrate that SB MMR is safe and well tolerated when given to children at this age range, and has an equivalent immunogenic profile compared to the widely used Merck MMR vaccine.

Evaluation of serological status of rubella & mumps in children below five years.

A cross-sectional study was carried out on 321 serum samples to detect rubella and mumps antibodies in children below five years and to assess the optimum age for immunization against rubella and mumps. Seropositivity to rubella was 33.3 per cent in children below nine months, 16.9 per cent at 9-12 months and 25.5 per cent by two years. Mean antibody levels for rubella were low at nine months to one year and remained so till five years of age. Similarly, seropositivity for mumps was 53.3 per cent below nine months, 20.3 per cent at 9-12 months and 40 per cent by two years. Mean antibody levels for mumps were low between nine months to two years with a slight rise by five years. The findings suggest that a large majority of children are at risk by the age of nine months in our population and the measles, mumps and rubella (MMR) vaccination at this age may be most beneficial.

Immunogenicity and reactogenicity of indigenously produced MMR vaccine.

OBJECTIVES: To study immunogenicity and reactogenicity of indigenously produced MMR vaccine and to assess the booster effect of MMR immunization on measles seroconversion. DESIGN: A longitudinal follow up. SETTING: Hospital based and home follow up, as required. SUBJECTS: 89 children already immunized for measles, between 15 to 24 months of age for immunogenic evaluation and 866 subjects for the reactogenic component. METHODS: Prevaccination and postvaccination samples collected one and four weeks after vaccination were studied by ELISA for IgG and IgM antibodies against the three diseases. A clinical follow up of immunized children was done at 3 days, 7 days, 6 weeks and 6 months after immunization. RESULTS: IgG positivity 4 weeks after immunization rose from 75% to 100% for measles, from 12% to 92% for mumps, and from 13% to 99% for rubella. Only mild side effects including pain and swelling in 37 (4.3%) cases, mild fever in 51 (5.9%) cases, cough in 40 (4.6%) cases and a transient rash in 7 (0.8%) cases were observed. CONCLUSIONS: The indigenously manufactured MMR vaccine has an excellent immunogenicity and low reactogenicity with a booster effect for measles seroconversion in children already immunized for this disease.