Diagnostic algorithm for the confirmation of cases of measles and rubella in Mexico

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Diagnostic algorithm for the confirmation of cases of measles and rubella in Mexico.

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Inmunidad humoral a tétanos, sarampión y rubéola en niños con leucemia linfoblástica aguda luego del tratamiento quimioterápico / Humoral immunity to tetanus, measles and rubella in children with acute lymphoblastic leukemia after chemotherapy

Los regímenes de quimioterapia y los avances en el soporte clínico han mejorado la supervivencia de los niños con leucemia linfoblástica aguda. Son temas de preocupación las secuelas del tratamiento, entre ellas, el daño inmunológico inducido por la terapia inmunosupresora, que se refleja en la pérdida de niveles protectores de anticuerpos provistos por inmunizaciones previas. Nuestro objetivo fue evaluar la presencia de títulos protectores de anticuerpos para sarampión, rubéola y tétanos en pacientes con leucemia linfoblástica aguda luego de haber finalizado el tratamiento quimioterápico. Se incluyeron 61 niños con leucemia linfoblástica aguda asistidos en el Hospital Garrahan, que habían finalizado el tratamiento, como mínimo, 6 meses antes y con vacunación completa previa al diagnóstico. Las tasas de anticuerpos protectores fueron sarampión: 46% (IC 32-59); tétanos: 53% (IC 40-67); rubéola: 60% (IC 47-63). Estos resultados refuerzan la necesidad de reconsiderar la revacunación en este grupo de pacientes.

Chemotherapy regimens and clinical support advances have improved survival in children with acute lymphoblastic leukemia. The after-effects of treatment are a reason for concern, including damage to the immune system induced by immunosuppressive therapy which is reflected in the loss of antibody protection provided by prior immunizations. Our goal was to assess the presence of measles, rubella, and tetanus protective antibody titers among patients with acute lymphoblastic leukemia after completing chemotherapy. Sixty-one children with acute lymphoblastic leukemia seen at the Hospital Garrahan were included; patients had finished their chemotherapy at least 6 months earlier and had a complete immunization schedule before diagnosis. The rates of protective antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60% (CI 47-63) for rubella. These results strengthen the need to reconsider revaccination in this group of patients.

Humoral immunity to tetanus, measles and rubella in children with acute lymphoblastic leukemia after chemotherapy. / Inmunidad humoral a tétanos, sarampión y rubéola en niños con leucemia linfoblástica aguda luego del tratamiento quimioterápico.

Chemotherapy regimens and clinical support advances have improved survival in children with acute lymphoblastic leukemia. The after-effects of treatment are a reason for concern, including damage to the immune system induced by immunosuppressive therapy which is reflected in the loss of antibody protection provided by prior immunizations. Our goal was to assess the presence of measles, rubella, and tetanus protective antibody titers among patients with acute lymphoblastic leukemia after completing chemotherapy. Sixty-one children with acute lymphoblastic leukemia seen at the Hospital Garrahan were included; patients had finished their chemotherapy at least 6 months earlier and had a complete immunization schedule before diagnosis. The rates of protective antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60% (CI 47-63) for rubella. These results strengthen the need to reconsider revaccination in this group of patients.

Los regímenes de quimioterapia y los avances en el soporte clínico han mejorado la supervivencia de los niños con leucemia linfoblástica aguda. Son temas de preocupación las secuelas del tratamiento, entre ellas, el daño inmunológico inducido por la terapia inmunosupresora, que se refleja en la pérdida de niveles protectores de anticuerpos provistos por inmunizaciones previas. Nuestro objetivo fue evaluar la presencia de títulos protectores de anticuerpos para sarampión, rubéola y tétanos en pacientes con leucemia linfoblástica aguda luego de haber finalizado el tratamiento quimioterápico. Se incluyeron 61 niños con leucemia linfoblástica aguda asistidos en el Hospital Garrahan, que habían finalizado el tratamiento, como mínimo, 6 meses antes y con vacunación completa previa al diagnóstico. Las tasas de anticuerpos protectores fueron sarampión: 46% (IC 32-59); tétanos: 53% (IC 40-67); rubéola: 60% (IC 47-63). Estos resultados refuerzan la necesidad de reconsiderar la revacunación en este grupo de pacientes.

Comparative Estimates of Crude and Effective Coverage of Measles Immunization in Low-Resource Settings: Findings from Salud Mesoamérica 2015.

Timely and accurate measurement of population protection against measles is critical for decision-making and prevention of outbreaks. However, little is known about how survey-based estimates of immunization (crude coverage) compare to the seroprevalence of antibodies (effective coverage), particularly in low-resource settings. In poor areas of Mexico and Nicaragua, we used household surveys to gather information on measles immunization from child health cards and caregiver recall. We also collected dried blood spots (DBS) from children aged 12 to 23 months to compare crude and effective coverage of measles immunization. We used survey-weighted logistic regression to identify individual, maternal, household, community, and health facility characteristics that predict gaps between crude coverage and effective coverage. We found that crude coverage was significantly higher than effective coverage (83% versus 68% in Mexico; 85% versus 50% in Nicaragua). A large proportion of children (19% in Mexico; 43% in Nicaragua) had health card documentation of measles immunization but lacked antibodies. These discrepancies varied from 0% to 100% across municipalities in each country. In multivariate analyses, card-positive children in Mexico were more likely to lack antibodies if they resided in urban areas or the jurisdiction of De Los Llanos. In contrast, card-positive children in Nicaragua were more likely to lack antibodies if they resided in rural areas or the North Atlantic region, had low weight-for-age, or attended health facilities with a greater number of refrigerators. Findings highlight that reliance on child health cards to measure population protection against measles is unwise. We call for the evaluation of immunization programs using serological methods, especially in poor areas where the cold chain is likely to be compromised. Identification of within-country variation in effective coverage of measles immunization will allow researchers and public health professionals to address challenges in current immunization programs.

Seroprevalencia contra agentes ToRCH en mujeres indígenas en edad fértil, estado Zulia, Venezuela / Prevalence of infectious agents in indigenous women of childbearing age in Venezuela

Introducción. El termino ToRCH comprende a los patógenos Toxoplasma gondii, virus de la rubéola, citomegalovirus y virus herpes simple 1 y 2. En mujeres embarazadas expuestas pueden ser causa de abortos y malformaciones congénitas en el neonato. Objetivo. Determinar la seroprevalencia de infección por los agentes causantes del síndrome ToRCH en mujeres en edad fértil de algunas comunidades indígenas yukpa de Venezuela. Materiales y métodos. En el año 2007 fueron seleccionadas 109 muestras de 151 mujeres, en edades comprendidas entre 14 y 40 años. La detección de anticuerpos se hizo por el método de inmunoensayo enzimático indirecto o ELISA de Smartest Diagnostics™. Resultados. El 85,5 % presentó anticuerpos contra T. gondii, el 95,4 % para rubéola, el 75,2 % para citomegalovirus y el 97,2 % para el virus herpes simple 1 y 2. Se observa que el 21,1 % y el 30,2 % presentaron relación entre la variable aborto y las infecciones por citomegalovirus y virus herpes simple 1 y 2, respectivamente. Conclusiones. Existe alta seroprevalencia de infecciones por los agentes causantes del síndrome ToRCH en mujeres en edad fértil de la etnia indígena yukpa. Las condiciones sanitarias precarias y el consumo de agua contaminada con ooquistes, favorecen la adquisición de la infección por T. gondii. El hacinamiento, el inicio a temprana de edad de la actividad sexual y el número de parejas, pueden incidir en la presencia de citomegalovirus y virus herpes simple 1 y 2.

Introduction. The ToRCH syndrome includes the following infectious pathogens: Toxoplasma gondii, rubella, cytomegalovirus and herpes simplex virus 1 and 2. In susceptible pregnant women, these pathogens can cause abortions and congenital malformation in the newborn babies. Objective. The seroprevalence of infection by ToRCH agents was determined in women of childbearing age in several Venezuelan Yukpa indigenous communities. Material and methods. In 2007, 109 samples were selected from 151 women with an age range of 14 to 40 years old. The determination of antibodies against ToRCH agents was carried out through the indirect enzyme immunoassay technique by ELISA´s technique of Smartest Diagnostics. Results. Of the 109 samples, 85.5% presented antibodies against T. gondii, 95.4% for rubella, 75.2% for cytomegalovirus and 97.2% for and herpes simplex virus 1 and 2. A relationship between abortion and infection by cytomegalovirus and herpes simplex virus 1and 2 was noted in 21.1% and 30.2% of women presented, respectively. Conclusions. The findings show a high prevalence of ToRCH agents in women in childbearing age in Yukpa indigenous communities in Venezuela. Poor sanitary conditions and consumption of water contaminated with oocysts may be an important way of transmission of T. gondii. Overcrowding in the communities, sexual activity at an early age and number of partners and may be related to the presence of cytomegalovirus and herpes simplex virus HSV-1 and 2.

[Prevalence of infectious agents in indigenous women of childbearing age in Venezuela]. / Seroprevalencia contra agentes ToRCH en mujeres indígenas en edad fértil, estado Zulia, Venezuela.

INTRODUCTION: The ToRCH syndrome includes the following infectious pathogens: Toxoplasma gondii, rubella, cytomegalovirus and herpes simplex virus 1 and 2. In susceptible pregnant women, these pathogens can cause abortions and congenital malformation in the newborn babies. OBJECTIVE: The seroprevalence of infection by ToRCH agents was determined in women of childbearing age in several Venezuelan Yukpa indigenous communities. MATERIAL AND METHODS: In 2007, 109 samples were selected from 151 women with an age range of 14 to 40 years old. The determination of antibodies against ToRCH agents was carried out through the indirect enzyme immunoassay technique by ELISA´s technique of Smartest Diagnostics. RESULTS: Of the 109 samples, 85.5% presented antibodies against T. gondii, 95.4% for rubella, 75.2% for cytomegalovirus and 97.2% for and herpes simplex virus 1 and 2. A relationship between abortion and infection by cytomegalovirus and herpes simplex virus 1and 2 was noted in 21.1% and 30.2% of women presented, respectively. CONCLUSIONS: The findings show a high prevalence of ToRCH agents in women in childbearing age in Yukpa indigenous communities in Venezuela. Poor sanitary conditions and consumption of water contaminated with oocysts may be an important way of transmission of T. gondii. Overcrowding in the communities, sexual activity at an early age and number of partners and may be related to the presence of cytomegalovirus and herpes simplex virus HSV-1 and 2.

Issues and controversies with vitamin A in childhood.

Vitamin A deficiency is common in the developing world. Vitamin A supplementation (VAS) has been used to prevent or treat vitamin A deficiency and to decrease mortality and morbidity in children. However, there are still controversial issues in relation to the role of universal VAS in different populations. Thus, studies that look at mortality outcomes reveal that VAS decreases mortality in children >6 months of age; however, there is still controversy on the extent to which reduction in morbidity from diarrhea and respiratory infection, other than measles, decreases mortality. Studies in infants 1-5 months old show no protective effect of VAS on mortality; whether this is secondary to environmental influences (breastfeeding), or interactions with DTP vaccine, needs to be further investigated. Studies with VAS in newborns have resulted in contrasting results in countries in Africa and Asia; trials are underway to better understand this. VAS does not have a universal protective effect on lower respiratory tract infection in children; some studies reveal an increase in respiratory morbidity associated with VAS, especially in well-nourished children; in contrast, VAS may confer some protection to malnourished children. The interaction of VAS with different vaccines is under current debate; some discussions are presented.

Prevalence of antibodies against measles, mumps, and rubella before and after vaccination of school-age children with three different triple combined viral vaccines, Rio Grande do Sul, Brazil, 1996 / Prevalencia de anticuerpos contra sarampión, paperas y rubéola en niños en edad escolar antes y después de la vacunación con tres vacunas triples antivirales combinadas diferentes, Rio Grande do Sul, Brasil, 1996

OBJECTIVE: We evaluated the seroprevalence for measles, mumps, and rubella in school-age children (6-12 years old) before and after the administration of three triple combined viral vaccines. METHODS: In two municipal schools of Rio Grande do Sul, Brazil, 692 blood samples were collected before vaccination and 636 samples 21 to 30 days after vaccination during 1996. IgG antibody seropositivity was investigated by enzyme-linked immunosorbent assay (measles and mumps with Enzygnost [Behring, Marburg, Germany]; rubella with Rubenostika [Organon Teknica, Boxtel, the Netherlands]). The vaccines compared were: A: E-Zagreb, L-Zagreb, and Wistar RA 27/3 (Tresivac); B: Moraten, J-Lynn, and Wistar RA 27/3 (M-M-R II); and C: Schwarz, Urabe AM-9, and Wistar RA 27/3 (Trimovax). RESULTS: Before vaccination, 79.2 percent [95 percent confidence interval (CI) = 76.0 percent-82.2 percent] of the samples were positive for measles, 69.4 percent (95 percent CI = 65.8 percent-72.8 percent) for mumps, and 55.4 percent (95 percent CI = 51.6 percent-59.2 percent) for rubella. After vaccination with the A, B, and C vaccines, seropositivity was 100.0 percent, 99.5 percent, and 100.0 percent, respectively for measles; 99.5 percent, 94.5 percent, and 92.0 percent for mumps; and 92.6 percent, 91.3 percent, and 88.6 percent for rubella. CONCLUSIONS: About one-fifth (20.8 percent) of the schoolchildren who could have been vaccinated against measles at age 9 months had levels of antibodies insufficient for protection. In the sample of schoolchildren without previous vaccination against mumps and rubella, high proportions of susceptible levels were found. All vaccines were immunogenic, but vaccine A yielded a seroconversion rate of 99.5 percent for the mumps component, which was significantly higher than the other two vaccines (P < 0.01).

OBJETIVO: Se evaluó la seroprevalencia para sarampión, paperas y rubéola en niños en edad escolar (6-12 años) antes y después de la administración de tres vacunas triples antivirales combinadas. MÉTODOS: Se colectaron 692 muestras de sangre antes de la vacunación y 636 muestras entre 21 y 30 días después de la vacunación a niños de dos escuelas municipales de Rio Grande do Sul, Brasil, durante 1996. Se investigó la seropositividad de anticuerpos de la clase IgG mediante un ensayo de inmunoadsorción enzimática tipo ELISA (sarampión y paperas con Enzygnost [Behring, Marburgo, Alemania] y rubéola con Rubenostika [Organon Teknica, Boxtel, Países Bajos]). Las vacunas comparadas fueron: a) E-Zagreb, L-Zagreb y Wistar RA 27/3 (Tresivac); b) Moraten, J-Lynn y Wistar RA 27/3 (M-M-R II); y c) Schwarz, Urabe AM-9 y Wistar RA 27/3 (Trimovax). RESULTADOS: Antes de la vacunación, 79,2 por ciento (intervalo de confianza [IC] 95 por ciento: 76,0 a 82,2) de las muestras fueron positivas para sarampión, 69,4 por ciento (IC 95 por ciento: 65,8 a 72,8) para paperas y 55,4 por ciento (IC 95 por ciento: 51,6 a 59,2) para rubéola. Después de la vacunación con las vacunas A, B y C, la seropositividad fue de 100 por ciento, 99,5 por ciento y 100 por ciento, respectivamente para sarampión; de 99,5 por ciento, 94,5 por ciento y 92,0 por ciento para paperas; y de 92,6 por ciento, 92,3 por ciento y 88,6 por ciento para rubéola. CONCLUSIONES: Alrededor de un quinto (20,8 por ciento) de los escolares que pudieron haber sido vacunados contra el sarampión a los 9 meses de edad tenían niveles de anticuerpos insuficientes para protegerlos. En la muestra de escolares sin vacunación previa contra paperas y rubéola se encontró una alta proporción de niños susceptibles. Todas las vacunas fueron inmunogénicas, pero la vacuna A produjo una tasa de seroconversión de 99,5 por ciento para el componente de paperas, significativamente mayor que la de las otras dos vacunas (P < 0,01).

Prevalence of antibodies against measles, mumps, and rubella before and after vaccination of school-age children with three different triple combined viral vaccines, Rio Grande do Sul, Brazil, 1996.

OBJECTIVE: We evaluated the seroprevalence for measles, mumps, and rubella in school-age children (6-12 years old) before and after the administration of three triple combined viral vaccines. METHODS: In two municipal schools of Rio Grande do Sul, Brazil, 692 blood samples were collected before vaccination and 636 samples 21 to 30 days after vaccination during 1996. IgG antibody seropositivity was investigated by enzyme-linked immunosorbent assay (measles and mumps with Enzygnost [Behring, Marburg, Germany]; rubella with Rubenostika [Organon Teknica, Boxtel, the Netherlands]). The vaccines compared were: A: E-Zagreb, L-Zagreb, and Wistar RA 27/3 (Tresivac); B: Moraten, J-Lynn, and Wistar RA 27/3 (M-M-R II); and C: Schwarz, Urabe AM-9, and Wistar RA 27/3 (Trimovax). RESULTS: Before vaccination, 79.2% [95% confidence interval (CI)=76.0%-82.2%] of the samples were positive for measles, 69.4% (95% CI=65.8%-72.8%) for mumps, and 55.4% (95% CI=51.6%-59.2%) for rubella. After vaccination with the A, B, and C vaccines, seropositivity was 100.0%, 99.5%, and 100.0%, respectively for measles; 99.5%, 94.5%, and 92.0% for mumps; and 92.6%, 91.3%, and 88.6% for rubella. CONCLUSIONS: About one-fifth (20.8%) of the schoolchildren who could have been vaccinated against measles at age 9 months had levels of antibodies insufficient for protection. In the sample of schoolchildren without previous vaccination against mumps and rubella, high proportions of susceptible levels were found. All vaccines were immunogenic, but vaccine A yielded a seroconversion rate of 99.5% for the mumps component, which was significantly higher than the other two vaccines (P<0.01).

Rubella and measles seroprevalence among women of childbearing age, Argentina, 2002.

To assess rubella and measles susceptibility among women of childbearing age we conducted a cross-sectional seroprevalence study in four cities and one rural area in Argentina. A convenience sample of women aged 15-49 years seeking care in public health-care institutions was selected (n=2804). Serum specimens were tested for rubella and measles IgG antibody titres. The overall susceptibility to rubella and measles was 8.8 and 12.5% respectively. Seroprevalence differences were found for both rubella (P<0.001) and measles (P=0.002) across sites. Rubella seroprevalence was higher in women aged >or=40 years than in younger women (P=0.04). Measles seroprevalence tended to increase with age (P<0.001). Approximately 15% of women aged 15-29 years were not immune to measles. No risk factors were associated with rubella seronegativity; however, age (P<0.001) and having less than four pregnancies (P<0.001) were factors associated with measles seronegativity. Our findings support the introduction of supplemental immunization activities targeting adolescents and young adults to prevent congenital rubella syndrome and measles outbreaks over time.

Serological surveillance of measles in blood donors in Rio de Janeiro, Brazil / Vigilancia serológica de sarampión en donantes de sangre de Río de Janeiro, Brasil

OBJETIVOS: Determinar la proporción de personas seronegativas a anticuerpos contra el sarampión entre los donantes de un banco de sangre de la ciudad de Río de Janeiro, Brasil, y describir sus características sociales y demográficas, con el fin de explorar el uso eventual de los bancos de plasma para complementar la vigilancia serológica con datos que permitan apoyar el programa de erradicación del sarampión en la ciudad de Río de Janeiro y en otras localidades. MÉTODOS: Se estudió la presencia de inmunoglobulinas G contra el sarampión en muestras de plasma de 1 101 donaciones de sangre consecutivas realizadas en noviembre de 2000 en HEMORIO, el mayor banco de sangre del estado de Río de Janeiro, mediante un ensayo inmunoenzimático comercial y una prueba de neutralización por reducción de placas. Se calculó la proporción (y el intervalo de confianza (IC) de 95 por ciento) de las muestras negativas a anticuerpos contra el sarampión en la totalidad de las donaciones y en subgrupos conformados según la edad, el sexo, el vecindario de residencia, la educación y la ocupación laboral. La significación estadística de las diferencias entre las proporciones y entre sus tendencias lineales se determinó mediante la prueba de ji al cuadrado. RESULTADOS: Del total de donantes de sangre, el 6,9 por ciento (IC95 por ciento: 5,4 a 8,4 por ciento) resultó seronegativo al sarampión. Las mujeres tuvieron una mayor proporción de resultados seronegativos (10,1 por ciento; IC95 por ciento: 6,8 a 13,4 por ciento) que los hombres (5,6 por ciento; IC95 por ciento: 4,0 a 7,2 por ciento). En relación con la edad, 86,8 por ciento de las personas seronegativas nacieron entre 1971 y 1982. La seronegatividad fue inversamente proporcional a la edad (ji al cuadrado = 58,0; P < 0,0001). En cuanto a la ocupación laboral, los estudiantes presentaron la mayor proporción de seronegativos (17,8 por ciento), mientras que en lo referente a la educación, la mayoría de las personas susceptibles a la enfermedad se encontraban en la categoría de "estudios universitarios incompletos" o "estudios secundarios incompletos". La proporción de seronegativos entre las diferentes áreas de residencia estuvo entre 2,1 por ciento y 11,4 por ciento. CONCLUSIONES: El plasma de los bancos de sangre puede ser una fuente útil y conveniente de datos complementarios para la vigilancia serológica en adultos, tanto de sarampión como de otras enfermedades infecciosas para las que se hayan implementado...

Objetivos. Determinar la proporción de personas seronegativas a anticuerpos contra el sarampión entre los donantes de un banco de sangre de la ciudad de Río de Janeiro, Brasil, y describir sus características sociales y demográficas, con el fin de explorar el uso eventual de los bancos de plasma para complementar la vigilancia serológica con datos que permitan apoyar el programa de erradicación del sarampión en la ciudad de Río de Janeiro y en otras localidades. Métodos. Se estudió la presencia de inmunoglobulinas G contra el sarampión en muestras de plasma de 1 101 donaciones de sangre consecutivas realizadas en noviembre de 2000 en HEMORIO, el mayor banco de sangre del estado de Río de Janeiro, mediante un ensayo inmunoenzimático comercial y una prueba de neutralización por reducción de placas. Se calculó la proporción (y el intervalo de confianza (IC) de 95%) de las muestras negativas a anticuerpos contra el sarampión en la totalidad de las donaciones y en subgrupos conformados según la edad, el sexo, el vecindario de residencia, la educación y la ocupación laboral. La significación estadística de las diferencias entre las proporciones y entre sus tendencias lineales se determinó mediante la prueba de ji al cuadrado. Resultados. Del total de donantes de sangre, el 6,9% (IC95%: 5,4 a 8,4%) resultó seronegativo al sarampión. Las mujeres tuvieron una mayor proporción de resultados seronegativos (10,1%; IC95%: 6,8 a 13,4%) que los hombres (5,6%; IC95%: 4,0 a 7,2%). En relación con la edad, 86,8% de las personas seronegativas nacieron entre 1971 y 1982. La seronegatividad fue inversamente proporcional a la edad (ji al cuadrado = 58,0; P < 0,0001). En cuanto a la ocupación laboral, los estudiantes presentaron la mayor proporción de seronegativos (17,8%), mientras que en lo referente a la educación, la mayoría de las personas susceptibles a la enfermedad se encontraban en la categoría de "estudios universitarios incompletos" o "estudios secundarios incompletos". La proporción de seronegativos entre las diferentes áreas de residencia estuvo entre 2,1% y 11,4%. Conclusiones. El plasma de los bancos de sangre puede ser una fuente útil y conveniente de datos complementarios para la vigilancia serológica en adultos, tanto de sarampión como de otras enfermedades infecciosas para las que se hayan implementado actividades de inmunización y vigilancia. Este enfoque puede ser beneficioso en otras regiones de Brasil y en otros países en los que se pueda contar para la vigilancia con el plasma de los donantes de sangre. El empleo del remanente de los sueros de los pacientes y del plasma de los donantes de sangre representa una solución de compromiso entre la representatividad y la oportunidad, y el buen uso de los recursos

Serological surveillance of measles in blood donors in Rio de Janeiro, Brazil.

OBJECTIVES: To estimate the proportion of individuals seronegative for measles antibody among blood donors from a blood bank in the city of Rio de Janeiro, Brazil, and to describe their social and demographic characteristics, with the goal of exploring the potential use of plasma banks to supplement serological surveillance with relevant data in order to support the program of measles elimination in the city of Rio de Janeiro and elsewhere. METHODS: Plasma samples from 1 101 consecutive blood donations made in November 2000 at HEMORIO, the largest blood bank in the state of Rio de Janeiro, were tested for measles immunoglobulin G, using a commercial enzyme immunoassay and a plaque reduction neutralization test. We calculated the proportion (and 95% confidence interval (CI)) of samples seronegative for measles antibody for the total sample of blood donors and also for subgroups categorized by age, sex, neighborhood of residence, education, and occupation. We used the chi-square test to assess the statistical significance of differences in proportions and linear trends in proportions. RESULTS: Of the total group of blood donors, 6.9% of them (95% CI: 5.4%-8.4%) were seronegative for measles. Women had a higher proportion (10.1%; 95% CI: 6.8%-13.4%) of seronegative results than did men (5.6%; 95% CI: 4.0%-7.2%). In terms of age, 86.8% of seronegative individuals were born between 1971 and 1982. Seronegativity was inversely proportional to age (chi-square = 58.0; P < 0.0001). With regard to occupation, students had the highest proportion of seronegative individuals (17.8%). In terms of education, most of the susceptible persons were in the categories of "incomplete university degree" or "incomplete high school." For the various areas of residence the proportions ranged from 2.1% to 11.4%. CONCLUSIONS: Blood bank plasma may constitute a useful and convenient source of complementary data for serological surveillance in adults of measles and other infections for which immunization and surveillance activities are implemented. This approach could be beneficial to other areas in Brazil and other countries where plasma from blood donors is available for surveillance. The use of residual sera from patients and plasma from blood donors represents a tradeoff between representativeness and timeliness as well as economy of resources.

Comparison of immunoglobulin G subclass profiles induced by measles virus in vaccinated and naturally infected individuals.

A total of 258 human sera positive for measles antibodies were divided into four different groups: group 1 contained 54 sera from children after natural measles infection (immunoglobulin M [IgM] positive, early infection phase), group 2 contained 28 sera from children after measles vaccination (IgM positive, early infection phase), group 3 contained 100 sera from healthy adults (natural long-lasting immunity), and group 4 contained 76 sera from healthy children (postvaccinal long-lasting immunity). In the early phase of infection, the percent distributions of measles virus-specific IgG isotypes were similar between natural and postvaccinal immune responses. IgG1 and IgG4 were the dominant isotypes, with mean levels of detection of 100% (natural infection) and 100% (postvaccinal) for IgG1 and 96% (natural infection) and 92% (postvaccinal) for IgG4. In comparison, the IgG4 geometric mean titer (GMT) in the early phase of natural infection was significantly higher than the IgG4 GMT detected in the postvaccinal immune response (80 versus 13; 95% confidence interval). In the memory phase, IgG2 and IgG3 responses decreased significantly in both natural infection and postvaccinal groups, while IgG1 levels were maintained. In contrast, the IgG4 postvaccinal immune response decreased strongly in the memory phase, whereas IgG4 natural long-lasting immunity remained unchanged (9 versus 86%; P < 0.05). The results obtained suggest that IgG4 isotype could be used in the early phase of infection as a quantitative marker and in long-lasting immunity as a qualitative marker to differentiate between natural and postvaccinal immune responses.

Recent measles viral activity in Uruguai: serological and genetic approaches.

In the summer 1999, a measles outbreak occurred in Uruguai. During this outbreak 58 cases were recorded, 36 of which were laboratory confirmed as positive for measles virus (MV) IgM. The cases occurred in touristic places (Montevideo and Maldonado) predominantly among health facilities and tourist service personnel. Urine specimens collected between days 1 and 4 after the onset of the rash from seven cases were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nested PCR with primers specific for the carboxyl-terminal region of the nucleoprotein (N) gene. Three of these specimens/cases were positive for MV. Sequencing of 300 nucleotides (nt) of PCR products corresponding to a part of the carboxyl-terminal region of the MV N gene detected in these specimens MV of D6 genotype. The same nucleotide sequences and the same genotype were also previously observed for MV isolates from the 1997 epidemic in Brazil and the 1998 epidemic in Argentina, demonstrating that the D6 genotype was, and may be still circulating in South America.

Calibration and use of an in-house anti-measles IgG standard serum.

For the purpose of research a large quantity of anti-measles IgG working reference serum was needed. A pool of sera from five teenagers was prepared and named Alexandre Herculano (AH). In order to calibrate the AH serum, 18 EIA assays were performed testing in parallel AH and the 2nd International Standard 1990, Anti-Measles Antibody, 66/202 (IS) in a range of dilutions (from 1/50 to 1/25,600). A method which compared parallel lines resulting from the graphic representation of the results of laboratory tests was used to estimate the power of AH relative to IS. A computer programme written by one of the authors was used to analyze the data and make potency estimates. Another method of analysis was used, comparing logistic curves relating serum concentrations with optical density by EIA. For that purpose an existing computer programme (WRANL) was used. The potency of AH relative to IS, by either method, was estimated to be 2.4. As IS has 5000 milli international units (mIU) of anti-measles IgG per millilitre (ml), we concluded that AH has 12,000 mIU/ml.

Human parvovirus B19 infections among exanthematic diseases notified as measles

A total of 1397 sera collected from 1095 cases of exanthematic disease notified as measles in ES and RJ states during July 1992 to December 1994 were investigated. These sera were first tested for measles and rubella specific IgM. When they proved negative, they were tested for B19 specific IgM by an enzyme immunoassay. B19 infection was confirmed in 27 (2.5 per cent) of these cases. Sera from 194 negative cases for measles and rubella IgM received from other Brazilian states were also investigated and B19 infection was confirmed for 11 of them. Sera from these 38 IgM positive cases for B19, were tested for anti-B19 IgG by an enzyme immunoassay and for B19 DNA by dot blot hybridization. Anti-B19 IgG antibodies were detected in most of the acute sera. B19 DNA was detected in the acute serum of one patient that had been splenectomized before. As the exanthem caused by human parvovirus infection may be clinically diagnosed as rubella, it could be important to diagnose B19 infection in Brazil since it is becoming prevalent as the cause of rash in countries where rubella is controlled by vaccination.

Immunoglobulin M antibody response to measles virus following natural virus infection, primary vaccination, and reexposure to the virus.

Evaluation of the measles virus ELISA kit (Merck) to detect specific IgM as an indicator of primary measles antibody response was carried out. A modification of the manufacturer's cutoff value interpretation was introduced to allow for equivocal results in addition to positive and negative ones. With this modification, the test assayed gave an overall reproducibility of 96.16%. The IgM seropositivity rate for seroneutralization-confirmed measles cases was 100% for naturally infected measles subjects and 90% for primary measles vaccinated subjects. Individuals with positive neutralizing antimeasles antibodies in close contact with a confirmed measles case gave the following measles IgM ELISA results: 54.54% negative, 9.09% positive, and 36.36% equivocal, showing a booster with IgM antibody response on reexposure to the virus. Positive subjects with neutralizing antimeasles antibodies without recent contact with a measles case gave negative IgM results. IgM seropositivity was strongly associated with IgG seroconversion and clinical measles (p < 0.0001). The technique assayed performed adequately for the confirmation of both measles natural infection and primary vaccination and for the differentiation of primary and secondary antibody response, taking into account the modification in the cutoff value interpretation introduced and providing that the serum samples are obtained between days 5 and 30 after onset of rash.

Human parvovirus B19 infections among exanthematic diseases notified as measles.

A total of 1397 sera collected from 1095 cases of exanthematic disease notified as measles in ES and RJ states during July 1992 to December 1994 were investigated. These sera were first tested for measles and rubella specific IgM. When they proved negative, they were tested for B19 specific IgM by an enzyme immunoassay. B19 infection was confirmed in 27 (2.5%) of these cases. Sera from 194 negative cases for measles and rubella IgM received from other Brazilian states were also investigated and B19 infection was confirmed for 11 of them. Sera from these 38 IgM positive cases for B19, were tested for anti-B19 IgG by an enzyme immunoassay and for B19 DNA by dot blot hybridization. Anti-B19 IgG antibodies were detected in most of the acute sera. B19 DNA was detected in the acute serum of one patient that had been splenectomized before. As the exanthem caused by human parvovirus infection may be clinically diagnosed as rubella, it could be important to diagnose B19 infection in Brazil since it is becoming prevalent as the cause of rash in countries where rubella is controlled by vaccination.

Seroconversion to human herpesvirus 6 and human herpesvirus 7 among Brazilian children with clinical diagnoses of measles or rubella.

We collected acute-phase and convalescent-phase serum samples from Brazilian patients who presented with exanthem of unknown origin and evaluated these samples by means of an immunoblot assay for seroconversion to human herpesvirus 6 (HIV-6) or human herpesvirus 7 (HIV-7). Measles or rubella had been clinically diagnosed in all these patients, but their sera were negative for antibodies to both measles virus and rubella virus. Twenty percent of the patients clearly seroconverted to HHV-6 after manifestation of the exanthem, and 8% seroconverted to HHV-7. All seroconversions to HHV-6 occurred in children aged < or = 5 years; a 41% frequency of seroconversion to HHV-6 was noted among children between 3 months and 23 months of age, whereas seroconversions to HHV-7 were detected during infancy and through adulthood. Our data indicate that primary infections due to HHV-6 or HHV-7 can be misdiagnosed as measles or rubella.