Serum anti-tetanus and measles antibody titres in Ugandan children aged 4 months to 6 years: implications for vaccine programme.

To study the antibody response to tetanus toxoid and measles by age following vaccination in children aged 4 months to 6 years in Entebbe, Uganda. Serum samples were obtained from 113 children aged 4-15 months, at the Mother-Child Health Clinic (MCHC), Entebbe Hospital and from 203 of the 206 children aged between 12 and 75 months recruited through the Outpatients Department (OPD). Antibodies to measles were quantified by plaque reduction neutralisation test (PRNT) and with Siemens IgG EIA. VaccZyme IgG EIA was used to quantify anti-tetanus antibodies. Sera from 96 of 113 (85.0%) children attending the MCHC contained Measles PRNT titres below the protective level (120 mIU/ml). Sera from 24 of 203 (11.8%) children attending the OPD contained PRNT titres 0.15 IU/ml by EIA, a level considered protective. The overall concentration of anti-tetanus antibody was sixfold higher in children under 12 months compared with the older children, with geometric mean concentrations of 3.15 IU/ml and 0.49 IU/ml, respectively. For each doubling in age between 4 and 64 months, the anti-tetanus antibody concentration declined by 50%. As time since the administration of the third DTP vaccination doubled, anti-tetanus antibody concentration declined by 39%. The low measles antibody prevalence in the children presenting at the MCHC is consistent with the current measles epidemiology in Uganda, where a significant number of measles cases occur in children under 1 year of age and earlier vaccination may be indicated. The consistent fall in anti-tetanus antibody titre over time following vaccination supports the need for further vaccine boosters at age 4-5 years as recommended by the WHO.

Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits.

Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JEDetect™ MAC-ELISA (JEDetect), a differential testing algorithm was developed in which samples tested by JEDetect with positive results were subsequently tested by the DENDetect™ MAC-ELISA (DENDetect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JEDetect and DENDetect and were classified as JE- (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JEDetect and DENDetect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF.

Research priorities for global measles and rubella control and eradication.

In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibility of measles eradication concluded that (1) measles can and should be eradicated, (2) eradication by 2020 is feasible if measurable progress is made toward existing 2015 measles mortality reduction targets, (3) measles eradication activities should occur in the context of strengthening routine immunization services, and (4) measles eradication activities should be used to accelerate control and elimination of rubella and congenital rubella syndrome (CRS). The expert advisory panel also emphasized the critical role of research and innovation in any disease control or eradication program. In May 2011, a meeting was held to identify and prioritize research priorities to support measles and rubella/CRS control and potential eradication activities. This summary presents the questions identified by the meeting participants and their relative priority within the following categories: (1) measles epidemiology, (2) vaccine development and alternative vaccine delivery, (3) surveillance and laboratory methods, (4) immunization strategies, (5) mathematical modeling and economic analyses, and (6) rubella/CRS control and elimination.

Expansion of the global measles and rubella laboratory network 2005-09.

Enhancing measles surveillance with integration of epidemiologic and laboratory information is one of the key strategies for accelerated measles control and elimination. The World Health Organization (WHO) Global Measles and Rubella Laboratory Network (LabNet) has been developed since 2000 to currently include 690 laboratories serving 183 countries. The LabNet testing strategy follows well-validated, standardized procedures for confirming suspected cases and for monitoring measles and rubella virus transmission patterns. The strength of the LabNet is a strong quality assurance program that monitors the performance of all laboratories through annual proficiency testing and continuous assessment. In the 5-year period 2005-2009, the results of >1 million measles immunoglobulin M (IgM) tests have been reported by the LabNet and, in addition, sequence information on >7000 measles and 600 rubella viruses has been shared. Progress with the development of the LabNet during 2005-2009 is discussed.

An indirect immunocolorimetric assay to detect rubella virus infected cells.

An indirect immunocolorimetric assay (ICA) to detect rubella virus infected cells by the naked eye was developed. This assay was as sensitive and specific as an indirect immunofluorescent assay (IFA), could detect as little as 10 plaque forming units (pfu) of rubella virus in the initial inoculum and could detect viruses from throat swabs. This assay detected infection with viruses of all nine rubella virus genotypes available for testing. It could be utilized for virus quantitation and a neutralization assay. In addition to detecting rubella virus infection, this assay also allowed us to confirm measles virus infection. This assay should be useful for virus isolation from clinical samples.

Rubella and congenital rubella syndrome: global update

Se calcula que cada año nacen en el mundo más de 100 000 niños con síndrome de rubéola congénita (SRC). La Organización Mundial de la Salud (OMS) estandarizó en 1998 las definiciones de casos para la vigilancia del SRC y de la rubéola. En 2001, 123 países o territorios notificaron 836 356 casos de rubéola y se espera que el número de países se incremente a medida que se desarrolla, bajo la coordinación de la OMS, una red mundial de laboratorios para la detección del sarampión y la rubéola. Se están realizando investigaciones para mejorar la vigilancia de esta última enfermedad, entre ellas algunos proyectos encaminados a echar a andar la vigilancia y a comparan métodos diagnósticos, así como estudios de epidemiología molecular para lograr entender más a fondo los patrones de circulación del virus de la rubéola en el mundo. En 1996 una encuesta efectuada por la OMS reveló que 78 (36 per ciento) de los 214 países o territorios que habían notificado casos de la enfermedad aplicaban la vacuna contra la rubéola como parte de su régimen de vacunación estándar. Para fines de 2002 un total de 124 de esos 214 (58 per ciento) países o territorios aplicaban la vacuna antirrubeólica cuyo uso depende del nivel de desarrollo económico: 100 per ciento en países industrializados, 71 per ciento en países con economías en transición y 48 per ciento en países en desarrollo. Se dispone de una vacuna inocua y eficaz y se ha demostrado la eficacia de algunas estrategias de vacunación para la prevención de la rubeóla y el SRC. En un trabajo de posición de la OMS se ofrece orientación acerca de lo que entraña, desde el punto de vista programático, emprender la vacunación antirrubeólica. Se trata de una medida cuya efectividad y beneficios superan su costo, pero que exige un continuo fortalecimiento de los servicios de vacunación y sistemas de vigilancia habituales.

Rubella and congenital rubella syndrome: global update.

Worldwide, it is estimated that there are more than 100.000 infants born with congenital rubella syndrome (CRS) each year. In 1998, standard case definitions for surveillance of CRS and rubella were developed by the World Health Organization (WHO). In 2001, 123 countries/territories reported a total of 836.356 rubella cases. In the future more countries are expected to report on rubella as a global measles/rubella laboratory network is further developed under the coordination of WHO. Operational research is being conducted to improve rubella surveillance. This includes projects on initiating CRS surveillance, comparative studies on diagnostic laboratory methods, and molecular epidemiology research to expand the global understanding of patterns of rubella virus circulation. In 1996 a WHO survey found that 78 od 214 reporting countries/territories (36%) were using rubella vaccine in their routine immunization services. By the en of 2002 a total of 124 of the 214 counties/territories (58%) were using rubella vaccine. Rubella vaccine use varies by stage of economic development: 100% for industrialized countries, 71% for countries with economies in transition, and 48% for developing countries. A safe effective rubella vaccine is available, and there are proven vaccination strategies for preventing rubella and CRS. A WHO position paper provides guidance on programmatic aspects of rubella vaccine introduction. The introduction of rubella vaccine is cost-effective and cost-beneficial but requires ongoing strengthening of routine immunization services and surveillance systems.

Rubella and congenital rubella syndrome: global update

Worldwide, it is estimated that there are more than 100, 000 infants born with congenital rubella syndrome (CRS) each year. In 1988, standard case definitions for surveillance of CRS and rubella were developed by the World Health Organization (WHO). In 2001, 123 countries/territories reported a total of 836, 356 rubella cases. In the future more countries are expected to report on rubella as a global measles/rubella laboratory network is further developed under the coordination of the WHO. Operational research is being conducted to improve rubella surveillance. This includes projects on initiating CRS surveillance, comparative studies on diagnostoc laboratory methods, and molecular epidemiology research to expand the global understanding of patterns of rubella virus circulation. In 1996 a WHO survey found that 78 of 214 reporting countries/teritories (36 percent) were using rubella vaccine in their routine immunization services. By the end of 2002 a total of 124 of the 214 countries/territories (58 percent) were using rubella vaccine. Rubella vaccine use varies by stage of economic development: 100 percent for industrialized countries, 71 percent for countries with economies in transition, and 48 percent for developing countries. A safe and effective rubella vaccine is available, and there are proven vaccination strategies for preventing rubella and CRS. A WHO position paper provides guidance on programmativ aspects of rubella vaccine introduction. The introduction of rubella vaccine is cost-effective and cost-beneficial but requires ongoing strengthening of routine immunization services and surveillance systems (AU)