Rotavirus gastroenteritis hospitalizations in provinces with different vaccination coverage rates in Spain, 2013-2018.

BACKGROUND: Rotavirus (RV) vaccines are available in Spain since 2006 but are not included in the National Immunization Program. RV vaccination has reached an intermediate vaccination coverage rate (VCR) but with substantial differences between provinces. The aim of this study was to assess the ratio of RV gastroenteritis (RVGE) admissions to all-cause hospitalizations in children under 5 years of age in areas with different VCR. METHODS: Observational, multicenter, cross-sectional, medical record-based study. All children admitted to the study hospitals with a RVGE confirmed diagnosis during a 5-year period were selected. The annual ratio of RVGE to the total number of all-cause hospitalizations in children < 5 years of age were calculated. The proportion of RVGE hospitalizations were compared in areas with low (< 30%), intermediate (31-59%) and high (> 60%) VCR. RESULTS: From June 2013 to May 2018, data from 1731 RVGE hospitalizations (16.47% of which were nosocomial) were collected from the 12 study hospitals. RVGE hospital admissions accounted for 2.82% (95 CI 2.72-3.00) and 43.84% (95% CI 40.53-47.21) of all-cause and Acute Gastroenteritis (AGE) hospitalizations in children under 5 years of age, respectively. The likelihood of hospitalization due to RVGE was 56% (IC95%, 51-61%) and 27% (IC95%, 18-35%) lower in areas with high and intermediate VCR, respectively, compared to the low VCR areas. CONCLUSIONS: RVGE hospitalization ratios are highly dependent on the RV VCR. Increasing VCR in areas with intermediate and low coverage rates would significantly reduce the severe burden of RVGE that requires hospital management in Spain. Clinical trial registration Not applicable.

Lack of impact of the El Hierro (Canary Islands) submarine volcanic eruption on the local phytoplankton community.

The eruption of a submarine volcano south of El Hierro Island (Canary Islands) in October 2011 led to major physical and chemical changes in the local environment. Large amounts of nutrients were found at specific depths in the water column above the volcano associated with suboxic layers resulting from the oxidation of reduced chemical species expelled during the eruptive phase. It has been suggested that the fertilization with these compounds enabled the rapid restoration of the ecosystem in the marine reserve south of the island once the volcanic activity ceased, although no biological evidence for this has been provided yet. To test the biological fertilization hypothesis on the pelagic ecosystem, we studied the evolution and variability in chlorophyll a, from in situ and remote sensing data, combined with information on phytoplankton and bacterial community structure during and after the eruptive episode. Remote sensing and in situ data revealed that no phytoplankton bloom took place neither during nor after the eruptive episode. We hypothesize that the fertilization by the volcano did not have an effect in the phytoplankton community due to the strong dilution of macro- and micronutrients caused by the efficient renewal of ambient waters in the zone.

Multicenter prospective study on the burden of rotavirus gastroenteritis in children less than 3 years of age in Spain.

BACKGROUND: Rotavirus is acknowledged as an important cause of paediatric gastroenteritis worldwide. In Spain, comprehensive data on the burden of rotavirus disease was lacking. METHODS: A prospective, multicenter, observational study was carried out, during the winter season, from October to April 2014 in selected areas of Spain (Catalonia, Basque Country, Andalusia) to estimate the frequency and characteristics of acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) in children ≤3 years of age seeking medical care in primary care and emergency department centres. RESULTS: Of the 1087 episodes of AGE registered, 33.89 % were RVGE positive. The estimated incidence of RVGE, was 40.3 (95 % CI 36.1-44.8) episodes per 10,000 child-months in children ≤ 3 years of age and the 5-month (December-April) seasonal RVGE incidence rate was 2.01 [1.81-2.24] per 100 children. No vaccination and attending a day care centre were the main risk factors for RV infection. RVGE infected children presented more frequently with fever (63.9 % vs. 45.1 %, p = 0.009), vomiting (61.2 % vs. 44.3 %, p = 0.015), suffered more dehydration, and were hospitalised and went to the emergency room more often (41.7 % vs. 15.7 %, p <0.001) than non-RVGE infected ones. Children were usually more tired (77.5 % vs. 54.2 %, p <0.001), tearful, (47.2 % vs. 34.8 %, p <0.001), and easily irritated (76.5 % vs. 59.8 %, p <0.001), and parents were more concerned (41.7 % vs. 15.7 %, p <0.001) and suffered more working rhythm disturbances (39.0 % vs. 22.9 %, p <0.001). The cost for families of RVGE cases was significantly higher than the cost of non-RVGE infected ones (47.3 vs 36.7 euros, p = 0.011). Vaccinated children suffered less clinical symptoms and no hospitalization. Therefore, vaccination decreases the psychosocial stressors caused by the disease in the family. CONCLUSIONS: Rotavirus infections are responsible for a substantial proportion of AGE cases in children ≤3 years of age in Spain attended at primary care visits. RVGE episodes are associated with greater clinical severity, greater alterations in the child´s behaviour, and higher parental distress. The outcomes of the present study recommend that routine rotavirus vaccination in infants ≤3 years of age could considerably reduce the serious burden of this potentially serious childhood disease.

Clinical features of influenza disease in admitted children during the first postpandemic season and risk factors for hospitalization: a multicentre Spanish experience.

The main objectives of this study were to describe the characteristics of children with influenza infection during the postpandemic outbreak, and to compare sociodemographic and clinical data between patients who required hospitalization and those managed on an outpatient basis with a matched case-control study design. This is a multicentre paediatric study in Spain that included patients aged 6 month to 18 years in whom influenza infection was confirmed by real-time reverse transcription-polymerase chain reaction between December 2010 and March 2011. Among the 143 admitted patients, the main reason for admission was respiratory failure (123/143). In 55 there was some previously known disease. The median age was lower in patients without comorbidity (1.8 years: interquartile range 1.0-3.0 versus 5.3 years: interquartile range 1.3-10.7); p <0.01). The lag time from onset of symptoms to starting antiviral treatment was correlated with the length of hospital stay (Rho Spearman = + 0.32; p 0.01). Twenty patients required admission to the paediatric intensive care units, all due to respiratory failure. Children with chest X-ray opacities in more than one quadrant more frequently required admission to intensive care. Having a neurological disease conferred the highest risk of requiring hospitalization (OR 17.18) in a multivariate analysis. This study concludes that influenza in the paediatric population requiring hospitalization during the postpandemic season affected mainly children with neurological or pulmonary comorbidities and children of parents with a lower educational level. Most of the influenza infections caused respiratory symptoms, although neurological manifestations were also observed. Early initiation of oseltamivir was associated with a shorter length of hospital stay.

[Consensus document on vaccination against influenza in health care workers]. / Consenso sobre la vacunación frente a la gripe en el personal sanitario.

Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. Convinced that one of the best tools to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary.

Consenso sobre la vacunación frente a la gripe en el personal sanitario / No disponible

El personal sanitario se encuentra incluido cada año entre los grupos de riesgo con indicación para vacunarse frente a la gripe. No obstante, las coberturas vacunales entre el personal sanitario en nuestro país son muy bajas, no superando el 25%. Convencidos de que una de las mejores herramientas para aumentar estas coberturas entre los profesionales de nuestro país son las evidencias científicas, 19 Sociedades Científicas y Asociaciones Profesionales que agrupan a los profesionales sanitarios más directamente relacionados con la gripe como problema de salud, así como el Consejo General de Enfermería, se han reunidopara debatir y elaborar este documento de consenso con el objetivo de concienciar al personal sanitario sobre la conveniencia de su vacunación frente a la gripe y de los beneficios que de ella se derivan para sí mismos, para sus pacientes y para el resto de la población. Esta recomendación está basada en 3 pilares básicos: argumento de necesidad, de ética y de ejemplaridad

Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. Convinced that one of the best tolos to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary

The submarine volcano eruption at the island of El Hierro: physical-chemical perturbation and biological response.

On October 10 2011 an underwater eruption gave rise to a novel shallow submarine volcano south of the island of El Hierro, Canary Islands, Spain. During the eruption large quantities of mantle-derived gases, solutes and heat were released into the surrounding waters. In order to monitor the impact of the eruption on the marine ecosystem, periodic multidisciplinary cruises were carried out. Here, we present an initial report of the extreme physical-chemical perturbations caused by this event, comprising thermal changes, water acidification, deoxygenation and metal-enrichment, which resulted in significant alterations to the activity and composition of local plankton communities. Our findings highlight the potential role of this eruptive process as a natural ecosystem-scale experiment for the study of extreme effects of global change stressors on marine environments.

Immunogenicity and safety of AS03-adjuvanted H1N1 pandemic vaccines in children and adolescents.

Vaccines with acceptable efficacy profile against the H1N1 A/California/7/2009 virus are needed for use in children. The two studies presented here evaluated the immunogenicity and the reactogenicity/safety of A/H1N1/2009 vaccines containing either 3.75 µg haemagglutinin antigen (HA) and AS03(A)-adjuvant (3.75 µg HA/AS03(A) study) (N=210 [53, 57 and 100 in the 3-5, 6-9 and 10-17 years age strata, respectively]) or 1.9 µg HA and AS03(B)-adjuvant (1.9 µg HA/AS03(B) study) (N=244 [61, 65 and 118 in the 3-5, 6-9 and 10-17 years age strata, respectively]), given as two-dose series. Although the haemagglutination inhibition antibody titres were higher in the 3.75 µg HA/AS03(A) study, both vaccine dosages were highly immunogenic and exceeded regulatory acceptance criteria after the first and the second doses. Seroprotection rates reached 100% and seroconversion rates ranged from 98.2% to 99.1% after each dose of both vaccine dosages. Geometric mean titres increased from 456.5 to 1538.5 and from 297.9 to 1106.7 between the first and the second doses in the 3.75 µg HA/AS03(A) study and the 1.9 µg HA/AS03(B) study, respectively. Despite an observed slight increase of the reactogenicity following the second dose in the 3.75 µg HA/AS03(A) study, the vaccines safety profiles were considered clinically acceptable. In conclusion, both dosages of the AS03-adjuvanted A/H1N1/2009 pandemic influenza vaccines were highly immunogenic and well-tolerated in children and adolescents.

[Recommendations for the management of influenza in pediatrics (2009-2010).] / Recomendaciones sobre el tratamiento de la gripe en Pediatría (2009-2010).

Specific action plans from various institutions, governments and scientific societies have been identified and implemented to combat the A H1N1 2009 influenza virus pandemic. This document sets out the recommendations of the Spanish Association of Pediatrics for the management of influenza in children for influenza season 2009-2010. The risk factors for influenza A H1N1 2009 in pediatric patients, the clinical course, severity and complications are similar to seasonal influenza. In most cases, the diagnosis of influenza will be based on clinical suspicion, without viral subtype differentiation. In a patient with influenza virus infection, the criteria for referral and hospital admission will be based broadly on the signs of clinical severity or complications, regardless of the causative virus. Children with influenza but with no signs of clinical severity or complications do not require antiviral treatment. Physical measures of hygiene and isolation are essential to reduce the transmissibility of the disease. The influenza vaccines in infancy, for both seasonal influenza and for influenza A H1N1 2009, should be directed primarily at patients with risk factors.

Recomendaciones sobre el tratamiento de la gripe en Pediatría (2009–2010) / Recommendations for the management of influenza in pediatrics (2009–2010)

Ante la actual situación de pandemia de gripe causada por el virus A H1N1 2009, se han definido planes de actuación específicos desde distintas instituciones, administraciones y sociedades científicas. En este documento se definen las recomendaciones de la Asociación Española de Pediatría para el tratamiento de la gripe en la infancia para la estación gripal 2009–2010. Para la gripe A H1N1 2009, los factores de riesgo en edad pediátrica, el curso clínico, la gravedad y las complicaciones son similares a los de la gripe estacional. Además, el diagnóstico de gripe será, en la gran mayoría de los casos, por sospecha clínica sin diferenciación del subtipo viral. Ante un paciente con gripe, los criterios de derivación e ingreso hospitalario se basarán globalmente en la presencia de signos de gravedad clínica o de complicaciones, independientemente del virus causante. Los niños con gripe sin signos de gravedad ni complicaciones no requieren tratamiento con antivirales. Las medidas físicas de higiene y el aislamiento son fundamentales para reducir la transmisibilidad de la enfermedad. La vacunación antigripal en la infancia, tanto para gripe estacional como para gripe A H1N1 2009, debe dirigirse de forma prioritaria a los pacientes con factores de riesgo (AU)

Specific action plans from various institutions, governments and scientific societies have been identified and implemented to combat the A H1N1 2009 influenza virus pandemic. This document sets out the recommendations of the Spanish Association of Pediatrics for the management of influenza in children for influenza season 2009–2010. The risk factors for influenza A H1N1 2009 in pediatric patients, the clinical course, severity and complications are similar to seasonal influenza. In most cases, the diagnosis of influenza will be based on clinical suspicion, without viral subtype differentiation. In a patient with influenza virus infection, the criteria for referral and hospital admission will be based broadly on the signs of clinical severity or complications, regardless of the causative virus. Children with influenza but with no signs of clinical severity or complications do not require antiviral treatment. Physical measures of hygiene and isolation are essential to reduce the transmissibility of the disease. The influenza vaccines in infancy, for both seasonal influenza and for influenza A H1N1 2009, should be directed primarily at patients with risk factors (AU)

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine.

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by pneumococci. By the second year after introduction of the heptavalent pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence of invasive disease decreased by 64.3% in children less than 12 months of age, by 39.7% in children less than 24 months of age, and by 37.5% in children less than 60 months of age. The prevalence of clinical isolates of S. pneumoniae that lacked susceptibility to penicillin decreased by 58.2% among children less than 60 months of age. With an estimated coverage by four-dose heptavalent pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive pneumococcal infections in the Basque Country and in Navarre fell significantly after just 2 years of immunization, underscoring the importance of improving vaccination coverage under a universal childhood immunization program.

Las vacunas en la prevención de las enfermedades infecciosas en el niño. Estado actual y perspectivas futuras / Vaccinations in the prevention of infectious diseases in the child. Present state and future perspectives

No disponible

Vacunación antivaricela: descripción y controversia / No disponible

Las vacunas frente a la varicela disponibles comercialmente derivan de la vacuna desarrollada en Japón por Takahashi en 1974 y están constituidas por virus vivos atenuados procedentes de la cepa Oka. La vacuna existente en España es la de los laboratorios GlaxoSmithKline, Varilrix®, está estabilizada para poder conservarse a 2-8 °C durante 2 años, conservando un título superior a 103,3 unidades formadoras de placa (UFP). Existen, por parte de algunos autores, algunas controversias en la utilización de la vacuna contra la varicela, entre las que pueden mencionarse las siguientes: a) la varicela es una enfermedad benigna y, por lo tanto, la prevención tiene un escaso interés; b) la varicela es una enfermedad característicamente infantil y la vacunación puede producir un desplazamiento de la enfermedad hacia edades de la adolescencia y del adulto, en las que la enfermedad presenta más complicaciones y es más grave; c) no se conoce con exactitud la inmunogenicidad de la vacuna, la duración de la inmunidad y la efectividad de la misma; d) los vacunados podrían transmitir el virus vacunal a los contactos, algunos de los cuales podrían ser de alto riesgo de infección con las consecuencias negativas que de ello se deducen, y e) la vacunación podría incrementar la incidencia de zóster en los vacunados (AU)

No disponible

Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age.

An open, randomised, multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio (DTPa-HBV-IPV) vaccine administered in one injection mixed with Haemophilus influenzae type b (Hib) conjugate vaccine (Group 1) with that of a pentavalent DTPa-IPV vaccine mixed with a Hib vaccine (DTPa-IPV/Hib), simultaneously administered with HBV (Group 2) in two injections in opposite thighs, as a primary vaccination course, to healthy infants at 2, 4 and 6 months of age. A total of 235 completed the study, 120 from Group 1 and 115 from Group 2. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1: 40; Group 2: 31) to assess the immune response to vaccination. Local and general solicited symptoms were recorded by parents on diary cards. Seven hundred and five diary cards (Group 1: 360; Group 2: 345) were collected. The clinically relevant and most commonly reported local reaction was pain (infant cried when the limb was moved) in 2.5% (Group 1) and 1.2% (Group 2) of diary cards. Fever was more frequently reported in Group 1 (21% of diary cards) than in Group 2 (12% of diary cards). However only 3 and 2% of doses in Groups 1 and 2, respectively, were responsible for a rectal temperature between 38.6 and 39.5 degrees C and only one case (Group 2) had > or =39.5 degrees C. Other clinically relevant general symptoms were rarely recorded: irritability (2-2.8%), loss of appetite (0.3-0.6%) and drowsiness (0.3-0.3%). All subjects included in the immunogenicity analysis had seroprotective titres to diphtheria, tetanus, polio virus types 1 and 3, Hib. Almost all subjects were seroprotected for anti-polio type 2 and hepatitis B (with the exception of 1 subject in Group 1 for each antigen). The vaccines response rates to pertussis antigens were over 97 and 90% in Groups 1 and 2, respectively. This study shows that, from a clinical perspective, the DTPa-HBV-IPV/Hib vaccine given in a single injection has a similar reactogenicity and safety profile to that of two licensed vaccines (DTPa-IPV/Hib, HBV) given in two simultaneous injections to infants at 2, 4 and 6 months of age. This is a valuable advantage, since in some countries, such as Spain and the UK, an additional injection (for the administration of meningococcal C conjugate vaccine) has been recently included in the infants' vaccination calendars.

Epidemiology and economic impact of varicella in immunocompetent children in Spain. A nation-wide study.

The epidemiology and burden of varicella was assessed through the prospective study of 683 children under 15 years, by 58 primary care paediatricians working on seven autonomous communities of Spain. The mean age was 4.5+/-2.7 years, and 566 (83%) were secondary cases. There were 111 complications in 101 children (14.8%), skin superinfection being the most frequent (8.9%), followed by respiratory tract (4.5%) and eye (2.2%) infections. The mean number of visits to the paediatric clinic was 1.42 (95% C.I. 1.37-1.47), and 5.6% of the children were attended in the emergency department of a hospital previously. All children had at least one prescription, being antihistamines and antipyretics the most prescribed. Thirteen percent received systemic antibiotics and 11% acyclovir. Children were mainly cared by grandparents, and parents were off work for a mean of 0.97 days (1.61 if children under 5 years attended day-care facilities; 0.51 if they did not). Costs derived from medical attention totalled 32.5, and social indirect costs were 63.77.

[Prevalence pneumococcal meningitis in Spanish children]. / Prevalencia de meningitis neumocócica en niños españoles.

OBJECTIVE: To determine the prevalence of pneumococcal meningitis in the pediatric population in Spain. Material and methods Retrospective multicenter study performed in five autonomous communities (Catalonia, Galicia, Madrid, Navarre and the Basque Country) between January 1998 and December 2000. All patients aged between 0 and 14 years old with a diagnosis of pneumococcal meningitis (Streptococcus pneumoniae isolation or presence of Gram-positive diplococcus in the cerebrospinal fluid (CSF) and CSF with more than 20 cells) in all the hospitals of the five autonomous communities were included in the study. The pediatric population in these communities aged between 0 and 14 years old was 2,327,079. RESULTS: We detected 107 cases in 64 boys and 43 girls with a mean age of 1.19 years old (p 25-0.57; p 75-3.34). The incidence was higher in the first 2 years of life [72/107 (67 %)]. The overall annual prevalence in the five autonomous communities in the first 24 months of life was 8.26 per 100,000 children aged under 2 years (95 % CI: 3.45-15.76). The highest number of cases was detected in Catalonia and Madrid but the highest annual prevalence was found in the Basque Country with 15.52 cases per 100,000 children younger than 2 years old (95 % CI: 8.38-24.74). In the first 12 months of life the prevalence was high in all the autonomous communities, especially in the Basque Country with 22.76 cases per 100,000 newborn infants aged under 12 months (95 % CI 14.58-34.5). In the first 5 years of life the annual global adjusted prevalence per 100,000 children was as follows: Catalonia 3.21 (95 % CI: 1.31-5.11), Galicia 2.65 (95 % CI: 0.35-5.64), Madrid 3.49 (95 % CI: 1.36-5.61), Navarre 3.36 (95 % CI 5,08-11,81), the Basque Country 5.63 (95 % CI: 1.08-10.18). CONCLUSION: The prevalence of pneumococcal meningitis in children from different autonomous communities is high and is greatest in the Basque Country and in children aged under 2 years. This prevalence is similar to that of other European countries and the USA.

Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age.

This double-blind, randomised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine (DTPa-HBV) co-administered with three lots of Haemophilus influenzae type b conjugate (Hib) vaccine in one injection, as a primary vaccination course in healthy infants at 2, 4 and 6 months of age. 269 infants (8-11 weeks of age) were randomly allocated to three groups to receive DTPa-HBV/Hib vaccines, concomitantly with oral polio vaccine. Blood samples for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects. Local and general symptoms were recorded by parents on diary cards. All vaccinees had post-vaccination protective anti-D and anti-T (> or = 0.1 IU ml-1) antibodies, and 98% had protective anti-HBs antibody titres (> or = 10 mIU ml-1). There were no statistically significant differences between groups in post-vaccination anti-D, anti-T, anti-HBs antibody geometric mean titres (GMT), these being 3.49 IU ml-1, 5.92 IU ml-1 and 1109 mIU ml-1, respectively. All subjects responded to three pertussis components, i.e. pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Although statistically significant differences in GMTs of anti-PT, anti-FHA and anti-PRN were found between groups, these were not believed to be of any clinical relevance as the minimum GMTs were 60, 193 and 230 EL.U ml-1 for anti-PT, anti-FHA and anti-PRN, respectively. There were no statistically significant differences in anti-PRP antibody GMT (4.05 micrograms ml-1) between groups, 100% and 85% of subjects having titres > or = 0.15 and 1.0 microgram ml-1, respectively. No symptoms were reported for one third of the subjects. Fever (> 38 degrees C) was reported after 16% of doses, with < 1% having > 39.5 degrees C. Almost all local and general symptoms were mild or moderate, and lasted less than 48 h. No subject dropped out due to a severe adverse reaction. The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe, well-tolerated and immunogenic for all vaccine components.

Immune response to a combined hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine administered to infants at 2, 4 and 6 months of age.

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6-12 weeks of age) received three doses of DTPw-HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU.ml-1], anti-diphtheria and anti-tetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.