Streptococcus pneumoniae nasopharyngeal colonisation in children aged under six years with acute respiratory tract infection in Lithuania, February 2012 to March 2013.

serotypes among children in Lithuania are limited. A prospective study was carried out from February 2012 to March 2013 to evaluate the circulation of SPn serotypes among young children in five cities of Lithuania before the introduction of universal vaccination with pneumococcal conjugate vaccine (PCV). A total of 900 children under six years of age who presented to primary care centres or a hospital emergency department with acute respiratory tract infection (RTI) were enrolled in the study. The SPn colonisation rate was40.8% (367/900), with a peak at two and three years old(48.8% and 45.4%, respectively). Of the 367 SPn isolates, the most common serotypes were 6B (15.8%,n = 58), 19F (13.9%, n = 51), 23F (13.9%, n = 51), 15(10.1%, n = 37), 14 (9.5%, n = 35), 6A (9.3%, n= 34),11 (4.6%, n = 17), 3 (3.0%, n = 11) and 18C (3.0%, n =11); less frequent were 23 (non-23F) (2.7%, n = 10), 19A(2.2%, n = 8) and 9V (1.6%, n = 6). Serotypes 6A and 11 were more common in children under two years-old;18C was found only in children aged two to five years.The serotypes found might be an important predictor of the likely effectiveness of the PCVs currently available in Lithuania

Paediatric pneumococcal disease in Central Europe.

Streptococcus pneumoniae causes considerable global paediatric morbidity and mortality, despite the availability of safe and effective pneumococcal conjugate vaccines (PCVs). To justify the introduction of PCVs, accurate information on the burden of disease is required. Here, we present an appraisal of the pneumococcal epidemiological situation in 11 Central European countries. The data are based on study findings presented at the 12th Central European Vaccine Advisory Group (CEVAG) meeting, held on 21-22 May 2010 in Sofia, Bulgaria, and a literature review of the PubMed database using the search terms 'pneumococcal' or 'Streptococcus pneumoniae', in combination with 'otitis media', 'pneumonia', 'meningitis' or 'bacteraemia/sepsis', and '[Central European country name]'. The incidence of pneumococcal disease appears to be lower in Central Europe than previously reported for Europe as a whole, with the highest risk in infants aged 0-2 years. The fatality rates in the under fives from invasive infections are up to 40%. A paucity of comprehensive country-specific data on pneumococcal disease burden arises from the lack of homogenous surveillance programmes. Standardised, active surveillance systems are required for the accurate evaluation of the pneumococcal disease burden in the region. Only then can the need for vaccination be addressed.

Rotavirus genotypes co-circulating in Europe between 2006 and 2009 as determined by EuroRotaNet, a pan-European collaborative strain surveillance network.

EuroRotaNet, a laboratory network, was established in order to determine the diversity of co-circulating rotavirus strains in Europe over three or more rotavirus seasons from 2006/2007 and currently includes 16 countries. This report highlights the tremendous diversity of rotavirus strains co-circulating in the European population during three years of surveillance since 2006/2007 and points to the possible origins of these strains including genetic reassortment and interspecies transmission. Furthermore, the ability of the network to identify strains circulating with an incidence of ≥1% allowed the identification of possible emerging strains such as G8 and G12 since the beginning of the study; analysis of recent data indicates their increased incidence. The introduction of universal rotavirus vaccination in at least two of the participating countries, and partial vaccine coverage in some others may provide data on diversity driven by vaccine introduction and possible strain replacement in Europe.

Rotavirus surveillance in europe, 2005-2008: web-enabled reporting and real-time analysis of genotyping and epidemiological data.

BACKGROUND: The first European rotavirus surveillance network, EuroRotaNet, comprising 16 laboratories in 15 European countries, has been established. METHODS: Fecal samples from gastroenteritis cases positive for group A rotavirus antigen were collected from multiple European countries from 2005 to mid-2008 and were subjected to G and P genotyping. Epidemiological data collected included age, sex, geographical location, setting, dates of onset and sample collection, and clinical symptoms. RESULTS: A total of 8879 rotavirus-positive samples were characterized: 2129 cases were from the 2005-2006 season, 4030 from the 2006-2007 season, and 2720 from the ongoing 2007-2008 season. A total of 30 different G and P type combinations of strains circulated in the region from 2005 through 2008. Of these strains, 90% had genotypes commonly associated with human infections-G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]-and 1.37% represented potential zoonotic introductions. G1P[8] remained the most prevalent genotype in Europe as a whole, but the incidence of infection with G1P[8] rotavirus strains was <50% overall, and all 3 seasons were characterized by a significant diversity of cocirculating strains. The peak incidence of rotavirus infection occurred from January through May, and 81% of case patients were aged <2.5 years. Conclusions. Data gathered through EuroRotaNet will provide valuable background information on the rotavirus strain diversity in Europe before the introduction of rotavirus vaccines, and the network will provide a robust method for surveillance during vaccine implementation.

Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months.

Two studies were undertaken to investigate the concomitant administration of combined hepatitis A/B vaccine with a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with Haemophilus influenzae vaccine (DTPa-IPV/Hib), or with a measles-mumps-rubella vaccine (MMR), during the second year of life. On completion of the vaccination course, all subjects were seropositive or seroprotected against all antigens except for one subject who was seronegative for anti-PT. Seropositivity and seroprotection rates for all other antibodies were comparable to reference values for each vaccine component, indicating that the immunogenicity of MMR, DTPa-IPV/Hib and combined hepatitis A/B vaccines is not impaired by co-administration. All vaccines were well tolerated.

Antibody titres after primary and booster vaccination of infants and young children with a virosomal hepatitis A vaccine (Epaxal).

To evaluate the immunogenicity and tolerability of Epaxal in infants and children, 30 infants (aged 6-7 months) and 30 children (aged 5-7 years) received a single intramuscular dose of the aluminium-free virosomal hepatitis A virus (HAV) vaccine Epaxal and a booster dose after 12 months. Anti-HAV antibody titres were measured at baseline (before injection), at 1 and 12 months after primary vaccination, and 1 month after the booster vaccination. Sixteen evaluable infants had maternal anti-HAV antibodies at baseline. Complete seroprotection (titre >/= 20 mIU/ml) was achieved by all infants and children at Month 1 and at Month 12. Additionally, all subjects showed a strong antibody response to booster vaccination. In infants without maternal anti-HAV antibodies, the response was four-fold higher than in those with maternal anti-HAV antibodies. Both doses of Epaxal were well tolerated. These preliminary data suggest that Epaxal is an effective hepatitis A vaccine for children and infants from 6 months of age.

Neutralization activity and persistence of antibodies induced in response to vaccination with a novel mumps strain, RIT 4385.

BACKGROUND: We have previously shown that a new measles, mumps, rubella (MMR) vaccine, Priorix, with a novel mumps component elicits anti-mumps antibody titers comparable to the licensed M-M-R II vaccine. MATERIALS AND METHODS: To ensure that these antibodies had neutralizing activity against wild-type mumps virus, sera were prepared 2 and 18 months after vaccination of 12-24-month-old infants with either Priorix or M-M-R II and ELISA antibody titers and neutralizing activity were determined. RESULTS: After 2 months, Priorix and M-M-R II vaccines elicited comparable ELISA antibody titers and neutralizing activity. At 18 months ELISA seropositivity rates were 80-81% and 94-96% of vaccinees had neutralizing activity. All ELISA seropositives had neutralizing activity. CONCLUSION: These data suggest that both vaccines provided equivalent protection against mumps over this 18-month period.

Diphtheria in Lithuania, 1986-1996.

Diphtheria reappeared in Lithuania in 1986 and rose to epidemic levels by 1992. Between 1991 and 1996, 110 cases of diphtheria were registered, with an incidence of 0.03-1.15/100,000 population. Most cases (84%) and all 17 deaths occurred among persons >/=15 years, most of whom had never been vaccinated. Persons 40-49 years old had the highest average annual age-specific morbidity (1.70/100,000) and mortality (0.53/100,000) rates. Low levels of immunity among individuals 40-49 years old and migration to epidemic areas in Russia and Belarus contributed to the epidemic's occurrence. Between 1991 and 1995, toxigenic Corynebacterium diphtheriae strains were isolated from 84 of all registered patients (76%), and nontoxigenic strains were isolated from 13 (12%). By 1996, two mass vaccination campaigns, which provided one dose of vaccine to individuals 25-30 years old and three doses of vaccine to persons 31-60 years old, helped reduce the number of cases. The first campaign achieved 69% coverage; the second achieved 48% coverage.

Does concomitant injection of a combined diphtheria-tetanus-acellular pertussis - hepatitis B virus - inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines?

UNLABELLED: Does concomitant injection of a combined diphtheria-tetanus-acellular pertussis - hepatitis B virus - inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines? The immunogenic responses and local reactions to four Haemophilus influenzae type b (Hib) conjugate vaccines licensed for primary immunisation (Hiberix, ActHib, Pedvax, HibTITER) when administered concomitantly but in the opposite thigh with a candidate diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine were studied in 549 healthy infants at 3, 4.5 and 6 months of age. Local reactions were mild, but different between the four groups, a tetanus conjugate Hib vaccine showing the fewest reactions. All local reactions resolved without sequelae. There was no apparent general reaction. The immunogenic response was similar with all four vaccines, geometric mean concentrations ranging from 4.95 to 7.2 microg/ml. All but one subject had antipolyribosylribitol phosphate polysaccharide antibody titres > or =0.15 microg/ml, and 88.0% to 96% achieved high titres (>1.0 microg/ml) generally associated with long-term protection against Hib disease. CONCLUSION: There does not appear to be any interference with the immune response when current commercial Haemophilus influenzae type b conjugate vaccines are concomitantly administered with a candidate diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus vaccine as separate injections.

Reactogenicity and immunogenicity of a new live attenuated combined measles, mumps and rubella vaccine in healthy children.

OBJECTIVE: To compare the reactogenicity and immunogenicity of a novel live attenuated measles-mumps-rubella vaccine, SB MMR (Priorix; SmithKline Beecham Biologicals), with a widely used MMR vaccine, Merck MMR (M-M-R II; Merck & Co. Inc). METHODS: A total of 4702 healthy children, ages 9 to 24 months, were enrolled in 8 single blind, randomized, controlled trials. Reactogenicity (local and general solicited symptoms and all unsolicited symptoms) was assessed for up to 42 days postvaccination. Immunogenicity [seroconversion rates and geometric mean titers (GMT)] was assessed at 42 or 60 days postvaccination in 1912 subjects in 7 studies. In two studies the persistence of the antibodies at Month 12 postvaccination was assessed in 201 subjects. RESULTS: Local symptoms (pain on or immediately after injection; pain, redness and swelling within 4 days of injection) were reported less frequently after SB MMR than Merck MMR (P < 0.0001). General symptoms and all other events were similar between the two groups. Fever >39.5 degrees C was reported after 9.5 and 11.9% of the SB MMR and Merck MMR doses, respectively. At Days 42 to 60 postvaccination seroconversion rates for antimeasles antibodies were higher with SB MMR than with Merck MMR (98.7% vs. 96.9%, P < 0.031) but similar in both groups for anti-mumps and anti-rubella antibodies, GMTs being approximately 10% higher (P < 0.05) with Merck MMR than with SB MMR. At the Month 12 assessment the seropositivity rates and GMTs were similar in both groups. CONCLUSION: When administered as primary vaccination in children in the second year of life, the new SB MMR vaccine has been shown to be superior to a comparator vaccine in terms of local reactogenicity, with equivalent immunogenicity.

Comparative study of reactogenicity and immunogenicity of new and established measles, mumps and rubella vaccines in healthy children.

Concerns about the association of aseptic meningitis with measles-mumps-rubella (MMR) vaccines containing the Urabe Am 9 strain and the increasing worldwide demand for MMR vaccines, prompted the development of a new mumps vaccine strain (RIT 4385) by SmithKline Beecham Biologicals (SB) as part of a trivalent live attenuated MMR vaccine. The present study assessed the immunogenicity and reactogenicity of two lots of 'Priorix' with a widely used and established vaccine M-M-R II (Merck & Co. Inc.) as comparator vaccine. 255 healthy children, 12 to 24 months of age, were enrolled in a single-blind study and randomly allocated to receive a single dose of one of two lots of "Priorix" or M-M-R II vaccine. Vaccinees were followed up for six weeks post-vaccination for solicited and unsolicited symptoms. Immunogenicity was determined in pre- and 60 days post-vaccination sera using commercial immunoassays for measles, mumps and rubella antibodies. There were no significant differences in immune responses between groups for any of the three vaccine components. In initially seronegative subjects, the respective post-vaccination seroconversion rates for 'Priorix' lots 1 and 2, and M-M-R II were 100, 100 and 97.6% for measles antibodies, 91.7, 95.1 and 94% for mumps antibodies and 100, 100 and 100% for rubella antibodies, respectively. GMTs for the three groups were 3,076, 3,641 and 3,173 mIU/ml for measles antibodies, 934, 900 and 1,043 U/ml for mumps antibodies, and 86.4, 87.5 and 97.1 IU/ml for rubella antibodies, respectively. The incidence of local symptoms was significantly lower for both 'Priorix' lots (17.6 and 15.3% for lots 1 and 2, respectively) than for M-M-R II (37.6%). Fever > or = 38.1 degrees C during the six-week observation period occurred in approximately 25% of all subjects in all groups with no differences between the groups. No parotid/salivary gland swelling or signs of suspected meningism were reported, and there were no serious adverse events related to vaccination. The new MMR vaccine 'Priorix' containing the new RIT 4385 mumps strain was safe and had a significantly improved local tolerability profile over the comparator vaccine, M-M-R II, while eliciting an at least equivalent immune response.

Feasibility study of a combined diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine, and comparison of clinical reactions and immune responses with diphtheria-tetanus-acellular pertussis (DTPa) and hepatitis B vaccines applied as mixed or injected into separate limbs.

The feasibility of a combined diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine was assessed and a comparison made of immunogenicity and reactogenicity to DTPa and HBV vaccines mixed in one syringe and to concomitant but separate injections as a primary vaccination course in three groups of infants at 3, 4.5 and 6 months of age. All subjects attained protective levels of anti-HBs antibodies 1 month after the primary course with higher geometric mean titres (GMTs) in the combined or mixed vaccinations. GMTs for pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) were as good or better in the groups administered the combined formulation and the extemporaneously mixed vaccines than the separate administration. No serious adverse event related to the vaccination was reported in this study. Neither the combined formulation of DTPa and HBV vaccines nor the extemporaneous mixture increased the incidence or severity of adverse reactions compared with the separate administration of DTPa. This study shows the feasibility of a combined DTPa-HBV vaccine and the data support, in the interim, the mixing of DTPa and HBV vaccines which are tested in clinical trials for infant immunization.

Immunogenicity and reactogenicity of a combined DTPw-hepatitis B vaccine in Lithuanian infants.

UNLABELLED: A total of 120 healthy Lithuanian infants were enrolled in a double-blind, randomized trial to receive one of two lots of SmithKline Beecham Biologicals' combined diphtheria, tetanus, whole cell Bordatella pertussis hepatitis B (DTPw-HB) candidate vaccine administered according to a 0, 1.5, 3-month, primary immunization schedule (beginning at approximately 3-4 months of age). The immunogenicity (based on the antibody responses elicited by each of the four vaccine components) and the reactogenicity (based on documented solicited and unsolicited symptoms) of this candidate vaccine were evaluated. Of the 120 subjects enrolled, 100 were included in the analysis of immunogenicity. One month after the third vaccine dose, all infants had protective levels of antibodies against HBsAg and tetanus toxoid and all, except one infant, had protective levels of antibodies against the diphtheria toxoid (98.9%). At this time all subjects had responded to the B. pertussis component with antibody titres greater than or equal to the assay cut-off. Data collected for all enrolled infants were included in the analysis of reactogenicity. Most local symptoms were mild and occurred within the first 48 h following vaccination. Redness was the most frequently reported local symptom and irritability was the most frequently reported general symptom. One vaccine-related serious adverse event was reported (fever, diarrhea, vomiting and irritability). This event resolved within 20 h without any complications. CONCLUSION: The combined DTPw-HB vaccine was safe, well-tolerated and immunogenic for all four antigens when administered to a population of healthy infants beginning at 3-4 months of age.

Humoral immune response after hepatitis-B-vaccination: kinetics of anti-HBs antibodies and demonstration of HLA antigens.

Three injections monthly of 50 micrograms/ml hepatitis-B-vaccine (Hevac-B-Pasteur) and one booster injection after 12 months from the beginning of vaccination were given to 676 adult recipients. Anti-HBs was detected in 45.9 percent of persons one month after the first dose of vaccine, in 79.3 percent after the third dose and in 98.4 percent after the booster injection. A follow-up of 142 persons 3 years after the first dose of vaccine indicated that protective levels of anti-HBs were maintained in 95.1 per cent of all participants. HLA antigens were typed in 13 vaccine recipients with low anti-HBs titers (less than or equal to 10 ImU/ml) and in 26 recipients with high anti-HBs titers (greater than or equal to 20,000 ImU/ml). Significant differences of antigen frequency (p less than 0.05) were found for HLA A3 (decrease in high responders), and HLA DR7 (increase of in low, decrease in high responders). The results indicate genetic differences between high and low responding recipients of HBV vaccine.