Effect of change in sequence of administration of DTwP and Hepatitis B vaccines on perception of pain in infants: A randomized control trial

ObjectiveThis study was designed with objective to study pain response of infants to change in sequence of administration of Hepatitis B and DTwP vaccines.MethodsThis was a randomized parallel control trial. The study was carried out in the immunization clinic of the Department of Pediatrics, LLRM Medical College, Meerut. One hundred and thirty healthy term infants up to 4 months of age were injected either DTwP vaccine first or Hepatitis B vaccine first, followed one minute later by the other vaccine.ResultBaseline characteristics did not differ between the groups. The mean (SD) of AUC of MFCS and NIPS was significantly more in DF group as compared to HF group (for MFCS 25.5 ± 5.4 versus 22.5 ± 5.5, p < 0.01; for NIPS 31.77 ± 5.5 versus 27.64 ± 6.9, p < 0.01). Similarly mean (SD) of AUC of Heart rate and saturation of oxygen showed significant variation in DF group as compared to HF group (for heart rate 591.6 ± 55 versus 559.6 ± 49, p < 0.01; for SpO₂ 326.4 ± 12 versus 335 ± 8, p < 0.01).ConclusionThese results showed that infant experienced lesser pain when Hepatitis B was administered first than when DTwP vaccine was given first.     

Pertussis in infants under one year old: Risk markers and vaccination status—A case-control study

BackgroundPertussis is a contagious bacterial disease causing substantial health burden. Pertussis-related morbidity and mortality are highest in young infants. We investigated risk markers for pertussis and vaccination status in infants.MethodsReported pertussis cases under one year old during 1998–2011 in the Jerusalem district were matched to controls by birthdate and residence. Data sources included epidemiological investigations, health records and vaccination records (number and dates of DTP\DTaP doses scheduled at 2, 4, 6 months). Vaccine effectiveness was calculated by number of vaccine doses stratified by age group. Timeliness of vaccine doses was also evaluated.ResultsThe study population included 1268 infants under 1 year: 317 pertussis cases and 951 age-matched controls (mean age 3.95 ± 3, median 2.9 months). Low birthweight (<2500 g, 12.3% in cases vs. 6.3% in controls) and high birth order (4th and above) were found to be independent risk markers. Male gender and low socio-economic status were more frequent among cases. Some 40% of the cases (127/317) were hospitalized, most of them (111/127, 87.4%) were under 4 months (mean age 2.42 ± 2.05, median 1.8 months).The distribution of the number of pertussis vaccine doses 0, 1, 2 and 3 differed considerably being 42.2%, 32.7%, 15.6%, 9.5% vs. 13.7%, 41.9%, 22.9%, 21.5% among cases and controls (≥2 m), respectively. The overall vaccine effectiveness found was 72.9%, 76.1% and 84.4%, for the 1st, 2nd and 3rd doses of a pertussis vaccine. The infant's age at the first dose of pertussis vaccine was recorded with follow-up until age 18 months. Delay was more common among cases with a lower proportion vaccinated—78.9% at 18 months vs. 99% in controls.ConclusionsSpecific risk markers for pertussis in young infants were identified. Reported pertussis cases over age 2 months were significantly more likely to be unvaccinated and have delayed vaccinations. The vaccine effectiveness increased with the number of vaccine doses.     

Parents’ concerns about vaccine scheduling in Shanghai,China

BackgroundSeveral new vaccines have been introduced into China in recent years, but some parents in China have shown concerns about the scheduling of vaccinations for young infants. This study explores caregiver concerns about children receiving multiple vaccines during a single visit and about vaccine administration in infants <6 months, and assesses the degree to which these concerns are associated with ratings of the importance of different sources of vaccine information in Shanghai.MethodsCaregivers of children 8 months to 7 years presenting at immunization clinics in Shanghai completed a survey about vaccine co-administration and vaccine administration <6 months of age. Respondents provided ratings of information from different sources (Internet, family/friends, other parents) and trust in doctors. We analyzed vaccine concerns using linear regression analyses that included these information sources after adjusting for socioeconomic variables.ResultsAmong 618 caregivers, 64% were concerned about vaccine co-administration and 31% were concerned about vaccine administration to infants <6 months of age. Higher ratings of Internet as an important source of information were associated with greater concern about co-administration (β = 0.11, 95% CI: 0.00, 0.22) and concern about administration at <6 months of age (β = 0.17, 95% CI: 0.05, 0.28). Higher ratings given to information from other parents corresponded to 0.24 points greater concern about vaccine co-administration (95% CI: 0.04, 0.44). More trust in doctors and ratings of information from friends and family were not associated with vaccine concerns.ConclusionsCaregiver concerns about vaccine scheduling may limit China’s flexibility to add vaccines to its official immunization schedule. Reporting information about vaccine safety on the Internet and bringing groups of parents together to discuss vaccines might help to ameliorate concerns about vaccine scheduling.     

Immune response in infants after universal high-dose hepatitis B vaccination: A community-based study in Beijing,China

BackgroundVaccination of infants beginning at birth is recommended to prevent Hepatitis B virus (HBV) infection in China. Compared to 5 μg/dose vaccine administered in other regions in China, a three-dose HB recombinant yeast vaccine at 10 μg/dose has been administered for infants within 24 h after birth, 1 month and 6 months of age in Beijing since 2006. In a community-based retrospective cohort study, factors influencing immunologic vaccine response were evaluated.MethodsA total of 3670 infants who completed a 3-dose 10 μg recombinant HB vaccine regimen and born to hepatitis B antigen negative mothers were included. The effect on anti-HBs titers of maternal nutrient status, infants’ birth condition, growth factors, timeliness of vaccination, dosing interval and the interval until post-vaccination serologic testing (PVST) were evaluated.ResultsA total of 3666 infants with no markers of HBV infection were included in analysis. The mean anti-HB titers were 1767.17 mIU/ml. Only 16.9% of the infants completed their PVST within 30–59 days after the final dose of vaccination. Multivariate linear regression analysis showed that delay in PVST (β = −0.097, p < 0.0001) and maternal folic acid supplementation (β = 0.067, p = 0.002) were associated with log-transformed anti-HB titers. Also a trend toward significant association was observed between the calcium supplementation of infants and log-transformed anti-HBs titers (β = 0.062, p = 0.057). Longer interval between dose 2 and dose 3 was not observed to increase the anti-HB titers after cofactors adjustment.ConclusionsOur findings illustrate the importance of timing of PVST to avoid unnecessary revaccination. Multi-center large cohort studies should verify the effect and magnitude of folate and calcium supplementation on HB vaccine response.     

Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized,controlled phase III study in Indian infants

BackgroundRotavirus remains the leading cause of diarrhoea among children <5 years. We assessed immunogenic non-inferiority of a tetravalent bovine-human reassortant rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5.MethodsPhase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6–8, 10–12, and 14–16 weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above −10%. Each subject was evaluated for solicited adverse events 7 days and unsolicited & serious adverse events 28 days following each dose of vaccination.ResultsOf 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, −14.08% (95%CI: −20.4; −7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1 U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the −10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles.ConclusionBRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants.     

Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial

BackgroundThis study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children.MethodsIn this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2 + 1 doses at 3½–5–11 months or 6–8–11 months of age, 3 + 1 doses at ages 2½–3½–5–11 months. Children aged 2–10 years received 2 catch-up doses administered 2 months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2 + 1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1 month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7 days post-vaccination; serious adverse events (SAEs) throughout the study.Results754 infants and 404 children were enrolled. Post-primary vaccination, 98–100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48–77% for NHBA. Sufficiency of immune responses in infants receiving 2 + 1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95–99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination.ConclusionReduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage.FundingGlaxoSmithKline Biologicals SA.     

The effect of diarrheal disease on bivalent oral polio vaccine (bOPV) immune response in infants in Nepal

BackgroundA globally-coordinated phase out of all type 2 containing oral polio vaccine (OPV) is planned for April 2016 during which bivalent 1 + 3 OPV (bOPV) will replace trivalent OPV (tOPV) in routine immunization schedules and campaigns. Diarrhea impairs the immune response to tOPV, but the effect of diarrhea on bOPV is unknown.MethodsInfants aged 6 weeks to 11 months, who had received <3 doses of OPV and had mild-moderate diarrhea or no diarrhea, were recruited at five health facilities in Nepal. Neutralizing antibody titers to poliovirus types 1 and 3 were measured before and 28 days after bOPV administration. The effect of diarrhea and other factors on seroconversion or boosting in antibody titers to poliovirus was assessed by multivariable analysis.ResultsInfants with diarrhea, versus those without diarrhea, had reduced response for poliovirus types 1 (56% [87/156] vs 66% [109/164]) and 3 (34% [70/209] vs 52% [122/236]). After adjusting for other factors, infants with diarrhea had significantly reduced response for type 3 (odds ratio [OR] = 0.44, 95% CI 0.29–0.68), as did infants with >5 loose stools per day (OR = 0.36, 95% CI 0.21–0.62).ConclusionsDiarrhea reduced the immune response to bOPV. Provision of additional doses of polio vaccine is necessary to maintain high population immunity in areas with high prevalence of diarrheal disease.Clinical trial registryThis study is registered at clinicaltrials.gov as NCT01559636.     

Barriers to timely administration of birth dose vaccines in The Gambia,West Africa

ObjectiveAlthough vaccine coverage in infants in sub-Saharan Africa is high, this is estimated at the age of 6–12 months. There is little information on the timely administration of birth dose vaccines. The objective of this study was to assess the timing of birth dose vaccines (hepatitis B, BCG and oral polio) and reasons for delayed administration in The Gambia.MethodsWe used vaccination data from the Farafenni Health and Demographic Surveillance System (FHDSS) between 2004 and 2014. Coverage was calculated at birth (0–1 day), day 7, day 28, 6 months and 1 year of age. Logistic regression models were used to identify demographic and socio-economic variables associated with vaccination by day 7 in children born between 2011 and 2014.ResultsMost of the 10,851 children had received the first dose of hepatitis B virus (HBV) vaccine by the age of 6 months (93.1%). Nevertheless, only 1.1% of them were vaccinated at birth, 5.4% by day 7, and 58.4% by day 28. Vaccination by day 7 was associated with living in urban areas (West rural: adjusted OR (AOR) = 6.13, 95%CI: 3.20–11.75, east rural: AOR = 6.72, 95%CI: 3.66–12.33) and maternal education (senior-educations: AOR = 2.43, 95%CI: 1.17–5.06); and inversely associated with distance to vaccination delivery points (≧2 km: AOR = 0.41, 95%CI: 0.24–0.70), and Fula ethnicity (AOR = 0.60, 95%CI: 0.40–0.91).ConclusionVaccine coverage in The Gambia is high but infants are usually vaccinated after the neonatal period. Interventions to ensure the implementation of national vaccination policies are urgently needed.     

Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009–2010

BackgroundFollowing the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009–2010.MethodsWe telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009–2010 (n = 5365) in a separate study. Here we assessed preterm birth (<37 weeks), very preterm birth (<32 weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500 g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time.ResultsResults did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37 vs 6.28/100 births), very preterm births (5.30 vs 8.29/1000 births), LBW (4.19 vs 2.90/100 births), very LBW (4.54 vs 5.52/1000 births), small for gestational age (9.99 vs 9.24/1000 births), spontaneous abortion (7.10 vs 6.83/1000 pregnancies), stillbirths (7.10 vs 4.57/1000 pregnancies), and congenital anomalies (2.66 vs 2.43/100 births).ConclusionsAlthough constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009–2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV.     

The immunogenicity in healthy infants and efficiency to prevent mother to child transmission of Hepatitis B virus of a 10 μg recombinant yeast-derived Hepatitis B vaccine (Hep-KSC)

Background and AimsTo evaluate immunogenicity and efficacy of a 10 μg recombinant Saccharomyces cerevisiae-derived hepatitis B vaccine (Kangtai Biological Products Co. Ltd, Shenzhen, China) (Hep-KSC) in newborns.MethodsOverall 1197 infants born to mothers negative for HBV markers (NM group) and 534 born to HBsAg-positive mothers (PM Group) were enrolled. Infants in NM group were given 10 μg Hep-KSC, 10 μg Engerix-B or 5 μg Hep-KSC and those in PM group received 10 μg Hep-KSC or 10 μg Engerix-B at 0, 1 and 6 months, with an additional 200 IU HBIG at birth for the latter.ResultsFor NM Group, 10 μg Hep-KSC paralleled 10 μg Engerix-B but outperformed 5 μg Hep-KSC regarding seroprotective rate (95.06% vs 94.83% vs 89.67%, p = 0.0077) and anti-HBs geometric mean concentration (GMC) (798.87 mIU/ml vs 790.16 mIU/ml vs 242.04 mIU/ml, p < 0.0001) at 7 months. The proportion of infants with anti-HBs greater than 1000 mIU/ml was higher in 10 μg Hep-KSC than 5 μg Hep-KSC group (45.77% vs 11.93%, p < 0.0001) at 7 and 12 months. For PM Group, the HBsAg positivity rate in 10 μg Hep-KSC and 10 μg Engerix-B group was 1.60% and 4.27% at 7 months, respectively. In 10 μg Hep-KSC group, 93.61% and 91.29% achieved seroprotection at 7 and 12 months, respectively, and correspondingly 90.24% and 86.96% in 10 μg Engerix-B group. The anti-HBs GMC was comparable between 10 μg Hep-KSC and 10 μg Engerix-B group at 7 and 12 months (575.31 mIU/ml vs 559.64 mIU/ml; 265.79 mIU/ml vs 264.48 mIU/ml).Conclusions10 μg Hep-KSC might be appropriate for neonatal immunization with good immunogenicity and efficacy, especially for infants born to HBsAg-positive mothers.     

Effect of multiple,simultaneous vaccines on polio seroresponse and associated health outcomes

BackgroundAdministration of multiple simultaneous vaccines to infants, children, and military recruits is not uncommon. However, little research exists to examine associated serological and health effects, especially in adults.MethodWe retrospectively examined 416 paired serum specimens from U.S. military subjects who had received the inactivated polio vaccine (IPV) alone or in combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4 group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was present or absent.ResultsThe >4 group was associated with a higher proportion of polio seroconversions than the <3 group (95% vs. 58%, respectively, p < 0.01). Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded Tdap showed no difference between them (p > 0.1). However, the >4 subgroup that included Tdap had significantly more seroconversions than either the <3 subgroup that excluded Tdap or the >4 subgroup that excluded Tdap (p < 0.01). Overall, at least 98% of subjects were at or above the putative level of seroprotection both pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an analysis of 400 of the subjects in which clinic in- and outpatient encounters were counted over the course of 1 year following vaccinations, there was no significant difference between the 2 groups (p > 0.1).ConclusionA combination of >4 vaccines including IPV appeared to have an immunopotentiation effect on polio seroconversion, and Tdap in particular was a strong candidate for an important role. The dose of IPV we studied in our subjects, who already had a high level of seroprotection, acted as a booster. In addition, there appear to be no negative health consequences from receiving few versus more multiple simultaneous vaccinations.     

Tetanus,diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections

BackgroundTo protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36 weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2 months of age.MethodsThis retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2 months of age.ResultsInfants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2 months of age (RR, 0.91; 95% CI, 0.84–0.99), and the risk was 17% lower if vaccination was received between 27 and 36 weeks of pregnancy (RR, 0.83; 95% CI, 0.74–0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36 weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74–0.98).ConclusionsMaternal Tdap vaccination between 27 and 36 weeks of pregnancy was consistently protective against infant ARI in the first 2 months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.     

Safety,tolerability, and immunogenicity of 7-valent pneumococcal conjugate vaccine in older infants and young children in China who are naive to pneumococcal vaccination: Results of a phase 4 open-label trial

BackgroundThis postlicensure study was conducted to assess immunogenicity and safety of PCV7 catch-up regimens in previously unvaccinated older infants and young children in China.MethodsHealthy children 121 days to <72 months were grouped by age and immunized with 1 of 4 PCV7 dosing regimens. Serotype-specific IgG geometric mean concentrations (GMCs) and percentage of subjects with IgG ≥ 0.35 μg/mL were assessed before vaccination and 1 and 12 months postvaccination. The incidence of clinically important adverse events (AEs) and serious AEs (SAEs), AEs leading to study withdrawal, and protocol-related AEs were assessed throughout the study.ResultsPrevaccination serotype-specific GMCs were generally low in subjects <24 months; the majority of children 24 to <72 months had IgG concentrations ≥0.35 μg/mL. One month postvaccination, GMCs were similar across groups for the 7 PCV serotypes, ranging from 3.95 to 13.02 μg/mL; the highest antibody levels were observed for serotype 14. Regardless of dosing regimen, >90% of subjects had IgG ≥ 0.35 μg/mL for each PCV serotype. At 12-month follow-up, IgG GMCs ranged from 0.65 to 5.19, and all remained above prevaccination IgG GMC; >70% of subjects had IgG ≥ 0.35 μg/mL. Older children generally had the most robust immune response both at 1 month postvaccination and during 12-month follow-up. PCV7 was well tolerated. Pyrexia, which was mild to moderate in severity, was the most common AE. Two subjects reported SAEs (n = 4), and there was 1 study withdrawal; none of these were considered treatment related.ConclusionIn China, PCV7 catch-up vaccinations given to older infants and young children naive to pneumococcal vaccines resulted in a robust immune response to all serotypes; this response persisted after 1 year. PCV7 was well tolerated in Chinese infants and children.     

On birth single dose live attenuated OPV and BCG vaccination induces gut cathelicidin LL37 responses at 6 week of age: A natural experiment

In a cross sectional study, we show that infants who received single dose of live attenuated OPV and BCG vaccines within 48 h of birth, have higher excretion of human cathelicidin LL37 (p < 0.05) in stool at 6 wk of age. This response remained unchanged in multivariate analysis after adjusting for sex, mode of delivery, infant age, mother age birth weight and breast milk feeding pattern. This analysis also reveals that irrespective of vaccination, girl infants have higher human-beta-defencin2 (HBD2) and exclusively breastfed infants have higher total and anti-polio specific IgA to all three subtypes in stool (p < 0.05). However, vaccination induces anti-polio IgA responses only to infants who are exclusively breastfed. Thus on-birth live attenuated vaccination may provide non-specific beneficial effect against infections while exclusive breastfeeding enhance protection by boosting vaccine induced IgA. The result also suggests that in polio endemic area, exclusive breastfeeding may be sufficient for mucosal anti-polio responses during early infancy.     

Whooping cough surveillance in France in pediatric private practice in 2006–2015

BackgroundIncreasing incidence of whooping cough (pertussis) has been reported in many countries, attributed to a switch from whole-cell pertussis-containing vaccine (wPV) to acellular PV (aPV) and circulation of the pertactin non-producing Bordetella pertussis. The present study aimed to estimate the duration of immunity conferred by PVs in children in France with data from an ongoing pediatric ambulatory surveillance of pertussis.MethodsA total of 64 pediatricians throughout France enrolled children with suspected pertussis. A standardized data form was used to collect data on age sex, vaccination status, brand of wPV or aPV and source of infection. Confirmed cases were positive on culture and/or real-time Polymerase Chain Reaction (for B.-non-classified or B. pertussis or B. parapertussis) and/or pertussis serology.ResultsBetween October 2006 and December 2015, 149 cases of confirmed Bordetella infections were reported, 86 infected with B. pertussis and 55 B. non-classified. Fifteen children (10.1%) were not vaccinated, and 26 (17.4%) were partially vaccinated. The mean age was greater for children who received 4 doses of wPV (11.3 ± 2.2, p < 0.001) or a combination of wPV and aPV (10.5 ± 3.3, p < 0.001) than only aPV (7.2 ± 2.4 years). The mean duration of cough before a visit to a pediatrician was longer for children with wPV or a combination of wPV and aPV than only aPV (23.8 ± 10.1 and 25.0 ± 25.6 vs 13.6 ± 10.0 days).ConclusionDespite the use of a more sensitive diagnostic method and emergence of pertactin non producing B. pertussis, in France context, aPV-induced immunity still protects against pertussis; however, the mean duration of immunity is about 6 to 7 years, compared to 9 years for wPV vaccine, after the primary vaccination and one booster (3 + 1 doses).     

Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick injuries, and (iii) ensure better protection against pertussis as compared to vaccines containing acellular pertussis antigens. An approach to obtain a hexavalent vaccine might be reconstituting lyophilized polio vaccine (IPV-LYO) with liquid pentavalent vaccine just before intramuscular delivery. The potential limitations of this approach were investigated including thermostability of IPV as measured by D-antigen ELISA and rat potency, the compatibility of fluid and lyophilized IPV in combination with thimerosal and thimerosal containing hexavalent vaccine.The rat potency of polio type 3 in IPV-LYO was 2 to 3-fold lower than standardized on the D-antigen content, suggesting an alteration of the polio type 3 D-antigen particle by lyophilization. Type 1 and 2 had unaffected antigenicity/immunogenicity ratios. Alteration of type 3 D-antigen could be detected by showing reduced thermostability at 45 °C compared to type 3 in non-lyophilized liquid controls.Reconstituting IPV-LYO in the presence of thimerosal (TM) resulted in a fast temperature dependent loss of polio type 1-3 D-antigen. The presence of 0.005% TM reduced the D-antigen content by ∼20% (polio type 2/3) and ∼60% (polio type 1) in 6 h at 25 °C, which are WHO open vial policy conditions. At 37 °C, D-antigen was diminished even faster, suggesting that very fast, i.e., immediately after preparation, intramuscular delivery of the conceived hexavalent vaccine would not be a feasible option. Use of the TM-scavenger, l-cysteine, to bind TM (or mercury containing TM degradation products), resulted in a hexavalent vaccine mixture in which polio D-antigen was more stable.     

Effect of introduction of pentavalent vaccine as replacement for Diphtheria–Tetanus–Pertussis and Hepatitis B vaccines on vaccination uptake in a health facility in Nigeria

BackgroundThe introduction of a new vaccine into an immunization programme may affect the immunization system negatively or positively. The aim of this study is to determine the effect of the introduction of the pentavalent vaccine as replacement for DTP and Hepatitis B vaccines on timeliness, completion of the schedule and dropout rates among children attending a health facility.MethodologyThis was a retrospective cohort study which involved extracting immunization records of children attending the Institute of Child Health Child Welfare Clinic between June 2011 and May 2013. Pentavalent vaccine was introduced as a replacement for DTP and Hepatitis B vaccines in June 2012. The uptake, timeliness and dropout rates of different vaccines in the immunization schedule were determined for children who commenced immunization in the pre, peri and post introduction phases.ResultsA total of 1110 children were studied – 190, 410 and 510 who commenced vaccination in the pre, peri and post introduction phases of the pentavalent vaccine respectively. Uptake was significantly higher for all vaccines in the post introduction phase compared to pre and peri introduction phases (p < 0.001). Completion of the immunization schedule by 60.2% of the children who commenced vaccination in the post introduction phase was higher than the 31.6% and 41.7% for the pre and peri introduction phases respectively (p < 0.001). Significantly more visits were required to complete the schedule in the peri introduction phase compared to the pre and post introduction phases p < 0.001. Delay in receipt of the three doses of DTP/PENTA was significantly longer in the peri introduction phase compared to pre and post introduction phases.ConclusionThe introduction of pentavalent vaccine significantly improved uptake of vaccines and completion of the schedule but resulted in prolonged delay in receipt of vaccines during the introduction period.     

Effect of booster doses of poliovirus vaccine in previously vaccinated children,Clinical Trial Results 2013

BackgroundConsidering the current polio situation Pakistan needs vaccine combinations to reach maximum population level immunity. The trial assessed whether inactivated poliovirus vaccine (IPV) can be used to rapidly boost immunity among children in Pakistan.MethodsA five-arm randomized clinical trial was conducted among children (6–24 months, 5–6 years and 10–11 years). Children were randomized in four intervention arms as per the vaccines they received (bOPV, IPV, bOPV + vitamin A, and bOPV + IPV) and a control arm which did not receive any vaccine. Baseline seroprevalence of poliovirus antibodies and serological immune response 28 days after intervention were assessed.ResultsThe baseline seroprevalence was high for all serotypes and the three age groups [PV1: 97%, 100%, 96%, PV2: 86%, 100%, 99%, PV3: 83%, 95%, 87% for the three age groups respectively]. There was significantly higher rate of immune response observed in the study arms which included IPV (95–99%) compared with bOPV only arms (11–43%), [p < 0.001]; Vitamin A was not associated with improved immune response. Immune response rates in the IPV only arm and IPV + bOPV arm were similar [p > 0.5].ConclusionIPV has shown the ability to efficiently close existing immunity gaps in a vulnerable population of children in rural Pakistan.     

Pre-vaccination evolution of antibodies among infants 0, 3 and 6 months of age: A longitudinal analysis of measles,enterovirus 71 and coxsackievirus 16

BackgroundDue to waning levels of maternal antibodies (measles; enterovirus 71, EV71; and coxsackievirus A16, CoxA16), some infants may lose protection against infection prior to vaccination. Using a longitudinal design, we examine how maternal antibody levels evolve over time in infants prior to vaccination.MethodsIn 2013–2014, we collected sera at ages 0, 3 and 6 months from infants. We assayed for levels of measles IgG antibody (717, 233 and 75 sample sera tested at months 0, 3 and 6, respectively), and neutralizing antibodies for EV71 and CoxA16 (225, 217, and 72). Demographic and health information were collected, and a linear mixed model (LMM) was used to describe antibody levels over time.ResultsPre-vaccination monotonic antibody decreases were observed for measles (1410, 195 and 22 mIU/ml, p < 0.001), EV71 (1:19.9, 6.3 and 4.5, p < 0.001) and CoxA16 (1:16.3, 5.9, and 4.5, p < 0.001). At 6 months of age, only 2.7% (95%CI, 0.6–8.3), 6.8% (95%CI, 2.7–14.4) and 5.6% (95%CI, 1.9–12.7) of infants were antibody positive for measles, EV71 and CoxA16, respectively. LMM findings indicated that infants with higher antibody titers at birth experienced a greater loss of antibody level. An infection rate of 1.3% (95%CI, 0.1–6.1) was reported for both EV71 and CoxA16.ConclusionsFurther modifications of vaccination strategies for measles, earlier vaccination for EV71 infection, and deployment of a CoxA16 vaccine need to be considered to limit infection among the very young.