Global variations in immunisation strategies against pertussis in infancy

The efficacy of a whole cell pertussis vaccine and fimbriae against Bordetella pertussis and Bordetella parapertussis infections in a respiratory mouse model

Hepatitis B virus (HBV) is endemic in the Kingdom of Saudi Arabia. To prevent the chronic carriage of HBV in Saudi children, hepatitis B vaccine was added as the seventh immunogen in the expanded program on immunization (EPI). In the first year, the coverage of the first dose and third dose of HB vaccine was 90% and 73%, respectively. In a survey of 637 children, 603 (95%) were positive for antibody to hepatitis surface antigen (anti-HBs) without concomintant antibody to hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (HBsAg). A total of 592 (93%) with anti-HBs titer of > 10 IU/L were considered as responders to the vaccine. The majority (60%) of these responders had titers > 100 IU/L. Only one (0.3%) non-responder was positive for anti-HBc alone. Using historical control, the protective efficacy was estimated as 99%. Neither the gender of the recipient, schedule of the vaccination, nor the sourve of vaccine influenced the response to the vaccine. The successful integration of the HB vaccine into the EPI was due to the effectiveness of the EPI and the efficient primary health care system in Saudi Arabia.

The safety and immunogenicity of two formulations of an acellular pertussis vaccine as a booster at 17 to 19 months of age were assessed in children immunized at 2, 4 and 6 months of age with acellular or whole cell pertussis vaccine. In Study I 86 children primed with a five-component acellular vaccine combined with diphtheria and tetanus toxoids or with a whole cell pertussis-diphtheria-tetanus vaccine were boosted with the same vaccine. Local reactions (64% vs. 93%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) and systemic reactions (68% vs. 97%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) were less common after the fourth dose of acellular vaccine than after the fourth dose of whole cell vaccine. In Study II 96 children primed with either an acellular or whole cell pertussis vaccine were boosted with an acellular vaccine. Local adverse reactions after booster immunization with acellular vaccine were more common in children primed with acellular vaccine than those primed with whole cell vaccine (68% vs. 33%; relative risk, 2.1; 95% confidence interval, 1.3 to 3.3). Antibody response to pertussis toxin, filamentous hemagglutinin and fimbriae were higher before and 1 month after the booster dose in children primed with the acellular vaccine. We conclude that the acellular pertussis vaccine is safe and immunogenic when used for the booster dose in children primed with either whole cell or acellular vaccine but is associated with local reactions.

Vaccination is the most effective way of preventing pertussis disease. Turkey commenced a routine infant immunization program using whole cell (wP) pertussis vaccine in 1968. Immunization accelerated in 1985 after participation of Turkey in the Expanded Programme on Immunization initiated by the World Health Organization. Acellular vaccine (aP) replaced wP in 2008 and a booster was added to age 6 in 2010. The immunization programme was successful in reducing the morbidity rate from 20.58 per 100.000 in 1970 to the lowest level of 0.01 per 100.000 in 2009. However, reduction of vaccine-induced protection and reduced natural boosting of circulating Bordetella pertussis are likely to increase the susceptibility of the population. As a result, morbidity rate increased from 0.09 per 100.000 to 0.41 per 100.000 in 2015 compared to the previous year. The aim of this epidemiological study was to determine the seroprevalence of pertussis toxin (PT) antibodies among healthy people and its association with various social determinants in Manisa province in Turkey, 6 years after aP replaced wP vaccine. The study was conducted as a cross-sectional study with a sample of 1250 people that was randomly selected from the over 2 years of age population in Manisa in 2014. Seroprevalence of PT antibody was determined as the dependent variable of the study. Independent variables of the study were; gender, age, migration in the last 5 years, occupational class, perceived income, house ownership, number of people per room, annually per capita equivalent income. The presence of anti-PT IgG was detected by quantitatively using a commercially available ELISA kit. The antibody levels were categorized into groups according to pertussis infection or vaccination immune response status. The groups consisted of undetectable (< 5 IU/ml), mid-range (5-< 62.5 IU/ml: more than one year previously), high (62.5-< 125: with in 12 months) and very high (≥ 125 IU/ml: with in 6 months) antibody levels. The test results with ≥ 5 IU/ml were defined as seropositive. Level > 100 IU/ml detected among adolescent and adult participants indicated acute or recently recovered pertussis infection. Chi-square test was used to evaluate association between social determinants and pertussis seropositivity. The seroprevalence of the whole study population was 58.1% (95% CI 55.32-60.79) and no association was found with any of the social determinants. The highest seroprevalence was found among 2-9 age group (68.3%) followed by 70-79 age group (63.5%). The lowest seroprevalence was found among 20-29 age group (50.9%) followed by 10-19 age group (51.6%). When seropositivity levels according to ages were compared, it was found that there was a decrease one year after the first vaccination at 2nd, 4th and 6th months and the booster at the 6th year, with a lowest rate (19%) in 11 year-old. The highest seropositivity (77.3%) with a level of >100 IU/ml (13.6%) were detected at age 15 among all adolescent and adult participants. Adding an adolescent booster to immunization schedule and recommendation of vaccine to elderly people should be considered to reduce the incidence of pertussis disease in Turkey.

More than 2 billion people worldwide have been exposed to hepatitis B virus (HBV). To prevent these infections, Senegal and Cameroon integrated the HBV vaccine into their Expanded Program on Immunization (EPI) in 2005, as did the Central African Republic (CAR) in 2008. We evaluated the prevalence of HBV exposure and infection after the integration of the HBV vaccine in the EPI. An observational cross-sectional study was conducted among the hospitalized children 3 months to 6 years of age in Cameroon, CAR and Senegal. Plasma was collected for the detection of anti-HBc, anti-HBs and hepatitis B surface antigen in children with anti-HBc and anti-HBs. Between April 2009 and May 2010, 1783 children were enrolled, 19.4% of whom were anti-HBc positive. The percentage of children with anti-HBc was 44.4% among the children younger than 6 months, decreasing after 6 months to reach 18.8% at 12 months. This decline was followed by a rapid increase in anti-HBc positivity rate in CAR observed as early as 12 months of age compared with Cameroon and Senegal, where the anti-HBc increased between 18 and 36 months of age, respectively. The prevalence of hepatitis B surface antigen-positive children was significantly higher in CAR than that in Cameroon and Senegal (5.1% versus 0.7% and 0.2%; P < 0.001). Socioeconomic level, age and country were factors associated with the presence of anti-HBc. Passive transfer of anti-HBc maternal antibodies versus HBV exposure could be differentiated as early as 12 months of age. The low prevalence of anti-HBc and hepatitis B surface antigen among children born after the integration of HBV vaccine in the EPI in Cameroon and Senegal suggests a positive impact of HBV vaccination.

Current acellular pertussis vaccines have various shortcomings, which may contribute to their suboptimal efficacy and waning immunity in vaccinated populations. This calls for the development of new pertussis vaccines capable of inducing long-lived protective immunity. Immunization with whole cell pertussis vaccines and natural infection with Bordetella pertussis induce distinct and more protective immune responses when compared with immunization with acellular pertussis vaccines. Therefore, the immune responses induced with whole cell vaccine or after infection can be used as a benchmark for the development of third-generation vaccines against pertussis. Here, we review the literature on the immunology of B. pertussis infection and vaccination and discuss the lessons learned that will help in the design of improved pertussis vaccines.

Pertussis vaccination in Chinese children with increasing reported pertussis cases

Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.

Practice in Developing Countries

BackgroundAdverse cardiorespiratory events including apnea, bradycardia, and desaturations have been described following administration of the first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B (DTP-IPV-Hib) immunization to preterm infants. The effect of the recent substitution of acellular pertussis vaccine for whole cell pertussis vaccine on the frequency of these events requires further study.MethodsInfants with gestational age of ≤ 32 weeks who received their first DTP-IPV-Hib immunization prior to discharge from two Edmonton Neonatal Intensive Care Units January 1, 1996 to November 30, 2000 were eligible for the study. Each immunized infant was matched by gestational age to one control infant. The number of episodes of apnea, bradycardia, and/or desaturations (ABD) and the treatment required for these episodes in the 72 hours prior to and 72 hours post-immunization (for the immunized cohort) or at the same post-natal age (for controls) was recorded.ResultsThirty-four infants who received DTP-IPV-Hib with whole cell pertussis vaccine, 90 infants who received DTP-IPV-Hib with acellular pertussis vaccine, and 124 control infants were entered in the study. Fifty-six immunized infants (45.1%) and 36 control infants (29.0%) had a resurgence of or increased ABD in the 72 hours post-immunization in the immunized infants and at the same post-natal age in the controls with an adjusted odds ratio for immunized infants of 2.41 (95% CI 1.29,4.51) as compared to control infants. The incidence of an increase in adverse cardiorespiratory events post-immunization was the same in infants receiving whole cell or acellular pertussis vaccine (44.1% versus 45.6%). Eighteen immunized infants (14.5%) and 51 control infants (41.1%) had a reduction in ABD in the 72 hours post- immunization or at the equivalent postnatal age in controls for an odds ratio of 0.175 (95%CI 0.08, 0.39). The need for therapy of ABD in the immunized infants was not statistically different from the control infants. Lower weight at the time of immunization was a risk factor for a resurgence of or increased ABD post-immunization. Birth weight, gestational age, postnatal age or sex were not risk factors.ConclusionThere is an increase in adverse cardiorespiratory events following the first dose of DTP-IPV-Hib in preterm infants. Lower current weight was identified as a risk factor, with the risk being equivalent for whole cell versus acellular pertussis vaccine. Although most of these events are of limited clinical significance, cardiorespiratory monitoring of infants who are sufficiently preterm that they are receiving their first immunization prior to hospital discharge should be considered for 72 hours post-immunization.

BackgroundThe Expanded Programme on Immunization (EPI) is the most successful global childhood programme in reducing mortality and morbidity from vaccine-preventable diseases. Introducing the RTS, S/AS01 malaria vaccine into the routine health system added additional vaccination visits at 24 months. This study determined the factors contributing to compliance with EPI, including RTS, S/AS01 malaria vaccine schedules in the Central Tongu District of Ghana.MethodsA matched case–control study (1:1) was undertaken between December 2021 and February 2022 among caregivers of children aged 24 to 40 months. Mantel-Haenzel odds ratio and conditional logistic regression analysis were used to determine the strength of association between the level of compliance and independent variables.ResultsOf the 220 caregivers,110 were cases, and 110 were controls. Good knowledge about vaccines and vaccination schedules among caregivers was 62% (n = 139). Caregivers who earned income 46% (ORMH 0.54, 95% CI 0.29–1.00, p = 0.047); had immunization information 98% (ORMH 0.02, 95% CI 0.00–0.12, p = 0.001); with no obstacles accessing immunization services 98% (ORMH 0.02, 95% CI 0.00–0.12, p < 0.001) and had good knowledge about immunization schedules 70% (ORMH 0.30, 95% CI 0.15–0.61, p < 0.001) were more likely to comply with childhood vaccination. Knowledge of (EPI) services, including RTS, S/AS01 malaria vaccine, was associated with high compliance to overall immunization services and schedules 78% (AOR 0.22, 95% CI 0.06–0.78, p = 0.019).ConclusionNon-compliance with recommended EPI vaccinations, including RTS,S/AS01, was largely due to socio-economic factors, having information and knowledge about vaccines, immunization schedules, and access to immunization services. Healthcare providers can improve immunization coverage by emphasizing education on vaccines and vaccine schedules, using technologies and making services accessible in Ghana.

BackgroundIn addition to mass distribution campaigns, the World Health Organization (WHO) recommends the continuous distribution of long-lasting insecticidal nets (LLINs) to all pregnant women attending antenatal care (ANC) and all infants attending the Expanded Programme on Immunization (EPI) services in countries implementing mosquito nets for malaria control. Countries report LLIN distribution data to the WHO annually. For this analysis, these data were used to assess policy and practice in implementing these recommendations and to compare the numbers of LLINs available through ANC and EPI services with the numbers of women and children attending these services.MethodsFor each reporting country in sub-Saharan Africa, the presence of a reported policy for LLIN distribution through ANC and EPI was reviewed. Prior to inclusion in the analysis the completeness of data was assessed in terms of the numbers of LLINs distributed through all channels (campaigns, EPI, ANC, other). For each country with adequate data, the numbers of LLINs reportedly distributed by national programmes to ANC was compared to the number of women reportedly attending ANC at least once; the ratio between these two numbers was used as an indicator of LLIN availability at ANC services. The same calculations were repeated for LLINs distributed through EPI to produce the corresponding LLIN availability through this distribution channel.ResultsAmong 48 malaria-endemic countries in Africa, 33 malaria programmes reported adopting policies of ANC-based continuous distribution of LLINs, and 25 reported adopting policies of EPI-based distribution. Over a 3-year period through 2012, distribution through ANC accounted for 9 % of LLINs distributed, and LLINs distributed through EPI accounted for 4 %. The LLIN availability ratios achieved were 55 % through ANC and 34 % through EPI. For 38 country programmes reporting on LLIN distribution, data to calculate LLIN availability through ANC and EPI was available for 17 and 16, respectively.ConclusionsThese continuous LLIN distribution channels appear to be under-utilized, especially EPI-based distribution. However, quality data from more countries are needed for consistent and reliable programme performance monitoring. A greater focus on routine data collection, monitoring and reporting on LLINs distributed through both ANC and EPI can provide insight into both strengths and weaknesses of continuous distribution, and improve the effectiveness of these delivery channels.

The World Health Organization (WHO) recommends the discontinuation of oral poliovirus vaccine after eradication of wild poliovirus. Studies assessing inactivated poliovirus vaccine (IPV) immunogenicity in tropical countries, using the WHO Expanded Programme on Immunization (EPI) schedule, have been limited. We conducted a randomized clinical trial in Ponce, Puerto Rico. Infants were assigned to 1 of 2 study arms: those in the EPI arm received IPV at 6, 10, and 14 weeks of age, and those in the US arm received IPV at 2, 4, and 6 months of age. Neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested on serum specimens obtained before administration of the first dose of IPV and 28-45 days after administration of the last dose of IPV. Seroconversion rates for the EPI (n=225) and US (n=230) arms, respectively, were 85.8% and 99.6% for poliovirus type 1 (P<.001), 86.2% and 100% for poliovirus type 2 (P<.001), and 96.9% and 99.1% for poliovirus type 3 (P=.08). Seroconversion rates were lower among infants in the EPI arm who had high maternal antibody levels for all 3 poliovirus types (P<.001). The EPI schedule resulted in lower seroconversion rates for poliovirus types 1 and 2. These results are relevant for tropical countries planning to use IPV in a posteradication environment.

BackgroundAcellular pertussis (aP) vaccines replaced whole cell pertussis (wP) vaccines for the recommended childhood primary series in the United States in 1997. As women primed with aP vaccines in childhood enter reproductive age, it is unknown how maternal aP-priming will impact pertussis protection conferred to infants through Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination during pregnancy.MethodsInfants born at term to women who had been vaccinated with Tdap at 27-36 weeks’ gestation and ≥ 14 days prior to delivery were included. Geometric mean concentrations (GMC) of pertussis-specific antibodies (measured in IU/mL) in umbilical cord blood of infants born to women born after 1997 (aP vaccine primed) were compared with those born to women born before 1992 (wP vaccine primed).Results253 and 506 neonates born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger (19.3 v. 24.5 years), more likely to be Hispanic or non-Hispanic black and to have infants with lower birthweight (3264 v. 3392 grams, p< 0.01 for all). Gestation at Tdap receipt, gestational age at delivery, and interval between Tdap administration and delivery were not statistically different.Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were significantly lower among neonates born to aP-primed versus wP-primed mothers (PT: 17.3 v. 36.4, GMC ratio 0.475 (0.408 – 0.552) (Figure); FHA: 104.6 v. 121.4, GMC ratio 0.861 (0.776 – 0.958)). No significant differences were observed between the aP and wP-primed groups for anti- fimbriae (FIM) or anti-pertactin (PRN) antibodies ((FIM: 469.6 v. 577.2, GMC ratio 0.81 (CI 0.65 – 1.01); PRN 338.8 v. 292.6, GMC ratio 1.16 (CI 0.99 – 1.35)).Figure. Distribution of anti-PT antibody levels in cord blood in infants born to women who were primed with whole cell pertussis compared with acellular pertussis vaccines in childhood.*ConclusionThe type of pertussis vaccine a woman received during childhood significantly impacted her response to Tdap vaccination during pregnancy; the largest reduction was in anti-PT antibodies thought to be most important in preventing severe infection in infants. These findings suggest that infants born to aP-primed women who received Tdap during pregnancy may have less passive protection against pertussis during the first months of life than those born to wP-primed women.DisclosuresAll Authors: No reported disclosures

Vaccination Inequities in India: Current Status and the Way Forward