Universal Infant Immunization Research Articles

Australian vaccine preventable disease epidemiological review series: Hepatitis B, 2000-2019.

Hepatitis B vaccination was nationally funded for adolescents in 1996, with inclusion of universal infant immunisation under the National Immunisation Program (NIP) in May 2000. This study describes hepatitis B epidemiology in Australia in the two decades since 2000. This article analyses newly-acquired (within the prior 24 months) and unspecified (all other) hepatitis B notifications (2000-2019) from the National Notifiable Diseases Surveillance System; acute hepatitis B hospitalisations (2001-2019) from the National Hospital Morbidity Database; and acute (2000-2019) and chronic (2006-2019) hepatitis B deaths from the Australian Bureau of Statistics and Australian Coordinating Registry. Rates over the reporting period were described overall, and by age group, sex, and Aboriginal and Torres Strait Islander status (Aboriginal and/or Torres Strait Islander versus other [neither Aboriginal nor Torres Strait Islander, unknown or not stated]). Trend analyses were performed using Poisson or negative binomial regression. Additional analyses were performed for the cohort born after May 2000. The annual all-age notification rate per 100,000 per year declined (p < 0.001) from 2.13 in 2000 to 0.65 in 2019 for newly-acquired hepatitis B and from 38.3 to 22.3 for unspecified hepatitis B (likely to predominantly represent chronic hepatitis B). Newly-acquired and unspecified hepatitis B notification rates were lowest among children aged < 15 years. The most substantial reductions in notification rates of newly-acquired hepatitis B were among adolescents aged 15-19 years and young adults aged 20-24 and 25-29 years (respectively 17-, 11-, and 7-fold); these age groups also recorded the most substantial reductions in unspecified hepatitis B notifications (respectively 5-, 3.5-, and 2-fold). Newly-acquired hepatitis B notification and acute hepatitis B mortality rates were two- to threefold higher in males than females. The all-age newly-acquired hepatitis B notification rate in Aboriginal and Torres Strait Islander people decreased twofold between 2000 and 2019, but remained threefold higher than in other people. Acute hepatitis B hospitalisations also declined over the study period (p < 0.001) and followed similar patterns. There were no acute or chronic hepatitis B deaths among people born after May 2000; this cohort featured 52 newly-acquired and 887 unspecified hepatitis B notifications. Due to lack of data on country of birth (and hence eligibility for infant vaccination under the NIP or overseas programs), vaccination status and likely transmission routes, we were unable to assess factors contributing to these potentially preventable infections. Adolescent and infant immunisation under the NIP has led to significant reductions in notification rates of newly-acquired hepatitis B, and in acute hepatitis B hospitalisation rates, both overall and in Aboriginal and Torres Strait Islander people. Unspecified hepatitis B notification rates have also greatly decreased in children and young adults, likely largely due to the impact of overseas infant immunisation programs on prevalence in child and adolescent migrants. Work to improve completeness of variables within national datasets is crucial, along with enhanced surveillance of both newly-acquired and unspecified hepatitis B cases to investigate transmission routes, vaccination status and factors contributing to acquisition of hepatitis B, in order to optimise the impact of immunisation programs and ensure linkage with care.

Universal infant immunisation against respiratory syncytial virus and European inequalities: the pandemics lesson has not been learnt.

Universal infant immunisation against respiratory syncytial virus and European inequalities: the pandemics lesson has not been learnt.

Hepatitis B.

Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.

Asymptomatic hepatitis B carriers who were vaccinated at birth.

The long-term persistence of immunity following universal infant immunization against hepatitis B virus (HBV) and the need for a subsequent booster dose in adolescence remain under debate. With data derived from Long'an County, Guangxi, China, we reported previously that the prevalence of hepatitis B surface antigen (HBsAg) among adults born from 1987 to 1993 increases with age, although these individuals had received a first dose of the vaccine within 24 hours of birth. Here, we sought the source of transmission by comparison of genotypes among their family members using phylogenetic analysis of complete HBV S gene sequences. For comparison, we screened 2199 vaccinated individuals aged 5 to 17 in Cang Wu County and 1592 vaccinated individuals aged 3 to 7 in Ling Shan County in Guangxi for HBsAg carriers and investigate their family members. In total, 50 asymptomatic HBsAg carriers who were vaccinated at birth and 152 family members were analyzed. The results showed that 25% (95% CI: 6.0-44.0) of the HBsAg-positive children had not acquired their HBV infection from their mothers. This phenomenon showed a trend that increases with age. Antibody escape mutations were detected in 22.9% (95% CI: 11.0-34.8) of the isolates. In conclusion, a booster dose may be necessary for adolescence who were vaccinated at birth in highly endemic countries.

Occult hepatitis B virus and surface antigen mutant infection in healthy vaccinated cohorts and children with various forms of hepatitis and multiple transfusions

Despite the success of universal infant immunization initiated in Taiwan in 1984, occult hepatitis B virus infection (OBI) and circulating surface antigen mutants remain potential obstacles for eventual eradication of HBV infection. From 3299 apparently healthy, neonatally-vaccinated subjects (<30 years of age ) enrolled during 2014 serosurvey, we recruited all HBsAg-positive (n=17), all HBsAg-negative but anti-HBc-positive (n=132) and randomly selected HBsAg-negative and anti-HBc-negative subjects (n=411). These recruited subjects and 81 HBsAg-negative children with various forms of hepatitis and multiple transfusions were analysed for serum HBV DNA. In healthy, HBsAg-negative subjects, OBI frequency was higher in anti-HBc-positive than anti-HBc-negative individuals (8/90[8.9%] vs 8/301[2.7%], P=0.0192) aged <18-years, but was not different between anti-HBc-positive and anti-HBc-negative individuals (0/11[0%] vs 3/110[2.7%], P>0.05) aged 18 to 30 years. OBI occurred more frequently in children of HBsAg-positive mothers than in children of HBsAg-negative mothers (10/101 [9.9%] vs 1/75 [1.3%], P=0.025). The prevalence of surface 'a' determinant (aa110-160) mutants was 13.3% (2/15) in OBI subjects compared to 36.4% (4/11) in HBsAg-positive subjects (P>0.05). OBI was found in 30% (3/10) of serologic 'non-A to E' viral hepatitis, 14.3% (3/21) of chronic hepatitis C and 2.0% (1/50) of multitransfused, thalassemic children. In this highly immunized population, surface antigen mutant infection is uncommon and has low contribution to OBI development. HBsAg screening plus highly sensitive HBV DNA assays are needed for assurance of blood supply safety. Multiple transfusions from HBsAg-negative blood donors rarely result in persistent HBV infection. HBV might be related to some of serologic 'non-A to E' viral hepatitis.

Where we are in the fight against Hepatitis B Infection; Trends in Hepatitis B virus seroprevalence in Black Sea Region of Turkey

To determine new strategies for complete coverage of hepatitis B virus (HBV) vaccination, every country needs to take into concern factors of infection transmission in its own region. The aim of this study was to investigate the seroprevalence of hepatitis B among all age groups in northern Turkey using HBsAg and anti-HBs serological markers. The laboratory records of a total of 101648 patients of all ages attending a tertiary level hospital in Samsun, a Black Sea coastal city, between January 2014 and May 2016 were evaluated retrospectively. HBsAg and anti-HBs seropositivity was found to be 4% and 38.3%, respectively. There was a significant difference between HBsAg (χ2 = 209.08; P = 0.00), anti-HBs (χ2 = 124.12; P = 0.00) seropositivity, and immunization status. Although we found a statically difference between men and women (χ2 = 32.2 P = 0.00) for HBsAg seropositivity, there was no significant difference for anti-HBs (P = 0.22). In 1998, the universal infant immunization program changed the HBV epidemiology in Turkey, and resulted in an apparent trend towards reduced disease levels. However, prevalence of HBV infection is still high in adolescent and young adults. Therefore, a catch-up immunization program, education, and follow-up policy for these groups, in addition to routine infant immunization, will decrease the HBV infection rate, reducing morbidity and mortality rates, and will help to reduce hepatitis B transmission in Turkey.

Chronologic changes in serum hepatitis B virus DNA, genotypes, surface antigen mutants and reverse transcriptase mutants during 25-year nationwide immunization in Taiwan.

We investigated breakthrough infection and hepatitis B virus (HBV) genetic changes in immunized subjects after 25years of a universal infant immunization. Specifically, serum HBV DNA, genotypes, surface antigen mutants and nucleoside analog-resistant (NAr) mutants were assessed in 2853 subjects (<25years old) surveyed in 2009, and these data were compared with the data from previous serosurveys. A comparison across different age-stratified groups using the 2009 data revealed a significant increase in the seropositive rate of anti-HBc (5.51% vs 12.38%, P=.001) and HBV DNA (1.13% vs 3.96%, P=.007) between those 17-22 and 23-24years of age, possibly due to selective infant immunization in 1984-1986. Well-characterized NAr mutants, potential NAr mutants and surface "a" determinant mutants were detected in none, 15 (45.5%) and nine (27.3%) of 33 HBV DNA-positive subjects, respectively. Of 15 immunized, HBV DNA-positive young adults (18-24years), three (20%) carried "a" determinant mutants. Amongst 1176 HBsAg-negative subjects evaluated for occult HBV infection, those seropositive for anti-HBc had a higher seropositive rate for HBV DNA (10/110, 9.1% vs 7/1066, 0.66%; P<.001) and "a" determinant mutants (4/110, 3.6% vs 0/1066; P<.001) than those seronegative for anti-HBc. Overall, the HBsAg-positive subjects in six serosurveys showed no significant increase in genotype C frequency in the comparison between the vaccinated and unvaccinated cohorts (25/98, 25.5% versus 14/79, 17.7%, P=.188). Over the 25-year programme, there was no increase in the prevalence of genotype C in HBsAg carriers and no increase in breakthrough HBV infection or surface mutant prevalence beyond adolescence. Nucleic acid amplification should still be considered the primary screening method for occult hepatitis B detection in high-risk recipients.

Epidemiology of hepatitis B infection in Finland: Implications for immunisation policy

ObjectivesWe describe the current epidemiology of acute and chronic hepatitis B infections in Finland. We estimate the total incidence of chronic hepatitis B following from the current incidence of acute infections and the influx of chronic carriers of hepatitis B associated with net immigration. We evaluate the incidence of hepatitis B infections preventable by a universal vaccination programme among infants. MethodsWe analysed hepatitis B cases reported to the National Infectious Disease Register during 2004–2012 and used pre-developed methods to adjust for acute asymptomatic infections. We estimated the projected incidence of chronic infection by applying age-specific risks of chronic infection to the estimated incidence of acute infection. We estimated the influx of chronic carriers associated with immigration by utilising data on immigration during 2004–2012 and the WHO regional estimates of carriage prevalence. ResultsThe estimated incidence of acute hepatitis B infection in Finland, adjusted for asymptomatic infections, was 1.67 per 100,000 per year (95% Crl 1.43–1.94) which is 4.2-fold to the register-based incidence. The estimated lifetime risks of acute and chronic hepatitis B infections were 0.13% and 0.01%, respectively. We estimated that annually seven new chronic infections would result from infections acquired in Finland. These new chronic infections accounted for 1.2% of the total incidence of chronic infections. We estimated that eventually three chronic infections per year would be potentially preventable by a universal infant vaccination programme. ConclusionsPartly due to the fact that hepatitis B infections in neonates and in children are rare, a very limited number of chronic hepatitis B infections resulted from infection acquired within the country. A vast majority of chronic hepatitis B infections occurred among foreign-born persons and were therefore not preventable by a universal infant immunisation programme in Finland. Even with a targeted immunisation programme, the incidence of hepatitis B infection has remained low.

Rates of pneumonia among children and adults with chronic medical conditions in Germany.

BackgroundThe objective of this study is to evaluate rates of all-cause pneumonia among “at-risk” and “high-risk” children and adults in Germany—in comparison with age-stratified healthy counterparts—during the period following the 2006 recommendation for universal immunization of infants with pneumococcal conjugate vaccine.MethodsRetrospective cohort design and healthcare claims information for 3.4 M persons in Germany (2009–2012) were employed. Study population was stratified by age and risk profile (healthy, “at-risk” [with chronic medical conditions], and “high-risk” [immunocompromised]). At-risk and high-risk conditions, as well as episodes of all-cause pneumonia, were identified via diagnosis, procedure, and drug codes.Results and discussionRates of all-cause pneumonia were 1.7 (95 % CI 1.7-1.8) to 2.5 (2.4-2.5) times higher among children and adults with at-risk conditions versus healthy counterparts, and 1.8 (1.8-1.9) to 4.1 (4.0-4.2) times higher among children and adults with high-risk conditions. Rates of all-cause pneumonia among at-risk persons increased in a graded and monotonic fashion with increasing numbers of conditions (i.e., risk stacking).ConclusionsAn increased risk for all-cause pneumonia in German children and adults with a spectrum of medical conditions persists in the era of widespread pneumococcal vaccination, and pneumonia risk in persons with ≥2 at-risk conditions is comparable or higher than those with high-risk conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1162-y) contains supplementary material, which is available to authorized users.

Universal infant immunization and occult hepatitis B virus infection in children and adolescents: a population-based study.

To determine whether universal infant immunization affects occult hepatitis B virus (HBV) infection (OBI), serum samples from hepatitis B surface antigen (HBsAg)-negative subjects <18 years enrolled during six sequential seroepidemiological surveys conducted between 1984 (just before universal infant immunization) and 2009 were analyzed. Study subjects were divided into unvaccinated cohorts (born before 1984) and vaccinated cohorts (born after 1984). HBV-DNA positivity was determined by positivity of nested polymerase chain reaction in at least two of three regions (pre-S, S, and pre-core/core genes). OBI frequency was lower in vaccinated than unvaccinated antibody to hepatitis B core antigen (anti-HBc)-negative subjects (0 of 392 [0%] vs. 4 of 218 [1.8%]; P = 0.007), tended to be higher in vaccinated than unvaccinated anti-HBc-positive subjects (16 of 334 [4.8%] vs. 3 of 181 [1.7%]; P = 0.072), and was higher in vaccinated than unvaccinated subjects seropositive for both antibody to hepatitis B surface antigen (anti-HBs) and anti-HBc (13 of 233 [5.6%] vs. 3 of 170 [1.8%]; P = 0.025). By using known anti-HBc seropositivity rate in children in our serosurveys, the estimated OBI frequency per 10(4) HBsAg-negative subjects declined from 160.7 in unvaccinated cohorts to 11.5 in vaccinated cohorts. In vaccinated cohorts, OBI frequency was higher in anti-HBc-positive subjects than in anti-HBc-negative subjects (16 of 334 [4.8%] vs. 0 of 392 [0%]; P < 0.001). Subjects with OBI had much lower viral load (P < 0.001) and a trend of higher mutation rates in "a" determinant of HBsAg than age-comparable, HBsAg-positive subjects. Reduction of OBI in immunized subjects complements the well-documented universal infant immunization-related benefit of markedly reduced overt HBV infection. Breakthrough infections in immunized subjects seem to associate with more occurrence of OBI than natural infections in unvaccinated subjects. In the postvaccination era, anti-HBc seropositivity is a useful marker for OBI screening in HBsAg-negative subjects, and a very-low-level viral replication and HBsAg expression is the major mechanism underlying OBI.

Meningitis in a School-Aged Child due to Haemophilus influenzae Type E during the Post-Conjugate Vaccine Era-Monroe County, NY, 2011.

In late October 2011, the Monroe County Department of Public Health (MCDPH) was notified of a suspected case of meningitis in a 9-year old girl from Monroe County, NY. Laboratory testing at the New York State Department of Health (NYSDOH) Wadsworth Center confirmed the identification of Haemophilus influenzae serotype e (Hie) isolated from the patient’s cerebrospinal fluid (CSF) using real-time polymerase chain reaction (RT-PCR). The universal immunization of infants with conjugate H. influenzae type b (Hib) vaccine has significantly reduced the incidence of invasive Hib disease, including meningitis, one of the most serious complications for infected children. Not surprisingly, as the epidemiology of invasive H. influenzae continues to change, non-Hib serotypes will likely become more common. The findings reported here underscore the importance for clinicians, public health officials, and laboratory staff to consider non-Hib pathogens in pediatric cases of meningitis, especially when initial investigations are inconclusive.

Responding to Australia's National Hepatitis B Strategy 2010–13: gaps in knowledge and practice in relation to Indigenous Australians

The Australian National Hepatitis B Strategy 2010-13 outlines five priority areas for developing a comprehensive response to the hepatitis B virus (HBV): building partnerships and strengthening community action; preventing HBV transmission; optimising diagnosis and screening; clinical management of people with chronic hepatitis B (CHB); and developing health maintenance, care and support for people with HBV. A scoping study was used to map the main sources and types of evidence available on the epidemiology and natural history of HBV among Indigenous Australians as well as public health responses published since 2001 (January 2001-May 2013). Gaps in current knowledge were identified. While the literature documents the success of universal infant immunisation and indicates the potential for screening initiatives to identify infected and susceptible individuals, prevalence of CHB and hepatocellular cancer remain high in Indigenous Australians. Significant gaps in knowledge and practice were identified in relation to each of the five National Hepatitis B Strategy priority action areas. Successful implementation of the strategy in Indigenous communities and reducing the burden of HBV and hepatocellular cancer in Indigenous Australians will require increased investment in research and knowledge transfer across all priority areas.

Cost-effectiveness of new adult pneumococcal vaccination strategies in Italy

Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy. Particularly, different immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simultaneous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70 and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program. In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis (PM) cases, and related hospitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of pneumococcal CAP by the European Medicine Agency (differently from FDA, whose indications include all pneumococcal diseases in subjects ≥ 50 y), the model calculated also the possible impact of vaccination on CAP cases (non-bacteraemic), considering the rate of this disease due to S. pneumoniae. The results of the analysis show that, in Italy, an age-based PCV13 vaccination program in elderly people is cost-effective from the payer perspective, with costs per QALY ranging from 17,000 to 22,000 Euro, according to the adopted vaccination strategy. The subsequent PPV23 offer results in an increment of costs per QALY (from 21,000 to 28,000 Euro, according to the vaccination strategy adopted). Pneumococcal vaccination using the conjugate vaccine turned out to be already favorable in the second year of implementation, with incremental costs per QALY comparable to those of other already adopted prevention activities in Italy (for instance, universal HPV vaccination of 12 y-old girls), with further benefits obtained when extending the study period beyond the 5-y horizon of our analysis.

Hepatitis B and C

Hepatitis B and C

Hepatitis B virus transmission in pre-adolescent schoolchildren in four multi-ethnic areas of England

The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

Prevalence of Sexually Transmitted Infections (HIV, Hepatitis B, Herpes Simplex Type 2 and Syphilis) Among Asymptomatic Pregnant Women

To determine the current prevalence of four major sexually transmitted infections (STIs: HIV, Hepatitis B, Herpes simplex virus 2, and Syphilis) in asymptomatic pregnant women. This is a prospective study of 500 consecutive, apparently healthy asymptomatic pregnant women who were attending the antenatal clinic. The information regarding their socio-demographic and behavioral characteristics and obstetric performance was recorded. The blood samples was collected after obtaining their informed written consent from those who were tested for the HIV antibodies (NACO guidelines), HBsAg (ELISA test), HSV2-IgM (ELISA test), and Syphilis (VDRL and TPHA tests). The overall prevalence of one or the other four STIs studied was 4.8% with the highest prevalence of HBV (2.4%), followed by HSV-2 (2%), and HIV (0.4%). No woman tested positive for syphilis and multiple infections. All the infections were more common in illiterate, multigravida, monogamous women of low socio-economic status. High-risk sexual behavior of the husbands, history of STIs in husbands, and blood transfusions were the other factors associated with the prevalence of these infections. The relatively high prevalence of HBV and HSV-2 infections in asymptomatic pregnant women suggests that there is need of screening for HBV and HSV-2 infections along with the pre-existing screening for HIV and Syphilis and universal immunization of HBV high-risk infants.

Cost-Effectiveness Analysis of a Universal Infant Immunization Program with Meningococcal C Conjugate Vaccine in Brazil

Objective To analyze the cost-effectiveness of a meningococcal C vaccination program in Brazil. Methods A hypothetical cohort of 3,194,038 children born in Brazil in 2006 was followed for 10 years. A decision tree model was developed using the TreeAge Pro 2007 software program to compare universal infant vaccination with the current program. Epidemiological and cost estimates were based on data retrieved from National Health Information Systems and the literature. The analysis was conducted from the public health care system and societal perspectives. Costs are expressed in 2006 Brazilian reals (R$). Results At 94% coverage, the program would avoid 1,218 cases, 210 deaths, and 14,473 life-years lost, a reduction of, respectively, 45%, 44%, and 44%, for the 10-year period. Vaccination costs of R$320.9 million would not be offset by R$4 to R$7.9 million decreases in disease treatment costs. A national vaccination program would cost R$21,620 per life-year saved from the perspective of the health-care system and R$21,896 per life-year saved from society's perspective. Results were most sensitive to case fatality rate, disease incidence, and vaccine cost. Conclusions A universal childhood vaccination program against meningococcal C proved to be a cost-effective strategy, supporting the recent decision of the Brazilian government. These results could contribute to defining the most favorable price of the vaccine and to monitoring its impact on the population.

Effectiveness of the Monovalent G1P[8] Human Rotavirus Vaccine Against Hospitalization for Severe G2P[4] Rotavirus Gastroenteritis in Belém, Brazil

Brazil initiated universal immunization of infants with the G1P[8] human rotavirus (RV) vaccine in March 2006. This study evaluated vaccine effectiveness (VE) against severe rotavirus gastroenteritis (RVGE) hospitalizations. Matched case-control study conducted at 4 hospitals in Belém from May 2008 to May 2009. Cases were children hospitalized with RVGE age-eligible to have received 2 doses of the human RV vaccine (≥ 12 weeks of age and born after March 6, 2006). For each case, 1 neighborhood and 1 hospital control without gastroenteritis was selected, matching by birth date (± 8 and ± 6 weeks, respectively). Matched odds ratio of 2-dose RV vaccination in cases versus controls was used to estimate VE (1 - odds ratio × 100%). Of 538 RVGE cases, 507 hospital controls and 346 neighborhood controls included, 54%, 61%, and 74% had received both RV vaccine doses. VE against RVGE hospitalization was 75.8% (95% confidence interval [CI]: 58.1-86.0) using neighborhood controls and 40.0% (95% CI: 14.2-58.1) using hospital controls. VE in children 3 to 11 months and ≥ 12 months of age was 95.7% (95% CI: 67.8-99.4) and 65.1% (95% CI: 37.2-80.6) using neighborhood controls, and 55.6% (95% CI: 12.3-77.5) and 32.1% (95% CI: -3.7-55.5) using hospital controls. G2P[4] accounted for 82.0% of RVGE hospitalizations. G2P[4]-specific VE was 75.4% (95% CI: 56.7-86.0) using neighborhood controls and 38.9% (95% CI: 11.1-58.0) using hospital controls. Although fully heterotypic G2P[4] was the predominant RV strain, good VE was demonstrated. VE was highest in children aged 3 to 11 months. However, protection in children ≥ 12 months of age, important for optimal public health impact, was significantly sustained based on estimates obtained using neighborhood controls.

Changes in Childhood Diarrhea Incidence in Nicaragua Following 3 Years of Universal Infant Rotavirus Immunization

Although the pentavalent rotavirus vaccine was highly efficacious against rotavirus diarrhea in clinical trials, the effectiveness of vaccine under field conditions in the developing world is unclear. In October 2006, Nicaragua became the first developing nation to implement universal infant immunization with the pentavalent rotavirus vaccine. To assess the effect of the immunization program, we examined the incidence of diarrhea episodes between 2003 and 2009 among children in the state of León, Nicaragua. We extracted data on diarrhea episodes from health ministry records. We used scaled Poisson regression models to estimate diarrhea incidence rate ratios for the period following the program's implementation to the period before implementation. Following implementation of the immunization program, diarrhea episodes among infants were reduced (incidence rate ratios: 0.85, 95% confidence interval: 0.71-1.02) during the rotavirus season, but appear to have increased during other months. Although the immunization program appears effective in reducing diarrhea episodes during the rotavirus season, a large burden of diarrhea still persists during the remainder of the year.

Secular trend of the viral genotype distribution in children with chronic hepatitis B virus infection after universal infant immunization

Genotypes B and C are the major hepatitis B virus (HBV) genotypes in Taiwan, and genotype C is associated with more severe liver disease than genotype B. Whether the implementation of the hepatitis B immunization program has affected the secular trend of the HBV genotype distribution remains unknown. We thus investigated the HBV genotypes in hepatitis B surface antigen (HBsAg)-carrier children born before the implementation of the universal infant immunization program and in those born afterward. One hundred seven children who were infected with HBV despite appropriate immunization were enrolled as immunized cases with HBV breakthrough infection. Each case was matched with two unimmunized HBsAg carriers according to the age at enrollment. HBV genotypes were determined with molecular methods. Compared with unimmunized HBsAg carriers, more immunized children had HBsAg-positive mothers (65.9% versus 100%, P < 0.001) and were infected with genotype C (16.4% versus 42.1%, P < 0.001). Among the children born to HBsAg-positive mothers, the mothers' and children's HBV genotypes were highly concordant in both unimmunized [κ = 0.97, 95% confidence interval (CI) = 0.90-1.00] and immunized children (κ = 0.97, 95% CI = 0.92-1.00). After adjustments for gender, maternal age, and delivery mode, immunized HBsAg-carrier children born to HBsAg-positive mothers had a higher likelihood of genotype C infection than unimmunized children (odds ratio = 3.03, 95% CI = 1.62-5.65, P = 0.001). However, the increased genotype C to genotype B ratio was not seen in the HBsAg-carrier mother pool in the postimmunization era. In the postimmunization era, most HBV breakthrough infections are due to maternal transmission, and immunized children born to genotype C mothers may have a higher rate of breakthrough infection than those born to genotype B mothers.