Cost-Effectiveness of New-Generation Oral Cholera Vaccines: A Multisite Analysis

Objectives:  We evaluated the cost-effectiveness of a low-cost cholera vaccine licensed and used in Vietnam, using recently collected data from four developing countries where cholera is endemic. Our analysis incorporated new findings on vaccine herd protective effects.
Methods:  Using data from Matlab, Bangladesh, Kolkata, India, North Jakarta, Indonesia, and Beira, Mozambique, we calculated the net public cost per disability-adjusted life year avoided for three immunization strategies: 1) school-based vaccination of children 5 to 14 years of age; 2) school-based vaccination of school children plus use of the schools to vaccinate children aged 1 to 4 years; and 3) community-based vaccination of persons aged 1 year and older.
Results:  We determined cost-effectiveness when vaccine herd protection was or was not considered, and compared this with commonly accepted cutoffs of gross domestic product (GDP) per person to classify interventions as cost-effective or very-cost effective. Without including herd protective effects, deployment of this vaccine would be cost-effective only in school-based programs in Kolkata and Beira. In contrast, after considering vaccine herd protection, all three programs were judged very cost-effective in Kolkata and Beira. Because these cost-effectiveness calculations include herd protection, the results are dependent on assumed vaccination coverage rates.
Conclusions:  Ignoring the indirect effects of cholera vaccination has led to underestimation of the cost-effectiveness of vaccination programs with oral cholera vaccines. Once these effects are included, use of the oral killed whole cell vaccine in programs to control endemic cholera meets the per capita GDP criterion in several developing country settings.     

Trends in early childhood vaccination coverage: Progress towards US Healthy People 2010 goals

Objectives

To evaluate trends in national vaccination coverage from 2000 to 2007 among children aged 19–35 months for at least four doses of diphtheria–tetanus–pertussis vaccine (4 + DTaP), three doses of poliovirus vaccine (3 + Polio), one dose of measles–mumps–rubella vaccine (1 + MMR), three doses of Haemophilus influenzae type b vaccine (3 + Hib), three doses of hepatitis B vaccine (3 + HepB), one dose of Varicella vaccine (1 + Var), and the standard vaccine series of these six vaccines (4:3:1:3:3:1). To predict vaccination coverage levels in 2008–2010 for those vaccines that have not yet reached the Healthy People 2010 coverage targets of 90% for individual vaccines and 80% for the vaccine series.

Methods

Data were analyzed for 167,086 children aged 19–35 months in the 2000–2007 National Immunization Survey. Vaccination coverage trends were analyzed with weighted least squares linear regression models. Nonlinear Weibull and logarithmic regression models were fitted to these past results, and extrapolation was used to predict vaccination coverage levels for 4 + DTaP, 1 + Var, and the 4:3:1:3:3:1 series from 2008 to 2010.

Results

From 2000 to 2007, observed vaccination coverage increased significantly for four of the six vaccines and the standard vaccine series, and reached the 90% target for 3 + Polio, 1 + MMR, 3 + Hib, and 3 + HepB. Increases in coverage were not significant for 1 + MMR and 3 + Hib; however, coverage for these vaccines was consistently > 90% throughout the study period. Both Weibull and logarithmic regression models predicted that coverage with 1 + Var and the 4:3:1:3:3:1 series will surpass the 2010 target by 2008, while coverage with 4 + DTaP will fall short of the target at 86% in 2010.

Conclusions

The United States is well on the way toward reaching most of the Healthy People 2010 objectives for early childhood vaccination coverage. Enhanced efforts are needed to ensure that these trends continue, and to increase coverage with 4 + DTaP.     

Interchangeability of Quinvaxem during primary vaccination schedules: Results from a phase IV,single-blind,randomized, controlled,single-center,non-inferiority study

Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP–HepB–Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6–10–14 week schedule) of Tritanrix HB + Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB + Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB + Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB + Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720).     

Individual-, family- and community-level determinants of full vaccination coverage among children aged 12–23 months in western Kenya

To identify individual-, family-, and community-level determinants of full vaccination status at most challenging areas in Kenya, we conducted a cross-sectional study among children aged 12–23 months and their mothers. 1965 children were involved in this research and their mothers completed a questionnaire. Middle or high knowledge of vaccination schedule (Adjusted Odds Ratio (AOR) = 2.69, 95%CI: 2.01–3.60 or AOR = 8.12, 95%CI:5.50–11.97), medium/long birth interval or first birth (AOR = 2.46, 95%CI: 1.29–4.69 or AOR = 1.84, 95%CI:1.10–3.09 or AOR = 2.14, 95%CI: 1.20–3.84), less than 5 children under five years old (AOR = 1.39, 95%CI: 1.04–1.88) and highest community health worker's (CHWs) performance (AOR = 2.20, 95%CI: 1.39–3.47) were significantly associated with complete vaccination status in the final multiple regression model. In addition, a interaction between literacy and wealth was significantly related in full vaccination status (AOR = 1.38, 95%CI: 1.08–1.75). Increased frequency and quality of CHW visits could be effective intervention to enhance vaccination coverage. Future interventions focusing on vaccination coverage should be given more attention especially to high risk group identified in this study.     

A systematic review of the health outcomes related to household water quality in developing countries

In developing countries, the microbial contamination of household drinking water is implicated in the prevalence of various diseases. This systematic review is concerned with two health outcomes, general diarrhoea and cholera, and their relationship with water quality at point-of-use. Observational studies investigating this relationship are reviewed, as well as studies of home water treatment and storage interventions. For cholera, a clear relationship was found with contaminated water. Home water treatment and storage interventions were also found to reduce cholera. For general diarrhoea, no clear relationship was found with point-of-use water quality, although interventions did significantly reduce diarrhoeal incidence. Reasons for these apparently contradictory results concerning general diarrhoea are discussed and suggestions for further research offered. The policy implications of the findings are also discussed.     

Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting

Background

A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5–12 following MMRV vaccination as compared to the vaccines given separately (MMR + V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV.

Methods

Children ages 12–60 months who received a first dose of MMRV in February 2006–June 2007 in a managed care organization were included in the study. Subjects were optimally matched on age, sex, and calendar date of vaccination to children who received MMR + V concomitantly in November 2003–January 2006, before MMRV licensure. Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel, according to pre-specified criteria.

Results

During the 30 days post-vaccination, there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR + V cohorts, respectively. After review of available medical charts and adjudication, there were 84 cases of confirmed febrile convulsion, 44 (1.41/1000) and 40 (1.28/1000) in the MMRV and MMR + V cohorts, respectively (RR = 1.10, 95% CI = 0.72, 1.69). In days 5–12 following vaccination, a pre-specified period of interest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) (RR = 2.20, 95% CI = 1.04, 4.65).

Conclusion

These data suggest that the risk of febrile convulsion is increased in days 5–12 following vaccination with MMRV as compared to MMR + V given separately during the same visit, when post-vaccination fever and rash are also increased in clinical trials. While there was no evidence of an increase in the overall month following vaccination, the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine.     

Potential influence of seasonal influenza vaccination requirement versus traditional vaccine promotion strategies on unvaccinated healthcare personnel

In a prospective cohort study of 1670 healthcare personnel (HCP) providing direct patient care at Scott & White Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington, we examined the potential impact of twelve vaccine promotion strategies on the likelihood of being vaccinated. Internet-based surveys were conducted at enrollment (Fall, 2010) and at post-season (Spring, 2011), which asked HCP whether twelve vaccination promotion strategies would make them “much less” to “much more” likely to be vaccinated next season (on a 5-point Likert scale). Overall, 366 of 1670 HCP (22%) were unvaccinated. Half (50%) of unvaccinated HCP self-reported that a vaccination requirement would make them more likely to be vaccinated and most (62%) identified at least one strategy other than a vaccination requirement that would make them more likely to be vaccinated. In sub-groups of unvaccinated HCPs with specific barriers to vaccination, about one in three (range = 27–35%) indicated that interventions targeting specific vaccination barrier would increase the likelihood they would be vaccinated. However, in all cases, significantly more unvaccinated HCP reported that a vaccination requirement would increase the likelihood of vaccination than reported a targeted intervention would have this effect (range in difference scores = +11–23%).     

The end of the Australia antigen? An ecological study of the impact of universal newborn hepatitis B vaccination two decades on

Background

A universal newborn hepatitis B (HBV) vaccination program was introduced in the Northern Territory of Australia in 1990, followed by a school-based catch-up program. We evaluated the prevalence of hepatitis B infection in birthing women up to 20 years after vaccination and compared this to women born before the programs commenced.

Methods

A cohort of birthing mothers was defined from Northern Territory public hospital birth records between 2005 and 2010 and linked to laboratory confirmed notifications of chronic HBV, based principally on a record of hepatitis B surface antigen detection. Prevalence of HBV was compared between women born before or after implementation of the newborn and catch-up vaccination programs.

Findings

Among 10797 birthing mothers, 138 (1.3%) linked to a chronic HBV record. HBV prevalence was substantially higher in Aboriginal women compared to non-Indigenous women (2.4% versus 0.04%; p < 0.001). Among 5678 Aboriginal women, those eligible for catch-up and newborn HBV vaccination programs had a significantly lower HBV prevalence than older women born prior to the programs: HBV prevalence respectively 2.2% versus 3.5%, (OR 0.61, 95%CI 0.43–0.88) and 0.8% versus 3.5% (OR 0.21, 95%CI 0.11–0.43). This represents a risk reduction of respectively 40% and 80% compared to unvaccinated women.

Interpretation

The progressively greater reduction in the prevalence of chronic HBV in adult Aboriginal women co-inciding with eligibility for catch-up and newborn vaccination programs is consistent with a significant impact from both programs. The use of data derived from antenatal screening to track ongoing vaccine impact is applicable to a range of settings globally.     

Neutralizing antibody response after intradermal rabies vaccination in hemodialysis patients

Abnormal immune function in chronic hemodialysis (HD) patients could impair immunologic responsiveness to various vaccinations. Such inadequate response makes the HD patients to be at risk of certain fatal but preventable diseases including rabies. Although the effectiveness of rabies vaccination has been established in healthy subjects, the responsiveness of the current rabies vaccination has never been examined in HD patients. The effectiveness of post-exposure rabies vaccine was assessed in 20 stable thrice-a-week chronic HD patients who received adequate dialysis and did not have history of rabies vaccination during the last 20 years. All participants received the standard intradermal Thai Red Cross post-exposure rabies vaccination. Blood samples were obtained for determination of rabies neutralizing antibody (Nab) before the first dose (day 0) and on days 14 and 90 after vaccination. Prior to simulated vaccination, six of twenty patients already had Nab titers above the protective levels of 0.5 IU/mL while the remaining fourteen patients showed undetectable Nab. All subjects reached Nab titers above 0.5 IU/mL(acceptable level for rabies protection) by days 14 after vaccination. The geometric mean titers (GMTs) on days 14 after vaccination were 3.2 + 3.1 IU/mL (range 0.81–9.17 IU/mL). At day 90 after vaccination, 13 of 14 patients had Nab titers above the protective levels, resulting in the response rate of 92.8%. The GMTs of Nab on day 90 after vaccination were 5.09 + 1.79 IU/mL (0.42–25.0 IU/mL). There were no correlations between Nab titers and patient characteristics. No serious adverse reactions were detected. In conclusion, chronic HD patients receiving adequate dialysis have excellent protective immunological response after intradermal post-exposure rabies vaccination as WHO recommendation.     

CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation

Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral^® containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10–18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P < 0.01) and IFN-γ production (P < 0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P > 0.05). The IFN-γ production was significantly higher (P < 0.01) but the blast formation comparable (P > 0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P < 0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-γ as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.