Assessment of vaccine wastage rates,missed opportunities,and related knowledge,attitudes and practices during introduction of a second dose of measles-containing vaccine into Cambodia’s national immunization program

IntroductionMissed opportunities for vaccination (MOV) can result in inadequate protection against disease. Although healthcare provider reluctance to open multi-dose, lyophilized vaccine vials (particularly the measles-containing vaccine [MCV]) for every eligible child due to concerns about wasting vaccine is a known reason for MOV, little is known about providers’ related attitudes and practices.MethodsIn 100 randomly selected health facilities and 24 districts of Cambodia, we surveyed healthcare providers and their district supervisors regarding routine vaccine administration and wastage knowledge and practices, and child caregivers (five per facility) regarding MOV. Vaccine stock management data covering six months were reviewed to calculate facility and district level wastage rates and vaccine usage patterns for six vaccines, including a recently introduced second dose of MCV (MCV2).ResultsResponse rates were 100/100 (100%) among facility staff, 48/48 (100%) among district staff, and 436/500 (87%) among caregivers. Mean facility-level wastage rates varied from 4% for single-dose diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine to 60% for 10-dose MCV; district-level wastage rates for all vaccines were 0%. Some vaccines had lower wastage rates in large facilities compared to small facilities. The mean MCV wastage rate was the same before and immediately after MCV2 introduction. Providers reported waiting for a mean of two children prior to opening an MCV vial, and 71% of providers reported offering MCV vaccination less frequently during scheduled vaccination sessions than other vaccines. Less than 5% of caregivers reported that their child had been turned away for vaccination, most frequently (65%) for MCV.DiscussionAlthough the MCV wastage rate in our study was in line with national targets, providers reported waiting for more than one child before opening an MCV vial, contrary to vaccine management guidelines. Future research should explore the causal links between provider practices related to vaccine wastage and their impact on vaccination coverage.     

Could a single dose of pneumococcal conjugate vaccine in children be effective? Modeling the optimal age of vaccination

Using incidence rates from CDC's Active Bacterial Core surveillance and immunogenicity data from the Navajo/Apache trial of pneumococcal conjugate vaccine (PCV), we used Markov modeling to predict the optimal age to give a single dose of PCV. Antibody concentration thresholds of 0.35 and 1.0 mcg/ml were considered protective. Our outcome was vaccine serotype-specific invasive pneumococcal disease (IPD) incidence at 24 months. The models predicted the optimal age to vaccinate is 5-7 months with vaccine-induced immunologic memory and 8-10 months without memory. IPD reduction ranged from 15 to 62%, depending on model parameters. A single PCV dose in infants could prevent substantial IPD.     

Safety and immunogenicity of a measles–mumps–rubella–varicella vaccine given as a second dose in children up to six years of age

Two doses of measles–mumps–rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles–mumps–rubella–varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N = 390) aged 15–75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR + varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR + varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p = 0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.     

Increased measles–mumps–rubella (MMR) vaccine uptake in the context of a targeted immunisation campaign during a measles outbreak in a vaccine-reluctant community in England

Background

Following a measles outbreak in a vaccine-rejecting community between April and September 2011 in South-East England, local health agencies implemented a two-pronged measles–mumps–rubella (MMR) immunisation campaign from August to October offered at the local general practice where most cases were registered. The campaign included (a) accelerated vaccination of children earlier than scheduled (1st dose at 6–11 months, or 2nd dose at 18–39 months), (b) catch-up of those aged over 18 months who had had no MMR immunisations or were late for second MMR. We investigated the impact of the outbreak and campaign on the number of MMR doses given.

Materials and methods

In January 2012, we collected information on MMR vaccination for children registered at the practice aged 6 months–16 years on 1 August 2011, through the child health information system. We counted the number of MMR doses administered in 2011 and compared it to 2008–2010 data. We estimated the proportion vaccinated among the children eligible for the accelerated and catch-up campaign.

Results

The local practice administered 257 MMR doses in 2011, a 114% increase on the average for 2008–2010. Among children eligible for earlier MMR vaccination 5/26 (19%) received a first dose, and 34/57 (60%) a second dose. Among children eligible for catch-up, 20/329 (6%) received their first MMR and 39/121 (32%) their second. Of 1538 children, the proportion completely unimmunised for MMR declined by 3 percentage-points after the outbreak.

Discussion

Uptake of MMR vaccination significantly increased during the outbreak following the immunisation campaign. Those amenable to MMR vaccination seem to have benefited from the campaign more than those with no previous vaccinations. Future evaluations should address what made a few parents change their mind and have their children vaccinated for the first time during the outbreak.     

Priority setting for the introduction of rotavirus vaccine: what evidence was essential?

Rotavirus (RV) diarrhea is the most common cause of severe diarrhea in children worldwide and since 2006, vaccines have been available and recommended by WHO for use in all children. We developed protocols that countries could use to assess the burden of RV disease in their own countries and the cost-effectiveness of a program for vaccine introduction. A decade later and in the setting of extreme tiering of prices so that the poorest countries pay the least for the vaccine, more than 92 countries have introduced this vaccine into their national programs and more than 90 have not. Those countries that introduced determined by protocol that the burden of RV disease was substantial and the cost of vaccine reasonable, especially in low income settings where GAVI subsidizes the vaccines’ purchase. However, elsewhere, WHO's global recommendation has not been enacted leaving a majority of the world’s children still at risk of this severe and sometimes fatal disease. We remain with much to learn about how to encourage countries to make decisions that will improve the health of their own children.     

Infection, immunisation and atherosclerosis: is there a link?

Atherosclerosis is the predominant underlying pathology responsible for coronary heart disease (CHD). It bears all the hallmarks of a chronic inflammatory disease and typical atherosclerotic lesions contain activated macrophages and T-cells. There have been several reports of possible associations between prior exposure to a number of specific micro-organisms and subsequent CHD, and prospective epidemiological studies have reported that elevated plasma levels of particular acute phase reactants (APRs) are predictors of future cardiac events. Investigators have also shown that immunisations exacerbate atherosclerosis in experimental animal models. These data raise the possibility that immunostimulation associated with natural infection by certain organisms, or vaccination, may promote atherosclerosis. A hypothesis which may explain all these findings, is that the cellular--and perhaps humoral--responses associated with immune stimulation may enhance atherogenesis.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18–49 years of age,naive to 23-valent pneumococcal polysaccharide vaccine

BackgroundBased on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60–64 years of age have been published. The same study also included a cohort of adults aged 18–49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18–49 years of age compared with adults 60–64 years of age for whom PCV13 is approved.MethodsAdults naive to PPSV23 were grouped by age into 2 cohorts: 18–49 years (n = 899; further stratified by age into 3 subgroups 18–29, 30–39, and 40–49 years) and 60–64 years (n = 417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated.ResultsIn adults aged 18–49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60–64 years. Immune responses were highest in the youngest age subgroup (18–29 years). Local reactions and systemic events were more common in adults 18–49 years compared with 60–64 years and were self-limited.ConclusionImmune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.     

Monitoring virus strain variation following infection with VZV: is there a need and what are the implications of introducing the Oka vaccine?

Varicella zoster virus (VZV) is a stable virus showing relatively little variation. Nevertheless, recent data have shown there to be at least four distinct viral strains. For the most part these are geographically segregated, but in areas of the world such as the UK, where mixed populations live, there is evidence for spread of all the genotypes. Little is known about the biological differences, if any, between these strains, yet recent data have shown that even a single nucleic acid change can affect the biological behaviour of the virus. The Oka vaccine has been licensed for mass vaccination in the US and for limited use in the UK, particularly in seronegative healthcare workers. Virological surveillance is needed to support these programmes and study the effect on virus spread. Evidence for VZV superinfection of latently infected individuals with different strains, and the increasing detection of VZV in association with clinical conditions such as viral meningitis, suggest more data are needed on the transmissibility and biological properties of the virus.     

When, and how, should we introduce a combination measles-mumps-rubella (MMR) vaccine into the national childhood expanded immunization programme in South Africa?

This article briefly reviews the history and epidemiology of measles, mumps and rubella disease and the case for introducing combination measles-mumps-rubella (MMR) vaccine into the national childhood immunization schedule in South Africa. Despite adopting the World Health Organization's Measles Elimination strategy in 1996 and achieving a significant decrease the incidence of measles, added effort is needed in South and southern Africa to reach the goal to eliminate endogenous spread measles. Mumps is still common disease of childhood and while there are few sequelae, even the rare complications are important in large populations. Congenital rubella syndrome is seldom reported, but it is estimated that of the million or so children born every year in South Africa over 600 infants are affected to some degree by rubella infection. The naturally acquired immunity to rubella in women of childbearing age in South Africa has been estimated at over 90%, so that introducing a rubella containing vaccine in childhood may paradoxically increase the proportion of girls reaching puberty still susceptible to rubella. The elimination of endogenous measles and rubella is being achieved in many countries in South America, and despite the recent measles epidemic, must still be seriously considered for South and southern Africa. Current constraints and potential steps needed to reach the goal in South Africa are discussed.     

Effectiveness of the 10-valent pneumococcal conjugate vaccine among girls,boys, preterm and low-birth-weight infants – Results from a randomized,double-blind vaccine trial

BackgroundSeveral studies have shown differences in susceptibility to infections and immune response to vaccines by sex. Prematurely born infants are at higher risk for pneumococcal diseases, with lower effectiveness for some vaccines compared to term infants. We have reported the effectiveness of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) on several endpoints in the Finnish Invasive Pneumococcal disease (FinIP) vaccine trial. Now, we present the results of a post-hoc analysis evaluating PHiD-CV10 effectiveness in subgroups by sex, gestational age, and birth weight.MethodsThe FinIP trial was a phase III/IV cluster-randomized, double-blind trial. Infants enrolled < 7 months of age received PHiD-CV10 in two thirds of clusters (3 + 1 or 2 + 1 schedule) and hepatitis B vaccine as control in remaining third. Outcome data included invasive pneumococcal disease, pneumonia, tympanostomy tube placements, and antimicrobial purchases collected through national, routinely used health registers. Negative binomial model was used in the incidence and vaccine effectiveness estimation, and differences in incidences between subgroups were tested among control children.ResultsOf the 30,527 infants enrolled 51% were boys. The incidences of hospital-diagnosed pneumonia and otitis-related outcomes were higher among boys in control groups. There were no significant sex differences in the vaccine effectiveness estimates.Altogether, 1519 (5%) infants were born before 37th gestational week. The incidences of pneumonia outcomes were higher among premature infants when compared to term infants.The vaccine effectiveness estimates among preterm infants were not statistically significant except for antimicrobial purchases, but all point estimates were at the same level among preterm infants as among term infants. There was no significant difference between 2 + 1 and 3 + 1 schedules in any of the subgroups analysed.ConclusionPHiD-CV10 had a similar effectiveness in both sexes, and seemed to be protective in preterm infants.Trial registration: ClinicalTrials.gov NCT00861380 and NCT00839254     

A randomized,open-labelled,non-inferiority phase 4 clinical trial to evaluate the immunogenicity and safety of the live,attenuated, oral rotavirus vaccine,ROTAVAC® in comparison with a licensed rotavirus vaccine in healthy infants

BackgroundROTAVAC® (nHRV), derived naturally from the human 116E rotavirus (RV) neonatal strain, was licensed in India in 2015 based on promising results of a phase 3, safety and efficacy vaccine trial. As a pre-requisite for WHO prequalification, we compared the immunogenicity and safety of ROTAVAC® to those of a WHO-prequalified, Rotarix®.MethodsWe conducted a multicentre, open-labeled, randomized phase 4 clinical trial where 464 infants, 6–8 weeks of age were equally randomized to receive as licensed, the complete regimen of ROTAVAC® (3 doses; Group I) or Rotarix® (2 doses; Group II). Antibody responses (serum anti-RV Immunoglobulin A [IgA]) were measured by enzyme-linked immunosorbent assay (ELISA). The primary analysis was an assessment of non-inferiority of ROTAVAC® to Rotarix® for geometric mean concentration (GMC) for infants who received the complete regimen of either vaccine.ResultsThe GMC for Group I was 20.4 (95%CI: 17.6, 23.6) and that for Group II was 24.8 (95%CI: 20.3, 30.3), the GMC ratio was 0.82 (95% CI: 0.64, 1.05), thus meeting the non-inferiority criterion. Site-wise analysis of GMC titres revealed that one site had a peculiar pre-vaccination titre affecting only ROTAVAC® post-vaccination GMCs. Seroconversion rates were 35.3% (95%CI: 29.0, 41.9) and 31.0% (95%CI: 25.1, 37.4) for Groups I and Group II, respectively. There was no substantive difference in safety profiles between both vaccines.ConclusionsThe complete regimen of ROTAVAC® demonstrated immunological non-inferiority to the complete regimen of Rotarix® with a clinically acceptable safety profile. Because the demand for RV vaccines is increasing as more countries are expanding their immunization schedules, the lack of need of a buffering agent, low dose volume (0.5 mL), non-interference with other concomitantly administered vaccines, and conformance with WHO-prequalification requirements provide ROTAVAC® the potential for widespread global usage. Post completion of this study, ROTAVAC® is now a WHO-prequalified vaccine.Clinical Trials Registration: (CTRI Number: CTRI/2015/12/006428).     

Effectiveness of 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine for pneumonia among the elderly – Selection of controls in a case-control study

We conducted a case-control study to elucidate associations between pneumonia in elderly individuals and 23-valent pneumococcal polysaccharide vaccine (PPSV23) and seasonal influenza vaccine (influenza vaccine). Here, we examined selection of controls in our study using an analytic epidemiology approach. The study period was from October 1, 2009 through September 30, 2014. Cases comprised ≥65-year-old patients newly diagnosed with pneumonia. For every case with pneumonia, two patients with other diseases (one respiratory medicine, one non-respiratory medicine) who were sex-, age-, visit date- and visit hospital-matched were selected as controls. Odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for pneumonia were calculated using conditional logistic regression model. Similar analyses were also conducted based on the clinical department of controls. Analysis was conducted in 234 cases and 438 controls. Effectiveness of pneumococcal vaccination or influenza vaccination against pneumonia was not detected. Proportions of either vaccination in controls were greater among respiratory medicine (pneumococcal vaccine, 38%; influenza vaccine, 55%) than among non-respiratory medicine (23%; 48%). Analysis using controls restricted to respiratory medicine showed marginally significant effectiveness of pneumococcal vaccination (OR, 0.59; 95%CI, 0.34–1.03; P = 0.064) and influenza vaccination (0.64; 0.40–1.04; 0.072). However, this effectiveness might have been overestimated by selection bias of controls, as pneumonia cases are not necessarily respiratory medicine patients. In the analysis using controls restricted to non-respiratory medicine, OR of pneumococcal vaccination for pneumonia was close to 1, presumably because the proportion of pneumococcal vaccination was higher in cases than in controls. Because pneumococcal vaccine was not routinely administered during the study period, differences in recommendations of vaccination by physician in different clinical departments might have greatly affected vaccination proportions. When we select controls, we should consider the background factors (underlying diseases, clinical department, etc.) which affect physicians’ recommendation of vaccination.     

Measles,the media,and MMR: Impact of the 2014–15 measles outbreak

ObjectiveIn late 2014, a measles outbreak beginning in California received significant media attention. To better understand the impact of this outbreak, we conducted a survey to assess and compare among vaccine hesitant and non-hesitant new mothers how this outbreak affected vaccine knowledge, attitudes, vaccination plans, and media use.MethodsA cross-sectional email survey of English-speaking women with a child ⩽1 year old using a convenience sample of women from nine obstetrics and gynecology (OB/GYN) practices in Colorado assessed vaccine hesitancy, knowledge and attitudes about MMR vaccines and the outbreak, MMR vaccination plans before and after the outbreak, and use of and trust for media sources related to the outbreak.ResultsThe response rate was 50% (351/701). Knowledge about the outbreak was high and vaccination attitudes were mostly favorable. Forty-eight percent of respondents thought MMR vaccine was more important after the outbreak. Online news (76%), television news (75%), and social media (68%) were the most frequently used media sources, yet were highly trusted by only 18%, 22%, and 1% of respondents respectively. Government websites (34%) and information from a doctor’s office (34%) were infrequently used, but were highly trusted by 62% and 60% of respondents. Knowledge of the outbreak was lower among vaccine-hesitant respondents. Few mothers changed MMR vaccination plans after the outbreak.ConclusionsNew mothers had high levels of knowledge and favorable attitudes about vaccination after the 2014–15 measles outbreak. Media sources used the most are not the most trusted. Communication about outbreaks of vaccine-preventable diseases should include spread of accurate information to new media sources and strengthening of existing trust in traditional media.     

A phase 3, multicenter,single-arm,open-label study to assess the safety,tolerability, and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in Japanese participants aged 6–64 years who are considered to be at increased risk of pneumococcal disease and who are naive to pneumococcal vaccines

BackgroundThis open-label, single-arm, phase 3 study evaluated safety and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in pneumococcal vaccine-naive Japanese individuals aged 6–64 years at increased risk of pneumococcal disease (PD).MethodsParticipants received 1 PCV13 dose. Reactogenicity events were recorded for 7 days (individuals aged 6- to 17-year-old) or 14 days (individuals aged 18 to 64 years old) postvaccination. Adverse events (AEs) were collected for 1 month postvaccination. Opsonophagocytic activity (OPA) and anticapsular immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured for vaccine serotypes before and 1 month postvaccination. Post hoc analyses compared immunogenicity in participants categorized as at-risk (immunocompetent but having chronic medical conditions associated with increased PD risk) or high-risk (immunocompromised due to diseases/conditions and/or medications).Results206 participants aged 6- to 17-year-old (n = 53) and 18 to 64 years old (n = 153) completed the study. Reactogenicity events were generally mild to moderate in severity. AEs were reported in 16% (33/206) of participants; 1.0% (2/206) were severe. Six AEs were vaccine-related; most were associated with local reactions. No serious AEs occurred. Circulating antibody levels for all 13 serotypes increased postvaccination. OPA geometric mean fold rises (GMFRs) from prevaccination to 1 month postvaccination were 5.5–61.7; lower limits of the 2-sided, 95% CI were > 1 for all serotypes. IgG GMFRs were consistent with OPA analyses. In post hoc analyses, 55.8% (115/206) and 44.2% (91/206) of participants were categorized as at risk and at high risk of PD, respectively; OPA GMFRs from prevaccination to 1 month postvaccination were 3.9–635.1, with lower limits of the 2-sided 95% CIs > 1 for all 13 serotypes across these risk groups; IgG GMFRs were consistent with OPA analyses.ConclusionsPCV13 was well tolerated and immunogenic in Japanese individuals aged 6–64 years considered at increased risk of PD. Results were broadly comparable with past PCV13 studies in other Japanese and non-Japanese populations.Registration number: NCT03571607; JapicCTI-184024.     

Evaluation of effectiveness,safety and cost-benefit of the 23– valent pneumococcal capsular polysaccharide vaccine for HIV-Infected patients

IntroductionDue to the lack of understanding of the protective effects and safety of 23-valent pneumococcal polysaccharide vaccine (PPV23) in immune-deficient populations, the vaccination rate of PPV23 among HIV-infected patients is still very low in China. The main objectives of this study were to determine whether the efforts to assess measures for the prevention of pneumococcal pneumonia are still worthwhile, and provide designated vaccination program of HIV-infected persons for government policy based on.Methods60 HIV-infected adults in Lanshan county who had never been vaccinated with any pneumococcal vaccine were enrolled in this study, voluntary vaccination of PPV23 and One-year follow-up after vaccination can be completed.Result76.67% patients (46/60) had serologic response at 12 months after vaccine, CD4 count(≤500 cells/ul or > 500 cells/ul) and Month from diagnosis to first antiviral therapy (≤1 month or > 1 month) were related to antibody responses (p < 0.05).In this study, PPV23 was well tolerated, no adverse reaction was reported.11 Streptococcus pneumoniae pneumonia (9.17%,11/120) occurred in the Unvaccinated group and 1 case(1.67%,1/60)in the vaccination group within one year after vaccination(Fisher's exact probability, P = 0.225). The VE was 81.79%. The per capita benefit was 39.32 dollars, the benefit-cost ratio = 1.19. There are significant statistical differences between the vaccinated group and the non-vaccinated group in outpatient costs (p < 0.05, 95 %CI: 9.29–32.11), Medicine costs (p = 0.017, 95 %CI: 2.47–24.44), and disease related indirect costs (p = 0.038, 95 %CI: 0.93–33.63) within one year of vaccination.ConclusionOur study results showed that PPV23 can be safely and effectively administered to HIV-1 infected individuals and effectively preventing Streptococcal pneumonia. Considering the cost-benefit of vaccination among HIV-infected persons, as it has been reported in our study, it is necessary to promote the widespread use of the vaccine among HIV-infected persons in the future.     

Acute otitis media in the era of effective pneumococcal conjugate vaccine: will new pathogens emerge?

The immunogenicity of pneumococcal conjugate vaccine (PCV) in young infants and its serotype-specific efficacy in otitis media (OM) results in a modest reduction in total episodes of OM and a more substantial reduction in disease due to the most frequent pneumococcal serotypes. Since PCV will only prevent disease due to the most common serotypes, concerns about potential changes in the microbiology of OM have emerged. Insight into potential changes can be obtained from reviewing middle ear and nasopharyngeal isolates from studies of antimicrobial prophylaxis and bacterial polysaccharide immune globulin for prevention of OM and PCV for prevention of invasive pneumococcal disease, respectively. In children receiving PCV, a shift in serotypes of SP colonizing the nasopharynx has been observed. Since non-vaccine serotypes are already present in the community as the etiology of acute purulent OM, it is predictable that these non-vaccine serotypes will become more common especially in children less than two years of age.     

Epidemiology of invasive pneumococcal disease in the pre-conjugate vaccine era: South Africa, 2003–2008

Introduction

Dynamics of pneumococcal disease incidence and serotype distribution prior to introduction of pneumococcal conjugate vaccines (PCV) will assist in understanding effects of the vaccine over time and will be important in choosing the optimal PCV formulation.

Methods

We conducted active, laboratory-based, national surveillance for invasive pneumococcal disease (IPD) through the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) from 2003 through 2008. Over 130 laboratories report to this system. Pneumococci were serotyped using Quellung and isolates screened for resistance by disk diffusion; minimum inhibitory concentrations were determined on potentially resistant isolates. We used univariate and multivariable multinomial regression models to assess differences between serotypes.

Results

GERMS-SA identified 8674 cases among children <5 years. Overall, 58% (3849/6668), 65% (4314/6668), and 85% (5669/6668) of cases and 61% (455/751), 64% (482/751), 82% (616/751) of deaths were due to serotypes included in 7-valent PCV, 10-valent PCV and 13-valent PCV, respectively. Serotypes 6A and 19A accounted for 16% (527/3252) of penicillin non-susceptible disease. In 2008, reported incidence of IPD was 6-fold higher in children <1 compared to children 1–4 years of age: 87 per 100,000 population and 14/100,000, respectively. The relative risk of IPD was 21-fold (95% CI, 19–24) and 34-fold (29–41) greater in HIV-infected compared to HIV-uninfected children in the <1 year and 1–4-year-old age groups respectively. On multivariable analysis serotypes 6B (relative risk ratio (RRR) 0.7; confidence interval (CI) 0.5–0.9), 18C (RRR 0.3; CI 0.1–0.5), 1 (RRR 0.2; CI 0.1–0.4) and 8 (RRR 0.2; CI 0.1–0.4) were significantly less common in HIV-infected individuals than serotype 14.

Conclusions

All vaccine formulations have the potential to prevent most cases and deaths from IPD in children in South Africa. Vaccines with protection against 19A would be advantageous in South Africa.     

Early smallpox vaccine manufacturing in the United States: Introduction of the “animal vaccine” in 1870, establishment of “vaccine farms”, and the beginnings of the vaccine industry

For the first 80–90 years after Jenner’s discovery of vaccination in 1796, the main strategy used to disseminate and maintain the smallpox vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as “animal vaccine”, which referred to growing vaccine material from serial propagation in calves before use in humans. The use of “animal vaccine” had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of vaccine. The “animal vaccine” concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of “vaccine farms” were established in the U.S. and produced large quantities of “animal vaccine”. These “vaccine farms” were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of smallpox vaccine from individuals and from health authorities, and to make a profit. The “vaccine farms” evolved from producing only smallpox “animal vaccine” to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial vaccine companies. An important aspect that was never clarified was the source of the vaccine stocks used to manufacture the smallpox “animal vaccines”. Most likely, different smallpox vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal vaccines that are now recognized as “variants” more appropriately than “strains”. Further, clonal analysis of modern “animal vaccines” indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old smallpox vaccine specimens in an effort to better understand the origin and evolution of the vaccines that were used to eradicate the smallpox.     

Maternal knowledge,attitudes and beliefs regarding gastroenteritis and rotavirus vaccine before implementing vaccination program: Which key messages in light of a new immunization program?

In July 2010, the National Advisory Committee on Immunization (NACI) recommended the systematic administration of rotavirus vaccines for all infants in Canada. According to the Erickson and De Wals framework, multiple factors need to be evaluated before implementing such a decision, including the study of the acceptability of this vaccine by the general population. A cross-sectional survey was conducted from February 10 to February 18, 2011, at the Sherbrooke University Hospital Center in the province of Quebec. A questionnaire, based upon the Health Belief Model (HBM) and theoretical planned action, was self-administered to pregnant or early post-partum women. The variables collected included socio-demographic data, past experience with gastroenteritis, cues to vaccination and HBM dimensions. The associations between questionnaire variables and vaccination intention were assessed using univariate and multivariate analyses. Of the 343 respondents, only 29% had already heard about rotavirus vaccination and among these, the intention of vaccination was 74%. In multivariate analysis, having a perception of infant vulnerability to gastroenteritis (OR=2.3, 95% CI 1.3-4.0) and having no other child at home (OR=2.3, 95% CI 1.3-4.2) were factors positively associated with a higher intention of vaccination, contrary to having already heard about the rotavirus vaccine in the media (OR=0.5, 95% CI 0.2-0.9). The three cues independently associated with intention of vaccination were the reimbursement of the vaccine (OR=3.0, 95% CI 1.6-5.7), its recommendation by a doctor (OR=21.2, 95% CI 5.8-75.9) and its protection against the most severe forms of gastroenteritis (OR=4.4, 95% CI 1.4-13.6). To improve the success of this new vaccination program, several key messages should be integrated in the information made available to the general population: (1) rotavirus gastroenteritis is a mandatory infection for every child <5 years; (2) the vaccine is reimbursed and included in the provincial vaccination program; and (3) the vaccine protects against the worst forms of gastroenteritis. Finally, support should be offered to physicians as they play a key role in public acceptance of new vaccines.