Opportunities and challenges in delivering influenza vaccine by microneedle patch.

INTRODUCTION: Simple and efficacious delivery methods for influenza vaccines are needed to improve health outcomes and manage possible pandemics both in the United States and globally. One approach to meeting these needs is the microneedle patch (MNP), a small array of micron-scale needles that is applied to the skin like a bandage. METHODS: To inform additional technical developments and the eventual introduction of MNPs for influenza vaccination, we interviewed key opinion leaders in the United States for insights into the opportunities and challenges associated with this technology, particularly its potential for self-administration. RESULTS: All interviewees expressed high support for administration of influenza vaccine in MNPs by health care providers and for self-administration in groups supervised by a provider. Self-administration via prescription and over-the-counter purchase of MNPs received lower levels of support. Interviewees also highlighted priorities that should be considered in the ongoing development of an influenza vaccine MNP, such as confirming efficacy and ensuring safety for self-administration. For patient and health care provider acceptability, important attributes are ease of use, short wear times, and an easily accessible application site. DISCUSSION AND CONCLUSIONS: Stakeholders agreed that using MNPs can help increase coverage, facilitate easy and safe delivery, reduce the cost of vaccination, and decrease the global morbidity and mortality associated with influenza. Another opportunity for this delivery method is the potential for self-administration. The prospect of reduced provider training requirements, increased thermostability, and high patient and provider acceptability makes it an attractive option for use in remote and low-resource settings worldwide. However, in addition to the technological challenges associated with producing the patch, developers must be mindful of cost considerations and key product attributes or requirements, such as usability, wear time, and proper disposal, that can affect how the product will be received in the marketplace.

Current experience with school-located influenza vaccination programs in the United States: a review of the medical literature.

In the United States, all children 6 months through 18 years of age are recommended to be vaccinated against influenza annually. However, the existing pediatric immunization infrastructure does not have the capacity to vaccinate a high proportion of children each year. School-located influenza vaccination (SLIV) programs provide an opportunity to immunize large numbers of school-age children. We reviewed the medical literature in order to document the current U.S. experience to benefit future SLIV programs. Published reports or abstracts for 36 SLIV programs were identified, some of which spanned multiple years. The programs immunized between 70-128,228 students. While most programs vaccinated 40-50% of students, coverage ranged from 7-73%. Higher percentages of elementary students were vaccinated compared with middle and high school students. While many programs offered only intranasal vaccine, several programs have successfully used both the intranasal and injectable vaccines. Faculty and staff were immunized in some programs and uptake in this group varied considerably. Students were vaccinated quickly during school hours. Costs, where reported, ranged from approximately $20-$27 per dose delivered, including both vaccine and administration costs. The greatest need for future U.S. SLIV program implementation is the development of a financially sustainable model that can be replicated annually on a national scale.

The impact of school-located influenza vaccination programs on student absenteeism: a review of the U.S. literature.

A literature review was conducted to summarize the impact of school-located influenza vaccination (SLIV) programs on school absenteeism. Seven studies were identified: six peer-reviewed articles and one conference presentation. The number of students vaccinated ranged from 185 to 5,315, representing 35-86% of enrolled students. Six studies compared absenteeism for students in SLIV schools and control schools; all found absenteeism decreased in SLIV schools. Three studies compared absenteeism for vaccinated and unvaccinated students in SLIV schools; all found that absenteeism was reduced for vaccinated students. Benefits were also reported to extend beyond the vaccinated children; one study found that absenteeism was significantly reduced among high school students when elementary school students were vaccinated. The available evidence indicates that SLIV programs reduce student absenteeism during the influenza season. Additional research into sustainable funding sources and the comprehensive effects of SLIV programs on students, families, staff, and the community is warranted.

Estimating the risk of rabies transmission to humans in the U.S.: a Delphi analysis.

BACKGROUND: In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances. METHODS: We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario. RESULTS: The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing), estimated to have less than 1 in 1,000,000 (0.000001) risk of transmission. CONCLUSIONS: Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.

Optimizing protection against influenza in children eligible for the vaccine for children program.

BACKGROUND: Children eligible for the Vaccines for Children (VFC) program are immunized against influenza at lower rates and less likely to receive their second recommended dose. Live, attenuated influenza vaccine (LAIV) has higher vaccine efficacies (VEs) than trivalent, inactivated influenza vaccine (TIV). Increased use of LAIV could provide better protection against influenza for this vulnerable population. METHODS: Published VE estimates and vaccine utilization data from a nationwide study of randomly selected pediatric practices were used to model percentages of VFC children that would be immune following immunization. RESULTS: A total of 22,329 influenza vaccine doses were administered to 20,626 VFC-eligible children aged 24 months to 17 years in the study population. Among children recommended to receive 2 doses, only 1234 of 3018 (41%) aged 24 to 59 months and 469 of 1908 (25%) aged 5 to 8 years received their second dose. Of the vaccinated VFC population, 73% to 83% would be immune using LAIV compared with 53% to 68% with TIV. Differences in aggregate immunity were greatest among 24- to 59-month olds with 71% to 78% of LAIV immunized children immune compared with 48% to 60% with TIV. In this model, 29% to 47% more children aged 24 to 59 months would be immune prior to peak influenza season when vaccinated with LAIV. CONCLUSIONS: Because VE is higher and most VFC children fail to receive their second recommended dose, population protection is substantially higher with LAIV. Although LAIV cannot be given to all children, LAIV should be used preferentially for the VFC population, particularly for children aged 24 to 59 months and those needing 2 doses.

Strategies for implementing school-located influenza vaccination of children: a systematic literature review.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccinations for all children 6 months to 18 years of age, which includes school-aged children. Influenza immunization programs may benefit schools by reducing absenteeism. METHODS: A systematic literature review of PubMed, PsychLit, and Dissertation Abstracts available as of January 7, 2008, was conducted for school-located vaccinations, using search words "School Health Services" and "Immunization Programs"; limited to "Child" (6-12 years) and "Adolescent" (13-18 years) for PubMed and "mass or universal" and (immuniz(*) or immunis(*) or vaccin(*)) and (school or Child or Adolescen(*)) for PsychLit and Dissertation Abstracts. Fifty-nine studies met the criteria for review. RESULTS: Strategies such as incentives, education, the design of the consent form, and follow-up can increase parental consent and number of returned forms. Minimizing out-of-pocket cost, offering both the intramuscular (shot) and intranasal (nasal spray) vaccination, and using reminders can increase vaccination coverage among those whose parents consented. Finally, organization, communication, and planning can minimize the logistical challenges. CONCLUSIONS: Schools-based vaccination programs are a promising option for achieving the expanded ACIP recommendation; school-located vaccination programs are feasible and effective. Adhering to lessons from the peer-reviewed scientific literature may help public health officials and schools implement the expanded recommendation to provide the greatest benefit for the lowest cost. Given the potential benefits of the expanded recommendation, both directly to the vaccinated children and indirectly to the community, prospective, well-controlled trials to establish the cost-effectiveness of specific vaccination strategies should be high priorities for future research.

A survey of physician-led influenza immunization programs in schools.

To determine whether school-located immunization programs (SIPs) offer an efficient method of immunizing children aged 5 to 18 years now recommended for annual influenza immunization, the author interviewed 8 of 10 physicians (identified through media reports and personal communication) who independently conducted SIPs during 2005-2007. SIPs targeted 1 to 6 schools (mainly smaller private schools) and immunized

Hyperbaric oxygenation applied immediately after coronary occlusion reduces myocardial necrosis and acute mortality in rats.

1. Because in ischaemia there is a critical lack of O2, it has been reasoned that increasing O2 delivery to the ischaemic myocardium could serve as adjunctive therapy for acute myocardial infarction (MI). Accordingly, in the present study, the effect of early hyperbaric oxygenation (HBO) on mortality and MI size after coronary occlusion was examined in rats. 2. After coronary occlusion, male Wistar rats were randomly assigned to receive either HBO for 1 h in a hyperbaric chamber (100% O(2) at 253 kPa; n = 106) or ambient O2 as the control (n = 111). The extent of myocardial necrosis was assessed (triphenyltetrazolium) immediately after treatment in the HBO (n = 50) and control (n = 47) groups. The remaining rats were evaluated 24 h after occlusion to enable calculation of MI size and mortality. 3. Immediately after therapy, the size of the MI was significantly greater in the control group compared with that in the HBO group (40 +/- 3 vs 27 +/- 2% of the left ventricle (LV), respectively; P < 0.001). The 24 h mortality of control rats was higher than that of HBO rats (34 vs 16%, respectively; P = 0.02). Control rats that survived 24 h had a larger MI than did HBO rats that survived 24 h (40 +/- 4 vs 29 +/- 3% of the LV, respectively; P = 0.005). Furthermore, large necrotic areas (> 40% of the LV) were more frequent in control than HBO rats (55 vs 27% of infarcted hearts, respectively; P = 0.01). There was less pulmonary congestion observed in HBO rats compared with control rats. 4. In conclusion, early therapy with HBO during the onset of an acute ischaemic event decreases the necrotic area and reduces acute mortality. These data support further investigation of HBO as an adjuvant therapy for acute MI.

Transmission of imported vaccine-derived poliovirus in an undervaccinated community in Minnesota.

BACKGROUND: Oral poliovirus vaccine (OPV) has not been used in the United States since 2000. Type 1 vaccine-derived poliovirus (VDPV) was identified in September 2005, from an unvaccinated Amish infant hospitalized in Minnesota with severe combined immunodeficiency. An investigation was conducted to determine the source of the virus and its means of transmission. METHODS: The infant was tested serially for poliovirus excretion. Investigations were conducted to detect poliovirus infections or paralytic poliomyelitis in Amish communities in Minnesota, neighboring states, and Ontario, Canada. Genomic sequences of poliovirus isolates were determined for phylogenetic analysis. RESULTS: No source for the VDPV could be identified. In the index community, 8 (35%) of 23 children tested, including the infant, had evidence of type 1 poliovirus or VDPV infection. Phylogenetic analysis suggested that the VDPV circulated in the community for approximately 2 months before the infant's infection was detected and that the initiating OPV dose had been given before her birth. No paralytic disease was found in the community, and no poliovirus infections were found in other Amish communities investigated. CONCLUSIONS: This is the first demonstrated transmission of VDPV in an undervaccinated community in a developed country. Continued vigilance is needed in all countries to identify poliovirus infections in communities at high risk of poliovirus transmission.

School-based influenza immunization.

Annual influenza vaccination of schoolchildren will protect individual vaccines and, with high coverage, may protect entire communities. Because schoolchildren are more difficult to reach than preschoolers, school-based immunization programs may be needed to reach a high percentage of children. We offered free live, attenuated influenza vaccine to all healthy schoolchildren (K-12) in three Minnesota counties. Counties vaccinated from 33% to 58% of students. Overall, 41% of enrolled children were vaccinated. Elementary students were vaccinated at higher rates than older students. Administrative costs averaged $9.78 per dose delivered. School-based immunization programs offer the potential to achieve higher vaccination coverage of schoolchildren at modest cost.

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.

Smallpox and bioterrorism: public-health responses.

There is great concern that smallpox could be used for bioterrorism. The disease has a high mortality rate and can be spread by aerosols, and immunity in the population is low. Although an initial release of smallpox could infect a large number of people, secondary spread would likely be slow because of the long incubation period and the close contact required for transmission. Hospital personnel and household contacts are at the greatest risk of becoming infected. An outbreak of smallpox will be controlled through surveillance, containment, vaccination, and isolation of cases-the strategy used to eradicate the disease globally in 1978. Pre-exposure vaccination is recommended for hospital personnel likely to be exposed to smallpox while caring for patients during an outbreak.