James M. Hughes

Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli.

ENTEROTOXIGENIC strains of Escherichia coli elaborate two enterotoxins, a heat-labile toxin (LT) and a heat-stable toxin (ST), which cause diarrhoeal disease in humans1; ST-producing E. coli cause diarrhoea in adult volunteers2 and have been associated with epidemic diarrhoea in a nursery for the newborn3 and with sporadic adult diarrhoea among North American tourists to Latin America4 and the Navajo people in Arizona5. LT-producing strains are identified by the ability of culture filtrates to cause fluid accumulation in rabbit ileal loops at 18 h (ref. 6) or by morphological alteration of Chinese hamster ovary (CHO) cells7 or of Y-l adrenal cells8. ST-producing strains are identified by the ability of culture filtrates to cause earlier fluid accumulation in rabbit ileal loops (peak accumulation at 6 h (ref. 6), or by fluid accumulation in the gut of the suckling mouse at 3 h (refs 9, 10). LT acts in a manner similar to cholera toxin (CT) by activating adenylate cyclase11. The mechanism of action of ST is unknown, however. Culture filtrates of a strain of E. coli that produced both LT and ST caused immediate net fluid secretion in canine jejunal segments without the 1-h delay characteristic of the response to CT12,13. In addition, culture filtrates caused an immediate increase in canine jejunal adenylate cyclase activity as measured by enzymatic generation of P32-cyclic AMP from P32-labelled ATP13, also in contrast to the delay in appearance of increased adenylate cyclase activity following exposure to CT12. The possibility that the early effect of ST was mediated by changes in cyclic nucleotide concentrations was investigated; culture filtrates of ST-producing strains of E. coli caused increased cyclic GMP concentrations in rabbit intestinal tissue and the cyclic GMP analogue 8BrcGMP mimicked ST in magnitude and time course of intestinal fluid accumulation in both rabbits and suckling mice.

Reducing stunting among children: the potential contribution of diagnostics

Stunting affects ~ 147 million children in developing countries. Studies have pointed to a relationship between stunting and different pathogens that are associated with diarrhoeal illness. New easy-to-use tools for diagnosing these pathogens could help to identify children at risk for growth shortfall, and reduce the prevalence of stunting and the large burden of disease associated with it.PREFACE The numbers of acquired immunodeficiency syndrome (AIDS)-related deaths among infants in developing countries are exceptionally high, largely because human immunodeficiency virus (HIV) infection remains undiagnosed in many cases. Current HIV testing methods are either impractical for developingcountry settings or inaccurate for use in infants. There is an urgent need to develop and deploy a new, easy-to-use HIV test, which could transform the management of paediatric HIV/AIDS in developing countries and avert millions of infant deaths.

Impact of a physician recommendation and parental immunization attitudes on receipt or intention to receive adolescent vaccines

Four vaccines are recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices for adolescents. Parental attitudes may play a key role in vaccination uptake in this age group. In 2011, we conducted a cross-sectional survey among parents of adolescents in one county in Georgia to identify parental attitudes toward adolescent vaccination, reasons for vaccine acceptance or refusal, and impact of a physician recommendation for vaccination. Physician recommendation was reported as one of the top reasons for receipt or intent to receive any of the vaccines. Physician recommendation of any of the four vaccines was associated with receipt of Tdap (p < 0.001), MCV4 (p < 0.001), and HPV (p = 0.03) and intent to receive Tdap (p = 0.05), MCV4 (p = 0.005), and HPV (p = 0.05). Compared with parents who did not intend to have their adolescent vaccinated with any of the vaccines, parents who did intend reported higher perceived susceptibility (3.12 vs. 2.63, p = 0.03) and severity of disease (3.89 vs. 3.70, p = 0.02) and higher perceived benefit of vaccination (8.48 vs. 7.74, p = 0.02). These findings suggest that future vaccination efforts geared toward parents may benefit from addressing the advantages of vaccination and enhancing social norms. Physicians can play a key role by providing information on the benefits of adolescent vaccination.

Global public health security.

National public health institutes will play a key role in implementation of the revised International Health Regulations.

Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination, and self-reported barriers to vaccination among secondary school teachers and staff.

Objective: Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Methods: Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers’ attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Results: Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, P=0.05) and self-efficacy (OR 4.46, P=0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, P=0.014) and social norms (OR 1.39, P=0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Conclusions: There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers’ influenza vaccine uptake may enhance future influenza immunization efforts.

Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome

Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges.

Antimicrobial Resistance, Food Safety, and One Health: The Need for Convergence

Antimicrobial resistance is a complex, multifaceted, urgent global health problem. There is increasing concern about the emergence of multidrug-resistant superbugs. These superbugs result in infections responsive to treatment with few if any currently available antimicrobial agents, reviving memories of the preantibiotic era and evoking concerns about a postantibiotic era. Use of antibiotics exerts selective pressure on pathogens as well as on commensal organisms that are part of the normal flora of humans, animals, and the environment; this favors the emergence of resistant strains and sometimes involves the food supply. Addressing this urgent threat requires implementation of a multifaceted strategy that has been articulated in the past few years; implementation will require sustained political will, investment in systems and research, and a One Health approach involving improved communication, cooperation, and collaboration among the many professional disciplines and organizations with important roles to play at the intersection of human, animal, and environmental health. Priorities include strengthened human and animal health surveillance and monitoring for resistant organisms, antimicrobial stewardship programs, infection-control programs, development and approval of new antimicrobial agents, research on innovative therapeutic approaches, development of rapid diagnostic tests and new vaccines, and educational programs that target professional groups and the public.

Multicomponent Interventions to Enhance Influenza Vaccine Delivery to Adolescents

OBJECTIVE: To compare school- versus provider-based approaches to improving influenza vaccination coverage among adolescents in rural Georgia. METHODS: We used a nonrandomized, 3-armed design: (1) a middle- and high school-based influenza vaccination intervention in 1 county; (2) a provider-based influenza vaccination intervention in a second county; and (3) a standard-of-care condition in a third county. Interventions also included distribution of an educational brochure, school presentations, and community-based outreach to enhance vaccine knowledge and awareness among adolescents and their parents. RESULTS: During the 2008–2009 influenza season, 70 (19%) of 370 students were vaccinated in the school-based county and 110 (15%) of 736 students were vaccinated in the provider-based county, compared with 71 (8%) of 889 students in the standard-of-care county (risk ratio [RR]school: 2.4 [95% confidence interval (CI): 1.7–3.2]; RRprovider: 1.9 [95% CI: 1.4–2.5]). During 2009–2010, seasonal influenza vaccination coverage was 114 (30.4%) of 375 of students in the school-based county, 122 (16.9%) of 663 of students in the provider-based county, and 131 (15.2%) of 861 students in the standard-of-care county (RRschool: 2.3 [95% CI: 1.9–2.9]; RRprovider: 1.2 [95% CI: 0.97–1.5]). CONCLUSIONS: Special efforts to promote influenza vaccination among rural, predominantly black students were associated with increased vaccination coverage. The school-based influenza vaccination intervention was associated with the highest levels of vaccination coverage. This study revealed the efficacy of school-based influenza education to improve vaccination rates among adolescents.

Rural parents' vaccination-related attitudes and intention to vaccinate middle and high school children against influenza following educational influenza vaccination intervention

Objective: This study examined changes in parental influenza vaccination attitudes and intentions after participating in school-based educational influenza vaccination intervention. Methods: Participants were drawn from three counties participating in a school-based influenza vaccination intervention in rural Georgia (baseline N=324; follow-up N=327). Data were collected pre- and post-intervention from phone surveys with parents’ with children attending middle- and high-school. Attitudes, beliefs, vaccination history, and intention to vaccinate were assessed. Results: Parents who participated in the intervention conditions reported significantly higher influenza vaccination rates in their adolescents, relative to a control group, as well as increased vaccination rates post-intervention participation relative to their baseline rates. Intervention participants reported greater intention to have their adolescent vaccinated in the coming year compared to control parents. Significant differences were observed post intervention in perceived barriers and benefits of vaccination. Conclusions: These findings suggest that a school-delivered educational influenza vaccination intervention targeting parents and teens may influence influenza vaccination in rural communities. Future influenza vaccination efforts geared toward the parents of rural middle- and high-school students may benefit from addressing barriers and benefits of influenza vaccination.

Development, theoretical framework, and evaluation of a parent and teacher-delivered intervention on adolescent vaccination.

The Advisory Committee on Immunization Practices recommended immunization schedule for adolescents includes three vaccines (tetanus, diphtheria, and acellular pertussis [Tdap]; human papillomavirus [HPV] vaccine; and meningococcal conjugate vaccine [MCV4]) and an annual influenza vaccination. Given the increasing number of recommended vaccines for adolescents and health and economic costs associated with nonvaccination, it is imperative that effective strategies for increasing vaccination rates among adolescents are developed. This article describes the development, theoretical framework, and initial first-year evaluation of an intervention designed to promote vaccine acceptance among a middle and high school–based sample of adolescents and their parents in eastern Georgia. Adolescents, parents, and teachers were active participants in the development of the intervention. The intervention, which consisted of a brochure for parents and a teacher-delivered curriculum for adolescents, was guided by constructs from the health belief model and theory of reasoned action. Evaluation results indicated that our intervention development methods were successful in creating a brochure that met cultural relevance and the literacy needs of parents. We also demonstrated an increase in student knowledge of and positive attitudes toward vaccines. To our knowledge, this study is the first to extensively engage middle and high school students, parents, and teachers in the design and implementation of key theory-based educational components of a school-based, teacher-delivered adolescent vaccination intervention.