The Lancet Infectious Diseases
Jun 2015 Volume 15 Number 6 p615-746
http://www.thelancet.com/journals/laninf/issue/current

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Articles
Statistical power and validity of Ebola vaccine trials in Sierra Leone: a simulation study of trial design and analysis
Dr Steven E Bellan, PhD, Juliet R C Pulliam, PhD, Carl A B Pearson, PhD, David Champredon, MSc, Spencer J Fox, BS, Laura Skrip, MPH, Prof Alison P Galvani, PhD, Manoj Gambhir, PhD, Ben A Lopman, PhD, Prof Travis C Porco, PhD, Prof Lauren Ancel Meyers, PhD, Jonathan Dushoff, PhD
Published Online: 14 April 2015
DOI: http://dx.doi.org/10.1016/S1473-3099(15)70139-8
Summary
Background
Safe and effective vaccines could help to end the ongoing Ebola virus disease epidemic in parts of west Africa, and mitigate future outbreaks of the virus. We assess the statistical validity and power of randomised controlled trial (RCT) and stepped-wedge cluster trial (SWCT) designs in Sierra Leone, where the incidence of Ebola virus disease is spatiotemporally heterogeneous, and is decreasing rapidly.
Methods
We projected district-level Ebola virus disease incidence for the next 6 months, using a stochastic model fitted to data from Sierra Leone. We then simulated RCT and SWCT designs in trial populations comprising geographically distinct clusters at high risk, taking into account realistic logistical constraints, and both individual-level and cluster-level variations in risk. We assessed false-positive rates and power for parametric and non-parametric analyses of simulated trial data, across a range of vaccine efficacies and trial start dates.
Findings
For an SWCT, regional variation in Ebola virus disease incidence trends produced increased false-positive rates (up to 0·15 at α=0·05) under standard statistical models, but not when analysed by a permutation test, whereas analyses of RCTs remained statistically valid under all models. With the assumption of a 6-month trial starting on Feb 18, 2015, we estimate the power to detect a 90% effective vaccine to be between 49% and 89% for an RCT, and between 6% and 26% for an SWCT, depending on the Ebola virus disease incidence within the trial population. We estimate that a 1-month delay in trial initiation will reduce the power of the RCT by 20% and that of the SWCT by 49%.
Interpretation
Spatiotemporal variation in infection risk undermines the statistical power of the SWCT. This variation also undercuts the SWCT’s expected ethical advantages over the RCT, because an RCT, but not an SWCT, can prioritise vaccination of high-risk clusters.
Funding
US National Institutes of Health, US National Science Foundation, and Canadian Institutes of Health Research.

Maternal and Child Health Journal
Volume 19, Issue 6, June 2015
http://link.springer.com/journal/10995/19/6/page/1

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Commentary
New Dialogue for the Way Forward in Maternal Health: Addressing Market Inefficiencies
Katharine McCarthy, Saumya Ramarao, Hannah Taboada
Abstract
Despite notable progress in Millennium Development Goal (MDG) five, to reduce maternal deaths three-quarters by 2015, deaths due to treatable conditions during pregnancy and childbirth continue to concentrate in the developing world. Expanding access to three effective and low-cost maternal health drugs can reduce preventable maternal deaths, if available to all women. However, current failures in markets for maternal health drugs limit access to lifesaving medicines among those most in need. In effort to stimulate renewed action planning in the post-MDG era, we present three case examples from other global health initiatives to illustrate how market shaping strategies can scale-up access to essential maternal health drugs. Such strategies include: sharing intelligence among suppliers and users to better approximate and address unmet need for maternal health drugs, introducing innovative financial strategies to catalyze otherwise unattractive markets for drug manufacturers, and employing market segmentation to create a viable and sustainable market. By building on lessons learned from other market shaping interventions and capitalizing on opportunities for renewed action planning and partnership, the maternal health field can utilize market dynamics to better ensure sustainable and equitable distribution of essential maternal health drugs to all women, including the most marginalized

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Methodological Notes
Post-disaster Health Indicators for Pregnant and Postpartum Women and Infants
Marianne E. Zotti, Amy M. Williams, Etobssie Wako
Abstract
United States (U.S.) pregnant and postpartum (P/PP) women and their infants may be particularly vulnerable to effects from disasters. In an effort to guide post-disaster assessment and surveillance, we initiated a collaborative process with nationwide expert partners to identify post-disaster epidemiologic indicators for these at-risk groups. This 12 month process began with conversations with partners at two national conferences to identify critical topics for P/PP women and infants affected by disaster. Next we hosted teleconferences with a 23 member Indicator Development Working Group (IDWG) to review and prioritize the topics. We then divided the IDWG into three population subgroups (pregnant women, postpartum women, and infants) that conducted at least three teleconferences to discuss the proposed topics and identify/develop critical indicators, measures for each indicator, and relevant questions for each measure for their respective population subgroup. Lastly, we hosted a full IDWG teleconference to review and approve the indicators, measures, and questions. The final 25 indicators and measures with questions (available online) are organized by population subgroup: pregnant women (indicators = 9; measures = 24); postpartum women (indicators = 10; measures = 36); and infants (indicators = 6; measures = 30). We encourage our partners in disaster-affected areas to test these indicators and measures for relevancy and completeness. In post-disaster surveillance, we envision that users will not use all indicators and measures but will select ones appropriate for their setting. These proposed indicators and measures promote uniformity of measurement of disaster effects among U.S. P/PP women and their infants and assist public health practitioners to identify their post-disaster needs.

The Milbank Quarterly
A Multidisciplinary Journal of Population Health and Health Policy
June 2015 Volume 93, Issue 2 Pages 223–445
http://onlinelibrary.wiley.com/doi/10.1111/milq.2015.93.issue-2/issuetoc

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Review Article
Advocacy for Health Equity: A Synthesis Review
LINDEN FARRER*, CLAUDIA MARINETTI, YOLINE KUIPERS CAVACO andCAROLINE COSTONGS
Article first published online: 4 JUN 2015
DOI: 10.1111/1468-0009.12112
Abstract
Context
Health inequalities are systematic differences in health among social groups that are caused by unequal exposure to—and distributions of—the social determinants of health (SDH). They are persistent between and within countries despite action to reduce them. Advocacy is a means of promoting policies that improve health equity, but the literature on how to do so effectively is dispersed. The aim of this review is to synthesize the evidence in the academic and gray literature and to provide a body of knowledge for advocates to draw on to inform their efforts.
Methods
This article is a systematic review of the academic literature and a fixed-length systematic search of the gray literature. After applying our inclusion criteria, we analyzed our findings according to our predefined dimensions of advocacy for health equity. Last, we synthesized our findings and made a critical appraisal of the literature.
Findings
The policy world is complex, and scientific evidence is unlikely to be conclusive in making decisions. Timely qualitative, interdisciplinary, and mixed-methods research may be valuable in advocacy efforts. The potential impact of evidence can be increased by “packaging” it as part of knowledge transfer and translation. Increased contact between researchers and policymakers could improve the uptake of research in policy processes. Researchers can play a role in advocacy efforts, although health professionals and disadvantaged people, who have direct contact with or experience of hardship, can be particularly persuasive in advocacy efforts. Different types of advocacy messages can accompany evidence, but messages should be tailored to advocacy target. Several barriers hamper advocacy efforts. The most frequently cited in the academic literature are the current political and economic zeitgeist and related public opinion, which tend to blame disadvantaged people for their ill health, even though biomedical approaches to health and political short-termism also act as barriers. These barriers could be tackled through long-term actions to raise public awareness and understanding of the SDH and through training of health professionals in advocacy. Advocates need to take advantage of “windows of opportunity,” which open and close quickly, and demonstrate expertise and credibility.
Conclusions
This article brings together for the first time evidence from the academic and the gray literature and provides a building block for efforts to advocate for health equity. Evidence regarding many of the dimensions is scant, and additional research is merited, particularly concerning the applicability of findings outside the English-speaking world. Advocacy organizations have a central role in advocating for health equity, given the challenges bridging the worlds of civil society, research, and policy.

New England Journal of Medicine
June 4, 2015 Vol. 372 No. 23
http://www.nejm.org/toc/nejm/medical-journal

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Perspective
International Health Care Systems
Brazil’s Family Health Strategy — Delivering Community-Based Primary Care in a Universal Health System
James Macinko, Ph.D., and Matthew J. Harris, M.B., B.S., D.Phil.
N Engl J Med 2015; 372:2177-218 1June 4, 2015 DOI: 10.1056/NEJMp1501140
[Initial text]
Brazil has made rapid progress toward universal coverage of its population through its national health system, the Sistema Único de Saúde (SUS). Since its emergence from dictatorship in 1985, Brazil — which has the world’s fifth-largest population and seventh-largest economy — has invested substantially in expanding access to health care for all citizens, a goal that is implicit in the Brazilian constitution and the principles guiding the national health system.1 The SUS comprises public and private health care institutions and providers, financed primarily through taxes with contributions from federal, state, and municipal budgets. Health care management is decentralized, and municipalities are responsible for most primary care services as well as some hospitals and other facilities. All publicly financed health services and most common medications are universally accessible and free of charge at the point of service for all citizens — even the 26% of the population enrolled in private health plans (see table)
An important innovation in the system has been the development, adaptation, and rapid scaling up of a community-based approach to providing primary health care…

Pediatrics
June 2015, VOLUME 135 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

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Article
Tdap Vaccine Effectiveness in Adolescents During the 2012 Washington State Pertussis Epidemic
Anna M. Acosta, MDa,b, Chas DeBolt, RN, MPHc, Azadeh Tasslimi, MPHc, Melissa Lewis, MPHd, Laurie K. Stewart, MSc, Lara K. Misegades, PhD, MSb, Nancy E. Messonnier, MDb, Thomas A. Clark, MD, MPHb, Stacey W. Martin, MSb, and Manisha Patel, MD, MSb
Author Affiliations
aEpidemic Intelligence Service, Scientific Education and Professional Development Program Office,
bMeningitis and Vaccine Preventable Disease Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, and
dBiostatistics Office, Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and
cCommunicable Disease Epidemiology, Washington State Department of Health, Shoreline, Washington
Abstract
BACKGROUND: Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among adolescents who have received all acellular vaccines are limited.
METHODS: To assess Tdap VE and duration of protection, we conducted a matched case-control study during the 2012 pertussis epidemic in Washington among adolescents born during 1993–2000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were included; 3 controls were matched by primary provider clinic and birth year to each case. Vaccination histories were obtained through medical records, the state immunization registry, and parent interviews. Participants were classified by type of pertussis vaccine received on the basis of birth year: a mix of whole-cell and acellular vaccines (1993–1997) or all acellular vaccines (1998–2000). We used conditional logistic regression to calculate odds ratios comparing Tdap receipt between cases and controls.
RESULTS: Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95% confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95% CI: −0.03% to 58%).
CONCLUSIONS: Tdap protection wanes within 2 to 4 years. Lack of long-term protection after vaccination is likely contributing to increases in pertussis among adolescents

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Article
First Pertussis Vaccine Dose and Prevention of Infant Mortality
Tejpratap S.P. Tiwari, MDa, Andrew L. Baughman, PhD, MPHb, and Thomas A. Clark, MD, MPHa
Author Affiliations
aMeningitis and Bacterial Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, and
bDivision of Global HIV/AIDS, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
Abstract
BACKGROUND: American infants are at highest risk of severe pertussis and death. We investigated the role of ≥1 pertussis vaccinations in preventing pertussis-related deaths and risk markers for death among infants aged <42 days.
METHODS: We analyzed characteristics of fatal and nonfatal infant pertussis cases reported nationally during 1991–2008. Infants were categorized into 2 age groups on the basis of eligibility to receive a first pertussis vaccine dose at age 6 weeks; dose 1 was considered valid if given ≥14 days before illness onset. Multivariable logistic regression was used to estimate the effect of ≥1 pertussis vaccine doses on outcome and risk markers.
RESULTS: Pertussis-related deaths occurred among 258 of 45 404 cases. Fatal and nonfatal cases were confirmed by culture (54% vs 49%) and polymerase chain reaction (31% vs 27%). All deaths occurred before age 34 weeks at illness onset; 64% occurred before age 6 weeks. Among infants aged ≥42 days, receiving ≥1 doses of vaccine protected against death (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]: 0.11–0.74), hospitalization (aOR: 0.69; 95% CI: 0.63–0.77), and pneumonia (aOR: 0.80; 95% CI: 0.68–0.95). Risk was elevated for Hispanic ethnicity (aOR: 2.28; 95% CI: 1.36–3.83) and American Indian/Alaska Native race (aOR: 5.15; 95% CI: 2.37–11.2) and lower for recommended antibiotic treatment (aOR: 0.28; 95% CI: 0.16–0.47). Among infants aged <42 days, risk was elevated for Hispanic ethnicity and lower with recommended antibiotic use.
CONCLUSIONS: The first pertussis vaccine dose and antibiotic treatment protect against death, hospitalization, and pneumonia.

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Special Article
Strategies to Decrease Pertussis Transmission to Infants
Kevin Forsyth, MD, PhDa, Stanley Plotkin, MDb, Tina Tan, MDc, and Carl Heinz Wirsing von König, MDd
Author Affiliations
aDepartment of Paediatrics and Child Health, Flinders Medical Centre, Flinders University, Adelaide, Australia;
bDepartment of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania;
cNorthwestern University, Feinberg School of Medicine, Chicago, Illinois; and
dLabor;Medizin Krefeld MVZ, Krefeld, Germany
Abstract
The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be vaccinated. Older infants are at risk when their vaccination schedules are incomplete. Infants also bear the greatest disease burden owing to their high risk for pertussis-related complications and death; therefore, protecting them is a high priority. Two vaccine strategies have been proposed to protect infants. The first involves vaccinating pregnant women, which directly protects through the passive transfer of pertussis antibodies. The second strategy, cocooning, involves vaccinating parents, caregivers, and other close contacts, which indirectly protects infants from transmission by preventing disease in those in close proximity. The goal of this review was to present and discuss evidence on these 2 strategies. Based on available data, the GPI recommends vaccination during pregnancy as the primary strategy, given its efficacy, safety, and logistic advantages over a cocoon approach. If vaccination during pregnancy is not feasible, then all individuals having close contact with infants <6 months old should be immunized consistent with local health authority guidelines. These efforts are anticipated to minimize pertussis transmission to vulnerable infants, although real-world effectiveness data are limited. Countries should educate lay and medical communities on pertussis and introduce robust surveillance practices while implementing these protective strategies.

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Commentary
Epidemic Pertussis and Acellular Pertussis Vaccine Failure in the 21st Century
James D. Cherry, MD, MSc
Author Affiliations
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California
[Initial text]
In this issue of Pediatrics Acosta et al1 present a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap) vaccine effectiveness study in adolescents in Washington State during the first 6 months of 2012. Their findings support the previous Tdap effectiveness data from Wisconsin.2 The duration of Tdap effectiveness is disappointing, particularly because case-control studies tend to inflate efficacy.3
In 4 recent publications (including 1 article in Pediatrics) I have discussed epidemic pertussis and why vaccines fail.4–7 Before discussing why Tdap vaccine effectiveness wanes so rapidly, it seems worthwhile to discuss how rapidly protection wanes after a natural infection in the pre-Tdap era and to take a realistic look at the resurgence of pertussis.
The resurgence of pertussis is often attributed to the switch from whole-cell pertussis vaccines to acellular products. However, the increase in reported pertussis began ∼14 years before the universal use of diphtheria-tetanus-acellular pertussis (DTaP) vaccines in childhood commenced. The 2 greatest contributors to the resurgence of pertussis are greater awareness and more sensitive diagnosis (the routine use …

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 6 June 2015)

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What Factors Might Have Led to the Emergence of Ebola in West Africa?
Kathleen A. Alexander, Claire E. Sanderson, Madav Marathe, Bryan L. Lewis, Caitlin M. Rivers, effrey Shaman, John M. Drake, Eric Lofgren, Virginia M. Dato, Marisa C. Eisenberg, Stephen Eubank
Published: June 4, 2015
DOI: 10.1371/journal.pntd.0003652
Abstract
An Ebola outbreak of unprecedented scope emerged in West Africa in December 2013 and presently continues unabated in the countries of Guinea, Sierra Leone, and Liberia. Ebola is not new to Africa, and outbreaks have been confirmed as far back as 1976. The current West African Ebola outbreak is the largest ever recorded and differs dramatically from prior outbreaks in its duration, number of people affected, and geographic extent. The emergence of this deadly disease in West Africa invites many questions, foremost among these: why now, and why in West Africa? Here, we review the sociological, ecological, and environmental drivers that might have influenced the emergence of Ebola in this region of Africa and its spread throughout the region. Containment of the West African Ebola outbreak is the most pressing, immediate need. A comprehensive assessment of the drivers of Ebola emergence and sustained human-to-human transmission is also needed in order to prepare other countries for importation or emergence of this disease. Such assessment includes identification of country-level protocols and interagency policies for outbreak detection and rapid response, increased understanding of cultural and traditional risk factors within and between nations, delivery of culturally embedded public health education, and regional coordination and collaboration, particularly with governments and health ministries throughout Africa. Public health education is also urgently needed in countries outside of Africa in order to ensure that risk is properly understood and public concerns do not escalate unnecessarily. To prevent future outbreaks, coordinated, multiscale, early warning systems should be developed that make full use of these integrated assessments, partner with local communities in high-risk areas, and provide clearly defined response recommendations specific to the needs of each community.

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 6 June 2015)

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Research Article
Updated Global Burden of Cholera in Endemic Countries
Mohammad Ali , Allyson R. Nelson, Anna Lena Lopez, David A. Sack
Published: June 4, 2015
DOI: 10.1371/journal.pntd.0003832
Abstract
Background
The global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. We overcame the limitation with the use of a spatial modelling technique in defining endemic countries, and accordingly updated the estimates of the global burden of cholera.
Methods/Principal Findings
Countries were classified as cholera endemic, cholera non-endemic, or cholera-free based on whether a spatial regression model predicted an incidence rate over a certain threshold in at least three of five years (2008-2012). The at-risk populations were calculated for each country based on the percent of the country without sustainable access to improved sanitation facilities. Incidence rates from population-based published studies were used to calculate the estimated annual number of cases in endemic countries. The number of annual cholera deaths was calculated using inverse variance-weighted average case-fatality rate (CFRs) from literature-based CFR estimates. We found that approximately 1.3 billion people are at risk for cholera in endemic countries. An estimated 2.86 million cholera cases (uncertainty range: 1.3m-4.0m) occur annually in endemic countries. Among these cases, there are an estimated 95,000 deaths (uncertainty range: 21,000-143,000).
Conclusion/Significance
The global burden of cholera remains high. Sub-Saharan Africa accounts for the majority of this burden. Our findings can inform programmatic decision-making for cholera control.
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Author Summary
The global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. If a country did not report cases even though the country had cholera, the country was classified as cholera free. This time we addressed this limitation by using a spatial modelling technique, which helped us define the cholera-endemic countries based on access to improved water and sanitation in the country as well as cholera incidence in neighboring countries. Our new estimate illustrates 2.9 million of cases and 95,000 deaths in 69 endemic countries, with the majority of the burden in Sub-Saharan Africa. The sustained high burden of cholera points to the necessity for integrated and improved control efforts, and these findings may help programmatic decision-making for controlling the disease in endemic countries.

PLoS Pathogens
http://journals.plos.org/plospathogens/
(Accessed 6 June 2015)
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Pearls
A 21st Century Perspective of Poliovirus Replication
Nicolas Lévêque, Bert L. Semler
Published: June 4, 2015
DOI: 10.1371/journal.ppat.1004825
Featured in PLOS Collections
Why Poliovirus Replication Has Been Studied for More Than 50 Years

Poliovirus is the etiologic agent of poliomyelitis, an acute flaccid paralysis affecting 1%–2% of infected patients and, on rare occasions, causing death by paralyzing muscles that control the throat or breathing. A striking feature of infection is lifelong disabilities that may affect survivors of the acute disease. Transmitted by the fecal—oral and oral—oral route, this virus (three serotypes) was one of the most feared pathogens in industrialized countries during the 20th century affecting hundreds of thousands of children every year, via outbreaks during warm summer months. Although there are highly effective vaccines to control poliomyelitis, it remains endemic in a few countries, from which spread and outbreaks continue to occur throughout the world. Since its discovery in 1908, poliovirus has been intensively studied to better understand and control this formidable pathogen. The history of poliovirus is not, however, limited to the fight against the disease. Poliovirus replication studies also have played important roles in the development of modern virology since poliovirologists and, more generally, picornavirologists have been pioneers in many domains of molecular virology. Poliovirus was, for example, the first animal RNA virus to have its complete genome sequence determined, the first RNA animal virus for which an infectious clone was constructed, and, along with the related rhinovirus, the first human virus that had its three-dimensional structure solved by X-ray crystallography. Indeed, the history of over half a century of poliovirus replication studies is marked by major discoveries, many of which are summarized here and illustrated in Fig 1…

Revista Panamericana de Salud Pública/Pan American Journal of Public Health (RPSP/PAJPH)
March 2015 Vol. 37, No.
http://www.paho.org/journal/index.php?option=com_content&view=article&id=158&Itemid=266&lang=en

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Prevalence of cholera risk factors between migrant Haitians and Dominicans in the Dominican Republic [Prevalencia de los factores de riesgo de cólera entre los inmigrantes haitianos y los dominicanos en la República Dominicana]
Andrea J. Lund, Hunter M. Keys, Stephanie Leventhal, Jennifer W. Foster, and Matthew C. Freeman

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Adequação da assistência pré-natal segundo as características maternas no Brasil [Adequacy of prenatal care according to maternal characteristics in Brazil]
Rosa Maria Soares Madeira Domingues, Elaine Fernandes Viellas, Marcos Augusto Bastos Dias, Jacqueline Alves Torres, Mariza Miranda Theme-Filha, Silvana Granado Nogueira da Gama e Maria do Carmo Leal

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A systematic review of nursing research priorities on health system and services in the Americas [Revisión sistemática de las prioridades de investigación de enfermería en sistemas y servicios de salud en la Región de las Américas]
Alessandra Bassalobre Garcia, Silvia Helena De Bortoli Cassiani,and Ludovic Reveiz

Tropical Medicine & International Health
July 2015 Volume 20, Issue 7 Pages 821–966
http://onlinelibrary.wiley.com/doi/10.1111/tmi.2015.20.issue-7/issuetoc

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Pneumococcal carriage in rural Gambia prior to the introduction of pneumococcal conjugate vaccine: a population-based survey (pages 871–879)
Effua Usuf, Henry Badji, Abdoulie Bojang, Sheikh Jarju, Usman Nurudeen Ikumapayi, Martin Antonio, Grant Mackenzie and Christian Bottomley
Article first published online: 6 APR 2015 | DOI: 10.1111/tmi.12505
Abstract
Objective
To evaluate pneumococcal colonisation before and after the introduction of pneumococcal conjugate vaccine (PCV) in eastern Gambia.
Methods
Population-based cross-sectional survey of pneumococcal carriage between May and August 2009 before the introduction of PCV into the Expanded Program on Immunization. Nasopharyngeal swabs were collected from all household members, but in selected households, only children aged 6–10 years were swabbed. This age group participated in an earlier trial of a nine-valent PCV between 2000 and 2004.
Results
The prevalence of nasopharyngeal pneumococcal carriage in 2933 individuals was 72.0% in underfives (N = 515), 41.6% in children aged 5–17 (N = 1508) and 13.0% in adults ≥18 (N = 910) years. The age-specific prevalence of serotypes included in PCV7, PCV10 and PCV13 was 24.7%, 26.6% and 46.8% among children <5 years of age; 8.5%, 9.2% and 17.7% among children 5–17 years; and 2.5%, 3.3% and 5.5% among adults ≥18 years. The most common serotypes were 6A (13.1%), 23F (7.6%), 3 (7.3%), 19F (7.1%) and 34 (4.6%). There was no difference in the overall carriage of pneumococci between vaccinated and unvaccinated children 8 years after the primary vaccination with three doses of PCV (48.3% vs. 41.1%).
Conclusion
Before the introduction of PCV, serotypes included in PCV13 accounted for about half the pneumococcal serotypes in nasopharyngeal carriage. Thus, the potential impact of PCV13 on pneumococcal disease in the Gambia is substantial.

Vaccine
Volume 33, Issue 28, Pages 3159-3262 (22 June 2015)
http://www.sciencedirect.com/science/journal/0264410X/33

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Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS) United States, 2000–2013
Original Research Article
Pages 3171-3178
Beth F. Hibbs, Pedro L. Moro, Paige Lewis, Elaine R. Miller, Tom T. Shimabukuro
Abstract
Importance
Vaccination errors are preventable events. Errors can have impacts including inadequate immunological protection, possible injury, cost, inconvenience, and reduced confidence in the healthcare delivery system.
Objectives
To describe vaccination error reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and identify opportunities for prevention.
Methods
We conducted descriptive analyses using data from VAERS, the U.S. spontaneous surveillance system for adverse events following immunization. The VAERS database was searched from 2000 through 2013 for U.S. reports describing vaccination errors and reports were categorized into 11 error groups. We analyzed numbers and types of vaccination error reports, vaccines involved, reporting trends over time, and descriptions of errors for selected reports.
Results
We identified 20,585 vaccination error reports documenting 21,843 errors. Annual reports increased from 10 in 2000 to 4324 in 2013. The most common error group was “Inappropriate Schedule” (5947; 27%); human papillomavirus (quadrivalent) (1516) and rotavirus (880) vaccines were most frequently involved. “Storage and Dispensing” errors (4983; 23%) included mostly expired vaccine administered (2746) and incorrect storage of vaccine (2202). “Wrong Vaccine Administered” errors (3372; 15%) included mix-ups between vaccines with similar antigens such as varicella/herpes zoster (shingles), DTaP/Tdap, and pneumococcal conjugate/polysaccharide. For error reports with an adverse health event (5204; 25% of total), 92% were classified as non-serious. We also identified 936 vaccination error clusters (i.e., same error, multiple patients, in a common setting) involving over 6141 patients. The most common error in clusters was incorrect storage of vaccine (582 clusters and more than 1715 patients).
Conclusions
Vaccination error reports to VAERS have increased substantially. Contributing factors might include changes in reporting practices, increasing complexity of the immunization schedule, availability of products with similar sounding names or acronyms, and increased attention to storage and temperature lapses. Prevention strategies should be considered.

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Estimates of pertussis vaccine effectiveness in United States air force pediatric dependents
Original Research Article
Pages 3228-3233
Greg Wolff, Michael Bell, James Escobar, Stefani Ruiz
Abstract
Background
Pertussis vaccination compliance is critical for reduction in the prevalence of disease; however, the current acellular pertussis vaccine may not provide sufficient protection from infection. This study examined acellular pertussis vaccine effectiveness (VE) for Air Force dependents less than 12 years of age.
Methods
We conducted a case-control study among Air Force pediatric dependents from 2011 to 2013, comparing cases with positive pertussis test results to controls who received the same lab tests with a negative result. Our study population was categorized by age group and vaccination status based on the Centers for Disease Control and Prevention recommended pertussis vaccination schedule. VE was calculated with respect to vaccination status and pertussis lab results.
Results
We compared 27 pertussis laboratory positive cases with 974 pertussis laboratory negative controls, 2 months to <12 years old. Comparing completely vaccinated to non-vaccinated patients, the overall VE was 78.3% (95% confidence interval (CI): 48.6, 90.8; p < 0.001). VE was highest among those 15 months to <6 years old: 97.6% (95% CI: 78.5, 99.7; p < 0.001). Children 6 to <12 years old had the lowest VE: 48.5% (95% CI: −74.0, 84.7; p = 0.28). Comparing partially vaccinated patients to nonvaccinated patients yielded 64.2% (95% CI: −7.2, 88.1; p = 0.06) overall VE.
Conclusions
Acellular pertussis vaccination was effective at preventing laboratory confirmed pertussis among our Air Force pediatric dependent population, with highest protection among completely vaccinated, young children. Older children received the lowest amount of protection. Partial vaccination had near significant protection. Our overall calculated pertussis VE corroborates other pertussis VE studies looking at similar age groups.

Vaccine
Volume 33, Issue 27, Pages 3065-3158 (17 June 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/27

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Cost-effectiveness of norovirus vaccination in children in Peru
Original Research Article
Pages 3084-3091
Andrew J. Mirelman, Sarah Blythe Ballard, Mayuko Saito, Margaret N. Kosek, Robert H. Gilman
Abstract
Background
With candidate norovirus (NV) vaccines in a rapid phase of development, assessment of the potential economic value of vaccine implementation will be necessary to aid health officials in vaccine implementation decisions. To date, no evaluations have been performed to evaluate the benefit of adopting NV vaccines for use in the childhood immunization programs of low- and middle-income countries.
Methods
We used a Markov decision model to evaluate the cost-effectiveness of adding a two-dose NV vaccine to Peru’s routine childhood immunization schedule using two recent estimates of NV incidence, one for a peri-urban region and one for a jungle region of the country.
Results
Using the peri-urban NV incidence estimate, the annual cost of vaccination would be $13.0 million, offset by $2.6 million in treatment savings. Overall, this would result in 473 total DALYs averted; 526,245 diarrhea cases averted;153,735 outpatient visits averted; and 414 hospitalizations averted between birth and the fifth year of life. The incremental cost-effectiveness ratio would be $21,415 per DALY averted; $19.86 per diarrhea case; $68.23 per outpatient visit; and $26,298 per hospitalization. Using the higher jungle NV incidence rates provided a lower cost per DALY of $10,135. The incremental cost per DALY with per-urban NV incidence is greater than three times the 2012 GDP per capita of Peru but the estimate drops below this threshold using the incidence from the jungle setting. In addition to the impact of incidence, sensitivity analysis showed that vaccine price and efficacy play a strong role in determining the level of cost-effectiveness.
Conclusions
The introduction of a NV vaccine would prevent many healthcare outcomes in the Peru and potentially be cost-effective in scenarios with high NV incidence. The vaccine cost-effectiveness model could also be applied to the evaluation of NV vaccine cost-effectiveness in other countries. In resource-poor settings, where NV incidence rates are expected to be higher.

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Influenza vaccination coverage of Vaccine for Children (VFC)-entitled versus privately insured children, United States, 2011–2013
Original Research Article
Pages 3114-3121
Anup Srivastav, Yusheng Zhai, Tammy A. Santibanez, Katherine E. Kahn, Philip J. Smith, James A. Singleton
Abstract
Background
The Vaccines for Children (VFC) program provides vaccines at no cost to children who are Medicaid-eligible, uninsured, American Indian or Alaska Native (AI/AN), or underinsured and vaccinated at Federally Qualified Health Centers or Rural Health Clinics. The objective of this study was to compare influenza vaccination coverage of VFC-entitled to privately insured children in the United States, nationally, by state, and by selected socio-demographic variables.
Methods
Data from the National Immunization Survey-Flu (NIS-Flu) surveys were analyzed for the 2011–2012 and 2012–2013 influenza seasons for households with children 6 months–17 years. VFC-entitlement and private insurance status were defined based upon questions asked of the parent during the telephone interview. Influenza vaccination coverage estimates of children VFC-entitled versus privately insured were compared by t-tests, both nationally and within state, and within selected socio-demographic variables.
Results
For both seasons studied, influenza coverage for VFC-entitled children did not significantly differ from coverage for privately insured children (2011–2012: 52.0% ± 1.9% versus 50.7% ± 1.2%; 2012–2013: 56.0% ± 1.6% versus 57.2% ± 1.2%). Among VFC-entitled children, uninsured children had lower coverage (2011–2012: 38.9% ± 4.7%; 2012–2013: 44.8% ± 3.5%) than Medicaid-eligible (2011–2012: 55.2% ± 2.1%; 2012–2013: 58.6% ± 1.9%) and AI/AN children (2011–2012: 54.4% ± 11.3%; 2012–2013: 54.6% ± 7.0%). Significant differences in vaccination coverage among VFC-entitled and privately insured children were observed within some subgroups of race/ethnicity, income, age, region, and living in a metropolitan statistical area principle city.
Conclusions
Although finding few differences in influenza vaccination coverage among VFC-entitled versus privately insured children was encouraging, nearly half of all children were not vaccinated for influenza and coverage was particularly low among uninsured children. Additional public health interventions are needed to ensure that more children are vaccinated such as a strong recommendation from health care providers, utilization of immunization information systems, provider reminders, standing orders, and community-based interventions such as educational activities and expanded access to vaccination services.

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Burden of invasive pneumococcal disease (IPD) in Sri-Lanka: Deriving a reasonable measure for vaccine introduction decision making
Original Research Article
Pages 3122-3128
S. Kularatna, P.R. Wijesinghe, M.R.N. Abeysinghe, K. Karunaratne, L. Ekanayake
Abstract
Purpose
The lack of evidence on the disease burden has been an obstacle for decision-making on introducing pneumococcal vaccines in Sri-Lanka. Hence, the purpose of this study is to determine the incidence of invasive pneumococcal disease among children under five-years of age in Sri-Lanka’s Colombo district.
Methods
In a community-based study, using a sample of 2310 children, we identified syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis). The estimates of annual cumulative incidence of invasive pneumococcal disease were derived by having applied proportions of laboratory confirmed invasive pneumococcal disease among all-cause syndromes associated with pneumococcal infection obtained from the hospital-based invasive bacterial disease sentinel surveillance and findings of the community-based study to population parameters of the district. The estimates of invasive pneumococcal pneumonia and sepsis based on low-sensitive, culture confirmation were adjusted by a correction factor.
Results
The annual cumulative incidence of all-cause clinical syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis) were 1.3, 0.52, 0.39 per 100 children, respectively. The estimate of adjusted, invasive pneumococcal disease cumulative incidence was 206.3 per 100,000 while estimates of pneumococcal pneumonia, meningitis and sepsis cumulative incidence were 147.9, 13.2 and 45.2 per 100,000 under-five children.
Conclusion
Reasonable estimates of invasive pneumococcal disease could be derived by using incidence of clinical syndromes associated with pneumococcal disease obtained from population-based studies and proportion of pneumococcal infection among all-cause clinical syndromes associated with pneumococcal disease generated from hospital-based sentinel surveillance. These estimates may help informed decision-making on introduction of pneumococcal conjugated vaccine.

Vaccine
Volume 33, Issue 26, Pages 2955-3064 (12 June 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/26

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Poliovirus immunity in newly resettled adult refugees in Idaho, United States of America
Pages 2968-2970
Clay Roscoe, Ryan Gilles, Alex J. Reed, Matt Messerschmidt, Rebecca Kinney
Abstract
Background
In the United States, vaccines have eliminated wild poliovirus (WPV) infection, though resettling refugees may lack immunity and importation of WPV remains a concern.
Methods
A cross-sectional survey was performed to determine the prevalence of poliovirus immunity in adult refugees resettling in Boise, Idaho, U.S.A.; immunity was evaluated using two definitions: serotypes 1, 2 and 3 positive, or serotypes 1 and 3 positive.
Results
This survey evaluated 795 adult refugees between August 2010 and November 2012. Poliovirus immunity in adults >18 years was 55.3% for serotypes 1, 2 and 3 combined, and 60% for serotypes 1 and 3 only.
Conclusion
This study demonstrated a WPV immunity rate of <60% in a recently resettled adult refugee population in the United States, reinforcing the need to ensure poliovirus immunity in all newly arrived adult refugees, either by expanding pre-departure immunization or by screening for immunity at resettlement and vaccinating when indicated.

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Determinants of maternal immunization in developing countries
Original Research Article
Pages 2971-2977
Jayani Pathirana, Jerome Nkambule, Steven Black
Abstract
Background
Maternal immunization is an effective intervention to protect newborns and young infants from infections when their immune response is immature. Tetanus toxoid vaccination of pregnant women is the most widely implemented maternal vaccine in developing countries where neonatal mortality is the highest. We identified barriers to maternal tetanus vaccination in developing African and Asian countries to identify means of improving maternal immunization platforms in these countries.
Method
We categorized barriers into health system, health care provider and patient barriers to maternal tetanus immunization and conducted a literature review on each category. Due to limited literature from Africa, we conducted a pilot survey of health care providers in Malawi on barriers they experience in immunizing pregnant women.
Results
The major barriers of the health system are due to inadequate financial and human resources which translate to inadequate vaccination services delivery and logistics management. Health care providers are limited by poor attendance of Antenatal Care and inadequate knowledge on vaccinating pregnant women. Patient barriers are due to lack of education and knowledge on pregnancy immunization and socioeconomic factors such as low income and high parity.
Conclusion
There are several factors that affect maternal tetanus immunization. Increasing knowledge in health care providers and patients, increasing antenatal care attendance and outreach activities will aid the uptake of maternal immunization. Health system barriers are more difficult to address requiring an improvement of overall immunization services. Further analyses of maternal immunization specific barriers and the means of addressing them are required to strengthen the existing program and provide a more efficient delivery system for additional maternal vaccines.

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Vaccines4Kids: Assessing the impact of text message reminders on immunization rates in infants
Original Research Article
Pages 2984-2989
Victoria Niederhauser, Melissa Johnson, Abbas S. Tavakoli
Abstract
The purpose of this study was to examine the effect text messages (TM) immunization reminders have on immunization rates in the first 7 months of life. This randomized-control trial enrolled 57 parent/infant dyads and had a 74% completion rate (43) at the end of the study period. The study was approved by Committee on Human Subjects at the University of Hawaii Institutional Board Review. All participants completed a demographics form and a Barriers to Immunization Survey (SHOTS survey) at the start and end of the study. Parents received TM at 4, 7, 12, 15, 20, & 23 weeks of child’s age. The intervention group received immunization reminders and the control group received healthy baby messages. In the overall mixed model, between enrollment and 7 months of age, the barriers to immunizations decreased for all parents significantly. There were no significant differences in immunization rates between groups at 7 months of age. Positive responses from regarding TM interventions show this is a promising intervention, but further research is required regarding how to address behavior change and motivation for health prevention behaviors with TM.

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Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14
Original Research Article
Pages 3003-3009
Ivo M. Foppa, Po-Yung Cheng, Sue B. Reynolds, David K. Shay, Cristina Carias, Joseph S. Bresee, Inkyu K. Kim, Manoj Gambhir, Alicia M. Fry
Abstract
Background
Excess mortality due to seasonal influenza is substantial, yet quantitative estimates of the benefit of annual vaccination programs on influenza-associated mortality are lacking.
Methods
We estimated the numbers of deaths averted by vaccination in four age groups (0.5 to 4, 5 to 19, 20 to 64 and ≥65 yrs.) for the nine influenza seasons from 2005/6 through 2013/14. These estimates were obtained using a Monte Carlo approach applied to weekly U.S. age group-specific estimates of influenza-associated excess mortality, monthly vaccination coverage estimates and summary seasonal influenza vaccine effectiveness estimates to obtain estimates of the number of deaths averted by vaccination. The estimates are conservative as they do not include indirect vaccination effects.
Results
From August, 2005 through June, 2014, we estimated that 40,127 (95% confidence interval [CI] 25,694 to 59,210) deaths were averted by influenza vaccination. We found that of all studied seasons the most deaths were averted by influenza vaccination during the 2012/13 season (9398; 95% CI 2,386 to 19,897) and the fewest during the 2009/10 pandemic (222; 95% CI 79 to 347). Of all influenza-associated deaths averted, 88.9% (95% CI 83 to 92.5%) were in people ≥65 yrs. old.
Conclusions
The estimated number of deaths averted by the US annual influenza vaccination program is considerable, especially among elderly adults and even when vaccine effectiveness is modest, such as in the 2012/13 season. As indirect effects (“herd immunity”) of vaccination are ignored, these estimates represent lower bound estimates and are thus conservative given valid excess mortality estimates

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Special Section on Aeras Meeting Reports on Tuberculosis Vaccine Development; Edited by Stefan H.E. Kaufmann
Aeras-sponsored meeting reports: Aerosol TB vaccines, whole mycobacteria cell TB vaccines, and prevention of sustained Mycobacterium tuberculosis infection
Pages 3035-3037
Stefan H.E. Kaufmann

Vaccine
Volume 33, Supplement 2, 8 June 2015, Pages B29–B33
http://www.sciencedirect.com/science/journal/0264410X/33/supp/S2

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Supplement: Enhancing Vaccine Immunity and Value
An update of the progress and future needs of research and policies for enhancing vaccine value, based on the symposium organised by Novartis

Introduction to the supplement
Pages B1-B2
Rino Rappuoli
Abstract
In July of 2014, a symposium entitled “Enhancing Vaccine Immunity and Value” was held in Siena, Italy. The focus of the symposium was on how to best meet the challenge of developing and implementing vaccines for future disease targets. Vaccination has been responsible for averting estimated 3 billion cases of disease and more than 500 million lives to date through the prevention of infectious diseases. This has largely been responsible for dramatic increases in life span in developed countries. However, with the demographics of the world’s population are changing, with many adults now surviving into their 80s, we now face the challenge of protecting the aging and other underserved populations not only against infectious diseases but also against cancer and other chronic conditions that occur in older adults. To face this challenge, we must harness new technologies derived from recent advances in the fields of immunology, structural biology, synthetic biology and genomics that promise a revolution in the vaccine field. Specifically, vaccine adjuvants have the potential to harness the immune system to provide protection against new types of diseases, improve protection in young children and expand this protection to adults and the elderly. However, in order to succeed, we need to overcome the non-technical challenges that could limit the implementation of innovative vaccines, including controversies regarding the safety of adjuvants, increasing regulatory complexity, the inadequate methods used to assess the value of novel vaccines, and the resulting industry alienation from future investment. In this supplement, we have assembled manuscripts from lectures and discussions of the symposium last July that addressed two related questions: how to improve vaccine efficacy using breakthrough technologies and how to capture the full potential of novel vaccines.

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Valuing vaccines: Deficiencies and remedies
Review Article
Pages B29-B33
David E. Bloom
Abstract
Current evaluation models for the value of vaccines typically account for a small subset of the full social and economic benefits of vaccination. Health investments yield positive economic benefits via several channels at the household, community, and national levels. Underestimating, or worse, not considering these benefits can lead to ill-founded recommendations regarding the introduction of vaccines into immunization programs. The clear and strong links between health and wealth suggest the need to redesign valuation frameworks for vaccination so that the full costs may be properly weighed against the full benefits of vaccines.

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Bridging the gap: Need for a data repository to support vaccine prioritization efforts
Review Article
Pages B34-B39
Guruprasad Madhavan, Charles Phelps, Kinpritma Sangha, Scott Levin, Rino Rappuoli