Cost-effectiveness of Adult Vaccination Strategies: Pneumococcal Conjugate vs. Polysaccharide Vaccine

February 22/29, 2012, Vol 307, No. 8, pp 749-874

Original Contributions
Cost-effectiveness of Adult Vaccination Strategies Using Pneumococcal Conjugate Vaccine Compared With Pneumococcal Polysaccharide Vaccine
Kenneth J. Smith, Angela R. Wateska, Mary Patricia Nowalk, Mahlon Raymund, J. Pekka Nuorti, Richard K. Zimmerman
JAMA. 2012;307(8):804-812.doi:10.1001/jama.2012.169

Context  The cost-effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) compared with 23-valent pneumococcal polysaccharide vaccine (PPSV23) among US adults is unclear.

Objective  To estimate the cost-effectiveness of PCV13 vaccination strategies in adults.

Design, Setting, and Participants A Markov state-transition model, lifetime time horizon, societal perspective. Simulations were performed in hypothetical cohorts of US 50-year-olds. Vaccination strategies and effectiveness estimates were developed by a Delphi expert panel; indirect (herd immunity) effects resulting from childhood PCV13 vaccination were extrapolated based on observed PCV7 effects. Data sources for model parameters included Centers for Disease Control and Prevention Active Bacterial Core surveillance, National Hospital Discharge Survey and Nationwide Inpatient Sample data, and the National Health Interview Survey.

Main Outcome  Measures Pneumococcal disease cases prevented and incremental costs per quality-adjusted life-year (QALY) gained.

Results In the base case scenario, administration of PCV13 as a substitute for PPSV23 in current recommendations (ie, vaccination at age 65 years and at younger ages if comorbidities are present) cost $28 900 per QALY gained compared with no vaccination and was more cost-effective than the currently recommended PPSV23 strategy. Routine PCV13 at ages 50 and 65 years cost $45 100 per QALY compared with PCV13 substituted in current recommendations. Adding PPSV23 at age 75 years to PCV13 at ages 50 and 65 years gained 0.00002 QALYs, costing $496 000 per QALY gained. Results were robust in sensitivity analyses and alternative scenarios, except when low PCV13 effectiveness against nonbacteremic pneumococcal pneumonia was assumed or when greater childhood vaccination indirect effects were modeled. In these cases, PPSV23 as currently recommended was favored.

Conclusion  Overall, PCV13 vaccination was favored compared with PPSV23, but the analysis was sensitive to assumptions about PCV13 effectiveness against nonbacteremic pneumococcal pneumonia and the magnitude of potential indirect effects from childhood PCV13 on pneumococcal serotype distribution.

Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Hib

February 22/29, 2012, Vol 307, No. 8, pp 749-874

Original Contributions
Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b
Yuelian Sun, Jakob Christensen, Anders Hviid, Jiong Li, Peter Vedsted, Jørn Olsen, Mogens Vestergaard
JAMA. 2012;307(8):823-831.doi:10.1001/jama.2012.165

Context  Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002.

Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months.

Design, Setting, and Participants  A population-based cohort study of 378 834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort.

Main Outcome  Measures Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study.

Results  A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100 000 person-days), 32 children after the second (1.3 per 100 000 person-days), and 201 children after the third (8.5 per 100 000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100 000 person-days), 12 children after the second (5.7 per 100 000 person-days), and 27 children after the third (13.1 per 100 000 person-days) vaccinations. The relative incidences from the SCCS study design were similar to the cohort study design. Within 7 years of follow-up, 131 unvaccinated children and 2117 vaccinated children were diagnosed with epilepsy, 813 diagnosed between 3 and 15 months (2.4 per 1000 person-years) and 1304 diagnosed later in life (1.3 per 1000 person-years). After vaccination, children had a lower risk of epilepsy between 3 and 15 months (HR, 0.63; 95% CI, 0.50-0.79) and a similar risk for epilepsy later in life (HR, 1.01; 95% CI, 0.66-1.56) vs unvaccinated children.

Conclusions  DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy.

Editorial: Prevention of Pneumococcal Infection With Vaccines

February 22/29, 2012, Vol 307, No. 8, pp 749-874

Prevention of Pneumococcal Infection With Vaccines: An Evolving Story
Eugene D. Shapiro
JAMA. 2012;307(8):847-849.doi:10.1001/jama.2012.194

Extract [first 150 words per JAMA convention]
The first vaccines to prevent pneumococcal infections, crude preparations of killed bacteria, were developed by Sir Almroth Wright in 1911 to try to alleviate the high mortality and morbidity among gold miners in South Africa.1 Discovery that antibodies against purified polysaccharides of the capsular surface of pneumococci were protective led to development of polysaccharide vaccines that were marketed in the 1940s. These vaccines were commercial failures because the advent of antimicrobials led to a perception that pneumococcal infections were no longer a major threat.2 Subsequent evidence of the persistence of significant morbidity from pneumococcal infections, as well as mortality rates of 25% to 30% in patients with invasive (including bacteremic) pneumococcal infections despite early treatment with antimicrobials, led to redevelopment of a polysaccharide vaccine, approved in the United States in 1977, that contained 14 of the more than 90 serotypes of pneumococci (responsible for about 80% of invasive …

Community-based treatment of severe childhood pneumonia

The Lancet  
Feb 25, 2012  Volume 379  Number 9817  p685 – 776

Community-based treatment of severe childhood pneumonia
Robert E Black, Shams El Arifeen

In 2010, an estimated 7·6 million children died before their fifth birthday, and more than a million of these deaths were due to pneumonia.1 Although progress is being made in expanding the use of vaccines to prevent pneumonia, many countries have yet to introduce these vaccines, especially the pneumococcal vaccine.2 Correct breastfeeding of children can also help prevent pneumonia deaths, but a high prevalence of suboptimum breastfeeding practices (eg, low rates of exclusive breastfeeding up to 6 months of age) is seen in all regions of the world.

Editorial: Avian influenza and the dual-use research debate

The Lancet Infectious Disease
Mar 2012  Volume 12  Number 3  p167 – 254

Avian influenza and the dual-use research debate
The Lancet Infectious Diseases

Since the first human cases of infection with avian influenza H5N1 were reported 15 years ago, the disease has caused 344 deaths among 583 known cases—a case fatality of nearly 60%. Despite the highly lethal nature of this virus, it is very rarely transmitted from birds to people, and even less frequently, if ever, transmitted from person to person. Nonetheless, the possibility of the virus mutating or recombining with another to develop pandemic potential is a bleak prospect for public health. So it is not surprising that the news that two groups of researchers have purposefully generated H5N1 strains that are transmitted easily in aerosols among ferrets, a widely used model of human influenza transmission, has generated a fierce debate about the conduct and dissemination of dual-use research, as reported in this month’s Newsdesk.

Series: Mass gatherings – modelling and research

The Lancet Infectious Disease
Mar 2012  Volume 12  Number 3  p167 – 254

Infectious disease surveillance and modelling across geographic frontiers and scientific specialties
Kamran Khan, Scott JN McNabb, Ziad A Memish, Rose Eckhardt, Wei Hu, David Kossowsky, Jennifer Sears, Julien Arino, Anders Johansson, Maurizio Barbeschi, Brian McCloskey, Bonnie Henry, Martin Cetron, John S Brownstein

Infectious disease surveillance for mass gatherings (MGs) can be directed locally and globally; however, epidemic intelligence from these two levels is not well integrated. Modelling activities related to MGs have historically focused on crowd behaviours around MG focal points and their relation to the safety of attendees. The integration of developments in internet-based global infectious disease surveillance, transportation modelling of populations travelling to and from MGs, mobile phone technology for surveillance during MGs, metapopulation epidemic modelling, and crowd behaviour modelling is important for progress in MG health. Integration of surveillance across geographic frontiers and modelling across scientific specialties could produce the first real-time risk monitoring and assessment platform that could strengthen awareness of global infectious disease threats before, during, and immediately after MGs. An integrated platform of this kind could help identify infectious disease threats of international concern at the earliest stages possible; provide insights into which diseases are most likely to spread into the MG; help with anticipatory surveillance at the MG; enable mathematical modelling to predict the spread of infectious diseases to and from MGs; simulate the effect of public health interventions aimed at different local and global levels; serve as a foundation for scientific research and innovation in MG health; and strengthen engagement between the scientific community and stakeholders at local, national, and global levels.

Research agenda for mass gatherings: a call to action
John S Tam, Maurizio Barbeschi, Natasha Shapovalova, Sylvie Briand, Ziad A Memish, Marie-Paule Kieny

Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs.

Antiviral resistance during the 2009 influenza A H1N1 pandemic

The Lancet Infectious Disease
Mar 2012  Volume 12  Number 3  p167 – 254

Antiviral resistance during the 2009 influenza A H1N1 pandemic: public health, laboratory, and clinical perspectives
Aeron C Hurt, Tawee Chotpitayasunondh, Nancy J Cox, Rod Daniels, Alicia M Fry, Larisa V Gubareva, Frederick G Hayden, David S Hui, Olav Hungnes, Angie Lackenby, Wilina Lim, Adam Meijer, Charles Penn, Masato Tashiro, Timothy M Uyeki, Maria Zambon, on behalf of the WHO Consultation on Pandemic Influenza A (H1N1) 2009 Virus Resistance to Antivirals

Influenza A H1N1 2009 virus caused the first pandemic in an era when neuraminidase inhibitor antiviral drugs were available in many countries. The experiences of detecting and responding to resistance during the pandemic provided important lessons for public health, laboratory testing, and clinical management. We propose recommendations for antiviral susceptibility testing, reporting results, and management of patients infected with 2009 pandemic influenza A H1N1. Sustained global monitoring for antiviral resistance among circulating influenza viruses is crucial to inform public health and clinical recommendations for antiviral use, especially since community spread of oseltamivir-resistant A H1N1 2009 virus remains a concern. Further studies are needed to better understand influenza management in specific patient groups, such as severely immunocompromised hosts, including optimisation of antiviral treatment, rapid sample testing, and timely reporting of susceptibility results.