Current level of influenza pandemic alert raised from phase 4 to 5
29 April 2009 — Based on assessment of all available information and following several expert consultations, Dr Margaret Chan, WHO’s Director-General raised the current level of influenza pandemic alert from phase 4 to 5. She stated that all countries should immediately activate their pandemic preparedness plans. At this stage, effective and essential measures include heightened surveillance, early detection and treatment of cases, and infection control in all health facilities. (accessed 29 April 2009)

Statement by WHO Director-General, Dr Margaret Chan
29 April 2009
Swine influenza

Ladies and gentlemen,

Based on assessment of all available information, and following several expert consultations, I have decided to raise the current level of influenza pandemic alert from phase 4 to phase 5.

Influenza pandemics must be taken seriously precisely because of their capacity to spread rapidly to every country in the world.

On the positive side, the world is better prepared for an influenza pandemic than at any time in history.

Preparedness measures undertaken because of the threat from H5N1 avian influenza were an investment, and we are now benefitting from this investment.

For the first time in history, we can track the evolution of a pandemic in real-time.

I thank countries who are making the results of their investigations publicly available. This helps us understand the disease.

I am impressed by the work being done by affected countries as they deal with the current outbreaks.

I also want to thank the governments of the USA and Canada for their support to WHO, and to Mexico.

Let me remind you. New diseases are, by definition, poorly understood. Influenza viruses are notorious for their rapid mutation and unpredictable behaviour.

WHO and health authorities in affected countries will not have all the answers immediately, but we will get them.

WHO will be tracking the pandemic at the epidemiological, clinical, and virological levels.

The results of these ongoing assessments will be issued as public health advice, and made publicly available.

All countries should immediately activate their pandemic preparedness plans. Countries should remain on high alert for unusual outbreaks of influenza-like illness and severe pneumonia.

At this stage, effective and essential measures include heightened surveillance, early detection and treatment of cases, and infection control in all health facilities.

This change to a higher phase of alert is a signal to governments, to ministries of health and other ministries, to the pharmaceutical industry and the business community that certain actions should now be undertaken with increased urgency, and at an accelerated pace.

I have reached out to donor countries, to UNITAID, to the GAVI Alliance, the World Bank and others to mobilize resources.

I have reached out to companies manufacturing antiviral drugs to assess capacity and all options for ramping up production.

I have also reached out to influenza vaccine manufacturers that can contribute to the production of a pandemic vaccine.

The biggest question, right now, is this: how severe will the pandemic be, especially now at the start?

It is possible that the full clinical spectrum of this disease goes from mild illness to severe disease. We need to continue to monitor the evolution of the situation to get the specific information and data we need to answer this question.

From past experience, we also know that influenza may cause mild disease in affluent countries, but more severe disease, with higher mortality, in developing countries.

No matter what the situation is, the international community should treat this as a window of opportunity to ramp up preparedness and response.

Above all, this is an opportunity for global solidarity as we look for responses and solutions that benefit all countries, all of humanity. After all, it really is all of humanity that is under threat during a pandemic.

As I have said, we do not have all the answers right now, but we will get them.

Thank you.

Statement by WHO Director-General, Dr Margaret Chan
27 April 2009

Swine influenza

The Emergency Committee, established in compliance with the International Health Regulations (2005), held its second meeting on 27 April 2009.

The Committee considered available data on confirmed outbreaks of A/H1N1 swine influenza in the United States of America, Mexico, and Canada. The Committee also considered reports of possible spread to additional countries.

On the advice of the Committee, the WHO Director-General decided on the following.

–    The Director-General has raised the level of influenza pandemic alert from the current phase 3 to phase 4.
. The change to a higher phase of pandemic alert indicates that the likelihood of a pandemic has increased, but not that a pandemic is inevitable.
.  As further information becomes available, WHO may decide to either revert to phase 3 or raise the level of alert to another phase.
. This decision was based primarily on epidemiological data demonstrating human-to-human transmission and the ability of the virus to cause community-level outbreaks.

–    Given the widespread presence of the virus, the Director-General considered that containment of the outbreak is not feasible. The current focus should be on mitigation measures.

–   The Director-General recommended not to close borders and not to restrict international travel. It was considered prudent for people who are ill to delay international travel and for  people developing symptoms following international travel to seek medical attention.

–  The Director-General considered that production of seasonal influenza vaccine should continue at this time, subject to re-evaluation as the situation evolves. WHO will facilitate the process needed to develop a vaccine effective against A(H1N1) virus.

–    The Director-General stressed that all measures should conform with the purpose and scope of the International Health Regulations.

Current phase of alert in the WHO global influenza preparedness plan

Pandemic Preparedness

In the 2009 revision of the phase descriptions, WHO has retained the use of a six-phased approach for easy incorporation of new recommendations and approaches into existing national preparedness and response plans. The grouping and description of pandemic phases have been revised to make them easier to understand, more precise, and based upon observable phenomena.

Phases 1-3 correlate with preparedness, including capacity development and response planning activities, while Phases 4-6 clearly signal the need for response and mitigation efforts. Furthermore, periods after the first pandemic wave are elaborated to facilitate post pandemic recovery activities.

The current WHO phase of pandemic alert is 4.

In nature, influenza viruses circulate continuously among animals, especially birds. Even though such viruses might theoretically develop into pandemic viruses, in Phase 1 no viruses circulating among animals have been reported to cause infections in humans.

In Phase 2 an animal influenza virus circulating among domesticated or wild animals is known to have caused infection in humans, and is therefore considered a potential pandemic threat.

In Phase 3, an animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Limited human-to-human transmission may occur under some circumstances, for example, when there is close contact between an infected person and an unprotected caregiver. However, limited transmission under such restricted circumstances does not indicate that the virus has gained
the level of transmissibility among humans necessary to cause a pandemic.

Phase 4 is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause “community-level outbreaks.” The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Any country that suspects or has verified such an event should
urgently consult with WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion.

Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.

Phase 6, the pandemic phase, is characterized by community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a global pandemic is under way.

During the post-peak period, pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave.

Previous pandemics have been characterized by waves of activity spread over months. Once the level of disease activity drops, a critical communications task will be to balance this information with the possibility of another wave. Pandemic waves can be separated by months and an immediate “at-ease” signal may be premature.

In the post-pandemic period, influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and
evaluation may be required.

WHO Update 2: Swine flu illness in the United States and Mexico

“26 April 2009 — As of 26 April 2009, the United States Government has reported 20 laboratory confirmed human cases of swine influenza A/H1N1 (8 in New York, 7 in California, 2 in Texas, 2 in Kansas and 1 in Ohio). All 20 cases have had mild Influenza-Like Illness with only one requiring brief hospitalization. No deaths have been reported. All 20 viruses have the same genetic pattern based on preliminary testing. The virus is being described as a new subtype of A/H1N1 not previously detected in swine or humans.

Also as of 26 April, the Government of Mexico has reported 18 laboratory confirmed cases of swine influenza A/H1N1. Investigation is continuing to clarify the spread and severity of the disease in Mexico. Suspect clinical cases have been reported in 19 of the country’s 32 states.

WHO and the Global Alert and Response Network (GOARN) are sending experts to Mexico to work with health authorities. WHO and its partners are actively investigating reports of suspect cases in other Member States as they occur, and are supporting field epidemiology activities, laboratory diagnosis and clinical management.

On Saturday, 25 April, upon the advice of the Emergency Committee called under the rules of the International Health Regulations, the Director-General declared this event a Public Health Emergency of International Concern. WHO is not recommending any travel or trade restrictions.”

http://www.who.int/csr/don/2009_04_26/en/index.html

Statement by WHO Director-General, Dr Margaret Chan on H1N1
25 April 2009

“Swine influenza In response to cases of swine influenza A(H1N1), reported in Mexico and the United States of America, the Director-General convened a meeting of the Emergency Committee to assess the situation and advise her on appropriate responses.

The establishment of the Committee, which is composed of international experts in a variety of disciplines, is in compliance with the International Health Regulations (2005).

The first meeting of the Emergency Committee was held on Saturday 25 April 2009.

After reviewing available data on the current situation, Committee members identified a number of gaps in knowledge about the clinical features, epidemiology, and virology of reported cases and the appropriate responses.

The Committee advised that answers to several specific questions were needed to facilitate its work. The Committee nevertheless agreed that the current situation constitutes a public health emergency of international concern.

Based on this advice, the Director-General has determined that the current events constitute a public health emergency of international concern, under the Regulations.

Concerning public health measures, in line with the Regulations the Director-General is recommending, on the advice of the Committee, that all countries intensify surveillance for unusual outbreaks of influenza-like illness and severe pneumonia.

The Committee further agreed that more information is needed before a decision could be made concerning the appropriateness of the current phase 3.”

http://www.who.int/mediacentre/news/statements/2009/h1n1_20090425/en/index.html

FAQ: http://www.who.int/csr/swine_flu/swine_flu_faq.pdf

MMWR Dispatch: Update: Swine Influenza A (H1N1) Infections — California and Texas, April 2009 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0424a1.htm

The U.S. Department of Health and Human Services issued a nationwide public health emergency declaration in response to recent human infections with a newly discovered swine influenza A (swine flu) virus. HHS said “the formal declaration of a Public Health Emergency (PHE) is a tool that facilitates HHS’ preparation and mobilization for disasters and emergencies,” and “will help HHS prepare for prevention and mitigation activities by enabling Food and Drug Administration (FDA) emergency use authorizations of drugs, devices, or medical tests under certain circumstances.”  Specifically, the PHE “will enable the FDA to review and issue emergency use authorizations (EUAs) for the use of certain laboratory tests to help detect the newly discovered strain of influenza and for the emergency use of certain antivirals.”

Acting HHS Secretary Charles Johnson commented, “HHS is taking these steps today to be proactive in responding to this new influenza virus by offering national tools in support of community-led preparedness and response efforts. The declaration allows us the flexibility, while we learn more about the virus and its impact in the United States, to take additional steps to fully mobilize our prevention, treatment and mitigation capabilities should those actions become necessary.” In addition to the declaration, HHS said leaders are working together across operating divisions to coordinate response to the swine flu outbreak. “For example, the FDA, the National Institutes of Health, and the Centers for Disease Control and Prevention are working together to develop a vaccine precursor that could be used to develop a vaccine for this swine flu virus.” To date, there have been 20 confirmed cases of swine Influenza A (swH1N1) in California, Texas, Kansas, New York, and Ohio. No deaths in the U.S. have been reported due to the illness. Additional cases of the virus have been confirmed in Mexico and Canada.

The public health emergency declaration is available at www.hhs.gov/secretary/phe_swh1n1mhtml.

Eighty countries and territories will be participating in “vaccination week” campaigns in the Americas (25 April-2 May) and Europe (20-26 April). These campaigns against diseases such as influenza, measles, rotavirus, rubella and yellow fever are being combined with advocacy and social outreach activities to boost awareness of the importance of immunization. These annual initiatives focus on increasing immunization coverage, immunizing vulnerable and hard-to-reach populations as well as promoting the use of new and existing vaccines.

– Vaccination Week in the Americas
– European Immunization Week

http://www.who.int/immunization/newsroom/regions_unite_millions_vaccinated/en/index.html

Rwanda became the first developing nation to introduce Prevenar, Wyeth’s pneumococcal conjugate vaccine. The first doses were administered in a rural clinic east of Kigali to Rwandan children as “the first step in the rollout of the national pneumococcal immunisation programme, which aims to vaccinate nearly all Rwandan children younger than one by the end of 2009, and all Rwandan infants on a routine basis, thereafter.” Rwanda’s Health Minister Dr. Sezibera commented, “This is a proud day for Rwanda and an important milestone for the developing world. We are committed to saving the lives and improving the health of our most precious national resource – our children. With the introduction of this vaccine, our goal of significantly reducing child death in Rwanda will now be within reach.” Dr. Julian Lob-Levyt, CEO of the GAVI Alliance, said, “We applaud the Rwandan government for taking this step, and we are proud to join them in launching a new era in the delivery of vaccines designed to close the gap between rich and poor countries and improve child mortality throughout the developing world. If fully rolled out in GAVI countries, the pneumococcal vaccine could save the lives of more than 440,000 children by 2015. This would help achieve Millennium Development Goal 4. Today’s event would not be possible without the commitment of public and private partners who are making vaccines available to the poorest countries.”

(Business Wire, 22 April 2009)

The CDC received reports of 1,505 cases of malaria among persons in the United States, including one transfusion-related case and one fatal case, with onset of symptoms in 2007. The highest estimated relative case rates of malaria among travelers occurred among those returning from West Africa. Of 701 U.S. civilians who acquired malaria abroad, 441 (62.9%) reported that they had not followed an appropriate chemoprophylactic drug regimen. Persons at risk for malaria infection should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites.

Malaria Surveillance United States, 2007   MMWR Surveillance Summaries, April 17, 2009 / Vol. 58 / No. SS-2

Sanaria Inc. said that, with support from the PATH Malaria Vaccine Initiative (MVI), it has “initiated a Phase 1 clinical trial — the first tests in adult volunteers — of its unique malaria vaccine candidate. Unlike other malaria vaccine candidates, Sanaria’s approach deploys a weakened form of the whole malaria parasite harvested from irradiated mosquitoes instead of small portions of the parasite.” Sanaria’s vaccine candidate will be assessed in healthy US volunteers at two sites in Maryland — the US Naval Medical Research Center Clinical Trials Center in Bethesda and the Center for Vaccine Development at the University of Maryland School of Medicine in Baltimore. Recruitment has begun for the safety and efficacy study that will involve some 104 volunteers, with inoculation of the first groups expected to begin in mid-May.

Dr. Christian Loucq, Director of MVI, commented, “Initiation of this trial expands the spectrum of malaria vaccines in clinical development today. This trial marks a major achievement in a collaborative development effort that aims to determine whether Sanaria’s vaccine candidate is safe and effective.”

(PRNewswire, 23 April 2009)

The International Vaccine Institute (IVI) said a new oral cholera vaccine it developed has been licensed in India, “paving the way for the worldwide use of a low-cost cholera vaccine that is suitable for use in developing countries, where most cholera cases occur.”  Dr. John Clemens, Director-General of the IVI, said,”The licensure of the vaccine in India, where national regulatory authority is approved by the World Health Organization (WHO), paves the way for a wider use of the vaccine in cholera-endemic populations in Asia and elsewhere. We are delighted that the vaccine will be produced by Shantha Biotechnics, in Hyderabad, a company with a strong record of supplying high-quality vaccines to United Nations agencies, such as UNICEF.”

IVI said cholera remains an important public health problem in the developing world. In 2007, 177,963 cholera cases and 4,031 deaths were reported to WHO from 53 countries, with 94 percent of cases reported from Africa. The true figures are likely to be much higher, due to under-reporting, and as many as 120,000 deaths are estimated to occur each year from the disease. A recent outbreak in Zimbabwe has infected nearly 80,000 people, killing at least 4,000 since last August.

IVI noted that “despite recommendations from WHO for the use of new-generation oral cholera vaccines in 2001, no country has yet introduced cholera vaccines into its immunization program, with the exception of Vietnam, which has been using a locally produced oral cholera vaccine since 1997 following technology transfer from Swedish scientists. There is only one internationally licensed oral cholera vaccine that is currently available. But this vaccine, Dukoral produced by Crucell/SBL Vaccines, is too expensive ($30 in Scandinavia, $18 in Bangladesh) for developing country populations who need the vaccine most, and has been used mainly by travelers from developed countries.”

http://www.ivi.org/event_news/news_view.asp?enid=95

Journal of Infectious Diseases
15 May 2009  Volume 199, Number 10
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARY
Human Adenovirus 14a: A New Epidemic Threat
Gregory C. Gray and Margaret L. Chorazy
Center for Emerging Infectious Diseases, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City

MAJOR ARTICLE
Outbreak of Severe Respiratory Disease Associated with Emergent Human Adenovirus Serotype 14 at a US Air Force Training Facility in 2007
Jacqueline E. Tate,1; Michel L. Bunning,3; Lisa Lott,4; Xiaoyan Lu,1; John Su,2,6; David Metzgar,7; Lorie Brosch,3; Catherine A. Panozzo,1; Vincent C. Marconi,5; Dennis J. Faix,7; Mila Prill,1; Brian Johnson,1; Dean D. Erdman,1; Vincent Fonseca,6; Larry J. Anderson,1 and Marc-Alain Widdowson1

Background.In 2007, a US Air Force training facility reported a cluster of severe respiratory illnesses associated with a rare human adenovirus (Ad) serotype, Ad14. We investigated this outbreak to better understand its epidemiology, clinical spectrum, and associated risk factors.

Methods.Data were collected from ongoing febrile respiratory illness (FRI) surveillance and from a retrospective cohort investigation. Because an Ad7 vaccine is in development, Ad7 antibody titers in pretraining serum samples from trainees with mild and those with severe Ad14 illness were compared.

Results.During 2007, an estimated 551 (48%) of 1147 trainees with FRI were infected with Ad14; 23 were hospitalized with pneumonia, 4 required admission to an intensive care unit, and 1 died. Among cohort members ( ), the Ad14 infection rate was high (50%). Of those infected, 40% experienced FRI. No cohort members were hospitalized. Male sex (risk ratio [RR], 4.7 [95% confidence interval {CI}, 2.2-10.1]) and an ill close contact (RR, 1.6 [95% CI, 1.2-2.2]) were associated with infection. Preexisting Ad7 neutralizing antibodies were found in 7 (37%) of 19 Ad14‐positive trainees with mild illness but in 0 of 16 trainees with Ad14 pneumonia ( ).

Conclusions.Emergence of Ad14, a rare Ad serotype, caused a protracted outbreak of respiratory illness among military recruits. Most infected recruits experienced FRI or milder illnesses. Some required hospitalization, and 1 died. Natural Ad7 infection may protect against severe Ad14 illness.

1Division of Viral Diseases and 2Office of Workforce and Career Development, Centers for Disease Control and Prevention, Atlanta, Georgia; 337th Medical Group, US Air Force, 4Epidemic Outbreak Surveillance, Modernization Directorate, Office of the Air Force Surgeon General, and 5Infectious Disease Service, Wilford Hall US Air Force Medical Center, Lackland Air Force Base, San Antonio, and 6Texas Department of State Health Services, Austin; 7Naval Health Research Center, San Diego, California

MAJOR ARTICLE
A Community‐Based Outbreak of Severe Respiratory Illness Caused by Human Adenovirus Serotype 14
Paul F. Lewis,1,a,b; Mark A. Schmidt,1,a; Xiaoyan Lu,3; Dean D. Erdman,3; Mary Campbell,2 ; Ann Thomas,1; Paul R. Cieslak,1; La Donna Grenz,1; Laura Tsaknardis,1; Curt Gleaves,2; Brian Kendall,2,b and David Gilbert2

Background.Human adenoviruses (Ads) typically cause mild illnesses in otherwise healthy hosts. We investigated a community‐based outbreak that had substantial morbidity caused primarily by Ad14, an uncommon serotype.

Methods.We retrospectively reviewed the medical records of all patients with confirmed cases of Ad infection from 1 November 2006 through 31 July 2007 in Oregon. Isolates were typed by sequencing. We analyzed clinical and laboratory variables to identify risk factors for severe Ad14 disease.

Results.Ad14 first emerged in Oregon in 2005. Of 67 cases of Ad infection detected during the study period, 40 (60%) involved Ad14. Most of the 38 Ad14‐infected patients who had medical records available for review presented with fever and cough; 29 (76%) required hospitalization, 23 (61%) required supplemental oxygen, 18 (47%) required critical care, 9 (24%) required vasopressors, and 7 (18%) died. Lobar infiltrates on chest radiographs suggestive of bacterial pneumonia were common among those needing hospitalization. Older age, chronic underlying condition, low absolute lymphocyte counts, and elevated creatinine levels were associated with severe illness. Except for 1 case of possible hospital transmission, we identified no epidemiological links among patients.

Conclusion.Ad14 emerged in Oregon in 2005 and became the predominant circulating type by 2007. Infection with this uncommon virus was primarily associated with a community‐acquired pneumonia syndrome and caused substantial morbidity and mortality.

1Oregon Public Health Division and 2Providence Portland Medical Center, Portland; 3Centers for Disease Control and Prevention, Atlanta, Georgia

The Lancet
Apr 25, 2009  Volume 373  Number 9673  Pages 1399 – 1494
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Resistance to the Affordable Medicines Facility for malaria?
The Lancet

“Last week, an innovative financing mechanism, the Affordable Medicines Facility for malaria ( AMFm), was officially launched. The AMFm will make the most effective treatment for malaria, artemisinin combination therapies (ACTs), more affordable and so has the potential to save thousands of lives. The Global Fund to Fight AIDS, Tuberculosis and Malaria will manage the new scheme.”

The Lancet Infectious Disease
May 2009   Volume 9  Number 5  Pages 265 – 330
http://www.thelancet.com/journals/laninf/issue/current

Incubation periods of acute respiratory viral infections: a systematic review
Original Text
Justin Lessler PhD, Nicholas G Reich BA, Prof Ron Brookmeyer PhD, Prof Trish M Perl MD, Prof Kenrad E Nelson MD, Derek AT Cummings PhD

Summary
Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8-6·3) for adenovirus, 3·2 days (95% CI 2·8-3·7) for human coronavirus, 4·0 days (95% CI 3·6-4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3-1·5) for influenza A, 0·6 days (95% CI 0·5-0·6) for influenza B, 12·5 days (95% CI 11·8-13·3) for measles, 2·6 days (95% CI 2·1-3·1) for parainfluenza, 4·4 days (95% CI 3·9-4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4-2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.

The Lancet Infectious Disease
May 2009   Volume 9  Number 5  Pages 265 – 330
http://www.thelancet.com/journals/laninf/issue/current

H5N1 influenza vaccination policy in Japan Michiaki Masuda, Shigeo Sugita, Kazumichi Kuroda, Hidekazu Nishimura Vaccine preparedness and the timely use of stockpiled vaccines are important issues for tackling pandemic influenza.1 In Japan, based on the government’s Pandemic Influenza Preparedness Action Plan (PIPAP),2 the National Institute of Infectious Diseases, affiliated with the Ministry of Health, Labour and Welfare (MHLW), took the initiative to develop H5N1 vaccines in collaboration with domestic manufacturers. Consequently, production of H5N1 inactivated whole-virion vaccine containing aluminium hydroxide gel adjuvant was approved in October, 2007, for two Japanese manufacturers.

The Lancet Infectious Disease
May 2009   Volume 9  Number 5  Pages 265 – 330
http://www.thelancet.com/journals/laninf/issue/current

Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease
Original Text
Philippe Brouqui MD a , Vincenzo Puro MD b, Francesco M Fusco MD b, Barbara Bannister MSc c, Stephan Schilling MD d, Per Follin MD e, René Gottschalk MD f, Robert Hemmer MD g, Helena C Maltezou MD h, Kristi Ott MD i, Renaat Peleman MD j, Christian Perronne MD k, Gerard Sheehan MD l, Heli Siikamäki MD m, Peter Skinhoj MD n, Giuseppe Ippolito MD b, for the EUNID Working Group‡

Summary
The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.

Vaccine
Volume 27, Issue 22, Pages 2905-3012 (14 May 2009)
http://www.sciencedirect.com/science/journal/0264410X

Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: Benefits of mortality reduction versus risk of fatal intussusception
Pages 2916-2922
Manish M. Patel, Andrew D. Clark, Roger I. Glass, Harry Greenberg, Jacqueline Tate, Mathuram Santosham, Colin F.B. Sanderson, Duncan Steele, Margaret Cortese, Umesh D. Parashar
Abstract
Introduction
Recently developed rotavirus vaccines have the potential to reduce diarrhea mortality in children in developing countries. Available data to date do not indicate risk of intussusception with these new vaccines. To avoid a potential unanticipated risk post-licensure, it is recommended that rotavirus immunization be initiated before 12 weeks of age when background intussusception rates are low. This policy could exclude a substantial number of children from vaccination, especially in developing countries where delays in vaccination are common.
Methods
We conducted a scenario analysis to assess the potential benefits of mortality reduction from rotavirus versus the risk of fatal intussusception when the first dose of the vaccine is strictly administered by 12 weeks of age compared with a free strategy with vaccine administered before 1 year of age using data on rotavirus disease, vaccine safety and efficacy, and current diphtheria-tetanus-pertussis vaccination rates, and by incorporating hypothetical risks of intussusception.
Results
In developing countries, assuming vaccine efficacy of 50% and 75% for doses 1 and 2, respectively, and a hypothetical sixfold and threefold increased relative risk of intussusception within 7 days of doses 1 and 2, respectively, initiating rotavirus immunization before 12 weeks of age would prevent 194,564 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events. Administration of the first dose to infants up to 1 year of age would prevent an additional 54,087 rotavirus-associated deaths (total = 248,651) while potentially resulting in an additional 1226 intussusception deaths (total = 2332).
Conclusion
In developing countries, the additional lives saved by broadening the age restrictions for initiation of rotavirus vaccination would far outnumber the hypothetical excess intussusception deaths that would accompany such an approach

Vaccine
Volume 27, Issue 22, Pages 2905-3012 (14 May 2009)
http://www.sciencedirect.com/science/journal/0264410X

Human papillomavirus immunisation of adolescent girls and anticipated reporting of immune-mediated adverse events
Pages 2954-2958
Torbjörn Callréus, Henrik Svanström, Nete Munk Nielsen, Sigrid Poulsen, Palle Valentiner-Branth, Anders Hviid
Abstract
Determining incidence rates of potential adverse events before and after an immunisation programme is initiated, provides a useful framework for the evaluation of vaccine safety concerns. Human papillomavirus vaccination (HPV) of adolescent girls has recently been introduced in Denmark. Using a nationwide hospitalisation registry we estimated incidence rates of immune-mediated disorders before HPV vaccination in a cohort of 418,289 Danish girls aged 12-15 years. We further estimated the expected number of cases of immune-mediated disorders occurring in temporal relationship to a hypothetical HPV vaccination schedule purely by chance. Our results and analytical approach provides a framework for the evaluation of adverse event reports following immunisation of adolescent girls.

Vaccine
Volume 27, Issue 22, Pages 2905-3012 (14 May 2009)
http://www.sciencedirect.com/science/journal/0264410X

Singaporean men’s knowledge of cervical cancer and human papillomavirus (HPV) and their attitudes towards HPV vaccination
Pages 2989-2993
Marian Pitts, Anthony Smith, Samantha Croy, Anthony Lyons, Richard Ryall, Suzanne Garland, Mee Lian Wong, Tay Eng Hseon
Abstract
Little is known of men’s knowledge of cervical cancer and its links with human papillomavirus (HPV), or of their attitudes and beliefs about HPV vaccination. This is despite men’s sexual behaviour contributing to HPV transmission and their potential role in deciding whether their children are vaccinated against HPV. To address this, a comprehensive survey was conducted in Singapore where plans are underway for an HPV vaccination program. A representative sample of 930 Singaporean men was found to have moderate knowledge of cervical cancer but poor knowledge and awareness of HPV. Although these men showed strong support for HPV vaccination, overall findings highlight the importance of including men in education campaigns that aim to decrease the incidence of cervical and other HPV-related cancers and to increase the uptake of HPV vaccination.

The Weekly Epidemiological Record (WER) for 17 April 2009, vol. 84, 16 (pp 133-140) includes: Resurgence of wild poliovirus types 1 and 3 in 15 African countries, January 2008-March 2009.”

Introduction
The global Polio Eradication Initiative began in 1988. By 2006, transmission of indigenous wild poliovirus (WPV) type 2 had been interrupted globally, and transmission
of indigenous type 1 and type 3 (WPV1 and WPV3) had been interrupted in all but 4 countries worldwide. (The countries where transmission has not been interrupted are Afghanistan, India, Nigeria and Pakistan.)1 During 2002-2006, 20 previously polio-free countries were affected by importations of WPV1 originating from Nigeria;2, 3, 4 3 polio-free African countries were affected by WPV1 importation originating from India.1 (Polio-free countries are those that have no evidence of indigenous WPV transmission for >12 months and where subsequent cases are determined by genomic sequencing to be of external origin.)

Relatively few importations occurred in 2007; by the end of that year, 5 countries with importations still had not interrupted WPV1 outbreaks. During 2008 and early 2009, additional WPV1 and WPV3 importations occurred in 15 countries in Africa, including the 5 countries that had not interrupted outbreaks resulting from the earlier importations.

This report summarizes information on new WPV importation events and outbreaks occurring from January 2008 to the end of March 2009 as well as information on persistent outbreaks5 following importation into previously polio-free African countries as of 24 March 2009.
http://www.who.int/wer/2009/wer8416.pdf

Stanford University School of Medicine researchers announced the need for additional participants to complete the first study of a new vaccine against malaria. The NIH-funded Phase-1 clinical trial, underway at both Stanford and Vanderbilt University, “aims to test the safety of and immune response to different doses of the vaccine in a total of 72 healthy adults.”  Results from this study will allow a second trial to begin in Africa this year. Cornelia Dekker, MD, medical director of the Stanford-Lucile Packard Children’s Hospital Vaccine Program, said, “This a chance for those who know that malaria causes millions of deaths every year to step forward and help in the search for preventive vaccine. It’s through the testing of promising vaccine candidates that we may find out how to eradicate malaria.” The Stanford/Packard study “is looking to enroll healthy adults, ages 18 to 45. Over a 12-month period, participants will make 17 clinic visits to Stanford Hospital and will receive three injections into the upper arm muscle of either the vaccine or a placebo. Participants will receive $30 reimbursement for each non-vaccination clinic visit and $60 for each vaccination visit.” http://vaccines.stanford.edu/clinical_trials.html.

Novavax reported preclinical study results “showing that an investigational H1N1 virus-like particle (VLP) vaccine based on the 1918 Spanish influenza strain protected against both the Spanish flu and a highly pathogenic H5N1 avian influenza strain.” Novavax said the study, published in the March 25, 2009 online issue of the Journal of Virology, was conducted by scientists from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA and Novavax under a Collaborative Research and Development Agreement. Dr. Gale Smith, Vice President of Vaccine Development at Novavax, said, “The discovery that a VLP-based influenza vaccine candidate created through cell-based recombinant technology has the potential to protect against diverse strains of influenza has significant implications for both pre-pandemic and pandemic preparedness. A broadly protective vaccine administered prior to and during the first wave of a pandemic could prevent widespread morbidity and mortality from a newly emerged pandemic influenza strain and allow time for the development of strain-specific vaccines.”

(PRNewswire-FirstCall, 14 April 2009) www.novavax.com

[Editor’s Note: While we do not endorse any commercial market research organization or their work, we will share abstracts of such work where the information provides perspective for vaccine ethics and policy]

World Vaccines Market 2008-2013: Future Forecast, Critical Trends and Developments published by Renub Research

Market Overview

“The vaccines landscape is very different now as compared to few years back. With increasing public awareness about preventive healthcare and increased spending by governments for the same has once again put spotlight on the vaccines. Quality of life is expected to increase markedly with introduction of newer vaccines covering more and more diseases. Due to this vaccines, which were perceived as low margin business before, have now emerged as one of the most lucrative segments in the pharmaceutical industry. Moreover with the success of a number of blockbuster products, the market place has changed dramatically. Pharma major’s today look upon vaccines as a driver for their future growth.

“Already vaccines have become big business for pharmaceutical giants like GlaxoSmithKline, sanofi pasteur and Merck & Co. For e.g. GSK Bio, GSK’s vaccines arm, accounted for 8.4 percent of GSK’s pharmaceutical turnover in 2006. And it is expected that by 2012 companies like GSK, Sanofi-aventis, Merck & Co., and Wyeth vaccines arm will fetch them more than 10 percent of sales from vaccine as a percentage of overall pharma sales.

“Sector-wise, basic pediatrics share is declining as most of the vaccines in this sector are either off patent or newer and more effective vaccines have replaced them. Proprietary pediatrics and cancer pediatrics will define the future growth going forward. Vaccines like Prevnar (Pneumococcal vaccines), Gardasil (Cervical cancer vaccines) have crossed the sales of US$ 1 Billion by 2007. In fact Prevnar became the first vaccine to cross the US$ 2 Billion annual sales in 2007.

“With the growth in international travel vaccine market of adult/travel sector is also going to grow further. Malaria vaccines, Typhoid Vaccines and Japanese Encephalitis Vaccines are expected to grow further in the market. Malaria vaccine which is expected to launch in 2010 or 2011, is forecasted to be worth US$ 419 Million market by 2025. Typhoid vaccine market for travelers is expected to grow with a CAGR of 4 percent from 2003 to 2014.

“…Geographic segment-wise, China and India’s vaccine market will grow considerably in future and the Japanese vaccine market has also started to open up further from regulatory and political barriers. Overall the worldwide vaccine market had registered revenue of US$ 21 Billion in 2008.”

http://www.researchandmarkets.com/research/bd84fc/world_vaccines_mar

Vaccine
Volume 27, Issue 21, Pages 2731-2904 (11 May 2009)
http://www.sciencedirect.com/science/journal/0264410X

Health-care provision factors associated with child immunization coverage in a city centre and a rural area in Kabul, Afghanistan
Pages 2823-2829
Shafiqullah Hemat, Takehito Takano, Masashi Kizuki, Taufiq Mashal

Abstract
A total of 1327 households were surveyed in Kabul province, Afghanistan to evaluate child immunization coverage and its association with distance to health facilities, attendance at antenatal care, the place of delivery and contact by outreach activity. The proportion of fully immunized children, those who had received at least 1 dose of BCG, 3 doses of DPT, and 1 dose of measles vaccine, was 84.5% in the city centre and 60.7% in the rural area. Fully immunized status was positively associated with close proximity to a health facility (odds ratio [OR] = 1.92, [95%CI, 1.08, 3.39]), and attendance at antenatal care (OR = 1.39, [95%CI, 1.00, 1.93]) in the city centre, and outreach contact (OR = 11.6, [95%CI, 6.92, 19.4]) in the rural area after adjustment for demography, socio-economic factors, participation in health education and experiences of hardship. Attendance at antenatal care in the rural area (OR = 1.91, [95%CI, 1.35, 2.72]), and institutional delivery in the city centre and rural area (OR = 2.83, [95%CI, 1.20, 6.71]; OR = 2.17, [95%CI, 1.01, 4.64], respectively) were positively associated with antigen specific coverage. Improving multiple community conditions including health-care provision and socio-economic factors through close partnership among various sectors promotes the immunization program.

Vaccine
Volume 27, Issue 21, Pages 2731-2904 (11 May 2009)
http://www.sciencedirect.com/science/journal/0264410X

Community pharmacy involvement in vaccine distribution and administration
Pages 2858-2863
Salisa C. Westrick, Suntaree Watcharadamrongkun, Jeanine K. Mount, Michelle L. Breland

Abstract
This study identified the type and number of doses of vaccine purchased, distributed, and administered in community pharmacies. Telephone interviews were conducted with 1704 community pharmacies in 17 states (response rate = 69.1%). The 17-state population-level projections reveal that about 10% of hepatitis A, hepatitis B, meningococcal, MMR, and tetanus-containing vaccines for adults were administered in pharmacies and 90% were distributed to other sources for administration during July 2004-June 2005. Further, 24.1% of diphtheria-tetanus-pertussis for children (DTaP), 30.4% of influenza, 36.2% of pneumococcal polysaccharide, and 68.1% of travel vaccines in pharmacy inventory were administered in pharmacies, while the rest of vaccine doses were distributed to other immunizers.

WHO recommended “routine vaccination of young adolescent girls to protect again human papillovirus (or HPV), which causes cervical cancer, in all countries where the prevention of cervical cancer and/or other HPV-related diseases is a public health priority, vaccine introduction is programmatically feasible, sustainable financing can be secured, and the cost-effectiveness of vaccination strategies in the country or region has been duly considered.” The recommendation is presented in a position paper published in the Weekly Epidemiological Record at http://www.who.int/wer/2009/wer8415.pdf

WHO noted that use of the two HPV vaccines marketed internationally should be introduced as part of a coordinated strategy to prevent cervical cancer and other HPV-related diseases. This strategy should include education about reducing behaviours that increase the risk of disease, cervical screening, and diagnosis and treatment of precancerous lesions and cancer.

http://www.who.int/immunization/newsroom/recommendation_HPV_vaccination/en/index.html

The Weekly Epidemiological Record (WER) for 10 April 2009, vol. 84, 15 includes: Outbreak news – Meningococcal disease, African meningitis belt; Human papillomavirus vaccines WHO position paper; WHO Strategic Advisory Group of Experts on immunization: request for nominations.

http://www.who.int/wer/2009/wer8415.pdf

The GAVI Alliance announced that it “has fast tracked a US$55 million contribution to establish a stockpile of meningococcal vaccines and pay for reactive campaigns in the highly endemic African ‘meningitis belt’ countries.” GAVI said its contribution “will fund 45 million doses of vaccines through 2013 to support emergency outbreak responses in the most vulnerable countries.” Nina Schwalbe, Director of Policy at the GAVI Alliance, said, “It is the responsibility of GAVI and its partners UNICEF and WHO, to ensure timely access to life-saving existing vaccines.” The stockpile will be supplied with polysaccharide meningococcal vaccines, until a forthcoming conjugate vaccine becomes available. The funds are being channelled through UNICEF and the World Health Organization (WHO), two key members of the GAVI Alliance.

The GAVI media release noted that, due to the global shortage of meningococcal vaccine, a special mechanism was established in 1997 to ensure that the population most in need would receive the life-saving vaccine in a timely manner. This mechanism includes the careful review of country requests for vaccines for outbreak response by the International Coordination Group (ICG) for meningitis, members of which include the International Federation of Red Cross and Red Crescent Societies, Médecins Sans Frontières, UNICEF and WHO. Now, with the US$55 million GAVI grant, “the meningitis vaccine stockpile will provide a speedy response for epidemic control for the next five years.”

Shanelle Hall, Director of Supply at UNICEF, said, “Having funds available upfront to finance this vaccine is truly life-saving,” said. “This is a critical development because when a meningitis epidemic breaks out in the most vulnerable areas of the world, vaccines need to be deployed immediately to stop the spread and protect children and their families.” Routine immunisation is not possible with the currently available polysaccharide vaccine, currently the only meningococcal vaccine available to combat the recurring epidemics in developing countries. The vaccine “is not very effective in children under two years of age because they lack the ability to develop antibodies.” A conjugate vaccine conferring long-term protection is expected to be available later this year in developing countries. GAVI “has already committed US$ 29.5 million to introduce this new conjugate vaccine as soon as it is available for preventive campaigns in the two years to come. In the interval before the conjugate vaccine is available, polysaccharide vaccines protect at-risk populations and ensure a speedy response to epidemics.”

http://www.gavialliance.org/media_centre/press_releases/2009_04_09_Meningitis_A.php

Save the Children, PneumoADIP, Hedge Funds vs. Malaria & Pneumonia, and the GAVI Alliance “joined with Save the Children Artist Ambassadors Gwyneth Paltrow and Hugh Laurie” to establish an annual World Pneumonia Day on November 2, 2009.  The event is intended to increase awareness about and investments in prevention, diagnosis and treatment of pneumonia, which the media releases described as the “world’s top child killer” and world’s most neglected disease, killing more than 2 million children annually.

Charles MacCormack, president and CEO of Save the Children, said, “Pneumonia is the world’s number one killer of children. But with new vaccines, early diagnosis and proper treatment with antibiotics that cost less than a dollar, a child’s health can improve and lives can be saved.” Dr. Orin Levine, a pneumonia expert and associate professor at Johns Hopkins Bloomberg School of Public Health, commented, “In wealthier countries, we don’t often see life-threatening child pneumonia. It’s easy to forget that around the world, pneumonia is still killing more than 5500 kids every day. Pneumonia is both common and extremely serious, but with existing tools like vaccines and antibiotics, we can save more than a million children every year.”

The organizations have created a website to support the effort at http://www.WorldPneumoniaDay.org and a Facebook presence at  http://tinyurl.com/WorldPneumoniaDay

Full media release at: http://www.gavialliance.org/media_centre/press_releases/2009_04_06_World_Pneumonia_Day.php

The U.S. Food and Drug Administration “cleared for marketing” a new, more rapid test for the detection of influenza A/H5N1, a disease-causing subtype of the avian influenza A virus that can infect humans. The test, called AVantage A/H5N1 Flu Test, detects influenza A/H5N1 in throat or nose swabs collected from patients who have flu-like symptoms. The test identifies in less than 40 minutes a specific protein (NS1) that indicates the presence of the influenza A/H5N1 virus subtype. Previous tests cleared by the FDA to detect this influenza A virus subtype can take three or four hours to produce results. Daniel G. Schultz, M.D., director of the FDA’s Center for Devices and Radiological Health, commented, “This test is an important tool to help quickly identify emerging influenza A/H5N1 infections and reduce exposure to large populations,” said. “The clearance of this test represents a major step toward protecting the public from the threat of pandemic flu.” AVantage A/H5N1 Flu Test is manufactured by Arbor Vita Corporation, located in Sunnyvale, California

http://www.fda.gov/bbs/topics/NEWS/2009/NEW01987.html

JAMA
Vol. 301 No. 14, pp. 1407-1498, April 8, 2009
http://jama.ama-assn.org/current.dtl

NEWS AND ANALYSIS
Progress in Global Measles Control and Mortality Reduction, 2000-2007
JAMA. 2009;301(14):1430-1431.
[Extract per JAMA convention]
Despite the availability of a safe and effective vaccine since 1963, measles has been a major killer of children in developing countries (causing an estimated 750,000 deaths as recently as 2000), primarily because of underutilization of the vaccine.¹ At the World Health Assembly in 2008, all World Health Organization (WHO) member states reaffirmed their commitment to achieving a 90% reduction in measles mortality by 2010 compared with 2000, a goal that was established in 2005 as part of the Global Immunization Vision and Strategy.² This WHO-UNICEF comprehensive strategy for measles mortality reduction¹ focuses on 47 priority countries.* The strategy’s components include (1) achieving and maintaining high coverage (>90%) with the routinely scheduled first dose of measles-containing vaccine (MCV1) among children aged 1 year; (2) ensuring that all children receive a second opportunity for measles immunization (either through a second routine dose or through . . .

The Lancet
Apr 11, 2009  Volume 373  Number 9671   Pages 1223 – 1310
http://www.thelancet.com/journals/lancet/issue/current

Perspectives
Hongjie Yu: monitoring avian influenza in China
Mark Honigsbaum
“To many people the prospect of taking charge of an immunisation programme for an area twice the size of Texas would be daunting, especially when their brief was to eradicate polio-a disease rarely seen today in the west. But when Hongjie Yu was offered the chance, shortly after graduating from China Medical University, in 1994, to join the Center for Disease Control and Prevention in Liaoning he didn’t hesitate. Yu was to spend 7 years in Liaoning-a province in northern China with a population of 40 million-during which time he travelled in the province coordinating the delivery of polio and other vaccines to remote towns and villages.”

Vaccine
Volume 27, Issue 19, Pages 2529-2630 (28 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Estimating vaccination coverage: Validity of household-retained vaccination cards and parental recall
Pages 2534-2539
Elizabeth T. Luman, Tove K. Ryman, Mariana Sablan
Abstract
Public health programs rely on household-survey estimates of vaccination coverage as a basis of programmatic and policy decisions; however, the validity of estimates derived from household-retained vaccination cards and parental recall has not been thoroughly evaluated. Using data from a vaccination coverage survey conducted in the Western Pacific’s Northern Mariana Islands, we compared results from household data sources to medical record sources for the same children. We calculated the percentage of children aged 1, 2, and 6 years who received all vaccines recommended by age 12 months, 24 months, and for school entry, respectively. Coverage estimates based on vaccination cards ranged from 14% to 30% in the three age groups compared to 78-91% for the same children based on medical records. When cards were supplemented by parental recall, estimates were 51-53%. Concordance, sensitivity, specificity, positive and negative predictive values, and kappa statistics generally indicated poor agreement between household and medical record sources. Household-retained vaccination cards and parental recall were insufficient sources of information for estimating vaccination coverage in this population. This study emphasizes the importance of identifying reliable sources of vaccination history information and reinforces the need for awareness of the potential limitations of vaccination coverage estimated from surveys that rely on household-retained cards and/or parental recall.

Vaccine
Volume 27, Issue 19, Pages 2529-2630 (28 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age
Pages 2540-2547
Scott A. Halperin, Bruce Tapiero, Francisco Diaz-Mitoma, Barbara J. Law, Agnes Hoffenbach, Pamela S. Zappacosta, David Radley, Barbara J. McCarson, Jason C. Martin, Laura E. Brackett, John W. Boslego, Teresa M. Hesley, Prakash K. Bhuyan, Jeffrey L. Silber
Abstract
Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12 μg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3 μg or 6 μg]), and in hepatitis B surface antigen (HBsAg, 10 μg or 15 μg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity.

Vaccine
Volume 27, Issue 19, Pages 2529-2630 (28 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Attitudes towards HPV immunization of Italian mothers of adolescent girls and potential role of health professionals in the immunization program
Pages 2625-2629
Alberto E. Tozzi, Lucilla Ravà, D. Stat, Elisabetta Pandolfi, Maria G. Marino, Alberto G. Ugazio
Abstract
We assessed the knowledge of Italian mothers of adolescent girls about HPV and HPV vaccination, their willingness to immunize their daughters, and their perception of the role of different medical specialists in the HPV immunization strategy by a telephone interview. Fifty-four percent of the 807 interviewed mothers reported to have ever heard about HPV, and 84% of them were willing to immunize their daughters. Pediatricians most frequently provided information on HPV vaccine (31%), and were perceived as the preferred immunization providers (77%). Acceptance of HPV immunization was high and was not associated with knowledge of HPV.

[Editor’s Note: The following are excerpts from an open letter to the G20 from Dr Julian Lob-Levyt, CEO of the GAVI Alliance, and Professor Michel Kazatchkine, Executive Director of The Global Fund, on the eve of the G20 Summit held in London on 2 April 2009]

“…Over the past eight years we have seen a dramatic scale-up of investments to improve health for the world’s poor.  Those investments have been transformed into dramatic successes in the fight against the diseases of poverty. Between programmes supported by GAVI and the Global Fund alone, seven million deaths have either been averted or prevented. Other bilateral and multilateral efforts can show that their support has enabled similar results.    With a concerted effort we can jointly ensure that the ambition to meet the Millennium Development Goals (MDGs) can be realised.

“The G20 is meeting at a time of extraordinarily difficult challenges. the economic crisis that has engulfed the world is threatening to wipe out decades of hard-earned progress in reducing poverty. Relatively small reductions in financing could have dramatic negative effects on health services and lead to a loss of momentum that could take decades to repair.  As so often before, it is the poorest, particularly women and children, who will bear the brunt of this crisis.

“…Over the past few years, we have learned valuable lessons. We can now expand the experiences in fighting specific diseases into programmes to reduce child mortality more generally and to improve women’s health.  Investments in new vaccines to prevent pneumonia and diarrhoea – the two largest child killers – will have a significant impact on MDG4. Investments in proven prevention and treatment technologies can have a dramatic impact on the AIDS, TB and malaria burden.

“We are building a body of knowledge about what works in strengthening health systems to ensure a balanced, sustainable delivery of health services in a developing-country context.  Through the International Health Partnership we are putting the OECD’s principles of aid effectiveness into practice. The experience in institutions tailored to finance performance, such as GAVI and the Global Fund, provide important lessons in other fields of finance for development.

“We look forward to building on the successes of the past years, and continuing the progress towards a world where we can bring millions out of poverty and accelerate development and prosperity by reducing the burden of infectious and vaccine-preventable diseases.

“Now is the moment to invest in health.  It works.  It saves millions of lives.”
http://www.gavialliance.org/media_centre/statements/25_04_09__G20_letter_Global_Fund_GAVI.php

The Bill & Melinda Gates Foundation announced the opening of Round 3 of Grand Challenges Explorations, “a five-year, $100 million initiative to encourage bold and unconventional research on new global health solutions.” The Grand Challenges Explorations initiative “focuses on research areas where creative, unorthodox thinking is most urgently needed.” The topic areas for which proposals will be accepted in this round are:

– creating Low-Cost Diagnostics for Priority Global Health Conditions

– creating New Tools to Accelerate the Eradication of Malaria

– creating New Vaccines for Diarrhea, HIV, Malaria, Pneumonia and Tuberculosis

– creating New Ways to Induce Mucosal Immunity

Explorations offers researchers the chance to win $100,000 grants to further their research. Proposals are being accepted online at Grand Challenges in Global Health through May 28, 2009. Grand Challenges Explorations http://www.gatesfoundation.org/press-releases/Pages/round-three-grand-challenges-explorations-090402.aspx

PATH released a new briefing paper which reports that “rotavirus vaccines have the potential to save more than 2.5 million lives by 2025.” PATH notes that the vaccines are already in use in North America, Latin America, and Europe, and “are urgently needed in Africa and Asia-where the disease burden is greatest.” Every child in the world, regardless of socio-economic status or country of origin, will likely contract rotavirus by age three, and is responsible for more than 500,000 deaths and two million hospitalizations annually. More than 85 percent of these deaths occur in developing countries in Africa and Asia, where access to simple, lifesaving treatments can be severely limited.

Dr. John Wecker, director of Immunization Solutions at PATH, said, “Rotavirus is one of the most deadly diseases children in the developing world face. Vaccination holds the key to making this disease one of the most preventable. We need to stand ready to deliver vaccines to children in Africa and Asia, where most rotavirus deaths occur.” In April, the WHO will review results from a large-scale clinical trial in Africa of the GSK vaccine. Findings from similar trials of Merck’s RotaTeq conducted in Africa and Asia will be available later in fall 2009. These rotavirus vaccine trials provide critical evidence on vaccine performance in real-world settings.

Briefing Paper: “Common Virus and Senseless Killer: A Briefing Paper on Rotavirus,”: http://www.path.org/publications/details.php?i=1685

Wyeth Pharmaceuticals announced that it submitted a Biologic License Application (BLA) to the U.S. Food and Drug Administration for Prevnar 13 (Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM(197) Protein)). Last year, the FDA granted Prevnar 13 Fast Track designation, which is designed to facilitate review of products that address serious or potentially life-threatening conditions for which there is an unmet medical need. Wyeth said Prevnar 13 is designed to protect against the 13 most prevalent serotypes associated with pneumococcal disease (PD), the leading cause of vaccine-preventable death worldwide. Seven of these serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) are included in Prevnar, Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM(197) Protein) – “the current global standard in PD prevention in infants and young children.” The six additional serotypes (1, 3, 5, 6A, 7F and 19A) are associated with the greatest remaining burden of invasive disease. Both Prevnar 13 and Prevnar use CRM(197) – an immunological carrier protein with a 20-year history of use in pediatric vaccines, Wyeth said.

Wyeth noted that the Prevnar 13 submission to the FDA includes data from 13 Phase 3 studies, involving more than 7,000 infants and young children, and that it has initiated its global pediatric filings in late 2008 and, to date, has submitted regulatory applications for the 13-valent candidate vaccine in more than 40 countries worldwide. Prevnar 13 is also being studied in global Phase 3 clinical trials in adults, with regulatory submissions expected in 2010.

Pneumococcal disease “is complex and describes a group of illnesses, all of which are caused by the bacterium Streptococcus pneumoniae. PD affects both children and adults and includes invasive infections such as bacteremia/sepsis and meningitis, as well as pneumonia and otitis media (middle ear infection).”

(PRNewswire-FirstCall, 31 March 2009)

Children’s Hospitals and Clinics of Minnesota received the Immunization Excellence Award on 30 March 2009 at the National Influenza Vaccine Summit in Dallas, Texas. The award is co-sponsored by the American Medical Association and the Centers for Disease Control and Prevention. Mitch Rothholz, National Influenza Vaccine Summit Executive Committee Member and Awards Committee Chair, said, “These awards recognize champions within the immunization community who are making a difference within their communities. Children’s Hospitals and Clinics of Minnesota’s program integrated many elements and stakeholders to achieve a growth in the number of healthcare worker vaccinations and will serve as a best practice model for others.”

Patricia Stinchfield, CPN, director of pediatric infectious disease at Children’s, said. “Healthcare professionals can transmit influenza to vulnerable children up to two days before showing any signs that they are ill. Influenza can be fatal to some patients, such as infants who are too young to be immunized, or patients with suppressed immune systems. That’s why Children’s works so hard to limit exposure of influenza to children at the hospital.” In 2008, the program helped increase the hospital’s employee immunization rate to 74 percent, a 10 percent increase from the previous year. Children’s promotes the immunization program through newsletters, personal letters, presentations to workers, computerized tracking programs, and public postings of departmental vaccination rates.

(PRNewswire, 26 March 2009)

The U.S. Food and Drug Administration approved IXIARO, a vaccine to prevent Japanese encephalitis (JE) which is caused by a mosquito-transmitted virus found mainly in Asia. IXIARO will be the only vaccine for JE available in the United States. In Asia, JE affects about 30,000 to 50,000 people each year, resulting in 10,000 to 15,000 deaths. JE is rarely seen in the United States, with very few cases reported among civilians and military traveling from the United States to Asia. The virus that causes JE affects membranes around the brain and mild infections can occur without apparent symptoms other than fever and headache. In people who develop severe disease, JE usually starts as a flu-like illness but can worsen, causing high fever, neck stiffness, brain damage, coma, or even death. The disease is transmitted via infected mosquitoes; it is not spread from human to human. IXIARO is a second-generation JE vaccine, in that it is  manufactured using cell culture technology. IXIARO is manufactured by Intercell Biomedical, Livingston, U.K.

http://www.fda.gov/bbs/topics/NEWS/2009/NEW01981.html

The Weekly Epidemiological Record (WER) for 3 April 2009, vol. 84, 14 (pp 109-116) Includes: Outbreak news: – Cholera, Zimbabwe – update; Progress towards interrupting wild poliovirus transmission worldwide, 2008.

http://www.who.int/wer/2009/wer8414.pdf

New England Journal of Medicine
Volume 360 – April 2, 2009 – Number 14
http://content.nejm.org/current.shtml

Editorial
From India to the World – A Better Way to Prevent Cervical Cancer
Mark Schiffman, M.D., M.P.H., and Sholom Wacholder, Ph.D.
[Initial text per NEJM convention]
“In this issue of the Journal, Sankaranarayanan et al. report the results of a randomized clinical trial of screening for cervical cancer involving more than 130,000 women in India. The authors conclusively showed that a single round of screening for human papillomavirus (HPV) dramatically reduced the incidence of advanced cervical cancer and cervical-cancer mortality within 8 years far more than a single conventional cytologic test or visual inspection of the cervix with acetic acid (VIA). The implications of the findings of this trial are immediate and global: international experts in cervical-cancer prevention should now adapt HPV testing for widespread implementation…”