VACCINE FINANCE AND SUPPLY

1. New 10-valent pneumococcal conjugate vaccine approved - greater supply security for developing country markets

A 10-valent pneumococcal conjugate vaccine has been approved for use in children by the European regulatory authorities (EMEA), ensuring expanded global manufacturing supply of these lifesaving vaccines and providing added protection against important serotypes. The new vaccine, called Synflorix, is manufactured by GlaxoSmithKline and is the first licensed vaccine to include serotypes 1, 5, and 14 (the serotypes required to be eligible for the Advance Market Commitment – see next story below). The vaccine uses a novel protein carrier that may also confer protection against non-typable Haemophilus influenzae(NTHi), another cause of otitis media and pneumonia. It has also been licensed in Canada, and efforts are already underway by the manufacturer and the WHO to gain approvals for procurement through UNICEF, which is important for assuring access to many developing country programs.

This is the second vaccine licensed to help prevent childhood pneumococcal disease and represents a major step forward for global prevention efforts. The addition of more serotypes holds the prospect of expanded health impact. With two suppliers offering pneumococcal conjugate vaccines countries can now expect greater supply security. Finally, as the first pneumococcal conjugate vaccine licensed on the basis of immunogenicity data it establishes an important precedent for the field.

Stay tuned for additional news on pneumococcal conjugate vaccine supply in upcoming additions. A 13-valent pneumococcal conjugate vaccine manufactured by Wyeth is expected to be available this year or early in 2010.

2. Target Product Profile for AMC-eligible pneumococcal vaccines approved

The Target Product Profile (TPP) for the Pneumococcal Advanced Market Commitment (AMC)was developed by the World Health Organization at the request of the AMC Secretariat. On December 11, 2008 the Independent Assessment Committee (IAC) officially endorsed the TPP, making it the definitive set of guidelines for determining the characteristics of AMC-eligible pneumococcal conjugate vaccines. The TPP sets out the standards a vaccine must meet in order to be eligible for sale under the AMC program and the IAC determines whether a candidate vaccine meets the TPP specifications. To meet the TPP, a vaccine must meet or exceed 13 requirements. Specific requirements in the TPP relate to the projected public health impact, vaccine safety, and suitability of the product for use in developing country health systems. More information can be found at: http://vaccineamc.org/progress.html

3. 9th Annual Meeting of the Developing Country Vaccine Manufacturer’s Network held in Cape Town, South Africa

The 9th Annual General Meeting of the Developing Countries Vaccine Manufacturers Network (DCVMN) was held in Cape Town, South Africa from 16 to 19th of November, organized and hosted by the Biovac Institute of South Africa. Participants heard an update on the pneumococcal Advance Market Commitment (AMC) and the target product profile (see above), which has now been officially endorsed. More information on the AMC and target product profile is available on www.vaccineamc.org.

The meeting featured the breadth of vaccines and biologicals supplied by these manufacturers, many of whom have ongoing programs to develop pneumococcal (and other) vaccines for infants. Other presentations included updates from various manufacturers, an overview of the prequalification process, activities of the Developing Country Vaccine Regulatory Network (DCVRN), an update from project Optimize, and presentations from resource members on a variety of other new technologies and trends, including packaging, aseptic filling, microneedles, disposable technologies and available support. For more information, please visit: www.dcvmn.com

4. Germany commits further support for life-saving vaccines in developing countries

In December, the German Parliament approved a one-year grant of four million Euros to increase its support for the efforts of the GAVI Allianceto bring life-saving vaccines to children living in developing countries. This brings the total support provided by the German Development Ministry to 12 million Euros since 2006. GAVI Alliance Executive Secretary Dr Julian Lob-Levyt welcomed the donation, saying, “We are delighted to see Germany once again joining other G8 members, like the United States, the United Kingdom and France, who provide long-term commitments to GAVI… Additional supporters are crucial in order for us to continue to make an impact on life-threatening diseases such as Haemophilus influenzaetype b (Hib), hepatitis B and pertussis.” The GAVI Alliance will require US$ 3 billion through 2015 to continue existing programs and expand support to new life-saving vaccines.

5. ProVac Workshop on the Cost-effectiveness of New Vaccine Introduction in the Americas: the Case of Pneumococcal Conjugate Vaccine

The Third Regional ProVac Meeting was convened in Asuncion, Paraguay on December 2-4, 2008. ProVac’s objective is to enhance national capacity to make evidence-based decisions regarding new vaccine introduction in the PAHO region. This workshop was focused on the ProVac cost-effectiveness model to evaluate the conjugate pneumococcal vaccine. While sustainable introduction of new vaccines requires urgent evaluation, participating countries also acknowledged the critical need to protect the gains in immunization and to complete the unfinished agenda of ensuring every district achieves >95% vaccination coverage. Countries also requested ProVac to continue its current approach of country technical support, which includes regional and subregional workshops, site visits, distance learning, and exchange of information.

More information about ProVac can be found at: http://www.paho.org/english/ad/fch/im/Provac.htm

VACCINE INTRODUCTIONS

6. Updated map of pneumococcal vaccine introduction worldwide now available

Ever wonder which countries are using the pneumococcal conjugate vaccine already or who’s planning to use it? An updated map of worldwide introduction of childhood pneumococcal vaccines is now available on the PneumoADIP website. To view this and other maps, please visit our website and click on the Maps tab: http://www.pneumoadip.org/#/Maps/

7. Hib vaccine introduced in Pakistan; pneumoccocal disease remains major source of morbidity and mortality among Pakistani children

Pneumonia caused primarily by pneumococcus and Hib remains a major source of childhood morbidity and mortality in Pakistan, with an estimated 92,000 deaths from pneumonia among children under age five each year. With GAVI support, Pakistan is in the final stages of introducing the Hib conjugate vaccine throughout the country. Vaccination against Hib disease is in the form of a pentavalent vaccine that adds protection against Hib to a vaccine that also protects against diphtheria, tetanus, pertussis, and hepatitis B. While GAVI also provides support for pneumococcal conjugate vaccine introduction, Pakistan has not yet decided to introduce this vaccine. The Asian Strategic Alliance for Pneumococcal Disease Prevention (ASAP) urged the Pakistani government to also adopt the pneumococcal vaccine into the National Immunization Programme in order to protect children from invasive pneumococcal disease.Professor Iqbal Memon, Convener of ASAP Pakistan Chapter, said, “As doctors and parents, we know the devastating impact the death of a child has on everyone… We want to tell everyone that this situation is avoidable - pneumococcal disease is preventable by vaccination.”

8. Bangladesh introduces Hib vaccine to prevent pneumonia and meningitis

Although most people think of diarrheal disease when they think about child deaths in Bangladesh, it’s actually pneumonia that kills the most children of any infectious disease in that country. But Bangladesh is taking action against this killer. The Government of Bangladesh recently announced the introduction of the Hib vaccine into its routine immunization program, which is estimated to save about 20,000 children's lives annually."This life-saving vaccine represents an important step forward in preventing childhood diseases in Bangladesh", said A.M.M. Nasir Uddin, Secretary of the Ministry of Health and Family Welfare in Bangladesh. "It will greatly help our country to achieve Millennium Development Goal 4 which aims at reducing under-five mortality." The Hib vaccine is a part of a combination vaccine that will protect children against Hib, diphtheria, tetanus, pertussis, and hepatitis B. The introduction of this vaccine in Bangladesh is carried out with financial and technical support from the GAVI Alliance and its key partners including UNICEF, WHO and the Hib Initiative.

MEDIA

9. Mali pediatrician advocates for pneumococcal vaccine in developing countries

In the UK’s Guardian Weekly of December 16, Malian pediatrician, longtime PneumoADIP collaborator, and PACE member, Dr. Samba Sow discussed his efforts to fight pneumococcal disease in West Africa. He explained, “I’m trying hard to raise public awareness so that we can place the same importance and attract the same commitment to pneumococcal disease as we do to HIV, and accelerate the introduction of the vaccine into the developing world. If this were done now, by 2030 we would be able to save the lives of 7 million children.” Dr. Sow shared his personal experiences treating children with pneumococcal pneumonia in Mali: “We often send patients home to wait for the results of their blood samples – usually because the hospital is full or the parents don’t have enough money to stay – but by the time we go to bring them back again, we often find a funeral, or the parents tell us the child died a couple of hours after they left the hospital. This is all the more tragic because it’s a vaccine-preventable disease.” He noted that authorities hope to introduce pneumococcal vaccine in Mali in 2009.

10. Nigerian Pediatricians Call for Use of Vaccines to Fight Childhood Pneumonia

Members of the Pediatric Association of Nigeria called for the inclusion of Hib and pneumococcal vaccines in the National Program on Immunization. William Ogala, President of Nigeria’s Pediatric Association, explained “The Hib vaccine is safe, effective and available now, but Nigeria has not started to use it. Many other African countries have adopted the Hib vaccine, and have prevented child deaths from pneumonia.” He noted that the use of both Hib and pneumococcal vaccines, the leading causes of life-threatening pneumonia, is critical to reduce the number of deaths of children under age five. An estimated 6 million Nigerian children contract pneumonia each year, leading to approximately 200,000 deaths.

11. Pediatricians in India urge use of pneumococcal and Hib vaccines to prevent pneumonia among children – India receives GAVI funding for Hib vaccine

At the annual meeting of the Indian Academy of Pediatrics held in Bangalore, India Jan. 22-25th, pediatricians convened to discuss means to prevent childhood pneumonia.Pneumonia remains an under-recognized problem in India, despite the fact that it kills more than 400,000 children here each year. “In our wards every day we see child wasting away from pneumonia,” said Dr. Jagdish Chinnappa, a pediatrician at Manipal Hospital. “There is no time to wait--we must take all measures, including making preventative vaccines part of India's routine immunization programme, to protect children and families from this emotionally and financially devastating illness,” said Chinnappa.

Hib and pneumococcus account for almost half of the total child pneumonia deaths in India. The government of India has indicated that they plan to introduce Hib into the Universal Immunization Program this year and that they plan to introduce pneumococcal vaccines gradually beginning as early as 2010. Earlier this week, it was announced that India will receive a US$260 million grantfrom the GAVI Alliance to introduce Hib vaccine.

12. 2008 PACE Year in Review report now available

To view the 2008 Annual Report of the Pneumococcal Awareness Council of Experts (PACE), please click here. The report provides an overview of the Council’s 2008 accomplishments in pneumococcal advocacy, including the recruitment of 114 organizations to sign PACE’s Global Call to Action on Pneumococcal Disease Prevention, the launch of the Call to Action at a global press event in Washington, DC and Turkey’s decision to introduce pneumococcal conjugate vaccine into its national immunization program following PACE’s media campaign in Istanbul. For more information on PACE, visit www.sabin.org.

RESEARCH

13. Meta-analyses produce conflicting results on protective benefit of adult pneumococcal polysaccharide vaccine

A meta-analysis published in the January 6th edition of the Canadian Medical Association Journalsuggests limited protective benefit of vaccinating adults with pneumococcal polysaccharide vaccines (PPVs). These vaccines to protect against 14 and, more recently, 23 strains have been approved in the US, Canada and many other countries for use in adults and the elderly to prevent invasive pneumococcal disease and pneumococcal pneumonia. PPVs are distinct from the childhood formulations – pneumococcal conjugate vaccines – which are specifically formulated to protect against strains common in children and contain a “conjugate” which makes the vaccine more effective in a child’s underdeveloped immune system. Although a dozen meta-analyses have been published in recent years, this is the first to stratify results based upon the quality of study methodology. In a random effect model of all studies, Huss et alfound significant reduction in the risk of presumptive pneumococcal pneumonia and all-cause pneumonia, but the effect was not observed when only studies of “high quality” (double blind and studies with concealment of allotment) were included. The authors suggest that future studies focus on the use of protein conjugate vaccines in adults and the elderly.

In an accompanying commentary in CMAJ, Andrews and Moberlysuggest that the conclusions drawn by Huss et alexceed the scope of the meta-analysis performed. In late 2008, the pair published a Cochrane reviewof PPVs and found in their own meta-analysis a combined odds ratio of developing invasive pneumococcal pneumonia of 0.26 (95% CI 0.15-0.46) in vaccinated adults versus unvaccinated adults. The commentary in CMAJ by Andrews and Moberly states “evidence does not support a change in policy for pneumococcal polysaccharide vaccination to prevent invasive disease in adults.” Indeed, WHO recommendations, while taking into account the study by Huss et al, are essentially unchanged, urging the continued use of PPVs in adults, especially the elderly and the chronically ill. Published studies, and several more in progress, are currently evaluating the use of pneumococcal conjugate vaccines in adults and the elderly. See “Success of PCV in children renews interest in use of the vaccine in the elderly” in the October 2008 edition of the PneumoFOCUS for more information.

14. Zinc may protect children against acute lower respiratory infection

In the December 2008 edition of the Journal of Nutrition, Coles et alreported the results of a study to evaluate the effect of zinc prophylaxis on the association between nasopharyngeal colonization with Streptococcus pneumoniae(Spn) and acute lower respiratory infection (ALRI). In the study, researchers determined the nasopharyngeal carriage prevalence of Spn among 550 children aged 1-35 months with ALRI living in a rural district of Nepal, compared to healthy age- and season-matched controls. The study was nested in a community-randomized trial in which children were randomized to receive either 10 mg of zinc or a placebo daily to evaluate the effect of zinc on morbidity and mortality. They found that Spncarriage increased the risk of ALRI in the placebo group, but not in the zinc group. The odds of ALRI among Spncarriers in the placebo group was estimated to be 30 times higher than in the zinc group. The researchers concluded that “zinc supplementation may significantly weaken the association between [Spn] carriage and the risk of ALRI in young children living in areas of endemic zinc deficiency.”

15. Pneumococcal conjugate vaccines reduce drug-resistant Streptococcus pneumoniae

In the December 12, 2008 issue of The Lancet Infectious Diseases, Dagan and Klugman reviewevidence that pneumococcal conjugate vaccines (PCVs) reduce the prevalence of drug-resistant Streptococcus pneumoniae(DRSP), concluding that “conjugate vaccines have had a major effect in reducing the absolute incidence of DRSP, not only in immunized children, but also in their contacts.” Specifically, PCVs significantly reduced the prevalence of penicillin-resistant S. pneumoniae, erythromycin-resistant S. pneumoniae, and multi-drug resistant S. pneumoniae. PCVs can also reduce DRSP in unvaccinated individuals through herd immunity and their use can lead to a concomitant reduction in antibiotic use. The authors report that most clinically significant DRSP strains are confined to seven serotypes (6A, 6B, 9V, 14, 19A, 19F, 23F), five of which are included in the 7-valent PCV (6B, 9V, 14, 19F, 23F). PCV7 has also been shown to reduce the incidence of 6A through cross protection from 6B. Prevalence of serotype 19A, however, has not been reduced by the use of PCV7, and its prevalence has been found to be on the rise in some populations, including those not using PCV7. Continued exposure of non-PCV7 serotypes to antibiotic pressure may reduce the overall impact of PCVs on DRSP. Further strategies to reduce DRSP include expansion of PCV serotype coverage in new vaccine formulations, development of protein-based vaccines, and further limitation of antibiotic use.

16. Researchers review trends in pediatric invasive pneumococcal disease in Santiago, Chile, 1994-2007

Lagos et alreviewed the results of systematic surveillance of pediatric invasive pneumococcal disease (IPD) in Santiago, Chile from 1994-2007 in the December 15, 2008 issue of The Journal of Infectious Diseases. Surveillance yielded three data sets: 1) IPD cases among patients aged 0-14 years, 2) cases of bacteremia detected among febrile ambulatory patients aged 0-35 months in emergency departments, and 3) nasopharyngeal carriage of pneumococcal serotypes based on repetitive culturing among 524 healthy newborns followed from birth through age 23 months. Of IPD cases requiring hospitalization, 79% occurred among patients aged 0-59 months. Among infants aged 0-5 months, meningitis and sepsis comprised 48% of all IPD cases; and among those 6-35 months old, bacteremic pneumonia comprised 44% of all IPD cases. Serotype 1 peritonitis was particularly common among females aged 5-14 years. Among all ages, children with meningitis and sepsis had high case fatality rates (14-29%), and were more likely to die if from sepsis (29%) versus bacteremia without a focus (0.4%).

Lagos et alalso reported notable serotype trends: Serotype 5 was significantly more common among hospitalized patients less than 36 months of age versus ambulatory patients of the same age, and serotype 18C was more common among ambulatory patients. The annual incidence of serotype 18C was stable over time, whereas those of serotypes 1 and 5 varied substantially from year to year. Serotypes 14, 5, and 1 were more common among invasive isolates versus nasopharyngeal isolates. Overall, this paper provides valuable insights into the inter-annual variability in serotype-specific rates of invasive pneumococcal disease incidence rates and highlights the ability of serotypes 1 and 5 to increase and decrease dramatically between years, a fact that will need to be considered when evaluating serotype-specific changes in incidence following the introduction of conjugate pneumococcal vaccines.

17. Individuals with asthma may be at increased risk of invasive pneumococcal disease

Researchers from the Mayo Clinic recently published the results of a retrospective case-control studyto assess the relationship between asthma and serious pneumococcal disease (SPD). Cases were 174 residents of Rochester, Minnesota who had SPD – defined as either invasive pneumococcal disease or pneumococcal pneumonia or both – between 1964 and 1983, age- and sex-matched to control subjects. All subjects were merged with the Rochester Epidemiology project database to determine asthma status, which was confirmed by medical record review. The researchers found the odds ratio of having a history of asthma to be 6.7 (95% CI 1.6-27.3, p=0.1) among adults with SPD compared to those without SPD, and 2.4 (95% CI 0.9-6.6, p=0.09) among those of all ages with SPD compared to those without SPD. These results correspond to a 17% population-attributable risk of SPD on asthma in the adult population. The authors caution that these findings should be confirmed in another population-based study setting but suggest that in the interim, consideration should be given to including asthma as an indication for pneumococcal vaccination in adults.

ANNOUNCEMENTS

PneumoADIP is recruiting for 3 new positions.Our group is expanding its work in pneumonia to study the etiology of pneumonia in children worldwide. We are currently recruiting for 3 key positions: Clinical/Microbiology Technical Expert; Sr. Research Project Coordinator; and Biostatistician. For details on these positions or on the PATH positions below, please visit http://pneumoadip.org/Careers.cfm.

PATH is currently seeking three people to join the policy and advocacy division: a Government Affairs Officer for PATH, as well as a Coalition Managerand Public Policy Research Analystfor the Global Health Technologies Coalition (GHTC).

If you know a seasoned advocate, coalition manager, or policy researcher with a passion for global health, the ability to communicate effectively with policymakers through research and advocacy, and a desire to work with talented public health advocates and experts, please visit http://www.path.org/employment.phpInterested candidates can also contact PATH recruiter, Laura Retzler, in the Seattle office at lretzler@path.org; 206.788.2086 (direct).

UPCOMING EVENTS

The Childhood Pneumonia & Meningitis: Recent Advances Sympsosiumwill take place on January 31 in Karachi, Pakistan. Hosted by the Pneumococcal Awareness Council of Experts (PACE) and Aga Khan University, this one-day symposium will bring together regional infectious disease experts to discuss opportunities for pneumococcal disease prevention throughout South Asia and the Middle East. The event will feature Dr. Zulfiqar Bhutta, PACE member and Head of Maternal and Child Health at Aga Khan University, and Dr. Ciro A. de Quadros, PACE Co-chair and Executive Vice President of the Sabin Vaccine Institute, among other notable guests. PACE is a project of the Sabin Vaccine Institute. For more information about PACE, visit www.sabin.org

The 2009 Annual Meeting of the American Association for the Advancement of Science (AAAS), the premier showcase for multidisciplinary advances in science, technology and engineering, will take place in Chicago, Illinois (USA), February 12-16, 2009. The theme, "Our Planet and Its Life: Origins and Futures," recognizes 2009 as the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of his book "On the Origin of Species by Means of Natural Selection." For more information, go to: http://www.aaas.org/meetings/

The 4th Regional Pneumococcal Symposiumwill take place in Johannesburg, South Africa, March 2-3, 2009. Featuring the latest developments in pneumococcal disease prevention, this symposium is a collaborative effort of the Sabin Vaccine Institute, GAVI’s PneumoADIP, US Centers for Disease Control and Prevention, Kenya Pediatric Society, South African Pediatric Association and The University of the Witwatersrand. This event brings together scientific experts, key decision makers, and public health professionals from around the world. Registration is now open at: www.pneumosymposium.com

The 12th Annual Conference on Vaccine Researchwill take place in Baltimore, Maryland from April 27-29, 2009 and is sponsored by the National Foundation for Infectious Diseases. Registration and other information can be found at: http://www.nfid.org/conferences/vaccine09/

The 7th World Congress on Health Economicswill take place July 12-15th, 2009 in Beijing, China. Early registration will remain open until May 31st. Scholarships for students and developing country scholars are available. More information and registration can be found by visiting: http://www.healtheconomics.org/congress/2009/