Groups call for action to prevent Pneumococcal Disease

On October 15th at the UK’s House of Lords, the All Party Parliamentary Group on Pneumococcal Disease Prevention in the Developing World (APPG) released its report entitled “Improving Global Health by Preventing Pneumococcal Disease”. The report is the result of an exhaustive 6-month inquiry that gathered evidence from dozens of international experts representing academia, public health practice, ministries of health, civil society organizations, industry and others. Formed in January 2007, this group of more than 20 parliamentarians sought to investigate the burden of disease in terms of mortality, morbidity and country and family level economics and to examine the UK’s participation in the pneumococcal Advance Market Commitment (AMC) and other efforts to control the disease.

UK government has committed US$450 million to the pneumococcal AMC, an innovative financing mechanism designed to eliminate product design, supply and financing obstacles to the introduction of pneumococcal vaccines in the developing world. The APPG concluded in this report that “the AMC should accelerate the availability of affordable, effective pneumococcal vaccines to the world’s poorest children in a sustainable manner.” Recommendations are given by the Group to the UK and other governments, donors and international organizations aimed at sustaining political will, increasing awareness, continued support of research and surveillance activities and increased international coordination of efforts. In the report’s conclusion, the Group stated “the APPG finds convincing evidence that pneumococcal disease is a serious, preventable cause of death and disability in need of urgent action.” To download a copy of the report, click here.

One week later, on October 24th, the Pneumococcal Awareness Council of Experts (PACE), a project of the Sabin Institute was joined by more than one hundred civil society and professional societies in calling for immediate action on pneumococcal disease. The 113 organizations and societies from around the globe were signatories of a Call to Action on Pneumococcal Disease Prevention launched in Washington, DC. Speakers at the event included Sabin’s president, Dr. Peter Hotez, Dr. Matthew Moore of the CDC, Dr. Orin Levine from GAVI’s PneumoADIP, and representatives of signatory organizations from Costa Rica, Kenya, Burkina Faso and the United States.

Also during the PACE Call to Action event, the Hon. James Kimonyo, Ambassador of the Republic of Rwanda to the United States, accepted the PACE Global Leadership Award on behalf of the Rwandan Ministry of Health which was presented in recognition of that government’s efforts to protect Rwandan children by making immunization against pneumococcal disease routine. Earlier this year, Rwanda became the first African country to obtain support from the GAVI Alliance for the introduction of childhood pneumococcal vaccine into their routine childhood immunization program. PneumoADIP joins PACE in congratulating the Rwandan Ministry of Health on their leadership. With its strong immunization program, and one of the highest risks of child death due to pneumococcal disease in the world, Rwanda’s children are expected to benefit substantially from pneumococcal conjugate vaccination. For more information about PACE and the Call to Action, please visit: http://sabin.org/programs/PACE/index.html

Research News:

1. MMWR/WER report on the progress of pneumococcal vaccine introduction worldwide

On October 24th, the Morbidity and Mortality Weekly Report and the Weekly Epidemiologic Record published “Progress in Introduction of Pneumococcal Conjugate Vaccine Worldwide, 2000-2008”. An analysis of the breadth of PCV introduction efforts was undertaken utilizing a WHO database of countries using PCV7 (the only currently licensed pneumococcal conjugate vaccine), together with data on countries’ economic standings and a categorization of countries based upon mortality and disease prevalence characteristics. This analysis found that although PCV7 had been licensed in 90 of the 183 WHO member states by August of 2008, routine use has been established in only 26. Furthermore, 92% of the countries who have introduced the vaccine are classified as high-income and have low childhood mortality and disease prevalence.

None of the 72 poorest countries in the world – all of which are eligible for financial assistance from the GAVI Alliance (“GAVI-eligible”) – have introduced PCV7 by August 2008. (Eleven countries have, however, applied and eight have been approved for assistance.) This is significant because >98% of pneumococcal disease mortality occurs in low-income countries. In addition 82% of GAVI-eligible countries have a mortality rate of >50 per 1,000 live births in children under 5, a rate which, according to the 2007 WHO position paper on pneumococcal vaccines, should be the priority countries for PCV introduction.

The article goes on to highlight some of the hurdles to widespread implementation experienced during the introduction of other vaccines and describes factors found to be important for facilitating vaccine introduction. Concluding that “several of these factors are now in place for the introduction of PCV”, the article calls for the development of strategies to support middle-income and other non-GAVI-eligible countries in their bid to introduce lifesaving pneumococcal vaccines.

2. Success of PCV in children renews interest in use of the vaccine in the elderly

In an invited article in the November issue of Clinical Infectious Diseases (e-published Oct. 9) Jackson and Janoff review the use of pneumococcal polysaccharide vaccine (PPV) in adults and suggest a potential role of pneumococcal conjugate vaccine (PCV) use in older adults for preventing nonbacteremic pneumonia and invasive pneumococcal disease. The authors note that several studies have demonstrated PPV’s ability to reduce the risk of invasive pneumococcal disease in older adults, while routine use of PCV has had significant direct benefits in preventing IPD in children and, through herd effects, in adults. The authors cited also a recent study by de Roux et al (CID 2008; 46; 1015-1023) that compared the antibody responses to a dose of PPV (followed by PCV booster) or a dose of PCV (followed by PPV or PCV booster), among adults 70 years of age or greater who had never received any pneumococcal vaccine. The study found that the response to the seven serotypes common to both PPV and PCV was greater after an initial dose of PCV than after PPV as the first dose. Taken together with evidence of PCV’s ability to protect children against pneumonia, the authors conclude that the use of PCVs, among other new vaccination strategies, could help to further reduce the risk of pneumococcal infections, including nonbacteremic pneumonia, in older adults.

3. Childhood pneumonia found to impose high economic burden in Pakistan

In the November issue of Health Policy and Planning (e-published Aug. 28), Hussain et alpublished research into the overall financial burden of pneumonia, severe pneumonia, and very severe febrile disease among children under age three in northern areas of Pakistan. The researchers collected data from interviews with caretakers seeking care for children at a health facility in order to approximate the household costs of these diseases. These data were analyzed together with estimates of health provider costs. The total societal average cost per episode was estimated at US$22.62 for pneumonia, US$142.90 for severe pneumonia and US$62.48 for very severe febrile disease. World Bank figures indicate that the per capita income in Pakistan is less than US$900 per year, emphasizing the high relative costs of treatment. The study authors estimated the total cost of $236 million for childhood pneumonia in 2002 in Pakistan to be $236 million. Hussain et al thus conclude that “there is strong economic justification to focus on preventive measures in order to decrease treatment costs of childhood pneumonia” and have called upon the Ministry of Health to expand access to existing interventions, and to explore innovative strategies to reduce associated costs to both households and the health system.

Media News:

4. South African government increases funds and begins introduction of diarrhea and pneumonia vaccines

The South African Finance Minister announced last week that additional funds will be allocated to provide for the national introduction of three new childhood vaccines, according to Bua News online. The vaccines are aimed at reducing deaths from Hib and pneumococcal pneumonia and rotaviral diarrhea. These new allocations are included in the Adjusted Appropriation Bill, announced as part of the Medium-Term Budget Policy Statement in the National Assembly of South Africa. Districts in the Eastern Cape of the country launched rotavirus and pneumococcal conjugate vaccine programs in September of this year. The Ministry of Health expects to complete rollout the vaccines nationwide, together with Hib-containing pentavalent vaccine, by April of 2009. PneumoADIP congratulates South Africa on their important decision to prioritize the prevention of these deadly diseases for all South African children.

5. Promising results in trials of 13-valent pneumococcal conjugate vaccine

At the joint annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America Wyeth presented data from Phase III trials showing that their investigational 13-valent pneumococcal conjugate vaccine (PCV13) is as immunogenic, and likely to be as effective, as the existing pneumococcal 7-valent pneumococcal conjugate vaccine (Prevnar) in preventing pneumococcal disease from the seven serotypes in the original formulation. In addition, the new formulation offers expanded coverage for six additional serotypes. PCV13 would cover 13 common pneumococcal serotypes associated with serious pneumococcal disease in infants and children, including 19A which has been implicated in increases in disease cases among some populations recently. According to their website, Wyeth plans to complete U.S. and other global filings for pediatric use of PCV13 in the first quarter of 2009.

Interview with Drs. Barocchi and Masignani from Novartis’ protein vaccine project

Dr. Michèle Barocchi received her MPH and PhD in Infectious Diseases and Immunology at the University of California, Berkeley. She has trained with the Brazilian Ministry of Health and joined Novartis Vaccines and Diagnostics (formerly Chiron Vaccines) in 2003. Dr. Vega Masignani holds a PhD in biotechnology and, with Dr. Rino Rappuoli (Global Head of Vaccines Research for Novartis Vaccines and Diagnostics), pioneered the “reverse vaccinology” approach first used to identify vaccine candidates against Neisseria meningitidis. Together, Drs. Barocchi and Masignani co-coordinate Novartis’ research group working on a pneumococcal protein vaccine.

Why is  Streptococcus pneumoniaea  research priority for your group?

“Childhood pneumonia is the leading cause of mortality in children less than 5 years of age, responsible for approximately 2 million deaths each year. Sadly, more than 90% of children affected by invasive pneumococcal diseases are in developing countries. Vaccines research and development are without a doubt the most effective solutions for the prevention and control of pneumococcal disease worldwide.”

What progress has your group made in the research and development of new tools to fight pneumococcus?

“Rino Rappuoli’s group at Novartis was the first to “mine” bacterial genome sequences (Meningococcus B) in the quest for new vaccine candidates. This involved the in silico identification of all major surface proteins, based on the assumption that these sites were accessible to antibody binding during infection, a concept eventually termed Reverse Vaccinology. This system has proved to be powerful in a variety of vaccine candidates for Group B Meningococcus, and more recently for Group B Streptococcus.

We believe that a multi-disciplinary approach is necessary to tackle this complexity of developing new tools to fight pneumococcal disease. We are currently working on the development of a serotype-independent vaccine through reverse vaccinology, and recently identified the pneumococcal pilus, a very potent immunogen, able to elicit cross-protection of different serotypes."

What more needs to be done?

"Molecular epidemiological studies based on continued surveillance, such as those set up by the PneumoAIDIP will be critical in the continued success of any vaccine program by determining geographical serotype distribution and theoretical vaccine coverage. Additionally, the pneumococcal pan-genome, that is, the genomic comparative analysis of epidemiologically important strains will be fundamental to the development of a protein-based vaccine. The identification of immunogenic surface antigens and assessment of their efficacy will be imperative in the development of a vaccine with the ability to protect independent of serotype.

Ultimately, licensure of new vaccines will depend on the evidence of a functional immune response to vaccination, therefore, we are actively moving forward to establish a “standardized” in vitro correlate of protection for protein antigens (along the lines of the WHO reference OPA assay for carbohydrates).”

What traits will be important for the next generation of pneumococcal vaccines?

“The next generation of pneumococcal vaccines should have the ability to cover, ‘universally’, all of the 91 S. pneumoniaeserotypes. The vaccine will need to be safe and effective in infants and should be accessible to all populations in need, regardless of where they live. Ultimately, the choice of a pneumococcal vaccine should be determined not merely by its immunogenicity and efficacy but also the ease of integration in local immunization programs and affordability in terms of price by the lowest income countries, where the burden of the disease is the heaviest.”

Upcoming Events:

The National Foundation for Infectious Diseases, Emory Department of Medicine – Division of Infectious Diseases and Emory Vaccine Center will sponsor a Clinical Vaccinology Course, from November 14-16, in Bethesda, MD. Early registration is available until October 8. For more information, please visit: http://www.nfid.org

BIT will host their 1st annual World Vaccine Congressin Guangzhou, China from December 1-5, 2008. The theme will be "Building an Olympian Meeting Platform for Vaccine World” and the meeting is devoted exclusively to the research on vaccines and associated technologies for disease prevention and treatment. For more information, please visit: http://www.bitlifesciences.com/wcv2008/

The American Society of Tropical Medicine and Hygienewill hold their 57th Annual MeetingDecember 7-11, 2008 in New Orleans, Louisiana. Registration must be completed by Nov. 13th and more information can be obtained on the conference website: http://www.astmh.org/meetings/index.cfm

The Centers’ for Disease Control AnnualMaternal and Child Health Epidemiology Conferencewill take place December 10-12, 2008 in Atlanta, GA. Health professionals working with maternal and child health data, programs, or policies, particularly at the national, state, tribal, and local levels are encouraged to attend. More information can be found by visiting: http://www.cdc.gov/reproductivehealth/MCHEpi/2008/AboutConference.htm