PneumoFOCUS

Bulletin of GAVI's PneumoADIP at Johns Hopkins Bloomberg School of Public Health
PneumoADIP: Pneumococcal Vaccines Accelerated Development and Introduction Plan

Volume 5 , No. 2, February 2008

1. New genome data now available from 5 pneumococcal strains common in developing countries

Researchers now have access to the complete genomes of five geographically diverse S. pneumoniae isolates. The sequencing was performed by The Institute for Genome Research (TIGR, now known as the J. Craig Venter Institute) and involved an analysis of clinically important strains from Bangladesh, Ghana, Taiwan, Hungary and Brazil. PATH supported the research. Among the isolates included in the sequences are serotype 1 and 5 isolates. This is important information because these serotypes are prone to cause epidemics and because reviews of the distribution of serotypes causing invasive disease worldwide generally show that they are relatively more important in developing countries than they are in the United States and Europe.

The data will help researchers and manufacturers to develop the next generation of pneumococcal vaccines by allowing them to identify and prioritize protein vaccine candidates whose sequences are homogenous with global strains. The entire data set, sequence, and annotation information have been submitted to Genbank for public release. For more information about the sequencing project and the data generated, including comparisons between these five new genomes and previously published S. pneumoniae genomes, please visit the Streptococcus Pneumoniae Comparative System.

2. GSK files novel pneumococcal vaccine for approval by European Union

GlaxoSmithKline announced the acceptance for review of its experimental childhood vaccine, Synflorix, by European authorities on January 31st. Synflorix is  administered in three doses during the first year of life, and stimulates immunity to 10 capsular serotypes of S. pneumoniae. Synflorix adds serotypes 1, 5, and 7F to the same seven that are in the currently licensed Prevnar (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F). A novel feature of Synflorix is that it uses an outer membrane protein of non-typeable H. influenzae (“protein D”) as the “carrier” protein for most of the pneumococcal serotypes. Non-typeable H. influenzae are an important cause of ear infections in young children and may be involved in other serious infections like pneumonia. Clinical studies with a similar candidate vaccine showed some evidence that the protein D was able to prevent ear infections due to non-typeable H. influenzae.

There is no evidence yet that this vaccine prevents meningitis or pneumonia due to H. influenzae type B (Hib), and therefore, it is critical that efforts continue to vaccinate all children everywhere with Hib conjugate vaccines. Where children are not vaccinated against it, Hib persists as a leading cause of bacterial meningitis and pneumonia.

As part of its plans for global access, GSK plans to seek WHO pre-qualification for Synflorix. This step is critical to facilitating its inclusion in developing country vaccination programs, said William Haussdorff, director of worldwide biologicals epidemiology at GSK’s vaccine unit, in a recent interview.

3. Global Action Plan for the Prevention and Control of Pneumonia publishes first meeting report

The Global Action Plan for Pneumonia (GAPP) has published its first meeting report. GAPP, which is organized by WHO and UNICEF and includes the Hib Initiative, PneumoADIP, and others, is a coalition of organizations working to control and prevent pneumonia worldwide. Among the technical consensus statements, both Hib and pneumococcal vaccination were cited as being key to achieving improved childhood survival. All countries are recommended to take steps to achieve Global Immunization Vision and Strategy (GIVS) targets for measles and pertussis containing vaccines, while for countries that have not yet done so, it was recommended that they add Hib and conjugate pneumococcal vaccines to their national immunization programmes, especially if child mortality is high. Other stipulated measures for pneumonia prevention include effective case management at the community and health facility levels, promotion of exclusive breastfeeding and appropriate complementary feeding, reduction of indoor air pollution and strategies to prevent mother-to-child HIV transmission and improvements to overall HIV case management. Click here to download the report

4. New comprehensive text on pneumococcal conjugate vaccines published by the American Society for Microbiology

The American Society for Microbiology (ASM) Press recently published, Pneumococcal Vaccines: The Impact of Conjugate Vaccines, a compilation of chapters from the world’s experts on pneumococcal vaccines. The book describes the development of the vaccines, their remarkable impact on respiratory and other pneumococcal infections, and their wider impact on public health. For professionals in academia, public health, government, or industry, the book serves as a useful summary of the current knowledge on pneumococcal vaccines with particular emphasis on the years after the introduction of PCV. Key features include an overview of the biological basis for PCV, methods to measure and monitor the effects of vaccine introduction, manufacturing and product release, efficacy, and safety issues, worldwide potential of the vaccines, and the impact of vaccination on childhood respiratory disease, including antibiotic resistance. The book includes chapters by PneumoADIP faculty Orin Levine and Kate O’Brien and many of the PneumoADIP’s sponsored researchers.

5. The 3rd Regional Symposium on Pneumococcal Disease in Istanbul, Turkey a success

Over 200 participants attended the 3rd Regional Pneumococcal Symposium in Istanbul, Turkey, February 13 – 14, 2008. The symposium was hosted by the Sabin Vaccine Institute in partnership with GAVI’s PneumoADIP. Presentations were made from leading experts on the latest developments in pneumococcal disease research and efforts for prevention. As well as local participants, there was also representation from the Middle East, Europe and N. America. Presentations from the symposium will be posted at a later date on the Sabin Vaccine Institute Web site: www.sabin.org

6. Interview with David Murdoch, author of review “Laboratory Diagnosis of Invasive Pneumococcal Disease”

Dr. David Murdoch, professor and the head of pathology at the University of Otago, Christchurch, New Zealand, is the co-author of Laboratory Diagnosis of Invasive Pneumococcal Disease, published in the March 15 issue of Clinical Infectious Diseases, 2008:46:926-32. The article is one of only a small selection that has ever been published focusing on the challenges of laboratory detection of pneumococcal disease. PneumoFOCUS spoke to Dr. Murdoch and asked him about surveillance, detection and available tools for diagnosing the elusive pneumococcus.

Detection and surveillance in resource poor settings:
“We are still reliant on blood and CSF for culture-based methods. The only additional tool is the NOW antigen detection test. Additional training, following standardized procedures and increasing capacity has to be the focus if we want to improve results.”

Undetected pediatric pneumococcal disease:
“I think the impression is that we are missing at least a third to a half of the cases. In reality, I think the majority of cases missed are in children; this is based on results of vaccine efficacy or probe studies. We see a much greater decrease in disease compared to the proportion that we have with culture-confirmed disease. In addition, when some researchers have used more invasive tests, such as aspiration methods, they find that a large number of additional cases of pneumococcal disease, which would have otherwise not been identified.”

Challenges to surveillance of pneumococcal disease:
“Globally, we are dealing with the limitations of existing tools and under-diagnosis is a major concern. Even in developed countries, clinicians will only get positive results in a minority of cases and then start asking the question: Should we spend money on tests? This devaluing of tests impacts surveillance. With no tests, we have no surveillance data and that coupled with the widespread use of antibiotics leads to difficulty in attaining culture confirmed pneumococci. In Nepal, when kids present at the hospital we test for antibiotics and one third test positive.”

“We also have to take into account that surveillance is usually dependent on the presence of laboratory facilities and that the location of these facilities will impact on surveillance data. In some countries you may get all of your data from a big city, thereby not reflective of disease burden in the whole country. Data from rural areas could be quite different.”

In your article you refer to: “an urgent need for improved diagnostic tests for pneumococcal disease—especially tests that are suitable for use in under-resourced countries”
“Pneumococcal disease is such a common disease and yet development of new diagnostics for this disease has never had a high priority. The urgency was not there. This is changing, but still there are not a large number of people working on [developing new diagnostic methods]. That might reflect the fact that the task is difficult. An example of this is if we try and detect pneumococci from a site not normally sterile like sputum – if it’s positive you are left with the question: Is this real or just because the sample is contaminated?”

Investments to increase detection of S. pneumoniae and other bacterial causes of pneumonia and meningitis in developing country settings:
“The most important investments are in enhancing laboratory capacity, having facilities to culture samples - in short: microscopy, laboratory facilities and training. By improving laboratory capacity we also increase the ability to diagnose other infections or organisms.”

7. CDC’s ABCs study examines overall benefits of PCV7 in eight U.S. states, 1998 – 2005

Results of a recent study using the CDC’s Active Bacterial Core surveillance (ABCs), a population-and laboratory-based system, ongoing since 1995, in California, Connecticut, Georgia, Maryland, Minnesota, New York, Oregon and Tennessee, showed substantial reductions in Invasive Pneumococcal Disease (IPD) among children less than 5 years of age, 5 years following PCV7 introduction in 2000. Overall IPD rates in 2005 were 77% lower in this age group compared with average rates in 1998 – 1999, preventing an estimated 13,000 cases of IPD from any serotype in 2005 alone. Results of this analysis also showed increases in non-PCV7-type disease among vaccinated and unvaccinated populations but in the general U.S. population, these increases have been small relative to declines in PCV7-type disease. These findings suggest that expanded valency conjugate vaccines for children which protect against serotype 19A would help to improve prevention efforts, as this was the most common serotype causing IPD among children under 5 years of age in 2005. MMWR 2008 Feb. 57 (06); 144-148.

8. Descriptive epidemiology of S. pneumoniaeand H. influenzaenasopharyngeal carriage in Kilifi District, Kenya

In order to assess the epidemiology of S. pneumoniaetransmission and disease, which has been shown to vary significantly by geography and ethnic group, the effects of age, sex, season and urbanization were assessed on the prevalence of nasopharyngeal (NP) carriage and the circulating serotypes of pneumococci in a community in coastal Kenya where IPD incidence is high. Results from the 2 cross-sectional nasopharyngeal swab surveys conducted revealed that pneumococcal carriage was highest among children less than 5 years of age. Significant risk factors for pneumococcal carriage were rainy season, coryza, and co-culture of noncapsulate H. influenzae. Among 279 S. pneumoniaeisolates, 40 serotypes were represented and the distribution of serotypes varied significantly with age. In children less than 5 years old, the most commonly isolated serotypes were 19F, 6B, 6A, and 23F. Serotypes 1, 5, and 7F were not identified from any of the participants of any age.7-valent vaccine-types, vaccine-related types, and nonvaccine types comprised 47%, 19% and 34% of strains from children less than 5 years of age, and 25%, 28% and 47% among all people older than age 5, respectively. This study is the first population-based survey of NP carriage of S. pneumoniaeand H. influenzaeconducted in East Africa and will be important in evaluating the overall success of PCV in the region. Abdullani et al. Ped Infect. Dis. J. 2008 Jan. 27 (1): 59-64.

9. Estimating age-stratified pneumococcal-serotype-specific data prior to PCV7 introduction in the UK

Country baseline data on pre-existing immunity is important in analysis of vaccine efficacy following PCV7 introduction. The age-specific baseline levels of pneumococcal-serotype-specific IgG in England for nine pneumococcal capsular polysaccharides (1, 2, 4, 6B, 9V, 14, 18C, 19F, and 23F) were measured using a validated multiplex bead assay, in a cross section of the population during 2000 to 2004. (PCV7 became part of routine childhood immunization in the UK in 2006.) It was found that children less than 1 year of age had the lowest serotype-specific IgG responses, which increased from 1 year onwards, remaining high in adults. An inverse relationship was found to exist between protective levels of serotype-specific IgG and age-specific IPD incidence for each serotype, with the exception of the elderly. These data provide insight into the natural immunity to various pneumococcal serotypes prior to vaccine introduction in the UK, and will be important for an assessment of overall vaccine efficacy in this population over time. Balmer et al. Clin. Vacc. Imm. 2007 Nov. 14 (11): 1442-1450.


Upcoming Events

March 9-14, 2008 – Biology of Acute Respiratory Infections Conference - Ventura, California
The goal of this conference is to “foster communication among individuals and groups which are studying this common and important problem from distinct vantage points, to develop and encourage creative and multidisciplinary approaches to discovery”.

March 17-20, 2008 – 42nd National Immunization Conference - Atlanta, Georgia (USA)
The CDC will be hosting the 42nd annual conference in Atlanta, the objectives of which are “to provide information that will help participants provide comprehensive immunization coverage for all age groups and explore innovative strategies for developing programs, policy, and research to promote immunization coverage for all age groups.”

March 16-19, 2008 – 6th International Emerging Infectious Disease Conference - Atlanta, Georgia (USA)
In addition to the NIC conference held the same week in Atlanta, CDC will be hosting the 6th IEIDC. “The conference brings together public health professionals to encourage the exchange of scientific and public health information on global emerging infectious disease issues. Major topics to be included are current work on surveillance, epidemiology, research, communication and training, bioterrorism, and preventions and control of emerging infectious diseases, both in the United States and abroad.”

April 11-13, 2008 – International Congress of Tropical Pediatrics - Manila, Philippines
The 8th annual ICTP will be held in Manila with the theme “Improving Child Survival: A Continuing Challenge” which underscores a firm resolve to “continuously improve the health of children in the tropics. Child’s rights and survival, emerging and re-emerging diseases, new and underutilized vaccines, new and appropriate procedures, skills and medical equipment and products” will all be part of the program for the Congress.

April 21-24, 2008 – World Vaccine Congress - Arlington, Virginia (USA)
The WVC, to be held in Washington, DC, is aimed at the vaccine industry and bills itself as “the definitive strategic meeting place for the vaccine industry in the United States, Canada, as well as Central and South America.” Speakers from PAHO, GAVI, Wyeth, GSK and Indian Immunologicals, among others, are already on the program.

May 2-6, 2008 – Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting - Honolulu, Hawaii (USA)
The PAS 2008 Annual Meeting is a partnership of four primary pediatric organizations and an Asian organization: The American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, the American Academy of Pediatrics and the Asian Society for Pediatric Research. The PAS Annual Meeting is the largest international meeting focusing on research in child health while providing a unique venue for interdisciplinary scientific interactions.

May 5-10, 2008 – International Advanced Course on Vaccinology in Asia-Pacific Regions - Seoul, Korea
The course aims to strengthen the capacity of countries in vaccinology by providing participants with a comprehensive overview of the vaccine continuum, from vaccine development, evaluation and regulatory principles, to production, post-licensure, introduction and policy issues. Deadline for applications is March 15th.

May 19-24, 2008 – World Health Assembly - Geneva, Switzerland
The World Health Assembly is the supreme decision-making body of the World Health Organization. It meets in Geneva in May each year, and is attended by delegations from the 193 Member States. The main function of the Health Assembly is to determine the policies of the Organization.

June 8-12, 2008 – The 6th International Symposium on Pneumococci and Pneumococcal Diseases will be held in Reykjavik, Iceland
The deadline for submission of abstracts is February 1st and early registration must be completed by April 1. More information may be found at  http://www.congress.is/ISPPD-6/

June 19-22, 2008 – International Conference on Infectious Disease - Kuala Lumpur, Malaysia
Convened by the International Society for Infectious Diseases, the 13th annual ICID will be hosted by the Malaysian Ministry of Health and will again welcome delegates from over 100 countries. The program will include plenary talks by world renowned experts in the science of infectious diseases and other important topics presented by international luminaries in the field. The abstract deadline has been extended to March 1st.


Job Announcements

The International Vaccine Institute (IVI), Seoul, Korea, is seeking Research or Associate Scientists. Applicants should have MD, Ph.D., or equivalent degree and training in epidemiology and/or infectious disease, with experience in clinical vaccine trials, licensing pathways and disease surveillance. For more information please contact Dr. Luis Jodar (ljodar@ivi.int).