MEDIA

1. Many countries falling short on progress towards MDGs, increased aid needed

Developed countries need to increase aid commitments substantially in order to boost progress towards Millennium Development Goals (MDG), advocated United Nations Development Program (UNDP) officials at a meeting in London this month. While progress has been made towards targets for poverty and extreme hunger, areas in particular need of focus include vaccinations, malnutrition, maternal health, and gender inequities. Douglas Alexander, Britain’s international development secretary, called for international ratification of an action plan to double aid commitments for maternal and child health as well as basic education. Mr. Alexander also announced a new commitment from the UK for a development package to include $230 million for the GAVI Alliance to provide vaccines against pneumonia and diarrhea to children in the world’s poorest countries (see Finance and Supply section below for more details.)

2. Advance market commitment secures 600 million doses of PCVs for developing countries

The GAVI Alliance recently announced the supply agreement with GlaxoSmithKline and Pfizer for pneumococcal vaccines under the Advance Market Commitment (AMC). While full details will be released in the coming weeks, it is expected that the two vaccine manufacturers will each provide an average of 30 million PCV doses per year for use in developing countries. The terms of the AMC include a 10-year commitment to sell the vaccines at a short-term initial price of $7 per dose, followed by a longer-term price of $3.50. Two developing country manufacturers have also signed on to the AMC, though their products are still under development. This first-ever AMC was formally launched last June through a cooperative partnership among the GAVI Alliance, the World Bank, WHO and UNICEF, five national governments, and the Bill and Melinda Gates Foundation. The work of the PneumoADIP (now the International Vaccine Access Center and PneumoACTION) also contributed significantly to this achievement and we’re proud to have been a part of this successful partnership for child health.

RESEARCH

3. 15-valent PCV shows antibody response in infant rhesus monkeys

In light of the geographic diversity of serotype distributions and recent apparent increases in non-vaccine serotypes, researchers from Merck Research Labs and BioProcess Research and Development have developed a 15-valent PCV, now in the early stages of testing. The vaccine includes serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F. In a late-breaking submission to ISPPD-7, the team reported the results of a vaccine trial in infant rhesus monkeys, whose immune systems, like those of human infants, require a conjugated vaccine. The subjects were vaccinated on a three-dose schedule at two month intervals with either PCV-15 or PCV-7. Multi-array electrochemiluminescence assays were used to measure serotype-specific IgG antibodies. “The results indicate that antibody responses to PCV-15 and Prevnar® were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were > 10-fold higher than baseline for the added 8 serotypes”, researchers reported. Functional antibody titers were also observed for all 15 serotypes using a multiplexed opsonphagocytosis assay. The vaccine is planned to enter clinical trials in the near future.

4. Advances in protein-based pneumococcal vaccines highlighted at ISPPD-7

A special ISPPD session was devoted to recent advances in protein-based vaccines and considerations for future development. Early results from Intercell AG’s IC47 phase I safety and immunogenicity study were presented. The protein-based vaccine utilizes the C-terminal PASTA domains of the StkP, which has been shown to be critical in pneumococcal bacterial cell division, multiplication and virulence.

Researchers from Novartis Vaccines and Diagnostics and Research Serology also presented work on applying a common correlate of immune protection to protein antigens, reporting “Sera raised against pilus antigens gave a percentage of killing that was comparable to that obtained using sera from conjugated vaccines or from whole inactivated bacteria.” Accordingly, pilus antigens were identified as potential candidates for the development of protein-based pneumococcal vaccines.

Lastly, Dr. Orin Levine gave a presentation on the challenges to licensing protein-based vaccines, a process which has yet to be fully defined. New protein-based vaccines could be licensed based on safety and immunogenicity comparisons to existing vaccines, clinical effectiveness comparisons, or instead through a parallel pathway in which the vaccines are licensed first in adults (generating serologic correlates for immune protection) and then in children. With the multiple options available for licensing new vaccines, developers were urged to carefully consider the benefits and drawbacks of each approach when bringing new vaccines to market.

5. Investigators analyze factors involved in national policy decisions to adopt the Hib vaccine

A team of researchers from the Johns Hopkins Bloomberg School of Public Health and Hib Initiative investigated the factors associated with countries’ time to decision to adopt routine Hib vaccination. They used a multivariate model to analyze data from 147 countries from 1990 to 2007, controlling for Gross National Income, region, and burden of Hib disease. Results revealed that receipt of GAVI support accelerated the time to decision by 63%. The presence of two or more neighboring countries that had adopted the Hib vaccine accelerated decisions to adopt by 50%, which may occur through a process of policy diffusion. Results also showed that higher vaccine prices correlated with slower decision-making to adopt Hib; for each 1% increase in vaccine costs, the time to decision to adopt vaccination was delayed by 2%. The adoption of Hib vaccine accelerated when GAVI set long-term predictable co-financing policies, and decelerated for countries subject to a period of vaccine price uncertainty (2004-2006). These results suggest that both supply- and demand-side factors have played important roles in accelerating national adoption of Hib vaccine and emphasize the potential for formal and informal networks to facilitate policy diffusion. Further, given the current financial need to meet country demand, donors have an opportunity to prevent a predictable loss of momentum in country uptake.

6. Trial demonstrates efficacy of the 7-valent pneumococcal conjugate vaccine in HIV-infected adults

PCV7 effectively protects HIV-infected adults from recurrent infection with vaccine-type pneumococci, according to a double-blind, randomized, placebo-controlled clinical efficacy trial appearing in the New England Journal of Medicine. Dr. Neil French and colleagues followed 496 adolescents and adults in Malawi with a prior episode of documented invasive pneumococcal disease, 88% of whom were HIV-positive, from February 2003 through October 2007. Participants received two doses of PCV7 four weeks apart. The primary endpoint of the study was pneumococcal disease caused by vaccine serotypes or serotype 6A (which has been shown to benefit from cross-protection of a related serotype contained in the vaccine). Of the 67 episodes of pneumococcal disease in 52 HIV-positive patients, 24 total episodes were caused by either vaccine serotypes or serotype 6A. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group (vaccine efficacy 74% with 95% CI 30-90). Vaccine efficacy was highest in the first 12 months after vaccination (85%), compared to the subsequent time period (25%). The authors conclude, “The pneumococcal conjugate vaccine provides an additional therapeutic intervention for improving the care of HIV-infected adults that is both simple and safe to administer, which makes its use highly relevant in Africa.”

7. Research shows influenza is a major contributor to childhood pneumonia in a tropical developing country

In a study published in the Pediatric Infectious Disease Journal, Brooks and colleagues investigated the role of influenza in childhood pneumonia. From April 1, 2004 to December 31, 2007, researchers conducted longitudinal prospective active surveillance among randomly selected households in a low-income urban area in southeast Dhaka, Bangladesh. A total of 12,062 children under age five presented to clinic with eligible febrile and respiratory illnesses; 2,370 nasopharyngeal washes were collected, yielding 321 influenza isolates. This represented an adjusted influenza incidence of 102 episodes/1,000 child-years. During this period, there were 8,198 pneumonia episodes, representing 311 episodes/1,000 child-years. Ninety influenza-positive children (28%) developed pneumonia during their illness. Those who developed pneumonia were younger than those who did not (23.4 vs. 29.7 months, p < 0.001). Nearly half (47%) of influenza-related pneumonia was due to Influenza A (H3N2), which was nearly 3 times more strongly associated with pneumonia than other influenza viruses, such as H1N1 or Influenza B. Overall, influenza was associated with 10% of all childhood pneumonia. These results suggest that influenza may be a major, under-appreciated contributor to childhood pneumonia in tropical and subtropical urban settings, both through a high incidence of infection and high prevalence of pneumonia. Additional research is needed on the effects of influenza vaccine on pneumonia in countries with a high burden of child pneumonia.

8. Study indicates that recently licensed PCV13 has the potential to further reduce invasive pneumococcal disease in the United States

In order to characterize the burden of IPD potentially preventable by use of the newly licensed 13-valent pneumococcal conjugate vaccine (PCV13), and in the context of widespread use of the 7-valent vaccine in the US population, researchers analyzed surveillance data from 2007. The results, published in the CDC’s Morbidity and Mortality Weekly Report, showed that of the 427 IPD cases of known serotypes among children age under five years of age, 64% were caused by serotypes that would now be covered by PCV13. Based on the 2007 rate of IPD in children under age five (22 cases per 100,000), an estimated 4,600 cases of IPD occurred that year, approximately 2,900 of which are estimated to have been caused by PCV13 serotypes. Following a review of data on immunogenicity, safety, and cost-effectiveness of PCV13, in February 2010 the Advisory Committee on Immunization recommended PCV13 for all children aged 2–59 months, and for children aged 60–71 months with medical conditions that increase their risk for pneumococcal disease or complications. Post-licensure surveillance of PCV13 will be important in determining its effectiveness in sub-populations, as well as its effect on non-PCV13 serotype IPD.

9. Sickle Cell Trait, Hemoglobin C Trait, and Invasive Pneumococcal Disease.

In a recent issue of the journal Epidemiology, Poehling and colleagues published the results of a study testing the hypothesis that sickle cell trait or hemoglobin C trait is an independent risk factor for invasive pneumococcal disease (IPD). Over 10 years, researchers followed a study population of more than 128,000 children born in Tennessee, identifying 415 episodes of invasive pneumococcal disease (IPD), of whom 2.4% had sickle cell disease, 7.2% sickle cell trait, 1.9% hemoglobin C trait, and 88.4% normal hemoglobin. The study showed that before PCV7 introduction in the year 2000, disease rates/100,000 child-years were 2,941 for African Americans with sickle cell disease, 258 for African Americans with sickle cell trait or hemoglobin C trait and 188, 172, and 125 respectively for African Americans, caucasians, and Hispanics with normal hemoglobin. Rates declined for all groups following introduction of PCV7. Controlling for age, sex, time, and high-risk conditions, African Americans with sickle cell trait or hemoglobin C trait had 77% (95% CI 22–155) and 42% (95% CI 1–100) higher rates of IPD than African Americans and caucasians with normal hemoglobin. The authors suggest that these findings may at least partially explain historically higher rates of IPD among African American children, but further study is needed to determine the biological mechanism underlying this increased risk.

FINANCE AND SUPPLY

10. Britain to double contributions to GAVI Alliance; Donors meet to discuss remaining $4.3B funding gap for vaccine introductions

The outlook for vaccine financing was bolstered this month by Britain’s pledge to double GAVI Alliance contributions, totaling 150 million GBP (US$230 million) over the next ten years. The announcement was welcomed for its generous commitment as well as the predictability it offers program planners. In late March, the GAVI Alliance hosted international donors in The Hague to discuss the $4.3 billion in funding that is still needed to reach global immunization goals and MDG 4 to reduce child mortality. The funding gap represents 60% of the $7 billion needed to introduce Hib, PCV, and rotavirus vaccines in over 40 developing countries. Current donor commitments and contributions can be found on the GAVI Alliance website.

11. Researchers find vaccine wastage rates can outweigh benefits of decreased storage capacity for multi-dose vials

In anticipation of PCV introductions in developing countries over the next few years, researchers from WHO and Johns Hopkins evaluated the tradeoffs between cold chain storage needs and wastage related to vaccine vial size. The study found that wastage rates varied by vial size, with median rates for single, 2- and 10-dose vials at 5%, 7% and 10% respectively. At the same time, the range of wastage rates increased with larger vial sizes, with up to 27% and 44% wastage rates for 2- and 10-dose vials. The authors emphasized the need to monitor wastage data and make decisions regarding the optimal vial size with attention to cold chain storage capacity and wastage rates.

12. PCV7 cost-effective in Argentina under multiple sets of assumptions

In the March 8 issue of Vaccine, Giglio and colleagues reviewed the cost-effectiveness of 7-valent pneumococcal conjugate vaccine in Argentina. A Markov analytic model was used to calculate cost per life year gained based on vaccination costs and projected changes in disease burden. At $26.50 per dose, vaccination costs under a four-dose regimen for a five-year birth cohort totaled $73,823,806. Vaccination would prevent 159 deaths and over 90,000 cases of pneumococcal disease, including 4,594 pneumonia cases, 756 bacteremias, 70 cases of meningitis, with acute otitis media accounting for the remaining cases of disease. The incremental cost per life year gained was $5,599.42, and when herd effects were taken into account, the cost dropped to $2,821.83. Argentina has a per capita GDP of $11,670, indicating that the vaccine is cost-effective, and very cost-effective when herd immunity and reduced vaccine prices are considered.

13. Impact of indirect effect assumptions on cost-effectiveness calculations reviewed

This month in Vaccine, Rozenbaum and colleagues questioned the inclusion of net-indirect vaccine benefits in cost-effectiveness calculations in European studies. Net-indirect benefits that account for herd immunity protection and serotype replacement effects have been used to project reductions in disease burden primarily among the elderly following the initiation of infant vaccination programs. Cost-effectiveness ratios in European countries including these indirect effects were estimated at €16,750 per QALY and €18,360 per life year gained. In contrast, when these effects were not included in the analysis, cost-effectiveness ratios were €72,360 per QALY and €104,790 per life-year gained. Researchers pointed out the need to better model the indirect effects of vaccine introduction in order to accurately assess economic outcomes.

ANNOUNCEMENTS

Announcing the World Pneumonia Day Photo Contest

Would you like to tell the story of pneumonia in your region and win a new Nikon digital camera? We invite you to submit your photos and short stories related to pneumonia to the World Pneumonia Day Photo Contest for a chance to spread the word about pneumonia. Finalists from each region will have their work featured at an exclusive Washington DC event this summer as well as on several virtual venues. Judges will include Nicholas Kristof of the New York Times and Ann Curry from NBC’s Today Show. Act now—submissions are due on May 31, 2010. Please visit http://www.photoshare.org/contest/wpd/2010/worldpneumoniadayphotocontest.php for more details and to participate.

UPCOMING EVENTS

The Geneva Forum Towards Global Access to Health will be held on April 19-21, 2010 in Geneva, Switzerland. Details are available at http://www.ghf10.org/.

The 8th Annual Vaccination Week in the Americas is planned for April 25 to May 1, 2010. PAHO will partner will countries in the Caribbean and Latin America to offer vaccinations for vulnerable populations. Additional information and supplementary materials are available at:
http://new.paho.org/hq/index.php?option=com_content&task=blogcategory&id=1820&Itemid=2059.

American Medical Seminars is hosting a continuing medical education program titled Pediatric Infectious Diseases: An Evidence-Based Approach. The seminar will be held on April 26-30, 2010 in Sarasota, Florida. Additional information and registration is available at:
http://www.ams4cme.com/www/LiveSeminars/SEMLA-2420100426.aspx.

The 28th Annual Meeting of the European Society for Paediatric Infectious Diseases will take place in Nice, France on May 4-8, 2010. This year’s themes are immunization in special circumstances and better diagnosis of paediatric infectious diseases. Visit http://www2.kenes.com/espid2010/Pages/Home.aspx for more information.

The Global Health Council's 37th Annual International Conference on Global Health, Dateline 2010: Global Health Goals & Metrics, will take place in Washington D.C. June 10-14, 2010. Additional information on this conference, which will examine metrics, progress and challenges on global health goals, is available at http://www.globalhealth.org/conference_2010/.


July 11-14, 2010, the International Conference on Emerging Infectious Diseases will be held in Atlanta, Georgia. Visit http://www.iceid.org/ for additional information about the conference.