SAFETY AND EFFICACY OF PNEUMOCOCCAL CONJUGATE VACCINE

Pneumococcal vaccine is proven effective for preventing serious pneumococcal disease including pneumococcal meningitis, sepsis, and x-ray confirmed (radiologic) pneumonia. This effectiveness is established in clinical trials and documented by systematic reviews of all available data. The protection afforded by pneumococcal vaccines is greatest in populations where access to care is poorest and the risk of pneumonia death is greatest. As a measure of protection, x-ray proven pneumonia is a better marker for vaccine effectiveness than clinical pneumonia because the majority of "clinical pneumonia" cases are either not pneumonia or are milder forms of pneumonia that do not result in death. (Key references 1-4)

Safety is the number one concern for all vaccine programs. WHO’s committee on vaccine safety recently reviewed all the available evidence and concluded that “The current evidence on the safety of multivalent pneumococcal conjugate vaccines is reassuring. Clinical trials and post marketing surveillance in countries that introduced the vaccines have not identified major safety concerns. While there has been a weak and inconsistent signal of increases in reactive airway conditions in some studies, these effects have not been consistently observed.” (http://www.who.int/vaccine_safety/topics/pneumococcal/en/index.html) 

Similarly, a review prepared for the WHO by DeStefano and colleagues concludes “the evidence did not identify any major safety problems with PCV7 or any other pneumococcal conjugate vaccine, with the possible exception of reactive airway disease, which may bear further scrutiny as additional data become available.” Ongoing safety evaluations will monitor this issue but it is incorrect to conclude at this stage that the vaccine significantly increases the risk of asthma or that this risk is life-long, as some media reports have alleged. (Key references 5-6)

Prevention of pneumococcal disease is critical because antibiotic treatment is far less than 100% effective. Furthermore, antibiotic resistance is increasing.  A reliance on antibiotics alone will lead to unnecessary deaths and disability which will primarily occur in those populations and areas where access to care is most limited. (Key reference 7)

Key references:

1.  Lucero MG, Dulalia VE, Parreno RN, Lim-Quianzon DM, Nohynek H, Makela H, Williams G. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD004977. DOI: 10.1002/14651858.CD004977.
2.  Klugman KP, Cutts F, Adegbola RA et al. Meta-analysis of the efficacy of conjugate vaccines against invasive pneumococcal disease. In: Pneumococcal vaccines: the impact of conjugate vaccines. Editors: Siber GR, Klugman KP, Makela KP. 2008. ASM Press: Washington, DC.
3.  Madhi SP, Klugman KP. Efficacy and safety of conjugate pneumococcal vaccine in the prevention of pneumonia. In: Pneumococcal vaccines: the impact of conjugate vaccines. Editors: Siber GR, Klugman KP, Makela KP. 2008. ASM Press: Washington, DC.
4.  Madhi SA, Whitney CG, Nohynek H. Lessons learned from clinical trials evaluating pneumococcal conjugate vaccine efficacy against pneumonia and invasive disease. Vaccine 2008 June 16;26 Suppl 2:B9-15.
5.  DeStefanoF, Pfiefer D, Nohynek H. Safety profile of pneumococcal conjugate vaccines: systematic review of pre- and post-licensure data. Bull WHO 2008; 86:373-80.
6.  Wise RP Post-licensure saftery surveillance for 7-valent pneumococcal conjugate vaccine JAMA 2004; 292:1702-10.
7.  Invasive Bacterial Infection Surveillance Group. Lancet 1999; 353:1216-21.

RESEARCH:

1. SAGE Subgroup publishes review of conjugate vaccines against Hib, meningococcal and pneumococcal disease

In the August edition of Vaccine, Trotter et al review the use of conjugate vaccines in the prevention of disease caused by H. influenzae, N. meningitides  and S. pneumoniae.  The review covers studies from the US, Europe and developing countries and found overall high efficacy for both the Hib and pneumococcal conjugate vaccines studies. For example, post-licensure surveillance for Hib disease has found near elimination in Europe and dramatic declines in developing nations following introduction, as well as sustained reductions in Hib colonization. Carriage of MenC declined by 66% in teenagers a year after conjugate vaccine introduction. and in countries such as England, Spain, Canada, and the Netherlands where it is routinely used. Unpublished data from the CDC cited by the authors shows an 80% decline in disease caused by PCV7 serotypes in adults age 65 or older since routine childhood immunization began in the US and a concomitant decline of 50% in infants too young to be vaccinated. The authors urge further consideration of the indirect effects of conjugate vaccine use as well as more complete investigations of alternative dosing schedules that might increase the indirect impact of the vaccine program.

2. PCV7 impact on community acquired pneumonia in Washington state

A retrospective cohort study of children and adults from Washington state between 1998 and 2004 was conducted by identifying presumptive outpatient and hospitalized episodes of community-acquired pneumonia (CAP). Nelson et al used further patient information to validate these episodes and have published the results in the September issue of Vaccine. Of a total 28,831 episodes identified among all ages, the authors found the group of children under one year of age to have a significantly lower risk of confirmed outpatient CAP in the period after introduction of PCV7 (2003-4) compared to during vaccine introduction (2001-2) (IRR 0.74, 95% CI 0.58-0.95). Although the authors found this statistically significant 26% reduction in confirmed outpatient CAP in children under one after vaccine introduction, no such consistent relationship was found in adult age groups.

3. Brazilian slum inhabitants at high risk for carriage of Streptococcus pneumoniae, including resistant strains

In the September issue of the Journal of Infection, Reis and colleagues report the results of a household survey of Brazilian urban slum inhabitants for nasopharyngeal carriage of pneumococcal serotypes. Of 262 subjects surveyed, 36% were found to be colonized with S. pneumoniae. Children under age 5 and those attending schools were at increased risk (OR 8.0 and 2.7, respectively). 51% of carriers were colonized with serotypes found in the PCV7 vaccine. 10% of isolates were found to be resistant to penicillin while 28% were resistant to cotrimoxazole.

4. Indirect effects of PCV7 use on carriage in American Indian populations

A group-randomized Phase III efficacy trial of PCV7 was conducted by Millar et al among southwestern American Indian communities and published ahead of print in the October issue of Clinical Infectious Disease. Study subjects were vaccinated with PCV7 and controls were administered the MenC conjugate vaccine. Although the study found that decreases in PCV7-type carriage were offset by increases in non-vaccine serotypes, adults and unvaccinated children under age 5 years were found to be significantly less likely to be colonized with vaccine-type pneumococcus than those living with a MenC-vaccinated control individual (OR 0.57 for adults and 0.57 for unvaccinated children under age 5 years as well).

In an editorial in the same issue of CID, Chiara Azzari and Massimo Resti say “…continued surveillance of pneumococcal carriage and IPD for serotype changes and possible serotype replacement is essential, and if performed with specific and sensitive methods… will help us predict the impact of PCV7 and new pneumococcal conjugate vaccines.”

5. Review of the link between bacterial meningitis and development of epilepsy

Murthy et al of the CARE Hospital in Hyderabad, India published, in the August issue of Epilepsia, a review of the link between unproved seizures, including epilepsy, and episodes of bacterial meningitis. Worldwide, at least 890,000 episodes of bacterial meningitis occur each year and the authors estimate that those episodes will result in late-onset unprovoked seizures among 4.2% of survivors. S. pneumoniae appears to carry the highest risk of developing  epilepsy after a bout with bacterial meningitis. Together, Hib, meningococcus and pneumococcus account for 80% of bacterial meningitis globally and the authors state that  “implementing vaccination programs against the three most important meningeal pathogens can reduce the burden of bacterial meningitis and probably thereby associated epilepsy.”

MEDIA:

6.    African countries commit to introduction of new meningococcal vaccine when it becomes available

Health ministers from countries belonging to the African meningitis belt have committed to introduction of the new MenAfriVac, a conjugate meningococcal A vaccine, which was developed through a product development partnership between WHO and PATH. Phase I clinical trial of the vaccine in adults aged 18 to 35 years was successfully completed in The Gambia and Mali, and follow-up trials have been completed in 2 to 29 year olds in these countries. The vaccine is safe in testing and is going to be manufactured by an Indian company. At the 58th session of the WHO Regional Committee for Africa, held in Yaounde, Cameroon, from September 1-5, ministers from various countries committed to several actions, including preparation for comprehensive meningitis control plans, implementation of meningitis control strategies, improvements in information exchange for epidemic response, and contributions to epidemic control activities.

7.    Pneumonia vaccination important for diabetics

Using healthcare databases from Denmark, researchers from Aarhus University Hospital published findings that suggest that diabetes is associated with a 24 to 75 percent increase in the relative risk of hospitalitzation due to pneumonia. The risk of pneumonia-related hospitalization was increased by 4.4-fold in subjects with type 1 diabetes and by 1.2-fold in those with type 2 diabetes. The authors state that these results emphasize the value of influenza and pneumococcal immunization, particularly for patients with longer diabetes duration, and the importance of improved glycemic control to prevent pneumonia-related hospitalization among diabetic patients.

8.    Study recommends modifying pneumonia treatment guidelines in developing countries

A study published in The Lancet by researchers at the Johns Hopkins School of Public Health and the International Centre for Diarrhoeal Disease Research, Bangladesh, builds on evidence that local health facilities are able to correctly treat and manage severe childhood pneumonia. The study suggests that more children will be correctly treated if only the most urgent cases are referred to hospitals. Senior author Robert Black states, “One of the main concerns with treating severe pneumonia at first-line health facilities was safety. Our study shows that it is both safe and very effective”.

9. McKinsey conducts research into ways to accelerate decision-making for vaccine introduction

In the September issue of the McKinsey Quarterly, researchers from the firm will report on three key recommendations for accelerating vaccine introduction, the UK’s TimesOnline reported on September 26th. These recommendations are based on in-depth interviews with key figures in Mexico, Mauritania, Egypt and Zambia. McKinsey analysts found that the involvement of international experts, finance ministers and “cross-border cooperation” can be key elements in facilitating decision-making related to vaccine introduction and cited a “broad failure to share information across countries” as a factor contributing to the traditional delays between vaccine development and introduction into low and middle-income countries.

Results from Online PneumoADIP Poll

A PneumoADIP web-based poll – surveying our readers on what they believe to be the biggest threat to reducing child deaths from pneumonia. Poverty was the leading answer (35%), followed by low immunization (29%), then HIV/AIDS (20%), malnutrition (12%) and antibiotic resistance (4%).  To participate in our latest poll, please visit our website at www.preventpneumo.org.

Upcoming Events:

The All-Party Parliamentary Group on Pneumococcal Disease Prevention in the Developing World launches its report on October 15th, 2008 at the House of Lords, London, England.  The APPG is the only group of its kind in the world, and recently conducted an exhaustive review of evidence on pneumococcal disease and efforts to prevent it, including the Advance Market Commitment, by reviewing written and oral testimony from tens of international experts.  For more information, please visit: http://www.appg-preventpneumo.org/

Together with nearly 100 professional societies, the Pneumococcal Awareness Council of Experts (PACE), a program of the Sabin Vaccine Institute, will launch its global call to action with a press event on October 24th at the National Press Club in Washington, DC.  For more information please visit: www.sabin.org/pace

The 48th ICAAC/IDSA 46th Annual Meeting will take place in Washington, DC October 25-28th. The American Society for Microbiology presents the 48th annual Interscience Conference on Antimicrobial Agents and Chemotherapy in conjunction with the Infectious Disease Society of America’s 46th annual meeting. Registration is available online and on site. For more information, please visit: http://www.icaacidsa2008.org/

The American Public Health Association’s 136th Annual Meeting & Exposition will be held from October 25-29, in San Diego, California. Deadline for early and discounted registration is August 15. For more information, please visit: http://www.apha.org/meetings

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

On November 15, the Kenya Pediatric Association will hold its 2nd Annual Running for Child Survival in Nairobi. The event will be a 3km walk and a 10km run within Nairobi. KPA’s mission is to Promote Better Child Health in Kenya, Enhance Knowledge on Child Health and Improve the Management ,Prevention as well as Eradication of Paediatric and other related diseases through Collaboration, Research, Advocacy, Education, Training, Sharing of Experiences and Implementation of Best Strategies. The goodwill ambassador of Running for Child Survival and former World Record Marathon Holder, Mr. Paul Tergat will flag off the event. He and the other participants will be joined by children from many of Nairobi’s orphanages and schools and immunization and de-worming of children, especially street families, will take place at the Uhuru Park Grounds on the day of the event.

The Global Ministerial Forum on Research for Health will be held in Bamako, Mali, November 17-19 2008. It will bring together up to 1000 policy-makers and researchers to focus on the key linkages between the health sector and research, science and technology, higher education, and the global innovation system. For more information, please visit: www.bamako2008.org