Saving lives

P n e u m o c o c c a l D i s e a s e . S e r i o u s . C o m m o n . P r e v e n t a b l e n o w .

PneumoADIP Progress Repor t 2005 An Innovative

Breakthrough Approach

to Accelerating Access

to Pneumococcal Vaccines

for the World’s Children

Protecting children

Faster than everbefore

GAVI’s PneumoADIP

The PneumoADIP ApproachGAVI’s PneumoADIP is a small, dedicated team based at the Johns Hopkins Bloomberg School of Public Health and is supported by a $30 million grant from The GAVI Alliance. PneumoADIPaims to achieve its goals through partnership with countries, donors, academia, internationalorganizations and industry, and coordinates its activities through a strategic alliance with WHO.PneumoADIP is organized around three main areas of activities:

2 3

CommunicateValue

Esta

blis

hVa

lue

Deliver Value

1. Establish Value – Establishing the value of vaccination by demonstrating the burden of meningitis and pneumoniacaused by pneumococcal bacteria and the value of preventionthrough vaccination.

2. Communicate Value – Communicating effectively to keydecision makers information about disease burden and the valueof vaccination by ensuring that research data are communicatedthrough appropriate and effective communication channels.

3. Deliver Value – Delivering the value of the vaccine byensuring that there is a predictable supply of quality vaccineat an affordable price, an adequate system to deliver it to thechildren who need it, and the financing to sustain its use.

PneumoADIP supports the countries… where vaccines are needed most.

Mission Statement

PneumoADIP’s mission is to improve

child survival and health by accelerating

the evaluation of and access to new,

life-saving pneumococcal vaccines

for the world’s children.

An effective and successful PneumoADIP

could lead to millions of lives saved

through earlier and faster access to vaccines.

1 Dot = 1,000 deaths

Pneumonia deaths in children <5PneumoADIP Activities Started On or Before 2005

PneumoADIP Activities to Start in 2006Source: PneumoADIP, 2005 Source: Estimates based on William, BG Lancet Infect. Dis. 2002

A Message from Dr. Julian Lob-LevytExecutive Secretary of GAVI

PneumoADIP is remaining true to its name by accelerating the pace at which pneumococcal vaccinesbecome available to the developing world. The rapid success of the program is something to be proudof, and it is with great pleasure that I am able to introduce PneumoADIP’s second Progress Report.

Sustainable financing to support immunization programs in the developing world is one of the keycomponents required for the continued success of the ADIP model. This is now more of a reality thanever before. The past year brought several historic advances in immunization financing. The creationof the International Finance Facility for Immunization (IFFIm) gives the GAVI Alliance significantlyincreased resources. The challenge undertaken by the Group of 7 (G7) countries towards developmentof Advance Market Commitments (AMCs) for vaccines is a signal that the momentum for innovativeapproaches to financing continues to grow. This momentum has the potential to have a major impacton our ability to accelerate the introduction of pneumococcal vaccines in the poorest countries.

GAVI’s mission is to save children's lives and protect people's health through the widespread use ofvaccines. Pneumococcal disease is the leading vaccine preventable cause of death among childrenunder 5 in developing countries. Pneumococcal vaccines could also significantly contribute to the Millennium Development Goal of reducing child mortality by two-thirds by the year 2015.PneumoADIP is itself evidence of GAVI’s commitment to work towards assuring that all childrenhave access to life-saving vaccines.

Immunization against vaccine-preventable diseases is still far from universal. I believe that this can be partly attributed to a general lack of understanding about the potential economic benefits from immunization. But this is changing as the evidence grows. Immunization programsrepresent more than an investment in health. In addition to giving protection against killer diseases,vaccines protect people against the long-term adverse effects of illness. Improving the health of a population improves individual prospects for education and work—resulting in healthier communities and wealthier countries.

Immunization is amongst the most cost-effective public health interventions. Greater recognition of its wider benefits should enable us to mobilize and sustain the political will needed to assure allchildren gain access to vaccines. Over the past year, an extraordinary team has been working to makepneumococcal vaccination a reality for children the world over. This second annual Progress Reportfrom PneumoADIP, describes how that team and its partners are helping to make this happen.

With regards,

Dr. Julian Lob-LevytExecutive Secretary, GAVI

A Message from Dr. Julian Lob-Levyt, GAVI 5

An Introduction by Dr. Orin Levine, PneumoADIP 7

Highlights of 2005 8-9Summary of key achievements of PneumoADIP and collaborators

Establishing Value 10-23Description of key activities of the PneumoADIP research team

Communicating Value 24-33Description of key activities of the PneumoADIP communications team

Delivering Value 34-43Description of key activities of the PneumoADIP vaccine and supply team

About PneumoADIP 44-46

4 5

What is pneumococcal disease?Streptococcus pneumoniae is a bacterium that causes serious illnesses, including pneumonia,meningitis, sepsis, and ear infections. It is the most common cause of bacterial pneumoniamortality, killing up to 1 million children under 5 annually. It is also the most severe cause of bacterial meningitis worldwide. More than 90 strains (or serotypes) exist, of which 7 to 11serotypes cause most serious disease in children. Pneumococcal disease kills up to 1% of all children born in high mortality areas, and pneumococcal meningitis leaves about 50% of surviving children with life-long disabilities. Children with HIV/AIDS are 20- to 40-timesmore likely to get pneumococcal disease than children without HIV/AIDS. With both antibioticresistance and HIV infections increasing, there is an urgent need for life-saving pneumococcalvaccines in developing countries.

The following report documents progress made by PneumoADIP during 2005. It outlines ways inwhich the international community is working together to accelerate access to life-saving vaccineagainst a serious common disease for children in the developing world. We hope you will find thereport to be both informative and inspiring.

Table of Contents

An Introduction by Dr. Orin LevineExecutive Director, PneumoADIP

Last year’s Progress Report outlined the aims of GAVI’s PneumoADIP and the work carried out from its inception in June 2003 to the end of 2004. I am now very proud to introduce the latestProgress Report, detailing the major achievements of the past year.

Impressive advances have been made, both in increasing the area of the world covered by pneumococcal disease surveillance and research and in publicizing PneumoADIP’s message that accelerated introduction of vaccine is both necessary and feasible.

Researchers all over the world are now collecting surveillance data that will establish the huge burden of pneumococcal disease in the developing world. Meanwhile, vaccine trials are demonstratingconclusively that the vaccine is highly effective in tackling the disease and reducing childhoodmortality. PneumoADIP’s coordinated communications efforts mean that more health policy makersare aware of these facts than ever before.

One particularly exciting area is the work to develop innovative financing mechanisms designed to bridge the gap between developing countries’ demand for vaccine doses, donors’ ability to pay for them, and manufacturers’ need to plan and sustain their production. We hope that in 2006, we will see major progress in this area and perhaps even a firmer commitment tofinance vaccine procurement.

For all the advances and achievements reported in this document, pneumococcal disease remains a major cause of preventable childhood mortality. The task in front of us is still enormous, and it is essential that everyone involved continues to work together towards our collective goal.

With my very best wishes,

Dr. Orin LevineExecutive Director, GAVI’s PneumoADIP at Johns Hopkins

Step 1 Build a credible demand forecast to establish terms for affordable, sustainable supply and financing

Step 2 Donors and industry commit to binding agreements to finance and supply vaccines for developing countries

Step 3 Support evidence-based demand for vaccine introduction in developing countries

6 7

Donor

Industry

Country

Donor

Industry Country

JUNE 2003

Before PneumoADIP PneumoADIP Efforts PneumoADIP Mission

THE NEAR FUTURENOW

Together we can save the lives of 3.6 million children by 2025.

0

200,000

400,000

600,000

800,000

900,000

1,000,000Lives savedwith no action

100,000

300,000

500,000

Child

hood

deat

hsca

used

bypn

eum

ococ

cald

isea

se

Based on WHO estimates of pneumococcal mortality in children <5 years of age

700,000

20072009

20112013

20152017

20192021

20232025

3.6 millionlives saved by 2025with accelerated

introduction

Source: PneumoADIP Analysis, 2005

Committing funds to finance pneumococcal vaccines is the next step to protecting the world’schildren from the #1 vaccine-preventable disease.

Steps in Accelerating Vaccine Introduction – Finding the Solution Space

8 9

Vaccine Supply and Financing

1. Developed a credible strategic demand forecast for pneumococcal vaccine introduction in the 72GAVI-eligible countries. This demand forecast represents an important milestone on the path tosustainable, affordable vaccine supply for developing countries because it allows decision-makers indonor countries, the vaccine industry, and developing country governments to see the size andtiming of the commitments each must make to achieve routine vaccination for all children.

2. Provided a convincing case to Group of 7 (G7) finance ministry representatives that the G7 shouldpilot the innovative financing mechanism called Advance Market Commitment by investing $1.5billion or more to procure pneumococcal vaccines for developing countries over the next 15 years.This analysis catapulted pneumococcal vaccines onto the list of candidates for financing thathad included malaria, HIV/AIDS, TB, and others before PneumoADIP contributed its case.Recent reports from the G7 have highlighted pneumococcal vaccines in the same financingcandidate list with malaria and HIV/AIDS. A G7 decision on which vaccines to select for thepilot is expected in 2006.

3. Built a comprehensive forecast of pneumococcal vaccine supply from 2006-2025 that includesprojections of the roles for both multi-national and emerging market suppliers, and conjugate andcommon protein vaccines. This supplier analysis is an important step in assuring an affordable,sustainable supply of pneumococcal vaccines for developing countries.

Communications

1. Documented a 7-fold increase in media coverage of pneumococcal disease and vaccine issues,driven in large part by PneumoADIP’s media outreach efforts. An independent analysis conductedby ECHO Research shows that PneumoADIP’s efforts to communicate key, evidence-basedmessages are raising awareness of pneumococcal disease as a global health problem and vaccines as a realistic solution.

2. Broadcasted to over 250 million households in January 2005, the BBC World documentary “Kill or Cure?” focused on the human face of pneumococcal disease. The success of the 1st film led to the commissioning of a 2nd BBC World documentary “Kill or Cure?” Special – aboutpneumococcal vaccines. This 2nd film looks at the great public health impact of routinepneumococcal immunization in the U.S. and efforts underway to protect children from dying of pneumococcal disease worldwide.

3. Assured widespread coverage of the results of The Gambian pneumococcal vaccine trial.Recognizing the importance of translating the scientific findings from this historic trial intomessages for general audiences, PneumoADIP collaborated with the trial sponsors to conductmedia outreach efforts including a press conference in Washington, DC. These efforts led tocoverage of the trial’s results by over 100 networks in the US and Europe, and numerous printpublications in North America, Europe, Africa, and Asia, including front page coverage in theNew York Times and the Baltimore Sun.

Research and Surveillance

1. In collaboration with the WHO,

a Established rigorous, systematic methods for estimating the global, regional, and local burden of pneumococcal disease. PneumoADIP scientists are working with WHO colleagues to create country, region, and global estimates of pneumococcal disease burden based on a comprehensive review of the literature, and using advanced modeling and meta-analytictechniques. These methods are being developed in collaboration with GAVI’s Hib Initiative.

b Implemented standard methods for conducting pneumonia and meningitis surveillance bysupporting networks of investigators throughout the world. The use of standard case-definitions,reporting formats, and laboratory methods by a broad range of surveillance and researchgroups is helping assure data of similar quality and accuracy from all countries. By workingthrough networks, WHO and PneumoADIP promote the sharing of best practices and recentdata across countries and sites. To date more than 42, 000 clinical specimens have beencollected in 13 countries using PneumoADIP support.

2. Selected 8 field sites in Asia for further development as sites that can evaluate the public healthimpact of pneumococcal vaccines in the region. PneumoADIP used an open, competitive processto solicit applications from potential field sites and an expert review committee to select theones for further development. 26 applications were received from sites representing 10 Asiancountries and then evaluated with field site visits by technical reviewers.

3. Awarded 20 Small Grants to support local investigators in 17 developing countries establish and communicate the burden of pneumococcal disease and the value of vaccination. Three rounds of applications in 2005 to PneumoADIP’s Small Grants Program produced 48 applications. A competitive process and expert review were used to select the highest priority grants for funding.

Highlights of 2005

10 11

Activities Started On or Before 2005

Activities to Start in 2006

PneumoADIP Activities in 56 Countries

Pneumococcal Disease is on the Map in 56 Countries with PneumoADIP Support

The past year has seen significant progress towards PneumoADIP’s aims of establishing the burden of pneumococcal disease, extending surveillance to areas not previously covered, and communicating the effectiveness of the pneumococcal vaccine. This section of the report describes some of the PneumoADIP-funded research going on across the world.

Maria Deloria Knoll, Director of Research at PneumoADIP

Establishing Value

Source: PneumoADIP, 2005

Ongoing Work to Quantify Pneumococcal Disease BurdenStreptococcus pneumoniae is a serious,common, and preventable global healthproblem. WHO estimates that pneumo-coccal diseases, mainly pneumonia andmeningitis, kill more than 1.6 millionpeople annually. This includes up to 1 million childhood deaths, makingpneumococcal disease the number onevaccine-preventable cause of childhooddeath worldwide.

Decision makers in developing countriesneed accurate data at a local andregional level in order to justifydedicating resources to combating this disease. Supporting research andsurveillance in these countries to providesuch data is one of PneumoADIP’sstrategic goals.

12 13

Source: WHO official mortalitiy rates — June 2003* Provisional estimates

Pneumococcal disease*

Measles

Hib

Rotavirus*

Tetanus

HepB

Deat

hs/Y

ear

0

200,000

400,000

600,000

800,000

100,000

300,000

500,000

700,000

900,000

Children Under 5

Leading Causes of Vaccine-Preventable Death in Children <5 Years Old

~42,000 Blood & CSF SpecimensCollected Across All Surveillance Sites

%of

allp

ositi

veCS

Fsp

ecim

ens

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

50,000

2003 2005

Source: PneumoADIPsponsored surveillanceCSF: Cerebrospinal Fluid

Expansion of PneumoADIP Projects Globally

#of

Coun

tries

2003

10 1116

2429

56

2006

0

10

20

30

40

50

60

Source: PneumoADIP, 2005

“Robust disease burden data areessential for introducing a new vaccine.PneumoADIP is gaining the advantage bygathering this evidence to aid the decisionto introduce pneumococcal vaccines.”

Hanna Nohynek, National Public Health Institute, Finland

15

Growth and Comparability of Regional Surveillance Networks

In the past two years, the value of pneumococcalsurveillance networks has been more evident than ever. With technical and financial supportfrom PneumoADIP and WHO, the pneumococcalsurveillance networks are collecting standardizedpneumococcal disease data and communicatingtheir local data to regional network partners,including surveillance sites, ministries of health,multilateral organizations, and donors supportingvaccination. In 2006, new networks continue theexpansion of pneumococcal disease surveillance all over the world.

14

EMRO- Morocco- Egypt- Syria- Yemen- Tunisia- Pakistan

SIREVA II- 21 countries

netSPEAR- Kenya- Uganda- Ethiopia- Tanzania- Burundi- Eritrea- Rwanda

IBIS/SAPNA- India- Nepal- Sri Lanka

IVI- Vietnam

IEIP/MOH/CDC- Thailand

ICDDR.B- Bangladesh

Pneumococcal Surveillance Networks: Meningitis, Pneumonia, Sepsis

netSPEAR The Network for Surveillance of Pneumococcal Disease in the East Africa Region is apneumococcal and Hib disease surveillance network operating in seven countries in EastAfrica. It works in conjunction with the WHO/AFRO Pediatric Bacterial Meningitis Networkin many surveillance sites.

ICDDR,B The International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B): Center for Health and Population Research aims to establish the value of pneumococcal vaccine by determining the local burden of childhood pneumococcal disease and pneumonia inBangladesh and the distribution of serotypes causing severe pneumococcal infections. It has recently received a funding boost from the Bangladesh Government (see p. 14).

IBIS/SAPNA The Invasive Bacterial Infections Surveillance/South Asian Pneumococcal Alliance bringstogether a consortium of Nepalese and Sri Lankan hospitals and an existing Indian surveillancenetwork in an ambitious project to better define the regional burden of pneumococcaldisease. The investigating team has made close links with national health policy makers, to ensure that the data gathered will help to influence health policy in these countries.

IEIP The Thai International Emerging Infections Program is including microbiologic surveillanceinto its existing population-based pneumonia surveillance program. By collecting bloodcultures from hospitalized patients with pneumonia, this project aims to estimate theincidence of pneumococcal pneumonia in persons of all ages in Thailand.

IVI The International Vaccine Institute in Vietnam is conducting a pilot study of hospital-basedpneumococcal disease in Khanh Province, in efforts to document the local pneumococcaldisease burden.

EXIS

TIN

GN

ETW

ORKS

NEW

NET

WOR

KSIN

2006SIREVA II This project aims to contribute to the development of a regional epidemiological surveillance

network for vaccine-preventable childhood respiratory diseases due to pneumonia, influenza,and meningitis in Central and South America. The network includes selected sentinel hospitals,public health laboratories, and epidemiological surveillance units of the health ministries inparticipating countries.

EMRO This project aims to contribute to the development of a regional epidemiological surveillancenetwork for vaccine-preventable childhood respiratory diseases due to pneumonia andmeningitis in the Eastern Mediterranean region. The project will add onto the existingbacterial meningitis network currently operating in the region and will include hospitals and public health laboratories in participating countries.

Bangladesh Surveillance ProjectReceives Government Funding

Two years ago in Bangladesh,researchers from multiple institutionsembarked on an ambitious pneumo-coccal surveillance network project,coordinated by ICDDR,B, to providepopulation-based data on pneumococcaldisease for policy makers. Recently, thegovernment of Bangladesh committedadditional funding to this project for thenext 2 years, ensuring the continuationof key hospital-based activities through2007. This commitment signals gov-ernment recognition of pneumococcaldisease as a public health priority. Theadditional funding comes from a grantthat the government of Japan earmarkedfor the Bangladesh government foraddressing the health of the poor.

The project has had close links with thegovernment from the outset, workingclosely with surveillance partners inpublic hospitals. ICDDR,B itself alsohas longstanding good relations withthe Bangladesh government. As theproject has progressed, governmentcolleagues have become increasinglyenthusiastic about pneumococcal disease surveillance.

At the start of the project, collabora-tors were reluctant to perform blood cultures – microbiologists had fewresources, and clinicians had no experience of blood cultures helpingin the management of patients. Byproviding technical support and somekey supplies, the project enabledmicrobiologists to isolate organisms,and the clinicians were quick toappreciate the information. Key peoplethus overcame their initial reluctanceand became advocates of blood cultureand the importance of pneumococcusas a pathogen.

“Working with PneumoADIP has really linked me into a much larger community of people working on pneumococcal disease in Asia.Their efforts to get everyone using similar surveillance methods are especially valuable.”

Samir Saha, Professor of Microbiology, Bangladesh Institute of Child Health

Source: PneumoADIP

Expansion of Small Grants ProgramPneumoADIP is delighted to have greatly expanded its Small Grants Program, which enablesbroader geographic involvement and a greater variety of projects than is possible by other means.Small grants can represent a great investment in developing countries, achieving a lot in a shorttime and sowing the seeds for larger projects. In many cases, data from different projects may be complementary, acting as pieces of a puzzle that build up to create a bigger picture.

16 17

Latin America- Guatemala- Dominican Republic

Africa- Togo- Burkina Faso- Democratic Republic of Congo- Kenya- Tanzania- Mozambique- Nigeria

Pneumococcal Small Grants Projects

North Africa & Asia- Egypt- Jordan- Lebanon- Pakistan

Eastern Europe- Georgia - India

- Bangladesh- Viet Nam- Fiji

Source: PneumoADIP

Cost Effectiveness Vaccinating children in developing countries against pneumococcal infection has Study great potential to save lives and reduce disability, but will also require substantial

new financing. In order to assist decisions about investment in pneumococcal vaccine purchase and to help inform PneumoADIP priorities, Dr. Tracy Lieu and her colleagues are undertaking a cost-effectiveness analysis of pneumococcal vaccination in GAVI-eligible developing countries. Preliminary analyses indicate that pneumococcalvaccinations in GAVI-eligible countries are highly cost effective in saving lives and averting treatment costs and long-term costs due to disability. The aim of this project is to provide robust estimations of lives saved and costs averted per cost of vaccination – these types of comparable units of cost and benefits would facilitate decision makers to prioritize interventions.

Global Disease PneumoADIP is supporting WHO to develop official estimates of global pneumococcalBurden Estimate disease burden, including deaths in children. These figures will assist countries when

prioritizing among the many health needs of children and help with efforts to increasefinancing by illustrating the potential health benefits of vaccination.

Binax Study This multi-site study aims to evaluate the utility of Binax Now® (an antigen test forStreptococcus pneumoniae) as an adjunct to culture for the diagnosis of pneumococcalmeningitis in a variety of settings. Particularly in rural areas, a rapid test tool likeBinax Now® may improve the diagnosis and treatment of children with meningitis andwith documenting local pneumococcal meningitis. This study is being built on theexisting pneumococcal surveillance networks.

Tracheal Aspirate In China, local researchers will conduct a study designed to evaluate the usefulnessStudy of the orotracheal aspiration (OTA) method, a clinical technique for diagnosing

pneumococcal pneumonia, among children under 3 years of age. Testing the specificityand sensitivity of alternative diagnosing techniques such as OTA provides researchersand clinicians better ways to diagnose, document and treat pneumococcal disease.

Vaccine Trial PneumoADIP and WHO support ancillary studies from pneumococcal vaccine clinical Ancillary Studies trials in South Africa, The Gambia and the Philippines. Funding for these ancillary

studies allows researchers to conduct various in-depth analyses on their existingvaccine trial data. The majority of the ancillary studies evaluate the usefulness of various diagnostic techniques in confirming pneumococcal disease cases at diversegeographic settings in order to better estimate the potential health and economicimpact of pneumococcal vaccination.

Other Research Activities

Small Grants Program: Other Research Projects

Some projects focus on assessing the short- and long-term disability and developmental consequences of pneumococcal disease in order to better estimate the lifelong disease burden.Others aim to assess the costs of treating pneumococcal disease to families and health systems,establish evidence-based messages about pneumococcal vaccines for informing health professionals,and assess risk factors for pneumococcal disease.

1918

Burkina Faso Capacity building and operational research on bacterial meningitis due to and Togo Streptococcus pneumoniae in the Bobo-Dioulasso region and the proportion of

bacteremic pneumococcal disease among people hospitalized with pneumonia in Burkina Faso (Association pour l’aide a la Médecine Préventive).

Congo, Prevalence of invasive cerebrospinal disease, resistance profiles, and serotype Dem. Rep distributions of pediatric infections due to Streptococcus pneumoniae in Kinshasa,

Democratic Republic of the Congo (Kinshasa School of Public Health and UCLA).

Dominican Burden of disease and serotype prevalence in children aged under 5 years in Santo Republic Domingo (Robert Reid Cabral Children’s Hospital, University of Miami and partners).

Egypt Hospital-based prospective surveillance of severe pneumonia and bacteremicpneumococcal pneumonia in children 1 to 23 months old in Alexandria Governorate,Egypt (NAMRU3, Cairo)

Guatemala Incidence of invasive pneumococcal disease in children hospitalized in Guatemala City(Johns Hopkins Bloomberg School of Public Health and University of Guatemala City).

Jordan Study on serotypes and sensitivity pattern of pneumococcal isolates leading to invasivedisease in tertiary care centers in Jordan (Jordan University School of Medicine, JordanUniversity Hospital, and the Islamic Hospital).

Lebanon Establishing a pilot surveillance program for pneumococcal infections in Lebanon(American University of Beirut and partners).

Mozambique Surveillance of bacterial meningitis among children under 15 years of age hospitalizedin the Manhiça Hospital, Mozambique (Manhiça Hospital).

Nigeria Serotypes and antibiotic sensitivities of invasive S. pneumoniae in Ile-Ife, Osun State (Obafemi Awolowo University Teaching Hospital Complex).

A study of invasive pneumococcal disease among children in Ibadan City, Nigeria(University of Ibadan/University College Hospital)

Pakistan Enhanced surveillance for invasive pneumococcal disease in children in Sindh, southern Pakistan (Aga Khan Univeristy).

Tanzania The serotype distribution of carriage and invasive pneumococcal isolates from childrenin northern Tanzania (Kilimanjaro Christian Medical College, Tumaini University, Royal Free & University College Medical School).

Bangladesh Follow-up of pneumococcal meningitis cases to determine long-term impact (Dhaka Shishu (Childrens) Hospital, Johns Hopkins Bloomberg School of Public Health and partners).

Fiji A cohort study to assess quality of life in young Fijian children with a history of bacterial meningitis (Fiji Pneumococcal Project (FiPP) is a collaborative project between the University of Melbourne, the Fiji Ministry of Health (MoH), and the FijiSchool of Medicine (FSM)).

Prospective meningitis burden of disease study and rapid assessment of neurologicaloutcomes in children in Fiji: part 2, extension of laboratory work (Fiji PneumococcalProject (FiPP) is a collaborative project between the University of Melbourne, the FijiMinistry of Health (MoH), and the Fiji School of Medicine (FSM)).

India Risk factors and consequences of S. pneumoniae colonization in the nasopharynx of infants in Vellore, India (Christian Medical College).

Kenya Long-term survival and disability in children who survived pneumococcal meningitis treated in a district hospital in Kenya (Kenya Medical Research Institute, Kilifi District Hospital).

Presenting the case for improved childhood vaccination in Kenya (Kenya PediatricAssociation).

Viet Nam Socio-behavioral study and healthcare utilization survey of community-acquired pneumonia, meningitis, and sepsis in children of an urban and rural community in Viet Nam (Khanh Hoa Health Service).

Cost-of-illness associated with invasive pneumococcal diseases in children, Khanh Hoa Province, Viet Nam (Khanh Hoa Provincial Public Health Service).

As a result of the large response to the third round of funding, a fourth round was solicited in October, 2005. The award has been increased to $40,000, and more than 20 applicationshave been received.

Small Grants Program: Surveillance Projects

Many of the projects focus on establishing new and/or strengthening existing surveillance networks,in order to gather valuable local data on pneumococcal disease (prevalence, serotype distribution,and antimicrobial resistance). Many of the surveillance project sites are in settings where localdata on pneumococcal disease have never been systematically collected previously.

“PneumoADIP’s small grant allowed me to start some surveillance locally.Without it, I couldn’t have gotten this idea off the ground.”Adegoke Falade, Department of Paediatrics, University College Hospital,University of Ibadan, Ibadan, Nigeria

Site Selection

Twenty-six sites in 10 different Asian countries expressed an interest in participating, and 23 of these were selected for further evaluation, with at least one from each of five sub-regions. After a rigorous 11-month review process, in May 2005 PneumoADIP was able to announce theselection of sites in seven countries for further development as potential sites for large-scale vaccine evaluation.

Selected Sites 1. Kamalampur, Bangladesh 5. Sa Kaeo and Nakon Phanom, Thailand2. Karachi, Pakistan 6. Nha Trang, Vietnam3. Colombo, Sri Lanka 7. Ulaanbaatar, Mongolia4. Shivgarh, India 8. The Hib Probe Study sites, India

These sites represent the diversity of Asia and form a foundation for building a firm evidencebase in Asia to support decisions on vaccine introduction.

Establishing the Potential for Pneumococcal VaccineAnother of PneumoADIP’s goals is to help researchers demonstrate the effectiveness of the pneumococcal conjugate vaccine in developing countries around the world; ultimately to strengthenthe case for the widespread introduction of the vaccine.

Asian Field Site Development Initiative

Based on the recommendations from PneumoADIP’s scientific advisors, PneumoADIP created theAsian Field Site Development Initiative in May 2004 with the goal of identifying and developingsites that represent the diversity of Asia, where the impact of the pneumococcal vaccine can beevaluated. These sites are of considerable interest to the vaccine manufacturing industry, asinformation on potential vaccine impact in Asia is lacking.

20 21

Asian Field Sites

Rationale behind the initiative

Before this initiative, only one large-scale trial of a pneumococcal conjugate vaccine was underway in Asia (in Bohol, Philippines), which, while valuable, was not likely to be sufficiently representative to support evidence-based introduction in all of the diversesub-regions of Asia. PneumoADIP does not at present have sufficient funds to supportlarge-scale studies but hopes to contribute to overcoming the gap in the evidence base by identifying potential sites, investing in site development, and developing possible studydesigns. If successful, PneumoADIP’s investments should attract industry to supply thevaccine and draw donors willing to fund the studies. The investments will also provide critical data for country-based decisions.

Source: PneumoADIP

22

Gambia Trial Shows Efficacy ofPneumococcal Conjugate Vaccine

The Gambian Government and theBritish Medical Research Council (MRC)conducted a randomized, placebo-controlled, double-blind, multicenterstudy of 9-valent pneumococcal vaccinein children in eastern Gambia. Theresults were published in The Lancetin March 2005.

This was the first major randomized,controlled vaccine clinical trial innearly 20 years to show significantreduction in child mortality. The trialresults were:

• overall reduction of childhoodmortality by 16% in childrenvaccinated with the 9-valent

• the 9-valent was 77% effective inpreventing pneumococcal infectionscaused by the vaccine serotypes

• 37% fewer cases of pneumonia in the children who received thevaccine compared with children who received the control vaccine.

A previous study showed that this vaccine was effective in reducing thenumber of pneumococcal infections in children in urban South Africa. Butmany of the children suffering frompneumococcal disease in Africa live inrural areas with high infant mortalityrates, significant rates of malariatransmission and very limited access tohealthcare. The Gambia is representativeof these areas, and the results of thestudy suggest that the deaths causedby pneumococcal infections in ruralAfrica are preventable.

The study investigators, led by Felicity Cutts of the MRC, concludedthat pneumococcal conjugate vaccinehas a high efficacy against radiologicalpneumonia and invasive pneumococcaldisease in a rural African setting, and can substantially reduce hospitaladmissions and improve child survival.They recommended that pneumococcalconjugate vaccines should be madeavailable to African infants.

GOOD NEWSThree North American publications in autumn 2005 highlighted the value of childhood pneumococcal conjugate vaccination in improving public health.

US Data Show Value of Vaccine

The US Centers for Disease Control and Prevention (CDC) reported surveillance data on invasive pneumococcal disease in the USA before and after the introduction of the 7-valent vaccine,describing the public health impact as “phenomenal.” The incidence of vaccine-type invasive pneumococcal disease declined by 94% in the target age group, even though the coverage rate during the surveillance period was only 68%. A significant decrease in incidence was also seen in unvaccinated age groups, as a result of herd immunity due to decreased transmission from vaccinated children to unvaccinated contacts. (CDC. MMWR 2005; 54: 893-897.)

Vaccine Reduces Health Disparities in Alaska

A study in Alaska found that pneumococcal conjugate vaccine helped to eliminate a longstandinghealth disparity. Before the 7-valent vaccine was introduced, Alaska Native children (especiallythose in rural areas) had reported rates of pneumococcal disease among the highest in the worldand three times higher than in other children in the state. Within 4 years of introduction of the vaccine, this disparity had been virtually eliminated. The excess risk for disease due to the vaccineserotypes decreased from 175 cases per 100,000 per year to only 5 cases per 100,000 followingintroduction of the vaccine. (Hennessey et al. Vaccine 2005; 23: 5464-5473.)

Health Impact of Vaccine Demonstrated in Canada

A recent report in the Canadian Medical Association Journal summarized trends in pneumococcal disease incidence from 1998 to 2004 based on prospective population-based surveillance data from the Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) team.Following introduction of universal immunization of infants with 7-valent pneumococcal vaccine in 1992, a prompt and large decline in the incidence of invasive pneumococcal infection amongchildren under 2 years of age occurred in the Calgary region. As in the US, herd immunity wasseen, with an associated fall in the incidence of PCV7 serotype invasive disease among adults aged over 65 years. (Kellner et al. CMAJ 2005; 173: 1150-1151.)

What data do the regional surveillance networks provide to facilitate informed decision-making about pneumococcal vaccine introduction?

Pneumococcal disease burden: Quantifying who andhow many people are getting pneumonia, meningitisand sepsis in a country or region as a result ofS. pneumoniae infection

Pneumococcal bacteria serotype: Identifying the most common types of S. pneumoniae bacteria in a country or region

Pneumococcal bacteria antibiotic resistance:Identifying which antibiotics (used in a countryor region to treat people with S. pneumoniaeinfection) may no longer be as useful because the bacteria have already begun to “resist” or not be affected by the antibiotics

These three types of data facilitate decision-makers in finding the best solution to prevent pneumococcaldisease at the local level.

Why is it very important that the data that the local and regional surveillance networks collect are comparable across borders?

There are many ways to collect the three types ofdata about pneumococcal disease; however, in orderfor the data to be most useful for both scientists andpolicy makers anywhere, the data must be collectedin the same way or a comparable way.

Pneumococcal disease (as all diseases) occureverywhere and are not limited by any borders. As long as data are comparable across borders,estimating disease burden for areas withoutsurveillance is possible.

“In the US, the benefits of childhood pneumococcal vaccination have exceeded everyone’s expectations. The next challenge is to speed this life-saving vaccine to children everywhere.”

Anne Schuchat, Director, National Immunization Program, CDC

“Current evidence points to aneffective pneumococcal vaccinethat could begin to save lives now.We cannot afford to wait untilanother million children die next year. We must act now.”

Adenike Grange, President of theInternational Pediatric Association

23

Communicating Value

24 25

It has been a particularly successful year for the communications team here at PneumoADIP. Encouraging results emergingfrom PneumoADIP-funded research and that of its partners have enabled the team to widely publicize essential information onpneumococcal disease and prevention through vaccination. This section of the report describes our coordinated efforts toplace pneumococcal disease firmly on the world map and, more significantly, higher up the international health agenda.

Hans Kvist, Communications Director at PneumoADIP

New Vaccine Said to Offer Hope Against Deadly Bacterium

In Africa, pneumonia vaccine offers hope Tests of drug in Gambia lessened overall mortality by 16 percent for children

Experimental Wyeth Vaccine Reduced African Child Deaths

Doctors hail child pneumonia jab

Pneumonia vaccine cuts deaths in African children

Poverty leads 10 million children to an early grave

Frühes Impfen rettet Leben

Impfen senkt Kindersterblichkeit

Schutz für Millionen von Kindern

Global Communication of The Gambia Vaccine Trial Results

The results of the pneumococcal vaccine trial in the Gambia led by Professor Felicity Cutts of the Medical Research Council were published in The Lancet on 26 March 2005. PneumoADIPcoordinated global communications efforts on behalf of the trial sponsors to publicize the results of the trial.

The media campaign focused on the message that this was the first major randomized controlledvaccine trial in nearly 20 years to show a significant reduction in child mortality (16% reductionin all-cause mortality). Materials aimed at communicating science effectively were developed withspecific sets for the US and European media. These materials formed part of a global mediacampaign surrounding the publication of the paper in The Lancet.

A news conference for US print and broadcast media took place in Washington and included a 3-minute promotional film made in association with Rockhopper TV. C-Span covered the event live,and reporters from the News Hour on PBS were present. Over 100 broadcast networks in the USand Europe and numerous print publications worldwide covered the trial results. The New YorkTimes, Baltimore Sun, and CBS-Radio all conducted interviews during the event. In Europe,Ruder Finn London and its affiliate network secured extensive press coverage across the continent.Newspapers that covered the story included The Guardian, The Daily Mail, Libération, Le Quotidiendu Médicin, Vesa Vanhalakka, and Medi Uutiset. In addition, BBC, Reuters, Associated Press,and Agence France Presse all wrote pieces on the trial results.

This global campaign was successful in achieving its aim of raising awareness of pneumococcaldisease as a leading cause of death in children and infants and the need for an effective vaccinein the developing world.

Spreading the Word on Pneumococcal Disease

Coordinated and Proactive Communications Efforts Raise Awareness

PneumoADIP commissioned independent research from Echo Research to assess whetherpneumococcal disease has moved up the media agenda since PneumoADIP has been in operation. When PneumoADIP started in June 2003, research showed that pneumococcal diseasewas mentioned infrequently in the media, mainly in relation to use of existing vaccines in thedeveloped world, and Internet searches brought up no results. The new research covered the period April 2003 to September 2005, focusing on English-language coverage (print and online) in key donor countries.

Pneumococcal disease coverage increased as PneumoADIP stepped-up its communications efforts. Coverage during the first 9 months of 2005 was more than seven-fold higher than in theequivalent period of 2004 (122 vs 17 articles). None of the pneumococcal disease stories wasassessed as negative – all were either neutral or positive. The focus of 45% of pneumococcaldisease articles was in the developing world; PneumoADIP was responsible for generating 36% of these, and 13% were related to The Gambia vaccine trial.

PneumoADIP’s coordinated communications program has thus been successful in helping to raise the profile of pneumococcal disease, increasing awareness of the associated burden and the existence of life-saving vaccines. The launch of the Hib Initiative in December 2005 willimpact future media coverage of pneumococcal and Hib disease.

26 27

“The international community’s tasknow is to continue to work togetherproductively to make the pneumococcalconjugate vaccine widely available tochildren in Africa.”Dr Lee Jong-wook, Director-General of the World Health Organization

“The Gambia Vaccine Trial results are fantastic news for global health. The results extend the findings of previous trials by showing that pneumococcal vaccines protect the world’s most vulnerable children — those living in rural Africa — from pneumococcal disease. At PneumoADIP, our work is just beginning as we take on the ambitious goal of assuring access to this vaccine for every child, everywhere.”

Professor Orin Levine, Executive Director, PneumoADIP

BBC News Online covered the story under the headine Pneumonia vaccine saves children

In an end of year review of favorite papers in infectious disease The Lancet(Vol 5, December 2005) ranks The Gambia pneumococcal vaccine trial paper 5 out of 35.

Quarterly Trend in Media Coverage of Pneumococcal Disease

0

10

Q2

Favo

rabl

eM

edia

Cove

rage

Q3

2003 2004 2005

Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3

20

30

The Gambiapneumococcalvaccine trial

published

Source: PneumoADIP, 2005

Asia Documentary Filming in Alaska, India, Nepal

In January 2005, BBC World aired a documentary on pneumococcal disease as part of its “Kill or Cure?” series highlighting neglected diseases in the developing world. This provided an early opportunity to highlight pneumococcal disease as a serious, common yet preventable disease affecting many children.

In December 2005, PneumoADIP was proud to participate in the production of a “Kill or Cure?”Special BBC World documentary on pneumococcal disease, due to be aired early in 2006. This follow-up film took an in-depth look at the success of routine pneumococcal immunization in NorthAmerica (Alaska), highlighting the severe burden of disease in India and Nepal and efforts underwayto introduce pneumococcal vaccines where they are needed most. The documentary featured supportive statements by Norwegian Prime Minister Mr. Jens Stoltenberg and Dr. Raj Bahn of India.

29

PneumoADIP Press Briefing – Dhaka, Bangladesh

During the second annual meeting of PneumoADIP-supported investigators from around the world,PneumoADIP and WHO gave a press briefing entitled“Bacterial Pneumonia and Meningitis: Understanding the Burden of Pneumococcal Disease.”

The briefing – in Dhaka, Bangladesh on 18 January2005 – was attended by all the local daily newspapersand weekly magazines, three regional television stations, and two international wire services (Associated Press

and Reuters). The journalists attending heard presentations from several of the lead investigators,including Dr Samir Saha, Professor of Microbiology at the Bangladesh Institute of Child Heath,who runs a PneumoADIP-supported disease surveillance project.

The main focus of the briefing was on emphasizing the importance of preventing unnecessarychild deaths, a message that was given extra impact by Dr Saha’s local information. The prioritywas to sensitize journalists to the issues and raise awareness ahead of future announcementsand/or calls to action in the area.

PneumoFOCUS Newsletter Dedicated to Pneumococcal Issues

The PneumoADIP Communications team produced and distributed its monthly newsletter,PneumoFOCUS, dedicated to all sector news about pneumococcal disease and pneumococcalvaccines in 2005. PneumoALERT, special issues, informed PneumoADIP colleagues about breakingnews such as the airing of the BBC World documentary in January, The Gambia vaccine trial resultsin March, and ISPPD-5 deadlines. The newsletter is a good way of keeping up to date withPneumoADIP’s activities, as well as information on meetings, funding opportunities, and otherpneumococcal vaccine-related news. Visit www.preventpneumo.org to download past issues andsubscribe to PneumoFOCUS.

More Visitors to PneumoADIP Website – Around the Clock Resource

The PneumoADIP website (www.preventpneumo.org) continues to change to reflect the dynamicdevelopments in pneumococcal disease prevention. Since its redesign in 2004, the website servesas a resource to a steadily increasing number of visitors. The popularity of the website was given aboost by the media campaign surrounding the publication of The Gambia vaccine trial results inMarch; the number of visits to the website increased almost four-fold during the media campaign.

28

Far left: Filming thesequence of transportingblood and cerebrospinal fluid samples from hospital to the laboratory

Left: Filming the sequence of standardized laboratoryprotocol necessary to “find pneumo”

“Finding Pneumo” — Educational Video Production

To support effective surveillance efforts at the country-level, PneumoADIP partnered withnetSPEAR and staff at local health facilities to film the critical stages involved in collecting blood and cerebrospinal fluid samples, preserving the integrity of the samples, and processingthese in the laboratories. The resulting footage will form the basis of an educational video to help laboratory staff remove the barriers in isolating the Streptococcus pneumoniae bacteria –“finding pneumo” and more accurately document local disease burden.

Above: Rockhopper TV filming localscenes in Alaska

Left to right: A young girl living in a New Delhi slum, India; A young Indianfolds stickers in a New Delhi slum,India; Dr. Shrestha working in a busypediatric ward in Kathmandu, Nepal

PneumoADIP Speakers at Meningitis Research Foundation Conference

Nearly 300 international scientists, clinicians, vaccine manufacturers, and technical agencies attendedthe Meningitis Research Foundation’s conference in London in November 2005. CommunicationsDirector Hans Kvist spoke about PneumoADIP’s mission and strategies during a session entitled“Control of pneumococcal disease: ensuring equitable access to life-saving vaccines.” Dr. RichardAdegbola from The Gambia, Dr. Andrew Pollard from Nepal, and Dr. Anthony Scott from Kenyaspoke about pneumococcal disease surveillance projects and vaccine trials in Africa and Asia.

PneumoADIP’s presence at this conference introduced its work to a wider audience and gaveattendees a closer look at the ADIP model. In conjunction with the international conference,PneumoADIP and the MRF coordinated media outreach efforts in the UK. As a result, BBC WorldService Radio devoted an entire program of its Health Matters series to meningitis, focusing onthe difficulty of diagnosing meningitis and the development of life-saving pneumococcal vaccines.

netSPEAR Annual Meeting in Kilifi, Kenya

At their 3rd Annual Meeting, netSPEAR and its partners organized a press conference withKenyan broadcast and print journalists. In an interview with Kenyan newspaper The Daily Nation,PneumoADIP’s Executive Director, Orin Levine, discussed recent progress and challenges inpneumococcal disease control and prevention in the November 24, 2005 issue.

GAVI Partners’ Meeting

The PneumoADIP team took part in the 3rd GAVI Partners’Meeting in New Delhi, India. The December 2005 event broughttogether over 500 delegates representing donors, countries andinternational organizations. PneumoADIP participated in a journalistbriefing session about new vaccines and the potential to savemillions of lives if they are introduced into developing countries.The meeting was opened by India’s Prime Minister Dr. ManmohanSingh, who was joined at the event by Norwegian Prime MinisterJens Stoltenberg and Bill and Melinda Gates, the co-founders of the Bill & Melinda Gates Foundation.

30 31

Fifth International Symposium on Pneumococci and PneumococcalDiseases (ISPPD-5)

PneumoADIP is proud to be the firstsponsor of ISPPD-5 and to sponsor a special travel grant for developingcountry researchers. ISPPD-5 will takeplace on 2–6 April 2006 at Alice Springs,Central Australia. This exciting locationhas great significance for pneumococcalresearch, as Aboriginal children incentral Australia have the highest rate of invasive pneumococcal diseasereported in the literature, now beingaddressed by government-funded conjugate vaccine. The ISPPD is the only international forum focusingentirely on the study of Streptococcuspneumoniae and pneumococcal disease.Alice Springs, capital of the Australianoutback, boasts a convention centrewith modern facilities and offers aunique location for the conference.

For more information, visitwww.isppd5.com.

ISPPD-6 is planned to take place in Iceland in 2008.

Defining the Way Ahead

“New Vaccines” Meeting

PneumoADIP hosted a meeting in Baltimore, USA in June 2005, bringing together public andprivate organizations looking at ways to introduce“new” vaccines (such as pneumococcal, rotavirus,HPV, malaria, HIV, tuberculosis, and Japaneseencephalitis) into the developing world. The purposeof the meeting was to discuss common challengesand areas of potential collaboration. The objectivesincluded identifying and gaining consensus aboutstakeholders, as well as creating strong andconsistent messages that make the case for new vaccines.

Effectively Communicating Science

From day one PneumoADIP has invested incommunications as an essential component of itsADIP model. The results of the past year furtherillustrate that without meeting the challenge ofcommunicating science effectively, key messageswill never be heard.

Media outreach is just one of the tools that have beenadopted to communicate exciting and compellingdata, about a future where new vaccines can bemade available to the children that need them.

PneumoADIP’s next step is to continue working with its partners to make information aboutpneumococcal disease accessible to all audiences,and to further highlight the economic sense ofinvesting in prevention through immunization.

"One strength of PneumoADIP is that it reaches out to the scientific and technical communities to make sure its strategy is based on the best, most recent data available."

David Goldblatt, University College London Institute of Child Health

Above: Delegates convene at the 2005 GAVI Partners’ Meeting in New Delhi, India Far right: India’s Prime Minister Dr. Manmohan Singh makes his welcoming speech

"PneumoADIP realized early that the successful vaccinetrial in The Gambia had to be translated into action.Through a collaborative approach, they translated scientific data into public dialogue about getting thevaccine to those most in need – as fast as possible."

Regina Rabinovich, Bill and Melinda Gates Foundation

Perceptions of Pneumococcal Disease

Survey Respondents Say Vaccine Introduction is Feasible, Though Not Without Challenges

PneumoADIP conducted a web-based survey in the summer of 2005 to assess the perceptions of the technical community in relation to the financing and pricing of childhood pneumococcalvaccines. The 90 respondents to the survey identified themselves as researchers and cliniciansworking in industry, technical agencies, NGOs, or other areas.

The nine questions in the survey related to perceptions of the costs of manufacturing pneumococcalconjugate vaccines, expectations for pricing, and awareness of the financing available to developingcountries through GAVI’s Vaccine Fund.

The main findings of the survey were:

• 71% responded that they thought multivalent pneumococcal conjugate vaccines can be made affordable to developing countries

• 50% responded that it costs US$6 or more to manufacture a dose of the licensed 7-valent pneumococcal vaccine

• 50% responded that, after 10 years of financing by GAVI, the maximum price per dose that developing countries and their donor partners can sustain is between US$1 and US$2

• 77% responded that researchers can influence donors and policy makers in decisions about the introduction of pneumococcal vaccine

• 74% responded that companies should expect to make a profit on vaccines that are supplied to developing countries

• 27% of respondents had a “maximum price” estimate that was equal to or higher than their estimate of the costs of manufacturing

Most respondents were generally optimistic that conjugate vaccines can be made affordable,although the responses to individual questions were not always consistent with this optimism. It appeared that most respondents overestimated the costs of manufacturing multivalent pneumococcal conjugate vaccines, with only 27% estimating a manufacturing cost less than the “maximum” price per dose that countries can sustain. In addition, most respondents underestimated the amount of funding that GAVI has available.

So the good news is that there is clearly more “solution space” for the funding of pneumococcalvaccines than the technical community believes, optimistic though they were overall. Respondentswere also optimistic about the ability of researchers to influence donors and policy makers.

Survey respondents tended to overestimate the costs of vaccine manufacturing and to underestimatethe amount of financing available to introduce new vaccines, so the actual funding gap is actuallysmaller than it appears to the technical community.

Expanded Program on Immunization (EPI) Managers Voice Their Views

In July 2005, PneumoADIP representatives and a WHO/IVB/EPI representative met with 25 EPImanagers from 10 South East Asian countries during the 5th Meeting for SEAR EPI managers inNew Delhi, India. Discussion focused on the EPI managers’ key priorities when introducing a newvaccine, limitations in health systems, and weaknesses in communication messages.

Lack of disease burden evidence was seen as the major obstacle to vaccine introduction. Evidenceof vaccine efficacy was also needed. The cost of vaccine was ranked lower in importance, possiblybecause the managers felt there is little room for negotiation on this issue. In addition to criticalstudies (e.g. cost–benefit and disease burden studies, pilot projects), political advocacy was considered vital to overcome willingness to pay barriers.

Four major communication issues were identified:

1. A need for improved knowledge of the vaccine and its target population, even among well educated individuals

2. Information on the level of pneumococcal disease in the specific region – “disease burden ownership”

3. More thorough discussion of the results of the Gambia trial

4. The need for vaccines to be perceived as an investment, rather than an expense

These discussions allowed the views of a group of people with a critical role and uniqueperspective in vaccine distribution to be heard and enabled PneumoADIP to adopt its strategy by incorporating their suggestions.

32 33

35

PneumoADIP is working to ensure that developing countries are willing to introduce pneumococcal vaccine, the donor community is willing to finance it, and manufacturers are ready and able to produce the doses needed.This section of the report describes the progress that has been made on all of these fronts in 2005.

Angeline Nanni, Director of Vaccine Finance and Supply at PneumoADIP

Delivering Value

34

The Pneumococcal Vaccine Market The introduction of new vaccines into developing countries can only be accelerated by ensuring an affordable, sustainable supply. To meet this challenge, the global supply capacity must exceedthe demands of high and middle income countries. Low income countries have the largestdemand for vaccine doses on a global basis, but represent the smallest potential market in revenue because of the need for a much lower price per dose. These are challenging problems,but PneumoADIP’s supply analyses and forecasting can help overcome the obstacles to achievingaffordable, sustainable supply.

High Demand in Low Income Countries

PneumoADIP conducted a global market assessment to develop a firm economic basis for engaging industry, donors and countries. By developing a global assessment tool to calculate the potential vaccine demand in every country in the world in both the private and public sectors, PneumoADIP demonstrated that a potential billion dollar market exists for pneumococcalvaccines in low income countries. Without this robust global analysis, industry may continue to overlook the low income countries in favor of high and middle income markets. Multi-national and emerging suppliers are beginning to recognize the potential of the pneumococcal vaccine market in low income countries.

36 37

Supplying the Demand

Industry needs incentives now to accelerate their manufacturing capacity in order to supply thedeveloping country market. Without this global action, the supply will slowly increase but may not be sufficiant to meet demand in the countries that have the highest need. With no adequatesupply, the accelerated introduction of vaccine into GAVI-eligible countries will not be possible.PneumoADIP understands that assuring adequate capacity to supply GAVI-eligible countries is both a prerequisite for accelerating vaccine introduction and important for assuring the pricing that isneeded to sustain vaccine use.

Existing and Emerging Candidates

The first multi-valent pneumococcal conjugate vaccine, which targets seven serotypes, has been launched globally and used to safely vaccinate more than 30 million children. A 9-valentconjugate vaccine has now been demonstrated to protect children, including those infected withHIV, in clinical trials in The Gambia and South Africa. There are also 10- and 13-valent conjugatevaccines in clinical development, and more than 20 other conjugate and protein-based vaccinesare in the early stages of research and development. In addition to the vaccines being developed bymulti-national suppliers, vaccine manufacturers in India, China, Cuba and other emerging marketcountries are also engaging in research and development of multi-valent pneumococcal conjugatevaccines. The technical challenge in manufacturing multi-valent conjugate vaccines is the nexthurdle that must be overcome.

“PneumoADIP’s team includes people with private sector experience. Thiscomes through in their understanding ofhow to approach vaccine manufacturers.”

Michel Gréco, former executive, Aventis Pasteur Vaccines

2005 Potential Global Vaccine Market Summary

High IncomeMarkets

43M

$2.3B

Vaccine Market (Million doses)

Vaccine Market ($Billion)

Middle IncomeMarkets

131M

$3.4B

Low IncomeMarkets

178M

$1.3B

Total

352M

$7.1B

Source: PneumoADIP Analysis (Global Market Assessment), 2005

Launched

Prevnar(7-valent)

Clinical trialPhase III

9-valent

7-valent

Discontinued

11-valent

Steptorix10-valent

Expectedlaunch 2008

Clinical trialPhase II

Clinical trialPhase I

2005 Pneumococcal Vaccine Pipeline

DevelopmentStage

Multinational

Emergingsuppliers

Pre-clinicalStage

~20 vaccinesin research/Pre-clinical

stage(includes

conjugate &protein-based

vaccines)

>5 multi-valent conjugatevaccine projects

13-valent

Source: PneumoADIP analysis based on data from WHO 8 WB BCG Study, 2005

Sustainability and Consensus Building are Key

The Demand Forecasting Model

Reducing uncertainty about demand is a critical success factor when introducing a new vaccine indeveloping countries and credible forecasting can dramatically improve the quality of key operationaldecisions. PneumoADIP has taken an integrated approach to this by modeling various scenarios andusing sustainability (the key to accelerated vaccine introduction) as a critical constraint. The resultingdemand forecasting model is a tool that allows decision makers (e.g. country representatives,donors, and suppliers) to understand the sensitivity of their decisions, whilst retaining the flexibilityto work in a dynamic environment and allow forecast updates.

The goal in forecasting demand is to ensure that an adequate supply of high quality vaccine will match demand in the defined population. The model has been designed to demonstrate the impact ofdecisions based on a country’s need for the vaccine, willingness to accept it, and ability to introduceand invest in it. A key role for the model is consensus building among the key decision makers.

38 39

72 of the World’s Poorest Countries are Eligible for GAVI Funding

GAVI-Eligible Countries

“PneumoADIP’s innovative approaches to supply and financing are helping the whole field of vaccines.”

Susan McKinney, Senior Technical Advisor for Immunization, USAID

“A key to the success of global health programs is the ability to generate, effectively use and clearly communicate the vital information. In the immunizationfield, the PneumoADIP team is a pioneer in the credible demand forecasts and rigorous estimates of cost-effectiveness. This is precisely the sort of information that is needed for decision makers to make the right choices.”

Ruth Levine, Director of Programs and Senior Fellow,Center for Global Development

A new Way to Break the Vicious Cycle

Credible Demand Forecasting to Facilitate Decision Making

The introduction of new vaccines in developing countries has in the past been delayed due to a lack of incentives andadequate planning to address both supply and demand issuesbefore launching vaccines. A vicious cycle existed, whereinuncertain demand led to limited supply, which in turn keptprices relatively high and further increased the uncertainty of demand. Over the last year, PneumoADIP has worked with a variety of stakeholders to develop and test an innovative demand forecasting model to help break this cycle.

The demand forecasting model developed by PneumoADIP is unique in its emphasis onconsensus-building and sustainability. It brings together countries, donors, and manufacturers in an interactive model designed to underpin the accelerated development and introduction ofpneumococcal conjugate vaccine in developing countries.

Limited supply

Higher

pric

es

Uncertain

demand

Incre

ased productioncapacity

Lowe

r pric

es

Predictabledemand

PneumoADIP efforts

A vicious cycle existed,

wherein uncertain demand

led to limited supply, which

in turn kept prices relatively

high and further increased

the uncertainty of demand.

Promoting Global Investment Through Innovative Financing MechanismsCost-effectiveness analysis has shown that the cost-effectiveness for routine pneumococcalvaccination in low income countries is consistent with World Bank benchmarks for a “goodinvestment” of health resources in low-income countries. With an international commitment tofinance the vaccine, the global community can begin to assure a sustainable, affordable supply of vaccines as early as 2007.

PneumoADIP analyses suggest that, with a firm commitment from donors and countries, it should be possible to get early access to life-saving pneumococcal vaccines and achieve sustainable supplyat affordable prices. PneumoADIP is working with industry, governments, international agencies,and non-government organizations to develop a business model to link vaccine demand and supply,and permit the accelerated introduction of pneumococcal vaccines in low income countries.

Advance Market Commitments

An AMC is a binding contract, typically offered by a government or other financial entity, used toguarantee a viable market if a vaccine or other medicine is successfully developed. This ensuresthat manufacturers do not produce large quantities of vaccine that cannot be paid for and will notbe used and that donor funding is only used to buy vaccines that are demanded by developingcountries. As part of an AMC, suppliers commit, in return for the guaranteed price until themaximum AMC investment is met, to producing and selling further doses at a fixed and sustainableprice for eligible countries.

The idea behind AMCs is that the market price in wealthy countries allows manufacturers torecover research and development costs and other early investments. The AMC pays higher pricesfor early developing country access, so that manufacturers recover the investments needed tosupply developing countries. The long-term price is set by the AMC at a lower level, but one thatsustains supply and demand.

41

Ensuring Vaccine Supply and Matching It to Demand

PneumoADIP is working closely with vaccine manufacturers, both multi-nationals and emergingsuppliers, to develop a supply strategy able to meet the developing country demand forecast as described above. This was showcased at the annual meeting of Developing Country VaccineManufacturers Network (DCVMN) in Puna, India and a PneumoADIP-hosted demand forecastroundtable meeting in Baltimore, Maryland. In both events, the methodology and assumptionsused in the model as well as the model were demonstrated and feedback on country data, vaccinepricing and country introduction dates were gathered. The Baltimore event brought togethersuppliers and the public sector. The roundtable provided a forum for meaningful discussion to further develop a successful public-private partnership in accelerating vaccine introduction. The group was able to provide PneumoADIP with constructive feedback to ensure a robust andaccurate forecasting tool.

40

For the demand forecast, it wasassumed that countries and donorswould co-pay together on the pricefor the vaccine with the co-paygradually increasing over time.After GAVI support ends, it is pro-jected that the vaccine price willbe affordable and sustainable bythe 61 countries in the forecast.The underlying assumption is thatcountries will agree to early vaccineintroduction only if the price atthe end of the period is less thanor equal to their “willingness topay” for sustaining the vaccine.

The model assumes that the vaccines that will be demanded by countries will be available from2010 onwards, and that country adoption depends on having evidence of the disease burden andbenefits of pneumococcal vaccination. A major part of this process was to divide the 72 GAVI-eligiblecountries into segments that were more or less likely to adopt the vaccine between 2010 and2024. It was recognized that several countries would be unlikely to adopt a new vaccine withinthis timeframe as a result of economic, political, and/or social strife.

Estimated Demand Forecast for GAVI-eligible CountriesGiven Long-Term Affordable Price to Countries

Dose

s(M

)

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

2021

2022

2023

2024

2025

0

20

40

100

60

80

120

140

200

160

180

Source: PneumoADIP Analysis (Draft Base Case Demand Forecast), 2005

The results of the demand forecast serve to reassure:

• Developing countries that affordable vaccine prices and sustained financing are possible

• Donors that the financing early access pays off with lower prices later

• Manufacturers that accelerated introduction will not require impossibly large numbers of doses

Assumptions in Demand Forecasting Model

1. Country Maximum price a country is willing to pay for the vaccine to sustain uptake (based on expert input, and experience with other vaccines)

2. Donors Funding strategy (willingness to buy of funding agency)

3. Suppliers Purchase price of vaccine (set by supplier)

Potential Time to Adoption in GAVI-Eligible Countries

Segments Time Frame # of Countries

Early Adopters 2010-2015 26

Early Majority Users 2016-2020 22

Late Adopters 2021-2025 13

The purpose of pneumococcal vaccine demand forecasting is to estimate the quantity of vaccinethat will be demanded in the public sector of 72 GAVI-eligible countries over the next 20 years.This is not an estimation of need, but rather an effort to realistically assess the actual demandgiven the existing constraints. The process involves changing the inputs for the three key variables(see box below) and re-analyzing the results until a point is reached at which countries, donors,and manufacturers are all willing to invest and supply the vaccine. Only when each of the keystakeholders has made a commitment has the goal been reached.

An AMC will thus provide the incentive for existing suppliers to increase capacity by creating a more attractive lower income country market. In addition, it can provide an attractive market for late-to-market vaccines that may otherwise not be economically viable if focused only onhigher and middle income markets.

Pneumococcal vaccine use in developing countries is currently limited by the inadequate supply of existing vaccine for developing countriesand prices that are unaffordable to funders andcountries. Advance market commitments are aninnovative, market-based solution to overcomethese challenges and accelerate the introduction of new, life-saving vaccines to the poorest countries of the world.

42

International Finance Facility for Immunization (IFFIm)

The aims of PneumoADIP have beengiven a boost by Eurostat (the statisticaloffice of the European Union), which on2 August 2005 approved an innovativemechanism of securing funds for child-hood vaccinations. The InternationalFinance Facility for Immunization(IFFIm) was proposed by UK Chancellorof the Exchequer Gordon Brown as a means of creating a fund of US$4billion, with the aim of saving thelives of 5 million children by 2015and many more thereafter.

The IFFIm, a precursor to the proposedInternational Finance Facility, is seenas a major step towards improving thelives of the world’s poorest people. Itis supported by the Bill and MelindaGates Foundation, GAVI’s Vaccine Fund,and UNICEF, and will receive initialfinancial contributions from France,Italy, Spain, Sweden, Norway and the UK.

The innovative mechanism approvedby Eurostat will enable donor countriesto go to the international bond marketto obtain funds (on the back of legally-binding long-term donor commitments)to speed the purchase of currentlyavailable vaccines and earmark fundsfor new vaccines. The money borrowedwill not count towards European countries’ debts. This mechanism hasthe merit of providing a predictableflow of resources to the immunizationchallenge. The UK has pledgedUS$1.8 billion over 15 years to theIFFIm. Through frontloading, this willallow US$950 million to be disbursedbefore 2010, even though UK contri-butions over the same period will be$394 million.

The result should be greatly expandeddistribution of existing vaccines and more rapid availability of newvaccines. This is clearly in line withPneumoADIP’s aim of acceleratingaccess to pneumococcal vaccines forthe world’s children and is thus anextremely welcome development.

For more information, visitwww.iffim.com.

“The International Finance Facility for Immunization – IFFIm – will help poor children in the developing world get the vaccines that children in thedeveloped world take for granted.”

Hilary Benn, UK Secretary of State for International Development

GOOD NEWS

Global Immunization and Vaccine Strategy

At the 58th World Health Assembly in Geneva in May 2005, WHO and UNICEF unveiled the ambitious Global Immunization and Vaccine Strategy (GIVS) aimed at preventing millions of deaths annually worldwide by providing equal access to vaccines (including pneumococcal conjugate) for all. Governments officially committed to adopting this strategic framework for2006–2015, which provides an array of approaches to suit each country’s epidemiologic and health infrastructure needs.

New Vaccine Expected

GlaxoSmithKline announced in June 2005 that it expects to launch its childhood 10-valent pneumococcal conjugate vaccine (Streptorix) in the next 5 years. So, from as early as 2010, two suppliers should be able to provide childhood multivalent pneumococcal vaccines to thegrowing market, making it more likely that vaccine supply will be able to meet the needs of the world’s poorest countries.

Wyeth: Prevnar and commitment to developing countries

New Jersey, USA – April 21, 2005. According to a Wyeth press release detailing their annualMeeting of Stockholders, Robert Essner, Chairman, President and Chief Executive Officer, said“Wyeth researchers are continuing to work on new versions of Prevnar which expand its usefulnessglobally for both children and adults, and we are working with international agencies to help provideaccess to Prevnar in the developing world.” Essner’s public announcement is extraordinary. Thismarks the first time any industry executive has publicly asserted a company’s commitment tomaking pneumococcal vaccines available to people in developing countries – where 90% ofpneumococcal pneumonia deaths in children occur.

Open letter to G8 nations from world vaccine manufacturers

G8 Summit – June, 2005. Multi-nationals and emerging vaccine manufacturers collectively submitted a letter to G8 nations urging governments to commit to financing the vaccine market in low-income countries. This signifies that there is cohesive effort from the industry to entervaccine markets in the low-income countries provided that there is global leadership to sustainaffordable vaccines.

43

PneumoADIP Team

As PneumoADIP continues to expand its activities all over the world to accomplish the program’s mission, the team is also growing...

Orin S. LevineExecutive DirectorBefore coming to Johns Hopkins as an Associate Professor in the Department ofInternational Health, Dr. Levine spent 5 years at the CDC followed by 3 years with the US National Institutes of Health. Dr. Levine has authored/coauthored more than50 original research papers and book chapters, including more than 25 on the subject of meningitis and pneumonia and their prevention by vaccination.

Maria Deloria KnollDirector of ResearchDr. Knoll has over 15 years’ experience in the design, conduct, and analysis of clinical trials and epidemiologic studies. She spent 13 years at the National Instituteof Allergy and Infectious Diseases at the NIH and, most recently, 3 years at the FeinbergSchool of Medicine at Northwestern University. Her clinical trials experience includesclose working relationships with many large and mid-sized vaccine manufacturers.

Katherine L. O’BrienDeputy Director of ResearchFor the past 5 years Dr. O’Brien has been a faculty member and the AssociateDirector of Infectious Disease Studies for the Center for American Indian Health atthe Johns Hopkins Bloomberg School of Public Health. Her research has focused onvaccine preventable diseases of childhood, with a particular emphasis on S. pneumoniae.Dr. O’Brien is a consultant to WHO on pneumococcal conjugate vaccine trials.

Angeline NanniDirector of Vaccine Finance and SupplyBefore joining PneumoADIP, Ms. Nanni worked for Baxter Healthcare Corporation as a Senior Manager in the Vaccines Commercial Division, where she was responsible for the strategic planning and market research for new pipeline products. Prior toworking in industry, Ms. Nanni worked at Johns Hopkins Bloomberg School of PublicHealth in Departments of Epidemiology and Mental Health for 7 years.

Hans Kvist Director of Communications Before joining PneumoADIP, Mr. Kvist worked as Global Communication Manager forNovartis in Switzerland. Mr. Kvist came to the PneumoADIP team with more than 20years of experience from the pharmaceutical industry. For the past 15 years Mr. Kvisthas worked with communications on a global level where his work has included scientificsymposia program development, publication planning, and public relations.

Earl WallDirector of Strategic Planning and ManagementMr. Wall is the Director of Strategic Planning and Management. He also serves as the Director of Program Development at the Center for Refugee and Disaster Response,Johns Hopkins Bloomberg School of Public Health. Mr. Wall comes to the PneumoADIP,with more than 20 years of experience in the developing world. He spent 17 yearsworking for CARE International.

PneumoADIP’s Sponsors and Allies

The GAVI AllianceGAVI was launched by a coalition of public and private sector partners in 2000 tocombat a global trend of declining routine immunization coverage and to accelerateaccess to new and life-saving vaccines.

Visit the GAVI website at: www.vaccinealliance.org.

World Health OrganizationWHO is the United Nations specialized agency for health. It was established on 7 April 1948. WHO’s objective, as set out in its constitution, is the attainment by all peoples of the highest possible level of health. Health is defined in WHO’s constitution as a state of complete physical, mental, and social well-being and notmerely the absence of disease or infirmity.

PneumoADIP coordinates its activities through a strategic alliance with WHO. In addition to its Geneva-based headquarters, the WHO organizational structure includes a series of six regional offices corresponding to unique geographical regions, and, ofcourse, country-based offices in nearly every country of the world. These regional officesinclude teams of people working closely in advising, supporting, and providing technicalassistance to immunization and health policy makers in developing countries. Theirunique perspective on regional and country issues makes them invaluable in the processof evaluating and introducing new vaccines. Visit the WHO website at: www.who.int.

Meningitis Research FoundationThe Meningitis Research Foundation (MRF) is a national registered charity establishedin 1989. From small beginnings, the Foundation has grown into an international charityat the forefront of fighting death and disability resulting from meningitis and septicemia.Since its inception, thousands of people have become members of the Foundation,working together to help achieve its vision of a world free from meningitis and septicemia.The MRF funds research to prevent meningitis and septicemia, and to improve survivalrates and outcomes. It also promotes education and awareness to reduce death and disability, and gives support to people affected by meningitis and septicemia. Visit the MRF website at: www.meningitis.org.

Johns Hopkins Bloomberg School of Public HealthAs a leading international authority on public health, the Johns Hopkins BloombergSchool of Public Health is dedicated to protecting health and saving lives. Every day,the School works to keep millions around the world safe from illness and injury bypioneering new research, deploying its knowledge and expertise in the field, and educating tomorrow’s scientists and practitioners in the global defense of human life.Visit the school’s website at www.jhsph.edu.

44 45

Thomas Cherian, MDCoordinator, ad interim, EPI, World Health OrganizationDr. Thomas Cherian is a scientist in the Initiative for Vaccine Research at WHO, coordinating a team responsible for research on vaccines against respiratory and vector-borne pathogens. Previously, Dr. Cherian was a Professor of Paediatrics at the ChristianMedical College in Vellore, India. He is also a Senior Associate in the Department ofInternational Health at the Johns Hopkins Bloomberg School of Public Health, Baltimore.He has authored/coauthored more than 90 scientific articles and book chapters.

Ellen Lee Medical EpidemiologistDr. Lee completed her residency and internship in pediatrics at the Children’s Hospitalof New York-Presbyterian, at Columbia University Medical Center. Dr. Lee’s internationalresearch experience has taken place over the past ten years in Africa, South Americaand the Caribbean. Prior to joining PneumoADIP, Dr. Lee spent 2 years as an EISOfficer at CDC in Atlanta, Ga., where she served as principal investigator for a studyevaluating the impact of Haemophilus influenzae type b (Hib) vaccine in Uganda.

Farzana MuhibResearch Project CoordinatorMs. Muhib manages all the data and research for the PneumoADIP team. Previously,Ms. Muhib worked at the CDC, where she was a survey coordinator for a nationalHIV/AIDS Behavioral Research project. She also developed a technical assistancemanual for state and local health departments to conduct rapid assessments ofHIV/AIDS risk behaviors.

Michelle Moncrieffe-Foreman Communications ManagerMs. Moncrieffe-Foreman is the Communications Manager for PneumoADIP. She has a background in journalism, health communications and community-based programs.Most recently, Ms. Moncrieffe-Foreman worked as a consultant for the American LungAssociation of Minnesota. Prior to that, she spent ten years working as a journalist andcommunications consultant in the United States, Tanzania, and the United Kingdom.

H. Benedicta KimCommunications ManagerMs. Kim is the Communications Manager for PneumoADIP. She has a background in journalism, research, small business management, and community-based programs.Most recently, Ms. Kim worked as a consultant for the PneumoADIP website. Prior tothat she was a research assistant at JHSPH Center for Prevention and Early Intervention.

Avanti JohnsonAdministrative Project AssistantMs. Johnson is the Administrative Project Assistant for the PneumoADIP team. She is responsible for the administrative support to the directors and other members of the team, as well as the coordination of travel and budget management, data maintenance, and scheduled payments for sub-agreements.

Doctoral candidates from Johns Hopkins Bloomberg School of Public Health are also part of the PneumoADIP team: Rebekah Heinzen, MHS; Jennifer Moisi, MS, MHS;Nitya Nair; Chizoba Wonodi, MBBS, MPH

46

Photo Credits

PneumoADIP (Maria Knoll, Hans Kvist, Angeline Nanni) and Selina Haylock (unless noted otherwise)

The photographs contained in this document are for educational and non-commercial use only. Any use of these photographs requires explicit, prior authorization in writing.

Enquiries for permission should be addressed to pneuadip@jhsph.edu

Cover On location in Alaska, India, Kenya, Nepal

p.2 On location in India

p.4, 10 On location as part of Asian Field Site Evaluation

p.13 A laboratory in a rural district in Kenya

p.16, 17, 19 On location in Asia, Africa

p.23 A young girl plays outside on a sunny day in Alaska

p.24 A mother and baby attend a rural vaccination clinic in Kenya

p.27 On location in Kenya

p.28 An expert panel of pneumococcal scientists speaks to local journalists in Bangladesh as part of the annualPneumococcal Surveillance Network Investigators Meeting in January, 2005

p.30 Full house – journalists attend press conference for The Gambia pneumococcal vaccine trial results at Washington, DC in March, 2005

p.33 On location in Asia

p.34 On location in Bangladesh

p.43 A toddler receives vaccination in a rural village in Alaska

Progress Report developed by healthcare communications agency Ruder Finn UK Ltd. and designed by Interlink Healthcare Communications.

47

This work was performed under a collaborative arrangement with the PneumoADIP at Johns Hopkins Bloomberg School of Public Health and was funded by GAVI, the Global Alliance for Vaccines and Immunization.

www.preventpneumo.org

Contact Information: GAVI’s PneumoADIP Johns Hopkins Bloomberg School of Public Health 615 North Wolfe Street E8536 Baltimore, MD 21205 USA

Tel: +1 (410) 502 2629 Fax: +1 (410) 502 3732 E-mail: pneuadip@jhsph.edu

© 2006 Pneumococcal Accelerated Development and Introduction Plan at Johns Hopkins (PneumoADIP). All rights are reserved.