Double Standards and Neglect: The Story of Meningitis Vaccines

Introduction

Bacterial meningitis (*) kills more than 170,000 people each year. Although sporadic cases are detected in developed countries, the vast majority of deaths and suffering happen in Africa. Epidemics regularly hit countries in the area referred to as the African meningitis belt, which stretches across the continent from Senegal to Ethiopia. The total population at risk in the countries affected is around 300 million.

Approximately one third of all the deaths related to bacterial meningitis are caused by different strains, or serogroups, of the Neisseria meningitidis bacterium; serogroups A, B, C, Y and W135 are the most common. The first so-called polysaccharide vaccines to respond to the outbreaks were developed in the 1960's and 1970's, and they continue to be used today, particularly in developing countries. The effectiveness of these vaccines is relatively high (85%) in adults, but it wears off after two to three years in children, who are most vulnerable to meningitis.

In the hope of increasing the vaccine's effectiveness and providing long-term protection against meningitis, a new class of vaccines, referred to as conjugate vaccines, is being developed. But these products will not be available until 2006 at best.

New threat facing Africa

Traditionally, 80-85% of the meningitis epidemics in Africa have been caused by Group A meningitis, against which there is a vaccine. But a new threat is emerging: the last outbreak in Burkina Faso in February-May 2002 was due to a W135 strain, presumably originating from Saudi Arabia and transmitted to the Burkina Faso population through pilgrims travelling to and from Mecca. The epidemic infected almost 13,000 people and killed over 1,400.

W135 has not been previously registered in Africa on a large scale. Although predicting epidemics is complicated, there is a substantial risk that the strain will spread to neighbouring countries. However, the continent and the international community are not prepared for such an epidemic.

Different standards for different continents

Without treatment, bacterial meningitis kills up to 50% of the patients. Even if the disease is diagnosed early and treated with appropriate drugs, the case fatality rate is still as high as 5-10%, and 15-20% of those who survive will suffer from neurological after-effects such as deafness or mental retardation. Timely mass vaccinations remain the most effective means of limiting the spread of epidemics. The World Health Organization (WHO) has estimated that responsive mass immunizations have managed to prevent up to 70 % of expected cases in individual meningitis outbreaks in Africa.

In wealthy countries, the threshold for action is low. For instance, a meningococcal meningitis epidemic was declared earlier this year in Clermont-Ferrand, France, after 18 cases of meningitis had occurred within a year. As a result, a total of 80,000 babies, children and young adults were vaccinated. Similarly, in the UK, large numbers of people considered at high risk have been vaccinated when a few individual cases were reported. These expensive measures are readily taken by health authorities in industrialised countries, although the benefits of large-scale responses in these circumstances have not been proven.

As a comparison, African epidemics have been known to reach enormous proportions. In the most recent outbreak in Burkina Faso, which lasted 19 weeks, the number of cases recorded went from 100 cases during the first week to a peak of 2,300 cases per week.

At present, only two companies, Aventis Pasteur and GlaxoSmithKline (GSK), manufacture a quadrivalent polysaccharide vaccine that immunizes against A, C, Y and W135.

But between them, the two companies have divided the world meningitis vaccine market as they see it: Aventis Pasteur covers need in the US (2 million doses per year), while GSK supplies for consumers in Europe and the Middle East (10 million doses). Africa has been left out of the equation: it isn't considered a lucrative market, so the companies do not have plans to produce enough vaccine to cover Africans, although they are the hardest hit. Aventis Pasteur donated 25,000 doses to Burkina Faso at the time of the spring epidemic, and GSK has said small quantities could be made available for the next epidemic. But both companies have argued that there simply isn't enough production capacity to cover all of Africa. The estimated need for the next five years is 20-50 million doses.

Obviously, it is not just a question of availability. The current price of the quadrivalent polysaccharide vaccine - ranging from US$50 per dose in the US to US$4 per dose in the Middle East - is a barrier that places this vaccine definitely out of reach of African people and governments. Experts estimate that the production costs of a quadrivalent polysaccharide are around US$0.40-0.80, so setting an affordable price - not more than US$ 1 per dose -- for Africa should not be impossible.

A long term solution: conjugate vaccines

The new generation of vaccines, the conjugates, differ from polysaccharides in that a carrier protein has been added to the antigen. Conjugate vaccines protect the immunized individuals for a longer period, and reduce the number of asymptomatic carriers of the bacteria within the population. These vaccines could be introduced into the standard Expanded Programmes on Immunization (EPI) to help prevent massive epidemics in the long term - a very promising strategy for Africa.

Like the polysaccharides, the conjugate vaccines can contain antigens against up to four meningitis serogroups. A monovalent conjugate C is already available in the EU countries. However, the development of mono- or bivalent (A, C) versions of conjugate vaccines for developing countries was halted at the end of the 1990's because of lack of projected profit. Governments and donors were not willing to invest in what could have become a major public health tool for poor countries.

The development of a conjugate monovalent serogroup A vaccine was picked up by PATH, a WHO-led international initiative, in 2001, and it has been estimated that the first vaccines resulting from their efforts could reach the developing world market by 2006 at the earliest.

Commercial companies are developing a quadrivalent conjugate vaccine to cover need in Europe and the US. The companies involved in the R&D process have as yet not expressed a clear, public commitment to cover the market in developing countries at an affordable price.

What are the next steps?

In a WHO-led strategy meeting in Ouagadougou, Burkina Faso, in September 2002, governments, meningitis experts, international relief organisations and NGOs such as MSF agreed unanimously that a vaccine containing an antigen against W135 must be made available to the African countries at risk at less than US$1 per dose. Various strategies and approaches to achieve this were discussed. For MSF, the determining factor is the affordability of the vaccine.

WHO has since been negotiating a deal with GSK regarding the production of a trivalent (A+C+W135) polysaccharide vaccine. So far, GSK has agreed to make three million doses available for the next epidemic season at US$1 per dose for use in an impact study and to complete the registration dossier. The International Coordination Group (ICG) for meningitis vaccines, of which MSF is a member, is currently attempting to establish a stock of five million doses of trivalent vaccine and ten million doses of bivalent vaccine for the next epidemic seasons, and has launched an appeal aimed at donor countries to fund the stock of vaccines, treatments and equipment for an amount of ten million euros (see text of the ICG appeal).

Until now, GSK has not committed to producing more than three million doses at the target price of US$1 a dose. Given that the estimated need for the next five years is 20 to 50 doses, MSF believes that a sustainable solution should rely on more than one producer and will keep stepping up its efforts to help involve different producers in the negotiations and to achieve an affordable solution.

A vaccine for the millions of Africans potentially affected by meningitis outbreaks during the next few weeks and months is badly needed. If nothing is done, thousands will die or suffer serious neurological damage - while the means to protect them was there all along.

• WHO, ICG and the countries affected by large epidemics need to support and implement an affordable short-term solution
• Donor governments need to respond by funding the emergency stock
• Multinational companies need to cooperate by making available vaccines including an antigen against W135 at an affordable price - less than US$1 per dose.

(*) Meningitis is a potentially fatal infection of the brain membrane. It is characterized by sudden onset of intense headache, fever, nausea, vomiting, photophobia, and stiff neck.

Médecins Sans Frontières (MSF) has been working to curb meningitis epidemics in Angola, Burkina Faso, Cameroon, Central African Republic, Niger, Chad, Rwanda, Burundi and Ethiopia during the past ten years. One of the major users of meningitis vaccines in Africa, MSF vaccinates 3-5 million people against meningitis every year.

Médecins Sans Frontières / Campaign for Access to Essential Medicines Rue du Lac 12, CP 6090, 1211 Geneva, Switzerland Tel ++41-22-8498 405 Fax ++41-22-8498 404 www.accessmed-msf.org

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