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 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. Given the possibility that W135 could be at the core of the next outbreak in Africa, this vaccine could be used to replace the usual response, the bivalent vaccines against A and C, and would thus provide a useful medium-term tool to protect the population until a more viable long-term solution is found. 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 argue 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 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. Yet, in negotiations with WHO, GSK has communicated a price at around US$3.5 to 4 per dose, and even this under certain conditions only. This would amount to as much as US$200 million for the 50 million doses necessary. 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 order to respond to the next epidemic season which could begin as soon as November 2002, the only solution is making the current quadrivalent polysaccharide vaccine available at an affordable price for Africa. Intense negotiations regarding price and availability have been going on between WHO, the two companies, and NGOs like MSF involved in vaccination campaigns in Africa. MSF maintains that the price should not exceed US$1 per dose. But the best offer so far, by GSK, is US$3.5. Until a quadrivalent conjugate vaccine becomes available, another medium-term solution to the crisis would be the development of a monovalent polysaccharide vaccine against W135, which could be made available as early as end of 2003 since the technical know-how already exists - if a company commits to producing it at an affordable price (less than 0.50 cents per dose) for African countries. The necessary technology could also be transferred to manufacturers based in developing countries. It is clear to all parties that responding to the meningitis crisis in Africa is a challenge. But if the will is there, things can happen fast: In Brazil, where Group A meningitis emerged as a new strain in the 1974, Merieux (now merged into Aventis Pasteur) prepared 90 million doses of monovalent polysaccharide A vaccine in six months to deal with the epidemic. If such a fast-tracking manoeuvre was possible with the know-how and technology that was available more than 25 years ago, it must be feasible today. A speedy emergency solution for the millions of Africans potentially affected during the next few months and years 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 and the countries affected by large epidemics need to promote and support an affordable short-term solution instead of accepting to take a "treatment only" approach in the next year * Donor governments need to assist in funding a feasible, affordable emergency solution * Multinational companies need to cooperate by choosing one or all of the following options: a) offering existing quadrivalent vaccines to developing countries at an affordable price, i.e. less than US$1 per dose b) agreeing to produce the monovalent polysaccharide W135 at less than US$0.50 per dose (as a comparison, the existing bivalent polysaccharides cost US$0.25 per dose) c) offering to transfer the technology necessary for another producer in developing countries. (*) 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.Introduction 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. Contacts at MSF: Dr Bernard Pécoul tel 41-22-8498 405 Dr Graciela Diap tel 34-61-6933 622 Dr Anne-Valérie Kaninda-Meyers tel 33-(0)6-1227 7374 Laura Hakokongas tel 41-22-8498 402