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Meningitis in Africa - tackling W135

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Médecins Sans Frontières (MSF) has warned that thousands may die unnecessarily this year if suitable vaccines are not made available. Their appeal is urgent, because the dry season started in Africa last month. The crux of the problem lies in the fact that not enough vaccines against W135 are manufactured to treat a major outbreak.

Bacterial meningitis is one of the scourges of Africa. It strikes during the dry season, when temperatures fall at night and people huddle together for warmth. It devastates communities, and children are especially at risk. Meningitis epidemics regularly sweep across Africa from Ethiopia to Senegal, killing around 25,000 people each year. Globally, around 170,000 people die each year as a result of bacterial meningitis. About half those infected die, having had no treatment, and the rest are often left with a permanent disability, such as mental retardation, deafness, or paralysis.

The threat has now become more intense to the 300 million Africans at risk from the disease with the emergence of Neisseria meningitidis serogroup W135. It came of age on this war-ravaged and poverty-ridden continent this year during an epidemic in the West African nation of Burkina Faso. Some 12,000 people were infected, of whom 1500 died. It was the first time that N meningitidis W135 was identified as the main causal agent in a major epidemic.

In Burkino Faso, Jean-Baptiste Koama, a health adviser for Plan International, a humanitarian child-centered non-governmental organisation, experienced the deadly results of W135 first hand, treating patients during this year's outbreak in his country. "We were first of all surprised by the extent of the epidemic. We had never had an epidemic of W135", he explained. "Naturally, it was frustrating, because it was, above all, children [who were affected]. Vaccines were not available in sufficient quantities and they were expensive", he said.

Public-health experts are predicting that the W135 strain could spread to other countries on the continent, posing a severe threat since the vaccines used in Africa today do not protect against this serotype. A vaccine against W135 does exist, but supply is limited and the cost is exorbitant and cannot be met by cash-strapped African countries. Médecins Sans Frontières (MSF) has warned that thousands may die unnecessarily this year if suitable vaccines are not made available.

Their appeal is urgent, because the dry season started in Africa last month. The crux of the problem lies in the fact that not enough vaccines against W135 are manufactured to treat a major outbreak. The emergence of W135 in Burkina Faso during this year's 19-week outbreak highlighted the fundamental difficulties of providing essential pharmaceuticals at an affordable price and in sufficient correct quantities to Africa's millions. "It was a surprise to have this big outbreak.

A lot of people were expecting an outbreak but the fact that this strain was involved was something new", noted Bernard Pecoul, director of MSF's Campaign for Access to Essential Medicines ). Meningitis is a bacterial infection of membranes around the brain and spinal cord, and is spread through close contact with an infected person. "The signs you get are headaches, fever and a stiff neck, sometimes vomiting. When the skin is touched, it is very sensitive", said Koama.

The most serious epidemics usually occur every 6-8 years. The largest single outbreak in history was in 1996, when 200,000 people were infected and 20 ,000 died. "Each time it is catastrophic, a disaster in terms of numbers of people killed or affected and the effect on the economy.

The situation is dramatic each time . . . if we were confronted with the situation of 1996 with the implication of W135 we would be in trouble", said Pecoul. Approximately one third of all deaths related to bacterial meningitis are caused by N meningitidis, of which serogroups, A, C, Y, and W135 are the most common. The Y strain of the disease has been detected only in industrialised countries. W135 was identified 2 years ago in Saudi Arabia, and was spread to other countries by Muslims returning from the Hajj pilgrimage to Mecca. Oil-rich Saudi Arabia has deeper pockets than many African states and the competition between rich and poor countries for a limited stock of vaccines has also pushed up costs.

Saudi Arabia has ordered that everyone making the pilgrimage to Mecca must be vaccinated against W135. Meningitis vaccines also are not used in standard childhood vaccination programmes. This makes demand even more uncertain since drug companies are discouraged from manufacturing in large quantities. The vaccines currently used in Africa do not protect against the W135 serotype. Until now most of the meningitis epidemics that have affected Africa have been caused by group A meningitis, against which there is a vaccine. The first vaccines were developed in the 1960s and 1970s, and their effectiveness is relatively high at 85% especially in adults. A quadrivalent vaccine--which protects against A, C, Y, and W135--does exist but it costs around US$5 per dose, or up to $50 per dose in the USA. The vaccine currently used in Africa costs around 25 cents. Another problem is that the quadrivalent vaccine has mostly been used by western travellers and high-risk groups and has therefore been produced in only small quantities.

So there is a problem of production capacity as well as cost. Organisations, such as MSF and WHO, have been negotiating intensely with the two main vaccine manufacturers - GlaxoSmithKline and Aventis Pasteur - to drag the price down to a level that will allow African authorities to build up stocks in preparation for the big epidemics.

Their efforts paid off when GlaxoSmithKline agreed to provide 3 million doses of a trivalent vaccine that protects against W135 at around $1 per dose. "This year, when we tried to buy the vaccines, we were faced with higher prices. Now, we have got it down to around $1 per dose", said David Heymann, WHO's executive director of communicable diseases. WHO estimates it will need between 2 and 5 million doses of the vaccine to prepare for likely outbreaks early next year. The estimated need for the next 5 years is between 20 and 50 million doses. But money is still needed up-front to pay for the vaccines, even at the lower price. United Nations agencies and non-governmental organisations have joined forces to appeal for E10 million ($10 million) to combat the W135 serotype, warning that if the money is not forthcoming, thousands will die unnecessarily.

The problem is that most organisations only provide funds after a major epidemic has started, which is often too late. Longer-term, physical stocks of vaccines must be built up in susceptible countries and areas and the market must be secured. "The first thing to do is establish a stock for the outbreak. We want to avoid the situation of humiliation in Burkina Faso where we had to say the vaccines we had were not useful", said MSF's Pecoul. National governments also need to put aside a part of their budgets to pay for vaccines, and avoid the political fallout of appearing helpless in the face of a major epidemic.

And pharmaceutical companies will have to be persuaded that if they produce more of the vaccine, it will be bought and used in sufficient quantities to assure a profit. Koama stresses the importance of "a reasonable price", and says his country is emphasising the need to teach people more about the illness. Early diagnosis can be key, and to this end, public-health organisations are placing advertisements in local newspapers to raise awareness. "We can reduce the rate of mortality for these epidemics", Koama said. "The faster people are taken care of the less complications there are", he added. WHO also stresses the need for strengthened laboratory surveillance to identify and report cases of meningitis, and also determine which strain is involved.

There is a glimmer of hope on the horizon, in the shape of conjugate vaccines, which will provide long-term protection against meningitis and reduce the number of asymptomatic carriers of the bacterium. The Gates Foundation has donated $70 million to develop a conjugate vaccine through the Meningitis Vaccine Project. A monovalent conjugate C vaccine is already available in European Union countries but the development of such monovalant or bivalant (A, C) vaccines for the world's poorest countries was stopped at the end of the 1990s because it was not deemed sufficiently profitable. Commercial companies are developing quadrivalent conjugate vaccines for the European and US markets, but have not so far committed to providing these vaccines to developing world markets at an affordable price.

The development of a conjugate monovalent A strain vaccine was taken over by the Proram for Appropriate Technology in Health, a WHO-led initiative last year. But the first vaccines will not be ready to market until 2006 at the earliest. "The only reason it has not been developed is because the market is not profitable in Africa . . . if we have this kind of vaccine it would be a major tool to organise a preventive strategy", Pecoul said. Then again, getting the vaccine at what Koama calls a "reasonable price" will be key. "The problem with the conjugate vaccine is that it will be very expensive. We anticipate it will be well over $1", said Heymann.