Author Archives: Declan Butler

Spanish Ebola case highlights risks to health-care workers

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A nurse who cared for an Ebola patient repatriated to a Madrid hospital has contracted the disease, the Spanish health ministry announced on 6 October. But the news is, unfortunately, not surprising.

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{credit}US National Institute of Allergy and Infectious Disease{/credit}

Although Ebola is relatively difficult to catch in the community because infection requires contact with the bodily fluids — such as blood or vomit — of an infected person, close contacts and health-care workers treating patients with Ebola have long been recognized as being most at risk of contracting the virus.

Health-care workers have already paid a heavy price in the current epidemic in west Africa: as of 1 October, the World Health Organization estimates that 382 have contracted Ebola, and 216 of them have died.

Spanish authorities will investigate how the nurse at the Carlos III hospital came to be infected, and whether there were any shortcomings in infection control — such as in the personal protective equipment supplied, training in its use or hospital hygiene. As someone who recently treated an Ebola patient, the nurse would have been considered a contact at risk of exposure to the virus, and have been monitored for any symptoms such as fever, that could signal the onset of Ebola. Such surveillance of contacts is crucial to preventing any onward spread of virus.

It’s important to remember that people with Ebola don’t become infectious until they start showing symptoms, so monitoring of contacts of an Ebola-infected patient for fever is usually considered sufficient, with them being isolated only at the first hint of illness — although some authorities may choose to quarantine high-risk contacts. Such early isolation is crucial to limit the number of people they could come into contact with.

A key question for Spanish authorities will be whether there was any delay between when the nurse first showed symptoms and when she was isolated. They will then try to trace every single person she was in contact during that period and monitor them for symptoms for 21 days, the maximum incubation period of the disease (see ‘How disease detectives are fighting Ebola’s spread‘ for an explainer of this process of ‘contact tracing’).

That contacts of the nurse might in turn become infected cannot be ruled out, but the case does not raise any major threat of an outbreak of Ebola in Europe. Risk assessments of the current outbreak have long factored in the prospect that infected people would occasionally travel from the epicentre of the epidemic in west Africa to distant unaffected areas, and that healthcare workers are among those most at risk of secondary infections.

The Spanish case raises legitimate concerns as to the preparedness of hospitals to safely treat Ebola patients, and spotlights the need for health facilities everywhere to review their own precautions and practice. But even with the best training and equipment, the infectious nature of bodily fluids that carry Ebola means that accidental infections of health-care workers treating patients with the virus will unfortunately continue.

In its latest risk assessment, the the European Centre for Disease Prevention and Control reiterated that “if a symptomatic case of [Ebola] presents in an EU Member State, secondary transmission to caregivers in the family and in healthcare facilities cannot be ruled out.” Europe’s well developed public-health services are, however, well placed to quickly stamp out any further chains of transmission using contact tracing.

The big lessons of the new Spanish case, as in the recent case of a traveller from Liberia diagnosed with Ebola in Dallas, Texas, are the same: that unless the international community acts far faster, and on a far larger scale, to tackle Ebola at its source in west Africa, exported cases and the repatriation of sick health-care workers will continue — and family, and health-care workers caring for them, will continue to become infected with Ebola.

WHO postpones decision on destruction of smallpox stocks — again

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The stalemate continues over the question of when to destroy the last stocks of the virus that causes smallpox, a killer disease that was eradicated in 1980. One of the World Health Organization’s (WHO) two advisory committees on smallpox supports the stocks’ destruction, and the other opposes it. Last weekend, health ministers of the WHO’s 194 member states again postponed a decision and decided to set up a third WHO smallpox advisory committee in a bid to broker a consensus.

The issue came up again on the agenda of the annual meeting of the World Health Assembly, the WHO’s top decision-making body, which was held in Geneva, Switzerland, from 19 to 24 May. It was last discussed at the 2011 assembly, which reaffirmed that the stocks of the variola virus should be destroyed but deferred to this year’s meeting discussion on any date of destruction.

A central question remains whether research of public-health importance is still needed on the virus, or whether the last stocks should be destroyed to eliminate the threat of an accidental release from the two labs where they are held — at the US Centers for Disease Control and Prevention in Atlanta, Georgia, and the Russian State Research Center of Virology and Biotechnology in Koltsovo, near Novosibirsk.

The final agenda of this year’s meeting, however,  asked ministers only to take note of a WHO update report to the assembly on progress on completing needed research. The WHO’s ‘advisory committee on variola virus research’ (ACVVR), which oversees and approves any research using the stocks, felt that live virus was no longer needed to develop diagnostics and vaccines, but was still needed to develop antiviral drugs. By contrast, its ‘advisory group of independent experts to review the smallpox research programme’ (AGIES) felt that there was no research justification for holding on to the stocks.

Although the ACVVR reached a consensus on antivirals, there was considerable debate about this among its members. Some argued, for example, that with two promising drugs — tecovirimat and brincidofovir — close to licensing, virus stocks were no longer needed. Others felt that the virus should be kept in case these drugs failed to get licensed, requiring the development of other compounds.

The AGIES considered the same issues but swung towards virus being no longer needed to develop antivirals — it also suggested that should a future need arise to develop new drugs, live virus could in any case be recreated from viral DNA. The ACVVR is often perceived as being more focused on research interests, and the AGIES on public-health aspects.

By the time the WHO assembly got to discussion of destruction of smallpox stocks, it was near the end of the last day of the meeting. It quickly became clear that there were sharply divided opinions and no consensus, according to Glenn Thomas, a WHO spokesman. The decision to setup a third expert group is intended to bring together a mix of scientists and public-health and other experts to review all the elements of the debate and take the issue forward, says Thomas.

For the moment, the precise terms of reference of the group, or its composition, have yet to be decided. The latter will be important, as the destruction of the variola stocks is also a political issue. The United State is strongly opposed to destruction of the virus stocks, largely because — like many other developed countries — it wants to pursue research that it believes might help to protect against a bioweapons attack by rogue states or terrorists, who may have access to undeclared stocks (see ‘WHO to decide fate of smallpox stocks‘).

Some scientists are also keen for smallpox research using live virus not to be stopped, but continued and expanded. Two members of the ACVVR, Clarissa Damaso, of the Federal University of Rio de Janeiro in Brazil, and Grant McFadden, of the University of Florida in Gainesville, have argued, for example, that the WHO’s restricting of smallpox research to tightly circumscribed public-health applications has limited fundamental research that could advance public health. In an opinion piece published 1 May in the journal PLoS Pathogens, along with Inger Damon, head of the poxvirus and rabies branch of the Centers for Disease Control and Prevention in Atlanta, Georgia, they argue that: “the research agenda with live variola virus is not yet finished and that significant gaps still remain”.

But the majority of the health ministers of the WHO member states — including those of many poorer countries, who view the risks of an accidental release as outweighing any research benefits — want the stocks of virus destroyed at some point. The question for the WHO assembly is, as always, when? But yet again, it has kicked that can down the road.

Novel China flu seems to pose low risk to humans

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The H10N8 avian flu strain, first detected in humans in a 73-year-old woman in eastern China this month, seems, despite the woman’s death, to pose little immediate risk to people, preliminary information has shown. The sequence of the virus has not yet been published, but Nature has learned that the haemagglutinin surface protein shows none of the worrisome amino-acid changes that typically would allow the virus to infect humans. This means that, unlike H7N9, which is behind the current fatal flu outbreak in the southern Guangdong province, the virus cannot easily jump from poultry or other birds to humans.

One possible explanation for the fatal case is that the elderly woman’s health status left her more vulnerable to the H10N8 virus than healthier individuals, in which case this H10N8 infection may be no more than a rare event. The woman, who was hospitalized on 30 November and died on 6 December, is reported to have been immunocompromised and to have had heart disease, myasthenia gravis and other illnesses.

The World Health Organization, in a fact sheet on H10N8 published on 19 December, nonetheless noted: “Given the potentially unpredictable behaviour of influenza viruses, vigilance and close monitoring is needed.” If the virus is widespread in birds, some further sporadic cases could occur, it added.

The sequence also suggests that the virus, like H7N9, does not cause serious disease in birds, which means it would likewise spread silently in poultry. This would complicate surveillance of the virus were H10N8 to become a problem.

The WHO also noted that increasing surveillance for flu and severe acute respiratory-tract infections (SARI) means that “it is not unexpected to start to detect human infections with a variety of non-seasonal influenza subtypes”. In May, the first infection of humans with H6N1 avian flu was detected in Taiwan in a woman who recovered, and no new cases of the virus have since been reported. It is possible that in the past many flu viruses occasionally jumped to humans but quickly disappeared before being detected.

Meanwhile, surveillance that picked up eight serious cases of people hospitalized with SARI in Montgomery County, Texas, has caused a scare, as none of the patients initially tested positive for influenza, raising concerns that the cases might be a novel flu. Four of them subsequently died. However, two patients have since tested positive for the 2009 H1N1 pandemic flu virus, which is now just another seasonal flu strain. Investigations are ongoing, with H1N1 activity high in the area, but for the moment this scare has the appearance of a false alarm.

Mutant-flu researchers appeal Dutch court ruling on export permits

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The Erasmus Medical Center in Rotterdam, the Netherlands, where researchers led by Ron Fouchier created mammalian-transmissible strains of the H5N1 avian flu virus, this week appealed a September court ruling obliging it to request an export permit before submitting such research for publication.

Export controls are part of an international legal regime intended to prevent exports of technology or information that could result in proliferation of chemical or biological weapons — including ‘dual-use’ materials that can have both legitimate and malicious uses. H5N1 is one of a list of more than a hundred dangerous human, animal, and plant pathogens that fall under export control laws.

Last year, the Dutch government invoked European export control legislation to oblige Fouchier and the centre to obtain an export permit before publishing a paper in Science describing how he engineered the strains. Fouchier initially threatened to defy the government by publishing without a permit, but conceded under protest. He applied for a permit in April, and the government granted it a few days later. (See “The Netherlands grants export licence for mutant flu work” and the Nature Special on Mutant flu.)

Although Erasmus MC acquiesced to the government, it also filed a legal challenge, arguing that it should not have needed to apply for a permit – on the grounds that the work fell under exemptions in EU export control laws for ‘basic research’, and that it described methods that were already in the public domain (see “Court upholds need for export permits for risky flu research“). One goal of the challenge was also to have future papers on similar research exempted from the need to apply for an export permit before publishing.

On 20 September, however, a ruling by the district court of the North Holland region of the Netherlands rejected these arguments, affirming that the research had practical goals beyond basic research, and that its methodology was novel — and so did not qualify for exemption. The court also argued that the need to prevent the proliferation of biological weapons outweighed the few weeks of delay necessary for government review of such papers.

It’s this ruling that Erasmus MC has now decided to appeal, just as the six week window in which it could do so drew to a close. Fouchier was unavailable for comment. A spokesman for the centre says that because the case is under appeal, Erasmus MC and its staff may not discuss the issues with the media.

Court upholds need for export permits for risky flu research

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The researcher who created mammalian-transmissible strains of the H5N1 avian flu virus, raising fears they could cause a pandemic, has failed in an attempt to overcome government restrictions on the publication of his papers (see Nature‘s mutant flu special).

Ron Fouchier, of the Erasmus Medical Center in Rotterdam, the Netherlands, lost a court case in which he tried to have publication of papers describing the production of such strains exempted from government export controls, which require researchers to obtain an export permit before publishing.

Fouchier says that he and his colleagues will meet with lawyers next week to decide whether to appeal against the 20 September ruling by the district court of the North Holland region of the Netherlands. They have six weeks in which to act. “We do not want to give up,” says Fouchier, adding that he cannot yet say whether he will pursue an appeal until the meeting with his lawyers.

The Dutch government last year told Fouchier he had to apply for an export permit before being able to publish a paper on his engineered strains in Science. It argued that 2009 European Union (EU) legislation on export controls require an export permit for ‘dual-use’ materials and information that can have both legitimate and malicious uses — including dangerous pathogens such as H5N1.

Fouchier had at first threatened to defy the government and publish the paper without applying for an export permit but reluctantly gave in after the government warned that he could face up to six years in prison, plus fines, for doing so. The government finally granted him a permit in April last year.

Fouchier said at the time that all the paper’s co-authors and the board of directors of their institutions had agreed to seek a permit only “under protest”. At the same time, they initiated a legal challenge to dispute the necessity of them having to apply for one. Fouchier argued that the research fell under two exceptions in EU export control law, including one for “basic scientific research” that was “not primarily directed towards a specific practical aim or objective”. The paper also fell under another exception for information that is in the public domain, he argued, on the grounds that the methods were already well known. Fouchier also argued that the obligation to apply for a permit hampered access to the results of scientific research.

The court noted that the law was intended to counter the proliferation of weapons of mass destruction, including biological weapons, and that H5N1 was among those dangerous organisms specified in the law — akin to the US Commerce Control List. It ruled that because the researchers showed how to convert an avian flu into a mammalian-transmissible virus, that was by definition a practical purpose going beyond basic research.

The court also ruled that the study went beyond known methods, by selecting and detailing the specific changes necessary to obtain mammalian-transmissible strains, so was therefore not already in the public domain. That a top journal such as Science was willing to publish the paper also indicated its novelty, it added.

All this pointed to there being a legal requirement to apply for an export permit so that proliferation risks could be assessed, said the court in its ruling. It argues that the export permit system does not have any impact on most research, and causes only a few weeks delay during review of the application. Any such drawback is outweighed by the need to counter any proliferation of biological weapons, it said. Fouchier says that while the export-control review process is eight weeks, it can be extended, and that it also offers officials the option of blocking publication.

Fouchier says that he finds the court’s arguments “weak”. “They are of the opinion that our work is not basic scientific research,” he says. “They claim our goal was to make a dangerous virus airborne. However, the goal was to increase fundamental understanding of airborne transmission of bird flu virus.”

He asserts that the court’s rejection of his argument (that the methods were already in the public domain because he had only added to them), would mean that only researchers following published procedures would benefit from this exception to the export control rules.

Fouchier was one of 22 flu researchers who in August argued for the need to perform similar experiments to genetically engineer versions of H7N9 — which emerged earlier this year in China — that are more transmissible and pathogenic in mammals (see ‘Handle with care‘). The ruling suggests that any European researchers wanting to publish such work would first need to obtain export permits.

In one sense, the court’s conclusions are a reaffirmation of existing legislation in the face of a challenge, rather than setting any new precedent. Fouchier argues, however, that it “provides an opportunity for European governments to control and censor scientific publications, which in my opinion is unacceptable”.

The court argued that, more broadly, decisions on what is and what is not research with potential consequences for international proliferation cannot be left to individual researchers without compromising states’ obligations under United Nations Resolution 1540, passed in 2004, which requires states to adopt legislation to counter the proliferation of nuclear, chemical and biological weapons. “Apparently, the court thinks that export control officers are in a better position to judge scientific publications,” says Fouchier.

England too finds narcolepsy link with pandemic flu vaccine

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The case for a link between a vaccine used during the 2009 H1NI ‘swine flu’ pandemic and a serious sleeping disorder known as narcolepsy was bolstered by a study published yesterday.

Studies in several other countries have found an association between administration of GlaxoSmithKline’s Pandemrix and narcolepsy, a disorder causing excessive daytime sleepiness, which in turn is often accompanied by cataplexy — sudden muscle weakness. Now, in a small study published in the British Medical Journal, researchers have found further evidence of the link in some patients with narcolepsy in the United Kingdom.

The team reviewed case notes for 245 people, aged from 4 to 18 years old, from sleep and neurology centres in England. Seventy-five of the people had developed narcolepsy since the beginning of 2008 and 11 had been vaccinated with Pandemrix. From this, the researchers concluded that the vaccine caused a 14-to-16-fold increase in risk of narcolepsy, which they estimate would correspond to 1 in 52,000–57,500 vaccinations being associated with narcolepsy.

The association between Pandemrix and narcolepsy has become well established since the first reports in Sweden and Finland in 2011. Two Europe-wide reviews providing further analysis of the link between Pandemrix and narcolepsy (summary) were published last September by the Vaccine Adverse Events Surveillance and Communication consortium, funded by the European Centre for Disease Control and Prevention (see here  and here for the full reports).

The association found will require further investigation into the safety of the ASO3 adjuvant formula used in Pandemrix. Such additives are used in some vaccines to boost the immune response so that each vaccine dose can be smaller, allowing global vaccine capacity to be stretched to cover several times as many people. Without that multiplier effect, there would in a pandemic be only enough vaccine to cover a fraction of the world’s population (for some of Nature‘s stories on this issue during the 2009 H1N1 pandemic, see ‘Regulators face tough flu-jab choices‘, ‘US ramps up swine flu protection‘, ‘US puts flu vaccines on trial‘ and ‘Vaccine decisions loom for new flu strain‘).

But ultimately the situation remains the same as Nature reported in 2011:

Side effects of vaccines are part of any public health response risk equation. No amount of clinical trials can detect rare side-effects in advance, as statistically one would need impractically large population-size experimental cohorts to pick up very low incidence rates. Instead, regulators use pharmacovigilance once vaccines have been deployed to spot early on any problems. With some 30.8 million Europeans, including this author, already vaccinated with Pandemrix since autumn 2009, no serious safety concern has been detected.

Although anti-vaccine groups will no doubt leap on the preliminary reports from Scandinavia to scream “side-effects,” the sober reality is that not using modern and safe vaccines causes many more people to become ill or die than any rare side-effect.

US justice system ‘overreach’ blamed in suicide of Internet-freedom activist

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This weekend, the Internet world mourned one of its heroes: Aaron Swartz, 26, a prodigy, programmer and well-known Internet activist, who hanged himself in his New York apartment on Friday. Swartz was to face an imminent trial for having downloaded some 4 million articles from JSTOR, a not-for-profit scholarly archive hosted by the Massachusetts Institute of Technology (MIT). He faced extraordinarily severe charges — see here and here — carrying a possible penalty of 35 years in prison, and more than US$1 million in fines. Swartz is reported to have suffered from serious depression, but some — including his immediate family — have explicitly alleged that the pending charges contributed to his suicide. (Btw; serious depression is more common than one might think; see ‘Global survey reveals impact of disability‘ though few commit suicide.)

Online commentators have expressed indignation at the disproportion between the charges and Swartz’s alleged act. Lawrence Lessig, a law researcher at Harvard University in Cambridge, Massachusetts, has posted a must-read analysis here. Alex Stamos, an expert witness for the defence in the case, also argues that the charges were over the top. Other analyses worth reading include those from Glenn Greenwald and from The Economist.

In a statement, Swartz’s family said: “Aaron’s death is not simply a personal tragedy. It is the product of a criminal justice system rife with intimidation and prosecutorial overreach. Decisions made by officials in the Massachusetts U.S. Attorney’s office and at MIT contributed to his death. The US Attorney’s office pursued an exceptionally harsh array of charges, carrying potentially over 30 years in prison, to punish an alleged crime that had no victims.”

Rafael Reif, the president of MIT, in a statement yesterday said:  “I want to express very clearly that I and all of us at MIT are extremely saddened by the death of this promising young man who touched the lives of so many. It pains me to think that MIT played any role in a series of events that have ended in tragedy.“ He also announced that he had asked Hal Abelson, a leading computer scientist, to assess MIT’s response in the case. JSTOR also released a statement, which mentioned its widely appreciated decision not to pursue charges in the case after Swartz returned the files he had taken.

Meanwhile, a campaign has also started on Twitter calling for researchers to post their papers openly online in reaction and commemoration — at hashtag #pdftribute.

In passing, Swartz was a past invitee to Science Foo Camp, an annual invitation-only informal gathering of hundreds of leading scientists, technologists and other leading creative lights, organized by Nature in collaboration with Google and O’Reilly Media — see here and here. See Swartz’s own account of part of the 2007 meet here.

European food authority to open up GMO data

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The European Food Safety Authority (EFSA) today made public almost all supporting documents and data submitted by Monsanto for the authorization in 2003 of its genetically modified maize (corn) NK603. The data were released alongside the announcement by the EFSA that it intends to embark on a broad transparency initiative designed to make data from its risk assessments more available to the broad scientific community and other interested parties.

The move is consistent with the recommendations of an external evaluation of the EFSA by Ernst & Young last September, which called on the EFSA to increase transparency over how it reached its decisions on applications. James Ramsay, a spokesman for the EFSA, which is based in Parma, Italy, says that the plan to release more data in the future is still in the “very early stages” and that a final scheme will be announced after further discussion with stakeholders. The EFSA announcement follows a similar move by the European Medicines Agency, which this year will make public all clinical-trial data it gets from industry as part of product registration.

The EFSA said that it chose to make the NK603 data publicly available first because of the level of public interest in response to a French-led study published in September, which claimed that rats fed the maize or glyphosate herbicide suffered adverse health effects including increased incidence of tumours. The 500-MB download contains all data apart from a small amount of commercially confidential information, says Ramsay. The French study has been roundly criticized by scientists and authorities as being methodologically flawed.

“While the Authority has already made available these data upon specific request on several occasions, any member of the public or scientific community will now be able to examine and utilise the full data sets used in this risk assessment,” the EFSA said in a statement.

Gilles-Eric Séralini, a molecular biologist at the University of Caen, France, who led the study, has refused to make his raw data available until the EFSA made its NK603 data available. Séralini had already scheduled a press conference for tomorrow afternoon at the European Parliament to hand his data over to a bailiff. Séralini says that he welcomes the EFSA move but also wants raw data on glyphosate-safety studies. The researcher also intends to announce tomorrow that he will pursue several of his critics for libel.

Family cluster of novel coronavirus cases reported in Saudi Arabia

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The World Health Organization (WHO) this afternoon reported four new laboratory-confirmed cases of a novel coronavirus infection, bringing the total number of cases identified since June to six. Two of the people infected are from the same household, raising the possibility of human-to-human transmission of the virus, although it’s also possible that they both contracted it independently from an animal source in the area. Three of the new cases occurred in Saudi Arabia (where one patient died) and a fourth case was reported in Qatar. The WHO gave few further details of the cases, such as their age, sex or current medical condition.

That the new cases have been found probably reflects increased surveillance for the virus since its identification as a novel virus. They follow two cases reported earlier — a 60-year-old man from Saudi Arabia who fell ill and died in June, and a 49-year-old man from Qatar who fell ill in September and has since recovered (see ‘SARS veterans tackle coronavirus‘). None of the contacts of those two men are known to have contracted the virus, which suggests that the virus probably doesn’t transmit, or doesn’t transmit easily, between humans. The novel coronavirus, identified as such in September, is genetically most closely related to bat coronaviruses, and bats (and possibly intermediate animal hosts) are likely to be the virus’s reservoirs.

Among this new batch of cases, two of the four people infected in Saudi Arabia were from the same family, living in the same household — one died and the other recovered. Moreover, two other family members showed similar symptoms, and one has died; the WHO is waiting to find out whether the fatal case tests positive for the coronavirus too. The recovered patient tested negative. Household clusters of cases of a novel virus raise the possibility of human-to-human transmission, and so immediately catch the attention of epidemiologists, who, along with clinicians and virologists, will be urgently seeking to tease out the probable source of infection, how the people contracted the virus and whether they each caught it independently from an animal reservoir or there is any human-to-human transmission going on.

The WHO gave no description of the symptoms, but the cases in June and September had severe pneumonia and acute renal failure. What’s also striking so far is the very high case mortality rate — so far two out of six cases, and three out of seven if the unconfirmed fatal case tests positive. Now, one can’t put a firm figure on case mortality rates until one knows the true number of deaths and cases, in particular as more asymptomatic or recovered cases may be going unnoticed — pinning that down will require more surveillance and epidemiology data, including seroprevalence surveys to test whether people not showing infection have antibodies to the virus (meaning they have been exposed to it). But the symptoms are serious, and the death rate in this particular cluster reinforces the impression that the mortality rate is high.

Not surprisingly, WHO is urging all countries to continue careful surveillance for severe acute respiratory infections, and warns that until more is known, it would be “prudent to consider that the virus is likely more widely distributed than just the two countries which have identified cases”. The WHO also seems to have upped the urgency of screening. Its current novel coronavirus case definition only calls for testing any unexplained pneumonias in places “where infection with novel coronavirus has recently been reported or where transmission could have occurred”. Today’s report says that testing of such cases for the novel coronavirus should be considered “even in the absence of travel or other associations with the Middle East”, adding that any clusters of serious pneumonia, or cases of such illness in health-care workers, “should be thoroughly investigated regardless of where in the world they occur”. For the moment, there’s no evidence that the virus transmits between people, but scientists and public-health officials will be keeping a close eye on it and seeking to quickly understand every aspect of the virus and its ecology.

Malaria programme gets kiss of death from Global Fund

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It appears that the Affordable Medicines Facility — Malaria (AMFm) is being scuttled by the Global Fund to Fight AIDS, Tuberculosis and Malaria. The AMFm is a multimillion-dollar programme to get effective drugs — artemisinin-based combination therapies (ACTs) — to remote rural villages, where local stores are often the main providers of medicines.

That’s my first take on the Global Fund’s announcement this afternoon, delivered towards the end of a two-day meeting of its board, which began yesterday in Geneva, Switzerland. The fund intends to end AMFm’s stand-alone status, and instead “integrate” the AMFm into its existing core system of providing grants to countries to purchase drugs, bed nets and other malaria-control measures.

Meanwhile, just in: the Fund announced a few minutes ago that it has nominated as its new executive director Mark Dybul, a former head of the President’s Emergency Program for AIDS Relief (PEPFAR), who now co-directs the Global Health Law Program at the O’Neill Institute for National and Global Health Law at Georgetown University in Washington DC. It follows the resignation of Michel Kazatchkine in February (see ‘Global health hits crisis point‘).  More on that later.

The idea behind the AMFm was to make ACTs the frontline treatment, something which has been badly hindered by their much higher price than older antimalarials. Although these older drugs, such as chloroquine, are cheap, they are often ineffective because the parasite has developed resistance to them.

AMFm’s strategy was to first guarantee a market of large bulk orders, allowing it to negotiate large cuts in the price of the drugs from pharmaceutical companies. It then gave importers in affected countries — both in the public and private sector — a subsidy on their purchases, to bring the final price to the consumer down to a level competitive with older drugs. It was also intended to compete with artemisinin monotherapies, which are a recipe for generating drug resistance against the only drug class that is truly effective against malaria.

A full-blown country-level trial of the AMFm concept in eight countries — Cambodia, Ghana, Kenya, Madagascar, Niger, Nigeria, Tanzania (including Zanzibar) and Uganda — began in July 2010 and runs until December 2012. It has had its critics — see ‘Malaria plan under scrutiny’ — but in anyone’s reasonable terms it has already been remarkably successful in many important ways within a very short period ( see the 31 October Lancet paper ‘Effect of the Affordable Medicines Facility—malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data’).

The Global Fund’s press release detailing its plans is entitled ‘Board approves integration of AMFm into core Global Fund grant processes‘, and much of its soothingly reassuring content would perhaps have many thinking that the AMFm’s integration into the Global Fund’s core grants system is good news. But it is in effect being killed. There’s will be no new money ringfenced for the AMFm once it runs through its current funding up to the end of 2013, which means that any countries wanting to set aside cash for the private sector will be required to take this from their country grants from the Global Fund. In reality, that will probably translate into AMFm activities simply being terminated in most countries, leading to local price rises in ACTs, and the drugs disappearing off the shelves of local pharmacies. AMFm’s clout in negotiating bulk pricing deals internationally will also probably be weakened.

Here’s what a group of AMFm’s supporters wrote in the Lancet on 31 October about what ‘integration’ of the AMFm into the Global Fund would mean (from’The Affordable Medicines Facility—malaria: killing it slowly‘):

“In November, 2012, the Board of the Global Fund will vote to either continue AMFm in a modified form after December, 2013, or terminate the programme. There is a strong push from donors (though not from countries) to integrate AMFm into the regular Global Fund model, whereby countries would choose how much of their country budget envelopes, which are already committed to other priorities supporting the public sector, to reallocate to AMFm. We believe that this approach will create instability in artemisinin demand, lower the number of ACT manufacturers, increase ACT prices, and abandon the millions who depend on AMFm-subsidised ACTs. Most importantly, it will kill a programme that, when fully implemented, rapidly met its benchmarks despite the many constraints, expectations, and unrealistic timelines imposed on it. We must acknowledge that an efficient approach to subsidising antimalarial drugs has worked, making them available in the private sector where people go to buy them.”

The Global Fund’s board has decided AMFm’s fate, and there is probably no going back on that. But the world now urgently needs a strategy that works with the private sector to keep down ACT prices, particularly in Africa.