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11-Feb-2008

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Contact: Josh Eveleth
jeveleth@plos.org
415-624-1234
PLOS

Fake malaria drugs made in China; how the winter vomiting virus evolves

Study finds evidence of fake malaria drugs being manufactured in China

A unique collaborative study between scientists, public health workers and police has led to the arrest of alleged traders of fake anti-malarial drugs in China. The epidemiological investigation, involving teams from across the globe and published in this week's PLoS Medicine, highlights the growing threat posed by fake pharmaceuticals and the complexities of tracking down those responsible for their manufacture.

Fake anti-malarial drugs are an increasingly serious problem, particularly in South East Asia and Africa. In countries such as Myanmar (Burma), the Lao PDR, Cambodia and Viet Nam, with a large burden of malaria, as many as half of all purchased artesunate tablets, one of the most effective of anti-malarial drugs, are counterfeit.

The new collaborative investigation, known as "Operation Jupiter," was coordinated by the International Criminal Police Organisation (INTERPOL), the World Health Organization's Western Pacific Regional Office, and the Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme, in close cooperation with Chinese authorities. Scientists from five other laboratories analysed the composition of 391 samples of genuine and fake artesunate tablets collected across SE Asia, and also studied their packaging.

Most of the fakes examined contained no artesunate. Some contained a wide range of potentially toxic wrong active ingredients, including banned pharmaceuticals such as metamizole, and raw materials, such as safrole, used for the manufacture of the drug ecstacy.

Of additional great concern for public health, the counterfeiters sometimes included dangerously small amounts of artesunate in the tablets. This may be done to foil screening tests of drug quality, but these doses are too low to be effective at treating malaria yet high enough to encourage the spread of malaria parasites resistant to the medicine.

Dr Paul Newton (Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme), the study's lead author, said: "Artesunate, as part of artemisinin-based combination therapy, is vital for malaria treatment and is one of the most effective weapons we have against this terrible scourge."

"Those who make fake anti-malarials have killed with impunity," he said, "directly through the criminal production of a medicine lacking active ingredients and by encouraging drug resistance to spread. If malaria becomes resistant to artesunate, the effect on public health in the tropics will be catastrophic."

In addition to analysing the chemistry of the samples, researchers used a technique known as forensic palynology to study pollen contamination within the fake tablets with the aim of tracking down the likely location of manufacture. The pollen evidence suggested that at least some of the counterfeit artesunate came from southern China, and this was supported by examination of the mineral calcite, found in some of the samples.

Armed with these findings by INTERPOL, Chinese authorities arrested a suspect in China's Yunnan Province in 2006. He is alleged to have traded 240,000 blisterpacks of counterfeit artesunate, enough to "treat" almost a quarter of a million adults with a medicine with no activity against a potentially fatal disease. Whilst the Chinese authorities were able to seize 24,000 of these packs, the remainder are alleged to have been sold at crossings on the border of Yunnan and Myanmar (Burma), accounting for almost a half of all blisterpacks of artesunate sold to the region.

Citation: Newton PN, Fernandez FM, Plancon A, Mildenhall DC, Green MD,et al. (2008) A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia. PLoS Med 5(2): e32.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE

VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050032

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-02-newton.pdf

Related image for press use: http://www.plos.org/press/plme-05-02-newton-genuine-artesunate.jpg

Caption: Genuine artesunate anti-malarial tablet.

Related image for press use: http://www.plos.org/press/plme-05-02-newton-fake-artesunate.jpg

Caption: Counterfeit artesunate anti-malarial tablet.

Related image for press use: http://www.plos.org/press/plme-05-02-newton-fake-artesunate-detail.jpg

Caption: Counterfeit artesunate anti-malarial tablet with fake 'X-52' stamp as seen under UV light.

CONTACT:

Craig Brierley
Wellcome Trust
215 Euston Road
London NW1 2BE
United Kingdom
+44 20 7611 7329
c.brierley@wellcome.ac.uk


Researchers discover how noroviruses cause repeated outbreaks of "stomach flu"

Norovirus, a common cause of gastroenteritis ("stomach flu"), could potentially be controlled by a vaccine. But because the virus evolves to avoid the immune system, the vaccine might have to be modified from year to year, according to new research published in PLoS Medicine by Ralph Baric of the University of North Carolina, Chapel Hill, and colleagues.

Noroviruses, which are highly contagious, cause nausea, vomiting, and diarrhea. While most people recover within a few days, the very young and old may experience severe disease. Although maintaining hydration is essential, there is no specific treatment for infection. As with influenza, epidemics of norovirus infection occur periodically (often in closed communities such as cruise ships), and most people have several norovirus infections during their lifetime. This winter the UK has seen almost twice as many norovirus cases compared to the same period last year.

Noroviruses infect cells after attaching to molecules called histo-blood group antigens (HBGA) present on the cell surface. HBGAs comprise a family of complex sugar molecules that exist in great variety among human beings. The researchers found that this variety provides the key to understanding how norovirus outbreaks continue to occur, even in populations that have previously been exposed to noroviruses and therefore harbor antibodies against them.

By analyzing noroviruses isolated from several outbreaks, the researchers found that the viruses evolved to avoid attack by antibodies the hosts developed against them. Over time, some viruses selected in this way attain a shape that enables them to bind to one of the other forms of HBGA, and thereafter are not only resistant to previously existing antibodies, but are also able to infect cells carrying that particular form of HBGA. These viruses can then cause a new outbreak, and the cycle repeats itself.

This continuing evolution of new replacement strains suggests that vaccines could be designed to protect against norovirus infection, but that, as with influenza vaccines, ongoing epidemiologic surveillance and reformulations of norovirus vaccines will be needed.

In a related perspective article, Ben Lopman and colleagues at the UK Health Protection Agency, who were not involved in the study, discuss the evolution of noroviruses and the implications of this research for the control of future outbreaks.

Citation: Lindesmith LC, Donaldson EF, LoBue AD, Cannon JL, Zheng DP, et al. (2008) Mechanisms of GII.4 norovirus persistence in human populations. PLoS Med 5(2): e31.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE

VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050031

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-02-baric.pdf

CONTACT:

Ramona DuBose
University of North Carolina at Chapel Hill
Director of Communications
210 Pittsboro Street
Chapel Hill
+ 1 919-966-7467
ramona_dubose@unc.edu


Related PLoS Medicine perspective article:

Citation: Lopman B, Zambon M, Brown DW (2008) The evolution of norovirus, the "gastric flu." PLoS Med 5(2): e42.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE

VERSIONS OF YOUR REPORT: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050042

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-02-lopman.pdf

CONTACT:

Ben Lopman
Imperial College London
Department of Infectious Disease Epidemiology
St Mary's Campus
London, W2 1PG
United Kingdom
+ 44 207 594 3631
blopman@gmail.com

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About PLoS Medicine

PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org

Everything published by PLoS Medicine is Open Access: freely available for anyone to read, download, redistribute and otherwise use, as long as the authorship is properly attributed.



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