News (Updated March 8, 2009)

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Ray of hope for drug-resistant TB

06 Mar 2009 18:19:00 GMT

Sharon Davis

  Untreatable cases of extensively drug-resistant tuberculosis (XDR-TB) could be tackled with a combination of two existing drugs  one of which was developed over 30 years ago.

Laboratory studies, published in Science last week (27 February), showed that a combination of the drugs meropenem and clavulanate inhibited the growth of 13 separate strains of XDR-TB.

They also inhibited the growth of drug-susceptible laboratory strains and those that mimic the 'latent' state of TB  an inactive phase of TB which is difficult to treat.

The researchers, from the US National Institute of Allergy and Infectious Diseases and the US-based Albert Einstein College of Medicine, are optimistic that if the results are reproduced in humans, an effective XDR-TB treatment could be produced in a relatively short time.

Meropenem belongs to a class of antibiotics called b-lactams. These widely-used drugs have never proved useful in TB treatment as Mycobacterium tuberculosis possesses an enzyme that breaks them down. But clavulanate inhibits the enzyme, allowing meropenem to kill M. tuberculosis when the two are used in combination.

Phase II clinical trials of the drug combination will commence on about 100 patients in South Korea by the end of the year.

A smaller trial on 15-20 TB patients in South Africa  half of whom will also be HIV-infected  will hopefully begin by mid-2009, says Brian Currie, professor of medicine at the Albert Einstein College of Medicine who will design and run the trial, along with Willem Sturm, dean of the Nelson Mandela School of Medicine in Durban , South Africa .

Currie says South Africa was chosen as a test site due to its high prevalence of XDR-TB.

He told SciDev.Net that clavulanate was not yet approved in South Africa and the trials would instead use an oral preparation of amoxicillin-clavulanate, which is approved, along with meropenem.

This combination was also tested in the current research, and while not as effective as meropenem and clavulanate, it is still superior to other drugs, says Currie, and its use will bypass an estimated 12-month delay before preparations of clavulanate are approved.

 

Common ingredient offers AIDS protection

By Maggie Fox, Health and Science Editor Maggie Fox, Health And Science Editor Wed Mar 4, 5:30 pm ET

WASHINGTON (Reuters) – A cheap ingredient used in ice cream, cosmetics and found in breast milk helps protect monkeys against infection with a virus similar to AIDS and might work to protect women against the virus, researchers reported on Wednesday.

The compound, called glycerol monolaurate, or GML, appears to stop inflammation and helps keep away the cells the AIDS virus usually infects, the researchers said.

While it does not provide 100 percent protection, it might greatly reduce a woman's risk of being infected, and she could use it privately and without hurting her chances of pregnancy, the researchers reported in the journal Nature.

And it costs pennies a dose, Ashley Haase and Pat Schlievert of the University of Minnesota reported.

"For years, people have used the compound as an emulsifying agent in a variety of foods ... it is in breast milk," Schlievert told reporters in a telephone briefing.

GML is being considered as an additive to tampons because it interferes with bacteria, particularly those that can cause a potentially fatal infection called toxic shock syndrome.

If it can be shown to work safely in women, GML might provide the first easy route to a microbicide -- a gel or a cream that women could use vaginally to protect themselves from infection with the human immunodeficiency virus, or HIV, which causes AIDS.

HIV infects 33 million people globally and has killed 25 million. It is transmitted sexually, in blood and breast milk. In Africa , it is most commonly passed during heterosexual contact.

PROTECTING WOMEN

AIDS experts say many victims are married women whose husbands will not use condoms and who are often trying to have children. They need a safe and private way to protect themselves.

A microbicide (pronounced my-CROW-buh-side) might also protect men who have sex with men.

Haase and Schlievert's team tested GML, carried in KY jelly, in macaque monkeys. They put the gel into the vaginas of the monkeys and then applied SIV, a monkey version of HIV.

Four out of five monkeys never became infected and tests showed GML affected the immune response.

HIV is particularly hard to fight because it infects the very immune cells the body uses to attack a virus. When HIV infects an area such as the vagina, the CD4 T-cells rush to defend against it. The body sends out signaling chemicals called cytokines to call in more T-cells.

HIV can then infect them all and spread through the body.

GML appears to stop the cytokine call for help and stops so many T-cells from rushing to the area, Haase and Schlievert said. This in turn reduces the opportunity for HIV to take hold.

"This result represents a highly encouraging new lead in the search for an effective microbicide to prevent HIV transmission that meets the criteria of safety, affordability and efficacy," they wrote.

Even if it was only 60 percent effective, such a gel could prevent 2.5 million HIV cases over three years, they said.

They said they plan to study their gel in more monkeys for longer periods of time to ensure the gel is not simply delaying infection rather than preventing it.

(Editing by Will Dunham)

 

Scientists make HIV strain that can infect monkeys

Tue Mar 3, 2009 2:11am EST

By Will Dunham

PhotoWASHINGTON (Reuters) - Scientists have created a strain of the human AIDS virus able to infect and multiply in monkeys in a step toward testing future vaccines in monkeys before trying them in people, according to a new study.

This strain of HIV, the human immunodeficiency virus, was developed by altering a single gene in the human version to allow it to infect a type of monkey called a pig-tailed macaque, the researchers said on Monday.

The genetically engineered virus, once injected into this monkey, proliferates almost as much as it does in people, but the animal ultimately suppresses it and the virus does not make it sick, they said.

The strain is called simian-tropic HIV-1, or stHIV-1.

Researchers hope to be able to test possible new AIDS drugs and vaccines in monkeys before trying them in people.

There is a "cousin" virus to HIV called SIV, or simian immunodeficiency virus, that causes a disease similar to AIDS in certain types of monkeys.

But this monkey AIDS virus is not identical to the one that infects people and is not a perfect substitute for testing drugs and vaccines against HIV.

"If our research is taken further, we hope that one day perhaps in the not-too-distant future, we'll be able to make vaccines that are intended for use in humans and the very same product will be able to be tested in animals before human trials," Paul Bieniasz of the Rockefeller University in New York, one of the researchers, said in a telephone interview.

Scientists have struggled to create an AIDS vaccine.

"If you make a drug that's effective against HIV, sometimes it works against SIV and sometimes it doesn't. So that basically devalues SIV as an animal model for doing experiments involved with developing drugs," Bieniasz said.

"Now if you want to develop a vaccine, essentially what you have to do is to make a parallel vaccine for HIV and for SIV. You can test the SIV vaccine in animals and then have to make the leap of faith that the same approach would work equivalently in humans."

Writing in the journal Proceedings of the National Academy of Sciences, the scientists said in making the genetically engineered virus they removed the HIV version of a gene, known as vif, and inserted the SIV version. This gene acts to thwart proteins made by the monkey that that kill viruses.

Bieniasz said the scientists may need to make additional changes in the stHIV-1 to make it better for testing vaccines.

The genetically engineered virus infects the monkeys and during the early course of infection is a reasonably good mimic of what happens in HIV-infected people, Bieniasz said.

But after initially spreading in the monkey's body, the animal succeeds in suppressing the virus -- not completely clearing the virus but driving it to very low levels.

"The slight problem is the monkeys don't go on to develop AIDS, they don't get sick," Bieniasz said.


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