News (Updated February 14, 2010)

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HIV spread among men traced

February 11, 2010

CBC News

Scientists have made a key discovery in pinpointing how HIV is transmitted in men who have sex with men.

The researchers hope that by better understanding how HIV spreads during human sex, that they'll be better able to stop the epidemic.

"By knowing the origin of the transmitted virus, scientists may be able to develop new vaccines, vaginal microbicides and drugs to prevent the spread of sexually transmitted HIV," study author Dr. Davey Smith, an associate professor of medicine at the University of California San Diego , said in a release.

Semen is made up of sperm, white blood cells and the fluid around these cells, known as seminal plasma.

HIV in semen comes in two contagious forms — DNA in the white blood cells and free-floating RNA in the seminal fluid.

Until now, researchers did not know whether HIV RNA or DNA was transmitted during sex.

Smith and his colleagues used genetic analysis to trace the ancestral history of the virus in six pairs of men, the source partners, who sexually transmitted their HIV to other men, the recipient partners.

To investigate, the researchers compared the virus found in the recipients to the DNA and RNA versions in the men who infected them.

RNA was the closest match, leading the team to conclude HIV originated from RNA in the seminal fluid of the source partners.

The findings are reported in this week's issue of Science Translational Medicine.

Davey's team only looked at males, so the findings may not apply to HIV transmission in women.

The results also need to be tested in larger samples of pairs to determine which features of viral genomes are linked with transmission.

Abbott Laboratories receives FDA approval for heat-stable formulation of HIV drug

NORTH CHICAGO , Ill. (AP) - Abbott Laboratories said Thursday it received Food and Drug Administration approval for a heat-stable version of the HIV treatment Norvir.

The approval is for a new formulation of the tablet, which allows it to be stored at room temperature rather than in a refrigerator. The drug is used in combination with other antiretroviral medications to treat HIV.

 

'HIV home test kits must be regulated'

2010-02-12

The sale of HIV home testing kits must be regulated by the government, the SA Medical Association has said.

Sama chairman Dr Norman Mabaso said in a statement on Friday that this was necessary to prevent the kits from being sold to private individuals without any counselling.

Sama's call comes after the launch of the home kit was put on hold following concerns that there was no legal obstacle to stop the kit from being distributed to individuals.

"Home testing for HIV has important implications for the individual, especially in respect of HIV counselling procedures," Mabaso said.

"Although Sama fully supports testing, as it is essential for people to know their status, we do not support the ad hoc sale of home testing kits.

"We will do everything in our power to make presentations to government to ensure that devices of this nature are distributed responsibly.

"Sama implores government to regulate the sale of these kits and also make it compulsory for counselling to be available via the merchant when it is sold." - Sapa

 

Make STD testing mandatory

Rosa Freedman

guardian.co.uk, Monday 8 February 2010 18.00 GMT

We all know the risks of unprotected sex, thanks to public education campaigns. And there have also been efforts to encourage people to seek an STD test, notably for chlamydia, which can cause infertility: another 200,000 people were diagnosed with it in the UK in 2008. Yet important elements in our society seem to encourage people not to find out whether they have an STD. Their sexual partners, meanwhile, would prefer not to contemplate it. So STDs are transmitted to people who have not had the opportunity to consent to that risk of infection. Draconian as it may sound, the only way around this might be mandatory testing for STDs.

Private medical coverage has become widespread, and companies often encourage members to improve their health, such as by using a gym regularly, through discounts on their premiums. Yet those same companies are effectively discouraging STD testing by the way they treat potential customers who have been infected. Health insurance is particularly difficult to obtain for those with HIV. Premiums may be greatly increased for those with other STDs. A person who has engaged in risky behaviour is incentivised not to discover his or her status for fear of falling foul of these companies.

Criminal law offers similar disincentives. A person may be prosecuted if, knowing they have a disease, they engage in unprotected sexual intercourse and infect his or her partner. Prosecution will depend on whether the other party was told of the STD before intercourse took place, giving them the choice to consent to risk of infection. Failure to disclose may result in a charge under the Offences Against the Person Act 1861. Spreading diseases requires heavy sentencing, for both deterrent and punitive reasons. Criminal law becomes asinine where it deals with diseases spread by a person ignorant of his or her status. Such persons can defend a charge on the basis that lack of knowledge negates the duty to disclose.

In the event of an epidemic, various methods are used to contain the threat and prevent its spread. Isolation, mandatory treatment and other measures may be introduced. The spread of sexually transmitted diseases – including HIV, which is again on the rise in England – can be classed as an epidemic. Mandatory testing, knowledge of status and the legal incentive to pass on that information, would limit that spread. Tests could be carried out at annual GP check-ups, or when a person seeks other medical treatment from doctors or in hospitals, and the results kept on their confidential NHS records.

Mandatory testing would not necessarily mean that STD carriers cannot engage in unprotected sex. It would result in carriers knowing their status, and requiring them to tell the other person of, and obtain their consent to, the risk of infection. Informed consent may allow unprotected sex depending on the STD's classification under the different criminal "harms", as serious diseases like HIV cannot be consented to under current law. Criminal convictions would deter failure to disclose, and punish those ignoring that duty.

An individual's right to decide whether to find out their status is trumped by other people's rights to know the risk of infection. Would compulsory tests be unpopular? Probably. But while insurers continue to discriminate against people with STDs, and advertising and educational campaigns will only go so far in preventing further infections, mandatory testing would enable people to stop infecting others without realising it.

 

3-D Structure of Bullet-Shaped Virus With Potential to Fight Cancer, HIV Revealed

Assembly of bullet-shaped VSV virion. (Credit: UCLA)

ScienceDaily (Feb. 11, 2010) — Vesicular stomatitis virus, or VSV, has long been a model system for studying and understanding the life cycle of negative-strand RNA viruses, which include viruses that cause influenza, measles and rabies.

More importantly, research has shown that VSV has the potential to be genetically modified to serve as an anti-cancer agent, exercising high selectivity in killing cancer cells while sparing healthy cells, and as a potent vaccine against HIV.

For such modifications to occur, however, scientists must have an accurate picture of the virus's structure. While three-dimensional structural information of VSV's characteristic bullet shape and its assembly process has been sought for decades, efforts have been hampered by technological and methodological limitations.

Now, researchers at UCLA's California NanoSystems Institute and the UCLA Department of Microbiology, Immunology and Molecular Genetics and colleagues have not only revealed the 3-D structure of the trunk section of VSV but have further deduced the architectural organization of the entire bullet-shaped virion through cryo-electron microscopy and an integrated use of image-processing methods.

Their research findings appear this month in the journal Science.

"Structures of individual rhabdovirus proteins have been reported in Science and other high-profile journals, but until now, how they are organized into a bullet shape has remained unclear," said study author Z. Hong Zhou, UCLA professor of microbiology, immunology and molecular genetics and a member of the CNSI. "The special shape of VSV-- a bullet head with a short, helical trunk-- has lent to its evasion from three-dimensional structural studies."

Based on their research into the structure of VSV, the team proposed a model for the assembly of the virus, with its origin at the bullet tip. Their data suggest that VSV assembles through the alternating use of several possible interaction interfaces coded in viral protein sequences to wind its protein and RNA chain into the characteristic bullet shape.

"Our structure provides the first direct visualization of the N and M proteins inside the VSV virion at 10.6-Ĺ resolution. Surprisingly, our data clearly demonstrated that VSV is a highly ordered particle, with the nucleocapsid surrounded by, instead of surrounding, a matrix of M proteins," said lead study author Peng Ge, a visiting graduate student at UCLA from Baylor College of Medicine. "To our amusement, the sequence in assembling viral protein and RNA molecules into the virus appears to rhyme with the first several measures of Mozart's piano sonata in C-Major, K.545." (This musical correlation is illustrated in the paper's supplementary movie 2.)

The findings could help lead to advances in the development of VSV-based vaccines for HIV and other deadly viruses, according to the researchers.

"Our structure provides some of the first clues for understanding VSV-derived vaccine pseudotypes and for optimizing therapeutic VSV variants," Zhou said. "This work moves our understanding of the biology of this large and medically important class of viruses ahead in a dramatic way. The next stage of research for our team will be to reveal the details of molecular interactions at the atomic scale using advanced imaging instruments now available at CNSI."

The Electron Imaging Center for Nanomachines (EICN) lab at the CNSI has Cryo-EM instrumentation, including the Titan Krios microscope, which makes atomically precise 3-D computer reconstructions of biological samples and produces the highest-resolution images available of viruses, which may lead to better vaccines and new treatments for disease.

In addition to Z. Hong Zhou and Peng Ge, the research team included colleagues from the laboratory of Ming Luo, professor of microbiology at the University of Alabama at Birmingham , and Stan Schein, UCLA professor of psychology.

The research was supported by the National Institutes of Health.

 

XDR TB emerging despite good adherence, due to sub-optimal treatment and bad infection control

Keith Alcorn, Wednesday, February 10, 2010

Extensively drug-resistant tuberculosis is most likely emerging as a result of delays in diagnosis, sub-optimal treatment and poor infection control, not failures in patient adherence, a newly published study of XDR TB cases in a South African gold mine suggests.

Drug-resistant TB is an emerging concern in South Africa , and in 2006 a cluster of XDR TB cases was identified in KwaZulu Natal, leading to national attempts to implement improved infection control and drug susceptibility testing.

However, drug-resistant TB remains a major challenge for South African and other nations in the region, where high rates of tuberculosis are being exacerbated by HIV infection, which makes people exposed to TB much more likely to develop active disease.

The study, published this week in the US Centers for Disease Control online journal Emerging Infectious Diseases, looked at 128 patients diagnosed with drug-resistant TB at a single gold mine in the North West province of South Africa between January 2003 and November 2005.

Although the gold mine had achieved a cure rate above 85% in the treatment of new smear-positive cases by 2001, following the introduction of directly observed treatment that ensured optimal adherence, new cases continued to rise and the incidence of drug-resistant TB was also growing.

Investigators from Stellenbosch University, Harvard University School of Public Health and West Vaal Hospital identified 128 drug-resistant TB cases among 3003 TB cases notified at the gold mine’s hospital. Eighty-four were HIV-positive, seven were HIV-negative and the remainder had an unknown HIV status. Sixty-two per cent of those with MDR TB had a CD4 count below 200, indicating advanced HIV infection, but only 8% were already receiving antiretroviral therapy at the time of MDR TB diagnosis.

Only 31% of those who were diagnosed with MDR TB were cured; 35% died, with the remainder still receiving treatment at the time of the analysis.

The investigators found that 74 mTB isolates showed similarity to at least one other isolate, indicating transmission, and they were grouped in 11 transmission clusters, the largest of which involved 42 patients. The investigators calculated that 71% of patients had acquired drug-resistant TB from another patient.

Multi-drug resistant isolates were more likely to be found in clusters than single-drug resistant isolates; strains that were classified as XDR TB or pre-XDR (MDR with resistance to the second-line agents kanamycin or ofloxacin) were 27 times more likely to be found in a cluster than isolates with less drug resistance (OR 27.42, p<0.001), and no additional risk factors for clustering were identified in the multivariate analysis.

In the largest cluster, of 42 patients, three-quarters of patients had been hospitalised for non-MDR TB (in a general TB ward) at the same time as another patient in the cluster was admitted to the hospital with MDR TB care. Since all patients with TB received care on the same ward until diagnosed with MDR TB, it is not hard to see how such a large cluster could have emerged within a single facility.

In addition 92% of MDR TB patients in the cluster had worked in the same mine shaft as another person in the same MDR TB cluster, and 85% lived in the same dormitory as another MDR TB case prior to diagnosis.

Fifty-nine per cent of MDR TB patients in any cluster had a previous history of TB treatment.

The authors make a number of recommendations for curtailing the spread of MDR TB within hospitals and workplaces:

Ensure that everyone who is eligible for antiretroviral therapy is getting it, in order to reduce the number of individuals susceptible to developing active TB.

 

Greater efforts to identify infectious cases through intensified case finding, active screening and improved education about TB symptoms.

 

More frequent sputum smear examinations to identify infectious cases, and more frequent culture-based diagnosis to identify cases before they become infectious.

 

Development and implementation of rapid drug susceptibility testing in order to identify MDR cases, plan appropriate treatment and separate from susceptible patients.

 

Better infection control measures on general wards, outpatient waiting areas and TB wards.



Reference
Calver AD et al. Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa . Emerging Infectious Diseases 16 (2): 264-271, 2010.



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