Monday, November 30, 2009
A rare parasitic disease, which normally only is transmitted by contaminated water, has been shown to be transmitted by gay sex between HIV-positive men. In the industrial world the disease is virtually absent, but that could change.
For this observation, Taiwanese researcher Chieng-Ching Hung received a doctorate from the University of Antwerp and the Institute of Tropical Medicine Antwerp.
Amebiasis, an infection with the single-celled amoeba Entamoebia histolytica, normally is very rare. You only catch it in a few developing countries where the amoeba is endemic, and where hygiene is somewhat substandard, leading to contact with contaminated water. It only becomes dangerous when the amoeba invades your intestinal lining and causes a bloody diarrhea, or when it enters the bloodstream, where it, among other things, causes liver abscesses. All in all amebiasis takes some 70,000 lives a year, worldwide.
For some time now, physicians suspected the disease to be a bit overrepresented among HIV-positive male homosexuals. But it was difficult to come to conclusions from small numbers, and in addition the classical diagnostic test (putting the stool under the microscope) was not really dependable. Hung used modern molecular techniques, pinpointing the amoeba more precisely and, what's more, showing which amoebas were closely related. In other words: who had got the infection from whom.
In Taiwan, seropositive (HIV-infected) gay men were shown to be infected much more often with the amoeba than the healthy population, and also than seropositive heterosexuals. Also, Hung found men from different regions nevertheless to be infected by closely related amoebas. The most reasonable explanation is that the infection happened through homosexual (oral-anal) contact.
In today's mobile world this means that those people in turn can transmit the infection to regions where it normally is absent.
Not only amebiasis marches in the wake of HIV; Hung also confirmed in his Taiwanese cohort what is seen elsewhere: tuberculosis and hepatitis B and C are more virulent in combination with HIV, and more often present.
The UK government has launched a campaign to encourage young people to talk more openly about sex and contraception.
The teenage pregnancy rate in the UK is Europe's highest and ministers want to change attitudes towards safer sex.
People aged 16 to 24 should not be too embarrassed to talk openly with partners, friends, parents and health professionals, ministers argue.
A recent survey suggested 26% of people in that age group never discussed contraception with their partners.
The "Contraception. Worth Talking About" advertising will not feature any people, but will show snippets of "contraception conversations" in speech bubbles, in a variety of everyday scenarios, such as in a shopping centre, or in front of the television.
The campaign comes after figures earlier this year showed the government's target of halving teenage pregnancy rates by 2010 is likely to be missed.
Data published in February showed there were 41.9 conceptions per 1,000 15 to 17 year olds in 2007 - up from 40.9 the year before.
There have also been concerns about rising rates of sexually transmitted infections, particularly chlamydia, among teenagers and young adults.
The Department of Health said a lack of knowledge and communication, as well as misinformation and poor attitudes, were hindering safer sex in young people. A spokesman said a survey had suggested that 92% of people could not name the 15 types of contraception options available to them.
15 TYPES OF CONTRACEPTION
· Cap with spermicide
· Combined pill
· Contraceptive injection
· Contraceptive patch
· Contraceptive vaginal ring
· Diaphragm with spermicide
· Female condom
· Female sterilization
· Intrauterine device (IUD)
· Intrauterine system (IUS)
· Male condom
· Male sterilization (vasectomy)
· Natural family planning
· Progestogen-only pill
One in five said they felt awkward discussing contraception with friends, and 26% never discussed contraception with their partner.
Hilary Pannack, chief executive of the sex education charity Straight Talking, agreed young people needed to be more comfortable with talking about contraception.
But she added: "Young people also need a reason not to get pregnant and by employing teenage parents to deliver a program in schools to enable young people to understand the realities of early pregnancy and parenting, Straight Talking is providing a vital element of the prevention service which is largely being ignored.
"Normalizing information about contraception, in particular information about condoms being the best protection from STIs, is important.
"However, there does need to be a relationship context for this information.
"We need to discuss self respect and communication as well as the 15 different types of contraception."
New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Scientists know that an HIV-neutralizing antibody called b12 binds to gp120, an HIV surface protein, at one of the few areas of the virus that does not mutate: the site where gp120 initially attaches to human immune cells. It was thought that exposing the human immune system to this site on gp120 would generate antibodies that, like b12, can neutralize HIV. Studies have found that for unknown reasons, however, the vast majority of antibodies that recognize this site do not block the virus from infecting cells. Now a new study solves this puzzle, suggesting that antibodies must home in precisely on the site of initial gp120 attachment to successfully neutralize HIV.
The gp120 protein usually appears on the surface of HIV and on infected cells in inactive forms of viral debris or non-functional viral spikes. Only rarely do gp120 molecules appear on the surface of the virus in a functional viral spike, which contains a cluster of three gp120 molecules, known as a trimer, in specific alignment. HIV uses this functional viral spike to bind to immune cells and infect them.
The new study shows that most antibodies able to bind to non-functional forms of gp120 cannot bind to gp120 in the functional viral spike and therefore cannot neutralize HIV. Further, the study demonstrates that the reason most anti-gp120 antibodies similar to b12 cannot bind to the functional viral spike is because of the way these antibodies attach to gp120. A close examination of two such antibodies illustrated that their binding positions on gp120 cause a key portion of the protein either to swing in or flare out in positions incompatible with the trimer structure. In contrast, the position of b12 antibody binding allows gp120 to neatly form its normal trimeric structure.
The scientists conclude that generating HIV neutralizing antibodies will require teaching the immune system to make antibodies that precisely target the site of vulnerability on gp120 as it appears in the functional viral spike rather than targeting the plentiful forms of viral debris such as single gp120 molecules.
Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.
Lei Chen et al
Science, 2009; Vol. 326. no. 5956, pp. 1123 – 1127 DOI: 10.1126/science.1175868
Link to Science abstract
Much has been learned about HIV-1. However, basic aspects of person-to-person transmission and of the progressive intercellular infection that depletes the immune system of its vital T cells remain imperfectly understood.
In a paper published November 6 in the online journal PloS Pathogens, Professor Don Lamb's group at the Ludwig-Maximilians-Universitaet (LMU) in Munichs's Department of Chemistry and Biochemistry, together with colleagues in Heidelberg, describe in detail how new virus particles assemble at the membrane of infected cells, and are released to attack healthy cells nearby. The new findings could help provide clues as how to interrupt the process of intercellular viral spread.
As many of us have learned from personal experience, computer viruses, which contain short pieces of malicious code and arrive in anonymous packages, can gum up data-processing routines. This definition also fits their biological counterparts, which generally comprise compact genomes packed in protein shells, and enter cells via specific portals. For example, the retrovirus HIV-1 has only nine genes in its RNA genome and infects cells by binding to specific receptors. Inside the cell, the genetic material is copied and 15 viral proteins are synthesized. They interact to pack the genomic RNA into new viral particles. These are then extruded from the cell, wrapped in an envelope of membrane bearing viral proteins that direct the parcel to the next susceptible cell.
The basket that encases the viral RNA is constructed from the Gag protein. Gag is highly versatile: It can bind to the inner face of the cell membrane, to the viral RNA, to itself (to form the shell around the RNA) and to cellular proteins that extrude the newly assembled particle into the extracellular medium. Indeed, Gag can form virus-like particles in the absence of other viral proteins. For their experiments, Professor Lamb's team used cultured cells containing eight of the HIV-1 genes, one of which coded for a fluorescent form of Gag.
"We adopted our custom-built microscope specifically for the experiment, visualizing Gag in the cellular plasma membrane by Total Internal Reflection Fluorescence Microscopy while alternately switching to Wide-Field Fluorescence Microscopy to get a deeper view into the cell," explains Lamb. This allowed the team to track single Gag particles and follow the assembly process, in real time.
Once virus assembly is switched on within an infected cell, the membrane surface of the cell becomes covered with viruses in one to two hours. Each virus is assembled individually at the plasma membrane on the time scale of minutes, rejecting the idea of a reusable assembly platform that is believed to exist for other viruses. By tracking individual viruses, the scientist could follow the processes of assembly from initiation of assembly through to release, learning that it takes about 25 minutes to produce an HIV virus. Hence, a lag of 15-20 minutes precedes release of the enveloped virus, presumably because it takes time for the hijacked cellular budding machinery to close off the virus and release it into to the extracellular medium.
"Using a 'photoconvertible' version of the famous green fluorescent protein -- whose discovery and utilization in biological systems were honored with the Nobel prize in chemistry in 2008 -- attached to the Gag protein, we were able to convert the color of membrane bound Gag proteins from green to red," says Lamb. "Thereby, we could determine that viruses were assembly from protein delivered directly from the cytosol or had only arrived recently to the plasma membrane." The new findings add an important dynamic dimension to the process of intercellular viral spread. If they help find ways to interrupt it, HIV-1 could finally be stamped as "undeliverable."
Dynamics of HIV-1 Assembly and Release.
Sergey Ivanchenko, William J. Godinez, Marko Lampe, Hans-Georg Kräusslich, Roland Eils, Karl Rohr, Christoph Bräuchle, Barbara Müller, Don C. Lamb
PLoS Pathogens, 2009; 5 (11): e1000652 DOI: 10.1371/journal.ppat.1000652
Link to PLoS Path article
The World Health Organization is changing its advice on HIV drugs, asking that they be given sooner and to breastfeeding mothers with the virus.
Experts say the advice is based on the most up-to-date information available and will cut infection rates and save lives. But it will mean many more people needing treatment, which will cost more money and time.
The World Health Organization (WHO) wants adults and adolescents to receive anti-retroviral therapy (ART) before their immune system strength falls below 350 cells per cubic millimeter of blood, regardless of whether they show symptoms.
It also wants the drug Stavudine, widely used in developing countries because of its low cost and widespread availability, to be phased out in favor of Zidovudine or Tenofovir, which do not have the same long-term and irreversible side effects.
And for the first time, the WHO is calling for breastfeeding mothers, or their babies, to be given the drugs to prevent transmission of the disease.
Falling prices and increased testing have led to a marked rise in the number of people in the poorest parts of the world receiving treatment for HIV.
The number of people on anti-retrovirals had risen by a million by the end of 2008, a 36% increase from the previous year, the WHO said.
But despite the progress, less than half of those needing treatment, currently receive it.
The WHO estimates that since the availability of effective HIV drugs in 1996, some 2.9 million lives have been saved.
Rapid advice: antiretroviral therapy for HIV infection in adults and adolescents.
World Health Organization. November 30, 2009.
Link to WHO report [pdf]
Keith Alcorn covers the report in more depth for Aidsmap (November 30, 2009)
WHO recommends earlier treatment and phase-out of d4T
Sunday, November 29, 2009
By playing the video game Rock Band for an hour, Kansas State University students were able to help a pair of psychology professors with their research to understand how people can achieve flow while at work or while performing skilled tasks.
Clive Fullagar, a professor, and Patrick Knight, an associate professor, found that -- like Goldilocks -- most people achieve flow with work that is neither too easy nor too hard but just right.
"For those students who have a moderate level of skill at Rock Band, the song has to be moderately challenging and match his or her skill level for optimal enjoyment to occur," Fullagar said. "That has broad implications for teaching. It means that if we want students to enjoy or get a lot of satisfaction out of classes, we need to assign them challenging tasks but make sure that they have the skills necessary to meet the challenges of those tasks."
In a psychology lab in K-State's Bluemont Hall, students played guitar in the game. In an adjacent room, the researchers watched a monitor with the same screen shot that the subjects saw. The researchers could control what songs students played and how much of the feedback they saw.
This isn't the first time that a video game has been used to study flow. Others have used Tetris, but Fullagar and Knight said that the nature of the game wouldn't have allowed them adequate control for this study. To make Tetris meet a player's ability level, researchers slowed down the rate at which the blocks fell onto the screen. This also limited performance because players couldn't finish as many lines.
"With Rock Band, it's the same speed and the same notes no matter what your ability level is," Knight said. "We can control that and look at differences in performance in a more objective way."
Flow is a state of mind that occurs when people become totally immersed in what they are doing and lose all sense of time. It's an intrinsically motivating state, which means that people are engaged in the task for the pure enjoyment of performing the task and not for some extrinsic reward.
In another study that tracked architecture students over the course of a semester, Fullagar found that achieving flow was likely to result in a good mood and have a positive impact on psychological health. The findings appeared in September in the Journal of Occupational and Organizational Psychology.
Research has shown that the types of work that lead people to achieve flow have some common traits, including being goal directed, providing feedback and giving a sense of meaning to the worker. Moreover, flow occurs only when the person feels in control of the process.
The researchers also have studied flow with architecture and music students but said that tasks that result in flow don't have to be creative or skill-intensive in an artistic sense. Knight said some graduate students describe achieving flow when analyzing their data. Fullagar had an accounting major in one of his classes describe achieving flow by filling out income tax returns.
"In speaking to her it made so much sense," Fullagar said. "She has this skill that can help somebody by having a meaningful impact on their financial situation. And every single income tax return presents a unique challenge. This shows that people find flow in very different areas."
In the future, Fullagar and Knight would like to study whether there's a group effect to flow.
"With Rock Band you can test several subjects at once as they play in a band," Fullagar said. "What happens when one member is in flow? Is there a contagion and do other people get in flow, or does it make them feel inferior?"
Knight said, "Another way we might look at that is what happens when one of the band members bombs out."
The researchers said other potential areas of study include the effect of having subjects help set their own goals and whether people in flow actually perform better or just perceive that they do.
Flow at work: An experience sampling approach
Fullagar, Clive J.; Kelloway, E. Kevin
Journal of Occupational and Organizational Psychology, Volume 82, Number 3, September 2009 , pp. 595-615(21)
Link to JOOP abstract
Food waste contributes to excess consumption of freshwater and fossil fuels which, along with methane and carbon dioxide emissions from decomposing food, impacts global climate change. In a new PLoS One paper, Kevin Hall and colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases calculate the energy content of nationwide food waste from the difference between the US food supply and the food eaten by the population. The latter was estimated using a validated mathematical model of human metabolism relating body weight to the amount of food eaten.
The researchers found that US per capita food waste has progressively increased by about 50% since 1974 reaching more than 1400 Calories per person per day or 150 trillion Calories per year. Previous calculations are likely to have underestimated food waste by as much as 25% in recent years.
This calculated progressive increase of food waste suggests that the US obesity epidemic may have been the result of a "push effect" of increased food availability and marketing with Americans being unable to match their food intake with the increased supply of cheap, readily available food.
Hall and colleagues suggest that addressing the oversupply of food energy in the US could help curb to the obesity epidemic as well as reduce food waste, which would have profound consequences for the environment and natural resources. For example, food waste is now estimated to account for more than one quarter of the total freshwater consumption and more than 300 million barrels of oil per year representing about 4% of the total US oil consumption.
The Progressive Increase of Food Waste in America and Its Environmental Impact.
Kevin D. Hal, Juen Guo, Michael Dore, Carson C. Chow
PLoS ONE, 2009; 4 (11): e7940 DOI: 10.1371/journal.pone.0007940
Link to PLoS ONE article
Saturday, November 28, 2009
The smoking ban in Wales has not displaced secondhand smoke from public places into the home. A study of 3500 children from 75 primary schools in Wales, published in the open access journal BMC Public Health, found that they were exposed to similar amounts of secondhand smoke before and after legislation, which should reassure those worried that exposure to smoking at home could increase following the ban.
Dr Jo Holliday and colleagues at Cardiff University's School of Social Sciences carried out the study, funded by the Welsh Assembly Government. They measured the levels of cotinine, a marker of exposure to cigarette smoke, in the saliva of approximately 1750 year 6 children before and after the ban, as well as asking the children about their experiences of passive smoking.
Holliday said, "Concerns have been expressed regarding the potential displacement of smoking from public places into the home, affecting non-smokers and, in particular, children. We found that the smoke-free legislation in Wales did not increase second-hand smoke exposure in homes of children aged 10-11. Nevertheless, the home did remain the main source of children's exposure".
The researchers point out that the measured levels of passive smoking still represent a public health concern. According to Holliday, "Almost 40 percent of children had a cotinine concentration above 0.17ng/ml, a level associated with lung dysfunction, and almost six percent of children had salivary cotinine concentrations higher than those of non-smoking Scottish bar workers prior to the introduction of similar legislation in Scotland".
Changes in child exposure to secondhand smoke after implementation of smoke-free legislation in Wales: a repeated cross-sectional study.
Jo C Holliday, Graham F Moore and Laurence AR Moore.
BMC Public Health, 2009 9:430doi:10.1186/1471-2458-9-430
Link to BMC abstract
Scientists have revealed how environmental irritants such as air pollution and cigarette smoke cause people to cough, in research published in the American Journal of Respiratory and Critical Care Medicine. The authors of the study, from Imperial College London and the University of Hull, have identified the reaction inside the lungs that can trigger coughing when a person is exposed to particular irritants in the air. They suggest that their findings may ultimately lead to the development of new treatments for chronic coughing.
Coughing is the most common reason for people visiting a family doctor. Treatment options are limited for people with chronic coughing; a recent study concluded that over-the-counter remedies are ineffective and there is increasing concern about the safety of these therapies in children.
This new study indicates, for the first time, how coughing can be triggered when a person is exposed to certain irritants in the air. It shows that the irritants can switch on receptor proteins called TRPA1 on the surface of nerve endings in the lungs. This switches on sensory nerves, which then trigger a cough reflex. The researchers say coughing could potentially be treated by blocking TRPA1 receptors, to stop irritants in the air from setting off this chain reaction. They hope that this could ultimately help millions of people whose lives are affected by chronic coughing.
Professor Maria Belvisi, corresponding author of the study from the National Heart and Lung Institute at Imperial College London, said: "For some people, chronic coughing can be annoying and uncomfortable, but for others it can be distressing and can have a severe impact on their quality of life. Many people say that certain things in the air can make them cough and we are very excited that we have shown, for the first time, exactly what is probably happening inside the lungs. Now that we think we have cracked the mechanism, we can start investigating whether we can stop people from coughing excessively by blocking the receptor protein that triggers it."
To reach their conclusions, the researchers first looked at sensory nerves from mice, guinea pigs and humans, and showed that the receptors on the sensory nerves were activated by a number of irritants, including a key compound in cigarette smoke (acrolein) and a chemical called cinnamaldehyde. The researchers then blocked the receptors and showed that these substances no longer activated the nerves.
To establish whether activating the receptor causes coughing, the researchers looked at the effect of acrolein on guinea pigs, as they have a coughing reflex. The researchers assessed the guinea pigs' coughing after inhaling acrolein. The compound caused coughing and the higher the concentration the more the guinea pigs coughed. The researchers then showed that blocking the receptor using a drug significantly reduced the guinea pigs' coughing response to the compound.
Finally, researchers led by Professor Alyn Morice at the University of Hull looked at the effect of inhaling the chemical cinnamaldehyde in humans. Ten healthy, non-smoking volunteers inhaled the chemical, as well as control substances. The researchers measured their cough response on five occasions, 2-3 days apart. All of the volunteers coughed after inhaling the compound.
TRPA1 Agonists Evoke Coughing in Guinea Pig and Human Volunteers
Mark A. Birrell, Maria G. Belvisi, Megan Grace, Laura Sadofsky, Shoaib Faruqi, David J. Hele, Sarah A. Maher, Véronique Freund-Michel, and Alyn H. Morice
American Journal of Respiratory and Critical Care Medicine 2009; 180: 1042-1047. doi: 10.1164/rccm.200905-0665OC
Link to AJRCCM abstract
Dr. Carme Espinet and colleagues at the University of Lleida, Lleida, Spain have discovered that a precursor to nerve growth factor (pro-NGF) may play a pathogenic role in Alzheimer's disease. They present these findings in the December 2009 issue of The American Journal of Pathology.
Alzheimer's disease is a degenerative, terminal form of dementia that affects over 35 million people world-wide. Oxidative stress, which occurs in the early stages of Alzheimer's disease, may modify molecules, resulting in loss or alteration of their function.
A precursor to nerve growth factor (pro-NGF) is expressed at high levels in Alzheimer's disease-affected individuals, and accumulation of pro-NGF may lead to neural cell death. The study showed that pro-NGF is modified in an Alzheimer's disease stage-dependent manner by oxidative stress and that modified pro-NGF blocked processing to mature NGF and led to neuronal cell death. Furthermore, injection of modified pro-NGF or pro-NGF derived from human Alzheimer's disease patients into mice resulted in cognitive and learning impairment, suggesting that modified pro-NGF may provide a novel pathogenic pathway for Alzheimer's disease.
Dr. Espinet's group suggests "that intra-cerebroventricular administration of AGE/ALEs modified pro-NGF to mice impairs learning tasks, thus reinforcing the idea that pro-NGF could have a relevant role in the ethiopathogenesis of the disease."
Cell Death and Learning Impairment in Mice Caused by in Vitro Modified Pro-NGF Can Be Related to Its Increased Oxidative Modifications in Alzheimer Disease.
Anton Kichev, Ekaterina V. Ilieva, Gerard Piñol-Ripoll, Petar Podlesniy, Isidro Ferrer, Manuel Portero-Otín, Reinald Pamplona, and Carme Espinet
American Journal Of Pathology, 2009; DOI: 10.2353/ajpath.2009.090018
Link to AJP abstract
Science Daily (Nov. 27, 2009)
— A new study from researchers at the University of Cincinnati (UC) and the Cincinnati Department of Veterans Affairs Medical Center reaffirms that some patients with HIV experience an improved quality of life following their diagnosis.
These findings are being published in the November issue of the journal AIDS Patient Care and STDs.
Joel Tsevat, MD, principal investigator of the study, and a team of researchers conducted two sets of interviews and completed chart reviews of 347 HIV outpatients from three U.S. cities in 2002-2004.
"Approximately 1.1 million Americans are infected with HIV," says Tsevat, a physician and researcher in the department of internal medicine. "Substantial increases in life expectancy for people with HIV have sharpened the focus on their quality of life. Although many studies have examined quality of life in patients with HIV, little information is available comparing quality of life with HIV versus quality of life before being diagnosed."
Researchers looked at demographic and clinical characteristics of patients, HIV-specific health status, symptoms, health concerns, spirituality/religion, social support, self-perception and levels of optimism.
"In two interviews, conducted a year to 18 months apart, patients compared their current life with life before being diagnosed with HIV," he says. "We found that many patients said their life is better than it was before their diagnosis, although results of such comparisons often change over time."
Results after the first interview showed that 109 patients (31 percent) said their lives were better after diagnosis, 98 (28 percent) said they were worse, and the remainder -- 140 patients -- said their lives were about the same or that they were undecided.
After the second interview, approximately one-fifth of patients changed their answers to indicate life improvement after diagnosis; one-sixth changed answers to reflect a feeling of life deterioration.
"Change in perception for the better was positively associated with religious coping, whereas change in perception for the worse was associated with factors such as the study site, sexual orientation, shorter duration of HIV, lower levels of spirituality and lower positive religious coping scores," Tsevat says. "The two main factors associated with the feeling that life has improved, relative to pre-diagnosis, were optimism and spirituality."
But he continues that additional studies are needed to look further into these factors and how they relate to HIV and other chronic illnesses.
"To see that patients not only cope and adapt to such a serious illness but can actually reach a point where they believe that life is better than before being diagnosed with HIV offers hope for numerous people infected with a virus that once meant only suffering and death," he says. "Future work should explore whether interventions can improve quality of life among those with a less favorable view of life with HIV."
Change in Quality of Life after Being Diagnosed with HIV: A Multicenter Longitudinal Study
Joel Tsevat, Anthony C. Leonard, Magdalena Szaflarski, Susan N. Sherman, Sian Cotton, Joseph M. Mrus, Judith Feinberg
AIDS Patient Care and STDs. November 2009, 23(11): 931-937. doi:10.1089/apc.2009.0026
Link to AIDS Patient Care and STDs abstract
Friday, November 27, 2009
A third of new HIV diagnoses in the UK in 2008 were made so late that the individuals had a significant risk of developing an AIDS-defining illness, new figures from the Health Protection Agency show.
Overall there were 7,298 new HIV diagnoses in the UK, a figure which is comparable to 2007. Gay men and Africans continue to be the focus of the UK’s HIV epidemic.
Concern is expressed by the HPA about the high proportion of patients who only have their HIV infection detected when their CD4 cell count is below 200 cells/mm3.
A total of 2,310 patients had a CD4 cell count below this level at the time of their diagnosis in 2008. Such a CD4 cell count indicates that these patients had been infected with HIV for a number of years and have sustained immune damage meaning that they are vulnerable to potentially life-threatening infections.
Late diagnosis of HIV is a problem across Europe. There were 525 HIV-related deaths in the UK last year, and the reason underlying many of these deaths will be late diagnosis of HIV.
Antiretroviral therapy means that most HIV-positive patients now have the chance to live a near normal lifespan. However, undiagnosed individuals are not able to take advantage of treatment than can mean a significantly longer and healthier life.
This point was made by Dr Valerie Delpech of the HPA: “HIV is a serious infection but if diagnosed early, there are very good treatment options. Of concern is that over 22,000 people remain unaware of their infection in the UK and cannot therefore benefit from effective treatment.”
There is increasing epidemiological data that the majority of new HIV transmissions involve individuals whose infection is undiagnosed.
Gay men remain a major focus of the HIV epidemic, accounting for 38% of new diagnoses. The 2,760 infections diagnosed amongst gay men in 2008 are due to continued HIV transmissions in this population and increased levels of testing.
However, 58% of new diagnoses were amongst heterosexuals. The majority of these 4,220 infections were acquired abroad.
Needle exchange programs have helped control the HIV epidemic amongst injecting drug users in the UK, but there were nevertheless 170 new diagnoses amongst this population in 2008.
Link to Aidsmap article
People in China living with HIV and AIDS face widespread discrimination and stigma, with even medical workers sometimes refusing to touch them, according to a U.N. survey released on Friday.
China's Health Ministry and UNAIDS estimate that the country has between 97,000 and 112,000 people infected with AIDS.
But more than 40 percent of people surveyed in a new UNAIDS report said they had been discriminated against because of their HIV status. More than one-tenth said they had been refused medical care at least once.
Chinese AIDS activist Yu Xuan, talking at a news conference to unveil the report, recounted the story of a friend who was refused an urgent operation because of her HIV status, and who ended up dying as a result.
"I don't want people to have the kind of experiences I have had," said Yu, who also has AIDS.
China has long faced a problem in tackling a disease which officials once refused to acknowledge, and where for many people taboos surrounding sex remain strong, limiting public or even private discussion.
Deputy Chinese Health Minister Huang Jeifu said the government would work harder to address issues related to AIDS stigma and ignorance, but admitted it would be difficult.
"The biggest obstacle is that there is not enough education or publicity about AIDS. Society does not know enough about the disease, and people think you can get it just from touch, talking, shaking hands or eating together," Huang said. "This is a huge problem."
The government will launch a video campaign to break the stigma of AIDS featuring Chinese and NBA basketball star Yao Ming which will be shown on 20 large outdoor screens in 12 cities, but will likely have their work cut out.
The survey found that some children with infected parents but who were not necessarily infected themselves had been forced to leave school.
"Many of the respondents knew who they could go to for support in addressing discrimination and taking action against those that violate their rights," the report said.
"Unfortunately, the success rate when addressing problems encountered is very low."
Commonwealth states must repeal discriminatory, anti-gay laws
As the Commonwealth heads of government gather in Trinidad and Tobago for their biennial meeting today, civil society groups have called on member states to repeal discriminatory legislation left behind from the colonial era. In particular they call for laws criminalizing sex between men to be repealed.
The Port of Spain Civil Society Statement, agreed on Wednesday, called on Commonwealth countries to “work to actively remove and prevent the establishment of legislation which undermines evidence-based effective HIV prevention, treatment and care available to marginalized and vulnerable groups, such as sexual minorities, sex workers and drug users”. Moreover, the civil society groups called on member states to “legislate anti-discrimination acts in support of people with HIV by 2011”.
Only six of 53 Commonwealth nations have repealed laws criminalizing gay men and other sexual minorities. Moreover the Ugandan parliament is considering an Anti-Homosexuality Bill which would impose the death penalty on HIV-positive gay men who continue to have sex as well as criminalizing homosexual conduct and any public acknowledgement of the existence of homosexuality.
Stephen Lewis, the former UN Special Envoy on HIV/AIDS in Africa said that “if the Commonwealth does not address this issue of the Uganda law and the accelerating homophobic legislation in the Caribbean, then the lofty principles of the Commonwealth lie in tatters”.
He stressed that criminalizing homosexuality discourages access to prevention and treatment services. However he noted that legislative change is possible: every single Latin American country has now removed anti-gay legislation, thereby facilitating HIV prevention. India's High Court struck down a statute dating from colonial times which criminalized sex between men in July 2009.
Writing in The Guardian, British human rights activist Peter Tatchell argues: "For two decades, successive Commonwealth leaders have shown a systematic, persistent failure to challenge homophobic discrimination and violence – no matter how extreme."
He also highlights the penalties attached to consenting sex between men in some Commonwealth countries. "Same-sex relations carry maximum penalties of life imprisonment in Uganda, Bangladesh, Guyana and Sierra Leone. It is 20 years plus flogging in Malaysia, and 14 years in Nigeria, Kenya, Malawi and Papua New Guinea. Twelve states in Nigeria have sharia law and the death penalty."
The majority of Commonwealth states are in Africa and Caribbean, the two regions with the highest HIV prevalence in the world.
The global number of swine flu deaths has jumped by more than 1,000 in a week, latest figures from the World Health Organization (WHO) show.
At least 7,826 people are now known to have died following infection with the H1N1 virus since it first emerged in Mexico in April.
Europe saw an 85% increase in the week, with the total number of deaths rising from at least 350 to at least 650.
However, in most cases the virus continues to produce mild symptoms.
An overwhelming majority of patients usually recover, even without medical treatment, within a week.
The biggest rise in deaths was recorded in the Americas, where the death toll rose to 5,360 - a rise of 554 cases in one week.
In this latest survey of swine flu developments, the WHO notes that many countries have stopped counting individual cases of swine flu, particularly of milder illness, and the case count is likely to be significantly lower than the actual number of cases that have occurred.
In people infected with human immunodeficiency virus (HIV), high-risk behavior, HIV infection itself, as well as late initiation and early discontinuation of anti-HIV therapy all contribute to substantial decreases in life expectancy, United States researchers report.
Using a comprehensive computer model of HIV disease, the researchers simulated cohorts of HIV-infected individuals and compared them with uninfected individuals who had similar demographic characteristics.
"We estimated that for people in the United States living without HIV, life expectancy beginning at age 33 is an additional 43 years," first author Dr. Elena Losina, of Massachusetts General Hospital, Boston, told Reuters Health.
"High risk behavior, such as substance abuse, on average, accounts for an 8 year reduction in life expectancy," Losina added.
HIV infection itself reduces life expectancy by an additional 12 years and a late start or premature discontinuation of HIV treatment further reduces life expectancy to a total of 23 years, she and colleagues report in the journal Clinical Infectious Diseases.
"The current therapy for HIV is very effective," Losina commented, "but unless HIV-infected patients initiate treatment on time and stay on treatment, the treatment benefits would be truncated substantially."
Minorities, especially minority women, tend to initiate therapy later and are more likely to drop off from care, and this "leads to disproportional losses in life expectancy in these population groups," she said.
"There is a critical need for people with HIV to begin care in a timely way and to remain in care," senior investigator Dr. Kenneth A. Freedberg, also from the Massachusetts General Hospital, said in a statement. "HIV testing for all adults in the United States, as currently recommended, with effective linkage to care, will have important survival benefits."
Racial and Sex Disparities in Life Expectancy Losses among HIV Infected Persons in the United States: Impact of Risk Behavior, Late Initiation, and Early Discontinuation of Antiretroviral Therapy
Elena Losina, Bruce R. Schackman, Sara N. Sadownik, Kelly A. Gebo, Rochelle P. Walensky, John J. Chiosi, Milton C. Weinstein, Perrin L. Hicks, Wendy H. Aaronson, Richard D. Moore, A. David Paltiel, and Kenneth A. Freedberg
Clinical Infectious Diseases, Volume 49, Issue 10, Page 1570–1578, Nov 2009 DOI: 10.1086/644772
Link to CID abstract
Thursday, November 26, 2009
Long-term HIV treatment has not caused a deterioration in kidney function among French patients, investigators report in the December 15th edition of Clinical Infectious Diseases. “Renal function is remarkably stable over seven years among combination antiretroviral therapy-treated patients”, they comment.
Although the investigators did find some evidence of deterioration in kidney function, they note that this was to be expected in an ageing population. They believe the long-term stability of kidney function in the majority of patients can be attributed to good control of HIV replication.
Treatment with the protease inhibitor indinavir (Crixivan) was also associated with deterioration in kidney function during the first 16 months of antiretroviral therapy. Although this drug is now rarely used, the investigators believe that this finding still has relevance and recommend “clinicians should closely monitor renal function in combination antiretroviral therapy-treated patients, especially those who have been exposed to indinavir.”
HIV-positive patients have an increased risk of kidney disease. HIV itself can be a cause, and for this reason timely initiation of antiretroviral therapy is recommended for patients with evidence of renal dysfunction, or a significant risk of this developing.
HIV treatment, however, especially the first-line drug tenofovir (Viread, also in the combination pills Truvada and Atripla) have also been associated with a deterioration in kidney function.
Long-term evolution and determinants of renal function in HIV-infected patients who began receiving combination antiretroviral therapy in 1997-99, ANRS CO8 APROCO-COPILOTE.
Catherine Leport, Vincent Bouteloup, Jérôme Rossert, Michel Garré, Laura Iordache, Pierre Dellamonica, Serge Herson, François Raffi, and Geneviève Chêne; for the ANRS CO8 COPILOTE study group
Clinical Infectious Diseases 49: 1950-54, 2009 DOI: 10.1086/648445
Link to CID abstract
Wednesday, November 25, 2009
Researchers from the University of Michigan determined that only 663,000 of the approximately 3.9 million Americans with hepatitis C virus (HCV) infection received antiviral therapy between 2002 and 2007. Treatment rates appear to be declining, in part because only half of the patients know they are infected. If this disturbing trend continues, by 2030 less than 15% of liver-related deaths from HCV will be prevented by antiviral therapy.
This study, the first to analyze nationwide practice patterns for HCV treatment, is published in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.
HCV is a common blood-borne infection that slowly damages the liver by causing inflammation of liver tissue, which can lead to cirrhosis, chronic liver disease, and liver cancer. In the U.S., HCV is a major public health burden and the leading cause of liver transplantation. According to the Centers for Disease Control and Prevention (CDC) 8,000-12,000 deaths occur each year due to HCV. While the incidence of new infections has declined, past studies point to a twofold to fourfold increase in death over the next 20 years due to widespread cases with longstanding infection.
Michael Volk, M.D., M.Sc., and colleagues obtained data of new patient prescriptions for pegylated interferon alpha-2a and -2b, sold under the brand names Pegasys and Peg Intron, respectively, and filled between 2002- 2007. Results of the prescription audit showed there were 126,000 new prescriptions for pegylated interferon products in 2002 and by 2007 that figured declined to 83,000 prescriptions. Researchers project fewer than 1.4 million patients would be treated cumulatively with antiviral medication by 2030 if the downward trend continued.
To further understand the decrease in antiviral therapy, researchers investigated treatment decisions using data from the National Health and Nutrition Evaluation Survey (NHANES) Hepatitis C Follow-Up Questionnaire. They discovered that 49% of respondents were previously unaware of their diagnosis and 24% of patients with HCV were not recommended for treatment by their physician. Approximately 9% of those surveyed did not follow up with their doctors regarding their HCV, 8% refused treatment, and only 12% received treatment. "It is concerning that half of all people with hepatitis C in the U.S. are unaware of their diagnosis," said Dr. Volk. "Even with the development of new and better medications on the horizon, such medications will have less than optimal impact unless more patients are diagnosed and referred for treatment."
The study further suggested that barriers to HCV screening may be attributed to lack of health insurance, limited access to standard medical care, and lower priority for testing by primary care doctors. "This is unfortunate," added Dr. Volk, "since young patients who don't go to the doctor often may be the best candidates for antiviral therapy." The authors conclude that increased public health efforts are needed to improve access to antiviral therapy, and recommend further research of health services delivery and quality of care for HCV patients.
Public health impact of antiviral therapy for hepatitis C in the United States
Michael L. Volk, Rachel Tocco, Sameer Saini, Anna S. F. Lok.
Hepatology, 2009; 50 (6): 1750 DOI: 10.1002/hep.23220
Link to Hepatology abstract
Scientists in China are reporting discovery of unusual liver proteins, found only in males, that may help explain the long-standing mystery of why the hepatitis B virus (HBV) sexually discriminates -- hitting men harder than women.
Shuhan Sun, Fang Wang and colleagues note that chronic hepatitis B seems to progress and cause liver damage faster in men, with men the main victims of the virus's most serious complications -- cirrhosis and liver cancer. Men infected with HBV also are 6 times more likely than women to develop a chronic form of the disease. About 400 million people worldwide have chronic hepatitis B, including a form that is highly infectious and can be transmitted through blood, saliva, and sexual contact.
In experiments with laboratory mice, the scientists found abnormal forms of apolipoprotein A-I (Apo A-I), a protein involved in fighting inflammation, in the livers of infected male mice but not infected females. They then identified abnormal forms of these Apo A-I proteins in blood of men infected with HBV, but not in women. In addition to explaining the gender differences, the proteins may provide important markers for tracking the progression of hepatitis B, the scientists suggest.
An Altered Pattern of Liver Apolipoprotein A-I Isoforms Is Implicated in Male Chronic Hepatitis B Progression.
Fu Yang, Yixuan Yin, Fang Wang, Ling Zhang, Yuqi Wang and Shuhan Sun
Journal of Proteome Research, 2009; 091008145148093 DOI: 10.1021/pr900593r
Link to JPR abstract
An innovative treatment for HIV patients developed by McGill University Health Centre researchers has passed its first clinical trial with flying colors. The new approach is an immunotherapy customized for each individual patient, and was developed by Dr. J-P. Routy from the Research Institute of the MUHC in collaboration with Dr. R. Sékaly from the Université de Montréal. "This is a vaccine made for the individual patient -- an "haute couture" therapy, instead of an off-the-rack treatment" said Dr Routy.
By "priming" the immune system, as with a vaccine, to fight the specific strain of HIV/AIDS infecting a given patient, the scientists believe they have developed a therapy that shows immense promise and could be an even more effective weapon against the virus than the anti-retroviral cocktails currently in use. The results of the first-stage clinical trials, which tested the therapy in conjunction with anti-retroviral drugs, were published in Clinical Immunology. Phase 2 of the clinical trial, which is nearly complete, is testing the therapy's efficacy on its own at 8 different sites in Canada.
The new therapy uses dendritic cells which are removed from each HIV-infected patient and subsequently multiplied in-vitro. Dendritic cells present material from invading viruses on their surface, allowing the rest of the immune system to identify and attack the invaders. "They are the "grand conductors" of the immune response," explains Dr Routy. "With them, you push the immune system, in all its functions, at the same time." In the current trial, dendritic cells were exposed to a sample of HIV RNA (ribonucleic acid) specific to the patient involved. This exposure encouraged the cells to develop defenses specific to that viral strain. The modified cells -- called AGS-004 -- were then injected back into the patients.
Not only were there few reported side-effects from the AGS-004, but the researchers also measured increased levels of CD8-lymphocytes in the patients -- the "attack" cells of the human immune system that the treatment is intended to mobilize, thus confirming that the intervention was targeted and controlled.
By boosting the immune system in this way, Routy hopes to develop an HIV/AIDS treatment that will require fewer injections and less long-term toxicity for patients than antiretrovirals.
Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy.
Jean-Pierre Routy et al
Clinical Immunology, 2009; DOI: 10.1016/j.clim.2009.09.009
Link to Clinical Immunology abstract
Tuesday, November 24, 2009
Children exposed prenatally to tobacco smoke and during childhood to lead face a particularly high risk for ADHD, according to research done at Cincinnati Children's Hospital Medical Center.
The study estimates that up to 35 percent of ADHD cases in children between the ages of 8 and 15 could be reduced by eliminating both of these environmental exposures. This could translate into up to 800,000 children
"Tobacco and lead exposure each have their own important adverse effect," says Tanya Froehlich, M.D., a physician in the Division of Developmental and Behavioral Pediatrics at Cincinnati Children's and the study's lead author. "But if children are exposed to both lead and prenatal tobacco, the combined effect is synergistic."
"Although we tend to focus on ADHD treatment rather than prevention, our study suggests that reducing exposures to environmental toxicants might be an important way to lower rates of ADHD," says Robert Kahn, MD, MPH., a physician and researcher at Cincinnati Children's and the study's senior author.
The researchers found that children exposed prenatally to tobacco smoke were 2.4 times more likely to have ADHD. Those with blood lead levels in the top third had a 2.3 fold increased likelihood of ADHD, despite levels well below the Centers for Disease Control action level of 10 micrograms per deciliter. Dr. Froehlich and her colleagues found the risk of ADHD more than eight times higher for children exposed to both tobacco and lead compared to unexposed children.
Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder
Tanya E. Froehlich, Bruce P. Lanphear, Peggy Auinger, Richard Hornung, Jeffery N. Epstein, Joe Braun, and Robert S. Kahn
Pediatrics, Nov 2009; doi:10.1542/peds.2009-0738
Link to Pediatrics abstract
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