Coronavirus particles with their characteristic spiky halos.
Virus R Us
Initially, the recent death of a Saudi Arabian man from an unidentified viral infection renewed fears of another SARS panic, which swept around the world in 2003, infecting more than 8,000 people and killing almost 1,000.
It turns out, however, that while the mysterious virus superficially resembled SARS, it was in fact more closely related to coronaviruses that infect Southeast Asia bats. Coronaviruses get their name from their characteristic halo of projecting membrane proteins.
The identification, reported by Dutch virologists who managed to sequence the entire viral genome of 30,118 letters in less than a month, is reassuring in some ways: The virus doesn’t appear to be particularly virulent and hasn’t yet acquired the ability to jump from human to human. Researchers suspect the Saudi Arabian man was infected via an “amplifier” animal, such as a civet cat. When a virus jumps species, it typically doesn’t travel directly from originating host to humans. Amplifier animals get their name because they serve as intermediary steps, providing a place for viruses to replicate and increase in numbers, boosting their infectiousness.
On the other hand, the new viral threat is one of several recent reminders that the world is full of ever-changing potential microbial dangers. In Missouri, for example, researchers recently identified a new “Heartland virus.” In Central Africa, a new form of hemorrhagic fever has been discovered.
In the latter case, the term “new” is relative. The virus was only recently reported in PloS Pathogens, but the three cases described are three years old. (Tissues samples from the patients – two of whom died – had languished in a freezer in Kinshasa, Zaire until a smart doctor realized what they were.)
Hepatitis C: expert urges testing
Hepatitis is an inflammatory disease of the liver and a major, if unrecognized, health crisis in the United States. The disease has multiple forms, identified by their alphabetized viruses. The most problematic form is hepatitis C or HCV.
An estimated 3.2 million Americans – mostly Baby Boomers born between the years 1945 and 1962 – are infected with HCV. Though the disease can be cured, most persons with HCV don’t even know they’re infected. Its symptoms typically do not become obvious until the disease is well-advanced. More than 15,000 Americans die from HCV each year.
Recently, the U.S. Centers for Disease Control urged all Baby Boomers to be tested for HCV. The CDC estimates the one-time testing could identify more than 800,000 additional persons with the virus, and perhaps ultimately save more than 120,000 lives.
We asked Alexander Kuo, MD, medical director of the Liver Transplant Program at the UC San Diego Liver Center and a leading researcher in on-going HCV clinical trials, about the CDC’s recommendation, why HCV is more problematic than other forms of hepatitis and the prospects of new treatments.
Question: Do you agree with the CDC’s recommendation that all Baby Boomers be tested for hepatitis C? Why is that particular age-demographic targeted?
Answer: I do. The old recommendation was to only test people who had documented risk factors for hepatitis C such as blood transfusions before 1992, a history of intravenous drug use or tattoos. Unfortunately, healthcare providers are not very good at asking these questions of their patients, perhaps out of embarrassment or being uncomfortable with these subjects or due to a lack of time. Also, patients themselves often do not remember what they did 30 years ago so their histories can be less than reliable.
Since the majority of patients infected with hepatitis C in this country were born between 1945 and 1965, it makes sense to simply screen everyone in this age group. The prevalence of infection in this group in high enough to make this strategy cost-effective.
Q: Why is hepatitis C more problematic than A or B infections?
A: Hepatitis A is usually a self-limited viral infection that makes people ill for 1-2 weeks, then resolves with no long-term effects. It is usually spread through contact with contaminated food, the so-called fecal-oral route of transmission. After a resolved infection, people usually develop immunity against re-exposure. There is also an effective vaccine against hepatitis A.
Hepatitis B and C are different in that exposure can lead to long-term chronic infection. Chronic infection with hepatitis B or C can lead to inflammation of the liver and ultimately cirrhosis, liver cancer or death. Most people infected with chronic hepatitis B or C have no symptoms until the damage to the liver is very advanced. That’s why hepatitis C is often called the “silent epidemic.”
Q: There are vaccines for A and B, but not C. Why has C so far defied vaccine efforts?
A: Vaccines against hepatitis A and B are available and work by inducing the production of antibodies against these viruses by our immune system. These antibodies are protective because they bind to the virus and can prevent it from gaining a foothold in our bodies. Hepatitis C is a master at evading our immune system. It mutates rapidly and exists in our bodies as a “swarm” of closely related viruses, each with slightly different genetic make-ups. These factors make it very difficult to develop effective antibodies that can neutralize the virus. In addition, having antibodies against hepatitis C does not appear to be enough to prevent infection. Evidence suggests that you also need to stimulate a separate part of your immune system, the so-called cell-mediated immune response in order to prevent or clear the infection.
Q: How is C treated? How effective are current therapies?
A: One important thing to note about hepatitis C is that there is a cure. Hepatitis C exists in nature as six distinct strains, also known as genotypes. In the United States, Western Europe and Japan, genotype 1 is the most common followed by genotypes 2 and 3. Genotype 4 is most common in Egypt and the Middle East, genotype 5 is most common in southern Africa, and genotype 6 is most common in Southeast Asia, through there is significant geographic overlap.
For patients with the most common strain, the genotype 1 infection, the current standard of care is to treat with a combination of three medications for 24 to 48 weeks: pegylated interferon alfa, ribavirin and a protease inhibitor (telaprevir or boceprevir are the two new drugs that were approved by the FDA in May 2011). Pegylated interferon is a subcutaneous infection that stimulates your immune system to fight against viral infections. Patients are taught to self-administer the injections once per week with a tiny needle similar to the way diabetes self-administer insulin. Ribavirin is an oral medication that has various anti-viral actions in the body that patients generally need to take twice a day. The protease inhibitors are a new class of anti-hepatitis C drugs called Direct Antiviral Agents (DAAs). These medications are small molecules that directly bind and inhibit the action of various components of the hepatitis virus machinery that it uses to make copies of itself and survive. With these new drugs between 70-75% of patients with genotype 1 infection can be cured.
Patients with genotype 2 or 3 infection are currently treated with a combination of pegylated interferon alfa and ribavirin only yielding cure rates of up to 80% after 24 weeks of treatment.
Q: What’s happening in terms of new research?
A: We are currently in a very exciting time in hepatitis C research. There are an impressive number of new investigational agents in the drug development pipeline from multiple pharmaceutical companies. These agents are focusing on directly inhibiting the viral machinery by targeting various viral proteins necessary for survival. The most promising new agents target the hepatitis C viral protease NS3/4, the polymerase NS5B, and NS5a, which is necessary for viral assembly. The future of hepatitis C treatment is likely going to be a combination of well-tolerated, oral DAAs that no not include interferon. This will greatly increase the number of patients who would be eligible for treatment since many current patients with advanced liver disease, severe psychiatric illnesses, or autoimmune conditions are not eligible for interferon-based therapies.
Last week, the World Health Organization issued a global warning to travelers visiting Yosemite National Park, where three people have died recently after contracting the hantavirus and at least eight others have become sick.
First described roughly 20 years ago in the Four Corners region, the hantavirus is exceedingly rare (about 600 documented cases in the U.S.) but extremely deadly. Symptoms are fast-acting and virulent. There is no vaccine or cure. According to a Scientific American report, it kills more than one in three people who contract it.
Hantavirus is spread through contact with infected rodents, particularly wild deer mice, most often by inhaling dust contaminated with their droppings or urine. It is not transmitted human-to-human. In the United States, the result can be hantavirus pulmonary syndrome, a particularly deadly form of pneumonia. In Central and South America, the virus is also associated with hemorrhagic fever with renal syndrome. This form is very uncommon in the United States.
Though cases of hantavirus and infected rodents have popped up throughout the United States, the disease is most commonly associated with the high deserts of the U.S. Southwest. Its deadly appearance in Yosemite is alarming since very little is known about how hantavirus is spread.
One such effort to learn more is work done by University of Utah researchers in 2008 who released wild deer mice coated (above) with different colors of harmless fluorescent powder at 12 desert sites, then trapped dozens of mice the next day to determine how much exposure other mice had to colored mice. Their finding: Bigger, older mice were most likely to infect other deer mice with the hantavirus.
With no effective treatment or cure available, experts say the best remedy for hantavirus is to avoid contact with rodents as much as possible.
Prevention Still the Best Medicine: three questions for Davey Smith about HIV
From the Berlin Patient to the recent approval by the FDA of the drug Truvada for prevention of AIDS, the tide seems to be turning in the now 30-year long fight against HIV/AIDS. For many people living with HIV it is no longer a death sentence but a manageable disease. But the battle isn’t over yet. A recent paper in The Lancet reports that cases of drug-resistant HIV in sub-Saharan Africa are on the rise and in the U.S. there are approximately 50,000 new cases of the disease each year.
With the International AIDS Conference back in the U.S. for the first time in 22 years, we’d thought it was the perfect time to ask Davey Smith, MD, associate professor of medicine in the Division of Infectious Diseases at UC San Diego School of Medicine and recipient of the 2012 Avant-Garde Award for HIV/AIDS research from NIDA three questions about HIV.
Question: What are some of the most effective strategies in helping limit the spread of the HIV virus? Does sex education have an impact?
Answer: I think the most proven effective ways to currently prevent HIV are: condoms, needle exchange, male circumcision, know your HIV status, and receive effective HIV treatment if you are infected. I think sex education should include explanation on all of these issues. People who are informed on the real risks of HIV transmission can make better choices on how they want to reduce their risks.
Q: Needle exchange has proven effective in preventing the spread of HIV amongst drug users and yet these programs remain taboo. How do you tackle prevention in these high risks groups when effective programs like needle exchange are often not supported and in some communities are illegal?
A: This is one of those situations where a scientist must also be an activist. Research cannot just end when the paper is published. We sometimes must educate the public and those who make the laws about why programs like syringe exchange are needed.
Q: Are you optimistic that we’ll see a cure for HIV/AIDS in the next 5 years or does prevention remain our best hope?
A: I go to work every day with the hope and drive for two goals- a cure and a vaccine for HIV. I think I will see both of these things accomplished in my lifetime, but probably not in five years. In the mean time we must continue our prevention efforts.
Photo: HIV particles on a cell by Thomas Deerinck at the National Center for Microscopy and Imaging Research at UC San Diego
Swimming with salmonella
It’s summer and thus time for the National Resources Defense Council’s annual report on the state of the nation’s beaches. In other words, where you enjoy a nice, safe dip and where the scariest menaces in the water are not big, bad sharks.
Rather, they’re tiny, terrible, teeming pathogens like salmonella bacteria, pictured above invading a cultured human cell in this false-colored micrograph from the National Institute of Allergy and Infectious Diseases.
Salmonella are indicator bacteria, a microbe used to detect and estimate the level of fecal contamination in water. A gram of human feces contains approximately 100 billion bacteria, not to mention pathogenic viruses, protozoa and parasites. Exposure to salmonella (which can come as well from tainted food or certain animals) can cause a host of ailments, from gastrointestinal disorders to typhoid fever.
The NRDC’s report was not encouraging. It found that the number of days that beaches around the country were closed or under health advisories reached 23,481 last year, slightly better than the previous year but still the third-highest total in the report’s 22-year history.
In these scanning electron micrographs from Thomas Deerinck at the National Center for Microscopy and Imaging Research at UC San Diego, multitudinous HIV-1 particles exit from a cultured HeLa cell. The image is false-colored.
HIV prevention in a pill
Just three decades ago, a diagnosis of HIV/AIDS was akin to a death sentence. Infected persons often had just months to live. A lot has changed, particularly since the advent of antiretroviral drugs. Prescribed in the early stages of the infection, these drugs (usually taken in combination) often reduce HIV/AIDS to a chronic but livable condition. Patients can enjoy relatively normal, full lives for decades after diagnosis.
HIV/AIDS research may be on the cusp of the next, big advancement: Today, the California HIV/AIDS Research Program of the University of California announced three grants totaling more than $11 million to test a potential HIV prevention pill among high-risk HIV-uninfected persons in California. One of the teams is based at UC San Diego and headed by lead project investigator Richard Haubrich, MD, a professor in the UC San Diego School of Medicine and Antiviral Research Center.
Haubrich, with colleagues at UC San Diego and elsewhere, will enroll 400 study participants identified at high-risk of contracting an HIV/AIDS infection. (These are uninfected men who have sex with men or transgender women, all living in San Diego, Los Angeles and Long Beach). Each study participant will receive with a daily pill that combines two antiretroviral drugs (tenofovir and emtricitabine), manufactured and provided for the study by Gilead Sciences, Inc. The prevention pill is part of a larger intervention effort called “Pre-Exposure Prophylaxis with antiretroviral drugs” or PrEP. The researchers will also develop and study ways to help identify, engage and retain HIV-infected persons in interventional treatment programs.
“There is no question that biomedical HIV prevention strategies, such as PrEP in HIV-uninfected and initiation of early antiretroviral therapy in HIV-infected people, can prevent future HIV infection,” said Haubrich. “The key is to empower people to initiate and maintain strict adherence to therapy. Ultimately, we hope these efforts will result in a reduction of new HIV infections in high-risk populations and improved clinical outcome for those who are currently HIV-infected.”
The UC San Diego-based program received a $5.6 million grant and will run for four years. The other two, related efforts are based at UC Los Angeles and the East Bay AIDS Center in Oakland. You can read the full news release from the UC Office of the President here.
Photos from AMC’s The Walking Dead
Once Again, UC San Diego Health System Takes a Bite out of the Zombie Apocalypse
In May the CDC issued guidelines for The Zombie Apocalypse. We interviewed Jay Doucet, MD Associate Professor of Clinical Surgery & Director, Surgical Intensive Care Unit for UC San Diego Health System to assess our readiness for such an event. We know what people at home should do: “Get a kit. Make a plan.” But is our Health System ready to deal with this kind of disaster?
Dr. Doucet says yes, we are.
Question: How would we get information that a deadly disease is infecting people?
Answer: If a new infectious disease were to appear, reports from hospitals and physicians to County Public Health officers would be the first step in identifying whether there was an occurrence of disease greater than would otherwise be expected at a particular time and place – typically called an “outbreak.” Epidemiologists and Infectious Disease specialists in government and universities would look at clinical data, samples, time and geography, to determine the source of the infections. Typically these are either “common source” – where all victims acquire the infection from the same source, such as contaminated food or water – or is “propagated” — where transmission occurs from person to person.
In many of the movies about Zombies, although the origin of the infection is unclear, bites from affected individuals seem to spread the condition. Often there is portrayal of an asymptomatic period, and then disease obviously affects the brain, and is highly lethal, which resembles the real disease rabies in some ways. This would make clinicians and scientists suspect a viral cause, probably a blood borne virus.
While finding a cure for Zombieism would be a focus for national laboratories in agencies such as the CDC, the military and universities, the most important initial control measures would focus on preventing spread. This could include quarantine or isolation of infected individuals and protective measures for the population such as school or work closures. Since Zombies are usually violent and likely non-complaint patients, such measures may be involuntary, and there are laws which permit such measures to be enforced.
The severity of the outbreak may require the declaration of a state of emergency by responsible elected officials, which allows emergency resources to be deployed.
Information about the outbreak would come from several sources. Hospitals and Health Care providers receive alerts from County and State Public Health officials via electronic alerts about potential outbreaks. The public would be informed media briefings from public officials and by agencies such as County Public Health and the CDC. Websites such as http://ready.gov, http://www.bt.cdc.gov and http://www.sdcountyemergency.com are good sources of current information too.
Q: How will we deal with the walking well vs. the walking dead?
A: Hospitals are required by regulatory agencies such as the Joint Commission to have an “All-Hazards” disaster plan – a plan that can deal with any future known or unknown hazard. UC San Diego has three full-time staff dedicated to Emergency Preparedness and Responses.
One of the early priorities is control of access to the facility. Hospitals may be overwhelmed during disasters by worried-well persons, family members looking for loved ones, new volunteer providers, media and even public officials, all demanding access.
Control of access to the facility is an important component of emergency plans and exercises. Extra security will be seen at entrances and some entrances may be closed. Patients who are acutely ill or injured may be first seen outside the facility by providers in a “triage area” before entering the facility. Patients who are not ill or injured, but are simply worried about exposure to an infectious agent, such as Zombie saliva, may be observed in an area or building outside the hospital where infectious disease precautions may be used. Large numbers of worried well may be told to wait at home in voluntary quarantine and return if they suspect the onset of symptoms.
Non-compliant or violent individuals are actually part of All-Hazards plans and exercises. Since Zombies are popularly portrayed as a health threat and a security threat, both health organizations and law enforcement agencies would cooperate in protecting health facilities. Such cooperative schemes were actually practiced during recent “Golden Guardian” and “Golden Phoenix” exercises in California and at UC San Diego.
Q: What about barricades?
A: During exercises or events, patients and families may actually see barriers or checkpoints around their hospital. However, there will always be someone who will greet them at the facility. The first hospital personnel they meet may be accompanied by a security officer or law-enforcement officer, who may be armed. In a large scale event, the military may assist civil authorities in protecting key infrastructure, including hospitals. Patients seeking attention will still be seen, but hospital personnel may be wearing a mask and protective clothing until the visitors or patients can be asked about infectious exposures and symptoms.
Q: What general tips do you have for preparedness?
A: Emergency preparedness requires all of us to think and take action. Every person who is able should take action. The key things to do at home are to:
- Make a plan for events with your family.
- Prepare a disaster kit.
- Stay informed.
Workplaces and schools should have preparedness plans too.
Q: And finally, Dr. Doucet: are you ready for the Zombie apocalypse?
A: Absolutely! UC San Diego Health System is prepared!
A false-colored yellow neutrophil, one of several types of white blood cells that comprise the body’s immune system, engulfs anthrax bacteria (orange).
Scientists at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences have uncovered how the body’s immune system launches its survival response to the notorious and deadly bacterium anthrax. The findings, reported online today and published in the June 22 issue of the journal Immunity, describe key emergency signals the body sends out when challenged by a life-threatening infection. (More)