Sunday, December 11, 2011

HIV Vaccine potential-sketchy or promising?

Duke University is working on developing HIV vaccines. The idea behind the vaccine is that it owuld bind to hte GP-120 glycoportein on HIV's envelope.

The paper refers to a previous trial in which Thailand developed a vaccine that was "partially effective"

I think this article is interesting in that it mentions the specific receptor that vaccine is expected to bind to. But it doesn't elaborate on the mechanism of action after binding and how it work. Also, the "partially effective" vaccine form Thailand sounds kind of sketchy - I'm curious to learn how it was partially effective and how the researchers tested it.
Overall, this article proposes a good idea, hopefully there will be a HIV vaccine in the future.

-Michelle Jin

Monday, December 5, 2011

China to manufacture vaccines for global market

After meeting WHO international standards for vaccine regulation in March, China is now poised to make a splash in the global vaccine scene. Groups like GAVI (which purchases enough vaccines to cover 50 million children annually) are particularly excited about this move, which will result in more favorable prices. China currently produces almost 1 billion doses of vaccines a year.

However, you can't discuss Chinese vaccines without being reminded of their current track record - 2007 saw 93 deaths due to Chinese cough syrup, for example. In 2008, hundreds of thousands of infants were poisoned by powdered milk tainted with melamine; shockingly, even more powdered milk was found to be contaminated in 2009. Suffice to say that scandals like these do not inspire confidence in the ability of Chinese manufacturers to produce safe products in massive quantities.

With that in mind, we can anticipate the need for a regulatory body to ensure that these vaccines continue to be produced to international standards. However, one Chinese health expert, Yanzhong Huang, says that such an agency wouldn't be enough - what China needs is "the market economy, democracy, media monitoring, civil society, as well as a well-developed business ethics code." In short, China needs to change the way it does business before people in the international market will feel comfortable using their vaccines. (This could lead to a whole separate discussion on Chinese society and economy, but that's really beyond the scope of our class, so I'll just change tack here.)

Chinese-produced vaccines will likely be tough to deliver to the American public, if current exemption rates from childhood vaccines are any indication. Relevant comment is relevant:

"If they started producing all vaccines in china and phased out the American made ones I would refuse every last chinese vaccine. If my kid has to go unvaccinated because i dont wanna risk her being killed by a tainted chinese pharmaceutical then so be it. I know if they allow the chinese to produce vaccines the population of unvaccinated children will spike and spiral out of control. This decision will singlehandedly lead to the return of polio and other diseases like smallpox."

Sounds like closed-mindedness with a dash fearmongering, right? Sure, but that doesn't change the possibility that some sub-par Chinese vaccine product will slip through the cracks, especially at the volume at which they'll be produced.

We're going to need some intense regulation of these vaccines, but the manufacturing capacity provided by China's facilities will be a boon to immunization and eradication efforts worldwide.

-Alan Le

P.S. Pardon the lateness! Looking forward to seeing everyone's models :]

Washington Times: China positions itself to become major player as vaccine provider

Monterey County Herald: China to enter vaccine market

Sunday, December 4, 2011

Breakthrough discovery on mechanism of prion disease

Researchers from the University of Alberta doing studies on prion disease have discovered a new property of prion diseases that changes the way we think about prion diseases. While studying BSE, the researchers found that prion particles as well as bystander proteins were being destroyed in the brains of infected individuals for up to 7 months before the animal started showing symptoms. This means that the brain "fights back" more than was previously thought. Additionally, the study shows that prion diseases can change depending on the brains reaction, and might not be irreversible. If we can learn from how the brain fights off the infection for those months before symptoms appear, we may be able to gain insight into possible treatments for prion diseases.

--Sarah Kaewert

HIV+ Philadelphia teen denied entry to school

Someone's already written this up (whoops) but speaking of both "dual-use" science controversies and flu...I read about the controversy over the engineered H5N1 that's super infectious! It's interesting that they proposed the type of censorship that I was thinking about in the last problem set (i.e. publish generally, to get specifics you need clearance)—but just who would get access to the classified information? I tend to think of bioterrorists like I think of suicide bombers (using crappy kitchen tech), but the truth is that some legit scientists could definitely turn bioterrorist (i.e., the guy sending anthrax, a top researcher for the government who apparently was a co-creator of the vaccine). My brother recently told me about the plot line of a novel series/videogame called "Rainbow 6" in which the bioterrorists work for a biotech firm, and plan to throw virus into the fans at the Sydney Olympics in order to kill everyone off (except themselves, who are of course vaccinated) and thus save the ecological world from destruction. It's scary how "bioterrorists" could come from within our own institutions.


A 13 year old boy was denied admission to a private boarding school in Philadelphia because "it was necessary to protect the health and safety of the 1,850 enrolled in the institution." The AIDS Law Project is, of course, suing the school for discrimination, interestingly enough under the "Americans with Disabilities Act." I guess there's not really a medical-condition-specific discrimination law? A 6-year-old in Jakarta, Indonesia was also thrown out of school because her father is HIV+; she may be able to get in if she proves she is not HIV+.

It's interesting that there's still so much prejudice over HIV, even in America. (I mean, what's the likelihood that this 13 year old would spread it to his classmates? How much unprotected sex/needle drug usage is there in that school?) Even more for a 6-year-old whose father has it. I thought ostracization happened in Africa, or decades ago in America. For shame.



WHO Weighs in on European Measles Outbreak

The WHO, through an issue of their publication the Weekly Epidemiological Record, has announced that 26,000 cases of measles have occurred throughout Europe from January 2011 to October 2011. This figure is a steep rise from any previous and indicates the possibility of a continued outbreak of the deadly disease. They have placed blame mainly on fallout from the autism-vaccine controversy created by Andrew Wakefield and failure by European governments to properly enforce vaccinations as over 90% of cases where in unvaccinated people or people of unknown status. European governments have already begun responding to the outbreak, with France launching a high-profile campaign to drive up vaccination rates in reaction to 6 deaths and 14,000 cases experienced there.
These cases present a rather large set-back for the established goal of eliminating measles in Europe by 2015 and for world-wide eradication. Indeed, the European outbreak has also been tied to international outbreaks as a result of infected travelers to foreign countries. This just goes to show that the existence of a highly effective vaccine and even strong political will does not guarantee effective control of a disease.

-Zachary Herrera


US Reflection on HIV/AIDS Awareness

According to the Centers for Disease Control, only one quarter of Americans with an HIV infection have the infection under control. By "under control," they means that they have a suppressed viral load - less than 200 copies in the bloodstream per milliliter of blood. Contributing to this low percentage is the fact that an estimated 1 in 5 people with HIV don't realize they they are infected and of those that are aware, only 51% receive medical care and treatment. Modern day treatment, while not eliminating HIV, is very effective in controlling the virus - 77% of those on ongoing care and antiretrovirals have suppressed levels of the virus. [Although couldn't this be from the latent nature of the infection too?]

According to this article, not only are men who have sex with men are the population most severely affected by HIV in the US, they are less likely than other sex-groups to get tested and receive preventative testing. In response to this data, the CDC have launched a new national campaign to encourage black gay and bisexual men to get tested for HIV called Testing Makes Us Stronger. Research shows that black men do not engage in riskier sexual behavior than other LGBT communities, but that there is already a higher HIV presence in their population - so testing, behavior improvement (condoms, e.g.) and appropriate medical care are especially important in these communities. This is the latest campaign in the Act Against AIDS, the CDC's broad effort to fight HIV complacency nationwide.

read the full article here.

Emily Pollock

Hep C updates

The Montefiore Medical Center in New York is now urging members of the baby boomer population to get tested for hepatitis C, as they are more likely to have shared unsanitary needles because of tattoos, drug use, piercings or blood transfusions. Hep C can be asymptomatic for years, and the worry is that many people from this generation might be carrying the virus without knowing it. With a blood test and treatment from two new drugs that were released last May, doctors are seeing almost double the cure rate of the disease as they have in the past. There is still no vaccine to prevent the infection and, if left untreated, hep C can lead to liver failure or cancer, which is why doctors are pushing for people to get tested.

In other Hep C news, this week Delhi became the first city in India to offer Hepatitis C screening. Additionally, the government is offering to provide financial help to poor citizens who need a liver transplant as a result of Hep C.

-Emily Mitchell

Cold Sore Susceptibility Gene-1

Cold sores are lesions around the mouth, lips, nose, and even chin and fingers caused by an infection of the herpes simplex type 1 virus. Over 70% of the population is infected with this virus with outbreaks varying from person to person. These outbreaks are a direct result of the virus remaining in the body and unpredictably causing an immune response (the sores). Although there is no treatment for the virus, there are medications that help treat the cold sores. This reality, however, may soon change.

A recent study published in the Journal of Infectious Diseases identified a 3-megabase region on human chromosome 21 that contains 6 candidate genes associated with cold sores through the use of single nucleotide polymorphism scans. A two-point linkage analysis resulted in a positive correlation between the frequency of cold sore outbreaks and 2 SNP's within the C21orf91 region. The researchers even proposed that C21orf91 be defined as the Cold Sore Susceptibility Gene-1.

C21orf91 in no way increases your chances of being infected with herpes simplex virus 1 in the first place, it is simply correlated with the frequency of cold sore outbreaks. Genetics, according to an infectious disease professor, Dr. Kriesel, are only responsible for 21% of the cold sore outbreaks- the remaining 79% is attributed to environmental factors, the viral strain, and a number of other variables.

Kriesel, John D et al. C21orf91 Genotypes Correlate With Herpes Simplex Labialis (Cold Sore) Frequency: Description of a Cold Sore Susceptibility Gene. J Infect Dis. (2011) 204 (11): 1654-1662.

-Angela Ceseña

Another Wakefield?

Malcolm Brabant, a BBC reporter, was believed to have a psychotic episode after getting a yellow fever vaccine. It's reported that he had a fever of 40C after the injection followed by delusions of being Jesus. Eventually, he's forced to go off air to recover. No one in his family history had any mental illness.

I thought the beginning of the article was interesting - describing the reporteras "award-winning" and juxtaposing that with the yellow fever psychosis. This puts vaccines in a bad light and may prompt other people to reject vaccination. Although the article mentions that no causal relationship was drawn between the vaccine and his psychosis, the title and the majority of the paper implies this.

-Michelle Jin


WHO Concerned Over a New Flu Virus Spreading From Pigs to Humans

After criticism in Europe that the World Health Organization claimed 2009's swine flu to be a pandemic when in fact the outbreak was comparatively mild, the WHO is being cautious in raising alarm to a new flu virus that has been spreading from pigs to humans. It is an Influenza A virus of the H3N2 subtype, but sufficiently different from current viruses that the H3N2 component of the flu vaccine is not expected to help protect against this new strain.

10 outbreaks of the strain have been isolated in Maine, Indiana, Pennsylvania, and Iowa. In each case, the patient was a child under 10 (with one exception of a 58-year old). This might be because most 21-year-olds (and older) are likely to have had exposure to similar viruses in the past and therefore have a degree of immunity. In the first 7 infections, the virus passed from pigs to humans, but the last 3 cases (in Iowa) were clear cases of human-to-human transmission.

Immunity among the older population would likely prevent the virus from ever becoming a full-blown pandemic, but there is still a possibility the virus could spread child-to-child across countries. The CDC is currently conducting serological research to determine specific vulnerability to the virus; it has also asked the manufacturers who produce seed strains for vaccine companies to produce a vaccine candidate for this new H3N2 strain. WHO is also in the process of devising a name for the virus such that it wouldn't be a problem for any specific agricultural interests (as was the case with objections to the name "swine flu").

I think the proper steps are being taken in regard to the emergence of this new strain - both in developing a preemptive vaccine and in creating a epidemiological system of how to handle the spread of the virus in the chance of increased transmissibility. My personal opinion is that it's also better to be on the safe side and have the general population overly cautious of the virus, rather than to be too worried of garnering criticism and therefore not mounting enough of a response soon enough.

Article here:

-Elena Higuchi

Green tea has superpowers against Hepatitis C?

In a recent study published in the December issue of Hepatology, German scientists from the Hannover Medical School have determined that a certain flavonoid, which is a class of plant secondary metabolites, called EGCG (epigallocatechin-3-gallate), may have a significant role in preventing the Hepatitis C virus from entering liver cells. Their findings could have incredible impacts on the lives of liver transplant patients, who are always at high risk for HCV infection (which according to WHO, affects up to 170 million people worldwide and is the most common cause of chronic liver disease/hepatitis, cirrhosis, and hepatocellular carcinoma). Using EGCG for this particular case may therefore become an important antiviral strategy for the prevention of HCV reinfection following liver transplants.

According to these researchers, "[Their] study explored the potential effect these flavonoids have in preventing HCV reinfection following liver transplantation.” They not only found that this antioxidant EGCG inhibits HCV entry into the cells by inhibiting viral attachment to the cell (which is the initial step in the infection process), but also viewed that the application of this molecule during inoculation prevented the rapid "spread" of the Hepatitis C virus. They specifically announced that "pretreatment of cells with EGCG before HCV inoculation did not reduce the infection, however, application during inoculation inhibited the rapid spread of the HCV."

The actual mechanism of this process however is still in the "uncertain" stage. The authors have suggested that EGCG may actually be preventing the Hepatitis C virus' entry by acting on the host cell, as opposed to acting on the virus, as the green tea catechin was not found to alter the density of virus particles.

Nevertheless, this could have huge implications on future treatments of patients susceptible to chronic hepatitis, primary liver cancer or those who have just received liver transplants. Go green tea!!

- Julie Saffarian

Saturday, December 3, 2011

Who Says Curing AIDs is Impossible?

What is one lesson that Dr. Bob has taught us this year? If people say something is impossible, perhaps it just has not been done yet. A recent article in the New York Times expand on the idea that finding a cure for HIV (something that is usually thought to have insurmountable challenges) may not be as far away as we think.

In 2008 a patient dubbed the “Berlin Patient” was HIV positive when he was diagnosed and treated for leukemia. He was treated with bone marrow transplants which effectively replaced his immune system with the donor’s immune system. It just so happened that his donor was one of Northern Europe’s 1% that are resistant to HIV because they lack CCR5, the human receptor for HIV that allows them to enter immune cells. With his immune system effectively replaced with an HIV resistant immune system, the Berlin Patient has been able to survive 4 years supposedly virus free.

With this knowledge scientists are trying to develop a therapy similar to the Berlin Patient’s treatment for HIV. However, bone marrow transplants are expensive, risky, and require a donor with immunologically matching bone marrow. All this makes it a very tricky process.

Nevertheless, scientists have come up with a plan: “modify a patient’s own immune cells to make them resistant to infection by eliminating CCR5” (NYTimes). Now they have succeeded in doing just that in a patient.

The Trenton patient’s white blood cells were treated with gene therapy to produce zinc-finger nucleases that effectively disrupt CCR5 gene. The treated cells were returned to the patient and a month later he stopped taking his anti-virals.

At first, the level of HIV in his body increased sharply. However, then it fell back to undetectable amounts even before the 12-week period had ended. The patient’s immune cell counts also shot up.

What’s remarkable is that only a portion of his cells became genetically altered after the treatment and it still worked. It’s amazing that it worked at all because most of his CD4 cells had CCR5 gene expression.

Five other patients who received the same treatment did not have such successful outcomes but it is an interesting start to a possible new treatment for the disease. What is most interesting is that some scientists think that getting rid of as little as 10% of CD4 CCR5 gene expression (and therefore saving them from infection) could free up the immune system to control the virus. Patients who genetically have a percentage of their immune that are resistant to HIV (lack CCR5) would be even more likely to overcome disease by this treatment.

The article, New Hope of a Cure for H.I.V. can be found at

--Elena Jordan

Monday, November 28, 2011

Major Disappointment for AIDS Research

A microbicide gel that had once been considered a major mechanism for preventing AIDS in sub-Saharan Africa was reported to not be effective on Friday, and its clinical trial was canceled. The microbicide gel is a vaginal gel that a woman can place in her vagina prior to sexual intercourse. This was not only microbiologically intelligent, but also culturally sensitive because many women are not in a position to refuse sex or demand a condom of their partner in certain areas of the world where HIV runs rampant.

In 2010, a clinical trial of this gel was reported to be very effective, with almost 54% of infections being prevented. This trial's participants were divided into three categories: a control group, a group containing a pill of Tenofovir (the active drug), and the microbicide gel (containing Tenofovir and a booster drug). In September, the pill group was canceled because it, too, was shown to be ineffective.

It was shown that so far in this trial, 6% of women had become infected with HIV. While it is safe, just not effective, it ethically cannot continue.


More Parents Opting Out of Vaccinations for Their Children

School records are showing that more and more parents are choosing not to vaccinate their children. Depending on the state, parents can opt out of "mandatory" vaccinations by checking a box for medical, religious, or even philosophical reasons. Vaccination rates still remain high overall - as high as 90% for more "traditional" vaccines such as polio, measles, and Hepatitis B. Yet in 8 states, 1 in 20 kindergarteners aren't receiving their vaccines. This is counterproductive to many state officials' goals of reaching 100% vaccination.

The information shows that parents who choose to opt out of vaccinations are often geographically clustered together. Some rural counties in northeastern parts of Washington have exemption rates as high as 20 or even 50%.

I find this type of information extremely frustrating, especially after reading the following quote:
"We are being told this by every government official, teacher, doctor that we need vaccines to keep us safe from these diseases. I simply don't believe that to be true. I believe all the diseases in question were up to 90 percent in decline before mass vaccines ever were given. I don't think vaccines are what saved the world from disease. I think effective sewer systems, nutrition, and handwashing (are the reasons)"

Yay America.

-Elena Higuchi


Sunday, November 27, 2011

WNV and the public

A study published in Health Affairs found that climate change could cost more than $14 billion. This study examined 6 case studies of events related to climate change (i.e. hospitalization, premature deaths, injuries, etc). Most of the estimated health costs are due to premature deaths ($740 in health care costs) The researchers claim that the $14 estimate is most likely an underestimation and the actual health cost could be much greater.

In order to prevent such monumental health costs, researchers suggest reducing carbon emission and invest more money in climate change research and prevention strategies. Examples of climate change related events that contribute to the health care cost include: heat waves, hurricanes, infectious disease (WOOHOO!), wildfires, and river flooding.

I think this article is interesting because although most people know that anthropogenic climate changes are "bad" it's hard to conceptualize how bad it is. By putting a price on the related health costs, it will help mobilize prevention measures.

On a personal note, I picked this article because over Thanksgiving dinner, I met someone from LA who has a son in elementary school. She told me that some parents were protesting for the schools to close in order to prevent their kids from WNV (arbo virus) because they though it's transmitted through direct contact or respiration. It was really interesting to get her perspective on this climate related disease and realize how the public needs to be informed more about the diseases so it could be prevented in the appropriate manner.

-Michelle Jin

GAVI Alliance Board Agrees to Fund Joint HPV and Rubella Vaccine Intervention

The GAVI alliance (former Global Alliance for Vaccines and Immunization) has recently agreed to fund the joint introductions of the HPV and rubella vaccine to nine of the 57 developing countries it serves. A total of two million women and girls will be protected from cervical cancer and a total of 588 million children will have received the rubella vaccination by 2015 if the organization’s goals are met.

Approximately 275,000 women die each year from cervical cancer- 90 percent of these women are in developing countries. If no program or change is implemented, statistics show that this number can rise to 430,000 by the year 2030. Change, however, is a viable option- the HPV vaccine has been shown to prevent 70% of cervical cancer cases.
The board’s decision will rely heavily on pharmaceutical company’s compliance and negotiations to try and secure a sustainable price for the vaccines. Earlier this year, in June, Merck announced a 67% reduction in HPV vaccine prices for the Gavi alliance, resulting in a tentative price of $5 per dose.

The Gavi board also mentioned a potential fund for distributions of a Japanese encephalitis vaccine once the World Health Organization prequalifies an effective vaccine and discussed the rollouts of pneumococcal and rotavirus vaccines to countries with high levels of unvaccinated children.

Original Source:

-Angela Ceseña

Chimeric Oncolytic Measles Virus

One of the challenges facing the deployment of oncolytic viruses to fight tumors in humans is the immune response they generate. Naturally, we would think that viruses for which most of the target population has immunity to (e.g. those abrogated by the MMRV vaccine) are ineligible therapeutic candidates, but researchers are finding new ways to make host immunity a non-issue. For example, using Measles Virus (MV) to fight cancer would normally be inefficient because most people are vaccinated at an early age. Because strong immunosuppression during oncolytic therapy is a risky option, scientists have developed a method of 'shielding' the pathogen from the host.

Researchers from the Mayo Clinic replaced measles virus glycoproteins with modified CDV (canine distemper virus) glycoproteins that are able to attach to cancer cells via an attached antibody. The shielded MV was successful in eliminating tumors in murine models and was also successful in evading human antibodies. THis study was a proof of concept for chimeric viruses.


More evidence for link between HCMV and cancer

Until now, a link between Human cytomegalovirus and glioblastoma multiforme, a type of brain cancer, has only been supported by a few scientists. A new study at the University of Wisconsin at Madison has provided more supporting evidence for the claim, however. The team looked at three things in their study: whether HCMV was present in 75 glioblastoma multiforme samples; if so, whether the entire genome of the virus was present; and which cells within the tumor were infected. Their results showed that HCMV is statistically more likely to be present in glioblastoma multiforme tumors than in other types of brain tumors and that the entire genome was present in infected cells, but that very few of the tumor cells were infected with the virus. They postulate that this is because HCMV might only infect tumor stem cells, which would be something that has not been seen before in oncogenic viruses.

Keep in mind that this does not show a causal link between HCMV and cancer, unlike other viruses such as HPV, HCV and EBV.

-Emily Mitchell

GAVI to purchase and distribute HPV vaccine in developing countries

As you may already know, 275,000 HPV-related cervical cancer deaths occur each year, with 88% of those deaths happening in developing countries. The Global Alliance for Vaccines and Immunization (GAVI, consisting of groups such as the WHO, UNICEF, and vaccine manufacturers) has announced plans to work with manufacturers such as GlaxoSmithKline and Merck to acquire full courses of the vaccine at special rates.

The success of this program, of course, depends on a couple of crucial factors:

First, can GAVI actually find a partner to provide enough doses to meet their goal of vaccinating 2 million women and girls?

Second, GAVI wants to distribute the vaccines in 9 currently-unspecified countries. Social or political instability can hinder GAVI's efforts in affected regions, just like with poliovirus vaccination. Daniel Berman of Doctors Without Borders has expressed concern that GAVI's delivery of the vaccine may fall short. However, Dagfinn Hoybraten, a GAVI chairman, responded with claims of a 90% compliance rate in a Rwanda vaccine trial. Whether this can be applied on a larger scale, in additional countries, remains to be seen.

Source: Washington Post

-Alan Le

Controversial H5N1 Research Still Under Review

Last September, Ron Fouchier, a Dutch virologist, announced at a conference in Malta that he had succeeded in creating a strain of H5N1 that could readily infect ferrets and transmit between them via airborne transmission. Due to the similar interactions between the immune systems of ferrets and humans with influenza viruses, this implies that this virus could do the same for humans and touch off a global pandemic were it to be released. Since this announcement, debate has raged over whether or not this research was safe or justifiable and over the fate of the unpublished data and modified virus strain. While Fouchier wishes for the data to be published and the results made completely open to the scientific community, his paper remains under review by the National Science Advisory Board for Biosecurity and others have condemned his research, arguing that the resulting data should not be published because of the potential for misuse.

Fouchier has defended his work on the grounds that it proves the potential for H5N1 to infect humans in the same manner as seasonal flu and thus presents a possible risk for a global pandemic. Still, the debate over the nature of the experiment, the fate of the virus, and whether or not to publish the data closely mirrors the smallpox debate covered in class. In the end, both of these debates should, in principle, be resolved by judging the benefits versus risks of taking action, here the scientific potential of continuing and replicating this research versus the threat of misuse. These may prove to not be the only factors in play as seen by a recent Daily Mail article that describes the virus as having the potential to 'wipe out civilization'. While these are clearly inflammatory and speculative properties, this research frankly has all of the hallmarks of a bad cautionary story of “Science Gone Wrong” written all over it. The public's reaction has yet to be seen, and the potential for a serious backlash could affect the decision to publish.
-Zachary Herrera
NPR Article:
Daily Mail Article:

RNAi makes a comeback

Back in 2006, when the Nobel prize was awarded for the discovery of RNA interference, many companies hoped that the future of pharmaceuticals might lie in the ability to silence certain genes using RNAi. This process works fairly well in the lab, but it proved so difficult to make it work in an actual human that many companies gave up on the concept.

However, Alnylam Pharmaceuticals has come out with an RNAi drug that has been shown to be effective in humans. This is the first time RNAi has ever been shown to work outside of the lab. While the drug is still in its earliest stage of testing, the drug made a statistically significant difference on patients who took high doses of it. The disease used in testing is TTR-mediated amyloidosis, which basically causes a buildup of proteins that causes nerve damage. The drug aimed to silence the TTR gene, and was delivered into the body in lipid packets, which were carried to the liver, where TTR genes are expressed.

Even if this particular drug doesn't prove to be completely effective, this breakthrough is exciting because it shows that RNAi drugs probably can work in humans.

--Sarah Kaewert

Saturday, November 26, 2011

Annual childhood flu vaccines may not be as effective as we think...

According to a study done at the Erasmus Medical Center in Rotterdam, the Netherlands, vaccinating children annually against the influenza virus may interfere with their development of cross-reactive killer T cells to flu viruses. In this study, blood samples were collected from children with cystic fibrosis, who were vaccinated every year against the flu due to their weaker immune system, and also from healthy children who were NOT vaccinated. The analysis of the results showed that while both samples contained the virus-specific killer T cells, the samples from the constantly-vaccinated children with cystic fibrosis indicated less of a natural "increase" in their number annually. In other words, the healthy unvaccinated children demonstrated a natural increase of the virus-specific killer T cells every year, with age, while those who were vaccinated annually did not.
Researchers concluded that vaccination could thus potentially interfere with the induction of these killer T cells..

Then should the annual vaccination of children with cystic fibrosis, or defective immune systems in general, be stopped?

- Julie Saffarian

HIV1 Group N Spreading Outside of Cameroon's Borders

The rare strain HIV-1 group N seems to have spread outside of Cameroon. This is according to an article released in this month’s Lancet. Previously, cases had been isolated to within Cameroon but this week a man in France with HIV like symptoms tested positive for the this rare infection which for his case has been linked to sexual relations with a partner in Togo.

An HIV Ag/Ab ELISA was used to determine the infection but it was only weakly positive. An HIV-1 western blot also showed weak reactivity. Serotyping samples, showed clear reactivity against group-N-specific antigens. This prompted full-length sequencing through which scientists were able to determine that the infection was with HIV-1 group N.

The first case of HIV-1 group N was reported in a Cameroonian woman in 1998. Since then over 12,000 HIV-1 patients have been screened but there have been only 12 cases of N group reported. Until now these cases were all reported within Cameroon. With a French patient turning up positive and his case linked to sexual relations in Togo, it seems that the disease has spread outside of Cameroon’s borders.

HIV-1 group N is more closely related to SIV isolated from wild chimps than HIV-1 groups M (major), O (outlier) or P. Symptoms in the 57-year-old man living in France included fever, rash, lymphadenopathy, and genital ulceration. These were reported 8 days after returning from Togo.

--Elena Jordan

Lancet Article at:

Tenofovir microbicide trial in Africa cancelled

A microbicidal gel containing the antiviral drug tenofovir, that had shown lots of promise in stopping AIDS transmission in earlier trials, was cancelled on Friday because it wasn't working. The other parts of the trial, which were testing tenofovir in pill form, have also been cancelled due to lack of results.

This is a big disappointment in the fight against AIDS, because many researchers had such high hopes for this drug. Over 5,000 women were enrolled in the trial, which started in 2009, and since some data is still being collected, researchers aren't yet able to examine the data for answers as to why the gel failed to be effective in preventing the HIV transmission. Data will continue to be collected until 2012, so no definitive answers can be found until then, but researchers think the failure to be effective might lie in that too few women used the gel on a regular basis, it caused inflammation that allowed the virus to enter the body more easily, or that the dosing schedule was incorrect.

--Sarah Kaewert

New swine flu virus discovered...

...but apparently it's nothing to worry about. The CDC has confirmed 10 cases this year of a new strain of influenza A, S-OtrH3N2 (doesn't quite have the same catchiness as "H1N1"), that originated in pigs. However, unlike the H1N1 scare of a few years ago, this new strain doesn't show signs of being dangerous. For one thing, it's treatable with antiviral medication. Also, the cases have been spread across the country (Pennsylvania, Indiana, Iowa, Maine), which means the disease hasn't expressed itself in outbreaks or clusters.

Even though this new strain of flu isn't as dangerous as many of the other viruses discussed on this blog, flu viruses are interesting (among many other reasons) because they mutate often and so are changing all the time. The article mentions that even though it might seem like there are more strains of flu popping up than ever before, the increase in numbers is probably due more to technological advances in diagnostic techniques than an actual rise in the numbers of flu strains. Additionally, the article lists two examples of novel flu strains that weren't so harmless as this new H3N2 virus: the H1N1 outbreak of a few years ago, and the devastating 1918 epidemic. It's interesting to think that each year's new flu mutation may turn out to be relatively benign or quite dangerous.

--Sarah Kaewert

Wednesday, November 23, 2011

Biosecurity Super-Lab

A lab in Geelong, Australia that opens in March holds some of the highest tech available, in order to allow scientists to study live SARS, Hendra, Nipah, and Ebola viruses. It boasts an array of powerful live-cell imaging microscopes to allow researchers to watch virus-host interactions in real time, space-suit like sterile suits, and Dr. Linfa Wang's collection of emerging bat viruses (the largest in the world).

I found the security measures fascinating. Everything that goes in is incinerated, even the jewelry you didn't take off. Nothing comes back out unless it's been thoroughly sterilized, and anyone who visits is subjected to a 3-minute shower and wash. Afterwards, you're instructed to avoid common viral reservoirs, like birds, pigs, and cows.

I'd love to visit and experience the ultra high-techness of the place. (I bet I'd just prance around in the silly suits for a while.) Working there with these awe-inspiring live viruses on a daily basis would be a dream! And also the start to many a zombie movie...



Tuesday, November 22, 2011

neutralizing antibody against Sudan virus

Researchers have isolated a neutralizing antibody against Sudan virus, a species of ebolavirus and virulent pathogen. This antibody was identified by injecting lab mice with geneticall engineered viruses to make more copies of virus coat within the infected mouse. Researchers then isolated the mice's antibodies by harvesting B cells and culturing them in lab. Researchers then tested each antibody extracted from the mice B cells and found that antibody 16F6, neutralized Sudan virus in the petri dish and delayed mice death.

The antibody-antigen protein binding strategy is similar to another ebolavirus species Ebola-Zaire and has great potential to serve as vaccine and therapy against ebolavirus infections.

An experimental vaccine with protein coats from Ebola and Sudan viruses was given to monkeys and results showed that it induced immunity against the viruses. However, specific mechanisms by which the vaccine work is currently elusive. Because this is the first time that anyone has isolated neutralizinga ntibody against Sudan virus, much has to be done in order to test its effectiveness and safety as vaccine.

I think the way that the research is carried out is very interesting because what if the researchers never find a neutralizing antibody? It seems like a broad shot-gun approach. But it would be very nice to be able to make a vaccine against the Sudan virus.

Michelle Jin


Sunday, November 20, 2011

Promising news for potential Ebolavirus vaccine

Just today, Scientists from the Scripps Research Institute and the US Army's Medical Research Institute of Infectious Diseases have reported their findings regarding an antibody that is able to neutralize Sudan virus, one of the major species of Ebolaviruses (which is part of Filoviridae), through its particular way of attaching to the virus. It has been seen that the antibody tends to "link" two segments of the viral coat protein, thus blocking the freedom of movement or in other words, paralyzing the virus, and enabling it from infecting a cell. This protein-linking mechanism was also found to be the strategy of another neutralizing antibody, which is effective against the Ebola-Zaire virus, which is more commonly known.
These two viruses, the Sudan and Ebola-Zaire virus, were first discovered as they caused significant outbreaks in Sudan and Zaire (today's Democratic Republic of Congo), in 1976. They resulted in serious cases of hemorrhagic fevers, killing about 90% of those that had been infected. Up to this day, there has been no vaccines against these viruses, although one was developed from Ebola and Sudan viral proteins to provide protection against these viruses in monkeys. However, it is unclear whether these vaccines would work in humans.
Thus, these new findings could open the door to a potential vaccine or antibody-based therapies to protect against these dangerous Ebolaviruses.

Have a great break everyone!

- Julie Saffarian

HSV and DNA Mismatch Repair Proteins

DNA Mismatch Repair Proteins are a highly conserved group of proteins from prokaryotes to higher eukaryotes and perform a number of important functions to maintain the integrity of the genome within an organism. Mutations in these genes can cause several forms of early-onset cancer. They also play an undefined role in signaling cell cycle checkpoints as well as apoptosis. Kareem Mohni and other scientists studied these cells in Herpes Simplex Virus-cell interactions to shed some light on the methods of HSV DNA replication. Specifically, they looked at MSH1 and MSH2, which usually function together in an MSH2-dependent manner.

This paper shows a novel pathway in that , in HSV replication, MSH1 does not act in an MSH2-dependent manner. Depletion of MSH1 exerted a very strong effect viral infection - specifically on immediate-early viral gene expression. MSh1 also localizes to ND10 nuclear bodies, which in turn are recuited viral replication compartments following infection. MSH2 however, is not localized to the ND10 bodies and had a later effect on gene replication.

Check out the article here.

-Emily Pollock

Happy Thanksgiving Break!

Wednesday, November 16, 2011

Salivary Gland Cancer Tied to latent CMV

Scientists at USC claimed to have rigorously confirmed that Human Cytomegalovirus (hCMV) is an oncovirus that can be directly linked to mucuoepidermoid carcinoma, or cancers of the salivary gland. Their findings were published online over the weekend in the journal Experimental and Molecular Pathology, with publication pending but likely soon. In the paper, they claim that hCMV satisfies all of Koch's postulates, as modified for viruses and cancers by their own standards. This translates to 4 major observations:

1. Proteins indicative of the presence of hCMV are seen in cancerous cells.
2. These proteins are not seen in healthy cells.
3. The levels of proteins expressed by hCMV correlate with the severity of the cancer.
4. The presence of hCMV causes the upregulation of a known oncogenic pathway.

If these claims hold up under outside scrutiny and independent confirmation, these findings mean that another member can definitively be added to the roster of oncoviruses: CMV. This would represent an interesting addition considering that CMV is so common and has been thought to typically present little danger to healthy people outside of the common risk-groups(immuno-compromised, organ transplant patients, or newborn infants). If it indeed causes cancer at a non-trivial rate, this may also indicate the birth of a larger field of anti-CMV treatments looking at decreasing the global rate of CMV infections in order to control cancer, much like the modern anti-HPV campaign.

Press Release
Journal Article(Publication Pending):
-Zachary Herrera

Oh Norovirus...

Human norovirus, which belongs to the Caliciviridae family, is the most common cause of acute gastroenteritis, and affects about 1 in 15 Americans each year. According to the CDC, it leads to about 70,000 hospitalizations, and more than 500 deaths annually, and the disease it causes tends to be one of the more unpleasant of those that leave healthy people unscathed in the long run, with diarrhea and vomiting that typically last for 48 hours.
Researchers from Emory University have recently answered a crucial question regarding these dangerous viruses: If well water becomes contaminated with noroviruses, for instance, from leaking sewer lines, then how long would these noroviruses survive in that body of water, and when would it be safe to drink from that well? The answer is least 61 days, and probably far more.

The test they performed consisted of a safety-tested virus stock solution. They placed a known amount of this solution into a container of groundwater and tested the virus's infectivity at various days, starting from 0 and ranging to about 61 days. The volunteers for this study drank from the water and became infected, exhibiting a range of unpleasant symptoms. Unfortunately due to funding issues, the researchers could not conduct the experiment past 61 days, but found that volunteers who had drank the water 61 days after contamination with notovirus still became severely infected. Now you may think that volunteering for such an experiment is quite an odd idea: who would want to experience extreme diarrhea? And possibly even risk being hospitalized? The researchers of this study were actually themselves surprised to see that most volunteers had a desire to test their immunity, and see whether they were actually capable of getting sick..

The important conclusion from the study was that Norovirus may in fact remain infective far longer than 61 days, a significant evidence for the need to treat groundwater used for drinking. The researchers stored the groundwater at room temperature in the dark, and used reverse transcription PCR to calculate how much viral RNA remained after exactly 622 days, and again after 1,266 days. They found no reduction in the amount of viral RNA after the first interval, but saw very little at the end of the second interval.

To read more, here's a good link!

- Julie Saffarian

Tuesday, November 15, 2011

Flu-V: immunity in 1 shot

A company called SEEK is pioneering a "universal flu vaccine" that would only need to be injected once and would provide T-cell immunity to all influenza strains for many years. As you probably know, current flu vaccines are annual because the influenza surface epitopes mutate too quickly for last year's vaccine to be very effective. Scientists find the current viruses circulating, predict what the major flu strains will be in any given year, and combine a few of them into a shot/spray to administer during flu season.

SEEK used computer models to compare known influenza epitopes and find ones that are conserved throughout the years. They specifically looked at ones that T-cells recognize, i.e. that have been processed internally in infected cells and presented through HLA molecules. These conserved epitopes are then mass-synthesized (rather than grown in eggs as normal flu vaccine). The trial is currently in Phase II, and shows promising results in being able to lower viral levels. It's also probably a lot cheaper and able to be mass produced.

SEEK's is fairly interesting

Virophiles, which genes are likely used for this vaccine and how does induction of T cell immunity help reduce viral titers?
Since the vaccine relies on processed antigens found in the interior of cells, SEEK's conserved epitopes probably rely on chunks of viral polymerase, IFN-suppressing enzymes, or perhaps even capsid proteins (which aren't generally available on the surface of Orthomyxo). These genes are unlikely to change in sequence much over the years.
The vaccine, unlike many conventional ones, does not rely on recognition of surface epitopes and won't generate a humoral (antibody) response. Instead, it produces cytotoxic T cells which recognize and kill virus-infected cells. Memory cells of this population could recognize a subsequent infection and kill infected cells, stopping the virus from replicating. Although this response itself is not complete without the neutralizing effects of antibody-mediated immunity, activation of these cells probably hinders the initial growth of the viral population to significantly dampen the progression of the flu. It is also possible that the vaccine's ability to activate helper T cells plays a role, as these cells can strengthen the overall immune response and help activate B cells.


Smallpox and Liver Cancer

While the smallpox vaccine worked wonders by eradicating a deadly disease, it may have uses in future medicine. A recent study has emerged in which patients with liver cancer received live attenuated Vaccinia virus [smallpox vaccine].

Vaccinia has been found to preferentially infect cancer cells because their production of antiviral interferon has been turned off signals that attract Vaccinia have been turned on.

More research has to be done to determine the causality of the Vaccinia virus on patient health outcomes but from this preliminary study, patients who received vaccine survived for longer than patients who did not.

More can be read at:
--Elena Jordan

Monday, November 14, 2011

Yellow Fever in Ghana

The Upper West Region of Ghana has recorded 3 cases of Yellow Fever this year 2011. While the three infections are in the same region of Ghana, they are located in separate municipalities. Ghana has not seen any cases of Yellow Fever in the past 6 years, so this is particularly troublesome. The medical director of a major hospital in Jirapa, Ghana, Dr. Richard Wodah, has announced a mass vaccination campaign that will begin by focusing on children above a year old. He also called upon people to sleep under mosquito nets and keep children aware.

Ghana is an area where Yellow Fever is endemic, so sporadic cases arise here and there. The potential of this to go into a larger outbreak should not go unnoticed, especially when taking in travel and tourism into account. The vaccine campaign stated above must begin quickly or the disease will be difficult to keep track of.


United States will spend $433 million on experimental smallpox drug?

Currently, smallpox is one of 12 pathogens that the U.S. has classified as being a possible material biothreat to the country. Because of this, the government is in talks with Siga Technologies Inc. to buy $433 million worth of a smallpox drug to add to the country's biodefense arsenal. This would buy 1.7 million doses, which comes to about $255 per dose. The drug in question is called ST-246, and it's an antiviral pill that is designed to be taken if a person has missed the window for inoculation after being exposed to smallpox. However, is hasn't been tested on humans, for obvious ethical reasons, and the jury is out as to whether animal testing would prove anything where human effectiveness is concerned.

The United States currently has $1 billion worth of smallpox vaccine, which is enough to vaccinate the whole country. However, it has to be given within four days of exposure to reliably save lives. In contrast with ST-246, this vaccine costs only $3 per dose.

This deal is surrounded by political controversy, as some consider that the deal is more of a political alliance than a national security plan. Additionally, some scientists think that it's an enormous waste of money to buy this much of an untested vaccine in defense of a threat which may never appear.,0,6088814.story

Competition between HPV strains?

The two vaccines used for HPV protect against 4 strains of the virus which are most known to cause cancer. There are more than 40 other types of the virus, however, and scientists are beginning to worry that these types will become stronger as the vaccine fights off the four others.

Researchers are just beginning to look into this possibility to see if it has any implications for new HPV infections. A preliminary study published just this month looked at over 2,000 men in Kenya who have HPV to see how many types of the virus most people were infected with. The study showed that being infected with one type of the virus is not related to being infected with any other type. This shows that there is not a concerning amount of competition between the types of viruses.

The next, and more important, step is to see whether there is a difference between the number of types of HPV in a person before they are vaccinated and after they are vaccinated. This will show whether targeting the four types that we now target could put people at risk of infection from the other types of HPV.

-Emily Mitchell

Testing new smallpox vaccines

Since cases of clinical smallpox no longer exist, efficacy testing of new vaccines in humans is not really possible. The old method of human testing, which involved vaccination and revaccination + an assessment of the patient's reaction (or lack of) to secondary challenge (usually a skin lesion), encountered the problem of patients developing heart problems (also, it was quantitative).

Thus smallpox vaccine development had to use the FDA's "animal rule," which allowed for animal models (two or more) to be surrogates for human testing, assuming the effectiveness, dosage, and responses to the vaccine can be extrapolated from the animal trials. But even here, vaccine development encounters another problem: there isn't a suitable animal model that would model human smallpox infection. So, researchers have been looking at the immunity given by their vaccines toward variola-like mice and monkey strains. Protection new vaccines such as MVA (uses attenuated vaccinia) confers onto humans might never truly be known until smallpox reemerges.


2004;291(15):1825. doi: 10.1001/jama.291.15.1825

Smallpox Antiviral Pill?

Did you know that America has $1 billion worth of smallpox vaccine stored away?

The Obama administration has pushed through a contract for an additional $433 million of ST-246, an antiviral pill manufactured by Siga Technology. Each dose is over $200. This pill hasn't been tested thoroughly, but promises to combat smallpox when it's already been contracted, after the vaccine would be useful.

Issues are being raised as to whether or not we need more defense against bioterrorist threats, the safety and usefulness of Siga's pill (which is not yet FDA approved since it can't ethically be tested in humans), its short shelf life (3 years), and the manner in which Siga acquired the contract (apparently, they was little competition for the contract). The only known smallpox in existence is held by the U.S. and Russia.

LA Times Article

I didn't know we even had smallpox vaccine owned by the government, although it makes a lot of sense. At the same time, I'm not sure that stockpiling these drugs would be all that epidemiologically useful. Since smallpox is most contagious when symptoms are obvious and the patient is bed-ridden, dedicated wards where these patients and their contacts could be isolated/quarantined and cared for by vaccinated health workers might actually be more effective than mass-vaccinating everyone, especially given that the vaccine can be dangerous in immunocompromised people. But, in our extremely mobile world, it may be hard to stop the spread of a reemergent smallpox, and the populace may clamor for a drug. I also think it would be awesome to develop an antiviral that could combat smallpox, if ST-246 does what it promises, because so far the only treatment is vaccination.


smallpox vaccine might be helpful in cancer treatment

A genetically engineered smallpox vaccine, named JX-594, was shown to reduce risk of death by 60% among patients with liver cancer, according to a phase 2 clinical trial. JX-594 is a derivitive of vaccinia virus, the common virus used to vaccinate children against smallpox. This study was conducted by researches from UCSD and Jennerex Inc, a biotech company. Thirty patients were enrolled in this study and monitored for mortality. 66% of the participants given high dose of JX-594 were alive after one year, versus 23% among participants who received low-dose vaccine.
The vaccine was relatively safe, with no known side effects other than acute flu-like symptoms. The possibility of using vaccines as anti-cancer therapy yields great potential in future therapeutic measures against cancers.
I think this article is interesting because not only does the vaccine protect against smallpox like the conventional vaccinia virus, it also could protect against cancers. If subsequent phases of clinical trial were to be successful, the same concept could be applied to anti-cancer treatments.

-Michelle Jin

Polio Outbreak: Denied by UN in Madagascar, Confirmed by WHO in China

"No matter how long a country has been polio-free, as long as global polio eradication has not yet been achieved, the risk for importation remains and constant vigilance is required," states Helen Yu of the World Health Organization in Beijing.

China experienced a polio outbreak during the last week of October of this year with ten confirmed cases, six occurring in children under three years of age. According to the World Health Organization, this infectious strain of WPV1 is genetically similar to the strain that was circulating in Paksitan. The last case of polio infection in China was over a decade ago, in 1999, when a strain of polio was imported from India. This reaffirms the notion that disease eradication is only possible when the eradication refers to an international level- otherwise, the risk of disease importation remains a viable possibility.

A few countries away, during the same time frame, Madagascar faced a polio outbreak- this outbreak, however, was caused by a wild type. Days after the initial report was released, Unicef made a clarification stating that the infection was in fact vaccine-induced. There were three reported cases of vaccine-derived poliovirus that were partially attributed to low immunity on behalf of the population in the island of Madagascar. This low immunity, is in part due to a combination of the recent fuel shortages that don’t allow for proper storage and refrigeration of the vaccine and a reduction of 250 clinics which have led to a drop in vaccination rates to less to 40% in the southern part of the country. During a nine year period (2000-2009), Madagascar experienced 14 vaccine-derived polio cases leading to 400 confirmed polio cases. Not to mention, 14,000 children who have not been immunized as a result of the financial situation and lack of resources, were paralyzed by the virus.

"Outbreak Notice: Polio"

"Madagascar: UN denies polio outbreak"

-Angela Ceseña

Sunday, November 13, 2011

How Measles Spreads So Quickly

Measles is one of the most contagious viruses in the world- more than 10 million children are affected each year and roughly 120,000 of the infected die. While a vaccination is available, measles still remains a significant health problem both in the US and globally.
Originally published in Nature online, a report from researchers at the Mayo Clinic sheds some light on just how measles spreads so quickly. Upon exposure, the virus hijacks those cells patrolling the lungs to infect the host, and travels to other immune cells throughout the body. The infected cells deliver their cargo to cells that specifically express the receptor protein nectin-4 - which are located in the trachea. The reproduction of virus in the trachea (and possibly subsequent immune response) provokes a cough, which the newly reproduced are in the perfect position to be carried through, ready to infect the next host.
What is particularly interesting about this finding, aside from the particulars of transmission, is that the receptor protein nectin-4 has been linked by other studies as a biomarker of ovarian, breast, and lunch cancer. Following the ideologial trend that modified viruses may be less toxic than other cancer-treatment alternatives, this finding could prove fruitful to the development of anti-cancer viruses for cancers that express the nectin-4 protein.

read the article here.

-Emily Pollock

Engineered Smallpox Virus Could Act as a Vaccine for Breast and Ovarian Cancer

As it stands, tumor-associated antigens (TAAs) often elicit either a very weak immune response, or no immune response. We've studied in class how smallpox viruses have a remarkably large virion and large chain of genomic material. Its genome allows for the insertion of several genes, including ones that can code for TAAs as well as for proteins that help stimulate T-cell response. After vaccination, the modified smallpox virus can produce both the tumor-associated antigens as well as co-stimulatory T-cell proteins, so that T-cells can better learn to recognize TAAs and respond against preexisting TAAs (from real cancer cells) in the body.

This wouldn't be a typical vaccine in the sense that it would prevent disease; rather, it would help treat preexisting cancer and help the immune system mount a more effective response against cancerous cells. A pilot study testing the vaccine in humans has showed promising results, and the vaccine is currently being further researched. Although it may not be an end-all cure for cancer as of yet, I think it could be a major step in that direction - no matter what, it certainly acts as an effective mediator of cancer, which is encouraging for everyone.

Published study here
Article here

- Elena Higuchi

Tuesday, November 8, 2011

Chickenpox lollipops for kids?

You've probably heard of chickenpox parties, in which parents bring their kids to get infected at a young age and thus gain immunity. Now, it appears that some parents have been selling lollipops coated with their infected children's saliva, shipping them out to customers around the country for $50 a pop (no pun intended). Bit of a ripoff though, since varicella is infectious through the respiratory route, not oral.

Let's not forget the fact that it's illegal to ship diseased or viral substances across state lines like this, and that there's a serviceable vaccine out there. Many parents out there want the "best" for their kids; in this case, they opt for a full-blown infection rather than the vaccine. Not that their concerns are without merit; in the U.S., the duration of protection by the vaccine is only about 10 years, though this does depend on exposure to wild varicella during the protected state.

Bonus fact: I caught chickenpox in middle school despite being vaccinated. Fun times, fun times.

-Alan "sorry for the sleepily-written blog post" Le


Gut Bacteria Helping Out Viruses?

Since the 1950's scientists have thought of the body's bacteria as helpers in fighting off infection by out-crowding potential pathogens. But recent research with the mouse mammary tumor virus (MMTV) and a poliovirus show that some viruses rely on an interaction with the bacteria of the gut to produce an infection. In the case of MMTV, Tatyana Golovkina and colleagues at the University of Chicago in Illinois have shown that the virus covers itself with bacteria molecules present in the host's gut, and those molecules interact with TLR4 to establish an infection.
Julie Pfieffer at the University of Texas Southwestern Medical Center in Dallas reports similar findings in mice infected with poliovirus. Poliovirus expression in humans requires the presence of a human poliovirus receptor (PVR) and those PVR-transgenic mic susceptible to poliovirus infection by forced immunodeficiency where then tested. Some were untreated, and others were given an antibiotic treatments to decreased the intestinal bacteria by a millionfold. The mortality of the untreated mice (with bacteria) was twice that of the antibiotic-treated mice.

These findings are interesting because they chance the way we can think about the infectivity of certain viruses that replicate in the gut - possible applications for prophylactic treatments?

Julie Pfieffer's research with poliovirus
Article in Science Magazine

Emily Pollock

Monday, November 7, 2011

Why polio is sticking around

Despite many years of eradication efforts, the world is still not free of polio. So far in 2011 there have been fewer than 500 cases worldwide, but getting rid of those last (comparatively) few cases has been eluding health officials for years. The four main polio holdouts, where the disease is endemic, are Pakistan, Afghanistan, Nigeria and India. Overcrowding, conflict, natural disasters and political will are cited as roadblocks on the path to complete eradication.

While there have been fewer cases this year than last, polio has also reemerged in countries where it had been thought to be eradicated, like China and Kenya. One critic of polio eradication said in the article that spending so many billions on eradication efforts is a waste of money, and we should instead be putting that money toward something that affects more people, like malaria or malnutrition.

--Sarah Kaewert

Current Outbreak of Polio in China

The World Health Organization has reported that 18 new cases of Polio have occurred in Xinjiang Province, China. Half of the cases are extremely young children, and the other half are in young adults. This is particularly worrisome because with polio, up to 90% of infected cases will not exhibit symptoms for quite some time. While only 1% will be affected with paralysis, because the disease is transmitted via the fecal-oral route, it is very hard to track epidimiologically.

Travel advisories have been issued for people traveling to this area. Polio vaccinations prior to arriving are highly recommended. Additionally, Guam has been warned because it is popular destination after traveling through Xinjiang. The doctors there are on alert for any possible cases.


A Parasite, of a Parasite, that fights a Parasite, is our friend?

Given our current inability to fight dengue on the molecular level (vaccines) and the difficulty mosquito abatement programs are facing with regard to the ever increasing range of Aedes aegypti, some researchers have turned their focus to possible microbial mechanisms that'll limit the spread of DENV. One technique in particular--the infection of Aedes aegypti with a symbiotic Wolbachia bacterium--has shown promise in providing immunity to DENV for this dipteran species. A suggested Wol-DENV control program would involve releasing infected A. aegypti and letting them mate and reproduce with wild mosquitoes will lead to population-wide immunity; issues that have to be addressed are the fitness of Wol-infected mosquitoes, and potential ramifications of infection.

* Wolbachia is a natural symbiont for many arthropods and have been found to be essential for the reproductive cycles of some species.
* Although Aedes albopictus is the original Wolbachia host (what a coincidence!), Wolbachia can thrive in A. aegypti as well.
* Wolbachia is transmitted vertically in insects

Source: Bian et al. THe Endosymbiotic Bacterium Wolbachia Induces Resistance to Dengue Virus in Aedes aegypti. PLoS 2010

- NGUyen -

India making progress toward polio eradication

India seems to be on the fast track to eradicating polio! From 2009 to 2010, India and Nigeria experienced a 94% reduction in the number of polio cases. In 2010, 42 cases of polio were reported in India. In 2011, only one case has been reported (and that was at the beginning of the year). These huge strides can largely be attributed to increased vaccine coverage among children in endemic areas and in migrant populations.

This is pretty exciting! Results like these really emphasize the exponential decay of the number of infections, thanks to vaccines. I'll try and dig up more information about the specific techniques used to bring about this change.



3 November 2011

13 May 2011

HPV vaccine finally recommended routinely for boys!

CDC reports that HPV is the most common STI, partially due to the fact that there are more than 40 types of HPV that affect both males and females. Most people are asymptomatic and in 90% of cases, HPV naturally clears up within 2 years. Among those who show symptoms, common signs include genital wart and cervical cancer. Recently according to Infectous Disease News, CDC's Advisory Committe on Immunization Practices approved recommendation of HPV vaccine to 11-12 year old boys because the vaccine "was safe, efficacious and cost-effective enough to warrant routine usage in this population."

In 2009, CDC's recommendations were permissive, meaning that health care providers could give vaccines to boys, but not routinely. The change to routine administration has potential to reduce HPV prevalence more than before.

My feelings - Why did it take so long for CDC to make recommendations routine! I's interesting that the vaccine was thought to be safe and effective for girls years before it was approved for boys, even though the safety and efficacy should not change. This is really optimistic for reducing HPV though!

-Michelle Jin


HPV routine recommendation finally approved for boys!

CDC reports that HPV is the most common STI, partially due to the fact that there are more than 40 types of HPV that affect both males and females. Most people are asymptomatic and in 90% of cases, HPV naturally clears up within 2 years. Among those who show symptoms, common signs include genital wart and cervical cancer. Recently according to Infectous Disease News, CDC's Advisory Committe on Immunization Practices approved recommendation of HPV vaccine to 11-12 year old boys because the vaccine "was safe, efficacious and cost-effective enough to warrant routine usage in this population."

In 2009, CDC's recommendations were permissive, meaning that health care providers could give vaccines to boys, but not routinely. The change to routine administration has potential to reduce HPV prevalence more than before.

My feelings - Why did it take so long for CDC to make recommendations routine! I's interesting that the vaccine was thought to be safe and effective for girls years before it was approved for boys, even though the safety and efficacy should not change. This is really optimistic for reducing HPV though!

Michelle Jin


Sunday, November 6, 2011

Cause of Viral Encephalitis Outbreak in India Likely An Enterovirus.

An outbreak of encephalitis in the state of Uddar Pradesh in Northern India has killed over 400 people, with the majority of deaths being children. In a region beset with poverty, systemically poor hygiene, and lack of health care, the virulence of the disease has been amplified by the mysterious and sudden nature of it. Though the region often experiences outbreaks of encephalitis annually, in accordance with the monsoon, those outbreaks have traditionally been the result of Japanese Encephalitis Virus, which is spread by mosquitoes. Indeed, massive vaccination efforts and the allocation of funds by the central government towards treating JEV have greatly reduced its incidence in the region. As reported in the attached article, however, this disease is thought to be caused by a virus that is transmitted through contaminated water, a fecal-oral route, and is thought, though not known, to be an enterovirus. Though examinations based on a combination of PCR and viral chip technology, researchers hope to be able to pinpoint the exact nature of this regionally emerging virus. Failing a major breakthrough, its identification may not directly affect the current outbreak, but it could serve as a valuable tool for researching and treating what could be an emerging viral disease. Still, doctors involved place most of the blame for the current outbreak on poor hygiene standards and under-performing sanitation systems. Without an overhaul of these systems, this encephalitis may become endemic to the region, continuing to claim lives and displacing JEV as a local scourge.
(Identifying Virus):
(Outbreak, October 21, 2011)

Eradicating Polio: the TED talk

Instead of reading an article about polio, I decided to watch the TED talk that Bruce Aylward, the head of the polio eradication program at WHO, gave this past March in which he described the efforts of the past 20 years to eradicate polio and the changes that have been made recently which are showing very promising results.

The program has been working to eradicate polio since the 1980s, and did so effectively across the globe except in four locations: Northern Nigera and India, Souther Afghanistan, and neighboring Pakistan. There are three types of polio and Type II has been completely eradicated, but types I and III still persist in these areas. Last year there was an alarming outbreak of polio in countries that had not seen the disease in years, emphasizing the importance of complete eradication as opposed to simply control of the virus. With the amount of interconnectedness and around the world traveling that goes on today, having the virus persist in even one country can still put the entire world at risk. Aylward therefore claimed that "the scientific miracle of this decade ought to be eradication of polio."

Complete eradication of a disease has been tried six times in history and has been successful only once, with small pox. Aylward called eradication the "venture capital of public health" in that it is very expensive but when successful, the pay off both financially and socially makes it completely worth the initial monetary cost. He cited a congressman who claims that the cost of eradicating small pox now pays itself off every 26 days and that the eradication of polio would save the poorest countries in the world $50 billion in the next 25 years alone (saving in costs of treatment and vaccination mainly).

Eradicating polio is more complicated than eradicating small pox because there are more people who have the disease and because the vaccine is fickle and especially sensitive and prone to deteriorating when exposed to heat. Recently, the program decided to create a new vaccination which would be more effective at targeting the remaining two types of polio. The first results of this new vaccine were received in 2009: in Afghanistan, it had twice the impact as the old vaccine; In the northern regions of India, not a single case of polio-induced child paralyzation has been reported in the past six months for the first time in history; Nigeria saw a 95% reduction in cases over the past year.

With these results, Bruce concluded that the combination of smart people, smart technology and smart investment can make the goal of eradicating polio a reality.

watch it here:

-Emily Mitchell

International Clusters of Hev68

Human enterovirus 68, Hev68, was first discovered in 1962 after being isolated from 4 pediatric cases in California. A recent Morbidity and Mortality Weekly Report shows that the prevalence of infections attributed to this picornavirus have substantially increased in the previous years. From 2008 to 2010, six clusters of viral outbreaks were identified in the United States (3 clusters: Georgia, Pennsylvania, and Arizona), the Phillipines, Japan, and the Netherlands.

The viral infections have been shown to disproportionately affect children. All 21 cases in the Phillippines were pediatric cases, 2 of which were fatal; Japan had a record high of 120 Hev68-positive cases, one of which was fatal; the Netherlands had 24 cases, 3 of which were nosocomial infections, and the three clusters in the US had a total of 39 cases.

The virus was identified through reverse transcriptase-polymerase chain reaction (RT-PCR) testing which targeted the 5’non-translated region of the strand, and through partial sequencing of structural protein genes VP4 – VP2 and VP1. The increase in number of reported cases can either be attributed to an improvement in diagnostics and medical technology or to an emergence of Hev68. It could also be a combination of the two.

Symptoms of Hev68 infections range from relatively mild illness to severe respiratory illness requiring mechanical medical ventilators and intensive care. Many times, these symptoms are confused for the flu or other respiratory infections. With the prevalence of the infection in the six clusters, the CDC recommends that human enterovirus 68 should be a candidate for cases involving respiratory diseases.


-Angela Ceseña

Polio Outbreak in Angola

Angola (a country on the western coast of South Africa) recently declared a state of emergency after one 14-month-old boy tested positive for the polio virus. The case is thought to be linked to a series of 9 outbreaks in the past year that took place in the Democratic Republic of Congo. The state of emergency was declared in an effort to rapidly control the disease, and prevent an Angolan polio outbreak similar to last year's - 33 cases in one year. (This year thus far, there have only been 4.)

Even one case of polio can spread the virus to any unvaccinated individual in the area (particularly the young). It is primarily spread through contaminated food and water. Once the virus is consumed, it multiplies in the intestine, whereafter it can spread to the nervous system (causing the debilitating effects we see among polio patients).

This past year, there was a country-wide effort in Angola to immunize all children under 5, a likely cause for the incredible decrease in polio cases since last year. The vaccine is orally administered in 3-4 doses within a given year - usually an infant's 1st year.

I find this to be a somewhat motivating article. Despite the potential for a further polio outbreak, this is a case where public authorities made the right decision in declaring a state of emergency potentially preliminarily. Angola seems to be making the right choices regarding mass-immmunization (bringing back to mind the precept that the entire population has to be vaccinated to prevent disease...). If only we could get our own politicans to be so open-minded about vaccination! (uurrrrgh HPV vaccination!!!)


-Elena Higuchi

Polio-free India and prevention of outbreaks in the rest of the world..

India, a country on which polio has always had a terrible impact, has not reported a single polio case in over 200 days. The country's only polio case reported this year was on January 13 from West Bengal. Along with the absence of new cases, the program responsible for detecting polioviruses in the sewage systems (The National Polio Surveillance Project, or NPSP) in three main areas of the country isn't detecting any either. The sewage surveillance is considered an extremely important component of the early warning system. When polioviruses are found to be circulating in sewage, cases of paralytic polio often follow up.
According to Hamid Jafari, project manager of WHO-NPSP, "Both Type 1 and Type 3 polio viruses were detected in the sewage samples from Delhi during 2010," but since August 2010, when viruses were last seen in the sewers of New Delhi, and early November 2010, when they were last found in the sewers of Mumbai, no more cases of sewage-circulation poliovirus have been detected. Despite these promising news, India is still at a high risk of being a victim of the importation of viruses from elsewhere, especially its neighboring countries such as Pakistan.

Pakistan has recently been confirmed by the World Health Organization (WHO) as a main "exporter" of poliovirus, something that could really be destroying all of India's efforts to remain polio-free if not controlled properly. A cautious New Delhi has therefore intensified surveillance at the India-Pakistan border in Wagah to minimize the import of the virus as efficiently as possible since September 13. In the past month, India has reported the vaccination of 115 children, all below five years of age, who entered the country from Pakistan with the bivalent polio vaccine. Dr. Balwinder Singhm, one of Punjab's immunization officers, reported to "Times of India" about a month ago that "active searching operations" are being carried out at the borders and that "all hospitals near the border have confirmed that there has not been one missed case of acute flaccid paralysis (AFP) to spot any signs of polio being imported. Information boards at Wagah and Attari in three languages - English, Hindi and Urdu - are asking all those coming from Pakistan to immediately contact the health booth if their children aged below five years feel sudden weakness in any part of the body or have been feeling it over the past six months."

Currently, the Global Polio Eradication Initiative (GPEI) says that about 16 countries are facing outbreaks owing to the import of the poliovirus, which is a significant number. Pakistan is amongst the top exporters, having a recorded 136 total cases of paralytic polio to date this year, with over 100 cases caused following the transmission of the P1 strain. It is also the only Asian country this year to have reported the P3 virus, which is on the verge of elimination elsewhere on the continent.
On another sad note, earlier this fall, China reported that viruses from Pakistan had triggered China's first polio outbreak in over 10 years. To date, China has reported 18 cases. (For more information, visit the Global Polio Eradication Initiative website, which provides great information and the most recent updates on the number of polio cases)

The WHO has said: "travelers to and from Pakistan should be fully vaccinated, and travellers to the country who in the past have had three or more doses of oral polio vaccine (OPV) should have another one before they travel. Some countries require travelers from Pakistan to be fully immunized against polio before they grant an entry visa."
Similarly to the WHO's recommendations, the UK has required all travelers coming from countries where polio is endemic to show proof of having received the oral polio vaccine at least 6 weeks prior to travel, and the Kingdom of Saudi Arabia has issued vaccination requirements for travelers of all ages undertaking the Umrah and the Hajj pilgrimages. This should be an effective contradiction to what a great number of Muslim populations believe of the vaccine (especially in Pakistan where so many people refused immunization), as Elena has described in detail below, and will hopefully act as an effective message to increase the number of vaccinations in countries such as Pakistan.

Read more at:

- Julie Saffarian

Saturday, November 5, 2011

Polio Vaccine Myths Affecting Vaccination Campaign in Pakistan

This past Friday, the guardian printed an article about potential reasons for a rise in polio cases in Pakistan. Here is a summary:
In the federally administered tribal areas (Fata) of Pakistan, polio is on the rise. Within the Kyber Agency (a region within Fata) alone, it is estimated that more than 200,000 children have regularly missed immunization since 2009 and nationally 84 cases of polio have been reported so far this year.

What is causing so many people to not get their immunizations for polio, a potentially life threatening and crippling disease? While there is an inaccessibility problem due to security concerns, another huge reason for lack of immunization it seems is reluctance from parents perhaps related to beliefs in rumors about the negative health impacts the vaccine has.

The rumors often start when religious leaders launch campaigns against the polio vaccination through sermons and radio broadcasts. A very influential rumor begun by Maulana Fazlullah, a leader of a banned militant organization and important religious cleric, said that the polio drops cause impotency and infertility and it is an American conspiracy to sterilize and reduce the population of Muslims. Another rumor says that the polio drops are made out of pig fat and therefore forbidden by Muslims. In the past sermons have declared children who died or became paralyzed by the virus martyrs for not falling for western conspiracy.

It doesn’t help that most polio vaccines used in Pakistan are manufactured in WHO laboratories around the world including the USA. Furthermore, news reports about the fake vaccination campaign used by the CIA to track down Bin Laden only help strengthen misconceptions about the polio vaccine.

However, with the resurgence of polio, now religious leaders have joined the campaign led by the National Research and Development Foundation and Unicef to get rid of myths about the polio vaccine. About Five thousand scholars of the Deobandi sect (a school of religious thought which the majority of the people of the tribal belt belong to) have joined the campaign.

Clerics have helped resolve vaccine refusal cases, over 8,000 in Fata in one week of march alone. Religious scholars have issued Fatwas in favor of vaccinations. Health workers rely on working with religious scholars to successfully accomplish their education and vaccination campaigns. In some cases a scholar accompanies the health-worker in their rounds. Before parents would not even allow the health-workers to enter their homes. Now, the partnership with religious scholars and proving make the campaign a lot more successful.

Interestingly, clerics and religious scholars who support the vaccination campaign often take a quote from the Qur’an that sounds very similar to a possible modern public health mission statement. The quote talks about the importance of healing a single human being equal to healing human kind.

--Elena Jordan

Read more at:

Thursday, November 3, 2011

And we have yet to discover so much more about our amazing immune system...

We all know that when the human body becomes infected with a new virus, the immune system is rapidly activated in order to build a response to the intruding pathogen. In the case of the Influenza viruses, a sort of "inborn" protective mechanism is generated by the immune system that helps to fight the virus. Very recently, a new component of this mechanism, a protein called "Mx" (which stands for Myxovirus resistance), has been added to the definition of this immune response.
As we have seen with new strains influenza viruses in the past, such as with the H5N1 bird flu virus or the swine flu virus, these types of viruses have the property of "jumping" from humans to animals at a surprising pace, making it very difficult to control their spread. Although as humans we do not possess any sort of pre-exisiting immunity to these viruses, our immune system is able to rapidly generate a defense mechanism to prevent influenza viruses to replicate and proliferate uncontrollably in the body.
The protein Mx has been described as playing a crucial role in this process, through maintaining the spread of the viruses under control. The exact mechanism through which this protein accomplishes this task was previously unknown, but has recently been described by virologists from the Institute of Medical Microbiology at the Freiburg University Medical Center and biochemists from the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch, Germany. These researchers have, through building a molecular and atomic-level model of the protein, discovered that Mx is a molecular machine that develops its power when all the individual molecules have joined each other to form a ring-like network. A central element of the formation of these ring structures is the special part of Mx known as the stalk, which functions similarly to a "clamp", restricting and deactivating the components of the influenza virus in the infected cell. How are these Mx proteins activated in the first place? Their production has been linked to signals received from interferons, which as we know, are proteins released by cells upon infection with a pathogen. Thus under normal conditions, the protective Mx protein is not found in our healthy, virus-lacking cells.

These new findings about the Mx protein could revolutionize the treatment against influenza viruses, and researchers truly believe that they will form the basis for the formation of new antiviral drugs and for the understanding of other members of this family of proteins.

Read more here!

- Julie Saffarian

Monday, October 31, 2011

Dengue outbreak in Lahore, Pakistan

There's a huge dengue (fever) outbreak in Lahore, Pakistan. The monsoon season hit early and hard, so the temperature and amount of standing water is ideal for mosquito breeding. Over the past month and a half-ish, more than 30,000 people have gotten sick. Hospitals are crammed, and individual health workers sometimes test more than 1000 patents a day. Many have recovered, but 323 people have died. (Interestingly, the only day no one's died is Sunday: the 9th, 23rd, and 30th.) That's pretty amazing, even in a population of 6 million.

It's amazing to me that epidemics can be spread through mosquitos. I think of epidemics as being spread by coughing, but in this case if you're sick and a mosquito bites you and then bites the person next to you in bed, you've effectively infected the other person. Thus, sick patients aren't wearing masks, but are shrouded in mosquito nets! I think they're spraying and sucking viruses up in an effort to contain the mosquito population. See pictures.

The other article.


Nonlytic Escape of Poliovirus

It is assumed that for most naked viruses, the egress of newly formed virions involves only cell lysis, but a study by Karla Kirkegaard, formerly of Stanford, show that nonlytic release via phagosomes was also possible.

A important link to understanding this other method of viral exit is the fact that all eukaryotic +ssRNA viruses replicate genetic material on membranes in the cytoplasm (e.g. mitochondrial, ER, Golgi).

Kirkegaard postulates that polioviruses and some other nonlytic viruses can induce and be ecapsulated by cytoplasmic double-layered membranes, in which they mature and are eventually shipped out to the extracelluar fluid.

Despite the normal use of this autophagy pathway to degrade intracellular components, the digestive properties of said double-layered membranes seem to be ineffective or inhibited by nonlytic viral invaders.

Inhibition of cellular autophagy resulted in a lower yield intracellular viruses (because they are dependent on these membrane surfaces) but an even lower yield of extracellular virus; this is consistent with the non-lytic escape hypothesis.
Furthermore, experiments in which cells were polarized such that vesicles would only exit in one direction and infected with poliovirus showed virion emergence from the predicted side of the membrane.



Hantavirus in India

A case of hantavirus infection has been discovered in the Karimnagar District of Hyderabad, India. This is considered the first reported case of hantavirus in the state, and Yashoda Hospital specialists are apprehensive of future cases to come. The man, Bhagavan Rao, was admitted to the hospital with cough and shortness of breath, only to fall into intense cardiac arrest the day afterwards. He was revived, placed on a ventilator, and appears to be slowly recovering. He is non-responsive and probably blind.

His physician, Dr. M V Rao, sent samples to Mumbai under suspicion of hantavirus. They came back positive, and Dr. Rao presence of rodents in the area, especially deer mice. This poses interesting questions in relation to the 1993 outbreak in the Four Corners Area of the United States. Should precipitation increase in the Karimnagar District, should the hospital take precautions in preparation of more hantavirus cases?


Act supporting research into antibacterial-resistant solutions introduced to Senate

The GAIN Act (Generating Antibiotic Incentives Now) was introduced into Senate last week. It's currently supported by both democrats and republicans in the House and the Senate, however, so far it has taken a backseat to the overshadowing issues of economic crisis.

This act seeks to make research into solutions for antibiotic-resistant bacteria profitable enough to attract pharmaceutical companies to devote their resources to the problem. Pfizer and Johnson&Johnson, both large pharmaceutical companies, have recently shut down some or all of their antibacterial resistance research, because the profits are miniscule when compared to other drugs they manufacture. The mot profitable drugs for large pharmaceutical companies are those that have to be taken for years and even decades. Drugs that would fight antibiotic-resistant bacteria would only need to be taken for a few days.

These shutdowns come at a bad time, as deaths from anti-biotic resistant diseases have reached a high this last year, causing about 70,000 deaths in the United States. These infections are mostly hospital-acquired, and are often MRSA or vancomycin-resistant enterococci. Additionally, these infections cost the U.S. healthcare system up to $34 billion a year.

The author of this article was pessimistic that the incentives offered by the GAIN Act would be enough to encourage pharmaceutical companies to continue their research. Until this issue becomes a crisis, it's just more profitable to make other drugs.

--Sarah Kaewert