Monday, January 31, 2011

H1N1 death toll rises to 25 in Italy

It has been one month since the start of 2011 and already 25 people have been killed by the H1N1 virus in Italy. 14 more are in hospital beds receiving medical attention. Due to the high infection rate of the italian population, the Italian Health Minister, Ferruccio Fazio, has launched a campaign encouraging the administration of influenza vaccinations to all (especially those who are immunocompromised, children, and pregnant women).

What interests me is the diverse group of people affected. Italy protrudes into the center of the mediterranean and is a destination of immigration (both legal and illegal) from all areas of the mediterranean. It makes sense therefore that the incidence of disease, relative to the population size, is higher in Italy. Since influenza so readily mutates, perhaps the strains that affect this group of very diverse hosts are different as well.


Biological challenges and technological opportunities for Respiratory Syncytial Virus Vaccine (RSV) Development

A recent paper published December 28, 2010 discusses the production of a vaccine against RSV. This virus does not currently have any good forms of treatment, and it is suggested that vaccination would be the best way to tackle the illness in the population. One major argument for producing a vaccine is that RSV is not known to have any intermediate host or animal reservoir and so successful vaccination could completely change the ecology of the disease. However, there are major challenges that scientists are encountering in producing a viable vaccine for RSV.

One barrier is the early age of infection of RSV. RSV is most common among infants who are an extremely immunological fragile population and cause an array of complications when it come to developing vaccines.

Another set of challenges has to be with the way RSV interacts and activates the immune system. RSV has the capacity to evade innate immunity by limiting type I interferon responses (IFN). Two RSV proteins, NS1 and NS2 (non-structural) are encoded at the beginning of the geonome and collaborate to inhibit IFN-associated genes. RSV also hs mechanisms to inhibit TLR signaling. The effect is especially bad for infants who have a weak innate immune response.

Other factors that present hurdles to vaccine development are that RSV does not produced adaptive immunity to prevent reinfection, there is a history of RSC vaccine-enhanced disease, and they lack an aminal model for RSV.

The two current solutions that are being worked on are live attenuated viruses. Live attenuated viruses are attractive because they can be given parentally or mucosally, which among infants is safe. Live attenuated RSV and replication-competent chimeric viruses are in advanced clinical trials.

- Lauren Platt

Source: Graham, B. Biological challenges and technological opportunities for Respiratory Syncytial Virus Vaccine (RSV) Development. Immunological Reviews. 2011. 239: 149-166.

Sunday, January 30, 2011

From Russia with love: Influenza outbreak

by Laura Huaman

As reported by the WHO, flu in Europe is spreading from west to east and is slowly increasing, with some European countries reporting widespread and others regional spread.

According to Moscow’s health chief Leonid Pechatnikov, over 90,000 people got infected with flu in the city over the past week. The A/H1N1 strain is also going around, with 93 people infected in Moscow and killing a few people across Russia including in Chelyabinsk region in the Urals.

Since January 31, elementary and middle schools in Moscow will have five days off due to the influenza outbreak. As a result, about 550,000 students will not go to school in this quarantine period. About 300 schools have been closed.

On a positive (?) note, the Russian capital is ready for the epidemic and has enough hospital beds and drugs to care and treat any flu victims. It will be interesting to see how these prevention methods work in the rise of the epidemic. It is a good sign that health centers are starting to prepare for a greater outbreak.


Rotavirus Vaccine is super effective

Two rotavirus vaccines, one live attenuated and the other a hybrid of bovine and human rotaviruses, have been used in routine infant vaccinations since 2006 in the United States and Europe. The vaccines produce immunity 80% and 98% of the time in industrial nations and 39% to 77% in developing nations. Because of the vaccine’s success in the United States and Europe, other countries have adopted it as part of their infant vaccinations. A review of the vaccine’s effect in El Salvador, Panama, and Mexico since 2008 has shown positive results. There has been a decrease in childhood mortality due to diarrhea, a decrease in the severity of cases, and a decrease in the number of hospitalizations because of diarrhea.

Two important conclusions have been drawn from these studies. First, the vaccine should be included in standard infant vaccinations around the world. Second, the benefits go beyond the protection of those that are inoculated. Vaccination generates herd immunity so the decline in cases is greater than would be expected. Furthermore, the pattern of vaccination combined with the reduction in cases suggests that infants are important in the transmission of rotavirus. As a result, we can optimistically look forward to a precipitous decline in the number of rotavirus cases in the world.


There is much more information about the implications of the rotavirus vaccine studies in this Pediatric Infectious Disease Journal article:

Type B Influenza is a moving target for the flu vaccine

The CDC has found that about 8% of the Type B influenza viruses that have been collected and characterized in the United States this year are from the Yamagata lineage. Protection against this strain of influenza is not included in the seasonal vaccine. As a result, even those who have been given the influenza vaccine may contract this Type B strain. Luckily, Type B influenza makes up only about a third of the influenza viruses collected so a very small percentage of the flu viruses in the population will not be covered by the vaccine. A few cases slipping through the cracks is normal because the vaccine only protects against three strains of the flu each year as recommended by the WHO. My personal takeaway is that it is still important to wash you hands whether you get the flu vaccine or not.


HIV prevention & the female condom: “The international denial of a strong potential”

by Laura Huaman

The failure of recent trials to show the efficacy of
new microbicide candidates and the diaphragm,
make the promotion of the female condom as a
life-saving intervention more prominent than

-John McConnell, Editor, Lancet Infectious Diseases, 2008

The female condom (a transparent sheath with the same length as the male condom and a flexible ring at each end), which was introduced in 1984, has not received as much attention as expected, given the number of women with HIV globally and the increased support for women’s right to health. On the contrary, as Peters et al comment, the female condom has been marginalized in the international response to HIV/AIDS. In a new article published by Radboud University in the Netherlands, the authors analyze the views and actions of “users, providers, national governments, and international public policymakers […] using a framework to evaluate access to new health technologies in poor countries.” The article argues that barriers to universal access to female condoms mainly arise from issues of acceptability at the international policy level, and not, as it is usually believed, due to users’ or local governments’ unwillingness. The authors concluded that global public policy makers hide behind the argument of high prices and the myth that there is no demand and thus no market for the female condom. Female condom programmes have been “sabotaged by problematising acceptability among users.”

The article reminded me of my experience teaching about HIV/AIDS and reproductive health to a group of mamas in a Tanzanian village outside of Arusha. Most of the women my group and I got to talk to had never heard about the female condom. When we went to the duka (a local stand store) to find out if they sold any, they didn’t. However, the organization I was working with, SIC, did leave female free female condoms for the dukas to try to sell. Some of the women we had spoken to did buy the female condoms and were excited about purchasing more.

Indeed, the female condom is an incredible strategy to reduce the risk of HIV infection and gives autonomy to women to protect themselves and not to solely rely on their partners. Female condoms for preventing HIV and other STIs are also cost effective, as the reading suggests. Even though some men in certain parts of the world may oppose women’s use of female condoms, teaching women about them and making them accessible to them is still a form of empowerment, and thus a method to reduce to the risk of infection with HIV and/or other STIs.

Anny, P. "The Female Condom: The International Denial of a Strong Potential." Reproductive health matters 18.35 (2010):119.


Malaysia Releases 6,000 Genetically Modified Mosquitoes into the Wild

Over the protests of environmental groups and NGOs, Malaysia has released 6,000 genetically modified mosquitoes into the wild, hoping to drive down incidents of mosquito-borne dengue fever. The experimental mosquitoes, all male, were engineered to produce offspring that quickly die in hopes that shortening life spans will thin the population of Aedes species (dengue fever is carried by females).The experiment was conducted less to see if the GM mosquitoes’ offspring would die off earlier and more to see how the 6,000 mosquitoes themselves would fare in the wild. That also happens to be the sticking point for environmental groups and locals who are incensed that the Malaysian government went ahead with the experiment over their protests. Tweaking genomes, critics say, could lead to unforeseen and uncontrollable consequences. It’s the first experiment of its kind in Asia, but naturally everyone isn’t thrilled with the idea of releasing altered DNA into the ecosystem.

This, to me at least, seems wildly irresponsible, releasing 6,000 mosquitos into the wild with no knowledge of the possible consequences. If the mosquitos somehow have other unforeseen genetic effects, it will be incredibly difficult to reverse these effects, as 6,000 mosquitos will produce too many offspring to possibly kill/control.

-Catalina Angel

Full article:

Hepatitis B Blood Screening: Nucleic Acid Testing

Hepatitis B is an important blood-borne virus that has posed a major public health risk because of significant spread through donated blood. Infection with Hepatitis B has serious consequences, including liver failure. Today, all banked blood in the United States is tested for Hepatitis B and other particularly devastating diseases in order to prevent infection in the recipient. However current tests only look for the hepatitis B surface antigen and antibodies against hepatitis B core antigen. This means that detection of the virus is only possible after the donor has seroconverted, leaving a hole for potentially infected blood to enter the system.

The new method in this paper uses nucleic acid testing rather than antibody testing to directly identify the pathogen. Using their methods, researchers were able to identify some donors who tested positive but were negative using the traditional methods. The tests successfully detected HBV, HCV, and HIV in the seronegative blood samples. This more sensitive test may translate in greater reduction in transmission of HBV, HCV and HIV in the future.


Several Measles Cases Reported in Brisbane with Potential Exposure to a Movie Theater and Mall

Queensland Health officials have reported that there are have been three distinct cases of measles in Brisbane over the past several weeks. One 21 year old man was known to have contracted the virus after disembarking from a flight in the city. Two other adolescent patients were traveling in India when they contracted the disease and had since returned to Brisbane before experiencing symptoms. Public Health officials are worried that all three may have passed the extremely infectious disease on to others. The 21 year old man visited a major shopping mall and was known to have made several transactions in addition to eating at the food court during his infectious period. One of the adolescents visited a movie theater during his infectious period. The other adolescent visited Stamford Village and went shopping at a grocery store.

Because measles is so contagious (R0 = 15-18), it is very likely that one or all of these individuals passed measles on to a new host. While vaccination coverage for measles has been high in Australia, worries about Autism have caused vaccination for measles and other diseases to decline in the same manner as in other parts of the world. Based on the incubation period for measles, 10 days, individuals who became infected at the mall will soon begin to show symptoms. Queensland health officials are urging all individuals with potential exposure to get an additional vaccination and to watch for the symptoms of the disease. Health officials are currently in a 'wait and see' mood to determine if this will become an outbreak, or if vaccination levels were effective at creating herd immunity.


Paraguay en route to be free of canine rabies

The article I read was national news shared by the country about the WHO and PAHO’s, Pan American Health Organization) recognition of the state for “enhancing the leadership of the eradication” of the canine rabies disease. With strong leadership it seems as though Paraguay will soon be certified to be free of canine rabies.

There was actually a 13th Meeting of Directors of Rabies Program in Latin America that was held last August in Buenos Aires, Argentina!

I am not too knowledgeable about the rabies disease, so I thought it was a good quick summary of the disease and beneficial as a national announcement to help make others aware of the dangers of rabies.

We briefly reviewed rabies on the first day of class, but here is the summary from the article. Rabies is caused by a rhabdovirus that leads to acute encephalitis, disease of the central nervous system, with a mortality near 100%. The virus is found in both animals and humans, in the saliva and secretions of infected animals. The virus spreads through the lymphatic vessles and attacks the nervous system, with a variable incubation period, ranging fromone to six months. The patient suffers from hydrophobia, which often leads to dehydration, as well as spasms and foamy salivation. The infection of the nervous system continually worsens and leads to attacks of rage followed by paralysis. The disease has no current cure, but the rabies vaccine that can be given at the initial incubation has shown to be very effective.


Saturday, January 29, 2011

Using MicroRNAs to Combat Flaviviruses

In this recent NIH study, researchers Heiss, Maximova and Pletnev demonstrate microRNAs (miRNAs) incorporated into the flaviviral genome of a chimeric tick-borne encephalitis/dengue virus (TBEV/DEN4) alter virulence in numerous cell lines and rhesus monkeys. Beginning with an in vitro analysis on Mosquito C6/36, Vero and rat neural cells, it was found that the presence of highly expressed miRNAs incorporated into the TBEV/DEN4 genome limited viral replication in developing primary neurons. They go on to illustrate the necessity of incorpated-miRNA attenuation by showing a significant decrease/abolishment of neurovirulence in mice. They illustrate sufficiency by making a single point mutation of the miRNA target sequence, restoring neurovirulence. Lastly, they conduct an analysis on viremia in rhesus monkeys, demonstrating a lower and shorter viral titer with the miRNA modified viruses.

Though they do not suggest any approaches to clinical applications, they do assert from this analysis and their experience with the mir-T9 virus, that attempts to target the flavivirus genome using microRNA would not be beneficial for vaccine development.

Brian L. Heiss, Olga A. Maximova, and Alexander G. Pletnev. Insertion of MicroRNA Targets into the Flavivirus Genome Alters Its Highly Neurovirulent Phenotype. Journal of Virology, February 2011, p. 1464-1472, Vol. 85, No. 4

- Vy Tran

Gaps Remain In China's Ability To Detect Emerging Infectious Diseases Despite Advances Since The Onset of SARS and Avian Flu

China has made many improvements with respect to tracking outbreaks since the SARS outbreak in 2003. At the time, China was not equipped to successfully isolate the virus with effective nationwide surveillance and SARS quickly became a global scare. After the SARS outbreak, the government in China devoted substantial funding for the creation of a public health surveillance infrastructure (from county to national level) and created many centers for disease control and prevention. The centers receive reports on symptoms and diseases from doctors but it is not standard for specimens to be sent in. China also lacks a database (like PulseNet in the US) for identifying particular strains of disease. In order for their program to be able to prevent the spread of disease and provide a plan of action for treatment, pathogen-based surveillance should be implemented.


A Novel Approach to Rabies Vaccines

Yongjun Wen and colleagues at the University of Georgia, Athens have a new and clever proposition for a Rabies virus vaccine: engineering viruses with an immunological beacon.

As discussed in the paper, the current state of the Rabies vaccine is not ideal. At least four doses must be administered over the course of two weeks at a high cost ($600 for four shots), local reactions and extreme inaccessibility to developing countries. Recent endeavors have been made in attempt to combat these issues.

Previous research by this group provided evidence that recruitment and/or activation of dendritic cells (DCs), the most effective antigen-producing cell, is important in enhancing the immune response against Rabies Virus (RABV). In this present study, they go on to engineer recombinant viruses(rRABV) with different immunologic "beacons" (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage-derived chemokine [MDC], macrophage inflammatory protein 1 [MIP-1]) that recruit and/or activate DCs.

Using both in vitro and in vivo techniques, the rRABVs were shown to induce maturation (differentiation from monocytes to immature DCs) and activation of DCs from mouse marrow, induce in vivo recruitment and activation of DCs and other immune cells upon rRABVs intramuscular injection, and confer greater immunogenicity without causing an increase in virulence or obvious clinical symptoms. From these data, Wen et al. go on to propose applying rRABVs in vaccines.

Yongjun Wen, Hualei Wang, Hua Wu, Fuhe Yang, Ralph A. Tripp, Robert J. Hogan, and Zhen F. Fu. Rabies Virus Expressing Dendritic Cell-Activating Molecules Enhances the Innate and Adaptive Immune Response to Vaccination. J. Virol. February 2011 85: 1634-1644.

Direct link:

Also, regarding the photo, here is the unintentionally hilarious context I discovered while googling for Rabies images:

- Vy Tran

DTP Vaccine Administered Simultaneously with Measles Vaccine Is Associated with Increased Morbidity and Poor Growth in Girls- A Randomized Trial from Guinea-Bissou

A study was recently conducted in Guinea-Bissou, West Africa regarding the common occurrence of administering the DTP (diphtheria-tetanus-pertussis) and the measles vaccine at the same time. It is currently recommended that the measles vaccine be given at 9 months of age (after the 3 doses of DTP have already been given). However, many of the children in the population aren't able to go to the doctor to match this specific schedule. It has become very common for children to receive MV and DTP on the same visit. This study aimed to look at the risks associated with this practice.

The researchers enrolled children ages 9 months-48 months into 2 groups, one which received MV+DTP+OPV (the polio vaccine was constant between the two groups) and one which only received MV+OPV. All participants had previously received 2 doses of DTP. The Bandim Health Project (a recent infrastructure created to monitor health in Guinea-Bissou) documented morbidity and mortality in the two groups every three months. The results were most significant for the girls, with increased morbidity in the MV+DTP+OPV group from higher rates of diarrhea, use of medication, febrile disease with vesicular rash, and hospitalizations.

Although this article might be significant as an argument to keep to the recommended vaccine schedule, the evidence to directly link the administration of MV+DTP+OPV to increased morbidity seemed unsatisfactory to some degree, as there is likely a lot of variation in the lifestyles of each group that could have led to infection (if the behavior of the 2 groups was controlled more tightly, the results would seem less like correlation). Given the fact that the trial could have been more tightly controlled, it might have been unwise to publish results condemning vaccine use in case it triggers uneasiness among the population


AFLOCKALYPSE: HPAI update, as seen by the medical community and in pop culture.

ProMED Mail 25 January 2011,, SNL.


Confirmation of H5 subtype positive isolate from a dead oriental magpie robin in the Yuen Long region on January 19th suggests that the Mai Po Nature Reserve (MPNR) and three poultry farms may be at risk for HPAI, now under enhanced surveillance. Currently no abnormal deaths of signs have been observed in the flocks. The Agriculture, Fisheries and Conservation Department (AFCD) has responded strongly, ordering the disinfection of the park in which the dead magpie was discovered, issuing advisory messages to poultry farmers, pet shop owners, and pet owners, inspecting farms and the wholesale market. Since the 4th of the month, the AFCD has inspected nearly four hundered villages, but has not uncovered unauthorized poultry. The current maximum fine for the unauthorized holding of chickens, ducks, geese, pigeons, or quails is approximately US$6400, and repeat offenders may face a fine of US$12,800.


Following the discovery of 20 dead chickens on January 23, with 5 of 6 birds testing positive for H5N1, approximately 410 000 chickens were ordered culled this month in Miyazaki. Just prior, after 36 chickens were revealed dead at another farm on January 21, leading to the killing and incineration of 10 200 birds this past weekend. HPAI subtype H5N1 was also detected in isolates from wild birds in the area (23 January 2011). The first national case concerning HPAI in domestic poultry occurred in November 2010, and these recent developments inflate concerns for health and prosperity in the Shimane Prefecture. Miyazaki is recognized as a major poultry producer, and development of the regional outbreak suggests a major economic blow that could cripple the local industry.


The overnight death of possibly 5,000 red-winged blackbirds in Arkansas suggested the possibility of an outbreak of HPAI, but recent results published by the University of Georgia in their Southeastern Cooperative Wildlife Disease Study have ruled out viral, bacteria, and poison causes, and point towards blunt-force trauma.

Others have suggested alternate causes… go to 43:00.


Rotavirus Vaccine Success

A study published in the Pediatric Infectious Disease Journal recently shows that rates of hospitalization from rotavirus infection have gone down significantly in countries where rotavirus vaccination has become part of routine childhood immunizations. The study included the United States, Australia, Mexico, and El Salvador, all countries where the rotavirus vaccine has recently become routine. The vaccine has shown effectiveness not only among young children, but has shown a decrease in disease among older children and adults as a result of herd immunity. Rotavirus is a significant cause of disease among young children and adults worldwide, and these studies suggest that governments and international donors should put a high priority on rotavirus vaccination.


Friday, January 28, 2011

Oh, Canada! PDV erupts?

ProMED Mail 22 January 2011, a report from my homeland...

Premature deaths of harp seal adults and pups have risen in recent weeks, with storm surges in the Atlantic bringing corpses ashore in January 2011, mainly along the coast of Newfoundland and Labrador, but also in the St. Lawrence region. Confirmed deaths are currently in the low hundreds so far, but there are also reports of premature births, or “early pupping”. Harp seals (Phoca groenlandica) migrate south on the east coast of Canada in late fall/early winter to breed, with regular parturition occurring at the end of February and early March. On average, about a quarter of pups in their first year suffer premature death—this does not account for the washed up seals, as this mortality soon declines with age, leveling off to approximately four percent.

A possible cause of the mortalities is porcine distemper virus (PDV), which is enzootic in the population. PDV is a morbillivirus (genus shared by viruses causing human disease, including measles), part of the paramyxoviridae family. Though epizootics have slain thousands of seals across the Atlantic, major viral epizootics have not been previously observed in Canada, possibly due to herd immunity, with 83% of seals in a Canadian sample seropositive for PDV. Poor ice conditions and herd size may contribute to the susceptibility of the population to epizootic.


Tanzania Sets Up Yellow Fever Vaccine Checks at Border Crossings with Uganda

As the outbreak of yellow fever in Uganda continues to spread, officials in East Africa concluded a meeting discussing disease prevention strategies in the region. Over 190 cases of yellow fever have been reported in Uganda so far with 48 confirmed deaths. The Tanzanian Health Minister has ordered border officials to require proof of yellow fever vaccination before allowing individuals to cross the border. Similar measures have been implemented in major airports throughout the country. In addition to screening for prior vaccination, public health officials are administering the vaccination at these locations.

So far there have been no reports of yellow fever in Tanzania, but public health officials were not ruling out the possibility, either because of individuals who crossed the border before the increased measures were implemented. In addition, the vaccine may take up to 10 days to confer immunity to yellow fever, so it is possible that even individuals who receive the vaccine at the border could bring the disease into the country.


Wednesday, January 26, 2011

Smallpox Safari presents....The Death of Smallpox

From Bob's smallpox seminar, mostly for entertainment value:

Nina aka "smallpox"

Poxvirus A33 protein

Smallpox, the first eradicated virus, was successfully eliminated thanks to the Vaccinia virus vaccination. Vaccines against Vaccinia have largely targeted the poxvirus protein A33 (a conserved protein within the chordopoxvirinae subfamily). It wasn't until very recently, however, that the structure and function of this protein was identified.

The A33 poxvirus protein structure was studied through many methods. However, in X-ray crystallography of the protein it was discovered that the structure revealed C-type lectin-like domains, occurring in dimers. This bore remarkable resemblance to the CTLD structure seen in the binding of NK cells (specifically, "long-loop," dimeric protein binding). In further investigations of gene expression and protein folding, scientists realized that, just as CTLD in NK cells, A33 facilitates interactions with both viral and host ligands, acting as a binding protein.

In order to test it's efficacy as a binding protein, mutations and truncated versions of the A33 pox protein were made and tested in vitro. It was found that the viruses with mutations or truncated A33 proteins were much less virulent than the WT. All experiments supported the hypothesis that the pox proteins were CTLDs, and all findings implicated A33 as a crucial binding ligand.

Though smallpox has been eradicated, the identification of the viral CTLD B-sheet binding structure helps us understand common mechanisms of viral invasion and replication. Furthermore, as we observed in tests of the truncated proteins, the binding proteins (which seem to have similar dimeric domains as our own cells) are important to viral virulence. Therefore, perhaps targeting the CTLDs/ binding proteins of not only poxviridae but also other viral families as well could lead the discovery of new forms of vaccines.


Using rabbitpox to model smallpox transmission in the lab

As we've discussed in class, the fear of smallpox as bioterror weapon has stimulated research toward new treatments and vaccines. However, because the new treatments developed cannot be tested on humans, it is important to find comparable animal models to use in safety and efficacy trials.

In this study, scientists used rabbitpox to simulate smallpox due to its airborne transmission. Researchers found that when rabbits were exposed to low levels of the virus, the effects of rabbitpox on rabbits were similar to the effects of smallpox on humans. Transmission, incubation, prodromal phase, clinical signs, skin lesions, and complications were all comparable. Rabbitpox caused "viral dissemination, secondary lesions, and animal-to-animal transmission and lethality". Because these results are similar to what we know about human exposure to smallpox, the rabbits were seen to be a successful animal model for smallpox.

As with all animal models, using rabbits has its limitations. The paper notes that because there are no knock-out rabbit strains, it is difficult to study all types of disease pathogenesis and how the host-immune system might respond in various cases. In addition, their are few immunological reagents that can be used with rabbits. However, overall they found the rabbit to be an "excellent animal model" that will enable the testing of new vaccine and antiviral developments against smallpox.


Tuesday, January 25, 2011

Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18

Coxsackievirus is in the picorna family and is a (+) ssRNA, nonenveloped virus.

January 18, 2011

This paper explores the oncolytic potential of Coxsackieviruses A13, A15, and A18. Oncolytic virotherapy works because the specificity of lytic viral infection can be used to selectively kill malignant cells while leaving normal host cells intact.

This study looks at Malignant melanoma, which affects the skin cells responsible for pigment. To find these cells, microbiologists have identified a cell surface molecule, ICAM-1, that is overexpressed in cancerous cells. Biologists use ICAM-1 as a marker in order to understand the progression and metastasis of the cancer.

To help virotherapy be more successful, the strategy of using a subset of Coxsackieviruses that are unrelated but still recognize the receptor is used. It concluded that Coxsackieviruses A13, CVA15 and CVA18 have high potential for cancer therapy because their entry receptor is already expressed in abundance on the surface of affected cells.

-Lauren Platt

Au, G., Beagley, L., Haley, E., Barry, D. and Shafren, D. Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18. Virology Journal. 8:22, doi:10.1186/1743-422X-8-22.

HepC Patient Charged with Attempted Murder after Spitting on Nurse

An Alaskan Man by the name of Andre LaFrance was initially charged with attempted murder because he spat on a nurse. This man is also infected with Hepatitis C and state troopers say the 29 year-old man “’intentionally transferred a dangerous bodily fluid’ onto the hospital employee.”

The patient was admitted to the hospital under reports of a drug overdose, but examination suggested this was not true. LaFrance also stated he was suicidal and would harm himself. Thus, the staff attempted to restrain him until the troopers would arrive. He threatened to spit on whoever put restraints on him, and he did just that.

It has been updated that the initial charge of attempted second-degree murder was reduced to third-degree assault. He is currently under suicide watch, and precautions are being taken because of his infection with Hepatitis C.

Hepatitis C is contagious through blood and bodily fluids, and the chances of catching the virus through saliva is quite low.


Hepatitis C Virus: Flavivirus, +ssRNA, enveloped

Monday, January 24, 2011

Potential New Target for HIV Therapy

Recent studies at the University of Rochester Medical Center and Emory University have opened up a new area of investigation for HIV therapy.

The research is based on the idea that HIV likes to "hide" from the immune system in macrophages. Unlike most cells that HIV infects, macrophages lack sufficient levels of dNTP (deoxynucleoside triphosphate), the molecule that the virus needs to build its "viral machinery". Instead, macrophages have rNTP (ribonucleoside triphosphate). This study monitored the effects of blocking HIV interaction with rNTP.

Results showed that blocking HIV's interactions with RNTP limited HIV's potential to replicate within macrophages by over 90%. This suggests that HIV will use rNTP instead of dNTP to replicate if rNTP is the only resource around.

Most current HIV drugs target dNTP. The researchers claim that these results show promise for the development of new, non-toxic, HIV-related drugs that use rNTP as a target. They suggest that using rNTP targets could even slow HIV earlier in the infection process because macrophages are one of the first cells infected by HIV in the genital tract. The next step will be to test rNTP targeting compounds (which have already been used in developing anti-cancer therapies) to see if they are effective against HIV.


Undiagnosed Hemorrhagic Fever, India

Another patient in India has been hospitalized because of an undiagnosed Hemorrhagic fever. This patient, Sampat Jain, is currently being taken care of in Mumbai's Kasturba hospital awaiting diagnosis by doctors and tests from the National Institute of Virology. After observing all the patients signs and symptoms and performing numerous test, authorities originally named Crimean-Congo Hemorrhagic fever a potential cause of the disease.

Crimean-Congo Fever is part of the family, Bunyaviridae. It is and RNA virus that is particularly prevalent in East and West Africa, with a mortality rate of 30%. This disease is arbo, spread mostly by ticks, and often infects those who handle animals. Health officials surveyed the surrounding area and neighboring families, but have not reported any more cases.

In the first of the two sources below, it was announced that the probable cause of illness was CCHF. This seemed unlikely, though, when considering the means of transmission and the geographic areas affected. (The virus is neither endogenous nor common in the area.) On sunday officials declared that the patient did not have CCHF. However, both human patients and cattle (large mammals who also carry the virus) are still being tested for the virus.

Further tests have yet to be performed, but so far the patient's fever, brain hemorrhage, and renal failure have left him in critical condition.


btw last week there were several cases of mystery hemorrhagic fevers in Gandhingar, India. Perhaps the same virus is responsible for this Mumbai's case as well.

Potential vaccine for Chickungunya virus

Inovio Pharmaceuticals has announced that a recent study testing a vaccine for the Chickungunya virus had positive results. Chikungunya is an insect borne virus found in Africa and Asia and it is transmitted to human by Aedes mosquitoes. Chikungunya is in family Togaviridae and is a +ssRNA virus. The main reservoir for the virus is monkeys. The Makonde root, kungunyala, means to bend up, which is a reference to the posture of people with severe arthritic symptoms. Chikungunya causes fever, joint pain rash and eye inflammation. Currently there are not any approved vaccines for Chikungunya. The vaccine provided 100% protection in mice and is also being studies on rheus monkeys with good results.

Hannah Harrison

Pediatric AIDS Foundation attempts to reduce MTCT of HIV in Zimbabwe

The Elizabeth Glaser Pediatric AIDS Foundation is leading a five-year, $45 million campaign to eliminate pediatric AIDS in Zimbabwe. The money for the project came from a grant from the Children’s Investment Fund Foundation. The program will focus on prevention of mother-to-child transmission of HIV (PMTCT). Particular attention will be given to women in rural areas without access to health services. It is thought that 13% of pregnant women in Zimbabwe are HIV positive and that few of these women are receiving any prenatal care. When drugs are given for PMTCT, women often only receive a single dose of Navirapine and are not given the significantly more effective new drug therapies.

The Pediatric AIDS Foundation is directing their resources towards testing, training services and counseling for women. They are, however, relying on the government of Zimbabwe to provide the drugs for PMTCT. The Pediatric AIDS Foundation has suggested that the money for drugs will come from the Global Fund to Fight AIDS, TB and Malaria but due to corruption, political instability and a ruthless dictator, many organizations are reluctant to provide the government of Zimbabwe with money.

While the Pediatric AIDS Foundation is attempting to reduce pediatric HIV infection, testing programs are useless if drugs are not available to women who test positive. It is also unclear from the article what kind of training will be provided to health workers. Zimbabwe has an enormous problem with the ‘brain drain’ and many trained medical professional leave the country after receiving training. It remains to be seen how the Pediatric AIDS foundation will ensure that the $45 million is spent on long-term sustainable HIV prevention.

Hannah Harrison

Molecular Dating in the Evolution of Vertebrate Poxviruses

Babkin, I. V. and Babkina, I. N. Molecular Dating in the Evolution of Vertebrate Poxviruses. Intervirology. 2011. 2-8. DOI: 10.1159/000320964

This study used the Bayesian relaxed clock method to look at the evolutionary history of vertebrate poxviruses that have a AT-rich genome. In order to provide estimates for divergence, this technique is based on a probablishtic moel of the change in evolutionary rates.

Before this study, the authors did a study on the molecular evolution rates of a different group of poxviridae Orthopoxvirus and concluded that the rate of mutation accumulation in the genome was 1.7-4.8 x 10-6 nucleotide substitutions per site per year. This number is considerably lower than the rate of genomes for RNA virses, but it is 2 orders of magnitude higher than the molecular evolution of their host.

The use of molecular dating of viruses is still being verified and validated, particularly with DNA viruses that have an extended genome. These viruses generally have a lower rate of mutation accumulation in their genomes. The Bayesian relaxed clock is generally accepted because it takes into account an inconstant evolutionary rate.

The methodology also considers historical data, such as in this case the genetic relation between two virus strains from West Africa and South American which independently evolved from a common ancestor for a known time period.

When performing evolutionary analysis, highly conserved genes that are a result of stabilizing selection allow a high reliability. Also, it is good to select the geomic loci with a low probability of recombination events.

The results were that the rate of accumulation of nucleotide substitutions is estimated at 0.5-7 x 10-6 nucleotide substitutions per site per year. This meant that Avipoxvirus is estimated to have diverged from the ancestor 249 + or – 69 Tya.

-Lauren Platt

Source: Babkin, I. V. and Babkina, I. N. Molecular Dating in the Evolution of Vertebrate Poxviruses. Intervirology. 2011. 2-8. DOI: 10.1159/000320964

Sunday, January 23, 2011

Rabies in Indonesia

2 residents of Indonesia’s Nusa Penida district of Indonesia have died of rabies. These cases are assumed to have spread from a rabies epidemic on the nearby island of Bali. The district has issued an “extraordinary situation” alert in response to the deaths.

Dog bites were responsible for both of the identified cases. In light of this information, other residents who have been recently bitten by dogs are now suspect rabies cases.

According to The Bali Times, officials have responded to the rabies deaths by killing more than 1,000 stray dogs. Unfortunately, Nusa Penida is inhabited by many wild dogs that live in the surrounding wilderness so eliminating the rabies threat will require a long term investment.


Hantavirus spread in the Four Corners region has been linked to the decline of Aspens

According to the New York Times, a decline in the aspen population occurred in 2004. As a result, the deer mice population in the same areas have increased. These deer mice are carriers of the Sin Nombre virus. Sin Nombre is a Hantavirus with a 40% fatality rate and causes about 20-40 cases each year in the United States mostly concentrated in the Southwest. Deer mice in areas that have experienced a die-back of aspens are 3 times as likely to carry the virus. The virus has very little effect on the mice themselves. Humans become infected through a respiratory route, often dirt with deer mouse saliva or urine in it.

Further loss of aspens is projected as a consequence of climate change. Increases in the population of deer mice and therefore the Sin Nombre virus are likely. This change in the threat of an infectious disease due to climate change is probably just one of the first of many similar stories we will see unfolding as we shape the environment.


UNICEF and Gates Foundation support Angola's efforts to eradicate polio

Anthony Lake of UNICEF and Tachi Yamada of the Gates Foundation will have arrived in Angola by this weekend and support the Angolan government in its efforts to eradicate polio. Angola has been certified polio-free for its third year in 2004, but faced an outbreak of 32 cases of poliomyelitis in Luanda in 2010. This is a major setback in trying to interrupt the transmission of polio around the world, especially because 1 case of poliomyelitis indicates that there are at least 200 others who are infected with no symptoms. UNICEF and the Gates Foundation hope to interrupt transmission of polio by vast immunization coverage throughout the country and also aim to restructure the public health system of Angola.

The last case of poliomyelitis reported was on December 23rd, 2010. So it has been an entire month that the world has not seen a polio case.... Although it is depressing to say this, polio is probably still around.


Sex, Race, and Geography Influence Health Outcomes Following Primary HIV Infection

Women, nonwhites, and people in the southern United States who were newly infected with HIV and followed for an average of four years experienced greater HIV/AIDS-related morbidity compared to men and people of other races living in other regions of the country.The findings, published in the February 15 issue of The Journal of Infectious Diseases, underscore the urgent need to improve the health of these populations in order to reduce HIV-related morbidity and mortality in the U.S.

During the course of the study (1997-2007), the frequency of HIV-related illnesses in women was more than double that of men, with nonwhite women having the most negative outcomes. After eight years of infection, HIV-related events affected 64 percent of nonwhite women, and AIDS-defining events occurred in 22 percent of nonwhite women. In comparison, HIV-related and AIDS-defining events occurred in 21 percent and 6 percent of individuals in other combined race and sex groups, respectively.
The data representing subjects from the southern U.S. show that race and region play a major role in health outcomes of both women and men infected with HIV. Eight years following their diagnosis, 78 percent of nonwhites and 37 percent of whites in the southern U.S. had experienced one or more HIV/AIDS-related event, compared to 17 percent of nonwhites and 24 percent of whites in other geographic locations.
The authors hypothesized that the disparities could be attributed to the influence of socioeconomic factors, including "access to health care, health behaviors, lifestyle, and environmental exposures." Delayed therapy may be one factor affecting increased morbidity in HIV-infected individuals living in the South; however, socioeconomic factors probably also play a role. 
It was concluded that "understanding the causes of poor health outcomes among HIV-infected women, nonwhites and people from the South is a critical first step. In addition, development of strategies or interventions to improve health outcomes in these populations is essential."

Full Article:
-Catalina Angel

AIDS Virus Changes in Semen Make It Different Than in Blood

HIV-1 may undergo changes in the genital tract that make it different in semen than in blood, according to a study led by researchers from UNC Chapel Hill. The new findings are significant because the nature of the virus in the male genital tract is of central importantce to understanding the transmission process and the selective pressures that may impact the transmitted virus.

In the study, viral populations from blood and semen samples collected from 16 men with chronic HIV infection were compared. Using single genome sequencing, they analyzed the gene coding for the major surface protein of the virus in the samples. The results?

"The sequence differences between the blood and the semen were like a flashing red light, it was a big hint about the biology of virus in the seminal tract" said Swanstrom. "When we looked at sequences in the blood, we hardly found any that were the same, it was a very complex and diverse population. But when we looked in the semen, suddenly we were getting the same sequence over and over again."

They found two mechanisms that significantly altered the viral population in the semen, called clonal amplification and compartmentalization. In the former, one to several viruses are rapidly expanded over a short period of time such that the viral population is relatively homogeneous (compared to complex population in the blood). In the latter, the virus replicates in T cells in the seminal tract over a long period of time, creating a separate population of virus that is both complex and distinct from the virus in the blood.

Full article:

-Catalina Angel

Mosquito Saliva Enhances West Nile Virus Infection?

University of Albany researchers, Linda Styer and colleagues have recently provided evidence that saliva from a common West Nile virus vector, Culex tarsalis, enhances West Nile virus (WNV) infection in mice.   In order to characterize transmission, they assessed WNV in a mouse model.  Mice were inoculated with WNV via mosquito and needle and physiological observations were made. In mosquito-bitten mice, they noted a higher degree of early viremia, elevated spread to peripheral tissues, and faster neuroinvasion than the needle-inoculated mice. As the researchers note, this is the first paper that examines the differences in transmission in WNV between one infected mosquito and inoculation by needle.


Linda M. Styer, Pei-Yin Lim, Karen L. Louie, Rebecca G. Albright, Laura D. Kramer, and Kristen A. Bernard
J. Virol. February 2011 85: 1517-1527; published ahead of print December 8, 2010, doi:10.1128/JVI.01112-10

- Vy

Saturday, January 22, 2011

Increased Potency of Inactivated Trivalent Polio Vaccine with Oil-in Water Emulsions

Since the Great Polio Eradication effort in 2000, four countries are still struggling with endemic levels of polio: India, Afghanistan, Pakistan, and Nigeria.  There has been social and political resistance to the polio vaccine, in these areas (especially Pakistan) but an even larger problem lies in the fact that the current vaccine (OPV, oral polio vaccine) has low seroconversion (antibodies for polio are not found at protective rates) and occasionally becomes infectious in certain geographical areas.  A new version of the vaccine, delivered by injection (IPV), seems like a more effective version of of the vaccine.  The major drawback, especially considering the countries that need the vaccine, is that the price of IPV is much higher than OPV.  
In an effort to create IPV at a lower cost, researchers are working on adding adjuvants to the vaccine.  This same method was utilized to make a greater number of H5N1 vaccines at a low cost.  Adjuvants are materials that can enhance the immune response so that a lower dose of the inactivated trivalent polio vaccine will be needed.  The researchers used multiple groups of rats for testing, one group was given the full dose of IPV and the other groups were given the vaccine with the various adjuvants.  The vaccine with adjuvants tested similarly to the vaccine alone on virus-neutralization titers.  The next step is to figure out the most effective adjuvant, based on the results and those commonly used in practice.


Hantavirus in the Americas (Chile and Argentina)

Two deaths in Chile (Casablanca, Biobio) and three hospitalizations in Argentina (Oran) resulted from hantavirus this past week.

The deaths in Chile included a 41-year-old woman, who died of cardiovascular failure, and a 3 1/2-year-old child. These two infections brought the number of Chilean hantavirus cases in 2011 to three. Health authorities responded by testing the victims' family members for hantavirus infection and monitoring their health. Additionally, calls for increased public health measures, including ventilation of buildings, proper disposal of trash, and education of the local population, are being implemented.

In Argentina, the three cases were males. One patient has been released from the hospital, one is recovering in the medical clinic, and one remains in critical condition. The source of their infection appears to be associated with the "rural and recreational activities" in which the males were involved.

As discussed in class, hantavirus is a bunyavirus that leads to Hantavirus Pulmonary Syndrome, in which fluid leaks into the lungs, causing the patient to drown internally. Hantavirus is transmitted by rodent resevoir (sigmodontine) via their urine and feces.  They look cute, but beware!


Undiagnosed Hemorrhagic Fever in Mumbai, India

A 48-year-old man from Mumbai has been hospitalized with a hemmorhagic fever. The patient was disoriented, had a high fever, had kidney and liver problems, and was bleeding in the brain. His platelet count was low (which is consistent with the indications of hemmorhagic fever that we discussed in class). Despite treatment, he is not recovering, and his prognosis does not look hopeful. The man's hemmorhagic fever occurred only days after three CCHF (an arbovirus in bunyaviridae) cases were found in Ahmedabad, a neighboring city.

The patient's tests for malaria, dengue, and leptospirosis were all negative, and further samples are being sent to the National Institute of Virology. The article states that the virus is most likely an arbovirus (perhaps CCHF) or an adenovirus. Meanwhile, the patient will be kept under 4th degree of isolation. The article is unclear about what this means specifically, but it seems to be analogous to Dr. Bob's explanation of the biosafety of diseases (with 4 being the highest concern level). To prevent infection of medical staff, treatment has been administered to hospital employees.


P.S. The article says the patient "has shown clinical symptoms of viral hemorrhagic fever". It seems like it should have said signs according to our definitions, but perhaps adding in the "clinical" before it changes the way "symptoms" is used?,F2400_P1001_PUB_MAIL_ID:1000,86769

The limitations of the Shingles Vaccine

The shingles vaccine, Zostavax, is generally only available for seniors above 60 years of age.  The vaccine is considered “off label,” meaning that medications are “prescribed by a practitioner for a purpose not listed on the products label, resulting in a cost of about $280 per vaccine.

In the US alone, there are about one million of cases each year, a rate of 1 in every three persons affected by shingles.  Those that have had chicken pox are most vulnerable because the herpes zoster virus is often reactivated.

Shingles is a virus that remains dormant in the nerve cells of the spinal cord and the most common symptom are a stripe of blisters that look similar to the shingles on a roof.  The effects of shingles can vary from minimal symptoms, to severe nerve endings damage and death that can lead to postherpetic neuralgia.  The pain can range any time between a few months to years.

However, the Zostavax vaccine, produced by Merck has many limitations in our current healthcare situation.  Many are not aware of the vaccine, and it is also not widely publicized because those on Medicare do not always qualify.  You must be over 65 years of age and under Plan D.  Even then, the shot costs $160 and reimbursement is a difficult proves.  To make matters worse, Zostavax must be prescribed and ordered from the pharmacy.  If the pharmacy does not administer the shot, the patient must return to the doctor’s office with the vaccination for it to be administered.  This makes the vaccination so much more inconvenient and must deter many patients and practitioners from following through with the vaccination.

Finally, Merck has stated that the vaccine is difficult to produce on a large scale because there is a limited amount of the live, but weakened chicken pox virus.  There are simply not enough vaccinations produced to be effectively administered.


Clam Pollutant Traps! (Not virus-y, but cool!)

Dr. Bob spoke in class about how eating clams can be dangerous because clams are "filter feeders". When they eat, they filter water while absorbing not only nutrients, but also other particles that are present in the water like toxins and pollutants. They can be exposed to large numbers of water toxins because they continue to filter water over and over as they feed, each time accumulating toxins and pollutants in their tissues via this "bioaccumulation".

Because water toxins and contaminants (such as pesticides, lead, and arsenic) are generally expensive to identify and locate, scientists have begun using clams as a way to trap pollutants. The clams then can be tested at the lab to see if any toxins are present in that water source. This provides a less expensive, easier way to figure out which potentially dangerous substances may be located in a given place. The clams have already been used to find a banned Maryland pesticide that was leaking into the water.


Genetic Variety of Virus Causing AIDS as a Time Indicator

Researchers in a Swiss HIV Cohort Study are developing ways to figure out when a patient contracted HIV.  Currently, there is a test that can only establish time of infection during the acute phase, which is 8 weeks after contracting the virus.  Being able to establish a time of infection for a broader spectrum of patients would enable doctors to plan a more specific plan of treatment for patients and would provide epidemiological data.

The method the researchers are developing centers around the fact that viruses evolve once they have infected a host, partially as a defense mechanism against antiviral drugs.  They believe that they can look at the variation of virus within a specific patient in order to estimate how long he/she has been infected.  The preliminary results show that the virus differentiates rapidly the first eight years of infection and then slows down. This is only the beginning of their project and they hope to increase precision with further research.

Friday, January 21, 2011

Viruses splitting water?

Popular Science 4 December 2010

A team at MIT is looking to viruses for a new method of splitting water molecules into hydrogen and oxygen, hoping for means as simple and efficient as those used by plants during photosynthesis. They have assembled a modified virus that should do exactly that, designed with “oxidizing machinery”, a zinc porphyrin pigment and iridium oxide catalyst, normally employed by plants in water oxidation. The virus is the critical piece here because it supports specific arrangement of the pigment and catalyst. The engineered bacteriophage M13 serves as a “biological scaffold,” spacing the porphyrins and iridium such that oxidation rate is quadrupled.

Results are promising, but the team has yet to deal with the issue of disintegrated hydrogen atoms, which are useless as a bunch of electrons and protons. If intact hydrogen atoms can be recovered from the process, the MIT team may have a functional, self-sustaining, water-splitting device in their possession, ready to be adapted for commercial use.