auto to NOTo

Autoimmune disorders are diseases in which the body mistakenly attacks itself, causing diseases such as diabetes mellitus or multiple sclerosis for example. Scientists strive to combat these diseases by finding therapies that treat or neutralize the immune response against self cells. However, a barrier that these scientists often face is that neutralization doesn’t always just apply to the part of the immune system that is attacking the wrong cells but often attacks the cells that are working properly which leaves the body vulnerable to a plethora of sicknesses.

A team in Utah is attempting to separate the effects of different therapies on cells of the immune system that cause damage while keeping the normally functioning cells in tact. Their study, which was conducted on mice, seeks to target a surface protein PD-1 which plays a key role in regulating the immune system.

Both B and T cells express this regulatory protein; however, in those with autoimmune disorders this protein become ineffective. The team focused on creating a molecule that would deplete the store of this protein in the B and T cells in order to avoid long-term damage done by this malfunctioning cells. 

The molecule that they sought to create was composed of three parts: an anti PD-1 antibody, an albumin-binding domain protein, and the Pseudomonas exotoxin. The three components work together to bind the cells expressing PD-1 and killing them, while maintaining the ability to continue to circulate through the blood stream to find other damaging cells.

The molecule was shown to delay the onset of type 1 diabetes in mice from the usually 19 weeks to 29 weeks. However, the most significant results were in mice with multiple sclerosis who showed stopped paralysis progression and even in some cases regained the ability to walk again. 

Although these results are very optimistic, the study was only done on a limited number of a mice and has not been conducted in humans. This therapy might be beneficial if a similar PD-1 protein is found in humans. 

Although scientists do not exactly understand how the body attacks the beta cells in patients with type I diabetes, scientists have also tried therapies that help to protect these beta cells by manipulating the patients stem cells. These stem cells have the ability to become multiple different types of cells and may be coaxed into becoming beta cells in the lab which would allow for regenerative therapy if scientists are able to implement them back into the body successfully. The regenerated beta cell would have the ability to “hide from the immune system” by adding molecules that the body already recognizes. Labs are now trying to screen for genes that produce these protective properties, however a specific genes that were identified were obvious choices for a successful therapy. 


It’s about THIMErosal

What is thimerosal?

Thimerosal is a preservative that contains mercury that was used regularly in the United States, until 1999 when the American Academy of Pediatrics and Public Health Service Agencies called for a reduction or elimination of the vaccine in order to take precautions. The type of mercury found in thimerosal is ethlymercury which is cleared at faster rates than other types of mercury exposure and less likely to cause harm. When thimersoal enters the body, it is eliminated fairly quickly which makes it a low risk for accumulating harmful levels in the body.

Although it has been showed to be very safe and effective, the most common side effect are minor reactions such as swelling or redness at the site of injection. Thimerosal is implemented into vaccine in order to prevent the growth and reproduction of bacteria and fungi. This is done because vaccines can contain more than one does and there is potential of the syringe needle that enters a vial being contaminated by germs which can cause illness.

In the late 1990s, single dose preservative free vaccines were spread widely across high-income countries because of the concerns that the mercury contained in thimerosal may build up and cause toxicity. Although, this fear is false it has had great impact on low and middle income countries where vaccine preventable diseases thrive, because multidose vials of vaccine containing the preservative are critical in immunization programs abroad. The switch to single dose vials increases the cost of shipping, cold-chain storage, manufacturing, administration, and waste handling.

In 2013, multidose vaccines containing the ingredient thimerosal were used in almost 120 countries and saved the lives of 1.4 million people annually so a potential ban would prove catastrophic. This method of vaccine is responsible for the manufacturing of tetanus toxoid, diphtehria- tetanus-whole cell pertussis, and the Hep B vaccine. Utlimately a ban would be an injustice to many. Complying with a ban of the ingredient would require the countries involved to use only single dose vaccines which would put a strain on the public health infrastructure of many countries and they also may face interruptions in the supply of vaccines.

After rigorous review, thimerosal was approved for multidose vials of vaccine in accordance with the World Health Organization (WHO) standards. Although it is possible to replace this ingredient with other preservatives on the market, none compare to the viability of thimersosal. Replacing thimerosal could also cause instability in vaccine safety and efficacy and would require progressive and detailed testing which may prove very time-consuming.

In conclusion, thimerosal has not revealed any evidence that it causes harm, except for acute local hypersensitivity reactions to those who may be allergic. Although, thimerosal has been proven safe some infants exposed to cumulative levels of mercury found within the preservative that exceed EPA recommendation for those under 6 months of age. However, other products are available and formulated without thimerosal that can eliminate the risk for those under 6 months.

Glass vials for liquid samples. Laboratory equipment for dispensing fluid samples.

You’ve only got one shot

Can you believe that it was only a little over 30 years ago that the first case of HIV appeared in the United States? After its arrival, no one could have predicted what destruction it could bring with it. Over 675,000 people have died from the progression of HIV into AIDS since the 1980’s, however; medical breakthroughs are on the rise to prevent HIV positive individuals from progressing into AIDS rapidly and reducing their viral loads to such low levels that it is almost impossible to transmit the disease to another individual. In fact, those who are HIV positive life span is almost nearly the same to that of unaffected individual.

Although the HIV epidemic has significantly decreased, Americans are still reaching the AIDS stage which continues to motivate scientists to develop a better vaccine for those at risk of HIV. When HIV was first discovered, the hope was to develop a one time vaccine that would combat this deadly disease. Currently, the Uhambo vaccine requires a five step process which takes up to a year complete and people may need to repeat vaccination every few years which is not only time consuming but also can become expensive. A one shot vaccine would allow an easily manufactured, effective vaccine for global HIV vaccination drives. However, the optimism for a “one and done” vaccine slowly faded with realization that the vaccine has very powerful virulence factors that allow the virus to integrate its DNA into the host cell and cause very individualized symptoms. However, new studies have renewed hope in a single-shot vaccine!

Currently, HIV is being combated with multi-shot injection strategies with the goal to slowly allow the immune system to find and destroy the virus. However, researchers from Scripps Reasearch Institute in La Jolla, California have developed a single usage HIV vaccine that may alter the approach of fighting HIV. This vaccine, SOSIP BG505 env trimmer, triggers the body to create bNAbs, which are antibodies that are normally seen in HIV patients that have been infected with the disease for many years. In fact, this unique study is the first time that scientists have been able to induce this type of reaction in a mammal other than cows which proves optimistic but also a barrier as it may not respond in humans.

The vaccine works by a viral like particle (VLP) with the shape of the trimer which is comparable to that of a fidget spinner that an important protein gp120 from the virus needs to also adopt in order to infect host cells. This makes it difficult for the virus to change the shape of the protein without losing function because the trimer exposes parts of the protein that are normally conserved. The result is that the virus is neutralized and can’t mutate certain responses.

The hope for this vaccine is that it will create a “complete response” to HIV in the chance that HIV exposure does happen. Researchers hope that it will not only be able to turn away the virus but also contain it in the chance that infection does occur. The study included 78 monkeys and compared antibody response of those with the highest and lowest immune reactions.

The results showed that the vaccine was only somewhat effective in those who produced a low immunity response with two of the monkey contracting HIV after 6 weekly doses of the vaccine. However, only one monkey in the high response group contracted HIV in the first round, one in the second round, and two in the third round, with the rest of the monkeys making it successfully through the trials without contracting the infection.

Although this has not yet been tested on humans, researchers are optimistic about the concept study and will be looking at the safety and efficacy of the new vaccine in the upcoming months in hopes that a one-shot vaccine may one day be effective.

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Mycobacterium Tuberculosis is on the prowl

Mycobacterium Tuberculosis is spread via air droplets which are breathed into the lungs, where the disease can lay dormant or spread.

Multi-drug resistant tuberculosis is on the rise globally– and its a HUGE problem! Multi-drug resistant TB is caused by a resistance to the two most commonly used front line defense against the bacteria. It is estimated that 10.0 million people were infected with tuberculosis with 1.6 million of them dying from the disease with 87% of those affected being from developing countries. Currently those being treated with resistant TB endure a lengthy (can last up to two years), costly treatment often with toxic side effects and a success rate of only 60%. Often times in developing countries, multi-drug resistant TB is either misdiagnosed or went undetected due to inaccurate tests, which ultimately leads to higher mortality rates.

In a study conducted by researchers from the Institute of Social and Preventative Medicine (ISPM), 634 patients were evaluated from different developing countries including Côte d’Ivoire, the Democratic Republic of the Congo, Kenya, Thialand, Peru, South Africa and Nigeria. It was found that only 7% of the TB cases were monoresistant, 26% were multiresistant,and 5% were resistant against an extensive amount of antibiotics. A whopping 60% of the TB cases in patients that resistance was inaccurately not found died from insufficient treatment. After these findings, researchers recommend investigating the sequencing of the bacteria’s entire DNA in each individual case of TB; however, there is a lot of work that needs to be done in order to make these test accessible in developing countries.

In a study led by Queen Mary of London, Vitamin D was found to speed up the clearance of TB in a random sampling of 1,850 patients receiving antibiotic treatment. Lead researcher Professor Adrian Martineu investigated adding vitamin D in addition to the antibiotic treatment in hopes to boost the immune system in order to clear the bacteria without soling relying on the antibiotics that had become resistant. This study was a novel approach to combating tuberculosis since a lot of focus has been on investigating new antibiotics that the bacteria is not resistant to. The addition of vitamin D added no adverse side effects and opened the door to “host-directed” therapies,” which are therapies that boost the immune system. Although the study was not conducted on a large enough population to justify clinical recommendation, it opened the door for further investigation and a rationale to conduct further clinical trials.

Polio: an all time low!

Poliomyelitis aka polio is a highly infectious disease that infects the nervous system often causing paralysis and even death. Polio affects children under the age of 5 who have not been fully vaccinated through the fecal oral route. There are currently 3 types of polio virus: including type 1, type 2, and type 3. Although there is no cure for the disease, large efforts have been underway to eradicate this disease.

Polio which has plagued the world is now at an all time low with only 33 cases reported in 2018. In fact, efforts to combat this disease has resulted in a 99.9% decrease in cases since 1988. Since eradication efforts began, the disease has been eliminated in more than 120 countries; however, the stubborn disease still remains endemic in three countries. Eradication efforts began 30 years ago, and currently there is a global push for complete eradication of polio by 2023. In fact, the U.S. government plays a huge role in this effort by providing funding of more than $235 million dollars in 2018.

So what interventions have been so successful at eliminating this disease? Several strategies have been used in order to prevent the spread of polio. Ensuring greater than 80% of routine immunization of infants under the age of one by giving at least three doses of oral poliovirus vaccine (OPV) has proven very effective in reducing the number of polio cases. Along with the OPV, inactivated Polio Vaccine IPV is also another vaccine that prevents the disease. Mass immunization campaigns and heightened polio surveillance to detect any new cases and targeted campaigns also called “mop-up” campaigns to respond to any possible outbreaks in specific areas are also interventions currently taking place to battle polio. Mass immunization in conjunction with routine immunity allows communities to build herd immunity and plays an important role in protecting those who have not been immunized or may only be partially immunized. In order for herd immunity to be effective in eliminating the disease, high levels of immunization must be sustained. During campaigns, volunteers vaccinate thousands, even millions of children. Secondary efforts include the support from health care workers, communication campaigns, community engagement, and new scientific and technological advances.

Although OPV is easily administered and the still the main preventative to vaccinate children, eventually a switch to inactivated poliovirus vaccine (IPV) will be phased in over the next several years. This allows for prevention of outbreaks that are caused by circulating vaccine-derived polioviruses since OPV contains attenuated virus. IPV which is given intravenously and requires a trained health care worker targets all three types of wild poliovirus whereas OPV only protects against two wildtype. IPV is used in conjuction with OPV to strengthen the immune system in many countries.

Although the vaccine is relatively cheap, efforts to vaccinate the most at risk population still serves as a challenge because these endemic regions are often geographically isolated or struggle with extreme poverty or conflict. These factors make it hard for health care workers to access these areas. For example, a recent attack on health care workers involved in vaccinating for polio in Pakistan highlighted concerns that may hamper progress for complete eradication.

Each country has its own specific immunization schedule. Some countries use only OPV or IPV alone whereas others use a combination. Although OPV is very effective, it can in very rare cases cause paralysis known as vaccine associated paralytic poliomyelitis (VAPP). In order to combat this rare disease, starting in 2016 there was a campaign for all countries to include at least one dose of IPV. IPV has proven very safe and effective in humans whether used alone or alongside OPV and no serious adverse affects have been reported thus far. IPV has been used in the US since 2000 in order to eliminate the possible risk of contracting circulating poliomyelitis or VAPP.

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HPV, not for me!

Human papillomavirus is the most commonly transmitted viral infection. Although there are many types, many do not cause problems and often times go unnoticed clearing up on their own. However, a handful of strains can progress into a nightmare– cancer– specifically cervical cancer. Usually spread between sexually active men and women, it does not require penetration to cause infection but can also be spread via skin-to- skin genital contact as well. Once infected, it takes about 15-20 years to develop into cervical cancer for those women with healthy immune systems, but those who are immunocompromised cancer may develop in only 5-10 years!

Thankfully, there is a vaccine to combat this common infection. Primary prevention begins as early as the ages of 9-14 in order to ensure that the vaccine is given before becoming sexually active. Currently, there are three vaccines that protect against HPV 18 and 16 which are known to cause a whopping 70% of cervical cancer, the third vaccine also protecting against another 20% of cervical cancer. Although post-marketing surveillance and clinical trials have shown that these vaccines are very safe and effective against preventing viral infection against HPV, these vaccines are not effective if the virus has already been obtained such as in unvaccinated sexual active individuals.

Although it was originally approved for people ages 9-26, the Food and Drug Administration (FDA) recently expanded its approval for the vaccine Gardasil 9 in 2018 to also include men and women between the ages of 27- 45. The vaccine is taken in two doses with several months separating each dose for those 9-14, and those who are older it is given in three doses. The reasoning for expanding the age range of individuals who are vaccinated stems from the fact that although many individuals will or have already encountered strains of HPV, the probability that they have encountered all of the nine strains that Gardisal 9 protects against is unlikely, and thus there is added benefit to vaccinating the older population. The FDA based their decision on data of the original Gardisal vaccine which included 3200 women ages 27-45 where the long-term follow up showed Gardisal was effective in preventing genital warts, persistent infections, and precancerous lesions. The version of Gardisal 9 that is currently on the market was approved in 2014 and doubled the number of strains that it protects against.

Although the vaccine has helped to prevent countless infections, many people were skeptical of the vaccine when it first became available for administration. The vaccine can cause allergic reactions, fainting, blood clots, and less likely Guillain-Barre Syndrome (GBS). However, the big opposition came when 56 girls had died from the vaccine as of September 2010, as well as deaths of 6 children in vaccine trials in India. Many people feared that it was a money making scheme from big pharma with the vaccine being one of the most expensive on the market. However, the vaccine has been nearly 100% effective in preventing precancerous lesions in HPV strains 16 and 18 and also genital warts. In fact between the years 2014-2017 29 million doses of Gardisal 9 had been administered and only 4 confirmed cases of GBS were reported and fatality rate of zero, meaning although negative side effects are possible they are not probable.

The vaccine has definitely done way more good than harm!

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Wakefield Wakes the Anti-vaccers

Andrew Wakefield. Former British Doctor. Father of the modern anti-vaccination movement.

Wakefield was a gastrointestinal surgeon until his license was revoked in 2010 after being found guilty of abuse of mentally handicapped children via invasive and unnecessary medical procedure, dishonesty, and non-ethical actions during his research.

After being approached by parents of children with autism and stomach problems who claimed their children began showing developmental issues after receiving the measles, mumps, and rubella vaccination which had been recently introduced at the time, Wakefield questioned whether there was a link between the MMR vaccine and children with autism.

Wakefield, along with 12 other co-authors conducted a study in which they hypothesized a link between autism and bowel disease as a precipitating event of the MMR vaccination and their findings were published in The Lancet in 1998. As Wakefield called for the return of the single jab vaccinations instead of the MMR vaccine, news sources began backing his ideas.

Wakefield eventually became a documentary producer and avid campaigner against the vaccine, pointing out a rise in the diagnosis of autism since the vaccine was developed. Interest groups and concerned parents helped propagate the myth Wakefield had created via online platforms spreading fear of not only the MMR vaccine but concern about the ingredients that were involved in many vaccines including Mercury, and Aluminum. These concerns led to a steep decrease in vaccinations following his publication which coincided with multiple outbreaks of the measles in the decade after.

Unfortunately, trust in a medical professional with scientific reportings lit a fire within individuals skeptical of vaccines. Peer reviewers and the medical community were also trusted to stop sloppy science from being published. It was also the responsibility of news media to provide evidence-based reporting and not report with confidence findings that have been largely refuted and questioned. All of these factors helped to contribute to the modern epidemic of vaccine hesitancy.

In 2004, journalist Brian Deer from Sunday Times published an investigation into the claims of Wakefield and the financial interest behind the study, claiming he had been funded by solicitors involved in legal action against the MMR manufacturer. Following this investigation, the GMC also opened an investigation against Wakefield and two of his co-authors.

Wakefield’s paper was a case series based on 12 child patients; however, patients were recruited through biased anti-MMR campaigns and many of the children’s symptoms were edited to support his findings. Not only had Wakefield conducted an unethical study, but he was also found guilty of scientific misrepresentation in which he had reported that his sample population was consecutive when in fact it was selective which introduced major sampling bias. BUT– the climax to his fraudulence involved picking and choosing data that best suited his hypothesis, falsifying facts along the way. Not only was his sampling not random, but he was not made blind the results which also was a potential source of bias as direct oversight of results to the patient could have influenced findings.

Wakefield’s analysis of his results led to him to conclude that a “new syndrome” called “autistic enterocolitis” had a causal relationship with the MMR vaccination– not only sparking fear within the public but WAKING the antivaccination campaigners.

The Smaller, the Better

Bacteria sure are stubborn. Good news scientists are even more stubborn.

Scientists are developing a new solution to the increasing problem of antibiotic resistance by rendering bacteria ineffective as opposed to killing them which lessens selective pressures that allow for resistant strains.

In the U.S. antibiotic resistance is responsible for 23,000 deaths per year and as antibiotic misuse continues this number is sure to grow. In fact, for some infections, no antibiotic is able to combat the organism– a scary thought considering the rate at which a lot of bacteria developed resistance.

Dr. Shoham from Case Western Reserve University School of Medicine treated mice with small molecules that inhibited Staphylococcus Aureus resistant to methicillin from producing and secreting toxins which allowed the treated mice to survive a sepsis infection. Only one-third of untreated mice were able to survive. This finding is significant as it may mean that resistant bacteria may not need to be treated with antibiotics in order to cure sepsis. Depending on the strength of a person’s immune system, those suffering from a MRSA infection may only need to take a dose of small molecules rather than an antibiotic to clear an infection.

Scientists have also started looking at insects for ways to combat antibiotic resistance. Who would have thought the creepy crawly bugs wandering inside your home could someday save your life– or rather the microbes that reside within their microbiota. Many of the microbes that live in insects compete with each for survival in a game of biochemical warfare. Whats their weapon? Natural antibiotics.

Specifically, the compound cyphomycin, which is found in Brazilian fungus-farming ants has been isolated and although it is far from being an FDA approved drug, there is hope that it may be useful to treat yeast infections. This opens the door for the discovery of other natural antibiotics found in species-specific insects.

far from being an FDA approved drug, there is hope that it may be useful to treat yeast infections. This opens the door for the discovery of other natural antibiotics found in species-specific insects.

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HPV G2G

HPV (human papillomavirus) is the most common sexually transmitted infection. Although most cases are for the most part harmless and the innate immune system can rid the infection, some cases can lead to genital warts or even CANCER!

HPV is spread through sexual skin-skin contact, specifically the interaction between vagina, cervix, vulva, penis or anus, and can even spread to the mouth and throat during oral sex. There are over 200 different types of HPV, 40 of which are spread from the genitals. Other types of HPV cause warts such as the common wart on your hand or the plantar wart on your foot.

Although there is no cure for HPV, there are treatments and vaccinations available to combat this infectious agent. For example, Gardisal 9 can protect against 9 different subtypes of HPV that cause various cancers of the genitalia. However, this vaccination is only effective when given before an individual is sexually active to decrease any risk of contracting the disease.

Recently, researchers at the University of Alabama at Birmingham have conducted preclinical experiments to study the effects of repurposed vorinostat, belinostat, and panobinostat to treat HPV. Investigation into the effects of these drugs has been hampered, however, because of the inability to propagate HPV in conventional cell culture because HPV thrives by differentiating the epithelium of the mouth and genitalia into a thick squamous epithelium in which it reactivates its DNA replication. However, Louise Chow and Thomas Broker from the UAB Department of Biochemistry and Molecular Genetics has been able to produce a “raft culture” from human keratinocytes to simulate the progressive activity of the virus.

These scientists hypothesized that drugs that inhibit histone deacetylases (HDACs) would disrupt replication which requires the alteration of histone proteins that wind DNA and package dense chromosomes within the viral genome.

When the drugs vorinostat, belinostat, and panobinostat (all of which inhibit HDACs) not only did it disrupt DNA replication but it also resulted in cell death which could be very beneficial in treating HPV cancers as it battles the overgrowth of these overtaken cells.

Vaccs on. Vaccs off

Should I get my child vaccinated? This question has become very popular recently, as more people are deciding against getting their children vaccinated. The antivaccination trend is just as contagious as the measles.

But why? Guaranteed protection from the chicken pox without ever having an itch sounds pretty great to me! 

Vaccine hesitancy is the refusal to vaccinate despite the availability for any reason that may include confidence, complacency,  and convenience. In fact, some states do not require vaccination upon entry into high school. For example, Washington is one of 17 states that allows parents to send their children off to school without proper immunization for reasons such as personal disagreeances.

But what cultivates this new trend? Sobo, a professor at San Diego State University conducted a study in which she interviewed families in California who attended schools with low vaccination rates. Sobo found that skepticism about vaccination was mostly “socially cultivated,” meaning that those parents uncertain about modern medicine influenced the decisions of their peers in their community.

Although we might think it is crazy to refuse a vaccination that protects you from highly contagious brutal infections, the study also found that most parents protesting vaccination are often very highly educated individuals.

So what would make them risk the health of their children?

Often times, families who live in a progressive community create an environment where making a decision outside of the progressive platform has large social costs. Think about it: if you accidentally attend a formal party in jeans and a tee shirt, although someone may not directly tell you to your face that you are out of dress code, the next time you attend a similar party you’ll probably dress up more just based off the premise of not standing out.

How can we combat this phenomenon?

A study conducted by Arede et. al developed an approach to fight the resistance against vaccinations by choosing to target adolescents and children based on the idea that this age group’s emotional state is more easily influenced comparatively to older individuals. Their framework included familiarizing their target group with the concept of herd community (the idea that vaccinations not only protect yourself but others around you), correcting misinformation such as the false accusation that Measles is linked to Autism, and that each individual plays a major role in being able to eradicate some of these infectious agents.

Why is vaccination so important?

Choosing to not vaccinate your children, puts those who are too young or do not have access to the vaccine susceptible to disease. The decisions you make have direct impacts on others. Emmanuel Bilodeau chose not to vaccinate his children for the MMR (measle, mumps, and rubella) vaccination because of the fear that it caused Autism. After taking a family trip abroad to Vietnam, Bilodeau learned that his son had contracted measles. Unfortunately, before he learned of his diagnosis his son had spread the infection to eight others at his school including his siblings.

Measles has the ability to cause serious complications including pneumonia, encephalitis, and even death! I don’t know about you, but I would be pretty mad if my baby contracted pneumonia because of the decision of a family to not vaccinate their children. But you decide.