Author: thejoyfulexplorerblog

Trastuzumab (Herceptin) is a monoclonal antibody that can be used to treat some type of breast cancers and stomach cancers. Monoclonal antibodies are man-made complexes that resemble antibodies an act in the same manner as an antibody produced by the body. They are made to react to a specific antigen in order to alert the immune system of the invader to destroy it. They can also be used to neutralize the ability of the pathogen to continue to negatively affect the body. Monoclonal antibodies can be made in four different ways: murine, chimeric, humanized, and human, and are named based on what they are made of. Trastuzumab is a humanized antibody, meaning that it is made from a human protein that has been attached to a smaller portion of a mouse protein. It is also considered a naked monoclonal antibody.

Trastuzumab is a monoclonal antibody that recognizes the HER2 protein that is present on many breast and stomach cancer cells. By attaching, it tags these cancerous cells for the immune system to then kill and destroy. It is considered a naked monoclonal antibody because it does not have any type of radioactive material or drug attached to it. It works by attaching itself to the antigen that it recognizes (the HER2 transmembrane protein) on HER2 positive cells. Because the presence of HER2 on the cell works to increase the growth of that cell, by attaching itself to the HER2 protein, the HER2 protein does not become activated and the cell does not grow. It is important that the cancerous cells are tested for the presence of the HER2 transmembrane protein before treatment begins. It works as a mediator of antibody-dependent cellular cytotoxity, meaning that it recognizes the antigen and then Natural Killer cells are able to attack and destroy the infected cell. Some of the possible side effects of taking Trastuzumab are:

• Heart problems
• Fever and chills
• Nausea
• Vomiting
• Pain (sometimes at the site of the tumor)
• Headache
• Dizziness
• Shortness of breath
• Severe shortness of breath
• Fluid in or around the lungs
• Weakening of the valve between the heart and the lungs
• Not enough oxygen to the body
• Swelling of the lungs
• Scaring of the lungs
• Low white and red blood cell count
• Muscle pain
• Infusion reactions
• Increased cough
• Rash

Taking Trastuzumab has been linked with neutropenia and when taking in conjunction with chemotherapy (as it is usually recommended when treating breast cancer) can cause large negative impacts on the immune system. This can affect the way that the body is able to amount an immune response to other disease causing pathogens. It is important that anyone taking Trastuzumab takes careful precautions to avoid any sick individuals and is considered immunocompromised. Because the drug helps to activate ADCC, it is helping to activate the innate immune system through the Natural Killer cell assistance. The Natural Killer cells are able to recognize the Trastuzumab that has recognized and linked to the HER2 transmembrane protein. Then the Natural Killer cell can release perforins and granzymes in order to induce apoptosis in the cancerous cell. The results of treatment with Trastuzumab have been very positive, and I believe that this is the future of treating cancers. To be able to specifically engineer an antibody that recognizes the cancerous cells in the body and directs the immune system to attack just these is the most effective way to eliminate cancerous cells while keeping normal cells alive. I believe that soon chemotherapy will be less popular and monoclonal antibodies such as Trastuzumab will be the more common course of treatment with overall better outcomes.

When discussing the novel Coronavirus, there are two major tests that are under development currently. These tests are 1) to determine whether or not a patient currently has COVID-19 2) to determine if a patient has been COVID-19 positive in the past, indicating that they may be immune to a future COVID-19 infection. Today, I want to talk about the second type of test, as the first is currently being used for diagnosing the public, and although there are many ways to improve this process, it is currently more understood. In order to form a test to see if a patient has been infected by COVID-19, you must determine if their bodies have antibodies that bind to the virus. When your body becomes infected once, it begins by making IgM (antibody M) this is a generic antibody that is not especially great at identifying COVID-19 but is the first response while your body works on something better. Then, your body begins making a better antibody, IgG to fight the COVID-19 and IgM levels begin to drop off. Now the question becomes, do these antibodies stick around forever, allowing you to know that you have been infected in the past?

This has become a current question in the quest on finding a test to see if you have been infected. Based on a New York Times article from April 10^th, this is one of the major issues. Sometimes antibodies do not stick around for longer than a few weeks, therefore the test may not be able to determine if you have been infected. However, it would not matter if you had been infected at that point, because what allows your body to fight better the next time you are exposed to the same viral particle is the fact that those antibodies allow your body to respond much faster and at a very high level. If test development does occur and a person only has IgM antibodies, then it could be determined that they may still have COVID-19 virus in their system because the IgG response has not yet had time to mount. If the person being tested has both IgM and IgG antibodies, then it would follow that the person being tested is in the time frame when the body is upregulating IgG and downregulating IgM. This would also mean that the person has active COVID-19 in their body. If the person being tested has primarily IgG antibody, this would most likely mean that they were infected by COVID-19 in the past and have antibodies in the blood that would help you fight COVID-19 better if it re-entered your body.

The reason why it is important to know if someone is immune to COVID-19 is not because they would then never have the virus in their body again, but it is because they would be able to fight it off much faster and most likely not infect others. This is because the virus would not have the capability to proliferate to a level of being infectious to others. One article I read from CNN mentioned the implications of knowing if someone was immune to the novel coronavirus. It discussed the idea of an immunity certificate. Personally, I think that the test to determine if someone had antibodies to COVID-19 in their bodies would be very helpful. However, as our world returns back to “normal”, I get worried that this may be a new way that we can discriminate and divide ourselves. I can see that maybe one days those who are do not have immunity certificates would be banned from things like sports games or educational settings. Although I know that this is unlikely, the idea of papers and potentially having another way to discriminate against those in our society is something that makes me on edge.

Immunotherapy to treat cancer diagnosis is the future of cancer therapy, and on the forefront of immunotherapy is dendritic cell and T-cell therapy. Dendritic cells are the primary antigen presenting cells of the immune system and T-cells are the backbone of the acquired immunity. One specific type of T-cell therapy that I decided to focus on for my blog post today was the CAR T-cell therapy. Chimeric Antigen Receptor T-cell therapy. This type of therapy works by taking blood from a patient who has tumor cells within their body and taking out the T-cells from that blood sample. Then a T-cell receptor (what allows the T-cell to recognize foreign things in the body) will be created to recognize the cancerous cell type. The modified T-cell would then be put back into the patient. Now, the patient has T-cells that can recognize and eliminate the cancerous cells faster.

In order to understand the current status of CAR T-cell therapy, I read two articles about current research happening in order to see the effectiveness of CAR T-cell therapy. One article I read mentioned that CAR T-cell therapy worked very well against a certain type of blood cancer (Diffuse large B-cell lymphoma) but that there were drawbacks. One of the major drawbacks is that many patients developed therapy-related severe cytokine release syndrome and neurological toxicity limit. These mostly occurred in patients with a large tumor burden and it did seem that patients with a lower tumor burden. This other article that I found showed that CAR T-cell therapy may be useful in types of cancer outside of just blood cancer. Glioblastomas have been seen as a good potential target for CAR T-cell therapy (one of the most aggressive brain cancers).

I think that T-cell and dendritic cell therapies are the future of cancer therapy because they are actually fighting the thing that is trying to be eliminated. The drawback of chemotherapy is that it targets all cells that are replicating. This means that normal cell that replicate often are also being targeted. Which therapies such as CAR T-cell therapy, there is a specificity to the target of elimination that is not occurring with traditional chemotherapy. Because of the harmful side effects including the cytokine response, I believe that we are still far away from using these therapies as common medical treatment to cancers. However, new biological technology is exciting, and we should continue to fund and support innovative therapies like these.

These have been some crazy past three weeks. From the beginning of spring break, my friends and I flew to Las Vegas and rented two campervans to trek across Utah, Arizona, and Nevada, stopping at 5 major national parks. This had been a dream of mine for many years, and because Nevada still had yet to have any COVID-19 cases, we felt that it would be alright to travel here for spring break. I mean after all, we would be away from society in a campervan for the week. Little did we know that while we were driving through spotty service, the entire country was in the beginning of one of the most unexpected and craziest moments in history.

Once we returned to cell service, we had clear glasses into reality. Our travel back would be putting us at risk for becoming infected and potentially spreading COVID-19 to our friends and family back in North Carolina who were awaiting our arrival. We moved our flight home one day early and began our journey through the airport with hand sanitizer and Clorox wipes in hand. I truly don’t think that it had set in, and as I met my friend who attends Duke the next day to help her pack up her things, I thought that Duke administrators were over-exaggerating and that UNC would remain open for classes. Oh was I mistaken.

My transition into social distancing and being in my home every day for the entire day outside of my daily walks and runs has been alright. Classes have given me some needed structure, and my family has been brought together in this time. The major effects that I have felt come from the fact that my family’s income is linked to an industry that is being very hurt currently. The hopes of my parents in their savings and financial peace have become very different in a matter of weeks. However, in saying this, we have centered around the belief and faith in God and His plan for this world. We know that ultimately His name will be glorified and His plans are greater than ours. This is the hope that has allowed me to continue on in these drastic times. I hope that it can be a reminder for all who read that the Lord is in control and does care for you.

Human Immunodeficiency Virus is a sexually transmitted disease that wreaks havoc on the adaptive immune system of a person who has been infected. HIV can also be transmitted through the sharing of syringe or other drug administration apparatuses. The virus targets the CD4 helper T-cells that then decrease the individual’s ability to respond to any sort of infection. Persons who become infected usually die from opportunistic infections. An opportunistic infection is one that is able to proliferate because of the persons compromised immune system from the effects of HIV. Although this is a terrible STD, we have come leaps and bounds in developing therapies and prevention methods.

One effective prevention method is a drug called post-exposure prophylaxis (PEP). This drug is to be taken after an individual believes that they may have been exposed to HIV (less than 72 hours after exposure). This medication is an antiviral and when effective, will prevent an individual from becoming HIV positive. A study in AIDS and Behavior showed that the stigma surrounding HIV/AIDS has prevented many people from using PEP and that awareness and pharmacy access directly related to PEP willingness. This study also found that being female and having a partner who has tested positive for HIV were also factors that increased an individual’s willingness to use this prevention strategy.

One recent article that I came across has to do with the current coronavirus epidemic and relates to an outbreak of HIV that occurred in Indiana in 2015. This current article spoke about how reluctant the then Governor Pence was at initiating a needle exchange program. Needle exchange programs are a low-cost prevention strategy that allows people to change their needles out for clean needles in order to reduce the number or reused dirty needles. The article mentioned his response to the HIV outbreak because now Vice President Pence is the point-person for the current COVID-19 epidemic. I hope that his experiences in the nature of the importance of time will prompt him to act quickly in the COVID-19 efforts.

A superbug is a pathogen that has evolved the necessary ability to become resistant to the antimicrobial drug that would work successfully against it in the past. There are many problems with superbugs, the first being that if one bacterium has become resistant to all known antibiotics, then there is not defense that health-care providers can work with in order to help patients with this strain of bacteria. There are a few reasons why we are now seeing many antimicrobial resistant bacteria currently. The first reason is bacterial mutation and conjugation. Through the process of replication, bacterial genome can mutation and sometimes create a beneficial mutation for the bacterium that allows it to survive in the presence of antimicrobial drugs. Bacterial conjugation allows these beneficial mutations to be shared among bacteria, multiplying the number of bacteria that can benefit from this mutation. Antimicrobial resistance can also be attributed to over-prescription of antibiotics, individuals prematurely stopping their prescribed antibiotics, and the overuse of antibiotics in the farming industry.

On superbug that has become antimicrobial resistance is the vibrio cholera bacteria. These bacteria produce the Cholera Disease which has been a common cause of death in countries with poor water sanitation and fecal exposure to water sources. One article mentioned the antibiotic resistance of Vibrio cholerae strains from the 1990s in Siberia and Far East Russia. This research is aimed at understanding the mutations that these cholera bacteria gained, the epidemiology of cholera and establishing the origin of strains. This can help researchers with the current cholera antibiotic resistance fight. Another article I found addressing V. cholerae antimicrobial resistance documented the current strains of V. cholerae in India that are resistant to the currently used antibiotics. Although cholera is one disease that can usually be aided with an immense amount of fluids and electrolytes for some healthy adults. There are many other pathogens that are also evolving the ability to evade our known antimicrobial drugs.

Antibiotics are hugely important for the way that we treat even simple things like a UTI but also more harmful pathogens like C. difficile. It is of the utmost importance that we cut back the amount of prescription of these valuable antibiotics outside of their intended usage and change the agriculture industries usage. If we do not, I think it will become more and more common to see the already present antimicrobial resistant related deaths in our hospitals when patients are unable to be treated with the antibiotics we have. We are currently in a race against the microbes in developing new antibiotics and potentially novel ways to treat patients with bacterial infections such as phage therapy.

Polio is a disease that can be life threatening and is a major cause of worldwide mortality and morbidity due to the poliovirus. There have been major efforts to eradicate polio globally because there are currently two vaccines that work to prevent the contraction of the disease. An article from the Journal of Infectious Diseases explained that there two vaccines are the IPV and the OPV vaccine. The OPV vaccine is administered orally and is a live attenuated vaccine that provides more local protection and proliferates in the intestines. The OPV has a major drawback in that a minimum of 6 doses are required in order to have immunity and that it has more of a chance of mutation once inside the recipient. This can sometimes lead to contraction of polio in a very few number of recipients of the vaccine. In Hispaniola about 20 years ago, a polio outbreak began from a vaccine derived poliovirus (VDPV).

The other vaccination is the IPV (inactivated polio vaccine) according to an article from the journal of infectious diseases. This vaccination is used in addition to the OPV in countries with less access to medical care for the people. However, in countries with better access to health care for their people, the normal routine for providing immunization is a series of IPVs without any OPVs. This is because the IPV is more expensive than the OPV. In 2016, the Global Polio Eradication Initiative changed their protocol for the plan to eradicate polio and included the addition of at least one dose of IPV in the vaccination plan and changed the OPV to reduce the likelihood of VDPV.

The current situation of the polio virus is that it is still persisting in Pakistan and Afghanistan. According to an article from Correspondence, the plan to eradicate polio in these countries is on a failing path. Based on what the article mentions, it does not seem as though polio will be eradicated unless the Pakistani and Afghanistan governments begin to take ownership of their own national public health in vaccinating their people. This is frustrating to me because although I know that there are many other important initiatives for spending for the Afghanistan government, vaccinating their people feels like the fastest and most long-lasting resolution for health. Also, the fact that the Pakistani and Afghanistan government is not spending the money to complete the eradication has drastic effects for the entire world in that there is still the potential of transmission for the global population. I believe that eradication is a burden for the global population with an increased burden on the Pakistani and Afghanistan governments.

Until recently, scientists believed that the microbiome was neither hurting not helping humans in their daily life processes. They believed that the interactions between the microbiome and human organs and processes was minimal. However, recently they have seen that this is not the case. In fact, a paper called The Oral Microbiota May Have Influence on Oral Cancer explains that an imbalance in the microbiota of a human, either too much of a microorganism or too little can cause chronic infection and systemic disease. This shows that our microbiome indeed can have drastic effects on human health.

The paper mentioned above was aimed at understanding the microbiome of tumor versus normal tissues. They found that there was a significant different in the microbiome make up of a tumorous area versus a normal area of tissue. In a similar way, in 1990, the pathogenic role of Helicobacter pylori was discovered, showing that the presence in most cases of gastric tumors, Helicobacter pylori was present. The researcher even swallowed the bacteria to prove the relationship between this microbiota and cancer. These results from the paper mentioned above may be used in future research to target those differences for more highly specialized cancer therapies. This is research that is ongoing and ultimately could result in using the microbiome to eliminate cancer in the body.

Along the same lines, another current research study is aimed at understanding the oral microbiota in general between ages, lifestyle habits, and family. They have found that the amount of sugar that someone prefers can be traced back to the specific make-up of the microbiota. This is revolutionary seeing as how before scientists did not believe that the composition of the microbiome had anything to do with human health. I was brainstorming extensions of this research that could include microbiome transplants to change taste bud preferences to improve overall diet. In learning about these two studies and brainstorming the uses of this research to aid human health, I began to realize how powerful the microbiome really is. I believe it is safe to say that in the coming future, a person’s microbiome analysis will be more common in normal medical processes.

The influenza has had especially detrimental effects in this particular flu season due to the shortcomings of the strain predictions that scientists made in the spring to prepare for the upcoming flu season. Influenza is an enveloped RNA virus with lipid membrane receptors neuraminidase and hemagglutinin. Because the flu is a segmented virus, meaning that its RNA genome is segmented with a high mutation rate, the flu has high genetic drift and genetic shift, one of its most meaningful virulence factors. This is the primary reason why a new vaccine must be created every year and why the vaccine created many not be accurate once months of mutation has occurred. This year in particular, we have seen a low percentage of effectiveness of the flu vaccine. However, in comparison to the highest prevalence years in the past, 2019/2020 does not seem to be record-breaking.

This year, Influenza B/Victoria has been the most prevalent, and the director of the National Institute of Allery and Infectious Diseases, Dr. Anthony Fauci, has even said that this year’s immunization is “not an awful match, but it’s not a very good match.” The CDC released data that this year’s vaccine is a 58% match for the B/Victoria strain. Although this is the most prevalent strain, the more harmful strain, H1N1 is a “very good match” for this year’s vaccine. This information proves that although getting the flu shot does not mean that there is a 0% chance of you or your child getting the flu, there is a much higher chance that getting the vaccine will decrease the life-threatening symptoms and harm of the flu. For some other strains like the H3N2, this year’s flu vaccination is only 32% effective. However, this strain is much less prevalent. Therefore, the effects of the lack of effectiveness have not been felt.

From this year’s flu, the CDC estimates already there have been 210,000-370,000 hospitalizations and 12,000-30,000 deaths. These deaths are usually found in populations that are already immunocompromised, the elderly and children, or infants why have not developed a full immune system. Something that I found most interesting in doing this research was that there are scientists working to create a universal flu shot that individuals would only have to receive once in their lifetime. They are working on targeting a part of the flu virus that does not mutate in order to kill all strains effectively despite mutation. So far, this vaccine would most likely take at least a decade to be developed and approved by the FDA. I believe that this could completely change the landscape of medicine especially pertaining to flu deaths. Before completing this blog post, I had no idea that the flu was so deadly and affected so many people outside of the week-long sickness I have seen in my family and friends.

In 1998, Andrew Wakefield published a highly controversial paper detailing the potential linkage of the Measles, Mumps, and Rubella (MMR) vaccine and the onset of autism and bowel disease. An article from the British Medical Journal explains that the cohort studied consisted of 12 patients that were all self-referred. After the paper was published, other scientists worked to verify these findings independent of Wakefield and his project. However, none of these independent projects have been able to prove the same linkage of the onset of autism and bowel disease from the MMR vaccination. In an article detailing the deep investigation into the motives and details surrounding the Wakefield study, NPR reported that there was support from a lawyer who was trying to file product liability suits against vaccine producers. There was also talk of creating a new business to make a new MMR vaccine for large profits.

Although it is clear now that the information that Wakefield presented was fraudulent and that the conclusion he drew from this fake data was incorrect, there have still been major repercussions in the public’s health. The above article from NPR reported that vaccination rates in the UK fell to a low of 80% in 2003-2004 because of the visibility of the study and the media response that arose. This can be compared to the 95% vaccination rate necessary for herd immunity in a population. Another repercussion can in the number of cases that signified that in 2008 measles was declared as endemic in England and Wales. Not to mention the repercussions for the autism community. The scientific efforts of those researchers working to learn more about the causes of autism were halted by the newsworthy false claims that required attention.

In my opinion, this paper was one case where an immoral motive that was most likely thought to harmless had massive repercussions and harm to an innocent population. This is why peer-review and ethical research is of the utmost importance today in the constantly advancing medical field. As herd immunity is lost in the decrease of vaccinated individuals, those individuals who are immunocompromised or unable to be vaccinated for other reasons are now at risk for contracting these dangerous and sometimes lethal infections like measles, mumps, and rubella. This case especially opened my eyes to the impact that researchers have on overall public health.