I chose to look at the well known monoclonal antibody Humira in this blog post.

Antibodies like IgM, IgD, IgG, IgA, and IgE are made and released upon an infection to protect us. In some cases, antibodies like IgE are activated in response to particles that are not harmful to us. This can lead to allergies and autoimmune disorders. MedNet explains that monoclonal antibodies are synthetically made to counteract the proteins that attack our normal tissues when no harmful substances are present. These antibodies are made from cloned immune cells that bind to specific antigens.

According to the Humira Prescribing Report, Humira blocks tumor necrosis factor (TNF) by directly binding to TNF. TNF is naturally produced by the immune response to cause inflammation. When people have too much TNF, it can lead to Rheumatoid Arthritis, Crohn’s Disease, Ulcerative Colitis, Plaque Psoriasis, and Hidradenitis Suppurativa. Humira is used to treat these through inhibiting TNF binding to immune cells that cause chronic inflammation. Humira is administered commonly through bi-weekly subcutaneous injections at the site of inflammation, or through pills. Some patients see benefits after 2 to 3 week and others take months.

SIDE EFFECTS:

Redness

Rash

Swelling

Itching

Bruising

Headache

Rash

Upper respiratory infection

Hep B in people who carry it in their blood

Allergic reactions

Hives

Trouble breathing

Swelling of your face

Nervous system problems

Blood problems

Heart failure

Liver problems

Lupus syndrome

Psoriasis

In addition to these side effects, you cannot take Humira if you have a positive TB test in the event that the Humira causes the TB to reactivate from the latent to the productive state. Additionally, you can not take Humira if you have latent Hep B virus for the same reason. The report also states that there is an increased risk for serious infections leading to hospitilization or death, including sepsis, invasive fungal infections, and other opportunistic pathogens. Lastly, forms of lymphoma and other tumors have occured taking Humira, especially in children. These are all possible risks that come with taking a TNF blocker because TNF is important in preventing tumorogenesis, spesis, and viral replication. The presence of Humira primarily decreases the innate immune response because TNF is primarily released upon activation of macrophages. This then activates lymphocytes, NK cells, and granulocytes to fight off infection. Pathogens that your immune system could have easily fought off before become more of a challenge with decreased TNF. It is important to research and read all of the possible side effects to determine if the risk is greater than the reward regarding your health while on this drug.

As the global pandemic continues, many, including me, are wondering what kinds of tests the scientific community have produced to help identify people infected with Covid-19. One of these types of tests typically used are antibody response tests. These can tell us a number of things, including if you have been infected in the past or are in a current infection. By analyzing antibody titers, scientists and doctors can obtain information on the amount of each type of antibody a patient has produced. Having only IgM antibody titers typically indicates a T independent response to pathogens, since no antibody class switching has occured yet. Having both IgM and IgG antibody titers can indicate that the patient is in a current infection or recovering from one since these are produced by the adaptive immune system upon invasion. Having primarily IgG titer suggests that the patient’s immune system has activated a secondary response, indicating that they have already seen this pathogen before. If we could determine who was IgG positive, we could detect asymptomatic people and prevent them from spreading infection unknowingly.

One of the Covid- 19 tests that is being circulated now is a serology test that is being used to try to quantify the number of cases, including those that are asymptomatic or have recovered. According to an article published by Johns Hopkins Bloomberg School of Public Health, serology tests are blood based tests that can be used to identify whether people have been exposed by looking at their immune response. There are many serology assays, of which the most common one being used is the rapid diagnostic test (RDT). These tests use blood samples to test patients for antibodies IgG and IgM, or viral antigen. It is recommended in this test to have baseline (before infection) numbers of IgG and IgM titers in order to see how much they have increased by.

Additionally to antibody tests, there are RNA tests that are being used to tell if someone is infected with Covid-19. An article published in American Society for Microbiology states that most Covid-19 tests identify viral RNA through nucleic acid amplification, using PCR. These tests have to have to have viral RNA present in the sample and so they are generally taken from the nasopharynx and oropharynx. Following swabbing, the samples are placed into a liquid to release virus RNA from the swabbed solution. This viral RNA is extracted and then amplified. This article also states that true clinical sensitivity of any of these tests are unknown, so a negative test does not negate the possibility that the individual is infected. They also point out that detected of viral particles does not equate to living virus that can be transmitted from that patient. These acute illness tests can be very useful but also have pitfalls that healthcare providers must be aware of. In my opinion, it would be more useful to know more basic information about the virus more broadly which not many people know, especially not the public.

As we have learned in lecture, dendritic cells are the best APCs, or antigen presenting cells our body has. When dendritic cells bind to foreign and possibly pathogenic material, they digest foreign material and present it for other cells to detect. Through differentiating into key players, and activating our adaptive immune system, dendritic cells are crucial in eliciting an immune response. This response regularly saves our lives when there is an invader. As we can see, these cells might be a powerful target for therapeutic methods.

In addition to the powerful responses dendritic cells can elicit, there are also blockades in place to restrict this immune response in order to prevent our body’s response to becoming harmful to us. Dendritic Cell (DC) Therapy is a fairly new and emerging way of treating cancer patients with vaccines. This therapy works by injecting and promoting dendritic cells to upregulate anti-tumor T cells in response to cancerous tumor cells. Researchers in this field have more recently been exploring molecular pathways that dampen DC’s ability to elicit a T cell response. In an article posted in Science Daily called “Potential boost to immunotherapy,” researchers have recently identified a specific pathway that regulates our immune system cells in lung cancer tumors. This pathway suppresses DC cells leading to anergy, which allows tumors to grow. By downregulating this pathway, researchers were able to increase the number of DC cells, which increases their cancer fighting ability in lung cancer patients.

I explored many clinical trials on the Clinical Trials database. I found that the most recently completed trial using dendritic cell vaccines in lung cancer patients just ended in November of 2019. I read the report and it showed many side effects of this type of therapy including anorexia, nausea, fatigue, weight loss, hyperglycemia, muscle weakness, and hair loss. I also did some research on dose pricing of dendritic cell vaccines and it turns out I did not find any in the US, but one resource stated that in Japan, a years worth of dendritic vaccines were around 2 million yen or $19,000 in the US. However, I do not know if there can be a direct currency transfer because our health systems might work differently. In the US, prices may be much higher if private pharmaceuticals make them so, which I suspect to be the case.

March 24th was World Tuberculosis day, however, unsurprisingly it was greatly overran by Covid-19 news coverage. In fact, in almost every article I read about TB, coronavirus was included as either a comparison or a reminder of how weak our immune systems really are to novel pathogens. According to an article published by Infection Control Today, named “Beware of the World’s Most Deadly Infectious Disease: Tuberculosis,” 10 million people had it in 2018, and 4 million people in 2020 will die from it. The article also reports that the 10 million cases (1.5 million deaths) in 2018 from TB has declined from 2% and 5% respectively since 2017 This can possibly be attributed to extra measures and can indicate their positive effect, giving health care providers and public health officials more incentives to keep fighting this disease.

Additionally, according to an article published called “Tuberculosis is the World’s Deadliest Infectious Disease,” tuberculosis kills more people than any other infectious disease. The deaths from Tuberculosis every day amount to about 4,000. Tb is difficult to treat because medications have to be taken over 6 months including a cocktail of four different antibiotics. Many patients develop resistant to Tb medication which prolongs and complicates treatment measures, and can increase transmission. As we learned in class, there is MDR, XDR, and TDR resistant strains of TB which poses a huge health crisis since antibiotics are having less and less success.

Moving forward, a statement released by the WHO places time as a central theme in treating TB. They aim to “accelerate the TB response to save lives and end suffering, building on a high level commitments by the Heads of State at the 2018 UN High-Level Meeting on TB.” This plan includes scaling up access, treatment, and prevention to ensure more resources are dedicated to TB research. They also want to ensure that there is a global strategy to control the disease that is responsible for huge social burdens. This task might implement community-wide screening regardless of symptoms in some areas of the world.

This entire situation is hard. I am a graduating senior and this semester was supposed to be great and filled with friends, UNC traditions, soccer, Chapel Hill in the spring, and many many other things I had to say goodbye to early. I am most upset about graduation and do not quite understand how they decided to cancel/postpone/whatever it so early. All my years of schooling lead up to this moment- all the sleepless nights, work ethic… everything, and now I feel like it will not get properly celebrated. I also did not know that my last soccer game would be my last or that my last practice was the last time I’d see my team all together. I did not know many things were my last at UNC. I can’t even remember the details of my last soccer game here- a sport that has somewhat defined me up to this point is now gone and I can’t even remember how I played in my last ever competitive game. There is no proper closure to my time at UNC.

Despite all my frustrations laid out in the first paragraph, I am very thankful that I am able to stay at home with my family, and in a place with internet connection where I can continue my classes. I think of those who are under more stressful circumstances whether it be moving back to another country, financial problems because of unemployment, or poor home life situations. While I am thankful to be here, it is definitely an adjustment. It is hard to study at home and to stay on top of all the assignments that are pouring in, taking the place of class time and projects. Some of my professors have seemed to be more lenient to try to work with us, and some have not but instead keep piling up the work.

On the other hand, I am trying to be optimistic about the circumstances and make them the best that I can. I think this is a time to rest, release, redefine, and realign. I want to come out of this cocoon as a butterfly, ready to tackle the world and my ambitions. I am going to optometry school next year so am trying to focus on all the positive and exciting things I have ahead of me. Overall, I am frustrated but optimistic and will appreciate “normal” so much more after all of this.

In the latest Situation report 53 posted March 13th, five new countries have reported cases of COVID-19 in the past 24 hours. Additionally, the WHO UN foundation and partners launched its first Solidarity Response Fund today. Hubei has the most confirmed cases at 67786 and the most deaths at 3062. The United States has 1264 confirmed cases, 277 confirmed new cases, and 36 deaths. While the WHO has developed interium guidance for lab diagnosis, advise on mask use and home care, and clinical management, there still seems to be a shortage of necessary test kits to determine diagnosis. This can be a target of concern because if not enough people are getting tested, then there are in reality many more undiagnosed cases.

The WHO also posed case definitions, for example a suspect case is a patient with acute respiratory illness (fever and at least one sign and symptom of respiratory disease), and with no other etiology that can fully explain the clinical presentation. I think that this is very difficult to explain and also detect because the symptomes are so much like other colds, flu, etc that people do not want to go get tested. I am worried that people will not want to go get tested if they have symptoms because they do not want to go to the doctor and risk picking up the virus. A probable case is a suspect case for whom testing COVID-19 is inconclusive and a confirmed is when the test kit is positive. I also fear the the hospitals and health care clinics will be over crowded with people getting sick and being tested.

The epidemic in the United States keeps on growing since the first case in late February. According to the CDC, as of March 13th, there are 1629 cases, 41 deaths, and 47 states reporting cases. I believe the numbers are much larger however, because clinics do not have enough test kits. 138 cases are travel related, 129 cases are close contact related, and the other 1362 are under investigation. The states with the largest number are California, Washington, and New York. North Carolina is under an intermediate category. Also, since COVID-19 has a two week incubation period, illnesses that began during March are now just being reported, and many others may have it without knowing. As we learned in class, long incubation periods allow for more spread of the disease because people do not show symptoms.

According to an article published in September of 2019 in Discover, four main STIs are on the rise. These four are not the mainstream STIs you hear about, but nevertheless should be treated with the same caution. One of them is called Mycoplasma genitalium. This bacterium has the smallest bacterail genome known. The CDC first acknowledged this as an STI in 2015, but scientists have known about it since the 80’s.

Targets for infection are the urethra and genital tract and can cause inflammation similar to gonorrhea and chlamydia. Other symptoms are scrotum pain and swelling for men, and damage to the fallopian tubes in women, causing vaginal bleeding and infertility. According to an article published in Pharmaceutical Journal, this bacterium is able to invade and adhere to reproductive tracts through sexual contact. Oral-genital transmission is possible but there are low rates of pharyngeal Mgen. Some further complications can occur in infected people suhc as reactive arthritis and epididymo-orchitis which is pain and swelling in the scrotum.

Mgen is very resistant to antibiotics, and only more expensive ones such as moxifloxacin are able to be effective. Mgen has many symptoms similar to other STIs, so doctors can often misdiagnose and prescribe wrong treatments for it, causing prolonged symptoms. According to the article published in Pharmaceutical Journal, misprescription of single-dose azithromycin for non-specific genital infections has caused selection pressures driving Mgen antibiotic resistance through macrolide resistance. Another factor contributing to misdiagnosis the fact that Mgen takes so long to grow which is impractical because it can takes weeks to months to culture. There fore, the molecular assay to diagnose is the most time efficient but lacks sensitivity and adequate laboratory validation.

From lecture, we learned that HPV is one of the most common sexually transmitted disease, and has the potential to cause cervical cancer as well. Therefore, it is crucial for sexually active men and women to receive the Gardasil vaccination which can protect up to 80% of HPV infections. According to an article published by the Mayo Clinic, the HPV vaccine can prevent most cases of cervical cancer if given before a girl is exposed to the virus. Additionally, it can prevent vaginal and vulvar cancer in women. The article also states that in theory, vaccinating boys and girls can help protect girls from the virus by decreasing transmission.

The vaccine is routinely recommended for girls and boys ages 11-12, before sexual contact is experienced. The CDC now recommends that health care providers administer two doses of the HPV vaccine at least six months apart instead of the previous 3 dose schedule. Researchers also say that the vaccine can still provide protection from some strains even if you receive the vaccine after you have become sexually active. Clinical trials show that the vaccine prevents infection in nearly 100% of persistent cervical infections with HPV types 16 and 18 that cause about 70% of cervical cancers. Clinical trials also found that Gardasil 9 is as effective as Gardasil for the prevention of disease caused by 4 shared HPV types based on similar antibody responses.

According to an article published by the National Cancer Institute, the World Health Organization stated that the Gardasil 9 and Gardasil HPV vaccines have equivalent efficacy and the Cervarix vaccine has been found to provide partial protection against a few HPV types no included in the vaccine that can cause cancer, called cross-protection. The article then goes on to state that a 2019 meta-analysis of girls-only HPV vaccination in 14 countries including 60 million vaccinated people showed strong evidence of the vaccine’s effectiveness. Infections with HPV 16 and 18 decreased in 83% of girls 15-19 years old, anogenital warts decreased 67% in the same age group, and prevalence of precancerous lesions that can lead to cervical cancer decreased 51%. Before the HPV vaccines were licensed they were tested for safety and the most common problem was brief soreness and local injection site symptoms. These seem like similar problems experienced with other vaccines and I think that the benefits of receiving the vaccine far outweigh the risks. It is important for everyone to get vaccinated in order to provide some sort of herd immunity and possible elimination of the disease.

In an increasing world of antibiotic resistance, it is crucial for the public and health care providers to be conscious and educated about when they should/can be used and when they cannot. Like we mentioned in class this week, antibiotics are a miracle drug and unfortunately many strains of bacteria we used to be able to treat are becoming antibiotic resistant. One of these growing antibiotic resistant bacteria on its way to becoming a superbug is Klebsiella pneumonia Carbapenamase (KPC). In a study conducted by Sapkota et al and published in “Scientific Research” identified that out of their infected patient population, 60% had bacteremia and 100% had already been treated with higher antibiotics like Carbapenams. In their study, only 9 out of 15 patients could be treated and discharged.

Their studies pointed more broadly to an emerging pan drug epidemic. KPC is considered a multi-drug resistant (MDR) organism on its way to becoming a super bug and identified as an urgent threat to human health by the World Health Organization and CDC. As we discussed in class, a super bug is a strain of bacteria that has become resistant to all antibiotics, and can transfer its resistance via horizontal gene transfer to other bacteria. In KPC, the gene it carries for its MDR is the ST-258 gene which carries resistance to carbapenamases and is responsible for several recent outbreaks in various countries. Carbapenamases are able to cleave the carbapenam B-lactam rings our antibiotics use to kill bacteria. With no B-lactam ring, antibiotics are useless to KPC.

KPC is not the only emerging super bug, but just one among many. A recent article published by the NIH, “Death from pan-resistant super bug,” explains how Acinetobacter baumannii has also emerged as a pan-resistant super bug causing fatal infections to vulnerable populations, especially those in the hospital. This past year, a patient died of this now pan-resistant bacteria due to a fatal pneumonia caused by the resistance to antibiotics. The article further explains that the pathogenicity is not due to virulence factors, but rather its resistance to antibiotics and ability to persist on surfaces of beds, curtains, walls, medical devices, and hand sanitizers. The emergence of these super bugs have caused intense research but it seems to me like the bacteria are able to spread resistance, especially in hospital settings, faster than we are able to counter them. In this situation, prevention is ideal but seems impossible because society as a whole is doing things to promote their resistance.

According to an article published by CNN health, a new study reveals that vaccines can prevent fatal complications from measles. Almost a third of all measles have complications like pneumonia, hepatitis and viral meningitis. Like we learned about in class, it also suppresses the body’s immune system and makes people vulnerable to complications in every organ of the body. Anti-vaccination campaigns have lead to increased cases of measles in children and adults. In fact, in the past year 1,282 cases of measles were reported in the US, the greatest number since 1992. Fortunately, the measles vaccine can prevent the disease, and protect our bodies from the immune wipe that measles causes, along with over complications.

According to a Mayo Clinic article updated in 2020 regarding the measles vaccine, the Measles Virus Live is an immunizing agent used to prevent infection. It works by causing your body to produce antibodies, but it does not protect you against Rubella, or German Measles that we learned about in class. This requires a separate immunization. The immunization is recommended for infants up to 12 months old, because the antibodies received from the mother may interfere with the effectiveness of the vaccine. This vaccine also requires two doses in order to prevent infection.

Another article by the CDC says that two doses of MMR vaccine are 97% effective against measles and it is an attenuated (weakened) live virus vaccine. This means that after the infection the viruses causes harmless infection and few to no symptoms arise. This is important to educate the public on because many anti-vax people convince others that health care providers are giving their children measles. However, the vaccine will actually help their children fight off measles when the actual disease is present, which can be the difference between life and death. It is important to correct people on false notions that vaccines are bad for people and cause infection because this is not the case at all. Vaccines save millions of people from becoming sick with serious diseases each year.