Author: cgwalter

Humira® (adalimumab) is a recombinant human IgG1 monoclonal antibody (mAb). Monoclonal antibodies are man-made antibodies that are highly specific for a single epitope of an antigen. These antibodies are mass produced in various ways, often using animal models/single B cell clone, by introducing an antigen (harmful substances that the host recognizes as being foreign) of interest to a mouse. For example, polyclonal B cells from the mouse’s spleen can then be fused to myeloma cells. This fusion results in forming hybridoma cells which are then cultured and allowed to continue to produce antibodies to the antigen. Generating monoclonal antibodies are useful because they have high affinity to only one epitope of your antigen of interest and can be produced from almost any substance. Also, since these monoclonal antibodies are produced from a single clone of B cells, all molecules in a preparation will have the same constant and variable regions and, thus, the same functional characteristics and specificity. These monocolonal antibodies can later be developed into immunoassays that detect or purify that antigen of interest. Therefore, there are significant biomedical value, including use in medications. Non-proprietary drug names end in the suffix -mab. Also, sometimes the monoclonal antibodies used need to be made more “human” in order to improve their therapeutic effectiveness. This is accomplished using recombinant DNA techniques that function to replace most of the animal-derived antibody molecule with human equivalents. When this happens it creates what is called a rhuMAb (recombinant humanized monoclonal antibody). The therapeutic value of these drugs are improved in humans because rhuMAbs have a longer half-life than standard monoclonal antibodies and the human immune system is less likely to destroy them. Non-proprietary medications composed of rhuMAbs have names ending in -zumab.

The FDA-approved the monoclonal antibody drugs adalimumab (Humira, Amjevita) in 2002 which is specific for human tumor necrosis factor (TNF). Humira is made by joining together DNA molecules and is thus recognized as a biologic. Because Humira is an immune supressant drug, patients typically must have an inadequate response to conventional medications to be considered. Humira is a tumor necrosis factor-α blocker, meaning that it blocks the inflammatory effects of tumor necrosis factor alpha (TNF-alpha) in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn ‘s disease of the intestine and ulcerative colitis. As part of the inflammatory response mechanism of the immune system, a protein called tumor necrosis factor, also known as TNF, is naturally produced by the body’s immune system. Humira works by binding to TNF-alpha molecules and blocking them from attaching to and attacking healthy cells. When TNF-alpha concentrations are high it can be very damaging to the body so blocking those cytokines helps reduce the damaging effects of excess TNF.

Inflammation is not all bad, it is the body’s reaction to injury and it is a necessary process for the repair of that injury. Consequently, TNF-alpha is a cytokine that is produced by macrophages, monocytes, endothelial cells, neutrophils, smooth muscle cells, activated lymphocytes, astrocytes, and adipocytes in the body. TNF-alpha has many functions, such as mediating expression of genes responsible for making growth factors, cytokines, transcription factors, and receptors. When TNF is secreted by the body, it promotes inflammation and results in various signs, such as in the case of arthritis, include pain, fever, tenderness, and joint swelling. For example, the inflammation in Crohn’s disease can result in perforations or narrowing in the intestine. By blocking TNF-alpha, the consequences in the joints and intestine are reduced/slowed or prevented.

Inflammation plays an essential role in shaping the ensuing adaptive immune responses. One of the consequences of blocking TNF-alpha and reducing its prolonged inflammatory response is that it can lower the ability of your immune system to fight infections. Therefore, people being treated with HUMIRA have an increased chance of developing serious infections, hospitalization or even death. Additionally, patients may experience serious adverse events such as increase the chance of getting lymphoma, skin or other cancers. I think that’s why HUMIRA is a last resort drug because there have been cases of unusual cancers in children, teenagers, and young adults using TNF blockers. In fact, some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma which can often results in death.

Although there can be serious consequences to taking a TNF blocker, typical side effects include headache, rash, nausea, stomach upset. Also, adalimumab also has been associated with serious infections such as tuberculosis and sepsis (bacteria in the blood) and fungal infection. In some cases people have developed active tuberculosis (TB), including reactivation of latent TB. Latent TB can become active again in cases of weakened immune system so these patients have frequently presented with disseminated or extrapulmonary disease. Since adalimumab suppresses the immune system, it can be associated with minor infections of the urinary tract, respiratory tract, and sinuses, hypersensitivity reactions (including anaphylaxis ), reduced levels in the blood of platelets and red cells (aplastic anemia ), and may increase the risk of reactivating hepatitis B virus in chronic disease. Therefore, I think that TNF-alpha can be a double-edged sword. In the initial inflammatory response it can be invaluable in responding to and repairing wounds and infection but prolonged inflammation due to elevated levels of TNF-alpha can lead to damaging of healthy tissue and the inflammatory devastation seen in the earlier mentioned diseases. Severe side effects include heart failure, liver problems/failure and nervous system weakness.

I am very impressed that our body’s are so well equipped to protect us from invading pathogens and substances it recognizes as being foreign. However, too much of a good thing can lead to serious consequences to the homeostasis that our body needs. In this case we see how inflammation is a useful defense of our immune system but too high levels of inflammatory cytokines can lead to damage to normal tissue and result in disease. In the case of HUMIRA, patient’s and clinicians have to balance the pros and cons of risk/benefit assessments and can have positive results under careful and well monitored treatment.

We are in the midst of a global pandemic, similar to but with greater mortality, to what the world experienced during the coronavirus infection outbreak in 2002-2003 by Severe Acute Respiratory Syndrome (SARS) and in 2011 by Middle East Respiratory Syndrome (MERS). The new corona virus is leading to more deaths in part because it is highly contagious and believed that SAR-CoV-2 is probably being spread via asymptomatic-infected individual. What is intriguing is that since these are all coronaviruses there are similarities between COVID-19 in its genome in that it is closely related to SARS-CoV and MERS-CoV. Therefore, researchers are using accumulated clinical and experimental data on these previous viruses, to make hypothesis and even predict how the host immune system may deal with and even evade the novel corona virus. One of the recent topics that emerged in the treatment and innoculating using convalescent sera. Using convalescent sera is a form of passive antibody therapy (PAT). PAT involves administering antibodies against a given agent, in this case serum from a recovered COVID-19 patient, to a susceptible individual (i.e. an exposed healthcare worker). The exposed healthcare worker can be helped to prevent or even treat a COVID-19 infection, particularly during early exposure. This is in contrast to the other endeavor, which is to develop an active vaccination which would require the induction of an immune response which usually takes 5-10 days to develop an immune response that results in antibody production. Thus, since no active vaccine has yet been developed passive antibody administration is the only means of providing immediate immunity to susceptible persons.

So that brings the question, what does the use of convalescent sera for COVID-19 look like? Basically, when an individual becomes sick with COVID-19 and recovers, they have circulating virus-neutralizing antibodies that could be used to innoculate an exposed COVID-19 patient. Recovering patients can be screened and identified for those with high titers of neutralizing antibody. These serum containing virus-neutralizing antibodies can be administered in a prophylactic manner to prevent infection in high-risk cases. Therefore, vulnerable individuals with underlying medical conditions, health care providers, and individuals with exposure to confirmed cases of COVID-19 can get immediate antibodies to fight early viral particles before their systems are overloaded with virus. Additionally, in some cases, convalescent serum could potentially be used in individuals with early onset of clinical disease to reduce symptoms and potentially even mortality. Although there is great historical precedence in using convalescent sera to prevent disease, the efficacy of these approaches to treat an established infection is not yet known.

The main draw back to the humoral immune response is that it takes time to produce antibodies naturally. However, the production of neutralizing antibody are vital and plays a protective role by limiting infection and producing memory that respond in a later phase to prevents re-infection in the future. Based on research from other pandemic corona virus, the anticipated mechanism of action of SARS-CoV-2 by which passive antibody therapy would mediate protection is also viral neutralization. There have been some less conclusive results that other mechanisms may be possible to a lesser degree, such as antibody-dependent cellular cytotoxicity and/or phagocytosis. In addition to convalescent sera, possible sources of antibody for SARS-CoV-2 are from preparations generated in certain animal hosts, such as genetically engineered cows that produce human antibody. These animal host sources are important until more individuals contract COVID-19 and recover, at which time the number of potential donors will continue to increase.

Initially, all B cells are programmed to differentiate into plasma cells that secrete IgM. IgM antibodies are the first to respond during the primary response. However, during the T-dependent response, helper T cells secrete cytokines that induce some activated B cells to switch the original genetic program and differentiate into plasma cells that secrete other antibody classes. There are some cases, like an immune response to a T-independent antigen, that will only produce IgM and will never develop memory to that infection. The IgM will just wane over time with limited availability. These individuals would only have IgM antibody titers because they would lack the appropriate response that would have led to class switching. Conversely, B cells located in the lymph nodes most commonly class switch to IgG production. Patients responding to COVID-19 infection would have both IgM and IgG antibody titers. In addition, all memory plasma cells would secrete IgG so if patients were exposed to a secondary infection of COVID-19 they would primarily have IgG antibody titer. In fact, in a preliminary study, there was limited serology details of SARS-CoV-2 reported. One patient showed peak specific IgM at day 9 after disease onset and the switching to IgG by week 2. Some intriguing data showed that some of the patients that were confirmed COVID-19 showed some cross-reactivity with earlier SARS-CoV, but not other coronavirus. Interestingly, sera from all patients were able to neutralize SARS-CoV-2 in an in vitro plaque assay, suggesting a possible successful mounting of the humoral responses. Finally, both IgG and IgM antibodies started to increase on around day 10 after COVID-19 symptom onset, and most patients had seroconversion (class switching) within the first 3 weeks. It was also observed that the IgG and IgM antibody level against the SARS-CoV-2 internal nucleoprotein and the surface spike receptor binding domain correlated with neutralizing activity. If it was possible to screen and determine who was IgG positive we would be able to tell who has been infected and recovered and these would no longer be able to infect others.

I think the topic of using COVID-19 convalescent sera is so useful because it could be used to treat individuals with early symptoms and prevent disease in those exposed. Doctors and nurses in the front line today who have been exposed to known cases of COVID-19, some of whom have developed disease, are being quarantined. Once these healthcare workers are in quarantine they can no longer treat patients, which threatens to collapse the health care system. So far it is showing promise and it is anticipated that convalescent serum will prevent SARS-CoV-2 infection in those to whom it is administered, whether healthcare worker or among family members caring for COVID-19 patients at home.

Currently, many people living with a HIV+ health status can have their viral load reduced to undetectable using a life-long antiretroviral therapy (ART). ART has proven to be effective but it has to be taken indefinitely to prevent rebound of viremia and re-emergence of symptomatic disease. There are several avenues that HIV attains latency, but one of these latency mechanisms includes the recruitment of histone deacetylases (HDACs) to the region on the HIV long terminal repeat (LTR) promoter. This mediates the formation of a repressive chromatin environment that inhibits LTR expression and HIV viral production. Therefore, when ART is taken continuously it helps prevent latent disease from the persistence of long-lived viral reservoirs in host cells. However, this potential for recurrent disease remains the unfortunate limitation to HIV eradication using ART so the need for continual research and developing innovative therapies to control HIV-1 infection beyond the limitations currently available with ART.

Consequently, previous studies have demonstrated that HDAC inhibition serves as an antagonist for the repression of HIV transcription so it has been investigated as a tool to reverse HIV latency in humans. Additionally, exposure to a known HDAC inhibitor vorinostat (VOR) has been shown to induce HIV antigen expression at a sufficient enough level to allow for host viral clearance in vitro. The above mentioned case study presents the results of combining a validated latency reversing agent (VOR) along with an immunotherapeutic (AGS-004) shown to generate a HIV-specific immune response. AGS-004 is a dendritic cell (DC)-based immunotherapy. The agent/vaccine consists of matured autologous DCs co-electroporated with in vitro transcribed ribonucleic acid (RNA) encoding autologous HIV antigens. Having these antigens helps to achieve DC functionality. According to the study, “this vaccine was reported to induce HIV-specific effector/memory CD8 T-cell responses in HIV-infected individuals who had initiated ART during acute or chronic infection.” The results were not completely what they hoped for since there were “no measurable impact on the replication competent reservoir as measured by QVOA assay.” However, there was some promise shown that DC-based HIV vaccines can have a slight improvement in HIV specific T cell responses. I think having DC immunologic therapy is promising and for all the millions of people living with this chronic disease.

Finally, T cell and DC-based immunotherapies have also been tested for the treatment of cancer patients but it has only shown limited success. One of the problems observed was the ineffective activation of specific T-cells by the injected dendritic cells in vitro. However, it is showing promise in vitro since memory T-cells were generated and induced an immune response that could circumvent the ineffective T-cell activation. Therefore, this approach demonstrated that it could greatly enhance the efficiency of cancer immunotherapy if it could be made to be reproducible in vivo. This is especially exciting since cancer and HIV affect so many of us in one way or another and it is claiming the lives of many of our loved ones. Maybe during our generation we’ll see the emergence of a refined methodology where DC-based immunotherapy could induce the appropriate T cell response that would provide the needed break-through for these deadly diseases.

Tuberculosis (TB) is an infection that is caused by the bacteria Mycobacterium tuberculosis and most commonly affect the lungs. TB is a topic that I’m close to because I’m from Jamaica, WI and was vaccinated (BCG) as a child for TB. Since moving to the US, I’ve had to go through the routine regimen of antibiotic treatment, occasional x-rays and more recently the quantiferon-TB-Gold blood test that detects levels of the bacteria Mycobacterium tuberculosis. I’ve been in the US since I was 8 so it’s been years of going through TB screening and at this point I’m pretty used to it. Also, TB is one of the leading cause of death in many parts of the world so it’s still a formidable disease, therefore I understand the need for caution and the endeavor to prevent the spread of this infectious disease. In fact, there are over 10 million cases of TB worldwide and almost 1.5 millions of death just in 2018 alone. Apparently, there are over 1.7 billion people living with TB worldwide. TB has become so rampant in parts of the world because it has become difficult to control. Tuberculosis (TB) is impeded by the problem of drug-resistance and in many cases the emergence of multi-drug resistance. Although most cases of TB in the United States (US) are from non-US natives, it is still a growing threat that the US has to contend with. In many parts of the world, TB is the number one killer of those infected with HIV and one-third of the world’s population has latent TB. Latent TB is a state where people are infected with TB but it is in its dormant state where the disease has the ability to be reactivated.

TB has become difficult to treat because the first-line antibiotic treatment that are commonly available have become ineffective against the bacteria due to drug resistance. Therefore, the current standard for treatment after a positive TB test is combination therapy for 6 months using first-line antibiotics for 2 months and 4 additional months with a different combination. Evidently, most Mycobacterium tuberculosis (Mtb) strains are defined as being resistant to at least isoniazid and rifampin, which are the two most commonly used bactericidal drugs and are essential for the treatment of the disease. What is the cause for the rise in drug resistance and even multi-drug resistance? Well, there are clinical, biological and microbiological factors that account for this problem; first, of these include patients not being compliant with the long duration of treatment advised by their physicians. Patients either stop taking the drug early or they frequently miss doses or they take the medication irregularly so that they don’t maintain serum levels high enough to effectively keep growth at bay. Another reason for drug-resistance relates to the complexity and poor vascularization of granulomatous lesions. Lacking proper vascularization means that the treatment drugs can not be properly distribution to some sites. When this happens resistance develop since the bacteria is shielded and can give rise to the formation of non-replicating, drug-tolerant bacilli inside the granulomas. Additionally, mutations can develop that provide a molecular mode of resistance or the bacilli can also have intrinsic drug resistance. Finally, in developing lands that may be financially deficient, physicians may have inferior regimen selection options, and inadequate drug supply that make adherence to the 6-months therapy virtually impossible.

Despite the challenge of drug resistance there is still a concerted effort being made to end the TB epidemic by 2030.  Currently, globally, TB incidence is falling at about 2% per year. However, the desire is for this rate to increase to reach around 4–5% annually in order to reach the 2030 milestones towards ending TB.  Not only is Tuberculosis a curable disease but it’s also very preventable. Currently, there are eight countries that carry the majority of the burden of TB and account for two thirds of the total cases; this includes India leading the count, followed by, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa.  TB is airborne and spread from person to person when people with lung TB cough, sneeze or spit, they propel the TB bacteria into the air.  This infection has a very low ID₅₀ since a person only needs to inhale a few of these bacteria to become infected.  Therefore, it’s no wonder why Multidrug-resistant TB (MDR-TB) remains a public health threat and a community crisis.  In 2018, WHO estimates that there were almost a half-million new cases with resistance to rifampicin, which is the most effective first-line drug, of which 78% had MDR-TB.  Since adherence is such a key element to MDR-TB, consideration is being given to shortening the duration of therapy.  A massive effort is being made to ramp up testing in high risk areas to help with diagnosis and early intervention and treatment.  The political declaration of the UN indicated billions of dollars dedicated to TB preventive and treatment for a latent TB infection. Finally, in 2016, WHO recommended 4 new diagnostic tests that can provide a rapid molecular evaluation of type of TB a person is infected with. One of them is called the Xpert MTB/RIF. Also, there are 3 other tests to detect resistance to first- and second-line TB medicines. These test along with support to the patient by a health worker or trained volunteer are helping with treatment adherence and reducing deaths associated with the disease.

This Meme has become the theme of the past few weeks. I work at a retail facility and we’ve been out of hand sanitizer for weeks. Even when the shelves do get restocked the supply is exhausted in minutes. I’ve had to explain to my children about this virus in as simple terms as possible and I was surprised to see that they are being affected more than I realized. My youngest son was expressing how he was afraid that he could die from getting infected and is afraid to go outside, even just to play. He felt that the virus was “scary”. The biggest disruption is the closure of schools which provide some semblance of structure and normalcy that has been ripped away. Although my children are not the biggest fans of school, they sincerely miss their teachers, friends and activities that they are involved in. Plus, what’s the fun in staying home when you are confined to the home and not able to spread your wings with the various forms of entertainment that keeps us preoccupied? However, they expressed sentiments that they understand why the dramatic isolation is necessary.

I’m having mixed emotions about how I feel. A part of me feels like as a society we needed to slow down and re-evaluate what’s really important in life. I know I’m so busy all the time that it’s hard to find time to appreciate the little things that bring me joy. With that being said I’m grateful that all my loved ones are safe and besides the inconvenience of having to stay at home, we have a lot to be grateful for. My only concern is how I will manage my children being home during the day where they have remote learning also, plus I still have to go to work. So far it has been ok, I’ve just had to be a lot more organized and managing my time more effectively. It is a challenge but I think the UNC community and the NC community at large has been emphasizing that we are all in this together so that is reassuring that although these are unprecedented times by working together we can accomplish amazing things. I think it’s also a great lesson to my children about overcoming adversities and no matter how difficult times get, we should stay focus on our goals but be flexible enough to make adjustments where needed. The cool thing is they see me doing my homework and it inspires them to complete their assignments too.

While I’ve been home I’ve been using this time to deepen my relationship with God and his son Jesus. As a christian these are bible fulfulling times where a lot of what we’ve learned from the bible is being played out in real time. For instance, Jesus gave his followers incite as to what to recognize when world conditions would take a turn for the worse. These times on earth are referred to as “the last days” (2Tim 3:1-5). Although God’s kingdom is ruling in heaven, Satan the Devil and his demons have been expelled to the vicinity of the earth where they are influencing mankind and the conditions that humans are facing. In fact, the disciples asked Jesus in Matt 24:3, 7…”Tell us, when will these things be, and what will be the sign of your presence and of the conclusion of the system of things?…and the answer, found at Luke 21:10, 11…”for nation will rise against nation and kingdom against kingdom, and there will be great earthquakes in one place after another, food shortages and pestilence”…However, there is hope for the future because soon Jesus will remove Satan’s influence and will destroy the Devil’s supporters and reverse the destructive effects (Rev 20:1-3). Eventually, the bible at Rev 21:4 says “death will be no more, neither will mourning nor outcry nor pain be anymore”. So at the end of the day I feel encouraged because I know that God is in control and it strengthens my resolve to deepen my love for God and his promise through his son Jesus.

One of the things that also give me comfort is seeing how so many of my neighbors have been carrying out acts of kindness. Practicing social distancing is not natural to me because I’m such a hugger and desire emotional connections. However, people are adapting and despite social distancing they are being encouraging to each other and helping those that can not get out to run errands and get much needed supplies and groceries. I know that I’ve been running errands for friends and loved one and bringing toilet paper (which has become more valuable than a golden nugget these days) and other needed grocery items. I’ve been picking up take-out for people who can’t get out on their own and I’ve been doing it all with my own limited resources and finances. Additionally, at work at a public major retailer I’m cheerful and positive, helping to keep people’s mind off our current crisis. At work, I’ve submitted to the most sincere form of humility, volunteering to clean/sterilize company equipment and frequently touched surfaces. I try to take on the menial tasks with enthusiasm and public service because if my sterilizing surfaces helps to keep people from getting sick then I feel my efforts have been rewarded. These are challenging times and we truly are in this together.

I wanted to continue my discussion of the novel coronavirus (Covid-19) that was first identified in Wuhan City, China. It is spreading quickly and leaving it’s mark. Many are succumbing to the grips of the virus, particularly our elderly population, those with underlying respiratory conditions and/or immunocompromised. To date, there are over 320,000 confirmed cases of the infection, claiming almost 14,000 lives worldwide. In NC alone, almost 6500 test have been administered, resulting in 255 confirmed cases. Gratefully, none of those positive tests have resulted in any fatalities. However, the efforts of the COVID-19 response team lead the governor of our state to issue several Executive Orders, including declaring a state of emergency, closing all schools and restricting restaurants and mass gatherings. These are unprecedented measures being taken at an attempt to flatten the predicted bell curve that represents the course of this viral disease. Flattening the curve would result if we are able to avoid too many people getting sick at the same time especially since resources are limited. If less people are infected then the peak of the curve would be lower than expected and we would be successful in flattening the curve.

One of the interesting findings that has emerged from the review of Covid-19 cases is the problem of asymptomatic transmission. Researchers in Texas, in the field of infectious disease found that at least 10% of cases, in a chain of transmission, included patients that were infected by somebody who has the virus but does not yet have symptoms. They were able to calculate the serial interval to be 4 days. To the measure serial interval, the scientists take into account the time it takes for symptoms to appear between two infected people: how long it takes for the infection to spread. Apparently, the 4 day serial interval is very short , attributing to why the COVID-19 outbreaks is spreading so quickly and is predicted to be difficult to eradicate which is the reason why officials are moving quickly and aggressively to curb the impending threat. In fact, asymptomatic transmission makes containment more difficult and explains why “extensive control measures including isolation, quarantine, school closures, travel restrictions and cancellation of mass gatherings may be warranted.” A CNN report of 24 passengers on a flight to Israel where seven of the 24 passengers tested positive for coronavirus. Interestingly, four of the seven passengers displayed no symptoms, yet when specimens were tested, it was discovered that the viral load of the four asymptomatic specimens were higher than the viral load of the three symptomatic specimens. The viral load tells us the relative concentration of virus in someone’s respiratory secretions and a higher load is synonymous with someone that is more likely to spread the infection to other people.

Speaking of spreading infection, I read an interesting article entitled, “A coronavirus cautionary tale from Italy: Don’t do what we did”. The article revealed how citizens refused to change their behavior because Italians failed to take the virus seriously. Also, the information coming from the government were less-than-urgent appeals to the public to slightly change habits regarding social interactions. However, many Italians “just didn’t see the need to change our routines for a threat we could not see.” The result of ignoring a situation that could have been preventable is that now the country is in lockdown and thousands of people are needlessly dying. Apparently, the number of deaths are disproportionate in Italy due to its large elderly population. Additionally, the hospitals were not equipped to handle the massive number of cases and it reminded a health care worker of “war time” where difficult triage decisions needed to be made about who to treat and who not. Many are saying that the overload to the health care system put it on the verge of collapse. Consequently, there just wasn’t enough beds for everyone so some people who were not able to get medical care were just dying in their homes. The warning went out to the US because we only have roughly 45K ICU beds but the outbreak is predicted to need more that 200K ICU beds if we are not successful in flattening the curve. The author remorsefully remarks that “when everybody’s health is at stake, true freedom is to follow instructions.” I hope many of us heed the warning and stay home as much as possible so we don’t have regrets and lose countless lives prematurely in death because COVID-19 created inconveniences in our lives that we didn’t want to adhere to.

Last week I discussed the common STD HPV but wanted to further that forum. One of the interesting findings I came across when researching HPV was how the concept of sexual activity shaped provider’s and parent’s decisions on whether to vaccinate children against HPV. One of the parental concerns was that if children became vaccinated it would prematurely introduce them to engaging in sexual activity and children being labeled as “sexually active”. On the other hand, some providers have fear that pushing the HPV vaccine would harm their relationship with parents and even jeopardize their ability to subsequently effectively treat their patients. I was new to this notion that parents and providers were facing a social/stigmatizing dilemma that could pose a risk to patients’ health. In fact, HPV vaccination preference is often based of the combined efforts of the providers’ concerns and the parent’s confronting their fears of early sexual activity, and “the patient’s risk of imminent sex to decide whether the vaccine’s benefits to the patient are worth pushing vaccination and risking relational harm.” As a striving clinician, I would probably be biased towards pushing the potential benefits of treatment while being sensitive to parental concerns and social stigmas. However, I would probably feel so excited to be able to present this life-saving opportunity that I must admit that the conversation would be frustrating if emphasis was placed on potential fears in lieu of the impending threat/risk to the patient’s health and future well being. I think these type of issues demonstrate the need for clinician’s to be trained to be culturally sensitive so they can best serve the needs of their communities where viewpoints may differ or even opposing.

Another common STD, HSV-type 1 and 2, are two categories of the Herpes Simplex virus that result in a lifetime of being infectious. HSV-1 is highly contagious and commonly transmitted from oral contact and causes mouth sores via contact with the HSV-1 virus in sores, saliva, and surfaces in or around the mouth. The symptoms of oral herpes vary and can include painful blisters or open sores called ulcers in or around the mouth. The open sores are often found on the lips and are given the common term “cold sores.” When a person is infected they will often experience a tingling, or burning sensation around their mouth, which can sometimes become itchy. These events frequently occur before the appearance of the sores themselves and recur periodically after initial infection during latent infections. HSV-2 is usually sexually-transmitted through contact with genital surfaces, skin, sores or fluids of someone infected with the virus and leads to genital herpes. Symptoms of genital herpes are characterized by blisters or open sores occurring on the genitalia or anus of the infected person. Sometimes, these blisters are accompanied by a fever, body discomforts and aches and swollen lymph nodes, indicating an immune response. Since HSV infections are incurable, after the initial exposure with HSV-2, recurrent disease is likely, albeit less severe than the first outbreak, and reducing in frequency over time. In some cases infected persons may experience identifying symptoms such as sensations of mild tingling or shooting pain in the legs, hips, and buttocks before the occurrence of genital ulcers. Despite these varying symptoms, it is important to note that having oral-genital direct contact can lead to cross-infections, where oral HSV-I infection can result in genital herpes and vice-versa.

HSV are highly contagious, so it’s no wonder that it is estimated that approximately 2/3rd of the global population are infected with HSV-1 and around 400 million are infected globally with HSV-2. What people may not know is that HSV-1 and HSV-2 infections are often asymptomatic yet patients are still contagious and can infect others. Also, infections with HSV-2 increases the likelihood of becoming infected with HIV. With these elevated levels of exposure and associated risks it is reasonable that attempts are being made to develop a vaccine to prevent these diseases. When a vaccine is administered in an effective amount, they are a useful tool to inducing an antigen-specific immune response. One current protocol includes a RNA (e.g., mRNA) vaccine that may be used to induce a balanced immune response against herpes simplex virus (HSV). When injected it would comprise both cellular and humoral immunity, without risking the possibility of a common concern, insertional mutagenesis (mutations caused by addition of one or more base pairs). Conveniently, the RNA vaccines have many important features that allow them to be useful to treat and/or to prevent various genotypes and strains of HSV. Some of these features include having antigenic polypeptides that have at least 95-99% identity to several HSV (HSV-1 and HSV-2) glycoproteins, immunogenic fragments capable of inducing an immune response, or amino acids sequence coding for proteins involved in the fusion of viral and cellular membranes. Because of these features, they produce a superior immune response noticed in the much larger antibody titers observed. Finally, they are better than some commercially available anti-viral therapeutics in producing early responses to treatment thereby improving pharmaceutical efficacy.

I feel that with all the adverse effects associated with acquiring a STD it’s really a parents due diligence to ensure their children are prepared to face the dangers they will encounter as sexual activity is a more than likely eventuality. I would hope that parents wouldn’t use the fear of sexual exposure as a crutch to making healthy choices for their child, although I am aware of cultural differences in how such topics are presented. Therefore, since HPV and HSV are sexually transmitted diseases with lifetime consequences, it is only reasonable to have open discussions with the adolescents including the prevention AMC’s like abstinence, monogamy and use of condoms. Regardless of parental fears, I feel it is worth it to introduce alternative options to having sex, such as just not engaging in it – waiting until they are older or goodness forbid until they are in the confines of a marriage; realistically though, it’s fair to also discuss safer options if they do become sexually active such as having only one disease-free partner or using physical barriers like condoms. I think a clinician can be helpful along with a parent but I mostly believe this is a parental role. Additionally, I feel a valuable skill for clinicians, if they do become involved with this discussion, is being “culturally competent” where one makes decisions taking into account their ability to effectively communicate with people of different cultures and avoiding imposing one’s personal views. Gaining knowledge of other’s cultural practices encompasses developing a positive attitude towards different viewpoints and embracing world views that may differ from what one is used to.

The CDC considers the Human papillomavirus (HPV) as the most common sexually transmitted infection in the United States. It is estimated that greater than 79 million people are infected with this virus, ranging from those in their teens to early 20’s at the time they were infected. About 14 million people become newly infected each year. HPV is so common that almost every person who is sexually-active will get HPV at some time in their life if they don’t get the HPV vaccine.Most cases of HPV are self-resolving but when HPV does not go away on its own, it can cause health problems like genital warts and cancer. It is important to know that the types of HPV that result in genital warts are not the same as those types involved in cancers.

Some health consequences that are caused by HPV can be prevented by getting the HPV vaccines. However, the current recommendations for the vaccine are on average around ages 11 or 12 years (although one can start as early as age 9 years) and for everyone through age 26 years. Therefore, parents are having to now make decisions about getting this additional vaccine to help protect their children. Moreover, the vaccination is not recommended for individuals older than age 26 years because it is shown to be less beneficial; but, depending on individual risk/benefit assessment some adults age 27 through 45 years, who are not already vaccinated, may decide to get the HPV vaccine. I think that it’s great to now have some additional options to make informed decisions about life-saving vaccines.

The HPV vaccine can halt transmission of the virus and can reduce or eliminate developing various life-threatening cancers later in life. I think that HPV vaccination makes sense because it could prevent more than 90% of cancers caused by HPV—this could save potentially an estimated 32k+ cases ever year from ever developing. This is because before HPV vaccines were introduced, thousands of women and men were plagued with the typical genital warts caused by HPV every year. In reality, this accounts for about one in 100 sexually active adults in the U.S. has genital warts at any given time. Additionally, despite screening and treatment options improving, tens of thousands of women living in the U.S. will be diagnosed with cervical cancer, and more than 4,000 women die. I believe that the vaccine does bring a lot of hope. In fact, since the introduction of the HPV vaccine in 2006, incidence of HPV infections have already started to decline; particularly for the HPV infections with strains 16 and 18, that most readily lead to eventual cancer diagnosis, dropped significantly (~80%+) among girls ages 13-19 and by 66 percent among women ages 20-24 up to 8 years after vaccination. These results are according to a recent systematic review. Additionally, since nearly all cervical cancers are caused by HPV infections, the vaccine is helpful because cervical cancer may take decades to develop after initial HPV infection. Therefore, getting vaccinated against HPV infection is your best protection from cervical cancer.

One of the infectious diseases we studied so far is the highly contagious measles. Measles are caused by a single-stranded enveloped RNA paramyxovirus that replicates in the respiratory tract. I was intrigued to learn that measles have re-emerged as global concern with thousands of deaths in the past several years. In the article, “Measles: An Overview of a Re-Emerging Disease in Children and Immunocompromised Patients,” written by Misin et al., explains that despite the availability of safe and effective vaccinations, in recent years, hundreds of thousands of new measles cases were reported worldwide, which resulted in thousands of deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is speculated to be caused by the ongoing refusal of vaccination coverage.

Measles is especially dangerous because it can lead to complications involving almost all organs and systems. Measles destroys the epithelium, favoring bacterial superinfections. The measles vaccines are attenuated viral vaccines that replicate within the host to induce protective immunity. However, in order to achieve protective efficacy, or herd immunity, we need a level of immunity within the entire population. More precisely, to obtain her immunity for measles we require vaccination coverage ranging from 93% to 95% with two doses of measles vaccine. If parents opt out of vaccinating their children then those numbers drop significantly and we see the trend of re-emergence of the disease in the population. Nevertheless, the choice these select small minority of parents that opt out of vaccination protocols endanger the lives and health of their own children and, crucially, others as well, at risk.

This phenomenon of herd immunity is especially useful in the community because there are always some in any society who cannot, or will not, be immun-ized. Reasons vary but include people that cannot be vaccinated for medical reasons, such as immunocompromised, pregnant, etc, or because they are too young since some vaccines are attenuated and require a developed immune system to offer protection. Also, some may be poor and lack access to healthcare. Therefore, it is vital to establish and maintain that community immunity to protect the population at large. Although all states have laws to impose vaccination requirements, some still find loopholes to avoid this requirement. Theses loopholes include religious affiliations, moral and philosophical objections and other conscientious exemptions. Unfortunately, it’s taking some devastating new outbreaks to open that dialogue again and converting some to be vaccine believers. More policies are being implemented to reduce the number of non-medical exemptions that are issued in hopes of minimize further outbreaks. I think that it is nice that we live in a society with liberal “free choices” but I feel that when those “free choices” impose a significant risk to those who have not made similar choices then it’s infringing on other people’s free rights. At the end of the day, who should have the final authority on who has priority to impose their free right? The person exposing others to risk, or the person being exposed? Obviously, legislature is only one means to combat these issues but maybe continual educational campaign could be beneficial to help further demystify the fears of vaccination and help move this discussion forward.

In the late 1800’s, medical associations were established linking bacteria to the cause and proliferation of various infectious diseases. However, there were not effective treatments available to treat these infections so death was common place even due to simple scratches, cuts and operations. Thanks to the discovery, albeit accidental, of the first antibiotic penicillin by Alexander Fleming in the late 1920’s, the tides began to shift in the treatment of bacterial infections. Antibiotics are naturally produced compounds that are made by mold or bacteria. Throughout the 20th century, antibiotics have been considered a “wonder drug” and a “miracle drug” and production of antibiotics became a priority goal, revolutionizing the practice of medicine and saving millions of lives. With that being said, sadly, many original antibiotics are no longer effective at treating bacteria that they once were able to combat. This is because bacteria have gotten smarter and some gained the ability to modify themselves in some way to resist the effects of antibiotics. In fact, there are real and emerging fears that the 21st century may see a reversion back to pre-antibiotic days when common infections and minor injuries could result in unfortunate deaths.

Antibiotic resistance is a serious concern both to research and the medical community at large. Microorganism can acquire resistance to antibiotics due to genetic changes such as horizontal gene transfer or spontaneous mutations. Moreover, recent research suggests resistant bacteria are a natural feature of all microbial populations, more so than a modification of existing bacteria. Regardless of their mode to attain resistance against antibiotics, it is evident that this trend is alarming. Even more egregious is the prominence of “superbug”. Superbug is a commonly used term to describe strains of bacteria that are resistant to the majority of antibiotics commonly used today. Superbugs have developed resulting in a common cause of pneumonia, some urinary tract and skin infections. One of those bacteria that have upgraded to the level of superbug is Staphylococcus aureus. Historically, there are many antibiotics effective against the staphylococci, yet over the last several decades antibiotic resistance, particularly resistance to beta-lactam antibiotics, has plagued antimicrobial therapy of S. aureus. Additionally, S. aureus is instrumental in displaying its varying ability to develop resistance to beta-lactam antibiotics, including developing “methicillin resistance” in a strain referred to as methicillin-resistant Staphylococcus aureus (MRSA).

What is causing this rise in antibiotic resistant microorganism? Well, there are many theories, including misuse over the years by physician and patients using antibiotics for treating infections that didn’t require antibiotics. This is because antibiotics not only kills the bad bugs that are causing infection but they can also deplete useful microbiota. Also, not taking the antibiotics like they are prescribed to maintain levels high enough in the blood to attack the bacteria. When blood levels of antibiotics drop below critical concentrations needed to combat bacteria, then resistant organism can emerge and proliferate. Additionally, antibiotics have become a regular staple in animal feed to help animals gain weight. It is thought that the levels present in feed is sufficient to help produce meatier animals but it results in over exposure to low doses of the medication, resulting in the bacteria developing resistance. So what are the ramifications of antibiotic resistance to the world as we know it? Well, we would see a re-emergence of simple infections leading to once preventable mortalities. Without antibiotics infections can overwhelm the body’s immune system system and may lead to deadly infections in the blood like bacteremia or septicemia causing death.

Given these costly outcomes to antibiotic resistance in the world it is no wonder that a lot of business producing foods are now advertising that their meats are “antibiotic free” but what does this term really mean? The linked consumer report mentions how for some companies that is just an advertising selling point. But some brands are making a concerted effort, noteably, the organic industry. According to the Department of Agreculture organic seal it means that animals were not giving antibiotics while being raised, including meat, poultry, dairy, and eggs. For other industry, this means that animals were not given antibiotic medically used to treat people—such as amoxicillin, erythromycin, and tetracycline.

Recently there has been discussions about how to treat cholera outbreaks in places like India. However, with the emergence of antibiotic resistance (ABR) in Vibrio cholerae, this has led to difficulties in case management since antibiotics have been established to be used in conjunction with early initiation of fluid and electrolyte replenishment using Oral Rehydration Salts (ORS) to reduce the duration and volume of diarrhea. It is suggested that antibiotics be used only in severe cases of cholera infection since the indiscriminate prescription of antibiotics is showing an emergence of resistance in the species.

Overall, the inappropriate use of antibiotics in humans and animals have resulted in a major threat to global public health because of the development of resistance of bacteria to these drugs. This is of global concern because we are seeing the loss of live and financial consequences to antimicrobial resistance. Thankfully, the problem has a public health platform that can be used to implement changes in the way doctor’s prescribe and how patient’s use antibiotics. Unfortunately, the development of new antimicrobial drugs have slowed significantly so we as a community need to be cognizant of our role in the problem and work with our health care provides to ensure that we don’t lose this gift we have in antibiotics.