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Health and Disease

“Saviour Siblings”: Taking a look at PTT

By Asmita Anand

Published 2:05 EST, Sun October 3rd, 2021

What are Saviour Siblings?

A saviour sibling can be best described as a child created using IVF and genetic diagnostics. They will provide an organ or cell transplant for a sibling who is critically ill and suffering from a fatal disease.

For certain diseases, a human leukocyte antigens identical stem cell transplant can be the only treatment. While stem cell therapy is a very attractive option, finding a donor can be a challenge.

The Technology Behind Saviour Siblings

Preimplantation tissue typing (PTT) is a technology that allows us to test and select embryos in order to treat children in need of stem cell transplants. PTT is also sometimes called HLA tissue typing. Preimplantation HLA typing is a great solution for children requiring stem cell transplants. It is a common treatment used to treat blood diseases such as thalassemia, sickle cell anaemia, and malignant diseases such as leukaemia and lymphoma. [1]

PTT or PGD-HLA was first introduced clinically in 2001 to treat Fanconi Anaemia (FA), a rare but serious genetic disorder that mainly affects the bone marrow. [2] For conditions such as Fanconi anemia, the only treatment option is bone marrow transplantation, which will restore hematopoiesis. Due to the high rate of transplant-related mortality, using HLA identical cord blood transplantation is increasingly attractive. It will help avoid complications and produce a better outcome. PTT provides realistic hope as a radical treatment option for those suffering from congenital and acquired bone marrow failures. FA is the first disorder in which cord blood stem cell transplantation has been performed.

The Procedure

By selecting embryos for the new sibling, we can ensure that the new sibling can provide an exactly matched tissue donation to the child suffering from the life-limiting disease, and hence act as a saviour. Apart from serving as a donor of pluripotent haematopoietic stem cells, the new sibling will also be screened for the same disease through preimplantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) is used when either one or both parents carry a known genetic mutation and seek to transfer a non-affected embryo. [3] It involves the analysis of artificially fertilised embryos in order to find one with the desired genotype. [4] Preimplantation genetic testing for monogenic disorders (PGT-M) combines both in vitro fertilisation (IVF) in conjunction with PTT.

PGT-M is a standard biopsy procedure performed on cells from a blastocyst embryo. It will also determine whether the embryo has the same inherited genetic mutation that has caused the life-limiting disease in the older child. It is done by testing for the single gene mutation associated with the disease.

The first step would be to create an embryo through IVF treatment. IVF involves the following steps: ovarian stimulation, oocyte retrieval, sperm retrieval, and fertilisation. During IVF, the egg retrieved from the uterus will be fertilised with sperm in a laboratory to produce a zygote. After IVF, the embryo biopsy will be prepared by removing a small number of trophectoderm cells (layer of cells on the outer edge of the blastocyst). While testing occurs for any abnormalities, the embryos will be frozen and preserved for implantation.

Once you find out the results of the biopsied cells, you can then select an embryo free from the same life-limiting genetic disease and simultaneously also a tissue match. This is vital so that the umbilical cord blood of the new sibling can provide stem cells to treat the existing sibling who has the disease.

These unaffected embryos will then be assessed for their HLA compatibility with the sick sibling to find a tissue match. Then, the unaffected and tissue-matched embryo will be ready to be transferred to the woman’s uterus. Once the new sibling has been born as a viable donor, the umbilical cord blood will be taken and used for hematopoietic stem cell transplantation. Umbilical cord blood is a great source of hematopoietic stem cells(HSCs) and has a higher concentration of HSCs than adult blood. These multipotent HSCs will then be used to treat the existing sibling.

Should it be used? Ethical considerations, benefits, and risks

PGT-M is a technically demanding procedure and involves the use of highly specialized molecular biology techniques. [5] Many arguments favouring and condemning PTT are based on the welfare and commodification of the donor sibling. [6]

Many who are against PGD may view it as selective breeding and “reproductive discrimination.” However, it is important to note that PGT-M currently cannot be used to select embryos for ‘designer babies’ as we are still not capable of scientifically determining certain characteristics. It is only used to test for a single genetic mutation.

Another common protest is that the donor baby may not be born for the right reasons and is used as a “medical commodity.” It’s vital to consider the reasons and intention of the parents to have another child. For some, this new baby may not act as a burden as they genuinely wish to have more children. But for others, the same cannot always be said as it’s difficult to gauge the parent’s true motives.

It is also reasonable to question whether individuals should be able to select an embryo simply on the basis that the child born may be the source of life-saving therapies for a sibling.

PGT-M also can be considered ethically problematic, considering affected embryos will be discarded. For some, this is not an issue as they are discarded at a very early stage of development and aren’t as severe as terminating a pregnancy at a later stage. PGD provides the advantage that difficult decisions to terminate a fetus are removed since only tissue-matched embryos will be implanted in the mother’s uterus.

Aside from ethics, we need to also consider the practicalities and other effects of the procedure. Down the line, it can potentially cause psychological effects on the saviour sibling as it may have only come into existence to save their older sibling. Furthermore, there can also be an emotional impact on other family members, along with risks imposed on the mother during the ART (Assisted reproductive technology) cycle. [7]

We also need to consider to what extent the saviour sibling is really “saving” their older sibling. Are cells being removed from the umbilical cord and blood, or is bone marrow or an organ being taken? It’s obvious that removing an organ would cause much more damage to the donor sibling, showing that the spectrum the treatment can cover poses its own issues as to whether it can qualify as ethical. Moreover, it opens up the question of how far we will go with this technology. Because it is reassuring that there are existing strict policies and regulatory frameworks for most genetic biotechnology groups, it is unlikely the technology will be misused, and harm to the donor sibling will be minimised.

Lastly, it is also expensive. The procedure itself is costly and can present another limitation, especially if more than one treatment cycle is necessary before a match and the unaffected embryo is found and pregnancy is achieved.

On the other hand, you could also argue that the care and treatment for a disease long-term are costly, and the procedure may end up being less expensive overall, provided that the treatment works. Not only this, but the child will be free of the disease and won’t suffer anymore.

In summary, PGT-M is highly valued when it succeeds despite its complexities and has been described as “a triumph for common sense.” [4]

Conclusion

PGT-M is an evolving technology, which means there are still more improvements that can be made. This ranges from the current protocols in place to databases containing more thorough information on the outcome of the procedure.

At the moment, we are also facing both technical and biological limitations to the PGD-HLA procedure’s success. These include the limited outcome of finding a suitable embryo and the low rates of live births after using IVF and ART. [7] However, we can improve such limitations by rectifying the issues behind this low IVF success rate (e.g., obtaining better-quality oocytes for biopsy and PGD).

Overall, PTT offers the opportunity to save a life and is something which I believe can be an amazing tool, provided there are no indications for it to cause harm to all members involved and that it is used for the right intentions. Personally, if I grew up knowing I’d saved a life, especially my sibling’s, I would be overjoyed the minute I was born!

Asmita Anand Youth Medical Journal 2021

References

[1] Preimplantation Tissue Typing. (2019, February 16). IAKENTRO. https://en.iakentro.com/assisted-reproduction/preimplantation-genetic-control/preimplantation-tissue-typing/

[2] Verlinsky, Y. (2001). Preimplantation Diagnosis for Fanconi Anemia Combined With HLA Matching. JAMA, 285(24), 3130. https://doi.org/10.1001/jama.285.24.3130

[3] Preimplantation Genetic Diagnosis, What is PGD – Testing Services. (2016, May 3). Houston Fertility Institute. https://www.hfi-ivf.com/your-treatment-options/genetic-testing/preimplantation-genetic-diagnosis

[4] Boyle, R. J., & Savulescu, J. (2001). Ethics of using preimplantation genetic diagnosis to select a stem cell donor for an existing person. BMJ, 323(7323), 1240–1243. https://doi.org/10.1136/bmj.323.7323.1240

[5] O. (2019, August 8). Pre-implantation Genetic Diagnosis (PGD) – ORH Fertility Clinic. Overlake Reproductive Health. https://fertileweb.com/reproductive-medicine/pgd/

[6] Liu, C. K. (2007). ‘Saviour Siblings’? The Distinction between PGD with HLA Tissue Typing and Preimplantation HLA Tissue Typing. Journal of Bioethical Inquiry, 4(1), 65–70. https://doi.org/10.1007/s11673-007-9034-9

[7] Traeger-Synodinos, J., Kakourou, G., Destouni, A., & Kanavakis, E. (2013). Eleven years of preimplantation genetic diagnosis for human leukocyte antigen matching: is there room for improvement? Expert Review of Hematology, 6(3), 215–217. https://doi.org/10.1586/ehm.13.29

Pre-implantation tissue typing (PTT) | Human Fertilisation and Embryology Authority. (n.d.). HFEA. Retrieved 7 August 2021, from https://www.hfea.gov.uk/treatments/embryo-testing-and-treatments-for-disease/pre-implantation-tissue-typing-ptt/

I. (2020a, November 25). Embryo Testing: The Difference Between PGT-A and PGT-M. IGENOMIX – With Science on Your Side. https://www.igenomix.com/blog/fertility-challenges/embryo-testing-difference-pgt-and-pgt-m/

Kuliev, A. (2014). Preimplantation HLA typing: Practical tool for stem cell transplantation treatment of congenital disorders. World Journal of Medical Genetics, 4(4), 105. https://doi.org/10.5496/wjmg.v4.i4.105

In vitro fertilization (IVF) – Mayo Clinic. (2019b, June 22). Mayoclinic. https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716

Kuliev, A., & Rechitsky, S. (2016). Preimplantation HLA typing for stem cell transplantation treatment of congenital and acquired bone marrow failures. Hematology & Medical Oncology, 1(2). https://doi.org/10.15761/hmo.1000108

A. (n.d.). Embryo HLA Typing. British Cyprus Fertility Hospital. Retrieved 7 August 2021, from https://www.cyprusivf.com/embryo-hla-typing/

Categories
Health and Disease

Eating Disorders And Adolescents During The Pandemic:

By Parineeta Karumanchi

Published 3:14 EST, Thurs September 30th, 2021

Introduction:

A phenomenal upsurge in the number of adolescents suffering from eating disorders shows that the impact the coronavirus pandemic had on them was deep, systematic, and significant. The mother of a severely affected anorexia nervosa patient from Canada described how she had to rush her daughter more than 10 times to the hospital during the pandemic. Peyton Crest, a former 18-year-old from Minnesota says that she developed anorexia before but has relapsed twice since the pandemic began. These cases are only 2 amongst the hundreds of teenagers who have been placed at a higher risk of developing or maintaining eating disorders because of the pandemic. Emerging evidence supports the theory that the pandemic has led to an increase in eating disorders amongst adolescents. This article explores how eating disorders have significantly escalated during the COVID-19 pandemic amongst adolescents whose lives have been uprooted and upturned since it began in November of 2019.

What are eating disorders?

To begin with, eating disorders are complex mental illnesses that manifest themselves physically in the form of abnormal eating habits. They can be described as bio-psycho-social which means that there are genetics, psychological factors, and social influences all at play. The most commonly known eating disorder is anorexia nervosa which is characterized by a distorted perception of weight. Combined with very restrictive eating patterns and a relentless pursuit to lose weight, anorexic patients suffer from severe malnourishment. Bulimia nervosa is just the opposite of anorexia nervosa; people engage in uncontrollable eating for a certain time until they are painfully full, after which they purge excessively to compensate for the calories gained. 

Adolescence is a developmental milestone during which peer-to-peer social comparison is a significant aspect. Physical isolation has caused some teenagers to feel that their life is spinning out of control and to combat this, they resort to binge eating as a coping mechanism. Stefan Ehrlich, professor of psychological and social medicine said research has shown food restriction can lead to resistance to ghrelin, the “hungry hormone” produced by the gut that prompts people to seek food—a process “reinforced when adolescents are isolated from their peers.” This proves that social isolation can have detrimental effects on their mental health, leading to impoverished social and interpersonal lives.

Social media and its impact on the youth:

Moving on, another influential aspect of eating disorders is social media. Although social media apps like Instagram and Facebook were created to strengthen social ties, research has shown that it in fact leads to social withdrawal while increasing feelings of loneliness and anxiety. Social media offers a medium of constant comparison where your status is determined by the number of followers you have or the number of likes you gain for each post. In a survey of 227 female university students, women reported that they tend to compare their own appearance negatively with their peer group and with celebrities on social media. Limited physical interaction due to lockdown orders has caused more time to be spent on social media where unrealistic, surgically altered men and women are portrayed as what beauty is, making body image diversity biased to what they see online. To reach up these standards, teens start exercising and eating healthy. This positive start is the prelude to a tragic turn, however. As they try to achieve immaculate face structures and super-toned bodies, they start to submerge themselves under stress, insecurities, and mental illnesses like depression.

Recent data suggest that, in the US, an increased number of people have been getting their ‘news’ from social media than printed newspapers. Given the strict journalistic values around credibility and the complete lack of anything like that in the social media sphere, this is a major concern. The Internet, today’s technology landscape, due to its ubiquitous presence has been heavily relied on by teenagers where they discover nonsensical dieting plans and abnormal regimes that are falsely advertised to be transformative and healthy when in reality, they only contribute to atypical lifestyles. Eventually, these inconsistent eating habits lead to eating disorders. The image below shows how significantly eating disorders have risen.

SOURCE:  Published by John Elflein , Apr 22, 2021

Figure 1: Number of U.S. individuals with eating disorders in 2018-2019, by condition

Conclusion:

The pandemic has left an air of ever-increasing uncertainty, highlighted by post-traumatic stress and psychological disturbances. The focus of the course of the pandemic has been on minimizing its spread and since most of the medical resources have been concentrated here, a limited amount of attention has been given to the pandemic’s wider impacts. The global picture of people facing eating disorders is skewed, representing statistics coming from a limited number of countries only. “The belief that eating disorders are confined to high-income countries is a dangerous myth that perpetuates health disparities,” says Cynthia Bulik, professor of eating disorders at the University of North Carolina. Paediatrician Kritika Malhotra says that one out of 4 girls and one out of 5 boys have “distributed eating habits and behaviors in India.” This shows how widespread eating disorders are and the severity of this is only worsening with the pandemic. 

It has been estimated that 20 million women and 10 million men in the U.S. suffer from eating disorders during their lifetime as reported by the National Eating Disorders Association. The mean age of onset for most eating disorders is 12.5 years and this is only decreasing with the pandemic. Rates of obesity among children have been going off the charts since the pandemic began, contributing to increased cases of certain cancers, diabetes, hypertension, heart disease, and strokes. With close to 2 billion COVID cases confirmed worldwide and the contagion scale is still rising in affected countries as new strains of the virus are being discovered, it is taking an enormous toll on teenagers’ lives. It is on us to do everything we can to take steps and partner with our communities to safely return some normalcy to their lives.

Parineeta Karumanchi, Youth Medical Journal 2021

References:

Feinmann, J. (2021). Eating disorders during the covid-19 pandemic. Bmj. doi:10.1136/bmj.n1787

Oakes, Kelly. “The Complicated Truth about Social Media and Body Image.” Bbc.com, BBC Future, 12 Mar. 2019, http://www.bbc.com/future/article/20190311-how-social-media-affects-body-image.

Categories
Health and Disease

Treatments of Parkinson’s Disease Motor Symptoms

By Catherine Duan

Published 4:06 EST, Tues September 29th, 2021

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, currently affecting nearly one million individuals throughout the United States alone1. Despite its pervasiveness, no treatments currently exist to ameliorate the underlying processes of neurodegeneration, with existing therapies focusing purely on symptom management2. The purpose of this review is to provide a panoramic discussion of the mechanisms utilized by four primary treatment options – 1) pharmacotherapy, 2) gene therapy, 3) deep brain stimulation, and 4) stem cell therapy; to examine research regarding the safety and efficacy of each; and to set forth an evidence-based recommendation for future research, investment, development, and treatment. After reviewing research regarding the safety, capability, and associated adverse events for each of the four therapies, I suggest that a combined administration of the drug L-dopa with a dopa-decarboxylase inhibitor and gene therapy exhibits the greatest potential for future development given results in human clinical trials and relatively low risk of adverse events.

Introduction

Parkinson’s disease is a chronic degenerative neurological disorder with early symptoms including bradykinesia, tremor, and freezing of gait3. Later stages of the disease manifest in frequent infection, Parkinson’s disease dementia, and even death4. While the causes of PD are unknown, major pathological markers include degeneration of midbrain dopaminergic neurons in the substantia nigra and an abundance of Lewy bodies in the remaining substantia nigra dopamine neurons5. PD is characterized largely by dopamine deficiency in its initial stages, which evolves to cause both motor and nonmotor symptoms as the disorder progresses. PD-induced death of substantia nigra dopamine neurons dysregulates the output of the entire basal ganglia circuit, a brain region important for motor control6. The globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr) become hyperactive as a result of diminished striatal inhibition. This is further enhanced by heightened excitatory inputs from the subthalamic nucleus (STN) that result from decreased inhibitory control from the globus pallidus external (GPe)7 (Figure 1b). The dysregulation of basal ganglia output is considered to be the major cause behind the movement disorders associated with PD, and therefore is the site that most PD treatments are targeted. In this review, I focus on therapies aimed at treating the effects of motor deterioration, namely dyskinesia, following the decline of nigrostriatal dopamine neurons. 

Although no disease-modifying treatment for PD currently exists, symptomatic therapies such as pharmacotherapy and deep brain stimulation have been employed to improve the quality of life for diagnosed individuals2. The drug L-dopa, often coadministered with dopa-decarboxylase inhibitors such as Carbidopa, works by increasing the diminished dopamine supply to the striatum (Figure 1b, I). It has been established as the gold standard of therapies and is now prescribed to nearly every PD patient upon diagnosis8. Another more recently established treatment is deep brain stimulation (DBS), which centers around the implantation of electrodes designed to regulate abnormal activity in the GPi and STN caused by irregular dopaminergic levels (Figure 1b, II).

While both of these treatments offer therapeutic value, each come with their own set of complications. L-dopa loses the ability to suppress Parkinsonian motor symptoms evenly throughout the day, which ultimately leads to frequent fluctuations in symptom presentation known as on and off states9; dopa-decarboxylase inhibitors (DDC-I) are often administered with L-Dopa to ameliorate off-state effects10. DBS also appears initially effective, but requires invasive neurosurgery with a high risk of severe adverse events11

Given the issues with efficacy and side effects of pharmacotherapies and DBS, there exists a growing demand for other treatment options. Recent insights in treatment fields such as gene therapy and stem cell therapy also offer renewed hope for more effective therapeutic outcomes. Gene therapy (Figure 1b, III) targets the striatum in hopes of enhancing the expression of certain genes that can upregulate dopamine, therefore mitigating symptoms caused by decreased dopamine concentrations. Stem cell therapy (Figure 1b, IV) aims to implant adapted stem cells to replace damaged dopaminergic neurons, thereby offsetting the effects of dopamine deficiency. 

In this review, outcomes are quantified through Section III of the Unified Parkinson’s Disease Rating Scale (UPDRS), a rating tool used in which higher scores correspond to greater severity of motor symptoms in disease progression12. Given their relatively high efficacy and low occurrence of adverse events, I recommend that a dual approach of gene therapy with the drugs L-dopa and Carbidopa be utilized as a baseline path for treatment and research.

Figure 1: Simplified schematic diagram of basal ganglia circuitry in normal (A) and parkinsonian (B) states. Perpendicular dashes represent inhibitory projections, while arrows represent excitatory projections, with the relative thickness of each line being indicative of the magnitude of effect. Gold circles indicate regions in which each respective treatment acts. The absence of dopamine neurons results in hyperactivity from the GPi and SNr along with decreased inhibitory control of the GPe.

Pharmacotherapy

Of the few existing treatments of PD, pharmacotherapy is considered the primary choice, administered either as a stand-alone treatment or as a baseline regiment upon which additional therapies are administered. The goal of most PD pharmaceutical treatments is to replenish diminishing dopamine concentrations in the striatum; however, dopamine itself is a water-soluble molecule and therefore incapable of penetrating the blood-brain barrier (BBB) if ingested orally. L-dopa, a dopamine precursor, is a commonly prescribed drug that can pass through the BBB, allowing for uptake by brain dopaminergic neurons and conversion to dopamine13. To further increase dopamine concentrations, dopa-decarboxylase inhibitors (DDC-I) such as Benserazide and Carbidopa are often simultaneously administered to decrease the peripheral breakdown of L-dopa by endogenous dopa-decarboxylase10.

Initial administration of L-dopa and DDC-Is is commonly characterized by substantial amelioration of parkinsonian symptoms and high tolerability. As a representative example, one randomized, double-blind procedure controlled study found that patients receiving 600 mg of daily L-dopa and Carbidopa scored an average of 9.2 points lower on the total UPDRS 42 weeks after treatment started compared to their baseline score before starting. Further, another trial studying effects at 102 weeks found a mean difference of 9.8 units14. Clinical data from this and other studies4,15,16 indicates that L-dopa and DDC-Is play a significant role in reducing Parkinson’s Disease symptoms. 

While combined administration of L-dopa and DDC-Is has a long history of successful use in treating PD, pharmacological upregulation of dopamine has its limits. Given the simultaneous administration of a DDC-I, L-dopa has a half-life of only 1.5 to 2 hours. Thus, the duration of action starts at around 2 to 4 hours before decreasing due to the deterioration of dopaminergic neuronal storage abilities17. This rapid catabolism of dopamine leads to pulsatile stimulation and inconsistent delivery to receptors, which in turn results in a wide range of dyskinesias and increased motor complications in the off-state18. In the aforementioned trial, later results demonstrate a 40% chance of increased motor complications after a period of 4 to 6 years due in part to L-dopa’s pulsatile stimulation and also overall disease progression10. Strategies for reducing the off state and extending the effective length of treatment include increasing the dosage of dopaminergic medication, adding another dopaminergic medication, dose fractionation, or adding catechol-O-methyltransferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs) to inhibit the breakdown of L-dopa and dopamine and prolong their effects19

Gene Therapy

In general, gene therapy employs therapeutic genes to treat disorders by correcting, replacing, or silencing defective genes20. In terms of the treatment of movement disorders like Parkinson’s, it typically offers selective restoration of dopamine concentration to the striatum through the upregulation of dopaminergic signaling21. While there are multiple ways to administer gene therapies, most make use of non-replicating viral vectors, such as a recombinant adeno-associated virus (AAV) and lentivirus, to deliver treatments to targeted areas22

There are two gene therapies currently in consideration for the treatment of PD symptoms, both of which work to target similar molecular pathways in the brain. The first, Aromatic L-Amino Acid Decarboxylase (AADC) gene therapy, involves anatomically focal supplements of the AADC enzyme that enables an increased rate of conversion from L-dopa to dopamine in transduced cells21. Treatments target the post-commissural striatum, the target of the nigrostriatal dopamine neurons that die off during PD. The medium spiny neurons of the post-commissural striatum do not degenerate during Parkinson’s, and previous studies have exemplified the potential for these cells to express transgenes for extended periods of time23

The second therapy employs a combined approach of AADC with the genes tyrosine hydroxylase (TH) and guanosine triphosphate cyclohydrolase I (GCH1). TH converts L-tyrosine to L-dopa, while GCH1 catalyzes the synthesis of the essential tyrosine hydroxylase cofactor, tetrahydrobiopterin. Unlike the AADC gene alone, collective transduction of TH-AADC-CH1 to the putamen allows dopamine to be synthesized in non-dopaminergic areas of the striatum without the use of L-dopa24.  

Both therapies have shown success in treating PD symptoms. Initial administration of AADC gene therapy with L-dopa and DDC-Is in a phase I open-label safety study of intrastriatal infusion demonstrated at 6 months that all subjects showed improvement in total UPDRS scores. UPDRS motor scores decreased from 38.6 to 24.6 in the off-state and from 15.5 to 11.2 in the on-state. Postoperatively, results at 1 and 2 years showed continuing improvements in total mean UPDRS scores for the combined cohorts: off-state 37% at 1 year and 38% at 2 years, and on-state 32% at 1 year and 22% at 2 years25

Similarly, therapies utilizing TH-AADC-CH1 also yielded positive results. In a multicenter phase ½ open-label trial with 12-month follow-up, significant improvements were demonstrated in average UPDRS motor scores off medication at 6 months, where the mean score decreased from 38 to 26, as well as at 12 months, where scores decreased from 38 to 2726

The most common adverse events from AADC gene therapy were headaches and short-lived discomfort at the surgical site, while more serious effects included hemorrhaging in 2 of the 10 patients25. Similar results were observed at postoperative appointments for TH-AADC-CH1 trials, during which treatment-related adverse events included mild dyskinesias and on-off phenomena. No serious adverse events related to the study drug or surgical procedure were reported26. Given these promising results, further trials are in progress in order to provide greater insight into both forms of treatment.

Deep Brain Stimulation

While the status quo of PD management is mainly pharmacological, relying on L-dopa and dopamine agonists, deep brain stimulation (DBS) represents a commonly prescribed neurosurgical treatment11. Experimental data in nonhuman models of PD has established that neuronal activity in the subthalamic nucleus (STN) and globus pallidus pars interna (GPi) is strikingly exaggerated in the parkinsonian state, and lesions in these areas can lead to dramatic improvement of motor symptoms27. Thus, the goal of deep brain stimulation is to minimize the pathological influences of irregular activity from the STN and GPi caused by the loss of dopaminergic inputs to the dorsal striatum. DBS mimics the neuronal effect of lesions with reduced risk of permanent neurological deficit by stimulating implanted electrodes in the brain target. Despite its widespread use and success in treating PD, the actual therapeutic mechanisms by which DBS operates are still relatively obscure28.

Operations are frequently categorized into two divisions based on the region of implantation, usually in the GPi or STN, with studies showing that both are safe and effective for the management of symptoms29. The STN is generally considered to be the preferred target for practical and theoretical purposes30, but comparative studies are relatively limited and have not demonstrated significant clinical benefits to one location versus another31.

Four longitudinal studies reviewed the long-term consequences of both procedures at various times after surgical operation to juxtapose the effects of DBS in the GPi and STN given continued administration of L-dopa and DDC-Is. Three months after the procedures were performed, a series of double-blind, crossover evaluations determined that as compared to no stimulation, STN stimulation was correlated to a median improvement in the UPDRS motor score from 50 to 27, while GPi stimulation resulted in a median improvement from 44 to 28. In comparison to the base levels, there were significant improvements in the UPDRS motor scores at each visit with stimulation in both the off- and on-medication state27. At a 12 month follow-up, off-medication motor scores improved by 39% for GPi and 48% STN stimulation, while dyskinesia was reduced by 89% through stimulation at the GPi and 62% through the STN29.

After 24 months, DBS remained effective in both the GPi and STN. Patients receiving STN stimulation required lower doses of dopaminergic agents than those receiving pallidal stimulation but experienced increased levels of depression and a greater decline in visuomotor processing speed11. Four years post-operation, STN and GPi DBS continued to display significant improvements of 50% and 39%, respectively, compared to baseline UPDRS scores. The daily dosage of L-dopa was significantly reduced (35%) in the STN-treated group only32. These studies show a significant and substantial therapeutic benefit for at least 3–4 years in a large cohort of patients with severe Parkinson’s disease. 

At three-month follow-up appointments in the aforementioned studies, cognitive and behavioral complications such as depression, confusional state, and lack of impulse control were only observed with STN stimulation. By six months, adverse events included intracranial hemorrhage in 7 of 91 patients along with resulting neurological deficits and persistent dysfunction (hemiparesis, aphasia, and cognitive dysfunction). Stimulation was frequently associated with muscle twitch and paresthesia, but these were typically transient and disappeared with adjustment of the stimulator settings27. In one-year appointments, the most frequent perioperative complications included mild delirium, transient anxiety, and deterioration of cognitive facilities29. During two-year appointments, serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months; these included confusional state, device complications, and depression11. At four-year follow-ups, adverse events included cognitive decline, speech difficulty, instability, gait disorders, and depression. These were more common in patients treated with DBS of the STN32

Stem Cell Therapy

The primary cause of PD is the loss of nigrostriatal dopamine neurons resulting in severely impaired motor and mental functionality; thus, transplantation of functional tissue would theoretically revitalize the striatum and partially restore the striatal release of dopamine, resulting in significant clinical benefits. As such, stem cell therapy (SCT) centers on the possibility of utilizing stem cells as an interminable source of dopaminergic neurons for transplantation33. Stem cells can self-proliferate and are multipotent; self-proliferation being the ability to divide and reproduce into the same type of cell, and multipotency being the potential to differentiate into a wide range of different cell types34. As a result of multilineage differentiation potential and proliferative capabilities, stem cells allow for the implantation of new cells to replace damaged ones35

Since the first clinical trials in the late 1980s using fetal midbrain tissue to replace lost DA neurons, hundreds of patients worldwide have undergone neural fetal tissue grafting, with many showing long-term graft survival, good clinical outcomes, and physiological release of dopamine over decades36. Throughout the progress of stem cell therapy, many different types of cells have been used for DA neuron derivation and differentiation, drug screening, and cell therapy for PD37. Of these, mesenchymal stem cells (MSCs) have received the greatest attention38.

Mesenchymal stem cells, also termed bone marrow stromal cells, can be readily harvested from patients or donors for use in therapies39. Bone marrow, umbilical cord blood, and adult adipose-derived stromal tissue have been used as sources of MSCs for autologous grafts. Through animal models and in vitro trials, MSCs have demonstrated immense capability to stimulate endogenous neural growth and induce synaptic formation38. Additionally, they display relatively less immunological reaction in respect to other adult stem cells due to the lack of major histocompatibility complex II. To date, these cell types have demonstrated positive safety profiles and high potential in human clinical trials38

In research utilizing MSCs, a clinical trial in advanced PD patients using unilateral transplantation of autologous bone marrow-derived MSCs into the sublateral ventricular zone reported modest clinical improvement with no adverse effects. In this trial, there were no PET assessments before and after transplantation in order to determine graft survival or changes of DA striatal function35. Thus, the mechanisms underlying the reported modest improvements are still relatively obscure.

Conclusion

Overall, pharmacotherapy is by far the most frequently studied and administered treatment, given that it is almost universally prescribed upon a PD diagnosis. The combination of L-dopa and Carbidopa resulted in a change in UPDRS score of 9.2-9.8 units and was received with minimal side effects, making it a clear candidate for continued use. Deep brain stimulation in the GPi and STN resulted in drastic UPDRS score changes of 16 and 23, respectively, but both were accompanied by a dangerously high frequency and magnitude of adverse events that dramatically disincentivized frequent administration. AADC and TH-AADC-CH1 gene therapy resulted in UPDRS score differences of 12-14 while offering comparatively few occurrences of detrimental side effects. Stem cell treatments also exhibit promise in ameliorating PD motor symptoms, although results are still inconclusive given the absence of available clinical data utilizing UPDRS to gauge the efficacy of stem cell therapy.

Based on these findings, I recommend a combined administration of the drugs L-dopa and Carbidopa with gene therapy as a platform for future treatment and development. This treatment course offers significant benefits in ameliorating the motor symptoms of PD while retaining a relatively low hazard regarding potential adverse events. For instance, while deep brain stimulation offers a greater reduction in UPDRS motor scores40, it also carries the significant risk (over 50%) of adverse events such as hemorrhage, persistent dysfunction, and cognitive decline caused by device and operation complications11. It is worth noting that research into and advancements of each of these treatment categories is ongoing, but as of right now, gene therapy appears to show the greatest promise for treatment and further development.

At this time, potential targets of genetic treatment for Parkinson’s have been identified and categorized as either disease-modifying or non-disease-modifying based on mechanisms of therapy. While this review focuses primarily on non-disease-modifying treatment options, disease-modifying gene therapies such as GDNF, NRTN, BDNF, and Nurr1 have recently become the subject of a great deal of attention and could potentially present not only symptomatic treatments but monotherapeutic cures for PD, given their capacity for neurorestoration and neuroprotection20. With further development enhancing safety and efficacy, it is possible that symptomatic therapy may be able to functionally cure Parkinson’s motor symptoms, enabling patients to lead fully satisfying lives.

Catherine Duan, Youth Medical Journal 2021

References

1. Marras, C. et al. Prevalence of Parkinson’s disease across North America. npj Park. Dis. 4, (2018).

2. Oertel, W. & Schulz, J. B. Current and experimental treatments of Parkinson disease: A guide for neuroscientists. Journal of Neurochemistry vol. 139 325–337 (2016).

3. Borrione, P. Effects of physical activity in Parkinson’s disease: A new tool for rehabilitation. World J. Methodol. 4, 133 (2014).

4. Sveinbjornsdottir, S. The clinical symptoms of Parkinson’s disease. J. Neurochem. 139, 318–324 (2016).

5. Blandini, F., Nappi, G., Tassorelli, C. & Martignoni, E. Functional changes of the basal ganglia circuitry in Parkinson’s disease. Progress in Neurobiology vol. 62 63–88 (2000).

6. Alexander, G. E. Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin. Neurosci. 6, 259 (2004).

7. Weinberger, M. & Dostrovsky, J. O. A basis for the pathological oscillations in basal ganglia: The crucial role of dopamine. NeuroReport vol. 22 151–156 (2011).

8. Lewitt, P. A. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Movement Disorders vol. 30 64–72 (2015).

9. Wearing off and motor fluctuations | European Parkinson’s Disease Association. https://www.epda.eu.com/about-parkinsons/symptoms/motor-symptoms/wearing-off-and-motor-fluctuations/.

10. Dong, J., Cui, Y., Li, S. & Le, W. Current Pharmaceutical Treatments and Alternative Therapies of Parkinson’s Disease. Curr. Neuropharmacol. 14, 339–355 (2016).

11. Follett, K. A. et al. Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson’s Disease. N. Engl. J. Med. 362, 2077–2091 (2010).

12. Unified Parkinson’s Disease Rating Scale – an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/medicine-and-dentistry/unified-parkinsons-disease-rating-scale.

13. Haddad, F., Sawalha, M., Khawaja, Y., Najjar, A. & Karaman, R. Dopamine and levodopa prodrugs for the treatment of Parkinson’s disease. Molecules vol. 23 (2018).

14. Oakes, D. et al. Levodopa and the Progression of Parkinson’s Disease. N. Engl. J. Med. 351, 2498–2508 (2004).

15. Yahr, M. D., Duvoisin, R. C., Schear, M. J., Barrett, R. E. & Hoehn, M. M. Treatment of Parkinsonism With Levodopa. Arch. Neurol. 21, 343–354 (1969).

16. Jankovic, J. Levodopa strengths and weaknesses. Neurology 58, S19–S32 (2002).

17. Jost, W. H. Pharmacological treatment of motor symptoms in Parkinson’s diseases. Nervenarzt 88, 373–382 (2017).

18. Dorszewska, J., Prendecki, M., Lianeri, M. & Kozubski, W. Molecular Effects of L-dopa Therapy in Parkinson’s Disease. Curr. Genomics 15, 11–17 (2014).

19. Connolly, B. S. & Lang, A. E. Pharmacological treatment of Parkinson disease: A review. JAMA – Journal of the American Medical Association vol. 311 1670–1683 (2014).

20. Axelsen, T. M. & Woldbye, D. P. D. Gene therapy for Parkinson’s disease, an update. Journal of Parkinson’s Disease vol. 8 195–215 (2018).

21. Sudhakar, V. & Richardson, R. M. Gene Therapy for Parkinson’s Disease. Prog. Neurol. Surg. 33, 253–264 (2018).

22. Leff, S. E., Spratt, S. K., Snyder, R. O. & Mandel, R. J. Long-term restoration of striatal L-aromatic amino acid decarboxylase activity using recombinant adeno-associated viral vector gene transfer in a rodent model of Parkinson’s disease. Neuroscience 92, 185–196 (1999).

23. Björklund, A. et al. Towards a neuroprotective gene therapy for Parkinson’s disease: Use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res. 886, 82–98 (2000).

24. Muramatsu, S. I. et al. A phase i study of aromatic l-amino acid decarboxylase gene therapy for parkinson’s disease. Mol. Ther. 18, 1731–1735 (2010).

25. Christine, C. W. et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73, 1662–1669 (2009).

26. Palfi, S. et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: A dose escalation, open-label, phase 1/2 trial. Lancet 383, 1138–1146 (2014).

27. Group, T. D.-B. S. for P. D. S. Deep-Brain Stimulation of the Subthalamic Nucleus or the Pars Interna of the Globus Pallidus in Parkinson’s Disease. N. Engl. J. Med. 345, 956–963 (2001).

28. Beudel, M. & Brown, P. Adaptive deep brain stimulation in Parkinson’s disease. Park. Relat. Disord. 22, S123–S126 (2016).

29. Anderson, V. C., Burchiel, K. J., Hogarth, P., Favre, J. & Hammerstad, J. P. Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch. Neurol. 62, 554–560 (2005).

30. Kim, H. J. et al. Long-term cognitive outcome of bilateral subthalamic deep brain stimulation in Parkinson’s disease. J. Neurol. 261, 1090–1096 (2014).

31. Dayal, V., Limousin, P. & Foltynie, T. Subthalamic nucleus deep brain stimulation in Parkinson’s disease: The effect of varying stimulation parameters. Journal of Parkinson’s Disease vol. 7 235–245 (2017).

32. Rodriguez-Oroz, M. C. et al. Bilateral deep brain stimulation in Parkinson’s disease: A multicentre study with 4 years follow-up. Brain 128, 2240–2249 (2005).

33. Lindvall, O. & Kokaia, Z. Prospects of stem cell therapy for replacing dopamine neurons in Parkinson’s disease. Trends in Pharmacological Sciences vol. 30 260–267 (2009).

34. Zhang, Q., Chen, W., Tan, S. & Lin, T. Stem Cells for Modeling and Therapy of Parkinson’s Disease. doi:10.1089/hum.2016.116.

35. Politis, M. & Lindvall, O. Clinical application of stem cell therapy in Parkinson’s disease. BMC Medicine vol. 10 1–7 (2012).

36. Sonntag, K. C. et al. Pluripotent stem cell-based therapy for Parkinson’s disease: Current status and future prospects. Progress in Neurobiology vol. 168 1–20 (2018).

37. Parmar, M., Grealish, S. & Henchcliffe, C. The future of stem cell therapies for Parkinson disease. Nature Reviews Neuroscience vol. 21 103–115 (2020).

38. Bagheri-Mohammadi, S. et al. Stem cell-based therapy for Parkinson’s disease with a focus on human endometrium-derived mesenchymal stem cells. Journal of Cellular Physiology vol. 234 1326–1335 (2019).

39. Trounson, A. & DeWitt, N. D. Pluripotent stem cells progressing to the clinic. Nature Reviews Molecular Cell Biology vol. 17 194–200 (2016).

40. Jarraya, B. et al. Dopamine gene therapy for Parkinson’s disease in a nonhuman primate without associated dyskinesia. Sci. Transl. Med. 1, 2ra4-2ra4 (2009).

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Health and Disease

Pediatric Cancers Compared to Adult Cancers

By Michelle Li

Published 11:04 EST, Mon September, 20th, 2021

Introduction

Pediatric cancers refer to cancers that affect children under the age of 18 years old, while adult cancers are those that occur in people over 18. However, age is not the only difference between pediatric and adult cancers. There are a number of other key differences in the onset, progression, and treatment between the two that need to be taken into consideration. 

Onset and Development of Pediatric and Adult Cancers

The most significant difference between pediatric and adult cancers is that it is more common for adults to be diagnosed with cancer compared to children. According to the American Cancer Society, approximately 10,500 new cancer cases in children (ages 0-14) and 5,090 cases in adolescents (ages 15-19) will be diagnosed in the United States in 2021; this amounts to a total of 15,590 estimated new pediatric cancer cases (“Cancer Facts & Figures”). An expected 1.9 million new cancer cases are expected to be diagnosed in the United States 2021 (“Cancer Facts & Figures”). Only a small fraction of those cases are pediatric patients with cancer while the vast majority are adult cases. While this can be partially attributed to the differences in population percentages, the causes of pediatric and adult cancers also provide a partial explanation. According to the World Cancer Research Fund, at least 18% of diagnosed cancer cases in the United States are connected to body fatness, lack of exercise, alcohol consumption, or lack of nutrition in diet (“Diet and Physical Activity: What’s the Cancer Connection?”). As all four are lifestyle or environmental factors, adults are more likely to have been exposed to these factors over longer periods of time, contributing to the higher diagnoses of cancer in adults. Pediatric cancers are usually unrelated to these lifestyle choices, as children have most likely not been exposed to certain factors due to their age (specifically in the case of alcohol or tobacco) or have been exposed for shorter periods of time (Vahey). 

Additionally, the connection to lifestyle or environmental factors may also partially explain the difference in common types of cancers for children and adults. The most common pediatric cancers are leukemia, brain and central nervous system cancers, lymphoma, bone cancer, and neuroblastoma, among others (Watson). Common cancers for adults, on the other hand, include lung, breast, colon, kidney cancer, etc (“Cancer Statistics”). As children are less exposed to the lifestyle and environmental factors found to be related to cancer diagnoses, they are also less likely to have cancers related to those factors; for instance, children who have not been exposed to cigarette smoke are less likely to develop lung cancer. The opposite is true for adults who may make the choice to smoke tobacco products and, as a result, become more exposed to cigarette smoke and experience higher rates of lung cancer. Interestingly, the common types of adult cancers begin in specific organs, while the common pediatric cancers don’t occur in the same pattern (Vahey).

Progression: How Pediatric and Adult Cancers Act

In terms of progression of pediatric and adult cancers, pediatric cancers are often more aggressive and progress faster than adult cancers (Vahey). Pediatric cancers are also more likely to have moved to other organs by the time of diagnosis. This may also be partially attributed to the lack of useful screening tests for pediatric cancers; a number of screening tests are available for adult cancers, which may result in earlier detection for adults and diagnoses before the cancer has spread to other parts of the body (Vahey). 

Treatment

Another difference between pediatric and adult cancers lies in their prognosis. In general, children have a better prognosis compared to adults, as two-thirds of pediatric cancer cases are cured (Vahey). However, survival rates vary greatly depending on the type of cancer.

Treatment also differs between pediatric and adult cancer patients. Children’s bodies react differently and experience different risks than adults, and this is still true for cancer treatments. Besides the different considerations based on age, treatment also varies based on the type of cancer, the affected tissues, and the spread of the cancer. Since pediatric cancers spread faster and have often moved to other parts of the body by the time of diagnoses, surgery is not as likely to cure a pediatric cancer patient (Vahey). However, children’s bodies respond more positively to chemotherapy. This may be explained by the fact that chemotherapy is effective against fast-growing cancers — which pediatric cancers tend to be (“Treating Children with Cancer”). Additionally, children’s bodies may also recover better compared to adults after high doses of chemotherapy, which would allow for more intense treatments with higher chances of effectively treating the cancer. The possibility of more short and long term effects is still present, though (“Treating Children with Cancer”). In contrast, children’s bodies do not respond better to radiation therapy. In fact, children experience more serious side effects than adults who have undergone radiation therapy (“Treating Children with Cancer”). Different factors must be considered when treating pediatric patients with cancer than when treating adults. In addition to the different options for treatment for certain cancers, healthcare professionals must also consider how a pediatric patient will respond to a treatment, even if it has proven to be effective in adults with cancer.

Conclusion

Pediatric and adult cancers vary greatly in their onset, progression, and treatment. The difference in patient ages translates to different common cancers by age group, different developments in progression, and different treatments. Ultimately, the fact that pediatric cancers diverge so much from adult cancers speaks to the importance of considering the differences between pediatric and adult patients in healthcare settings for not only cancer but other conditions as well. 

Michelle Li, Youth Medical Journal 2021

References

“Cancer Facts & Figures 2021.” National Cancer Society, http://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2021.html. Accessed 28 July 2021.

“Cancer Statistics.” National Cancer Institute, http://www.cancer.gov/about-cancer/understanding/statistics. Accessed 29 July 2021.

“Diet and Physical Activity: What’s the Cancer Connection?” American Cancer Society, http://www.cancer.org/cancer/cancer-causes/diet-physical-activity/diet-and-physical-activity.html. Accessed 28 July 2021.

“Treating Children with Cancer.” National Cancer Society, http://www.cancer.org/cancer/cancer-in-children/how-are-childhood-cancers-treated.html. Accessed 26 July 2021.

Vahey, Marianne, and Cameron Howell. “Childhood Cancers.” The Gale Encyclopedia of Cancer: A Guide to Cancer and Its Treatments, edited by Deirdre S. Hiam, 5th ed., vol. 1, Gale, 2021, pp. 517-27. Gale Health and Wellness, link.gale.com/apps/doc/CX8067200154/HWRC?u=mlin_m_newtnsh&sid=bookmark-HWRC&xid=ea00a342. Accessed 28 July 2021.

Watson, Stephanie. “Pediatric Cancer.” The Gale Encyclopedia of Cancer: A Guide to Cancer and Its Treatments, edited by Deirdre S. Hiam, 5th ed., vol. 3, Gale, 2021, pp. 1622-27. Gale Health and Wellness, link.gale.com/apps/doc/CX8067200495/HWRC?u=mlin_m_newtnsh&sid=bookmark-HWRC&xid=5600b57e. Accessed 28 July 2021.

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Health and Disease

The 30 Minute Malaria Test

By Kyle Phong

Published 7:55 EST, September 17th, 2021

What is Malaria?

Malaria is a disease transmitted by mosquitoes that affects around 230 million people worldwide. The common symptoms of malaria consist of fever, chills, body aches, nausea, vomiting, and headaches. Without treatment, the infection can significantly worsen, causing seizures, comas, and death. This illness is particularly detrimental towards rural and underdeveloped countries where there are low funds and a lack of infrastructure to take the proper measures.  

Vecteezy, “Malaria Infographic”

Testing for Malaria

Currently, there are rapid diagnostic tests (RDTs) for malaria, but it comes with several drawbacks. It cannot detect malaria in its early stages, determine its severity, and occasionally give false positive and negative results. In Nanyang Technological University, Singapore, a team led by Dr. Quan wanted to create a test for malaria that was both accurate and inexpensive to produce.   

For RDTs, malaria-infected blood is examined under a microscope by an expert. Both factors are uncommon in rural locations, significantly delaying the diagnosis. The image below displays the only available RDT for malaria in the US.  

CDC, “BinaxNOW Malaria Test”

The new test kit from Nanyang Technological University does not rely as heavily on laboratory equipment as it only needs water and a blood sample. Requiring a mere ten microliters of blood or less than one drop, the kit mixes this with water which releases the malaria parasites. Malaria parasites digest blood to grow and proliferate, creating hemozoin as a by-product. The kit proceeds to pump blood through an area of chemical patches that light up hemozoin. A light detector called the Raman spectrometer records the frequency and strength of these flashes of light to determine the presence of malaria as well as its severity.  

Nanyang Technological University, “Malaria Test Kit”

In order to confirm the accuracy of this new test, the research team added early-stage malaria-infected blood into the kit. They found that the test detected these early-stage parasites, making them more sensitive than RDTs available in the United States. Due to the test’s sensitivity, it can quantify the number of parasites in the blood sample. Physicians can utilize this test to track how well the patient is fighting against malaria.  

Conclusion

Dr. Quan and his team hope to cooperate with an industry partner in order to continue conducting more trials and further improve this testing kit. It is estimated that the test would cost about $1 for the US to manufacture, meaning it could be utilized in the field on a large scale. In the future, these test kits will pave way for underserved populations to gain easier access to important public health resources.

Kyle Phong, Youth Medical Journal 2021

References

Center for Disease Control and Prevention, “Malaria”, 30 June 2021

https://www.cdc.gov/parasites/malaria/index.html

Center for Disease Control and Prevention, “Malaria Diagnostic Tests”, 19 February 2020

https://www.cdc.gov/malaria/diagnosis_treatment/diagnostic_tools.html

Nanyang Technological University, “Rapid malaria test kit could aid diagnosis in developing countries”, 29 June 2021

https://www.ntu.edu.sg/news/detail/rapid-malaria-test-kit-could-aid-diagnosis-in-developing-countries

News Medical Life Sciences, “Rapid test kit for malaria delivers results in 30 minutes”, 29 June 2021

https://www.news-medical.net/news/20210629/Rapid-test-kit-for-malaria-delivers-results-in-30-minutes.aspx

ScienceDirect, “Towards malaria field diagnosis based on surface-enhanced Raman scattering with on-chip sample preparation and near-analyte nanoparticle synthesis”, 15 September 2021

https://www.sciencedirect.com/science/article/abs/pii/S0925400521007310?via%3Dihub

Vecteezy, “Malaria Infographic”

https://www.vecteezy.com/vector-art/1778112-malaria-symptom-information-infographic

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Health and Disease

Yellow Fever: A Rare Infectious Tropical Disease

By Mary Mai

Published 12:35 EST, September 12th, 2021

You’ve probably heard the term “yellow fever” being thrown around the internet. Urban Dictionary defines this term as males having preference over women with Asian descent but in this article, we will not be diving into this internet slang. Instead, we will be diving into the topic of a very serious infectious tropical disease commonly known as yellow fever. 

Yellow fever, also known as bunyavirus infection, is a viral infection that can affect the liver, kidneys, and the gastrointestinal tract which is a tract from the mouth to the anus. Mosquitos are the most common carrier of this yellow fever disease and typically located near the Carribean Islands and Africa. In this article, we will be diving into all there is to know about the yellow fever disease. From all the symptoms to even the causes and treatment for this disease. 

CAUSES OF YELLOW FEVER

A human is able to contract the yellow fever infection when they have been bitten by a mosquito that also carries the disease. This mosquito is known to be called the Aedes Aegypti Mosquito and is known to do really well in human habitations. A simple bite from the mosquito can be extremely harmful and if bitten by one can also contract the yellow fever disease. This mosquito is also known to spread and can carry dengue fever, zika fever, mayaro, and many more.

SYMPTOMS OF YELLOW FEVER

Symptoms of yellow fever can impact different parts of the human body, often beginning with severe headaches and delirium. Yellow fever can also impact your eyes causing redness and also causing the eyes to be more sensitive to light. Common symptoms also include muscular problems like aches and seizures and also liver issues like hepatitis, which  is inflammation of the liver. There are also many symptoms that affect the stomach like nausea, abdominal pain, and even cause vomiting as well. People with yellow fever may also experience decreased urination as well as bleeding in the mouth and nose. Another symptom of yellow fever is a slower heart rate. 

TREATMENT/CURE FOR YELLOW FEVER

Currently, like many other diseases there is no cure for yellow fever because it is an infection that multiplies over time that cannot be killed by anti biotics. However, prevention for yellow fever does exist and those who live in continents that are mostly affected are highly encouraged to take the vaccination in order to prevent contraction of yellow fever. Those who travel to continents with yellow fever are also recommended to take the vaccine as well. However, those who have contracted the disease go through many treatments including oral rehydration therapy. ORT (oral rehydration therapy) involves drinking water with sugar and salt in order to treat dehydration, this can also be given by a nasogastric tube.

CONCLUSION

Like many other diseases, yellow fever is very complicated and harmful to human beings. Symptoms of yellow fever range from delirium and weak eyesight, to bleeding and hepatitis. The cause of all these symptoms come from a small mosquito known as the Aedes Aegypti Mosquito which is known to be very common for carrying the Yellow Fever disease. Being bitten by one of these mosquitoes can cause yellow fever but thankfully, there are medical interventions that can help prevent someone from contracting this disease. Overall, yellow fever is very harmful and those who live or plan on moving to places with higher risk of yellow fever should proceed with caution. Diseases like yellow fever aren’t curable and can cause many complications. Thankfully, with the help of prevention vaccines that are available to many of us and to those who live in countries that are affected by this disease, many of us can stay safe from the yellow fever mosquito and live a life that is yellow fever free.

Mary Mai, Youth Medical Journal 2021

Works Cited

“Delirium.” Mayo Clinic. Mayo Foundation for Medical Education and Research, 01 Sept. 2020. Web. 01 July 2021.

“Gastrointestinal Tract.” Encyclopædia Britannica. Encyclopædia Britannica, Inc. Web. 01 July 2021.

“Yellow Fever.” NORD (National Organization for Rare Disorders). Web. 01 July 2021.

“Yellow Fever: Causes, Symptoms, And Treatment.” Netmeds. Web. 01 July 2021.”Yellow Fever: Symptoms and Treatment.” WebMD. WebMD. Web. 01 July 2021.

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Health and Disease

Down Syndrome : A Genetic Chromosome Disorder

By Neha Menon

Published 11:30 EST, Tue September 7th, 2021

Introduction

Most people are born with 46 chromosomes. What are chromosomes? In very simple terms they are structures inside the nucleus of a cell made up of DNA and other proteins. They are typically genetic material and hence they provide a child with genetic and hereditary characteristics. Going back to the first sentence: most people are born with 46 chromosomes. People with Down Syndrome [DS], however, are born with one extra chromosome. This explains why the syndrome is also more commonly called trisomy 21–because in this condition, one is born with an extra copy of their 21st chromosome. The effects of this are commonly a lag in both physical and mental developments. However, the range of these lags or delays can differ from patient to patient and the ability to live with ease also depends. According to the World Health Organization, the predictable incidence of DS is between 1 in 1,000 to 1 in 1,100 live births all over the world.

The scope of this article covers the causes of the syndrome, effects, types and finally some lesser-known facts about Down Syndrome!

Causes of Down Syndrome

As mentioned previously, parents pass on their genes to the child through chromosomes. There is a lot of process and details within this procedure but to understand the causes of the syndrome, it will suffice to know what is mentioned above. Each cell in the child is supposed to have 46 chromosomes, (23 pairs) which are half from the mother and half from the father. 

In situations where the child goes on to develop Down Syndrome, one chromosome cannot separate fully, resulting in 3 copies of the 21st chromosome instead of 2. 

Symptoms of Down Syndrome 

The presence of DS in people typically causes slowed mental and physical development. As mentioned above, this lag or delay in development varies from person to person depending on several factors including the type of DS diagnosed in them (which is discussed in greater detail shortly). Some featured symptoms are (keep in mind that even these differ vastly):

  • Flattened face
  • Small head
  • Short neck
  • Protruding tongue
  • Upward slanting eyelids (palpebral fissures)
  • Unusually shaped or small ears
  • Poor muscle tone
  • Broad, short hands with a single crease in the palm
  • Relatively short fingers and small hands and feet
  • Excessive flexibility
  • Tiny white spots on the coloured part (iris) of the eye called Brushfield’s spots
  • Short height

Some other symptoms are cognitive disabilities such as slowed learning and memory.

Types of Down Syndrome 

There are 3 types of DS: Trisomy 21, mosaicism and translocation. Out of these, the first is the most common. The name is very self-explanatory; trisomy 21 refers to the fact that there is an extra copy of the 21st chromosome in every cell of the body. Mosaicism is very similar, however, it’s different in that not all cells have an extra copy of the 21st chromosome; only some do. Hence there are also lesser symptoms and of lesser intensity in this form. In the 3rd mention form translocation,  there are three 21 chromosomes, but one of the 21 chromosomes is attached to another chromosome. Out of these three given types of Down Syndrome, trisomy-21 is the most prevalent: about 95% of people with DS have this type. 2% of people with DS have mosaic DS and 3% of people with DS have the translocation type. 

Other than the main differences between these 3 types, some other differences that the type of DS can have an influence on are the severity of the symptoms. As mentioned above, every individual’s symptoms vary vastly.

Facts! (https://www.dosomething.org/us/facts/11-facts-about-down-syndrome)

  • The exact cause of the extra chromosome that triggers Down syndrome is unknown.
  • One in every 691 babies in the U.S. is born with Down syndrome, making it the most common chromosomal condition.
  • There are more than 400,000 people living with Down syndrome in the U.S.
  • In 1983, the average life expectancy of a person with Down syndrome was a mere 25-years-old. Today, it is 60.
  • Children and adults with Down syndrome share some common features, but naturally, the individuals will more closely resemble their immediate family members.
  • Since the 1970s, public schools have been required by law to provide free and appropriate education to children with Down syndrome.
  • The likelihood of giving birth to a child with Down syndrome increases with maternal age, however, 80% of babies with Down syndrome are born to women under 35 years of age because this age group gives birth most frequently.
  • Roughly 25% of families in the U.S. are affected by Down syndrome.
  • While behaviour, mental ability, and physical development vary from person to person, many individuals with Down syndrome grow up to hold jobs, live independently, and enjoy normal recreational activities.

Neha Menon, Youth Medical Journal 2021

References

Team, T. H. (2019, October 29). Down Syndrome: Causes, Types, and Symptoms. Retrieved from https://www.healthline.com/health/down-syndrome

Facts about Down Syndrome. (2021, April 06). Retrieved from https://www.cdc.gov/ncbddd/birthdefects/downsyndrome.html

Down syndrome. (2018, March 08). Retrieved from https://www.mayoclinic.org/diseases-conditions/down-syndrome/symptoms-causes/syc-2035597711 Facts About Down Syndrome. (n.d.). Retrieved from https://www.dosomething.org/us/facts/11-facts-about-down-syndrome

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Health and Disease

Aducanumab (Aduhelm), a cure to the tragedy of Alzheimer’s Disease?

By Asmita Anand

Published 11:20 EST, Sun September 5, 2021

Introduction

One of the most common types of dementia in the UK, Alzheimer’s disease (AD) is a physical disease that affects the brain.[1] It is estimated that in 2040 there will be over 1.5 million people with dementia in the UK at the current rate of prevalence.[2] Despite the alarmingly high figures, research is being undertaken to tackle this with 126 different agents currently being assessed to treat Alzheimer’s.[3] Recently, the FDA approved a new drug, aducanumab, for clinical use in Alzheimer’s patients after reviewing evidence on its effectiveness in slowing the progression of symptoms in people with early-stage AD.

What we know:

The effect of Alzheimer’s on the brain

In order to understand how aducanumab treats Alzheimer’s, we must understand the effect AD has on the brain. AD is a neurodegenerative disease. During Alzheimer’s, vital communication between neurons is disrupted as many neurons stop functioning, which results in cell death and leads to shrinking of the brain. This process is known as cerebral atrophy. AD disrupts important processes in neural networks such as communication, metabolism, and repair.[4] As these neurons die, a person suffering from AD will begin to lose the ability to think, remember, make decisions and function independently. This is due to pathological changes and damage to multiple brain structures such the cerebrum, cortex and hippocampus.

The exact cause of AD is still unknown. Many scientists believe that two proteins called ‘beta-amyloid’ and ‘tau’ play a huge role in the toxic changes that occur in the brain. Both of these proteins form the buildup of two abnormal pathologies. The first pathologies are plaques (composed of beta-amyloid) which build up slowly in the neurons and are found scattered between nerve cells. The second pathologies are neurofibrillary tangles formed inside cells which result from the accumulation of abnormal tau. But it is important to note that these are not the only factors which contribute to AD. Furthermore, it is due to the lack of universal acceptance of the amyloid hypothesis that aducanumab has been so heavily criticised, which is explored in further detail below. [5] [6]

What are the current treatment options for AD?

At the moment, treatment for AD revolves around helping patients maintain mental function, slow down progression of symptoms, and manage and ease behavioural symptoms. There are several pharmaceuticals available which can help manage symptoms of Alzheimer’s. Acetylcholinesterase inhibitors are the main drugs used to treat AD in the UK. These include donepezil, galantamine, and rivastigmine. These work by preventing the enzyme acetylcholinesterase from breaking down acetylcholine, a critical neurotransmitter. Levels of acetylcholine are very low in patients with AD due to nerve cell death. By preventing breakdown of this vital chemical, acetylcholine levels will increase, leading to reduction in some symptoms of AD. [7]

The last approved drug was memantine in 2004, which is an oral medication. Unlike the cholinesterase inhibitors which are considered ‘symptomatic’ treatment, memantine is considered a ‘neuroprotective’ drug as it may slow the underlying progression of AD. In AD, too much glutamate leaks out of damaged brain cells, and these high concentrations can result in over-excitation of nerve cells, which leads to cell death.[8] [9] Memantine protects the nerve cells by dampening the excitatory effect of the neurotransmitter glutamate. [10]

What is aducanumab (aduhelm)?

It is an antibody infusion targeting amyloid beta protein (Aß), a defining feature of the biology of AD.[11] Current drugs aim at suppressing cognitive symptoms whereas aducanumab is aiming to tackle the underlying cause of AD, which is to both stop and cure it. Aducanumab is aiming to do this by targeting amyloid, clumps researchers believe are responsible for brain cell death.

The antibody will preferentially bind to aggregated amyloid-beta. This will reduce the presence of amyloid plaques in hopes to slow AD progression.[12] These plaques are also responsible for the inability to perform simple tasks and memory loss.

Back in March 2015, an early-stage clinical trial provided evidence that aducanumab drastically reduced beta-amyloid plaques in the brain. However there were some flaws within this trial such as small testing groups but also the assumption that beta-amyloid oligomers decreased. The latest updates have found that the intermediate deposits, ‘beta-amyloid oligomers’ may be the real culprit and not the end state ‘beta-amyloid plaques’.[13] [14] Four years later and Biogen announced that the development of aducanumab will be discontinued. That is until a couple months later the announcement that the FDA would now be considering it for marketing approval.

The Problems:

The Controversy

The FDA granting accelerated approval is under much speculation. As mentioned earlier, the amyloid hypothesis has influenced a large proportion of Alzheimer’s disease research. The amyloid hypothesis is still doubted by many professionals with its more recent ‘failed’ drug trials adding further doubt.[15] The FDA’s ignorance towards data from the trial which showed no slowing in disease progression is alarming considering the “FDA’s own advisory committee last November voted 8 to 1 against approving the drug, citing “lack of strong evidence that the drug works.”[16] In fact, a member of the of the FDA’s expert panel for nervous system therapies has even gone as far to resign over the FDA ruling, STAT reported.[17]

Even if we were to ignore the lack of data proving any clinical benefits of aducanumab on declining disease progression, the question of whether there is a connection between plaque reduction and cognitive improvement still remains uncertain. Some believe beta-amyloid may not be the underlying cause of the disease at all and hence aducanumab may not be the answer.

Furthermore, we need to be realistic. Professor John Hardy of neuroscience at University College London, said: “We have to be clear that, at best, this is a drug with marginal benefit which will help only very carefully selected patients.” It is likely that aducanumab will be better for those with mild AD and cognitive impairment, as opposed to those with advanced AD.

It’s Future and the Challenges that lie ahead

The potential side effects are another reason to approach aducanumab treatment with caution. Patients undergoing aducanumab treatment will need continual monitoring due to its main side effect, amyloid-related imaging abnormalities (ARIA). ARIA-E refers to cerebral edema or brain swelling, whereas ARIA-H refers to cerebral microhemorrhages or micro bleeds in the brain.

While many have heavily criticised the approval, others are praising it with caution under the acknowledgement that it is far from a cure. The accelerated approval of aducanumab (as opposed to standard approval) is paving a new path for other treatments of neurodegenerative diseases. The ‘accelerated approval’ pathway is used for treatments that are “reasonably likely” but not certain to help patients. Furthermore, the revival of aducanumab is also bringing more interest towards research for treatments of neurodegenerative diseases. As Mario Carrillo, chief science officer at the nonprofit Alzheimer’s Association, has said: “History has shown us that approvals of the first drug in a new category invigorates [sic] the field”.

In order for us to ensure aducanumab could truly be the way forward for AD treatment, companies marketing the drug, Biogen and Eisai, should verify its clinical benefits with further study. While the amyloid hypothesis may be doubtful, there is no reason to give up in this direction of treatment yet.

Conclusion

Uncertainty still remains over aducanumab’s future impact; it is yet to be available in the UK and Europe. Nevertheless aducanumab is providing a spark of hope for our endless search for treatments of AD, as it is the first treatment in a very long time. With dementia research having been chronically underfunded in the UK, the need for new life-changing treatments is only increasing.

As it stands currently, aducanumab is not exactly a cure for Alzheimer’s and there are still many more obstacles we will have to overcome. However, it undoubtedly is a remarkable moment and marks a great milestone in dementia research.

Asmita Anand, Youth Medical Journal 2021

References

[1]Jackie, et al. “What Is the Difference between Dementia and Alzheimer’s Disease?” Alzheimer’s Society, 17 July 2018, www.alzheimers.org.uk/blog/what-difference-between-dementia-and-alzheimers-disease.

[2]“Alzheimer’s Society’s View on Demography.” Alzheimer’s Society, 2020, www.alzheimers.org.uk/about-us/policy-and-influencing/what-we-think/demography.

[3]Cummings, Jeffrey, et al. “Alzheimer’s Disease Drug Development Pipeline: 2021.” Alzheimer’s & Dementia: Translational Research & Clinical Interventions, vol. 7, no. 1, 2021. Crossref, doi:10.1002/trc2.12179.

[4]“What Happens to the Brain in Alzheimer’s Disease?” National Institute on Aging, 2017, www.nia.nih.gov/health/what-happens-brain-alzheimers-disease.

[5]“How Alzheimer’s Changes the Brain.” YouTube, uploaded by National Institute On Aging, 23 Aug. 2017, www.youtube.com/watch?v=0GXv3mHs9AU.

[6]Leonard, Wendy Mph. “Causes of Alzheimer’s Disease.” Healthline, 2 Sept. 2017, www.healthline.com/health/alzheimers-disease-causes.

[7]“How Do Drugs for Alzheimer’s Disease Work?” Alzheimer’s Society, www.alzheimers.org.uk/about-dementia/treatments/drugs/how-do-drugs-alzheimers-disease-work. Accessed 2 July 2021.

[8]“Alzheimers Drug Treatments | Royal College of Psychiatrists.” RC PSYCH ROYAL COLLEGE OF PSYCHIATRISTS, 2015, www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/alzheimers-drug-treatments.

[9]Liou, Stephanie. “About Glutamate Toxicity – HOPES Huntington’s Disease Information.” HOPES Huntington’s Disease Information, 18 Nov. 2014, hopes.stanford.edu/about-glutamate-toxicity.

[10]Kernisan, Leslie Mph. “4 Medications FDA-Approved to Treat Alzheimer’s & Other Dementias: How They Work & FAQs.” Better Health While Aging, 19 June 2021, betterhealthwhileaging.net/faqs-medications-for-alzheimers-dementia.

[11]Jack, Clifford R., et al. “NIA-AA Research Framework: Toward a Biological Definition of Alzheimer’s Disease.” Alzheimer’s & Dementia, vol. 14, no. 4, 2018, pp. 535–62. Crossref, doi:10.1016/j.jalz.2018.02.018.

[12]Staff, Bns. “Aduhelm (Aducanumab).” Alzheimer’s News Today, 1 July 2021, alzheimersnewstoday.com/aducanumab.

[13]Yu, Han. “We’ve Got the First Alzheimer’s Drug in Decades. But Is It a Breakthrough?” The Guardian, 2 July 2021, www.theguardian.com/commentisfree/2021/jun/28/alzheimers-drug-aducanumab-approval-dementia.

[14]Sevigny, Jeff, et al. “The Antibody Aducanumab Reduces Aβ Plaques in Alzheimer’s Disease.” Nature, vol. 537, no. 7618, 2016, pp. 50–56. Crossref, doi:10.1038/nature19323.

[15]Sabbagh, Marwan Noel, and Jeffrey Cummings. “Open Peer Commentary to ‘Failure to Demonstrate Efficacy of Aducanumab: An Analysis of the EMERGE and ENGAGE Trials as Reported by Biogen December 2019.’” Alzheimer’s & Dementia, vol. 17, no. 4, 2020, pp. 702–03. Crossref, doi:10.1002/alz.12235.

[16]Doheny, Kathleen. “Controversial New Alzheimer’s Drug: What to Know.” WebMD, 9 June 2021, www.webmd.com/alzheimers/news/20210609/controversial-new-alzheimers-drug-what-to-know.

[17]STAT. “Member of FDA’s Expert Panel Resigns over Alzheimer’s Therapy Approval.” STAT, 9 June 2021, www.statnews.com/2021/06/08/fda-expert-panel-resigns-alzheimers-approval/?utm_campaign=KHN%3A First Edition&utm_medium=email&_hsmi=132618545&_hsenc=p2ANqtz-83Omcd8InGsFZ56X_VCnvMvUv0khIW5KtkCzv_xmhbJZHfTbrddSvG8vTBOry6QTzlKkA4sVxAEFsNru_nBzJj4xYUhw&utm_content=132618545&utm_source=hs_email.

“Amyloid-Related Imaging Abnormalities.” Wikipedia, 2021, en.wikipedia.org/wiki/Amyloid-related_imaging_abnormalities.

Servick, Kelly. “Alzheimer’s Drug Approved despite Doubts about Effectiveness.” Science, 2021. Crossref, doi:10.1126/science.abj8372.

Alexander, G. Caleb, et al. “Evaluation of Aducanumab for Alzheimer Disease.” JAMA, vol. 325, no. 17, 2021, p. 1717. Crossref, doi:10.1001/jama.2021.3854.

Schneider, Lon. “A Resurrection of Aducanumab for Alzheimer’s Disease.” The Lancet Neurology, vol. 19, no. 2, 2020, pp. 111–12. Crossref, doi:10.1016/s1474-4422(19)30480-6.

Categories
Health and Disease

The Plague in the Modern Day

By Michelle Li

Published 8:21 EST, Mon August 30, 2021

Introduction and History

The plague is a disease that is caused by the bacterium Yersinia Pestis. The Black Death, one of the most notable pandemics in history, was a result of the transmission of Y. pestis from rats and fleas to humans, making it a zoonotic disease (Frey, “Plague). This transmission often occurred through flea bites or contact with the body fluid of an infected animal. The plague takes on three different forms depending on the affected area of the body: bubonic (affecting lymph nodes), pneumonic (affecting the lungs), and septicemic (affecting the blood). The Black Death is characterized by both the swelling of lymph nodes, which turn black as a result of bubonic plague, and the blackening of skin, resulting from septicemic plague (Frey, “Plague). An estimated 75 to 200 million lives were lost before the end of the Black Death (Frey, “Bubonic Plague”). Today, the number of fatalities resulting from (and cases of)  the plague are not even remotely close to the numbers seen during the Black Death; the recorded numbers are not zero, however. 

Plague in the modern day

Cases of the plague, although much less frequent, still exist today. A majority of the present day cases of the plague occur in developing countries. In fact, the plague is still endemic to (regularly found in) Madagascar, Peru, and the Democratic Republic of the Congo (Frey, “Bubonic Plague). Madagascar reports more plague cases than any other single country, averaging 200 to 400 cases every year (Hardman).

A portion also occurs in the United States. The Centers for Disease Control and Prevention (CDC) reports between 1 to 17 cases of the plague each year in the United States (with an average of 7 reported cases per year). Plague in the United States occurs in western, rural areas; northern New Mexico, northern Arizona, southern Colorado, California, southern Oregon, and western Nevadea are the most affected regions. 80% of these U.S. cases are in bubonic form (“Plague in the United States”). 

Figure 1: This figure shows a world map of plague cases reported to the World Health Organization (WHO) by country between 2000 and 2009 (Centers for Disease Control and Prevention)

There are about 5,000 cases of the plague reported to the World Health Organization (WHO) each year worldwide, and 95% of these cases occur in Africa. Interestingly, the only two continents that are plague-free are Australia and Antarctica (Frey, “Plague”). 

More “recent” plague outbreaks include an outbreak of pneumonic plague in Surat, India in 1994, where 876 cases of infections, including 52 deaths, were reported to the WHO (Frey, “Plague”). The most recent outbreak in Madagascar occurred in 2017 and resulted in 2,575 confirmed or probable cases of bubonic and pneumonic plague, including 221 deaths (World Health Organization 2017). Even more recently, the WHO began reporting on an ongoing outbreak of suspected pneumonic plague in the Dominican Republic of Congo in January of 2020. As of May 2021, there are a total of 564 suspected pneumonic plague cases, including 43 deaths (World Health Organization 2021).

Antibiotics

Today, the plague is treatable with antibiotics. 80% to 90% of patients with bubonic plague that received rapid diagnosis and appropriate treatment will survive; the survival rates for septicemic plague and pneumonic plague are lower in comparison at 75% and 50%, respectively (Frey, “Bubonic Plague”). If left untreated however, each form of the plague is still fatal a majority of the time. Bubonic plague has a mortality rate of 60% to 70% in untreated cases, while untreated septicemic and pneumonic plague both have a mortality rate of 100%. Pneumonic plague, specifically, is 100% fatal if left untreated for 48 hours (Frey, “Bubonic Plague”). 

Streptomycin, an antibiotic discovered in the 1940s, is one of the first-line treatments for plague (Hardman). Gentamicin, chloramphenicol, and tetracycline are alternatives that can also be administered. It is important that the administration of antibiotics is started as soon as possible (Cua). 

The Future

Some scientists have also considered the association between climate and plague. The conditions following warmer weather in the spring and wet weather in the summer are beneficial for fleas and bacteria, which play key parts in the spread of plague (Hardman). Additionally, outbreaks of plague among local animals (called epizootics) most commonly occur after wet winters and cool summers; these epizootics could also affect humans (Frey, “Plague”). In the case of the plague outbreak in Surat, India, rainfall also influenced the spread of plague, as flooding increased contact with drowned, infected animals that were not disposed of (Frey, “Plague”). Similarly to other climate sensitive and infectious diseases, the effects of global warming may increase the number of outbreaks of plague in animals and, in turn, in human populations (Hardman). 

Lastly, the animal reservoirs of the plague (the host animal populations that infectious diseases survive off of) make the disease impossible to eradicate (Frey, “Plague”). Rats play a large role in the spread of the plague. Controlling that spread—considering their sheer numbers and the scope of human capabilities—proves to be near impossible. Surveillance of animal populations and careful reporting of plague cases, however, is still important in preventing plague (Frey, “Plague”).

Conclusion

The plague is an infectious disease that is well known due to its connection to the Black Death, one of the most notable epidemics in history. While the occurrence of the plague has changed since medieval times, the high mortality rates of untreated plague cases have remained and are currently affecting different regions of the world. Considering its connections to climate change and recent developments, the plague is not a disease of the past, but rather, one that is still relevant to the modern world. 

Michelle Li, Youth Medical Journal 2021

References

Centers for Disease Control and Prevention. “World Plague Map – 2000 to 2009 – CDC.” Wikimedia Commons, commons.wikimedia.org/wiki/File:World_Plague_Map_-_2000_to_2009_-_CDC.jpg. Accessed 30 June 2021. Map.

Cua, Arnold, and Rebecca J. Frey. “Plague.” The Gale Encyclopedia of Medicine, edited by Jacqueline L. Longe, 6th ed., vol. 7, Gale, 2020, pp. 4067-71. Gale Health and Wellness, link.gale.com/apps/doc/CX7986601475/HWRC?u=mlin_m_newtnsh&sid=bookmark-HWRC&xid=851c3f42. Accessed 1 July 2021.

Frey, Rebecca J., PhD. “Bubonic Plague.” The Gale Encyclopedia of Emerging Diseases, edited by Deirdre S. Hiam, Gale, 2018, pp. 45-52. Gale Health and Wellness, link.gale.com/apps/doc/CX3664800021/HWRC?u=mlin_m_newtnsh&sid=bookmark-HWRC&xid=0a3632e4. Accessed 1 July 2021.

—. “Plague.” The Gale Encyclopedia of Public Health, edited by Brigham Narins, 2nd ed., vol. 2, Gale, 2020, pp. 847-51. Gale Health and Wellness, link.gale.com/apps/doc/CX7947900220/HWRC?u=mlin_m_newtnsh&sid=bookmark-HWRC&xid=d93f373c. Accessed 1 July 2021.

Hardman, Lizabeth. “Plague Today and Tomorrow.” Plague, Lucent Books, 2010, pp. 74-87. Diseases & Disorders. Gale Health and Wellness, link.gale.com/apps/doc/CX1334700011/HWRC?u=mlin_m_newtnsh&sid=bookmark-HWRC&xid=8b9c5d6d. Accessed 1 July 2021.

“Plague in the United States.” Centers for Disease Control and Prevention, http://www.cdc.gov/plague/maps/index.html. Accessed 30 June 2021.

World Health Organization. Weekly Bulletin on Outbreaks and Other Emergencies. 15 Dec. 2017. World Health Organization, apps.who.int/iris/bitstream/handle/10665/259709/OEW50-1015122017.pdf;jsessionid=9E1F0CC89024B909F1E30F0B1064B43A?sequence=1. Accessed 30 June 2021.

—. Weekly Bulletin on Outbreaks and Other Emergencies. 27 June 2021. World Health Organization, apps.who.int/iris/bitstream/handle/10665/342077/OEW26-2127062021.pdf. Accessed 30 June 2021.

Categories
Commentary COVID-19 Health and Disease

The Exoticization of Epidemics

By Rhea Argwal

Published 1:30 EST, Tue August 24, 2021

Abstract: 

During an epidemic, scientists tend to search for sources of the outbreak. If the outbreak has foreign origins, scientists often enlist the help of anthropologists to study local practices and customs since cultural awareness is necessary for any public health campaign or outbreak control. However, the role of anthropologists seems to extend further than that. Anthropologists identify ‘risky behaviours’ present within a society which may escalate an outbreak. Yet, these ‘risky behaviours’ always tend to be rooted in cultural contexts. Scholars tend to ignore socioeconomic factors, such as overcrowding, poverty, etc., which may have a greater hand to play in the proliferation of a disease through a population. This instinctive ignorance lets slip the presence of racism and Eurocentric bias in the subconscious beings of scientists and researchers. 

Ebola and Africa [1980s]

The Ebola Virus Disease (EVD), a rare and fatal disease, was first discovered in 1976 in the Democratic Republic of Congo (DRC) (Centers for Disease Control and Prevention , 2021). After an incident on a shipping boat in 1989, Western media’s interest in the virus erupted. Due to its foreign origins, media and Western society linked the source of the outbreak to practices in African culture (Jones, 2011). 

The Ebola virus is a zoonotic disease meaning that the virus had been transferred from animals — specifically nonhuman primates (monkeys, gorillas, and chimpanzees) — to people. Thus, enlightened with this information, scholars proposed the Bushmeat Hypothesis: “hunting, slaughtering, and eating infected gorilla or monkey meat is the primary cause of the virus’s entrance to a new population (Jones, 2011).

This argument became one of the dominant explanations of the Ebola outbreaks as it provided a correlation between cultural practice and a viral outbreak. However, doing so overshadowed other arguments which may have been greater factors at play; factors such as overcrowding, poor sanitation, and inadequate provision of healthcare, exacerbated by a legacy of colonialism were responsible for much of Ebola’s spread. However, cultural factors were emphasised more than sociopolitical and economic factors. Africans were presumed to have beliefs rooted in witchcraft and superstitions which may have hindered efforts by doctors and scientists to control the outbreak (Jones, 2011). Disputing this notion was a Harvard professor and a medical anthropologist, Paul Farmer, who was at the forefront of the Ebola epidemic control. The failure to control the outbreak did not occur due to local customs and traditions but rather due to distrust in the healthcare system and the government. 

People fled the medical system, not because of superstitions, but mostly when the medical system was unable to rescue or treat its patients as constituted.”

(Paul Farmer in an interview with Ashish Jha on Lessons from Ebola)

Due to the lack of adequate hospital infrastructure, doctors had implemented a disease control paradigm that concentrated its efforts on isolating suspected cases and confirmed cases without providing actual care (unlike the current COVID-19 care centres). This approach was rendered ineffective. Distrust in the healthcare system further grew and people started turning to traditional healing systems as a desperate resort. 

The erroneous depictions of the Western media and the presumptions of Western society of the Ebola outbreak reveal the lingering presence of racism in our society and the remnants of colonialism. Additionally, it affirms the presence of bias in biomedical research.

AIDS as a Haitian Disease [the 1980s]

It is the 1980s. Haiti, a Caribbean country, has been receiving widespread publicity as the possible birthplace for AIDS. Acquired Immunodeficiency Virus (AIDS) is a chronic and fatal condition caused by the human immunodeficiency virus (HIV); HIV is a sexually transmitted infection (STI) that weakens one’s immune system. A severely damaged immune system progresses into AIDS as it is unable to protect the body from infections or cancers that a person with a healthy immune system wouldn’t normally acquire (Mayo Clinic, 2020). Upon the emergence of an AIDS epidemic, scientists begin investigating the sources of the outbreak. In an eruption of imagination, Western society and media speculated that voodoo rites, sacrificial practices, the eating of cats, and ritualized homosexuality, were the causes of the epidemic – “a rich panoply of exotica” (Farmer & Kim, Anthropology, Accountability, and the Prevention of AIDS, 1991). The speculations gave rise to stereotypes that were enforced time and time again by the U.S. press. Also notable was the media representation of Haitian-Americans: black, poor, immigrants, and associated with cult-like religious practices. As media sensationalized and misrepresented the Haitian-American community, incidents of harassment began to propagate. People of Haitian origin bore the stigma of a fatal condition. The statement of one Haitian-American physician mirrors this sentiment: 

“After all the wild theories of voodoo rites and genetic predisposition were aired and dispelled, and the slip-shod scientific investigation was brought to light, the public perception of the problem remained the same that if Haitians have AIDS, it is very simple because they are Haitians (Farmer & Kim, Anthropology, Accountability, and the Prevention of AIDS, 1991).”

However, none of the speculations and gossip surrounding the epidemic had any epidemiological research to back them up.  As a matter of fact, declarations of plausible theories of the sources of the outbreak by scientific researchers had slowly begun unravelling the lies illustrated by the press. On December 1, 1982, the following statement was made: 

“Homosexuals in New York take vacations in Haiti, and we suspect that this may be an epidemic Haitian virus that was brought back to the homosexual population in the United States.” 

(Dr. Bruce Chabner of the National Cancer Institute, 1982) 

At the 1988 conferences of the American Anthropological Association, researchers congregated to discuss “Ethical Considerations in Anthropological Research.” The focal point of the meetings was the failure to lighten the burden of stigma on the Haitian-American community, aggravated by the spread of misinformation. Further addressed was the economic damage of Haitian businesses, which were boycotted by tourists and investors, and the rise in unemployment within the Haitian-American community. Nevertheless, in February 1990, the Food and Drug Administration (FDA) ruled that no person of Haitian origin will be allowed to donate blood (Farmer & Kim, Anthropology, Accountability, and the Prevention of AIDS, 1991). The incessant discrimination against the community, not only resulted in economic damage but also a decline in the mental and emotional health of members of the ethnicity. All this, due to the deep-rooted racism in a system that embraced popular societal opinion rather than verified scientific research. 

SARS – CoV – 2 (COVID-19) Pandemic [2020]: Hate Crimes Against South East Asians

SARS-CoV-2, colloquially known as COVID-19, originated in Wuhan, the capital city of the Hubei province, China. The virus evidently has zoonotic origins (similarly to Ebola) with genetic similarities to bat genomes. The COVID-19 virus first caused a viral outbreak in the Hubei province region, soon spread to surrounding provinces and all over China. In China, it has declared an epidemic. Subsequently, the virus infiltrated borders and crossed seas through international travel and infected millions of people; On March 11, 2020, the World Health Organization (WHO) had declared the COVID-19 viral outbreak, a pandemic (World Health Organization, 2020). 

Proclaimed as a zoonotic disease, researchers began investigating the source of the animal-to-human transfer and traced it back to the Wuhan Southern China Seafood Market where wild animals were being sold. The bushmeat theory, first proposed during the Ebola outbreak, found new ground almost 40 years later in the SARS-CoV-2 epidemic. However, the magnitude of this viral outbreak significantly surpassed the Ebola epidemic; millions, if not billions, of lives, have been affected around the world; trillions of dollars are being spent on reviving an economy that has seen its deepest slump since the Great Depression. Now, at a very vulnerable state, with dear lives lost, people need someone to take blame and responsibility. Hate incidents and crimes against the Chinese and Asian communities increased. The pandemic had given rise to stigma and discrimination. News media picked up on this sentiment and began referring to the SARS-CoV-2 virus as the “Chinese virus,” or the “Wuhan virus.” Associations of such may have provoked people to detest a community that was struggling with an outbreak, too (Xu, et al., 2021). 

“Pandemics do not materialise in isolation. They are part and parcel of capitalism and colonisation. The countries that struggled to contain and control major epidemics in the recent past, from Haiti to Sierra, had deficient public health systems prior to these crises, partially as a result of their colonial histories. Moreover, products of capitalism – from war to migration to mass production and increased travel – contribute massively to the proliferation of diseases.”

(Edna Bonhomme, Postdoctoral Fellow at the Max Planck Institute for the History of Science in Berlin, on the topic of COVID-19 and Inequality (Bonhomme, 2020))

In the three occurrences discussed above, there seems to also be three recurrent themes. Firstly, the sudden media interest in the three cases amplified the racialization of these epidemics. Arguably, the media played the biggest role in the dramatization of the epidemic’s events. Unexpectedly, scholars often also shared the view proposed by the popular press. The prejudices and biases present in these scholars subconsciously affected their judgements in an epidemic control centre or a research centre, thus adversely influencing the healthcare quality available in these countries. Additionally, in the media frenzy, the western way of living was enforced as the norm, painting foreign cultures as exotic. This is where the remnants of colonialism become apparent once again. Lastly, through analysis of media reports and scholarly articles or journals, one can understand that some researchers subliminally undermine indigenous knowledge and accept biomedical research as the divine truth. 

Media Manipulation: Sensationalism 

Western media portrayals in each of the three case studies seem to have subconsciously depicted Western ways of living as norms by contrasting them with the ways of living of other ethnic communities. This juxtaposition depicts the complex and vibrant cultures of various ethnic groups around the world as simply exotic. Exotic, meaning interesting, different, and ‘other’. The exoticization of an ethnic community and its practices alienates its members, thus leaving them more susceptible to racial discrimination. This dramatization is not only demeaning for an ethnic community but also an exploitation of the credibility the masses of people associate with news media reporting. 

Systematic Racism, Stigma, & Discrimination

The existence of systematic racism, ingrained within institutions — in the laws, policies, and decisions — are mainly what hinders the provision of healthcare in epidemic control centres; it is what distorts epidemiological research. The erroneous conclusions of such scientific and anthropological research attribute the causes of an epidemic to local practices, traditions, and customs of an ethnic community while hardly considering sociopolitical or economic factors. This, in addition to media sensationalism, places a degrading spotlight on a community that may be suffering as well. Stemming from such situations is stigma and racial discrimination. At a moment when people are at their most vulnerable state, systematic racism and media sensationalism give rise to hate crimes as currently seen occurring against the South East Asian community due to the COVID-19 pandemic. 

Worth Found in Indigenous Knowledge 

When planning epidemic centre controls in different countries, scientists and anthropologists often study the local practices, customs, and traditions — indigenous knowledge. However, the lens with which this body of knowledge is viewed indicates that scholars believe indigenous knowledge serves to hinder the provision of healthcare rather than aid its use. Subliminally, all scholars undermine indigenous knowledge and regard it as ‘backwards’. Associated with many of these communities is a cumulative body of knowledge and know-how honed through years of observations, experiments, and reflections. Although these practices have been developed through years of observations, it is not possible to ascertain their reliability or accuracy since they have not been assessed by the wider intellectual community as of now due to there being notions that indigenous knowledge is retrogressive and anti-development. If we aspire to put in the effort to inspect the accuracy of indigenous knowledge, we may be able to verify that the majority of their claims may be accurate and, in fact, useful in developing future theories or innovations, instead of labelling them as regressive. 

Conclusion

In conclusion, the notion that any ethnic community’s customs or traditions hamper epidemic control efforts should be challenged. Publishing unverified scientific information that may be linking the source and spread of an outbreak to an ethnic community can prove to be very degrading and even detrimental for members of a community, leaving them predisposed to scorn and resentment. Although our world has come a long way from its colonizing history, the legacy and remnants of it can still be seen today in the form of the exoticization of ethnic practices through systematic racism. 

Rhea Agarwal, Youth Medical Journal, 2021 

Bibliography

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Bonhomme, E. (2020, May 18). COVID-19 and Inequality: The Racialization of Pandemics. (t. G. (GRIP), Interviewer)

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Centres for Disease Control and Prevention. (2021). History of Ebola Virus Disease. Retrieved June 27, 2021, from https://www.cdc.gov/vhf/ebola/history/summaries.html

Economic Development Department. (2020). Systematic Racism. Cabinet Secretary Keyes on Systemic Racism & the Role of Businesses. https://gonm.biz/stories/cabinet-secretary-keyes-on-systemic-racism-the-role-of-businesses. 

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