PATHOPHYSIOLOGY

Medical Diagnosis:

Chronic Obstructive Pulmonary Disease (COPD)

Definition:

Chronic Obstructive Pulmonary Disease (COPD) is chronic inflammation and fibrosis of the air ways, specifically the peripheral airways and lung parenchyma (Barnes, 2017).

Cellular Description:

Chronic Obstructive Pulmonary Disease (COPD) is chronic inflammation of the air ways, specifically the peripheral airways and lung parenchyma (alveoli and bronchioles) which leads to expiratory airflow limitation.  The disease is a combination of diseases including emphysema, chronic asthma, and chronic bronchitis.  Emphysema is destruction of lung parenchyma, bronchitis is inflammation and excess mucus production, and asthma is tight and swollen airways (Wu, 2019).  COPD manifestations include mucus hypersecretion, airway narrowing and fibrosis, destruction of parenchyma, and vascular changes (Chronic obstructive, n.d.).

The mechanism of inflammation is prompted by mast cells in response to foreign particles or infection in the airways.  Mast cells release histamine, PGD2, and cys-LTs all of which contract the smooth muscles of the airways, increase the production of mucus, attract inflammatory cells, induce tissue destruction, impair defense mechanisms, and increase microvascular leakage.  Lipid mediators, cytokines, and chemokines also seek to recruit inflammatory cells to the lungs.  Lung cells including endothelial cells, epithelial cells, and fibroblasts contribute to the inflammatory process by releasing chemical mediators.  Both the innate and adaptive immunity are active in COPD.  The innate immune system attracts macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and dendritic cells.  The adaptive immune system brings in T and B lymphocytes.

Macrophages contribute immensely to the marked inflammation in chronic obstructive pulmonary disease.  In patients with COPD, an increase in the number of macrophages in the lungs, airways, and parenchyma is observed.  These macrophages seem to have a greater chemotactic response, or increased activation, to CXCL1, a chemokine, than do the macrophages from normal smokers and from non-smokers (Barnes, 2017, p. 11).  This immense infiltration of macrophages yields more inflammatory proteins and reactive oxygen species.  “Macrophages likely play an orchestrating role in COPD inflammation by releasing mediators such as tumor necrosis factor-a (TNF-a), interleukin 8 (IL-8), and leukotriene B4 (LTB4), which promote neutrophilic inflammation” (Chronic obstructive, n.d.).  Macrophages also demonstrate decreased phagocytic uptake of bacteria which “may predispose [the patient] to chronic colonization of the lower airways by bacteria such as

Haemophilus influenzae

or

Streptococcus pneumoniae”

(Barnes, 2017, p. 12).  Colonization of bacteria predisposes COPD patients to increased acute exacerbations.  COPD macrophages also fail to clear apoptotic cells in the lungs which can contribute to the lack of resolution of inflammation.

Neutrophilic chemotactic factors are released from the respiratory tract to attract neutrophils.  Once present, neutrophils “secrete serine proteases, including neutrophil elastase (NE), cathepsin G and proteinase-3, as well as MMP-8 and MMP-9, which may contribute to alveolar destruction” (Barnes, 2017, p. 13).  Neutrophil elastase and serine proteases stimulate goblet and submucosal cells in the central and peripheral airway to increase in number (metaplasia) which yields mucus hypersecretion.  This explains why neutrophils are found exceedingly in sputum samples of COPD patients.  Patients with COPD typically have paralyzed cilia which inhibits the excess mucus from effectively being removed thus it occupies the airway lumen increasing obstruction (Barnes, 2017).  The mucus hypersecretion in the peripheral airways causes damage to and decline in function of the alveoli.

T lymphocytes are also present in COPD along with macrophages and neutrophils.  T lymphocytes, specifically CD8+, released perforin, granzyme-B, and tissue necrosis factor-a all of which cause cytolysis and apoptosis of alveolar epithelial cells.  This is thought to be responsible for the persistent inflammation seen in COPD (Chronic obstructive, n.d.).

The invasion of these cells into the lungs is most often caused by cigarette smoke.  “Cigarette smoke activates macrophages and epithelial cells to produce TNF-a and may also cause macrophages to release other inflammatory mediators, including IL-8 and LTB4” (Chronic obstructive, n.d.).  The inflammation caused by cigarette smoke or the inflammatory response leads to repeated cycles of repair and damage to the peripheral airways.  In the effort to repair the airways epithelial cells and macrophages secrete fibrogenic mediators to activate mesenchymal cells including fibroblasts and myofibroblasts.  Fibroblasts attempt to repair the damage in the alveoli but leave behind scar tissue and collagen.  This is known as fibrosis and is an irreversible narrowing of the airways.  Fibrosis limits the lungs ability to recoil and increases airway resistance.

As inflammatory cells infiltrate the lungs, bronchoconstriction occurs in response to mediators released by the cells.  Blood to the airways is reduced in COPD due to a decrease in vascular-endothelial growth factor which can lead to tissue hypoxia.  Endothelial damage within the vessels also occurs and alters the vascular tone and cell proliferation. “Thickening of the intima is the first structural change, followed by an increase in vascular smooth muscle and the infiltration of the vessel wall by inflammatory cells, including macrophages and CD8+ T lymphocytes14” (Chronic obstructive, n.d.).  This all leads to pulmonary hypertension.

If neutrophilic inflammation, fibrosis, and ineffective bacterial phagocytosis by macrophages is persistent, lower airway inflammation will inevitably lead to pathologic changes and progression of chronic obstructive pulmonary disease.  Systemic inflammation also follows as inflammatory cells circulate throughout the body.

In addition to inflammation, the body experiences an imbalance in proteinases and anti-proteinases and oxidative stress.  These manifestations are thought to arise as a consequence of inflammation or by environmental or genetic factors.  Inflammatory cells release proteinases which some are capable of degrading the alveolar elastin and collagen and others cause mucus gland hyperplasia.  Oxidant/antioxidant imbalance is also seen in COPD with a variable amount of hydrogen peroxide and nitric oxide generated by cigarette smoke or released from inflammatory cells.  The imbalance is typically more oxidants than antioxidants.  This imbalance can lead to cell dysfunction or death and lung extracellular matrix damage.  It also adds to the imbalance between proteinases and anti-proteinases by inactivating anti-proteinases and activating proteinases.  Oxidants promote inflammation, contribute to airway narrowing, and constricts airway smooth muscles (Chronic obstructive, n.d.).

With the extensive effect COPD has on the airways, it is of no surprise that there are multiple co-morbidities associated with the disease including cardiovascular disease, diabetes, depression, skeletal muscle dysfunction, lung cancer, metabolic syndrome, and osteoporosis (Rosenberg & Kalhan, 2017).

Epidemiology:

• COPD is the 4th commonest cause of death worldwide, and 3rd in developed countries like the UK.
• COPD is the 5th ranked cause of disability.
• There are 251 million cases of COPD globally.
• It affects 10% of people over the age of 45.
• In developed countries, it is predominantly caused by cigarette smoking.
• COPD effects women and men about equally, which demonstrates the about equal use of cigarette smoking in males and females.
• In low- and middle-income countries, COPD is most often due to wood smoke (biomass) exposure and not due to cigarette smoking.
• Systemic inflammation was associated with a 2-4-fold increased risk of cardiovascular disease, diabetes, lung cancer and pneumonia.
• 70% of COPD patients have systemic inflammation, and 16% of those have persistent inflammation with increased mortality and exacerbations.
• “System inflammation is (also) associated with greater decline in lung function.”

(Barnes, 2017).

• “Those hospitalized for acute exacerbations of COPD are at an increased risk of one-year mortality of at least 18%” (Rosenberg & Ravi, 2017).

• $50 billion dollars is spent every year in the US to treat acute exacerbations of COPD.

(Rosenberg & Kalhan, 2017)

Risk Factors:

• Cigarette smoking
• Secondhand smoking
• Workplace irritants
• Industrial chemicals
• Cooking fumes
• Air pollution
• Pipe smoke
• Age
• Genetics
• Low socioeconomic status
• Prematurity

(Wu, 2019)

Signs & Symptoms


(Differentiate between Early vs. Late signs/symptoms)

Treatment

Medications



(drug classification and a


brief


description of how the med works)



,, Diet,








Lifestyle, Surgery,








Activity

• Shortness of breath (early)
• Breathlessness (early)
• Inability to exercise (early)
• Difficulty breathing (early)
• Chest tightness (early)
• Fatigue (early)
• Fever
• Frequent respiratory infections
• Confusion
• Exacerbations of these symptoms
• Chronic cough
• Producing more mucus than normal
• Swelling in the ankles, feet, legs (severe COPD)
• Weight loss (severe COPD)
• Reduced muscle strength
• Reduced endurance (early)
• Wheezing (early)
• Tissue hypoxia (late)
• Cyanosis (late)
• Respiratory acidosis (late)
• Fibrosis of lower airways (late)
• Pulmonary hypertension (late)
• Hypertension
• Decline in lung function measured by amount of air forcibly exhaled in one second (FEV1)

(Wu, 2019)

COPD cannot be cured but there are therapies to decrease the complications and side effects.

• 
  Corticosteroids-
  
  reduce inflammation.

• 
  Antibiotics
  
  (ex. macrolide)- kill existing bacteria and inhibit growth of bacteria.

(Barnes, 2017)

• 
  Long acting beta-2 agonists
  
  – relaxes airway smooth muscle tone which leads to reduced respiratory muscle activity and decreases airway resistance. Helps the patient breathe easier.
• 
  Long acting muscarinic antagonists
  
  (ex.  tiotropium)- bronchodilator.
• 
  Dual agent long-acting bronchodilators
  
  (ex. fluticasone/salmeterol)- inhalers with combined medicines to improve lung function, reduce exacerbations, dilate the smooth muscle of the bronchi.
• 
  Bronchoscopic therapies
  
  (work in progress)- lung volume reduction surgery to prolong life for people with COPD.

(Rosenberg & Kalhan, 2017)

• 
  Smoking cessation.
  
• 
  Oxygen therapy.
  
• 
  Pulmonary rehabilitation.
  

(Wise, 2018)

Diagnostics


(Labs, Radiology, Biopsy, others)

Tests:








List all diagnostic tests that you would expect to be completed with this diagnosis. Give expected values and/or descriptions of each test.

• 
  Chest x-ray
  
  – changes can include lung hyperinflation, rapid tapering. Of hilar vessels, bullae, prominent hilla.
• 
  Chest CT
  
  – may reveal abnormalities.
• 
  Pulmonary function testing
  
  – FEV1, forced vital capacity (FVC), flow-volume loops.
• Abnormalities in these may indicate COPD

• Increased total lung capacity
• Increased functional residual capacity
• Increased residual volume
• Decreased vital capacity
• Decreased single-breath diffusing capacity for carbon monoxide

• 
  Alpha-1 antitrypsin levels
  
  – to detect deficiency.
• 
  ECG
  
  – done to exclude any cardiac conditions that could cause symptoms of dyspnea.
• 
  Echocardiography
  
  – assesses for pulmonary hypertension.
• 
  Evaluate PaO2 and PaCO2.
  
• 
  Assessment of sputum
  
  – indicates neutrophil levels, bacteria present (infection).

(Wise, 2018)

ADD: what are the normal values for these and what are the values in COPD?

References (APA format)

• Barnes, P. J. (2017, March 1).
  
  Cellular and molecular mechanisms of asthma and COPD
  
  , pp. 1 -24. Retrieved November 2, 2019, from https://spiral.imperial.ac.uk:8443/handle/10044/1/51388.
• Chronic obstructive pulmonary disease pathogenesis, pathology, and pathophysiology (n.d.).
  
  In Institute for continuing education
  
  . Retrieved November 3, 2019, from http://ceu.org/cecourses/990709/copd_course_patho.htm.
• Rosenberg, S. R., & Kalhan, R. (2017, June 9).
  
  Recent advances in the management of chronic obstructive pulmonary disease
  
  . Retrieved November 2, 2019, from   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473415/.
• Wise, R. A. (2018, November).
  
  Chronic obstructive pulmonary disease (COPD) – pulmonary disorders
  
  . Retrieved November 2, 2019, from https://www.merckmanuals.com/professional/pulmonary-disorders/chronic-obstructive-pulmonary-disease-and-related-disorders/chronic-obstructive-pulmonary-disease-copd.
• Wu, Brian (2019, September 30).
  
  Pathophysiology of COPD: What happens, causes, and symptoms
  
  . Retrieved November 2, 2019, from  https://www.medicalnewstoday.com/articles/315687.php.

Introduction

Streptococcus pneumoniae

is a gram-positive capsular, bacterial pathogen, which is responsible for many diseases, ranging from fairly harmless (acute otitis media and sinusitis) to deadly (pneumonia, bacteraemia and meningitis). Those effected are the paediatric, elderly and the immunocompromised, with pneumococcal infection being the leading cause of pneumonia in children worldwide. This infection is pandemic, with 23,886 confirmed cases of invasive pneumococcal disease being reported in the EU in 2017 alone (ECDC,2017). Those who are at a greater risk of contracting the disease are individuals with other health conditions such as diabetes, asthma, chronic obstructive pulmonary disease, cardiovascular disease, human immunodeficiency virus (HIV) and sickle cell disease to name but a few (Daniels et al., 2016). Despite it causing disease,

S. pneumoniae

can colonise the upper respiratory tract asymptomatically.

The bacteria have evolved over time to be able to colonise the respiratory tract of children and healthy adults, which is where it usually resides as a highly adapted commensal (Weisner et al., 2018). They can attach to the nasopharyngeal surface and from here spread to other organs such as the ears and lungs, travel through the blood stream or remain as a coloniser (Normak-Henriques and Tuomanen, 2013). The main role of the capsule is to protect the bacteria from host enzymes, bacteriophages and host immune cells, such as phagocytes. Therefore, acting as a great virulence factor due to its capacity to help the bacterium evade assault from the host immune system (Ford, 2014) and, it is thus frequently a target for vaccine development. Another important feature are the pili, which adorns the cell surface of the bacteriumand is crucial for attachment to epithelial cells (Normak-Henriques and Tuomanen, 2013) – once again acting as a great virulence factor.

S. pneumoniae

is often transmitted via person-to person contact, usually from asymptomatic carriers (such as children), and requires contact with nasal secretions or contaminated surfaces (Zafar et al., 2017).

Depending on the area of the body that has been infected, the symptoms of

S. pneumoniae

can vary and often, symptoms cannot be distinguished from other bacterial infections (ECDC, 2014). According to Normak-Henriques and Tuomanen (2013),

S. pneumoniae

causes more deaths than any other disease globally. It has a plastic genome and can easily and quickly remodel it through uptake and incorporation of external DNA from other pneumococci or from closely related oral streptococci species. Due to its plastic genome, it has been able to become highly resistant to antibiotics such as meropenem, vancomycin, teicoplanin, linezolid and, quinupristin/dalfopristin (Ford, 2014). Its plasticity has thus, allowed it to evade a vaccine-induced immune response. The lethality of

S. pneumoniae

is therefore as a result of an accumulation of factors such as its virulence factors, a shift from commensal to pathogenic interaction in host, high carriage rates and its genetic plasticity. These are some of the reasons as to why WHO included

S. pneumoniae

as one of 12 priority pathogens in 2017 (Weisner et al., 2018). Moreover, the above reasons are prime examples as to why vaccines for these bacteria have been created. Additionally, the bacteria have several different serotypes (distinct surface structures) which makes creating vaccines to eradicate the disease as whole more problematic. The 10 most common serotypes for 2017 in the EU were 8, 3, 22F, 19A, 12F, 9N, 15A, 10A, 11A and 23B (ECDC,2017). The number of serotypes used in a vaccine is determined by the prevalence of that serotype and this is why new vaccines are readily being created. The purpose of this essay is to outline some the main treatments for

S. pneumoniae

and to compare two vaccination treatments – one glycoconjugate vaccine and one whole cell vaccine.

Figure 1.

Picture taken from Van der Poll and Opal (2016). Diagram of the

Streptococcus pneumoniae

bacterium. The polysaccharide capsule depicted, is one of the main targets for vaccine development due to the fact that the capsule is one of the main virulence factors that enables the bacteria to evade host immune response. The pili, which are illustrated, allows for the bacterium to attach to host cell surfaces to commence cell assault. Pneumococcal serine-rich repeat protein (PsrP) is also shown and it mediates attachment to the lung epithelial cells and is encoded by a pathogenicity island.

Treatments

The mainstay treatment for individuals with

S. pneumoniae

is usually antibiotic therapy – specifically amoxicillin in less severe cases. Oral amoxicillin should be used as the first line of response in the management of community acquired pneumonia in the UK – guidelines set by National Institute for Clinical Excellence (NICE) and British Thoracic Society (BTS). Amoxicillin should be taken from between five and seven days, solely depending on the stage of illness. For those individuals that present with suspected pneumococcal or bacterial meningitis, NICE recommends intravenous cefotaxime alongside amoxicillin or ampicillin. Once further diagnosis has been carried out, such as taking a culture sample from cerebrospinal fluid (CSF), the antimicrobial treatment should be tailored further once the causative agent has been confirmed. The British Infection Association (BIA) recommended penicillin-based agents and cephalosporins in the treatment of community-acquired pneumonia. However, if a patient has highly resistant

S. pneumoniae

, ofloxacin and vancomycin have been suggested to use. (Brown et al., 2017).

As aforementioned, antibiotic resistance for

S. pneumoniae

is a cause for concern. However, amoxicillin was created by adding an amino group onto penicillin to combat antibiotic resistance. The mechanism of amoxicillin is as follows: due to it being a beta lactam, it has the ability to bind to penicillin-binding proteins that inhibits a process called transpeptidation. This then results in the activation of autolytic enzymes in the bacterial cell wall. This process leads to lysis of the cell wall and thus bacterial cell death. Another way of combatting antibiotic resistance to amoxicillin is by using amoxicillin and a beta lactamase inhibitor in conjunction e.g. clavulanic acid. They work by “binding irreversibly to the catalytic site of an organisms’ penicillinase enzyme, which causes resistance to the original beta lactam ring. Although this doesn’t directly cause bacterial cell death, when used with amoxicillin, they allow for amoxicillin to perform correctly on those organisms that produce penicillinase activity (Akhavan and Vijhani, 2019).

Apart from solely antibiotic therapy, there are other ways of treating pneumococcal infections such as adjuvant anti-inflammatory therapy. The role of which is to enhance the body’s immune response to the antibiotics. The first example of an adjuvant are macrolides which have both anti-inflammatory and antimicrobial activities – targeting the pathogen and host immune cells. They target the pathogen by having selective inhibitory effects on the protein synthesis of bacterial cells and by suppressing the production of pneumococcal adhesins, invasins and cytotoxins. For the anti-inflammatory activity, the macrolides target neutrophil-mediated inflammation by suppressing the synthesis of neutrophil-mobilising chemokines and cytokines (e.g. tumour necrosis factor), thus inhibiting neutrophil influx. Another adjuvant are corticosteroids, which are “broad-spectrum anti-inflammatory agents”, most commonly used for penicillin-susceptible meningitis. Corticosteroids work by reducing the inflammation caused by the bacterial assault. Another crucial adjuvant are statins, which once again are anti-inflammatory agents. They work by interfering with G-protein receptor-mediated signalling in immune cells. They also activate the enzyme heme oxygenase-1, which mediates synthesis of essential anti-inflammatory proteins (Feldman and Anderson, 2014).

Using antibiotic therapy as form of treatment is a beneficial thing to do as it can slow down the growth of the bacteria, thereby reducing the damaging effects on the body. Additionally, they are fast acting and can begin to work within a few hours of beginning the course of treatment. However, antibiotic resistance can ensue if the antibiotics are consumed regularly, hence reducing the beneficial effect. Also, longer courses of treatments can have a damaging effect to the body’s immune system and may also cause damage to the digestive tract. Nonetheless, as mentioned earlier, there are ways to overcome this issue by using anti-inflammatory adjuvants. Vaccines can be used as a preventative measure against acquiring infectious diseases and is often looked to as a course of action for eradicating pneumococcal diseases – amongst many other types.

Glycoconjugate Vaccine

Glycoconjugate vaccines are carbohydrate antigens chemically linked to a protein. The covalent linkage allows for bacterial surface carbohydrates to evoke a long-lasting T cell memory response, which is accompanied by polysaccharide-specific B cell differentiation into plasma cells. Should the immune system come across the pathogen again, plasma cells will proliferate and release mature antibodies that can eliminate the disease in the immunised individual (Berti and Adamo, 2018). The aim of the study carried out by Kaplonek et al. (2018), was to improve on “the already licensed vaccine Prevnar13 (13-valent) and Synflorix (10-valent) by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines and to create a pentavalent semisynthetic glycoconjugate vaccine (sPCV5)” (Kaplonek et al., 2018). Synflorix is a pneumococcal vaccine that contains 10 of the common most serotypes of

S. pneumoniae

, whereas Prevnar 13 is also a pneumococcal vaccine but has 13 of the most common serotypes of

S. pneumoniae

and can be used on all ages. In the study, the oligosaccharide antigens were conjugated to CRM197 (a non-toxic variant of diphtheria toxin isolated from

Corynebacterium diphtheriae

). There were eleven groups of 10- to 12-week old female New Zealand White (NZW) rabbits for the immunisation experiment, with about 3-6 rabbits per group. The control groups were as follows: group one had a combination of all five synthetic glycoconjugates (sPCV5), group two had a combination of Prevnar13 ( serotype antigens ST2 and ST8) and Synfloxrix (serotype antigens ST2, ST3 and ST8) with non-vaccine serotypes, group three had Prevnar13 only, group four had Synflorix only and group five had a placebo (CRM197 and 125µg of aluminium). Each rabbit received four doses of vaccine in a final volume of 0.5mL. On day 0, the rabbits were immunised and boosted with the same vaccine on days 14, 28 and 119. The rabbits were bled at days 0, 14, 21, 35, 119 and 126 for their sera. These antibody responses were then analysed using ELISA and glycan microarray.

The results obtained from the ELISA and glycan microarray showed that the rabbits that had been immunised with the glycoconjugates induced strong anti-glycan antibody titres. Additionally, the co-formulated vaccines (Prevnar and Synflorix) elicited strong immune responses but were weaker than those observed with immunisation from only one serotype – this is due to a weaker serotype-specific antibody response. sPCV5 elicited a stronger polysaccharide-specific antibody response compared to Prevnar and Synflorix (the marketed vaccines). Overall, the serum dilutions found, that are necessary for killing 50% of the bacteria, are considered “biologically significant” for industry standard of a successful vaccine.

The 23-valent polysaccharide is not effective in infants and therefore, having a pentavalent vaccine that is able to be used on all age groups is beneficial, especially with the added serotypes covered to broaden the immune capabilities. Co-formulating vaccines is not as efficacious because it produces a weakened immune response compared to those with a single vaccine. This could possibly be due to the increased amount of serotypes involved, which means the immune system would have to deal with all of those serotypes thus, causing a slower immune response. This could also be said for adding serotypes to the pentavalent vaccine if they wanted to increase the amount in the future to cover more serotypes. Although this study had efficacious results, it can be argued that the results may not be applicable as the test subjects were rabbits. Rabbits may have a different immune response than humans and the vaccines may work better or worse in the rabbits compared with the humans – only when the tests are carried out on humans can it be fully applicable. Moreover, the paper does not appear to have any thorough statistical analysis to compare results from each control group in the study, therefore reducing the validity of the results as comparison between groups is hard to be done without statistical analysis.

Whole Cell Vaccine

The next vaccine to be discussed, conducted by Campo et al. (2019), uses the whole bacterium of

Streptococcus pneumoniae

in the vaccine, referred to as whole cell vaccination (WCVs). As the name suggests, whole cell vaccines use the entirety of the cell to produce a vaccine and thus an immune response resulting in immunity. The aim of this study is to produce a vaccine that is able to be used in developing countries where it may be too expensive to get vaccinated. Using a whole cell vaccine should be more economical for those who wish to get vaccinated. 42 healthy U.S adults aged 18-40 participated, using a randomised double-blind trial where four cohorts were compared (the pharmacists who were injecting the vaccine or placebo were not blinded). The participants had no sign of chronic health conditions or history of pneumococcal disease or infection. Of the four, one cohort received a placebo of saline injections, the second cohort received 100µg of WCV, the third 300µg of WCV and the fourth received 600µg of WCV, all of which were absorbed to aluminium hydroxide adjuvants. Every 28 days, each participant was given three injections and their serum samples were taken pre-vaccination. At 28, 56 and 84 days, their serums were taken, following the first injection to assay for immunoglobulin G (IgG) responses (day 0) – as referred to in figure 2. The samples were then analysed with a panproteome microarray which included more than 2100 probes. The purpose of using the panproteome microarray is that it provides information on responses to proteins encoded by the core and accessory genome as well as variants of diverse core loci (DCL), which corresponds to genes that can be identified in almost all isolates based on their location in the chromosome. In

S. pneumoniae

, there are four loci that encodes for important pneumococcal surface proteins.

Flow Chart Depicting the Sample Collection of Data

Figure 2.

Flow chart taken from Campo et al., (2018) depicting the sample collection of data for the trial. 12 individuals constituted the placebo trial with the first sample of serum being taken on day 0 before vaccine dose. 10 individuals constituted the 100µg, the 300µg and the 600µg cohorts being vaccinated with the WCV, with each of them having their serum levels taken on day 0 before the vaccine dose. Each individual’s in the cohorts had differing time points.

130 samples were studied from 35 of the 42 trial participants, for 27 individuals, all of the four timepoints were analysed. At least the initial and final samples were available for two further people and at least one timepoint was analysed for six more people. Of these individuals, 35 of the them were the placebo, 32 from cohort 1 (100μg dose), 29 from cohort 2 (300μg dose) and 34 from cohort 3 (600μg dose). For the samples, there were no biological repeats done as they had already done a pilot study which showed that there were reproducible differences between the individuals. A Kruskal-Wallis test was carried out that showed no significant difference in individuals’ median IgG binding to S. pneumoniae proteins between cohorts before vaccination. This indicates that the WCV did not raise IgG binding to a high proportion of

S. pneumoniae

proteins across all of the cohorts. However, an ANOVA test was carried out for the change from day 0 to day 84 and a significant difference between the cohorts was found. Therefore, showing that the WCV did have an effect on the vaccinated cohorts when considering per-probe, and not per-individual data. The difference in results showed could be as a result of individual differences in the subsets.

The trial used differing concentrations of the WCV which is good as it enables a comparison to be made between the different concentrations, and allows for the right dosage of drug to be formulated for public use. The idea of using a whole cell vaccine has great ethical implications as it is said to be more cost-effective and enables those from poor incomes such as third world countries to be able to have access to the vaccine. The trials were carried out on humans which means that the study is more applicable as the results from the trials will have more validity as the immune responses from the trials are human responses and thus have real world relatability. The results from this trial could be in-part due to anamnestic responses received from previously recognised antigens, which may have caused the individual’s immune response to be limited to the WCV-induced IgG response. In addition, not all individuals in each cohort had their serum collected and tested for the four timepoints of day 0, day 28, day 56 and day 84. This reduces the reliability of the study as not only were there no biological repeats, but the results were lacking in a large enough sample size for each cohort to make the results more valid. In addition, the overall sample size was lacking as there were not enough participants to see whether there would be an effect of the vaccine. This is because there could be confounding variables such as whether the participants were male or female (not stated in the study) and participants were all from America so things like diet and ethnic background also need to be taken into account.

Conclusion

In conclusion, both vaccines found efficacy in their trials, however the whole cell vaccine is more applicable as it was done on humans and their immune response, as opposed to the glycoconjugate vaccine trial which was carried out on rabbits. On the other hand, it can be argued that the data collected for the trial was inadequate to make a fair comparison as not all of the participants’ serum was tested for all four of the timepoints (every 28 days). Despite that, the vaccine has real world application. For example, the vaccine is said to be more economical and therefore can hopefully be used in countries that are impoverished, and for those individuals who are unable to afford the more expensive vaccines. This is beneficial as it means that more people should be able to get vaccinated and the risk of acquiring the disease should become lower. This is also beneficial for issues such as antibiotic resistance, as herd immunity will mean that less individuals will be susceptible to getting the disease as the immune system would be primed to fight off the infection if/or when it enters the body. Therefore, antibiotic resistance to these bacteria would be of less importance as the majority of individuals would be immune, providing that the most prevalent serotypes are vaccinated against e.g. by using a similar technique to that of Kaplonek et al. (2018). Important questions to be asked about the whole cell vaccine is whether it would require more than one dose – if so, would it still be the cheaper option for those from poorer backgrounds?

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Introduction

The global era is getting more competitive and dynamic. For the proper development of health and social care, learners should be acquired skilled knowledge about caring as well as the proper understanding of personal development. There are many departments in health and social care; they are delivers health care facilities in various different of organizations by seeing the idea of care that provides the rights of the patient. The care training provides the great support to the patient by providing their safety and make sure they are safe in all phases of the care organization and service. To cope up with the present business environment every persons should prove themselves as more personnel and professional.

Task-1

1.1: Personal values and principles agree or conflict with the principles of support for working in health and social care.

Personal values develop from situations with the external world and can change over time. Personal values developed early in life may be resistant to change. Ex: culture,

religion

, and political party. Values exist, whether one recognize him or not. Life can be much easier when one acknowledges ones values – and when one make plans and decisions that honor him. Personal values influence personal character through internally. Basically, a person’s values and principles depend on his or her personal character and so on.

In health and social care settings there are principles which run the practice of healthcare workers to confirm that quality care is delivered for service users. They are 5 principles in health and social care practices:

• Confidentiality
• Communications
• Promoting antidiscrimination practice
• Rights
• Acknowledging individuals believe and identities.

1.2: The way of personal culture and experience influence my work as a care practitioner.

Personal Culture is defined as the patterns of ideas, customs and behaviors shared by particular persons. Personal Culture may contain all or a subset of the following features: –

• Civilization, Language, Religion & spiritual beliefs, Masculinity socio-economic class.

To work in an area of health and social care especially as a practitioner greatly depends on personal beliefs and mind set up activities. Personal Culture and experience are influence by several ways, like:

• 
  Positivity:
  
  positivity greatly influenced a personal mental behavior. If he/she positively treat toward something that will gives him a fruitful result.
• 
  Helpful mentality:
  
  in every spare of life there must be needed a helpful mind. The actions and the work of practitioner haven’t any time requirement.so it’s very crucial.
• 
  Smooth behavior:
  
  the behavior of practitioner should be firm and smooth.
• 
  Ethically strong:
  
  The factors that are compulsory to be ethical have the great impact on the profession of practitioner.
• 
  Quality of work:
  
  The practitioner should have able to qualifying for conducting the profession.it is expressed on the legal social welfare and the well-being of the society.

1.3: New development and changes to personal values can change work practices in health and social care setting.

The definite needs and wants of the immediate of health and social care sector greatly depends on the positive attitude of works. The availability of actual work makes more well-organized values of working in health and social sector. The workers works mentality drives the actions of health and social sector. The worker should complete their activities which depend upon what customers prepare and search. The service which given by the provider of health and social sector certify the ability of the emerging level of the precision. As we know the development of health and social sector is greatly improving day by day. The emergence of work gets aspiration by the changes values. The personal values significantly changing with in an eye stream by the growth of the health and social sector.

Task 2

2.1: SWOT analysis showing the key strengths, skills, ability and learning style relation to job role, weakness, opportunities and threats.

SWOT analysis is the act of a person’s internal and external criteria. Strengths and weakness is internal phenomenon and opportunities and threats are external phenomenon. My SWOT about the regarding assignment is given below:

• 
  My strengths:
  
  internal efforts which gives me more confident to dine this job:

• Greater work support.
• Building interpersonal communication network.
• Positive strategies taken by me.
• Maintain specific location and additional funding.

• 
  My weakness:
  

• High costs are prime obstacle to continue my work.
• The obsolete data.
• The workforce diversity also created barriers.
• Insufficient record preserves system.

• 
  My opportunities:
  
  My chances of work cause so many effects on externally. These are written below-

• Services provided by others.
• Faithfulness of well-wishers.
• Greater sources of external data.

• 
  Threats to me :
  

• Service provide by competitors.
• The service provided by practitioner in several campaign
• Nervousness in facing viva

2.2: Divide a plan over a period week of personal development goals

The action for the plan for a practitioner is a total of a mental work. A plan over period weeks of personal development goals are as follows:

• 
  Making an weakened plan or schedule:
  
  At the beginning of the weakened personal development goals the practitioner have to make a plan or schedule that will provides the overall blue print for the personal developmental goals.
• 
  Collection of relating information:
  
  For everything we want to collect some related information which must be logical and objective oriented.
• 
  Identify the weakness:
  
  To find out where the lacking’s of practitioner
• 
  Correct the weakness:
  
  After identifying the weakness practitioner have to correct the weakness and make a good use of it.
• 
  Controls of errors:
  
  Finally the practitioner controls the errors by using effective leadership.

2.3: Monitor and revise the plan in accordance with my role as a care practitioner.

A practitioner has to monitor overall plan to make his goal successes. He should through focus on the adapted plan, also follow the rules, regulation and ethics of the proposed plan. A practitioner has to be honest in his duty.

As a practitioner I have to do arrange the duty of my work. The rules should be monitored as well as monitored by me. As a practitioner the following proposed plan is monitor and revise by me:

• I should have the great skills of presentation as a practitioner.
• I encourage teams to work harmoniously
• I prepare my daily activities as regular basis.
• I maintain my responsibilities in time.
• I am able to provide effective service properly.
• Positive mentality is the key aspects of my work environment.

This personal behavior helps me to proper monitor and accomplishes my plan easily.

2.4: discussion of how my key skills, ability and learning style fits in with my role and evaluate the extent to which my weakness hinder my development and evaluate the role of my development plan in helping me achieve professional competency in accordance with your role as a care practitioner.

The academic knowledge and skills should be easily taken by me if I were a well care practitioner. I have to take proper decision to solve my problem efficiently. The success of all care practitioner is highly depends on the working capability and the efficiency. One should be dedicated himself on service accurately.

I should be authentic in case of responsibility my work. An appropriate job plan also should be taken by me. All types of barriers of work solved by me with very logically. Moreover, my positive attitude toward work helps me to gain my objectives. Therefore, I should keep in mind that I am working as a care practitioner who is the best sympathizer of the environments.

Task 3

3.1: explanation with specific examples what steps a nurse would take to ensure that he/she does not cross professional boundaries.

Professional boundaries are the spaces between the nurse’s power and the client’s vulnerability. In relationships with any level of well-being and closeness, boundaries are needed to separate individuals applicably.

Professional boundaries support key elements of the nurse practitioner-Patient relationship:

• trust, compassion, mutual respect, and empathy

# Steps should be taken by


a


nurse

• 
  
  Education starts at the entry into practice level in nursing programs.
• Continued in higher nursing education programs.
• 
  
  Policies of sexual delinquency and boundary defilements should be updated and made part of the staff’s annual education.
• 
  
  Should be informed about their own state’s nurse practice act
• Be secret in case of sharing personal matter.
• Speak relevant and logical topics
• Should be emphasize on proper value of time

References: National Council of State Boards of Nursing (NCSBN)

3.2: Discussion of promoting and supporting the rights of the service user at work and evaluate the outcome.

In health and social care center the service user must consume the proper rights. Proper service makes a user more delight. There has a series of rights which should provide for a service user-

• 
  Privacy of the user:
  
  The privacy of the user should be ensured all time. The promoting and supporting the rights of the service user mainly depend on the proper privacy maintain of user.
• 
  Needs of the user:
  
  the service provider must be identified the actual needs of the user and finally he satisfy his needs by providing greater service.
• 
  Security of user:
  
  The user should be maintained his safety and security.
• 
  Personal satisfaction and independence:
  
  By providing superior service the provider raise the satisfaction level of the user and independence also increases through personal choice.
• 
  Value of choice
  
  : The choice of service user should be kept in mind if the service user.

3.3: The possible conflicts that may arise and critically discuss methods of conflict resolution where professional boundaries have been crossed

In an organization conflict is a common matter. It may be arise for a lot of reasons. Such as-

• Conflict among the channel members
• Conflict due to work roles
• Conflict through one department to another department
• Boss with subordinates
• miscommunication with senior and junior employees

The upper miss adjustment can resolve by the following way-

• Proper communication web should be established with channels member and subordinates.
• Discussion in problematic area
• Ensure the proper understanding with the employees
• Maintaining good relationship eth other department
• Cooperating

Task 4

4.1: My own personal contribution to minimizing barriers to effective network

I am able to produce, monitor and revise plans for personal improvement in developing the skills and abilities required of a health and social care practitioner. I have to take some special contribution to minimizing barriers to effective network. These are below-

1. Study my Action Plans.
2. Dedication to achieve.
3. I just working there as a teammate.
4. I Identify barriers from term in achieving the goal.
5. Create our targets to ensure development in future.
6. Make a favorable environment.

Finally I assigned as myself with the every working step including proper communication and management and control as well.

4.2: Explanation of the limit of care role and its impact on my exercise of power in times of emergencies.

Every human being has limitation on their working environment. I myself also faced lots of problem in care role that impact on my exercise of power in times of emergencies. The common limitations are writing down:

• 
  The limit of care role
  

• Faced unfavorable work environment.
• Poor work routine hampered my task.
• Nature of the work.
• Lack of positive attitudes from supervisor.
• Defective equipment.

• 
  Impact on my power in emergencies:
  
  we know that power is the sign of satisfaction. But when some limitation occurs instantly with me my power being hampered. The negative impact of regarding my power decreases are below-

• Suffered from mental pressure.
• Decreases physical fitness.
• Negative attitude toward workforce environment.
• Boringness.
• Negative practices of ethics.

4.3: My contribution to minimizing barriers to effective teamwork

Every worker should be positive minded to perform his or her assigned works. The mentality also should be positive to conduct communication with others. But in there are a lot of barriers that hampers to do effective team work. By using my patience and efficiency I apply myself fully to bring an effective team combination.

Always I try to provide my best effort in my job. By seeing this majority of my colleagues are motivated and they also devoted their all experience and knowledge to the work. My innovative ideas help all to work combined as a team.

Moreover, I give enough encourage to my teammates during the job period.

4.4: Ideas to improve personal contribution to team work

A positive idea can change everything as well as it can be a key for improving personal contribution to team work. My ideas are given below:

• Exchanging information
• Friendship
• Effective cooperation
• Discussion with teammates
• Be honest and ethical mentality
• Ensure of chain of command rules

Conclusion

The work competence and perfection of walks depends of stability of work and devotion. For actual health and social care service, there must be needed to manage, maintain, and establish that require completing total action in terms of health and social care service. The beauty of real life can be found in social and health care service. That makes an individual to develop strong personality and perfection.