CRITICAL REVIEW OF THE CASE STUDY ON ACUTE PHARYNGITIS INTRODUCTION
Acute pharyngitis is the sudden inflammation of the pharynx which may due to viral(mostly) or bacterial(less likely) infection. This infection is in the upper respiratory tract and is always associated with a rapid onset of a sore throat, pain and difficulty in swallowing, enlarged and tender lymph nodes in the neck, fever and enlargement of the tonsils. It has been known to be one of the 5 most common reasons patients visit a primary care physicians in UK.
INFECTIOUS AGENTS OF ACUTE PHARYNGITIS The symptoms described in the case study are appear to describe acute pharyngitis, which is the painful inflammation of the pharynx and surrounding lymphoid tissue, this is because the boys symptoms seem relatively severe and long lasting (36 h). Most acute infections (40%-80%) are cause by viruses. Other causes are bacterial, fungal (although not generally noted as a routinely causative agent) and irritants such as chemicals and pollutants. The following shows the range of different infectious agents that are causatives of acute pharyngitis; Bacteria Arcanobacterium haemolyticum- a much less common cause of pharyngitis seen in predominantly in teenagers and young adults. Corynebacterium diphtheria - rarely seen in the United States but it should be considered with an appropriate travel history to Africa, Asia/South Pacific, South America, Haiti, Albania, and the former Soviet Republic countries. Mycoplasma pneumonia - a cause of pharyngitis in teenagers and young adults. Neisseria gonorrhoeae - considered if suspecting child abuse. Streptococci, groups C and G - a cause of self-limited pharyngitis in young adults. Streptococcus pyogenes [group A strep (GAS)] - this is the most common bacterial cause of pharyngitis. Viruses Adenovirus - causes pharyngitis, conjunctivitis, and acute respiratory disease. Epstein-Barr virus - causes infectious mononucleosis, which is seen predominantly in the 15–25 year-old age group and frequently starts with pharyngitis. Other respiratory viruses - rhinovirus, coronavirus, parainfluenza virus, influenza A and B viruses, coxsackievirus, cytomegalovirus. Generally, during diagnostics in determining the causative agent of the infection, GAS being the most common cause is the expected tested for, along with groups being tested for if needs be. The two lab tests which will identify GAS are firstly the rapid strep test which detects GAS by detecting a carbohydrate (N-acetylglucosamin) which is unique to GAS. Secondly a throat culture is taken which will allow the organism to grow on an incubated blood agar plate. The rapid strep test has 95-100% specificity, however its sensitivity is not so high. It takes between 5- 10 minutes for a strep test to be completed, as compared to 48h for a culture to be completed. So where the strep test proves positive there is no need for further tests due its high specificity, however where the result is negative, further tests need to be taken due to its low sensitivity. The sample from the negative test is cultured on a blood agar plate, this incubated over night at 35-17°C 18-24h and for a further 24h. Where there is Streptococcus pyogenes present colonies will be seen. The type of hemolysis Streptococcus pyogenes presents, α, β or γ is can be determined by observing agar plates after the colony growth time has passed. The characteristics of α-hemolysis is the green colouration of the agar immediately surrounding the colony due to incomplete destruction of red blood cells, β cells have a clear area directly around them where complete lysis of red blood cells has occurred, γ hemolysis is where no hemolysis has occurred, so red blood cells remain and there is no change in the area surrounding the colonies. As Group A Strep is β hemolytic, so where the signs are shown, there is a diagnosis of it being the cause of acute pharyngitis. Where there is no sign of any of these sub-types, further testing is employed, a catalase test was used. PATHOGENESIS Introduction Group A Streptococcus (GAS) is a pathogen that causes acute bacterial pharyngitis in human and it can be spread through aerosols among individuals, or by eating contaminated food (Bisno et al., 2003) . The site of infection of GAS is in the pharyngeal mucosa, where it causes pharyngitis (Carapetis et al., 2005). The pathogen enters the body through the ciliated epithelium in the nose, which results in edema and hyperemia of the nasal mucous membranes. This condition induces high secretory activity of the mucous glands thus causing disruptive symptoms (Red Book, 2006). GAS pharyngitis pathogenesis is divided into three stages as follows: adherence to the pharyngeal epithelium, collection of nutrients needed for proliferation and avoidance of the host immune response (Bisno et al., 2003). Survival of GAS in blood GAS is open to the elements of human plasma at the points of inflammation where it causes superficial infections as a result of vascular seepage, which is facilitated by the action of M protein interacting with fibrinogen and the b2-integrin adhesion molecule on the neutrophils surface. This consequently leads to an inflammatory cascade which involves the discharge of heparin-binding protein and induces vascular seepage (Herwald et al., 2004). Shock is underlined by the pathophysiological mechanism of vascular permeability, cross linking of the M protein and fibrinogen with b2-integrin might be instrumental in what causes or leads to the development of streptococcal toxic shock syndrome. Plasma is a rich medium that aids bacterial growth. It also contains immune system components that GAS must elude to survive, including opsonizing antibodies and complement. The normal function of hosts defences is disrupted by the several interactions between plasma proteins and GAS proteins (Walker et al., 2005). Also, GAS expresses surface proteins that have a high affinity for several human plasma proteins such as albumin, fibrinogen, a2-macroglobulin, IgG and plasminogen (McArthur et al., 2006) which suggests that the pathogen has evolved mechanisms to capture and to use host proteins for enhanced survival in vivo. Epithelial cell adherence Recent discovery reveals that GAS pili-like cell surface structures are key factors in pharyngeal epithelial cell adherence and biofilm formation. Pili are programmed by genes found in the fibronectin, collagen-binding, T-antigen, FCT, gene region and are composed of the main pilus subunit (spy0128 in the serotype M1 strain SF370) and two ancillary proteins (Mora, et al., 2005). The principal pilus subunit tallies with the T antigen of the Lancefield T serotypes, which is one of the major GAS classification scheme. Assembly of GAS pili depends on a sortase encoded by genes in the FCT region and in M3 strains, on a signal peptidase encoded upstream of the T antigen (Zahner, et al., 2007). Other GAS proteins are also involved in epithelial cell adherence. For example, the serotype M3 GAS emergence has been connected to the accumulation of a bacteriophage-encoded phospholipase A2 (SlaA) whose mechanism of action appears to involve penetrating host cells hence allowing adherence and binding to host epithelium. The The ability of A ΔslaA strain to cause pharyngitis in the cynomolgus macaque is impaired thus providing a significant support for the key role of SlaA in GAS pharyngeal pathogenesis (Sitkiewicz et al., 2006). Intracellular invasion GAS is mainly an extracellular pathogen, the past decade data have shown that the organism may invade and persist within epithelial cells (Wang et al., 2006). The exact role of this event in GAS pathogenesis is yet unclear. Many of the proteins that are involved in GAS epithelial cell invasion also take part in adherence, this includes FnBPs, M protein and streptocococcal collagen-like protein. This protein is located on the cell wall and it is required for invasive infection. T cells when exposed to the M protein cross-react with similar epitopes on human cardiac myosin and laminin, leading to the pathogenesis of rheumatic heart disease, (Guilherme, etal, 2006). The signalling pathways mediating GAS invasion begin with bacterial binding to eukaryotic cell surface integrins, which results in actin cytoskeletal rearrangement and GAS internalization (Purushothaman et al., 2003). The binding of GAS with integrin-bound Fn leads to upregulation of growth factor β1, which in turn triggers cell surface expression of 5 integrin and Fn, this consequently makes the cells better targets for streptococcal binding (Wang et al., 2006). Immune system avoidance For GAS to cause pharyngitis and start the colonization of the oropharynx, the host innate immune response must be overcome for a periods of time (Ashbaugh et al., 2000; Virtaneva et al., 2005). GAS has modified several mechanisms for escaping the host innate immune response as observed in M protein and hyaluronic acid capsule (Cunningham, 2000). There are other immune proteins which add to GAS pharyngitis such as streptococcal inhibitor of complement (Sic), and secreted DNases . ScpA is a cell surface serine protease that specifically cleaves C5a, thereby decreasing C5apolymorphonuclear (PMN) leucocyte binding and subsequent PMN recruitment (Brown et al., 2005). Sic is a protein secreted to produce protean effects on host immunity at the back of pharynx. In the course of pharyngitis, the gene that encodes Sic is quickly upregulated (Virtaneva et al., 2005). In addition to preventing the complement membrane attack complex, Sic gets involved with pharyngeal immune defence function such as lysozyme, b-defensins, and the cathelicidin LL-37. Due to the interaction of Sic with proteins of the immune system, the bactericidal activity against GAS is strongly reduced.
EPIDEMIOLOGYPharyngitis mainly affects young children with much greater frequency compared to the adult population. It is estimated that 15-30% of Pharyngitis cases among children in the cooler months are due to GAS. Only 10% of adult cases of Pharyngitis are due to GAS. The peak occurrence of bacterial and viral Pharyngitis occurs in the school-aged child aged 4-7 years. Pharyngitis, especially GAS infection, is rare in children younger than 3 years. Mycoplasma pneumoniae, Chlamydia pneumoniae and Arcanobacterium haemolyticus are other bacterial that causes Pharyngitis but these are rare. Antibiotics covering atypical pathogens should not routinely be used to treat Pharyngitis (Twefik T. L., 2005) If a patient is presented with rhinorrhea, cough and hoarseness, doctors will usually test that patient for Group A Streptococcus. It has been shown that it is almost impossible to differentiate between Group A Streptococcus and Pharyngitis caused by viral infection. Rhinovirus and adenovirus are the most common etiological agents and each account for 6-20% of all cases of Pharyngitis, both viral and non-viral. A doctor may order a throat culture. Usually temperature checks are performed along with examinations of the throat, ears, nose, neck and lungs. Pharyngitis is common worldwide and is usually a disorder that affects children. Pharyngitis results in over 15 million hospital visits per year in the United State alone. Acute pharyngitis is the most common cause of a sore throat and is diagnosed in more than 1.9 million people a year in the United States (Marx, John 2010). Pharyngitis is caused by numerous microorganisms. However, 90% of sore throats in adults and 60–75% of in children are caused by viruses. Streptococcus pyogene (b-hemolytic Group A Streptococcus) is the most common bacterial cause of acute pharyngitis (Chamberlain N. R., 2009). Bacterial epidemiology is dominated by beta-haemolytic streptococci group A but other streptococcal groups notably group C and have been incriminated. Other responsible bacteria like Haemophilus spp., Staphylococcus spp. and Corynebacterium spp., are extremely rare but most probable. Mycoplasma pneumoniae and perhaps Chlamydia pneumoniae are probably found more frequently (Gehanno P. et al, 1992). Although GABHS Pharyngitis is usually a self-limited entity, on average, a single episode in a child results in 1.9 days absence from school and a parent missing 1.8 days from work to care for the child (Pfoh E. et al., 2008). Children with GABHS Pharyngitis experience symptoms for an average of 4.5 days.
CLINICAL ASPECT Acute pharyngitis presents with the symptoms; fever, sore throat, headache, tonsilar exudates, red posterior pharynx and many swollen and tender cervical lymph nodes (Harari et al, 2009; Fox et al, 2006; Bisno et al, 2002). The 6 year old boy has these symptoms thus, indicating a sore throat infection. The infectious agent needs to be determined from his clinical history, epidemiological features and subsequent confirmation with appropriate laboratory tests.
The 6 year old boy is also of school age or he maybe attending a day care which are places where acute pharyngitis can be contacted easily when in close proximity with the airborne droplets of a person infected. He may also have contacted it from a family member who is infected as according to Bisno et al, (2002), there is a 40% chance of contacting acute pharyngitis from an infected member of the family.
From the boys’ history, he had been in good health prior to the symptoms in late September and is thus, immunocompetent and the disease therefore had a sudden onset. According to Carey, Schuster and McGowan (2008), there are two major causes of pharyngitis in an immunocompetent patient:
· Viral and,
· Bacteria.
This thus rules out fungi as the infectious agent in this patient.
According to Fox et al (2006), sore throats tend to present in patients in autumn and winter period. As the patient presented with his symptoms in late September which is part of the autumn period, this further suggests that he may have sore throat. Fox et al (2006) further stated that group A β-hemolytic streptococcus (GABHS) is the most important causative agent of sore throat and that this bacteria is responsible for approximately one-third of sore throats in children of 5 to 15 years. It is therefore highly likely that he has GABHS as his age falls within this range.
A clinical diagnosis of acute sore throat resulting from GABHS as according to Bisno et al, (2002) can be made using the ‘sore throat decision rule’. This involves looking out for 4 symptoms. They are:
throat exudates,
enlarged sub-mandibular glands,
fever, and
absence of runny nose and cough.
If;
0 or 1 of the above sign/symptom is present in the patient then, GABHS is unlikely.
2 of the above signs/symptoms are present in the patient then, diagnosis is uncertain and further laboratory testing should be considered.
3 or 4 of the above signs/symptoms are present in the patient then, GABHS is likely.
When this rule is used it identifies most patients needing treatment and thus decreases antibiotic use for the treatment of sore throat by approximately 80% (Bisno et al, 2002).
The patient has 4 of the above signs/symptoms thus GABHS is likely.
The above is further supported by Carey, Schuster and McGowan (2008) as they stated that clinical clues to ascertain infection by Streptococcus Pyogenes are;
· the age of the patient as Strep throat usually occurs in young children of school-age
· absence of a cold symptoms and runny nose indicating a probable strep throat infection as opposed to a viral on, and
· Presence of classic signs and also symptoms of S. pyogenes pharyngitis which are; tonsillar exudates, fever, cervical lymphadenopathy with absence of cough.
Chamberlain (2010) stated that clinical and epidemiological factors must be looked at for appropriate diagnosis. Table 1 below shows the clinical and epidemiological factors to be considered as they are suggest bacterial causative agent if present in a patient. Almost all these factors are signs and symptoms as well as epidemiological factors in the 6 year old boy and thus, suggest bacterial etiology i.e. S pyogenes as the infectious agent.
TABLE 1: Clinical and Epidemiologic Findings Useful in the Diagnosis of Pharyngitis Epidemiologic findings suggestive of Streptococcus pyogenes as the etiologic agent
Patient aged 5–15 years
Presentation in winter or early spring
History of exposure
Sudden onset of signs and symptoms
Clinical findings suggestive of Streptococcus pyogenes as the etiologic agent
Sore throat
Fever
Headache
Nausea, vomiting, and abdominal pain
Inflammation of pharynx and tonsils
Patchy discrete exudate
Tender, enlarged anterior cervical nodes
Features suggestive of a virus as the etiologic agent
Conjunctivitis
Coryza
Cough
Diarrhea
Note: These findings, either individually or collectively, cannot definitively predict the presence of S pyogenes pharyngitis. They can identify persons with a high probability of being diagnosed with S pyogenes pharyngitis (and for whom throat culture or rapid antigen detection testing is indicated) or a low probability of S pyogenes pharyngitis (neither culture nor rapid antigen detection testing is necessary).
When commenting on epidemiological features, Bisno et al (2002) further contended that the when age of a patient falls between 5-15 years, no child abuse or travel, GABHS should be highly suspected as the causative agent. The patient fits this description and it can thus be said that he has acute pharyngitis caused by GABHS.
According to Chamberlain (2010), any delay in treating S pyogenes pharyngitis over 9 days after symptoms have begun makes the patient to be at a risk of developing rheumatic fever and also suppurative complications. Thus, strategies must be used to appropriately diagnose the infectious agent causing acute pharyngitis as they will require antimicrobial therapy and hence unnecessary treatment of patients who are diagnosed with acute pharyngitis of viral origin is avoided (Chamberlain, 2010). Two methods are used for this diagnosis: 1. Rapid strep test and, 2. Throat culture (Kim, 2009)
1. Rapid strep test. A swab from both tonsils and posterior pharyngeal area from the patient is collected to test for by detecting group A–specific carbohydrate N-acetylglucosamine. Sensitivity of this test varies but the specificity is superb if compared to culture with a range of 95–100% generally (Kim, 2009; Bisno et al 2002). Thus, a positive antigen test indicates GAS and therefore, a throat culture confirmation is neither needed nor necessary. However, confirmation must be carried out with a throat culture if the antigen test is negative (Kim, 2009).
2. Throat culture. A swab is taken from the same places as is taken for the rapid antigen test. The specimen is grown on agar blood plates. If GABHS is the etiologic agents, there would be b-hemolytic colonies which are catalase-negative, are gram-positive cocci and also exhibit sensitivity to Bacitracin (Chamberlain, 2010). This test is more sensitive than the rapid antigen test. Though the rapid test is readily available in the Doctors’ office and takes 5 to 10 minutes to perform, the throat culture takes 48 hours to complete thus, leading to the use of the rapid antigen tests more often (Chamberlain, 2010).
It follows that, if the rapid antigen detection test is positive, the throat culture is not required and thus treatment should commence with antibiotics e.g. penicillin. However, if rapid antigen detection test result is negative, a throat culture needs to be carried out (Chamberlain, 2010; Kim, 2009).
THERAPIES
Patients with GAS pharyngitis, empirical treatment should be done immediately to prevent complications, to reduce the infection and transmissibility, and to induce clinical improvement of symptoms. Patients with a higher level of suspicion of GAS pharyngitis but delayedculture results can also be given empirical antibiotics. Alternatively antibiotics can be withheld until the culture is positive for S pyogenes. Delaying the treatment for GAS doesn't have any effect on rheumatic heart disease or the strain of S pyogenes. The latter will reduce the inappropriate antibiotic usage and control the antibiotic resistance.
Selecting antibiotic primarily depend on the way it is to be administered, its effect, cost and condition that is not limited the antibiotic. Penicillin V or amoxicillin is used for around ten days. Intramuscular penicillin G benzathine may be administreted in patients who are unable to complete the ten days period. Macrolides like erythromycin, azithromycin are alternatively used in penicillin allergic patients. Absence of penicillin-resistant GAS compels a cheaper alternative than latest antibiotics which are expensive. Penicillin is not able to prevent nasopharyngeal carriage in patients with frequent GAS pharyngitis . Amoxicillin/clavulanate or rifampin may be used in such patients. Antibiotics should not be used in patients with negative throat RADT/cultures.
Pharyngitis caused by anaerobic bacteria may respond to penicillins or clindamycin.Yersinia pharyngitis is treated with latest cephalosporin. Mycoplasma pharyngitis is treated by doxycycline or macrolides. Symptomatic oropharyngeal in immunodeficient patients are treated by acyclovir ten days. Amantadine or neuraminidase inhibitors are used to treat Influenza A pharyngitis if the patient is presented immediately after the start of symptoms. Antiretroviral therapy maybe used for HIV acute retroviral syndrome. Fluids, gargling with warm and salty water, nonsteroidal anti-inflammatory drugs and rest of voice are some symptomatic relief. Gargling with Chamomile, Blackberry, sage may also help.
CONCLUSION
The location of the pharynx makes it an easy target for infection entering via the nose and mouth by aerosols from an already infected person or by eating food contaminated with the etiological agent. Though viruses are the main infectious agents of the pharynx, bacterial agents also account for a lower percentage. Many features like epidemiological factors such as; the season of the year and age of the patient, clinical factors and usefulness together with the availability of treatment must also be taken into perspective for diagnostic purposes.
The 6 year old boys’ medical history indicated the absence of previous health problems thus, this was just an opportunistic bacterial infection. The patients’ age was considered, the season in which the disease occurred, the rapid onset of the disease, as well as the common diseases in children of his age group and they all were pointers suggesting acute pharyngitis. Though numerous diseases had very similar symptoms, the sore throat decision rule with defining signs/symptoms i.e. presence of throat exudates, enlarged sub-mandibular glands, fever, and absence of runny nose and cough are classic symptoms/signs of acute pharyngitis caused by group A β-hemolytic streptococcus. The infectious agent can further be confirmed using either a rapid strep test or throat culture or both.
GABHS usually left untreated can be good opportunity for complications to arise e.g. Kidney damage. Thus, it is highly advisable to treat all cases of GABHS related acute pharyngitis.
The treatment plan is most likely to include an analgesic for pain relief and oral Penicillin/its derivatives e.g. amoxicillin as the patient is still young. Amoxicillin is easily absorbed and is thus most likely to be prescribed for treatment of acute pharyngitis in comparison to other treatments. Misuse of antibiotics should also be taken into consideration so as to avoid resistance. GABHS vaccines are also being developed. An approach to this has been to put together small amino-terminal M-protein peptides in order to produce vaccines which are multivalent and would exhibit opsonic antibodies against GAS serotypes.
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Bisno, A. L., Gerber, M. A., Gwaltney, J. M. Jr., Kaplan, E. L. and Schwartz, R. H. (2002) 'Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis' Clinical infectious disease, 35(2), 113-25.
Boccazzi, A., Tonelli, P., and Ceruti, R. (2000). 'What's new in Streptococcal pharyngitis?'International Journal of Antimicrobial Agents, 16(3), 287-9.
Edwards, A.M., Manetti, A.G., Falugi, F., Zingaretti, C., Capo, S., Buccato, S., Bensi, G., Telford, J. L., Mar (2008) 'Scavenger receptor gp340 aggregates group A streptococci by binding pili.' Molecular Microbiology, 68(6), 1378-1394.
Gehanno, P., Portier, H. and Longuet, P. (1992) 'Current status on the epidemiology of acute pharyngitis and post-streptococcal syndromes.' La Revue du praticien, 42(3), 284-7.
Guilherme, L., Kalil, J. and Cunningham, M. (2006) 'Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease.' Autoimmunity, 39(1), 31-9.
Fox, J. W., Marcon, M. J. and Bonsu, B. K. (2006) ‘Diagnosis of Streptococcal Pharyngitis by detection of Streptococcus Pyogenes in posterior pharyngeal versus oral cavity Specimens.’ Journal of Clinical Microbiology, 2593-2594.
Harari, B. L., Darenberg, J., Nea,l S., Siljander, T., Strakova, L., Tanna, A., Ekelund, C. R. K., Koliou, M., Tassios, P.T., Van der Linden, M., Straut, M., Vuopio-Varkila, J., Bouvet, A., Efstratiou, A., Schalen, C., Henriques-Normark, B., the Strep-EURO study group and Jasir, A. (2009) ‘Clinical and microbiological characteristics of severe Streptococcus pyogenes Disease in Europe.’ Journal of clinical microbiology, 47(4), 1155–1165.
Herwald, H., Cramer, H., Morgein, M., Russell, W., Sollenberg, U., Norrby-Teglund, A., Flodgaard, H., Lindbom, L. and Bjorck, L. (2004) 'M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage.' Cell, 116, 367–379.
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Pfoh, E., Wessels, M. R., Goldmann, D. and Lee, G. M. (2008) 'Burden and economic cost of group A streptococcal pharyngitis.' Pediatrics, 121(2), 229-34.
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Walker, M. J. (2005) 'Is plasminogen deployed as a Streptococcus pyogenes virulence factor?' Trends Microbiology, (37)13, 308-313.
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CRITICAL REVIEW OF THE CASE STUDY ON ACUTE PHARYNGITIS INTRODUCTION
Acute pharyngitis is the sudden inflammation of the pharynx which may due to viral(mostly) or bacterial(less likely) infection. This infection is in the upper respiratory tract and is always associated with a rapid onset of a sore throat, pain and difficulty in swallowing, enlarged and tender lymph nodes in the neck, fever and enlargement of the tonsils. It has been known to be one of the 5 most common reasons patients visit a primary care physicians in UK.
INFECTIOUS AGENTS OF ACUTE PHARYNGITIS
The symptoms described in the case study are appear to describe acute pharyngitis, which is the painful inflammation of the pharynx and surrounding lymphoid tissue, this is because the boys symptoms seem relatively severe and long lasting (36 h). Most acute infections (40%-80%) are cause by viruses. Other causes are bacterial, fungal (although not generally noted as a routinely causative agent) and irritants such as chemicals and pollutants. The following shows the range of different infectious agents that are causatives of acute pharyngitis;
Bacteria
Arcanobacterium haemolyticum- a much less common cause of pharyngitis seen in predominantly in teenagers and young adults.
Corynebacterium diphtheria - rarely seen in the United States but it should be considered with an appropriate travel history to Africa, Asia/South Pacific, South America, Haiti, Albania, and the former Soviet Republic countries.
Mycoplasma pneumonia - a cause of pharyngitis in teenagers and young adults.
Neisseria gonorrhoeae - considered if suspecting child abuse.
Streptococci, groups C and G - a cause of self-limited pharyngitis in young adults.
Streptococcus pyogenes [group A strep (GAS)] - this is the most common bacterial cause of pharyngitis.
Viruses
Adenovirus - causes pharyngitis, conjunctivitis, and acute respiratory disease.
Epstein-Barr virus - causes infectious mononucleosis, which is seen predominantly in the 15–25 year-old age group and frequently starts with pharyngitis.
Other respiratory viruses - rhinovirus, coronavirus, parainfluenza virus, influenza A and B viruses, coxsackievirus, cytomegalovirus.
Generally, during diagnostics in determining the causative agent of the infection, GAS being the most common cause is the expected tested for, along with groups being tested for if needs be. The two lab tests which will identify GAS are firstly the rapid strep test which detects GAS by detecting a carbohydrate (N-acetylglucosamin) which is unique to GAS. Secondly a throat culture is taken which will allow the organism to grow on an incubated blood agar plate.
The rapid strep test has 95-100% specificity, however its sensitivity is not so high. It takes between 5- 10 minutes for a strep test to be completed, as compared to 48h for a culture to be completed. So where the strep test proves positive there is no need for further tests due its high specificity, however where the result is negative, further tests need to be taken due to its low sensitivity. The sample from the negative test is cultured on a blood agar plate, this incubated over night at 35-17°C 18-24h and for a further 24h. Where there is Streptococcus pyogenes present colonies will be seen. The type of hemolysis Streptococcus pyogenes presents, α, β or γ is can be determined by observing agar plates after the colony growth time has passed. The characteristics of α-hemolysis is the green colouration of the agar immediately surrounding the colony due to incomplete destruction of red blood cells, β cells have a clear area directly around them where complete lysis of red blood cells has occurred, γ hemolysis is where no hemolysis has occurred, so red blood cells remain and there is no change in the area surrounding the colonies. As Group A Strep is β hemolytic, so where the signs are shown, there is a diagnosis of it being the cause of acute pharyngitis. Where there is no sign of any of these sub-types, further testing is employed, a catalase test was used.
PATHOGENESIS
Introduction
Group A Streptococcus (GAS) is a pathogen that causes acute bacterial pharyngitis in human and it can be spread through aerosols among individuals, or by eating contaminated food (Bisno et al., 2003) . The site of infection of GAS is in the pharyngeal mucosa, where it causes pharyngitis (Carapetis et al., 2005). The pathogen enters the body through the ciliated epithelium in the nose, which results in edema and hyperemia of the nasal mucous membranes. This condition induces high secretory activity of the mucous glands thus causing disruptive symptoms (Red Book, 2006). GAS pharyngitis pathogenesis is divided into three stages as follows: adherence to the pharyngeal epithelium, collection of nutrients needed for proliferation and avoidance of the host immune response (Bisno et al., 2003).
Survival of GAS in blood
GAS is open to the elements of human plasma at the points of inflammation where it causes superficial infections as a result of vascular seepage, which is facilitated by the action of M protein interacting with fibrinogen and the b2-integrin adhesion molecule on the neutrophils surface. This consequently leads to an inflammatory cascade which involves the discharge of heparin-binding protein and induces vascular seepage (Herwald et al., 2004). Shock is underlined by the pathophysiological mechanism of vascular permeability, cross linking of the M protein and fibrinogen with b2-integrin might be instrumental in what causes or leads to the development of streptococcal toxic shock syndrome. Plasma is a rich medium that aids bacterial growth. It also contains immune system components that GAS must elude to survive, including opsonizing antibodies and complement. The normal function of hosts defences is disrupted by the several interactions between plasma proteins and GAS proteins (Walker et al., 2005). Also, GAS expresses surface proteins that have a high affinity for several human plasma proteins such as albumin, fibrinogen, a2-macroglobulin, IgG and plasminogen (McArthur et al., 2006) which suggests that the pathogen has evolved mechanisms to capture and to use host proteins for enhanced survival in vivo.
Epithelial cell adherence
Recent discovery reveals that GAS pili-like cell surface structures are key factors in pharyngeal epithelial cell adherence and biofilm formation. Pili are programmed by genes found in the fibronectin, collagen-binding, T-antigen, FCT, gene region and are composed of the main pilus subunit (spy0128 in the serotype M1 strain SF370) and two ancillary proteins (Mora, et al., 2005). The principal pilus subunit tallies with the T antigen of the Lancefield T serotypes, which is one of the major GAS classification scheme. Assembly of GAS pili depends on a sortase encoded by genes in the FCT region and in M3 strains, on a signal peptidase encoded upstream of the T antigen (Zahner, et al., 2007). Other GAS proteins are also involved in epithelial cell adherence. For example, the serotype M3 GAS emergence has been connected to the accumulation of a bacteriophage-encoded phospholipase A2 (SlaA) whose mechanism of action appears to involve penetrating host cells hence allowing adherence and binding to host epithelium. The The ability of A ΔslaA strain to cause pharyngitis in the cynomolgus macaque is impaired thus providing a significant support for the key role of SlaA in GAS pharyngeal pathogenesis (Sitkiewicz et al., 2006).
Intracellular invasion
GAS is mainly an extracellular pathogen, the past decade data have shown that the organism may invade and persist within epithelial cells (Wang et al., 2006). The exact role of this event in GAS pathogenesis is yet unclear. Many of the proteins that are involved in GAS epithelial cell invasion also take part in adherence, this includes FnBPs, M protein and streptocococcal collagen-like protein. This protein is located on the cell wall and it is required for invasive infection. T cells when exposed to the M protein cross-react with similar epitopes on human cardiac myosin and laminin, leading to the pathogenesis of rheumatic heart disease, (Guilherme, etal, 2006). The signalling pathways mediating GAS invasion begin with bacterial binding to eukaryotic cell surface integrins, which results in actin cytoskeletal rearrangement and GAS internalization (Purushothaman et al., 2003). The binding of GAS with integrin-bound Fn leads to upregulation of growth factor β1, which in turn triggers cell surface expression of 5 integrin and Fn, this consequently makes the cells better targets for streptococcal binding (Wang et al., 2006).
Immune system avoidance
For GAS to cause pharyngitis and start the colonization of the oropharynx, the host innate immune response must be overcome for a periods of time (Ashbaugh et al., 2000; Virtaneva et al., 2005). GAS has modified several mechanisms for escaping the host innate immune response as observed in M protein and hyaluronic acid capsule (Cunningham, 2000). There are other immune proteins which add to GAS pharyngitis such as streptococcal inhibitor of complement (Sic), and secreted DNases . ScpA is a cell surface serine protease that specifically cleaves C5a, thereby decreasing C5apolymorphonuclear (PMN) leucocyte binding and subsequent PMN recruitment (Brown et al., 2005). Sic is a protein secreted to produce protean effects on host immunity at the back of pharynx. In the course of pharyngitis, the gene that encodes Sic is quickly upregulated (Virtaneva et al., 2005). In addition to preventing the complement membrane attack complex, Sic gets involved with pharyngeal immune defence function such as lysozyme, b-defensins, and the cathelicidin LL-37. Due to the interaction of Sic with proteins of the immune system, the bactericidal activity against GAS is strongly reduced.
EPIDEMIOLOGYPharyngitis mainly affects young children with much greater frequency compared to the adult population. It is estimated that 15-30% of Pharyngitis cases among children in the cooler months are due to GAS. Only 10% of adult cases of Pharyngitis are due to GAS.
The peak occurrence of bacterial and viral Pharyngitis occurs in the school-aged child aged 4-7 years. Pharyngitis, especially GAS infection, is rare in children younger than 3 years. Mycoplasma pneumoniae, Chlamydia pneumoniae and Arcanobacterium haemolyticus are other bacterial that causes Pharyngitis but these are rare. Antibiotics covering atypical pathogens should not routinely be used to treat Pharyngitis (Twefik T. L., 2005)
If a patient is presented with rhinorrhea, cough and hoarseness, doctors will usually test that patient for Group A Streptococcus. It has been shown that it is almost impossible to differentiate between Group A Streptococcus and Pharyngitis caused by viral infection. Rhinovirus and adenovirus are the most common etiological agents and each account for 6-20% of all cases of Pharyngitis, both viral and non-viral. A doctor may order a throat culture. Usually temperature checks are performed along with examinations of the throat, ears, nose, neck and lungs. Pharyngitis is common worldwide and is usually a disorder that affects children. Pharyngitis results in over 15 million hospital visits per year in the United State alone. Acute pharyngitis is the most common cause of a sore throat and is diagnosed in more than 1.9 million people a year in the United States (Marx, John 2010).
Pharyngitis is caused by numerous microorganisms. However, 90% of sore throats in adults and 60–75% of in children are caused by viruses. Streptococcus pyogene (b-hemolytic Group A Streptococcus) is the most common bacterial cause of acute pharyngitis (Chamberlain N. R., 2009).
Bacterial epidemiology is dominated by beta-haemolytic streptococci group A but other streptococcal groups notably group C and have been incriminated. Other responsible bacteria like Haemophilus spp., Staphylococcus spp. and Corynebacterium spp., are extremely rare but most probable. Mycoplasma pneumoniae and perhaps Chlamydia pneumoniae are probably found more frequently (Gehanno P. et al, 1992). Although GABHS Pharyngitis is usually a self-limited entity, on average, a single episode in a child results in 1.9 days absence from school and a parent missing 1.8 days from work to care for the child (Pfoh E. et al., 2008). Children with GABHS Pharyngitis experience symptoms for an average of 4.5 days.
CLINICAL ASPECT
Acute pharyngitis presents with the symptoms; fever, sore throat, headache, tonsilar exudates, red posterior pharynx and many swollen and tender cervical lymph nodes (Harari et al, 2009; Fox et al, 2006; Bisno et al, 2002). The 6 year old boy has these symptoms thus, indicating a sore throat infection. The infectious agent needs to be determined from his clinical history, epidemiological features and subsequent confirmation with appropriate laboratory tests.
The 6 year old boy is also of school age or he maybe attending a day care which are places where acute pharyngitis can be contacted easily when in close proximity with the airborne droplets of a person infected. He may also have contacted it from a family member who is infected as according to Bisno et al, (2002), there is a 40% chance of contacting acute pharyngitis from an infected member of the family.
From the boys’ history, he had been in good health prior to the symptoms in late September and is thus, immunocompetent and the disease therefore had a sudden onset. According to Carey, Schuster and McGowan (2008), there are two major causes of pharyngitis in an immunocompetent patient:
· Viral and,
· Bacteria.
This thus rules out fungi as the infectious agent in this patient.
According to Fox et al (2006), sore throats tend to present in patients in autumn and winter period. As the patient presented with his symptoms in late September which is part of the autumn period, this further suggests that he may have sore throat. Fox et al (2006) further stated that group A β-hemolytic streptococcus (GABHS) is the most important causative agent of sore throat and that this bacteria is responsible for approximately one-third of sore throats in children of 5 to 15 years. It is therefore highly likely that he has GABHS as his age falls within this range.
A clinical diagnosis of acute sore throat resulting from GABHS as according to Bisno et al, (2002) can be made using the ‘sore throat decision rule’. This involves looking out for 4 symptoms. They are:
If;
When this rule is used it identifies most patients needing treatment and thus decreases antibiotic use for the treatment of sore throat by approximately 80% (Bisno et al, 2002).
The patient has 4 of the above signs/symptoms thus GABHS is likely.
The above is further supported by Carey, Schuster and McGowan (2008) as they stated that clinical clues to ascertain infection by Streptococcus Pyogenes are;
· the age of the patient as Strep throat usually occurs in young children of school-age
· absence of a cold symptoms and runny nose indicating a probable strep throat infection as opposed to a viral on, and
· Presence of classic signs and also symptoms of S. pyogenes pharyngitis which are; tonsillar exudates, fever, cervical lymphadenopathy with absence of cough.
Chamberlain (2010) stated that clinical and epidemiological factors must be looked at for appropriate diagnosis. Table 1 below shows the clinical and epidemiological factors to be considered as they are suggest bacterial causative agent if present in a patient. Almost all these factors are signs and symptoms as well as epidemiological factors in the 6 year old boy and thus, suggest bacterial etiology i.e. S pyogenes as the infectious agent.
TABLE 1: Clinical and Epidemiologic Findings Useful in the Diagnosis of Pharyngitis
Epidemiologic findings suggestive of Streptococcus pyogenes as the etiologic agent
Source: http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/uriphyn.htm
When commenting on epidemiological features, Bisno et al (2002) further contended that the when age of a patient falls between 5-15 years, no child abuse or travel, GABHS should be highly suspected as the causative agent. The patient fits this description and it can thus be said that he has acute pharyngitis caused by GABHS.
According to Chamberlain (2010), any delay in treating S pyogenes pharyngitis over 9 days after symptoms have begun makes the patient to be at a risk of developing rheumatic fever and also suppurative complications. Thus, strategies must be used to appropriately diagnose the infectious agent causing acute pharyngitis as they will require antimicrobial therapy and hence unnecessary treatment of patients who are diagnosed with acute pharyngitis of viral origin is avoided (Chamberlain, 2010). Two methods are used for this diagnosis:
1. Rapid strep test and,
2. Throat culture (Kim, 2009)
1. Rapid strep test.
A swab from both tonsils and posterior pharyngeal area from the patient is collected to test for by detecting group A–specific carbohydrate N-acetylglucosamine. Sensitivity of this test varies but the specificity is superb if compared to culture with a range of 95–100% generally (Kim, 2009; Bisno et al 2002). Thus, a positive antigen test indicates GAS and therefore, a throat culture confirmation is neither needed nor necessary. However, confirmation must be carried out with a throat culture if the antigen test is negative (Kim, 2009).
2. Throat culture.
A swab is taken from the same places as is taken for the rapid antigen test. The specimen is grown on agar blood plates. If GABHS is the etiologic agents, there would be b-hemolytic colonies which are catalase-negative, are gram-positive cocci and also exhibit sensitivity to Bacitracin (Chamberlain, 2010). This test is more sensitive than the rapid antigen test. Though the rapid test is readily available in the Doctors’ office and takes 5 to 10 minutes to perform, the throat culture takes 48 hours to complete thus, leading to the use of the rapid antigen tests more often (Chamberlain, 2010).
It follows that, if the rapid antigen detection test is positive, the throat culture is not required and thus treatment should commence with antibiotics e.g. penicillin. However, if rapid antigen detection test result is negative, a throat culture needs to be carried out (Chamberlain, 2010; Kim, 2009).
THERAPIES
Patients with GAS pharyngitis, empirical treatment should be done immediately to prevent complications, to reduce the infection and transmissibility, and to induce clinical improvement of symptoms. Patients with a higher level of suspicion of GAS pharyngitis but delayedculture results can also be given empirical antibiotics. Alternatively antibiotics can be withheld until the culture is positive for S pyogenes. Delaying the treatment for GAS doesn't have any effect on rheumatic heart disease or the strain of S pyogenes. The latter will reduce the inappropriate antibiotic usage and control the antibiotic resistance.Selecting antibiotic primarily depend on the way it is to be administered, its effect, cost and condition that is not limited the antibiotic. Penicillin V or amoxicillin is used for around ten days. Intramuscular penicillin G benzathine may be administreted in patients who are unable to complete the ten days period. Macrolides like erythromycin, azithromycin are alternatively used in penicillin allergic patients. Absence of penicillin-resistant GAS compels a cheaper alternative than latest antibiotics which are expensive. Penicillin is not able to prevent nasopharyngeal carriage in patients with frequent GAS pharyngitis .
Amoxicillin/clavulanate or rifampin may be used in such patients. Antibiotics should not be used in patients with negative throat RADT/cultures.
Pharyngitis caused by anaerobic bacteria may respond to penicillins or clindamycin.Yersinia pharyngitis is treated with latest cephalosporin. Mycoplasma pharyngitis is treated by doxycycline or macrolides. Symptomatic oropharyngeal in immunodeficient patients are treated by acyclovir ten days.
Amantadine or neuraminidase inhibitors are used to treat Influenza A pharyngitis if the patient is presented immediately after the start of symptoms. Antiretroviral therapy maybe used for HIV acute retroviral syndrome.
Fluids, gargling with warm and salty water, nonsteroidal anti-inflammatory drugs and rest of voice are some symptomatic relief. Gargling with Chamomile, Blackberry, sage may also help.
CONCLUSION
The location of the pharynx makes it an easy target for infection entering via the nose and mouth by aerosols from an already infected person or by eating food contaminated with the etiological agent. Though viruses are the main infectious agents of the pharynx, bacterial agents also account for a lower percentage. Many features like epidemiological factors such as; the season of the year and age of the patient, clinical factors and usefulness together with the availability of treatment must also be taken into perspective for diagnostic purposes.The 6 year old boys’ medical history indicated the absence of previous health problems thus, this was just an opportunistic bacterial infection. The patients’ age was considered, the season in which the disease occurred, the rapid onset of the disease, as well as the common diseases in children of his age group and they all were pointers suggesting acute pharyngitis. Though numerous diseases had very similar symptoms, the sore throat decision rule with defining signs/symptoms i.e. presence of throat exudates, enlarged sub-mandibular glands, fever, and absence of runny nose and cough are classic symptoms/signs of acute pharyngitis caused by group A β-hemolytic streptococcus. The infectious agent can further be confirmed using either a rapid strep test or throat culture or both.
GABHS usually left untreated can be good opportunity for complications to arise e.g. Kidney damage. Thus, it is highly advisable to treat all cases of GABHS related acute pharyngitis.
The treatment plan is most likely to include an analgesic for pain relief and oral Penicillin/its derivatives e.g. amoxicillin as the patient is still young. Amoxicillin is easily absorbed and is thus most likely to be prescribed for treatment of acute pharyngitis in comparison to other treatments. Misuse of antibiotics should also be taken into consideration so as to avoid resistance.
GABHS vaccines are also being developed. An approach to this has been to put together small amino-terminal M-protein peptides in order to produce vaccines which are multivalent and would exhibit opsonic antibodies against GAS serotypes.
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