Complete+Wiki


 * Infectious Agents **

The 40 year old patient can be said to be suffering from Legionnaires’ disease, a form of lobar pneumonia. The bacterium, //Legionella pneumophillia//, //(L. pneumophillia// ) was discovered in 1977, and is the principal infectious agent of Legionnaires disease. // L. pneumophilia // is  the major infectious agent in many cases of //Legionellosi// //disease//  (Bartman //et al//, 2007). It is the most common legionella species associated with human disease, it has been reported that it caused up to 15% of Community aquired pneumonia (Marrie, 1989). //L. pneumophila, // is an evolving human pathogen that resides in natural environments as a parasite of freshwater occupying non-marine water sources that have contents rich in algal and iron, it has an aerobic metabolism which allows it to exist for short periods outside of aquatic environment (Hoffma, 2007). //L. pneumophilla,// is a gram-negative coccobacilii, and a non-sporulating forming flagellated bacilli of the //Legionella// genus. The bacterium is a non-capsulated, rod-like, facultative intracellular parasite of protozoa (Rathore, 2006). //L. pneumophilla // is not a free living organism as it is an intracellular parasite of amoeba, amoeba and human macrophages are the main hosts of //L. pneumophila// (Fields, 1996). It has a life cycle with two phases, a replicative phase which is subsequently followed by an infectious phase//.// (Swanson, 2007) //L. pneumophillia // serotype 1 is the main cause of Legionnaires’ disease and frequently found from environmental sources. (Palaz, 1996)

According to the patient’s condition it can be suggested that he might be suffering from an atypical pneumonia due to the presence of a pulmonary pathogen named //Legionella Pneumophilia// (Newton H.J. //et al//, 2010). Therefore, //L. pneumophilia// have been shown to enter into monocytes through not only coiling phagocytosis but also through conventional phagocytic mechanisms, such as direct inhalation, aspiration of oropharyngeal contents, direct spread from the mucosal membrane and haematogenous spread (Ganong W.F. //et al//, 2006) (Cirillo //et al//, 2001). The bacteria //L. pneumophilia// has micro dimensions (Fig. 1), which allows it to be engulfed by the alveoli easily and grow within it as an intracellular parasite. Although this pathogen activity could be demobilized by mucociliary action, the deterioration of this defence at a certain level will compromise mucociliary clearance, therefore allowing the hazard progression of the pneumonia (Madigan //et al//, 2009).    Figure 1: The Legionella Pneumophilia (‍Scharstuhl E. (2011). The primary host defence is usually characterized by cell-mediated immunity response against //Legionella// infection where the activation of further macrophages will allow the production of cytokines that will control antimicrobial activity against this pathogen (Cirillo //et al//, 2001).During infection, //L. pneumophilia// generates a reproduction vacuole within eukaryotic cells which will then affiliate with mitochondria and then obtain components of the endoplasmic reticulum. This will therefore not only lead to the encoding of a Type IVb secretion system (T4bSS) through Icm/Dot genes, but will also bring the aid of antibodies and complements, until cellular endocytic physiology is completely compromised, therefore, permitting the pathogen to have entree to an atypical rough ER-bounded phagosome (Cirillo //et al//, 2001)(Fig.2). The capability of survival and the intracellular trafficking of this pathogen inside the host depend on the early activity of Icm/Dot genes, which will therefore involve effector proteins, such as Ank proteins, enhancing the host endosomes destruction (Pan X //et al//, 2008). <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">According to Allen L.-A.H. (2003), with the progression of the infection, Icm/Dot become vital, and phagosomes incorporated with amplified bacteria, will therefore obtain lysosomal properties. Once the infection is stabilized, this pathogen will not only promote fibrinopurulent pneumonia but will also affect other organs such as kidney, liver, brain, lymph nodes as it can be observed by this patients clinical background (i.e. multisystem failure, abnormal liver and renal function) (Rathore M.H. //et al//, 2009).However, Legionella activity could be quickly defeated by PMNs (polymorphonuclearleukocyte) or completely annulled by the action of MPO-derived oxidants (myeloperoxidases), in cell-free systems (Allen L.-A.H., 2003). <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Figure 2: Infection Cycle of //L. pneumophilia//. (Machner M.P., 2011) <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;"> <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">
 * <span style="color: black; font-family: 'Times New Roman','serif'; font-size: 16px;">Pathogenesis **

**<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 16px; text-decoration: none;">Epidemiology ** <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">The transmission of //Legionella pneumophilia// involves contaminated water systems disseminating the water as aerosols, sprays, or mists. Legionella transmission occurs via the inhalation of aerosols of contaminated water and is not contagious. This provides direct access for the bacteria to its site of action: the lungs. The likelihood of having the disease depends on the level of contamination in the water source, the susceptibility of the person exposed, and the degree of exposure (Muder //et al.,// 1986). People with compromised defence mechanisms may not be able to fight infection by //L. pneumophila//. Thus smokers and those with chronic cardiovascular or pulmonary conditions are more prone to infection. In addition, people suffering from cancer, diabetes or kidney failure, or those on immuno-suppressant drugs, are also more susceptible to infection as they have an insufficient immune system. (CDC, 2011). Most outbreaks of Legionnaire’s disease have been associated with poorly maintained artificial water systems. Thus certain preventive measures can be implemented in attempt to control infection by //L pneumophilia//. Regular cleaning and disinfection, temperature control, and the addition of biocides all contribute to minimising the growth of the bacteria. Monitoring for scale and sediment build-up, and routine upgrading and repair of the systems is also vital for Legionella control. Ventilation systems in hospitals can also contribute to legionella infection by the airborne route. Thus the use of high-efficiency filters should be used to remove contaminants. Legionella Risk Assessments should be carried out regularly to ensure Legionella control. (EWGLINET, 2005)Although Legionnaires’ disease occurs worldwide, it is highly under-diagnosed in developing countries and is thus mainly reported from industrialised countries. In England and Wales, there are around 400 cases a year. Around 40% of these cases were related to foreign travel (HPA, 2011).In the United States, between 8,000 and 18,000 people a year hospitalised with Legionnaires’ disease (CDC, 2011). Occurrence rates for Legionnaires’ disease were collected by the European Centre for Disease Prevention and Control (ECDC) from 25 EU countries, Iceland, and Norway for 2009. In total, 5518 cases of Legionnaires’ disease were reported, meaning that 11.2 cases occurred per million (ECDC, 2011). The graph below in Fig.3 shows the occurrence of Legionnaire’s disease cases recorded by ECDC from 1988 till 2007.

<span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">The establishment of national surveillance systems, research studies, and clinical methods of diagnosis may contribute to the increasing number of cases in certain countries. The upsurge in cases in 2006 occurred over the summer months, indicating that the disease exhibits a seasonal trend. This could be due to the fact that //Legionella// bacteria thrive in warm water, or because in the summer seasons, people tend to use more aerosol-generating devices such as showers, fountains, and air conditioning units, all of which are potential sources of //L. pneumophila// (Howland & Pope, 1983). <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;"> <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;"> <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">The graph in Fig.4 shows the cases of Legionnaires’ disease by age and gender recorded by ECDC. 77% of these reported cases were people of 50 years of age or older. Even though the risk of acquiring Legionnaires’ disease increased with age in both genders, males were around 3 times more susceptible to infection than females. This could be because males tend to be more exposed to //Legionella//-harbouring sources. **<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 16px; text-decoration: none;">Clinical Aspects ** <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Symptoms of Legionnaires disease of appear 2-14 days after exposure to the bacteria. More than 50 Legionella species are described but //Legionella pneumophilia// is the cause of more than 95% of all Legionnaires diseases and can be fatal. Mortalilty of patients with pneumonia may exceed 30 % for the elderly (Krojgaard, Louise H 2011) <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍As the infection increases the symptoms may also increase. Further symptoms may include the following; coughing with a yellow/green mucus production, chest pain, shallow breathing, shortness of breath, fever, chills, fatigue after short periods of physical activity, sinus infections and in some cases asthma may also occur (Reischl U //et al//, 2002). <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍Legionnaires disease displays two clinical syndromes; Legionnaires disease and Pontiac fever, this together is known as legionellosis. <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍The Pontiac fever is what causes the flu like symptoms which were mentioned above (Guyard C //et al//).When Pontiac fever is displayed then the patient has mild forms of legionellosis. Legionnaires disease causes pneumonia in severe cases of legionellosis, whereas Pontiac fever doesn’t cause pneumonia, which shows the patient in this case has severe forms of Legionnaires disease. <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍Pleural effusion is when vast amounts of fluid collect in the pleural space, this impairs the ability of the lungs to expand and move, restricting breathing. <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍As this fluid amount increases, the ability to breath of the patient decreases further. There is also an additional risk that this fluid can become infected leading to emphysema. Emphysema is when this infected fluid causes the build-up of pus (Kawanami, t //et al//, 2011). This build up of pus leads to the symptoms worsening; increased chest pain, dry cough, increased fever and weight loss. <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍There are two types of pleural effusion;Transudate pleural effusions and exudate pleural effusions. Transudate pleural is caused by fluid which has leaked from blood vessels into the pleural space (Cianciotto, N, 2001). Exudate pleural effusions are caused by inflammation of the pleura, drug reactions, blocked blood vessels, amongst other causes leading to restrictions in breathing. **<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 13px;">‍ ** <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Diagram 1: It displays the abnormal quantity of pleural fluid between the surfaces of the lungs and chest cavity (Wedro B., 2011). <span style="color: black; display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">‍Severe symptoms of pneumonia also include cyanosis. Cyanosis is when the skin of patient with progressed cases of pneumonia turns to a blue/purple colour (Declercka, p //et al//, 2009). This is caused by a lack of oxygen in the blood. These symptoms will show in both adults and children but children will display and increased shortness in breath. Other severe symptoms also include confusion. **<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 16px; text-decoration: none;">Therapies & Treatments **
 * <span style="display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Figure:3 - occurrence of Legionnaires' disease cases (TRDuk, Legionella Prevent) ||
 * <span style="display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Figure:3 - occurrence of Legionnaires' disease cases (TRDuk, Legionella Prevent) ||
 * <span style="display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Figure: 4 - cases of Legionnaires' disease by age and gender (TRduk, Legionella Prevent) ||
 * <span style="display: block; font-family: 'Times New Roman',serif; font-size: 13px; text-align: justify;">Figure: 4 - cases of Legionnaires' disease by age and gender (TRduk, Legionella Prevent) ||

<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 13px;">A 40 year old man suffering with //Legionella Pneumophilia// is currently being treated with trimethoprim-Sultamethoxazole for his respiratory infection and abnormal liver and renal function. Because of the man’s age and abnormal liver and renal function, it would be better suited not to keep him on this course of antibiotics for too long a time as trimethoprim-Sultamethoxazole can cause severe liver damage and also renal impairment up to acute renal failure. (Cramer, 2003) So, the next class of antibiotics the patient will be put on is Macrolides; Azithromycin, Clarithromycin and Erythromycin. (Venkatesan, 1999)Azithromycin can be used to treat his bacterial infection, while Erythromycin can be given to him to treat his respiratory tract infection. And Clarithromycin will treat his mildly inflamed airways and pneumonia. The patient will also be given fluid and electrolytes intravenously administered through a drip and he will also be put on oxygen through a breathing machine or mask. (Equipment, 2008)If the patient builds a resistance to this class of antibiotics, or the symptoms persist or worsen, and become life-threatening to the patient, then they must be moved on to the class of antibiotics called the Quinolones, a group of potent synthetic antibiotics which are used to treat severe bacterial infections that have failed to respond to other antibiotics. Ciprofloxacin can be used to treat his respiratory tract infections and pneumonia, as can Moxifloxacin and Gatifloxacin, while Levofloxacin would be used to treat his bacterial infection. (Chemother, 2003), (Woodhead, 2001)While the patient is on this class of antibiotics, and as Levofloxacin is primarily eliminated by renal excretion, his renal function status must be taken into account and his serum levels must be monitored during therapy. This is to avoid an accumulation that may lead to a drug overdose. However, the antibiotic is also metabolised and partially cleared through the liver. This means that the dosage should be modified as he has impaired liver and renal functions. Duration or therapy and treatment will depend on his severity of the infection and the immunological competence of the patient. (Chemother, 2003) **<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 16px; text-decoration: none;">Conclusion ** // L. pneumophila //<span style="color: black; font-family: 'Times New Roman','serif'; font-size: 13px;"> is the major infectious agent in many cases of //Legionellosi// //disease.//This species are found worldwide and are ubiquitous in both natural and man-made environments. It is a gram-nagative, non-capsulated bacterium and the most common Legionella specie associated with human disease.Despite the fact that //L. pneumophilia// is an ecological organism, its typical capacity to reproduce inside the eukaryotic host cells and its aptitude to bypass ordinary pathogen supervision process in the host, have generate its expansion as a vital yet occasional purpose of hospital- and community-acquired pneumonia.Clinical diagnosis of Legionnaires’ disease is relatively difficult due to the non-specific presentation of the disease. Epidemiologic clues may include the use of a spa, recent pneumonia of a traveller, or recent plumbing work. Appropriate microbiological testing is required for the diagnosis of the disease, thus many cases may go un-diagnosed making the occurrence rates higher than known.Although the clinical aspects of //L. Pneumophilia// displays two types of diseases described as; Legionnaires disease and Pontiac fever, this patient shows symptoms from Legionnaires disease which is more severe.For the treatment of Legionnaires disease, a high level of suspicion and prompt initiation of adequate antimicrobial therapy are critical to improve clinical outcome. Specific therapy includes antibiotics capable of achieving high intracellular concentrations. Recommended therapy is 5-10 days if azithromycin is used. If other drugs are used, the duration should be 2-3 weeks. But, for the more severe of the disease, or immunocompromise, prolonged courses may be required.

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 * <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">References **