BLOOD LYMPHOCYTOSIS IN A PATIENT WITH PERTUSSIS. The lymphocytes in this blood smear from an 18-month-old child with a Bordetella pertussis infection have lobulated nuclei. Lymphocytosis is characteristic of this disorder and the lymphocyte morphology is often atypical. The cytology of the cells could be mistaken for neoplastic lymphocytes. (Wright-Giemsa stain) © The Johns Hopkins Autopsy Resource (JHAR). Image Archive.
Acute Bronchitis (“Chest Cold”)
Tracheobronchial infections without pneumonia comprise a spectrum of disorders with different clinical implications: acute bronchitis, chronic bronchitis, and bronchiectasis. Acute bronchitis or “acute simple bronchitis” in otherwise-healthy persons is extremely common, usually of viral etiology, and a common reason for overuse of antibiotics. The term “acute infectious bronchitis” is sometimes used to distinguish this entity from other causes of cough, and the term “tracheobronchitis” is sometimes used for accuracy since the trachea is also inflamed. However, “chest cold” is probably the best term for daily practice since it implies that antibiotics are seldom necessary. Bordetella pertussis, the agent of whooping cough, is now recognized as a cause of acute bronchitis in adults. Infection by either Mycoplasma pneumoniae or Chlamydia pneumoniae accounts for many of the stubborn cases in which symptoms fail to resolve or recur soon after treatment has been discontinued.
Infection of the tracheobronchial mucosa causes local inflammation, increased secretion of mucus, and damage to ciliated cells. Symptoms result both from the inflammatory response and also from the interruption of the mucociliary blanket that normally cleanses the lower respiratory tract. Most cases of acute bronchitis (95% by some estimates) are caused by viruses. All of the common viruses affecting the upper respiratory tract have been implicated: rhinoviruses, coronavirus, respiratory syncytial virus, adenoviruses, coxsackieviruses, influenza viruses A and B, and parainfluenza virus. In 2 studies in which attempts were made to establish a precise diagnosis, the etiology was established in only 16% and 29% of cases with viruses being the most common causes.
Mycoplasma pneumoniae and Chlamydia pneumoniae probably play minor roles in this illness, at least in most populations. However, M. pneumoniae probably causes more cases of bronchitis than pneumonia, and C. pneumoniae may be an important cause of acute bronchitis in college-aged students. Whether S. pneumoniae, H. influenzae, and M. catarrahalis cause chest cold in otherwise-healthy persons is unclear, but there is little support for the concept of "acute bacterial bronchitis" as a community-acquired disease. Recently it has been emphasized that Bordetella pertussis can infect adults, even when vaccinated, providing a reservoir for causing whooping cough among infants. Bordetella parapertussis causes a protracted illness similar to whooping cough but without systemic toxicity. Whether these observations can be generalized to other populations is undetermined.
The onset is typically preceded by a prodrome of at least 24 hours with symptoms of coryza and pharyngitis. A dry cough, signifying early inflammation of the upper airway, often evolves into a cough productive of moderate amounts of mucopurulent sputum. Fever, headache, myalgias, and retrosternal chest pain or discomfort may be present. Fever is most common when an influenza virus or Mycoplasma pneumoniae is the causative agent. The patient rarely looks toxic. Tracheal tenderness is often present. Auscultation may reveal a few coarse crackles with occasional wheezes in the chest, but there are no signs of consolidation.
Transmission electron photomicrograph of a hamster trachea ring infected with M. pneumoniae. Note the orientation of the mycoplasmas through their specialized tip-like organelle, which permits close association with the respiratory epithelium. M, mycoplasma; m, microvillus; C, cilia.
Both images used with permission. From Baseman and Tully, Emerging Infection Diseases 3
Figure Chlamydial inclusions © Bristol Biomedical Archive. Used with permission
Figure Chlamydial inclusions in an endothelial cell © Bristol Biomedical Archive. Used with permission
Acute Infectious Exacerbations of Chronic Bronchitis
Chronic bronchitis is defined by the American Thoracic Society (ATS) as excessive sputum production with cough, present on most days for at least 3 months a year and not less than 2 successive years, without an underlying etiology such as tuberculosis or bronchiectasis. This common disorder, affecting up to 25% of the adult population, can lead to full-blown chronic obstructive pulmonary disease (COPD), the fourth-leading cause of death in the United States. The extent to which acute exacerbations are due to treatable infections remains controversial.
Chronic bronchitis is caused mainly by cigarette smoking. Air pollution, cold and damp climates, heredity, frequent lower respiratory tract infections, and immunodeficiency disorders (such as common variable hypogammaglobulinemia or isolated IgA deficiency) play a role in some patients. The essential feature is anatomic change in the larger airways, including an increased number of mucus-producing goblet cells and mucosal gland hypertrophy in the bronchial walls. Increased bronchial secretions and impaired ability to handle them lead to chronic cough and disabling complications.
Current opinion holds that most acute exacerbations of chronic bronchitis are caused by viruses or by non-infectious agents. Viruses have been found in as few as 7% to as many as 64% of cases in which they were sought. By conservative estimate viruses cause about one-third of cases, the more common ones being influenza viruses A and B, parainfluenza virus, coronaviruses, and rhinoviruses. Cultures of sputum often show non-typable strains of Haemophilus influenzae, Streptococcus pneumoniae, and/or Moraxella catarrhalis. However, the extent to which these bacteria explain exacerbations in a given patient is hard to determine since they often colonize the damaged lower respiratory tract on a more-or-less permanent basis. Evidence suggests that repeated episodes of bacterial infections—especially when caused by H. influenzae—contribute to deterioration of pulmonary function. S. aureus and aerobic gram-negative rods occasionally cause exacerbations of chronic bronchitis. The pathogens associated with "atypical pneumonia" such as M. pneumoniae, C. pneumoniae, and L. pneumophila probably cause fewer than 10% of exacerbations. Evidence to date suggests that Chlamydia pneumoniae is more strongly associated with the underlying chronic bronchitis than with its acute exacerbations. However, Chlamydia pneumoniae can cause a stubborn respiratory illness lasting several weeks or longer and tending to relapse after each course of antibiotics. Figure
This PA x-ray depicts atelectatic, and bronchiectatic changes in this child’s right upper pulmonary lung field.
Atelectasis (a collapse of the lung) can be due to bronchiectasis (an enlargement of the bronchial tubes) and a decrease in the effectiveness of their ciliated mucosal lining, which renders the lungs unable to clear themselves of clogging mucous build-up.
CDC/ Dr. Thomas Hooten
Bronchiectasis
Bronchiectasis is an acquired disorder characterized anatomically by abnormal dilatation of bronchi and bronchioles and clinically by chronic productive cough and frequent lower respiratory tract infections. Its prevalence fell dramatically after the introduction of broad-spectrum antibiotics and widespread immunization against measles and pertussis. Although bronchiectasis is now uncommon, it often goes undiagnosed until far-advanced. Newer imaging studies now enable earlier diagnosis, and our understanding of its causes continues to improve.
Cigarette smoking, the major cause of chronic bronchitis, plays little role in bronchiectasis except for predisposing to recurrent infections. The basic problem in bronchiectasis is permanent structural damage to the walls of bronchi and bronchioles brought about by the concerted action of (1) infection and (2) impairment of the pulmonary toilet, airway obstruction, and/or a defect in host defenses.
In the past, bronchiectasis was associated especially with frequent or severe lower respiratory infections during childhood. Bronchiectasis continues to be associated with such infections - especially necrotizing pneumonias in which treatment is delayed - but the list of known causes has expanded. Bronchiectasis can be the earliest clue to cystic fibrosis presenting during adolescence or early adulthood. Staphylococcus aureus, Pseudomonas aeruginosa, and Pseudomonas cepacia are often isolated from these patients. Mycobacterium avium-intracelluare complex (MAC) infection is not infrequently associated with bronchiectasis, especially in older women and/or thin women. Allergic bronchopulmonary aspergillosis often leads to bronchiectasis, which might be prevented by early recognition of this syndrome. Immunodeficiency disorders, both congenital (hypogammaglobulinemia) and acquired (AIDS) predispose to bronchiectasis. The dyskinetic cilia syndromes are sufficiently common (about 1 in every 20,000 to 60,000 persons) that a case is likely to occur in every medium-sized city.
Patients with advanced bronchiectasis experience daily cough productive of large amounts of mucopurulent, thick, tenacious sputum. However, most patients produce lesser amounts of sputum, at least during the early stages, and cough may be nonproductive ("dry bronchiectasis") or even absent. Dyspnea and hemoptysis are common. Patients often give a history of repeated respiratory infections and sometimes give a history of recurrent pleuritic chest pain. Hard crackles are heard locally over the lung fields in about 70% of patients. Rhonchi and widespread expiratory wheezes are also common. Clubbing is present in only about 3% of patients. Plain chest x-rays (PA and lateral views) are usually abnormal.
Figure
This AP chest x-ray shows pneumonia of the left lower lobe with early consolidation, the etiology of which was unknown.
Pneumonia can be caused by a variety of agents including bacteria, viruses, and mycoplasmas, among others. Pneumonia remains an important cause of morbidity and mortality in the United States as both a primary, and secondary infection.
CDC/Dr. Thomas Hooten
Figure
This anteroposterior x-ray reveals a bilaterally progressive plague infection involving both lung fields.
The first signs of plague are fever, headache, weakness, and rapidly developing pneumonia with shortness of breath, chest pain, cough, and sometimes bloody or watery sputum, eventually progressing for 2 - 4 days into respiratory failure and shock.
CDC/Dr. Jack Poland
Acute Community-acquired Pneumonia: Overview
Pneumonia accounts for an estimated 45,000 deaths in the United States each year. It is the 6th most common cause of death and the most common infectious cause of death. Since it is not a reportable disease, the precise incidence is unknown. Estimates suggest that 4 million cases occur each year, prompting 10 million physician visits and 600,000 to 1.2 million hospitalizations and adding $23 billion to health care costs. Data suggest a 28-fold increased cost for managing the disease on an inpatient basis ($7,517 versus $264 for outpatient therapy). However, the mortality rate is 1% or less for patients managed as outpatients versus 14% to 25% for those admitted to the hospital. Physicians often overestimate the short-term mortality risk, but erring toward hospitalization is understandable given the potentially fatal nature of the disease.
Microorganisms can enter the lungs by aspiration, inhalation, or by way of the bloodstream (hematogenous pneumonia). Aspiration of bacteria that have colonized the oropharynx is by far the most common mechanism. Most humans aspirate small amounts of oropharyngeal secretions on a nightly basis. Microorganisms that are not removed by the mucociliary blanket are taken up and killed by pulmonary alveolar macrophages, the last line of defense. This process, called pulmonary clearance, is impaired by viral respiratory infections, tobacco smoke, chronic lung disease, alcohol, and many other factors associated with debilitating diseases. One or more chronic diseases are present in the majority of adult patients with pneumonia (58% to 89% of patients in various studies). Alcoholism predisposes to aspiration, but cigarette smoking is the main avoidable risk factor for community-acquired pneumonia in adults.
Inhalation of aerosolized particles is an important route of entry for many viruses including the influenza viruses and, most recently, the Hantaviruses. Bacteria that cause pneumonia by airborne transmission include M. tuberculosis, Yersinia pestis (plague), Bacillus anthracis (anthrax), and probably Legionella pneumophila (Legionnaire’s disease) and Francisella tularensis (tularemia). Spore-producing fungi such as Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis also cause inhalation pneumonia.
Hematogenous pneumonia classically develops from septic pulmonary emboli, frequently resulting in patchy or nodular bilateral pulmonary infiltrates sometimes accompanied by pleural effusions. In inner-city populations, a familiar scenario consists of bilateral pneumonia associated with S. aureus endocarditis on the tricuspid or pulmonic valves of injecting drug users. Another scenario consists of emboli from septic thrombophlebitis: for example, of the pelvic veins (pelvic inflammatory disease, septic abortion), internal jugular vein (the Lemierre syndrome) or any large vein where a catheter has been inserted. Hematogenous seeding of the lungs possibly explains some pneumonias caused by gram-negative bacteria and by unusually virulent organisms such as F. tularensis (tularemia).
The microbial cause of community-acquired pneumonia is usually difficult to determine. In prospective studies of patients requiring hospitalization, a cause is found in only 40% to 70% of cases. In primary care practice, a far greater fraction of cases are never diagnosed. Most of these cases respond to empiric therapy. Published data concerning the causes of pneumonia vary from one region to another, but some generalizations are possible. Mycoplasma pneumoniae has been determined to be the most common cause in some communities, when presumptive diagnoses were taken into account, followed by Streptococcus pneumoniae and Chlamydia pneumoniae. Adults with compromised host defenses are likely to have pneumococcal pneumonia, but can also have pneumonia due to H. influenzae, Moraxella catarrhalis, S. aureus, or aerobic gram-negative rods. There is wide agreement that S. pneumoniae is the most common cause of community-acquired pneumonia requiring hospitalization. An emerging and controversial area concerns the frequency of pneumonia caused by more than one microorganism. In one study, a second pathogen was found in about 10% of patients with pneumonia due to a conventional bacterial pathogen, but in 55% of patients in whom an "atypical" pathogen was found.
In 1938, the term "atypical pneumonia" was introduced to describe "an unusual form of tracheobronchopneumonia with severe constitutional symptoms". It later became customary to distinguish between "classical bacterial pneumonia" and "atypical pneumonia". This distinction was challenged during the 1990s when researchers found it difficult if not impossible to differentiate these illnesses on clinical grounds. Some authorities now suggest abandoning the term "atypical pneumonia". Others keep the term since it enriches our appreciation of the disease, forces us to consider unusual etiologies, and reminds us that the "atypical pneumonias" do not respond to β-lactam antibiotics. For these latter reasons and for the sake of clarity, we keep the terms here even while agreeing that in some cases it may be impossible to distinguish between "classic bacterial pneumonia" and "atypical pneumonia" in actual clinical practice.
"Typical pneumonia" is an alveolar disease whereas "atypical pneumonias" affects mainly the tracheobronchial mucosa and interstitium of the lung; hence, the different clinical manifestations.
Classical bacterial pneumonia begins with sudden onset of fever, chills, pleuritic chest pain, and productive cough. In the absence of impaired consciousness or inebriation, patients usually seek medical care within 6 hours of the onset of symptoms. Chills occur in about 50% and chest pain in about 30% of patients. Most patients are febrile although some, especially the elderly, may have normal or subnormal temperatures. The respiratory rate is usually increased. Physical examination often reveals signs of consolidation such as dullness to percussion, pectoriloquy, and egophony (e to a change). Lobar consolidation is present on chest x-ray in about one-third of patients. The white blood count is usually elevated with a shift-to-the-left. However, leukopenia rather than leukocytosis may be present and portends a poor prognosis.
Atypical pneumonia, on the other hand, usually begins gradually. The insidious onset is often brought out by asking, "When was the last time you were in your usual good health?" Constitutional symptoms are usually more prominent than the pulmonary symptoms. Chest pain is experienced as substernal discomfort. Cough is non-productive or productive of only scanty amounts of sputum. Relative bradycardia is frequently present. The trachea may be tender but the lung fields are essentially clear to auscultation, prompting one to be surprised by the extent of infiltrate present on chest x-ray. The white blood count is often normal or near normal. Modest elevation of liver enzymes (specifically, the aminotransferases - AST (SGOT) and ALT (SGPT) - is often present. Atypical pneumonia, in summary, seldom presents as an acute, life-threatening medical problem but forces the physician to expand the differential diagnosis.
Pneumococcal Pneumonia
Streptococcus pneumoniae remains the major cause of severe community-acquired pneumonia and, worldwide, a leading cause of death. It accounts for about two-thirds of cases of bacteremic pneumonia, and is the most common cause of pneumonia leading to hospitalization in all age groups. Some authorities believe that S. pneumoniae may cause up to one-half of all community-acquired pneumonias. There is concern that the incidence of pneumococcal disease may be increasing at the same time that drug resistance is becoming much more common. Primary care clinicians should strive to make pneumococcal vaccination an imperative for patients at increased risk.
S. pneumoniae is a common colonizer of the nasopharynx. Invasive pneumococcal disease occurs most often after a new serotype has been acquired, typically after an incubation of one to three days. Viral illness increases the incidence of disease presumably by interfering with normal host defenses. Risk factors for invasive pneumococcal disease include extremes of age, alcoholism, HIV disease, end-stage renal disease, sickle cell disease, diabetes mellitus, dementia, malnutrition, malignancies, diseases affecting B lymphocyte function (notably, multiple myeloma and hypogammaglobulinemia), and immunosuppressive disorders. Patients with asplenia are susceptible to fulminant pneumococcal disease. The pneumococcus does not invade cells as readily as do some of the other streptococci. However once in the lungs, it passes easily from one alveolus to another through the pores of Cohn until stopped by the dense hence the basis for lobar consolidation.connective tissue of a fissure
As classically described by previous generations of clinicians, S. pneumoniae causes a lobar pneumonia with by the sudden onset of fever with a single, hard-shaking chill, cough productive of rusty-colored mucopurulent sputum, and pleuritic chest pain. The patient presents with systemic toxicity including tachypnea. Physical examination reveals crepitant râles, tubular breath sounds, and signs of lobar consolidation (dullness to percussion, egophony with e to a change, and pectoriloquy). Today, however, pneumococcal disease is often a more subtle illness. Patchy infiltrates and bronchopneumonia are relatively common. It is often difficult to say precisely what represents pneumococcal pneumonia and what does not unless blood cultures are positive.
Figure
Haemophilus influenzae as seen using a Gram-stain technique.
During the flu outbreak of 1918 H. influenzae was termed Pfeiffer's Bacillus, where it was found in the sputum of many influenza patients, and thought to be the cause of influenza.
CDC Bacterial Pneumonia due to Agents other than S. pneumoniae
Among the numerous bacteria other than S. pneumoniae that sometimes cause acute community-acquired pneumonia, the most common are H. influenzae, S. aureus, Streptococcus pyogenes, miscellaneous aerobic gram-negative rods, and anaerobic "mouth flora" bacteria. Patients with these pneumonias often have significant underlying disease, severe pneumonia, or both. Therefore, hospitalization is usually indicated.
H. influenzae is a frequent cause of pneumonia in elderly patients and in patients with serious underlying diseases including chronic obstructive lung disease. The pneumonia usually has a patchy or segmental distribution characteristic of bronchopneumonia as opposed to lobar pneumonia. A sputum Gram’s stain showing small, pleomorphic gram-negative coccobacilli can be virtually diagnostic.
Staphylococcus aureus pneumonia, when community-acquired, tends to be an acute, fulminant about 1% of cases, except during influenza epidemics. Influenza virus infection markedly predisposes to staphylococcal colonization of the respiratory mucosa. Staphylococcal pneumonia tends to be a necrotizing process with abscess formation. The chest x-ray sometimes shows air pockets known as pneumatoceles, especially in children.
Streptococcus pyogenes (group A streptococcal) pneumonia is also uncommon except during influenza epidemics. This pneumonia is often accompanied by the rapid development of large empyemas. Chest tube drainage is often necessary, resulting in prolonged hospitalization.
Klebsiella pneumoniae is a relatively common cause of pneumonia in patients suffering from alcoholism. The pneumonia often assumes a lobar distribution. Classically, this pneumonia affects the upper lobes and causes a “bulging fissure” on chest x-ray. E. coli and other aerobic gram-negative rods are relatively common causes of pneumonia in the frail elderly. Pseudomonas aeruginosa, although a common cause of nosocomial pneumonia, is rarely associated with community-acquired pneumonia in patients without underlying lung disease or severe debility.
Pneumonia due to "mouth flora" bacteria - by which is meant a combination of anaerobic and aerobic bacteria with the anaerobes usually predominating - occurs most frequently in patients suffering from alcoholism and poor oral hygiene and results from aspiration. The sputum is usually copious and often foul smelling. "Mouth flora" pneumonia in an edentulous patient should prompt suspicion of underlying lung cancer. A foul odor to the breath is present in many but not all of these patients. This form of pneumonia is often associated with lung abscess and with empyema due to bronchopleural fistula.
Mycoplasma pneumoniae pneumonia
Formerly known as the "Eaton agent", Mycoplasma pneumoniae is the most commonly identified cause of atypical pneumonia although its precise incidence is unknown. Various investigators have determined this microorganism to be the cause of 13% to 27% of community-acquired pneumonias. It can also cause hospital-acquired pneumonias, and it has caused as many as 50% of pneumonias during epidemics in closed populations. Mycoplasma pneumoniae pneumonia becomes less common after age 40, but older persons may experience more severe manifestations.
M. pneumoniae is a cell-wall-deficient organism with particular affinity for the respiratory tract epithelium. Many of the disease manifestations are now thought to be immune-mediated. Close, prolonged contact promotes transmission by respiratory secretions. There is currently interest in the extent to which M. pneumoniae accompanies other agents as a co-pathogen. In one study, an additional pathogen was found in about two-thirds of patients with M. pneumoniae pneumonia who required hospitalization; S. pneumoniae was most commonly found, but Legionella species and Chlamydia pneumoniae were also identified.
It is estimated that of persons infected with M. pneumoniae, about 20% are symptomatic, about 70% develop a mild respiratory illness (pharyngitis and/or tracheobronchitis), and fewer than 10% develop pneumonia. The disease occurs in all age groups including toddlers and the elderly but peaks between ages 5 to 15 years.
After an incubation period of about 3 weeks, symptoms begin gradually with fever, headache, malaise, chills, sore throat, substernal productive, and cough. The cough is initially non-productive, paroxysmal, and worse at night. It commonly becomes productive later in the illness. Physical examination is usually unimpressive. Bullous myringitis (inflammation of the tympanic membrane with bullae) is uncommon, occurring at most in about 5% of patients, but has a high positive predictive value for M. pneumoniae infection. More commonly there is mild tenderness over the paranasal sinuses, mild erythema of the posterior pharyngeal mucosa, soft cervical lymphadenopathy, and tracheal tenderness. Scattered râles and wheezes may be present but are usually unimpressive.
The white blood count is normal in 75% or more of cases. Thrombocytosis can occur as an acute-phase response. Liver enzymes, notably the aminotransferases (AST and ALT), are often mildly elevated. The chest x-ray commonly shows infiltrates that are much more extensive than one would have suspected from physical examination. The most common pattern is a peribronchial pneumonia in which thickened bronchial shadows are surrounded by streaky interstitial infiltrates and patchy atelectasis. Other patterns include nodular infiltrates and hilar lymphadenopathy. The lower lobes are most commonly involved, and pleural effusions - which can be especially severe in patients with sickle cell disease - occur in up to 20% of patients when carefully sought.
Extrapulmonary manifestations of M. pneumoniae pneumonia sometimes dominate the clinical picture and include hemolytic anemia, rashes including the life-threatening Stevens-Johnson syndrome, central nervous system complications (about 0.1% of patients, especially children), cardiac complications, and polyarthritis.
Chlamydia pneumoniae pneumonia
Chlamydia pneumoniae, described in 1986 as the TWAR agent, has been determined by some researchers to be the third or fourth most common cause of community-acquired pneumonia, explaining perhaps 10% to 14% of cases (up to 28% in some series). Pneumonia is recognized most frequently among the elderly, in whom it can be severe.
Chlamydia pneumoniae is classified as a bacterium on the basis of its cell wall and growth properties. Unlike most bacteria, however, it grows only as an intracellular parasite. Serologic studies suggest that most humans gain experience with C. pneumoniae at some point in their lives, although immunity is short-lived. About 50% of all persons have antibodies by age 20, and up to 75% of elderly persons are seropositive. It is also thought that most infections (up to 90%) are asymptomatic. Transmission is probably person-to-person by respiratory secretions.
After an incubation period of several weeks, most patients experience gradual onset of non-specific upper and lower respiratory symptoms including those of sinusitis, otitis, and pharyngitis. Sore throat with hoarseness is often prominent among the initial symptoms and tends to be the dominant symptom in college-aged persons. Symptoms of pneumonia tend to develop slowly. Often, patients have experienced symptoms for several weeks before seeking medical care. The history sometimes suggests a biphasic illness, as follows: (1) upper respiratory infection with sore throat that resolved, then (2) lower respiratory infection with cough.
The severity is age-dependent. Children under age 5 seldom have evidence of significant disease. University students often present with a 10-day history of sore throat or hoarseness with minimal fever. The mean age of patients with pneumonia is about 56 years. Ronchi and râles are present on physical examination more frequently than in M. pneumoniae pneumonia, even among patients who do not complain of cough. The white blood count is usually normal. Chest x-ray may show one or more infiltrates, the most common finding being a single, patchy, subsegmental infiltrate.
Wheezing is sometimes present. Accumulating evidence suggests that C. pneumoniae sometimes precipitates adult-onset asthma. Reported extrapulmonary manifestations of C. pneumoniae infection include meningoencephalitis, cerebellar dysfunction, Guillain-Barré syndrome, reactive arthritis, and myocarditis. The possibility that C. pneumoniae might cause coronary artery disease has received much attention. High antibodies to C. pneumoniae have been observed in patients with chronic obstructive lung disease, sarcoidosis, and lung cancer but an etiologic link is unclear.
Chlamydia psittaci (Psittacosis; Ornithosis)
About 100 to 200 cases of psittacosis are reported in the U.S. each year, but the true incidence is thought to be much higher. Mortality can be high if the diagnosis is not suspected.
Chlamydia psittaci infects many and perhaps all species of birds, which may remain asymptomatic or show symptoms and signs of illness such as anorexia, dyspnea, and ruffled feathers. Strains of C. psittaci that are most virulent for humans tend to be those associated with psittacine birds (from the Latin psittacus, or parrot), such as parrots, parakeets, macaws, cockatoos, and budgerigars, and also with turkeys. Humans who develop psittacosis are commonly bird fanciers or work in poultry farms (notably, turkey farms), abattoirs, processing plans, pet shops, or veterinarians’ offices. The organism is usually acquired by inhalation, but human-to-human transmission occurs on rare occasions.
After an incubation period of 5 to 15 days, patients develop symptoms and signs of illness ranging in severity from mild to life threatening. Atypical pneumonia, the most characteristic form of the disease, is manifest by headache, fever, and non-productive cough. Chest x-ray is usually abnormal (75%) of cases, most commonly showing consolidation of one lower lobe. The radiographic findings are usually much more striking than the findings on auscultation of the chest. Psittacosis can also present as a typhoidal illness (fever, malaise, relative bradycardia, hepatosplenomegaly), a non-specific flu-like "viral syndrome", a mononucleosis-like syndrome, or as fever of unknown origin.
Figure
This micrograph of a biopsied lung tissue specimen stained with the CDC's modified Dieterle silver impregnation procedure, revealed small, blunt, pleomorphic intracellular, and extracellular bacilli, which stain brown to black against a pale yellow background; Mag. 500x.
Dieterle’s stain is a preparation used when Legionella pneumophila bacteria are suspected. Uranyl nitrate is applied in order to first sensitize the slide mount, which is subsequently treated with gum mastic, followed by an incubation period, after which the slide is soaked in silver nitrate. Lastly, the slide is “developed” in a hydroquinone, sodium sulfite, acetone, formaldehyde, pyridine, and gum mastic bath. The Legionella pneumophila bacteria, if present, will stain black. CDC
Figure
This silver-stained micrograph of a lung tissue specimen revealed the presence of Legionella pneumophila bacteria. The specimen was taken from a victim of the 1976 Legionnaires’ disease outbreak in Philadelphia.
CDC
Figure
Legionella pneumophila multiplying inside a cultured human lung fibroblast
CDC
Figure
Anteroposterior x-ray reveals bilateral pulmonary infiltrates in a patient with Legionnaires' disease CDC
Legionnaire’s disease
First identified in 1976 during an outbreak at an American Legion Convention in Philadelphia, Legionnaire’s disease is now recognized as a relatively common cause of both community-acquired and hospital-acquired pneumonia. The incidence exhibits wide geographic variation - from less than 1% to more than 16% of community-acquired pneumonias - reflecting to a large extent the degree of contamination of water reservoirs by the causative organisms. Unlike pneumonias due to M. pneumoniae and C. pneumoniae, cases that can be treated on an outpatient basis tend to be the exception rather than the rule.
Legionella species are gram-negative bacteria that stain poorly and survive intracellularly. More than 40 species, and more than 60 serogroups, of Legionella are now recognized. Legionella pneumophila is the most commonly encountered species, causing at least 80% of clinical infections.
Legionellosis seems to be a disease of human progress brought about by devices that maintain water at warm temperatures and produce aerosols. In water, the organisms multiply within amebas; in humans they multiply within alveolar macrophages. The disease is spread by water rather than by person-to-person contact. Contamination of water sources has been associated with numerous outbreaks in settings ranging from inner-city hospitals to luxury cruise liners.
Clinically severe cases of Legionnaire’s disease tend to occur in persons with compromised host defenses, most often in the setting of chronic obstructive pulmonary disease, immunosuppression, or advanced age. A mild form of Legionellosis, known as Pontiac fever, is a self-limited disease presenting as fever, malaise, headaches, and chills without pneumonia. Pontiac fever resolves within a few days without antibiotic therapy. Legionnaire’s disease, the more familiar and more severe form of Legionellosis, affects persons of all ages and presents with symptoms that overlap those of "classic bacterial" and "atypical" pneumonia.
After an incubation period of 2 to 10 days, patients experience the onset of fever, headache, anorexia, malaise, and myalgia. At this point, respiratory symptoms are usually not prominent, the cough being only minimally productive. Some patients have chest pain and, if the sputum is blood-tinged, pulmonary embolism is often suspected. Gastrointestinal symptoms with nausea, vomiting, diarrhea, and abdominal pain can also dominate the clinical picture. Alternatively, neurologic symptoms can be the presenting complaint, variably manifested as headache, lethargy, and change in mental status.
Fever is usually present. Relative bradycardia is found more often in older patients and in those with severe pneumonia. Examination of the chest usually shows râles and, later in the illness, signs of consolidation. The peripheral blood commonly shows leukocytosis and thrombocytopenia. Hyponatremia (serum sodium < 130 mEq/L) is more common in Legionnaire’s disease than in most other pneumonias. Hypophosphatemia also occurs. There is frequently evidence of liver and renal dysfunction. Hematuria and proteinuria are common. There is no characteristic feature on chest x-ray. The most common pattern is a patchy infiltrate involving one lobe, which progresses to consolidation. Infiltrates can assume a diffuse or interstitial pattern, and pleural effusions are common.
CHAPTER FOUR
Sunday, April 18, 2010
INFECTIOUS DISEASES
INFECTIOUS DISEASE
CLINICAL INFECTIOUS DISEASE
INTRODUCTION
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Mankind has three great enemies, fever, famine, and war. And of these by far the greatest, by far the most terrible, is fever.
―William Osler, 1897
Infectious disease is one of the few genuine adventures left in the world. . . however secure and well regulated civilized life may become, bacteria, protozoa, viruses, infected fleas, lice, ticks, mosquitoes and bedbugs will always lurk in the shadows ready to pounce when neglect, poverty, famine or war lets down the defenses.
―Hans Zinsser, 1935
This graph illustrates the trends in infectious disease mortality in the United States from 1900 to 1996. With exception of the influenza pandemic of 1918, death rates due to infectious diseases decreased until around 1980, at which time several factors (including HIV-related mortality and antibiotic resistance) caused these rates to rise. This increasing trend in infectious disease mortality continued throughout the 1980s and 1990s.
CDC
Propionibacterium acnes is a very common obligate anaerobic, non-spore forming rod, and the etiologic pathogen responsible for acne vulgaris, or pimples. It normally resides in the sebaceous glands of the skin.
CDC/Bobby Strong
EPIDEMIOLOGY
Infections still cause about one-third of all deaths worldwide and are the leading cause of death, mainly because of disease in developing countries. In developed countries including the United States, improvements in sanitation and hygiene during the 19th century lowered the death rates from infectious diseases even before the dramatic impact of antimicrobial agents and new vaccines. However, recent data suggest that mortality due to infectious diseases in the United States is actually increasing. Between 1980 and 1992, mortality from infections increased by 58% and age-adjusted death rates increased by 39% (figure 1), so that taken as a group infectious diseases became the third leading cause of death (up from fifth in 1980). The epidemiology and pathogenesis of infection can be discussed in several complementary ways.
First, consider the formula for infection:
Likelihood of infection ≈ virulence of microorganism X number of microorganisms
host resistance
Microorganisms are virulent to the extent that they cause disease in previously healthy individuals; that is, when host resistance is high. Virulence is sometimes defined in terms of the percentage of infected persons who develop serious disease or, in some instances, as the case-fatality rate. Host resistance can be reduced because of localized or systemic disease or injury. Damaged or abnormal tissue that is easily infected is sometimes called a locus minoris resistentiae (place of least resistance).
A second framework for understanding infections is the epidemiologic triad or chain of infection:
Reservoir Means of transmission Susceptible host
A third framework for understanding infections concerns exogenous versus endogenous microorganisms. Exogenous infections arise from the animate or inanimate environment, whereas endogenous infections arise from the patient's flora.
Infectious disease is usually an accidental event in a world in which each of us lives intimately with billions of microorganisms. In many cases we depend on them, as they on us, for survival. Death is undesirable from the microbe’s perspective as well as ours.
Diphtheria is an acute bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae and occasionally C. ulcerans. It is transmitted through respiratory droplets and personal contact. Diphtheria affects the mucous membranes of the respiratory tract, known as “respiratory diphtheria”, the skin, termed “cutaneous diphtheria”, and occasionally other sites including the eyes, nose, or vagina
CDC/ Dr. P.B. Smith
Figure 3
In respiratory infections, viral infection facilitates invasion by colonizing aerobic bacteria such as S. pneumoniae and H. influenzae, which in turn facilitates superinfection by “normal flora” anaerobes
NORMAL AND COLONIZING BACTERIAL FLORA
Colonization begins at birth and is of two types:
• Permanent colonization by bacteria that are more-or-less expected to be part of the normal flora at all times
• Transient colonization by potential pathogens.
Examples of the former include “diphtheroid” bacteria (Propionibacterium and Corynebacterium species) (figures 2 and 3) on the skin, viridans streptococci in the oral cavity, and E. coli, enterococci, and Bacteroides species in the colon. Examples of the latter include Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis in the upper respiratory tract. Colonization is by no means a haphazard event. Microorganisms have on their surfaces specialized molecules called adhesins that bind with specific receptors on host epithelial cells or with extracellular matrix materials. An appreciation of the major components of the bodys normal and colonizing bacterial flora promotes understanding of many of the common infections encountered in clinical medicine.
In respiratory infections, for example, viral infection facilitates invasion by colonizing bacteria such as S. pneumoniae and H. influenzae, which in turn facilitates superinfection by “normal flora” anaerobes such as Prevotella, Fusobacteria, and Peptostreptococcus species (figure 3).
Methicillin-resistant Staphylococcus aureus bacteria, commonly referred to by the acronym, MRSA; Magnified 9560x.
CDC/ Janice Haney Carr/ Jeff Hageman, M.H.S.
Dynamics of colonization and infection by Staphylococcus aureus.
Cutaneous abscess located on the thigh caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). A clinician had lanced the lesion in order to allow the pus contained therein, to be released.
CDC/ Bruno Coignard, M.D.; Jeff Hageman, M.H.S.
Staphylococcus aureus
Potential sites of colonization by S. aureus (figure 4) include the skin, the perineal area, and the gastrointestinal tract, but by far the most important site is the nasal mucosa (anterior nares). S. aureus nasal carriage is extremely common. At a given time, 20% to 40% of adults are likely to have positive nasal swab cultures for S. aureus. Many persons (up to 25% of the population) are permanent nasal carriers of S. aureus. Most people (about 60% of the population) exhibit intermittent colonization with S. aureus, while some persons never show colonization. Because most of us (whether we admit it or not) put our fingers in our noses on a regular basis, person-to-person transmission of S. aureus by hand contact is a universal phenomenon. Viral upper respiratory infection in patients with S. aureus nasal colonization sometimes results in wide dispersal of the organism in the immediate environment; this phenomenon has long been recognized in pediatrics as “cloud babies,” but recently “cloud adults” have also been reported. Some persons with staphylococcal nasal colonization are prone to develop styes, folliculitis, or furunculosis (boils). Most, however, remain asymptomatic until the organism is given the opportunity to invade the skin on account of a wound, abrasion, vascular access line, or surgical procedure. Occasional persons develop S. aureus pneumonia, especially during influenza epidemics since influenza A increases the density of staphylococcal colonization. Staphylococcal bacteremia can arise from colonization, local infection, trauma, foreign bodies, or pneumonia. Complications of staphylococcal bacteremia, which often presents as a nonspecific flu-like illness, include septic shock, endocarditis, and metastatic infection (figure 5).
Of great current concern is the spread in communities throughout the United States of S. aureus strains that are resistant to antibiotics (these are commonly called “methicillin-resistant” or MRSA strains) and that are associated especially with skin abscesses (figure 6) and furuncles and with severe necrotizing pneumonia. These strains typically express the Panton-Valentine leukocidin, an exotoxin that induces pore formation in polymorphonuclear neutrophils and monocytes, leading to activation, degranulation, and release of inflammatory mediators.
Brain abscess
In this aspirate, gram-positive cocci form chains with peculiar configurations resembling balls of yarn. Organisms of the Streptococcus anginosus group (historically known as Streptococcus milleri) grew on this culture. The S. anginosus group is commonly isolated from brain abscesses
© Rebecca Buxton and
The Microbelibrary (Used with permission)
Viridans Streptococci
Most of the α-hemolytic streptococci present in the normal flora are loosely known as “viridans” (Latin viridis, “green”) because they cause green hemolysis on blood agar plates, but numerous individual species are now recognized on the basis of physiological, biochemical, and molecular typing methods. Under normal circumstances these bacteria comprise the major aerobic component of the flora of the human mouth, making up nearly 50% of all bacteria that can be cultured from saliva. Individual species of viridans streptococci occupy distinct ecologic niches. Streptococcus sanguis and S. mitis adhere preferentially to the buccal mucosa; S. salivarius and S. mitis to the dorsal surface of the tongue; while S. sanguis, S. mitis, S. oralis, S. gordonii, and S. anginosus are frequently found in dental plaques. S. mutans, which adheres to teeth in large numbers and ferments dietary sugars into acids, is strongly associated with dental caries―no doubt the world’s most prevalent bacterial infection. One group of viridans streptococci, variably known as the “S. milleri group” or “S. anginosus,” is associated with purulent infections including brain abscess (figure 7). Nearly all of the viridans streptococci occasionally cause endocarditis, usually in persons with diseased heart valves. With these 3 exceptions, colonization by viridans streptococci is nearly always harmless; indeed, it is highly beneficial since it provides resistance to colonization by more virulent microorganisms.
Acute group A streptococcal pharyngitis in an 8-year-old female patient. Note the acute inflammation of the right tonsil. It is enlarged with adherent plaque
© Lewis Tomalty and
The Microbelibrary
Mechanisms of disease due to Streptococcus pyogenes
Streptococcus pyogenes (group A streptococcus)
S. pyogenes is a major pathogen not only because of the frequency of streptococcal pharyngitis (figure 8) and impetigo but also because of the potential for life-threatening complications. Complacency engendered by the declining incidence of acute rheumatic fever has given way to renewed concern because of the streptococcal toxic shock syndrome and necrotizing fasciitis. S. pyogenes is a frequent colonizer of the human pharynx, especially in children where carriage rates of up to 20% have been reported. Asymptomatic colonization is less common in adults. Streptococcal M protein enables the organism to resist phagocytosis and multiply in blood. The development of antibodies against M protein confers lasting immunity, but unfortunately the immunity is type-specific and more than 90 types of M protein have been identified. The diverse manifestations of S. pyogenes infection are summarized in figure 9.
The streptococcal toxic shock syndrome is, simply put, any streptococcal infection associated with the sudden onset of shock and organ failure. Portals of entry are apparent in most cases. Some cases are associated with necrotizing fasciitis. Both pyrogenic exotoxins and certain M proteins seem to be capable of acting as “superantigens,” causing massive release of monocyte cytokines and lymphokines.
Gram stain of a sputum specimen from a patient with pneumonia. The Gram stain shows encapsulated lancet-shaped gram-positive cocci associated with the polymorphonuclear leukocytes. Note the clear zone surrounding the organisms. This zone is consistent with a large polysaccharide capsule that is not picked up by the Gram stain. These Gram stain findings are consistent with Streptococcus pneumoniae
© Gloria Delisle, Lewis Tomalty and The Microbelibrary
Streptococcus pneumoniae
Increasing resistance to β-lactam antibiotics and other drugs makes the pneumococcus a common cause of otitis media, sinusitis, pneumonia, meningitis, and other serious infections more dangerous today than at any time since the pre-antibiotic era. Most humans are intermittently colonized in the nasopharynx by this organism, especially during midwinter. Prevalence studies indicate that 20% to 40% of children and 5% to 10% of adults are colonized at a given time. From the nasopharynx, pneumococci have access to the eustachian tubes, the ostia to the paranasal sinuses, and the tracheobronchial tree.
Percentage of Nosocomial Enterococci Reported as Resistant to Vancomycin in Intensive Care Units and non-ICUs, 1989-1994 CDC
Gram-positive Group D Streptococcus bacteria magnified 320X.
Streptococci are subdivided into groups based on what antibodies recognize their surface antigens. Group D contains five species, S. faecalis, S. faecium, S. durans, S. avium, and S. bovis. CDC/Dr. Richard Facklam
Enterococci, Streptococcus bovis, and Group B Streptococci
Group D streptococci formerly included the enterococci, S. bovis, and S. equinus. Newer classifications give enterococci their own genus with at least 12 species, of which Enterococcus faecalis (80% to 90%) and E. faecium are the major isolates from humans. Enterococci form a major part of the normal flora of the lower gastrointestinal tract, being the predominant aerobic gram-positive bacteria in stools. Enterococci occasionally cause community-acquired urinary tract infection and endocarditis. However, the ability of enterococci to cause disease by themselves (that is, as sole pathogens) is limited. Enterococci are commonly involved in hospital-acquired infections are frequently isolated from urine of patients with obstructive uropathy and from wounds including decubitus ulcers. Resistance to numerous antibiotics complicates treatment of enterococcal infection (figure 11).
Streptococcus bovis (figure 12) is occasionally found in the human gastrointestinal tract, especially in patients with cancer or precancerous lesions of the bowel; documented S. bovis bacteremia is an indication for colonoscopy. Group B streptococci (S. agalactiae), found in genital tract or colon in 5% to 40% of women, are of concern primarily because of neonatal and puerperal sepsis but also cause disease in adults with impaired host defenses.
Neisseria meningitidis
The meningococcus is one of the few microorganisms capable of killing a previously-healthy person within a few hours. However, asymptomatic colonization is relatively common, being found in 18% of “normal” family members over a 32-month period. Asymptomatic carriage of meningococci leads to the development of protective antibodies directed against the organism’s polysaccharide capsule. Most cases of invasive meningococcal disease occur among the newly colonized. Studies suggest that adult males often bring the organism into a household; respiratory transmission leads to colonization of other family members, with children being the most likely victims of invasive disease.
Haemophilus influenzae and Moraxella catarrhalis
Haemophilus influenzae is a small, pleomorphic, aerobic, gram-negative coccobacillus found mainly in the upper respiratory tract. Some strains contain a polysaccharide capsule, the major virulence factor, and are typed (a through f) according to the nature of the capsule. Most instances of life-threatening disease such as meningitis are caused by type b strains. Wide deployment of the conjugate vaccine against Haemophilus influenzae type b has greatly diminished the importance of this scourge of early childhood. Non-encapsulated strains are frequently associated with sinusitis, otitis media, exacerbations of chronic bronchitis in patients with COPD, and conjunctivitis. About 30% to 80% of healthy persons have nasopharyngeal colonization by non-encapsulated strains of H. influenzae. About 2% to 4% of children were colonized by type B strains prior to the vaccine. H. influenzae, like N. meningitidis, preferentially colonizes non-ciliated epithelial cells in the nasopharynx.
Moraxella catarrhalis, previously known as Neisseria catarrhalis and then Branhamella catarrhalis is a gram-negative diplococcus associated with upper and lower respiratory infections in both children and adults. Up to two-thirds of infants, but only 1% to 5% of healthy adults, are colonized by this microorganism, which causes a spectrum of disease similar to that caused by H. influenzae.
Gram Stain of Urine
These short to medium-long gram-negative bacilli look like typical enteric gram-negative bacteria; isolation of Proteus mirabilis confirmed that impression
© Rebecca Buxton and
The Microbelibrary (Used with permission)
E. coli and Other Aerobic Gram-Negative Rods
Escherichia coli, the major aerobic gram-negative rod (bacillus) found in the lower gastrointestinal tract, is of enormous importance in primary care because of its role in (1) the great majority of cases of community-acquired urinary tract infection (UTI); (2) occasional deep tissue infectious such as vertebral osteomyelitis in patients with underlying medical problems; (3) rare cases of colitis caused by enteropathogenic or enterohemorrhagic strains; and (4) the well-publicized problem of hemorrhagic colitis and hemolytic syndrome due to strains belonging to the 0157:H7 serotype. All humans (excepting those who have received broad-spectrum antimicrobial therapy) are probably colonized with E. coli, but asymptomatic colonization with enteropathogenic or enterohemorrhagic strains is rare if it occurs at all.
Proteus mirabilis causes up to 10% of community-acquired UTIs and presumably colonizes the normal human gastrointestinal tract. Other aerobic gram-negative rods cause infections in patients with underlying diseases who have received broad-spectrum antimicrobial therapy. Klebsiella, Enterobacter, and Serratia species are often found in the stool flora of patients who have received broad-spectrum antibiotics. Pseudomonas aeruginosa can be part of the normal fecal flora but, unlike E. coli or Proteus mirabilis, is rarely associated with community-acquired UTI in the absence of a predisposing factor such as urologic instrumentation. Acinetobacter species, which often resist the action of soap, can be found in the skin flora in up to 25% of persons but rarely cause community-acquired disease. Salmonella and Shigella species are not considered part of the normal intestinal flora.
ANAEROBIC BACTERIA
Anaerobic bacteria are operationally defined by their failure to grow on solid media in the presence of 10% carbon dioxide (or 18% oxygen). Most of the common aerobic bacteria encountered in medicine can grow under anaerobic conditions as well, and are therefore sometimes called “facultative” (that is, they can grow either aerobically or anaerobically). The term “anaerobic” is usually reserved for strict anaerobes. Quantitatively, these bacteria are the most important component of the normal human flora. Thus, saliva contains 107 to 108 anaerobic bacteria/mL; the terminal ileum 104 to 106/mL; and the colon, where anaerobes outnumber aerobes by a ratio of about 1000:1, 1011 or more per gram of stool (dry weight). Anaerobes are also highly prevalent in the normal flora of the skin, vagina, and periurethral tissues. Anaerobic bacteria are commonly found in odontogenic infections including infected root canals, chronic sinusitis, chronic otitis media, and pelvic inflammatory disease. Otherwise, anaerobic bacteria rarely assume importance in primary care unless (1) the patient has serious underlying disease or (2) the infection is of such severity that hospitalization is clearly indicated. This is the case because anaerobic bacteria cause serious infection only when there has been a major disruption of tissue (for example, a wound or perforated bowel) or when the oxidation-reduction potential has been lowered (for example, by ischemia, necrotic tumors, or foreign bodies). To the contrary, anaerobic bacteria are of major importance to human well being since they protect against colonization by more pathogenic organisms.
When anaerobic bacteria cause disease, they generally arise from the indigenous body flora. The major exception is the clostridial syndromes such as tetanus (Clostridium tetani) and botulism (Cl. botulinum). The species most commonly isolated from deep tissue infections include peptostreptococci (“anaerobic streptococci”), which are normally present in all of the sites mentioned above; Prevotella, Porphyromonas, and Fusobacterium species, which are normally present in the oral cavity; and the Bacteroides fragilis group of bacteria, which make up the bulk of the normal fecal flora. The most important clue to an anaerobic infection is its foul odor. This finding is diagnostic though present in only about one-half of cases. Other clues include tissue gas (observed as bullae or as crepitation on physical examination, or found on x-ray); tissue necrosis, the presence of multiple bacterial morphologies on Gram’s stain of a specimen, and the failure of bacteria to grow on a routine aerobic culture (“sterile pus”). Settings in which anaerobic bacteria should always be suspected include bite wounds, aspiration pneumonia, lung abscess, pleural empyema, brain abscess, necrotizing fasciitis, myonecrosis (gas gangrene), diabetic foot ulcers, decubitus ulcers, and septic thrombophlebitis.
Figure 14
When the prevalence of a disease in a population is extremely low, the probability that a positive test is a false -postive is very high even when the test is a good one
From Bayes’s theorem, it follows that the relationship between the prevalence of a disease and the probability that a screening test result is false-positive rather than true-positive is hyperbolic rather than linear.
DIAGNOSIS AND CLINICAL REASONING
Diagnosis is of two types: presumptive and definitive. Presumptive diagnosis is usually based on the history and physical examination, sometimes supported by laboratory and radiographic findings. Definitive etiologic diagnosis usually requires cultures and serologic methods. In primary care, most diagnoses of infectious diseases are presumptive. This is understandable, since the conditions most commonly encountered tend to be self-limited and often involve the upper respiratory tract. For seriously ill patients including hospitalized patients, definitive diagnosis is usually desirable although sometimes difficult to achieve. Some principles of diagnosis include the following:
• Assume the worst-case scenario
• Search for a syndrome
• Look for atypical features
• Pay attention to the peripheral blood smear
• Perform diagnostic testing only when the results will alter patient management, but arrange for close follow-up
• Arrange for follow-up (“tincture of time”)
• Document the level of diagnostic certainty
• “Think” tuberculosis and endocarditis
The major categories of clinical reasoning are, in ascending order of importance: (1) pattern recognition; (2) probabilistic thinking; and (3) pathophysiology. Consider, for example, an 18-year-old woman with chief complaint of burning on urination. Pattern recognition and probabilistic thinking suggests uncomplicated UTI and hence a quick prescription for a 3-day course of antimicrobial therapy. The pathophysiologic approach, however, would be to ask further questions directed at determining whether the dysuria is external rather than internal and whether risk factors for sexually transmitted disease (STD) are present. One then determines whether to perform a pelvic examination and obtain studies for STD as well as a urine culture before beginning therapy.
What diagnostic tests should be obtained, and when? Generations of medical students have learned such gems as Sutton’s law ("Go where the money is," after Willie Sutton, the bank robber), Occam’s razor ("Seek the one, simplest explanation," after William of Occam, the philosopher), and Anselm’s ass ("Do something; don’t just stand there in the middle" - the animal was tethered between 2 bales of hay, both just out of reach). A better and more sophisticated approach is to consider the properties of tests within the context of probability theory.
All clinicians must be familiar with “sensitivity,” “specificity,” and related terms. Sensitivity basically means “positive in disease”―we say a test is 99% sensitive if positive test results are obtained in 99% of persons to have the disease by one or another gold standard, such as biopsy or autopsy. Specificity basically means “negative in health”―we say that a test is 99% specific if positive test results are obtained in only 1% of persons who clearly do not have the disease. However, it is extremely important to consider “sensitivity,” “specificity,” and related concepts in the context of pre-test probability―the likelihood that the patient has the disease.
This concept is best captured by Bayes’s theorem, which holds that the likelihood that a positive test result is actually false-positive rather than true-positive varies inversely with the prevalence of the disease in the population. This concept can be grasped by careful study of figure 14. The likelihood that a positive test result is false-positive rather than true-positive is 100% if nobody in the population represented by the patient has the disease, but 0% if everybody has the disease. Between these extreme cases, the relationship is described not by a straight line but rather than by a hyperbolic curve. The upshot is that if the pre-test probability is extremely low, then the chances are overwhelming that a positive screening test result is actually a false-positive result even if the sensitivity and specificity of the test are superb.
Increasingly, the concept of pre-test probability is being expressed as the likelihood ratio, and nomograms are available for evaluating of the usefulness of a test.
INFECTION CONTROL
Rigorous infection control is a moral imperative and legal requirement. All medical personnel should know the basic principles of disease transmission and control. Let us briefly review disease transmission as it applies to preventing infection in the office setting:
• Contact transmission involves person-to-person or object-to-person touching of mucous membranes or open skin. This is an important means of transmission of staphylococci, Clostridium difficile, and some respiratory viruses including respiratory syncytial virus. Frequent handwashing is the major defense against contact transmission, but attention should also be paid to routine disinfection of stethoscopes, toys, bathroom fixtures, and other objects with patient care areas.
• Droplet transmission involves coughing, sneezing, or suctioning procedures (as in bronchoscopy), resulting in a spray of secretions capable of contacting conjunctiva, nasal mucosa, and lips within a 3-foot radius. This is an important means of transmission of meningococci, influenza viruses, and pertussis. The use of eye protection including goggles and shields during certain procedures is a defense against droplet transmission.
• Airborne transmission involves inhalation of particles that are much smaller than droplets, often referred to as “droplet nuclei.” This is an important means of transmission when organisms remain suspended in the air after coughing in the form of “droplet nuclei,” as in tuberculosis (pulmonary and laryngeal), chickenpox, and measles (rubeola). Masks, ultraviolet lights, and immunization constitute some of the defenses.
• Vehicle transmission by contaminated items, although now uncommon in health care settings as a result of tight regulations, still occurs and can cause outbreaks of even epidemics. Causes include use of expired medications or antiseptics, irrigation fluids that have been left in open containers, and use of diluted bleach solution that is over 24 hours old. Disease frequently involved organisms that survive well in water such as Pseudomonas species. Defenses include monitoring refrigerator temperatures, checking for expired medications, discarding irrigation solutions without preservatives at the end of the day of opening, and selecting disinfectants that do not require dilution.
• Vector transmission by insects or animals is extremely rare in today’s health care facilities.
All health care workers should know their tuberculin skin status and their immunization status against measles (rubeola), mumps, rubella, hepatitis B, and varicella-zoster virus. It is important to protect both our patients and ourselves—primum non nocere!
CLINICAL INFECTIOUS DISEASE
INTRODUCTION
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Mankind has three great enemies, fever, famine, and war. And of these by far the greatest, by far the most terrible, is fever.
―William Osler, 1897
Infectious disease is one of the few genuine adventures left in the world. . . however secure and well regulated civilized life may become, bacteria, protozoa, viruses, infected fleas, lice, ticks, mosquitoes and bedbugs will always lurk in the shadows ready to pounce when neglect, poverty, famine or war lets down the defenses.
―Hans Zinsser, 1935
This graph illustrates the trends in infectious disease mortality in the United States from 1900 to 1996. With exception of the influenza pandemic of 1918, death rates due to infectious diseases decreased until around 1980, at which time several factors (including HIV-related mortality and antibiotic resistance) caused these rates to rise. This increasing trend in infectious disease mortality continued throughout the 1980s and 1990s.
CDC
Propionibacterium acnes is a very common obligate anaerobic, non-spore forming rod, and the etiologic pathogen responsible for acne vulgaris, or pimples. It normally resides in the sebaceous glands of the skin.
CDC/Bobby Strong
EPIDEMIOLOGY
Infections still cause about one-third of all deaths worldwide and are the leading cause of death, mainly because of disease in developing countries. In developed countries including the United States, improvements in sanitation and hygiene during the 19th century lowered the death rates from infectious diseases even before the dramatic impact of antimicrobial agents and new vaccines. However, recent data suggest that mortality due to infectious diseases in the United States is actually increasing. Between 1980 and 1992, mortality from infections increased by 58% and age-adjusted death rates increased by 39% (figure 1), so that taken as a group infectious diseases became the third leading cause of death (up from fifth in 1980). The epidemiology and pathogenesis of infection can be discussed in several complementary ways.
First, consider the formula for infection:
Likelihood of infection ≈ virulence of microorganism X number of microorganisms
host resistance
Microorganisms are virulent to the extent that they cause disease in previously healthy individuals; that is, when host resistance is high. Virulence is sometimes defined in terms of the percentage of infected persons who develop serious disease or, in some instances, as the case-fatality rate. Host resistance can be reduced because of localized or systemic disease or injury. Damaged or abnormal tissue that is easily infected is sometimes called a locus minoris resistentiae (place of least resistance).
A second framework for understanding infections is the epidemiologic triad or chain of infection:
Reservoir Means of transmission Susceptible host
A third framework for understanding infections concerns exogenous versus endogenous microorganisms. Exogenous infections arise from the animate or inanimate environment, whereas endogenous infections arise from the patient's flora.
Infectious disease is usually an accidental event in a world in which each of us lives intimately with billions of microorganisms. In many cases we depend on them, as they on us, for survival. Death is undesirable from the microbe’s perspective as well as ours.
Diphtheria is an acute bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae and occasionally C. ulcerans. It is transmitted through respiratory droplets and personal contact. Diphtheria affects the mucous membranes of the respiratory tract, known as “respiratory diphtheria”, the skin, termed “cutaneous diphtheria”, and occasionally other sites including the eyes, nose, or vagina
CDC/ Dr. P.B. Smith
Figure 3
In respiratory infections, viral infection facilitates invasion by colonizing aerobic bacteria such as S. pneumoniae and H. influenzae, which in turn facilitates superinfection by “normal flora” anaerobes
NORMAL AND COLONIZING BACTERIAL FLORA
Colonization begins at birth and is of two types:
• Permanent colonization by bacteria that are more-or-less expected to be part of the normal flora at all times
• Transient colonization by potential pathogens.
Examples of the former include “diphtheroid” bacteria (Propionibacterium and Corynebacterium species) (figures 2 and 3) on the skin, viridans streptococci in the oral cavity, and E. coli, enterococci, and Bacteroides species in the colon. Examples of the latter include Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis in the upper respiratory tract. Colonization is by no means a haphazard event. Microorganisms have on their surfaces specialized molecules called adhesins that bind with specific receptors on host epithelial cells or with extracellular matrix materials. An appreciation of the major components of the bodys normal and colonizing bacterial flora promotes understanding of many of the common infections encountered in clinical medicine.
In respiratory infections, for example, viral infection facilitates invasion by colonizing bacteria such as S. pneumoniae and H. influenzae, which in turn facilitates superinfection by “normal flora” anaerobes such as Prevotella, Fusobacteria, and Peptostreptococcus species (figure 3).
Methicillin-resistant Staphylococcus aureus bacteria, commonly referred to by the acronym, MRSA; Magnified 9560x.
CDC/ Janice Haney Carr/ Jeff Hageman, M.H.S.
Dynamics of colonization and infection by Staphylococcus aureus.
Cutaneous abscess located on the thigh caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). A clinician had lanced the lesion in order to allow the pus contained therein, to be released.
CDC/ Bruno Coignard, M.D.; Jeff Hageman, M.H.S.
Staphylococcus aureus
Potential sites of colonization by S. aureus (figure 4) include the skin, the perineal area, and the gastrointestinal tract, but by far the most important site is the nasal mucosa (anterior nares). S. aureus nasal carriage is extremely common. At a given time, 20% to 40% of adults are likely to have positive nasal swab cultures for S. aureus. Many persons (up to 25% of the population) are permanent nasal carriers of S. aureus. Most people (about 60% of the population) exhibit intermittent colonization with S. aureus, while some persons never show colonization. Because most of us (whether we admit it or not) put our fingers in our noses on a regular basis, person-to-person transmission of S. aureus by hand contact is a universal phenomenon. Viral upper respiratory infection in patients with S. aureus nasal colonization sometimes results in wide dispersal of the organism in the immediate environment; this phenomenon has long been recognized in pediatrics as “cloud babies,” but recently “cloud adults” have also been reported. Some persons with staphylococcal nasal colonization are prone to develop styes, folliculitis, or furunculosis (boils). Most, however, remain asymptomatic until the organism is given the opportunity to invade the skin on account of a wound, abrasion, vascular access line, or surgical procedure. Occasional persons develop S. aureus pneumonia, especially during influenza epidemics since influenza A increases the density of staphylococcal colonization. Staphylococcal bacteremia can arise from colonization, local infection, trauma, foreign bodies, or pneumonia. Complications of staphylococcal bacteremia, which often presents as a nonspecific flu-like illness, include septic shock, endocarditis, and metastatic infection (figure 5).
Of great current concern is the spread in communities throughout the United States of S. aureus strains that are resistant to antibiotics (these are commonly called “methicillin-resistant” or MRSA strains) and that are associated especially with skin abscesses (figure 6) and furuncles and with severe necrotizing pneumonia. These strains typically express the Panton-Valentine leukocidin, an exotoxin that induces pore formation in polymorphonuclear neutrophils and monocytes, leading to activation, degranulation, and release of inflammatory mediators.
Brain abscess
In this aspirate, gram-positive cocci form chains with peculiar configurations resembling balls of yarn. Organisms of the Streptococcus anginosus group (historically known as Streptococcus milleri) grew on this culture. The S. anginosus group is commonly isolated from brain abscesses
© Rebecca Buxton and
The Microbelibrary (Used with permission)
Viridans Streptococci
Most of the α-hemolytic streptococci present in the normal flora are loosely known as “viridans” (Latin viridis, “green”) because they cause green hemolysis on blood agar plates, but numerous individual species are now recognized on the basis of physiological, biochemical, and molecular typing methods. Under normal circumstances these bacteria comprise the major aerobic component of the flora of the human mouth, making up nearly 50% of all bacteria that can be cultured from saliva. Individual species of viridans streptococci occupy distinct ecologic niches. Streptococcus sanguis and S. mitis adhere preferentially to the buccal mucosa; S. salivarius and S. mitis to the dorsal surface of the tongue; while S. sanguis, S. mitis, S. oralis, S. gordonii, and S. anginosus are frequently found in dental plaques. S. mutans, which adheres to teeth in large numbers and ferments dietary sugars into acids, is strongly associated with dental caries―no doubt the world’s most prevalent bacterial infection. One group of viridans streptococci, variably known as the “S. milleri group” or “S. anginosus,” is associated with purulent infections including brain abscess (figure 7). Nearly all of the viridans streptococci occasionally cause endocarditis, usually in persons with diseased heart valves. With these 3 exceptions, colonization by viridans streptococci is nearly always harmless; indeed, it is highly beneficial since it provides resistance to colonization by more virulent microorganisms.
Acute group A streptococcal pharyngitis in an 8-year-old female patient. Note the acute inflammation of the right tonsil. It is enlarged with adherent plaque
© Lewis Tomalty and
The Microbelibrary
Mechanisms of disease due to Streptococcus pyogenes
Streptococcus pyogenes (group A streptococcus)
S. pyogenes is a major pathogen not only because of the frequency of streptococcal pharyngitis (figure 8) and impetigo but also because of the potential for life-threatening complications. Complacency engendered by the declining incidence of acute rheumatic fever has given way to renewed concern because of the streptococcal toxic shock syndrome and necrotizing fasciitis. S. pyogenes is a frequent colonizer of the human pharynx, especially in children where carriage rates of up to 20% have been reported. Asymptomatic colonization is less common in adults. Streptococcal M protein enables the organism to resist phagocytosis and multiply in blood. The development of antibodies against M protein confers lasting immunity, but unfortunately the immunity is type-specific and more than 90 types of M protein have been identified. The diverse manifestations of S. pyogenes infection are summarized in figure 9.
The streptococcal toxic shock syndrome is, simply put, any streptococcal infection associated with the sudden onset of shock and organ failure. Portals of entry are apparent in most cases. Some cases are associated with necrotizing fasciitis. Both pyrogenic exotoxins and certain M proteins seem to be capable of acting as “superantigens,” causing massive release of monocyte cytokines and lymphokines.
Gram stain of a sputum specimen from a patient with pneumonia. The Gram stain shows encapsulated lancet-shaped gram-positive cocci associated with the polymorphonuclear leukocytes. Note the clear zone surrounding the organisms. This zone is consistent with a large polysaccharide capsule that is not picked up by the Gram stain. These Gram stain findings are consistent with Streptococcus pneumoniae
© Gloria Delisle, Lewis Tomalty and The Microbelibrary
Streptococcus pneumoniae
Increasing resistance to β-lactam antibiotics and other drugs makes the pneumococcus a common cause of otitis media, sinusitis, pneumonia, meningitis, and other serious infections more dangerous today than at any time since the pre-antibiotic era. Most humans are intermittently colonized in the nasopharynx by this organism, especially during midwinter. Prevalence studies indicate that 20% to 40% of children and 5% to 10% of adults are colonized at a given time. From the nasopharynx, pneumococci have access to the eustachian tubes, the ostia to the paranasal sinuses, and the tracheobronchial tree.
Percentage of Nosocomial Enterococci Reported as Resistant to Vancomycin in Intensive Care Units and non-ICUs, 1989-1994 CDC
Gram-positive Group D Streptococcus bacteria magnified 320X.
Streptococci are subdivided into groups based on what antibodies recognize their surface antigens. Group D contains five species, S. faecalis, S. faecium, S. durans, S. avium, and S. bovis. CDC/Dr. Richard Facklam
Enterococci, Streptococcus bovis, and Group B Streptococci
Group D streptococci formerly included the enterococci, S. bovis, and S. equinus. Newer classifications give enterococci their own genus with at least 12 species, of which Enterococcus faecalis (80% to 90%) and E. faecium are the major isolates from humans. Enterococci form a major part of the normal flora of the lower gastrointestinal tract, being the predominant aerobic gram-positive bacteria in stools. Enterococci occasionally cause community-acquired urinary tract infection and endocarditis. However, the ability of enterococci to cause disease by themselves (that is, as sole pathogens) is limited. Enterococci are commonly involved in hospital-acquired infections are frequently isolated from urine of patients with obstructive uropathy and from wounds including decubitus ulcers. Resistance to numerous antibiotics complicates treatment of enterococcal infection (figure 11).
Streptococcus bovis (figure 12) is occasionally found in the human gastrointestinal tract, especially in patients with cancer or precancerous lesions of the bowel; documented S. bovis bacteremia is an indication for colonoscopy. Group B streptococci (S. agalactiae), found in genital tract or colon in 5% to 40% of women, are of concern primarily because of neonatal and puerperal sepsis but also cause disease in adults with impaired host defenses.
Neisseria meningitidis
The meningococcus is one of the few microorganisms capable of killing a previously-healthy person within a few hours. However, asymptomatic colonization is relatively common, being found in 18% of “normal” family members over a 32-month period. Asymptomatic carriage of meningococci leads to the development of protective antibodies directed against the organism’s polysaccharide capsule. Most cases of invasive meningococcal disease occur among the newly colonized. Studies suggest that adult males often bring the organism into a household; respiratory transmission leads to colonization of other family members, with children being the most likely victims of invasive disease.
Haemophilus influenzae and Moraxella catarrhalis
Haemophilus influenzae is a small, pleomorphic, aerobic, gram-negative coccobacillus found mainly in the upper respiratory tract. Some strains contain a polysaccharide capsule, the major virulence factor, and are typed (a through f) according to the nature of the capsule. Most instances of life-threatening disease such as meningitis are caused by type b strains. Wide deployment of the conjugate vaccine against Haemophilus influenzae type b has greatly diminished the importance of this scourge of early childhood. Non-encapsulated strains are frequently associated with sinusitis, otitis media, exacerbations of chronic bronchitis in patients with COPD, and conjunctivitis. About 30% to 80% of healthy persons have nasopharyngeal colonization by non-encapsulated strains of H. influenzae. About 2% to 4% of children were colonized by type B strains prior to the vaccine. H. influenzae, like N. meningitidis, preferentially colonizes non-ciliated epithelial cells in the nasopharynx.
Moraxella catarrhalis, previously known as Neisseria catarrhalis and then Branhamella catarrhalis is a gram-negative diplococcus associated with upper and lower respiratory infections in both children and adults. Up to two-thirds of infants, but only 1% to 5% of healthy adults, are colonized by this microorganism, which causes a spectrum of disease similar to that caused by H. influenzae.
Gram Stain of Urine
These short to medium-long gram-negative bacilli look like typical enteric gram-negative bacteria; isolation of Proteus mirabilis confirmed that impression
© Rebecca Buxton and
The Microbelibrary (Used with permission)
E. coli and Other Aerobic Gram-Negative Rods
Escherichia coli, the major aerobic gram-negative rod (bacillus) found in the lower gastrointestinal tract, is of enormous importance in primary care because of its role in (1) the great majority of cases of community-acquired urinary tract infection (UTI); (2) occasional deep tissue infectious such as vertebral osteomyelitis in patients with underlying medical problems; (3) rare cases of colitis caused by enteropathogenic or enterohemorrhagic strains; and (4) the well-publicized problem of hemorrhagic colitis and hemolytic syndrome due to strains belonging to the 0157:H7 serotype. All humans (excepting those who have received broad-spectrum antimicrobial therapy) are probably colonized with E. coli, but asymptomatic colonization with enteropathogenic or enterohemorrhagic strains is rare if it occurs at all.
Proteus mirabilis causes up to 10% of community-acquired UTIs and presumably colonizes the normal human gastrointestinal tract. Other aerobic gram-negative rods cause infections in patients with underlying diseases who have received broad-spectrum antimicrobial therapy. Klebsiella, Enterobacter, and Serratia species are often found in the stool flora of patients who have received broad-spectrum antibiotics. Pseudomonas aeruginosa can be part of the normal fecal flora but, unlike E. coli or Proteus mirabilis, is rarely associated with community-acquired UTI in the absence of a predisposing factor such as urologic instrumentation. Acinetobacter species, which often resist the action of soap, can be found in the skin flora in up to 25% of persons but rarely cause community-acquired disease. Salmonella and Shigella species are not considered part of the normal intestinal flora.
ANAEROBIC BACTERIA
Anaerobic bacteria are operationally defined by their failure to grow on solid media in the presence of 10% carbon dioxide (or 18% oxygen). Most of the common aerobic bacteria encountered in medicine can grow under anaerobic conditions as well, and are therefore sometimes called “facultative” (that is, they can grow either aerobically or anaerobically). The term “anaerobic” is usually reserved for strict anaerobes. Quantitatively, these bacteria are the most important component of the normal human flora. Thus, saliva contains 107 to 108 anaerobic bacteria/mL; the terminal ileum 104 to 106/mL; and the colon, where anaerobes outnumber aerobes by a ratio of about 1000:1, 1011 or more per gram of stool (dry weight). Anaerobes are also highly prevalent in the normal flora of the skin, vagina, and periurethral tissues. Anaerobic bacteria are commonly found in odontogenic infections including infected root canals, chronic sinusitis, chronic otitis media, and pelvic inflammatory disease. Otherwise, anaerobic bacteria rarely assume importance in primary care unless (1) the patient has serious underlying disease or (2) the infection is of such severity that hospitalization is clearly indicated. This is the case because anaerobic bacteria cause serious infection only when there has been a major disruption of tissue (for example, a wound or perforated bowel) or when the oxidation-reduction potential has been lowered (for example, by ischemia, necrotic tumors, or foreign bodies). To the contrary, anaerobic bacteria are of major importance to human well being since they protect against colonization by more pathogenic organisms.
When anaerobic bacteria cause disease, they generally arise from the indigenous body flora. The major exception is the clostridial syndromes such as tetanus (Clostridium tetani) and botulism (Cl. botulinum). The species most commonly isolated from deep tissue infections include peptostreptococci (“anaerobic streptococci”), which are normally present in all of the sites mentioned above; Prevotella, Porphyromonas, and Fusobacterium species, which are normally present in the oral cavity; and the Bacteroides fragilis group of bacteria, which make up the bulk of the normal fecal flora. The most important clue to an anaerobic infection is its foul odor. This finding is diagnostic though present in only about one-half of cases. Other clues include tissue gas (observed as bullae or as crepitation on physical examination, or found on x-ray); tissue necrosis, the presence of multiple bacterial morphologies on Gram’s stain of a specimen, and the failure of bacteria to grow on a routine aerobic culture (“sterile pus”). Settings in which anaerobic bacteria should always be suspected include bite wounds, aspiration pneumonia, lung abscess, pleural empyema, brain abscess, necrotizing fasciitis, myonecrosis (gas gangrene), diabetic foot ulcers, decubitus ulcers, and septic thrombophlebitis.
Figure 14
When the prevalence of a disease in a population is extremely low, the probability that a positive test is a false -postive is very high even when the test is a good one
From Bayes’s theorem, it follows that the relationship between the prevalence of a disease and the probability that a screening test result is false-positive rather than true-positive is hyperbolic rather than linear.
DIAGNOSIS AND CLINICAL REASONING
Diagnosis is of two types: presumptive and definitive. Presumptive diagnosis is usually based on the history and physical examination, sometimes supported by laboratory and radiographic findings. Definitive etiologic diagnosis usually requires cultures and serologic methods. In primary care, most diagnoses of infectious diseases are presumptive. This is understandable, since the conditions most commonly encountered tend to be self-limited and often involve the upper respiratory tract. For seriously ill patients including hospitalized patients, definitive diagnosis is usually desirable although sometimes difficult to achieve. Some principles of diagnosis include the following:
• Assume the worst-case scenario
• Search for a syndrome
• Look for atypical features
• Pay attention to the peripheral blood smear
• Perform diagnostic testing only when the results will alter patient management, but arrange for close follow-up
• Arrange for follow-up (“tincture of time”)
• Document the level of diagnostic certainty
• “Think” tuberculosis and endocarditis
The major categories of clinical reasoning are, in ascending order of importance: (1) pattern recognition; (2) probabilistic thinking; and (3) pathophysiology. Consider, for example, an 18-year-old woman with chief complaint of burning on urination. Pattern recognition and probabilistic thinking suggests uncomplicated UTI and hence a quick prescription for a 3-day course of antimicrobial therapy. The pathophysiologic approach, however, would be to ask further questions directed at determining whether the dysuria is external rather than internal and whether risk factors for sexually transmitted disease (STD) are present. One then determines whether to perform a pelvic examination and obtain studies for STD as well as a urine culture before beginning therapy.
What diagnostic tests should be obtained, and when? Generations of medical students have learned such gems as Sutton’s law ("Go where the money is," after Willie Sutton, the bank robber), Occam’s razor ("Seek the one, simplest explanation," after William of Occam, the philosopher), and Anselm’s ass ("Do something; don’t just stand there in the middle" - the animal was tethered between 2 bales of hay, both just out of reach). A better and more sophisticated approach is to consider the properties of tests within the context of probability theory.
All clinicians must be familiar with “sensitivity,” “specificity,” and related terms. Sensitivity basically means “positive in disease”―we say a test is 99% sensitive if positive test results are obtained in 99% of persons to have the disease by one or another gold standard, such as biopsy or autopsy. Specificity basically means “negative in health”―we say that a test is 99% specific if positive test results are obtained in only 1% of persons who clearly do not have the disease. However, it is extremely important to consider “sensitivity,” “specificity,” and related concepts in the context of pre-test probability―the likelihood that the patient has the disease.
This concept is best captured by Bayes’s theorem, which holds that the likelihood that a positive test result is actually false-positive rather than true-positive varies inversely with the prevalence of the disease in the population. This concept can be grasped by careful study of figure 14. The likelihood that a positive test result is false-positive rather than true-positive is 100% if nobody in the population represented by the patient has the disease, but 0% if everybody has the disease. Between these extreme cases, the relationship is described not by a straight line but rather than by a hyperbolic curve. The upshot is that if the pre-test probability is extremely low, then the chances are overwhelming that a positive screening test result is actually a false-positive result even if the sensitivity and specificity of the test are superb.
Increasingly, the concept of pre-test probability is being expressed as the likelihood ratio, and nomograms are available for evaluating of the usefulness of a test.
INFECTION CONTROL
Rigorous infection control is a moral imperative and legal requirement. All medical personnel should know the basic principles of disease transmission and control. Let us briefly review disease transmission as it applies to preventing infection in the office setting:
• Contact transmission involves person-to-person or object-to-person touching of mucous membranes or open skin. This is an important means of transmission of staphylococci, Clostridium difficile, and some respiratory viruses including respiratory syncytial virus. Frequent handwashing is the major defense against contact transmission, but attention should also be paid to routine disinfection of stethoscopes, toys, bathroom fixtures, and other objects with patient care areas.
• Droplet transmission involves coughing, sneezing, or suctioning procedures (as in bronchoscopy), resulting in a spray of secretions capable of contacting conjunctiva, nasal mucosa, and lips within a 3-foot radius. This is an important means of transmission of meningococci, influenza viruses, and pertussis. The use of eye protection including goggles and shields during certain procedures is a defense against droplet transmission.
• Airborne transmission involves inhalation of particles that are much smaller than droplets, often referred to as “droplet nuclei.” This is an important means of transmission when organisms remain suspended in the air after coughing in the form of “droplet nuclei,” as in tuberculosis (pulmonary and laryngeal), chickenpox, and measles (rubeola). Masks, ultraviolet lights, and immunization constitute some of the defenses.
• Vehicle transmission by contaminated items, although now uncommon in health care settings as a result of tight regulations, still occurs and can cause outbreaks of even epidemics. Causes include use of expired medications or antiseptics, irrigation fluids that have been left in open containers, and use of diluted bleach solution that is over 24 hours old. Disease frequently involved organisms that survive well in water such as Pseudomonas species. Defenses include monitoring refrigerator temperatures, checking for expired medications, discarding irrigation solutions without preservatives at the end of the day of opening, and selecting disinfectants that do not require dilution.
• Vector transmission by insects or animals is extremely rare in today’s health care facilities.
All health care workers should know their tuberculin skin status and their immunization status against measles (rubeola), mumps, rubella, hepatitis B, and varicella-zoster virus. It is important to protect both our patients and ourselves—primum non nocere!
SWINE FLU
SWINE FLU
DEFINITION OF SWINE FLU
• Is a flu that occurs in pigs and in rare cases is passed from pigs to human. The strain now circulating is worrisome because it can pass from person to person. Like human flu, the effects of swine flu can range from mild to severe.
• It has human, pig and avian virus strains
INITIAL OUTBREAK IN U.S. AND MEXICO
• Analysis has suggested that the H1N1 strain responsible for the current outbreak first evolved around September 2008.
• The new strain was first diagnosed in two children by the CDC (Centers for Disease Control), on April 14 in San Diego County, California.
• The outbreak was first detected in Mexico City, where surveillance began picking up a surge in cases of influenza-like illness starting March 18, 2009.
• It was assumed as “late-season flu”
INTERNATIONAL CASES
• The outbreak comes at the beginning of the flu season for Southern Hemisphere countries such as New
Zealand, Australia, South Africa and parts of the South America.
• Other countries like Canada, UK, Spain, Germany, Italy and Panama also had cases with Swine Flu.
• On May 2, it was announced that a Canadian farm worker who had traveled to Mexico had transmitted the disease to a herd of pigs, showing that the disease can still move between species.
DEBATE OVER NAME
• Some authorities object to calling the flu outbreak “Swine Flu” to avoid suggestions that eating pork products carried a risk of infection.
• In the Netherlands, it was originally called “pig flu”
• National Health Institute and Media called it as “Mexican Flu”
• South Korea and Israel called it as “Mexican Virus”, then later it was called by the South Korean Press “SI”, short name for “Swine Influenza”
SCIENTIFIC NAME OR COMMON NAME
• Finland suggested the names “ Sika Flunssa” and Shalah Pietari Flunssa”
• Taiwan suggested the names “H1N1 flu” or “New flu”, which most local media now used it.
• The World Organization for Animal Health has proposed the name “ North American Influenza”
• The European Commission uses the term “novel flu virus”
• The WHO announced they would refer to the new influenza virus as Influenza A (H1N1) or “Influenza A (H1N1) virus
• The outbreak has also been called the “H1N1 influenza”, “2009 H1N1 flu” or “swine-origin influenza”.
GENES PRESENT IN SWINE FLU
• Haemagglutinin-similar to that of swine flu virus present in U.S. pigs since 1999
• Neuraminidase and Matrix Protein genes-resembled version present in European swine flu isolates
• RNA polymerase subunit-avian North America
• RNA polymerase subunit PB1 human 1993
H1N1 INFECTIONS AND TRANSMISSION
Influenza viruses happen naturally among pigs, hogs and boars. Swine influenza is very contagious among swine. It can make some domesticated pigs very sick.
It is unusual for humans to catch swine flu viruses, but occasional cases happen, usually in people who have contact with infected pigs. Swine flu viruses have also been reported to spread from person to person in the past but previous episodes of transmission were very limited.
The recent infections are caused by anew strain or type of the swine flu virus known as type A, which infects both human and animals, subtype H1N1. That is why the flu is called influenza A H1N1 or simply H1N1 flu.
Flu viruses are spread from person to person when infected people cough or sneeze, sometimes people may become infected by touching something with flu viruses on it and then touching their mouth or nose.
Infected people may be able to infect others beginning one day before symptoms develop & up to seven or more days after becoming sick, children, especially younger children, might be contagious for longer periods.
SIGNS AND SYMPTOMS
In children some emergency warning signs include:
Fast breathing or trouble breathing
Bluish skin color
Not drinking enough fluid
High or prolonged fever
You should also seek immediate medical attention if you notice changes in your childs’ mental status such as:
Not waking up
Not interacting
Extreme irritability and not wanting to be held
In adults, some emergency warning signs that need urgent medical attention:
Difficulty breathing, shortness of breath
Pain or pressure in the chest/abdomen
Sudden dizziness
Near-fainting/fainting
Confusion
Severe or persistent vomiting
High or prolonged fever
TREATMENT
Antiviral drugs are prescription medications that can help the flu by keeping flu viruses from reproducing in your body. These include pills, liquids or inhalers.
Antiviral medications must be taken within 48 hours after symptoms appear.
Other treatments that should work for H1N1 flu include rest, medications to bring down a high fever and drinking plenty of water. If complications happen & you become very sick, hospitalization may be needed.
Hospitalized patients may be given oxygen/ use a respirator. Children or teenagers with a flu should get plenty of rest and drink lots of liquids. The medicines that they take to relieve their symptoms should not contain aspirin. Giving aspirin to children and teenagers who have influenza can cause Reye Syndrome.
PREVENTION
1. Wash your hands often with soap and water.
2. Use alcohol to clean hands.
3. When sneezing or coughing cover your mouth and nose with your elbow
or use a tissue and throw away the tissue after used. Then, wash your
hands after you sneeze or cough.
DEFINITION OF SWINE FLU
• Is a flu that occurs in pigs and in rare cases is passed from pigs to human. The strain now circulating is worrisome because it can pass from person to person. Like human flu, the effects of swine flu can range from mild to severe.
• It has human, pig and avian virus strains
INITIAL OUTBREAK IN U.S. AND MEXICO
• Analysis has suggested that the H1N1 strain responsible for the current outbreak first evolved around September 2008.
• The new strain was first diagnosed in two children by the CDC (Centers for Disease Control), on April 14 in San Diego County, California.
• The outbreak was first detected in Mexico City, where surveillance began picking up a surge in cases of influenza-like illness starting March 18, 2009.
• It was assumed as “late-season flu”
INTERNATIONAL CASES
• The outbreak comes at the beginning of the flu season for Southern Hemisphere countries such as New
Zealand, Australia, South Africa and parts of the South America.
• Other countries like Canada, UK, Spain, Germany, Italy and Panama also had cases with Swine Flu.
• On May 2, it was announced that a Canadian farm worker who had traveled to Mexico had transmitted the disease to a herd of pigs, showing that the disease can still move between species.
DEBATE OVER NAME
• Some authorities object to calling the flu outbreak “Swine Flu” to avoid suggestions that eating pork products carried a risk of infection.
• In the Netherlands, it was originally called “pig flu”
• National Health Institute and Media called it as “Mexican Flu”
• South Korea and Israel called it as “Mexican Virus”, then later it was called by the South Korean Press “SI”, short name for “Swine Influenza”
SCIENTIFIC NAME OR COMMON NAME
• Finland suggested the names “ Sika Flunssa” and Shalah Pietari Flunssa”
• Taiwan suggested the names “H1N1 flu” or “New flu”, which most local media now used it.
• The World Organization for Animal Health has proposed the name “ North American Influenza”
• The European Commission uses the term “novel flu virus”
• The WHO announced they would refer to the new influenza virus as Influenza A (H1N1) or “Influenza A (H1N1) virus
• The outbreak has also been called the “H1N1 influenza”, “2009 H1N1 flu” or “swine-origin influenza”.
GENES PRESENT IN SWINE FLU
• Haemagglutinin-similar to that of swine flu virus present in U.S. pigs since 1999
• Neuraminidase and Matrix Protein genes-resembled version present in European swine flu isolates
• RNA polymerase subunit-avian North America
• RNA polymerase subunit PB1 human 1993
H1N1 INFECTIONS AND TRANSMISSION
Influenza viruses happen naturally among pigs, hogs and boars. Swine influenza is very contagious among swine. It can make some domesticated pigs very sick.
It is unusual for humans to catch swine flu viruses, but occasional cases happen, usually in people who have contact with infected pigs. Swine flu viruses have also been reported to spread from person to person in the past but previous episodes of transmission were very limited.
The recent infections are caused by anew strain or type of the swine flu virus known as type A, which infects both human and animals, subtype H1N1. That is why the flu is called influenza A H1N1 or simply H1N1 flu.
Flu viruses are spread from person to person when infected people cough or sneeze, sometimes people may become infected by touching something with flu viruses on it and then touching their mouth or nose.
Infected people may be able to infect others beginning one day before symptoms develop & up to seven or more days after becoming sick, children, especially younger children, might be contagious for longer periods.
SIGNS AND SYMPTOMS
In children some emergency warning signs include:
Fast breathing or trouble breathing
Bluish skin color
Not drinking enough fluid
High or prolonged fever
You should also seek immediate medical attention if you notice changes in your childs’ mental status such as:
Not waking up
Not interacting
Extreme irritability and not wanting to be held
In adults, some emergency warning signs that need urgent medical attention:
Difficulty breathing, shortness of breath
Pain or pressure in the chest/abdomen
Sudden dizziness
Near-fainting/fainting
Confusion
Severe or persistent vomiting
High or prolonged fever
TREATMENT
Antiviral drugs are prescription medications that can help the flu by keeping flu viruses from reproducing in your body. These include pills, liquids or inhalers.
Antiviral medications must be taken within 48 hours after symptoms appear.
Other treatments that should work for H1N1 flu include rest, medications to bring down a high fever and drinking plenty of water. If complications happen & you become very sick, hospitalization may be needed.
Hospitalized patients may be given oxygen/ use a respirator. Children or teenagers with a flu should get plenty of rest and drink lots of liquids. The medicines that they take to relieve their symptoms should not contain aspirin. Giving aspirin to children and teenagers who have influenza can cause Reye Syndrome.
PREVENTION
1. Wash your hands often with soap and water.
2. Use alcohol to clean hands.
3. When sneezing or coughing cover your mouth and nose with your elbow
or use a tissue and throw away the tissue after used. Then, wash your
hands after you sneeze or cough.
PRINCIPLES AND STRATEGIES OF TEACHING IN HEALTH EDUCATION SYLLABUS
UNIVERSIDAD DE ZAMBOANGA
SCHOOL OF ALLIED MEDICINE
Medical Technology Department
COURSE SYLLABUS
PRINCIPLES AND STRATEGIES OF TEACHING IN HEALTH EDUCATION
S.Y. 2009-2010 (First Semester)
Course Description : This course deals with the principles and
teaching/learning strategies in health education including adult learning, the roles of a teacher/medical technologist in different settings. It also includes strategies that enhance critical, clinical laboratory teaching, assessing and evaluating learning.
Course Credit : 3 units lecture (no laboratory)
Contact Hours : 3 hours per week
Total of 54 hours per semester
Prerequisite : Health Care
Placement : Fourth Year, First Semester
Course Objectives : At the end of the course, the students should be able to;
1. explain teaching/learning processes;
2. relate the learning experiences in the practice of
the profession;
3. internalize the values in different roles;
4. apply principles, methods and strategies in
different settings;
5. prepare a sample course syllabus;
6. recognize the values of traditional teaching
activity-based teaching, distance learning
teaching psychomotor skills;
7. assess critical thinking and clinical laboratory
Teaching;
8. evaluate learning.
Teaching Methodology: Brain Storming, Demonstration, Group Discussion, Lecture
Course Outline
PRE-MID
Contact Hours: 14 hours lecture
I. Introduction
1. Teaching and Learning Process
• Teaching
• Learning
Learning Theories
a. Classical Conditioning
b. Operant Conditioning
c. Social Conditioning
2. The “How” of Teaching
a. Strategies
b. Approach
c. Technique
d. Method
3. Teaching Approaches
a. Discovery
b. Conceptual
c. Process
d. Unified
4. Instructional Media
5. Health Education
II. Roles, Functions and Characteristics of a Health Professional in Education
The Teacher
a. Characteristics of a Good Teacher
b. Professional Competence
c. Interpersonal Relationship
d. Teaching/Evaluation Practices
e. The Teacher/Medical Technologist and his/her Roles in Guidance
f. As a Motivator
1. Ways to motivate the learners
2. Medical Technologist in the Community
III. Principles of Teaching and Learning
Teaching as a Process
a. As a Process or a “Giving Off Process”
b. As involving More of the Learner than a Teacher
c. As a System of Actions and Interactions
d. As an Adjunctive Act
e. As Providing the Learner with Basic Tools of Learning
f. As Inherently a Humane Activity
g. As Structuring the Learning Environment
h. As an Inquiry Process
i. As a Complex
j. As a Science and as an Art
k. Teaching Applying the Principles of other Significantly Related Disciplines
MID TERM
Contact Hours: 13 hours lecture
I. Learning Theories and Styles
1. Behavioral Theories
2. Cognitive Learning Theories
3. Social Cognitive Theory
4. Types of Learning
a. Signal Learning
b. Stimulus Response Learning
c. Chaining
d. Verbal Association
e. Discrimination Learning
f. Concept Learning
g. Rule Learning
h. Problem Solving
5. Learning Styles
a. Learning Style Models
-Kolb’s Theory of Experimental Learning
-Gregore Cognitive Styles Models
-Field Independence
-Dependence Model
b. Matching Learning Styles
II. Adult Learning
1. A Model of Adult Learning
2. Comparison of Pedagogy from Andradogy
3. Propositions of Learning
4. Gagne’s Condition of Learning
III. Planning and Conducting Classes
1. Planning Sequence
2. Course Syllabus
a. Primary Purpose
b. Functions
c. Developing a Course Outline/Syllabus
d. Formulation of Objectives: Types and Characteristics
e. Determination of Strategies/Methods to be used
f. Selection of Appropriate Instructional Materials
g. Determination of Time Allotment
h. Evaluation of Student Performance
i. Taxonomy of Objectives
1. Cognitive Domain
2. Affective Domain
3. Psychomotor Domain
j. Selecting and Organizing Content
k. Planning Assignments
l. Conducting a Class
PRE-FINAL
Contact Hours: 14 hours lecture
I. Teaching Strategies
a. Traditional Teaching
• Lecture Method
• Integrated Method
-Lecture/Discussion
-Lecture/Demonstration
-Demonstration/Return Demonstration
• Questioning Method
• Use of Audio-Visuals
• Interactive Lecture (Class Discussion)
• Film Showing Method
• Reporting Method/Discussion/Report Back Session
b. Other Common Teaching Methods
• Case Study Method
• Role Playing Method
• Buzz Session
• Debate Forum
• Panel Forum/Round Table Conference
• Symposium/Seminar/Workshop
• Deductive/Inductive
c. Activity-Based Teaching Strategies
• Cooperative Learning
• Simulations
• Problem Based Learning
• Self-Learning Modules
d. Computer Teaching Strategies
• Computer Technology and Learning
• Computer Assisted Instruction
• Computer Managed Instruction
• The Internet
II. Distance Learning
a. Advantages and Disadvantages of Distance Learning
b. Clinical Education in Distance Learning
c. Interactive Television Classes
d. Distance Learning via the Internet
III. Teaching Psychomotor and Promoting/ Assessing Critical Thinking
a. History of Teaching Psychomotor skills
b. Psychomotor Skills
-Phases of Skill Learning
-Promoting and Assessing Critical Thinking
c. Learning Psychomotor Skills
d. Teaching Skills
e. Assessment of Psychomotor Skill Learning
FINAL
Contact Hours: 13 hours lecture
I. Promoting and Assessing Critical Thinking
a. Aspects of Critical Thinking
b. Distinguishing Critical Thinking fro Other Technology Concepts
c. Ways we inhibit the Critical Thinking of Medical Technology Students
II. Strategies that Enhance Critical Thinking
a. Discussion
b. Asking Effective Questions
c. Test Interaction
d. Problem-Based Learning
e. Concept Mapping
f. Positive Learning Environment
g. Assessing Critical Thinking
III. Clinical Teaching
a. Purposes of Clinical Laboratory
b. Models of Clinical Teaching
c. Preparation for Clinical Instruction
d. Conducting a Clinical Laboratory Session
e. Evaluating Learner Progress
f. Clinical Laboratory Evaluation Tools
IV. Assessing and Evaluating Learning
a. Test Blueprint
b. Multiple-Choice Questions
c. True-False Questions
d. Essay-Type Questions
e. Test Item Analysis
f. Item Discrimination
REFERENCES:
Bustos, A. et al (1996). Psychological, Anthropological and
Sociological Foundations of Education, Revised Ed. II. Katha
Publishing Co. Inc., Philippines
De Young, Sandra (2002). Teaching Strategies for Nurse Educators.
Pearson, South Asia. New Jersey
Salandanan, Gloria (2008), Teaching Approaches and Strategies.
Revised Ed. Katha Publishing Co. Inc., Philippines
Larzabal, Amparo (1999). Theory and Practice in Student Teaching.
Katha Publishing Co. Inc., Philippines
SCHOOL OF ALLIED MEDICINE
Medical Technology Department
COURSE SYLLABUS
PRINCIPLES AND STRATEGIES OF TEACHING IN HEALTH EDUCATION
S.Y. 2009-2010 (First Semester)
Course Description : This course deals with the principles and
teaching/learning strategies in health education including adult learning, the roles of a teacher/medical technologist in different settings. It also includes strategies that enhance critical, clinical laboratory teaching, assessing and evaluating learning.
Course Credit : 3 units lecture (no laboratory)
Contact Hours : 3 hours per week
Total of 54 hours per semester
Prerequisite : Health Care
Placement : Fourth Year, First Semester
Course Objectives : At the end of the course, the students should be able to;
1. explain teaching/learning processes;
2. relate the learning experiences in the practice of
the profession;
3. internalize the values in different roles;
4. apply principles, methods and strategies in
different settings;
5. prepare a sample course syllabus;
6. recognize the values of traditional teaching
activity-based teaching, distance learning
teaching psychomotor skills;
7. assess critical thinking and clinical laboratory
Teaching;
8. evaluate learning.
Teaching Methodology: Brain Storming, Demonstration, Group Discussion, Lecture
Course Outline
PRE-MID
Contact Hours: 14 hours lecture
I. Introduction
1. Teaching and Learning Process
• Teaching
• Learning
Learning Theories
a. Classical Conditioning
b. Operant Conditioning
c. Social Conditioning
2. The “How” of Teaching
a. Strategies
b. Approach
c. Technique
d. Method
3. Teaching Approaches
a. Discovery
b. Conceptual
c. Process
d. Unified
4. Instructional Media
5. Health Education
II. Roles, Functions and Characteristics of a Health Professional in Education
The Teacher
a. Characteristics of a Good Teacher
b. Professional Competence
c. Interpersonal Relationship
d. Teaching/Evaluation Practices
e. The Teacher/Medical Technologist and his/her Roles in Guidance
f. As a Motivator
1. Ways to motivate the learners
2. Medical Technologist in the Community
III. Principles of Teaching and Learning
Teaching as a Process
a. As a Process or a “Giving Off Process”
b. As involving More of the Learner than a Teacher
c. As a System of Actions and Interactions
d. As an Adjunctive Act
e. As Providing the Learner with Basic Tools of Learning
f. As Inherently a Humane Activity
g. As Structuring the Learning Environment
h. As an Inquiry Process
i. As a Complex
j. As a Science and as an Art
k. Teaching Applying the Principles of other Significantly Related Disciplines
MID TERM
Contact Hours: 13 hours lecture
I. Learning Theories and Styles
1. Behavioral Theories
2. Cognitive Learning Theories
3. Social Cognitive Theory
4. Types of Learning
a. Signal Learning
b. Stimulus Response Learning
c. Chaining
d. Verbal Association
e. Discrimination Learning
f. Concept Learning
g. Rule Learning
h. Problem Solving
5. Learning Styles
a. Learning Style Models
-Kolb’s Theory of Experimental Learning
-Gregore Cognitive Styles Models
-Field Independence
-Dependence Model
b. Matching Learning Styles
II. Adult Learning
1. A Model of Adult Learning
2. Comparison of Pedagogy from Andradogy
3. Propositions of Learning
4. Gagne’s Condition of Learning
III. Planning and Conducting Classes
1. Planning Sequence
2. Course Syllabus
a. Primary Purpose
b. Functions
c. Developing a Course Outline/Syllabus
d. Formulation of Objectives: Types and Characteristics
e. Determination of Strategies/Methods to be used
f. Selection of Appropriate Instructional Materials
g. Determination of Time Allotment
h. Evaluation of Student Performance
i. Taxonomy of Objectives
1. Cognitive Domain
2. Affective Domain
3. Psychomotor Domain
j. Selecting and Organizing Content
k. Planning Assignments
l. Conducting a Class
PRE-FINAL
Contact Hours: 14 hours lecture
I. Teaching Strategies
a. Traditional Teaching
• Lecture Method
• Integrated Method
-Lecture/Discussion
-Lecture/Demonstration
-Demonstration/Return Demonstration
• Questioning Method
• Use of Audio-Visuals
• Interactive Lecture (Class Discussion)
• Film Showing Method
• Reporting Method/Discussion/Report Back Session
b. Other Common Teaching Methods
• Case Study Method
• Role Playing Method
• Buzz Session
• Debate Forum
• Panel Forum/Round Table Conference
• Symposium/Seminar/Workshop
• Deductive/Inductive
c. Activity-Based Teaching Strategies
• Cooperative Learning
• Simulations
• Problem Based Learning
• Self-Learning Modules
d. Computer Teaching Strategies
• Computer Technology and Learning
• Computer Assisted Instruction
• Computer Managed Instruction
• The Internet
II. Distance Learning
a. Advantages and Disadvantages of Distance Learning
b. Clinical Education in Distance Learning
c. Interactive Television Classes
d. Distance Learning via the Internet
III. Teaching Psychomotor and Promoting/ Assessing Critical Thinking
a. History of Teaching Psychomotor skills
b. Psychomotor Skills
-Phases of Skill Learning
-Promoting and Assessing Critical Thinking
c. Learning Psychomotor Skills
d. Teaching Skills
e. Assessment of Psychomotor Skill Learning
FINAL
Contact Hours: 13 hours lecture
I. Promoting and Assessing Critical Thinking
a. Aspects of Critical Thinking
b. Distinguishing Critical Thinking fro Other Technology Concepts
c. Ways we inhibit the Critical Thinking of Medical Technology Students
II. Strategies that Enhance Critical Thinking
a. Discussion
b. Asking Effective Questions
c. Test Interaction
d. Problem-Based Learning
e. Concept Mapping
f. Positive Learning Environment
g. Assessing Critical Thinking
III. Clinical Teaching
a. Purposes of Clinical Laboratory
b. Models of Clinical Teaching
c. Preparation for Clinical Instruction
d. Conducting a Clinical Laboratory Session
e. Evaluating Learner Progress
f. Clinical Laboratory Evaluation Tools
IV. Assessing and Evaluating Learning
a. Test Blueprint
b. Multiple-Choice Questions
c. True-False Questions
d. Essay-Type Questions
e. Test Item Analysis
f. Item Discrimination
REFERENCES:
Bustos, A. et al (1996). Psychological, Anthropological and
Sociological Foundations of Education, Revised Ed. II. Katha
Publishing Co. Inc., Philippines
De Young, Sandra (2002). Teaching Strategies for Nurse Educators.
Pearson, South Asia. New Jersey
Salandanan, Gloria (2008), Teaching Approaches and Strategies.
Revised Ed. Katha Publishing Co. Inc., Philippines
Larzabal, Amparo (1999). Theory and Practice in Student Teaching.
Katha Publishing Co. Inc., Philippines
GENERAL PATHOLOGY, HISTOPATHOLOGIC AND CYTOLOGIC TECHNIQUES SYLLABUS
UNIVERSIDAD DE ZAMBOANGA
SCHOOL OF ALLIED MEDICINE
Medical Technology Department
COURSE SYLLABUS
GENERAL PATHOLOGY, HISTOPATHOLOGIC AND CYTOLOGIC TECHNIQUES
S.Y. 2009-2010 (First Semester)
Course Description : This is divided into three. The first part deals with
the study of basic disease processes, correlating the etiology of disease with the course of development of anatomic and clinical changes brought about by the disease. The second part is a study of the histologic techniques essential in the production of histologic slides for the diagnosis of diseases including special staining procedures. The third part is the study and identification of cells in the diagnosis of diseases using cytologic technique.
Course Credit : 3 units (2 units lecture and 1 unit laboratory)
Contact Hours : 1 hour lecture and 3 hours laboratory per week
Total of 36 hours lecture and 54 hours laboratory per
semester
Prerequisite : Histology
Placement : Fourth Year, First Semester
Course Objectives : At the end of the course, the students should be able to;
1. discuss the basic concept of disease formation;
2. explain the physiologic changes brought about by
the various diseases;
3. discuss step by step procedure in tissue
preparation;
4. recognize the concepts of quality assurance
program in Histopathology laboratory;
5. Acquire the necessary skills required in the
preparation of slides for microscopic
examination of tissues from fresh state to
mounted state.
6. apply the knowledge acquired about diseases in
daily living;
7. manifest the following values: honesty, critical
thinking, empathy and value for life.
Teaching Methodology: Brain Storming, Demonstration, Group Discussion, Lecture
Course Outline
PRE-MID
Contact Hours: 9 hours lecture: 14 hours laboratory
I. Review : Fundamentals of Normal Histology
• Normal cell structure
• Cell in tissues, types and sub-types of tissues and their location
• Cellular adaptation: terminologies (atrophy, hypertrophy, hyperplasia, dysplasia, hypoplasia, agenesis etc.
II. Introduction to Pathology
• Definition of terms (pathology, pathogenesis, pathologist, medical technologist, autopsy, biopsy etc.)
• Divisions of p\Pathology
Gross and Microscopic Pathology
Anatomic Pathology
Clinical Pathology
• Nature of Diseases
Definition of terms (disease, health etiology etc.)
Describe manifestation of disease
Signs
Symptoms
Course of Disease
• Factors predisposing an individual to disease
Definition of terms (disease, health etiology etc.)
III. Etiology of Disease
• Classification of diseases according to the basic etiologic mechanisms, their features and laboratory findings
Hereditary disorders and congenital anomalies
Circulatory disorders
Metabolic disorders and disturbance
Deficiency diseases
Disorders of the immune system
Neoplasms
Disorders caused by air pollution, chemical and physical injuries
Extrinsic
Intrinsic
MID TERM
Contact Hours: 9 hours lecture: 13 hours laboratory
Routine Histotechniques
• Collection and Handling of Histological Specimens
• Steps in tissue processing
Fixation
-definition
-good characteristics of fixative agents
-components of fixative agents
-steps in fixation
-uses of fixative agents
Decalcification
-definition
-good characteristics of decalcifying agents
-components of decalcifying agents
-steps in decalcification
-uses of decalcifying agents
Dehydration
-definition
-good characteristics of dehydrating agents
-components of dehydrating agents
-steps in dehydration
-uses of dehydrating agents
PRE FINAL TERM
Contact Hours: 9 hours lecture: 14 hours laboratory
Routine Histotechniques
Steps in tissue processing
Clearing
-definition
-good characteristics of clearing agents
-components of clearing agents
-steps in clearing tissues
-uses of clearing agents
Impregnation
-definition
-good characteristics
-components
-steps in impregnation
-uses
Embedding
-definition
-good characteristics
-components
-steps
-uses
Trimming and Cutting of Tissue Sections
-definition
-good characteristics
-steps
FINAL TERM
Contact Hours: 9 hours lecture: 13 hours laboratory
Routine Histotechniques
Steps in tissue processing
Mounting of tissue sections
Staining
-definition
-good characteristics
-components
-steps
-uses
Difficulties encountered during tissue processing and the corresponding remedies
Special processing techniques
-Rapid processing techniques
-Preparation of bone marrow section
-Enzyme histo
Exfoliative cytology
-Definition of terms
-Collection of specimens
-Preparation, fixation, staining of smears
-vaginal cytology
LABORATORY EXERCISES;
1. Laboratory safety
2. Instrumentation
3. Paper Mold Making
4. Sharpening of Knife
5. General Procedure for Tissue Processing
6. Trimming
7. Rotary Microtome
8. Adhesive Preparation
9. Section Cutting
10. Staining of Sections
11. Mounting
12. Labeling
13. Pap’s Staining
REFERENCES: Gregorios, J. (2006). Histopathologic Techniques, 2nd Ed.Goodwill
Trading Co.,Inc. Philippines
Raphael, S. Lynch’s Medical Laboratory Technology, 4th Ed. MW
Publishing Inc. USA
SCHOOL OF ALLIED MEDICINE
Medical Technology Department
COURSE SYLLABUS
GENERAL PATHOLOGY, HISTOPATHOLOGIC AND CYTOLOGIC TECHNIQUES
S.Y. 2009-2010 (First Semester)
Course Description : This is divided into three. The first part deals with
the study of basic disease processes, correlating the etiology of disease with the course of development of anatomic and clinical changes brought about by the disease. The second part is a study of the histologic techniques essential in the production of histologic slides for the diagnosis of diseases including special staining procedures. The third part is the study and identification of cells in the diagnosis of diseases using cytologic technique.
Course Credit : 3 units (2 units lecture and 1 unit laboratory)
Contact Hours : 1 hour lecture and 3 hours laboratory per week
Total of 36 hours lecture and 54 hours laboratory per
semester
Prerequisite : Histology
Placement : Fourth Year, First Semester
Course Objectives : At the end of the course, the students should be able to;
1. discuss the basic concept of disease formation;
2. explain the physiologic changes brought about by
the various diseases;
3. discuss step by step procedure in tissue
preparation;
4. recognize the concepts of quality assurance
program in Histopathology laboratory;
5. Acquire the necessary skills required in the
preparation of slides for microscopic
examination of tissues from fresh state to
mounted state.
6. apply the knowledge acquired about diseases in
daily living;
7. manifest the following values: honesty, critical
thinking, empathy and value for life.
Teaching Methodology: Brain Storming, Demonstration, Group Discussion, Lecture
Course Outline
PRE-MID
Contact Hours: 9 hours lecture: 14 hours laboratory
I. Review : Fundamentals of Normal Histology
• Normal cell structure
• Cell in tissues, types and sub-types of tissues and their location
• Cellular adaptation: terminologies (atrophy, hypertrophy, hyperplasia, dysplasia, hypoplasia, agenesis etc.
II. Introduction to Pathology
• Definition of terms (pathology, pathogenesis, pathologist, medical technologist, autopsy, biopsy etc.)
• Divisions of p\Pathology
Gross and Microscopic Pathology
Anatomic Pathology
Clinical Pathology
• Nature of Diseases
Definition of terms (disease, health etiology etc.)
Describe manifestation of disease
Signs
Symptoms
Course of Disease
• Factors predisposing an individual to disease
Definition of terms (disease, health etiology etc.)
III. Etiology of Disease
• Classification of diseases according to the basic etiologic mechanisms, their features and laboratory findings
Hereditary disorders and congenital anomalies
Circulatory disorders
Metabolic disorders and disturbance
Deficiency diseases
Disorders of the immune system
Neoplasms
Disorders caused by air pollution, chemical and physical injuries
Extrinsic
Intrinsic
MID TERM
Contact Hours: 9 hours lecture: 13 hours laboratory
Routine Histotechniques
• Collection and Handling of Histological Specimens
• Steps in tissue processing
Fixation
-definition
-good characteristics of fixative agents
-components of fixative agents
-steps in fixation
-uses of fixative agents
Decalcification
-definition
-good characteristics of decalcifying agents
-components of decalcifying agents
-steps in decalcification
-uses of decalcifying agents
Dehydration
-definition
-good characteristics of dehydrating agents
-components of dehydrating agents
-steps in dehydration
-uses of dehydrating agents
PRE FINAL TERM
Contact Hours: 9 hours lecture: 14 hours laboratory
Routine Histotechniques
Steps in tissue processing
Clearing
-definition
-good characteristics of clearing agents
-components of clearing agents
-steps in clearing tissues
-uses of clearing agents
Impregnation
-definition
-good characteristics
-components
-steps in impregnation
-uses
Embedding
-definition
-good characteristics
-components
-steps
-uses
Trimming and Cutting of Tissue Sections
-definition
-good characteristics
-steps
FINAL TERM
Contact Hours: 9 hours lecture: 13 hours laboratory
Routine Histotechniques
Steps in tissue processing
Mounting of tissue sections
Staining
-definition
-good characteristics
-components
-steps
-uses
Difficulties encountered during tissue processing and the corresponding remedies
Special processing techniques
-Rapid processing techniques
-Preparation of bone marrow section
-Enzyme histo
Exfoliative cytology
-Definition of terms
-Collection of specimens
-Preparation, fixation, staining of smears
-vaginal cytology
LABORATORY EXERCISES;
1. Laboratory safety
2. Instrumentation
3. Paper Mold Making
4. Sharpening of Knife
5. General Procedure for Tissue Processing
6. Trimming
7. Rotary Microtome
8. Adhesive Preparation
9. Section Cutting
10. Staining of Sections
11. Mounting
12. Labeling
13. Pap’s Staining
REFERENCES: Gregorios, J. (2006). Histopathologic Techniques, 2nd Ed.Goodwill
Trading Co.,Inc. Philippines
Raphael, S. Lynch’s Medical Laboratory Technology, 4th Ed. MW
Publishing Inc. USA
HISTOLOGY SYLLABUS
UNIVERSIDAD DE ZAMBOANGA
SCHOOL OF ALLIED MEDICINE
Medical Technology Department
COURSE SYLLABUS
HISTOLOGY
S.Y. 2009-2010 (First Semester)
Course Description : This course deals with the study of the
fundamentals of cells, tissues and organs with emphasis on
microscopic structure, characteristics and functions.
Course Credit : 2 units (1 unit lecture and 1 unit laboratory)
Contact Hours : 1 hour lecture and 3 hours laboratory per week
Total of 18 hours lecture and 54 hours laboratory per
Semester
Prerequisite : Human Anatomy and Physiology
Placement : Third Year, First Semester
Course Objectives : At the end of the course, the students must be able to;
1. explain the fundamentals of cells and tissues;
2. explain the different characteristics and functions of the microscopic structure of human cells, tissues and organs;
3. recognize the morphologic/microscopic features of different groups of cells;
4. explain the cellular functions of organelles and their functional interrelationship;
5. manifest the following values: integrity, critical thinking, honesty, creativity and concern for others.
Teaching Methodology: Brain Storming, Demonstration, Group Discussion, Lecture
Course Outline
PRE-MID
Contact Hours: 4 hours lecture: 14 hours laboratory
I. Introduction/Orientation
• Definition of Terms
• Significance of Histology to the Med. Tech. Profession
II. The Cell
• Function and Structure
• Cell Physiology
• Cell Division
III. Epithelial Cells
• Forms and Characteristics
• Nomenclature and Specialization
• General Biology
MID TERM
Contact Hours: 5 hours lecture: 14 hours laboratory
I. Connective Tissue
• Composition
• Types
• Histophysiology
II. Adipose
III. Cartilage
IV. Bone
• Cells
• Types
• Histophysiology
V. Nervous Tissue
• Cells
• Cells
• Histophysiology
VI. Muscular Tissue
• Skeletal
• Smooth
• Cardiac
PRE-FINAL
Contact Hours: 4 hours lecture: 14 hours laboratory
I. Circulatory System
• Blood Vessels: Morphology: Characteristics
• Formed Elements of Blood
II. Integumentary System
• Skin: Structure: Functions
III. Lymphatic System
• Structure and Cells
FINAL
Contact Hours: 5 hours lecture: 14 hours laboratory
I. Respiratory System
• Upper
• Lower
II. Digestive System
• Structure, Parts and Functions
III. Excretory System
• Structure, Parts and Functions
IV. Reproductive System
• Male
• Female
LABORATORY EXERCISES: Microscopic Examination of;
1. Epithelial tissues: Simple and Stratified
2. Connective Tissue
3. Adipose Tissue Cells
4. Cartilage
5. Bone Cells
6. Nerve Cells
7. Muscle Cells: Smooth, Cardiac and Skeletal
8. Circulatory System: Blood Cells, Arteries, Veins
9. Skin
10. Lymphatic System Lymphocytes, Peyer’s Patches, Thymus, Spleen, Tonsil
11. Respiratory System: Upper and Lower
12. Digestive Tract: Stomach, Small Intestine, Liver
13. Excretory System: Kidney
14. Reproductive System: Male (testis) Female (Ovary, Uterus)
REFERENCES: Ross, Michael (1989). Histology and Text and Atlas. Williams and
Wilkins Publishing Company. USA
Klein, Robert (1999). Histology and Cell Biology. Mc Graw Hill. New
York
SCHOOL OF ALLIED MEDICINE
Medical Technology Department
COURSE SYLLABUS
HISTOLOGY
S.Y. 2009-2010 (First Semester)
Course Description : This course deals with the study of the
fundamentals of cells, tissues and organs with emphasis on
microscopic structure, characteristics and functions.
Course Credit : 2 units (1 unit lecture and 1 unit laboratory)
Contact Hours : 1 hour lecture and 3 hours laboratory per week
Total of 18 hours lecture and 54 hours laboratory per
Semester
Prerequisite : Human Anatomy and Physiology
Placement : Third Year, First Semester
Course Objectives : At the end of the course, the students must be able to;
1. explain the fundamentals of cells and tissues;
2. explain the different characteristics and functions of the microscopic structure of human cells, tissues and organs;
3. recognize the morphologic/microscopic features of different groups of cells;
4. explain the cellular functions of organelles and their functional interrelationship;
5. manifest the following values: integrity, critical thinking, honesty, creativity and concern for others.
Teaching Methodology: Brain Storming, Demonstration, Group Discussion, Lecture
Course Outline
PRE-MID
Contact Hours: 4 hours lecture: 14 hours laboratory
I. Introduction/Orientation
• Definition of Terms
• Significance of Histology to the Med. Tech. Profession
II. The Cell
• Function and Structure
• Cell Physiology
• Cell Division
III. Epithelial Cells
• Forms and Characteristics
• Nomenclature and Specialization
• General Biology
MID TERM
Contact Hours: 5 hours lecture: 14 hours laboratory
I. Connective Tissue
• Composition
• Types
• Histophysiology
II. Adipose
III. Cartilage
IV. Bone
• Cells
• Types
• Histophysiology
V. Nervous Tissue
• Cells
• Cells
• Histophysiology
VI. Muscular Tissue
• Skeletal
• Smooth
• Cardiac
PRE-FINAL
Contact Hours: 4 hours lecture: 14 hours laboratory
I. Circulatory System
• Blood Vessels: Morphology: Characteristics
• Formed Elements of Blood
II. Integumentary System
• Skin: Structure: Functions
III. Lymphatic System
• Structure and Cells
FINAL
Contact Hours: 5 hours lecture: 14 hours laboratory
I. Respiratory System
• Upper
• Lower
II. Digestive System
• Structure, Parts and Functions
III. Excretory System
• Structure, Parts and Functions
IV. Reproductive System
• Male
• Female
LABORATORY EXERCISES: Microscopic Examination of;
1. Epithelial tissues: Simple and Stratified
2. Connective Tissue
3. Adipose Tissue Cells
4. Cartilage
5. Bone Cells
6. Nerve Cells
7. Muscle Cells: Smooth, Cardiac and Skeletal
8. Circulatory System: Blood Cells, Arteries, Veins
9. Skin
10. Lymphatic System Lymphocytes, Peyer’s Patches, Thymus, Spleen, Tonsil
11. Respiratory System: Upper and Lower
12. Digestive Tract: Stomach, Small Intestine, Liver
13. Excretory System: Kidney
14. Reproductive System: Male (testis) Female (Ovary, Uterus)
REFERENCES: Ross, Michael (1989). Histology and Text and Atlas. Williams and
Wilkins Publishing Company. USA
Klein, Robert (1999). Histology and Cell Biology. Mc Graw Hill. New
York
IMMUNOLOGY AND SEROLOGY
LABORATORY TECHNIQUES FOR HEPATITIS A
• Total Anti-HAV Antibodies: Competitive Immunoassay
• ELISA
• RIA
- presence of IgG Ab indicates previous
infection
- presence of IgM anti HAV indicates a
recent infection
3 particles present in the sera of infected patients, reactive with anti-HBs Ab
Dane particle
- the intact infectious B virion
Spherical noninfectious particles without the viral genome
Tubular form that is also noninfectious
LABORATORY TECHNIQUES FOR Hepatitis B
• Immunofluorecence
• Rapid one-step immunodiagnostic assay
- uses latex agglutination, cassettes,
membrane test strips or dipsticks
Ex: Equipar , ACON
• Using Recombinant HBsAg to detect Anti-HBs Ab
- an automated enzyme immunoassay
• Detection of HBsAg using a modified Sandwich Assay
- detection: the fluorescence is measured in the
optical assembly, which is a component of the
automated instrument
HEPATITIS C
• Hepatitis C virus is a causative agent of non A and non B hepatitis
• Incubation period is 2- 5 months
• No evidence for transmission in breast milk
LABORATORY TESTS
Serological Tests based on enzyme immunoassay technology
Western blot (immunoblotting)
Tests based on molecular technology which assess viral load, or identify the HCV clade
CYTOMEGALOVIRUS
• Hybrid Capture Technique for detecting CMV-DNA
- based on signal amplification following
nucleic acid hybridization of CMV DNA to
a complementary RNA oligonucleotide
probe. The anti-hybrid Ab that are
affixed to a solid phase capture the hybrids.
• HCT is also available for diagnosis of herpes simplex virus, Chlamydia trachomatis, N. gonorrhoeae
EPSTEIN BARR VIRUS TESTS
Paul-Bunnell Davidson Differential Test for heterophile Ab (tube method)
Rapid Test for heterophile Ab (uses cards or slides)
- ex: Equipar, Seradyn Color Slide II Mononucleosis Test
Influenza Virus Tests
Detection of Anti-viral Ab
• Complement Fixation
• Hemagglutination Inhibition
• Single Radial Immunodiffusion
Detection of influenza A Ag (“point of care tests”)
• Endogenous viral encoded enzyme assay
• Optical immunoassay
POLIO
3 Factors contribute to the outcome of infection:
1. Virulence of polio strain
2. number of infecting virions
3. immunological status of individual
Laboratory Diagnosis
Complement Fixation
Hemagglutinationinhibition
Assays used to measure Anti-HIV Antibodies
Calypte HIV-1 Urine EIA Test
Seradyn Sentinel HIV-1 Urine EIA
- uses urine sample
Home Access HIV Test System
- uses dried blood spot (telemedicine)
OraSure HIV -1 Western Blot
- uses OMT (oral mucosal transudate)fluid
Novapath HIV-1 Immunoblot
- western blot; serum/plasma
HIV-1/HIV-2 ELISA Test Kit
- ELISA/ serum/plasma
Acon HIV-1/HIV-2
- Chromatographic immunoassay;serum
Cobas Core Anti-HIV-1/HIV-2-EIA
- Double antigen sandwich assay EIA;
serum/plasma
Cambridge Biotech HIV-1
- Western blot; urine, serum ,plasma
AxSYM HIV-1/HIV 2
- automated EIA; serum/plasma
- Western blot; urine, serum ,plasma
Assays that measures Anti-HIV Viral Load
Amplicor HIV-1 Monitor
-Amplification (cDNA, PCR); plasma
HIV-1QT
-Amplification (RNA); plasma
HIV-1 RNA
-Signal Amplification (bDNA); plasma
Test for Aspergillus Fumigatus
• Reverse Agglutination for serum aspergillus-uses latex particles that are coated with anti-aspergillosis galactomannan
• Sandwich Technique- detects Aspergillus Ag in patients serum
• Double Immunodiffusion Assay or Ouchterlony method- screen the presence of anti-aspergillus Ab in serum.
Tests for Cryptococcus neoformans
• Reverse Agglutination- used to indicate the Antibodies that are affixed to the particles( rather than Ag)
• Cryto-LA Test- rapid latex agglutination test that detects the polysaccharide Ag of Cryptococcus in serum or CSF
• Murex Cryptococcus Test- detects cryptococcal in CSF; rapid test (5 min.)
Test for Cryptococcus neoformans
• YA-Crypto Tube Agglutination
-is a tube Antigen system
-detects Antibodies
Tests for Candida Albicans
• Culture Media
Chromogenic medium
Oricult-N-System
-a culture system done for 48 hours at 37 degrees celcius or at room temperature for 5 days.
• Latex Agglutination Test (CANO-TEC)- uses rabbit anti-candida Ag coated beads to agglutinate candida
• Quik-Tri/CAN- reverse agglutination
- is a dual latex agglutination test that can differentiate candida from trichomonas.
BACTERIAL INFECTIONS IN SEXUALLY TRANSMITTED DISEASES
Venereal Syphilis: Treponema Pallidum
LABORATORY DIAGNOSIS
Serological tests for the diagnosis of syphilis are based on antigen/antibody interactions.
Two types of antibodies produced during infection with T. pallidum.
anti-lipoidal Ab and anti-T. pallidum antibodies
Non Treponemal Tests
Are screening procedures for diagnosis of syphilis and are used to detect antibodies to lipoidal materials.
These tests may not be useful until one to four weeks after the appearance of a chancre and this may give rise to false negative results because the antibody titer is not sufficiently high.
Standard Non Treponemal Tests
Rapid Reagin Plasma Test
Is a non treponemal screening test for syphilis and is recommended for screening plasma or serum samples for reagin antibodies.
Venereal Disease Laboratory Test
A non treponemal slide test in which flocculation is the endpoint.
The patient’s serum is heated.
Used to detect antibodies in cerebral spinal fluid specimens to detect neurosyphilis.
Standard Treponemal Test
Confirmatory test for the diagnosis of syphilis.
Measures the presence of antibodies to T. pallidum antigen
2 types:
Fluorescent treponemal antibody absorbed (FTA-ABS)
T. pallidum immobilization test (TPI)
TESTS
Second Generation FTA-ABS Test
Treponema Pallidum Hemagglutination Assay (Confirmatory Test)
Modified TPHA (Fast latex test)
Non Standard Non Treponemal and Treponemal Test
Enzyme-Linked Immonosorbent Assay
- Used for both infectious and non-infectious diseases
Syphilis Rapid Test Device
Rapid qualitative chromatographic immunoassay that uses the affinity of protein A for IgG antibodies to test for treponemal antibodies
GONORRHEA: NEISSERIA GONORRHOEAE
Laboratory Technique
Ligase Chain Reaction
-Is a nucleic acid amplification assay based on the ligase chain reaction.
GENITAL TRACT INFECTION:CHLAMYDIA TRACHOMATIS
Laboratory Diagnosis for Antigen Detection
Optical Immunoassay
Mainstream Immunoassay
Nucleic Acid Amplification
Upper Respiratory Tract Bacterial Infections
Atypical Pneumonia: Mycoplasma Pneumoniae
Laboratory Diagnosis
Tests that detect M. Pneumoniae
a. Specific antigentest
b. Amplification test ( Polymerase
Chain Reaction)
c. Culture
Detecting Antibodies
Compliment Fixation
Cold Agglutinin Antibody Titer
Indirect Immunofluorescence
STREPTOCOCCAL INFECTIONS: STREPTOCOCCACEAE
Laboratory Diagnosis
a. Antigen Detection: Antibodies or Nucleic
Acid Probes
b. Optical Immunoassay
c. Q test Rapid Antigen Group A Strep
Detection (Antibody Coated Liposomes)
d. Gen-Probe Group A Streptococcal
Direct Test
Serological Tests
Are used to detect the presence of antibodies specific for streptococcal antigens.
Antigens used for antibody detection include streptolysin O, DNAse B, Hyaluronidase and Streptokinase
Sera Test Aso (S-O)
Commercial kits (DNAse B)
Wampole (Streptonase B titer test)-for anti DNAse antibodies
WHOOPING COUGH: BORDETELLA PERTUSSIS
Laboratory Diagnosis
Antigen Detection Technique
-Uses direct fluorescent antibody
staining or nucleic acid amplification tech.,
the polymerase chain reaction,
followed by nucleic acid hybridization for
detection of amplicons, (more sensitive than DFA)
TESTS
ELISA
Detects anti-pertussis toxin IgG or IgA antibodies.
Passive Hemagglutination
Potential technique fot widespread screening
LYME DISEASE: BORRELIA BURGDORFERI
Laboratory Diagnosis
Immunochromatograhic Test
Indirect Fluorescent Antibody Assay
Compliment Fixation
Enzyme Immunoassays
Western Blot (confirmatory test of many infectious agents)
ROCKY MOUNTAIN SPOTTED FEVER: RICKETTSIA RICKETTSII
LABORATORY DIAGNOSIS
1. Weil-Felix Agglutination Test
2. Latex-R-rickettsii Agglutination test
LEPTOSPIROSIS: LEPTOSPIRA INTERROGANS
LABORATORY DIAGNOSIS
1. Lateral Flow Immunoassay
2. LEPTO Dri- Dot Agglutination
SALMONELLOSIS AND TYPHOID FEVER: SALMONELLA SPECIE
LABORATORY DIAGNOSIS
Chromogenic Culture Medium- selective for Salmonella species
Serological Tests
1. DIP-S-TICK Assay (enzyme immunoassay)
2. Widal Agglutination Test (counter immunoelectrophoresis)
MEASLES, MUMPS, RUBELLA AND VARICELLA
MEASLES
1. ELISA- detects anti-measles IgM
2. Indirect Immunofluorescence Antibody-detects anti-measles antibodies serum.
MUMPS
Laboratory Diagnosis
Enzyme-Linked Fluorescent Immunoassay (ELFA)
RUBELLA
LABORATORY DIAGNOSIS
Enzyme Immunoassay for Anti-Rubella Antibodies
Capture Immunoassay for IgM
Non Serological Test
Amplification techniques
VARICELLA
Laboratory Diagnosis
ELISA
• Total Anti-HAV Antibodies: Competitive Immunoassay
• ELISA
• RIA
- presence of IgG Ab indicates previous
infection
- presence of IgM anti HAV indicates a
recent infection
3 particles present in the sera of infected patients, reactive with anti-HBs Ab
Dane particle
- the intact infectious B virion
Spherical noninfectious particles without the viral genome
Tubular form that is also noninfectious
LABORATORY TECHNIQUES FOR Hepatitis B
• Immunofluorecence
• Rapid one-step immunodiagnostic assay
- uses latex agglutination, cassettes,
membrane test strips or dipsticks
Ex: Equipar , ACON
• Using Recombinant HBsAg to detect Anti-HBs Ab
- an automated enzyme immunoassay
• Detection of HBsAg using a modified Sandwich Assay
- detection: the fluorescence is measured in the
optical assembly, which is a component of the
automated instrument
HEPATITIS C
• Hepatitis C virus is a causative agent of non A and non B hepatitis
• Incubation period is 2- 5 months
• No evidence for transmission in breast milk
LABORATORY TESTS
Serological Tests based on enzyme immunoassay technology
Western blot (immunoblotting)
Tests based on molecular technology which assess viral load, or identify the HCV clade
CYTOMEGALOVIRUS
• Hybrid Capture Technique for detecting CMV-DNA
- based on signal amplification following
nucleic acid hybridization of CMV DNA to
a complementary RNA oligonucleotide
probe. The anti-hybrid Ab that are
affixed to a solid phase capture the hybrids.
• HCT is also available for diagnosis of herpes simplex virus, Chlamydia trachomatis, N. gonorrhoeae
EPSTEIN BARR VIRUS TESTS
Paul-Bunnell Davidson Differential Test for heterophile Ab (tube method)
Rapid Test for heterophile Ab (uses cards or slides)
- ex: Equipar, Seradyn Color Slide II Mononucleosis Test
Influenza Virus Tests
Detection of Anti-viral Ab
• Complement Fixation
• Hemagglutination Inhibition
• Single Radial Immunodiffusion
Detection of influenza A Ag (“point of care tests”)
• Endogenous viral encoded enzyme assay
• Optical immunoassay
POLIO
3 Factors contribute to the outcome of infection:
1. Virulence of polio strain
2. number of infecting virions
3. immunological status of individual
Laboratory Diagnosis
Complement Fixation
Hemagglutinationinhibition
Assays used to measure Anti-HIV Antibodies
Calypte HIV-1 Urine EIA Test
Seradyn Sentinel HIV-1 Urine EIA
- uses urine sample
Home Access HIV Test System
- uses dried blood spot (telemedicine)
OraSure HIV -1 Western Blot
- uses OMT (oral mucosal transudate)fluid
Novapath HIV-1 Immunoblot
- western blot; serum/plasma
HIV-1/HIV-2 ELISA Test Kit
- ELISA/ serum/plasma
Acon HIV-1/HIV-2
- Chromatographic immunoassay;serum
Cobas Core Anti-HIV-1/HIV-2-EIA
- Double antigen sandwich assay EIA;
serum/plasma
Cambridge Biotech HIV-1
- Western blot; urine, serum ,plasma
AxSYM HIV-1/HIV 2
- automated EIA; serum/plasma
- Western blot; urine, serum ,plasma
Assays that measures Anti-HIV Viral Load
Amplicor HIV-1 Monitor
-Amplification (cDNA, PCR); plasma
HIV-1QT
-Amplification (RNA); plasma
HIV-1 RNA
-Signal Amplification (bDNA); plasma
Test for Aspergillus Fumigatus
• Reverse Agglutination for serum aspergillus-uses latex particles that are coated with anti-aspergillosis galactomannan
• Sandwich Technique- detects Aspergillus Ag in patients serum
• Double Immunodiffusion Assay or Ouchterlony method- screen the presence of anti-aspergillus Ab in serum.
Tests for Cryptococcus neoformans
• Reverse Agglutination- used to indicate the Antibodies that are affixed to the particles( rather than Ag)
• Cryto-LA Test- rapid latex agglutination test that detects the polysaccharide Ag of Cryptococcus in serum or CSF
• Murex Cryptococcus Test- detects cryptococcal in CSF; rapid test (5 min.)
Test for Cryptococcus neoformans
• YA-Crypto Tube Agglutination
-is a tube Antigen system
-detects Antibodies
Tests for Candida Albicans
• Culture Media
Chromogenic medium
Oricult-N-System
-a culture system done for 48 hours at 37 degrees celcius or at room temperature for 5 days.
• Latex Agglutination Test (CANO-TEC)- uses rabbit anti-candida Ag coated beads to agglutinate candida
• Quik-Tri/CAN- reverse agglutination
- is a dual latex agglutination test that can differentiate candida from trichomonas.
BACTERIAL INFECTIONS IN SEXUALLY TRANSMITTED DISEASES
Venereal Syphilis: Treponema Pallidum
LABORATORY DIAGNOSIS
Serological tests for the diagnosis of syphilis are based on antigen/antibody interactions.
Two types of antibodies produced during infection with T. pallidum.
anti-lipoidal Ab and anti-T. pallidum antibodies
Non Treponemal Tests
Are screening procedures for diagnosis of syphilis and are used to detect antibodies to lipoidal materials.
These tests may not be useful until one to four weeks after the appearance of a chancre and this may give rise to false negative results because the antibody titer is not sufficiently high.
Standard Non Treponemal Tests
Rapid Reagin Plasma Test
Is a non treponemal screening test for syphilis and is recommended for screening plasma or serum samples for reagin antibodies.
Venereal Disease Laboratory Test
A non treponemal slide test in which flocculation is the endpoint.
The patient’s serum is heated.
Used to detect antibodies in cerebral spinal fluid specimens to detect neurosyphilis.
Standard Treponemal Test
Confirmatory test for the diagnosis of syphilis.
Measures the presence of antibodies to T. pallidum antigen
2 types:
Fluorescent treponemal antibody absorbed (FTA-ABS)
T. pallidum immobilization test (TPI)
TESTS
Second Generation FTA-ABS Test
Treponema Pallidum Hemagglutination Assay (Confirmatory Test)
Modified TPHA (Fast latex test)
Non Standard Non Treponemal and Treponemal Test
Enzyme-Linked Immonosorbent Assay
- Used for both infectious and non-infectious diseases
Syphilis Rapid Test Device
Rapid qualitative chromatographic immunoassay that uses the affinity of protein A for IgG antibodies to test for treponemal antibodies
GONORRHEA: NEISSERIA GONORRHOEAE
Laboratory Technique
Ligase Chain Reaction
-Is a nucleic acid amplification assay based on the ligase chain reaction.
GENITAL TRACT INFECTION:CHLAMYDIA TRACHOMATIS
Laboratory Diagnosis for Antigen Detection
Optical Immunoassay
Mainstream Immunoassay
Nucleic Acid Amplification
Upper Respiratory Tract Bacterial Infections
Atypical Pneumonia: Mycoplasma Pneumoniae
Laboratory Diagnosis
Tests that detect M. Pneumoniae
a. Specific antigentest
b. Amplification test ( Polymerase
Chain Reaction)
c. Culture
Detecting Antibodies
Compliment Fixation
Cold Agglutinin Antibody Titer
Indirect Immunofluorescence
STREPTOCOCCAL INFECTIONS: STREPTOCOCCACEAE
Laboratory Diagnosis
a. Antigen Detection: Antibodies or Nucleic
Acid Probes
b. Optical Immunoassay
c. Q test Rapid Antigen Group A Strep
Detection (Antibody Coated Liposomes)
d. Gen-Probe Group A Streptococcal
Direct Test
Serological Tests
Are used to detect the presence of antibodies specific for streptococcal antigens.
Antigens used for antibody detection include streptolysin O, DNAse B, Hyaluronidase and Streptokinase
Sera Test Aso (S-O)
Commercial kits (DNAse B)
Wampole (Streptonase B titer test)-for anti DNAse antibodies
WHOOPING COUGH: BORDETELLA PERTUSSIS
Laboratory Diagnosis
Antigen Detection Technique
-Uses direct fluorescent antibody
staining or nucleic acid amplification tech.,
the polymerase chain reaction,
followed by nucleic acid hybridization for
detection of amplicons, (more sensitive than DFA)
TESTS
ELISA
Detects anti-pertussis toxin IgG or IgA antibodies.
Passive Hemagglutination
Potential technique fot widespread screening
LYME DISEASE: BORRELIA BURGDORFERI
Laboratory Diagnosis
Immunochromatograhic Test
Indirect Fluorescent Antibody Assay
Compliment Fixation
Enzyme Immunoassays
Western Blot (confirmatory test of many infectious agents)
ROCKY MOUNTAIN SPOTTED FEVER: RICKETTSIA RICKETTSII
LABORATORY DIAGNOSIS
1. Weil-Felix Agglutination Test
2. Latex-R-rickettsii Agglutination test
LEPTOSPIROSIS: LEPTOSPIRA INTERROGANS
LABORATORY DIAGNOSIS
1. Lateral Flow Immunoassay
2. LEPTO Dri- Dot Agglutination
SALMONELLOSIS AND TYPHOID FEVER: SALMONELLA SPECIE
LABORATORY DIAGNOSIS
Chromogenic Culture Medium- selective for Salmonella species
Serological Tests
1. DIP-S-TICK Assay (enzyme immunoassay)
2. Widal Agglutination Test (counter immunoelectrophoresis)
MEASLES, MUMPS, RUBELLA AND VARICELLA
MEASLES
1. ELISA- detects anti-measles IgM
2. Indirect Immunofluorescence Antibody-detects anti-measles antibodies serum.
MUMPS
Laboratory Diagnosis
Enzyme-Linked Fluorescent Immunoassay (ELFA)
RUBELLA
LABORATORY DIAGNOSIS
Enzyme Immunoassay for Anti-Rubella Antibodies
Capture Immunoassay for IgM
Non Serological Test
Amplification techniques
VARICELLA
Laboratory Diagnosis
ELISA
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