Microbiology (Tortora, Funke, Case 13th Ed. 2019) PDF

24 Microbial Diseases of the Respiratory System W ith every breath, we inhale several microorganisms; therefore, the upper respiratory system is a major portal of entry for pathogens. In...

24 Microbial Diseases of the Respiratory System W ith every breath, we inhale several microorganisms; therefore, the upper respiratory system is a major portal of entry for pathogens. In fact, respiratory system infections are the most common type of infection—and among the most damaging. Some pathogens that enter via the respiratory route can infect other parts of the body, causing such diseases as measles, mumps, and rubella. The upper respiratory system has several anatomical defenses against airborne pathogens. Coarse hairs in the nose filter large dust particles from the air. The nose is lined with a mucous membrane that contains numerous mucus- secreting cells and cilia. The upper portion of the throat also contains a ciliated mucous membrane. The mucus moistens inhaled air and traps dust and microorganisms. The cilia help remove these particles by moving them toward the mouth for elimination. At the junction of the nose and throat are masses of lymphoid tissue, the tonsils, which contribute immunity to certain infections. Because the nose and throat are connected to the sinuses, nasolacrimal apparatus, and middle ear, infections commonly spread from one region to another. Microbes that escape these defenses may be able to cause infection. Such an infection caused by the Chlamydophila psittaci shown in the photograph is described in the Clinical Case in this chapter. ▶ When infecting a host cell, chlamydial bacteria produce infectious elementary bodies (small, brown) and noninfectious- reticulate bodies (red). In the Clinic As a nurse educator in a large urban hospital, you are asked to provide flu classes for patients and staff. Differentiate influenza from the common cold. What prevention measures will you recommend to your students? Hint: Read about the common cold on page 693 and influenza on page 709. Answers to In the Clinic questions are found online @MasteringMicrobiology. 688  CHAPTER 24   Microbial Diseases of the Respiratory System 689 Figure 24.1 Structures of the upper ­respiratory system. Q Name the upper respiratory system’s defenses against disease. Sinus Sinus Middle ear Nasal cavity Auditory (eustachian) tube Oral cavity Opening of Tongue auditory tube Tonsils Epiglottis Pharynx (throat) Larynx Spine (voice box) (backbone) Trachea (windpipe) Esophagus Structure and Function of the called the ciliary escalator (see Figure 16.3, page 450). If micro- organisms actually reach the lungs, phagocytic cells called Respiratory System alveolar macrophages usually locate, ingest, and destroy most of LEARNING OBJECTIVE them. IgA antibodies in such secretions as respiratory mucus, saliva, and tears also help protect mucosal surfaces of the 24-1 Describe how microorganisms are prevented from entering respiratory system from many pathogens. Thus, the body has the respiratory system. several mechanisms for removing the pathogens that cause air- It’s convenient to think of the respiratory system as being com- borne infections. posed of two divisions: the upper respiratory system and the lower respiratory system. The upper respiratory system con- CHECK YOUR UNDERSTANDING sists of the nose, the pharynx (throat), larynx (voice box), and ✓ 24-1 What is the function of hairs in the nasal passages? the structures associated with them, including the middle ear and the auditory (eustachian) tubes (Figure 24.1). Ducts from the sinuses (air-filled spaces in certain skull bones) and the nasolacri- mal ducts from the lacrimal (tear-forming) apparatus empty into CLINICAL CASE It’s for the Birds F the nasal cavity (see Figure 16.2, page 450). The auditory tubes or the past 2 days, Caille Nguyen has had a fever and feels from the middle ear empty into the upper portion of the throat. out of sorts. In fact, her entire family is sick. Her three The lower respiratory system consists of the trachea children, Gabbie, Steven, and Tre, also have fevers. Caille’s (windpipe), bronchial tubes, and alveoli (Figure 24.2). Alveoli husband, Art, and Gabbie and Steven have no appetite and are air sacs that make up the lung tissue; within them, oxy- are beginning to lose weight. Everyone has a dry cough. At gen and carbon dioxide are exchanged between the lungs and first Caille thinks the children are just sad because of the loss blood. Our lungs contain more than 300 million alveoli, with of Bitsy, their beloved cockatiel. The family had purchased the cockatiel from a local pet store 2 months earlier. an area for gas exchange of 70 or more square meters in an Unfortunately, Bitsy had an increasingly difficult time breathing average adult. The double-layered membrane enclosing the and could not stand erect; she had to be euthanized by a local lungs is the pleura, or pleural membranes. A ciliated mucous veterinarian the week before. membrane lines the lower respiratory system down to the What could be causing the Nguyen family’s symptoms? Read smaller bronchial tubes and helps prevent microorganisms on to find out. from reaching the alveoli. Particles trapped in the larynx, trachea, and larger bron- 689 706 707 709 711 715 chial tubes are moved up toward the throat by a ciliary action 690 PART FOUR Microorganisms and Human Disease Branch from the Pharynx pulmonary (throat) Bronchiole artery Blood Larynx Branch from capillaries (voice box) the pulmonary Trachea vein (windpipe) Right lung Left lung Bronchus Bronchiole Pleura Alveoli Heart Diaphragm (breathing muscle) Figure 24.2 Structures of the lower respiratory system. Q Name the lower respiratory system’s defenses against disease. Normal Microbiota of the microorganisms of the normal microbiota suppress their growth by competing with them for nutrients and producing Respiratory System inhibitory substances. The lung microbiome is described in the Exploring the LEARNING OBJECTIVE Microbiome box. 24-2 Characterize the normal microbiota of the upper and lower respiratory systems. CHECK YOUR UNDERSTANDING A number of potentially pathogenic microorganisms are part ✓ 24-2 Normally, the lower respiratory tract is nearly sterile. of the normal microbiota in the respiratory system. However, What is the primary mechanism responsible? they usually do not cause illness because the predominant Microbial Diseases of the Upper Respiratory System LEARNING OBJECTIVE opening by which the mucus leaves the sinus becomes blocked, 24-3 Differentiate pharyngitis, laryngitis, tonsillitis, sinusitis, and internal pressure can cause pain or a sinus headache. These dis- epiglottitis. eases are almost always self-limiting, meaning that recovery will usually occur even without medical intervention. As most of us know from personal experience, the respiratory Probably the most threatening infectious disease of the system is the site of many common infections. We will soon upper respiratory system is epiglottitis, inflammation of the discuss pharyngitis, inflammation of the mucous membranes epiglottis. The epiglottis is a flaplike structure of cartilage that of the throat, or sore throat. When the larynx is the site of prevents ingested material from entering the larynx (see F­ igure infection, we suffer from laryngitis, which affects our ability 24.1). Epiglottitis is a rapidly developing disease that can to speak. The microbes that cause pharyngitis also can cause result in death within a few hours. It is caused by opportunis- inflamed tonsils, or tonsillitis. tic pathogens, usually Haemophilus influenzae type b. The Hib The nasal sinuses are cavities in certain cranial bones that ­vaccine, although directed primarily at meningitis (page 622), open into the nasal cavity. They have a mucous membrane lining has significantly reduced the incidence of epiglottitis in the that is continuous with that of the nasal cavity. Infection of a sinus vaccinated population. involving heavy nasal discharge of mucus is called sinusitis. If the  CHAPTER 24   Microbial Diseases of the Respiratory System 691 EXPLORING THE MICROBIOME Discovering the Microbiome of the Lungs U ntil as recently as 2009, many do not use oxygen, they all share the ability environment or whether the microbiota are scientists and medical professionals to avoid oxygen’s toxic effects by producing evenly dispersed throughout the lungs or believed that healthy lungs are sterile, antioxidant enzymes, including peroxidase concentrated in specific areas. Depending based on findings from studies using and superoxide dismutase. on how discoveries proceed, we may one traditional culture techniques. However, Patients with chronic pulmonary day have lung disease therapies that use genetic studies related to the Human diseases such as asthma, cystic fibrosis, probiotics. Microbiome Project show this isn’t the case. or chronic obstructive pulmonary disease It would actually be remarkable if the alveoli (COPD) have a predominance of gram- didn’t routinely come into contact with at negative bacteria compared to individuals least some microbes, considering that the without chronic lung disease. One study average adult inhales over 10,000 liters of also found that nitric-oxide-metabolizing microbe-filled air every day. bacteria (Nitrosomonas spp.) were present The most common bacterial genera in the lungs of asthma patients. This is present in healthy lungs are Prevotella, notable in that airway inflammation in Veillonella, Streptococcus, and asthma patients is often diagnosed by Pseudomonas. These bacteria are also measuring exhaled nitric oxide. Higher- common members of the oral microbiome. than-normal levels indicate that the This suggests that, surprisingly, the primary airways may be inflamed. It could be that source of the lung microbiota is likely the the Nitrosomonas bacteria in lungs are mouth rather than inhaled air. Prevotella, responsible for this phenomenon that Veillonella, and Streptococcus are all clinicians use as a diagnostic tool. anaerobic bacteria. It may seem illogical for Lung microbiome research is new, species that don’t use oxygen to live in the so many unanswered questions remain. lower respiratory system, the site of gas For instance, researchers don’t yet know exchange. However, although these bacteria whether core species change with age or Staphylococcus sp. in the trachea. gram-positive bacterial group consists solely of Streptococcus CHECK YOUR UNDERSTANDING pyogenes, the same bacterium responsible for many skin and ✓ 24-3 Which one of the following is most likely to be associated soft tissue infections, such as impetigo, erysipelas, and acute with a headache: pharyngitis, laryngitis, sinusitis, or epiglottitis? bacterial endocarditis. Pharyngitis is characterized by local inflammation and a Bacterial Diseases of the fever (Figure 24.3). Frequently, tonsillitis occurs, and the lymph nodes in the neck become enlarged and tender. Another fre- Upper Respiratory System quent complication is otitis media (see page 693). The pathogenicity of GAS is enhanced by their resistance to LEARNING OBJECTIVE phagocytosis. They are also able to produce special enzymes, 24-4 List the causative agent, symptoms, prevention, called streptokinases, which lyse fibrin clots, and streptolysins, preferred treatment, and laboratory identification tests which are cytotoxic to tissue cells, red blood cells, and protec- for streptococcal pharyngitis, scarlet fever, diphtheria, tive leukocytes. cutaneous diphtheria, and otitis media. At one time, the diagnosis of pharyngitis was based on Airborne pathogens make their first contact with the body’s ­c ulturing bacteria from a throat swab. Results took overnight mucous membranes as they enter the upper respiratory system. or longer, but, beginning in the early 1980s, rapid antigen Many respiratory or systemic diseases initiate infections here. detection tests that were capable of detecting GAS directly on throat swabs became available. A physician can perform a Streptococcal Pharyngitis (Strep Throat) rapid test in the office. These rapid tests have high specificity. Streptococcal pharyngitis (strep throat) is an upper respi- However, negative samples should be cultured because of the ratory infection caused by group A streptococci (GAS). This varying sensitivity of these tests. (Specificity and sensitivity are 691 692 PART FOUR Microorganisms and Human Disease children in the United States. The disease begins with a sore throat and fever, followed by general malaise and swelling of the neck. The organism responsible is Corynebacterium diph- theriae, a gram-positive, non–endospore-forming rod. Its mor- phology is pleomorphic, frequently club-shaped, and it stains unevenly (Figure 24.4). Part of the normal immunization program for children in the United States is the DTaP vaccine, which protects against diphtheria, tetanus, and pertussis. In this name, the D repre- sents diphtheria toxoid, an inactivated toxin that causes the body to produce antibodies against the diphtheria toxin. C. diphtheriae has adapted to a generally immunized pop- ulation, and relatively nonvirulent strains are found in the throats of many symptomless carriers. The bacterium is well suited to droplet transmission and is very resistant to drying. A tough grayish membrane that forms in the throat in Figure 24.3 Streptococcal pharyngitis. Note the inflammation. response to the infection is characteristic of diphtheria (from the Q How is strep throat diagnosed? Greek word for leather). It contains fibrin, dead tissue, and bacte- rial cells and can totally block the passage of air to the lungs. Although the bacteria don’t invade tissues, those that have discussed in Chapter 18, page 507.) Actually, the majority of been lysogenized by a phage can produce a powerful exotoxin, patients seen for sore throats do not have a streptococcal infec- which then circulates in the bloodstream and interferes with tion. Some cases are caused by other bacteria, but most are protein synthesis. Historically, diphtheria was the first disease caused by viruses—for which antibiotic therapy is ineffective. for which a toxic cause was identified. Only 0.01 mg of this GAS should be confirmed and treated in children older than highly virulent toxin can be fatal. Thus, if antitoxin therapy is 3 years to prevent development of rheumatic fever. Fortunately, to be effective, it must be administered before the toxin enters GAS have remained sensitive to penicillin. the tissue cells. When such organs as the heart and kidneys are Pharyngitis is now most commonly transmitted by respi- affected by the toxin, the disease can rapidly be fatal. In other ratory secretions, but epidemics of streptococcal pharyngitis cases the nerves can be involved, and partial paralysis results. spread by unpasteurized milk were once frequent. Scarlet Fever When the Streptococcus pyogenes strain causing streptococcal Clubbed cells pharyngitis produces an erythrogenic (reddening) toxin, the resulting infection is called scarlet fever. When the strain pro- duces this toxin, it has been lysogenized by a bacteriophage (see Figure 13.12, page 375). Recall that this means the genetic information of a bacteriophage (bacterial virus) has been incorporated into the chromosome of the bacterium, so the characteristics of the bacterium have been altered. The toxin causes a pinkish red skin rash, which is probably the skin’s Palisade hypersensitivity reaction to the circulating toxin, and a high arrangement fever. The tongue has a spotted, strawberry-like appearance and then, as it loses its upper membrane, becomes very red and enlarged. Classically, scarlet fever has been considered to be TEM associated with streptococcal pharyngitis, but it might accom- 1 mm pany a streptococcal skin infection. Figure 24.4 Corynebacterium diphtheriae, the cause of It is usually a mild illness, but scarlet fever needs antibiotic diphtheria. This image shows the club-shaped morphology; the treatment to prevent later development of rheumatic fever. dividing cells are often observed folding together to form V- and Y-shaped figures. Also notice the side-by-side palisade arrangement. Diphtheria Q Are corynebacteria gram-positive or gram-negative? Another bacterial infection of the upper respiratory system is diphtheria. Until 1935, it was the leading infectious killer of  CHAPTER 24   Microbial Diseases of the Respiratory System 693 The number of diphtheria cases reported in the United States each year is currently five or fewer. The disease occurs mainly in unvaccinated children and travelers to developing countries. When diphtheria was more common, repeated con- Bulging eardrum tacts with toxigenic strains reinforced the immunity, which otherwise weakens with time. Many adults lack immunity because immunity wanes over time. A booster dose of vaccine should be administered every 10 years to maintain protective antibody levels. Some surveys indicate effective immune levels in as few as 20% of the adult population. In the United States, when any trauma in adults requires tetanus toxoid, it is usually combined with diphtheria toxoid (Td vaccine). Diphtheria is also expressed as cutaneous diphtheria. In this form of the disease, C. diphtheriae infects the skin, usually at a wound or similar skin lesion, and there is minimal systemic cir- Figure 24.5 Acute otitis media, with bulging eardrum. culation of the toxin. In cutaneous infections, the bacteria cause Q What is the most common bacterium causing middle ear slow-healing ulcerations that are covered by a gray membrane. infections? Cutaneous diphtheria is fairly common in tropical countries. are other S. pneumoniae, nonencapsulated H. influenzae, Morax- In the past, diphtheria was spread mainly to healthy carri- ella catarrhalis (more-ax-EL-lah ka-tar-RA-lis) and S. pyogenes. In ers by droplet infection. Respiratory cases have been known to about 30% of cases, no bacteria can be detected. Viral infec- arise from contact with cutaneous diphtheria. tions may be responsible in these instances; respiratory syncy- Laboratory diagnosis by bacterial identification is difficult, tial viruses (see page 708) are the most common isolate. requiring several selective and differential media. Identifica- Otitis media affects 85% of children before the age of 3 and tion is complicated by the need to differentiate toxin-forming accounts for nearly half of office visits to pediatricians—an isolates from strains that are not toxigenic; both may be found estimated 8 million cases each year in the United States. It is in the same patient. estimated that ear infections account for about one-fourth of Even though antibiotics such as erythromycin and penicil- the prescriptions for antibiotics; however, antibiotics should lin control the growth of the bacteria, they do not neutralize be prescribed only if the infection is caused by a bacterium. the diphtheria toxin. Thus antibiotics should be used only in Broad-spectrum penicillins, such as amoxicillin, are usually conjunction with antitoxin. the first choice for children. CHECK YOUR UNDERSTANDING ✓ 24-4 Among streptococcal pharyngitis, scarlet fever, or Viral Disease of the ­diphtheria, which two diseases are usually caused by the same genus of bacteria? Upper Respiratory System LEARNING OBJECTIVE 24-5 List the causative agents and treatments for the common cold. Otitis Media One of the more uncomfortable complications of the com- Probably the most prevalent disease of humans, at least those mon cold, or of any infection of the nose or throat, is infec- living in the temperate zones, is a viral disease affecting the tion of the middle ear, otitis media, or earache. The pathogens upper respiratory system—the common cold. cause the formation of pus, which builds up pressure against the eardrum and causes it to become inflamed and painful The Common Cold (­Figure 24.5). The condition is most frequent in early child- More than one virus is involved in the etiology of the common hood because the auditory tube connecting the middle ear to cold. In fact, there are hundreds—more than 200 different the throat is small and more horizontal than in adults and so is viruses that are members of several different families of viruses more easily blocked by infection (see Figure 24.1). are known to cause colds. Identification procedures that A number of bacteria can cause otitis media. Until this require isolation and culturing often fail to identify the cause century, S. pneumoniae was the most common cause of otitis of a cold. However, new techniques that use PCR to look for media. The conjugate vaccine to prevent S. pneumoniae pneu- the viral DNA or RNA make culturing unnecessary and fre- monia has reduced the incidence of otitis media caused by the quently turn up previously unknown cold viruses. Most cold strains in the vaccine. The bacteria most frequently involved viruses are rhinoviruses (30–50%); coronaviruses (10–15%)  Microbial Diseases of 694 PART FOUR Microorganisms and Human Disease DISEASES IN FOCUS 24.1 the Upper Respiratory System T he differential diagnosis for the appears in the throat. Gram-positive rods following diseases is usually based were cultured from the membrane. Use the on clinical symptoms, and throat table below to make a differential diagnosis swabs may be used to culture bacteria. For and identify infections that could cause example, a patient presents with fever and a these symptoms. For the solution, go to red, sore throat. Later a grayish membrane @MasteringMicrobiology Grayish membrane in the throat is a characteristic of this disease. Disease Pathogen Symptoms Treatment BACTERIAL DISEASES Epiglottitis Haemophilus influenzae Inflammation of the epiglottis Antibiotics; maintain airway Prevention: Hib vaccine Streptococcal Pharyngitis Streptococci, especially Inflamed mucous membranes of Penicillin (strep throat) Streptococcus pyogenes the throat Scarlet Fever Erythrogenic toxin-producing Streptococcal exotoxin causes Penicillin strains of Streptococcus pyogenes reddening of skin and tongue and peeling of affected skin Diphtheria Corynebacterium diphtheriae Grayish membrane forms in throat; Erythromycin and antitoxin cutaneous form also occurs Prevention: DTaP vaccine Otitis Media Several agents, especially Accumulations of pus in middle ear Broad-spectum antibiotics Streptococcus pneumoniae, cause painful pressure on eardrum if bacterial Haemophilus influenzae, and Prevention: pneumococcal S. pyogenes vaccine VIRAL DISEASE Common Cold Rhinoviruses, coronaviruses; Familiar symptoms of coughing, Supportive Enterovirus sneezing, runny nose are also important. However, 20–30% of viruses that cause colder weather in temperate zones. It is not known whether closer colds are classified by researchers as previously unknown. indoor contact promotes epidemic-type transmission or whether We tend to accumulate immunities against cold viruses dur- physiological changes increase susceptibility. ing our lifetime, which may be a reason why older people usually A single rhinovirus deposited on the nasal mucosa is often have fewer colds. Immunity is based on the ratio of IgA antibod- sufficient to cause a cold. However, there is surprisingly little ies to single serotypes and has a good short-term effectiveness. agreement on how the cold virus is transmitted to a site in the Isolated populations may develop a group immunity, and colds nose. Experiments with guinea pigs and the influenza virus disappear among them until a new set of viruses is introduced. show that viruses tend to be carried on airborne droplets of The symptoms of the common cold are familiar to all of water vapor. In the dry air (low humidity) typical of low tem- us. They include sneezing, excessive nasal secretion, and con- peratures, the droplets are smaller and remain airborne longer, gestion. The infection can easily spread from the throat to the facilitating person-to-person transmission. At the same time, sinuses, the lower respiratory system, and the middle ear, lead- the cooler air causes the cilia of the ciliary escalator to work ing to complications of laryngitis and otitis media. The uncom- more slowly, allowing inhaled viruses to spread in the upper plicated cold usually is not accompanied by fever. It is generally respiratory system. in the interest of a cold-causing virus not to make the cold Research has shown that during the first 3 days of a cold, sufferer too ill—the host needs to move around, shedding the nasal mucus contains a high concentration of cold viruses that virus to others, especially in mucus. multiply in nasal cells. (If mucus is green, the reason is that it Rhinoviruses thrive at a temperature slightly below that of contains many white blood cells with iron-containing compo- normal body temperature, such as might be found in the upper nents directed at destroying pathogens.) The viruses in mucus respiratory system, which is open to the outside environment. No remain viable on surfaces touched by contaminated fingers one knows exactly why the number of colds seems to increase with for at least several hours. The conventional wisdom is that the 694  CHAPTER 24   Microbial Diseases of the Respiratory System 695 virus is most likely transmitted through finger contact with Because colds are caused by viruses, antibiotics are of no the nostrils and eyes (tear ducts communicate with the nose). use in treatment. Symptoms can be relieved by cough suppres- Transmission also occurs when the cold viruses in airborne sants and antihistamines, but these medications do not speed droplets from coughing and sneezing land on suitable tissues recovery. There is still considerable truth in the medical adage in the nose and eyes. that an untreated cold will run its normal course to recovery in Enterovirus D68 (EV-D68) causes coldlike symptoms. In a week, whereas with treatment it will take 7 days. 2014, the United States experienced a nationwide outbreak of The diseases affecting the upper respiratory system are EV-D68 associated with severe respiratory illness. Small num- summarized in Diseases in Focus 24.1. bers of EV-D68 have been reported regularly since 1987. Chil- dren and teenagers are most likely to get infected with EV-D68 CHECK YOUR UNDERSTANDING and become ill because they do not yet have immunity from pre- ✓ 24-5 Which viruses, rhinoviruses or coronaviruses, cause vious exposures to these viruses. Some children may have diffi- about half of the cases of the common cold? culty breathing, although most people recover within a few days. Microbial Diseases of the Lower Respiratory System Many of the same bacteria and viruses that infect the upper bacterium, is responsible for damage to the ciliated cells, and respiratory system can also infect the lower respiratory system. pertussis toxin enters the bloodstream and is associated with As the bronchi become involved, bronchitis or bronchiolitis systemic symptoms of the disease. develops (see Figure 24.2). A severe complication of bronchi- Primarily a childhood disease, pertussis can be quite tis is pneumonia, in which the pulmonary alveoli become severe. The initial stage, called the catarrhal stage, resembles a involved. common cold. Prolonged sieges of coughing characterize the paroxysmal stage, or second stage. (The name pertussis is derived from the Latin per, meaning thoroughly, and tussis, meaning Bacterial Diseases of the cough.) When ciliary action is compromised, mucus accumu- Lower Respiratory System lates, and the infected person desperately attempts to cough up these mucus accumulations. The violence of the coughing LEARNING OBJECTIVES 24-6 List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for pertussis B. pertussis and tuberculosis. 24-7 Compare and contrast the seven bacterial pneumonias discussed in this chapter. 24-8 List the etiology, method of transmission, and symptoms of melioidosis. Cilium Bacterial diseases of the lower respiratory system include tuber- culosis and the many types of pneumonia caused by bacteria. Lesser-known diseases such as psittacosis and Q fever also fall into this category. Pertussis (Whooping Cough) Infection by the bacterium Bordetella pertussis results in pertussis, or whooping cough. B. pertussis is a small, obligately aerobic, SEM gram-negative coccobacillus. The virulent strains possess a 2 mm capsule. The bacteria attach specifically to ciliated cells in the Figure 24.6 Ciliated cells of the respiratory system infected trachea, first impeding their ciliary action and then progres- with Bordetella pertussis. Cells of B. pertussis (orange) can be seen sively destroying the cells (Figure 24.6). This prevents the cili- growing on the cilia; they will eventually cause the loss of the ciliated cells. ary escalator system from moving mucus. B. pertussis produces Q W  hat is the name of the toxin produced by Bordetella pertussis several toxins. Tracheal cytotoxin, a fixed cell wall fraction of the that causes the loss of cilia? B I G P I CTU R E Bioterrorism Biological agents were first tapped by armies, and now by terrorists. Today, technology and ease of travel increase the potential damage. History of Bioweapons Biological Weapons Banned in the Biological weapons (bioweapons)—pathogens intentionally used for Twentieth Century hostile purposes—are not new. The “ideal” bioweapon is one that The Geneva Conventions are internationally agreed upon standards disseminates by aerosol, spreads efficiently from human to human, for conducting war. Written in the 1920s, they prohibited deploying causes debilitating disease, and has no readily available treatment. bioweapons—but did not specify that possessing or creating them The earliest recorded use of a bioweapon occurred in 1346 was illegal. As such, most powerful nations in the twentieth century during the Siege of Kaffa, in what is now known as Feodosia, continued to create bioweapons, and the growing stockpiles posed an Ukraine. There the Tartar army catapulted their own dead soldiers’ ever-growing threat. In 1975, the Biological Weapons Convention plague-ridden bodies over city walls to infect opposing troops. banned both possession and development of biological weapons. The Survivors from that attack went on to introduce the “Black Death” majority of the world’s nations ratified the treaty, which stipulated that to the rest of Europe, sparking the plague pandemic of 1348–1350. any existing bioweapons be destroyed and related research halted. In the eighteenth century, blankets contaminated with smallpox were intentionally introduced into Native American populations by SEM 1 mm SEM the British during the French and Indian War. And during the Sino- 0.4 mm Japanese War (1937–1945), Japanese planes dropped canisters of fleas carrying Yersinia pestis bacteria, the causative agent of plague, on China. In 1975, Bacillus anthracis endospores were accidentally released from a bioweapon production facility in Sverdlovsk. TEM 2 mm (Clockwise from top left): Bacillus anthracis, Ebolavirus, and Vibrio cholerae are just a few microbes identified as potential bioterrorism agents. Emergence of Bioterrorism Unfortunately, the history of biowarfare doesn’t end with the A citadel in Ukraine, location of the first known biowarfare attack ratification of the Biological Weapons Convention. Since then, the in history. main actors engaging in biowarfare have not been nations but rather radical groups and individuals. One of the most publicized bioterrorism incidents occurred in 2001, when five people died Selected Diseases Identified as Potential Bioweapons from, and many more were infected with, anthrax that an army researcher sent through the mail in letters. Bacterial Viral Anthrax (Bacillus anthracis) Nonbacterial meningitis (Arenaviruses) Psittacosis (Chlamydophila Hantavirus disease psittaci) Botulism (Clostridium botulinum Hemorrhagic fevers (Ebola, toxin) Marburg, Lassa) Tularemia (Francisella tularensis) Monkeypox Cholera (Vibrio cholerae) Nipah virus infection Plague (Yersinia pestis) Smallpox Map showing location of 2001 bioterrorism anthrax attacks. 696  Play MicroFlix 3D Animation @MasteringMicrobiology Public Health Authorities Try to Meet the Threat of Bioterrorism One of the problems with bioweapons is that they contain living Vaccination: A Key Defense organisms, so their impact is difficult to control or even predict. When the use of biological agents is considered a possibility, However, public health authorities have created some protocols to military personnel and first -responders (health care personnel and deal with potential bioterrorism incidents. others) are vaccinated—if a vaccine for the suspected agent exists. New vaccines are being developed, and existing vaccines are being stockpiled for use where needed. The current plan to protect civilians in the event of an attack with a microbe is illustrated by the smallpox preparedness plan. This killer disease has been eradicated from the population, but unfortunately, a cache of the virus remains preserved in research facilities, meaning that it might one day be weaponized. It’s not practical to vaccinate all people against the disease. Instead, the U.S. government’s strategy following a confirmed smallpox outbreak includes “ring containment and voluntary vaccination.” A “ring” of vaccinated/protected individuals is built around the bioterrorism infection case and their contacts to prevent further transmission. Biological hazard symbol. New Technologies and Techniques to Identify Bioweapons Monitoring public health, and reporting incidence of diseases of note, is the first step in any bioterrorism defense plan. The faster a potential incident is uncovered, the greater the chance for containment. Rapid tests are being investigated to detect genetic changes in hosts due to bioweapons even before symptoms develop. Early-warning systems, such as DNA chips or recombinant cells that fluoresce in the presence of a bioweapon, are also being developed. Examining mail for B. anthracis. KEY CONCEPTS Vaccination is critical to preventing spread of infectious diseases, especially those that can be weaponized. (See Chapter 18, “Principles and Effects of Vaccinations,” pages 500–501.) Many organisms that could be used for weapons require BSL-3 facilities. (See Chapter 6, “Special Culture Techniques,” pages 161–162.) Pro Strips Rapid Screening System, developed by ADVNT Biotechnologies LLC, is the first advanced multi-agent biowarfare detection kit that Tracking pathogen genomics provides information on its source. tests for anthrax, ricin toxin, botulinum toxin, plague, and SEB (See Chapter 9, “Forensic Microbiology,” pages 258–260.) (staphylococcal enterotoxin B). 697 698 PART FOUR Microorganisms and Human Disease in small children can actually result in broken ribs. Gasping for air between coughs causes a whooping sound, hence the informal name of the disease. Coughing episodes occur several times a day for 1 to 6 weeks. The convalescence stage, the third stage, may last for months. Because infants are less capable of coping with the effort of coughing to maintain an airway, irre- Corded versible damage to the brain occasionally occurs. growth Diagnosis of pertussis is primarily based on clinical signs and symptoms. The pathogen can be cultured from a throat swab inserted through the nose on a thin wire and held in the throat while the patient coughs. Culture of the fastidious patho- LM 2.5 mm gen requires care. As alternatives to culture, PCR methods can also be used to test the swabs for presence of the pathogen, a Figure 24.7 Mycobacterium tuberculosis. The filamentous, red- procedure that is required to diagnose the disease in infants. stained funguslike growth shown here in a smear from lung tissue is Treatment of pertussis with antibiotics, most commonly responsible for the organism’s name. Under other conditions, it grows as slender, individual bacilli. A waxy component of the cell, cord factor, erythromycin or other macrolides, is not effective after onset of is responsible for this ropelike arrangement. An injection of cord factor the paroxysmal coughing stage but may reduce transmission. causes pathogenic effects exactly like those caused by tubercle bacilli. Q What characteristic of this bacterium suggests use of the CHECK YOUR UNDERSTANDING prefix myco-? ✓ 24-6 Another name for pertussis is whooping cough. This symptom is caused by the pathogens’ attack on which cells? Other mycobacterial diseases also affect people in the late stages of HIV infection. A majority of the isolates are of a Tuberculosis related group of organisms known as the M. avium-intracellulare In Europe during the seventeenth through the nineteenth centu- (a-ve-um ˉ ˉ in-trah-SEI-u-lar) ˉ complex. In the general population, ries, tuberculosis (TB) was responsible for an estimated 20–30% infections by these pathogens are uncommon. of all deaths. This probably exerted a strong selection pressure for Mycobacteria stained with carbolfuchsin dye cannot be genes that protected against TB in this population. However, in decolorized with acid-alcohol and are therefore classified as recent decades co-infection with HIV has been a prominent cause acid-fast (see page 66). This characteristic reflects the unusual of increasing susceptibility to infection and also of rapid progres- composition of the cell wall, which contains large amounts of sion from infection to active disease. Other factors are the increas- lipids. These lipids might also be responsible for the resistance ing populations of susceptible individuals in prisons and other of mycobacteria to environmental stresses, such as drying. In crowded facilities, as well as the elderly or undernourished. fact, these bacteria can survive for weeks in dried sputum and Tuberculosis is an infectious disease caused by the bacte- are very resistant to chemical antimicrobials used as antisep- rium Mycobacterium tuberculosis, a slender rod and an obligate tics and disinfectants (see Table 7.7, page 198). aerobe. The rods grow slowly (20-hour or longer generation Tuberculosis is a particularly good illustration of the eco- time), sometimes form filaments, and tend to grow in clumps logical balance between host and parasite in infectious dis- (Figure 24.7). On the surface of liquid media, their growth ease. A host is not usually aware of tuberculosis pathogens that appears moldlike, which suggested the genus name Mycobacte- invade the body and are defeated, which occurs 90% of the rium (myco means fungus). time. If immune defenses fail, however, the host becomes very ˉ Another mycobacterial species, Mycobacterium bovis (BO-vis), much aware of the resulting disease. is a pathogen mainly of cattle. M. bovis is the cause of bovine A tragic demonstration of individual variation in resis- tuberculosis, which is transmitted to humans via contami- tance was the Lübeck disaster in Germany in 1926. By error, nated milk or food. Bovine tuberculosis accounts for fewer 249 babies were inoculated with virulent tuberculosis bacte- than 1% of TB cases in the United States. It seldom spreads ria instead of the attenuated vaccine strain. Even though all from human to human, but before the days of pasteurized received the same inoculum, there were only 76 deaths, and milk and the development of control methods such as tuber- the remainder did not become seriously ill. culin testing of cattle herds, this disease was a frequent form Tuberculosis is most commonly acquired by inhaling the of tuberculosis in humans. M. bovis infections cause TB that bacillus. Only very fine particles containing one to three bacilli primarily affects the bones or lymphatic system. At one time, reach the lungs, where they are usually phagocytized by a a common manifestation of this type of TB was hunchbacked macrophage in the alveoli (see Figure 24.2). The macrophages deformation of the spine. of a healthy individual become activated by the presence of  CHAPTER 24  Microbial Diseases of the Respiratory System 699 the bacilli and usually destroy them. About three-fourths of in which the body’s defenses fail and the disease progresses to TB cases affect the lungs, but other organs can also become a fatal conclusion. However, most healthy people will defeat infected. a potential infection with activated macrophages, especially if the infecting dose is low. Pathogenesis of Tuberculosis 1 1–2 2 3 3If4the 4 5 5infection 6 6 7 7 8 8 9progresses, the host isolates the pathogens 9 1010 The pathogenesis of TB is shown in Figure 24.8. An important in a walled-off lesion called a tubercle (meaning lump or factor in the pathogenicity of the mycobacteria probably is that knob), a characteristic that gives the disease its name. the mycolic acids of the cell wall strongly stimulate an inflam- matory response in the host. The figure depicts the situation Interior of 1 Tubercle bacilli that reach the alveoli of the lung are alveolus ingested by macrophages, but often some survive. Blood capillary Infection is present, but no symptoms of disease. Alveolar walls Interior of alveolus Ingested tubercle bacillus Alveolar macrophage Bronchiole 2 Tubercle bacilli multiplying in macrophages cause a chemotactic response that brings additional macrophages and other defensive cells to the area. Infiltrating macrophage These form a surrounding layer and, in turn, an early (not activated) tubercle. Most of the surrounding macrophages are not successful in destroying bacteria but release Early tubercle enzymes and cytokines that cause a lung- damaging inflammation. 3 After a few weeks, disease symptoms appear as Tubercle bacillus many of the macrophages die, releasing tubercle bacilli and forming a caseous center in the tubercle. Caseous center The aerobic tubercle bacilli do not grow well in this Activated macrophages location. However, many remain dormant (latent TB) and serve as a basis for later reactivation of the Lymphocyte disease. The disease may be arrested at this stage, and the lesions become calcified. 4 In some individuals, disease symptoms appear as a Outer layer of mature mature tubercle is formed. The disease progresses as tubercle the caseous center enlarges in the process called liquefaction. The caseous center now enlarges and Tuberculous cavity forms an air-filled tuberculous cavity in which the aerobic bacilli multiply outside the macrophages. Tubercle bacillus 5 Liquefaction continues until the tubercle ruptures, allowing bacilli to spill into a bronchiole and thus be disseminated throughout the lung and then to the circulatory and lymphatic systems. Rupture of alveolar wall Figure 24.8 The pathogenesis of tuberculosis. This figure represents the progression of the disease when the defenses of the body fail. In most otherwise healthy individuals, the infection is arrested, and fatal tuberculosis does not develop. Q Almost a third of Earth’s population is infected with Mycobacterium tuberculosis—does a study of this figure show why this is not the same as a third of Earth’s population having tuberculosis?  700 PART FOUR Microorganisms and Human Disease 1 2 3 4When 5 6 the 7 8disease 9 10 is arrested at this point, the lesions slowly heal, becoming calcified. These show up clearly on X-ray films and are called Ghon’s complexes. (Computed tomography [CT] is more sensitive than X rays in detecting lesions of TB.) The bacteria may remain viable for years, in which case the disease is called latent TB. Such individuals are infected with M. tuberculosis but do not have TB. The only sign of TB infection is a positive reaction to the tuberculin skin test or TB blood test. Persons with latent TB infection are not infectious and cannot spread TB infection to others. 1 2 3 4 Macrophages 5 6 7 8 9 10ingest and surround the tubercle bacilli, forming a barrier outer layer. 1 2 3 4 5 6If the 7 8body’s 9 10defenses fail at this stage, the tubercle breaks down and releases virulent bacilli into the airways of the Figure 24.9 A positive tuberculin skin test on an arm. lung and then the cardiovascular and lymphatic systems. Q What does a positive tuberculin skin test indicate? Coughing, the more obvious symptom of the lung infec- tion, also spreads the infection by bacterial aerosols. Sputum may become bloodstained as tissues are damaged, and even- The initial step in laboratory diagnosis of active cases is a tually blood vessels may become so eroded that they rupture, microscopic examination of smears, such as sputum. According resulting in fatal hemorrhaging. The disseminated infection is to recent medical opinion, the commonly used 125-year-old called miliary tuberculosis (the name is derived from the numer- microscopic exam routinely misses half of all cases. Confirm- ous millet seed–sized tubercles formed in the infected tissues). ing a diagnosis of TB by isolating the bacterium poses difficul- The body’s remaining defenses are overwhelmed, and the patient ties because the pathogen grows very slowly. A colony might suffers weight loss and a general loss of vigor. At one time, TB take 3 to 6 weeks to form, and completing a reliable identifica- was also known as consumption. tion series may add another 3 to 6 weeks. Blood tests measure release of IFN-γ from white blood Diagnosis of Tuberculosis cells after exposure to mycobacterial antigen in a test tube. People infected with tuberculosis respond with cell-mediated They are the preferred tests for a person who has received BCG immunity against the bacterium. This form of immune vaccinations. response, rather than humoral immunity, develops because the Nucleic acid amplification tests (NAATs) can detect M. tuber- pathogen is located mostly within macrophages. This immu- culosis 1 to 2 weeks sooner than cultures and at the same time nity, involving sensitized T cells, is the basis for the tuberculin can determine resistance to a major TB antibiotic, rifampin. skin test (Figure 24.9), a screening test for infection. A positive Evidence indicates that, compared to the skin test, these test does not necessarily indicate active disease. In this test, rapid tests have higher specificity and less cross-reactivity with a purified protein derivative of the tuberculosis bacterium, BCG vaccination (see the discussion of TB vaccines, following). derived by precipitation from broth cultures, is injected cuta- They do not distinguish latent from active infection. These neously. If the injected person has been infected with TB in the assays seem likely to replace the tuberculin skin test for many past, sensitized T cells react with these proteins, and a delayed uses, especially where cross-reactivity with BCG vaccination is hypersensitivity reaction occurs in about 48 hours. This reac- a problem. If they could be adopted worldwide at centers for TB tion appears as an induration (hardening) and reddening of treatment, they would help avert millions of TB-related deaths. the area around the injection site. In this test, known as the Treatment of Tuberculosis Mantoux test, dilutions of 0.1 ml of antigen are injected and the reacting area of the skin is measured. The first effective antibiotic for TB treatment was streptomy- A positive tuberculin test in the very young is a probable cin, which was introduced in 1944. Streptomycin is still in use, indication of an active case of TB. In older individuals, it might and all of the currently used drugs were developed decades indicate only hypersensitivity resulting from a previous infec- ago. Even the short course of treatment for TB (there are varia- tion or vaccination, not a current active case. Nonetheless, it tions in the regimen, depending on sensitivity of the organism is an indication that further examination is needed, such as and other factors) requires the patient to adhere to a mini- a chest X-ray or CT examination to detect lung lesions and mum of 6 months of therapy. Multiple-drug therapy is needed attempts to isolate the bacterium. to minimize the emergence of resistant strains. This typically  CHAPTER 24  Microbial Diseases of the Respiratory System 701 includes four drugs, isoniazid, rifampin, ethambutol, and pyr- rifampin, is not due to a single gene. One new test, MTBDRsl, azinamide, which are considered first-line drugs. If the strain does identify resistance to fluoroquinolones. of M. tuberculosis is susceptible to the drugs, this regimen can lead to a cure. The likelihood that resistance may develop is Tuberculosis Vaccines increased because many patients fail to faithfully follow such a The BCG vaccine is a live culture of M. bovis that has been prolonged regimen, which can involve 130 doses of the drugs. made avirulent by long cultivation on artificial media. (BCG In addition to the first-line drugs, there are a number of stands for bacillus of Calmette and Guérin, the French scien- ­second-line drugs that can be used, mainly if resistance devel- tists who originally isolated the strain.) The BCG vaccine has ops to alternatives. These include several aminoglycosides, been available since the 1920s and is one of the most widely fluoroquinolones, streptomycin, and para-aminosalicylic acid used vaccines in the world. In 1990, it was estimated that (PAS). These drugs are either less effective than first-line drugs, 70% of the world’s schoolchildren received it. In the United have toxic side effects, or may be unavailable in some countries. States, however, the vaccine is currently recommended only The prolonged treatment is necessary because the tubercle for certain children at high risk who have negative skin tests. bacillus grows very slowly or is only dormant (the only drug People who have received the vaccine show a positive reaction effective against the dormant bacillus is pyrazinamide), and to tuberculin skin tests. This has always been one argument many antibiotics are effective only against growing cells. Also, against its widespread use in the United States. Another argu- the bacillus may be hidden for long periods in macrophages or ment against the universal administration of BCG vaccine is its other locations that are difficult to reach with antibiotics. very uneven effectiveness. Experience has shown that it is fairly Not surprisingly, problems have arisen with cases of TB that effective when given to young children, but for adolescents are caused by multi-drug-resistant (MDR) strains. These are and adults it sometimes has an effectiveness approaching zero. defined as being resistant to the two most effective first-line Worse, it has been found that HIV-infected children, who need drugs, isoniazid and rifampin. In addition, strains have arisen it most, frequently will develop a fatal infection from the BCG that are also resistant to the most effective second-line drugs, vaccine. Recent work indicates that exposure to members of the such as any fluoroquinolone, and to at least one of three inject- M. avium-intracellulare complex that is often encountered in the able second-line drugs, such as the aminoglycosides amikacin environment may interfere with the effectiveness of the BCG or kanamycin, as well as the polypeptide capreomycin. These vaccine—which might explain why the vaccine is more effec- cases, defined as extensively drug-resistant (XDR), are vir- tive early in life, before much exposure to such environmental tually untreatable and are emerging globally. An additional mycobacteria. A number of new vaccines are in the experimen- consideration is that anywhere from 30–90% of persons with tal pipeline, but they will require large numbers of human TB are also HIV positive—with the accompanying damage to samples and several years of follow-up to evaluate. the immune system. In one study, all patients testing positive for both HIV and XDR tuberculosis died within 3 months of Worldwide Incidence of Tuberculosis diagnosis. Tuberculosis has emerged as a global pandemic (Figure 24.10a). Obviously, there is a pressing need for new, effective drugs Estimates are that more than 10 million people develop active to treat TB, especially XDR cases. In 2012, bedaquiline was tuberculosis every year and that infections result in nearly approved to treat MDR TB. 2 million deaths annually. (Worldwide, the incidence of TB per capita is falling at about 1% a year. However, the world pop- Testing for Drug Susceptibility ulation is growing at about 2% a year—therefore, the total Solid-media culture-based methods for drug susceptibility number of new TB cases is still rising.) Probably a third of the testing can take as long as 4 to 8 weeks for finalized results. world’s population has latent TB. Also, HIV and tuberculosis However, M. tuberculosis grows faster in liquid media. These are almost inseparable, and tuberculosis is the leading direct assays are simultaneously useful for both diagnosis and deter- cause of death in much of the world affected by HIV. mination of drug susceptibility. The Microscopic-Observation TB incidence in the United States steadily decreased for Drug-Susceptibility Assay (MODS) is based on direct obser- decades (see Figure 14.11c, page 415). The incidence has been vation of the typical cording growth (see Figure 24.7) of approximately three cases per 100,000 people for the past few M. tuberculosis in liquid cultures, requires only 6 to 8 days, and years, with two-thirds of the cases occurring among foreign- is relatively inexpensive. The determination of susceptibility born people (Figure 24.10b). for rifampin can be considered a marker for potential resistance to other drugs. Recall that NAATs also rapidly test for rifampin Bacterial Pneumonias resistance. NAATs are needed to determine resistance to the The term pneumonia is applied to many pulmonary infections, other first-line and second-line anti-TB drugs. The biggest most of which are caused by bacteria. Pneumonia caused by problem is that most drug resistance, aside from resistance to Streptococcus pneumoniae is the most common, about two-thirds 702 PART FOUR Microorganisms and Human Disease KEY 0–24.9 25–99 100–199 200–299 ≥300 No data Not applicable (a) Estimated tuberculosis incidence worldwide in 2016, per 100,000 population (b) Reported tuberculosis Asian cases among American ethnic groups in 2016 U.S.-born Hispanic Black White Asian Foreign.-born Hispanic Black White 0 500 1000 1500 2000 2500 3000 Reported number of cases Figure 24.10 Distribution of tuberculosis. (a) Tuberculosis worldwide. (b) Tuberculosis in the United States. Rates among American ethnic groups. Source: World Health Organization (WHO), 2017; MMWR 65(11): 273–278, March 24, 2017. Q How can tuberculosis be eliminated? of cases, and is therefore referred to as typical pneumonia. Pneu- Pneumonias also are named after the portions of the lower monias caused by other microorganisms, which can include respiratory tract they affect. For example, if the lobes of the fungi, protozoa, viruses, and other bacteria, especially myco- lungs are infected, it is called lobar pneumonia; pneumonias plasma, are termed atypical pneumonias. This distinction is caused by S. pneumoniae are usually of this type. Bronchopneu- becoming increasingly blurred in practice. monia indicates that the alveoli of the lungs adjacent to the  CHAPTER 24  Microbial Diseases of the Respiratory System 703 bronchi are infected. Pleurisy is often a complication of various pneumonias, in which the pleural membranes become pain- fully inflamed. (See Diseases in Focus 24.2.) Pneumococcal Pneumonia Pneumonia caused by S. pneumoniae is called pneumococcal pneumonia. S. pneumoniae is a gram-positive, ovoid bacterium (Figure 24.11). This microbe is also a common cause of otitis media, meningitis, and sepsis. The cell pairs are surrounded by a dense capsule that makes the pathogen resistant to phagocy- Capsules tosis. These capsules are also the basis of serological differen- tiation of pneumococci into at least 90 serotypes. Most human infections are caused by only 23 variants, and these are the basis of current vaccines. Pneumococcal pneumonia involves both the bronchi and the alveoli (see Figure 24.2). Symptoms include high fever, TEM 1 mm breathing difficulty, and chest pain. (Atypical pneumonias Figure 24.11 Streptococcus pneumoniae, the cause of usually have a slower onset and less fever and chest pain.) The pneumococcal pneumonia. Some of the cocci in the photo are lungs have a reddish appearance because blood vessels are undergoing division and appear as extended ovals. The prominent dilated. In response to the infection, alveoli fill with some red capsule appears as a bright outline. blood cells, neutrophils (see Table 16.1, page 454), and fluid Q What component of the cell is the primary antigen? from surrounding tissues. The sputum is often rust colored from blood coughed up from the lungs. Pneumococci can invade the bloodstream, the pleural cavity surrounding the The pneumococcal polysaccharide vaccine, recommended lung, and occasionally the meninges. No bacterial toxin has for people with asthma and for older adults, protects against been clearly related to pathogenicity. 23 strains of the bacteria. A presumptive diagnosis can be made by isolating the pneumococci from the throat, sputum, and other fluids. Pneu- Haemophilus influenzae Pneumonia mococci can be distinguished from other alpha-hemolytic Haemophilus influenzae is a gram-negative coccobacillus, and streptococci by observing the inhibition of growth next to a a Gram stain of sputum will differentiate this type of pneu- disk of optochin (ethylhydrocupreine hydrochloride) or by monia from pneumococcal pneumonia. Children under 5 and performing a bile solubility test. A latex indirect agglutination adults over 65 are most at risk for infection. The Hib vaccine test (see Figure 18.7, page 512) that detects a capsule antigen of has reduced the incidence in children by 99%. Diagnostic iden- S. pneumoniae in the urine can be performed in a physician’s office tification of the pathogen uses special media that determine and, with 93% accuracy, can make a d ­ iagnosis in 15 minutes. requirements for X and V factors (see page 305). Third-generation There are many healthy carriers of the pneumococcus. Vir- cephalosporins are resistant to the b-lactamases produced by ulence of the bacteria seems to be based mainly on the carrier’s many H. influenzae strains and are therefore usually the drugs resistance, which can be lowered by stress. Many illnesses of of choice. older adults terminate in pneumococcal pneumonia. A recurrence of pneumococcal pneumonia is not uncom- Mycoplasmal Pneumonia mon, but the serological types are usually different. Before The mycoplasmas, which do not have cell walls, do not grow chemotherapy was available, the mortality rate was as high as under the conditions normally used to recover most bacterial 25%. This has now been lowered to 5–7%. About 90% of the pathogens. Because of this characteristic, pneumonias caused 900,000 infections that occur annually are in adults. by mycoplasmas are often confused with viral pneumonias. Antibiotic resistance is an increasing problem. Treatment The bacterium Mycoplasma pneumoniae is the causative agent usually begins with a broad-spectrum cephalosporin until of mycoplasmal pneumonia. This type of pneumonia was first antibiotic-sensitivity testing is done (see Figure 20.17, page 578). discovered when such atypical infections responded to tetracy- Possible drugs include a b-lactam, macrolide, or fluoroquinoline. clines, indicating that the pathogen was nonviral. Mycoplasmal A conjugated pneumococcal vaccine has been effective in pneumonia is a common type of pneumonia in young adults preventing infection by the 13 serotypes included in it. It has and children. It may account for as much as 20% of pneumo- also had an indirect herd effect shown by reduction in other nias, although it is not a reportable disease. The symptoms, diseases, such as otitis media, attributable to the pneumococcus. which persist for 3 weeks or longer, are low-grade fever, cough, DISEASES IN FOCUS 24.2 Common Bacterial Pneumonias P neumonia is a leading cause of illness A 27-year-old man with a history of and death among children worldwide and asthma is hospitalized with a 4-day history the seventh leading case of death in the of progressive cough and 2 days of spiking United States. Pneumonia can be caused by a fevers. Gram-positive cocci in pairs are variety of viruses, bacteria, and fungi. To prove cultured from a blood sample. Use the table that a bacterium is causing the pneumonia, below to identify infections that could cause the bacterium is isolated from cultures of these symptoms. For the solution, go to blood or, in some cases, lung aspirates. @MasteringMicrobiology. An optochin-inhibition test of the cultured bacteria on blood agar. Disease Pathogen Symptoms Reservoir Diagnosis Treatment Pneumococcal Streptococcus Infected alveoli of lung fill Humans Positive optochin Macrolides Pneumonia pneumoniae with fluids; interferes with inhibition test or bile Prevention: oxygen uptake solubility test; presence pneumococcal of capsular antigen vaccine Haemophilus Haemophilus Symptoms resemble Humans Isolation; special Cephalosporins influenzae influenzae pneumococcal pneumonia media for nutritional Prevention: Hib Pneumonia requirements vaccine Mycoplasmal Mycoplasma Mild but persistent Humans Isolation of bacteria Tetracyclines Pneumonia pneumoniae respiratory symptoms; low fever, cough, headache Legionellosis Legionella Potentially fatal pneumonia Water Culture on selective Azithromycin pneumophila media Psittacosis Chlamydophila Symptoms, if any, are fever, Birds Bacterial culture or PCR Tetracyclines (Ornithosis) psittaci headache, chills Chlamydial Chlamydophila Mild respiratory illness; Humans PCR Azithromycin Pneumonia pneumoniae resembles mycoplasmal pneumonia Q Fever Coxiella Mild respiratory disease Large mammals; Increasing antibody titer Doxycycline and burnetii lasting 1–2 weeks; can be transmitted chloroquine occasional complications via unpasteurized such as endocarditis occur milk and headache. Occasionally, they are severe enough to lead to be required for the slow-growing organisms to develop. Rapid hospitalization. Other terms for the disease are primary atypical PCR tests are becoming available; however, they are expensive (that is, the most common pneumonia not caused by the pneu- and have not been clinically validated. mococcus) and walking pneumonia. Treatment with antibiotics such as tetracycline usually has- When isolates from throat swabs and sputum grow on a tens the disappearance of symptoms but does not eliminate the medium containing horse serum and yeast extract, some form bacteria, which the patient continues to carry for several weeks. distinctive colonies with a “fried-egg” appearance (Figure 24.12). The colonies are so small that they must be observed Legionellosis with magnification. The mycoplasmas are highly varied Legionellosis, or Legionnaires’ disease, first received pub- in appearance because they lack cell walls (see Figure 11.24, lic attention in 1976, when a series of deaths occurred among page 316). members of the American Legion who had attended a meet- Diagnosis based on recovering the pathogens might not be ing in Philadelphia. Because no obvious bacterial cause could useful in treatment because as long as 3 or more weeks may be found, the deaths were attributed to viral pneumonia. 704  CHAPTER 24  Microbial Diseases of the Respiratory System 705 Men over 50 are the most likely to contract legionellosis, espe- cially smokers or the chronically ill. (See the Clinical Focus box on page 708.) L. pneumophila is also responsible for Pontiac fever, which is essentially another form of legionellosis. Its symptoms include fever, muscular aches, and usually a cough. The condition is mild and self-limiting. During outbreaks of legionellosis, both forms may occur. The best diagnostic method is culture on a selective charcoal– yeast extract medium. Serological tests to detect O antigen in urine are available. However, these tests detect only one sero- group. Azithromycin and other macrolide antibiotics are the drugs of choice for treatment. LM 175 mm Psittacosis (Ornithosis) Figure 24.12 Colonies of Mycoplasma pneumoniae, the cause The term psittacosis is derived from the disease’s association of mycoplasmal pneumonia. with psittacine birds, such as parakeets and other parrots. It was Q Could you see these colonies without magnification? later found that the disease can also be contracted from many other birds, such as pigeons, chickens, ducks, and turkeys. Therefore, the more general term ornithosis has come into use. Close investigation, mostly with techniques directed at locat- The causative agent is Chlamydophila psittaci (SIT-tah-se), ˉ a ing a suspected rickettsial agent, eventually identified a previ- gram-negative, obligate intracellular bacterium. The taxonomy ously unknown bacterium, an aerobic gram-negative rod now of this organism has recently been revised. The genus name known as Legionella pneumophila, which is capable of replica- has been changed from Chlamydia to Chlamydophila. This taxo- tion within macrophages. Over 44 species of Legionella have nomic change has also been made with C. pneumoniae (see the now been identified; not all of them cause disease. discussion of chlamydial pneumonia that follows). We will The disease is characterized by a high fever of 40.5°C, continue to use the generic terms chlamydial and chlamydiae. cough, and general symptoms of pneumonia. No person-to- One way chlamydiae differ from rickettsias, which are also person transmission seems to be involved. Recent studies have obligate intracellular bacteria, is that chlamydiae form tiny shown that the bacterium can be readily isolated from natu- ­elementary bodies as one part of their life cycle (see Figure ral waters. In addition, the microbes can grow in the water of 11.15, page 310). Unlike most rickettsias, elementary bodies air-conditioning cooling towers, perhaps indicating that some are resistant to environmental stress; therefore, they can be epidemics in hotels, urban business districts, and hospitals transmitted through air and do not require a bite to transfer were caused by airborne transmission. Recent outbreaks have the infective agent directly from one host to another. been traced to whirlpool spas, humidifiers, showers, decorative Psittacosis is a form of pneumonia that usually causes fever, fountains, and even potting soil. coughing, headache, and chills. Subclinical infections are very The organism has also been found to inhabit the water lines common, and stress appears to enhance susceptibility to the of many hospitals. Most hospitals keep the temperature of hot disease. Disorientation, or even delirium in some cases, indi- water lines relatively low (43–55°C) as a safety measure, and in cates that the nervous system can be involved. cooler parts