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Molds can assume various forms, starting with the basic hyphal structure that can then differentiate into various reproductive structures (conidia and spores). Chronically infecting strains are generally not transferred between cystic fibrosis patients; however, epidemic lineages have now emerged. In the remaining two-thirds of individuals, the treponemes per sist without causing signs or symptoms for years (latent syphilis. Passively administered antibody can protect humans against several infections including measles, hepatitis A and B. However, the increase typically occurs 3 to 4 weeks or more after the initial infection and is thus useless for the management of severely ill patients (in whom the incubation period may be as short as 2 or 3 days). During World War I, the Germans infected cattle destined for consumption by Allied forces with anthrax and glanders. This type of spread is accomplished by making intricate use of the host cytoskeleton. Serum and secretory (IgA) antibody response at different times after immunization with Salk vaccine (red line) or Sabin vaccine (blue line). Although rare, such mechanical obstructions do occur in children with an overload of worms in their intestines. Complications of chickenpox include cerebellar ataxia in otherwise healthy children and encephalitis in immunocompromised persons. From puberty until young adulthood, formation of apical cavities soon after primary infection is common. Microbes that elaborate lipase toxins thus eliminate potential host defenses and at the same time create a necrotic, nutritionally rich anaerobic milieu in which the microorganisms thrive. Although the infection is never cleared and lung function progressively declines, P. We do not understand how spirochetes kill so many epidermal cells to create a chancre or how the ulcer heals. In general, monocytes and macrophages come into play slowly, often hours after neutrophils have been actively combating invading microorganisms. Strongyloides infections may become chronic and produce symptoms for several decades. Because the Fc region is the portion recognized by phagocytes, the organisms may be less likely to be taken up by white blood cells when this portion of the immunoglobulin molecule is removed. It is also the cause of tinea versicolor, which usually appears on the chest or neck as hypopigmented or hyperpigmented patches with slight scaling. Note that the lactose repressor is an allosteric protein, capable of undergoing conformational changes under the influence of an effector. An example is the tubercle bacillus, which thrives in the portions of the body that are well oxygenated, such as the lungs. An example is the protozoa called Leishmania, which causes several severe tropical diseases. Pharyngeal and rectal gonorrhea are the result of nonvaginal intercourse, whereas ophthalmia (eye infection) is caused by the infection of the eyes of a neonate as it passes through the birth canal of the infected mother. Minimal swelling and erythema were evident in the area of tenderness, and the knee joint was normal with a full range of motion. It is characterized by Salmonella typhi invasion of the gut-associated lymph 610 Part 3: Pathophysiology of Infectious Diseases especially to developing countries, and prolonged duration of symptoms. The symptoms gradually abated, but he later developed a somewhat droopy eyelid on one side and transient aches in multiple joints, which also spontaneously resolved with time. An example of such an adhesin is invasin, a protein that recognizes normal cellular receptors on host cells called integrins. Infections of the intestinal tract can lead to local tissue damage or inflammation and cause bloody diarrhea or dysentery (see Chapter 17). Broad-spectrum, primarily intravenous and bactericidal, antibiotics directed against the most likely pathogens should be administered within 1 hour of diagnosis of 678 Part 3: Pathophysiology of Infectious Diseases septic shock or severe sepsis. The predictive value of a diagnostic test is influenced by the frequency of the infection in the population being tested. With a decline in the incidence of severe rotavirus illness due to vaccination, noroviruses may soon become the most common cause of gastroenteritis in this age group. They could now try to identify the risk factors for the clinical syndrome by carefully determining what epidemiologists call the time, place, and personal characteristics of the cases.
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The manifestations of congenital syphilis are varied and include life-threatening organ damage, silent infections, congenital malformations, and developmental abnormalities. Chloroquine resistance occurs by mutation of a vacuolar membrane protein that causes chloroquine to be pumped out of the food vacuole and permits heme detoxification to resume. As the list of enteric pathogens lengthens and an understanding of how they produce disease emerges, the practical challenge of diagnosis and treatment increases. Continuous inflammation within the gastric mucosa may be sufficient to lead to mucosal breakdown, erosive gastritis, and ultimately gastric ulceration. Mechanical barriers are highly effective, especially in the skin, which is covered with a thick layer of keratinized epithelium. The boxes shown in color indicate locations of the viral structural genes, and the open boxes indicate locations of the viral accessory genes. Group translocation: Also known as phosphorylation-linked transport, this energy-dependent mechanism is used to transport certain sugars. Under war conditions, frontline hospitals and evacuation facilities have ameliorated the damage caused by gunshot and shrapnel. An important biological characteristic of all herpesviruses is the capacity to establish lifelong latent infections, whether or not acute primary disease is evident. Less often in the United States, bloody watery diarrhea is caused by other pathogens, including Shigella, Salmonella, Campylobacter jejuni, or, more uncommonly, Yersinia enterocolitica. Encounter: Chlamydiae cause a wide variety of genital, ocular, and respiratory infections in humans; certain animal and avian isolates cause disease. These factors confer clear selective advantages on the microorganisms that produce them. Complement derives its name from the original belief that it complements, or completes, the action of antibodies. Epidemiologists must be aware of the various susceptibilities of members of the general population. An organism that goes undetected is able to reproduce, and it is this ability and not the ability to cause disease that is the main selective force in nature. The average life expectancy, that is, the age to which half of the population survives, is indicated by the black dots. It was not until 60 years later that Philippe Ricord correctly distinguished the two diseases. In every instance, local defenses of the gastrointestinal tract must be overcome for disease to occur. Phagosomes fuse with enzyme-laden lysosomes to form a phagolysosome for degradation of the microbial material into proteolytic fragments. The fear, panic, and quarantine measures that would result from such an epidemic could rapidly overwhelm health care resources and destabilize affected countries. All members of the genus Neisseria and related genera possess a cytochrome oxidase that can catalyze a color change in the presence of a specific reagent. The strongest antibody response to bacterial antigens is usually directed to surface antigens. As a consequence, this age group has an increased susceptibility to certain infections such as those caused by influenza virus, pneumococcus, and varicella. In any form of filariasis, diethylcarbamazine can produce systemic reactions, presumably resulting from the sudden release of filaria antigens from damaged microfilariae (as in Mr. Several weeks later, the sera from the immunized rabbits were prepared and used as the antibody source (antisera). If a necrotizing infection is suspected, the diagnosis should be confirmed by inspection of the fascia and muscle by surgical exploration. Bioinformatics methods of this metagenome sequencing data enables the placement of the sequences into taxonomical units without the need to culture the constituent organisms. First, the fetal membranes shield the fetus well from the microorganisms in the uterine environment.
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An explanation for the lack of permanent immunity is not clear, but the likely contributing factors are antigenic variation of the virus, inhibition of host immune responses mediated by viral proteins, and rapidly waning mucosal IgA in the upper respiratory tract. Intracellular localization may facilitate establishment of chronic infections and evasion of the host immune response as sometimes occurs with other facultative intracellular microorganisms. These pathogens can readily multiply because the resident microbiota at the level of the jejunum and upper ileum is scanty and thus pose no significant competition. Syphilis is a multistage disease, and each stage has a dramatically different clinical presentation. Other chapters discuss some of the more common agents of intestinal infections (see Chapters 16, 17, 37, 51, 53, 54, and 76). At the end of that period (the hepatocellular cycle), they are released once again into the bloodstream in a form that can invade red blood cells (merozoites). Sometimes the patient complains of chest pain, frequently pleuritic (exacerbated by respiratory motion). On the other hand, if local viral replication is still ongoing when these additional cells arrive, the virus is provided cellular fodder for additional rounds of replication, and the infection disseminates, becoming self-sustaining. Arthropods expose humans to agents that are otherwise restricted to animals or birds. In infants less than 1 year of age, it is often difficult to distinguish bacterial from aseptic meningitis. Although some persons develop serious (even fatal) illness, most develop a relatively mild disease with fever, recover spontaneously, and remain asymptomatic. Necrotizing infection of muscle is called myonecrosis, and when caused by gasproducing Clostridium bacteria, C. In a burned mouse model, strains deficient in any of a number of products (exotoxin A, elastase, or ExoS; see Table 18-2) persist in the wound but Adherence and Colonization Aside from their functions in motility, both these factors have other roles with respect to virulence. Recent progress has been made in vaccine development against meningococcal infection, but challenges remain for prevention of infection by N. Macrophages are capable of killing not only, relatively small intracellular parasite such as erythrocytic stage of malarial parasite, but also, when activated, larger parasite such as the larval stage of schistosomes. Proper education about disease transmission and frequent changes of gloves and outer clothing can reduce the spread of the spores. In the face of active infection, deciding whether to remove a fixation device or joint prosthesis to facilitate cure is often difficult and emotionally traumatic. In fact, there are negative outcomes including adverse drug effects and emergence of antimicrobial resistance. Impaired clearance of mucous predisposes these patients to chronic infection and inflammation, making them particularly susceptible to infections with Staphylococcus aureus and pseudomonas species. Another group of pneumonia pathogens, encountered less frequently, have animal or environmental reservoirs. Other parasites are geographically restricted to regions where specific conditions for transmission are present (Table 51-2). If the oropharynx is not colonized with virulent bacteria, a significantly larger amount of aspirated material. Slightly distinct from latency is a state of chronic infection, in which the microbe remains in an active infectious state at low level within the host. Others are ubiquitous in the environment, and healthy hosts are continually exposed with no dire consequences. Sanitation is particularly effective in reducing rates of parasitic infections transmitted through contaminated stool or urine, such as ascariasis, strongyloidiasis, and hookworm infection. In general, the more rapid the diagnosis, the sooner proper therapy can be instituted. Activities during the weekend included hiking through scrubby, grassy, and lightly wooded areas. The pathological processes leading to abscess formation include a massive influx of neutrophils and sequestration of the infected site. The major action of tetanus toxin is inhibition of neurotransmitter release and normal inhibitory input, thereby causing the lower motor neuron to increase resting tone and producing the characteristic reflex spasms (see Chapter 9). Microbes elaborate substances or organelles that are involved in the adherence and are known as adhesins (Table 8-1).
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In the United States, the original 7-valent pneumococcal conjugate vaccine has now been replaced by a 13-valent preparation. The physician drained the lesion, and a culture of the pus grew a group A -hemolytic streptococcus (S. B cells, however, have the ability to change the immunoglobulin isotype they 96 Part 1: Principles produce to IgG, IgE, or IgA, a process known as the isotype switch, and by doing so influence the ultimate nature of the humoral immune response. A second patient group for whom identification and treatment of asymptomatic bacteriuria is recommended is those undergoing a urological procedure with potential mucosal trauma and bleeding. A few hundred Shigella dysenteriae type 1 are sufficient to cause disease in many volunteers. Because most infectious diseases have short incubation periods, usually less than 2 weeks, active immunization is often ineffective for use as postexposure control. Many years later it was recognized that erythema migrans was often followed by a chronic skin disease (acrodermatitis chronica atrophicans), which had already continued on page 280 280 Part 2: Infectious Agents (continued) been described as a separate entity. When the parasite reaches the infective stage, it invades the human host, matures, replicates, and ultimately completes the life cycle by producing infective forms. Serotypes 1, 2, 5, and 6 are endemic in most populations, and 80% of all young adults have neutralizing antibodies to those types. Both viruses can be isolated from secretions collected from the oropharynx and the genital tract. Her physician then learned that rifampin, one of the four antituberculous drugs she was taking, induces the liver to accelerate the clearance of warfarin. Under these conditions, phage genes were expressed, but lacZ and any fusion proteins resulting from insertion of M. Spread in one or the other direction has different consequences: in the first case, it could lead to a generalized pneumonia and in the second, to pleurisy. However, phlebotomine sand flies are occasionally found in more temperate regions, and indigenous cases have been reported in the United States. It is likely effective through intermittent sterilization of the urine with high urinary antimicrobial levels. Diversity of several orders of magnitude are also added by an enzyme, terminal deoxyribonucleotidyl transferase (TdT), that removes or adds nucleotides between the V, D, and J genes in a process known as junctional diversity. Reinfection may then occur from larval invasion of the perianal skin, even if the patient has not been exposed to new external sources of infection. Congenital anomalies include premature birth, intrauterine growth retardation, and multiple organ failure. She suddenly developed an intense chill that lasted for about 30 minutes, followed by a fever to 40. Noroviruses cause outbreaks in nursing homes, on cruise ships, and in essentially any setting where individuals are confined in close contact. The smear shows lancet-shaped diplococci with many polymorphonuclear leukocytes, and no other prominent bacterial morphology is present. Evidence that education has an impact on sexual practices comes from experience in the gay community in San Francisco as well as in heterosexual populations in resource-limited countries where governments have openly advocated for strategies to curtail the epidemic. The inhibition usually involves one of three mechanisms: (1) a suicide substrate mechanism, in which an inhibitor forms a covalent bond with the active site of the enzyme. In fact, a vaccine against the disease was developed and was shown to be effective, but manufacturers have stopped development because of concern about the potential risk of arthritis resulting from vaccine administration. For all of their disease importance, adenovirus pathogenic mechanisms are not well understood. After an incubation period of 2 to 21 days, infected persons develop fever, myalgias, headache, retro-orbital pain, and prostration. The final pre-B cell stage occurs when or light chains replace surrogate light chains. Such defects render their phagocytes incapable of producing the reduced oxygen products. A wide variety of pathogens couple the expression of their specific virulence mechanisms with more general adaptations, like stress resistance. Ongoing malaria surveillance is therefore particularly important when large numbers of people from malaria-endemic areas enter nonmalarious areas where substantial numbers of Anopheles mosquitoes are present. Hyperimmune globulin and monoclonal antibodies have been tried unsuccessfully as a strategy to inactivate specific proinflammatory mediators or to prevent binding to their receptors. Diarrhea may be absent or transient; some patients may even complain of constipation.
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Prevention of infection is key to inhibiting arbovirus-induced morbidity and mortality. Early infection can also be diagnosed by detecting infection in reduviid bugs that have purposely been allowed to feed on the patient. The physician recognized the "macular rash" on the palms and soles and the lesion on his lip as characteristic of secondary syphilis. The largest single waterborne outbreak of Cryptosporidium infection in the history of the United States occurred in Milwaukee, Wisconsin, in 1993. Usually, entry of microorganisms into the circulation represents a brief phase of an infection centered primarily in another organ system. As mentioned above, M protein plays a role in adhesion to keratinocytes and prevents opsonization by complement through two mechanisms. Parasites can cause disruption of lymphoid cells or tissue directly (the soluble lymphotoxic factor of T. In fact, vaccination with the current pandemic H1N1 influenza vaccine protects mice against a challenge with the 1918 virus. Each colony that arose represented a single transformant that contained a plasmid with, potentially, a separate piece of the Y. Most colonized persons have asymptomatic, chronic gastritis, but approximately 10% develop gastric or duodenal ulcers. When bacterial conjunctivitis occurs alone, the most common causative agents include nontypeable H. The bacteria after successfully evading the innate defense mechanisms (mechanical barrier, antibacterial substances, phagocytosis, etc. Epidermodysplasia verruciformis differs in that it is often, but not always, inherited and usually manifests in childhood. Some commensal bacteria produce substances that inhibit newcomers, such as antibiotics or lethal proteins called bacteriocins. Rapid activation of plasma protein systems, including the complement and coagulation cascades and the kallikrein-kinin system, also ensues (Table 66-1). The source of secondary gut invasion may be bacteria from the bloodstream during the prolonged secondary bacteremia or bacteria shed in the bile that penetrate M cells. Lung abscesses can also result from infection with other organisms that destroy lung tissue, including S. During that process, the outer shell of the virus is removed leaving behind the transcriptionally active viral core. This property of the vaccine is more relevant in developing country like India, where majority do not turn up for the second and subsequent doses of the vaccines. Recrudescent typhus was described in the late 1800s in New York City among immigrants from eastern Europe, where epidemics of typhus were notorious. Much effort is directed toward the development of rapid diagnostic methods, but most still require one or several days (see Chapter 58). Scarlet fever was excluded on the basis of a negative rapid test for Streptococcus pyogenes. Immunization at 6 months of age will protect some of these infants, but many others will fail to respond because of the presence of maternal antibodies and immunologic immaturity. The FcRs on phagocytic cells recognize and bind conformationally changed Fcs but not immunoglobulins that have not bound an epitope. Consequently, microscopic examination of stool from a patient without characteristic clinical features and colonic ulcers may be misleading. Probiotics, including yoghurt, have not been found to be effective in preventing recurrent infection. Inhibition by sulfonamides then is dependent on the continued growth of the bacteria. The treatment of choice is trimethoprim/sulfamethoxazole, which is also a highly effective prophylactic regimen in high-risk populations. The typical result of this method and others is that the intensity of the fluorescence in the reaction vessel increases as more amplicons are generated. Vaccines are often administered to healthy persons to prevent disease in immunocompromised individuals.
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The prognosis with tuberculoid leprosy is better than that with lepromatous leprosy and, in some cases, tuberculoid leprosy is a self-limited disease. Because the parasite is infectious in the cyst stage and does not require a period of maturation in the environment, transmission of amebiasis is not restricted to warm climates. Superbugs in the coming new decade; multidrug resistance and prospect for treatment of Staphylococcus aureus, Enterococcus spp. Biopsies from two sites in the stomach were taken for histologic examination and culture. Thus, the use of influenza virus vaccines is cost-effective and brings added benefits to certain risk groups. Humoral immune responses, both antibodies and complement activation pathways, may be viewed as the arrows and missiles of the immune system that are aimed or lobbed at a distant enemy. In massive numbers, intestinal parasites can cause disease by contributing to the malnutrition of their host, occluding the intestinal lumen, or triggering a symptomatic immune response (Tables 54-1 and 54-2). Mutants deficient for such systems might survive within the host long enough to elicit an immune response before becoming growth-limited because of the mutation. Hematoxylin and eosin stain of Clostridium perfringens in muscle tissue from gas gangrene. Nucleocapsids exit the nucleus by sequential budding through the inner and outer leaflets of the nuclear membrane, acquire the tegument layer of protein in the cytoplasm, and eventually become enveloped in the secretory pathway. Had Houdini lived today and been in the hands of a competent physician, he would have been treated with antibiotics and surgical repair and would have had a good chance of surviving. After 2 or 3 days, the cells burst, liberating a new generation of infective merozoites that infect previously unparasitized red blood cells (the erythrocytic cycle). At this point in the epidemic, there are fewer than 50 perinatal transmissions in the United States each year. Meningococci employ a different strategy to avoid complement C3b peptidase cleaves the complement component into inactive fragments. Invasion of the bacteria can also be inhibited by restricting the motility, when antiflagellar antibodies are produced. Streptolysin O (O stands for "oxygen labile") binds to cholesterol in the cell membrane. Spread and Multiplication: Disease is characterized by three stages: primary syphilis, in which the organism is localized to a chancre, or skin lesion; secondary syphilis, in which the organism disseminates to distant sites; and tertiary syphilis, in which the immune response to the organisms leads to the destruction of tissue. This enzyme is necessary for human cells as well as for bacteria, but the amount needed to cause 50% enzyme inhibition is 0. Differentiating smallpox (variola) from the more common chickenpox (varicella) can be challenging, but several discriminating features make accurate diagnoses possible (Table 57-3). When given for 5 days before viral infection, interferon was 80% effective in preventing illness. Other outbreaks of adenovirus infections are seen among military recruits in the form of serious acute pneumonia. Chemotactic factors, derived both from bacteria and complement, are made in large amounts. Microsporidia belong to a phylum containing almost 1,000 species found ubiquitous among vertebrate and invertebrate animals and in the environment. Treatment fails because of rapid progression of the infection or underlying debility of the patient. Blood oxygen levels may be low, which may contribute to confusion and lethargy seen in Mrs. The recruitment of eosinophils is mediated by a specific factor, eosinophilic stimulation promoter, which is a product of T cell. Solid matrix antibody-antigen complexes can be designed to contain synthetic peptides representing both T cell epitopes and B cell epitopes; B. Several tolerance mechanisms have evolved to minimize potential harm caused by postdevelopmental selection-autoreactive cells. For example, in the case of the viral envelope glycoproteins, viral diversity may occur at such a rate that 15 new amino acid changes become fixed within the host each year. Following infection of the large bowel, these organisms adhere to colonic epithelial cells, causing a characteristic lesion in which the brush border is effaced by a dramatic change in cytoskeletal structures beneath the attached organism.
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Because the viral polymerase enzymes are structurally and biochemically distinct from host cell polymerases, they have been targeted for antiviral drug development much as the polymerases of other viruses such as human immunodeficiency virus and hepatitis B virus. Chlamydophila pneumoniae infects the respiratory epithelium where it can cause acute bronchitis and pneumonia, but chronic respiratory infection is linked to enhanced asthmatic disease. Factor D then cleaves factor B from the C3bB complex to yield C3bBb complex, which is C3 convertase of the alternative pathway. Small arrows indicate vegetations on the anterior mitral valve leaflet and the aortic valve. Rabies virus accumulates at the motor end plate of the neuromuscular junction and may use the acetylcholine receptor or a closely related structure to enter the distal axons of motor neurons. Several widely performed tests use antibodycoated latex beads (latex agglutination tests) to detect capsular material from C. The currently licensed vaccine is safe and well tolerated, with occasional mild side effects similar to natural measles virus infection, such as rash or fever. Those rare events are diagnostic puzzles because infected individuals typically have no histories of foreign travel. In the United States, fewer than 500 children per year die from infectious diarrhea, but more than 200,000 children under age 5 are hospitalized for diarrhea-induced dehydration. This procedure selects mutants, which are capable of growing in abnormal culture conditions and therefore, less capable of growth in natural host. An example is the use of oral vancomycin to treat diarrhea or colitis induced by Clostridium difficile (see Chapter 20). Although not yet proven, effective integration of prevention and treatment programs likely will be even more successful in reducing spread of the virus. Antibody-dependent cell-mediated cytotoxicity: Antibody binding to microbial epitopes causes a conformational alteration in the Fc portion of the antibody molecule. Brain abscesses, in contrast, are frequently caused by a mixture of bacteria derived from the microbiota of the mouth and oropharynx. Acquisition of arbovirus infection is seasonal because transmission depends on the presence of the insect vector. Forty-eight infants too young to be vaccinated following exposure were quarantined at home for the 21-day contagious period. However, excessive or uncontrolled inflammation, or inflammation induced by noninfectious causes, may produce substantial damage to the tissues and needs to be treated. Acyclovir Acyclovir is the prototype antiviral agent and standard against which all other antiviral drugs are compared. After 24 hours, she showed no clinical improvement, and the infection continued to ascend proximally. In general, the capsular polysaccharides are poor antigens for stimulating a protective immune response. As you know from recent, celebrated criminal cases, prosecutors also use laboratory methods when traces of blood or body fluids are the available clues. By morning, he was somewhat better, and by the following day, his symptoms had disappeared. The same bacterium tumbles generally left to right when the flagellum rotates clockwise. They excrete chelating compounds, known as siderophores, that bind iron with great avidity. Widespread use of conjugate pneumococcal vaccine appears to be beneficial in terms of preventing invasive pneumococcal infections as well as acute otitis media associated with vaccine strains. An intradermal skin test using purified protein derivative may or may not be positive in fulminant tuberculosis, but it should be positive when repeated after weeks to months of effective antituberculous therapy. Because these organisms reside within epithelial cells, obtaining an appropriate specimen requires rotating a fibrous swab on affected mucosal epithelium. Medical professionals are well aware of the importance of inoculum size in infection. So far, the connection between the rash and Lyme disease depended on retrospective evidence, which is subject to more bias because it depends on collecting exposure data from people who already know they are ill. The bacteria will probably be resistant to penicillin but sensitive to semisynthetic penicillins, such as nafcillin-that is, methicillin-sensitive S. Newly produced interferon is released into the extracellular fluid and binds to specific interferon receptors on adjacent cells.
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