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Endogenous versus Exogenous Encounters Microbial diseases are contracted in two general ways, exogenously and endogenously. Nonetheless, staphylococci possess a particularly complex but effective pathogenic strategy, and even healthy persons may be unable to combat S. Transformed cells can be recognized by their altered morphology, loss of contact-inhibited growth, and decreased nutritional requirements. A presumptive diagnosis of epiglottitis was made, and the child was taken to the operating room, where an endotracheal tube was inserted. Diagnosis: Still relies on virus isolation from clinical samples, including sputum and nose and throat washings or swabs, but rapid diagnostic tests are also available. Because the Sabin vaccine is administered orally, trained health care personnel are not required for its distribution. Superficial mycoses are caused by yeasts that colonize the stratum corneum of humans. For instance, macrophages that reside in the alveoli of the lungs-alveolar macrophages, also known as dust cells-can pick up inhaled infectious agents by phagocytosis. Two major theories have been proposed to account for the genetic basis of immune recognition. In addition to these three major human pathogens, at least six other Bartonella species were reported to cause human disease at low incidence, most prominently endocarditis (Table 26-1). For example, nitrofurantoin is concentrated in the urine Log number viable bacteria 58 Part 1: Principles and is effective in many cases of uncomplicated urinary tract infections. They are coughed up and then swallowed into the gastrointestinal tract where they continue their life cycle as adults. As mentioned earlier, a very small amount of weaponized anthrax (50 kg) could result in very high casualties (95,000). Her serum bilirubin and alkaline phosphatase levels were elevated, suggesting biliary obstruction. In assessing new drugs, pharmaceutical companies must carry 314 Chapter 30: Strategies to Combat Bacterial Infections 315 out complex and expensive trials that include laboratory work, experimental animals, and lengthy clinical studies. Completion of the synthesis of the first daughter strand produces a duplex molecule consisting of one parental strand and one daughter strand and leaves behind a displaced parental single strand. These findings gave impetus to the efforts to purify penicillin, a true antibiotic produced by the mold Penicillium and first detected by Alexander Fleming in 1928. For persons with immunosuppression, the recommended postexposure prophylaxis series includes five doses of vaccine administered on days 0, 3, 7, 14, and 28. Isolation of strains resistant to extended-spectrum cephalosporins has been reported, raising concern that gonococcus is attaining "superbug" status. Many physicians who studied these diseases thought that they were separate entities. The media used permit the growth of enteric bacteria and not others by inclusion of inhibitors, such as dyes. Therapy is directed toward elimination of the pathogen using antibiotics, an issue now complicated by multiple antibiotic resistance. This finding suggests that the "normal" intestine is in a constant state of chronic inflammation. Lung biopsy stained with hematoxylin and eosin from an immunosuppressed patient with pneumonia caused by Pneumocystis jiroveci. The organisms remain viable within macrophages by modulating the phagolysosomal pH and capturing essential growth factors from the cell. These viral functions insure host cell survival for an interval sufficient to allow production of progeny virus. A positive reaction is indicated by thickening (induration) of the skin several days after inoculation, which results from infiltration by mononuclear phagocytes and T cells. It is widely distributed throughout Asia and causes at least 10,000 deaths from encephalitis each year. One class of membrane-damaging toxins is pore-forming toxins, which insert directly into the host membrane to generate pores. Thus, a combined medical and surgical approach is often necessary in cases of intra-abdominal infection. Coinfections by Gonococci and Chlamydiae the high prevalence of gonococcal and chlamydial coinfection has prompted recommendations that patients with either infection be treated for both.

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The surface glycoproteins also define antigenic subgroups of some paramyxoviruses, a characteristic important for vaccine development. These infections can cause serious complications, such as rheumatic fever or glomerulonephritis. The type of T cells responsible for controlling infection varies depending on the type of parasite, the stages of infection and the cytokines they produce. He was stationed abroad for 3 years, on tours of duty in Korea, Panama, and Germany. For example, before the advent of the polio vaccine in the 1950s, about 50,000 cases of the disease occurred in the United States annually. Thus, in the 1990s this usually harmless commensal bacterium became one of the most feared nosocomial (hospital-acquired) infections, because it developed resistance to the last-line antibiotic against Gram-positive organisms, vancomycin. The life cycles of parasites provide important clues to understanding parasitic diseases and help in diagnosis and in the development of public health strategies. Intrinsic Protective Mechanisms Beyond the extrinsic protective mechanisms (anatomic barriers and innate and adaptive immune responses) discussed in Chapters 6 and 7, mammalian cells have evolved a number of intrinsic mechanisms that act to limit viral infections. As with many infectious agents, a vaccine would be one way to prevent future cases of Lyme disease. A peptide-binding cleft is formed between the first and second domains (see insert). Another way that bacteria avoid immune recognition is by altering their surface antigens in a genetically programmed way. How do the biochemical mechanisms of acyclovir translate into the in vitro potency of the drug for each herpesvirus The clinical response to acyclovir therapy in humans is similar to the in vitro activity of the drug. Encounter: Paramyxoviruses include causes of some of the oldest known viral diseases (measles and mumps) and several respiratory diseases (respiratory syncytial virus and parainfluenza virus). Although several antibiotics are still effective treatments for Bacteroidales infections, antibiotic resistance continues to be a significant problem. This type of spread is accomplished by making intricate use of the host cytoskeleton. Diagnosis: A characteristic Gram stain from the genital tract or cerebrospinal fluid can be diagnostic for gonococcal and meningococcal infection, respectively. Such damage was seen in children immunized with an inactivated measles virus vaccine who experienced severe disease when later infected with measles virus. There are three main kinds of interferons: interferon is produced by leukocytes, interferon- is produced by fibroblasts and epithelial cells, and interferon- is usually produced by T cells activated by specific antigens. That is the only form of the parasite found in peripheral blood and may be easily missed when parasitemia is low. Her wound showed no sign of infection, and her abdomen was no more tender than expected. The most commonly used medium is called "chocolate agar" because it contains heated blood and has the appearance of milk chocolate. The mutation is present in many patients with Crohn disease, a chronic inflammatory bowel disease associated with the inability to properly control the responsiveness to bowel bacteria. Activation usually involves a proteolytic cleavage and reduction of a disulfide bond that often holds the A and B domains together. In one pathway, they incorporate their genomes into that of their host and replicate in a benign, quiescent state in which most of their genes are not expressed or are expressed at low levels. After its licensure, this vaccine was found to be associated with an increased rate of intussusception of the intestine. Because of the obligatory role that arthropods play in the development of some protozoal and helminthic pathogens, their elimination from the environment can theoretically eradicate the respective diseases they cause in humans. For Shigella the system is used to transfer proteins that cause the host cell to take up the microbe. 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). In temperate climates, the infection is maintained in the food chain of wild carnivores by a "cycle of carnivorism. Multiple serotypes are now circulating in Latin America, the Caribbean, Africa, and Asia. Among other effects, the interferons prevent protein synthesis in virus-infected cells by initiating a chain of events that culminates in the inactivation of the cellular translation machinery.

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Special varieties of this medium are known as Thayer-Martin medium and Martin-Lewis medium; each contains unique antibiotics to inhibit other bacterial species and yeasts found in the genital tract. As we will see, often T cells stimulate B cells to proliferate, switch isotype, and differentiate into immunoglobulin-secreting (plasma) cells. As previously noted, the pneumococcus is one of the encapsulated pathogens that causes meningitis, an especially devastating disease. The anatomy of the vascular supply of the metaphysis predisposes the area to infection. A successful pathogen circumvents these mechanisms by completely enveloping its cell surface in a thick layer of hydrophilic polysaccharide, or capsule. M proteins may stabilize the interaction between viral glycoproteins and the lipid envelope, direct the viral genome to intracellular sites of virus assembly, or help in virus budding. Second, and perhaps more importantly, the underlying immune dysfunction can lead to inconsistent serologic responses. Protozoa evolve different mechanisms to enter inside the cell to have their intracellular existence. A measles epidemic occurred between 1989 and 1991, with most cases affecting unvaccinated children younger than 5 years. Inhibition by sulfonamides then is dependent on the continued growth of the bacteria. In addition, viruses (most commonly, rotavirus) and protozoa (Giardia, Cryptosporidium, and Cyclospora) can cause watery diarrhea. The most important measures include curtailing high-risk practices, such as multiple sexual contacts for both homosexual and heterosexual persons, the use of condoms, awareness of the danger of anal intercourse, and the use of uncontaminated needles for injection drug users. However, in many other instances, the demarcation is less clear because it is difficult to define precisely which organisms constitute the normal microbiota (see Chapter 2). Sophisticated genetic mechanisms enable the bacteria to express or not express many of its surface adherence components (a phenomenon called phase variation; see the paradigm) or to control their structure (antigenic variation). An alternative therapy was the induction of high fevers in individuals with neurosyphilis. However, it is still clinically useful to sort serovars into groups designated by the letters A, B, C, and so on. With prolonged B12 malabsorption (longer than 1 year), endogenous stores are depleted. With complete obstruction, the combination of pus and increased pressure leads to abscess formation, bacteremia, and symptoms of septic shock. Serum proteins are present in normal synovial fluid but in lower concentrations than in plasma. Although the organism is probably never completely eradicated, antipseudomonal antibiotic therapy leads to a decrease in the number of organisms in the sputum and improved pulmonary function. However, in a small number of people, disease progresses to chronic pulmonary infection that often cavitates and requires antifungal therapy. Other viruses, including many arboviruses, have the capacity to directly infect endothelial cells, including those of the microvascular circulation of the brain. The effectiveness is markedly enhanced by opsonization of the organisms to be ingested. Many of those surface components are antigenic, imparting different immunological characteristics to each stage of the parasite life cycle. On leaving the bone marrow, the naive B cells are fated to have a short half-life unless they receive additional signals from lymph node stromal cells that allow them to further develop. Because such compounds would not be aimed at the growth of the microbe, but only at the mechanisms that contribute to disease, theoretically, there would be greatly reduced selective pressure for resistance. However, it may also be the result of contamination of the sputum specimen as it passes through the 176 Part 2: Infectious Agents mouth of a colonized individual, in which case the clinical context is important and therapy is often empiric. These two functions, attachment and internalization, are also the subjects of intensive study in relation to bacteria; many of which are able to induce their own uptake into host cells after attachment.

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The normal plain film of the leg did not exclude osteomyelitis because it usually takes several weeks for characteristic radiographic changes in bone to appear (periosteal proliferation or elevation, loss of bone cortex, and bone lysis). Occurring as sporadic, iatrogenic, hereditary, and transmissible forms of disease, they are relentlessly progressive and uniformly fatal. We also carry viruses, fungi, protozoa, and occasionally worms, but in the healthy person, these microorganisms are present in smaller numbers than are the bacteria. Most of these involve defects in the stem cells that give rise to most or all of the cellular elements of the immune system, including T and B cells. Although it has mechanisms to avoid the immune response, the large variety of secreted substances cause considerable damage to host tissues. The phosphoryl group is then transferred to an aspartic acid residue on a response regulator protein, which is usually located in the cytoplasm. The virus is transmitted from the pregnant mother to the developing fetus, presumably following a maternal viremia and infection of the placenta. These epidemics are thought to be the result of a large increase in the number of deer in those parts of the country, and, by extension, the deer ticks that transmit this disorder. Other important causes of watery diarrhea include Shigella sonnei and Salmonella (see Chapter 17). First, nongrowing bacteria are still immunogenic and can elicit immune responses with both beneficial and detrimental results. Each day we are in contact with and ingest fecal microorganisms to a greater or lesser extent, depending on our age (which determines behavior) and the state of environmental sanitation. Hypersensitivity Reactions Like any weapon or tool, the immune system can harm its user if not properly controlled. Some of these factors are constitutive (always present), such as low pH in the stomach, fatty acids on the skin, and lysozyme, a bacteriolytic enzyme in tears, sweat, and saliva. With antimicrobial chemotherapy, the object is to optimize the therapeutic index, the ratio between the effective and the toxic dose. The clinical manifestations of respiratory tract infections depend on the causative agent. Prior to praziquantel, no medical treatment existed for cysticercosis (the tissue-invasive form of pork tapeworm infection). Patients may be ill for several weeks or even months before seeking medical attention. Therefore, when polyclonal antiserum is used in a diagnostic test, the likelihood is high that unwanted cross-reactions with other microorganisms will occur. The two properties that make the skin hostile to bacterial growth are exfoliation and dryness. Staphylococci spread from person to person, usually through direct contact or aerosols associated with upper respiratory viral or bacterial infections. In Lyme disease, the most common form of chronic central nervous system involvement affects memory, mood, or sleep, sometimes with subtle language disturbance. Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis and occurs primarily in Brazil and surrounding countries in South America. This manifestation, called "rheumatic heart disease," adversely affects the function of the heart. At the schizont stage, 8 to 12 merozoites are arranged peripherally around the central malarial pigment. In addition to providing clues about the cause of the disease, erythema migrans helped link Lyme disease in the United States to certain syndromes in Europe. The tissue cysts that develop in the animals are identical to those in humans (5, 6), but when the animals eventually die in the pasture (often from unrelated causes), dogs or wolves may eat their remains and ingest the tissue cysts. Worldwide, it is estimated that more than a million deaths occur annually as a result of this disease, making it one of the leading infectious causes of mortality. The bacterium is ingested by conventional phagocytosis and resides briefly in a membrane-bound phagosome. The National Survey for the Susceptibility of Bacteroides fragilis Group was initiated in 1981 to monitor the emergence of antibiotic resistance among intestinally derived clinical Bacteroidales species. Unlike cells of the innate immune system, those of the adaptive immune system, once stimulated to respond, have the ability to recall previous exposures to the same stimulus and to modify their response accordingly, a process called memory. The Rationale for revising the clinical and laboratory standards institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus.

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Physical examination revealed an ill-appearing, somnolent infant with mild dehydration and hyperactive bowel sounds. This chemical homing mechanism guides the neutrophils precisely and efficiently to their targets. These inclusions are highly pathognomonic-that is, indicative of the specific disease. Dermatophytes suppress host T cell responses and delay the cell-mediated destruction. Immunoglobulin is a generic term for a diverse group of globular molecules found in the blood and tissue fluids. Antibiotics are administered parenterally to achieve high serum concentrations, which are necessary to penetrate the depths of relatively avascular vegetations. What are some of the more severe symptoms that can be associated with primary genital herpes After attachment of the virion to a cell surface (1) and penetration by fusion (2), nucleocapsids are transported to the nucleus (3) via interaction with microtubules (4), docking at a nuclear pore (5) where the viral genome is released into the nucleus. Onchocerciasis is transmitted by Simulium black flies, and lymphatic filariasis is transmitted by mosquitoes. The swab is often treated with a drop of penicillin solution to kill other normally occurring bacteria that are sensitive to the drug (to which B. These individuals may receive preexposure vaccination (usually three doses of vaccine on days 0, 7, and 21 or 28) and two booster vaccinations (on days 0 and 3) if they ever have a known exposure (such as an animal bite). In most helminthic infections, the severity of the infection is proportional to the inoculum size (or the cumulative inoculum if exposure continues over time). To establish the diagnosis, the presence of virus or its components in active lesions can be demonstrated. Therefore, therapy must be continued for the duration of immunosuppression and possibly for life. That layer represents the replicative compartment of the skin, where cells continuously divide to replenish the desquamating surface and heal wounds. It is likely effective through intermittent sterilization of the urine with high urinary antimicrobial levels. These are dendritic cells named for their elongated, branchlike projections and comprise less than 1% of the cells in these tissues. Tularemia Tularemia, the disease caused by the Gram-negative bacterium Francisella tularensis, occurs naturally throughout North America and Eurasia. Unfortunately, the interpretation of a positive sputum culture is not always straightforward. Binding to the 30S ribosome subunit to inhibit protein synthesis, primarily at or near the initiation step, and to increase "miscoding" by the ribosomes and the production of "nonsense proteins" Two major mechanisms of resistance to aminoglycosides have been recognized in Gram-negative bacteria. Although pulmonary lesions may be granulomatous, the inflammatory response in the central nervous system is minimal. Human-to-human rabies virus transmission has not been well documented except in cases of organ or tissue transplantation. Itraconazole has become the drug of choice for the endemic mycoses, sporotrichosis, and dermatophyte infections. Unfortunately, resistance to all these agents has also been reported (as discussed later). Potentially effective public health measures and their rationales are shown in Table 55-2. Although all epithelia have protective tight junctions that do not allow passage of microorganisms, these epithelia can be traumatized, especially when subjected to high pressure or abrasions. Studies of the synthesis of poliovirus proteins have revealed several unexpected findings. Here, the discussion focuses on the basic concept of how bacterial toxins damage the host. Spotted fever and typhus rickettsiae have lipopolysaccharides that are antigenically distinct for each group.

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Determination of the particular virus responsible for the associated disease requires the use of serological and molecular methods that assay for the presence of specific viral proteins, antibodies directed against those proteins, or viral nucleic acid. The classic cases are trypanosomes, gonococci (the agents of relapsing fever), and influenza viruses (see Chapter 14 paradigm). Schematic view of the adenovirus particle with the locations of individual capsomeres shown. Fastidious organisms, such as Haemophilus influenzae and Ureaplasma urealyticum, infrequently cause infection but are not isolated with routine laboratory methods. In contrast, in subacute endocarditis, -hemolytic and nonhemolytic streptococci cause 60% of these infections, with enterococci, coagulase-negative staphylococci, and fastidious Gram-negative rods causing the remainder. The disease is common in many developing countries, where canine rabies perpetuates, and millions of people are vaccinated after being bitten by potentially rabid animals, mainly dogs. Toward the ileum, the environment is more favorable to bacterial life, but even there, the few organisms that gain a foothold must avoid being washed away. Antigen Presentation Specialized cells located at potential microbial portals of entry into the body. Extracellularly, the organisms are much more resistant than the other rickettsiae to the many deleterious effects of the environment. In fact, some infections are common in temperate zones; others are relatively rare but have major consequences when they go unrecognized, especially in immunocompromised persons. The heterogeneous pore-forming toxins constitute another class of membrane-damaging toxin. In a person with an intact spleen, the proportion of infected red blood cells is usually 0. After hearing a loud heart murmur on physical examination, her pediatrician obtained an echocardiogram that demonstrated mitral valve regurgitation and extensive damage to the valve leaflets. The spleen recognizes and removes older and less deformable red blood cells from the circulation, thus removing parasitized red blood cells from the circulation. A large number of cell-associated and secreted molecules participate in the pathogenesis of P. In contrast, other infectious agents, such as the pneumococcus, have several distinct capsular polysaccharide types, and immunity to one polysaccharide type does not confer immunity to the others. Thus, b-hemolytic streptococci (or "beta strep"), which cause most streptococcal infections, lyse red blood cells signified by a clear area around the colonies. Several important human pathogens persist within macrophages without being killed until specific T-lymphocyte cell-mediated immunity develops. Therefore, a single vaccine strain is effective at preventing disease caused by naturally circulating viruses. The rickettsiae are the dark, rod-shaped bacteria in the nucleus, about the same size as the mitochondria and smaller than most other bacteria. If the cell is latently infected, then the viral genome circularizes in the nucleus and persists as an episome (analogous to a plasmid) with only minimal transcription of viral genes. For example, patients with tuberculosis, histoplasmosis, or lung abscesses sometimes experience acute, rapidly progressing disease. Bacteria associated with infections in the head and neck regions are often commensals. However, several months later at home in Boston, he again sought medical attention because he had developed considerable pain and swelling in one knee. Infection in mid-adulthood has a much better immediate and probably long-term prognosis, presumably because of a reduced tendency to develop tissue necrosis. Interference of virusinfected cells allowed, for example, the first laboratory detection of rubella virus; although that virus does not produce visible damage to cells in culture, it does render them refractory to secondary infection with other viruses that can produce cytopathic damage. These organisms have managed to survive the host immune response, as discussed in the paradigm, by antigenic variation, phase variation, and the occupation of protective intracellular environments.

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As a result, the intensity of infection, called the worm burden, is determined by the size of single or repeated inocula. A large subpopulation of T cells is stimulated by superantigens, but these cells have specificities that are mostly unrelated to streptococcal antigens. Production of the outer surface protein VlsE is increased concomitant with the decrease in OspC production, and VlsE shares some general structural features with OspC. Even the most basic appreciation of adaptive immune mechanisms depends on understanding the role that soluble molecules and molecular badges play in immune function. Proteins in the tegument layer are located between the nucleocapsid and lipid envelope with viral envelope glycoproteins inserted through the lipid membrane. 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. All species cause similar but not identical clinical patterns and will generally be referred to as B. These "Fastidious" and Small Gram-Negative Rods Besides the organisms already mentioned, the Gramnegative rods include an important and heterogeneous group of genera. Electron micrograph of a glomerular tuft revealing electron-dense immune complex deposits in the mesangium (single arrow) and subendothelial capillary space (double arrow). However, human monocytes and macrophages do not make nitric oxide in any significant amounts; thus, the contribution of nitric oxide to microbial killing by these cells is negligible. Neutrophils are clearly involved in curbing the proliferation of the organism, as seen by the increased incidence of P. Due to our lack of knowledge on the epidemiology and virulence properties of these emerging pathogens, they are not further discussed in this chapter. All enteroviruses replicate in the central nervous system, but some also replicate in the heart (myocarditis), the respiratory tract (pleurodynia), or the mucous membranes of the eye (hemorrhagic conjunctivitis). The E1A proteins stimulate transcription indirectly by increasing the activity of endogenous host cell transcriptional factors. As with histoplasmosis, it appears that yeast cells can remain viable within granulomas for years and can be a source for later reactivation. These patients are at greater risk for infection with acid-sensitive bacteria like V. An immunization survey of the public schools revealed that more than 95% of their students had been vaccinated. Noncoding sequences include terminally redundant regions and unique regions near the ends of the genome. Lymphocytes contribute to host defense by producing antibodies and attacking infected cells through cytotoxic T lymphocytes, naturalkiller cells, and antibody-dependent cell-mediated cytotoxicity. Plasma cells can be viewed as "munitions factories," producing large quantities of immunoglobulin during their short lifespan of less than 30 days. The innate immune system does this elegantly by expressing germline-encoded pattern recognition receptors on cell surfaces, receptors that have been selected over time to recognize structures on potentially invasive organisms (see Chapter 6). Mutants that make either no O antigen or merely shortened chains become sensitive to hydrophobic compounds such as bile salts and antibiotics to which the wild type is resistant. Among their various activities, these cytokines mediate fever, weight loss, and night sweats. Infective endocarditis is the prototype of spontaneously occurring intravascular endothelial infection and is the focus of this chapter. Within the lymph node, B cells begin to synthesize both heavy chains and heavy chains and display both IgD and IgM monomers with identical specificity on their cell surface. In viral infection, histopathological studies of the lungs (or other affected tissues) show infiltration by large numbers of lymphocytes and plasma cells, suggesting that viral infection stimulates the recruitment of lymphoid cells rather than neutrophils. In another kind of rickettsiosis, called ehrlichiosis, the organisms grow in white blood cells. Initially, the most important factors in reducing the incidence of infectious disease were preventive measures, largely purification of the water supply and control of human wastes and disease vectors. The size of the viral inoculum, the concentration of virus in the blood, the virulence of individual virus strains, levels of circulating antibodies, and the efficiency of the innate immune response all are likely to determine whether an infection is symptomatic. Bioinformatics methods of this metagenome sequencing data enables the placement of the sequences into taxonomical units without the need to culture the constituent organisms.

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Thus, the clinical manifestations include chronic dermatitis and loss of eyesight (caused by nodules on the head with migration of microfilariae into the anterior chamber of the eye). The antifilarial drug diethylcarbamazine was given but discontinued when it produced shock and hypotension. Primary Tuberculosis In primary infection, airborne droplet nuclei reach the alveoli where multiplication begins. However, this modality is not available in many clinical laboratories, and a relatively high viral titer must be present in the stool specimen for the virus to be detected by this method. Prokaryotes differ from eukaryotes in important biochemical details, such as the composition of their ribosomes and lipids. Thus, cells treated with these drugs cannot recover, which is one reason why the aminoglycosides are bactericidal. Laboratory studies showed a normal leukocyte count, a slightly elevated level of serum sodium, a normal serum potassium level, and an elevated blood urea nitrogen level, also consistent with dehydration. It is currently believed that profuse bleeding is caused by the interaction of inflammatory cytokines and shigalike toxins, which damages blood vessels in the lamina propria. Filariform larvae of Strongyloides may penetrate the intestinal mucosa or the skin of the perianal region (autoinfection), sustaining infections in patients who have not been in endemic regions for several years. Nonetheless, the World Health Organization, Pan American Health Organization, and Centers for Disease Control and Prevention have set an agenda for measles virus elimination from the Western Hemisphere, with the goal of measles eradication within the next 10 to 20 years. Alternate open reading frames within the phosphoprotein gene encode two additional proteins designated V and C, which have roles in virus replication, pathogenesis, and host immune modulation. Second, interferons are present in extremely small amounts, indicating that they are very potent molecules. Common warts of the hands and other cutaneous surfaces are elevated, firm, fleshy lesions with a sharp border. The dashed line between stages (7) and (8) indicates that natural transmission does not occur in areas lacking the hard-bodied tick. These tests rely on agglutination of the organisms by antibodies present in patient sera. In broad terms, the spread of resistance genes increases with the use of drugs in a particular geographic area or medical center. Various properties of the invading agent and the host lead to an intricate and ever-changing interplay. As part of its insidious pathogenic profile, the gonococcus has evolved to maximize its transmissibility. Differentiating smallpox (variola) from the more common chickenpox (varicella) can be challenging, but several discriminating features make accurate diagnoses possible (Table 57-3). Mucous membrane edema is more likely to result in narrowing of the tracheal lumen in children due to their smaller airways and the presence of nonexpandable rings of cartilage present in the tracheal wall. Damage to the endothelium results in exposure of the underlying extracellular matrix and production of tissue factor, which triggers coagulation and formation of sterile vegetations (nonbacterial thrombotic endocarditis). An early diagnosis is sometimes possible, however, by taking a biopsy of a skin lesion and treating it with antirickettsial antibodies. The isolation of typhoid bacilli from various sources in the course of untreated typhoid fever. However, the larvae that emerge from eggs in the intestinal wall can be found in the stool of a person with Strongyloides infection, and their presence is diagnostic for that infection. In all species, they share common and recognizable neuropathologic features, namely the presence of small vacuoles within the neuropil, which produces a spongiform appearance, neuronal loss, and glial cell proliferation, which occur in the absence of an inflammatory response. An estimated 50 to 100 million cases of dengue fever and 250,000 to 500,000 cases of dengue hemorrhagic fever occur annually worldwide. Encounter and Entry: Prion diseases may occur as sporadic, iatrogenic, hereditary, or transmissible diseases. If the individual lacks specific adaptive immunity, the organisms may be opsonized by nonspecific or innate immunity.

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For instance, persons with schistosomiasis typically have bleeding from either the gastrointestinal tract (Schistosoma mansoni) or the urinary tract (S. Exceptions to the rule are agents that cause disease through production of a toxin, such as Clostridium botulinum, which produces the botulinum toxin that leads to botulism. A clear correlation exists between the severity of the cold and the amount of rhinovirus recovered from the respiratory tract. If all the endotoxin in the intestine were to enter the bloodstream, and if fever followed an absurdly linear response, body temperature would rise to about 1 million degrees. That is particularly useful in the diagnosis of serious systemic infections, providing an immediate and reasonably reliable identification of the causative agent. Arthropods are not simply passive agents that transfer parasites from one mammalian host to another. Cephalosporins are not generally recommended because they share with other -lactam antibiotics a somewhat lower efficacy, especially with short-course therapy. The sources of human-to-human transmission of viruses are acutely ill individuals or chronic carriers; pregnant women also can transmit viruses to their fetuses. Membrane-damaging toxins are often generally termed hemolysins, because they can cause lysis of red blood cells. Although these tests may be useful in guiding the initial therapy of the patient, none of them is sufficiently sensitive or specific to be relied upon as the sole method of diagnosis. The bactericidal action of the -lactam antibiotics requires the following steps: 1. He continued to have intermittent diarrhea, which was subsequently accompanied by anorexia and weight loss of about 10 pounds. The organisms frequently colonize the anterior nares and are found in approximately 30% of healthy individuals. Transesophageal echocardiogram from a patient with nonhemolytic streptococcal native aortic valve endocarditis. Chapter 57: Biological Agents of Warfare and Terrorism 571 to present within hours. However, the omentum and the loops of the small intestine drape themselves around areas of inflammation and serve to contain the infection. Cell-mediated immune responses are directed to curtail microbial stealth by determining whether infectious agents are sheltered within host cells and thus are beyond the "reach" of humoral immunity. The high fevers in these patients are consistent with the exceptional pyrogenicity of this and other superantigens. If they pause in the large intestine, they meet the populous normal microbiota that resists implantation by new species, in part by previous occupancy of adhesion sites on the gut wall and in part by producing inhibitory substances. It is not the only one; chemically distinct chemotaxins are also made by bacteria and by host cells. Intracellular herpesviruses reside within certain cells but do not proliferate; therefore, such a virus can avoid a host response and remain in a state called latency (see Chapters 41 and 42). Most local staphylococcal diseases are self-limiting by spontaneously draining through the skin; they do not typically result in metastatic infections. After several weeks, pairs of male and female adults move to the venous plexuses of the large intestine (S. In the lungs of mice infected with the high virulence virus, diffuse airspace obliteration is seen, with a majority of alveoli filled by inflammatory cells and debris. The solid line and open arrow (above and to the left of stage 1) indicate that the larvae of the parasite are unable to complete their normal life cycle in a human host. Consequently, susceptible organisms outside the urinary tract are not affected by nitrofurantoin. What should be suspected if the infection fails to respond to -lactam antibiotics When the pain started, she noted tenderness and serous (watery) discharge between her third and fourth toes. The retrovirus integration process resembles the mechanism of action of some transposable elements of bacteria (see Chapter 4, "Genetic Approaches to Studying Bacterial Pathogenesis"). Thus, protective immunity does not function in the long term against this master of disguise. To circumvent this problem, geneticists moved the transposase gene from within Tn5 to another location on the suicide plasmid. Thus, transport of this type takes place via a symport, which requires the simultaneous uptake of positive hydrogen and sugar molecules.

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Pseudomonads have minimal nutritional requirements, needing only acetate and ammonia as sources of carbon and nitrogen, respectively. In such an environment, toxins will be produced continuously during the course of the infection. Transformation by adenoviruses requires the products of the E1A and E1B regions, which transform cells largely by interacting with the cellular tumor suppressor products pRb and p53 (see the Paradigm Box). In these experiments, animals can be infected with strains differing only in one gene, and thus, any pathogenic differences can be attributed to the product of this gene. Fever, increased adhesiveness of endothelial cells and leukocytes, endothelial procoagulant activity Hypotension, capillary leak, decreased myocardial contractility, synthesis of "acute phase" proteins. This phenomenon has been called fabulation (after "Fab") and may serve to protect organisms from antibodies. Many microbes and all viruses inflict damage when they bind to host cell surfaces to facilitate entry. Occasionally, the parasite is found in the lumen of the appendix, although it rarely produces appendicitis. The phosphoryl group is then transferred to an aspartic acid in the receiver domain, then to a histidine in the C-terminal histidine phosphotransfer domain, and then finally to an aspartic acid residue on the response regulator protein BvgA. To colonize the human body, invading microorganisms must be able to resist host mechanisms that could dislodge or kill them, as well as compete successfully with other microbial species. Infected leukocytes can deliver virus to multiple organs and to skin by cell-to-cell contact. The study of bacterial overgrowth in the small intestine has helped us understand the normal relationship of the gut flora to gut function. The best example is influenza virus, which undergoes antigenic variation, producing a different strain. In the process of randomly generating receptors, the adaptive immune system can make receptors that recognize nonpathogens or receptors that recognize self molecules. Thus, antiretroviral therapy is efficacious in reducing the likelihood of transmission whether it is given to the infected or the uninfected member of a sexually active couple. Asymptomatic and transient low-grade bacteremia occurs in all of us on a daily basis following minor mucosal damage caused by toothbrushing or defecation, but those organisms are rapidly removed from the circulation and rarely ever cause us any harm. However, the rate of chlamydia among blacks was over eight times higher than that of whites in 2007 (1,398. Infectivity requires an intact outer capsid layer that helps establish acid stability, a critical characteristic for viruses that gain entry through the gastrointestinal tract. Specific organisms show preferences for the type of valve infected (native or prosthetic) and the event or site causing the endocarditis-inciting bacteremia. The frequency of toxic reactions in the kidney is so high that frequent monitoring of renal function and blood levels of the drug is required during aminoglycoside therapy. Because his sexual behavior put him at high risk of other sexually transmitted diseases, Mr. Because the "wall" microbiota faces different nutritional problems from the "lumen" microbiota, the selective pressures on these two populations are very different. When hair shafts are invaded, the organisms can be seen either within the shaft or surrounding it. This narrowing is more significant during inspiration and results in inspiratory stridor. Note that some of these organisms may be transmitted by more than one of these routes. Broad-spectrum antibiotics, which are effective against a wide range of bacteria, might be thought to be preferable to drugs with narrow spectra. Thus, empirical treatment directed against the most common pathogens is justifiable in acute otitis media. Particular side chains located on the -lactam ring permit the drugs to penetrate the outer membrane of Gramnegative bacteria, thus extending the list of susceptible organisms. She was discharged after 3 weeks, and by 3 months, all laboratory tests had returned to normal. It is not known if these infections are caused by spontaneous penetration or if the organisms enter through inapparent cuts and abrasions. Adding more of the drug only induces formation of greater amounts of enzyme, and as a result, resistance usually cannot be overcome even with massive doses.