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The erythrocytic cycle involves trophozoites cyclically infecting erythrocytes and the development of gametocytes blood pressure chart to keep track generic perindopril 8mg with mastercard. The sporogonic phase involves the development and sexual union of Plasmodium in the mosquito. It circulates in the blood and has an intracellular stage, infecting macrophages and heart muscle cells, and can cause fatal heart damage. American trypanosomiasis can be diagnosed by a xenodiagnosis, a procedure in which a physician allows an uninfected bug to feed on a person suspected of having the disease and then seeks the trypanosome in the bug. Adults feed on blood, lodge in the organs, and cause schistosomiasis, a potentially fatal disease. Yellow fever, caused by the virus Flavivirus and carried by Aedes mosquitoes, develops in three stages ending in jaundice. The type of endocarditis that develops slowly over a period of weeks or months is described as. A cardiologist examines a patient with history of drug abuse and a recent tooth extraction and notes darkening under the fingernails. Trypanosoma cruzi is expelled on the skin of the host in the feces of the kissing bug. Following a backpacking trip in Vermont, a hiker experienced flulike symptoms and noticed a round, red rash on her thigh. A horror movie portrays victims of biological warfare with uncontrolled bleeding from the eyes, mouth, nose, ears, and anus. The three parts of the life cycle of Plasmodium are the cycle, the phase, and the phase. On the figure of the life cycle of Plasmodium, label the three phases (A through C) and the name of the parasite at each stage (a through d). In the drawing of the life cycle of Ixodes and its role in Lyme disease, circle the organisms that might be infected with Borrelia. Why is it rare for healthy people with normal immune systems to have bacterial blood infections After Tony had been very ill with cardiac problems, his hospital chart listed the cause as "culture negative" endocarditis. In contrast, individuals in industrialized countries are ordinarily infected after puberty, and these older patients tend to have more severe reactions to infection despite better health and medical care. Why do geneticists say there is a single species of Brucella, yet many veterinarians say there are four species A blood bank refused to accept blood from a potential donor who had just had his teeth cleaned by a dental hygienist. An epidemiologist notices a statistical difference in the fatality rates between cases of Gram-positive bacteremia treated with antimicrobial drugs and treated cases of Gram-negative bacteremia-that is, patients with Gram-positive bacteremia are much more likely to respond to treatment and survive. Why is it more difficult to rid a community of a disease transmitted by arthropods (for example, Lyme disease or malaria) than a disease transmitted via contaminated drinking water (for example, cholera) Explain how each of the following could lead to the reemergence of malaria in the United States: (a) global warming, (b) increased travel of individuals from endemic regions to the United States, (c) increased immigration of individuals from endemic regions to the United States, and (d) laws protecting wetlands. Discuss why sickle-cell trait is advantageous to people living in malaria endemic areas but is not advantageous in malaria-free areas. Why are dengue, yellow fever, and malaria reemerging in areas where they have long been eradicated Why are ehrlichiosis and anaplasmosis considered emerging diseases given that they have been known for decades Why do physicians substitute trimethoprim and sulfamethoxazole for tetracycline when treating children and pregnant women infected with Brucella Most cases of tularemia in the United States occur in the late spring and summer months; very few cases ever occur in January. In 1861, yellow fever struck the Mississippi Valley, hitting Memphis, Tennessee, most forcefully. Half the citizens fled the city, and one-quarter of the remaining population died. Historical records indicate that the epidemic ceased only after winter frosts arrived. Suppose scientists developed a vaccine for dengue that induced the production of memory T cells. After reviewing the characteristics of infection and reinfection, would you argue for or against the use of such a vaccine Ebola hemorrhagic fever belongs to a group of diseases called "emerging diseases"-diseases that were previously unidentified or had never been identified in human populations. Emerging diseases are often first seen in developing countries such as the Democratic Republic of the Congo. Propose some methods in addition to those in the text that public health officials could take to prevent transmission of Schistosoma to humans. When Claire gets to the day care, one of the caregivers tells Claire that Hailey was a bit fussy and cranky in the morning and that a couple of other kids had been sick earlier in the week. After a few days, Claire is concerned-Hailey still has a fever, and she has started coughing more frequently. Hailey is taking a nap when Claire notices that Hailey sounds like she is wheezing or gasping for air after each cough. We begin our examination of respiratory anatomy by considering the upper respiratory system and the organs associated with it. Because the structures of the lower respiratory system resemble an upside-down tree with branches that gradually decrease in diameter while increasing in number, anatomists refer to it as the respiratory tree. In this analogy, the trachea is the trunk, the bronchi and smaller tubes are the branches, and the alveoli represent leaves. When the diaphragm contracts, the lungs inflate, and air flows from the nose through the pharynx and into the respiratory tree. A cartilaginous flap called the epiglottis folds over the opening of the larynx during swallowing to prevent food and liquids from entering the lower respiratory organs. Air flows from the larynx through the trachea, through the bronchi and bronchioles, and into the alveoli of the lungs. In the alveoli, oxygen enters the blood by passing through the thin walls of the alveoli and blood capillaries. Relaxation of the diaphragm, accompanied by contraction of a different set of small muscles attached to ribs, allows the lungs to deflate, and air flows out. The cilia beat synchronously about 1000 times per minute to carry mucus and trapped contaminants up to the pharynx. The mucus and its contents pass into the digestive system, where digestive juices destroy them. Further protection from pathogens is provided by alveolar macrophages, which enter the alveoli from blood capillaries and devour microorganisms. Secretory antibodies (IgA), which are present in tears, saliva, and respiratory mucus, also provide protection from many pathogens. The upper respiratory system collects air; filters dust, pollen, microorganisms, and other contaminants from the air; and delivers it to the lower respiratory organs. The upper respiratory system includes the following: the nose is the only external part of the respiratory system. The hairs filter large dust particles and organisms from the air, while the sticky mucus traps smaller particles and microbes. Sinuses, which are air-filled, hollow regions of bones in the skull, often share fluids-and infecting microorganisms-with the nasal cavity. Groups of lymphoid tissue called tonsils or adenoids are located near the junction of the nasal cavity, pharynx, and auditory tubes. The tonsils contain cells and chemicals to combat microbes in this frequent portal of entry. The mucus of the upper respiratory system contains antimicrobial chemicals, including defensins, lactoferrin, and lysozyme.

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During the bioterrorism attack of 2001 blood pressure medication safe for pregnancy buy perindopril 2mg lowest price, physicians learned that early and aggressive treatment of inhalational anthrax with antimicrobial drugs accompanied by persistent drainage of fluid from around the lungs increased the survival rate from less than 1% to almost 50%. An efficacious vaccine is available to select military personnel, researchers, people who work closely with animals, and health care professionals with anthrax patients. Viral Diseases of the Lower Respiratory System We have considered important bacterial and viral diseases of the upper respiratory system and bacterial diseases of the lower respiratory organs. Now we turn our attention to viral diseases of the lower respiratory system, beginning with influenza. Imagine being the only male elementary schoolchild in a midsized Swedish town because all of your peers died six winters ago; or imagine returning to college after a break, only to learn that half of your fraternity brothers had died during the previous two months. In this section we will learn about the characteristics of influenzaviruses that enable flu to produce such devastating epidemics, and we will examine some ways to protect ourselves. Because influenzaviruses rarely attack cells outside the lungs, so-called stomach flu is probably caused by other viruses or bacteria. Mutations in the genes coding for these glycoprotein spikes are responsible for the production of new strains of influenzavirus, via processes known as antigenic drift and antigenic shift. One virus of concern is H5N1, which kills more than 60% of people who contract the virus from infected birds. Fortunately, this virus does not move from person to person; people get it only from birds. Another virus, H1N1, caused a slow, worldwide pandemic beginning in 2009 in Mexico. In 2013, scientists became concerned about a rapidly expanding pandemic caused by another deadly influenzavirus, H7N9, which affects mainly the elderly, killing over 50% of its victims. Hundreds of millions of dollars are spent each year in the United States on antihistamines and pain relievers to alleviate flu symptoms. For another two days she ached all over and was dizzy; her head felt as if it could explode at any moment; and the nausea, frequent vomiting, and extreme tiredness were unrelenting. For over a week, her tired red eyes stared listlessly as she struggled to cope with a constantly running nose, severe sore throat, and a dry hacking cough. These viruses normally mutate, producing slightly different strains every year-a process called antigenic drift. About once a decade, however, different strains of influenzaviruses infect a single cell, and within it they exchange major pieces of rnA, producing a new, quite different strain of virus-a process called antigenic shift. The virus attacking Wang Fang was such a newly emerged influenzavirus, a strain that contained rnA from influenzaviruses of humans, birds, and swine in a novel combination. This new strain can have devastating and sometimes fatal effects on hosts because it has antigenic combinations that the adaptive immune system has never seen before, necessitating a prolonged defensive response before the body can conquer the infection. Wang Fang was exhausted and weak for another two weeks, but she survived the flu, though many other patients were not so fortunate. The flu is a common respiratory disease, second in prevalence only to common colds, yet it has characteristics that can produce devastating epidemics. For example, influenzavirus H5N1 has hemagglutinin subtype five and neuraminidase subtype one. Then go to MasteringMicrobiology to investigate further and record your research findings on the following question: How can a student distinguish the flu from a common cold In contrast, antigenic shift results in major changes in antigens every ten years, so epidemics occur about once a decade. Epidemiologists are concerned that a deadly pandemic of influenza A virus could recur if genes for antigens similar to those of the 1918 flu virus should combine in a new virus by antigenic shift. A virus of concern is H5N1, which kills more than 60% of people who contract the virus from birds. Epithelial cells lining the lungs endocytize the viruses; viral envelopes then fuse with the membranes of endocytic vesicles, releasing the viral genome into the cytoplasm. Nucleus 3 A new influenzavirus A, which can be very different from the original two viruses, exits cell. Early and accurate diagnosis is important because antiviral therapy must begin within 48 hours of infection to be effective. Prevention is by immunization with multivalent vaccines, which are at least 70% effective. Good personal hygiene, such as the use of hand antisepsis, can reduce the spread of flu. Portal of entry respiratory droplets enter through mucous membranes via close personto-person contact. Signs and symptoms High fever, headache and body aches, malaise, dry cough developing into pneumonia. Susceptibility Studies suggest that some people are genetically more susceptible than others are. Pathogenesis and Epidemiology Coronaviruses enter the body via respiratory droplets and adhere to lung cells. The virus destroys these cells, triggering the respiratory symptoms, and then spreads via the bloodstream to the heart and kidneys. By June, the disease had spread across the Middle East and into Africa, Europe, and Asia. Prevention limit travel to endemic areas, use handwashing precautions, quarantine infected persons and their contacts. As of 2012, no antiviral drug has proven universally effective against these viruses, though artificial passive administration of antibodies against the virus reduce viral replication. Annual community-wide outbreaks lasting four to six months are common during late fall, winter, and early spring. Some children develop tracheobronchitis, known commonly as croup (krp), which is inflammation of the trachea and bronchi, resulting in breathing difficulty accompanied by a barking cough. It is relatively unstable outside the body, surviving only about five hours in the environment or two hours on skin or used facial tissues. Pathogenesis As its name indicates, the virus causes syncytia to form in the lungs. Plugs of mucus, fibrin, and dead cells in the bronchioles make it difficult to breathe. Immunocompromised older patients and babies, especially those who are premature, are immune impaired, are exposed to tobacco smoke, attend day care, or have older school-aged siblings, are most at risk. Older children and most adults require no treatment because their disease is mild. For younger children, supportive treatment includes administration of oxygen, intravenous fluids, drugs to reduce fever, and antibiotics to reduce secondary bacterial infections. Ribavirin via inhalation in mist form is used to treat extreme cases in premature and immunocompromised infants. Handwashing and the use of gowns, goggles, masks, and gloves are important measures to reduce healthcare-associated infections. Diagnosis, Treatment, and Prevention Prompt diagnosis is essential if infected infants are to get the care they need. True story: A young Native American scores an impressive 44 points for his tribal team during a basketball game one night. Virulence factors Attaches to and enters human cells; intracellular replication cycle evades immune system; virus causes infected cells to fuse with their neighbors, so virus spreads without entering blood. Susceptibility Babies and the immunocompromised are most at risk of serious infection. Prevention Delay infection of newborns by proper aseptic technique, particularly handwashing. Pathogenesis Following inhalation, Hantavirus enters the blood via an unknown mechanism and travels throughout the body, infecting the cells that make up blood capillary walls, particularly in the lungs. The body responds with inflammation, which causes the capillaries to leak fluid into the surrounding tissue. Blood pressure drops precipitously, and about 50% of patients die from pneumonia and shock.

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It is used to treat packing and cooling water used in industrial canning and to treat work surfaces and utensils in industrial meat processing plants blood pressure chart low buy perindopril 8 mg cheap. Then a conventionally processed food is added to the aseptic package, which is sealed without the need for additional processing. The Use of Preservatives Humans have preserved foods with salt or sugar throughout history. Both chemicals draw water by osmosis out of foods and microbes alike, killing microbes on the food and retarding the growth of any subsequent microbial contaminants. Bacon is an example of a high-salt food; jellies are examples of high-sugar foods. Whereas salt and sugar act by removing water, some natural preservatives actively inhibit microbial enzymes or disrupt cytoplasmic membranes. Benzoic acid, produced naturally by cranberries, also interferes with enzymatic function. Cloves, cinnamon, oregano, and thyme (and, to some degree, sage and rosemary) produce oils that interfere with the functions of membranes of microorganisms. As we have seen, fermentation preserves some foods by producing an acidic environment that is inhospitable to most microbes. For other foods such as meats, the use of wood smoke during the drying process introduces growth inhibitors that help preserve the food. Other naturally occurring and synthetic chemicals can be purposely added to foods as preservatives. Acceptable preservatives are harmless and do not alter the taste or appearance of the food to any great extent. Organic acids, such as benzoic acid, sorbic acid, and propionic acid, are commonly used in beverages, dressings, baked goods, and a variety of other foods. Gases, such as sulfur dioxide and ethylene oxide, are used to preserve dried fruit, spices, and nuts. All such chemical preservatives inhibit some aspect of microbial metabolism, but many do not actually kill microbes; in other words, they are germistatic rather than germicidal. Benzoic acid, for example, has a largely antifungal function and does not affect the growth of many bacteria. Attention to Temperature During Processing and Storage In general, higher temperatures are desirable during food processing and preparation to prevent food spoilage, whereas lower temperatures are desirable for food storage. High temperatures, such as those of pasteurization, canning, or cooking, kill potential pathogens because proteins and enzymes become irreversibly denatured. However, heat does not inactivate many toxins; for example, botulism toxin may remain in cooked foods even when the bacteria that produced it are dead. Unlike heat, cold rarely kills microbes but instead merely retards their growth by slowing metabolism. Even freezing fails to kill all microorganisms and may only lower the level of microbial contamination enough to reduce the likelihood of food poisoning after frozen foods have been thawed. To prevent food spoilage, foods should be prepared at sufficiently high temperatures and then stored under conditions that do not facilitate microbial growth. Foods should be properly stored in appropriate containers, cold foods should be kept cold, foods should be cooked thoroughly, and leftovers should be refrigerated or frozen to reduce spoilage. Wrapping leftovers or putting them in containers enables foods to be stored away from exposure to air or contact that could result in contamination. One microbe for which cold storage does not suppress growth is Listeria monocytogenes (lis-tr- mo-n-s-tahje-nz), the causative agent of listeriosis and a common environmental bacterium. This bacterium is prevalent in certain dairy products, such as soft cheeses, and grows quite well under refrigeration; therefore, it is best to prevent its entry into foods. Spoiled food, if consumed, can result in illness from toxins produced by the microbes or from the microbes themselves, but Industrial Microbiology 785 not all foodborne illnesses result from actual food spoilage. Foodborne illnesses may also result from the consumption of harmful microbes or their products in food. Foodborne illnesses (food poisoning) can be divided into two types: food infections, caused by the consumption of living microorganisms, and food intoxications, caused by the consumption of microbial toxins instead of the microbes themselves. Typical signs and symptoms of food poisoning are generally the same regardless of the cause and include nausea, vomiting, diarrhea, fever, fatigue, and muscle cramps. Most outbreaks of food poisoning are common-source epidemics, meaning that a single food source is responsible for many individual cases of illness. Researchers identify the microbes involved in only about 14 million of the total cases. Department of Agriculture estimates the economic cost of food poisoning-due to loss of productivity, medical expenses, and death-at roughly $5 billion to $10 billion per year. Except for the protozoan Toxoplasma gondii (tok-s-plazm gond-), all are bacterial agents. Industrial Microbiology the potential uses of microorganisms for producing valuable compounds, as environmental sensors, and in the genetic modification of plants and animals makes industrial microbiology one of the more important fields of study within the microbiological sciences. In the sections that follow, we will examine the use of microbes in industrial fermentation, in the production of several industrial products, and in the treatment of water and wastewater. In industry, the word fermentation is used differently from its use in food microbiology or in the study of metabolism. Industrial fermentations involve the large-scale growth of particular microbes for producing beneficial compounds, such as amino acids and vitamins. Temperature, aeration, and pH are all regulated to maintain optimal microbial growth conditions. Generally, industrial fermentations start with the cheapest growth medium available, often the waste product from another process (such as whey from cheese production). Vats are typically made from stainless steel so that they can be cleaned and sterilized more easily. Recombinant organisms add to this diversity by producing pharmaceuticals, such as human insulin, which are not normally manufactured by microbial fermentations. In the sections that follow we consider a variety of industrial products produced by microbes, including enzymes, alternative fuels, pharmaceuticals, pesticides, agricultural products, biosensors, and bioreporters. Enzymes and Other Industrial Products Enzymes are among the more important products made by microbes. Pectinase, obtained from species of Clostridium, enzymatically releases cellulose fibers from flax, which are then made into linen. Proteases from a variety of microbes are used in meat tenderizers, spot removers, and cheese production. Streptokinases and hyaluronidase are used in medicine to dissolve blood clots and enhance the absorption of injected fluids, respectively. Some products made naturally by microorganisms are useful to humans as food additives and food supplements. Food additives generally enhance a food in some way, such as by improving color or taste, whereas food supplements make up for nutritional deficiencies. Amino acids and vitamins are two important microbial products used as supplements. Amino acids are either sold in tablet or powder form or combined to make new compounds, such as the sweetener aspartame (made from the amino acids phenylalanine and aspartic acid). Other organic acids, such as citric acid, gluconic acid, and acetic acid (vinegar), are also microbially produced to be used in food manufacturing. Citric acid is used as an antioxidant in foods, and gluconic acid is used medically to facilitate calcium uptake. Other industrial products made by microbes include dyes and cellulose fibers used in woven fabrics. Microbially produced biodegradable plastics can replace nonbiodegradable, petroleum-based plastics. Such large containers are used for growing microorganisms in the vast quantities needed for the largescale production of many industrial, agricultural, and medical products. In continuous flow production, the vat, also called a bioreactor, is continuously fed new medium while wastes and product are continuously removed. For this setup to work, the organism must secrete its product into the surrounding medium. Industrial products are produced as either primary or secondary metabolites of the microorganisms. Primary metabolites, such as ethanol, are produced during active growth and metabolism because they are either required for reproduction or by-products of active metabolism.

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There is a real possibility that we will enter a postantibiotic era arrhythmia or dysrhythmia buy discount perindopril 2mg on-line, in which some infections will be untreatable. There are a variety of reasons for this, including the economic with a mutation that confers drug resistance. One recent human trial used a mixture of bacteriophages specific for Pseudomonas aeruginosa to treat ear infections caused by the bacterium. These infections are found in the form of biofilms and have been extremely difficult to treat. One clear advantage to bacteriophage treatments is the extreme specificity of the phages-only one species of bacterium is affected, leaving the normal inhabitants of the body alone. Helping Nature Along Other novel approaches to controlling infections include the use of probiotics and prebiotics. Probiotics are preparations of live microorganisms that are fed to animals and humans to improve their intestinal biota. This can replace microbes lost during antimicrobial therapy or simply supplement the biota that is already there. Recent years have seen a huge increase in the numbers of probiotic products sold in grocery stores (figure 12. Experts generally find these products safe, and in some cases they can be effective. Probiotics are thought to be useful for the management of food allergies; their role in the stimulation of mucosal immunity is also being investigated. Prebiotics are nutrients that encourage the growth of beneficial microbes in the intestine. For instance, certain sugars such as fructans are thought to encourage the growth of the beneficial Bifidobacterium in the large intestine and to discourage the growth of potential pathogens. You can be sure that you will hear more about prebiotics and probiotics as the concepts become increasingly well studied by scientists. Clearly, the use of these agents is a different type of antimicrobial strategy than we are used to , but it may have its place in a future in which traditional antibiotics are more problematic. A technique that is being employed in some medical communities is the use of fecal transplants in the treatment of recurrent Clostridium difficile infections. This procedure involves the transfer of feces, containing beneficial normal biota, from healthy patients to affected patients via colonoscopy (figure 12. Policy makers are starting to create incentives for the discovery and manufacture of new antibiotics, although we should keep in mind that even new drugs will eventually become less effective over time as bacteria adapt to them. New Approaches to Antimicrobial Therapy Often, the quest for new antimicrobial strategies focuses on finding new targets in the bacterial cell and custom-designing drugs that aim for them. However, very recently a new approach has been in the spotlight: disabling host molecules that the invaders use to enhance their position. One promising development is to target a host cell protein that bacteria use to move from one cell compartment to another. In the domain of direct damage to the invading bacteria, there are many interesting new strategies as well. The good news is that there is now an uptick in research into novel antimicrobial strategies. When antibiotic resistance first became widely problematic, the specter of "no new drugs" was very real, because drug makers had drastically slowed their antibiotic development. They cannot be blamed; there was a time from the 1950s to the 1980s when the medical world assumed that eventually all infections could be wiped out with antibiotics. Eastern European countries have gained a reputation for using mixtures of bacteriophages as medicines for bacterial infections. The use of bacteriophages sputtered along until the middle of the 20th century, when antibiotics were discovered. Antibiotics quickly overtook bacteriophage therapy as the treatment of choice for all bacterial infections-in the West, at least. In the Soviet Union and other Eastern bloc countries that had little or no access to antibiotics, bacteriophage use continued. It had never been rigorously vetted according to modern standards of pharmaceutical testing, but it worked effectively throughout the 20th century in those places. In the early 21st century, we find ourselves with very few effective drug treatments for some antibiotic-resistant bacteria. The first major clinical trials of phage therapy started in Europe in summer 2015. The European Commission funded the study, which is examining the efficacy of the treatment on burn patients in France, Belgium, and Switzerland. And the United States National Institute of Allergy and Infectious Diseases in 2014 identified phage therapy as one of seven areas of emphasis in targeting antibiotic resistance. It will be at least 5 years before phage therapy passes through the rigorous testing required to bring a "drug" to market, but it still provides promise that we will have a weapon in our arsenal against drug-resistant infections. Before the middle of the 20th century, there were no effective treatments for human bacterial infections. He had obtained the bacteriophages by filtering stool samples from sick patients to remove bacteria and other particles, leaving only the tiny bacteriophages. Before administering the phage "soup," he and several other doctors drank some of it themselves to determine if it was safe, as indeed it proved to be. This method has had documented success in farm animals, and studies have shown a therapeutic effect in humans as well. Also, companies are now scrambling to create "gut microbiome" pills, in attempts to eliminate the "yuck" factor. It is not clear whether these will be as effective, since they have to traverse the stomach and small intestine before reaching the large intestine. At any rate, the gut microbiome seems to be so important for health, even outside the intestines, that you will probably see supplementation with healthy fecal bacteria used more broadly in the future. List five cellular or structural mechanisms that microbes use to resist antimicrobials. Discuss at least three novel antimicrobial strategies that are under investigation. In fact, estimates indicate that at least 5% of all persons taking an antimicrobial drug experience some type of relatively serious adverse reaction to it. The major side effects of drugs fall into one of three categories: direct damage to tissues through toxicity, allergic reactions, and disruption in the balance of normal microbial biota. The damage incurred by antimicrobial drugs can be short-term and reversible or permanent, and it ranges in severity from cosmetic to lethal. In the field of antimicrobial therapy, one must always remember the ancient axiom Graviora quaedum sunt remedia periculus ("Some remedies are worse than the disease"). Some potential toxic effects of drugs on the body, along with the drugs that may cause them, are detailed in table 12. Tetracyclines are contraindicated (not advisable) for children from birth to 8 years of age because they bind to the enamel of the teeth, creating a permanent gray to brown discoloration. They also cross the placenta and can be deposited in the developing fetal bones and teeth. However, the most common complaint associated with oral antimicrobial therapy is diarrhea, which can progress to severe intestinal irritation or colitis. Although some drugs directly irritate the intestinal lining, the usual gastrointestinal complaints are caused by disruption of the intestinal microbiota. This reaction occurs because the drug acts as an antigen (a foreign material capable of stimulating the immune system) and stimulates an allergic response. In the case of penicillin, for instance, it is not the penicillin molecule itself that causes the allergic response but a product, benzylpenicilloyl. Allergic reactions have been reported for every major type of antimicrobial drug, but the penicillins account for the greatest number of antimicrobial allergies, followed by the sulfonamides. People who are allergic to a drug become sensitized to it during the first contact, usually without symptoms. Once the immune system is sensitized, a second exposure to the drug can lead to a reaction such as a skin rash (hives); respiratory inflammation; and, rarely, anaphylaxis, an acute, overwhelming allergic response that develops rapidly and can be fatal. Antibiotics may be causing a wide array of unintended effects by changing the nature of our microbiome. Even before we had a clear picture of the absolute importance of the microbiome, it was obvious that antibiotic usage could have disruptive effects on our health. If a broad-spectrum antimicrobial is introduced into a host to treat infection, it will destroy microbes regardless of their roles as normal biota, affecting not only the 12.

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Complement fixation blood pressure 200 100 buy line perindopril, agglutination, and precipitation are covered further in section 17. Fc Binds To Biological Function 2 150,000 80% 23 Yes Yes Phagocytes Long-term immunity; memory antibodies; neutralizes toxins, opsonizes, fixes complement antibodies to aggregate, or agglutinate, antigens is the consequence of their cross-linking cells or particles into large clumps. In neutralization reactions, antibodies fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching normally. Functions of the Fc Fragment Although the Fab fragments bind antigen, the Fc fragment has a different binding function. In most classes of immunoglobulin, the Fc end can bind to receptors on the membranes of cells, such as macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes. In the case of opsonization, the attachment of antibody to foreign cells and viruses exposes the epitopes to which they are bound to phagocytes. Certain antibodies have regions on the Fc portion for binding complement; in some immune reactions, 2. There are other uses for the term antitoxin, notably, substances used to counteract snake bites and so on. For example, the Fc end of the antibody of allergy (IgE) binds to basophils and mast cells, which causes the release of allergic mediators such as histamine. Accessory Molecules on Immunoglobulins All antibodies contain molecules in addition to the basic polypeptide structure. Varying amounts of carbohydrates are affixed to the constant regions in most instances (table 15. Two additional accessory molecules are the J chain, which joins the monomers3 Disease Connection Researchers are exploiting the fact that antibodies have two Fab fragments and creating what they call "bispecific antibodies" to treat cancer. The Classes of Immunoglobulins Immunoglobulins exist as structural and functional classes called isotypes (compared and contrasted in table 15. The differences in these classes are due primarily to variations in the Fc fragment. The classes are differentiated with shorthand names (Ig, followed by a letter: IgG, IgA, IgM, IgD, IgE). It is a monomer produced by plasma cells in a primary response and by memory cells responding the second time to a given antigenic stimulus. It is by far the most prevalent antibody circulating throughout the tissue fluids and blood. It has numerous functions: It neutralizes toxins, opsonizes, and fixes (binds) complement; and it is the only antibody capable of crossing the placenta. The two forms of IgA are (1) a monomer that circulates in small amounts in the blood and (2) a dimer that is a significant component of the mucous and serous secretions of the salivary glands, intestine, nasal membrane, breast, lung, and genitourinary tract. To facilitate the transport of IgA across membranes, a secretory piece is later added. IgA coats the surface of these membranes and is found in saliva, tears, colostrum, and mucus. It provides the most important specific local immunity to enteric, respiratory, and genitourinary pathogens. During lactation, the breast becomes a site for the proliferation of lymphocytes that produce IgA. The very earliest secretion of the breast-a thin, yellow milk called colostrum-is very high in IgA. These antibodies form a protective coating in the gastrointestinal tract of a nursing infant that guards against infection by a number of enteric pathogens (Escherichia coli, Salmonella, poliovirus, rotavirus). As with immunity in utero, the necessary antibodies will be donated only if the mother herself has active immunity to the microbe through a prior infection or vaccination. IgM is a huge molecule composed of five monomers (making it a pentamer) attached by the Fc portions to a central J chain. With its 10 binding sites, this molecule has tremendous capacity for binding antigen. Its complement-fixing qualities make it an important antibody in many immune reactions. IgD is a monomer found in minuscule amounts in the serum, and it does not fix complement, opsonize, or cross the placenta. Its main function is that it is the receptor for antigen on B cells, usually along with IgM. IgE is also an uncommon blood component unless one is allergic or has a parasitic worm infection. Its biological role is to stimulate an inflammatory response through the release of potent physiological substances by the basophils and mast cells. Because inflammation enlists blood cells such as eosinophils and lymphocytes to the site of infection, it is an important defense against parasites. Unfortunately, IgE has another, more insidious effect-that of mediating anaphylaxis, asthma, and certain other allergies. Monitoring Antibody Production over Time: Primary and Secondary Responses to Antigens We can learn a great deal about how the immune system reacts to an antigen by studying the levels of antibodies in serum over time (process figure 15. This level is expressed quantitatively as the titer (ty-tur), or concentration of antibodies. During this time, the antigen is being concentrated in lymphoid tissue and is being processed by the correct clones of B lymphocytes. As plasma cells synthesize antibodies, the serum titer (concentration) increases to a certain plateau and then tapers off to a low level over a few weeks or months. It turns out that, early in the primary response, most of the antibodies are the IgM type, which is the first class to be secreted by plasma cells. Later, the class of the antibodies is switched to IgG or some other class (IgA or IgE). The secondary response is also called the anamnestic response (from the Greek word for "memory"). The advantage of this response is evident: It provides a quick and potent strike against subsequent exposures to infectious agents. This memory effect is the fundamental basis for vaccination, which we discuss later. It is a well-accepted principle that memory B and T cells are only created from clones activated by a specific antigen. This provides a much quicker and more effective response on the second exposure, and all exposures afterwards. But researchers are now investigating a phenomenon that has been suspected for some time and confirmed in rigorous studies. It seems that exposure to a particular antigen can result in memory cells to antigens that are chemically related to it, even if those antigens have not been seen by the host. This might explain the well-known phenomenon, seen most clearly in developing countries, that vaccines against one disease can provide some protection against others. In Africa, for example, vaccinating against measles also cuts deaths from pneumonia, sepsis, and diarrhea by one-third. The rate of antibody synthesis, the peak titer, and the length of antibody persistence are greatly increased over the primary response. The speed and intensity seen in this response are attributable to the memory B cells that were formed during the primary response. The earliest part of this response, the latent period, is marked by a lack of antibodies for that antigen, but much activity is occurring. As plasma cells synthesize antibodies, the serum titer increases to a certain plateau and then tapers o to a low level over a few weeks or months. Early in the primary response, most of the antibodies are the IgM type, which is the first class to be secreted by plasma cells. Later, the class of the antibodies (but not their specificity) is switched to IgG or some other class (IgA or IgE). If other microbes share those chemical signatures (epitopes), memory cells will react against them as well. This is a promising development, since it could result in the use of nonpathogenic microbes in vaccines to protect against more dangerous ones. Draw and label a graph illustrating the development of a secondary immune response.

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Because cysts are more resistant than ordinary cells to heat arrhythmia unspecified icd 9 code purchase perindopril 2mg with amex, drying, and chemicals, they can survive adverse periods. They can be dispersed by air currents and may even be an important factor in the spread of diseases such as amoebic dysentery. If provided with moisture and nutrients, a cyst breaks open and releases the active trophozoite. Both the cyst and trophozoite forms of protozoan pathogens can be identified through O & P (ova and parasite) testing of patient stool samples. This method, combined with immunology-based tests, is currently used for disease diagnosis in cases of giardiasis and cryptosporidiosis. The life cycle of a parasitic protozoan dictates its mode of transmission to other hosts. For example, the flagellate Trichomonas vaginalis causes a common sexually transmitted infection. Because it does not form cysts, it is more delicate and must be transmitted by intimate contact between sexual partners. In contrast, intestinal pathogens such as Cryptosporidium and Giardia lamblia (process figure 5. All protozoa reproduce by relatively simple, asexual methods, usually mitotic cell division. Several parasitic species, including the agents of malaria and toxoplasmosis, reproduce asexually by multiple fission inside a host cell. Ciliates participate in conjugation, a form of genetic exchange in which two cells fuse temporarily and exchange micronuclei. This process of sexual recombination yields new and different genetic combinations that can be advantageous in evolution. Classification of Selected Important Protozoa Taxonomists have problems classifying protozoa. We will use a functional way to categorize them, in a way that will be most useful in a clinical situation. The photo in the center shows a Giardia trophozoite (purple) emerging from its cyst form (orange). Most species form cysts and are free-living; the group also includes several parasites. Members include Trypanosoma and Leishmania, important blood pathogens spread by insect vectors; Giardia (see figure 5. Major locomotor organelles are pseudopods, although some species have flagellated reproductive states. Most amoebas are free-living and not infectious; nu tri ist or en ts ed 3 Mature cyst (dormant, resting stage) Entamoeba is a pathogen or parasite of humans; shelled amoebas called foraminifera and radiolarians are responsible for chalk deposits in the ocean. Trophozoites are motile by cilia; some have cilia in tufts for feeding and attachment; most develop cysts; have both macronuclei and micronuclei; division by transverse fission; most have a definite mouth and feeding organelle; show relatively advanced behavior (see figure 5. Although motility is absent in most representatives, it is exhibited by the male gametes of many members of this group. Life cycles of the apicomplexa are, as the name implies, quite complex, with well-developed asexual and sexual stages. Most sporozoa form thick-walled zygotes called oocysts, and this entire group of organisms is parasitic. Plasmodium, the most prevalent protozoan parasite, causes 130 Chapter 5 Eukaryotic Cells and Microorganisms Table 5. It is an intracellular parasite with a complex cycle alternating between humans and mosquitoes. Toxoplasma gondii causes infection (toxoplasmosis) in humans, which is acquired from cats and other animals. Just as with bacteria and other eukaryotes, protozoa that cause disease produce symptoms in different organ systems. Protozoan Identification and Cultivation the unique appearance of most protozoa makes it possible for a knowledgeable person to identify them to the level of genus-and often species-by microscopic morphology alone. Characteristics to consider in identification include the shape and size of the cell; the type, number, and distribution of locomotor structures; the presence of special organelles or cysts; and the number of nuclei. Medical specimens taken from blood, sputum, cerebrospinal fluid, feces, or the vagina are smeared directly onto a slide and observed with or without special stains. Occasionally, protozoa are cultivated on artificial media or in laboratory animals for further identification or study. Two flagellated protozoa that cause human disease are Trypanosoma brucei and Trypanosoma cruzi. Both species have long, crescentshaped cells with a single flagellum that is sometimes attached to the cell body by an undulating membrane. Both are found in the blood during infection and are transmitted by blood-sucking vectors. Note the protozoan characteristics that illustrate why they are informally placed into a single group. Important Protozoan Pathogens Although protozoan infections are very common, they are actually caused by only a small number of species often restricted geographically to the tropics and subtropics (table 5. Nevertheless, they are included among microorganisms because of their infective abilities and because a microscope is necessary to identify their eggs and larvae. On the basis of body type, the two major groups of parasitic helminths are the flatworms (Phylum Platyhelminthes) and the roundworms (Phylum Aschelminthes, also called nematodes). The flatworm group is subdivided into the cestodes, or tapeworms, named for their long, ribbon-like arrangement, and the trematodes, or flukes, characterized by flat, oval bodies (figure 5. Not all flatworms and roundworms are parasites by nature; many live free in soil and water. Because most disease-causing helminths spend part of their lives in the gastrointestinal tract, they are discussed in chapter 22. General Worm Morphology All helminths are multicellular animals equipped to some degree with organs and organ systems. In parasitic helminths, the most developed organs are those of the reproductive tract, with more primitive digestive, excretory, nervous, and muscular systems. In particular groups, such as the cestodes, reproduction is so dominant that the worms are reduced to little more than a series of flattened sacs filled with ovaries, testes, and eggs (see figure 5. Life Cycles and Reproduction the complete life cycle of helminths includes the fertilized egg (embryo), larval, and adult stages. In the majority of helminths, Suckers Scolex (a) Oral sucker Esophagus Ventral sucker Cuticle Uterus Vas deferens Ovary Testes Seminal receptacle 1 mm Immature eggs Fertile eggs 11. Note the suckers that attach to host tissue and the dominance of reproductive and digestive organs. In nematodes, the sexes are separate and usually different in appearance; in trematodes, the sexes can be either separate or hermaphroditic, meaning that male and female sex organs are in the same worm; cestodes are generally hermaphroditic. The host in which larval development occurs is the intermediate (secondary) host, and adulthood and mating occur in the definitive (final) host. A transport host is an intermediate host that experiences no parasitic development but is an essential link in the completion of the cycle. In general, the sources for human infection are contaminated food, soil, and water or infected animals; routes of infection are by oral intake or penetration of unbroken skin. In other cases, animals or insect vectors serve as reservoirs or are required to complete worm development. In the majority of helminth infections, the worms must leave their host to complete the entire life cycle. Even so, most eggs and larvae are vulnerable to heat, cold, drying, and predators and are destroyed or unable to reach a new host. To counteract this formidable mortality rate, certain worms have adapted a reproductive capacity that borders on the incredible: A single female Ascaris worm can lay 200,000 eggs a day, and a large female can contain over 25 million eggs at varying stages of development! If only a tiny number of these eggs make it to another host, the parasite will have been successful in completing its life cycle. They are identified in the laboratory by microscopic detection of the adult worm or its larvae and eggs, which often have distinctive shapes or external and internal structures. Distribution and Importance of Parasitic Worms About 50 species of helminths parasitize humans. Some worms are restricted to a given geographic region, and many have a higher incidence in tropical areas. This knowledge must be tempered with the realization that air travel, along with human migration, is gradually changing the patterns of worm infections, especially of those species that do not require alternate hosts or special climatic conditions for development.

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Aerobic Respiration Aerobic respiration is the metabolic scheme in which electrons are transferred from fuel molecules such as glucose to oxygen as a final electron acceptor blood pressure 40 over 20 safe 4mg perindopril. It is then converted (another reaction, another enzyme) to fructose-6-phosphate, and then another phosphate is added. The resulting molecule-fructose diphosphate-is more symmetrical and can be split into two 3-carbon molecules (process figure 8. From here to the end, everything that happens in glycolysis happens twice-once to each of the 3-carbon molecules. This results in two 3-carbon molecules with no phosphates-the all-important pyruvic acid. Although glycolysis is the main route to pyruvate production for most organisms, some microbes lack the enzymes for this pathway. There are alternate biochemical reactions such as the Entner-Doudoroff pathway (by Pseudomonas and Enterococcus species) and the pentose phosphate pathway (by some photosynthetic microbes). Our aim here is to focus on general principles, so we will restrict ourselves to glycolysis. Pyruvic Acid: A Central Metabolite Pyruvic acid occupies an important position in several pathways, and different organisms handle it in different ways (figure 8. In strictly aerobic organisms and some anaerobes, pyruvic acid enters the Krebs cycle for further processing and energy release. Facultative anaerobes can use a fermentative metabolism, in which pyruvic acid is re-reduced into acids or other products. The Krebs Cycle: A Carbon and Energy Wheel In glycolysis, the oxidation of glucose yields a comparatively small amount of energy and gives off pyruvic acid. In the following section, we examine the next phase of this process, the Krebs cycle. This set of reactions takes place in the cytosol of bacteria and is catalyzed by a group of enzymes (some of which are associated with the cytoplasmic membrane). To connect the glycolysis pathway to the Krebs cycle, for either aerobic or anaerobic respiration, the pyruvic acid is first converted to a starting compound for that cycle (process figure 8. Here we have an oxidation-reduction reaction, which also releases the first carbon dioxide molecule. In recent years, Enterococci that are resistant to the antibiotic vancomycin have become problematic, particularly in hospitals. They have an extremely flexible metabolism and can use a huge variety of substrates to produce energy. It can also serve as a source of raw material for synthesizing amino acids and carbohydrates. Note that this is an enlarged, more detailed view of the middle phase depicted in figure 8. It occurs in the cytoplasm of bacteria and the mitochondrial matrix of eukaryotes. The acetyl group remains attached to coenzyme A, forming acetyl coenzyme A (acetyl CoA) that feeds into the Krebs cycle. Keep in mind that all reactions described actually happen twice for each glucose because of the two pyruvates that are formed during glycolysis. The addition of water to fumaric acid (called hydration) results in malic acid (malate; 4C). This step brings the cycle back to its original starting position, where oxaloacetic acid can react with acetyl coenzyme A. Steps in the Krebs Cycle As you learned earlier, a cyclic pathway is one in which the starting compound is regenerated at the end. The Krebs cycle has eight steps, beginning with citric acid formation and ending with oxaloacetic acid. The flow of electrons down this chain is highly energetic and allows the active transport of hydrogen ions to the outside of the membrane where the respiratory chain is located. The step that finalizes the transport process is the acceptance of electrons and hydrogen by oxygen, producing water. The cytochromes contain a tightly bound metal atom at their center that is actively involved in accepting electrons and donating them to the next carrier in the series. The highly compartmentalized structure of the respiratory chain is an important factor in its function. The equivalent structure for housing them in eukaryotes is the inner mitochondrial membranes pictured in figure 8. Citric acid is converted to isocitric acid (isocitrate; 6C) to prepare this substrate for the decarboxylation and dehydrogenation of the next step. The remaining steps are needed not only to regenerate the oxaloacetic acid to start the cycle again but also to extract more energy from the intermediate compounds leading to oxaloacetic acid. The enzyme that catalyzes this reaction, succinyl dehydrogenase, is found in the bacterial cytoplasmic membrane and mitochondrial cristae of eukaryotic cells. Although the biochemical details of this process are rather complicated, the basic reactions consist of a number of redox reactions now familiar to us. Coupled to the transport of electrons is the simultaneous active transport of H+ into the periplasm by specific carriers. Note the differences in final electron acceptors in aerobic versus anaerobic respirers. As the carriers in the mitochondrial cristae H+ ions Intermembrane space Cristae transport electrons, they also actively pump H+ ions (protons) to the intermembrane space, producing a chemical and charge gradient between the outer and inner mitochondrial compartments. The sequence of electron carriers in the respiratory chain of most aerobic organisms is 1. These totals are the maximum yields possible but may not be fulfilled by many organisms. Summary of Aerobic Respiration Originally, we presented a summary equation for respiration. Six water molecules are produced in electron transport and 2 in glycolysis, but because 2 are used in the Krebs cycle, this leaves a net number of 6. We will first look at the system in bacteria, which have the components of electron transport embedded in a precise sequence on the cytoplasmic membrane. As the electron transport carriers shuttle electrons, they actively pump hydrogen ions (protons) into the periplasmic space, or the space between the wall and the cytoplasmic membrane, depending on whether the bacterium is gram-positive or gram-negative. Separating the charge has the effect of a battery, which can temporarily store potential energy. It is embedded in the membrane, but part of it rotates like a motor and traps chemical energy. The enzyme is then rotated back to the start position and will continue the process. The Terminal Step the last step, during which oxygen accepts the electrons, is catalyzed by cytochrome aa3, also called cytochrome oxidase. This large enzyme complex is specifically adapted to receive electrons from another cytochrome, pick up hydrogens from the solution, and react with oxygen to form a molecule of water. You have seen them in glycolysis, the Krebs cycle, and perhaps most importantly, in the electron transport chain. Those cells, of course, use the electron transport chain in their mitochondria to create energy. It is very hard to get things from your stomach into your brain, for example, because the brain excludes most things from entering by something called the blood-brain barrier. Some species lack one or more of the redox steps; others have several alternative electron transport schemes. Because many bacteria lack cytochrome oxidase, this variation can be used to differentiate among certain genera of bacteria. An oxidase detection test can be used to help identify members of the genera Neisseria and Pseudomonas and some species of Bacillus. Another variation in the cytochrome system is evident in certain bacteria (Klebsiella, Enterobacter) that can grow even in the presence of cyanide because they lack cytochrome oxidase. Cyanide will cause rapid death in humans and other eukaryotes because it blocks cytochrome oxidase, thereby completely blocking aerobic respiration, but it is harmless to these bacteria.

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Initially blood pressure zone quality 4 mg perindopril, the rash is macular, evolving in turn to papular, vesicular, and pustular appearance before eventually crusting over, leaving behind nonpigmented sites pitted with scar tissue. Variola major is a highly virulent form that causes toxemia, shock, and intravascular coagulation. People who have survived any form of smallpox nearly always develop lifelong immunity. It is vitally important for health care workers to be able to recognize the early signs of smallpox. The diagnosis of even a single suspected case must be treated as a health and law enforcement emergency. The symptoms of variola major progress as follows: After the prodrome period of high fever and malaise, a rash emerges; the rash typically develops first in the mouth. As lesions develop, they break open and spread virus into the mouth and throat, making the patient highly contagious. The virus invades the mucosa and multiplies in the regional lymph nodes, leading to viremia. Variola multiplies within white blood cells and then travels to the small blood vessels in the dermis. The lesions occur at the dermal level, which is the reason that scars remain after the lesions are healed. Transmission and Epidemiology Before the eradication of smallpox, almost everyone contracted the disease over the course of his or her lifetime, either surviving with lifelong immunity or dying. It is spread primarily through droplet transmission, although fomites such as contaminated bedding and clothing can also spread the disease. Traditionally, the incidence of smallpox was highest in the winter and early spring. Every year, 10 to 15 million people contracted the disease, and approximately 2 million people died from it. After 11 years of intensive effort by the world health community, the last natural case occurred in Somalia in 1977. Prevention A Note About Bioterror Agents the Centers for Disease Control and Prevention maintain a list of the most dangerous infectious agents that would be most logically used for a bioterror attack. Category A agents (the most dangerous) are those that are (1) easily disseminated or transmissible person-to-person; (2) result in high mortality rates; (3) could incite panic and social disruption; and (4) require special or unique actions for preparedness. Category A agents will be pointed out in the Disease Tables in the next six chapters. By the third or fourth day of the rash, the bumps become larger and fill with a thick, opaque fluid. A major distinguishing feature of this disease is that the pustules are indented in the middle (Disease Table 18. After 2 weeks, most of the lesions will have crusted over; the patient remains contagious until the last scabs fall off because the crusts contain the virus. A patient with variola minor has a rash that is less dense and generally experiences weaker symptoms than someone affected by variola major. The United States stopped using the vaccine in 1972 after a massive effort to eradicate the virus worldwide. Concerns have been expressed about the existence of smallpox stocks in some regions of the world. Iraqi prisoners captured in the 1991 Gulf War were reported to have high titers of antibodies to smallpox, which suggested they had been immunized. Currently, the United States has a large enough stockpile of smallpox vaccine to vaccinate the entire U. Some advocate the use of cidofovir, which is labeled for use in cytomegalovirus infection. If lesions become infected secondarily with bacteria, antibiotics can be used for treatment of that complication. Soon, red or blisterlike spots appear on the palms of the hands and soles of the feet and often the genitals, buttocks, knees and elbows (see Disease Table 18. It is transmitted via secretions (saliva, sputum, blister fluid, feces) through direct contact. The sick person will feel worst even before the lesions appear and is most contagious during the first week of illness, though many patients continue to shed contagious virus for days or weeks. But every year, hundreds of thousands of children in the developing world die from this disease (at last count, 430 a day), even though an extremely effective vaccine has been available since 1963. Health campaigns all over the world seek to make measles vaccine available to all, and have been very effective in doing so. Roughly 85% of children throughout the world received a single dose of measles vaccine in 2010, an increase of over 10% since 2000. Ironically, it seems that more work and education need to be done in developed countries now. Many parents are opting not to have their children vaccinated, due to unfounded fears about the link between the vaccine and autism. We would do well to remember that before the vaccine was introduced, measles killed 6 million people each year worldwide. Be very careful not to confuse it with the next maculopapular rash disease, rubella. In a small number of cases, children develop laryngitis, bronchopneumonia, and bacterial secondary infections such as ear and sinus infections. Children afflicted with leukemia or thymic deficiency are especially predisposed to pneumonia because of their lack of a natural T-cell defense. Affected patients are very ill and often have a characteristic dusky skin color from lack of oxygen. A large number of measles patients experience secondary bacterial infections with Haemophilus influenzae, Maculopapular Rash Diseases Table 18. The infectious conditions described in this section are those with their major manifestations on the skin. Its incidence is approximately one case in a million measles infections, and it afflicts primarily male children and adolescents. Instead, it spreads, unchecked, through the brain by cell fusion, gradually destroying neurons and accessory cells and breaking down myelin. The course of the disease invariably leads to coma and death in a matter of months or years. Measles during pregnancy has been associated with spontaneous miscarriage and low-birthweight babies. For best results, blood should be drawn on the third day of onset or later, because before that time titers of IgM may not be high enough to be detected by the test. Also, the method of comparing acute and convalescent sera may be used to confirm a measles infection after the fact. As you may recall, much higher IgG titers 14 days after onset when compared to titers at day 1 or 2 are a clear indication of current or recent infection. This knowledge allows health care providers to be on the lookout for complications and to be ahead of the game if a person who has had contact with the patient presents with similar symptoms. Pathogenesis and Virulence Factors the virus implants in the respiratory mucosa and infects the tracheal and bronchial cells. From there it travels to the lymphatic system, where it multiplies and then enters the bloodstream. The measles virus induces the cell membranes of adjacent host cells to fuse into large syncytia (sin-sish-uh), giant cells with many nuclei. The virus seems proficient at disabling many aspects of the host immune response, especially cell-mediated immunity and delayed-type hypersensitivity. The host may be left vulnerable for many weeks after infection; this immune response disruption is one of the reasons that secondary bacterial infections are so common. Because the disease is so contagious, good coverage with the vaccine in any given population (herd immunity) is required to prevent transmission to those who cannot receive the vaccine (and to babies too young to receive it). Measles immunization is recommended for all healthy children at the age of 12 to 15 months, with a booster before the child enters kindergarten. Failing that, the preadolescent health check serves as a good time to get the second dose of measles vaccine.