Chapter 23: Major Microbial Diseases Introduction

Chapter 23 (pages 933-990) concerns the subset of the microorganisms that are pathogens. Infectious diseases are caused by bacteria, viruses, fungi, and protozoa. However, all pathogens which infect the same body tissue must overcome similar problems in initiating a disease in that tissue. Therefore, the discussion of pathogens in this chapter is organized with an emphasis on the disease's mode of transmission and mode of action.

Microbes do not grow in air, but are transmitted through it, especially on dust particles. However, the organism must be relatively resistant to drying to be effectively transmitted. In general, Gram-positive bacteria such as Staphylococcus and Streptococcus survive longer under dry conditions than do Gram-negative species. Respiratory pathogens are released in aerosols by an infected host by sneezing, coughing, or talking. The density of pathogens in air will be greater in crowded indoor areas than outdoors.

Most bacterial pathogens of the respiratory tract are Gram positive species. They are susceptible to antibiotics such as penicillin, and effective vaccines can be constructed against them.

Streptococcus pyogenes is frequently part of the normal flora in the nasopharynx of healthy adults. However, low host resistance may result in strep-throat, with inflammation of the throat and a mild fever. Accurate diagnosis is important, because the bacterial infections can be treated with penicillin.

Some S. pyogenes strains carry a lysogenic bacteriophage which codes for the exotoxin that produces the rash of scarlet fever. If streptococcal infections are not completely eradicated, an autoimmune condition such as rheumatic fever may arise. Antibodies made against the streptococcal cell surface antigens may cross-react with heart and joint tissue, or cause kidney damage.

Streptococcus pneumoniae, a cause of bacterial pneumonia, is a member of the normal upper respiratory tract flora in many individuals. However, if it infects the lungs, a strong inflammatory response occurs which impairs lung function. Antiphagocytic capsules are an important virulence factor of the pathogen. The infection responds to penicillin; if untreated the infection may be fatal. Staphylococcus aureus is also commonly found in humans, particularly in the upper respiratory tract. However, strains of S. aureus have been linked to toxic shock syndrome (TSS).

Diphtheria is caused by Corynebacterium diphtheriae. The organism infects the throat and tonsils; neuraminidase may enhance its invasiveness. Its growth forms a pseudomembrane which makes breathing difficult. However, systemic effects are the result of an exotoxin which inhibits eukaryotic protein synthesis. The genetic information for the toxin is located on a prophage. Infection is prevented by immunization with DPT vaccine. Infected individuals are treated with antibiotics and antitoxin.

Legionella pneumophila can cause pneumonia in compromised hosts, such as the elderly. The organism is a normal inhabitant of many natural environments. It is transmitted to humans in aerosols generated from air conditioning units, where it can grow in cooling water.

Infants are susceptible to whooping cough, caused by Bordetella pertussis. Bacteria adhere to cells of the upper respiratory tract using a surface component called filamentous hemagglutinin antigen. The bacterium produces an exotoxin which promotes synthesis of cyclic AMP. The symptoms are a violent cough. A vaccine of killed cells is available.

Mycobacterium tuberculosis is responsible for the lung disease tuberculosis. Primary infection occurs by inhalation of droplets containing the bacteria. The microbes grow in the lungs, and induce a cell-mediated immune response which involves a delayed hypersensitivity reaction. The aggregation of activated macrophages around the focus of infection forms a tubercle which walls off the infection. However, bacteria remain viable in tubercles for years. If the host is stressed, these bacteria may be released and the lung infection will spread. To identify people who have been exposed to tuberculosis, tuberculin protein is injected under the skin; this produces a localized delayed-hypersensitivity reaction in individuals whose immune systems have responded to the presence of M. tuberculosis. Tuberculosis can be treated with the drug isoniazid, which blocks synthesis of a lipid unique to mycobacteria. Treatment must be continued for long periods to eliminate all pathogens embedded in tubercles.

Tuberculosis can also be caused by another mycobacterium, M. bovis, which is transmitted through milk from infected cattle. Pasteurization of milk has eliminated this threat. Another pathogenic mycobacterium is M. leprae. It is not a respiratory pathogen, but grows intracellularly in macrophages in the skin and causes leprosy. The disease is not highly contagious, and is transmitted by direct contact. Infections are more common in the tropics.

There are several viral infections of the respiratory tract. The most prevalent is the common cold, caused by rhinoviruses. No effective long-term immunity can be generated because there are more than 100 serologically different rhinoviruses. Because there are few antiviral drugs available, little can be done to treat the infection.

Influenza is transmitted from human-to-human through air. It is caused by influenza virus, which infects the mucous membranes of the upper respiratory tract. Symptoms of fever, chills, fatigue and headache last 3 to 7 days, and then recovery is rapid. In individuals with weakened defense mechanisms, (infants and the elderly), secondary infections such as bacterial pneumonia may occur, and these infections may be fatal. Influenza occurs in pandemics when a new virus strain of high virulence and novel antigenic structure arises. Antigenic shifts in the external protein coat arise because the segmented virus genome can reassort in cells infected with more than one virus. Modifications in hemagglutinin and neuraminidase proteins seem especially important in this regard, because immunity to influenza depends upon IgA antibodies against these proteins.

Several childhood diseases of viral origin are transmitted through air. Measles is caused by rubeola virus. A combination of humoral and cellular immunity eliminates the virus in about ten days. Mumps, like measles, is caused by a paramyxovirus. Rubella is due to a togavirus. The virus is transmitted from mother to fetus during the first trimester of a pregnancy, with severe effects. MMR vaccine, containing live attenuated viruses, provides protection against these three diseases. Varicella virus, of the Herpes group, causes chickenpox. The virus is disseminated by the bloodstream and causes a systemic rash. After recovery, virus may exist in nerve cells in latent form. A subsequent active infection of skin cells causes shingles.

Respiratory infections are difficult to control because there is no practical way to prevent transmission through air. Furthermore, some of the pathogens reside in healthy carriers, and therefore are widely disseminated.

Sexually-transmitted diseases (STD) are caused by a cross section of bacteria, viruses, and protozoa. Public health control is difficult because it requires information on sexual practices that are sensitive issues in society. All these diseases are transmitted by intimate direct contact. Note that many of them can be transmitted to newborns from infected mothers during birth.

Gonorrhea now occurs in epidemic proportions. The bacterium Neisseria gonorrhoeae infects mucous membranes, usually in the genitourinary tract. Infections in females often go unnoticed; therefore they can serve as carriers to disseminate the disease. In males, the infection causes a painful inflammation of the urethra. In the past, penicillin was effective in curing gonorrhea. However, penicillin-resistant strains harboring a plasmid which specifies a penicillinase are becoming prevalent. Infection does not confer protective immunity; therefore, reinfection is possible.

Syphilis is caused by the obligate anaerobe spirochete Treponema pallidum. There are three stages to the disease. After infection through breaks in the epidermis, the primary lesion is a chancre at the site of entry, usually on the genitalia. This disappears, but some microbes disseminate through the body to mucous membranes, joints, and the central nervous system. The secondary stage is a skin rash, caused by a hypersensitive reaction to the treponeme. In both stages, the individual is infectious. In the absence of penicillin treatment, some individuals enter the tertiary stage, in which severe symptoms in the cardiovascular or central nervous systems can occur due to hypersensitivity reactions.

The obligate intracellular parasite Chlamydia trachomatis is responsible for many cases of nongonococcal urethritis. The occurrence of this disease may exceed that of either gonorrhea or syphilis. This results because C. trachomatis causes an inapparent infection, so that unknowing carriers may disseminate the organism. Immunological tests are now used to diagnoses the occurrence of the organism. C. trachomatis is also the causative agent for lymphogranuloma venereum a disease which occurs most frequently in males.

Herpesviruses cause latent infections in humans. Those of type 1 cause cold sores, whereas type 2 cause blisters in the genital region. Genital herpes is incurable, but the blisters can be controlled with acyclovir.

The protozoan Trichomonas vaginalis can cause nongonococcal urethritis. In this instance, males are important asymptomatic carriers transmitting the disease. Transmission can be prevented by the use of condoms; metronidazole is used to treat infections.

HIV virus is the agent of the fatal disease AIDS. Fatalities result because the virus impairs the host's immune system, so that the host is susceptible to opportunistic infections by microbes that are rarely invasive in healthy humans. These include the protozoan Pneumocystis carinii, toxoplasmosis, and systemic yeast infections.

HIV virus specifically infects the CD4 class of T-lymphocytes, cells involved in the immune response. As a result, the end result of an HIV infection is a loss of CD4 cells. As the CD4 makes up about 70% of the T-cells, their loss causes the susceptibility to the opportunistic infections mentioned above. T cell function is lost because (a) cells producing virus stop dividing and (b) uninfected T cells become nonfunctional when they bind to infected cells and fuse to form syncytia. Overall lymphocyte function declines as the level of immune modulators produced by CD4 cells decreases.

While no cure is available for HIV infections, several drugs are reported to delay the onset of AIDS. Azidothymidine (AZT) is most commonly used drug and inhibits HIV replication. The genetic variability in the HIV virus has slowed the development of an effective vaccine.

Rabies is a zoonosis that can be transmitted to humans by an animal bite. It is caused by a virus of the rhabdovirus family, which attacks the central nervous system and if untreated, causes death. The incubation period is about two weeks in dogs, but up to nine months in humans. The virus proliferates in the brain; death is due to respiratory paralysis. Vaccines of attenuated live virus are available; because of the long incubation period, they can be administered after infection. An infected individual will also be passively immunized with antiserum. The reservoir of rabies virus is the wild animal population.

Rickettsial infections (typhus fever and Rocky Mountain Spotted fever) are transmitted by insect bites. The initial symptoms are fever, headache, and a rash. These bacteria are obligate intracellular parasites of phagocytic cells. Because rickettsias are not easily cultured, diagnosis employs immunological tests. These diseases are controlled by control of the insect vectors: lice, fleas, and ticks.

Lyme disease is transmitted to humans by tick bites. The disease is predominate in the upper Midwest but is spreading to all parts of the United States. It is caused by a spirochete, Borrelia burgdorferi which is transmitted to humans as the tick is feeding on blood. Although easily treated soon after infection, if the disease progresses to the chronic stage, severe neurological symptoms occur which are similar to the effects produced by the spirochete which causes syphilis.

Malaria is caused by protozoa of the Sporozoa group; Plasmodium vivax is the most widespread. A complete life cycle of this organism requires growth in both humans and mosquitoes of the genus Anopheles. Therefore, the distribution of the disease parallels the geographic distribution of Anopheles. The characteristic cycles of fever and chills are due to cycles of infection of red blood cells by merozoites and their release from these cells. Humans are infected by sporozoites that are formed in the mosquito; the mosquito is infected by gametocytes that arise in the human. Two drugs, chloroquine and primaquine, together eliminate parasites both inside and outside red blood cells. Disease control involves eliminating mosquitoes by either draining swamps which they inhabit or killing them with insecticides.

Humans who reside where malaria is endemic have evolved resistance mechanisms to Plasmodium. This may involve an altered hemoglobin with reduced affinity for oxygen in red blood cells. The parasites do not grow as well in these cells.

Yersinia pestis causes plague. Its reservoir is rodents. The bacterium is transmitted to humans via flea bites. The microbe infects the lymph nodes, which are then called buboes. A capsule and other surface components are important virulence factors which prevent phagocytosis. An exotoxin that inhibits respiration in mitochondria may be important in causing damage to the host. In this form of the disease, called bubonic plague, the bacteria cause a septicemia, and eventually death. If Y. pestis is inhaled, pneumonic plague results. This respiratory infection is highly contagious and fatal if untreated. Rapid diagnosis and antibiotic therapy can prevent death by this pathogen.

Foodborne disease can either be food poisonings, which result from ingestion of bacterial exotoxins that were synthesized in the food, or food infections, caused by growth in the body of bacteria that contaminated the food.

Staphylococcus aureus can grow in creamed foods that are not properly refrigerated, and produce a heat-stable enterotoxin. Vomiting and diarrhea occur a few hours after it is ingested.

Clostridium perfringens proliferates in meats left in warming trays. The bacteria which are ingested sporulate in the intestine, and during this process release an enterotoxin which induces diarrhea 8-22 hours after the contaminated food was consumed.

Clostridium botulinum is responsible for a fatal food poisoning. A heat-sensitive exotoxin is produced when the microbe grows in food which has been inadequately processed to kill endospores. If the food is not subsequently cooked, the toxin will cause paralysis.

Salmonella species may contaminate meat, poultry, and dairy products. The source of contamination is either the animal itself or food handlers. If the food is not adequately cooked before eating, the viable bacteria can infect the intestinal tract, and induce fever, vomiting, and diarrhea.

Campylobacter species cause bacterial diarrhea in children. Poultry is a major reservoir of the pathogen. It can also be transmitted by contact between children and dogs.

Infectious hepatitis is a viral disease transmitted via fecal contamination of water, food, or milk. The virus spreads from the intestine through the bloodstream to the liver, where it causes jaundice. Shellfish harvested from water contaminated with human feces are a major vehicle for the disease. Hepatitis types B and C also affect the liver. They are transmitted through blood.

Escherichia coli strains can cause diarrhea. This trait is plasmid-encoded (see text section 11.9). Disease occurs in travelers who have not encountered these strains previously; the local population has developed immunity due to IgA antibodies which prevent colonization of the intestinal mucosa.

Many intestinal pathogens leave the body in the feces. If drinking water supplies become contaminated with these feces, the pathogens can be transmitted to susceptible hosts. Widespread consumption of contaminated drinking water will lead to disease epidemics. In developed countries, the transmission of waterborne pathogens has been controlled by treatment of sewage, and purification of drinking water.

The most serious waterborne bacterial disease is cholera, caused by Vibrio cholerae. Cholera enterotoxin induces a severe diarrhea, which can result in loss of 20 liters of fluid per day and death by dehydration. However, fluid replacement permits survival of the host. Cholera still occurs where sewage is not properly treated. A large inoculum of bacteria must be ingested so that some cells survive the acidity of the stomach. These microbes attach to the epithelium in the small intestine and produce enterotoxin.

The protozoan Giardia lamblia causes gastrointestinal disease. A resting stage called a cyst is transmitted through water contaminated with feces of wild animals. The cysts germinate in the intestinal tract to form trophozoites which cause diarrhea. Unlike most waterborne pathogens, Giardia is resistant to chlorine treatment. The cysts can be removed by sedimentation or filtration of drinking water.

Entamoeba histolytica is an anaerobic protozoan which is transmitted as cysts in water. The growth of trophozoites that arise from cysts on and in intestinal mucosal cells causes ulceration of the mucosa and dysentery. If untreated, the protozoa may infect other body organs.

Water treatment can prevent the spread of waterborne pathogens in water supplies. However, it is often technically difficult to directly detect these pathogens in water. Therefore, indicator bacteria are used to detect fecal contamination of water. The coliform group is used, because they inhabit the intestinal tract of humans and warm-blooded animals, are present there in large numbers, and persist in natural and treated water in a similar way as actual intestinal pathogens. If high numbers of coliforms are found in a water supply, it indicates that the water has been contaminated with feces, and that it potentially (but not necessarily) contains intestinal pathogens. Note that the term "coliform" is an operational definition, and includes several species, not all of which are strictly intestinal bacteria.

The number of viable coliforms is quantified in water using a selective medium to exclude the growth of other organisms. To be considered safe for drinking, water must contain on average less than one coliform per 100 ml.

Drinking water is treated to remove pathogens, turbidity, color, and odor. Treatments differ with individual circumstances, but in general they include sedimentation, filtration, and chlorination. Sedimentation of particles may be accelerated by adding a coagulant to form large precipitates which settle more quickly. Sand filters remove most particles and microbes which did not sediment. To assure microbiological safety, chlorine is added to the water supply to kill microorganisms.

While bacteria, viruses and protozoa are important pathogens, fungi can cause a number of diseases. Fungi are primarily opportunistic pathogens, tending to attack medically compromised individuals. Fungi cause disease in three ways: production of an allergic or hypersensitivity reaction, production of toxic exotoxin termed mycotoxins and actual invasion and growth in the body termed mycosis.

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