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| INFECTIOUS DISEASE | BACTERIOLOGY | IMMUNOLOGY | MYCOLOGY | PARASITOLOGY | VIROLOGY | |
Dr Abdul Ghaffar |
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Let us know what you think |
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Logo image © Jeffrey Nelson, Rush University, Chicago, Illinois and The MicrobeLibrary |
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READING: Murray, et al.: Medical Microbiology, 3rd ed., Chapter 25, pp. 209-210; chapter 29, pp. 240-242 and chapter 34, pp. 271-275.
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TEACHING OBJECTIVES To know the general morphology and physiology the organisms To know epidemiology and clinical symptoms To understand the mechanisms pathogenesis To know the diagnostic, therapeutic and preventive procedures
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Zoonosis refers to a disease primarily of animals which can be transmitted to humans as a result of direct or indirect contact with infected animal populations.
BRUCELLOSIS Morphology and physiology Brucella are Gram-negative, nonmotile, coccobacilli. They are strict aerobes and grow very slowly (fastidious) on blood agar. In the host, they live as facultative intracellular pathogens. Epidemiology, transmission and symptoms Brucellosis is primarily a disease of animals and it affects organs rich in the sugar erythritol (breast, uterus, epididymis, etc.). The organism localizes in these animal organs and cause infertility, sterility, mastitis, abortion or resides as carriage. Humans in closed contact with infected animals (slaughterhouse workers, veterinarians, farmers, dairy workers) are at risk of developing undulant fever. There are 100-200 cases of brucellosis seen in the US, although the worldwide incidence is estimated at 500,000. Four different species of Brucella are known to infect humans: B. abortus (cattle), B. suis (swine), B. melitensis (goats/sheep) and B. canis (dogs). Although brucellosis has been eradicated in most developed countries through animal vaccination, it persists in many underdeveloped and developing countries. |
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WEB RESOURCES |
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Brucella abortus - Gram-negative, coccobacillus prokaryote; causes bovine spontaneous abortion due to its rapid growth in the presence of
erythritol (produced in the plancenta). SEM x 29,650
©
Dennis Kunkel Microscopy, Inc.
Used with permission
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B. abortus and B. canis cause a mild suppurative febrile infection whereas B. suis causes a more severe suppurative infection which can lead to destruction of the lymphoreticular organs and kidney. B. melitensis is the cause of most severe prolonged recurring disease. The bacteria enter the human host through the mucous membranes of the oropharynx (ingestion/inhalation routes), through abraded skin, or through the conjunctiva. Usually infection occurs by direct contact with infected material, although it may also occur by ingestion of milk or milk products. The bacteria are engulfed by neutrophils and monocytes and localize in the regional lymph nodes, where they proliferate intracellularly. If the Brucella organisms are not destroyed or contained in the lymph nodes, the bacteria are released from the lymph nodes resulting in septicemia. The organisms migrate to other lympho-reticular organs (spleen, bone marrow, liver, testes) producing granulomas and/or micro abscesses. Symptoms include fever, chills, sweats, fatigue, myalgia, profound muscle weakness, and anorexia. Joint involvement occurs often. Brucellosis may be either acute or chronic. Fatalities (0-3%) generally are due to endocarditis. Pathogenesis The symptoms in brucellosis are due to the presence of the organism and appear 2 - 4 weeks (sometimes up to 2 months) after exposure. While in the phago-lysosome, B. abortus releases 5'-guanosine and adenine which are capable of inhibiting the degranulation of peroxidase-containing granules and thus inhibit the myeloperoxidase-peroxide-halide system of bacterial killing. The intracellular persistence of bacteria results in granuloma formation in the reticuloendothelial system organs and tissue damage due to hypersensitivity reactions, mostly type-IV. Diagnosis Diagnosis is based on prolonged (at least a week) presence of undulating fever, myalgia, arthralgia and the history of exposure (contact with animals or consumption of unprocessed material from infected animals). Definitive diagnosis can be made by culturing blood samples on blood enriched media. The (fastidious) organisms grow very slowly (4-6 weeks in blood culture). B. abortus but not other Brucella grow better in 5% CO2 atmosphere. On blood agar, they produce white glistening colonies. Serology can be used to further confirm the diagnosis. Prevention and treatment Prolonged treatment with rifampin, which penetrates cells with streptomycin or tetracyclin is used to treat human Brucella infections. The control measures include animal vaccination and avoidance of infected material.
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PLAGUE Plague is caused by Yersinia pestis and is the disease known in the middle ages as the black death. This is because it frequently leads to gangrene and blackening of various parts of the body. Capillary fragility results in hemorrhages in the skin which also result in black patches. Morphology and physiology Yersinia pestis is a pleomorphic, Gram-negative, bipolar staining, facultatively aerobic, nonmotile, bacillus. Optimal temperature for growth is 28 degrees C. It is a facultative intracellular parasite. Epidemiology, transmission and symptoms The three documented pandemics of plague (Black Death) have been responsible for the death of hundreds of millions of people. Today, sporadic infections still occur. In the U.S., animal (sylvatic) plague occurs in a number of western states, usually in small rodents and in carnivores which feed on these rodents. Humans are infected by carrier rodent fleas or by contact with infected animals. The flea acquires the Y. pestis organisms during a blood meal from infected rodents. These organisms lose their capsule, multiply in the intestinal tract and partially block the proventriculus. During the feed on a human host the flea regurgitates some of the organisms into the wound. The bulk of non-capsular organisms are phagocytized and destroyed by neutrophils. However, few organisms are taken up by histiocytes which are unable to kill them and allow them to resynthesize their capsule and multiply. The encapsulated organisms, when they are released from histiocytes are resistant to phagocytosis and killing by neutrophils. The resulting infection spreads to the draining lymph nodes which become hot, swollen, tender and hemorrhagic giving rise to the characteristic black buboes whence the name of the disease, bubonic plague is derived. Within hours the organism spreads into the spleen, liver and lungs resulting in pneumonia. While in circulation, the organism causes diffuse intra vascular coagulation resulting in intra vascular thrombi and purpuric lesion all over the body. If untreated, the infection has a very high (unto 90%) mortality rate. The organism in exhaled in cough droplets, infect other humans in close proximity and cause pneumonic plague, which more difficult to control and has 100% mortality. Pathogenesis Many factors play direct and indirect roles in Y. pestis pathogenesis.
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WEB BOOK |
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Plague suits. The beak was filled with sweet smelling oils and vinegar
to counteract the smell of plague victims. Although physicians in the 1300's
did not know the cause of plague, the suits may have been effective to some
degree in that they kept fleas off and the shiny beak may have posed an
obstacle to the entry of fleas. Left From: Bubonic Plague by Ely Janis Right:
©
Bristol Biomedical Image Archive, University of Bristol. Used with
permission
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Diagnosis Diagnosis is based on appearance of buboes. The diagnosis is confirmed by culture of a lymph node aspirate. Extreme caution is warranted in handling of the specimen, as it is highly infectious. Prevention and Treatment Hospitalization and strict isolation are the rule. Streptomycin and tetracycline are highly effective. An effective formalin-killed vaccine is available but is recommended only for people at a high risk. The disease is internationally quarantinable and reporting of cases is mandatory. Control of urban plague is based upon flea and rodent control. |
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 Male Xenopsylla cheopsis (oriental rat flea) engorged with blood CDC
 Wayson stain of Yersinia pestis. Note the characteristic safety pin
appearance of bacteria CDC
Histopathology of spleen in fatal human plague - Necrosis and Yersinia
pestis. CDC/Dr. Marshall Fox
Capillary fragility is one of the manifestations of a plague infection, evident here on the leg of an infected patient.
CDC
Plague patient displying a swollen axillary lymph node CDC
Yersinia
pestis grows
well on most standard laboratory media, after 48-72 hours, grey-white to
slightly yellow opaque raised, irregular “fried egg” morphology;
alternatively colonies may have a “hammered copper” shiny
surface. CDC |
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WEB RESOURCES |
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Robert Koch's original micrographs of anthrax bacillus DOD
Anthrax Program
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ANTHRAX Morphology and physiology Bacillus anthracis is the causative agent of anthrax. It is a Gram-positive, aerobic, spore-forming large bacillus. Spores are formed in culture, in the soil, and in the tissues and exudates of dead animals, but not in the blood or tissues of living animals. Spores remain viable in soil for decades. Epidemiology, transmission and symptoms Anthrax is a major disease threat to herbivorous animals (cattle, sheep, and to a lesser extent horses, hogs, and goats). People become infected by the cutaneous route (direct contact with diseased animals, industrial work with hides, wool, brushes, or bone meal), by inhalation (Woolsorter's disease), or by ingestion (meat from diseased animals). |
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Cutaneous Anthrax DOD Anthrax Program
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accounts for more than 95% of human cases. Spores enter through small break in skin, germinate into vegetative cells which rapidly proliferate at the portal of entry. Within a few days, a small papule emerges that becomes vesicular. The latter is filled with blue-black edema fluid. Rupture of this lesion will reveal a black eschar at the base surrounded by a zone of induration. This lesion is called a malignant pustule; however, no pus or pain are manifested. The lesion is classically found on the hands, forearms or head. The invasion of the bloodstream will lead to systemic dissemination of bacteria. Pulmonary anthrax results from ingestion of meat-derived from an infected animal and leads to bacterial proliferation within the gastrointestinal tract, invasion of the epithelium and ulceration of the mucosa. The invasion spreads to the mesenteric lymph nodes and then to the bloodstream. Initially, there is vomiting and diarrhea followed by blood in the feces. Invasion of the bloodstream is associated with profound prostration, shock and death. Because of strict control measures, this form of anthrax is not seen in the U.S. |
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CASE REPORT |
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 Anthrax skin lesion on face of man CDC
Marked hemorrhage in mucosa and submucosa with arteriolardegeneration. CDC/Dr. Marshall Fox
 53 year old female, employed 10 years in the spinning department of a goat-hair processing mill. Cutaneous anthrax lesion on right cheek; lesion as seen on 4th day CDC
lesion as seen on 5th day CDC
lesion as seen on 6th day CDC
lesion as seen on 8th day CDC
lesion as seen on 11th day CDC
lesion as seen on 13th day CDC
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WEB RESOURCES Clinical
Anthrax Anthrax
FAQ Cipro |
Pathogenesis The virulence factors of B. anthracis include a number of exotoxins and the capsule.
A plasmid-encoded, heat-labile, heterogeneous protein complex made up of 3 components:
In vivo, these three factors act synergistically (for toxic effects). The protective antigen binds to surface receptors on eucaryotic cells and is subsequently cleaved by a cellular protease. The larger C-terminal piece of PA remains bound to the receptor and then binds either EF or LF, which enters the cell by endocytosis. Edema Factor, when inside the cells binds calmodulin-dependent and acts as adenylate cyclase. Lethal factor's mechanism of action involves activation of macrophages and production of cytokines which cause necrosis, fever, shock and death. Individually, the three proteins have no known toxic activity. Antibodies to protective antigens prevent PA binding to cells stop EF and LF entry.
Diagnosis Clinical diagnosis of anthrax can be confirmed by direct examination or culture. Fresh smears of vesicular fluid, fluid from under the eschar, blood, or spleen or lymph node aspirates are stained with polychrome methylene blue and examined for the characteristic blunt ended, blue-black rods with a pink capsule. In case of a negative finding, the specimen can be cultured on blood agar plates. Cultured organisms stain as Gram-positive long thin rods. Prevention and Treatment Penicillin and the 4-quinolone, Ciprofloxacin (Cipro) , are the antibiotics of choice. Antibody to the toxin complex is neutralizing and protective. There are two vaccines available. One is for use for immunizing cattle and other herbivorous animals and the other for humans.
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WEB TUTORIAL |
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Mediastinal widening
and pleural effusion on chest X-ray in inhalational anthrax CDC
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Anthrax, blood clot passed from anus © Bristol Biomedical Image Archive,
University of Bristol. Used with permission |
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Infection of
macrophages or parenchymal cells by Listeria monocytogenes
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LISTERIOSIS
Morphology and Physiology L.monocytogenes is a facultative intracellular, Gram-positive coccobacillus which often grows in short chains. It is different from other Gram-positive organisms in that it contains a molecule chemically and biologically similar to the classical lipopolysaccharide, the listerial LPS. The organism forms beta hemolytic colonies on blood agar plates and blue-green translucent colonies on colorless solid media. Upon infecting a cell (macrophages and parenchymal cells), the organism escapes from the host vacuole (or phagosome) and undergoes rapid division in the cytoplasm of the host cell before becoming encapsulated by short actin filaments. These filaments reorganize into a long tail extending from only one end of the bacterium. The tail mediates movement of the organism through the cytoplasm to the surface of the host cell. At the cell periphery, protrusions are formed that can then penetrate neighboring cells and allow the bacterium to enter. Due to this mode of cell-cell transmission, the organisms are never extracellular and exposed to humoral antibacterial agents (e.g., complement, antibody). L. monocytogenes is readily killed by activated macrophage. Epidemiology and symptoms Listeria monocytogenes is a ubiquitous organism found in the soil, vegetation, water, and in the gastrointestinal tract of animals. Exposure to the organism can lead to asymptomatic miscarriage or disease in humans. At greatest risk for the disease are the fetus, neonates, cancer patients and immuno-compromised persons. In the U.S., a number of recent outbreaks have been traced to cheese, cole slaw (cabbage), milk, and meat. The organisms can grow at 4 degrees C which means that organism replication continues in refrigerated foods. Laboratory isolation can employ a cold enrichment technique. Listeriosis has been categorized in two forms: 1) neonatal disease and 2) adult disease.
Pathogenesis Listeriolysin O, a β-hemolysin, is related to streptolysin, and pneumolysin and is produced by virulent strains. It disrupts the phagocytic vacuole and is instrumental in cell-cell transmission of the organism. The toxin is oxygen labile and immunogenic. Diagnosis Listeriosis is indicated when blood and CSF monocytosis is observed. The organism can be isolated on most laboratory media. Treatment and control Penicillin (ampicillin) alone or in combination with gentamycin have been effective. Immunity is cell-mediated.
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Thumb with skin ulcer of tularemia.
CDC/Emory U./Dr. Sellers
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TULAREMIA Morphology and physiology Francisella tularensis is a small, Gram-negative, non-motile, encapsulated, pleomorphic coccobacillus (short rod). It is a facultative intracellular parasite which grows poorly or not at all on most laboratory media and requires a special glucose cysteine blood agar for isolation. Care must be taken in handling the sample because of the low infectious dose. Epidemiology and symptoms Francisella tularensis is the causative agent of tularemia (a reportable disease in the U.S.). Unlike plague, tularemia occurs routinely in all 50 of the United States. Its primary reservoirs are rabbits, hares, and ticks. Man most commonly acquires tularemia via insect bites (ticks primarily, but also deer flies, mites, blackflies, or mosquitoes) or by handling infected animal tissues. Human disease (rabbit or deer fly fever) is characterized by a focal ulcer at the site of entry of the organisms and enlargement of the regional lymph nodes. As few as10 - 50 bacilli will cause disease in humans if inhaled or introduced intradermally, whereas a very large inoculum (~108 organisms) is required for the oral route of infection. Incubation period is 3 - 10 days. A small skin papule usually develops at the site of entry. Ulceration occurs together with fever, chills, malaise, fatigue, and usually lymphadenopathy. Bacteremia usually occurs and the bacilli then grow intracellularly in the reticuloendothelial system. Dissemination of the organisms through the bloodstream permits focal lesions to develop in numerous organs. The patient will normally exhibit one of several clinical syndromes. Ulcerogalndular form is most common (70 - 85%) in which a painful ulcerating papule which has a necrotic center and raised periphery develops at the site of infection. Other forms are glandular (lymphadenopathy without ulcer), typhoidal, pneumonic, oculoglandular and rarely oropharyngeal (pharyngotoncillitis with lymphadenopathy). Pathogenesis The capsule of the organism renders it resistant to phagocytosis. Intracellularly, the organisms resist killing by phagocytes and multiply. Most of the symptoms are due to cell-mediate hypersensitivity. Diagnosis F. tularensis is difficult to visualize in direct smears. The organism can be isolated from specimens of sputum, or lymph node aspirates inoculated on chocolate blood agar. Blood cultures are often negative. The organism grows very slowly and hence must be incubated for several days. The identity of the organism is confirmed with specific antisera. Prevention and treatment Streptomycin is the drug of choice for all forms of tularemia. Untreated, cases have a fatality rate of 5 - 15%. A live attenuated organism vaccine is available but its use is restricted to those persons who are at risk. Immunity appears to be cell mediated. One must avoid handling infected animals, watch out for ticks and utilize clean water supplies.
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WEB RESOURCES CDC |
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Erysipeloid- is an acute but very slowly evolving skin infection caused by
gram-positive bacillus (Erysipelothrix rhusiopathiae). ©
Mount
Allison Science Image Collection |
ERYSIPELOID This is an occupational disease of butchers, meat processors, farmers, poultry workers, fish handlers: swine and fish handlers are particularly at risk. The causative agent, Erysipelothrix rhusiopathiae, is a Gram-positive anaerobic rod which infects through skin abrasion while handling contaminated animal products or soil. Generally, the organism produces an inflammatory skin lesion, on fingers or hand, which is violaceus and has a raised edge. It spreads peripherally, as the discoloration in the central area fades. The painful lesion is pruritic and causes a burning or throbbing sensation. It lacks suppuration and thus is distinguishable from staphylococcal erysipelas. Diffuse cutaneous infection and septicemia are rare. The organism can be cultured easily on most laboratory media. It is easily treatable with penicillin.
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