SHQIP - ALBANIAN

BACTERIOLOGY - CHAPTER SEVENTEEN  

ZOONOSES   

LISTERIA, FRANCISELLA, BRUCELLA, BACILLUS, YERSINIA AND ERYSIPELOTHRIX

Dr Abdul Ghaffar
Professor Emeritus
University of South Carolina School of Medicine

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Logo image © Jeffrey Nelson, Rush University, Chicago, Illinois  and The MicrobeLibrary

Arnold Boecklin: The Plague 1898. Tempera on wood,  Kunstmuseum, Basel

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

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.

Morphology and physiology

Brucella are Gram-negative, non-motile, coccobacilli. They are strict aerobes and grow very slowly (fastidious) on blood agar. In the host, they live as facultative intracellular pathogens.

Epidemiology

Brucellosis is primarily a disease of animals and it affects organs rich in the sugar erythritol (breast, uterus, epididymis, etc.). The organisms localize in these animal organs and cause infertility, sterility, mastitis, abortion. They may also be carried asymptomatically. Humans in close contact with infected animals (slaughterhouse workers, veterinarians, farmers, dairy workers) are at risk of developing undulant fever. There are 100 to 200 cases of brucellosis seen in the United States annually, although the worldwide incidence is estimated at 500,000. Species of Brucella that are known to infect humans include:

• B. abortus (cattle)

• B. suis (swine)

• B. melitensis (goats/sheep)

• B. canis (dogs)

• B. ovis (goats/sheep)

There are other species of Brucella that infect many animals from whales to rats

Although brucellosis has largely been eradicated in most developed countries through animal vaccination, it persists in many underdeveloped and developing countries.

Ares where there is a higher risk of Brucella infection include:

• Areas around the Mediterranean

• Eastern Europe

• Asia

• Africa

• Caribbean

• Middle East

  Brucella spp. are poorly staining, small gram-negative coccobacilli (0.5-0.7 x 0.6-1.5 micrometer), and are seen mostly as single cells and appearing like “fine sand”   CDC

  Brucella spp. Colony Characteristics: A. Fastidious, usually not visible at 24h. B. Grows slowly on most standard laboratory media (e.g. sheep blood, chocolate and trypticase soy agars). Pinpoint, smooth, entire translucent,
non-hemolytic at 48h.  CDC

Brucella ovis in epididymis  © Bristol Biomedical Image Archive, University of Bristol. Used with permission

 

Transmission

Infection may occur by:

• Direct contact with infected animals or animal products

• Ingestion of animal products such as unpasteurized milk, milk products (including cheeses), undercooked meat. This is probably the most frequent cause of human Brucella infections and are of particularly important for tourists

• Breathing in bacteria/ This may occur in people in contact with infected animals or in laboratories where Brucella is handled.

• Entry through wounds or mucous membranes. In addition, to those mentioned above, this may occur in hunters. Infected game animals may include (CDC): Bison, elk, caribou, moose, feral hogs.

• Breast feeding. Person to person transmission is very rare but has been reported

• Sexual activity. Again this is very rare

• Possibly in tissue transplantation or organ transplant. Again, this is very rare.

CDC notes that it is especially important that expectant mothers who have been exposed to Brucella should consult a physician as post-exposure prophylaxis may be required.

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

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.

Symptoms include:

• Recurrent fever

• Chills

• Sweats

• Fatigue

• Myalgia,

• Profound muscle weakness

• Anorexia.

• Joint involvement occurs often

Brucellosis may be either acute or chronic.

Mortality due to Brucellosis is rare (less than 3%) and is generally due to endocarditis.

Pathogenesis

The symptoms of brucellosis are due to the presence of the organism and appear 2 to 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 to 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 (6 to 8 weeks) treatment with rifampin or doxycycline along with streptomycin or tetracyclin is used to treat human Brucella infections.

Control measures include animal vaccination and avoidance of infected material.

Dr. Alexandre Yersin in Front of the National Quarantine Station, Shanghai Station, 1936

World distribution of plague 1998 CDC

World distribution of plague 2000-2009
CDC

US distribution of plague by county 1970-2012
CDC

Cases of plague in the United States by year. 1970-2012
CDC

  Yersinia pestis - rod prokaryote (dividing); causes bubonic plague (SEM x20,800)   © Dennis Kunkel Microscopy, Inc.  Used with permission

Yersinia pestis. Fluorescent antibody identification CDC

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, non-motile 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. The last urban outbreak of plague occurred in the United States in 1924-25. There was an outbreak of plague in India in 1994. In both cases, rats were the vector.

Sporadic plague still occurs in the rural United States. Infected animals include:

• squirrels (rock and ground)

• wood rates

• prairie dogs

• mice

• chipmunks

• voles

• rabbits

• also carnivores may be infected by eating infected prey. In the United States, pneumonic plague has occurred in recent years from contact with infected cats that have been infected after eating infected rodents.

Humans are usually infected by carrier rodent fleas. The flea acquires the Y. pestis organisms during a blood meal from infected rodents. The bacteria lose their capsule, multiply in the intestinal tract and partially block the proventriculus. When the flea feeds on a human host, it may regurgitate some of the organisms into the wound.

Humans can also can be infected in other ways such as by contact with infected animals or handling carcasses of infected animals. This usually results in bubonic or septicemic plague.

Plague can also be spread in aerosols in a cough or sneeze from a person (or pet cat) with pneumonic plague.

The bulk of non-capsular organisms are phagocytized and destroyed by neutrophils. However, a 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 the circulation, the organism causes diffuse intra-vascular coagulation resulting in intra-vascular thrombi and purpuric lesions all over the body. If untreated, the infection has a very high (up to 90%) mortality rate. The organisms in exhaled in cough droplets, infect other humans in close proximity and cause pneumonic plague, which is more difficult to control and has 100% mortality.

Pathogenesis

Many factors play direct and indirect roles in Y. pestis pathogenesis.

Low calcium response (lcr)
This is a plasmid-coded gene that enables the organism to grow in a low Ca⁺⁺ (intracellular) environment. It also coordinates the production of several other virulence factors, such as V, W and yops (Yersinia outer proteins).

V and W proteins
These plasmid-coded proteins are associated rapid proliferation and septicemia.

Yops
A group of 11 proteins, which are coded by plasmids, are essential for rodent pathogenesis and are responsible for cytotoxicity, inhibition of phagocyte migration and engulfment and platelet aggregation.

Envelope (F-1) antigen
This is a protein-polysaccharide complex which is highly expressed at 37 degrees in the mammalian host but not in the flea and is anti-phagocytic.

Coagulase and Plasminogen activator
Both of these are plasmid-coded proteins. Coagulase is responsible for micro thrombi formation and plasminogen activator promotes the dissemination of the organism. It also destroys C3b on the bacterial surface, thus attenuating phagocytosis.

Diagnosis

Diagnosis is based on appearance of buboes (swollen lymph glands). 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. In cases of pneumonic and septicemic plague there may be no obvious signs.

Prevention and Treatment

Hospitalization and strict isolation are the rule for this serious but easily treatable disease.

Streptomycin and  gentamycin are highly effective but other effective antibiotics include tetracycline, fluoroquinalones and chloramphenicol. For most recent CDC recommendations go here.

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.

Summary of types and symptoms of plague

Bubonic plague
 

An axillary bubo and edema exhibited by a plague patient CDC/Margaret Parsons, Dr. Karl F. Meyer

This usually occurs as a result of a bite by an infected flea. The lymph nodes closest to the bite become swollen as the bacteria proliferate. They can then spread to other parts of the body.

Symptoms of bubonic plague

Sudden onset of

• Fever
• Headache
• Weakness
• Formation of buboes (swollen, tender lymph nodes). See below

Pneumonic plague

Anteroposterior chest x-ray of a plague patient revealing bilateral infection, greater on the patient's left side, which was diagnosed as a case of pneumonic plague, caused by the bacterium, Yersinia pestis. CDC/ Dr. Jack Poland

This is usually the result of inhaling aerosols from an infected patient or animal. It can also develop as the result of spread of bacteria to the lungs in other forms of plague that remain untreated. It is the most serious form of plague as it can easily be spread.

Symptoms of pneumonic plague

• Fever
• Headache
• Weakness
• Pneumonia (chest pain, cough with sometimes watery or bloody mucous, shortness of breath)

Septicemic plague

A 59 year-old man’s hands who had been infected by the plague bacterium, Yersinia pestis, after having come into contact with both an infected cat, and a dead mouse in his neighborhood. The gangrenous condition of the fingers had turned the dead digits black, and mummified. Two days after the exposure the patient developed fever and myalgias, and by the following day he had developed a left axillary bubo. Seven days after the initial exposure he became critically ill and was admitted to the hospital with multiple organ failure. Initial blood cultures were positive for double-curved, Gram-negative Y. pestis rods. The patient was treated with gentamicin and survived, but necrosis of the hands and feet developed during hospitalization. He subsequently required amputation of the hands and feet. CDC PHIL

Swollen lymph glands (buboes) caused by plague bacteria in bubonic plague CDC

This comes from flea bits or contact with an infected animal. It may the initial disease or the consequence of untreated bubonic plague.

Symptoms of septicemic plague

• Fever
• Chills
• Weakness
• Abdominal pain
• Shock
• Bleeding in skin and organs
• Skin, particularly at extremities, becomes black and necrotic

 

Male Xenopsylla cheopsis (oriental rat flea) engorged with blood CDC

Wayson stain of Yersinia pestis. Note the characteristic safety pin appearance of bacteria CDC

Symptoms in this plague patient include an inguinal bubo  CDC

  Histopathology of spleen in fatal human plague - Necrosis and Yersinia pestis. CDC/Dr. Marshall Fox 

Histopathology of lymph node in fatal human plague - Medullary necrosis with fluid and Yersinia pestis. CDC/Dr. Marshall Fox 

Gangrene is one of the manifestations of plague, and is the origin of the term "Black Death" given to plague throughout the ages  CDC

  Dark stained bipolar ends of Yersinia pestis can clearly be seen in this Wright's stain of blood from a plague victim

  Robert Koch's original micrographs of anthrax bacillus DOD Anthrax Program

Gram stain of anthrax DOD Anthrax Program

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). It is not contagious.

Anthrax due to Bacillus anthracis (blood smear) © Bristol Biomedical Image Archive, University of Bristol. Used with permission

Under a very high magnification of 31,207X, this scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria CDC/ Laura Rose/Janice Haney Carr 

Cutaneous Anthrax  DOD Anthrax Program

Cutaneous anthrax CDC

• Cutaneous anthrax 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 form inhalation of B. anthracis spores which are phagocytized by the alveolar macrophages where they germinate and replicate. The injured host cell and organisms infect the hilar lymph node where marked hemorrhagic necrosis may occur. The patient may manifest fever, malaise, myalgia, and a non-productive cough. Once in the hilar lymph node, infection may spread into the blood stream. Respiratory distress and cyanosis are manifestations of toxemia. Death results within 24 hours. This form of anthrax is of significance in biological warfare.

• Gastrointestinal 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. Without treatment of gastrointestinal anthrax, the majority of patients die but with antibiotic treatment, 60% or more survive.
   

• Injection anthrax is are and has not been seen in North America but has occurred in heroin users in northern Europe. Symptoms are similar to cutaneous anthrax but the infection may be deeper at the site of needle entry. The bacteria can spread more rapidly from site of infection to other parts of the body than is the case with cutaneous anthrax.
   

• Meningeal Anthrax. All forms of anthrax above can progress to meningeal encephalitis with deep brain hemorrhagic lesions and infection of the cerebro-spinal fluid. It is almost always fatal.

Summary of types and symptoms of anthrax

Cutaneous anthrax

Symptoms

• Blisters near site of infection

• After the blister, a painless ulcer appears with a black center with swelling. This is most often on the face, neck, arms or hands

	Cutaneous anthrax lesion on the volar surface of the right forearm CDC
	Development of cutaneous anthrax CDC

Pulmonary anthrax

Symptoms

• Cough

• Shortness of breath

• Nausea and stomach cramps

• Headache

• Confusion

• Severe sweats

• Fever and chills

• Malaise

Posteroanterior chest x-ray taken 4 mo. after the onset of anthrax in a 46 yr. old male. This patient worked for 2 yrs. as a card tender in a goat hair processing mill and contracted anthrax. X-ray revealed bilateral pulmonary effusion, and a widened mediastinum, which are hallmarks of the disease process. CDC/ Arthur E. Kaye

Gastrointestinal anthrax

Symptoms

• Fever and chills

• Headache

• Neck swelling

• Red face and eyes

• Sore throat, hoarseness and pain swallowing

• Nausea and bloody vomit

• Stomach cramps and stomach swelling

• Diarrhea, sometimes bloody

• Faintness

• Malaise

Injection anthrax

Symptoms

• Fever and chills

• Small blisters at site of drug injection

• A painless ulcer with a black center with swelling at site of injection after blisters appear

• Deep abscess at injection site

CASE REPORT

Inhalation Anthrax Case in Pennsylvania - 2006

Anthrax skin lesion on face of man   CDC

Anthrax skin lesion on neck of man   CDC

Marked hemorrhage in mucosa and submucosa with arteriolar
degeneration. CDC/Dr. Marshall Fox 

Histopathology of liver in fatal human anthrax. Dilated sinusoids, neutrophil infiltrate. CDC/Dr. Marshall Fox 

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

Pathogenesis

The virulence factors of B. anthracis include a number of exotoxins and the capsule.

Exotoxin
A plasmid-encoded, heat-labile, heterogeneous protein complex made up of 3 components: 

• Edema Factor (EF)

• Lethal Factor (LF)

• Protective Antigen (PA). 

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.

Capsule
The capsule consists of a polypeptide of D-glutamic acid which is encoded by a plasmid and is anti-phagocytic. It is not a good immunogen and, even if any antibodies produced, they are not protective against the disease.

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

Antibiotics

Penicillin and the 4-quinolone, Ciprofloxacin (Cipro), are the antibiotics of choice.

Anti-toxin

Antibody to the toxin complex is neutralizing and protective. This may be used in combination with antibiotics.

There are two vaccines available. One is for use for immunizing cattle and other herbivorous animals and the other for at-risk humans (certain laboratory workers, people who handle animals (veterinarians) and some military personnel.

Cipro information

Infection of macrophages or parenchymal cells by Listeria monocytogenes

  Listeria monocytogenes - rod prokaryote that causes listeriosis, meningitis and food poisoning  © Dennis Kunkel Microscopy, Inc.  Used with permission

Live sheep: listeriosis  © Bristol Biomedical Image Archive, University of Bristol. Used with permission

Listeria monocytogenes organisms in neutrophil (blood smear) © Bristol Biomedical Image Archive, University of Bristol. Used with permission

  Electron micrograph of a flagellated Listeria monocytogenes bacterium, Magnified 41,250X 
CDC/Dr. Balasubr Swaminathan; Peggy Hayes; Elizabeth White

  Electron micrograph of a Listeria bacterium in tissue.
CDC/Dr. Balasubr Swaminathan; Peggy Hayes; Elizabeth White

Listeriosis is serious disease which is almost always caused by eating contaminated food. It most affects newborn children, older and immunocompromized people and pregnant women. There are about 1,600 cases of listeriosis annually in the United States and about 260 deaths. In 2013, the incidence of listeriosis was 2.6 cases per million.

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 United States, 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.

Neonatal Disease
Neonatal disease can occur in two forms:

• Early onset disease, acquired transplacetally in utero
  In utero acquired infection (granulomatosus infantiseptica) causes abscesses and granulomas in multiple organs and very frequently results in abortion.
   

• Late onset disease acquired at birth or soon after birth.
  Exposure on vaginal delivery results in the late onset disease resulting in meningitis or meningo-encephalitis with sepsis within 2 to 3 weeks.

 Adult Disease
Infection in normal adults results in self-resolving flu-like symptoms and/or mild gastrointestinal disturbance. Chills and fever are due to bacteremia. In pregnant women, infection can lead to miscarriage, still birth or premature birth with life-threatening

In immunosuppressed individuals listeriosis can produce serious illness, leading to meningitis. It is one of the leading causes of bacterial meningitis in patients with cancer and in renal transplant recipients. In the elderly, the early symptoms may go unnoticed and the infection may lead to acute manifestations of sepsis (high fever, hypo-tension). A complication of the bacteremia is endocarditis.

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.

Thumb with skin ulcer of tularemia. CDC/Emory U./Dr. Sellers 

  Tularemia lesion on the dorsal skin of right hand  CDC/Dr. Brachman

Tularemia on the hand  CDC

Francisella tularensis bacteria stained with methylene blue  CDC/Dr. P. B. Smith

Reported cases of tularemia in the United States 1050-2010 CDC

Average annual incidence rate of tularemia by sex and age group  - United States, 2001-2010  CDC

Reported tularemia cases in the United States - 2004 - 2013 CDC

Reported cases of tularemia by month in the United States 2001-2010 CDC

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, rodents and ticks. People most commonly acquire 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.

In 2013, there were 203 cases of tularemia in the United States (incidence: 0.6 cases per million population). Because the disease is spread by ticks and flies, it is most common in the summer months.

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 and the infection can be life-threatening, although most cases are mild.

Forms of tularemia

Ulceroglandular tularemia
This form is most common (70 - 85% of cases) in which a painful ulcerating papule, which has a necrotic center and raised periphery, develops at the site of infection (usually from a tick or fly bite). The patient experiences a fever (which can be as high as 104 degrees F) together with lymph node swelling particularly in the arm pit and groin.

Glandular tularemia
This is acquired in the same way as ulceroglandular tularemia; however, there is lymphadenopathy but no ulcer.

Oculoglandular tularemia
This is often acquired when a person handling infected meat rubs the bacteria into the eye. There is inflammation of the eye and swelling of regional lymph glands.

Pneumonic tularemia
This is a very serious disease that comes from breathing in the bacteria in dust or aerosols. It results in difficulty breathing, chest pain and cough. It can also result from not treating other forms of tularemia resulting is dissemination to the lungs.

Oropharyngeal tularemia
In this form, the disease is acquired by eating or drinking contaminated food or drink. Patients experience pharyngotoncillitis with lymphadenopathy accompanied by mouth ulcers. This is a rare form of tularemia.

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.

WEB RESOURCES 
CDC-MMWR
Tularemia --- United States, 1990--2000

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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