Campylobacter

ORGANISM:

• Genus: Campylobacter
  
• Species: jejuni

GENERAL CONCEPTS:

The genus Campylobacter is a relatively recently discovered important human pathogen. The reason for this is that the organisms are microaerophilic, requiring low concentrations of oxygen only. Indeed, Campylobacter infections occur more often than Salmonella and Shigella diarrheas combined.

DISTINCTIVE PROPERTIES:

• Campylobacters are Gram-negative, curved rods (the name derives from the Greek "campylo", meaning curved). These organisms are microaerophilic and motile.
• Campylobacters possess a typical Gram-negative cell wall containing LPS endotoxin.
• There are approximately 50 heat-labile "K" (capsular) and "H" (flagellar) antigens and 60 different heat-stable "O" (somatic) antigens associated with different species of Campylobacter.
• These organisms are able to use amino acids and citric acid cycle intermediates for growth. C. jejuni grows best at 42°.

PATHOGENESIS:

• A relatively small inoculum is required to cause illness; as few as 800 bacteria can produce disease in healthy persons.
• Illness generally occurs following a 2-4 day incubation period when the bacteria multiply in the intestine, reaching numbers similar to Salmonella and Shigella infections (10⁶-10⁹ per gram of feces). Symptoms resemble an acute enteritis with fever, diarrhea, nausea and abdominal pain. The illness is generally self-limiting but may last a week.
• C. jejuni appears to produce an enterotoxin similar to both the cholera and Escherichia coli toxins.

EPIDEMIOLOGY:

• The genus Campylobacter is widely distributed among cattle, sheep, dogs, cats and other animals, existing as normal flora commensals.
• Human infection results from the ingestion of contaminated water, milk or undercooked foods. Outbreaks resulting from ingestion of raw clams have been reported.

DIAGNOSIS:

• Clinical: Clinical diagnosis is difficult since the symptomology is non-specific.
• Laboratory: Special methods are required for isolation. Growth occurs in 5% O₂, 10% CO₂, 85% N₂ at 42°. A Gram stain of fecal material may reveal curved ("seagull" or "comma") shaped organisms.

CONTROL:

• Sanitary: As with other fecal-oral diseases, sanitary means of control are most important. Proper disposal of feces, cooking foods, etc. can prevent disease.
• Immunological: None available.
• Chemotherapeutic: Erythromycin or tetracycline can be used for severe or prolonged illness.

Shigella

ORGANISM:

• Genus: Shigella
• Species: dysenteriae

GENERAL CONCEPTS:

• Shigella dysenteriae is responsible for bacillary dysentery, a disease most often associated with crowded, unsanitary conditions.
• Other species of Shigella may produce milder forms of diarrheal disease.

DISTINCTIVE PROPERTIES:

• Shigellae are facultative, non-motile, Gram-negative bacilli. They possess the heat stable endotoxin (LPS) characteristic of Gram-negative bacteria.
• Shigellae are pathogenic primarily due to their ability to invade intestinal epithelial cells.
• S. dysenteriae also produces a heat labile exotoxin that is a neurotoxin acting upon the gray matter of the central nervous system.

PATHOGENESIS:

Dysentery is an oral infection transmitted via fecal contamination of water or food. During the 1-4 day incubation period, penetration of bacteria into the mucosal epithelial cells of the intestine causes an intense irritation of the intestinal wall, producing cramps and a watery, bloody diarrhea.

HOST DEFENSES:

• Unlike the salmonellae, shigellae are acid tolerant. As a consequence, gastric acidity provides little protection against infection.
• Protective defenses include the normal flora, secretory IgA and phagocytosis.

EPIDEMIOLOGY:

• Dysentery and other shigelloses occur worldwide but the hosts are limited to humans and primates.
• Because of their acid tolerance, relatively few organisms are required to produce disease. Indeed, as few as 10 cells can cause disease in 10% of healthy persons; 200 cells may cause disease in 40% of persons.
• Contaminated food and water are the primary sources for contracting dysentery, but person to person transmission may occur because of the low dose required to produce disease.
• About 60% of cases occur in children aged 1-10 years.

DIAGNOSIS:

• Clinical: As with other diarrheal diseases, clinical diagnosis alone is equivocal. Diarrhea, fever and a watery bright red blood tinged stool are classical symptoms, but isolation of the organisms is required for confirmation.
• Laboratory: Shigella can be readily isolated and characterized using standard bacteriologic media or rapid identification systems. Shigellae are non-motile, incapable of fermenting lactose and do not produce H₂S. Serological techniques may be used for epidemiological characterization.

CONTROL:

• Sanitary: As with other fecal-oral diseases, dysentery is best prevented by assuring a safe water supply and proper disposal of feces.
• Immunological: No vaccines are currently available.
• Chemotherapeutic: The use of antibiotics is debatable because the disease is self-limiting. If required, ampicillin or a trimethoprim-sulphamethoxizole combination may be employed. Replacing lost fluids to prevent dehydration is most important for treating the disease.

Clostridium

ORGANISM:

• Genus: Clostridium
  
• Species: perfringens, tetani, botulinum, difficile

GENERAL CONCEPTS:

• The clostridia are opportunistic pathogens. Nonetheless, they are responsible for some of the deadliest diseases including gas gangrene, tetanus and botulism. Less life-threatening diseases include pseudomembranous colitis (PC) and food poisoning.
• Clostridia cause disease primarily through the production of numerous exotoxins.

DISTINCTIVE PROPERTIES:

• Clostridium species are Gram-positive, rod-shaped, spore-formers. These generally obligate anaerobes are ubiquitous saprophytes or part of our normal flora.
• Clostridia employ butyric fermentation pathways to generate energy and, as a result, often produce a foul odor.
• C. perfringens produces large rectangular spores and is non-motile. This species is most often associated with wound infections but these are generally polymicrobic.
• C. tetani produces terminal spores, giving it the appearance of a squash racket. This species is motile and produces a single antigenic type of exotoxin.
• C. botulinum produces oval subterminal spores and is motile. Different strains within this species produce one of 8 exotoxin types (A,B,C1,C2,D,E,F,G). Types C and D are encoded by bacteriophage that infect the bacteria.
• C. difficile produces large oval subterminal spores and two different toxins; toxin A (an enterotoxin causing fluid accumulation in the intestine) and toxin B (a cytopathic agent). Ordinarily, this species can't compete with normal intestinal flora but, when antibiotics eliminate these normal flora, C. difficile can flourish, producing disease.

PATHOGENESIS:

• C. perfringens: Gas gangrene results from an anaerobic tissue environment caused by poor blood supply due to trauma, surgery, etc. This acute disease is often fatal. One to six days following trauma, a generalized fever and pain is observed in the affected area. This leads to rapid muscle necrosis because of the release of bacterial exotoxins (lecithinases, hemolysins, collagenases, proteases, lipases). A spreading infection ensues. Gas gangrene generally involves muscle extremities where anaerobiosis can occur.
• C. tetani: Tetanus results from trauma or a puncture wound leading to tissue contamination. Tetanus is a non-invasive disease occurring because of the release of exotoxins. C. tetani produces a spasmogenic toxin that fixes to gangliosides thereby blocking the release of the neurotransmitter glycine. Glycine normally prevents contraction of antagonistic muscles; therefore, muscle spasms and convulsions (lockjaw) may occur. Cardiac failure can lead to death in approximately 55-65% of affected persons.
• C. botulinum: Botulism results from the ingestion of bacterially produced neurotoxins. Types A, B, E and F are the most toxic for humans. These protein exotoxins are often released in an inactive form; proteolytic cleavage activates them. Type A is the most potent exotoxin known (10 ng can kill a normal adult). These toxins block the release of the neurotransmitter acetylcholine resulting in double vision, slurred speech, decreased saliva, difficult swallowing and general weakness. Paralysis with accompanying respiratory failure can be fatal in about 20% of those affected. Botulism food poisoning can be observed about 18-36 hours following ingestion of preformed toxin, which is heat labile. Infant botulism may occur via germination of spores in the intestinal tract with subsequent toxin production, possibly accounting for some cases of Sudden Infant Death Syndrome (SIDS).
• C. difficile: Pseudomembranous colitis (PC) results predominantly as a consequence of the elimination of normal intestinal flora through antibiotic therapy. Symptoms include abdominal pain with a watery diarrhea and leukocytosis. "Pseudomembranes" consisting of fibrin, mucus and leukocytes can be observed by colonoscopy. Untreated pseudomembranous colitis can be fatal in about 27-44%.

EPIDEMIOLOGY:

• The clostridia are ubiquitous in the soil and some are part of the normal human flora.
• Heroin addicts are particularly susceptible to tetanus as a consequence of their life style.
• Poorly canned foods create an anaerobic environment. Unkilled spores germinate and produce toxin.
• PC patients secrete large numbers of spores in feces. This provides a reservoir.

DIAGNOSIS:

• Clinical:
  • Gas gangrene: Symptomology and the presence of bacilli in the wound.
  • Tetanus: Cramping and twitching around a wound, auditory hyperacuity and pain in neck and jaw. Tetanus is similar to strychnine ingestion so must exclude the latter.
  • Botulism: Difficult to diagnose. Must demonstrate a normal cerebrospinal fluid (CSF) to exclude other possibilities. The toxin is rarely found.
  • Pseudomembranous colitis: Demonstration of pseudomembranes by colonoscopy is diagnostic.
  • Laboratory: Members of the genus Clostridium can be differentiated from other bacteria by laboratory techniques including enzymatic digestion on egg-yolk agar plates and by using mice treated with or without antitoxin. For PC, the organisms can be isolated from feces.

CONTROL:

• Sanitary: Early cleansing of any wound, the surgical removal of affected tissues, suture sterilization and proper washing and canning of foods can prevent disease.
• Immunological: There are no vaccines available for gas gangrene and antitoxins are ineffective. The use of hyperbaric oxygen and chelating agents can help, however. A vaccine for tetanus made from the inactivated tetanus toxin ("toxoid") is available and required. Booster immunizations are recommended every 5 yrs or less to maintain high levels of circulating antitoxin. Botulism may be treated with antitoxin. PC patients should be certain to replace lost fluids and electrolytes to avoid dehydration.
• Chemotherapeutic: Penicillin or chloramphenicol may be employed but their use is debatable. For PC, vancomycin or metronidazole should be employed.

Streptococcus

ORGANISM:

• Genus: Streptococcus, Enterococcus
• Species: S. pyogenes (Group A), S. agalactiae (Group B), S. mutans (viridans), S. pneumoniae, E. faecalis (Group D)

GENERAL CONCEPTS:

• The streptococci are a very heterogeneous group of bacteria. Some members are a part of our normal flora while others are potent pathogens.
• The primary pathogens are S. pyogenes and S. pneumoniae but other species can be opportunistic.
• For example, S. agalactiae can produce severe neonatal disease including meningitis, pneumonia and bacteremia in infants aged 7 days up to 3 months. E. faecalis may be implicated in endocarditis and urinary tract infections. S. mutans is an important contributor to dental caries.
• The streptococci are generally delineated into groups according to the Lancefield method.
• As important as the acute diseases produced by these microorganisms are the later sequelae of Group A streptococci. These sequelae include i) rheumatic fever following respiratory infections and ii) glomerulonephritis following skin infections.

DISTINCTIVE PROPERTIES:

• Streptococci are Gram-positive, non-motile cocci that divide in one plane, producing chains of cells. S. pneumoniae is a lancet-shaped diplococcus (formerly genus Diplococcus).
• The streptococci are catalase negative (unlike Staphylococcus) and may be either facultative or obligate anaerobes.
• Hemolysis (alpha, beta) on blood agar is an important differential characteristic.
• Lancefield groupings are based on the serology of cell wall polysaccharides (18 groups were originally established by Rebecca Lancefield).
• The M proteins of group A serve as important virulence factors that help the organism resist phagocytosis.
• Lipoteichoic acids (LTA) mediate attachment to epithelial cells.
• Many antigenic moieties on the streptococcal cell surface resemble human muscle and connective tissue and these similarities may be responsible for the late sequelae. For example, S. pyogenes membrane Ags resemble cardiac, skeletal, smooth muscle, heart valve fibroblasts and neuronal tissue.
• The capsule of S. pyogenes is composed of hyaluronic acid (like host connective tissue) so it is non-antigenic while the capsule of S. pneumoniae is very antigenic and is its sole virulence factor.
• Toxins produced by streptococci include: streptolysins (S & O), NADase, hyaluronidase, streptokinase, DNAses, erythrogenic toxin (causes scarlet fever rash by producing damage to blood vessels; requires cell to be lysogenized by phage that encodes toxin).

PATHOGENESIS:

• S. pyogenes is the leading cause of bacterial pharyngitis and tonsillitis. It may also produce sinusitis, otitis, arthritis and bone infections. Some strains prefer skin, producing either superficial (impetigo) or deep (cellulitis) infections.
• S. pneumoniae is the major cause of bacterial pneumonia in adults. Its virulence is dictated by its capsule.
• Post-infection sequelae of S. pyogenes occur 1-3 weeks after acute disease. These sequelae include i) acute rheumatic fever (following pharyngeal infections) and ii) glomerulonephritis (following either pharyngeal or skin infections). These sequelae may be due to an altered immune response (autoantibodies). Glomerulonephritis results from deposition of Ag:Ab complexes on basement membrane of kidney glomeruli.
• Other species/groups include:
  • Group B strep (e.g. S. agalactiae) most often produce disease in animals but are also the leading cause of neonatal septicemia and meningitis.
  • Group D strep (e.g. E. faecalis) produce urinary tract infections and endocarditis.
  • Viridans species (e.g. S. mutans) are responsible for oral caries and subacute bacterial endocarditis following dental surgery.
  • Anaerobic streptococci may cause genital, brain or abdominal infections.

EPIDEMIOLOGY:

• These organisms are widely distributed in nature.
• Five to 15% of normal healthy individuals carry S. pyogenes.
• Carriage of S. pneumoniae (a solely human organism) is age dependent:

Age	% Carriage
Less than 5	40%
5 to 9	30%
10 to 15	17%
adults	6%
adults with children

DIAGNOSIS:

• Clinical: Diagnosis based solely upon symptomology is often not possible.
• Laboratory: To confirm the presense of S. pyogenes, throat swabs are used. For S. pneumoniae, sputum or blood samples are taken. The specimens may then be plated on blood agar for isolation of Gram-positive, catalase-negative cocci. Useful characteristics for differentiation include the pattern of hemolysis, bacitracin resistance or sensitivity and optochin resistance or sensitivity. Immunologically-based rapid test kits are often employed.

CONTROL:

• Sanitary: Since Streptococcus is a labile organism, close contact is required for spread; hence, avoiding contagious contacts can prevent disease.
• Immunological: Pneumococcal vaccines are available for persons at high risk, particularly the elderly.
• Chemotherapeutic: Penicillin is the drug of choice for S. pyogenes and S. pneumoniae, when the organisms are susceptible. Chemotherapy is given over a 10 and 7-145 days regimen, respectively. Group D streptococci are resistant to many antibiotics. Life long prophylaxis (low dose penicillin) is recommended for rheumatic fever patients.

Staphylococcus

ORGANISM:

• Genus: Staphylococcus
• Species: aureus, epidermidis

GENERAL CONCEPTS:

• The staphylococci are divided in two groups based on the presence or absence of the enzyme coagulase. This enzyme converts fibrinogen into fibrin, causing blood plasma to clot. The species called S. aureus is coagulase-positive while S. epidermidis (and other "non-pathogens") is coagulase-negative.
• Typically, staphylococci are opportunistic pathogens or saprophytes.

DISTINCTIVE PROPERTIES:

• Staphylococci are Gram-positive cocci usually arranged in clusters like a bunch of grapes. This appearance is due to the fact that staphylococci divide along two separate planes.
• The morphologically similar streptococci can be differentiated from staphylococci by testing for the enzyme catalase; staphylococci possess this enzyme while streptococci do not.
• Staphylococci possess both group specific and type specific antigens: 90% of S. aureus isolates have protein A. This substance is capable of binding the Fc portion of immunoglobulin IgG. This property helps the bacterium escape the potentially lethal effects of immunoglobulin action and also serves as the basis for some serological tests (coagglutination).
• Toxins produced by S. aureus include: hemolysins, leukocidins, enterotoxin, exfoliative toxin and toxic shock syndrome (TSS) toxin.
• Extracellular enzymes produced by S. aureus include: coagulase, fibrinolysin, DNAse, lipases and hyaluronidase.

PATHOGENESIS:

• Coagulase negative strains of Staphylococcus are generally non-invasive. Under certain conditions, however, they may cause severe disease (e.g. S. epidermidis and subacute endocarditis).
• S. aureus is a common cause of boils, sties and skin infections. Serious (life-threatening) infections (pneumonia, deep abscesses, meningitis) may occur in debilitated persons.
• S. aureus is the most common cause of Gram-positive bacteremia, most commonly involving hospital strains of the organism.
• S. aureus is also responsible for scalded skin syndrome and toxic shock syndrome. It is the most common cause of food poisoning. Symptoms occur only a few hours following ingestion of preformed enterotoxin but large amounts of toxin are required.

EPIDEMIOLOGY:

These organisms are ubiquitous. Prior to 1950, most staphylococci were sensitive to penicillin; now, most are resistant (hospital strains). Synthetic penicillins have been very useful but now resistance to vancomycin is spreading.

DIAGNOSIS:

• Clinical: Generally, a Gram stain of exudate from a lesion can demonstrate the characteristic Gram-positive cocci arranged in clusters.
• Laboratory: Isolation techniques employ blood agar, mannitol salt agar or potassium-tellurite agar. Bacteriophage testing or serotyping may be utilized.

CONTROL:

• Sanitary: There is virtually no possibility to eliminate these organisms because they are (and have been) a significant part of human normal flora. To control the spread of disease, however, clean hospitals and proper food handling are paramount.
• Immunological: Nothing really available. But, a new vaccine is in clinical trials (see ICAAC Report)
• Chemotherapeutic: Antibiotics can be used if life-threatening. One should use penicillin if the particular strain is susceptible. Otherwise, methicillin, oxacillin, cephalosporins or vancomycin may be required. Often, surgical drainage is an important treatment.

Chlamydia

ORGANISM:

• Genus: Chlamydia
• Species: trachomatis, psittaci

GENERAL CONCEPTS:

• The Chlamydia are obligate intracellular parasites.
• C. trachomatis is responsible for the diseases trachoma, inclusion conjunctivitis, lymphogranuloma venereum (LGV) and nongonococcal urethritis (NGU). In other words, oculourogenital infections.
• C. psittaci produces systemic diseases including psittacosis, ornithosis and pneumonitis.

DISTINCTIVE PROPERTIES:

• The Chlamydia have an unusual developmental cycle that involves two distinct forms: infectious elementary bodies and intracellular reticulate bodies. Elementary bodies attach and are internalized by susceptible host cells. Once inside, they reorganize into a replicative form (the reticulate body). Over a 24 hour period, these reticulate bodies divide and begin to reorganize back into elementary bodies. About 48-72 hours after infection, the cell is lysed and numerous infectious elementary bodies are released.
• The genome of Chlamydia is only 25% the size of E. coli, making it one of the smallest prokaryotes.
• The pathogenic mechanisms employed by Chlamydia are not well understood.

PATHOGENESIS:

• C. trachomatis is spread via the fingers to the urogenital area and vis versa. In contrast, C. psittaci is acquired from infected birds, usually via the respiratory route.
• Trachoma is an infection of the epithelial cells of the conjunctiva, producing inclusion bodies. Vascularization and clouding of cornea along with trichiasis (inward growth of eyelashes) can produce scarring that may lead to blindness.
• Inclusion conjunctivitis is a milder form that occurs in both children and adults. This form generally heals without scarring or blindness.
• Sexually transmitted nongonococcal urethritis (NGU) is similar to gonorrhea and occurs with greater frequency. In 1997, approximately 320,000 cases were reported to the Centers for Disease Control.
• In men, a condition termed lymphogranuloma venereum (LGV) involving inguinal lymphadenopathy ("buboes") can occur.

EPIDEMIOLOGY:

• Trachoma is prevalent in Africa and Asia, generally in hot and dry areas.
• The organisms are very persistent. Their habitat is similar to that of Neisseria and Haemophilus.
• Infection can occur via swimming in unchlorinated pools, sharing towels or by passage through the birth canal.

DIAGNOSIS:

• Clinical: Diagnosis of trachoma is usually good. Likewise, the genital vesicles associated with LGV are characteristic. NGU can only be suspected in the absence of laboratory findings.
• Laboratory: Iodine stained specimens usually show inclusion bodies that represent the replicating bacteria. The Chlamydia can be cultured in tissue culture and appropriate serological tests performed.

CONTROL:

• Sanitary: Good hygiene, treatment of sexual partners and the quarantine of birds all reduce the incidence.
• Immunological: No vaccine is available or likely since specific antibodies fail to neutralize elementary bodies in vivo.
• Chemotherapeutic: Tetracycline or erythromycin are drugs of choice.

Rickettsia

ORGANISM:

• Genus: Rickettsia, Rochalimaea, Coxiella
• Species: Rickettsia prowazekii (epidemic typhus), Rickettsia typhi (endemic typhus), Rickettsia rickettsii (spotted fever), Rochalimaea quintana (trench fever), Coxiella burnetii
• (Q fever)

GENERAL CONCEPTS:

• The Rickettsia are Gram-negative, obligate intracellular bacteria that infect mammals and arthropods.
• R. prowazekii is the agent of epidemic typhus. During World War I, approximately 3 million deaths resulted from infection by this bacterium. In World War II, the numbers were similar. This agent is carried by the human louse; therefore, disease is a consequence of overcrowding and poor hygiene.
• Rocky Mountain spotted fever and Q fever remain relatively common.

DISTINCTIVE PROPERTIES:

• These organisms are small, pleomorphic coccobacilli about 2 µm in length. Their structure is typical of Gram-negative bacteria.
• Rickettsia replicate in the cytoplasm and nucleus of their host cell; Coxiella replicate only in the phagolysosome.

PATHOGENESIS:

• Typhus, spotted fever and trench fever are transmitted via arthropod vectors; Q fever is acquired via inhalation or ingestion of contaminated milk or food.
• Within minutes, the bacteria enter host endothelial cells via an induced phagocytosis. The enzyme phospholipase A may help penetration.
• Replication of the bacteria causes lysis of the host cell and consequent spread to other cells.
• Initial replication occurs at the site of entry producing a local lesion. This is followed by dissemination via the vascular system producing vasculitis and a skin rash. These lesions may become necrotic.
• Virulence is probably due to many factors including release of endotoxin, the production of immune complexes and hypersensitivity reactions.
• A characteristic triad of symptoms include fever, headache and rash (no rash with Q fever).

EPIDEMIOLOGY:

• Epidemic typhus and trench fever are transmitted from human to human via the louse.
• Endemic (murine) typhus is primarily maintained in rodent populations and is transmitted via the flea. Humans are an accidental host.
• Spotted fever is found predominantly in animals and is transmitted by the tick. Humans are accidental hosts. Most cases of Rocky Mountain spotted fever in the US occur during the summer months in North and South Carolina, Kansas and Oklahoma.
• Q fever is found mostly in animals. Humans acquire disease primarily by inhalation of contaminated aerosols.

DIAGNOSIS:

• Clinical: These diseases present as febrile illnesses after exposure to arthropods or animal hosts or aerosols in endemic areas and are easily misdiagnosed. A delay in diagnosis may be partly responsible for the high mortality from Spotted fever. The spread of the rash is often characteristic: spread from the trunk to the extremities (centrifugal) is typical for typhus; spread from the extremities to the trunk (centripetal) is typical for spotted fever.
• Laboratory: The use of immunofluorescent antibodies to examine a biopsy can be diagnostic. The organism can be inoculated into tissue culture and grown over 4-7 days but this is very hazardous to personnel. The Weil-Felix test looks for the production of serum antibody that is reactive against Proteus OX19, OX2 or OXK antigens but it is not always reliable.

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CONTROL:

• Sanitary: Arthropod and rodent control are possible but difficult.
• Immunological: No vaccines are currently available.
• Chemotherapeutic: Tetracycline or chloramphenicol are drugs of choice.