HIV Virus Entry To a Cell

RETROVIRUS:Life-Cycle

Haemophilus

ORGANISM:

• Genus: Haemophilus
• Species: influenzae

GENERAL CONCEPTS:

• Haemophilus influenzae is responsible for producing a variety of infections including meningitis and respiratory infections.
• Six serological types (a,b,c,d,e,f) based on the antigenic structure of the capsular polysaccharides are recognized. Nonencapsulated strains are (by definition) nontypable.
• Other species of Haemophilus include: H. parainfluenzae (pneumonia, endocarditis), H. ducreyi (venereal chancre) and H. aegypticus (conjunctivitis).

DISTINCTIVE PROPERTIES:

• The genus Haemophilus is composed of Gram-negative coccobacilli.
• These organisms are fastidious and require factors X (hemin) and/or V (NAD).
• Haemophilus possess LPS in the cell wall but produce no apparent extracellular toxins.

PATHOGENESIS:

• The organisms colonize the nasopharynx and are spread by direct contact. Haemophilus are capable of penetrating the epithelium to produce a bacteremia that may lead to localization of the organisms in many organs. The capsule is Haemophilus' major virulence determinant yet unencapsulated strains produce ear, sinus and respiratory infections.
• H. influenzae type b is the most common cause of bacterial meningitis in children aged 6 months-2 years. It is uncommon in adults because of protective antibody.
• Cellulitis, conjunctivitis, epiglottitis and arthritis may also result from Haemophilus infection.
• For pneumonia in adult men, unencapsulated H. influenzae is second only to the pneumococcus (S. pneumoniae). Those affected are usually chronic smokers, alcoholics or elderly.

EPIDEMIOLOGY:

Spread of Haemophilus is human to human. Day care centers are common sites for transmission from healthy, unaffected adults to susceptible infants.

DIAGNOSIS:

• Clinical: A Gram stain of cerebrospinal fluid may reveal the organisms. One can also detect capsular material directly.
• Laboratory: The organisms are cultured on chocolate agar because it contains both factors X and V. Incubation in 10% CO₂ is required.

CONTROL:

• Sanitary: Avoidance of carriers is not always possible.
• Immunological: A vaccine against type b is available. Unfortunately, the vaccine is nonimmunogenic in infants where it is needed the most.
• Chemotherapeutic: Third generation cephalosporins are probably the drugs of choice because of their ability to cross the blood-brain barrier and their bactericidal activity.

Bordetella

ORGANISM:

• Genus: Bordetella
• Species: pertussis, parapertussis, bronchiseptica

GENERAL CONCEPTS:

• The genus Bordetella is responsible for respiratory disease in humans and animals. B. pertussis, in particular, is the etiologic agent of pertussis, more commonly known as whooping cough. B. parapertussis causes a milder form of pertussis, while B. bronchiseptica mostly affects animals but occasionally humans.
• Bordetella cause disease by producing toxins that impair ciliary function in the respiratory tract.

DISTINCTIVE PROPERTIES:

• Bordetella are Gram negative coccobacilli. They produce a capsule and are strict aerobes. Only B. bronchiseptica is motile.
• Bordetella possess the heat stable endotoxin LPS and produce several exotoxins. These include:
  1. Pertussigen: A 120 kD protein exhibiting the A-B model for toxin activity. Pertussigen is an ADP-ribosyl-transferase that interferes with the transfer of signals from cell surface receptors. Pertussigen is also involved in mediating attachment to respiratory epithelia.
  2. Adenylate cyclase toxin: this toxin increases cAMP levels, inhibiting immune effector cell functions.
  3. Tracheal cytotoxin: This toxin causes ciliostasis and extrusion of ciliated epithelia.
  4. Dermonecrotic toxin: This heat labile substance causes tissue destruction.
  5. Filamentous hemagglutinin: This is involved in attachment to host cells.

PATHOGENESIS:

• Whooping cough results from colonization and multiplication of Bordetella pertussis on the mucus membranes of the respiratory tract, in particular, the ciliated epithelial cells.
• Production of toxins irritates cells causing ciliostasis and leukocytosis.
• The hallmark of pertussis is the spasmatic cough that may last 6 weeks. Occasional secondary complications include encephalopathy, seizures and pneumonia.

EPIDEMIOLOGY:

• The mucus membranes of the respiratory tract are the organism's natural habitat.
• Disease generally follows direct contact with an infected person.
• Pertussis is generally a disease of infants (50% of cases occur in children less than 1 year old).
• The disease is highly contagious.

DIAGNOSIS:

• Clinical: Whooping cough requires a 7-14 day asymptomatic incubation period. This is followed by the catarrhal stage, which lasts 1-2 weeks. Symptoms include fever, rhinorrhea and a highly infectious cough. The next 2-4 weeks define the paroxysmal phase, during which the spasmatic ("whooping") cough is observed. Vomiting and leukocytosis (> 100,000 lymphocytes/mm³) are also evident. Finally, the convalescent phase marks the end of disease and may last 3-4 weeks or longer. During this period, secondary complications may occur.
• Laboratory: The organisms can be grown on Bordet-Gengou agar media after 3-4 days incubation. Immunological techniques may also be employed.

CONTROL:

• Sanitary: This very contagious disease requires quarantine for a period of 4-6 weeks.
• Immunological: Pertussis vaccine is a part of the required "DPT" schedule.
  
• Chemotherapeutic: Antibiotic prophylaxis (erythromycin) may be used for contacts. Treatment of disease with antibiotics does not affect its course.

Brucella

ORGANISM:

• Genus: Brucella
• Species: abortus (cow), melitensis (goat), suis (pig), canus (dog)

GENERAL CONCEPTS:

• The Brucellae are generally associated with animal infections but most are also pathogenic for humans.
• All human infections come from animals; there is no human to human transmission. Such diseases are called "zoonoses".
• B. melitensis is associated with a specific human disease called Malta fever.
• Brucellae are intracellular parasites.

DISTINCTIVE PROPERTIES:

• The genus Brucella is composed of Gram negative coccobacilli. Most are aerobic but grow best in a 5-10% CO₂-enriched environment. Their metabolism is oxidative.
• Brucellae possess a typical Gram-negative LPS endotoxin, as well as two major serological determinants; A and M.

PATHOGENESIS:

• Of the four species that cause disease in humans, B. melitensis and B. suis are more transmissible to humans, particularly via the oral route.
• These bacteria are intracellular parasites of the reticuloendothelial (RE) system (e.g. spleen, liver, bone marrow, lymph nodes and kidneys).
• Following exposure, the organisms may produce a localized abscess, which is followed by bacteremia. Phagocytosis by macrophages and intracellular multiplication leads to localization in the RE tissues. Disease may remain subacute or become chronic with initial symptoms of malaise, chills, weakness and intermittent fever. Granulomas in various RE tissues may occur as a result of a hypersensitivity reaction.
• In animals, multiplication occurs in the uterus because of the presence of erythritol, which the bacteria prefer to glucose. This localization can lead to abortion or excretion in milk (human source for infection).

EPIDEMIOLOGY:

• Brucella infections have a worldwide distribution but have been mostly eradicated in the United States.
• B. abortus affects primarily cows; B. melitensis affects goats and sheep; B. suis affects pigs; B. canus affects dogs. Humans generally acquire disease through occupational exposure, Thus, veterinarians, meat workers and animal handlers are those most likely to be afflicted.

DIAGNOSIS:

• Clinical: Symptoms of brucellosis are variable and diagnosis is, therefore, very difficult. Flu-like symptoms with limb and back pain, an intermittent fever with malaise may last up to 3 months for acute disease (a year or more for subacute or chronic disease).
• Laboratory: Isolation of Brucella from the blood is possible. Cultures must be incubated 3-4 weeks with added CO₂.

CONTROL:

• Sanitary: Pasteurization of dairy products and use of protective clothing prevent human infection. More importantly, systematic identification and elimination of infected animals and vaccination of animals reduces the reservoir.
• Immunological: Vaccination for persons at high risk is possible, but they must first be tested to ensure that no hypersensitivity already exists.
• Chemotherapeutic: Tetracycline or a tetracycline/streptomycin combination is generally curative.

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.