Lecture #15Lecture #15Bio3124Bio3124

Medical MicrobiologyMedical Microbiology Part I:Part I: Infections of Skin, Infections of Skin,

Respiratory & Respiratory & Gastrointenstinal tractsGastrointenstinal tracts

• Identification of pathogen is important– Determines method of treatment

• Clues to rapid identification– Signs and Symptoms– Testing of specimens– Knowing patient histories

• Environment

• Occupation and social activities

• Nutrition

• Previous medical history

Characterizing Microbial Diseases

Human infectious diseases

Source and origin of pathogens

• Airborne infections

• Arthropod-borne diseases

• Direct contact diseases

• Food-borne and water-borne infections

• Zoonotic infections

Human infectious diseases

By the site of infection,

• Skin and soft tissue infections

• Respiratory system infections

• Gastrointenstinal tract infections

• Genitourinary tract infections

• Central nervous system infections

• Cardiovascular system infections

• Systemic infections

Human skin infections

• Staphylococcal infections

– Boils and scalded skin syndrome

• Streptococcal infections

– Necrotizing faciitis

• Clostridial infections

– Gas Gangrene

• Viral skin infections

– Measles, Chickenpox , Smallpox

Staphylococcal infections

• members of genus of Staphylococcus

– gram-positive cocci, grape-like clusters

– facultative anaerobes and usually catalase positive

– normal inhabitants of upper respiratory tract, skin,

intestines, and vagina

– S. aureusS. aureus – coagulase positive, pathogenic

– S. epidermidisS. epidermidis – coagulase negative, less pathogenic

– many pathogenic strains are slime producers

Slime

• viscous extracellular glycoconjugate that allows bacteria to adhere to smooth surfaces and form biofilms

• inhibits neutrophil chemotaxis, phagocytosis, and antimicrobial agents

slime

Staphylococcal Skin infections• localized abscess and boils

– S. aureus established in a hair follicle, tissue necrosis– coagulase forms fibrin wall limiting spread– Liquefaction, abscess spreads – may be a furuncle (boil) or carbuncle

Furuncle Carbuncle

Toxic shock syndrome (TSS)

• caused by S. aureus strains that release toxic shock

syndrome toxin (TSST-1)

• disease results from body’s response to staphylococcal

superantigens

• Resulting in massive cytokine production leading to

circulatory collapse , shock and multi-organ failure

• clinical manifestations

– low blood pressure, fever, diarrhea, extensive skin rash,

and shedding of the skin

Staphylococcal scalded skin syndrome (SSSS)

• S. aureus that carry a plasmid-borne gene for exfoliative toxin (exfoliatin)

• A protease, weakens skin • epidermis peels off• Diagnosis

– isolation/identification of staphylococcus involved /use of commercial kits

– isolation and identification based on catalase test, coagulase test, serology, DNA fingerprinting, and phage typing

• Treatment, prevention, and control– antibiotic therapy: Vancomycin, cephalosporins, rifampin

• many drug-resistant strains– personal hygiene and aseptic management of lesions

Invasive Streptococcus A Infections

• Streptococcus pyogenes: important pathogen in the group

• causes invasive infections

• virulence is due to:

– Pyrogenic exotoxin A (SpeA), a superantigen

• nonspecific T cell activation and large amount of cytokine

production, damaging endothelial cells -> multiorgan failure

– rapid fluid loss from tissues

– A cystein protease (exotoxin B) breaks down host

proteins, cause further tissue damage

Necrotizing Fasciitis• clinical manifestations

– necrotizing fasciitis• destruction of sheath covering skeletal

muscle– myositis

• inflammation and destruction of skeletal muscle and fat tissue

– toxic shock-like syndrome (TSLS)• precipitous drop of blood pressure,

failure of multiple organs, and high fever

• Treatment: • Surgical removal of affected tissues,

amputation• Penicillin G therapy

Gas Gangrene or Clostridial Myonecrosis

• Agent: Clostridium perfringens

– gram-positive, spore-forming rod

– Cause gas gangrene, a necrotizing infection of skeletal

muscle or clostridial myonecrosis, produces H2

– secretes α-toxin, a lecithinase cause membrane damage

and cellular death

– tissue damaging enzymes eg. Collagenase → invasion

• transmitted by spores from soil, bowel microbiota or infected

tissues

Gas gangrene…• clinical manifestations

– severe pain, edema, drainage, and muscle necrosis

• diagnosis– recovery of appropriate clostridial

species and characteristic disease symptoms

• treatment, prevention, and control– surgical debridement, administration

of antitoxin, antibiotic therapy, and hyperbaric oxygen therapy

– prompt treatment of all wound infections and amputation of limbs

Chickenpox (Varicella) and Shingles (Herpes Zoster)Chickenpox (Varicella) and Shingles (Herpes Zoster)

• Highly contagious skin disease• varicella-zoster virus (VZV), Herpesviridae, dsDNA

enveloped virus, icosahedral symmetry• infects children 2-7 years old• humans serve as reservoir

• droplets carrying virus enter respiratory system • Incubation (10-23 days)• Day 0: infection of mucosa of URS, viral replication in lymph nodes• Day 6: enters blood stream (primary viremia) replication in liver and spleen• followed by secondary viremia• Day 10: moves to skin (vesicular rash)• vesicles erupt on face and upper trunk• filled with pus, rupture, covered by scabs

• Diagnosis: by symptoms• Lab tests: not required, if so ELISA for IgM or PCR• Prevention: attenuated varicella vaccine• Treatment: acyclovir (Zovirax) inhibits viral DNA polymerase

Chickenpox (Varicella) and Shingles (Herpes Zoster)Chickenpox (Varicella) and Shingles (Herpes Zoster)

Shingles (Herpes zoster)Shingles (Herpes zoster)

recovery→natural immunity

virus enters a latent stage, nucleus of cranial

nerves & dorsal ganglia

~ 500,000 cases per year in US

virus reactivated, weaker immune system,

(Herpes zoster virus)

migrates down nerve axon, replicates and

damages sensory nerves

painful vesicles called shingles along dorsal

trunk

syndrome is called post-herpetic neuralgia

Therapy: not required; if necessary acyclovir or

other antivirals such as Famvir can be prescribed

• caused by variola virus– large, brick-shaped virus– linear dsDNA virus of Poxviridae

• transmitted by aerosol or contact– humans are only natural host

• Enters to regional lymph node• Incubation period 12-14 days• Multiplies in macrophage and monocytes• Enters blood (viremia)• Prodromal stage: is the symptomatic

imminent attack of disease characterized by– Virus moves to epithelial cells in mouth and

throat– Severe head and body aches, high fever

(40C), malaise and vomiting– Infects the capillary epithelia of skin– Vesicles filled with pus form and later rupture

to leave a skin lesion

Smallpox (Variola)Smallpox (Variola)

Eradication of Smallpox• Protection achieved by vaccination

– Vaccina virus in a live virus vaccine

• use of vaccine is controversial because of its unknown efficacy

• Food and Drug Administration has not approved any treatment for smallpox

• 1977 – last case from a natural infection occurred in Somalia

• Why eradication was possible

– disease has obvious clinical features

– humans are only hosts and reservoirs

– there are no asymptomatic carriers

– short infectivity period (3-4 weeks)

Human respiratory tract infections

• Infection of upper/lower respiratory tract, mostly viral

• Seldom spread to other tissues

• Streptococcal infections of lungs

– Bacterial pneumonia

• Mycobacterial infections

– Tuberculosis

• Viral infections of respiratory tract

– Influenza

– Respiratory syncytial virus infection (RSV)

Streptococcal pneumonia• Opportunistic pathogen Streptococcus pneumoniae

– normal microbiota in upper R.tract– polysaccharide capsule and a toxin– rapidly multiplies in alveolar spaces

• Capsule prevents phagocytosis• rapid growth in alveoli• Bloody sputum• 13000-66000 death in US/year• occasionally results in otitis media• major opportunistic infection among AIDS patients

Streptococcal pneumonia…• diagnosis

– chest X-ray, gram stain, culture, and tests for metabolic products

• clinical manifestations– abrupt onset of chills, hard labored

breathing, chest pain, and rust colored sputum

• treatment, prevention, and control– antibiotic therapy with penicillin G

• resistant strains have appeared

– Vaccine: Pneumovax vaccinepooled collection of 23 different S.pneumonia capsular polysaccharides

Tuberculosis (TB)• Mycobacterium tuberculosisMycobacterium tuberculosis• At the time of identification by Robert Koch

responsible for 1/7 of deaths in Europe, and 1/3 of young adults

• ~ 1/3 of world’s population infected

• resistance to phagocytic killing– Mycolic acids in cell wall form hydrophobic barrier

– toxic to cells

– Inhibit phagosome-lysosome fusion

• Transmission– person to person– also transmitted from infected animals and

their products

TB - Course of Disease• M. tuberculosis not killed in lung phagocytes • tubercles form in alveolar lymphatic node

– composed of bacteria, macrophages, T cells and human proteins– subsequent changes in tubercle may occur

TB tubercle

• caseous lesion

– cheese-like consistency

• Ghon complexes

– calcified caseous lesion

• show up prominently in chest X-rays

• miliary tuberculosis: Tubercles liquefy and bacteria spread

• also called reactivation tuberculosis because bacteria reactivated at initial infection site

Persons Infected With TB

• develop cell-mediated immunity (sensitized T cells)

– basis for tuberculin skin test

• incubation period

– 4-12 weeks

• symptoms

– fever, fatigue, weight loss

– cough

• characteristic of pulmonary involvement

• may result in expectoration of bloody sputum

Tuberculosis…

• diagnosis

– observation of acid-fast bacteria, chest X-ray, DNA-

based tests, Mantoux or tuberculin skin test

• antimicrobial therapy

– Isoniazid, rifampin, pyrazinamide and ethambutol

• multi-drug-resistant strains of tuberculosis (MDR-TB) have

developed

• prevention and control

– rapid, specific therapy to interrupt spread, retreatment of

patients with MDR-TB, immunization, improved sanitation

and housing, and reduction in homelessness and drug

abuse

Influenza (Flu)

• caused by influenza virus• classified into subtypes based on

hemagglutinin (HA) and neuraminidase (NA)

– HA and NA function in viral attachment and virulence

– 16 HA and 9 NA antigenic forms are known; they recombine to produce HA/NA influenza subtypes

• clinical manifestations

– chills, fever, headache, malaise, and general muscle

aches and painful joints

– recovery usually within 3 to 7 days

– often leads to secondary infections by bacteria

• treatment, prevention, and control

– rapid immunologic tests for diagnosis of subtype

– symptomatic/supportive therapy

– Tamiflu, neuraminidase inhibitor shortens the course of

illness

• Prevention: inactivated virus vaccine

Influenza (Flu)

Gastrointestinal tract infections

• Bacterial diarrhea

– Enterohemorrhagic E.coli

• Peptic ulcer and gasteritis

– Helicobacter pylori

• Viral gastroenteritis

Enterohemorrhagic E.coli infection Reservoir: cattle, fecal contamination of water or food

since 1982; “Jack-in-the Box” 1993 hamburger outbreak in US

Walkerton, Canada (2000)

Agent: EHEC strain O157:H7

Shiga toxin -> cleaves host 28S rRNA

Signs and symptoms: diarrhea, fever, abdominal cramps

endothelial damage in different tissues

Platelet-fibrin micro-clots form leading too Kidney failure (Hemolytic Uremic Syndrome)o Skin hemorrhage (Purpura)o Brain hemorrhage, neurological disorder, coma, &

death

Diagnosis: positive test for EHEC in food stock or in patient,or testing positive for toxin

Treatment: cidal antibiotics not recommended due to toxin, statics in sever cases, supportive treatment for electrolytes

Gastritis and Peptic Ulcer

• caused by Helicobacter pylori, a spiral

microaerophilic G- bacterium

• Discovered in 1982 and initially named

Campylobacter pylori

– colonizes gastric mucus-secreting

cells

– produces urease, elevates pH

– releases toxins that damage

epithelial mucosal cellsH. pylori attached to gastric cells

H. pylori …• transmission probably from person to person

– common source has not been ruled out• diagnosis

– culture of gastric biopsy specimens, examination of stained biopsies, serological testing, urea breath test, tests for ammonia in urine, and detection of urease activity in biopsies

• treatment, prevention, and control– a combination of drugs to decrease stomach

acid and antibiotics to kill the bacteria

Viral GastroenteritisViral Gastroenteritis

• acute viral gastroenteritis– inflammation of stomach or intestines– important disease of infants and children– leading cause of childhood death in developing countries (5-

10 million a year)– usually spread by fecal-oral route

• caused by six major groups of viruses– Rotaviruses– Adenoviruses– Caliciviruses– Asteroviruses– Norwalk virus– Noroviruses

• Clinical manifestations:– Asymptomatic to mild diarrhea– Headache and fever– Or sever diarrhea with abdominal cramps– Vomiting– Death is due to loss of electrolytes

• Treatment: – usually self-limiting disease– Electrolytic replacement with isotonic solutions– symptomatic/supportive therapy

Viral GastroenteritisViral Gastroenteritis