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Module: Musculoskeletal and integumentary

Code: PC-103
Topic: Microbes affecting muscle, bone & joint
Program: Medicine
Academic level: Pre-clerkship-I, Semester II
Academic year: 2016/17
Instructor: Addisu M. (BSc, MSc)
E-mail: addisum22@gmail.com
8/8/2017 Addisu M. (BSc, MSc)
Microbes affecting the Muscle

Learning objectives:
At the end of this session, students will be able to:

Identify and characterize common microbes


infecting the muscle

Describe the pathogenesis of infections of muscle

Explain laboratory methods used to diagnose

muscle disease
Microbes affecting muscle

Healthy muscle is quite resistant to infection

Myositis: inflammation of muscle (voluntary)

Infectious myositis: cuased by pathogens

Bacteria
Viruses
Fungi
Parasites
Bacterial infections of the muscle
Relatively uncommon

Usually presents as focal infection

Routes:

Contiguous infection
Penetrating trauma
Vascular insufficiency
Hematogenous
Purulent infection - Pyomyositis
Pyomyositis
Occurs most often in the lower extremity; but
any muscle group can be involved
Pathogenesis:
Involves transient bacteremia in the setting of
pre-existing or concurrent muscular injury
Bacteremia muscle damage pyomyositis
Bacteremia without concurrent muscle damage
is unlikely to cause pyomyositis
Pyomyositis...contd

Staphylococcus aureus
Most common cause of pyomyositis

Route: hematogenous

MRSA: becoming increased

MRSA = Methicillin-resistant S. aureus


Pyomyositis...contd

Streptococcus pyogenes
2nd most common pathogen causing pyomyositis

Cause necrotizing myositis: aggressive, necrotizing

infection of skeletal muscle

Do not have evidence of gas formation in tissue

Manifested with fever, exquisite pain, and swelling

of the affected muscle with induration


Clostridium perferinges

Large, non-motile, spore forming

Found in colon of 25-35% of healthy people, under

certain conditions produce serious, life threatening


infections

Commonest clostridia associated with gas gangrene

Most frequent clostridia involved in soft tissue and

wound infections
Clostridium perfringens

Toxins and virulence factors include:


-toxin (lecithinase) - acts on lecithin, component

of cell membrane

Theta toxin: has haemolytic & necrotizing effect

DNase, hyaluronidase, collagenase: necrotising

toxins - favour necrosis and spread of infection.


Pathogenesis of Gas gangrene
Contamination with deep lacerated wounds (crush

injury, gunshot, knife wounds)

Mixed infection with aerobic pyogenic bacteria,


decreased blood supply - lowers O2 tension.

Vegetative cells multiply, ferment muscle


carbohydrates producing gas - distends tissues &
interferes with blood supply leading to tissue death
(myonecrosis).
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Mycobacterium Tuberculosis

Tuberculosis can involve virtually any organ

Skeletal muscle tuberculosis:

Routes: usually direct extension from neighboring infection and

rarely haematogenous

Pathogenesis: not clear but

o High lactic acid content

o Absence of reticuloendothelial cells

o Very rich blood supply

Help bacteria towards localization in the muscles


Emerging bacterial infections

Staphylococcus epidermidis Streptococcus pneumoniae


Neisseria species Streptococcus viridans
Streptococcus agalactiae Clostridium septicum
Peptostreptococci G-ve enteric bacilli

Aeromonas spp (G-ve rod) Escherichia coli: ESBL

Haemophilus influenzae Mycobacteria


Laboratory diagnosis

Gram staining

Acid fast staining (Mycobacterium suspects)

Hematoxylin-eosine stain (H & E)

Culture (aerobic, anaerobic) from blood and

wound

Susceptibility testing to direct specific therapy


Viral myositis

Ranges from common myalgias to rhabdomyolysis

Possible mechanisms of injury:

Direct invasion by the virus


Effect of myotoxic cytokines induced by
virus (TNF)
Immunologic processes
Viral myositis
Commonly isolated viruses

Influenza (type A, B) Echovirus


Coxsackievirus Cytomegalovirus
Epstein-Barr virus Measles
Herpes simplex virus Varicella-Zoster
Parainfluenza HIV

Adenovirus Dengue
Fungal myositis

Involvement is uncommon; usually described in cases

Symptom often overlap with that of bacterial myositis

Common fungi causing myositis:

Aspergillus spp. Candida spp


Pneumocystis jiroveci Cryptococcus neoformans
Coccidioides Histoplasma capsulatum

Diagnosis: Histopathologic and culture of muscle tissue


Parasitic myositis

Toxoplasma gondii
Tania solium
Trypanosoma cruzi Schistosoma spp
Sarcocystis spp Echinococcus spp
Entamoeba histolytica Toxocara canis

Plasmodium spp Onchocerca volvulus


Dracunculus medinensis
Microsporidia spp
Microbes affecting bone

Learning objectives:
At the end of this class, students will be able to:

Identify common microbes infecting the bone and their


routes of infection

Describe risk factors & pathogenesis of osteomyelitis

Explain manifestation & complications of osteomyelitis

Explain lab. methods used to diagnose osteomyelitis

8/8/2017 Addisu M. (BSc, MSc)


Microbes affecting bone
Healthy bone tissue is extremely resistant to infection

Mostly bacterial; but can be fungal, viral, parasitic

Infection of bone and bone marrow OSTEOMYELITIS

Acquired through:

Hematogenous route

Direct inoculation

Local spread- contiguous infection

Most often affects long bones in children and vertebral bones


in adults. Why?
8/8/2017 Addisu M. (BSc, MSc)
Microbiology of osteomyelitis

8/8/2017 Addisu M. (BSc, MSc)


Common microbes causing osteomyelitis

Often associated with age of patient/clinical scenario


Osteomyelitis Commonly isolated microbes

Infants (< 1 year) Strep.agalactiae (GBS), Staph.aureus, E.coli

Children (1 to 16 yrs) S. aureus, strep.pyogenes (GAS), H.influenza

Adults (> 16 years) Staph.epidermidis, S. aureus, Pseudomonas


aeruginosa, E. coli

Sickle cell disease Salmonella, S.aureus

Post-operative S.aureus, GAS, Enterobacteriaceae

Prosthetic joint S. aureus, S. epidermidis

IVDU S. aureus, P. aeruginosa


8/8/2017 Addisu M. (BSc, MSc)
Pathogenesis

Multifactorial and poorly understood

Entry: through blood, penetrating trauma (direct

inoculation) and from contiguous infections

Infection and inflammation

Blockage of blood vessels - Lack of oxygen and nutrients

Death of bone tissue formation of sequestrum

Acute osteomyelitis

8/8/2017 Addisu M. (BSc, MSc)


Pathogenesis...contd

I. Large inoculum of bacteria reaches the medullar channel


II. Pus resulting from inflammatory response spreads to vascular channels
III. Vascular channels compressed; resulting ischemia - bone necrosis

8/8/2017 Addisu M. (BSc, MSc)


Pathogenesis...contd

8/8/2017 Addisu M. (BSc, MSc)


Pathogenesis...contd

Persistence of infection in bone

Impaired immune and inflammatory responses

Reduced leukocyte number and activity

Adherence to sequestrum, substratum/each other

Biofilm formation - highly persistent and resistant

Protected from phagocytosis and antibiotics

Chronic osteomylitis
8/8/2017 Addisu M. (BSc, MSc)
Pathogenesis...contd

Local factors Microbes (direct inoculus,


Foreign body adjacent infection, blood)
Bone necrosis
Contamination Microbial adhesion to
Slow metabolism bone or implant
Risk
Covered in slime
factors
Intracellularity
Persistent infection
Biofilm formation
Osteolysis
Chronic osteomyelitis
Defect defence
8/8/2017 Addisu M. (BSc, MSc)
Osteomyelitis...contd

1. S.aureus: Pyogenic osteomyelitis


Most common cause of hematogenous osteomyelitis

Acute and chronic

Express affinity receptors for bone matrix components:

Fibronectin, fibrinogen, collagen, laminin

Favors adhesion to bone tissue

Grow in terminal vessel of metaphysis of long bones

Necrosis of bone and chronic suppuration

8/8/2017 Addisu M. (BSc, MSc)


Osteomyelitis...contd

Staphylococcal surface associated proteins

Lymphocytes, macrophages

Cytokines (IL-1, IL-6, TNF- and TNF-)

Increased osteoclastic activity


Decreased osteoblastic activity

Bone tissue loss osteolysis

8/8/2017 Addisu M. (BSc, MSc)


Osteomyelitis...contd

2. Staphylococcus epidermidis:
Coagulase negative Staphylococcus

Responsible for majority of chronic osteomyelitis


associated with orthopedic implants and pin tract
infections

Commonly isolated in chronic osteomyelitis patients

8/8/2017 Addisu M. (BSc, MSc)


Osteomyelitis...contd

3. M.Tuberculosis: Tuberculous osteomyelitis


Routes of infection:

Bloodstream

Long bones and vertebrae are favored sites. Why?

Contiguous focus of infection

Synovium: common site of initial infection

Adjacent spread, granulomatous inflammation,


caseous necrosis and extensive bone destruction
8/8/2017 Addisu M. (BSc, MSc)
Osteomyelitis...contd

MTB: Tuberculous osteomyelitis


Can occur in virtually any bone

Accounts for 10 to 35 percent of cases of EPTB

Almost 2 percent of all TB cases


Follows primary lung infection in endemic area

Associated with reactivated infection outside endemics

8/8/2017 Addisu M. (BSc, MSc)


Laboratory diagnosis
Blood: for haematogenous osteomyelitis

Culture: Isolation, susceptibility testing

Aerobic/anaerobic, and fungal

Bone biopsy: open or subcutaneous

Gram staining

Ziehl-Neelsen staining (AFB)

Culture: Isolation, susceptibility testing

Aerobic/anaerobic, and fungal


8/8/2017 Addisu M. (BSc, MSc)
Laboratory diagnosis...contd
Biopsy may mislead diagnosis;
Falsely positive:
Sampling error - inadequate, wrong sample
Contamination with skin Microbiota
Falsely negative:
Sampling error inadequate, wrong sample
Prior antibiotic therapy
Inability to culture fastidious organisms
Suboptimal culture methods
8/8/2017 Addisu M. (BSc, MSc)
Microbes affecting the joints

Learning objectives:
At the end of this class, students will be able to:

Identify common microbes infecting the joint and


their routes of infection

Describe risk factors & pathogenesis of arthritis

Explain lab. methods used to diagnose arthritis

8/8/2017 Addisu M. (BSc, MSc)


Arthritis

Infection of synovium and


synovial fluid

Seen in every ages

Hip joint in children


frequent
Knee in adults

8/8/2017 Addisu M. (BSc, MSc)


Septic Arthritis
Inflammation of joint/s secondary to microbes

Most common causes are bacterial origin:


Staphylococci and streptococci: most isolates

Usually monoarticular and monomicrobial; occur most


commonly in large peripheral joints
Important cause of morbidity and mortality particularly in
polyarthritis;

Severity of infection

Diagnostic delay
8/8/2017 Addisu M. (BSc, MSc)
Route of infection

8/8/2017 Addisu M. (BSc, MSc)


Septic Arthritis

Pathogenesis
Entry to joints

Blood, penetration, contiguous infections

Colonization & adherence: deposition in synovial mem.

Infection, inflammation, increased pressure, ischemia

Microbes can easily enter synovial fluid and create


characteristic purulent joint

Synovial tissue has no limiting basement mem.

8/8/2017 Addisu M. (BSc, MSc)


Septic Arthritis

Acute joint swelling, pain, erythema, warmth, and


joint immobility - common presentation

8/8/2017 Addisu M. (BSc, MSc)


Bacterial causes of septic Arthritis
Gram +ve cocci (staphylococci, streptococci), gram-ve
cocci, gram +ve bacilli, gram-ve rods, mycobacteria

Neisseria gonorrhea Staphylococcus aureus


Borrelia burgdorferi Staphylococcus epidermidis
P.aeruginosa Streptococcus pnewnonia
Escherichia coli Streptococcus pyogenes
M.tubercilosis Streptococcus agalactiae
Salmonella Haemophilus influenzae
8/8/2017 Addisu M. (BSc, MSc)
Septic Arthritis

Staphylococcus aureus (most common cause)

Streptococcal and other staphylococcal species

E.coli & Pseudomonas (neonates, immunodeficiency)


H.influenza: in children tempered by vaccination

N.gonorrhea (sexually active young adults)

Borrelia burgdorferi: tick bite

8/8/2017 Addisu M. (BSc, MSc)


1. Neisseria gonorrhea

Gram negative cocci; diplococci and fastidious

Produce no exotoxin - damage from intracellular growth

Virulence factors:

Fimbriae: attachment to host cells

Omp: inhibit complement, attach fimbriae firmly, pore

LOS: endotoxin, inhibit complement activation and


membrane attack complex formation

IgA protease: hydrolyses secretory IgA


8/8/2017 Addisu M. (BSc, MSc)
Neisseria gonorrhea
Disseminated infection usually common in young,
healthy sexually active adults

Often affect distal joints (fingers, wrists, elbow,


ankles, knees)

Females are more affected than males:

Asymptomatic nature of gonorrhea

Associated delay in diagnosis

Providing time to gain access to bloodstream


8/8/2017 Addisu M. (BSc, MSc)
2. Borrelia burgdorferi

Spirochete; spiral, or wavy with irregular coils

Motile with axial filament (endoflagellate), refractile

Highly flexible, move both by rotation and twisting

Obligate, tick borne (Ixodes)

Causes lyme disease - "Lyme arthritis

Do not produce toxins, migrating through tissues


8/8/2017 Addisu M. (BSc, MSc)
Borrelia burgdorferi

Pathogenesis:

Exit tick while it feeds on mammalian host and


establish infection in skin
Down regulation of outer surface protein A

Up regulation of outer surface protein C

Rapid multiplication

Dissemination

8/8/2017 Addisu M. (BSc, MSc)


Erythema chronicum migrans - early d/se

8/8/2017 Addisu M. (BSc, MSc)


Borrelia burgdorferi

Adherence to host cells and ECM proteins

Utilization of host protein - bind plasmin, digestion


of extracellular matrix components

Aid bacteria to move to blood stream

Evade immune clearance


Rapid down regulation of Osp C - no antibody

Complement not activated

Fever, myalgia, and arthralgia (migratory)


8/8/2017 Addisu M. (BSc, MSc)
Summary of bacterial arthritis
Exposure history Involved joints Pathogens

Cellulitis, skin infection Mono/polyarticular S.aureus, Streptococcus

Bites (dog, cat) Small joints (finger, toe) Pasteurella

Unpasteurized dairies Mono (sacroiliac) Brucella species

Intravenous drug use Axial joints P.aeruginosa, S. aureus

Nail through shoe Foot P. aeruginosa

Sexual activity Hands, wrists, ankles Neisseria gonorrhea

Prosthetic joints Hip, knee CoNS, S. aureus

Tick bite, erythema migrans Oligo (Knee , large joints) Borrelia burgdorferi

HIV infected Large weight joints MTB, fungi

8/8/2017 Addisu M. (BSc, MSc)


Viral Arthritis
Most forms present with acute polyarthritis, with
fever and characteristic rash
Small and large joints are involved
Commonly isolated viruses:
Parvovirus B19
Rubella: Transient arthralgia and arthritis in adults
Hepatitis B and C
Epstein-Barr virus
8/8/2017 Addisu M. (BSc, MSc)
Parvovirus
Simplest ssDNA viruses - small coding capacity

Viral replication is dependent on functions supplied by


replicating host cells or by coinfecting helper viruses

The only known parvovirus pathogenic for humans,


B19, has a tropism for erythroid progenitor cells.

Cause erythema infectiosum ("fifth disease") - common


childhood exanthema

Polyarthritis in adults hands, wrist, ankles, knees


8/8/2017 Addisu M. (BSc, MSc)
Laboratory diagnosis

Specimen: synovial fluid, blood, swab, urine, sputum,


swabs (urethral, cervical, rectal, pharyngeal), biopsy
Synovial fluid analysis (color, transparency, viscosity,
cellularity WBC and PMN )
Stained microscopy (Giemsa, gram, AFB)
Unstained microscopy (dark field)
Culture
Serology (ELISA) and Haematology - non-specific
Molecular tech - polymerase chain reaction (PCR)
8/8/2017 Addisu M. (BSc, MSc)
Laboratory diagnosis
Neither absence of organism on staining nor negative
synovial culture excludes diagnosis of septic arthritis;

Reasons for inability to obtain microbial proof of infection:

Prior use of antibiotics

Inappropriate culturing

Standards of microbiological laboratories

Changing patterns of organisms involved

Failure to obtain blood for culture

Failure to perform enough arthrocentesis


8/8/2017 Addisu M. (BSc, MSc)