Laboratory techniques

  • Gram stain – Most bacteria.
  • Acid-fast stain – Mycobacteria, nocardia.
  • Silver stain – Fungi, legionella, pneumocystis.
  • Periodic acid-Schiff – Fungi, amoeba.

Tissue damage is caused by direct cell death (contact or enter host cells), release of toxis/enzymes or damage of vessels, or induction of host immune response.

Inflammatory responses to infection

  • Suppurative/purulent inflammation – Reaction to acute tissue damage with vascular permeability, neutrophils by chemoattractants released by pyogenic bacteria. Pus is mass of liquefactive necrosis and neutrophils.
  • Mononuclear inflammation – Response to chronic inflammation, viruses, itnracellular bacteria or parasites. Type of cell accumulation depends on the infection. Granulomatous inflammation is accumulation of activated macrophages (epithelioid cells) which fuse to form giant cells; in response to agents resisting eradication stimulating T-cell immunity.
  • Cytopathic-cytoproliferative reaction – Viruses induce cell necrosis or proliferation, with sparce inflammatory cells. Include blisters, warts.
  • Tissue necrosis – Secreted toxins cause rapid and severe gangrenous necrosis (eg clostridium perfringens), with few inflammatory cells.
  • Chronic inflammation and scaring.


Obligate itnracellular. DNA or RNA. May have characteristic inclusion bodies. Those that may cause cancer include EBV, HPV, HBV, HTLV-1.


  • Adenovirus – URTI, LRTI, conjunctivitis, diarrhoea
  • Rhinovirus – URTI
  • Influenza A, B – Influenza
  • Respiratory syncytial virus – Bronchiolitis, pneumonia


  • Mumps virus – Paramyxovirus. Mumps parotitis (bilateral in 70%, enlarged) , pancreatitis, orchitis (marked oedema, focal haemorrhages, later scaring), encephalitis
  • Rotavirus – Childhood gastroenteritis
  • Norovirus – Gastroenteritis
  • Hepatitis A, B, C, D, E


  • Measles (rubeoloa) – Single-stranded RNA causing skin rashes, lymphoid follicular hyperplasia, peribronchial nd intersitial pneumonia
  • Rubella (German measles)
  • Herpesviruses – Double-stranded DNA, cause acute then latent infection. α-group includes HSV, VZV; β-group CMV; γ-group EBV, KSHV
    • Herpes simplex virus (HSV) 1, 2 – Acute vesicular eruption at oropharynx or genitals, resolving withi na few weeks. Latent infection in sensory ganglia. Reactiviation with or without symptoms, evading host immunity.
    • Varicella-zoster virus (VZV) – Acute chickenpox, reactivation shingles (herpes zoster). Latent infection in sensory dorsal root ganglia.
    • Cytomegalovirus (CMV) – Latent infection of monocytes and bone marrow progenitors. Acute infection transient immunosuppresion. Intranuclear basophilic inclusions. Affects 50-100% of population. Reactivation in immunocompromised.
    • Epstein-Barr virus (EBV) – Self-limiting lymphoproliferative infectious mononucleosis with genearilsed lymphadenopathy, splenomegaly, hepatitis, meningoencephalitis, pneumonitis. Latent infection of B-lymphocytes, which may induce proliferation and increases the risk of B-cell and Burkitt lymphoma (esp with immunocompromise), nasopharyngeal carcinoma.
    • Kaposisarcoma herpesvirus (KSHV, HHV-8) – Latent infection in lymphoid cells. Causes Kaposi sarcoma.
  • HIV – AIDS
  • West Nile virus – Arthropod-borne (arbovirus) transmited by mosquitoes. Fever, maculopapular rash, CNS infection.
  • Yellow fever virus

Skin/Genital warts

  • Human papillomavirus (HPV)


  • Poliovirus – Enterovirus, replicates in motor neurons of spinal cord or brainstem.
  • JC virus – PML


Most have cell wall with peptidoglycan. Prokaryotes with outer cell membrane, but lack membrane nuclei and organelles. Obligate itnracellular bacteria replicate inside membrane-bound vacuoles. Gram-negative bacteria have lipopolysaccharide (LPS) endotoxin as part of their outer membrane, induce immune system. Exotoxins are proteins secreted, which may be enzymse, neurotixns, superantigens (stimulate T-cells).

Gram Positive Bacteria

  • Staphylococcus – Form clusters like grapes
    • S.aureus – Skin lesiosn, abscessses, sepsis, osteomyelitis, pneumonia, endocarditits, food poisoning, toxic shock syndrome (TSS) from superantigens, scalded-skin syndrome.
    • S.epidermidis – Opportunistic infections of catehterised pts, prosthetic valves, drug addicts.
    • S.saprophyticus – UTIs in young women.
  • Streptococcus – Pairs or chains. Suppurative infections. Some have capsules that resist phagocytosis.
    • α-haemolytic – S.pneumoniae (pneumococcus) causes pneumonia, otitis media, sinusitis, meningitis, peritonitis. Viradans group includes normal oral flora; S.mutans causes dental caries.
    • β-haemolytic group A – S.pyogenes causes pharyngitis, scarlet fever (exotoxin), impetigo, rheumatic fever, TSS, glomerulonephritis, necrotizing fasciits.
    • β-haemolytic group B – S.agalactiae colonises the gemale genitals, causes neonatal meningitis/sepsis and chorioamnionitis.
    • β-haemolytic group D – Enterococci, cause endocarditis, UTIs.
  • Corynebacterium diphtheriae – Rod causes diptheria with infection of nasopharynx, oropharynx, larynx, trachea with exotoxins causing sloughing membranes
  • Listeria monocytogenes – Facultative intracellular bacillus causes food-borne infections, amnionitis, neonatal sepsis, meningitis, focal abscess in any organ (lung, liver, spleen, LN)
  • Bacillus anthracis – Anthrax spores from contaminated soil. May be cutaneous vesicles, inhalational (meningitis, shock), gastrointestinal (bloody diarhoea).
  • Nocardia – Branched chains resembling hyphae, found in soil. Opportunistic infections in immunocompromised. N.asteroides causes respiratory, CNS infection.

Gram Negative Bacteria

  • Neisseria – Diplococci
    • N.meningitidis – Meningitis, colonises oropharynx (in 10%)
    • N.gonorrhoeae – STD with male urethritis, female asymptomatic or PID.
  • Bordetella pertussis – Coccobacillus. Whooping cough (laryngotracheobronchitis), colonises brush border of bronchial epithelium. TOxin paralyses cilia.
  • Pseudomonas aeruginosa – Bacillus. Common in CF, severe burns, neutropenia, otitis externa. Can be very resistant to antibiotics.
  • Yersinia pestis – Facultative intraceuula. Bubonic plague causes leg ulcer and rupturing draining LN; pneumonic plaque necrotizing bronchopneumonia; septicaemic plague mononuclear-phagocyte system.


Aerobic bacilli wih mycolic acid waxy cell wall making them acid fast (retain stains on treatment with acid and alcohol). Wealky gram positive.

  • M.tuberculosis – Infection may or may not cause slincially significant disease. Delayed hypersensitivy to the antigens, detected by the tuberculin (Mantoux) skin test after 2-4 weeks of infection/vaccination, with T cell-mediated immunity.
    • Pulmonary TB – See Air Space
    • Intestinal TB – Drinking of contaminated unpasteurized milk, or swallowing infected material. TB seeds to lymphoid aggregates of small and large bowel, undergo granulomatous inflammation that may ulcerate.
  • M.avium-intraceuulare complex (MAI/MAC) – M.avium and M.intracelulare are seprate species, but have very similar diseases. MAC in soil, water, dust, domestic animals. Infection in ummunocompromise involving lungs, GIT. Abundant acid-fact bacilli within macrophages.
  • M.leprae – Leprosy (Hansen’s disease) – Obligate intracellular. Slowly progressive of skin and peripheral nerves, deformities. Remains endemic in poor tropical countries. Tuberculoid leprosy causes granulomatous inflammation aroudn nerves, chronic skin ulcers, contractures, paralysis, autoamputation of fingers/toes. Lepromatous leprosy affects skin, peripheral nerves, anteriro eye, URTI, testes, hands, feet with lipid-laden macrophages.


Gram negative, corkscrew-shaped with flagella. Visualisedo n sliver stains. Antibody to cardiolipin (rapid plasma reagin and venereal disease research laboratory VDRL tests).

  • Syphilis (Treponema pallidum subsp. pallidum) – Rising again in incidence, STD, transplacental spread. Cannot be grown in culture.
    • Primary syphilis – 3/52 after contact with raised red lesion (chancre) at penis/cervix/vaginal wall/anus, healing in 3-6/52. Haematogenous and lymphatic dissemination before appearance of the chancre.
    • Secondary syphilis – 2-10/52 after primary chancre in 75% untreated. Skin and mucocutaneous plaques, lymphadenopathy, constitutional Sx. Lasts several weeks before latent phase.
    • Tertiary syphilis – Rare treated, but 1/3 of untreated after >/= 5yrs. Cardiovascular syphilis (aortitis) – endarteritis of vasa vasorum with slowly progressive aortic root and arch dilatation, aortic insufficiency. Neurosyphilis – meningovascular disease, tabes dorsalis or general paresis (generalised brain disease); asymptomatic in 1/3 with CSF abnormality. Benign tertiary syphilis (syphilitic gummas) is gummas formation (nodular lesions ?delayed hypersensitivity) in any organ esp bones, joints, skin, mucous membranes of upper airways and mouth.
    • Congenital syphilis – Crosses placenta esp maternal primary or secondary syphilis (spirochetes most numerous), causing intrauterine or perinatal death in 25%, severe rash with sloughing, syphilitic osteochondritis and periostitis involving all bones.
  • Yaws (T.pallidum subsp. pertenue)
  • Pinta (T.pallidum subsp. careteum)
  • Lyme disease (Borrelia burgdorferi) – Trasmitted from rodents via Ixodes deer ticks. Common in USA, Europe, Japan. Stage 1 expanding skin lesions (erythema chronicum migrans) ± lymphadenopathy. Stage 2 (early disseminated stage) – haematogenous with secondary skin lesiosn, lymphadenopathy, migratory joint/muscle pain with synovial hypertrophy, arteritis, cardiac arrhythmias, meningitis with cranial nerve invovlement. Stage 3 (late disseminated, after 2-3yrs) – extensive erosion of large joint cartilage ± severe damage to large joints, polyneuropathy, encephalitis.

Anaerobic Bacteria

Many are normal flora (oropharynx, intestine, female genital tract, cause abscesses/peritonitis when introduced into normally sterile sites or balance upset. Abscesses are usually caused by mixed organisms of anaerobic and facultative aerobic bacteria (eg S.aureus, S.pyogenes). Usually discoloured foul-smelling pus, poorly walled off.

  • Clostridium – Gram-posotive bacilli, produce spores present in soil
    • C.perfringens, C.septicum – Cellulitis, myonecrosis in traumatic/surgical wounds with gas gangrene, uterine infection with illegal abortions, SB infection in iscahemia/neutropenia. Tissue necrosis required for bacteria to grow.
    • C.tetani – Puncture wounds and umbilical stump with release of neurotoxin (tetanospasmin) causing skeletal contraction (tatanus)
    • C.botulinum – Canned foods, neurotoxin causing respiratory and skeletal msucle paralysis (botulism)
    • C.difficile – Intestinal overgrowth in antibiotics, releases toxins to cause pseudomembranous colitis
  • Actinomycosis – Normal commencal in mouth and caecum. Cause chronic abscesses in mouth, lungs, GIT. Require other bacteria to aid in tissue invasion.

Obligate Intracellular Bacteria

  • Chlamydia trachomatis – Gram negative. Infectious form elemebtary body (EB) is metabolically inactive spore-like, taken up by endocytosis. Bacteria prevents fusion of endosome with lysosome, differentiates into the reticulate body that forms mroe EBs. Causes urogenital infections, lymphogranulosum venereum (chronic ulcerative genital infection), childhood ocular infection, conjunctivitis.
  • Rickettsia – Gram-negative rod. Cause vascular leakage due to endothelial damage, inducing peripheral oedema, pulmonary oedema, renal failure, shock.
    • Typhys fever (R.prowazekii and Orienta tsutsugamushi) – Wars, human deprivation transmitted by body lice or mites.
    • Rocky Mountain spotted fever (RMSF, R. rickettsii and others) – Transmitted by dog ticks in SE/S USA.


?Bacteria that lack a cell wall, has bacterial and viral charactersitics. Includes M.pneumoniae (atypical pneumonia), M.genitalium (PID).


Chitin-containing cell walls. Eukaryotes with cell membranes and membrane-covered organelles and nuclei. Grow as rounded yeast cells or chains of cells; or multicelullar filaments (hyphae) as molds; dimorphic fungi exist as yeast at body temperature and mold at room temperature. Most reproduce by budding, may have round cells (conidia) that easily become airborne. Mycoses are fungal infections, may be superficial/cutaneous (dematophytes, tinia, skin/hair/nails), subcutaneous (skin, SC, lymphatics), endemic (systemic in immunocompetent) or opportunistic (systemic and immunosuppressed or prostehtic devices).

Candida Albicans

Normal commensal of skin, mouth, GIT, vagina. Infection occurs when they breach the skin or mucosal barrier. Buds fail to detach and become elongated (pseudohyphae). Visible on H&E and fungal stains (silver, periodic acid-Schiff).

  • Superficial candidiasis (thrush) – Grey-white pseudomembrane on mucosal hyperaemia and inflammation. Includes candida oesophagitis (dysphagia), vaginitis (diabetic, pregnant, OCP), cutaneous (nail, nail folds, hair follicles, intertriginous skin, penile skin, diaper rash).
  • Invasive candidiasis – Immunocompromised haematogenous spread causing renal abscesses, myocardial abscesses, endocarditis (esp prosthetic valves or IVDU), brain microabscesses, meningitis, endophthalmitis, hepatic abscesses.

Cryptococcus Neoformans

Encapsulated yeast from soil and bird/pigeon droppings. In immunocompetent or more commonly immunocompromised (AIDS, leukemia/lymphoma, SLE, sarcoidosis, transplants) with high-dose corticosteroids. Stain red with periodic acidSchiff and mucicarmine. Negative image on india ink stain due to capsule. Primary pulmonary infection mild/asymptomatic. Spreads to CNS with meningoencephalitis expanding Virchow-Robin spaces with soap-bubble lesions.

Aspergillus Fumigatus

Ubiquitous mold causing allergy (ABPA), sinusitis, pneumonia, and invasive dsiease in immunocompromised. (neutorpenia, corticosterodis). Tranamitted by airborne conidia. Aspergilloma (myecetoma, fungal ball) is colonization with minimal/no tissue invasion, in pulmonary cavities. Invasive aspergillosis is an opportunistic infection. Target lesions is sharply defined necrotising pneumonia with haemorrhagic borders. Tends to invade blood vessles causing haemorrhage and infarction.


(Zygomycosis, phycomycosis). Bread mold fungi causing opportunistic infection, including Mucor, Rhizopus, Absidia, Cunninghamella. Immunosupppressed (neutorpenia, corticosteroids, diabetes, iron overload, burns, wounds, trauma). Most inhaed spores spread to sinuses, lung, GIT. Rhinocerebral mucormycosis esp diabetes, spread from sinuses to orbits/brain. Haemorrhagic pn eumonia and vascular thrombi with infarctions.

Pneumocystosis Jerovecii

(Previously Pneumocystis carinii). Yeast-like fungus. Causes pneumonia in immunocompromised esp HIV. In immunocompetent it is a very common silent infection.


Single-celled eukaryotic parasite, may be intracellular or extracellular. Transmitted by insects or faecal-oral route. Reside in blood or intestine.


Plasmodium falciparum (severe), P.vivax, P.ovale, P.malariae. Transmitted by female Anopheles mosquitoes throughout Africa, Asia, Latin America. The infectious sporozoite (in salivary glands of mosquito) transmitted to blood then invade hepatocytes -> multiply and releases multiple merozoites upon hepatocyte rupture -> invade RBCs, maturing into the trophozoite then schizont which produce more merozoites to infect more RBCs. Some develop into sexual form gametocytes that infect mosquitoes. Some have latent hypnozoites (P.vivax, P.ovale) that reside in hepatocytes. P.falciparum can infect any RBC causing profound anaema; others can only infect young or old RBC. RBC may form clumps (rosette) occluding small vessels. Species cannot grow well in HbS. Spleen is congested and enlarged, later thickened capsule and fibrous. Liver becomes enlarged and pigmented Kupffer cells. Malignant cerebral malaria is smal vessels occluded by the RBC causing perivascualr ring haemorrhages, focal ischaemia.

Toxoplasmosis Gondii

Obligate intracellular parasite. Primary host is the domestic cat, spread by ingestion of infected meat of faeces, can spread to foetus. Up to 50% of the worlds population is thought to be infected. Initial infection mild flu-like illness. May cause encephalitis in immunocompromised.


Entamoeba histolytica infection. Gastrointestinal infection may or may not be symptomatic, can remain latent for several years. If reaches the bloodstream may disseminate esp amoebic liver abscess. Usually transmitted by faecal-oral route, contaminated food and water.


Multicellular eukaryotic parasites, often from undercooked meat or via skin/insect bites. Helminths are parasitic worms. Most alternated between sexual reproduction in the definitive host and asexual multiplication in and intermediate host or vector. Adult worms do not multiply, but produce eggs or larvae.

Strongyloides Stercoralis

Worms live in soil, larvae penetrate skin -> haematogenous spread to lungs -> swallowed and mature in small bowel mucosa, producing eggs -> larvae passed in stool contaminating soil. May invade colonic mucosa reinitiating infection (autoinfection) esp immunocompromised (corticosteroids) with hyperinfection.

Tapeworms (Cestodes)

Require difinitive host (where reaches sexual maturity) and intermediate host (does not reach sexual maturity).

  • Cystircercosis (Taenia solium) – Consist of head (scolex) with suckers and hooklets attaching to intestinal wall, neck and flat segments (proglottids) that contain the eggs in teh tips. There are 2 routes of transmittion:
    • Ingestion of undercooked port containing larval cysts (cystercerci) -> attach to intestine and mature into adults, may frow up to metres, mild abdominal Sx.
    • Ingestion of food/water contaminated with human faeces containing larvae -> larvae hatch penetrating gut wall -> disseminate to encyst multiple organs (esp brain, muscles, skin, heart) -> cannot mature and eventually degenerate causing inflammation.
  • Hydatids (Echinococcus granulosus) – Dogs are definitive hosts, sheep usually intermediate hosts. E.multilocularis – foxes are definitive hosts, rodents intermediate. Humans are accidental intermediate hosts. Ingestion of contaminated food with eggs (dogs or foxes) -> hatch in duodenum -> larvae invade liver, lungs, bones, brain -> lodge in capillaries where most are destroyed, but others encyst, progressively increasing in size. Outer pericyst of fibrous capsule; chitinous layer exocyst; and inner nucleated germinative layer (endocyst) which may form daughter cysts. Degenerating scolices form ‘hydatid sand’ within the fluid. Exocyst may rupture with leak of fluid between the pericyst and exocyst, floating debris (water lily sign).


From freshwater snails in slow-moging water of tropical regions. Schistosome larvae (cercariae) penetrate human skin, migrate to lung, mature and mate in hepatic vessels with male-female pairs settling in the portal or pelvic veins. Released eggs incite granulomas and fibrosis, with inflammation allowing eggs to transfer across intestine and blader walls to stool/urine. S mansoni and S.japanicum cause periportal pipe=stem fibrosis ± inflammatory patches/pseudopolyps in the colon. S.haematobium deposits eggs in bladder walls causing cencentric calcification, uteral walls.

Lymphatic Filariasis

Nematodes Wurchereria bancrofti, Brugia malayi, B.timori transmitted by mosquitoes in Latin America, sub-Saharan Africa, Southeast Asia. Larvae released from mosquitoes develop within lymphatics into adults -> release microfilariae into bloodstream. Lymphatic obstruction causes lyphoedema and elaphantiasis. Lung involvement causes pulmonary eosinophilia.


Insects (lice, bedbugs, fleas) or arachnids (mites, ticks, spiders) that live on/in skin. May serve as vectors for other infection.