KICK THE BOARDS USMLE STEP 1 MICROBIOLOGY Prepared by Dr. Irfan Mir
KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
Prepared by Dr. IRFAN MIR
BACTERIOLOGY * Growth of Anaerobes inhibit by O2 because anaerobes lack Catalase & Superoxide Dismutase which detoxify H2O2 and super oxide which is toxic to bacteria. (O2 also cause oxidation of sulfahydryl group of enz). * Outer membrane found in Gram - ve bacteria where as Gram + ve lacks it. * Difference b/w ---- Clostridium Spore forming Bacteroids Non spore forming and lactamase +ve. * Anaerobic infection characterize by : Abscess formation / Foul smelling discharg / Gas in tissue / Necrotic tissue. ----------------------------------------------------------------------GRAM + ve COCCI : (Streptococcus & Staphylococcus) Gram + ve Cocci are divided on the basis of Catalase + ve & Catalase - ve Groups. Catalase + ve: 1. Staph Aureus produce yellow colonies. Protein A (virulence factor). Hemolytic. Coagulase & lactamase +ve. 2. Staph Epidermidis produce white colonies. Non hemolytic. Coagulase - ve. 3. Staph Saprophyticus are coagulase - ve. Catalase – ve: 1. Strep Pyogens ------- group A Hemolytic. ----- Bacitracin sensitive. 2. Strep Agalactae ------ group B Hemolytic. ----- Bacitracin resistant. Hydrolyze hippurate. 3. Strep Fecalis -- (Enterococcus) group D & Hemolytic or non. It grow in 6.5 Nacl. Habitat is Colon. 4. Strep Bovis (Non enterococcus) ------ group D hemolytic or non. Lancet shaped 5. Strep Pneumoniae (Pneumococcus) -- Hemolytic or non. -- Bile soluble. --- Optochin sensitive. 6. Strep Viridian ( S mitis, S mutans, S sanguis) -- Hemolytic or non -- Bile insoluble -- Optochin resistant. GRAM + ve RELATED INFECTIONS : 1. Staph Aureus ----------------------------- Endocarditis in prosthetic heart valve, Food poisoning, Carbuncle. 2. Staph Epidermidis ---------------------- Endocarditis in IV Drug addict and Pt with prosthetic heart valve. 3. Staph Saprophyticus ------------------ Osteomylitis and lower UTI. 1. Strep Pyogenes --------------------------- Pyoderma, RF, Pharyngitis, Glomerulonephritis. 2. Strep Agalactae -------------------------- Neonatal sepsis. 3. Strep Fecalis ------------------------------ UTI, Infective Endocarditis in 10 % of cases. (S fecalis is penicillin G resistant) 4. Strep Bovis -------------------------------- Colon Carcinoma. 5. Strep Pneumoniae ----------------------- Meningitis in very young and old person. Pneumonia (lung consolidation). 6. Strep Viridians ---------------------------- Infective endocarditis in 90 % of cases.
* Pathogenesis of Staph Aureus food poisoning is by stimulation of IL1 and IL2 release. * Virulence factor of Staph Aureus is protein A which binds to Fc portion of IgG thus preventing complement binding. * Staph Aureus produce lactamase. Drug of choice is lactamase resistant penicillin or vancomycin or both in resistant case. * Hemolysins cause hemolysis when colonies grow on blood agar plate, Streptococcus produce 2 type of hemolysins. 1. Streptolysin O is O2 labile ( inactivated by O2 ) 2. Streptolysin S is O2 Stabile ( cannot inactivated by O2 ). * Strep Pyogenes contain 3 virulence factor :1. M protein ---- determine group A Hemolytic infection and interfere with phagocytic ingestion. 2. Hyaluronidase ---- Hydrolyze the ground substance of the connective tissue. 3. Erythrogenic Toxin ---- Cause rash of scarlet fever (lysogenised by bactriophage carrying the gene for Toxin). Dx by Dick test * Rheumatic fever occur due to cross reaction b/w streptococcal Ag and Ag of joint & heart tissue. Usually 2 week after the pharyngitis with Sterp Pyogenes. * Glumerolunonephritis is initiated by AgAb complex on glomerular basement mem and Soluble Ag (M protein) may
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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be the inciting factor. It occur 2 - 3 week after skin infection with Strep Pyogens . * Pneumococci (Strep Pneumonie) cause meningitis in very young and old. It is identify by Quellung Reaction. It can be prevent from 23 type vaccine or penicillin. Pnemococcal virulence factor is polysacharide capsule which interfere with Phagocytes by IgA protease and elicit primary B cell response (i.e T cell dependant). Pneumococci produce no toxins and are lactamase - ve. GRAM - ve COCCI ( Gonococcus & Meningiococcus) : * Are Neisseria Gonococcus (Gonococcus) & Neisseria Meningitides (Meningiococcus). * Both are Oxidase + ve (ie Enz cytochrome c) & produce Endotoxins (Lipooligosaccharide LOS, & Lipopolysaccharide LPS). 1. N Gonococcus: Oxidase + ve. Produce Endotoxin LOS & Glucose, Contain Pilli, IgA protease. It contain no capsule. vs. 2. N Meningitides: Oxidase + ve. Produce Endotoxin LPS, glucose & maltose. Contain IgA protease & polysacchride Capsule. * Remember endotoxins are produce by only Gram - ve Bacteria’s. * Role of Endotoxins LOS, LPS is to cause fever, and provoke reaction that lead to shock. * Enz Oxidase (ie Enz cytochrome c) turn colonies black when expose to Phenylalanine as a result of oxidation. * Remember Meningococci ferment maltose where as gonococci does not. Both ferment Glucose. * Gonococci culture on Thayer Martin medium which is chocolate agar (contain Blood heated at 80 which inhibit toxic metal and fatty acid to promote bacterial growth, also Antibiotics to suppress normal flora). It can also be identified by glucose fermentation by fluorescent Ab stainig. * Complements are imp defense. C6 - C9 deficiency incidence of incidence of meningococcal & gonococcal bacteremia. * N Gonorrhea does not have capsule but it does have IgA protease and pili (virulence factor) both mediate attachment to mucosal surface and are antiphagocytic. Where as N Meningitides has polysaccharide capsule (virulence factor) which is antiphagocytic and induce protective Ab. (remember pili mediate attachment nonpiliated strains are avirulent). * IgA protease hydrolyze secretory IgA to promote attachment. * Meningiococci colonize the Oropharynx than enter the blood stream & spread to meninges and joints. (sp in immunodeficient pt). * Meningiococcal meningitis can be prevente by Rifampin (Rifampin secrete in saliva), and vaccine (contain A,C,Y,W135 strain but does not contain B strain). * Gonococci is resistant to penicillin due to plasmid mediated penicillinase production. TX of choice is ceftriaxone IM single dose. * N meningitides is most likely cause of meningitis epidemic. * Common organism cause meningitis in new born ( < 1 month of age ). 1. Listeria Monocytogenes (Gram + ve Rod) 2. E- coli ( because 25% of women have organism in vagina ). Gram - ve Rod * Common organism cause meningitis over 2 months of age. 1. H Influenza. ( also rank # 1 in 6 month to 6 yr age group) 2. Sterp Pneumonie ( it rank # 1 in adult ) 3. N meningitidis ( it rank 2nd to H influenza in causing meningitis, in children age 6 months to 6 years) * Gonococci cause Gonorrhea (STD) characterize by urethral exudates, TX of choice is Ceftriaxone, and Ophthalmia Neonatrum which can be treated with Erythromycin or silver nitrate.
GRAM + ve RODS
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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* It is divided on the bases of Spore forming and Non spore forming. SPORE FORMING: 1. Bacillus: * B. Anthracis -- Motile, Capsule (composed of D - glutamate). Habitat is soil. cause Anthrax. (Aerobes) * B. Cereus -- spores present on grain of rice.-- cause Food poisoning. 2. Clostridium -- * C. Tetani -- Toxin Tetanspasmin (protease) -- cause Tetanus (Anaerobes) * C. Botulinum -- Toxin Botulinin (protease) -- cause Botulism (food, wound, infantile type) * C. Perfringines -- Toxin (lecithinase) → Gas Gangrene, food poisoning, septic abortion. * C. Dificile -- Exotoxin A & B (enterotoxin, cytotoxin) -- cause PM enterocolitis. NON SPORE FORMING: 1. Cornybacterium Diptheriae --- Club shape, Non motile, Cell appear blue & granule red. EF2. (Aerobes) 2. Listeria monocytogenes --- Motile, Toxin listeriolysin O, hemolytic -- cause Meningitis, sepsis in new born & immunocompromised adult. * Mostly bacteria’s has Polysaccharide capsule but B. Anthracis capsule is composed of D - glutamate which is unique to it. * B. Anthracis invade host skin, mucous mem, Resp tract & produce Anthrax Toxins which contain 3 components, 1. Protective Ag 2. Lethal factor 3. Edema factor (Exotoxin) is adenylate cyclase, dependent of protective Ag for its binding & gain entry into the cell. * Tetanspasmin (Tetanus toxin) is protease which cleave the protein involved in mediator release. It reach to CNS in retrograde fashion via axon where it bind to ganglion side receptor & block release of inhibitory mediator Glycine at spinal synapses. * Tetanus can be prevented by cleaning the wound, Tetanus toxoids (vaccine), Tetanus Ig (in gross contamination of wound), Penicilllin * C. Botulinum acquired by contaminated food sp cane food, smoked fish. It Can be prevented by discarding swollen canes. * Botulinum can be occur in two more clinical forms. 1. Wound botulism 2. Infantile Botulism -- by ingestion of honey contaminated with spores (recover spontaneously). * Botulism toxin is Botulinin, it absorbed from gut reach to peripheral nerve synapse via blood where it block the release of Ach. It is isoprotease which cleave the protein involved in Ach release. * C. Perferingenes cause Gas gangrene associated with war wounds, road side accidents, septic abortion. \ \ Vegetative cells are normal flora of colon and vagina. Penicillin is prophylactic. * C. Perferingenes produce toxin (lecithinase) which damage the cell wall including erythrocytes. Degenerative enz produce gas in tissue. Exudate culture anaerobically shows Gram + ve Rods, spores are not seen, organism can be identified by sugar fermentation and organic acid production. * C. Perferingenes also cause food poisoning mechanism is unknown. * C. Dificile produce exotoxin A (enterotoxin) -- cause out pouring of fluid exotoxin B (cytotoxin) -- cause damage to colonic mucosa by ADP ribosylate, it is GDP binding protein that regulates actin in cytoskeleton. (results into pseudo membranous formation & diarrhea). * PM enterocolitis can also caused by antibiotics. Treatment of choice is Metronidazole or vancomycin. * Cornybacterium Diptheriae appear club shaped on gram stain arranged in palisade or in V or L shaped formation. Rod have beaded appearance. (Bead contain granule of polyphosphate, Remember Dye stains the cell blue and granule red). * Diphtheria toxin inhibit syn of ADP ribosylation of EF2 (elongation factor). Toxin is a single polypeptide with two domain one mediate binding and other possess enzymatic activity which cleave nicotinamide from NAD and transfer the remaining ADP ribose to EF2 thereby inactivating it. It effect all eukaryotes. * Diphtheria shows whitish gray adherent mem over the tonsils and pharynx.
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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* DNA that encodes Diphtheria toxin is part of genetic material of temperate Bacteriophage (bacteria infected by virus). Remember only lysogenized bacteria (the viral infected bacteria) produce toxins and cause dis. * Diphtheria vaccine contain diphtheria toxin, tetanus toxin & killed pertussis (on 2,4,6, month, than 1, 6 yr booster, than every 10 yrs booster). * Diphtheria once bound irreversibly to cell mem can not be neutralized so antibiotics should be given immediately. * Listeria monocytogenes Cause meningitis and sepsis in newborn and in immunocompromised adult. * Listeria transmitted by contact with animal feces, unsaturated milk, contaminated vegetable, unpasturized cheese (in USA), across the placenta in new born (1 - 4 week cause acute meningitis). * L monocytogenes toxin is Listeriolysin O which is similar to streptolysin O. it acts by producing holes in cell mem hemolysis. * Cell mediated immunity is imp in host defense. TX is Ampicillin in high doses. * Diphtheria confirmed by growth on Lofler’s Blood agar. GRAM - ve RODS * Gram - ve Rods are divided in 3 groups Enteric tract related, Respiratory tract related and zoonotics. * Remember Endotoxins are produce by Gram - ve bacteria’s. ? GRAM - ve RODS: 1. Lactose Fermenter: Slow Fermenter -- Serratia Opportunistic infection (Enteric tract. Contain O Ag) Fast Fermenter -- Enterobacter Opportunistic infection E. Coli -- H Ag meningitis, sepsis, UTI, traveler’s diarrhea. Klebsiella -- K Ag (identified by Quellung reaction) → Pneumonia 2. Lactose Non Fermenter: Oxidase - ve -- Shigella Bloody Dysentery (diarrhea). Salmonella -- H Ag, Widal test Enter colitis (Enteric fever), Typhoid. Proteus mirabilis -- (urease + ve), Weil Felix test UTI Providencia Morganella Oxidase + ve -- Pseudomonas Aerogenosa Nosocomial infection. 3. Other Gram - ve Rods : Vibrio -- comma shape, Exotoxin Choleragen (A & B subunit) Cholera. Campylobacter jejuni -- comma or S shape diarrhea (USA) Helicobacter Pylori -- Gastric ulcer. DX. urea breath test, serum Ab, biopsy. Bacteroids -- sepsis. * All Enteric tract Gram - ve Rods are facultative Anaerobes, ferment glucose (sugar varies), reduce nitrate to nitrite (as energy generation), Except Pseudomonas which is strictly aerobe and donot ferment glucose or reduce nitrate. They are oxidase + ve (enz cytochrome c) which derived energy from oxidation. Where as all Enteric tract gram – ve contain O Ag. * Enterobacteriaceae Ag ---- 1. O Ag is a cell wall Ag (outer polysaccharide portion of Lipopolysaccharide) 2. H Ag is a Flagellar Ag (protein) present in E. Coli and Salmonella only. * Lactose Fermentation is imp criterion for the identification of organism, that is 1. Non Fermenters form colorless colonies, it includes Shigella, salmonella, proteus, pseudomonas. 2. Lactose Fermenter form colored colonies, it includes E. coli, Klebsiella, Enterobacter, and Serratia (slow Fermenter). * E. Coli is the major cause of neonatal meningitis along with streptococci (Agalacteae). It occur during birth due of vaginal colonization of E coli in 25% of pregnant women. * Certain E. coli donot produce Toxin but are invasive and can cause diarrhea.
* E. Coli adhere by mean of pili once attached synthesize enterotoxin to produce diarrhea. It include Enterotoxins
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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1. Heat Labile Toxin ( LT ) ---- it stimulate Adenylate cyclase which results into outpouring of K+ cl- (diarrhea). 2. Heat stabile Toxin ( ST ) ---- it stimulate Guanylate cyclase. * E. Coli strain that cause neonatal meningitis contain specific capsular Ag called K1 Ag. * E Coli endotoxin is cell wall LPS cause sepsis, fever.1. O serotype of E. coli preferentially cause UTI 2. K1 erotype of E. coli preferentially cause meningitis, sepsis, DIC * E. Coli 0157: H7 identify on sorbitol agar Afebrile hemorrhagic colitis & Hemolytic uremic $ due to sheiga like toxin. * Salmonella change its flagellar H Ag by DNA rearrangement (reversibly alternate two type of H Ag) to evade immune response. * Enter colitis (Enteric fever) by salmonella is caused by invasion to epithelial and sub epithelial tissue of small and large intestine with resultant inflammation and diarrhea with or without blood. * Typhoid infection cause by Salmonella Typhi begins in small intestine, organism enter and multiply in non nuclear phagocytes of Payers Patches and spread to liver, gallbladder and spleen with resultant bacteremia and fever. * Gall Bladder inflammation carrier state for long time ( excrete bacteria in feces ). * Salmonella transmitted by ingestion of food and water contaminated by human feces and animal waste specially poultry & eggs. * Salmonella Typhi is transmitted by human only. * Salmonella Enteric fever DX by Widal test ( Ab titer in pts serum) and Slide Agglutinin test (can isolate salmonella). * Salmonella vaccines are 1. Acetone killed S typhi ( IM ). 2. Live attenuated S Typhi ( orally ). * TX of Enteric fever / septicemia is Ceftriaxone where as Typhoid can be treated with Ampicillin, or ciprofloxacin in chronic cases. * Shigella are transmitted by 4 Fs Finger, Flies, Food, Feces. Out breaks are food and water borne. * Shigella invades distal colon mucosa surface cause ulceration but rarely penetrate the gut wall or enter in blood. (unlike salmonella). * Shigella that does not produce enterotoxin still cause dis. Where as non invasive are non pathogenic. * Shegella dysentery is watery first and than bloody with mucous, also presents PMNs. TX is hydration, Ampicillin, TMP-SMX. * Serratia & Enterobacter are group together because they are similar in motility and several biochemical reaction both cause opportunistic infection, usually in IV catheterization, respiratory intubation, UT manipulation. * Serratia and nitrobacteria are highly resistant. TX of choice is Ceftriaxone and gentamicin combination. * Klebsiella cause pneumonia. Its capsule is K polysaccharide Ag which has antiphagocytic activity. * K Ag are identified by Quellung reaction. (Strep Pneumoniae have polysaccharide capsule is antiphagocytic and also identified by Quellung reaction) * Proteus distinguished by Urease production on TSI agar which form ammonia NH3 & CO2. Some Proteus are motile. * Urease from Proteus hydrolyze urea in urine to form NH3 which the PH of urine and encourage the formation of Struvite calculi composed of magnesium hydroxide Mg(NH4OH)2. Alkaline urine favor growth of proteus thats why tx also include Low urinary PH. * The O Ag of proteus (OX2, OX9, OXK) cross react with Rekittsial Ag. So Ag can be used to detect Ab against Rekittseas. This test called Weil Felix test or reaction. * Proteus can cause extensive renal damage. TX of choice is Ampicillin. For severe infection ampicillin & gentamicin. * P Aerogenosa are strictly aerobes, non fermenter, donot reduce nitrate and is oxidase + ve (cytochrome c) that it produce energy from oxidation. * Pseudomonas cause nosocomial infection produce characteristic blue green pus due to pigment Pyocyanin. The pigment pyoverdin under UV rays (fluorescent). * In Pseudomonas grow in water containing traces (humid environment). It remarkably stands disinfectant, grow in hexachloroprene soap solution, anti septic, and detergents. * Pseudomonas cause opportunistic infection in person with Neutrophil counts < 500 L. * Vibrio appear comma shape. After adherence vibrio secrete enz mucinase which dissolve protective glycoprotein
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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than secrete enterotoxin Choleragen (exotoxin). Choleragen contain 1. A (active) Subunit -- insert in cytosol & stimulate adenylate cyclase Cl + water. 2. B (binding) Subunit -- bind to ganglioside receptor on enterocyte. * Cholera is predisposed by malnutrition, poor sanitation, overcrowding. * Cholera TX is water & electrolyte replacement . Tetracycline is not necessary but may shorten the duration of symptoms. * Remember Choleragen stimulate adenylate cyclase and E. coli toxin stimulate guanylate cyclase both lead to diarrhea. * Campylobacter jejuni appear comma or S shape. It is motile, grow in 5% O2 at 45C, and is micophillic. * Domestic animals are reservoir of campylobacter.Transmission is fecal oral route. Prevent by proper sewage disposal & hygiene. * Campylobacter is 2nd leading cause of diarrhea in USA (after giardia) which is often accompanied by blood in stool. Its enterotoxin acts same as cholera toxin. * TX of choice Erythromycin or Ciprofloxacin. Campylobacter intestinalis cause bacteremia & TX of choice is Aminoglycosides. * Bacteroids Fragilis are predominant human flora of colon, also found in vagina and oral cavity. It is the single most common anaerobic isolate from the blood. It may cause sepsis. Thrombophlebitis is rare * Facultative aerobe like E.Coli utilize the O2 for its growth which results into O2 which promotes bacteroids growth. ( for this reason for therapy both should be treated ). * Bacteroids are lactamase +ve. TX of choice is metronidazole with cefoxitin. Alternatives are clindamycine and chloramphanicol. * B. Melaninogenicus is highly susceptible to penicillin G. * Aminoglycoside is used for facultative Gram - ve Rod or mixed infection. GRAM - ve ROD --- H. Influenza --- Factor X & V (for growth) -- Meningitis, URT infection, sepsis in children Pneumonia in adult (Resp Tract Coccobacillus) H. Ducreyi --- Chancroid (buboes) -- ( Sexually transmitted agent) L. Peumophilia --- conc of iron & cysteine for growth -- Atypical Pneumonia, Diarrhea (non bloody) B. Pertusis --- FHA (pertosis toxin) ---- Whooping Cough. * Hemophillus influenza Type b is responsible for most of the invasive dis. Its capsule is composed of Polyribitol phosphate. * Factor X (heme) and factor V (NAD) is required for growth of H. Influenza extracellularly. * H. influenza can be prevented by vaccine ( contain type b and diphtheria toxoid) or rifampin (secrete in saliva). * 3 imp encapsulated pyogenes are Pneumococcus, Meningococcus, and H. influenza. (Remember they all cause meningitis) * H. influenza TX is Penicillin, SMX-TMP, clarithromycin. * L. Pneumophilia requires high concentration of iron and cysteine for growth, it grow on buffered charcoal yeast agar. Legeonella Ag in urine is rapid mean of making DX. It’s habitat environmental water sources e.g air-condition, water tab, showers etc * Port of entry for Legionella is Respiratory tract. It effect tipically alcoholics, Aids pt, smokers, cancer pt, transplant pt sp Kidney. * L. Pneumophilia cause mild influenza like illness to severe Pneumonia, endocarditic (rare), mental confusion, non bloody diarrhea, cough, sputum is frequently scanty and non purulent. * Legeonella can be TX with Erythromycin, Rifampin, clarithromycin. Endocarditis need valve change and 3 - 12 month of therapy. * B. Pertusis attached with ciliated epithelium by mean of protein located on pili called filamentus hemagglutinin pertusin toxin (FHA), which stimulate adenylate cyclase cAMP and its dependant protein kinas activity. * Brodetella peptidogylycan damage ciliated cell. Adenylate cyclase inhibit bactericidal activity of phagocyte.
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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* B. pertusis donnot invade underlying tissue. * Killed pertusin Toxin given with diptheria and tetanus toxin (DPT vaccine) can cause post vaccine encephalopathy children.(rare). * Cellular vaccine of 4 Ag contain active pertusin toxin cant be used < 15 month of age where as DPT can be use at 2 month of age. * B. pertusis can be TX with Erythromycin. * H. Ducreyi infection common in world sp in tropical countries. It cause Chancroid (genital ulcers with buboes). * Chancroids can be treated with Erythromycin, SMX-TMP, ceftriaxone. * Atypical Pneumonia caused by ----------------------------------------- 1. L. pneumophilia 2. Mycoplasm 3. Psittacosis 4. Q fever ( R bernetti) 5. Viral --------------------------------------------------------------------------------------------------------------------------------------------------------------------------GRAM - ve Zoonotics * These are usually vector related which can be mosquito, bugs, wild or domestic animals. * Buboes are painful swollen lymphnodes. ? Gram - ve Rods ---- Brucella Melitensis ---- (in goats) Brucellosis (undulant fever) due to infected animal tissue or milk. ( zoonotics ) Brucella Abortus ---- (in cattle’s) Brucellosis (undulant fever) due to infected animal tissue or milk. Francisella Tularensis ---- tick bite ( among rodents like rabbit and deer ) ---- Tularemia Yersenia Pestis ---- Flea bite (USA Preirrie dog reservoir) -- Safety pin shape -- Plague (black death) Pasteurella Multocida ---- Cat or dog bite ---- wound infection, cellulites. * Brucellosis ( Undulant fever ) cause by ingestion of contaminated milk product or through skin contact with animal tissue e.g cattle sheep pig dogs etc. * B. Melitensis is localized to reticuloendothelial sys many cells killed by microphages but some survive & cause granulomatosis. epithelial giant cell formation with focal abscess and caseation. Osteomylitis is most common complication of undulant fever. * B. melitensis can be prevented by pasteurization of milk, vaccination of animals, or slaughtering of infected animal. * TX is usually Tetracycline other alternatives are SMX-TMP, Rifampin, Streptomycin. * Fransicella Tularensis transmitted among rabbit deer and other rodent by vector ticks, mites and lice. Human accidently infected by tick bite or inhalation. * F. Tularensis localize in reticuloendothelial cells with resultant granuloma formation, caseation, necrosis and abscess. * F. Tularensis can be prevented by vaccine in high risk group. TX of choice Streptomycin. Gentamicin in severe cases. * Pasteurella Multocida is transmitted only by cats and dogs bite. It cause wound infection and cellulites. High risk of osteomylitis and arthritis. * Pasteurella Multocida infection can be treated by penecllin, or tetracycline. * Yersenia Pestis transmitted among wild rodent by fleas. In USA prairrie dogs are main reservoir. Appear as safety pin. * More common in southwestern USA. Human infect by flea bite which result into swollen lymph node (Bubonic Plague) organism than enter into blood cause DIC & cutaneous hemorrhage. * Yersenia Pestis contain 5 virulence factor -- 1. Envelop Ag F1 (antiphagocytic) 2. Endotoxin 3. Exotoxin 4. V Ag 5. W Ag. * There are only two live bacterial vaccines BCG and vaccine for tularemia. * TX of choice streptomycin. Tetracycline is alternative. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
MYCOBACTERIUM -------- M. Tuberclosis -- Tuberculosis
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M. Bovis ----------- Cow milk ----- GI tuberculosis. M. Laprae ---------- Leprosy Nontuberculous mycobacteria M. Avium (MAC) -- Soil & water. Common cause of childhood cervical adenitis in USA. Disseminated MAC in AIDS. M. Intracellular --M. Fortuitum ------ Post traumatic and post operative soft tissue infection M. Cheloni --------- Pulmonary infection and disseminated disease * High lipid content of mycobacterium cell wall makes mycobacterium acid fast (that means it retain Carbofuchsin stain). * Organism grow very slowly -------- 8 weeks on Lowenstein - Jensen Agar. 2 weeks on Bectec medium by Niacin detection (exclusive to M. tuberclosis). Luciferose Assay detect drug resistance in few days. * Mycobacterium virulence factor is cord factor Trehalose Dimycolate which play imp role in pathogenesis. (Acidfast Bacillus) RODS
* M. Bovis found in cow milk cause GI tuberclosis (unless pesturized). Remember Strep Bovis cause carcinoma of colon. * M. Tuberclosum transmitted by respiratory aerosol droplet chiefly reside in the reticuloendothelial cells e.g macrophages. * First Tubercolsis lesion is (exudative) granulomatous surrounded by fibrous tissue with central caseating necrosis called tubercle. Parenchymal exudating lesion and draining lymph node together called Ghon Complex. * Tuberculin skin test --------- PPD test contain 5 tuberculin units called Mantoux Test. 10 mm of induration in 48 - 72 hrs is called + ve Test 5 - 9 mm in person who had not received BCG count infected. 5 mm consider + ve in AIDS pt. 15 mm consider + ve in person who had received BCG * Multiple Drug TX is used for the treatment of TB for 6 - 9 mon. -- 1. Isoniazid (6 mon) (induce hepatitis sp over age 35) 2. Rifampin ( 6 months ) 3. Pyrazinamide ( 2 months ) 4. Ethumbutal (should added in aids pt. all 4 for 12 mon) * Tuberclosis can be prevented by better housing and nutrition, Isoniazid (6 - 9 months), pasturization of milk, destruction of infected cattle. * M. Intracellular are highly drug resistant need 4 - 6 drug therapy. Clarithromicin, Ethumbutol, Rifabutin, rifampin, clofazemine. * M Fortuitum & cheloni is highly drug resistant. TX is Amikacin, Doxicyclin + surgical excision of lesion. * M Leprae cause leprosy which occur in 2 forms. 1. Lapromatous leprosy -- In which cell mediated response is poor but humoral response is intact however Ab are not protective. Shows hypopigmented macule, & cutaneous lesion. Foamy histiocytes is formed. Bacilli are regularly found in smear. Leprosy skin test is - ve. 2. Tubercloid leprosy -- cell mediated immune response limit the growth and results into granuloma. Lepromin skin test is + ve. * M Leprae cannot be grow in culture so DX is made by visualization of bacilli in acid fast stain and tubercloid leprosy few seen organism and typical granuloma is sufficient for DX. (Always remember that in leprosy False + ve serologic test for syphilis occur frequently) * TX -- Dapsone + Clofazemine for Lapromatous leprosy, vs. Dapsone + Refampin for Tubercloid Leprosy. (for 2 yrs approx)
GRAM + ve RODS
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* Include Actinomycetes, spirochetes. Mycoplasm (stain poorly because is wall less) * ACTINOMYCETES: A. Israelii (G +ve anaerobe) yellow sulfur granule: Abscess with draining sinus, PID with IUD. (Gram + ve Rods) Nocardia Asteroids -- G +ve acid fast aerobe -- Pul infection Abscess brain & kidney (in immunocompromised pt) * Actinomycetes are true bacteria resemble hyphae of the fungi because ti produce long branching filament. * A. Israelii is anaerobe and normal flora oral cavity. * A. Israelii cause abscess with draining sinus. It produce Sulfur granules (hard yellow granules) composed of mass of filament and are visible in pus. It cause abscess with draining sinus, abscess spread to brain and kidney in immunocompromised person. * Pelvic actinomycosis ( A. Israelii ) occur in women with intrauterine device from long time. * TX of A. Israelii is Penecillin G. * Nocardia Asteroid is acid fast Aerobe live in soil. It cause Pulmonary infection with abscess which can excess to brain & kidney. TX is TMP-SMX and surgical drainage of abscess. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Mycoplasm ------------- M. Pneumoniae -------------------- Atypical pneumonia (wall less Rod shape) M. Hominis --------------------------- PID M. Ureaplasm Urelaticum ----- Non gonococcal uretheritis * Mycoplasm are wall less organism so stain poorly with Gram stain. Antibiotics that inhibit cell wall syn are ineffective e.g penicillin. * Bacterial mem contain only cholesterol and grow slowly. * Mycoplasm transmitted by respiratory droplet. Tapered tip of the rod is point of attachment for bacteria. Organism inhibit ciliary motion and cause necrosis. Mycoplasm do not invade respiratory mucosa. * During M. pneumoniae (atypical Pneumoniae) autoantibodies are produce by host against RBC (cold agglutinin), brain, lung and liver cell. * Mycoplasm can be treated by Erythromycin or tetracycline. ( donot use cell wall syn inhibitor because mycoplasm is wall less ) --------------------------------------------------------------------------------------------------------------------------------------------------------------------------SPIROCHETE -------- T. Pallidum ------ Reservoir are human. Dark field immuoflorescense microscopy --- Syphilis. (Spiral Rod, thin wall) B. Burgdorferi -- Reservoir are white footed mouse & deer transmitted by tick bite (Ixodes Dommini ) Lyme’s disease. B. Recurrentis -- Transmitted by tick bite (ornithodores), person to person transmit by common louse --- Relapsing fever. B. Hermsii -------L. Interogans --- Present in urine of infected rat cat or dog etc. DX by serology or culture Leptospirosis (WEIL Disease) * Treponema Pallidum can be seen by dark field or immunofloresence microscopy. Organism cant be cultured. * Main reservoir of T. Pallidum are humans. ( remember C. Trachomatis reservoirs are human too ) * T. palladium transmitted by sexual contact & transplacentally to fetus (in 3rd month) with resultant congenital defect or still birth. * Stages of syphilis --- 1. Pri Syphilis -- Local non tender chancre formed in 2 - 10 week, ulcer heal spontaneously but Spirochete spread widely in tissue. 2. Sec Syphilis -- 1 - 3 month later maculopapular rash appear on palm and sole or moisy papule on skin or mucous mem. Moist papule on genitalia are called Condylomata lata. This stage may progress to meningitis, nephritis, hepatitis, may hal spontaneously or may progress. 3. Latent Syphilis -- No lesion appear but seologic test indicates continuous infection.
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Early latent syphilis -- last for year or two after secondary stage. Late latent syphilis -- last for many years, no symptoms, lead to Tertiary syphilis. 4. Tertiary Syphilis -- Show granuloma (gumma) on skin and bone. CNS involvement results into Tabes paresis. CV lesion results into aortitis aneurysm. Treponema rarely seen at his stage. * Maculopapular rash of Sec syphilis must be distinguished from rocky mountain fever that also produce rash on palm & sole. * Treponemal Tests 1. Non treponemal Ag test -- * Cardiologic (Ag) mixture of IgG & IgM are called Reagin Ab. (non specific test) * VDRL * RPR (rapid plasma reagin). 2. Treponemal Ag test -- * ( FTA-ABS ) Fluorescent treponemal Ab absorbed test. (specific test) * ( TPHA ) Treponema pallidum hem agglutinin test. * ( MNA-TP ) Hemagglutinin assay on micro titer plate. * TX is Benzathine penicillin G. Aqueus Penicillin G for neurosyphilis. Tetracycline and erythromycin are alternatives. * Jarisch Herxheimer Reaction --- characterize by fever, chill, myalgia, influenza like symptom due to lysis of treponema which results into endotoxin release. * Borrelia Burgdorferi reservoirs are white footed mouse and deer it transmitted by tick bite. It cause Lyme dis. * Lyme Dis is DX by serologic test, IgG & IgM rising titer with ELISA, Western Blot Analysis, and PCR. Culture is rarely + ve. * 3 Stages of Lyme dis -- 1st Stage -- Erythma chronicum migran, Red rash clear center at bite site. Flue like symptoms ( fever, chill, Fatigue, headache, arthralgia ). 2nd Stage -- Weeks or month later myocarditis, pericarditis, various form of heart block. Acute septic meningitis, Peripheral & Cranial neuropathy (bells Palsy). 3rd Stage -- Arthritis usually of large joint. Chronic progressive CNS dis also occur. * 1st stage can be treated by Doxycycline and amoxicillin where as 2nd & 3rd stage is treated with penicillin G or Ceftriaxone. * Leptospira Interogans secreted in urine of infected animal like Rat, cat, dogs ( domestic live stock). Incubation period is 10 days. * Organism could be ingested or pass through skin enter the blood (spirichetemia) and effect liver, kidney and brain. * 2 phases of leptospirosis. 1st Phase -- Fever, chill, intense headache. 2nd Phase (immune phase) -- Effect liver (jaundice, hemorrhage), uremia, Aseptic meningitis. * urine shedding of organism may continues from 6 - 11 months. * TX of choice is Doxycycline, Penecillin G. Doxycycline can be used as prophylaxis. It may show Jarisch herxheimer like reaction. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------CHLAMYDIA ---------- C. Psittaci ---------- produce glycogen. Present in bird feces ---- Atypical pneumonia. Shows (Obligate IC parasite) Levinthal - cole - lillie bodies. C. Trachomatis -- Trachoma, conjunctivitis, uretheritis, Genital tract inf (in both sexes), Pneumonia, lymphogranuloma venerium. C. Pneumoniae - Atypical pneumonia. * Chlamydia is obligate Intracellular parasite because they lack ability to produce sufficient energy to grow. * Chlamydia has spore like elementary bodies and reproduce by binary fission. * It appears as inclusion bodies in cell can be stain (important DX test). * Natural reservoir of C. Psittaci are birds feces where as C. Trachomatis reservoir are humans. * C Trachomatis is most commonly sexually transmitted Dis. (STD)
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Trachoma -- cause African blindness, chronic conjunctivitis. Genital tract inf (PID, cervicitis, salinities, epididimitis, prostates, proctitis), eye or respiratory tract inf. type L1 - L3 Lymphogranuloma venerium, (sexually transmitted). DX by Frei Test.
* C. Trachomatis -- type A,B,C type D - K
* Chlamydia infection is DX by --- Cytoplasmic inclusion by Giemsa stain, immunoflorescence. Elisa (by exudates) Serologic test. * C. Psittaci inclusion contain glycogen where as C. Pneumoniae do not contain Glycogen. (psittaci pneumonia show Levinthal cole lillie bod) * Chlamydia can be TX with tetracycline, Erythromycin, Azithromycin, ceftriaxone. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
RICKETTSIAE -------- R. Rickettsii -- transmitted by tics, mites & fleas bite -- Rocky mountain spotted fever. DX by (IC Parasite except R.Q) Weil-Felix test. Coxiella B --- transmitted by inhalation -- Q Fever ( pneumonia + hepatitis suggest Q fever). R. Typhii ----- not zoonotic because transmitted by human body louse (Pediculcus) Endemic typhus. R. Prowazkeii -- cause Epidemic typhus, Brill’s dis. Rickettsia T ------- Scrub Typhus, chigger borne typhus. R. Quintana ----- Trench fever (it is not intracellular parasite) * Rickettsia are obligate intracellular parasite except R. Quintana. * R. Rickettsii cause rocky mountain spotted fever, it results in DIC. Dis is DX by Weil-Felix test (antirickettsial Ab in serum). * Rocky M S Fever usually occur in spring & summer in East coast of USA. It can be prevented by vaccine and insect repellent. * Rickettsia cause cellulites damage to skin vessels Rash, edema, hemorrhage, fever, Petachie. (except C. Burnetti ) * Patechiae first appear on hand & feet than move toward trunck. DIC, circulatory collapse in severe cases. Delirium, coma can occur. * Rocky M S Fever can be TX by Tetracycline, or chloramphenicol. * Coxiella Burnetti cause Q Fever initially characterized by influenza like symptoms than pneumonia, hepatitis is frequent. Rash, endocarditic is rare. It can be prevented by vaccine. (pneumonia with hepatitis suggest Q fever) * TX is Tetracycline or chloramphenicol. * R. Typhi cause endemic typhus, it is not zoonotic disease because transmitted by human body louse (pediculus). It is associated with war and poverty. * R. Prowazkeii epidemic typhus and Brill’s Dis. It is associated with war and poverty. * R. Quintana cause Trench fever and it is exceptionally not a intracellular parasite. * WEIL-FELIX TEST -- Proteus valgaris Ag cross react with Rickettsial Ag ( only R. rickettsii, R. Tutsugamushi, R. Prowazkeii ) that’s why it is also used to detect Rickettsia in pts serum. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
VIROLOGY
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* Viruses are either DNA or RNA which are further classified into families and if they are enveloped, nonenveloped. * Remember human cell do not contain RNA polymerase. ? DS DNA V---- 1. HEPADNA V -- HBV ---- Hepatitis, Hepatocellular carcinoma. ( enveloped viruses )
2. HERPES V -- HSV I -- Gingivostomatitis, Herpes labialis, Keratoconjunctivitis, encephalitis, Diseminated inf. TX Acyclovir. HSV II - Genital herpes, neonatal herpes, aseptic meningitis ------ TX Acyclovir. VZV ---- Varicella (chicken pox), Zoster (shingles) ------ TX Acyclovir, Famcyclovir EBV ---- Infectious mononucleosis, Burkett lymphoma, B cell lymphoma, Nasopharyngeal carcinoma, thymic carcinoma. (no TX or Acyclovir) CMV -- Cytoplasmic inclusion dis, hetrophil - ve mononucleosis (in aids pt), Post surgical inf – Tx Gangcyclovir, Foscarnet. 3. POX V ------- SMALL POX V ------- (only DNA virus that replicate in cytoplasm) Small pox, encephalopathy VACCINIA V ---------- (replicate in cytoplasm)?. Cow pox (milkmaid blisters), Encephalopathy MALLOSCUM C V -- Small pink wart on skin.
* Hepadna, Herpes and Pox virus families are double stranded (DS) DNA enveloped viruses. * HSV I become latent in cranial sensory ganglia, where as HSV II become latent in sacral and lumbar ganglia, * VZV become latent in cranial and thoracic sensory ganglia (dorsal root ganglia of lumbar and sacral). ? * EBV become latent in B lymphocytes where as CMV reside in leukocytes, epithelial cells and kidney. * HSV I transmitted via saliva infection occur on face. Vs. HSV II transmitted sexually infection occur on genital area. * Oral genital sexual practice results into infection with switched location. It accounts for 20% of cases. * HSV attached to the cell surface at the site of Fibroblast growth factor (FGF) enter the cell uncoating of virus viral DNA enter in nucleus early viral mRNA transcribed by host cell RNA polymerase early protein synthesis in cytoplasm. Than viral DNA polymerase replicate the genome DNA shut off the early protein synthesis and late protein synthesis begin which is late structural protein protein enter the nucleus viron assembly viron obtain envelop by budding from nuclear mem. * Characteristic lesion of HSV is Multinucleated giant cell. TX of choice for both type of HSV infection is Acyclovir. * Acylovir course of action is viral Thymidine Kinase, and DNA polymerase. * DX of HSV infection -- Rapid DX by skin lesion by Tzanch smear (with giemsa stain) Rapid DX of encephalitis can be made by Flourescent Ab staining of brain biopsy. (CSF is worthless) Serologic TX in primary infection (neutralization test). * Varicella (chicken pox) is primary infection transmitted by respiratory droplet and direct contact with lesion than after recovery VZV become latent in lumbar & sacral dorsal root ganglia later in life it appears as a shingles (zoster) which is vesicular skin lesion and nerve pain. * Varicella (chicken pox) occur only once in life because immunity last life time where as zoster can still recur despite immunity. * VZV can be prevented by acyclovir, Famcyclovir, VZIG (varicella zoster Ig), vaccine (vaccine does not eliminate the latent state) * CMV transmit by Transplacentally (in fetus), mother’s milk (in infant), urine (in young children), sexually (in adults), blood, organ transplant like kidney.80% adults live in USA have Ab. * CMV in fetus cause Cytomegalic inclusion dis congenital dis (microcephaly, seizures, deafness, jaundice, purpura, hepatospleomegaly). CMV is one of the leading cause of mental retardation in USA. * CMV TX is Gangcyclovir and foscarnet. DX ? * EBV cause Infectious mononucleosis, Burkett’s lymphoma (in African child). B cell lymphoma & nasopharyngeal carcinoma ( in Chinese’s ), where as thymic carcinoma ( in USA ). * EBV is transmitted through saliva ( kissing ) sp in college students. It infect mainly lymphoid tissue. 90% people have
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY”
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Ab in USA. *There is no antiviral therapy. Acyclovir in life threatening infection. * Hetrophil Ab test is useful in early DX of infectious mononucleosis (by two week of illness). IgG VCA (viral capsid Ag) Ab response is used to detect prior infection of EBV where as IgM VCA Ab response shows early illness with EBV. * Small pox and Vaccinia virus contain DNA dependant RNA polymerase This enz is required for viral replication in cytoplasm. * The pox virus is the only exception that they replicate in the cytoplasm rather than nucleus. * vaccinia virus vaccine is no longer used because of high incidence of post vaccine incidence of post vaccine encephalitis, generalized vaccinia and vaccinia gangreniosa. Military personals are still vaccinated. * MCV cause small pink wart like benign tumor of skin the lesion is different from papilloma warts. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------DS DNA V-------- 1. Parvo v (SS) -- B19 V -- Exceptionally SS DNA V -- Erythma Infection (5th Disease) recover in 1-2 wks. (non enveloped v Transient Aplastic crises in pt who have preexisting hemolytic dis. Parvo is SS v) 2. Papova v -- HPV -- Carcinoma, Papilloma, warts -- TX Podophylin, IF, Liquid nitrogen, salicylic acid, or surgery. JCV -- Progressive multinodal leukoencephlopathy death. BKV -- associated with kidney transplant immunosupressed pt. 3. Adeno v -- Adeno V -- Pharyngitis, pneumonia, conjunctivitis, Keratoconjunctivitis, hemorrhagic cystitis, infantile gastroenteritis.
* Papova and Adeno viruses are DS DNA viruses where as Parvo virus (B- 19 v) are exceptionally single stranded (SS) DNA virus. * Adeno v are the only virus with fiber protruding from the capsid. Fibers are organ of attachment and hemagglutinin and are toxic to human cell when free. * Live attenuated vaccine of adeno v type 3,7,21 ( cause respiratory inf) is available for military personals. * Adeno v type 8, 19 keratoconjunctivitis. Type 11,12 hemorrhagic cystitis. Type 40,41 Infantile gastroenteritis. * HPV 16,18 Carcinoma of cervix, penis, anus and premalignant lesion (intraepithelial neoplasia). * HPV 1 skin and planter warts where as HPV 4,6,11 genital warts (condylomata acuminata). * Viral DNA integrated into host cell DNA in the vicinity of cellular proto-oncogene where HPV gene E6 & E7 interfere with the growth inhibitory activity of protein encoded by Tumor suppressor gene with resulting oncogenesis. * Koilocytes (Cytoplasmic vacuoles) are the hallmark of the infection by HPV in skin biopsy specimen. * Podophylin & IF is the TX of Genital warts. Liquid nitrogen can be used in skin warts. Other TX salicylic acid & surgical removal. * JCV is associated with progressive multinodal leukoencephlopathy death. * BKV is associated with immunosuppressed kidney transplant pt. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
SS RNA V ---- 1. Orthomyxo v -- Influenza v (A,B,C) -- exceptionally replicate in nucleus, 2 spikes -- Influenza.
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KICK THE BOARDS. USMLE STEP 1 “MICROBIOLOGY” (Enveloped v)
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TX is Amantadine, Ramantadine. 2. Paramyxo v ------- Measles v -- measles (koplik spots), Subacute Panencephalitis yrs after measles inf. (Giant cell formation Mumps v -- Mumps (orchitis, parotitis, Oophoritis, pancreatitis, meningitis) same spike) RSV -- contain fusion protein rather than hemagglutinin & Neuraminidase – Pneumonia, bronchiolitis in infant. TX: Aerosol Ribavirin. Para influenza v -- Croups & pneumonia (children), common Cold (adult). 3. Togo v -------- Alpha v -- Rubella -- Rubella (C malformation, PDA, cataract, deafness, mental retardation, Prog Encephalitis). Rubi v -- EEEV -- sever Encephalitis (atlantic / gulf state). Transmit by mosquito. Wild bird are reservoir. WEEV -- Encephalitis (west Mississippi). Transmitted by mosquito. Wild bird are reservoir 4. Rhabdo v ---- Rabies v -- cause rabies (encephalitis may occur). Negri bodies. TX is HDCV and RIG. 5. Retro v -------- HIV -- AIDS -- TX is Azydothymidine, Dideoxyinosine ( inhibit DNA syn). Saquinavir, Indinavir (inhibit protease). HTLV -- Tumor, leukemia, lymphoma. 6. Filo v ---------- Ebola v -- Hemorrhagic fever Marburg v -- Hemorrhagic fever 7. Corona v ----- Corona v -- URT infection, 8. Arena v ------- Lymphocytic chorio meningitis v -9. Delta v -------- HDV -- Hepatitis D 10. Flavi v -------- HCV -- Hepatitis C Hepatocellular carcinoma. (Arbovirus) YFV --Yellow Fever (tropical south America) Dengue v -- Brake bone fever (dengue), Hemorrhagic fever --- South Asia, Caribbean. St Luis encephalitis v -- Encephalitis -- urban USA 11. Banya v ------ California encephalitis v -- Encephalitis (North central US states). Transmit by mosquito. Small mammals are reservoir. (Arbovirus) Hanta v -- Korean hemorrhagic fever.
* Arena v, Banya v, Filo v, Orthomyxo v, Paramyxo v, & Rhabdo v have - ve polarity where as rest have + ve polarity except Delta virus. * Orthomyxo & Paramyxo v have helical nucleocapsid where as Togo v (rubella) have Icosahedral neucleocapsid. * Antigenic shift -- is the major change based on the reassortment of the genomic piece occur every 10 - 11 yrs. * Antigenic drift -- is the minor change base on mutation occur every yr. * Influenza virus (SS RNA v) envelop is covered with two different type of spikes, one spike contain hemagglutinin and binds to cell surface receptor to degrade protective mucous layer and initiate infection where as other spike contain Neuraminidase which cleave neuramic acid (sialic acid) to release progeny virus. * Influenza v specifically influenza A shows changes in antigenicity of surface protein (hemagglutinin and Neuraminidase) dramatically. These changes are attributed to reassortment of the segment of genome RNA (entire segment of RNA exchange). * Influenza viron RNA polymerase transcribed the segment genome into 8 mRNA which is translated into viron protein in cytoplasm than the helical ribonucleic protein assemble into cytoplasm viron are released by budding (neuraminidase play a role in release). Remember synthesis of progeny RNA genome occur in nucleus. * Influenza v have group specific and type specific Ag. The internal ribonucleic protein is the group specific Ag which
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group influenza into type A,B,C. where as hemagglutinin & neuraminidase are type specific Ag. * Ab against group specific Ag does not prevent dis where as Ab against type specific Ag (Hemagglutinin)does prevent dis. * Ab against neuraminidase does not neutralize the infection but do reduce infection. * TX of influenza is Amantadine inhibit uncoating of virus in host cell by binding to matrix protein in the viron transcription of virus does not occur. Other TX is Ramantadine (few side effects). * Influenza v vaccine consist killed A and B virus (made little protective IgA). Protection last 6 months. Vaccine should use in elderly people (> 65 yrs age) and in those with chronic respiratory and Cardiovascular condition * Influenza v is the only RNA v that replicate in the nucleus where as Small pox v & vaccinia v are only DNA v that replicate in Cytoplasm. * Paramyxo v cause measles, mumps, RTI, parainfluenza v infection. Paramyxo virus has non segmented genome, Hemagglutinin & neuraminidase are on the same spike. Infection cause Multinucleated Giant cell formation. * Paramyxo v RNA polymerase transcribe the - ve polarity genome into mRNA genome it self is not infectious rather hemagglutinin and neuraminidase is infectious. Some Paramyxo viruses cause hemolytic. * In children Paramyxo v cause Croups and pneumonia where as Common cold in adults. * Measles v infect URT epithelium enter blood infect reticuloendothelial cell and replicate again enter blood and reach to skin and cause rash. Rash cause primarily by catatonic T cell attacking on measles infected reticuloendothelial cells in the skin. Ab mediated vasculitis may play a role. Multinucleated giant cell are characteristic of lesion. * Measles characterized by Koplik spot (bluish gray spot on buccal mucosa). * Subacute Panencephalitis occur 1 / 1000 cases several yrs after by variant of measle v Dementia and death. * Immunity is life long after infection. IgG Ab play a role cell mediated immunity is imp. * Pt with agammaglobulinemia have normal course of dis and subsequently become immune. ? * Measles vaccine is live attenuated vaccine (SC at 15 month age) & later with booster. Usually combine with rubella & mumps. * Remember progressive encephalitis occur in pt with congenital Rubella. * Mumps v infect URT enter blood enter in parotid gland, testis, ovaries, pancreas, and in some cases meninges. * Mumps v contain 2 spikes, one contain hemagglutinin & neuraminidase, other contain cell fusion & hemolytic activities. * Orchitis can lead to sterility in male (pressure necrosis of spermatocytes by expansion of fibrous tunica albuginea. Immunoglobulin is not useful. * Mumps vaccine is live attenuated vaccine immunity last 10 yrs. Usually combine with rubella and measles vaccine. * RSV is major cause of pneumonia and bronchiolitis in infants. Spike are fusion protein (not hemagglutinin or neuraminidase). Fusion protein cause cell to fuse, forming syncytia. Out breaks occur in hospitalized infants in winter. TX Aerosolized ribavirin (if severe). * Rubella v is teratogenic in fetus (transmitted Transplacentally in 1st trimester) congenital malformation, patent ductus arteriosus, cataract, deafness, mental retardation and also Progressive encephalitis. * Amniocentesis can reveal rubella v in fluid, shows definite inf. (shows IgM & IgG titer long after maternal Ab has disappear). * Rubella vaccine is live attenuated vaccine usually combine with measles and mumps vaccine. Immunity last 10 yrs. Side effects are transient arthralgia in some women. * Rabies v can infect all animal. Post exposure immunization involve the use of both vaccine & immunoglobulin & wound cleaning. * Rabies may cause life threatening encephalitis. It transmit by animal bite. Decision to give post exposure immunization depends upon type of animal and vaccine status of animal. * Early symptoms are fever, malaise, myalgia, headache, vomiting paresthesia at the site of viral inoculation. Late in
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course can lead to excessive salivation with all signs of CNS irritation (like motor activity, combativeness, spasm, involuntary contraction of diaphragm etc). * Rabies can be DX by Flourescent Ab test, Negri bodies in Ammon horn of the brain. * Rabies vaccine made in human diploid cell, virus in vaccine is inactive. Human Diploid cell vaccine (HDCV) and Human Rabies Immunoglobulin (RIG) are recommended. 5 HDCV doses (different sites) + 1 RIG given once. * Dengue Virus hemorrhagic fever cause severe dis with 10% mortality rate. It can cause shock and hemorrhage specially into GIT and skin due to cross reacting Ab production at the time of second dengue infection. (Immune complex composed of virus & Ab are formed activate complement vascular permeability thrombocytopenia shock hemorrhage results).
RNA V ------- Picorna V (SS) -- Polio v -- 3 serotypes. Fecal oral route. Infect ant horn of spinal cord -- poliomyelitis. (nonenveloped v) Coxachie v (A & B) -- Herpangia, HFM dis (by A). Myocarditis, pericarditis, pancreatitis (by B). both cause meningitis & URT inf Echo v ---- aseptic meningitis, hemorrhagic conjunctivitis, diarrhea. HAV -------- hepatitis A Rhino v --- Common cold Calcivi v (SS) -- HEV ------------ hepatitis E. mortality rate in pregnant women. Norwalk v --- Gastroentritis in developed countries. Effect older children and adults. Illness is mild need no TX. Reo V -- Rota v -- Gastroentritis in children. Attached to adrenergic receptor. DX by stool by Elisa, RIA. Reo v (DS) -- Colorado tick fever v -- myalgia, malaise (rocky mountain). Transmit by mosquito. Disease subside with in week. * Picorna viruses are Entero v (infect enteric tract) except Rhino virus which cause common cold. * Picorna viruses are SS + ve polarity, nonenveloped viruses. * Polio v infect primates because the receptor they attached to are present only in primates cell mem. (transmitted by fecal oral route) * Polio has 3 serotypes (possess different antigenicity). Immunity against dis required the presence of Ab against all 3 serotype. * After uncoating Polio v genome RNA function as a mRNA and is translated to very large polypeptide called Non Capsid viral protein which than cleaved by protease to form Capsid protein that contain RNA polymerase which syn progeny RNA genome. * After replication of Polio v in or pharynx and small intestine (sp Lymphoid tissue) enter blood enter CNS (also spread retrograde by nerve axon) where it replicate again in motor neuron located in the ant horn of the spinal cord death of neuron which results into flaccid paralysis. * If Polio v infect Brain stem cause Bulbar poliomyelitis with Resp paralysis Death. (rarely damage cerebral cortex). * Polio vaccine may be killed or lived. Live vaccine is preferred because it induce IgA response too. * Coxachie v type A cause flaccid paralysis, myositis in mice (fatal), Herpangia, hand foot & mouth dis (in humans). * Coxachie v type B cause less severe Myocarditis, pericarditis, pancreatitis (type B4 suspect to cause juvenile diabetes), Pleurodynia, * Both groups cause Meningitis and URT infection. * Herpangia is characterize by fever, sore throat tender vesicle in oropharaynx. * Hand Foot & mouth dis characterize by vesicular rash on hand foot and ulceration in mouth. * Pleurodynia (devils grip, Bornholm dis) cause fever, severe pleuritic type chest pain. * Myocarditis and pericarditis shows sign and symptom of CHF. * Rhino v is acid labile, replicate at 33 C and has 100 serotype which made syn of vaccine impractical. It cause
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common cold and transmitted by respiratory droplet, contaminated hand and objects. * Reo v (Colorado tick fever virus) is DS RNA virus, Icosahedral capsid without envelop. Viron polymerase required for syn of mRNA and RNA templet. Tx is supported, illness usually subside with in a week. * Rota v is clinically imp Reo v because it cause gastroenteritis in young children, there site of attachment is adrenergic receptor. * Rota v can be DX by stool by Radioimmunoassay or Elisa. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Measles, mumps, Rubella, Polio, YFV all has live attenuated vaccine. * Guarnieri bodies found in variola.
Hepatitis v --- HAV (Picorna v) -- SS RNA v ------------------------- DX by IgM anti HAV. HBV (Hepadna v) -- DS DNA v. enveloped --------- HBsAg (acute or chronic inf), HBcAb (IgM) indicates acute or recent inf. HCV (Flavi v) -- SS RNA v. enveloped ---------------- HCV Ab in serum (Elisa). Enz immunoassay detect C200, C33c, C22-3 (by 3 -5 month) HDV (Delta v) -- SS RNA v. enveloped ---------------- HCV Ab (Elisa) HEV ( Calcivi v) -- SS RNA v. --------------------------- no test. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Virus Genome DNA polymerase Envelop Transmission Chronic state --------------------------------------------------------------------------------------------------------------------------------------HAV SS RNA No No Fecal oral route No Yes HBV DS DNA Yes Yes Blood / Sex Yes Yes HCV SS RNA No Yes Blood / Sex / Transplacentally / During birth Yes No HDV SS RNA No Yes Blood / sex Yes No HEV SS RNA No No Fecal oral route No No ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------HBV Antigens Acute dis window phase complete recovery chronic career state --------------------------------------------------------------------------------------------------------------------------------------------------------------------------HBs Ag + ve - ve - ve + ve HBs Ab - ve - ve + ve - ve HBc Ab + ve + ve + ve + ve HBe Ag + ve - ve HBe Ab - ve + ve ---------------------------------------------------------------------------------------------------------------------------------------
* Hbe Ag is an important indicator of transmissibility. * During window period only Hbc Ab (IgM) & Hbe Ab are present. (Most sensitive test is HBV DNA detection, not routinely required for DX) * Ab against HBV begin to form 2 month after exposure. * HBV DNA polymerase synthesize the missing portion of DNA (Double stranded close circular DNA) in the nucleus
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some Viral DNA integrate into hepatocyte DNA and some serve as a template for mRNA synthesis by cellular mRNA polymerase mRNA protein synthesis and sever as template for the Minus strand of progeny DNA (than minus strand serve as plus strand of the DNA genome). Than RNA dependant DNA syn take place in the cytoplasm, later progeny HBV released by budding through cell mem. (This is similar but different in process from retroviruses). * HAV infection results into life long immunity where as HBV life long immunity is mediated by humoral Ab against HBsAg. * HBV and HCV both predispose to Hepatocellular carcinoma. * HDV infection resembles Hepatitis B. HDV use HBV genome for replication and shows Hbs Ag on it. Both viruses when together cause more severe infection than alone. * HEV infection clinically resemble with Hepatitis A inf with the exception of high mortality rate in pregnant women. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Arbovirus ----- Toga v -------- EEEV ------------- encephalitis WEEV ------------ encephalitis Flavi v -------- SLEV ------------- encephalitis YFV --------------- Jaundice fever Dengue v -------- Break bone fever, dengue hemorrhagic fever Bunya v ------ CEV --------------- Encephalitis Reo v ----------CTFV ------------- CTF * All above viruses are transmitted by mosquito whereas other Arboviruses are transmitted by other vector (arthropod’s). ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Slow Viruses -------- JCV ----------------------------- Progressive multifocal leukoencephlopathy (PML) Measle v ----------------------- Subacute sclerosing Panencephalitis (SSPE) HIV ------------------------------ AIDS Kuru ----------------------------- By eating dead man’s brain. Tremor, Ataxia Death. in women. Cruetzfeldt Jakob Dis ---------- Dementia, Ataxia coma and death. Transmit Iatrogenically. * Slow viruses causes CNS dis. It is characterize by long latent period, a gradual onset and progressive invariably course. The term slow refer to dis not the rate of replication of virus. * PML is caused by JCV, it is a fatal demyelinating dis of CNS. Ab present in 75 % population shows wide spread infection. Usually occur < 15 yrs of age, more in male. CNS sign and symptoms, atrophy and ventriculomegaly. * SSPE caused by measles v & its variant. It results into inflammation of many area of brain. Initially shows personality changes and eventually dementia and death. It shows Measles Ab in blood and CSF. * Remember Progressive encephalitis occur with congenital rubella. * Kuru (fatal) occur by eating dead mans brain tremor, ataxia but not dementia (spongiform brain appearance). Occurrence in women. * Cruetzfeldt - Jakob dis dementia & ataxia coma & death. 90% cases sporadic,10% familial, iatrogenically (rare). -------------------------------------------------------------------------------------------------------------------------------------------------------------------------Retro Viruses --------- HIV (1 or 2) -------- AIDS HTLV ---------------- Carcinoma. Leukemia, Lymphoma. * HIV (SS RNA + ve Polarity, enveloped). HIV genome contain 3 typical retroviral genes gag, pol, env. env encodes gp160 which cleaves to form 2 surface enveloped GP 1. gp 120 -- interact with CD4 (mutate rapidly) gag ---- encodes internal core protein p24. 2. gp 41 ---- mediate cell fusion Pol ----- encodes several protein include viron reverse Transcriptase. tat ------ encodes the protein that enhance viral gene transcription. It also suppresses the syn of class I MHC protein there by reducing the ability of cytotoxic T cell to kill HIV infected cell. * HIV 1 is more common than HIV 2 which has 40% sequence homology with HIV 1. * Gene that encode gp120 mutate rapidly resulting in many antigenic variant, that’s why production of effective
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vaccine is difficult. * HIV is transmitted sexually and by blood, prenatal transmission is either via birth or breast milk. * HIV infect CD4 lymphocyte (helper T cell), macrophages and brain monocytes. * Acute stage of HIV begins 2 - 4 week after infection. It characterize by mononucleosis like symptom, fever, lethargy, sore throat, generalized lymphadenopathy, maculopapular rash, leucopenia with normal CD4 count. Ab appear with in 2 months. * Latent period measured in yrs, pt is asymptomatic but large amount of HIV is being produced by lymph node but remain sequestered with in lymph node. (remember virus does not enter in latent period) * Late stage in which CD4 count < 400/mm3 Aids. * Lab Test ------ Elisa ------------------------------ it detect Ab against HIV Ag. Western Blot Analysis ----- provide definitive DX PCR ------------------------------- very sensitive to detect HIV DNA in infected cell. * HIV TX : Azidothymidine (AZT, Zidovudine, Retrovir) is TX of choice -- it inhibit HIV replication by Interfering with proviral DNA syn. Dideoxyinosine (ddI, Dideoxycytidine, Videx) in pt who are intolerant to AZT -- it inhibit viral replication by interfering proviral DNA syn. Saquinavir, Indinavir are protease inhibitor but always used in combination with drug of choice.
Mycology FUNGAL DIS: 1. Cutaneous -- Malasazi -- Normal skin flora - Tinea versicolor (Pityriasis), cause catheter related sepsis. (All are Dermatophytes) Cure by catheter removal Microsporium -- Tinea Curaris. Effect inguinal area. Out break in children by Trichphyton Trichphyton -------- Tinea Captis -- out break in children by Trichphyton Epidermophyton - Tinea Pedis -- out break in children by Trichphyton Cladosporium ----- Tinea Negra -- out break in children by Trichphyton 2. Subcutaneous -- Sporothrix (Dimorphic) -- Sporotrichosis -Cladosporium - Chromomycosis -- wart like lesion -Philadophora -- Chromomycosis -- wart like lesion -Petrillidium ----- Mycetoma -- color granule in pus -Medurella ------- Mycetoma -- color granule in pus -3. Systemic -------- Coccidioides imitis - Coccidioidomycosis -Histoplasmosis - Histoplasmosis -- Cave exploration, dirt, bird dropping -- Acute or chronic pulmonary dis. Blastomyces - Blastomycosis -- from soil, rotting wood or vegetable -- Indolent pulmonary inf with fever. Paracoccidioides --- Paracoccidioidismycosis -- ulcer of mouth, oropharaynx, nose & draining lymphnode.
(All are Dimorphic) ?
4. Opportunistic -- Cryptococcus N - Cryptococcus (50% cases occur in AIDS pt) meningioencephalitis. DX by lumbar puncture Candida Albicans - Candidiasis (Moniliasis), Thrush -- in Pregnancy, diabetics, Aids, Or due to Glucocorticoid therapy. (MOLD) Aspergillus - Aspergillosis. V shaped 45 -- Lung invasion in immunocompromised pt tissue necrosis, infarction. (MOLD) Mucor, Rhizopus - Mucormucosis. Right angle 90 -- Sinus & lung inf in pt with organ transplantation (by mucor). Inf in pt with preexisting dis like Diabetic ketoacidosis (by Rhizopus)
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* Fungus exist in yeast (single cellular, Asexual) and Mold (long hyphae filament). * Dimorphism -- Fungal quality in which fungus exist in 2 different forms at 2 different temperatures. 1. It exist as mold at ambient temp 2. It exist as yeast at body temp --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Fungal Cell Wall Bacterial Cell Wall Human Cell Wall --------------------------------------------------------------------------------------------------------------------------------------Contain Chitin Contain Peptidoglycans Contain Chlesterol Sterol is present (ergisterol, zymosterol) Sterol absent (except mycoplasm) Eukaryotic Prokaryotic --------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Candida is the part of normal body flora, found in mucous mem of URT, GIT and vagina. * Some Fungus reproduce sexually (by mating) and produce sexual spores where as most fungi reproduce Asexually by forming Asexual spores called Conidia. e.g. Arthrospores produce by Coccidioidis imitis, Chlamydospores produce by candida, Blastospores produce by blastomyces, sporangiospore produce by Mucor & Rhizopus. * Fungi that do not form sexual spores are fungi imperfecti. * Fungal infection cause granuloma or suppuration. * Granuloma formation in Paracoccidioidomycosis, Histoplasmosis, Blastomycosis. * Suppuration formation in Aspergillosis, Sporotrichosis. * Lab Test -- Direct microscopy (treated with 10% KOH) Culture can be on Subourad’s Agar. Serologic test (complement fixation test) . Cryptococcus neoformans in CSF is DX by Latex Agglutinin test. * Amphotracin B and various other Azoles are toxic to fungus only because it efect only ergosterol which is not present in bacterial or human cell mem. Cutaneous and Subcutaneous Mycosis. * Dermatophytes infect only superficial keratinized structure like skin, hair, nail. * Dermatophytes spread from infected person by direct contact and by animals. * Typical Tinea lesion is characterized by pruritic papules, vesicles, broken hair, thicken broken nail, crust. * Tinea can also be identified by Fluorescence when exposed to UV light from wood lamp. * Infected person with hypersensitivity to fungus cause Dermatophytid (Id) Reaction which is circulating Ag in blood. * Sporothrix Schenckii (dimorphic) is acquired by trauma typically by thorn local pustule or ulcer along with draining lymphatic. Systemic Mycosis. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Infection
Geo Distribution
Site of inoculation
Skin test
Complement fixation test
--------------------------------------------------------------------------------------------------------------------------------------Coccidioidomycosis Histoplasmosis Blastomycosis Paracoccidioidomycosis
Mid SW USA,(CAL, AZ) Latin Ame Mississippi, Ohio river valley E Mississippi river, Central Amer Latin America
Lung Lung Lung Lung
5mm induration in 48 hrs 5mm of induration Skin test is of little value Skin test rarely helpful
CF Ab low initially, Rise with disseminated dis CF 1:32 Titer is DX No CF ( tissue biopsy) CFT + ve, (DX usually made by culture)
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Dimorphism
TX in Primary dis
TX in Disseminated dis
TX in meningitis
--------------------------------------------------------------------------------------------------------------------------------------Coccidioidomycosis Arthrospores in soil / Spherules or endospores in tissue Ketoconazole Histoplasmosis Mold in soil / Yeast in tissue Ketoconazole Blastomycosis Mold in soil / Yeast in tissue (single broad base bud) Itraconazole Paracoccidioidomycosis Mold in soil / Yeast in tissue (wheel appearance multiple bud) Itraconazole
Amphotrecin B Amphotrecin B Amphotrecin B Amphotrecin B
Fluconazole Itraconazole
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* Immunosuppressed person is a candidate for candidiasis, Candida Albicans as a normal flora appear as oval yeast but when invasive appear as budding tissue (Psuedohyphae). TX Nystatin, Ketoconazole, Ciclopirox. * Cryptococcus neoformans is an oral budding yeast surrounded by wide polysaccharide capsule which is striking feature. * Soil and bird dropping are habitat for C Neoformans. * Reduced cell mediated immunity results into Cryptococcal meningitis DX procedure of choice is lumbar puncture, by Latex Agglutinin test, Capsular Ag titer, + serologic test. Tx is Amphotrecin B with Flucytocine. In Aids IV Amphotrecin B alone. * Note: Cryptococcus is yeast cause dis in Aids pt whereas Cryptosporidium is Parasite Cause diarrhea in Aids pt. MOLD : * Aspergillus Hyphae is V shaped 45 with parallel wall where as Mucor hyphae are right angle 90 with irregular wall. * Aspergillus Conidia exist in radiating chain where as Mucor conidia exist in sporangium. * Aspergillosis occur in immunocompromised, abraded skin, burn wound. * Mucormycosis (Mucor, Rhizopus) occur in immunocompromised, Organ transplant pt, Diabetic ketoacidosis, leukemia, burnwound. * Mucormucosis paranasal sinus, nose & lung inf. Vascular invasion, hemorrhagic or ischemic necrosis are prominent finding. * Remember Mycoplasm is bacteria, Histoplasmosis is Fungus and toxoplasm is parasite. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
PARASITOLOGY
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PARASITES ---- 1. PROTOZOA ----- 1. Intestinal 2. Blood 3. Urogenital 2. METAZOA ------ NEMATODES (Round worm) ------------------------------------------- Intestinal Tisuue Platyhelminths (Flat worm) ----------- Trematodes (Tape worm) Cystodes (Flukes)
PROTOZOA - 1. INTESTINAL -- E. Histolytica -- nonmotile Cyst has 4 nuclei 8 Trophozoites(motile). Trophozoite has 1 nuclei - Tx metronidazole G. Lamblia ---- nonmotile Cyst has 4 nuclei 2 Trophozoites (motile). Trophozoite has 2 nuclei - TX metronidazole Cryptosporidium -- Severe Diarrhea in Aids pt. Blantidium Coli --- Dysentery Isospora Belli -----2. BLOOD -- T. Cruzi -- Chagas dis, Vector Ruduvid bug, South USA and South America -- TX Nifurtimox. T. Gambians -- Sleeping sickness, vector Tsetse fly T. Rhodiensi -- Sleeping sickness, Vector Tsetse fly L. Donovan -- Kala Azar. vector is Sand Fly L. Tropica -- Cutaneous Leishmaniasis. Vector is Sand fly L. Mexicana -- Cutaneous leishmaniasis. Vector is Sand fly. L. Brazilenis -- Mucocutaneous leishmaniasis. Plasmodium -- Malaria. Dx by thick and thin giemsa stain. TX is a/c to the type of parasite. Toxoplasma G -- Reservoir are Cats. Effect intestine than liver brain and lung. TX is Pyrimethamine & sulfadiazine. P. Carinii -- Pneumonia in immunocompromised pt. DX by lung tissue biopsy. TX is Pentamidine + TMP/SMX. Naegleria sp -- Meningitis Acanthamoeba -- meningitis Bebesia Microti -- Bebesiosis 3. Urogenital -- Tricomonas V -- Trichomoniasis. 4 flagella, central nucleus, jerky movement, Exist in Trophozoites form only. TX metronidazole.
* Antmoeba Histolytica ----- Motile (Trophozoites) contain 1 nucleus Non Motile (Cysts) contain 4 nuclei gives rise to 8 Trophozoites. * Giardia Lamblia ------------- Motile (Trophozoites) contain 2 nuclei and 4 pair of Flagella. Non Motile (Cysts) contain 4 nuclei gives rise to 2 Trophozoites. * Antamoeba H and Giardia L both transmitted by ingestion of cyst from fecal oral route. Antamoeba H has no animal reservoir where as Giardia has. Both can be DX by Trophozoites in stool. * Giardiasis is common in homosexual population. * Cryptosporangium (Cryptosporidium) are transmitted by fecal oral route and human are reservoir Diarrhea in Aids. * Trichomonas Vaginalis ------ Contain central nucleus, 4 flagella with jerky movement. Exist only in Trophozoites form. * T. Vaginalis transmitted sexually it infect vagina and prostate. TX of choice is Metronidazole. BLOOD TISSUE PROTOZOA:
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* Plasmodium Falciparum cause severe dis (Tertian malaria) because it infect RBC of every age. * Black water fever occur by P. Falciparum severe hemolysis, Kidney damage (hemoglobulinuria). * P. Ovale & P. Vivax produce Hypnozoites latent form of dis cause & every 3 day fever. It infect only Reticulocytes. * Plasmodium infection DX by Thick and Thin Giemsa stain. * Sporogony is the Sexual life cycle primarily in mosquito. * Shizogony is Asexual life cycle occur mainly in human. * Exoerythrocytic Phase -- in which sporozoites differentiate into merozoites. * Erythrocytic Phase -- in which merozoites differentiate into Ring shaped Trophozoites. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Protozoa
Type of dis
Type of RBC effected
Prophylaxis
Treatment
--------------------------------------------------------------------------------------------------------------------------------------P. Falciparum P. Vivax P. Ovale P. Malariae
Tertian Malaria (every 3 day fever) Infect RBC of all ages Tertian Malaria (every 3 day fever) Infect only Reticulocytes Vivax & Ovale Latent form of dis Infect only Reticulocytes Quartan Malaria (every 4 day fever) Infect only Mature RBC
Chloroquine (Mefloquine + Quinine + Fansidar in resistant cases) Primaquine (Mefloquine + Quinine + Fansidar in resistant cases) Primaquine (Mefloquine + Quinine + Fansidar in resistant cases) Chloroquine (Mefloquine + Quinine + Fansidar in resistant cases)
--------------------------------------------------------------------------------------------------------------------------------------* Fansidar is Sulfodoxine and Primethmine. --------------------------------------------------------------------* Toxoplasma Gondii reservoir are cats. Transmitted by ingestion of cyst or Transplacentally (cause congenital inf). * Toxoplasma G infect intestine than spread to brain, liver, lung, eyes in immunocompromised adult and new born. * Toxoplasmosis can be DX by IgM Ab (in acute inf) and Giemsa stain shows Trophozoites and cysts. * Cat should not fed raw meat to prevent inf. TX is Pyrimethamine and Sulfadiazine. * Pneumocyctis Carinii transmitted by inhalation of airborne cysts (may be yeast) pneumonia, predisposing factor are reduced T cells as in Aids pt. * DX by lung tissue biopsy (show sporozoits), immunoflourescence and immunoperoxydase staining. TX is TMP/SMX + Pentamidine. * Trypanosoma Cruzi Chagas dis vector is Ruduvid bug. Common in Rural south America (eg. Venezuela)and south USA. * T. Gambians or T. Rhodensi sleeping sickness vector is Tsetse fly. * Trypamastigoites enter in blood convert into Amastigoites (non flagellated) infect myocardium, glial, reticuloendothelial cells Chagas dis (megacolon, carditis RBBB). TX is Nifurtimox for acute dis or Benznidazole. * Sleeping sickness in which Metacyclic trypomastigoites enter blood spread to lymphnode and brain coma , demyelinating encephalitis and death. TX Eflornithine. * Trypanosome exhibit remarkable Ag variation (in 10 days) to evade host defense system. Diagnosis : --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Chagas dis vs. Sleeping sickness --------------------------------------------------------------------------------------------------------------------------------------Bone marrow or muscle biopsy Xenodiagnosis Serologic test like indirect fluorescent Ab test, Hemagglutinin test, Complement fixation test.
Blood examination shows trypomastigoites. CSF shows Trypomastigoites Serologic test (Elisa - IgM)
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* Leishmania Donovani Kala Azar (Visceral Leishmaniasis) where as L. Tropica Cutaneous Lieshmaniasis. Both
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caused by sandfly (vector). It shows Leishman Donovan bodies. (Leishman Donovan bodies are different from Donovan bodies which found in granuloma inguinal caused by Clamatobacterium granuloma a Gram -ve Rod) * Kala Azar Effect Reticuloendothelial cells (liver, spleen, bone marrow) Anemia, leukemia, thrombocytopenia (splenomegaly). It can be DX by Tissue biopsy, culture, Serologic test (indirect immunoflourescence test), IgG (imp but not DX), skin test. * TX of Kala Azar is sodium stibogluconate + Amphotrecin B or Pentamidine Isethionate. METAZOAS --- 1. PLATIHELMINTHS --------------------------------------------- Cestodes (Tape Worm) Trematodes (Flukes) TX Praziqualtal. 2. NEMATODES -------------- Intestinal Tissue (Round Worm)
CESTODES -- Taenia Solium -- Under cooked Pork meat. Ingested Larva enter the brain (seizures, hydrocephalus) via blood Cysticercosis. DX proglottids and eggs in the stool. TX Niclosamide Praziquantal, Albandazole. (Tape Worm) T. Saginata ------- Under cooked Cattle meat Taeniasis. DX by proglottids and eggs in the stool. TX Niclosamide. Diphylobothrium Latum -- Undercooked Fish meat Diarrhea. TX Niclosamide. Eccinococcus Granulosus -- Dog Excrete eggs in feces. Ingested by humans and sheeps (occur in Shepard’s). It cause Unilocular Hydatid Cyst disease. (inf may spread to brain, liver, lung and bone. TX is surgical removal of cyst it require protoscolicidal agent to inject in the cyst to kill organism. If cyst ruptures it may results in lethal anaphylaxis. TX is Albandazole. TREMATODES -- Shistosoma Mansoni -- Penetrate through skin. Infect colon veins. DX by ova in feces (large lateral spine). S America. Caribe, ME (Flukes, asexual) S. Japonicum -- Penetrate through skin. Infect small intestine veins. DX by ova in feces (Rudimentary spine). Far east S. Hematobium Life cycle occur In Snails -- Penetrate through skin. Infect vein of urinary bladder. DX by ova in urine (terminal spine). Africa, middle east (ME). Clonorchis Sinesis -- By eating raw fish. Infect GIT & viscera. DX by small brownish operculated egg in feces. Paragominus Westermani -- By eating raw crabs. Infect lung. DX by typical operculated egg in sputum and feces. INTESTINALS -- Enterobius Vermicularis -- pin worm - transmitted by egg ingestion. DX by scotch tape. incidence in daycare. TX mebendazole. (Round Worm) Tricuris Tricura -- Whip worm - transmitted by egg ingestion. DX by barral shape egg in stool. TX mebendazole. Ascaris lumbricoids -- DX by worm, eggs in stool. Occur in tropical & sub tropical area. Can also cause pneumonia. TX mebendazole. Ancyclostoma -- Transmitted by larval skin penetration. Typical eosinophilia, anemia. TX mebendazole. Nector -- Transmitted by larval skin penetration. Typical eosinophilia, anemia. TX mebendazole. Strogyloids -- transmitted by larval skin penetration. Striking eosinophilia, 1st infect lung than swallowing cause intestinal inf. TX Thiabandazole. Trichinella spiralis -- Trichinosis. Eosinophilia, myalgia & diarrhea. transmitted by raw or under cooked meat. DX Muscle biopsy or bentonite flocculation test (after 3 week). TX Thiabendazole Anisakis -- Transmitted by under cooked sea food. TISSUE --------- Wucheria B -- Elephantiasis (flariasis). Transmitted by mosquito in tropical area. Obstruct lymph node. (Round Worm) DX microfilaria circulate in blood in night. Tx is Diethylcarbamazine. Onchocerca Volvulus -- Transmitted by black fly in central America blindness. DX by biopsy of infected skin. Loa Loa -- Transmitted by Deer fly in tropical Africa. Adult worm crawling across conjunctiva of eye. DX by microfilaria in blood smear. TX surgical or Diethylcarbamazine. Toxocara Canis -- Ingestion of egg world wide Visceral larva migran. infect brain liver, eye. DX serologic test. TX Diethylcarbamazine. Ancyclostoma Casium -- By skin penetration world wide Cutaneous larva migran infect Cutaneous mem. TX Thiabandazole. Dracunculus -- Transmitted by copepode in tropical Africa & asia. 1st infect small intestine than skin (blistering), winding worm from skin. TX Niridazole, Metronidazole.
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