INFECTIOUS DISEASES

KOCHS POSTULATE
1. 2. 3. 4. The organism must always be found in the diseased animal. Organism must be isolated from diseased animals and grown in pure culture away from the animal. The organisms in pure culture must initiate and reproduce the disease when re-inoculated into susceptible animal. The organism should be re-isolated from experimentally infected animal.

Major Groups under Bacteria 1. Grafitus gram negative 2. Firmicutis gram positive 3. Tenericutis cell wall less (mycoplasma) 4. Archeobacteria Morphological Classification 1. Cocci 2. Rods (bacilli) 3. Curved or spiral Staining Properties Chemical nature of envelope component and structure imparts useful staining characteristics o Gram (-) o Gram (+) o Acid fast Infection presence of microorganisms in a host Disease host reaction to infection CATEGORIES OF MICROORGANISM 1. Bacteria 2. Spirochetes 3. Virus 4. Fungi 5. Protozoa 6. Parasites PATHOGENESIS 1. Measure of organisms capacity to cause disease 2. A function of virulence or pathogenic factors collaborated by bacteria o Toxins endotoxin, exotoxin o Toxic metabolite

MEDICINE INFECTIOUS DISEASES

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HOST RESPONSE TO INFECTION

First line of defense Bactericidal surface Secretions (epithelial cells) Free fatty acids Lysozymes Eg: Gastric Epithelium aide bile acid pH Achlorydia susceptible to C. vibrio Attracted by chemotactic factors migration) Directed by: 1. Microorganisms 2. Complement activation Phagocytosed microorganisms 1. Unaided 2. Trapped against mechanical barrier Eg: pulmonary alveolar membrane 3. Coated with AB complement Attracted by organisms Eg: M. tuberculosis Pneumococcal infections

Second line of defense

Polymorphonuclear (myeloperoxide enzyme system in the blood 6-8 hrs before going extravascular for several hours 2-4 days)

(for

cell

Not phagocytosed by PMNs

Protein CD4 T-lymphocytes IL-1

Macrophages with surface antigen Fixed in tissue/spleen Blood monocytes

T-lymphocyte express receptor IL-2 Proliferation of Humoral AB Ag-specific T-helper IgM IgG cells Natural AB

Against organisms host Never been exposed formed resulting from x-reaction Ag Eg: 1. N. lactamica from AB against N. meningococcus 2. E. coli induce AB to X-react with capsular surface Ag of H. influenza type B Recovery from infection

Third line of defense

Specific AB IgG Unless 1. Previous infection 2. Vaccination Specific cell-mediated immunity T-lymphocytes Lymphokines Activate Macrophage

Destroyed infected host cells

No AB/complement required

Organisms in a cell safe from AB

Destroy organisms previously impotent to destroy organisms not responsible for cell-mediated immunity Page 2

MEDICINE INFECTIOUS DISEASES

HOST ENVIRONMENT PATHOGEN RELATIONSHIP

Ecology study of interaction between living organisms and their environment CLASSIFICATION OF MICROORGANISMS 1. Neutral interferes in passive manner by: a. Using available food supply b. Excreting toxic metabolites (materials) with their waste products 2. Antagonists alteration in the physical environment or elaboration of AB specifically inhibitory for certain organisms Example: a. After tx with Penicillin normal flora streptococcus, neisseria, hemophilus are replaced by gram (-) enteric bacillus, pseudomonas b. Broad spectrum antibiotics chloramphenicol, tetracycline or combination with Penicillin, Cephalosporin, Aminoglycosides result in emergence of Candida species 3. Synergistic cooperative effort of 2 or more microbes producing a result that could not be achieved by a single microbe

HOST PARASITE INTERACTION

Ecosystems of normal microflora capacity of microorganisms to adhere to epithelial cells dwelling within ecologic niches of the body for prolonged periods. 1. External body surface 8 3 Skin 10 /cm aerobes and anaerobes o Example: S. epidermidis most consistently associated with serious infection of: Prosthetic valves, hip and joint, peritoneal dialysis shunts, CNS shunts It has hydrophobic natural capacity to produce adhesions promoting cellular polysaccharide Anterior Nares predominance of S. aureus in carriers Break in the epithelium can cause local infection or severe systemic infection Contaminants of GI tract 400-800 species 10 /gram E. coli round in normal bowel flora may gain access to urinary tract (Pyelonephritis)
8

2.

3.

STAGES OF INFECTION
1. Bacterial entry and colonization epithelial linings, mucosal tract, ciliary dyskinesia bind to respiratory mucin Staphylococcal protein bound to the host protein like fibrin, collagen, fibronectin

Ring of waldeyer faucial tonsils (mostly infected), nasapharyngeal tonsils, lingual tonsils 2. 3. Bacterial invasion and growth in host tissues and elaboration of toxic metabolites Host response Tissue invasion deeper layers of mucosal tissues via intracellular uptake traverses the epithelial cell function Example: Staphylococcal and Streptococcal producing hyaluronidase lipase, hemolysis Tissue tropism Example: N. gonorrhea Page 3

MEDICINE INFECTIOUS DISEASES

Major pathogens need not penetrate deeper Example: Cholera C. tetani

STAPHYLOCOCCAL INFECTION
Microbiology o Gram positive o Non-motile o Aerobic or facultative anaerobic o Catalase positive Name derived from Greek word staphylo typical; clustering of microorganisms as bunch of grapes S. aureus golden color of colonies growth anaerobically on solid media Properties of Pathogenicity 1. Ferments glucose anaerobically (mannitol to D-nase) 2. Sensitivity to lysostophan endopeptidase 3. Generally hemolytic on blood agar and production of coagulase and toxins Epidemiology 1. S. epidermidis o Coagulase negative o Normal flora of skin, mucus membranes, lower bowels S. aureus o Anterior nares o Peri-anal areas o Vaginal carriages o Menstruating females

2.

70-90% 5-20% 10%

Hospital employees may be cause of nosocomial infections Hospital patients with multiple skin punctures Drug abusers 3. S. saprophyticus o Urothelial cells 5% o Urethral or paraurethral areas

Mode of Transmission o Site of colonization broken skin localized Superficial abscess maybe harmless and self-limited o Lymphatic and blood

MEDICINE INFECTIOUS DISEASES

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Pathogenesis o Infection results from: 1. Bacterial virulence To survive harsh conditions Cell wall constituents Large peptidoglycan complex rigidity of wall can survive under unfavorable osmotic condition Coagulase high correlation with virulence causes plasma to clot by formation of thrombin Catalase degrades H202, protects organism during phagocytosis Persist intracellularly in phagocytosis Potential to acquire resistance to antibiotics 2. Host defenses Intact muco-cutaneous barrier Adequate number of neutrophils Removal of foreign body or devitalized tissues

Four hemolyses 1. Alpha dermanecrotic 2. Delta inhibits water reabsorption by elevating cAMP diarrhea 3. Exfoliative toxins 4. Enterotoxins EXFOLIATION TOXINS A & B Mediate dermatologic manifestations of: 1. Staphylococcal scalded syndrome 2. Bullae impetigo Toxins cause intraepidermal cleavage of the skin at the stratum granulosum bullae formation and denudation ENTEROTOXINS (ABC1C2C3D1E) In food poisoning due to S. aureus Increased intestinal peristalsis and induce vomiting by direct effect in the CNS enterotoxins B and C, may mediate toxic shock syndrome Toxic shock syndrome toxin-1 (TSST-1) is produced by over 90% of S. aureus recovered from women with menstrual toxic shock syndrome HOST FACTORS Staphylococci invade via plugged hair follicles and sebaceous glands, burns, insect bites, respiratory system by passive muco-ciliary clearance may be due to endotracheal tube depression as in viral infection neutrophils enter the area thrombosis of surrounding capillaries, fibrin deposited about the periphery, fibroblasts create avascular wall about area of thick cream pus into lymphatics, blood stream metastatic seeding in a diaphyseal ends of long bones in children, lungs, kidney, brain polymorphonuclear leukocytes major protective mechanism against staphylococci. DIAGNOSIS Gram stain and culture of purulent material and abundant neutrophiles containing intracellular organisms SPECIFIC DISEASES Superficial, follicles, furuncles or boil Carbuncles in the neck and upper part of back MEDICINE INFECTIOUS DISEASES Page 5

ANTIMICROBIAL RESISTANT S. AUREUS Over 90% in hospital and community strains of S. aureus are resistant to penicillin due to production of beta-lactamase genes of this enzyme usually carried by plasmids METHICILIN RESISTANT S. AUREUS True penicillinase resistant S. aureus Resistant to all beta-lactam antibiotics, as well as cephalosporin o Mechanism due to defect in the normal activation of autocolytic enzymes of the bacteria by cell wall Active antimicrobials o Treatment: Clavulonic acid beta lactamase inhibitor Susceptible to Rx Vancomycin Quinolones Ofloxacine (Inoflox) Norfloxacine (Lexinor) May be active against MRSA: resistance in widespread due to rapid single step mutation in the DNA gyrase

STREPTOCOCCAL INFECTIONS
Varieties found in normal flora 1. Respiratory 2. Gastrointestinal 3. Genitourinary CAUSING HUMAN DISEASE o Group A-Streptococcus (Lancefields, Streptococcus, Pyogenes) Streptococcus pharyngitis in school age children Post-infection syndrome of ARF Post-streptococcal GN o Group B (S. agalactase) Bacteria sepsis Meningitis in children Endometritis in parturient females Enterococcus important cause of UTI

Group Streptococcus suppurative infections 1. M protein major surface protein, resist phagocytic killing due to binding of plasma fibrinogen to Mprotein interfering with complement activation and disposition of opsonin complement fragment in the bacterial wall. Resistance maybe specific AB. 2. Elaborates polysaccharide capsule of hyaluronic acid, protects organsism from ingestion and killing by phagocytes; a weak immunogen unlike M-protein

MEDICINE INFECTIOUS DISEASES

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EXTRACELLULAR PRODUCTS 1. Streptolysin O toxins that damage cell membrane; accounts for hemolysis produced by the organism 2. Streptolysin S streptokinase, Dnase, proteases, pyrogenic exottoxin A, B, C 3. Exotoxin A rashes in scarlet fever PHARYNGITIS 20-40% of exudative pharyngitis common under 7 years old IP = 1-4 days by droplet infection o Sore throat o Fever o Chills o Malaise o Erythema and swelling of pharyngeal mucosa o Purulent exudative over post-pharyngeal wall and tonsillar pillars o Enlarged tender anterior cervical lymph nodes Diagnosis o Gold standard: Throat culture strile swab, rubbed vigorouylsy over both tonsillar pillars, most sensitive and specific o Adjunct: Latex agglutination Latex agglutination or enzyme immune-assay of swab specimen highly specific 85%, may preclude throat culture, however, rapid technique relative sensitivity is 55-90%, so that a negative result should be confirmed with throat culture. Usual course of streptococcal pharyngitis uncomplicated resolution of symptoms after 3-5 days. Early treatment shortens course to prevent suppurative complications and RF eradicate with o Oral penicillin 250 mg 4x a day x 10/7 or o SD injection with Benzathine Penicillin 1.2 m units

SKIN AND SOFT TISSUE INFECTIONS 1. IMPETIGO o Predisposition Scratch Insect bite Warm months o Prevention Adequate hygiene o Manifestations: Red papule vesicular pustular breakdown coalesce to form honey-like crusts (thick amber crust) Not painful Patient does not appear ill Fever is not a feature, unless it involves deeper tissues. o Culture: Group A Streptococcus can be isolated, with S. aureus appearing later more extensive bullous lesion that breakdown and leave thin paper like crust.

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DEEP SOFT TISSUE INFECTION Cause: o Group A Streptococcus 60% of cases most often with S. aureus o Hemolytic streptococcal gangrene (necrotizinf fasciitis) o Involves superficial and/or deep fascia of muscles of an extremity or trunk Manifestations: o Fever, malaise o Severe pain and tenderness at site evolves to anesthesia d/t infarction of nerves o Toxic appearance erythema or overlying skin, dusky, mottles, edema Management: o Early surgical exploration Findings: Necrosis Inflammatory fluid tracking along the fascial planes without involvement of muscles Extensive debridement STREPTOCOCCAL MYOSITIS With little or no involvement of fascia and overlying skin More commonly caused by S. aureus, occasionally by streptococcus Group A (fulminant form) Associated with severe systemic toxicity, bacteremia, and high mortality Management: o Surgical drainage o High dose penicillin PNEUMONIA and EMPYEMA Cause: o Group A Streptococcus Manifestations: o Pleuritic chest pain o Fever, chills o Dyspnea, cough o Pleural effusion (empyema fluid) Management: o Drainage to prevent fibrotic reaction o High dose penicillin PUERPERAL SEPSIS Cause: o Group A Streptococcus Site of carriage: skin, throat, anus and vagina o Group B Streptococcus Major cause of sepsis and meningitis in neonates, peripartum fever in women o S. agalactiae Identified by: Anti-serum specific for GBS Biochemical testing o Hydrolysis of sodium hippurate 98% o Production of cAMP factor 98-100% o Phospholipase production by group streptococcus, that results Blysine produced by anterior nares strain of S. aureus.

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INFECTION IN NEONATES st Within the 1 week of life (median: 20 hrs) Adults o related with pregnancy and parturition o peripartum fever o chorioamnionitis abdominal distention, adnexal tenderness o with underlying chronic illness DM, malignancy Management: o Pneumonia, Plyolenephritic abscess = Penicillin 12 million unit daily (10 days) o Endocarditis, Meningitis = 24 million unit daily CELLULITIS Erysepelas bright red appearance of the skin forming a plateau, sharply demarcated from surrounding normal flora, tender, warm, shiny swollen skin, has peau d orange texture d/t involvement of superficial lymphatics Superficial blebs or bullae may form usually in 2-3 days after onset Fever, chills o Usually Malar areas of the face, may extend over bridge of nose to contralateral malar area Lower extremities o Group A Streptococcus and other potential pathogens S. aureus

BOTULISM
paralytic disease that begins with cranial nerves involvement and progress caudally to involve extremities Etiology o C. botulinum potent protein involvement Anaerobic Gram (+) forms subterminal spore Found in oil and marine environment Elaborates most potent bacterial toxin Proteolytic activity; can digest food and produce spoiled appearance Classification 1. Food borne ingestion of preformed toxins 2. Wound botulism 3. Infact botulism ingestion of spores and production of toxins in intestines 4. Infant Adult 5. Indeterminate

8 Types of Toxins A Neurotoxic C2 TOXIN (cytoxin) causing vascular permeability and lethal, but not paralytic Neurotoxin ingested or produce in intestines or wound vascular system 1. CHOLINERGIC NERVE TERMINALS o Neuro- muscular junction o Post ganglionic parasympathetic nerve endings Peripheral ganglia (CNS not involved) 2. Irreversibly blocks release of neuro transmitters acetylcholine o Depresses calcium mediated release o Cure follows sprouting of new nerve terminals

MEDICINE INFECTIOUS DISEASES

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o o o

Resists degradation by acid and proteolytic enzymes Inactivated by heat at 100 degress C Spores are highly heat resistant 120 deg C for inactivation steam strerilizers/pressure cooker

Types A,B and E cause human disease Type G ass with sudden Death Types C and D causes animal disease Epidemiology o Food borne Botulism has been associated with home-canned foods, vegetables, fruits, condiments o Less common with meat and fish o Outbreaks in restaurants and school a. b. Food to be preserved as contaminated with spores Preservation does not inactivate the spores but kills other putrefactive bacteria that might inhibit growth of C. botulinum and also provide anaerobic conditions at a pH and temperature that allows generation and toxin production Food not treated to a temperature that destroys toxin before being eaten

c.

Clinical Manifestations o Incubation period 18- 36 hours o Symmetric Descending paralysis IS CHARACTERISTIC o Respiratory Failure DEATH o CRANIAL NERVE INVOLVEMENT MARKS MOST OF SYMPTOMS Diplopia Dysarthria Dysohagia Weakness progresses rapidly head neck arms and thorax legs Abdominal pain nausea and vomiting Occurs before or after paralysis Dizziness and blurring of vision Very dry mouth, sore throat Generally oriented, but maybe drowsy, agitated, anxious Typically no fever ptosis frequent, depressed pupillary reflex and fixed or dilated pupils in 50% of cases Suppressed Gag Reflex Deep tendon reflexes normal or decreased Common paralytic ileus severe constipation Urinary retention

o o o o o o o o o o

Diagnosis o Demonstration of toxin in serum by bio-assay in mice, but maybe negative in wound and infant botulism Afebrile mentally intact symmetric descending paralysis without sensory findings

MEDICINE INFECTIOUS DISEASES

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Differential diagnosis o Gullain Barre ascending paralysis sensory abnormality increase CSF protein o Myasthenia Gravis electromyography Appropriate antibody studies o Poliomyelitis Management o hospitalize and monitor o Trivalent vaccine Type A, B, E equine antitoxin 2 vials by IV or IM and IV May repeat after 2-4 hours Prognosis o Type a more severe than type B

TUBERCULOSIS
Chronic bacterial infection caused by Mycobacterium tuberculosis Types of Mycobacterium 1. M. leprae 2. M. bovis 3. M. avium Acid fast not decolorized by acid alcohol Transmission o Droplet TB bacilli from the nuclei for liquid droplets expelled during: Coughing Sneezing Talking o Evaporate Desiccated bacilli remain airborne for long periods

PATHOGENESIS A. Exposure Events In effected droplets aerosolized by a person with active tuberculosis

Key Points 1. Man is the only natural reservoir of TB bacilli 2. Significant exposure mean close contact Household members Officemates Hospital workers

Inhaled by susceptible person

1.

2.

No prior contact with TB therefore, no immunity, as signified by negative tuberculin test His immunity is not capable of neutralizing TB bacilli

MEDICINE INFECTIOUS DISEASES

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Alveolar Deposition B. Infection and Disease

1.

Usually in the lower lobes of the lungs

Local pneumonitis Alveolar macropahes phagocytize TB bacilli Cytokines secreted Attract effector (inflammatory) cells from circulation: neutrophils; lymphocytes; eosinophils Host immunity falters

1. 2.

Usually happens in the lower lung zoneGhons Focus May have transient fever

1.

2.

Can be mild or severe, as in Diabetes, steroid use, acquired Immune deficiency syndrome, and malnutrition Usually occurs years after primary infection

TB bacilli no longer under check. Rapid multiplication follows, tissue damge occurs

1. 2. 3.

Reactivation Tuberculosis for mild deficiency Typical lesions for severe immune deficiency Unusual or multiple sites- Disseminated or Miliary TB

CLINICAL SYMPTOMS A. No signs at all < 10% B. Lung symptoms only (local) 1. Cough 2. Dyspnea 3. Hempotysis 4. Back pain C. Constitutional symptoms 1. Fever 2. Chills 3. Anorexia 4. Malaise 5. Weight loss

Due to lung anatomic-physiologic changes TB healing does not permit recovery of damaged lungs, and therefore these symptoms may persist despite microbiologic cure. Produce by bodys reaction to substances Produced during on-going tissue dmage-TNF Lysis of TB bacilli Inflammatory effector cells Very useful in monitoring disease activity Most common manifestation

D. Combination E. Extra Pulmonary Symptoms 1. TB meningitis 2. Urinary TB

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Laboratory Diagnosis 1. Chest X-ray o For diagnosis o Assessment of treatment 2. Upper lobe location of fibrosis and cavitation, highly suggestive of PTB 3. Single X-ray can NEVER confirm PTB and disease activity o Lung cancer, Pneumonia can mimic TB o Sometimes lesion is smaller than 1 cm and may not be radiographically visible o Healed TB can also look exactly the same as active lesion o Therefore, chest X-ray findings MUST be evaluated and corrected with clinical status. 4. Sputum AFB smear o Only 30-60% of active TB is positive o Hence, negative test DOES NOT rule out TB o Treatment should be withheld until after sputum collection o 3 early morning sputum samples should be tested 5. Sputum TB bacilli culture o 100% diagnostic of TB o But results come out 4-8 weeks later o AFB culture and Drug Sensitivity Test- important in retreating a case of TB when drug resistant is likely History of Action Taken in PTB o Treatment of some kind------------- 65% 39% resort to self medication 26% Go to private practitioners 22% Attend to health centers 9% go to hospitals 4% take other action o 20% of total cases diagnosed and treated o of these dropped out RECOMMENDED REGIMEN 1. Initial Phase (2 months) INH------------------------------ any weight----------------------------- 300 mg + Rifampicin--------------------- < 50 kg---------------------------------- 450 mg > 50 kg---------------------------------- 600 mg + PZA------------------------------ < 50 kg---------------------------------- 1.5 gm 50-74 kg--------------------------------- 2.0 gm >75 kg------------------------------------ 2.5 gm Administer ALL 3 drugs in a single daily dose in an empty stomach for better absorption of Rifampicin Prevention of resistance INH Rifampicin Ethambutol Early bactericidal INH Ethambutoi Rifampicin Sterilizing Rifampicin PZA Ethambutol

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PRINCIPLES OF TREATMENT Population C inside macrophages Drugs: PZA- 25-35 mg/kg Rifampicin 15 mg/kg Population B Nodular Bacilli Cause of relapse Drugs: Rifampicin Acid medium Most active

Neutral Ph

Population A Cavitary Neutral pH Cause of infectiousness and Resistant mutants Drugs: Rifampicin INH 15 mh/kg Ethambutol 15-25 mg/kg 2.

inhibits growth of mutants in retreatment course Avoid relapse

Second Phase 4 months 2X weekly in empty stomach Rifampicin 15 mg/kg + INH 15 mg/kg WHO suggests treatment should be stopped at 4 months if: 1. CXR suggesting PTB 2. But, sputum NEGATIVE on direct smear, and culture RX 2 mo. SHRZ / 4 mo. HR 82-92% 2 mo. HRZ / 4 mo. HR 75-79% 2 mo. EHRZ/ 4 mo. HR 82-92%

60 mg 750 mg

Reactivated PTB affects: 1. Apical posterior segment of upper lobe 2. Superior segments of lower lobe Central necrosis with development of cavitation Satellite lesions develop Necrotic material may empty into bronchi transbronchial exudatives MANAGEMENT PROTOCOL o Suggestive signs and symptoms 1. Cough for 2 weeks or more with or without symptoms 2. Chest pain for 1 month or more 3. Hemoptysis or blood streaks at any time 4. Fever for 1 month or more 5. Progressive weight loss o Diagnosis 1. Combination of the above symptoms 2. Sputum examination --- identifies 68% of cases Examine 3 specimens, if possible 1. First spot specimen on consultation 2. Early morning specimen all sputum raised in the first 1-2 hours 3. Second spot specimen- when patient comes with early morning specimen Page 14

MEDICINE INFECTIOUS DISEASES

Cough > 3 weeks

2-3 sputum test

2 or more tests are (+)

Only 1 test is (+)

All tests are (+)

Treat as TB

Repeat 3 tests

Treat symptoms

1 or more tests is (+)

Repeat test if it gets worse

All negative Repeat test in a month Highly contagious forms of TB: 1. Laryngeal 2. Endobronchial 3. extensive cavitation Infectiousness correlates with 1. Number of bacilli in expectoration 2. Extent of Pulmonary disease 3. Frequency of cough Most patients become noninfectious within 2 weeks after initiation of appropriate chemotherapy.

LEPROSY (HANSENS DISEASE)

Chronic granulomatous infection which attack superficial tissues (skin and peripheral nerves) Etiology: Mycobacterium leprae discovered 100 years ago acid fast rod exceedingly slow in multiplication Epidemiology: direct human to human transmission fewer than with history of prior exposure among close family contacts of untreated Lepers: risk of disease is increased 8x attack rate can be as high as 10 % MEDICINE INFECTIOUS DISEASES Page 15

Site of entry: Skin or mucosa of upper respiratory tract Portal of exit:Nasal mucosa of untreated cases Incubation Period: 3 5 yrs 6 mos to several decades Pathogenesis: Bacilli are surrounded by a dense inert lipid capsule Produce no exotoxin Little inflammatory response 10 20 % of individuals develop signs of indeterminate leprosy 50 % will progress to full blown disease Polar Tuberculoid Leprosy>>has intense cellular response to M. leprae and Low Bacillary Load Tuberculoid Leprosy Not intense Low Lepromatous Leprosy Not detectable cellular immunity Intense bacillemia in stained peripheral blood No signs of fever and systemic toxicity Inc circulating CD4 Suppessor T-cells in cutaneous granuloma Monocytes macrophage cells engorged with M leprae unable to kill bacteria Subtle, goes unnoticed cutaneous involvement, extensive and roughly symmetric across the midline, macular, papular, nodular plaque Early symptoms ---Nasal stuffiness, epistaxis, obstructed breathing Progress to complete nasal congestion, laryngitis, hoarseness, septal perforation, nasal collapse saddle nose III defined border, raised indurated center, convex Diffused infiltration of dermis normal skin between lesions

Cellular response Bacillary load

Early or Indeterminate

CD4 + 4B4 HelperT-cells predominate in cutaneous non-caseating granuloma with Lymphos, Epitheloid cells, giant cells Bacillli frequently absent Subtle, usually cutaneous hypopigmented or hyperpigmented macules or papules first symptoms ----anesthetic or parathestic patch which may clear in a year

Lesions

Site of predilection

Circinated or gyrating central area atrophic & depressed sharply demarcated elevated margins less of normal skin organs sweat glands, hair follices Palpable ulnar, peroneal, greater auricular muscular atrophy esp. small muscles of hand contractures of hand & feet

facecheeks, nose, brows; ears; wrist; elbow; buttocks;knees Leonine facies loss of lateral portion of eyebrows, skin of face & forehead becomes thickened & corrugated Pendulous ear lobes Bacilli found in liver, spleen, bone marrow Page 16

MEDICINE INFECTIOUS DISEASES

Advanced cases

Trauma from excessive pressure, burns secondary infection plantar ulcers Resorption loss of phalanges Facial nerve involvement lagophthalmos, exposed keratitis Corneal ulcers blindness

Preferential involvement: Ulnar nerve near elbow Peroneal nerve where it passes around head of fibula Deep course of nerves are less severely involved Treatment Duration: minimum of 2 yrs Specific Chemotherapy 1. DAPSONE (DiphenylSulfone) Folate antagonist Mainstay therapy Safe in pregnancy Dose: 50 100 mg OD Half life: 24 hrs st Enough bacilli killed in 1 10 12 wks 2. RIFAMPIN Most rapidly bactericidal Usual dose: 600 mg /day Expensive, hence given 600 mg or 900 mg once/month CLOFAZIMINE Highly lipophilic Accumulates in skin, GIT, macrophages and monocytes Dose: 50 200 mg/day HL: 70 days Not safe for pregnancy

Painless lymphadenopathy ---inguinal and axillary Infiltration and scarring of testes sterility Gynecomastia common Diffused hyperesthesias involving painful portions of extremities No visceral organ has been assoc. Destructive lesions are limited to skin, peripheral nerves, anterior portion of eye, upper resp. tract above larynx Cold extremities

3.

CLOSTRIDIUM DIFFICILE
2 Major toxins o A Enterotoxin causing diarrhea o B Cytotoxin: measured in sensitive tissue culture Assay System -GOLD STANDARD for diagnosing Antibiotic associated Diarrhea 1. Overgrowth when antibiotics suppress normal flora Example: Clindamycin- most implicated cause 2. Many of the antibiotics that cause the disease are active against C. difficile Example: Metronidazole and vancomycin 3. May patients colonized with C. difficle do not develop diarrhea 4. Other bowel flora may inhibit toxin production 5. Toxin production and interaction of C. difficile with other bowel flora Page 17

MEDICINE INFECTIOUS DISEASES

Pathogenesis 1. Produce 2 major toxins, A and B; Toxin B is cytotoxic measured in sensitive tissue culture assay system GOLS STANDARD for diagnosing antibiotic associated diarrhea 2. Pathogenesis has centered on overgrowth of clostridium difficile, when antibiotics suppress normal bowel flora 3. Many patients who are colonized with C. difficile do not develop diarrhea 4. Critical factors in the pathogenesis of the disease include mechanism of toxin production and interaction with C. difficile with other bowel flora 5. Some antibiotics may actually trigger toxin production by the organism. Other bowel flora may suppress or inhibit toxin production. 6. When antibiotics climinate more sensitive bowel flora, more resistant organism may produce enzymes, such as beta-lactamase, that can inactivate antibiotics and, thereby facilitate growth of C. difficile. Toxins are detectable in stool. Antibiotic Associated Colitis: no other cause of diarrhea symptoms occur during antibiotic treatment or within 24 weeks post-antibiotic Any antibiotic can cause these symptoms. o Even vancomycin and metronidazole which can treat the disease o Clindamycin (Lincocin) first antibiotic to have caused the disease, most commonly implicated o Cephalosporin, then Penicillin Pathology o 4 categories appearance of the colon 1. Normal mucosa (colonic) 2. Mild erythema with some diarrhea 3. Granular, Friable, or Hemorrhagic mucosa Clostriudium difficile cytotoxin B in 15%-46% of stools 4. Pseudomembranous formation (colitis) Most characteristic form 95% have (+) toxin assays in stool o Exudative, punctuate raise plaques with skip areas or edematous, hyperemic mucosa o Enlarged and coalesce over large segments of intestine Most common manifestations 1. Watery diarrhea, voluminove with gross blood or mucus 2. Abdominal cramps, tenderness 3. Fever, leukocytosis Differential Diagnosis: o Ulcerative colitis o Crohns Disease Management o Discontinue offending antibiotics o Symptoms resolve in 2 weeks o Specific therapy shortens duration of symptoms o Rx: vancomycin PO 125 mg QID X 7-10 / 500 mg QID X 7 or Metronidazole 250 mg QID or 500 mg TID Relapse rate 8-9%

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CLOSTRIDIUM PERFRINGENS GRAM (+)

One of the most important bacteria o Encapsulated, non motile o Rarely sporulate in artificial media o Can be destroyed by boiling. Associated with food poisoning and enteritis necroticans Requires 14 amino acids and 6-7 additional factors for optimal growth, these are found in necrotic tissue. When bacteria leak into the blood smear, cannot rapidly multiply, blood stream NOT good media for growth, therefore bacteriema is usual benign in the absence of necrotic tissue. 4 Major toxins 1. Alpha initiated muscle infection o Gas gangrene o Hemolytic destroys platelets and polymorphonuclear, widespread capillary damage 2. Beta destroys liver mitochondria 3. Epsilon increases capillary permeability 4. IOTA increases capillary permeability Clinical manifestations 1. Intestinal disorders o Food poisoning with C. perfringens due to cooling and storage of foods cooked in bulk meat and poultry. Allowed to cool, the re-cooked the following day. o The bacteria survived first cooking. o During reheating, they sporulate and germinate o Epigastric pain, nausea, vomiting, watery diarrhea caused by heat labile toxin inhibits glucose transport damages intestinal epithelium protein loss into intestinal lumen 2. Enteritis necroticans (PIGBEL) o Etiology: Type C C. perfringes o Pathology: Acute ulcerative process in small intestines mucosa lifted off large denuded area pseudomembrane composed of sloughed epithelium gas dissect into submucosa source of organisms maybe patients own flora, because cultures of in gested meat have failed to yield the organisms. o Acute abdominal pain, bloody diarrhea, vomiting, peritonitis, shock, necrotizing enteritis DEATH

Management o Anti toxin against beta toxins of C. perfringes will change course the disease o Immunized children are protected.

CLOSTRIDIAL SEPTICEMIA
Primary infection uterus, colon, biliary tract o After septic abortion o Clostridium perfringens cause of majority of cases Clinical manifestations o 1-3 days after attempted abortion o Sepsis chills, fever, malaise, headache, severe myalgia, abdominal pain, nausea/vomiting, occasional diarrhea o Frequently bloody or brown vaginal discharge, oliguria, hypotension, jaundice, hemoglobinuria o Hemolysis due to Alpha toxin--- bronzing of skin, foul cervical discharge

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Laboratory o Increase WBC o Pink Hb-tinged plasma o Platelet decreased in DIC o Culture of exudates Treatment o Penicillin G sodium 20M u/day Or Chloramphenicol 4 Gm/day as alternative o Polyvalent Gas gangrene antitoxin- questionable efficacy

GAS GANGRENE AND OTHER CLOSTRIDIAL INFECTIONS

Genus Clostridium are gram (+) Spore forming Obligate anaerobes- some are quite aero-tolerant Ubiquitous in nature In clinical specimens and stationary phase, cultures may be gram (-) Normally in the gastro-intestinal tract and female tract Characteristically produce abundant gas in artificial medium and form subterminal spores 4 Major Disease Categories due to Clostridial infections 1. Intestinal disorders 2. Deep tissue suppuration infection- due to toxins 3. Skin and Soft tissue infection due to toxins

ANTHRAX
Acute bacterial infection most frequently in herbivorous animals Etiology: Bacillus anthracis 1. Large non motile 2. Encapsulated, chain forming 3. Aerobic, gram positive 4. With central and spore Virulence factors 1. Anthrax Toxins 2. Anti- phagocytic capsid Spore pf B. anthracis can survive for years in dry earth Destroyed by boiling for 10 minutes By treatment with oxidizing agents Potassium permanganate or dilute formaldehyde Most strain is susceptible to penicillin Pathogenesis o Extra cellular pathogen can evade phagocytosis o Invade the blood stream o Multiply rapidly and kill quickly o Capsular Anti-Phagocytic Polypeptide

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Anthrax Toxins 3 proteins 1. Protective antigenor 2. Edema factor 3. Lethal factor Clinical manifestations in Humans 1. Cutaneous Form most common 95% of anthrax found in exposed areas o Head, Neck, Face, Upper Extremities o Small red macules- maybe pruritic

o o o o 2.

Papular, vesicular, Pustular Ulcer with blackened necrotic eschar Surrounded by highly characteristic expanding zone of brawny edema- painless Painful non specific lymphadenopathy Afrebrile, no constitutional manifestations

Inhalational Anthrax Wool Sorters Disease o Similar with viral respiratory infection o 1-3 days increasing fever Dyspnea X-ray symmetrical widening Stridor hemorrhagic mediastinitis Hypoxic Hypotension Death within 24 hours

3.

Gastro intestinal Anthrax o Rare with high mortality o Fever o Nausea/ vomiting o Abdominal pain o Bloody diarrhea o Sometimes acsitis Penicillin G. Sodium = 2 M units 6 hourly until edema disappears Then oral to complete 7-10 day course

Rx:

TETANUS
Neurologic disorder characterized by 1. Increased muscle tone 2. Muscle spasm Caused by Tetanospasmin a powerful protein toxin elaborated by CLOSTRIDIUM TETANI

Microbiology Anaerobic mobile Gram positive rods Oval form, colorless terminal spores- creating tennis racket-shape or drumstick Found in soil, inanimate environment, animal feces,ocassionaly in human feces Spores survive in many years in the environment and resistant to disinfection, for 20 minutes

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Epidemiology Occurs sporadically Almost always affects non-immunized and partially immunized, or fully immunized who fail to maintain immunity with booster doses Entirely preventable by vaccination Pathogenesis Contamination of wound with spores Germination and toxin production in wounds with low oxidation- reduction potential in o Devitalized tissues o Foreign bodies o Active infection Clostridium Tetani do not evoke inflammation- port of entry appears benign, unless infected Toxin binds to peripheral alpha motor neuron terminals enters the axon, transported to nerve cell body in the brainstem and spinal cord by retrograde INTRANEURAL TRANSPORT Toxins cross the synapse to pre- sympathetic terminals and blocks release of inhibitory neuro-transmitters 1. Glycine 2. Gammabutyric Acid (GABA) Resting firing rate of Alpha Motor Neuron increases Rigidity Lessened activity reflexes, which limit polysynaptic spread of impulses (Glycinergic Activity)

Agonist and Antagonist maybe recruited rather than inhibited, thereby producing Spasm Loss of inhibition also may affect pre-ganglionic sympathetic neurons in the lateral gray matter of the spinal cord and produce sympathetic hyperactivity and high circulating catecholamine levels Tetanospasmin( likeButolinum Toxin) also may block neurotransmitter release at the neuromuscular junction---- weakness of muscles or even paralysis Recovery requires sprouting of nerve terminals.

Clinical Manifestation INCUBATION PERIOD

7 days after injury 15% within 3 days 10% after 14 days Increased tone in masseter muscle, sustained contraction of facial muscles---- trismus or locked jaw, risussardonicus grimace or smear Rigid Abdomen Stiff proximal limb muscles, except hands and feet Dysphagia or stiffness or pain in the Neck, shoulder, back muscles

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Differential Diagnosis TRISMUS Alveolar abscess Strychnic poisoning Dystolic drug reaction, phenothiazine, metoclopramide Hypocalcemictetany Meningitis, Encephalitis Rabies BUTOLISM Paralytic disease that begins with cranial nerve involvement, progress caudally to involve extremities GENERAL MEASURES ADMIT IN ICU Goals Therapy 1. Eliminate source of toxin 2. Neutralize unbound toxin 3. Prevent muscle spasms 4. Provide Respiratory support Admit in ICU for o Cardio-pulmonary monitoring o Protection of the airways o Minimize stimulation (in a quiet room) o Wound cleaned and debrided thoroughly o Antibiotics eradicate vegetative cells-source of toxin (if allergic to penicillin, give clindamycin, erythromycin, or metronidazole)

o Anti-toxins- to neutralize circulating and unbound toxins; toxins bound to neuronal tissues is unaffected antibodies do not penetrate blood/ brain barrier o Control of muscle spasm Muscle spasms are painful Laryngo spasm or sustained contraction of ventilator muscle threatens ventilation Ideal therapy should abolish spasmodic activity without causing oversedation and hypoventilation

RX o o o o Diazepam Titrated doses 250 mg/ day or more Lorazepam longer duration of action Midazolam short half-life, by continuous drip If unresponsive RX Vecuronium neuro muscular blockade with mechanical ventilation for severe spasm

Management Parenteral Penicillin 10-12 mU daily x 10/7 Anti- toxin 3,000- 6,000u in divided doses Tetanus immune globulin- promptly given 3,000-6000 IM in divided doses ( longhalf life) Antibody does not penetrate blood brain barrier Equine tetanus antitoxin short half-life up to 100,000u partly IM (10,000u may suffice)

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Control muscle spasm o Diazepam 3endodiazepam( GABA agonist) Titrate dose 250 mg/ day Respiratory care by incubation or tracheostomy Initiate active immunity because immunity is not induced by the small amount of toxin that produced the disease 3 DOSES st o 1 dose: 4-8 weeks apart nd o 2 dose: rd nd o 3 dose: 6- 12 mos. After 2 dose o Booster dose every 10 years

Manifestations Paroxysmal violent contractions, generalized pain, cyanosis--- threatened ventilation Slight stimulation will provoke spasm Reduced ventilation- apnea or laryngeal spasm Maybe febrile Increased DTRs Autonomic dysfunction commonly complicates severe cases o Labile or sustained blood pressure o Tachycardia o Arrhythmia o Hyperpyrexia o Profused sweating o Peripheral vasoconstriction Diagnosis entirely on clinical findings

SEXUALLY TRANSMITTED DISEASE

Extent of the problem 1. Rising incidence due to: o Freer sexual relations a major factor The great stimuli Oral contraceptives IUD easier transmission of STD than barrier contraceptives o The most 2 prevalent STDs Non-gonococcal urethritis and gonorrhea are often asymptomatic and has tendency to exhibit antimicrobial resistance. Increase in casual sexual activity, especially when combined with increase in leisure time Lack of reliable Chlamydia Diagnostic Test Ignorance- Failure to recognize infection Failure to believe it is serious to both Therefore, STD is most likely to be seen in sexually active single person in late teens and twenties, also in all sexually mature age groups. 2. Rise of resistant Strains Easy accessibility of anti-microbial promote self-medication alarming explosion of resistant strains and uncontrolled epidemics

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MODERN PROBLEMS AND PRACTICE 1. Rising incidence of chlamydial infections permanent complications salpingitis permanent infertility 2. Multiply widespread infection with gonorrhea and chlamydial infection Rx: Single dose of Penicillin for gonorrhea and course of Doxycyline- Gonorrhea and Chlamydial are susceptible Other treatment Cefixime(Zeprol) 200mg/100mg cap Ceftazidime (Fortum) 250mg vial Ceftriaxone (Rocephin) 250 mg vial The future Prevention- Public Education in awareness Sweden- use billboard advertising GONORRHEA N. gonorrhea Gram (), diplococci, flattened sides Site of invasion o Men distal urethral mucosa, rectum (homosexual men) Pharynx (homosexual men) o Women endocervical canal, urethra, also rectum Prepubertal vulva, vagina o Newborn conjunctiva Symptoms o IP 2-5 days ()1-10 days o Genital gonorrhea in men sudden burning sensation on micturition, purulent urethral discharge, meatal Erythema (infection) 25% - scanty mucopurulent exudate Few are asymptomatic Local complications o Acute epididymidtis infection of paraurethral ducts: Acute Prostatitis Infection of Cowpers glands and ducts o Median raphe of the penis o Periurethral tissues abscess or urethral stricture o Genital gonorrhea in women 50-75%- Asymtomatic Dysuria and vaginal discharge- not disturbing Cervical congestion and edema with purulent cervical discharge; pus expressed from the urethra or Bartholins glands. Local complications Infection of Bartholins glands abscess Acute salpingitis Gonococcal septicemia fever, arthralgia, septic spots on skin, hepatitis septic arthritis, endocarditis, meningitis Rectal gonorrhea very common in homosexual men 60% of women and genital gonorrhea give isolol of N. gonorrhea, rectal discharges, tenesmus Pharyngeal Gonorrhea- sore throat Vulvo-vaginitis- in pre pubertal girls- vaginal discharge Redness, selling of vulva Conjunctivitis, Opthalmia Neonotorum- with purulent discharge, inflammation, orbital edema MEDICINE INFECTIOUS DISEASES Page 25

ESCHERICHIA COLI INFECTIONS

E. coli a commensal in the GIT Pathogenic varieties 1. Enterotoxigenic E. coli (ETEC)Travellers diarrhea Fecal-oral route contamination of unbottled water, salad, vegetables Resist normal defense of acid pH within 1-2 days of exposure Enterotoxins on the GI mucosa Copious outpouring of fluid from GIT Frequent explosive BM Differential Diagnoses: Shigella, Salmonella, H. pylori, Cholera Vibrio 2. Entero-pathogenic(entero adherent) E.coli (EPEC)Childhood Diarrhea Binds to membraneous Peyers Patches Disrupts overlying mucus gel Entero- Invasive E. coli (EIEC) Provoke inflammatory manifestations of Bacterial Diarrhea- bloody and PMN leukocytes and fever Entero- Hemmorhagic E.coli (EHEC) Usually afebrile in the elderly and it is often confused with Ischemic Colitis

3. 4.

May develop Hemolytic Uremic Syndrome (Acute Tubular Necrosis) Urinary Tract Infections o Urinary tract is normally sterile o Most uncomplicated UTI (without FB, no pregnancy, no stones, no urinary obstructions) are d/t E. coli o Manifested as asymptomatic bacteriuria, urethritis, cystitis, pyelonephritis o Can be infected with P. aeruginosa and other Enterobacteriacaea Intraabdominal infections o Spillage of intestinal contents early septicemia resukting from perforated appendix, diverticulum, peptic ulcer, intraabdominal abscess, cholecystitis, ascending cholangitis

GRAM NEGATIVE INFECTIONS

N. meningitides normal flora in the oropharynx N. meningococcus cocci or diplococcic o Culture media Chocolate agar with blood Moist environemt Reduced 02 5% to 10% CO2 Pathogenesis: Outer membranes contains Lipo oligossacharides (LOS) Capsule contains Lipolysaccharide

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ENDOTOXIN

Binds to CD 14 on monocytes, macrophage and neutrophils

INFLAMMATORY CYTOKINES

IL- BETA IL 6 IL- 1 Tumor necrotizing Factor(TNFA Stimulates Leukocyte and Vascular endothelium Other cytokines and more TNF

Phospholipid-Derived Mediators Release arachidonic Acid by Phospholipase A

Cyclo-oxygenase pathway

Lipo-oxygenase pathway Leukotriene B4 Promote leuk. Local Vasc. Injury and thrombosis

Prostaglandin 1. 2. Fever, tachycardia, tachynea and Leukocytosis Induce shock D/C

Thrombaxane A2

Prostacycline Prostaglandine E2 Vasoconstriction and Peripheral Platelet Adhesion Ischemia & Vasodilation Shock

Incidence o 90%-95%- Meningococcemia and/or Meningitis o 30 % -50% - May have meningococcemia without meningitis Clinical Manifestations o Prodromes: Cough, headache, sorethroat , sudden spiking fever, chills, arthralgia, myalgia, tachycardia, tachypnea, hypotension o 75% develop Petechial rash most common in axilla, flanks, wrist, ankles Nodular as disease progresses crapings may demonstrate Gram negative Diplococci Severe cases of fulminant meningococcemia or Waterhouse Fredrichsen syndrome associated with vasomotor collapse and shock; 10% to 20% of cases with high levels of endotoxin. Abrupt onsety-profound postration in a few hours

o o

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o o

Generalized vasoconstriction- alert, palem circumoral cyanosis and cold extremities Dec. CO, Dec. BP, Dec. mental status Coma *Purpuric spots or larger ecchymosis wide spread petechiae or purpuric eruptions

Prognosis: o Levels of circulating endotoxin and cytokines- sensitive markers for fulminant disease and poor prognosis o Inspite of treatment, 40%-60% suffer from Cardio- Respiratory failure.

MENINGITIS
Primary in children 6mos.- 10yrs old Upper respiratory infection- Fever, vomiting, headache, lethargy 25% symptoms are abrupt and rapidly increases in severity 20% to 40%- with Meningococcemia Lab Diagnosis o CSF pressure o 1000-4000 PMN Treatment: Drug of Choice Penicillin G. 12-24 M U/day 2-4 M IV 4- HOURLY X 7/7 Or 4-5 days after afebrile Children 200,000-400,000 u/kg/day is 4- hourly divided doses Or Chloramphenicol 75-100 mg/kg/day Adults: 3-4 gm/day in 6 hourly divided doses by IV Ceftriaxone(Rocephin) Often empirically used when etiology of Meningitis is uncertain Cefuroxime

Recombinant IL-1 Monoctanol antibodies against IL beta and IL 6 Monoctanol antibodies against TNFa

SALMENOLLOSIS
Etiology-Salmonella Non encapsulated, Gram Negative Ferments glucose-produce H2S, black reaction product on triple Iron sugar(TSI) Ager; to distinguish isolates from Shigella- gives alkaline/Acid TSI reaction

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TYPHOID FEVER Caused by: 1. S. typhi- resides in bile, even in interior of stone, intermittently reach lumen of bowel and then excreted in stool. 2. S. paratyphi A 3. S. paratyphi B 4. Typhimirium, occasionally Epidemiology: Water- most common route Food Chronic carriers- 50years old, more on women, often with gallstone Pathogenesis; S. typhi-pass gastric barrier Small bowel Bacteremia

Ingested by mononuclear phagocytes Multiply intracellulary survival depends on 1. Microbial resistance to killing 2. Specific host T-lymphocytes- activates cell mediated immunity (under genetic control) Multiply intracellulary Survival depends on

Cytokines

Intracellular bacteremia surpassing critical threshold

Cholecystitis Intestinal Hemorrhage or perforation

Secondary bacteremia

Lipopolysaccharide Endotoxin

Invades gallbladder and Peyers patches

Persistent fever leucopenia

Bacteria regain entry into intestinal lumen recovered in stool culture beginning second week of clinical disease

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Clinical Manifestation o Incubation period 3-60days depending on 1. Inoculum size 2. State of host defense o Classicaly step like daily increase in temperature 40 degree Celsius-41 degree Celsius with Bradycardia o Headache, malaise, chills o Prolonged persistent fever 4-8weeks- Hallmark o Week 1- Rose Spots= small pale blanching slightly raised macules occasionally on the chest and abdomen

Maybe non blanching small hemorrhage Complications o Major characteristics of untreated typhoid fever Persistent high fever Severe Anorexia Weight Loss Change in sensorium o Acute severe infection with DIC and CNS involvement(Meningitis) Rapidly Death Weeks 3-4 Necrotizing cholecystitis or intestinal bleeding or perforation (Otherwise improving) Mild hepatomegaly-Hepatitis Pneumonia, Arthritis, Osteomyelitis, Parotitis, Orchitis

o o o

Laboratory findings o 25%- Leukopenia and Neutropenia- low in relation to fever- due to diagnosis See leukocytosis- in intestinal perforation and progression complications Isolation of organisms from blood- highest in the first week- 90% rd o 75%- positive stool culture on the 3 week o Serologic test- Widal Test Less reliable than blood culture o Agglutinating antibodies 0 Antigen1 640 titer suggestive but not specific X-reaction with serology D salmonella A and B H V1- rises later after 3-4 weeks of illness o DOT Immunosorbent Assay (DOT EIA)- uses specific protein to detect antibodies- IgM and IgG in a single specimen of patients serum- results come in 3-4 hours upon receipt of specimen. RESULT: Bluish Purple Dot- antibodies in typhoid fever patients

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Detection of IgM alone or with IgG- current infection IgG alone- convalescence

Treatment Gold Standard- Chloramphenicol 3-4 gm/day Children 50-75 mg/kg/day Afebrile 2gm/day or 30mg/kg/day(children) Or Amoxicillin 4-6 gm/day PO in 4 divided doses Trmithropsin/Sm2 640kg/3200 in 2 div. doses(adults) Ceftriaxone- rivals or better than chloramphenicol in rapidity of defervescence 2-4 gm/day x 9/7 Children-80mg/kg/day x 5/7

SHIGELLOSIS
Acute infectious Inflammatory Colitis Etiology o Slender, Gram Negative, Non motile o 4 Species 1. Shigella Dysenterae 2. S. flexueri 3. S. boydii 4. S. Sonnei Epidemiology o A person to person, mostly young children o Most concern- poor environmental sanitation and overcrowding Pathogenesis Oral ingestion Survive in low pH,passed through gastric acid barrier Invades colonic epithelial cells Cell to cell spread of infection Intracellular multiplication-cell damage- death Characteristic mucosal ulceration, may resemble pseudomonas With exudates containg desquamated colonic cell, PMN, RBC Swelling of capillary and venular endothelial cells with margination of neutrophils Glomerular damage and microangiopathic hemolysis Hemolytic Uremic Syndrome

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Clinical Manifestation o Dysentery characterized by frequent (10-20x) small volume stools consisting of blood, mucus and pus o Abdominal cramps and tenderness o Painful straining o (least likely to S. Sonnei) Diagnosis: o Specific Shigella cultures from stool with fecal leukocytes or bloody vey labile and should be quickly transferred to plates(Holding media- buffered glycerol suline) or it will not survive. Treatment o Commends multidrug resistant to chloramphenicol cotrimoxazole, sulfonamides o Tetracycline, streptomycin o Oral rehydration solution o Nalidixic acid 55mg/kg/dh x 5/7 o Fluoroquinolone(Ciprofloxacine) are highly effective) Contraindicated in children below 17yrs old and pregnancy due to cartilage toxicity

PSEUDOMONAS INFECTION
Ubiquitous, free living, opportunistic, gram negative pathogens, small aerobic, motile rod with single polar flagellum. Produces blue green pigment pyocyanin(aeroginosa=distinctive color of copper dioxide) Grows aerobically in most common media. Epidemiology o Widespread in nature- soil, water, plants, animals o Predilection for moist environment o Occasionaly, in healthy humans colonizing skin, extremities, ear, URT, or large bowel o Most infections are hospital acquired- potential reservoir Resp. Equipment Cleansing solution Disinfectant sinks Endoscope, physical therapy pool Vegetables and flowers Pathogenesis o Breach in cutaneous-mucosal barrier Trauma, Endo tracheal tubes, Catheter, IV drug abuse Compromised immunity Chemotheraphy Extreme of Age Diabetes Mellitus Hypogaaamaglobutemia Cystic fibrosis, Ca, AIDS Page 32

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Normal bacterial flora discripted by Broad Spectrum Antibiotic Therapy Exposed to reservoir in a hospital Environment

Malignant Transformation Local Bacterial Invasion

Oligopolyssacharide(Endoxin)

Exopolysaccharide-Exotoxin Clinical Manifestation o Respiratory- Pneumonia o CNS- Meningitis abscess o EAR- External otitis o EYE- Keratitis o BONE- Osteomyelitis o G.I- Necrotizing Enterocolitis o UTI- Ulcerative Lesime and Pelvis o Skin and Soft tissues- Necrosis surrounding erythema

DNA VIRUSES
(DEOXY NUCLEIC ACID) HERPER SIMPLEX (HSV, HSV2 HERPES VIRUS HOMINIS) Involves: a. Muco-cutaneous surfaces b. Central Nervous System c. Visceral Organs Pathogenesis

Primary replication in epidermis/ dermis Sensory autonomic nerve endings Intra- axon to nerve cell bodies/ ganglia

Peripheral sensory nerve endings to mucosal / skin surface

Centrifugal migration of virion

Producing large areas involve and distal to initial crop of vesicles

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Reactivated by: a. ultra violet b. immune- suppression c. trauma to skin (ganglia) Immunocompromised patient with defect in cell mediated immunity severe infection Causes 2 distinct Clinical entities: a. Varicella (Chicken pox) b. Herpes Zoster (Shingles)

VARICELLA- ZOSTER VIRUS INFECTION VARICELLA o Ubiquitous and extremely contagious infection which is usually a benign illness of childhood characterized by exanthematous vesicular rash, seeding from Nasopharynx Reticulo endothelial system viremia vesicles involving corium and dermis vesicular fluid become cloudy due to polymorphonuclear, degenerated cells and fibrin vesicles rupture release infectious virus or absorbed o Virus infects Dorsal Root Ganglia Remains latent infection is reactivated when immunity is lowered among the elderly (60-80 yrs old) Incubation Period: 10-21 days o Infectious 48 hrs prior to the onset of the vesicular rash until all vesicles are crusted Manifestations: o Rash o Low grade fever o Malaise o Macula papules vesicles scabs o In varying stages of evolution, successive crops of lesions appear in the trunk and face and rapidly involves all other parts of the body Secondary Bacterial Super Infection o most common complication

HERPES ZOSTER (SHINGLES) unilateral vesicular eruption within a DERMATOME associated with severe pain most commonly involved is T3 to L3 o Zoster Opthalmicus If ophthalmic branch of Trigeminal Nerve is involved onset is heralded as pain within dermatome that may precede lesions by 48 to 72 hours followed by an erythematous maculopapular rash which evolves rapidly to vesicular lesions Duration of Disease: 7- 10 days Branch of Trigeminal Nerve involved lesions on face, mouth, eye, tongue Ramsay Hunt Syndrome sensory branch of Facial Nerve is involved lesions in ear canal and tongue

o o o

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Management: Skin care and hygiene to prevent bacterial infection (tepid water bath and hot compress) Domeboro soaks for Herpes- Zoster Acyclovir 800mg p.o 5x daily for 5-7 days Children <12 years old 20mg/ kg every 6 hours

RABIES
Acute viral disease of the CNS affecting all mammals transmitted by infected secretions, usually saliva through bite of infected animal Etiology: o 2 forms 1. Urban- non- immunized domestic dog/ cat 2. Sylvatic- skunks, fox, racoons, bats, mongoose, wolf

Pathogenesis:

Live virus through epidermis/ mucus membranes

Primary Replication in striated muscles Up the nerve to CNS via peripheral nerve Axoplasm

Neuro- Muscular

In the CNS: replication within gray matter

Autonomic Nerve Salivary glands Adrenal Medulla

To other tissues: Kidneys Lungs Liver Skeletal muscles Skin Heart

Negri body Pathognomonic lesion Not demonstrated in 20% of cases but absence does not rule out rabies Eosinophilic Mass made up of finely fibrillar matrix Distributed throughout the brain particularly in: Ammons Horn Cerebral Cortex Brain Stem Hypothalamus Page 35

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Purkinje cell of cerebellum Dorsal Spinal Ganglia

Manifestations: A. Non- Prodromal 1-4 days 1. Non- specific o Fever 40C o Headache o Malaise o Myalgia o Increased fatigability o Anorexia o Nausea o Vomiting 2. Suggestive of Rabies- 50%- 80% of cases o Paresthesia with fasciculations at around site of bite- maybe related to primary repilation in dorsal nerve ganglia of sensory nerve at site of bite B. Acute Encephalitis 1. Excessive motor activity a. Muscle spasm b. Excitation c. Agitation 2. Meningeal Irritation a. Seizures b. Meningismus c. Episthotonus d. Facial Paralysis 3. Mental Aberration a. With lucid intervals, which get shorter b. Bizarre aberration of thought coma c. Confusion/ Hallucination 4. Hyperesthesia a. Excessive sensitivity to bright light, loud noise, gentle breeze 5. Upper Motor Neuron Paralysis a. Increased deep tendon reflexes b. (+) Babinski C. Brain Stem Dysfunction- shortly after 2 stage cranial nerve involvement 1. Hydrophobia o painful violent involuntary contraction of the diaphragm, accessory muscles of o respiration, laryngeal and pharyngeal initiated by swallowing fluids 2. Priapism and Ejaculation o involvement of amygduloid muscles o involvement of respiratory center causes apnea leading to death 3. Distinguish Rabies from other viral encephalitis o Median Survival: 4 days
nd

Post Exposure Prophylaxis 1. Local wound therapy o Wash with soap and water o 1%- 4% Benzylkonium Chloride- inactive virus Page 36

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2.

3.

Passive Immunity o Human Rabies Immunoglobulin 20 U/ kg 50% for local infiltration 50% IM gluteal Active Immunization o Human Diploid Cell Vaccine 1cc Intradeltoid or Antero-Lateral of thigh o Day 0- together with Human Rabies Immunoglobulin o Day 3, 7, 14, 28

WHO Recommendations for Rabies Treatment: Post exposure Treatment: Reemphasizes the importance of immediate and appropriate local wound treatment, and simultaneous and proper application of vaccine and immunoglobulin Regarding vaccine and immunoglobulin administration, the following points are stressed: a. The vaccine should administered into the deltoid muscle in adults and the antero-lateral zone of the thigh in small children whereas inoculation into the gluteal region should be discouraged b. Rabies antibody preparations (human rabies immunoglobulin or equine rabies immunoglobulin) may be administered in anticipation of active immunization only under exceptional circumstances (e.g. In the absence of vaccine). If rabies immunoglobulin has been administered prior to the vaccine, the first dose of vaccine should be increased to double or triple the normal amount and administered into several locations. c. Increasing the initial dose of vaccine should be considered for patients at higher risk such as those with underlying chronic disease (e.g. liver cirrhosis), patients who are immunodeficient, immunosuppresed and malnourished. Increasd initial dose might also be required for patients starting treatment after a delay of atleast 48 hrs or when rabies immunoglobulin is indicated but unavailable. d. A skin test is required when equine serum (equine rabies serum or equine immunoglobulin) is used. However, a positive reaction should not necessarily be regarded as contraindication provided that all necessary precautions are taken (adrenalin, antihistamines etc). The duration of the post- exposure treatment can be shortened through selected multisite post exposure regimens with potent vaccines (>2.5 IU/ ml), administered in association with rabies immunoglobulin whenever indicated. The recommended shortened regimens are: a. The 2-1-1 dose intramuscular schedule with 2 doses (1ml each) into each deltoid region at day 0 followed by 1 dose at day 7 and 1 dose at day 21. b. The multisite (e.g. 8 or 4 sites) intradermal schedule as currently used in Thailand, at days 0, 3, 7 plus 1 or 2 site(s) on day 30, but only in vaccination centers with staff well trained for intradermal injections. This regimen requires less than 2ml of vaccine in total. Rx: Lysovac N Berna (Purified Duck Embryo Rabies Vaccine)

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