Clinical Medicine Infectious Diseases

3 forms: bubonic and septic (acquired by flea bite), and pneumonic (transmitted person-person)

Eliminated 80% of Native American population.

• 500M infected
• 20-40M died
• 3 waves
• Unusual pattern of morbidity/mortality: mortality rate 2% vs 0.1%, young and healthy were dying

• Originated in India and spread via trade routes.
• Thought to be caused by “Miasma” (bad air)
• John Snow traced cause and considered father of modern epidemiology.

• Van Leeuwenhoek: discovered microbes
• Jenner: cowpox virus to make smallpox vaccine
• Semmelweiss: proposed etiology of puerperal fever
• Koch and Pasteur: advance germ theory
• Lister: initiated antiseptic principles

• Bacteria is present in all cases of the disease.
• Bacteria can be isolated and grown in culture.
• Disease can be reproduced by inoculation with bacteria.
• The same bacteria will be isolated from the experimental host.
• Limitations: some cannot grow in vitro, absence of animal model, diseases have multiple etiologies, diseases caused by normal flora, silent or subclinical infection,

• Aging infrastructure: infections related to contaminated water
• Influenza: next pandemic
• Bioterrorism: (Category A agents) Anthrax (Bacillus anthracis), Plague (Yersinia pestis), Tularemia (Francisella tularensis), Botulism (Clostridium botulinum), Smallpox

• US: pneumonia, sepsis, meningitis, Hep C
• World: malaria, infectious diarrhea, HIV/AIDS
• 25% of outpatient visits to PCP; URIs, STIs, UTIs
• Infections can result in chronic disease, malignancies; cervical, liver and gastric cancers, PUD, atherosclerosis

• Classic signs: rubor (erythema), calor (warmth), tumor (pain & swelling), functio laesa
• Infection can be peripheral or systemic

• Fever
• Chills or Rigors (visible chills, involuntary muscle contractions associated with sepsis and bacteremias)
• Myalgias
• Headache
• Anorexia
• Hypotension (shock)

• Inflammation due to infection that overwhelms the host.
• Diagnosis requires 2 or more of the following: Temp > 38°C (100.4°F) or < 36°C (96.8°F), Heart rate > 90, Respiratory rate > 20, WBC > 12k or > 10% bands
• Sepsis: SIRS + documented infection
• Severe Sepsis: Sepsis + organ dysfunction (hypoperfusion)
• Septic Shock: Sepsis – induced hypotension (SBP < 90)

• Changes in vascular function & permeability
• Leukocyte mobilization
• Release of acute phase reactants
• Release of biologically active mediators; cytokines, prostaglandins, bradykinins

• Core body temp average 37.5°C (98.6°F).
• Thermoregulatory center in the anterior hypothalamus.
• Hyperthermia is the uncontrolled increase in body temp due to dysfunction of the thermoregulatory center; heat stroke syndromes, adverse pharmacologic rxns, certain metabolic disorders.
• Fever varies over course of day; max oral temp 37.2°C (98.9°F) at 6am and max oral temp 37.7°C (99.9°F) at 4pm. White count also fluctuates.
• Low grade fevers may be significant in infants and elderly.
• Subnormal temp, especially in elderly and immunocompromised, can indicate severe infection.

• Infection; acute or chronic
• Connective tissue disease
• Malignancy
• Drug rxn
• Hyperthermia
• Fever of unknown origin (FUO)

• Fever + Localizing Symptoms
• Fever Only; no localizing symptoms
• Fever + Rash
• Fever + Lymphadenopathy

• Viruses: EBV, CMV, enteroviruses, various respiratory viruses
• Bacteria: no animal exposure (S. Typhi, Paratyphi, Listeria, S. aureus), animal exposure (Coxiella, Leptospira, Brucella, Ehrlichia), M. tuberculosis, H. capsulatum

• Viruses
• Maculopapular rash: EBV, CMV, HIV, measles, mumps, rubella, roseola, parvovirus B19
• Vesicular rash: Coxsackie A, HSV, VZV
• Bacteria: S. typhi, T. pallidum, GABHS (scarlet fever, TSS), S. aureus (TSS), N. meningitidis, N. gonorrhoeae, Borrelia, rickettsial diseases

• Generalized or Regional lymphadenopathy
• Viruses (generalized): EBV, CMV, HIV
• Bacteria (regional): tuberculosis, cat-scratch disease, tularemia, plague
• Protozoa: toxoplasmosis

• Neonates
• Hospitalized patients; nosocomial, post-operative
• Immunocompromised; HIV pts, neutropenic pts, pts on immunosuppressive therapy, elderly, pregnant women
• Travelers

• Documented fever ≥ 38.3°C (101°F) for a minimum of 3 wks with no clear diagnosis after 1 wk of work-up.
• Categories: classic (most commonly due to infection, malignancies, inflammatory disorders or drugs), nosocomial, neutropenic, HIV associated (usually due to CMV or indwelling lines)
• Differential diagnosis: neoplastic diseases (leukemia, Hodgkin and non-Hodgkin lymphoma, solid tumors), collagen vascular diseases, drug fevers, granulomatous disease (Sarcoid probably most common).

• Tuberculosis (especially disseminated disease)
• Abscesses (abdominal, pelvic, dental, tuboovarian)
• Endocarditis
• Sinusitis
• Osteomyelitis
• Viral infections (EBV, CMV, HIV)

• Meticulous history and physical exam (repeated)
• Always offer HIV testing
• Biopsy any suspicious lesions
• Consider bone marrow biopsy
• Rule out factitious disorder
• Some diseases have along incubation period.

• Tuberculosis
• STDs (chlamydia in females, HPV types 16 and 18, syphilis)
• Hep B
• Hep C
• Helicobacter pylori gastritis

• Onset, duration, characterization of current symptoms
• Medication use
• Occupational exposures, hobbies
• Sick contacts
• ETOH/drug use
• Travel
• Sexual activities

• Focused and guided by history and symptoms
• Examine skin and lymph, especially axilla and groin.
• Consider systemic febrile syndromes.
• Consider silent infections.

• Problem focused; ex. UA, rapid strep
• CBC diff
• Urine culture
• Routine chemistries
• Blood cultures
• ESR erythrocyte sedimentation rate
• CSF exam
• Joint fluid exam (N. gonorrhoeae)
• Serologic studies (IgM)
• Radiologic exam (ex CXR)

• Select therapy to cover microbes most likely to be causing patient’s infections.
• Order appropriate tests and cultures (based on PMH and PE) before initiating therapy.
• If causative organism is isolated, specific therapy should replace empiric therapy.

• Prevention; immunization history, risky behavior modification
• Identification of silent infections; treatment, prevention of complications, prevention of transmission.
• Risk counseling.

• HEENT: conjunctivitis, otitis externa, OM, rhinitis, sinusitis, pharyngitis
• Lungs: bronchitis, pneumonia
• Heart: pericarditis, endocarditis
• Abdomen: appendicitis, peritonitis, intra-abdominal abscesses, gastritis, gastroenteritis/ infectious diarrhea
• Skin: folliculitis, abscesses, furuncles, carbuncles, cellulitis, erysipelas, herpes labialis, genital herpes, chicken pox (varicella)/ shingles, necrotizing fasciitis, viral exanthems
• CNS: meningitis, encephalitis, meningoencephalitis
• Musculoskeletal: septic bursitis, septic arthritis, osteomyelitis
• GU: cystitis, pyelonephritis, STIs

• Conjunctivitis
• Dacryocystitis
• Blepharitis
• Sty (hordeolum)
• Keratitis

• Most common eye infection
• Viral or bacterial, both self-limiting, topical antibiotics often used.
• Viral Conjunctivitis: usually adenovirus
• Bacterial Conjunctivitis: S. pneumoniae, Haemophilus spp, Moraxella spp, Pseudomonas; infants add: N. gonorrhoeae, C. trachomatis

Infection of lacrimal sac 2° to obstruction

Infection of eyelid margins

• Staphylococcal abscess of eyelid.
• Treat with warm compresses, may add antibiotics.

• Infection of the cornea, can be viral, bacterial, fungal or parasitic (amoebic).
• Viral Keratitis: usually Herpes simplex
• Tx: avoidance of steroids is critical
• Bacterial Keratitis: (very aggressive course), P. aeruginosa, S. pneumoniae, Moraxella spp., staphylococci
• Tx: ↑ use of topical quinolones
• Contact lens use and corneal trauma are risk factors.
• Always ask if patient wears contact lenses!
• Must return if not better in 48 hrs.

• Otitis Externa
• Otitis Media

• Swimmer’s ear
• Infection of external auditory canal
• S/S: severe pain, itching, ± discharge, ↓ hearing (secondary to inflammation of EAC)
• Risk factors: any activity that leaves water in ear or mild mechanical trauma
• Etiologies: P. aeruginosa, Proteus, S. aureus
• Tx: topical antibiotics + hydrocortisone

• Infection of the middle ear.
• More common in children but can occur in adults
• Usually secondary to viral upper respiratory infection
• S/S: pain, occasionally purulent otorrhea
• Etiologies: H. influenza (primary), M. catarrhalis, S. pneumoniae, S. aureus, group A streptococci; occasionally viruses
• Tx: amoxicillin, macrolides (PCN allergic) (Azithromycin/Zithromax, Clarithromycin/Biaxin), amoxicillin + clavulanic acid (Augmentin), 2nd/3rd generation cephalosporin, IM ceftriaxone (long T½)

• Rhinitis
• Acute Rhinosinusitis

• Viral: common cold
• Large number of rhinovirus and coronavirus serotypes assure lifelong susceptibility
• Sx: headache, nasal congestion, sore throat
• Tx: symptomatic/supportive, topical decongestants, oral decongestants, mucolytics
• Antibiotics have no role; won’t prevent 2° bacterial infections

• Very common
• Usually follows viral upper respiratory infections.
• Most reliable sign is duration of symptoms: Nasocongestion that doesn’t improve after 7 days or nasocongestion + fever.
• Sx: headache, localized sinus pain/pressure, ± nasal discharge, fever
• Atypical symptoms in children
• Etiologies: S. pneumoniae, M. catarrhalis, H. influenzae, S. aureus
• Tx: amoxicillin, SMZ/TMP, cephalosporins, macrolides, quinolones (Levaquin, Avelox; last resort)

Pharyngitis

• Rapid test only or add culture? Culture is gold standard.
• Clinical Dx: Centor criteria; fever > 38°C, tender anterior cervical nodes (mono has tender posterior cervical nodes), lack of other respiratory symptoms, presence of an exudate
• Other S/S: smells bad, maculopapular rash (scarlet fever), beefy red appearance, ↑ WBC with ↑ neutrophils (mono has ↑ lymphocytes)
• Etiologies other than GABHS: Group C streptococci, N. gonorrhoeae, C. trachomatis, Mycoplasma spp., viruses including EBV, C. diphtheria, C. haemolyticum, anaerobic streptococci
• Tx: penicillin is drug of choice (DOC), single IM injection, cephalosporin (shorter course), erythromycin/azithromycin for PCN allergy, clindamycin for recurrence

• Bronchitis
• Bronchiolitis
• Pneumonia
• Common: mild to fatal
• Etiology related to age of patient, RSV, Human metapneumovirus, Influenza A & B
• CAP vs nosocomial
• Preceding viral infection can lead to bacterial 2° infection.
• Viral pneumonias common in young and old.

• Classically a bacterial infection but consider other etiologies
• Etiology: S. pneumoniae, M. pneumoniae, C. pneumoniae, Legionella spp., rare S. aureus
• S/S: pleuritic chest pain, productive cough, fever, rales on physical exam
• Dx: CXR (radiologic findings lag behind clinical findings), CBC with ↑ WBC with ↑ neutrophil, Gram stain & culture of sputum
• Tx: initiate empirically, tailor as indicated, 3rd generation cephalosporin (differ in ability to cover strep pneumo!), azithromycin/clarithromycin, amoxicillin + clavulanic acid, respiratory quinolones

• Etiologies: bacteria most common; also viruses and fungi
• S. aureus most common cause of all three
• Sexually active adolescents & young adults: N. gonorrhoeae, usually unilateral knee infection
• IVDU: P. aeruginosa
• Tx: joint aspiration is critical, penicillinase-resistant penicillin or vancomycin, ceftriaxone for Gram negative rods

• Rarely infectious in etiology.
• Can be sequelae of infection with bacteria or viruses.
• GABHS
• Chlamydia
• Enteric bacteria
• Hepatitis B, Hepatitis C
• Rubella
• Parvovirus B19

• Most cases caused by S. aureus
• Preceded by trauma, skin infection

• Usually an infection of the long bones
• Usually result of hematogenous spread from infected site
• Trauma an important factor
• Etiologies: S. aureus, P. aeruginosa, P. multocida
• Ulcers: polymicrobial; anaerobes
• Dx: x-rays, blood cultures important

• Superficial infection of hair follicle
• Usually bacterial (S. aureus)
• Can be viral (HSV) or fungal
• Hot tub: P. aeruginosa
• S/S: isolated papules, hair-bearing sites
• Tx: topical or systemic therapy, mupirocin or retapamulin, cephalexin or dicloxacillin; azithromycin for PCN allergy

• Abscesses
• Furuncle
• Carbuncles
• Etiology: almost exclusively S. aureus; consider MRSA
• Tx: incise & drain, systemic antibiotics

• Etiology: GABHS or S. aureus
• S/S: lesions may or may not be pruritic
• Tx: topical mupirocin or retapamulin, oral cephalexin, macrolide if PCN allergic

• Cold sores
• Most common manifestation of HSV-1 infection
• Prodrome of dysesthesia (tingling, burning) precedes development of lesions.
• Lesions: papule → vesicle → erosion → scab
• Triggers: stress, sun exposure
• Tx: topical penciclovir, oral valacyclovir, acyclovir
• Dx: cutaneous HSV, whitlow, gladiatorum

• Triggers: stress, fever / infection, antibiotics and sun exposure
• Other clinical manifestations: vertical transmission, encephalitis / meningitis, Bell’s palsy (suggested possible link), esophagitis, keratitis, folliculitis

• Bacterial infection of deeper layers of skin
• Etiology: almost always GABHS, also Gram – bacteria in immunocompromised patients
• S/S: poorly defined borders, more common on lower extremities, very painful, warm
• Risk: anything that causes break in intact skin, abrasions, lacerations, insect bites, fissuring
• Tx: cephalexin, amoxicillin + clavulanic acid, expanded spectrum quinolones, macrolides

• Cellulitis-like infection of skin, superficial only, face, legs
• Common in children, older adults
• Clue: raised borders
• Etiology: GABHS
• Tx: same as cellulitis, cephalexin, amoxicillin + clavulanic acid, expanded spectrum quinolones, macrolides

• Necrotizing cellulitis
• Necrotizing fasciitis (hallmark sign is pain out of proportion to physical findings)
• Myonecrosis
• Trauma & surgery increase risk but some cases idiopathic
• NF of perineum = Fournier’s gangrene; high mortality rate
• Etiology: GABHS ± S. aureus: anaerobes often involved also, often polymicrobial
• Tx: debridement, multiple antibiotic regimens

• Intra-abdominal abscesses
• Solid organ abscesses
• Extra-visceral abscesses
• Peritonitis (primary, secondary)
• Gastritis
• Appendicitis
• Diverticulitis
• Gastroenteritis / infectious diarrhea

• Liver most commonly involved
• Usually 2° to infection at other GI site, trauma or prior transplantation
• Spleen (2° SCD) or pancreas can also be affected
• Etiology: usually mixed infection, aerobic and anaerobic Gram negative rods, enterococci, usually polymicrobial
• Tx: drainage critical, regimen of multiple antibiotics

• Primary: aka spontaneous, almost exclusively in patients with ascites
• Etiology: mostly E. coli, other Gram – rods, enterococci
• Secondary: to anything that causes bowel leakage, trauma, surgery, high mortality rate, can also develop secondary to peritoneal dialysis
• Etiology: skin flora

• Epidemiology/ pathogenesis: many microbes (except fungi) are capable of causing diarrhea/ gastroenteritis, history/ exposure very important in determining etiology
• Travelers are at increased risk
• Viral: most acute diarrhea
• Bacterial: blood, fever
• Need stool workup if diarrhea not improving in 3 days.

• Invasive diarrheal disease
• Symptoms result from inflammatory response in colon
• Etiologies: Salmonella, Shigella. Campylobacter, C. difficile, Yersinia, V. parahaemolyticus, EHEC
• Tx: antibiotic therapy indicated for Shigella (SMZ/TMP or quinolone) and C. difficile (metronidazole), also severe cases of Campylobacter and Salmonella
• Consider non-infectious causes of inflammatory colitis.
• Don’t treat Salmonella (creates carrier state).
• Shigella usually transmitted person-person, fecal oral route.

• Bacterial: primarily organisms colonize but do not invade small bowel
• Toxin-mediated: enterotoxins → hypersecretion of isotonic fluid → watery diarrhea
• Etiologies: ETEC, V. cholerae
• Viral: produce same clinical picture but do so by invading gut epithelial cells
• Etiologies: rotavirus, noroviruses

• Results from ingestion of pre-formed toxins
• Etiologies: S. aureus, B. cereus, C. perfringens
• Sx: symptoms develop quickly after eating, clinically less diarrhea, more vomiting

• Meningitis
• Encephalitis
• Meningoencephalitis

Viral, bacterial, fungal or parasitic (protozoan) in etiology

• can be rapidly fatal
• S/S: altered mental status (AMS), unusual behaviors, ↓ level of consciousness, seizures
• Patients can present acutely or sub-acutely
• Acute presentation: fever, HA, neck stiffness, lethargy
• Sub-acute presentation: HA, focal neurological signs over days-months

• Majority of cases have acute presentation
• TB meningitis is exception
• Children, adolescents < 15yrs = ¾ of all cases
• Etiology age dependent.
• Neonates: Group B strep, E. coli, Listeria
• 0-5yo, 14-21yo: N. meningitidis; sporadic outbreaks among these groups in closed settings
• >5 yrs: S. pneumoniae (#1 cause)
• Listeria accounts for 10-15% of cases
• ~¼ of patients have abrupt, fulminating presentation
• Mortality rate high in this group
• Remainder have slower onset
• Dx: lumbar puncture essential
• CSF: 500-10,000 neutrophils/mcL; ↓glucose, protein,
• Gram stain positive for causative bacteria in 85% of cases
• Tx: IV penicillin or 3rd generation cephalosporin, ± vancomycin, prophylax contacts of patients with meningococcal meningitis

• Usually implies viral etiology
• CSF (direct exam and culture) negative
• Etiology: enteroviruses (95%): Coxsackie virus, ECHO, mumps, HSV, HIV
• Like bacterial meningitis more common in younger patients, Seasonal; summer and early fall.
• S/S: severe HA, fever, photophobia, development of focal neurologic signs worrisome for encephalitis or meningoencephalitis
• Dx: CSF has significantly lower WBCs, early neutrophils, later monocytes, normal glucose; normal to slightly increased protein
• Tx: (symptomatic) infection is benign, self-limiting, acyclovir, valacyclovir for HSV infections

• Signs/symptoms develop over weeks-months
• Bacterial or viral: HIV, M. tuberculosis, T. pallidum, B. burgdorferi (Stage 3 Lyme disease)
• Fungi and parasites also have role in chronic CNS infections

• Almost always viral
• Seasonal infection: this provides diagnostic clue
• Arthropod borne
• West Nile Virus: important emerging cause
• HSV: most common cause of viral encephalitis, no seasonal incidence, often preceded by upper respiratory prodrome
• CSF: lymphocytes, normal glucose, ↑ protein
• Nucleic acid amplification tests available for diagnosis.

• Cystitis
• Pyelonephritis
• Prostatitis
• Epididymitis
• STDs

• More frequent in women than men
• Incidence: increases with age, instrumentation (catheters), pregnancy, anatomic abnormalities of GU tract
• Ascending infections: endogenously acquired
• Etiology: E. coli accounts for majority of UTIs (80%)
• S/S Cystitis: frequency, urgency & dysuria; no back pain
• Older patients: no or unusual symptoms (AMS), can get urosepsis very quickly
• S/S Pyelonephritis: fever + CVA tenderness diagnostic
• Dx: WBCs, bacteria ± RBCs on urinalysis, WBC in pyelonephritis; culture, >105 bacteria = clinically significant
• Tx: minimum of 3 days for cystitis (7-14 days for pregnant women and children), 7-14 days for pyelonephritis, SMZ/TMP (monitor E. coli resistance), quinolone (Cipro), nitrofurantoin (Macrobid) 7 days, cephalexin (pregnancy)

• Keratitis
• Acanthamoeba keratitis
• Otitis Externa
• Acute Invasive Rhinosinusitis (mucormycosis)
• Chronic Non-Invasive Rhinosinusitis
• Allergic Fungal Rhinosinusitis

• Fungal pneumonias
• Endemic mycoses

• Histoplasmosis
• Coccidioidomycosis
• Blastomycosis

• Fungal arthritis
• Osteomyelitis

• Intertrigo
• Occluded skin
• Onychia / Paronychia

• General
• immunosuppression of any sort/ from any cause: solid organ, bone marrow and stem cell transplantation, extremes of age, immunosuppressive therapy (steroids, immunomodulating drugs: TNF inhibitors, etc), patients with AIDS, increased number of patients having major surgical procedures
• Keratitis risks: corneal injury involving plant material, pts with chronic disease of ocular surface, contact lens use
• Cutaneous Candidiasis Risks: occlusion/maceration
• Superficial Mucosal Candidiasis Risks: mild to moderate immunosuppression
• Deep Mucosal Candidiasis Risks: severe immunosuppression
• Dermatophytosis risks: occlusion, atopy, occupational exposure
• Tinea versicolor risk factors: high humidity, high rate of sebum production, application of “greasy” cosmetics
• Cryptococcosis Risks: HIV infection, pregnancy, long-term steroid therapy

• risks: corneal injury involving plant material, pts with chronic disease of ocular surface, contact lens use
• etiologies: Fusarium (↑↑ incidence; US incidence 25-65%), Aspergillus, Candida
• signs/symptoms: eye pain, foreign body sensation
• diagnosis: culture of corneal scrapings
• treatment: antifungal ophthalmic drops, natamycin for Fusarium; polyenes, oral azoles

• significant cause of suppurative keratitis in contact lens wearers
• Infection acquired secondary to improper handling of lenses or swimming, showering or hot tub use while wearing lenses
• symptoms: similar to fungal keratitis
• etiology: ~8 species of Acanthamoeba implicated in human disease
• treatment: difficult secondary to organism’s ability to encyst within cornea, chlorhexidine; polyhexamethyl biguanide, oral & topical azoles

• Etiology: Aspergillus species most commonly involved (>90% of fungal otitis externa), Candida species second most commonly involved
• Fungal OE can be acute or chronic; often results from overuse of topical antibiotics, fungal debris often visible in EAC
• treatment: topical acetic acid preparations; topical azoles, systemic therapy for severe cases

• 3 categories of disease
• Acute invasive: (aka mucormycosis)
• Etiology: caused by the Zygomycetes (Mucor, Absidia, Rhizopus), rapid, fulminant course in immunocompromised patients
• Chronic non-invasive: common in immunocompetent patients
• Etiologic agents: Aspergillus, Penicillium, many dematiaceous fungi: Alternaria, Cladosporium, Bipolaris
• Allergic fungal: enhanced response to environmental fungi, underlying allergic rhinitis common

Etiologic agents: Zygomycetes, hyaline Hyphomycetes, dematiaceous Hyphomycetes, endemic mycoses (only pneumonias likely to occur in immunocompetent patients; exception: allergic, non-invasive pulmonary aspergillosis), yeasts (including Pneumocystis pneumonia),

• Dimorphic fungi
• Most likely to present as CAP (community- acquired pneumonia) are Histoplasma, Blastomyces and Coccidioides
• Transmission: infections are acquired by inhalation; most go unrecognized as only small fraction of patients become symptomatic
• Natural course is spontaneous resolution unless: inoculum is very large, host is immunocompromised

• endemic mycoses causing systemic problems
• Histoplasmosis
• Coccidiomycosis
• Blastomycosis

• Etiology: Histoplasma capsulatum
• Endemic in Ohio/Mississippi River Valleys and associated with bird droppings (bat, chicken, starling)
• Clinical Presentation: ~5% of primary infections present as acute pneumonias, disseminated disease occurs mostly in immunocompromised patients, patients with chronic pulmonary disease may have persistent disease confined to lungs
• Tx: po itraconazole or IV amphotericin

• Etiology: Coccidioides immitis/posadasii
• geographically limited to North, South & Central Americas (US: California, Texas and Arizona)
• S/S: primary infection when it develops, = fever, cough, pleuritic pain ± arthralgias
• Disseminated disease: rare and can involve any organ. pregnancy increases risk of disseminated disease. African-Americans, Filipinos also at increased risk

• Etiology: Blastomyces dermatitidis
• organism is related to Histoplasma
• geographically limited to North America and parts of Africa. Endemic in Ohio/Mississippi River Valleys. Epidemics in NC, MN, IL, WS and VA common
• Clinical Presentation: primary pulmonary disease" resolution, chronic lung disease OR disseminated disease
• Disseminated disease: predilection for bones, skin, GU system
• Tx: itraconazole for 3 months

• Fungal arthritis & osteomyelitis quite rare
• Likelihood increased with immunosuppression
• Etiologic agents in immunocompetent patients: Candida species; often acquired secondary to trauma or surgery. Complication of steroid joint injections, endemic mycoses
• Dematiaceous fungi: post-traumatic
• Etiologic agents in immunocompromised patients: Candida species, Aspergillus species

• Less common than viral & bacterial CNS infections
• Fungi: meningitis
• Parasites: focal abscesses

• Immunocompetent hosts
• Etiologic agent: Cryptococcus neoformans, From pigeon droppings
• Risks: HIV infection, pregnancy, long-term steroid therapy
• 1° infection is pulmonary and usually asymptomatic; disseminated disease may involve any organ but high predilection for CNS
• Sx: severe headache, AMS; meningeal signs less prominent, skin lesions resemble bacterial cellulitis
• Dx: LP, CSF culture; capsular antigen detection
• CSF: increased protein; decreased glucose
• Tx: fluconazole po x 3 months; for more severe cases IV amphotericin B ± 5-flucytosine
• endemic mycoses, esp Histoplasma and Coccidioides

• Immunocompetent hosts
• Etiology: cysticercosis (Taenia solium)
• Amebic meningoencephalitis
• Etiologic agents: Naegleria species, Acanthamoeba species, Balamuthia mandrillaris
• Obtained from contaminated water
• Naegleria: organism invades CNS via cribriform plate; rapidly fatal infection in children and young adults
• Tx: amphotericin B ± rifampin
• Acanthamoeba: acquired via contaminated water; clinical disease = granulomatous encephalitis
• B. mandrillaris: Subacute meningoencephalitis
• Immunosuppression increases spectrum

• Tinea versicolor
• Dermatophytic infections
• Muco-cutaneous candidiasis
• Onychomycosis

• Occlusion/maceration are risks
• Intertrigo (skin opposing skin): axillae, groin, intergluteal, inframammary, webspaces of digits
• Occluded skin: under bandages/casts, on backs of bed-ridden patients
• Onychia/paronychia
• Paronychia: occupational exposure to water, finger nails and toe nails
• Fingernails: secondary to frequent hand-washing
• Toenails: secondary to occlusion
• Tx: nystatin, topical or oral triazoles

• Superficial: mild to moderate immunosuppression is a risk, oropharynx, vagina and angles of mouth (cheilitis)
• Deep: severe immunosuppression is risk, esophagus, tracheobronchial tree, bladder
• AIDS-defining illness
• Once deep mucosa is invaded Candida can become invasive
• Tx: nystatin, topical or oral triazoles
• New agents: echinocandins, caspofungin is prototype

• Superficial mycosis
• Infect skin, hair & nails
• Clinical manifestations referred to as tinea
• Infections transmitted person-to-person via fomites, animal-to-humans directly or via soil
• Risks: occlusion, atopy, occupational exposure
• Epidemiology: 3 genera responsible for disease; Epidermophyton, Trichosporon, Microsporum
• Dx: clinical or KOH scrape
• Tx: topical or oral azoles; allylamines

• Superficial mycosis
• Etiology: Malassezia furfur, lipophilic yeast
• Normal skin flora
• Risk factors: high humidity, high rate of sebum production, application of “greasy” cosmetics
• Clinical manifestations: hypo- (or hyper) pigmented lesions on face, trunk and upper extremities
• Dx: clinical or KOH preparation
• Tx: topical or oral azoles; selenium sulfide

• “Pinworms”
• Etiology: Enterobiasis vermicularis
• Most common parasitic intestinal infection
• Ingested eggs hatch in duodenum; migrate to cecum where they live
• At night females crawl out to perineum where they lay eggs
• Transmission: fecal-oral, inhalation
• Sx: severe rectal itching
• Dx: tape test; but often clinical
• Tx: albendazole (Vermox)

• Etiologic agent: Giardia lamblia
• Most common parasitic enteric pathogen
• Disease has 4 forms: asymptomatic infection (~60%), acute diarrhea , chronic diarrhea, malabsorption
• Transmission: fecal-oral, person-to-person or ingestion of contaminated food, water
• Dx: direct exam of stool. Immunoassay
• Tx: metronidazole, tinidazole, nitazoxanide

• After giardiasis most common parasitic enteric pathogen
• Etiology: > 10 species of Cryptosporidium implicated in disease
• Transmission: identical to Giardia, fecal-oral, person-to-person or ingestion of contaminated food, water
• Both immunocompetent & immunocompromised at risk
• S/S: range from mild diarrhea to severe enteritis, biliary complications not unusual in severe disease
• Dx: immunoassays; nucleic acid amplification
• Tx: usually none, nitazoxanide for more severe cases
• Isosporiasis (Isospora belli) & cyclosporiasis (Cyclospora cayetanensis) have similar epidemiology

• Etiologic agent: Entamoeba histolytica
• E. dispar, E. moshkovskii non-pathogenic species
• Infection rare in US; in developing world is second leading cause of deaths due to protozoal disease
• Suspect in immigrants, travelers back and forth to endemic areas
• S/S: disease range from asymptomatic carriage(most common) to severe dysentery
• Extra-intestinal disease: hepatic abscesses
• Dx: stool exam; antigen detection assays
• Tx: metronidazole is DOC

• Etiologic agent: Strongyloides stercoralis
• Endemic in southern US; increased incidence in Appalachia and in Puerto Rico
• Autoinfection plays important role in maintaining infection for years
• Sx: mild to severe, waxing/waning GI symptoms; persistent eosinophilia
• Dx: immunoassay; stool exam difficult
• Tx: ivermectin, thiabendazole, albendazole

• Blood and tissue protozoa
• Etiology: Plasmodium spp
• one of the most devastating infectious diseases worldwide (> 3 million deaths/year)
• 4 species of Plasmodium; each has different geographic distribution & treatment regimens
• ~1,000 “imported” cases in US each year
• Organism initially develops in liver then parasitizes RBCs
• Complex life cycle involving two hosts: female Anopheles mosquito and humans
• Travelers to endemic areas must be carefully advised
• Dx: thick and thin blood films
• Tx: determined by species/ areas of resistance

• Etiologic agents: molds are most common cause of invasive disease in stem cell/ solid organ transplant patients
• especially implicated: non-fumigatus species of Aspergillus, Zygomycetes, non-albicans species of Candida and hyaline septated fungi (hyalohyphomycoses)
• Important hyalohyphomycoses: Fusarium, Scedosporium, Acremonium, Paecilomyces

• Fungemia: may be self-limiting
• disseminated disease (organism isolated from 2nd site): retina, CNS, myocardium, liver/spleen
• Endocarditis frequent complication of fungemia
• Tx: long-term systemic anti-fungals

• Opportunistic infection that causes disease in a wide variety of immunocompromised patients
• Worldwide distribution
• Transmission: 1° acquired via inhalation
• S/S: SOB; interstitial pneumonia follows accompanied by significant hypoxia
• Dx: CXR— diffuse patchy infiltrates
• Tx: SMZ/TMP (Bactrim), Pentamidine, atovaquone ± steroids

• Etiology: Toxoplasma gondii
• Organism develops in intestinal cells of cat (but many animals are hosts); cysts mature in excreted feces
• Transmission: infection results from ingestion of infected oocytes or contaminated meat
• Most infections are asymptomatic
• Clinical manifestations of symptomatic disease:
• Acute disease: flu-like symptoms
• Congenital infection
• Reactive disease in immunocompromised patients; brain, eye and lung most common targets

• Be very careful with application of steroids on: axilla, face, and groin
• Don’t use Lamisil for Candida infections; only works on dermatophytes. Topical azoles work on BOTH Candida and dermatophytes

• Sanitation: Maintenance of drinking water supply, removal of refuse and sewage.
• Vector control: insecticides, pesticides
• Education
• Responding to public threats from IDs
• Screening for asymptomatic IDs: tuberculosis
• Reportable infections: varies by state
• Vaccinations

• Vaccinate animals
• Stay away!
• Post bite prophylaxis
• Insecticides/pesticides
• Proper clothing
• Inspection
• Personal Protective Measures: Hand washing, Cover nose/mouth, Gloves, Eye protection, Gowns, Proper clothing, Insect repellants, safer sexual practices

• Individuals who have 1 or more defects in body’s normal defense mechanisms-increased risk for infection.
• The key here is for the provider to think about different organisms than you would in the normal population.
• Risks: HIV, Congenital immunodeficiency, Corticosteroid therapy, Biological response modifiers, Hematologic malignancy, Chemotherapy, Asplenia , DM, Renal failure, Organ transplant
• Prevention: Thorough history and physical, Vaccines (Recommended vs. contraindicated; In general, killed vaccines can be given to all patients; live vaccines are contraindicated in patients with severe immunosuppression), Special populations (i.e. asplenia increases risk of encapsulated organisms), Close contacts and health care workers, Reducing exposures (Avoid tap water, raw/undercooked meat/eggs/seafood, fresh flowers, hand-washing, pet care), Prophylactic medications

• Safer sexual practices: Barrier methods
• Decreasing high risk behaviors
• Screening
• Treatment of contacts
• Reportable infections
• Vaccines (Hep B, HPV)

• Grade A and B recommendations: discuss with eligible patients and offer as priority
• Grade C recommendations: need not be provided unless individual circumstances warrant
• Grade D recommendations: negative recommendations (“don’t”); discourage use of services
• Grade I recommendations: discuss with patients the uncertainty surrounding these; evidence of their use has thus far failed to show a benefit

• High-intensity behavioral counseling to prevent sexually transmitted infections (STIs) for all sexually active adolescents and for adults and increased risk for STIs. Grade: B
• Current evidence is insufficient to assess the balance of benefits and harms of behavioral counseling to prevent STIs in non-sexually-active adolescents and in adults not at increased risk for STIs. Grade: I

• High risk adolescents and adults: Grade A (men having sex with men after 1975, Unprotected sex with multiple partners, Past or present IVDU, Those who exchange sex for money, Other STDs, Sex with HIV infected, bisexual or IVDU, Blood transfusion between 1978-1985)
• Pregnant women: Grade A
• Others: Grade C (CDC has different recommendation)

• Sexually active women < 25/high risk: Grade A
• Pregnant women ≤ 24 (older if high risk): Grade B
• Low-risk women ≥ 25: Grade C
• Asymptomatic Men: Grade I

• Sexually active women with increased risk: Grade B
• Pregnant women not at increased risk: Grade I
• Men at increased risk: Grade I
• Men/women without increased risk: Grade D

• Pregnant women: Grade A
• General population: Grade D

• General population: Grade D
• High-risk population: Grade I

• Increased risk: Grade A (men who have sex with men and engage in high-risk sexual behavior, commercial sex workers, persons who exchange sex for drugs, those in adult correctional facilities)
• Pregnant: Grade A
• General population: Grade D

• Weakened wild virus/bacteria
• Replicate in host → elicit immune response
• Uncontrolled replication. Because they work by replicating in the body we don’t give them to people in which replication may proceed uncontrolled.
• 1-2 doses for long term immunity
• Immunity equal to that caused by disease
• If cause disease then adverse reaction
• Theoretical risk of infection of fetus (only happened with small pox) so don’t give to pregnant women.
• Anything that would destroy the organism (heat, light) or prohibit replication in the body (circulating antibodies-from blood products or IV immunoglobulins) will make the vaccine ineffective.

• Culture grown organism is inactivated
• Do NOT replicate in the host
• Can NOT cause disease
• Require multiple doses (humoral immunity)
• NOT affected by circulating antibodies
• Can give to immunosuppressed
• Little cellular immunity conferred

• Passive immunity
• Babies receive passive immunity from their mothers.
• Short term

• Vaccination: leads to active immunity which is long-term or lifetime
• Immunoglobulin: passive immunity in which antibodies (human or animal) are injected and provide temporary protection

• Tetanus is only vaccine preventable disease that is infectious but not contagious
• 1° series completed by age 6: Other forms DT or DTaP available for kids <7, contain same amount of tetanus toxoid but more diphtheria.
• Adults without prior immunization: Td x 2 (4 weeks apart), followed by another in 6-12 months
• Adults with some prior immunization: Need total of 3
• Booster every 10 years: not generally recommended more frequently, Increased risk of local reactions
• Acute “dirty” injuries: TIG (Tetanus Immune Globulin)
• Adverse reactions: local, Arthus-like, ?Guillain-Barré Syndrome (GBS), Arthus-like reactions are exaggerated local reactions that occur from 2-8 hours after injection. GBS rare.
• If “allergy” and not life-threatening symptoms need allergy testing

• Adults born prior to 1957: considered immune*
• Adults born after 1957: one dose
• Adults born between 1963-1967: need one dose of current vaccine
• Students entering college, health care workers, traveling outside US: 2 doses, Separated by 4 weeks
• Do NOT vaccinate: Pregnant, Immunocompromised (except asymptomatic HIV with CD4 count ≥ 200)

• Adults born prior to 1957: immune
• Adults born after 1957: one dose
• 2nd dose: post secondary education, work in health care facility, international travelers
• Use MMR if need to revaccinate for measles
• ? Lifetime immunity
• Do not vaccinate: pregnant women (theoretical risk), immunocompromised

• Hep A is most frequently reported type of hepatitis in U.S.
• 2 shot series: 6-18 months apart
• Advised for: travelers to endemic areas and other high risk individuals, IV drug users (IVDU), men having sex with men, occupational risk, chronic liver disease, persons who receive clotting factor concentrates, parents of international adoptees
• Duration of immunity: ? Lifelong
• Immune globulin to exposed, unprotected patients
• Combination Hepatitis A and B vaccine is available for persons 18 and older: 3 injection series (0,1,6-12)

• 3 shot series: 0,1,6-12 months
• Recommendation: Men who have sex with men, IVDU, multiple sex partners (>1 in previous 6 months), diagnosed with other STI, commercial sex workers, HCWs, public safety workers, inmates
• end-stage renal disease, chronic liver disease
• others*
• HBIG (immune globulin) with vaccine for susceptible exposures
• Smokers, pts > 50, obese, and those with HIV may not develop immunity after 1st series

• Adults born prior to 1957: immune, except if woman who is likely to become pregnant
• Recommended for: all women of child-bearing age w/o evidence of immunity and health care workers (HCW) exposed to patients that might be pregnant
• CRS (Congenital rubella syndrome)
• Do NOT vaccinate: immunocompromised (may give if HIV+ and CD4 count ≥ 200).
• Anaphylactic reaction to neomycin is a contraindication

• Recommendation: Adults 65 and over, Residents of long-term care facilities, Adults of any age with chronic disease, asplenia, sickle cell disease, cochlear implant, alcoholism, and immunocompromised
• Revaccination: Single revaccination 5 or more years after the first, Immunocompromised, asplenia, chronic renal failure, >65, if first vaccination occurred before the age of 65 and at least 5 years earlier

• All individuals > 13 yo without evidence of immunity
• 2 dose series: 4 weeks apart
• Live attenuated virus
• Do NOT give: to pregnant women or immunocompromised (can give to HIV+ with CD4 count ≥ 200)
• Contraindicated with neomycin allergy (anaphylaxis)

• FDA approved 2006, ≥ 60 years old
• ± prior episode of zoster
• not for immunosuppressed

• Annual vaccine: best if precedes exposure by no more than 2-4 months
• 2 types: Inactivated (TIV), Live (nasal spray-FluMist)*
• Recommendation: Adults > 50, Pregnant women, Chronic Diseases (cardiopulmonary, metabolic, renal, hemoglobinopathy, immunosuppression), Health care workers, employees of assisted living facilities, Caregivers of children < 5 years
• Live vaccine for healthy, non-pregnant people < 50
• Live attenuated virus replicates in mucosa of UR tract, therefore may cause “cold” symptoms but not influenza. However, may transmit virus to susceptible people therefore should not be used in caregivers of severely immunocompromised
• Severe egg allergy is a contraindication

• Adacel licensed in June 2005
• Tetanus, diphtheria, and pertussis protection
• Approved for ages 11-64 as single dose for those completing Dtap series
• All adults should receive one Tdap, replacing usual Td, if last Td 10 years previous
• May give before 10 years if high risk
• Postpartum, close contact with infants <12 months, HCW with direct patient contact
• If > 2 yrs since last Td
• If starting initial series for tetanus, diphtheria, and pertussis, one dose should be Tdap

• Most common STD
• Gardasil (HPV4): first vaccine to prevent cervical cancer (June 2006)
• Recommend routine vaccination of girls age 11-12
• Women aged 13-26 not vaccinated
• 3 doses, 2nd given 2 months after first, and 3rd given 6 months after first
• 2009: recommendation for males ages 9-26 years
• Cervarix (HPV2): approved this year in US
• Recommended for females ages 10-25 years

• Meningococcal conjugate vaccine: Menactra® (MCV4)
• Recommended for college freshman living in dorms and persons 11-55 at increased risk
• Microbiologists working with N. meningitidis, military recruits, travelers to countries where epidemic, asplenia
• Adverse event: Guillain-Barré Syndrome
• Meningococcal polysaccharide vaccine (MPSV4)
• Preferred vaccine for persons ≥ 56 years old
• Revaccination with MCV4 is recommended after 5 years for adults who remain at increased risk

• MMR
• Varicella

• Meningitis-bacterial
• ciprofloxicin 500mg po x 1 or
• ceftriaxone 250 mg IM x 1 or
• rifampin 600 mg po q12hX4 doses
• Influenza
• oseltamivir (Tamiflu) 75mg daily
• zanamivir (Relenza) 2 inhalations daily
• 10 days if household contact
• 28 days if community outbreak
• Vaccine
• Treatment of asymptomatic illness
• Latent TB