Micro/id Set 5

Front 1

Define “zoonosis”.

Back 1

Zoonosis – any infectious disease that may be transmitted from other animals, both wild and domestic, to humans or from humans to animals

Front 2

Define “vector”.

Back 2

Vector – any animal that transmits an agent of human disease or plays an essential role in the agent’s life cycle. Examples – anopheline mosquitoes of malaria, snail hosts of shistomiasis, rodent reservoirs of leshmaniasis, Typically refers to arthropod vectors (mosquitoes, ticks, flies, lice, fleas, etc.)

Front 3

How do you get leptospirosis?

Back 3

Contact with contaminated animal or rodent urine (water or soil; skin abrasions or conjunctivae; domestic pets and livestock)

Front 4

What is the clinical presentation of leptospirosis?

Back 4

Fever, headache, myalgia, abdominal pain, conjunctival suffusion, Note – 5-10% of patients develop icteric form of Leptospirosis known as Weil’s disease

Front 5

What is Weil’s disease?

Back 5

An icteric form of leptospirosis that may precede renal failure, pulmonary hemorrhage, cardiac arrhythmias, ocular menifestations (uveitis, a late manifestation that may lead to blindness), and, in 5-15% of cases, death (increases with age)

Front 6

How do you diagnose leptospirosis? What are some of its complications?

Back 6

Diagnosis and Complications – culture during acute spirochetemia ONLY (1st week only); darkfield microscopy very insensitive (need >10^4 organisms/mL), IHC ~ unavailable; PCR more sensitive than culture, but need broad range of primers to amplify all serovars; Microagglutination test (MAT) to detect Leptospira spp. Antibodies (early as 5-7 days post-onset; single high titer acceptable, but seroconversion preferred)

Front 7

How do you treat leptospirosis?

Back 7

Treatment – doxycycline, penicillin, ceftriaxone + supportive care for Jarisch Herxheimer reaction

Front 8

How do you get brucellosis?

Back 8

Human Transmission: Oral contamination from domestic farm animals, Consumption of unpasteurized dairy products, Inhalation of aerosolized contaminated animal products,

Front 9

What are the clinical manifestations of brucellosis? (Compare classical vs. undulant forms)

Back 9

Classical febrile: Insidious onset of fever, sweating, malaise, headache, weight loss, Arthralgias, arthritis, myalgia, back pain, Acute infection (w/I 2 weeks of infection); Relapsing/Undulant (Malta Fever), Occurs >2 months after classical febrile brucellosis if untreated/undertreated/unrecognized, Liver involvement, arthritis, uveitis, oriepidymitis, May be chronic, lasting >1 year

Front 10

What are complications of brucellosis? [It’s almost as cool as syphilis!]

Back 10

Peripheral Arthritis (acute infection, non-erosive, involves knees, hips, ankles, wrists), Sacroilitis (acute infection), Spondylitis (lumbar spine, often results in residual damage, potential genetic association with HLA-B39), Epididymoorchitis (granulomatous inflammation), Abortion, Liver (hepatomegaly, granulomatous hepatitis), CNS (meningitis, meningoencephaitis, encephalitis, brain abcess; grave prognosis), Endocarditis (main cause of mortality, usually aortic valve, generally requires valve replacement surgery), Relapse (after inadequate treatment, usually within the 1st year after diagnosis and treatment)

Front 11

How does one make a diagnosis of brucellosis?

Back 11

Blood culture/bone marrow culture, Need BSL3 lab; AB detection (most common), Serum agglutination test

Front 12

How do you treat brucellosis?

Back 12

Treatment – doxycycline + rifampin orstreptomycin/netilomycin for 4-6 weeks

Front 13

If you obtain a bone marrow biopsy on a patient with brucellosis, what histological findings would you expect? [What other organism does that remind you of?]

Back 13

LIKE TB

Front 14

What diseases does Bartonella henslea cause?

Back 14

Cat-scratch disease, endocarditis, bacillary angiomatosis-peliosis (angeioproliferation), bacteremia, bacteremic syndrome

Front 15

What are the clinical manifestations of bartonella henslea?

Back 15

Clinical manifestations – regional lymphadenopathy with or without fever; kitten or cat scratch/bite; papule at inoculation site; characteristic histopathologic features

Front 16

How do you contract bartonella henslea?

Back 16

Contraction – contact with, bites or scratches of kittens/cats

Front 17

Describe Parinaud’s Oculoglandular Syndrome.

Back 17

Parinaud syndrome is an eye problem similar to conjunctivitis ("pink eye"). It usually affects only one eye and is accompanied by nearby swollen lymph nodes and an illness with a fever.

Front 18

What is the classic histologic change seen in cat scratch disease?

Back 18

Granulomatous lymphadenitis with “stellate microabscesses”

Front 19

Describe Oroya fever

Back 19

The acute phase of Bartonella infection; Clinical symptoms of bartonellosis are pleomorphic and some patients from endemic areas may be asymptomatics. The two classical clinical presentations are the acute phase and the chronic phase, corresponding to the two different host cell types invaded by the bacterium (red blood cells and endothelial cells).; Acute phase: (Carrion's disease = Oroya Fever) the most common findings are fever (usually sustained, but with temperature no greater that 39°C), pallor, malaise, nonpainful hepatomegaly, jaundice, lymphadenopathy, splenomegaly. This phase is characterized by severe hemolytic anemia and transient immunosuppression. The case fatality ratios of untreated patients exceeded 40% but reach around 90% when opportunistic infection with Salmonella spp occurs.

Front 20

What are the diseases caused by adenoviruses?

Back 20

Respiratory Infections (common cold, bronchitis, pneumonia, ARDS), Gastroenteritis, Conjunctivitis, Cystitis (often hemorrhagic) – usually in kids who have gotten immunosuppressive therapy of cell-mediated immune system

Front 21

What is the seasonal distribution of adenoviruses?

Back 21

Adenoviruses – year-round

Front 22

What is the seasonal distribution of rhinoviruses?

Back 22

Rhinoviruses – year round

Front 23

What is the seasonal distribution of influenza?

Back 23

Influenza (seasonal) – winter

Front 24

What is the seasonal distribution of enteroviruses?

Back 24

Enteroviruses – summer/fall

Front 25

Name 4 viruses that cause upper respiratory infections

Back 25

Rhinoviruses, Adenoviruses, Coronoaviruses, Paramyxoviruses

Front 26

What diseases are associated with enteroviruses?

Back 26

Meningitis, Encephalitis, Respiratory illness (coxsackie), Hand foot mouth disease (coxsackie), Hemorrhagic conjunctivitis (enteroviruses 70&71), Myocarditis (coxsackie)

Front 27

How does one get infected by enterovirus?

Back 27

Contract the virus via fecal-oral transmission (excreta from man getting into runoff, sewage, landfills, then contaminating water sources, which then contaminate crops, aerosols, shellfish, water supplies and can infect many people)

Front 28

Describe the clinical manifestations of polio

Back 28

90% are ASYMPTOMATIC, 9.9% result in mild respiratory illness, only 0.1% result in paralysis, Paralytic polio – myalgias followed by flaccid paralysis (usually asymmetric and involving legs>arms); can involve medullary respiratory centers IRON LUNG

Front 29

Which vaccine against polio do we now use and why?

Back 29

We currently use the inactivated form of the vaccine, as live attenuated version demonstrated a tendency for rare reverting to infectious wild-type poliocirus

Front 30

Describe the epidemiology of rubeola (measles).

Back 30

Geographic distribution: Worldwide; incidence depends on vaccination rates, Epidemic – countries with high vaccine coverage, Endemic – countries with poor vaccination rates, Age – dist’n has changed in countries with high vaccination rates, Routes of transmission – respiratory, aerosol, Attack rate – 99.9%, Mortality rate – In developing countries, 30% in infants 6-9 months

Front 31

Describe the pathogenesis of rubeola (measles)

Back 31

Systemic replication, First site – respiratory epithelium, Second site – local lymph nodes, Dissemination by infected monocytes departing from respiratory LNs (primary viremia), Epithelial/endothelial cells infected throughout body release virus into blood (secondary viremia)

Front 32

Describe the clinical symptoms of rubeola.

Back 32

Arise during VIREMIA, Prodrome – fever, cough, corzya, conjunctivitis, Koplik spots, Rash arises with immune response, Manifestation of cellular response,

Front 33

Describe prevention of rubeola (measles).

Back 33

Live attenuated vaccine, Given to infants 12-15 months of age, Has changed age dist’n of infection, Now very young infants and older children/young adults (10-22 years)

Front 34

Describe the incubation period of rubella.

Back 34

Incubation – 14-21 days

Front 35

Describe the transmission method of rubella.

Back 35

Transmission – respiratory

Front 36

Describe the symptoms of rubella.

Back 36

Symptoms – most asymptomatic; low-grade fever, lymphadenopathy, and conjunctivitis followed by rash on face, which spreads to the trunk and limbs and usually fades after 3 days.

Front 37

What is congenital rubella syndrome?

Back 37

Congenital Rubella Syndrome – Mental and growth retardation, heart defects, cataracts

Front 38

Describe the congenital rubella syndrome. Do all infants of infected mothers get CRS?

Back 38

Congenital Rubella Syndrome – growth retardation, mental retardation, malformation of heart and eyes, deafness, and liver/spleen/bone marrow problems,

Front 39

Do all infants of infected mothers get congenital rubella syndrome?

Back 39

NOT ALL INFANTS of infected mothers get CRN – need maternal exposure, maternal blood invasion, placental infection, entry into the baby’s blood, AND Fetal infection for the child to get CRN – all factors mediated by differences in virus itself as well as differences in the host. If mom gets rubella after 1st 20 weeks of pregnancy, likelihood of CRS drops precipitously.

Front 40

How is West Nile Virus transmitted?

Back 40

Transmitted by infected mosquitoes (when they bite humans)

Front 41

What are some common features of Herpesviruses? Are they small or LARGE viruses?

Back 41

Morphology: Outer envelope – buds from host membrane, DS DNA genome packed inside protein coat, Viral glycoprotein on outside of virion, HUGE genome (>100 kb) with over 50 genes encoding enzmes, structural, and nonstructural genes (modulators of host cell gene expression and host immune responses), Ubiquitous, Infection often asymptomatic, Common modes of replication, Productive infection à release of progeny virions (lytic infection), Latent infection (no virion production; acts as reservoir for recurrent disease; recurrent disease occurs as consequence of renewed replication OR cell proliferation – limited to tumor-inducing gamma herpesviruses only – EBV, HHV-8), All establish latent infections, Reactivation can produce disease

Front 42

Compare latent vs. lytic infections

Back 42

Lytic (Productive) infection à release of progeny virions, Latent infection (no virion production; acts as reservoir for recurrent disease; recurrent disease occurs as consequence of renewed replication OR cell proliferation – limited to tumor-inducing gamma herpesviruses only – EBV, HHV-8), Replication cycle during lytic infection, Virion entry via envelope fusion with cell membrane, Nucleocapsid transport to nucleus, Nuclear events, Viral gene transcription, Genome replication, Progeny nucleocapsid assembly, Nucleocapsids bud from nucleus, viral envelope formed from nuclear membrane, progeny virus released via exocytosis

Front 43

What are gene expression patterns of lytic and latent infections?

Back 43

Gene Expression Patterns: Lytic - Occurs in temporary cascade, Alpha (immediate early genes) – regulators of viral gene expression, Beta (early genes) – proteins req’d for genome replication, Gamma (late genes) – virion structural proteins, Latent - Restricted gene expression

Front 44

How many cell types are affected in lytic and latent infections?

Back 44

Lytic - Many different cells (usually >2); Latent - Few (usually 1 or 2)

Front 45

How are the various herpesviruses transmitted?

Back 45

Natural Modes: Mixing and matching of skin and mucous membranes, HSV-1, -2 – Skin + Genital tract, Secretions: Oral (HSV-1,-2, CMV, HHV-6, EBV), Respiratory tract (VZV), Transplacental (CMV, rare HSV, VZV); Iatrogenic Modes, Transfusion, Transplants

Front 46

Who is at risk for severe herpesvirus infections?

Back 46

Immunodeficient (i.e. HIV infected), Immunosuppressed (transplant recipients, cancer patients), Fetus/newborns, Malnourished, Burn victims, Malnourished, Burn victims

Front 47

What are common misperceptions about HSV1 and HSV2?

Back 47

Common perceptions – HSV-1 above the waist, HSV-2 below the waist, Actually, 20-50% of genital infections are HSV-1, and 5-20% of oral herpes infections are HSV-2

Front 48

Compare and contrast the clinical manifestations of genital HSV1 vs. HSV2

Back 48

Symptoms: Small red bumps, blisters (vesicles) or open sores (ulcers) in the genital, anal, or nearby areas, Pain or itching around genital area, buttocks, inner thighs.; Recurrence: In both cases, can occur after years of “silent” infection and are less severe than primary disease (shorter shedding duration, fewer lesions); shedding rates decline by 70% over 10 years, HSV-2 causes more recurrences than HSV-1, Frequency and severity of symptoms w/r/t recurrence – HSV-2>HSV-1

Front 49

What are the factors that affect HSV recurrences?

Back 49

Time since acquisition (shedding rats drop by 70% over 10 years), Virus type (genital herpes – HSV-2 causes more recurrences than HSV-1), Immune status (immunocompromised patients recur more frequently)

Front 50

What is the most common cause of preventable blindness in resource-poor countries? In economically- advantaged countries? [hint: both are infections]

Back 50

Resource-Poor Countries: Trachoma resulting from infection by Chlamydia trachomatosis, Developed world: HSV Keratitis, 2 pathogenic mechanisms – contact autoinoculation or trigeminal nerve othalmic root infection

Front 51

Describe neonatal herpes.

Back 51

Occurs in 1:3500-1:5000 deliveries, Transmission through infected birth canal (most women asymptomatic during labor), Presentation during 1st 1-2 weeks of life, Three syndromes: Skin, eye, mouth (SEM) (40%) – usually not fatal, but recurs; 30% develop neurologic sequelae, Encephalitis (35%), Disseminated (25%) – systemic HSV in blood; Occurrence of vesicles SEM (90%)>CNS(60%)>disseminated (20%)

Front 52

How is timing of infection in the mother different between HSV and rubella?

Back 52

HSV infection occurs during passage of fetus from birth canal (END of pregnancy) whereas CRS infection usually takes places within 1st 2 weeks of gestation

Front 53

Compare and contrast primary VZV infection vs. recurrence of infection.

Back 53

Primary Infection (Varicella): Chicken Pox, Severe Disease: Teens and adults (at risk for varicella pneumonia), Immunocompromised and newborns, Life-threatening pneumonia: Most common cause of sporadic encephalitis, Progressive, disseminated varicella; Herpes Zoster (Shingles): Reactivation in sensory ganglion, Lesions localized to innervated dermatome, Can disseminate in immunocompromised patients: >2 dermatomes, Across the midline

Front 54

What are diseases associated with CMV infection?

Back 54

Asymptomatic but disease can occur – mononucleosis, congenital infection, Those most at risk for disease = HIV, Organ and BMT

Front 55

Disease severity of congenital CMV is dependent upon what factor?

Back 55

Disease severity dependent upon maternal serostatus during pregnancy: Primary maternal infection – severe symptoms in about 25% of births: Jaundice, hepatosplenomegaly, petechial rash, cerebral calcifications, chorioretinitis, motor disability, About 20% survivors have late onset hearing loss, Reactivation during pregnancy – usually asymptomatic at birth, Late onset hearing loss (15%)

Front 56

What is the spectrum of diseases of CMV in immunocompromised hosts?

Back 56

HIV: Reactivation + disease when CD4<50, Retinitis, encephalitis, colitis (uncommon in HAART era); Bone Marrow Transplant, Common presentation – pneumonia after marrow engraftment, Prophalaxis w/ganciclovir; Solid Organ Transplant, Usually manifests as disease in allograft, Highest risk cases – CMV seronegative recipient receiving organ from seropositive donor

Front 57

T/F: Most atypical lymphocytes that are seen in EBV mononucleosis are B-cells

Back 57

T

Front 58

T/F: EBV is usually transmitted in saliva

Back 58

T

Front 59

T/F: 5% of adults worldwide have been exposed to EBV

Back 59

FALSE – 95% of adults have been exposed

Front 60

T/F: After clearing the infection, EBV persists at very low levels in the blood

Back 60

T

Front 61

T/F: Most patients infected with EBV have mononucleosis

Back 61

FALSE – Infection in childhood usually asymptomatic; infection in adolescence/adulthood associated with syndrome of infectious mono (25%-70%)

Front 62

T/F: In latent infections, viruses exist as episomes in infected B-cells.

Back 62

T

Front 63

T/F: Heterophile antibodies are used in the “monospot test” to diagnose mononucleosis

Back 63

T

Front 64

T/F: Heterophile antibodies are directed against structural proteins on the virus

Back 64

TRUE (IgM/IgG to viral capsid antigen)

Front 65

T/F: Infectious mononucleosis results in a polyclonal gammopathy

Back 65

F

Front 66

T/F: A person who has IgM anti-VCA has chronic mononucleosis

Back 66

FALSE – acute mono (IgM first kind of antibody produced in response to first challenge by particular antigen)

Front 67

T/F: A person who has IgG to the VCA and EBNA antigens most likely has been previously exposed to EBV (usually, past history of mononucleosis)

Back 67

T

Front 68

T/F: EBV can lead to the development of tumors

Back 68

T

Front 69

T/F: If the heterophile antibody test is negative in a patient with classic symptoms of mononucleosis, the most likely infection is CMV

Back 69

T

Front 70

Name all the tumors that have been associated with EBV infection.

Back 70

African Burkitt’s Lymphoma, B Cell Lymphoma in immunodeficient patients, Hodgkin’s Lymphoma (about 1/3 of cases in US associated with EBV), Nasopharyngeal Carcinoma, Gastric Carcinoma

Front 71

Describe the mononucleosis syndrome.

Back 71

Sore Throat, Swollen lymph nodes, lymphocytosis

Front 72

Name all the common organisms that can cause mononucleosis syndrome.

Back 72

Causative Organisms: EBV, CMV, acute HIV, ACUTE toxoplasmosis [I’ll make it easy: they are EBV, CMV, acute HIV, and ACUTE toxoplasmosis]

Front 73

What are the diseases caused by KSHV (or HHV-8)?

Back 73

Kaposi’s Sarcoma, Primary Effusion Lymphoma

Front 74

T/F: Rotaviruses and caliciviruses are the two most common agents of viral gastroenteritis

Back 74

T

Front 75

T/F: Enteroviruses are transmitted by the fecal oral route and often cause gastroenteritis

Back 75

FALSE – most enteroviruses are transmitted via oral-fecal route, but most often DON’T cause GI disease

Front 76

T/F: Vomiting and diarrhea are both common manifestations of viral gastroenteritis

Back 76

T

Front 77

T/F: Rotavirus is more likely to cause vomiting than other agents

Back 77

TRUE (96% vs. 58%)

Front 78

T/F: Rotaviruses primarily cause disease in winter months in the US

Back 78

T

Front 79

T/F: Rotavirus is THE most common cause of dehydrating infantile diarrhea in the world today.

Back 79

T

Front 80

T/F: Norovirus is a calicivirus

Back 80

T

Front 81

T/F: Caliciviruses cause major epidemics of gastroenteritis

Back 81

T

Front 82

T/F: Cruise-ship diarrhea is often associated with norovirus, a calicivirus.

Back 82

T

Front 83

T/F: Caliciviruses also cause outbreaks in camps and nursing homes

Back 83

T

Front 84

T/F: Norwalk virus is a calicivirus.

Back 84

T

Front 85

T/F: Rotavirus causes an osmotic diarrhea

Back 85

T

Front 86

T/F: There is a live oral attenuated rotavirus vaccine in the US today that makes use of human VP7 and monkey VP4 (reassortment vaccine)

Back 86

FALSE - INTUSSUCEPTION

Front 87

T/F: Caliciviruses have an effect on gastric emptying leading to nausea and vomiting

Back 87

T

Front 88

T/F: Some individuals cannot get infected with Norovirus

Back 88

TRUE – depends on presence/absence of receptor encoded by FUT2, O less protected than A/B blood type

Front 89

T/F: Heterosexual transmission of HIV is the most common route of transmission worldwide

Back 89

T

Front 90

T/F: The time from infection to full-blown AIDS varies but is generally 8-10 years

Back 90

T

Front 91

T/F: A normal CD4 count is about 1000 cells/µl

Back 91

T

Front 92

T/F: ELISA is a very sensitive test but it is not as specific so it picks up everybody who has HIV but some positive ELISA results are false positives (in other words, some people who test positive on the ELISA test don’t have HIV)

Back 92

T

Front 93

T/F: All negative ELISA tests undergo confirmatory testing using a more specific test, the Western blot

Back 93

F

Front 94

T/F: CD4 receptors are expressed by lymphocytes, monocytes, and dendritic cells so all these cells are susceptible to HIV infection

Back 94

T

Front 95

T/F: CD4 is sufficient to allow entry of the virion into the cell

Back 95

FALSE – also require co-receptor (CCR5 or CXCR4)

Front 96

T/F: A deletion in the co-receptor, CCR5, has been shown to make individuals much more resistant to infection with HIV

Back 96

T

Front 97

T/F: A partner is most infectious when they are acutely seroconverting because the viral load during acute seroconversion is so high

Back 97

T

Front 98

T/F: HIV is transmitted sexually in a very efficient manner

Back 98

F

Front 99

T/F: The reverse transcriptase enzyme has excellent proofreading ability

Back 99

F

Front 100

T/F: The viral DNA is integrated in the host’s cellular DNA

Back 100

T

Front 101

T/F: HIV can latently infect inactive cells. Once these cells are activated, the virus production increases.

Back 101

T

Front 102

T/F: HIV does not infect cells in the central nervous system

Back 102

F

Front 103

T/F: Acute HIV infection, also called the Acute Retroviral Syndrome, may present as a mononucleosis-like syndrome (sore throat, fatigue, myalgias, and fevers)

Back 103

T

Front 104

T/F: A transient decline in CD4 lymphocytes is common in early infection

Back 104

T

Front 105

T/F: Both antibody-mediated killing and cell-mediated killing help to control the virus within a few weeks after infection

Back 105

TRUE – transition from Pimary (acute) phase to latent infection

Front 106

T/F: HIV viral load is an independent predictor of HIV disease progression

Back 106

FALSE – also use T cell count

Front 107

T/F: Normal CD4:CD8 ratio is 2:1

Back 107

TRUE (about 1.6:1)

Front 108

T/F: Most opportunistic infections in HIV start once the CD4 count is below 200cells/ml

Back 108

T

Front 109

T/F: HIV-2 is more common in the US

Back 109

FALSE – West Africa

Front 110

T/F: HIV-2 tends to be a bit less aggressive than HIV-1

Back 110

T

Front 111

T/F: HAART was introduced around 1996

Back 111

T

Front 112

T/F: HAART has decreased morbidity and mortality from AIDS

Back 112

T

Front 113

T/F: CCR5 is the most frequent co-receptor used during sexual transmission

Back 113

T

Front 114

T/F: CXCR4 is a co-receptor that may become apparent right before the patient starts to clinically deteriorate (i.e. CD4 starts going down and patient becomes AIDS defined)

Back 114

T

Front 115

T/F: HIV can become latent in resting CD4 cells

Back 115

T

Front 116

T/F: The latent reservoir makes it impossible to cure HIV infection with current antiretroviral therapy despite adequate use for prolonged period of time

Back 116

T

Front 117

T/F: The development of resistance to an antiretroviral agent (e.g. AZT) precludes the future use of this agent even though we may not be able to detect the presence of a viral mutant 3 years later

Back 117

TRUE – Can never use again because of latent resistant reservoir

Front 118

T/F: Sexual transmission of HIV is highly efficient

Back 118

FALSE – 0.3% per sexual contact with HIV-infected person

Front 119

T/F: Almost half the adults living with HIV are women

Back 119

T

Front 120

T/F: 50% of new HIV infections are attributed to contact with an acutely infected partner

Back 120

T

Front 121

T/F: Studies have shown that circumcision helps to prevent HIV acquisition

Back 121

T

Front 122

At what CD4 count does each Herpes Zoster begin to cause increased problems?

Back 122

Herpes Zoster – 400

Front 123

At what CD4 count does each TB begin to cause increased problems?

Back 123

TB – 350

Front 124

At what CD4 count does each Thrush (candida of the mouth) begin to cause increased problems?

Back 124

Thrush (candida of the mouth) – 300

Front 125

At what CD4 count does each PCP begin to cause increased problems?

Back 125

PCP – 200

Front 126

At what CD4 count does each andida esophagitis (candida of esophagus) begin to cause increased problems?

Back 126

andida esophagitis (candida of esophagus) – 150-175

Front 127

At what CD4 count does each cryptococcal meningitis begin to cause increased problems?

Back 127

Cryptococcal meningitis – 100

Front 128

At what CD4 count does each MAC and CMV begin to cause increased problems?

Back 128

MAC and CMV - 50

Front 129

Describe the manifestations of the acute retroviral syndrome

Back 129

Fever (96%), Lymphadenopathy (74%), Pharyngitis (70%), Rash (70%)

Front 130

A patient presents with sore throat, generalized lymphadenopathy and rash 10 days after having unprotected sex with a commercial sex worker. You suspect acute HIV infection. T/F: You would order an ELISA to diagnose HIV

Back 130

T

Front 131

A patient presents with sore throat, generalized lymphadenopathy and rash 10 days after having unprotected sex with a commercial sex worker. You suspect acute HIV infection. T/F: A negative ELISA means the patient does not have HIV

Back 131

F

Front 132

A patient presents with sore throat, generalized lymphadenopathy and rash 10 days after having unprotected sex with a commercial sex worker. You suspect acute HIV infection. T/F: You would order an HIV PCR viral load test if the ELISA is negative

Back 132

T

Front 133

A patient presents with sore throat, generalized lymphadenopathy and rash 10 days after having unprotected sex with a commercial sex worker. You suspect acute HIV infection. T/F: You would expect that the patient’s viral load would be low in acute HIV infection

Back 133

F

Front 134

A patient presents with sore throat, generalized lymphadenopathy and rash 10 days after having unprotected sex with a commercial sex worker. You suspect acute HIV infection. T/F: You would order a serum RPR

Back 134

T

Front 135

How might HIV cause CD4 cell depletion?

Back 135

Loss of non-infected cells by immune activation – Untreated HIV infection is characterized by a high level of immune activation; activated T cells more prone to undergo apoptosis

Front 136

List several mechanisms by which HIV drug resistance occurs?

Back 136

RNA viruses have high rates of mutation., Reverse transcriptase has no editing/proofreading functions, Error rate of 3 bases in 100,000 (3 x 10-5), (1 error per genome in every 3 replication cycles), During acute infection (virus load 106-7/ml plasma) every base in the virus changes every day; In each patient, closely related viral variants co-evolve over time.; Drug resistance develops in the setting of partial suppression when there is replication (allowing mutation) and selective pressure (providing resistant mutants a growth advantage).; Point Mutations in reverse transcriptase that prevent drug binding; Single specific amino acid changes in reverse transcriptase that prevent drug binding; Specific amino acid change in HIV viral protease that diminishes binding of protease inhibitors to active site; secondary amino acid changes at sites distant from active site accumulating that confer increasing resistance by further diminishing protease inhibitor binding affinity

Front 137

What is the mechanism of action of lamivudine when treating Hepatitis B infection?

Back 137

Limivudine (3TC) is a cytidine analog that inhibits the viral RNA-dependent DNA polymerase activity of RT

Front 138

How do neuraminidase inhibitors work when treating influenza A? Of the two neuraminidase inhibitors, which one has better oral bioavailability?

Back 138

Zanamivir and Oseltamivir mimic sialic acid with substitutions enabling them to bind to the active site of NA more tightly than sialic acid, NA cleaves sialic acid from cellular receptors, which is essential for the release of virus from the cell and spread of infection; Oseltamivir has much better oral bioavailability than Zanamivir, which must be given IV or as an aerosol spray to upper airways

Front 139

What is the mechanism of action of acyclovir and what is it used to treat?

Back 139

Acyclovir is an analog of deoxyguanosing, which has an affinity for HSV TK about 200-fold greater than that of cellular TK. This given 40-100 fold more ACV-3P than GTP in infected cells. The ACV-3P competitively inhibits viral DNA polymerase (and to a much lesser extent, cellular DNA Pol). ACV can be incorporated into DNA< but causes chain termination, as it lacks the 3’ –OH needed to link it to the next NT., Low concentrations of ACV are effective against HSV-1; about 2 fold less active against HSV-2; about 10 fold less effective (generally not useful) against CMV, HHV-6

Front 140

What is the mechanism of action of Foscarnet and what is it used to treat?

Back 140

Forcarnet is a PPi analog that inhibits all herpesviruses by reversibly blocking the PPi binding site on DNA Pol, thereby inhibiting PPi cleavage from the NTP during DNA elongation. Viral DNA pol is about 100 fold more sensitive to Foscarnet inhibition than is cellular DNA Pol (hence its selectivity), Generally used to treat all hespesviruses, though higher doses are needed to treat CMV than other herpesviruses

Front 141

If a patient diagnosed with influenza A is treated with amantadine, and if this patient’s virus becomes resistant to amantadine, can you use a neuraminidase inhibitor?

Back 141

YES. Though resistance to Amantadine occurs rapidly (within 5 days in 30% of people on drug treatment as a result of AAs lining the M2 channel such that the drug no longer blocks ion flow), drug resistant mutants stay sensitive to other drugs like NA inhibitors.

Front 142

Is acyclovir used to treat CMV?

Back 142

Generally, no. It’s level of activity is very low against CMV.

Front 143

Why is ritonavir used in low nontherapeutic doses in combination with other protease inhibitors? What is the basis for that mechanism? What do you foresee as a problem when treating HIV infected patients with a regimen that contains ritonavir (hint: HIV + patients are taking A LOT of other medications too including antifungals!)

Back 143

Azoles also CYP450 inhibitors!

Front 144

Compare definitive host to intermediate host

Back 144

Definitive Host – an organism in which sexual reproduction of the parasite occurs, Intermediate Host – an organism that hosts an immature parasite stage or stage that reproduces asexually

Front 145

Describe some mechanisms by which parasites evade the immune response

Back 145

Antigenic variation (produce many different cell surface proteins that are functionally similar but structurally different enough to evade recognition by memory T, B cells), Invade cells and live, multiply inside them (i.e. multiply within macrophages to evade detection by lysosomal enzymes)

Front 146

How do parasites cause disease?

Back 146

Direct cellular damage, Mechanical obstruction/compression, Host immunologic response (eosinophilia, granulomas, elevated cytokine production), Other mechanisms (manifested as anemia, fever, organomegaly, malnutrition, rash, diarrhea)

Front 147

Which parasite is responsible for bloody diarrhea and liver abscesses? Where do you need to travel to get exposed to this parasite? [you will learn more about this parasite next week]

Back 147

Entamoeba histolytica (common cause of dysentery and may invade intestinal mucosa and spread to other organs, especially the liver, where it can produce abscesses)

Front 148

What is the classic immunological cell associated with parasitic diseases, especially tissue-invasive forms? HINT:

Back 148

Macrophages

Front 149

Compare the cell membrane of fungi and humans.

Back 149

Cell Membrane: Both have bilayer membrane, Cell membrane (not the cell wall) is the real barrier between the fungal cell and its environment, Sterols are incorporated into the lipid portion, IN FUNGI ONLY -- Most common sterol is ergosterol (NOT cholesterol) , In both cases, membrane helps maintain membrane fluidity, AmB and lipid formulations of AmB: , Bind directly to ergosterol in the cell membrane to form ionic pores, Cause oxidative damage to membrane components

Front 150

What classes of drugs work specifically on the fungal cell membrane?

Back 150

Azoles: Inhibit cytochrome P-450-dependent enzymes 14 alpha demethylase required to synthesize ergosterol , Allylamines: Inhibit squalene 2,3 epoxidase; disrupts ergosterol synthesis

Front 151

Describe the fungal cell wall. What classes of drugs work specifically on the cell wall?

Back 151

Cell Wall: Rigid, heteropolysaccharide wall resistant to hydrolysis and confers shape and stability to the organism, 90% polysaccharides and 10% peptides, (1®3)-b-D-glucans , (1®6)-b-D-glucans , mannans , chitin, galactomannan , Not a barrier to the environment, Multi-layered, Glucans compose inner fibrillar and inner matrix of cell wall, Glycopeptides compose inner and outer layers, Drugs: Echinocandins – target and inhibit 1,3-b-D-glucans,

Front 152

What are the classic and endemic dimorphic fungi?

Back 152

Classic – fungus exists in nature and at room temperature as a filamentous fungus and converts to a yeast in tissue or in lab – nutrient and T dependent: Coccidioides immitis , Histoplasma capsulatum, Paracoccidioides brasiliensis, Penicillium marneffei, Sporothrix schenckii, Endemic: Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, Penicillium marneffei

Front 153

Why is the cryptococcal capsule needed and why is it clinically relevant?

Back 153

Capsule – heteropolysaccharide capsule composed mainly of glucurnoxylomannan that has protective effect against host response, Clinical relevance – capsular antigen used in detection of organism in CSF

Front 154

How do we classify fungi based on host response and disease?

Back 154

Superficial, Mucocutaneous, Subcutaneous, Deep Mycoses, Opportunistic, Pathogenic

Front 155

Are fungal structures observed in tissue the same as those observed on laboratory medium?

Back 155

NOT NECESSARILY – Since pathogenic fungi can exist in several morphologic forms in tissue and can alter form based on T and nutrient conditions, the forms seen in tissue may differ form those seen in vitro

Front 156

Give an example of a superficial fungal infection

Back 156

Tinea versicolor

Front 157

Which dermatophytes are responsible for most of the cutaneous fungal infections?

Back 157

Microsporum spp., Epidermophyton floccosum, Tricophyton spp.

Front 158

Dermatophyte infections are commonly designated by the region of the body, which they inhabit. Name 7 of them. Which is most common in the US? Which is most common worldwide?

Back 158

Tinea pedis, Tinea capitis, Tinea corporis, Tinea barbae, Tinea crurus, Tinea unguinum, Tinea manuum, In the US – most derpatophyte infections involve Tricophyton spp. As the etologic agents (tinea capitis, tinea carbae, tinea corporis, tinea cruris, tinea pedis, and tinea unguium). Tinea capitis is most common in US, Worldwide, Microsporum spp. Commonly cause tinea capitis, tinea corporis, tinea cruris, and tinea pedis (most common worldsie – affects up to 70% adults), BUT NOT TINEA UNGUIUM. Please note: I Do NOT expect you to know which dermatophytes cause what and where! Just know the three most common causes (question #67) and know what the difference is between superficial and mucocutaneous infections] I will also NOT show you a picture of a dermatophyte and ask you to tell me what it is! The only antifungal drugs you are responsible for are those covered in the ANTIFUNGAL DRUG lecture! I will NOT ask you how to treat each dermatophyte!

Front 159

What is the key immunological mechanism that defends humans against these mucocutaneous infections?

Back 159

Cell mediated immunity

Front 160

How do we diagnose dermatophytic infections?

Back 160

Lab Diagnosis: KOH or calcofluor preparation of scale scraped from the leading edge of the lesion, Culture can be used to confirm the diagnosis, Tinea capitis is diagnosed on KOH exam of extracted hair if caused by Trichophyton species, as spores can attach to or reside on the hair shaft. Culture the extracted hair. Culture on Sabouraud dextrose agar with cycloheximide and incubated at 26-28° for up to 4 weeks. Any growth of dermatophytes is considered significant. Tinea capitis caused by M. audouinii or M. canis (also a cause of tinea corporis) fluoresces blue-green under Wood’s light examination.

Front 161

Define onychomycosis and what are the common organisms that cause it.

Back 161

Onchomycosis – an infection of the nail plate and/or nail bed that interferes with normal nail function, Primarily caused by dermatophytes (80-90%) usch as T. rubrum and T. metagrophytes var. interdigitale

Front 162

Why is PSO clinically relevant (in other words, if a patient presents with PSO, what else should you think about?)

Back 162

PSO occurs in immunocompromised hosts and is thought to be an early indicator of HIV infection

Front 163

What does sporotrichosis cause and what is the differential diagnosis of that lesion? How do you get sporotrichosis?

Back 163

Lymphocutaneous sporotrichosis: Differential Diagnosis: atypical mycobacterial infection: esp., Mycobacterium marinum, Cutaneous leishmaniasis: esp., Leishmania brasiliensis, Cutaneous nocardiosis, Syphilis ; Fixed Cutaneous Sporotrichosis: Differential Diagnosis: chromoblastomycosis, blastomycosis, Majocchi's granuloma, tuberculosis verrucosa cutis, verruca vulgaris

Front 164

How do you get sporotrichosis?

Back 164

You get the disease by being exposed to wood/woody sources such as moss.

Front 165

What are the most common pathogenic fungi?

Back 165

Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis., All are classical endemic dimorphic fungi

Front 166

What is the geographic distribution of the pathogenic fungi in the United States?

Back 166

Histoplasma capsulatum -- soil and caves enriched with bird or bat fecal material; Ohio-Mississippi River valley regions; Coccidioides immitis -- desert soil in SW USA, can cause infection with or without disease in immunocompetent or immunocompromised host; Blastomyces dermatitidis -- water in North Central and SE USA, Arkansas/Alabama, Minnesota/Wisconsin, Virginia; Paracoccidioides brasiliensis -- South America

Front 167

How do you acquire histoplasmosis? What are the diseases that it causes?

Back 167

Inhalation of asexual spores from environment; Diseases: 90-90% of hosts remain asymptomatic following low inoculums exposure or experience mild respiratory symptomatology), <5% have moderate to severe respiratory disease (patient and inoculum size-dependent), 1/1000 have disseminated infections – can occur in normal hosts, but more common in T cell compromised hosts, Disease of reticuloendothelial system – liver, spleen, lymph nodes, bone marrow

Front 168

Pathologically, how does histoplasmosis differ between different hosts (i.e. immunosuppressed vs. immunocompetent)

Back 168

Early, active infection: Intracellular – 3 µm elliptical budding yeast cells in cytoplasm of macrophages and monocytes; Normal/mildly immunosuppressed hosts: Granulomas are produced following the development of cellular immune responses – outer wall of epitheloid macrophages, lymphocytes, giant cells, and plasma cells with eventual central necrosis with few extracellular yeast cells, Old lesions – fibrosis and calcification occur; Immunosuppressed hosts, e.g. HIV+: Poorly formed granulomas, Histiocytosis occurs with many intracellular yeasts

Front 169

What diseases does Coccidoides immitis cause? Know what it looks like in tissue

Back 169

Severe infection characterizedby progressive local/disseminated cocididiomycosis, Observed in African-American, Philippine patients; Features: Arthroconidia – room T (hyphal form, transmissible form – boxcar-like structures), Spherules – in TISSUES -- CHARACTERISTIC

Front 170

What opportunistic fungal infections occur in patients with CMI deficiency? Phagocytic defect (for example: neutropenia)?

Back 170

CMI deficiency MCCP: Mucocutaneous candidiasis, Cryptococcosis, Pneumocystosis; Phagocytic Defect ICAZ: Invasive candidiasis, Aspergillosis, Zygomycosis

Front 171

What is the spectrum of infections caused by Candida spp.? Which is the most common species of Candida and where is it normally found?

Back 171

Mucocutaneous candidiasis: Oropharyngeal candidiasis (“thrush”), Esophageal candidiasis , Candida epiglottitis, Cutaneous candidiasis, Onychomycosis, Keratitis, Vulvovaginal candidiasis, Deeply Invasive Candidiasis: Candidemia, Endocarditis, Hepatosplenic candidiasis (chronic disseminated candidiasis), Acute disseminated candidiasis, Renal candidiasis; Candida albicans (germ tube +) – most virulent and most common member of genus; Candida spp. Are components of our normal flora – skin, oral, GI tract, female GU tract

Front 172

What are some risk factors for acquiring mucocutaneous candidiasis? Invasive candidiasis?

Back 172

Mucocutaneous Candidiasis CD4+ Immunosuppression: underlying diseases (HIV, diabetes), corticosteroids, pregnancy, age, antibacterial antibiotics, Invasive Candidiasis Decreased phagocytic activity, Altered barriers – vascular and urinary catheters, peritoneal dialysis, trauma, burns, cytotoxic drugs, Neutropenia, Transplantation – both BMT and solid tumor, Surgery – especially with other risks, Broad spectrum antibiotics, Hyperalimentation etc., Hemodialysis

Front 173

The lab calls you to say that yeast is growing from a culture and it is “germ-tube positive”. What is the most likely yeast species?

Back 173

CANDIDA ALBICANS!!!!

Front 174

What immunological cell is MOST critical in protecting the host from aspergillus infection?

Back 174

Neutrophils

Front 175

Describe the pathology of invasive aspergillosis (know what it looks like in tissue)

Back 175

Pathologenesis: Inhalation of conidia (2-5 µm): ~ 10% reach the alveoli, Normal host -> phagocytosis by macrophages & killing, Compromised host -> +/- phagocytosis, but no killing, Germination of conidia with hyphal invasion of lung parenchyma, Angioinvasion with thrombosis, ischemia, and infarction, +/- Hematogenous dissemination, Pathology: Angular dichotomously branching septate hyphae (2-5 µm), Hyphal invasion and thrombosis of blood vessels with necrosis of the tissue: angioinvasion, Veins can also be involved

Front 176

What are some classic radiological signs for aspergillosis

Back 176

Halo Sign – dense nodule surrounded by filigree, Crescent Sign – neutrophils hollowing out infarcted tissue; residual tissue forms crescent shape as airflow re-established

Front 177

What diseases does aspergillus cause?

Back 177

Invasive Pulmonary Aspergillosis +/- dissemination, Allergic syndromes in atopic individuals, Keratitis following corneal trauma, Fungal ball in an old TB cavity, impacted paranasal sinuses

Front 178

Compare the tissue appearance of aspergillus sp and those of the zygomycetes

Back 178

Aspergillus – Angular dichotomously branching septate hyphae (2-5 µm), Zygomycetes -- Wide (10-20 µm in diameter), ribbon-like, nonseptate (coenocytic) hyphae that branch infrequently, but at "right angles"

Front 179

What are diseases caused by zygomycetes?

Back 179

Colonization of an old TB lung cavity w/o invasion of lung parenchyma, Invasive infections: Rhinocerebral zygomycosis – diabetes mellitus + ketoacidosis (NOT CAUSED BY ASPERGILLUS), Pulmonary Invasive infection +/- dissemination (neutropenic patients)

Front 180

What is the classic risk factor for acquiring rhinocerebral mucormycosis? In other words, what patient population?

Back 180

Diabetics (who are ketoacidotic)

Front 181

What are the clinical diseases caused by Cryptococcus neoformans?

Back 181

Pulmonary – asymptomatic to mild to progressive, depending on patient and inoculums size, CNS – meningoencepahlitis, Disseminated disease

Front 182

What are risk factors for acquiring cryptococcal infection?

Back 182

T-cell compromise, High dose corticosteroids, Solid organ transplant recipients receive immunosuppressive therapy, HIV+ individuals w/ CD4 <100/uL

Front 183

What does the cryptococcal yeast look like under the microscope?

Back 183

Lesions are gelatinous due to the production of excess capsule, Spherical yeast cells are 4-20 µm with clear area surrounding where the capsule had been with a very narrow or pinched attachment between mother and daughter cells, Yeasts stain poorly with H & E, require PAS, GMS, or mucicarmine

Front 184

What is the main virulence factor for cryptococcosis?

Back 184

Heteropolysaccharide capsule, Glucuronoxylomannan – different side chains = different serotypes: A, B, C, D, Produced in excess and is detectable as an antigen for rapid diagnosis, Inhibits intracellular phagocytosis, Poor antigen and leukotactic molecule, Knockout mutants are less virulent and less neurotropic

Front 185

Describe the clinical presentation of PCP? Who is at risk? Radiologically, what does PCP look like? How do we make a diagnosis?

Back 185

Presentation -- predominantly an alveolar-interstitial pneumonia that presents with fever, dyspnea, and a non-productive cough, Extrapulmonary disease is uncommon, Risk factors – immunosuppression, corticosteroids, HIV infection, and age, Histology: Proteinaceous debris surrounding organism in alveolus (instead of air) à alveolar capillary block, Poor oxygen penetration, patient presents with shortness of breath (NOT chest pain); Radiological Image: Diffuse alveolar infiltrates (NO INFARCTIONS, it’s a respiratory disease), Diagnose using histology (BAL to get lung biopsy, then GMC and Wright-Giemsa stain), grow up organism in lab

Front 186

Case: HIV + patient with fevers, chills, night sweats X 3 weeks from Arizona

Back 186

Histoplasmosis infection caused by H. capsultatum., Pulmonary masses in CXR, Hyphal form of organism in culture, with clear hyphae and macroconidia