questions from Dr. Ryan

Question 1

1. Why can parvoviruses only replicate in rapidly dividing cells or cell co-infected with adenovirus?

Answer 1

Parvoviruses are the simplest of DNA viruses (ss, 5 Kb genome size) and do not encode a DNA polymerase or ancillary proteins to modify human (host) DNA polymerase.

Question 2

2. What is the other name for “fifth disease?” What are the symptoms?

Answer 2

2. Symptoms of erythema infectiosum include initial flu-like symptoms followed by a “slapped cheek” and/or lacy red rash (children) or polyarthritis (adults). About 50% of adults are seropositive for B19.

Question 3

3. How does parvo B19 cause anemia? Which patients are susceptible?

Answer 3

3. B19 causes anemia by lysing precursors to red blood cells, a consequence of replication in these cells. Individuals of concern include fetuses (first half of pregnancy), sickle cell patients, and immunocompromised patients.

Question 4

4. How was smallpox spread? What caused death?

Answer 4

4. Smallpox was spread by the respiratory route from ruptured lesions in the mouth and on the tongue. Death was essentially septic shock from damage to the endothelium during the “toxemic phase.”

Question 5

5. Distinguish smallpox from chickenpox.

Answer 5

5. Smallpox: firm, well defined vesicles with a depression in the middle which developed into a pustule that felt like a BB was inside; all lesions on a given body part are at the same stage, most found on head and extremities.Chickenpox: superficial vesicles that are not firm; lesions will be at various stages, mostly found on head and trunk.

Question 6

6. What is molluscum contagiosum?

Answer 6

6. Molluscum contagiosum is a pox virus infection. Childhood forms are mostly found in tropical regions, while a sexually-transmitted form is spread by direct skin-skin contact of lesions found on the lower abdomen. The lesions will spontaneously disappear in months to one year’s time.

Question 7

7. Compare and contrast variolation from vaccination.

Answer 7

7. Variolation: inhalation (or skin inoculation) of scab material from a smallpox patient. Fatality rate was 2.5% because the virus was attenuated (due to immune response?).Vaccination: initially performed with cowpox, but now performed with vaccinia, an attenuated lab strain. Liquid containing vaccinia is introduced into the skin using a bifurcated needle. Immunity wanes after 3 years and is absent after 20 years.

Question 8

8. Name 4 key reasons that enabled smallpox to be eradicated.

Answer 8

8. (1) Humans only reservoir. (2) No healthy carriers—death or clearance and survival. (3) No sub-clinical infections. (4) Effective vaccine.

Question 9

9. Name 3 severe, but non-life threatening adverse reactions to smallpox vaccination.

Answer 9

9. Generalized vaccinia, inadvertent inoculation, erythema multiforme (allergic skin reaction).

Question 10

10. Name 4 severe, but life threatening adverse reactions to smallpox vaccination.

Answer 10

10. Progressive vaccinia (T cell deficiency), encephalitis, eczema vaccinatum(can lead to shock, death), myopericarditis or heart attack.

Question 11

11. How is varicella-zoster virus spread?

Answer 11

11. VZV is highly communicable and is spread by the respiratory route, although skin vesicles are infectious until scabbed over (about 1 week).

Question 12

12. Compare and contrast chickenpox and shingles.

Answer 12

12. Chickenpox: Result of primary infection; initial itchy rash on scalp and trunk in children, adults have less rash and are at risk for severe pneumonitis.Shingles: Result of reactivated infection from sensory peripheral neurons. Often just one episode per life time, but extremely painful blistering vesicles along a single dermatome. If not treated promptly with ACV and steroids, patients are at risk for postherptic neuralgia that can last months, even years.

Question 13

13. Are the VZV vaccines live or killed?

Answer 13

13. Both the childhood (chickenpox) and elderly (shingles) vaccines are live attenuated viruses that can establish latency.

Question 14

14. What childhood illness do HHV-6 and -7 cause? What is the main symptom?

Answer 14

14. Roseola (exantham subitum) occurs before 6 years of life in the vast majority of children. The main symptom is a very high fever, but many children will exhibit the roseola rash.

Question 15

15. What is the causative agent of leprosy and how is it spread?

Answer 15

15. Leprosy is caused by Mycobacterium leprae and appears to be spread by small droplets from nasal secretions of lepromatous leprosy patients. Infectivity is low and the incubation period is estimated to be 2-7 years. Contraction of the disease requires prolonged close contact with an infected person.

Question 16

16. Distinguish tuberculoid vs lepromatous leprosy.

Answer 16

16. Tuberculoid leprosy causes single skin lesions on the face, limbs, and buttocks. Low numbers of organisms are present in the lesions and the patient is usually not contagious. Tuberculoid lesions can heal spontaneously and the prognosis is good.

Lepromatous leprosy is a progressive disease with the first signs being edema and rhinitis. Lesions are extensive on the face, buttocks, and limbs. Damage can be severe, with perforation of the nasal septum and collapse of the nose due to cartilage loss, loss of fingers to neurotrophic atrophy, and atrophy of testicles.

Question 17

17. How is leprosy diagnosed?

Answer 17

17. Because the organism cannot be grown in culture, leprosy is mostly a clinical diagnosis with confirmation from skin biopsies and the detection of acid-fast staining bacilli.

Question 18

18. Describe the transmission, symptoms, and diagnosis of Rocky Mountain Spotted Fever.

Answer 18

18. Rocky Mountain Spotted Fever is caused by Rickettsia rickettsia, which is transmitted to humans through tick bites. RMSF is a vasculitis (R. rickettsia replicates in the endothelia of small blood vessels) but the initial symptoms of infection are a high fever and severe headache followed within days by a rash that begins on the ankles and wrists. The rash spreads radially up the limbs and to the palms and soles. Muscle aches, especially in the calves, are also common. Left untreated, the vasculitis can lead to septicemia and disseminated intravascular coagulation, possibly resulting in amputations and neural deficits. RMSF can be tentatively diagnosed using the Weil-Felix test which detects anti-rickettsial antibodies that are cross-reactive to antigens from Proteus OX strains. The test must be confirmed with specific serology: looking for a four-fold rise in titer using an indirect immunofluorescence assay with rickettsial antigens.

Question 19

19. Compare and contrast HME and HGA.

Answer 19

19. Human monocytic ehrlichiosis (HME) is caused by Ehrlichia chafeensis and is transmitted by the Lone Star deer tick. E. chafeensis replicates in the cytoplasm of monocytes and produces a disease that symptomatically resembles a less severe form of RMSF. Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilia and is transmitted by the Ixodes deer tick. A. phagocytophilia replicates in the cytoplasm of granulocytes. HGA is characterized by fever and headache, but because it rarely results in rash, it is often called “Rocky Mountain Spotless Fever.”Both Ehrlichia and Anaplasma are closely related to Rickettsia spp. HME and HGA have been referred to collectively as Southern tick-borne disease in reference to the mild flu-like illness of each. Each can be diagnosed by Wright/Giemsa staining of blood smears and looking for the characteristic morulae found in infected monocytes or granulocytes.

Question 20

20. Describe the transmission, symptoms, and diagnosis of Lyme Disease.

Answer 20

20. Lyme Disease (LD) is caused by Borrelia burgdorferi and is transmitted by the Ixodes tick nymph. LD is characterized by three stages, if left untreated. The initial stage is characterized by flu-like symptoms and, commonly, a bull’s eye red rash (erythema chronicum migrans). The second stage is the result of disseminated disease and occurs weeks or months following the initial stage. Arthritis, facial palsy, or peripheral neuropathy are characteristic. Chronic LD can appear months or years after the initial, untreated, infection and is characterized by erosive arthritis, especially of the knees, and/or Bell’s palsy. Borrelia are spirochetes, and while some may be visualized by Gram staining, B. burgdorferi is too thin to be seen. Diagnosis is a two-step process: an ELISA serologic assay and a confirmatory Western blot used to rule out false positives of the ELISA.

Question 21

21. What is responsible for the recurrent fever seen in Borrelia-caused relapsing fever?
    Answers:

Answer 21

21. The recurrent fevers caused by B. hermsii in relapsing fever are attributed to phase variation, where new antigenic determinants emerge at a frequency of 1:1000 or 1:10,000. The antigenic variants escape the immune response to provide another round of symptoms.