Bugs, Drugs, and Thugs: Case Studies in Virology

1. Bugs, Drugs, and Thugs: Case Studies in Virology SAFMLS WORKSHOP 12 FEB 2008 DAVID G. WATSON, MAJ, USAF, BSC

2. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 A 9-year-old black female, a recent émigré fromHaiti, came to a Florida Emergency Room because of a fever, headache, sore throat and mild cough. Her parents say that she has been sick for 2-3 days. You note that she has a runny nose and a mild conjunctivitis. Her temperature is 39, pulse rate 110 beats/min, blood pressure 90/60 mm Hg, and respiratory rate 42/min. You note that her pharynx is very red and that she also has some bright red spots with white centers on her buccal mucosa. Her chest is clear. You take a throat swab and send the child home instructing the parents to return with the child tomorrow when you will have the results of the throat culture.

3. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 1 The throat swab is most commonly used to diagnose?  A) whooping coughB) influenza C) strep throatD) measles E) diphtheria Answer C) strep throat This is the most common use. The swab is streaked on blood agar. If beta hemolytic colonies are seen the bacteria are Group A or pathogenic Streptococci.

4. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 2 On the whole, would you agree with the decision to send this child home with no treatment or instructions for care?  A) Yes, because even if she had a strep throat, tomorrow is soon enough to start treatment and viral diseases can't be cured.B) No, because she may not come back and miss treatment for a disease that could result in rheumatic fever.C) No, because she had a highly communicable disease that you should have recognized.D) Both B and C have some merit. Answer D) Both B and C have some merit.Both the fact that she might not come back if she starts to feel better and the fact that she might have a communicable disease should weigh in your answer.

5. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 There are no beta hemolytic colonies seen on the blood agar plate the next day. The child does return and when you examine her again you notice a rash behind her ears and on her face. Careful examination of the rash shows that it is maculopapular. Question 3 The absence of beta hemolytic colonies on the blood agar plate means?  A) the child does not have scarlet feverB) the child does not have rheumatic feverC) the child does not have Rocky Mt. Spotted feverD) the child has measlesE) the child has German measles Answer A) the child does not have scarlet feverScarlet fever is caused by Group A beta hemolytic streptococci -- it can be thought of as a strep throat with a rash. This child would have beta hemolytic colonies on blood agar from the throat swab if she had scarlet fever.

6. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 4 The differential diagnosis for a child with a rash is quite large. Measles, German measles and Rocky Mt. spotted fever should be considered. What are some other agents that can cause a rash?  A) B19, HHV3, BordetellaB) chlamydia, Coxsackievirus, EEEVC) hantavirus, flu virus, HHV3D) Treponema pallidum, B19, Coxsackievirus Answer D) Treponema pallidum, B19, CoxsackievirusThese should all be included. T. pallidum causes syphilis and secondary syphilis presents with a rash. A good differential diagnosis for this child's disease would be measles, German measles, Rocky Mt. spotted fever, fifth disease, Coxsackievirus infection, secondary syphilis. You know its not scarlet fever because of the throat culture. A few parasitic diseases, that a recent emigrant could have, also have rashes.

7. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 5 You ask the parents if they have seen any ticks on the child or if she had been anywhere that she could have been bitten by a tick. This would bear on the diagnosis of which of the following?  A) measlesB) secondary syphilisC) fifth diseaseD) Rocky Mt. spotted feverE) Coxsackievirus infection Answer D) Rocky Mt. spotted feverThis rickettsial disease is spread by ticks.

8. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 6 What in the world causes fifth disease? A) an adenovirusB) a parvovirusC) a poxvirusD) a herpesvirusE) a picornavirus Answer B) a parvovirusIt’s called B19. B19 is a virus that commonly infects humans; about 50% of all adults have been infected sometime during childhood or adolescence. Parvovirus B19 infects only humans.

9. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 7 B19 usually causes a very mild disease. Two groups of people for whom it can be serious, however, are? A) teenagers and pregnant womenB) pregnant women and sickle-cell anemicsC) the sexually promiscuous and drug addicts D) alcoholics and asplenicsE) smokers and alcoholics Answer B) pregnant women and sickle-cell anemics Primary infection in pregnant women is very serious and can result in death of the fetus. In patients with sickle-cell disease, the virus can initiate a transient aplastic crisis. Typical giant proerythroblast seen in B19-associated pure red cell aplasia with highly uncondensed chromatin and pale purple intranuclear inclusions (bone marrow aspirate, hematoxylin-eosin, x1000).

10. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 8 What should have alerted you to the possibility of measles? A) the conjunctivitisB) the Koplik spotsC) the runny nose (coryza)D) the coughE) all of the above Answer E) all of the aboveThe combination of the three C's (cough, coryza, conjunctivitis) and Koplik spots should have been a red flag.

11. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 9 Why is it so important to diagnose measles? A) it can be curedB) the complications can be preventedC) the child needs to be vaccinated against measlesD) pregnant women exposed to the child need to have abortionsE) all unvaccinated contacts need to be protected Answer E) all unvaccinated contacts need to be protectedMeasles is a very serious and highly communicable disease and all unvaccinated contacts need to receive the vaccine. If contacts are less than 1 yr. old or immunocompromised, hyperimmune serum globulin is recommended.

12. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 10 How is measles normally prevented? A) DPT vaccineB) MMR vaccineC) killed viral vaccineD) live oral vaccineE) measles vaccine is no longer needed Answer B) MMR vaccineThis is measles, mumps and rubella – all are live attenuated viruses.

13. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 11 When is the MMR vaccine usually given? A) 2, 4, 6, 15 months and 4-6 years.B) 2, 4, 15 months and 4-6 years.C) 2, 4, 6, 15 months.D) 15 months and 4-6 years. Answer D) 15 months and 4-6 years. If you had attended my SAFMLS workshop last year on Vaccines, you would have known this!

14. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 12 Why is the MMR vaccine given so much later than the other childhood vaccines? A) the live viruses are dangerous until the children have some natural immunity.B) the vaccines don't work due to maternal antibody before this time.C) the immune system is not mature enough to make antibodies before this time.D) cellular immunity that is needed will not develop before this time. E) the vaccines can cause severe complications in children under 1 yr. old. Answer B) the vaccines don't work due to maternal antibody before this time. The maternal antibody neutralizes the vaccine virus.

15. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 13 What is/are the complication(s) of measles? A) SSPE (subacute sclerosing panencephalitis) B) viral pneumoniaC) bacterial pneumoniaD) encephalitis E) all of the above Answer E) all of the aboveThey can all occur and all be very serious!

16. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Question 14 How can measles be confirmed? A) heterophile antibodiesB) anti-measles IgGC) anti-measles IgMD) growth of the virus in tissue cultureE) all of the above Answer C) anti-measles IgMYou could also look for measles virus antigen using fluorescent antibodies to the virus.

17. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 A measles antigen detection assay tested positive for the measles virus. You send the child home but tell the parents to keep her isolated. Eight other children and four adults in the same house were given measles vaccine. One baby was given hyperimmune serum globulin. Twenty neighborhood children that had never been immunized were also immunized. Question 15 How is it that so many of this child's contacts were not previously vaccinated? A) the vaccine is only available in the USA and all the others were immigrants.B) the vaccine is expensive and only purchased by those who can afford it.C) the lowest socioeconomic classes have the poorest vaccination rates.D) the perceived high incidence of reactions to the vaccine make it very unpopular. Answer C) the lowest socioeconomic classes have the poorest vaccination ratesThey often "fall through the cracks," as it were. They either have not been taught that vaccinations are important, they don't know where to go to get them, or they don't have the money, time, or energy to do it.

18. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 The sick child appeared to be recovering but after 10 days had a resurgence of fever, severe headaches, and seizures. Question 16 This new development?  A) is normal in the course of measlesB) signals measles pneumoniaC) occurs in about 0.1% of measles casesD) is most likely unrelated to the measlesE) is SSPE Answer C) occurs in about 0.1% of measles casesMeasles encephalitis occurs in 1 out of every 1000 or 2000 cases.

19. Bugs, Drugs, and Thugs • Infectious Disease Case Study 1 Outcome: The child was hospitalized and given supportive care. Although many children suffer neurological deficits after measles encephalitis, this child recovered and was left with no sequelae. She grew up and, fondly remembering the kindness of the doctors who cared for her, went to Medical School at the University ofFlorida. Dr. Ertha Pascal-Trouillot later returned to her native country and, in 1991, became the first, and only, woman president of Haiti.

20. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 A 69-year-old male citizen of Mexico who arrived a month ago to visit his son and daughter-in-law in Florida for the summer, was evaluated at an urgent-care center for a 3-day history of increasing pain in his left jaw, chest and shoulder. He also complained of sore throat, anxiety, insomnia, nausea and vomiting. He said he had received a spider bite on his left jaw and that the pain had started after that. His daughter-in-law commented that he had been somewhat confused since arriving in Florida and that she couldn't remember a spider bite. He was transferred to the hospital and treated for chest pain, but evaluation ruled out cardiac disease and pneumonia. He rejected all oral fluids and continued to complain of the spider bite. He was sent to the mental health unit where he was noted to be anxious and have impaired memory. He was diagnosed with anxiety disorder and given tranquilizers and discharged.

21. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 1 Insects and other arthropods (ticks) are known to transmit a number of diseases of bacterial, viral, and parasitic origin. Are spiders implicated in the transmission of any common infectious diseases? A) yes B) no Answer B) noCertainly none that are common.

22. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 2 Which of the following groups of diseases are all transmitted by insects or ticks? A) yellow fever, Lyme disease, typhoid fever B) syphilis, gonorrhea, AIDS C) Rocky Mt. spotted fever, typhus, viral encephalitis D) rabies, viral encephalitis, Lyme disease E) African sleeping sickness, giardiasis, plague Answer C) Rocky Mt. spotted fever, typhus, viral encephalitisThese come from, respectively, ticks, fleas, and mosquitoes.

23. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 3 Which of the following microbes can cause chest pain? A) influenza virus B) Streptococcus pneumoniae C) Coxsackievirus B D) rabies virus E) all of the above Answer E) all of the aboveBut by different mechanisms.

24. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 4 Which of the following groups of infectious diseases cause neurological changes? A) cat scratch disease, measles, meningitis B) AAV infection, mycoplasma pneumonia, tetanus C) meningitis, viral encephalitis, rabies D) chicken pox, measles, rotavirus infection E) gonorrhea, syphilis, Herpes infection Answer C) meningitis, viral encephalitis, rabiesAll these are infections of the brain or brain covering and all can cause some type of neurological change.

25. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Two days later the gentleman returned in acute distress. He complained of a headache and also a terrible thirst. He had a fever of 39.6, hypersalivation, inability to swallow, and a staggering gait. As the technician tried to take a routine blood sample, the man tried to bite her. The doctors and nurses stated that they had ever seen anything quite like it. However, a nurse from the Philippines thought she recognized the disease immediately.

26. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 5 What rare disease did the nurse think she recognized? A) encephalitis B) leishmaniasis C) meningitis D) cysticercosis E) rabies Answer E) rabiesThe hydrophobia, hypersalivation, and biting behavior are all almost unique to rabies. It is endemic in the Philippines so the nurse might well recognize it.

27. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 The doctors decided, instead, to do a spinal tap to diagnose the man's disease. Question 6 What diseases might they be considering when they ordered the spinal tap? A) meningitis B) encephalitis C) both A and B D) neither A nor B Answer C) both A and BBoth are possibilities.

28. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 7 What are the most common causes of acute meningitis? A) Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae B) Listeria monocytogenes, Escherichia coli, and Streptococcus agalactiae C) measles, mumps, and herpes viruses D) cryptococcus and histoplasmosis fungi E) enteroviruses Answer A) Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae These three bacteria are the most frequent causes of meningitis.

29. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 The lab results on the blood and CSF evaluation showed the following: CSF: 2 red blood cells, 1 neutrophil, and 9 lymphocytes/ml CSF glucose: 67 mg/dL (normal 40-80) CSF protein: 163 mg/dL (normal 15-45) CSF gram stain: negative Blood count: 12,100 leukocytes/ml Blood glucose: 98 mg/dL

30. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 8 The CSF glucose and protein profile is most characteristic of? A) bacterial infection B) viral infection C) fungal infection Answer B) viral infectionCSF protein is slightly high and glucose is normal. This is indicative of a viral infection. The lymphocytes also are indicative of a virus. Based on the analysis of the CSF and the negative Gram stain, the doctors decided he had a viral encephalitis.

31. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 9 EEEV, WEEV, VEEV and St. Louis Encephalitis virus all cause encephalitis. How are these viruses transmitted? A) from horses B) by bird droppings C) by mosquitoes D) by mosquitoes or ticks E) via the respiratory route from other infected humans Answer C) by mosquitoesThe mosquitoes transmit it from the birds to humans. Note: Two types of encephalitis are transmitted by ticks, but not the four listed here.

32. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 While in the hospital, his condition rapidly deteriorated, and even though he was placed on respiratory support he died the next day. Brain specimens were sent to the Department of Pathology where rabies was diagnosed on the basis of Negri bodies and detection of rabies antigen by a positive reaction after staining with fluorescent anti-rabies antibody.

33. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Subsequent correspondence with his family in Mexico revealed that a puppy had bitten him on the neck two weeks before he came to Florida (i.e., about six weeks ago). He had thoroughly cleaned the bite site and because it was not deep, he had not worried about it. The family stated that the puppy had been taken to another neighborhood and abandoned because it had tried to bite both humans and other animals.

34. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 10 What behavior occurs in rabies that does not occur in other viral encephalitides? A) excessive salivation B) hydrophobia C) biting (snapping) D) all of the above E) none of the above Answer D) all of the aboveYes, they all do.

35. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 11 How did the man get rabies? A) the spider bite B) the puppy bite C) the drinking water in Mexico D) via the respiratory route E) from a corneal transplant Answer B) the puppy biteAny mammal can transmit rabies, but dogs are a very common source, especially in underdeveloped countries. In Florida it is usually raccoons. People have also gotten rabies from a corneal transplant. Several times in fact. But the patient didn't have a corneal transplant that we know of. Furthermore, there is usually periorbital pain with corneal-transmitted rabies.

36. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 12 How could the man's rabies have been prevented? A) vaccination prior to the bite B) vaccination after the bite C) prophylactic interferon after the bite D) hyperimmune globulin E) B and D Answer E) B and DPost-exposure vaccination works with rabies because of the long incubation period. However, hyperimmune serum globulin is also given in the case of a bite by a possibly rabid animal.

37. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 13 Who discovered that rabies could be prevented by post-exposure vaccination? A) Salk B) Sabin C) Jenner D) Koch E) Pasteur Answer E) PasteurIt was almost 100 years after the world's first vaccine for humans (Jenner's smallpox vaccine) that Pasteur developed the second--rabies.

38. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Question 14 What other viruses are in the same family as rabies? A) EEEV B) Lyme disease virus C) California Encephalitis virus D) Norwalk virus E) none of the above Answer E) none of the aboveVesicular Stomatitis virus (VSV) is in the same family as rabies, the rhabdoviruses, but it mostly just causes disease in cows. It is used, however, as a model to study rhabdoviruses.

39. Bugs, Drugs, and Thugs • Infectious Disease Case Study 2 Outcome: Twenty health care workers who had helped care for the gentleman were given rabies vaccination. His son and daughter-in-law also received it. None of the known contacts became sick. Health authorities in Mexico were notified and administered vaccine to 4 children who had reportedly played with the dog. The abandoned puppy was never found, but they identified a 10-block area in which all owned dogs were vaccinated and all strays were destroyed. No other cases were reported.

40. Bugs, Drugs, and Thugs • Infectious Disease Case Review Scorecard So…. How did you do? Add up your correct # of answers. 29 - 30 Correct: You must have your Ph.D.! 27 - 28 Correct: You must be working on your Masters Degree! 25 - 26 Correct: You must be a Lab Technician 22 - 24 Correct: You must be an Administrator 19 - 21 Correct: You must be a Lab Commander 16 - 18 Correct: You must be doing a lot of PT! 15 or less Correct: You must be a Physician!