In May of 2004, an Arkansas man, Mr X, visited two hospitals in Texas with severe mental status changes and a low-grade fever. Neurologic imaging indicated findings consistent with a subarachnoid hemorrhage, which expanded rapidly in the 48 hours after admission, leading to cerebral herniation and death.
Question 1 - Single Best Answer
What does the fact that the donor had a fever MOST LIKELY indicate?
A) He had an infection.
B) He had a viral infection.
C) He was going to die
D) He had a pulmonary embolism
E) All of the above
Question 2 - Single Best Answer
What region of the body is responsible for temperature regulation?
A) kidney
B) liver
C) hypothalamus
D) blood brain barrier
Question 3 - Single Best Answer
What are three of the four major groups of pathogens that usually cause infectious diseases? Bugs Database
A) symbionts, commensals, parasites
B) measles, mumps, and Herpes
C) prokaryotes, metakaryotes, and eukaryotes
D) viruses, bacteria, and fungi
E) protozoa, worms, and bacteria
F) Staphylococcus, influenza, and AIDS, and malaria
In spite of all these leading questions about infections and fever, it was determined that Mr. X's fever did not indicate an underlying cause for his death and donor eligibility screening and testing did not reveal any contraindications to transplantation. The patient's family agreed to organ donation. Lungs, kidneys, and liver were therefore recovered. The liver and kidneys were transplanted into three recipients on May 4 at a transplant center in Texas. The liver recipient was a man with end-stage liver disease. He did well immediately after transplantation and was discharged home on postoperative day 5. Twenty-one days after transplant, the patient was readmitted with tremors, lethargy, and anorexia. The patient's neurologic status deteriorated rapidly during the next 24 hours and he became febrile; he required intubation and critical care support. A lumbar puncture indicated a mild lymphocytic pleocytosis (25 white blood cells/mm3) and a mildly elevated protein.
Question 4 - Single Best Answer
In general, what can one tell about an infection from a change in numbers of white cells?
A) Whether there is one or not
B) Whether the cause is viral or bacterial
C) Both of the above are true
This man's spinal fluid profile indicates a possible viral infection. (Had he had a bacterial meningitis there would have been PMN's in his spinal fluid.) His neurologic status continued to deteriorate. Six days after admission, an MRI indicated diffuse encephalitis. The patient subsequently died.
Question 5 - Single Best Answer
Was the man's death a likely failure of his liver transplant?
A) Yes
B) No
Question 6 - Single Best Answer
Was his death likely due to infection of the wound?
A) Yes
B) No
Question 7 - Single Best Answer
Could he have become infected with a virus directly from the transplanted organ?
A) Yes
B) No
We know so far that all three patients that received organs from Mr. X died of a probable virus infection (see response to correct answer of previous question). Now we would like to know the exact cause.
Question 8 - Single Best Answer
Why is it important to diagnose a disease?
A) Prognosis
B) Treatment
C) Epidemiology
D) all of the above
Now, before talking about exact causes we need to think a little bit about how viruses are classified.
Question 9 - Single Best Answer
What are two major STRUCTURAL groups of viruses?
A) viruses with no protein coat, just plain nucleic acid, and viruses with coats
B) viruses with lipid coats and viruses with protein coats
C) protein viruses and nucleic acid viruses
D) naked viruses and enveloped viruses
Question 10 - Single Best Answer
What are the two major GENETIC distinctions of viruses?
A) cellular or acellular
B) DNA or RNA
C) mRNA or tRNA
D) ribosomes or no ribosomes
Question 11 - Single Best Answer
How many groups of viruses, BASED ON THEIR REPLICATION SCHEMES, are there?
A) 2
B) 4
C) 6
D) 493
Question 12 - Single Best Answer
What kind of cells can viruses replicate in?
A) eukaryotic cells
B) bacterial cells
C) fungal cells
D) all of the above
Question 13 - Single Best Answer
What kinds of viruses could infect the brain? (Note: SEE the Bugs database, in the Pathogens file, under brain.)
A) measles, polio, coxsackie virus
B) rabies, vaccinia, influenza
C) polio, rabies, EEEV (Eastern Equine Encephalitis Virus)
D) Streptocuccus pneumonia, Hemophilus influenzae, Neisseria meningitidis
Question 14 - Single Best Answer
How can a viral infection be diagnosed?
A) Culture
B) Serology ....detection of the host's antibodies
C) Detection of viral antigens
D) Detection of viral nucleic acids
E) All of the above
Question 15 - Single Best Answer
How would you diagnose polio?
A) acid fast stain
B) blood smear
C) serology
D) Dane particle
E) Negri bodies
Question 16 - Single Best Answer
How would you diagnose rabies?
A) serology
B) Dane particle
C) Negri bodies or mouse inoculation
D) evidence of a bite wound
In all the three patients that had received organs from Mr. X, histopathologic examination of central nervous system tissues revealed an encephalitis with viral inclusions suggestive of Negri bodies; the diagnosis of rabies in all three recipients was confirmed by immunohistochemical testing and by the detection of rabies virus antigen in fixed brain tissue by direct fluorescent antibody tests (Fig 1). Electron microscopy of CNS tissue of one of the renal transplant recipients also identified characteristic rhabdovirus inclusions and viral particles. (Fig 2).
There are, in general, four routes by which viruses (or any microorganisms) can be transmitted. These are respiratory, oral, sexual, percutaneous (needles, wounds, bites).
Question 17 - Single Best Answer
How is rabies usually transmitted?
A) insect bite
B) respiratory droplets
C) sexually
D) bite of a carnivorous animal
E) ingestion of the virus through contaminated food
Question 18 - Single Best Answer
What kind of virus is rabies? (Note: The highly astute will have gotten a hint above; for the others, go to the Bugs database and click on Rabies virus)
A) Rhabdoviridae
B) ssRNA (-)
C) helical
D) enveloped
E) all of the above
Question 19 - Single Best Answer
Are enveloped viruses more or less stable in the environment?
A) More
B) Less
Question 20 - Single Best Answer
What directly determines where, in the body, a virus will replicate? This is called a tropism. Rabies, for instance, has a tropism for brain tissue.
A) the viral RNA
B) the viral DNA
C) the matrix protein
D) attachment proteins on the viral surface and cell surface receptors.
Question 21 - Single Best Answer
If it had been realized that the three transplant patients had been exposed to rabies BEFORE THEY HAD ANY SYMPTOMS, what could have been done to prevent the disease, if anything?
A) nothing
B) acyclovir and other antiviral drugs
C) anti-rabies antibodies
D) rabies immunization
E) more than one of the above
Question 22 - Single Best Answer
Were the hospital personnel or family members of the three patients at risk?
A) High risk
B) Very low risk
C) No risk
Question 23 - Single Best Answer
Has "nosocomial" transmission of rabies been previously reported?
A) Yes
B) No
This is a very sad case ending with four deaths. It still has not been determined how Mr. X contracted the rabies that he spread via his organs. You might ask yourselves what you could have done to prevent the tragedy, had you been a practicing physician involved with any of these cases. The chain of responsibility in medicine is sometimes long and complicated and it is hard to know what one person could have done. However, it certainly could never hurt to check all the details. More importantly, better policies are obviously needed, and you could be involved in that!