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Microbio Takehome Exam #5

Q1: What herbal treatment is useful for treating some latent herpes infections? And what other non-herpes viral infections may also be improved by this herb?

Licorice may interfere with herpes during latency by inhibiting the expression of Kaposi sarcoma–associated herpes virus (KSHV) latent genes. Kaposi sarcoma is characterized by tumors in tissues below the surface of the skin, often found in patients with immunodeficiencies like HIV and AIDS. Glycyrrhizic acid, which is found in licorice, can kill KSHV infected but latent cells by altering levels of LANA and v-cyclin. Glycyrrihizic acid is the first known anti-viral agent to specifically targets the expression of a herpesvirus gene required to maintain the virus in the latent state. Any virus with a latent phase may possibly be treated in this way, but more research needs to be done to establish its efficacy.

A side note of interest: researchers at U Fla College of Medicine have found that delta-9 tetrahydrocannbinol aka THC from marijuana may block the spread gamma herpes viruses which cause cancers (esp Karposi's Sarcoma Virus and EBV which leads to Burkitt's lymphoma and Hodgkin's disease). Findings published online in BMC Medicine suggest the possibility of antiviral drugs based on nonpsychoactive derivatives of THC. Gamma herpes viruses can remain dormant in WBC's for a long time. Reactivation increases the infection and cancer risk. In rats, if the infected cells grown in the presence of THC die when the virus reactivates. THC has no effect on herpes simplex 1. The USF researchers suggest that THC selectively inhibits the spread of gamma herpes viruses by targeting the gene ORF50.

Q2: A 25 year old woman has had a sore throat for 3 days. On exam, throat is red, no exudate, no beta-hemolytic colonies in throat culture. Two cervical lymph nodes are palpable, enlarged, tender. Body temp: 101.5. Enlarged spleen. Heterophile antibody test shows that sheep RBC's agglutinate w/ pts serum. Dx?

MONO. Mononucleosis is a viral infection causing fevers, sore throat, and swollen lymph glands, especially in the neck. It may be caused by Epstein Barr Virus or Cytomegalovirus. The monospot test aka heterophil test is quickly detects a recent mono infection by looking for two antibodies. A sample of blood is placed on a microscope slide and mixed with test substance. If mono is present, the blood clumps (agglutinates). Monospot testing can usually detect antibodies 2 to 9 weeks after a person is infected. It generally is not used to diagnose mono that started more than 6 months earlier.

A second test that may be used is the EBV antibody test. A series of tests can detect different types of antibodies to help determine whether you were infected recently or sometime in the past. Newer tests quickly identify EBV on genetic material other than blood.

Q3: At what age does the WHO recommend vaccinating for measles in developing countries? Why is the age for vaccination different in the US? Is there evidence that vaccination against measles prevents other childhood disease?

The WHO is attempting to vaccinate children in certain high risk developing countries with higher risk at the age of 9 months or shortly thereafter. The 47 countries that account for more than 95% of global measles deaths are mostly in SE Asia, Africa and the eastern Mediterranean region. The second immunization is to occur before age 15, and will hopefully incur full immunity in those whose initial response was not as good. This second round of vaccine administration is intended to also immunize the children who were too old to get the first shot under this new program (started in 2000). The goal is to reduce under-five years child mortality rate by two-thirds by the year 2015 compared with 1990 levels.

In the US the MMR vaccine is administered at 12-15 months and 4-6 years. The Americas had fewer than 1000 deaths from measles in 2006, so the differing requirements for the states are probably due to the fact that the disease is already controlled.

The MMR vaccine prevents an assortment of childhood diseases including Measles, Mumps and Rubella. There are at least two strains of measles prevented by this vaccine. I found no evidence of other diseases being influenced by vaccination.

Q4: 52 year old man has Hep C antibodies. Is he infected? What is possible? How do you find out if he has an active infection? What are next steps to determine health status, what organs are we concerned about? What can patient do to avoid transmitting the virus? What dietary or lifestyle changes will help? Should he stop smoking?

One positive Hep C antibody test tells you only that the patient was exposed to the virus. His infection could be acute, chronic, or no longer present. True diagnosis requires a series of blood tests to establish if the patient is infected, and if so, what stage of infection one is in. At each stage there are posibilities of false positives and negatives. The first test is for Anti-HCV (antibody to HCV. The EIA (enzyme immunoassay) or CIA (enhanced chemiluminescence immunoassay) test is usually done first. If either of those tests is positive, confirm using RIBA (recombinant immunoblot assay).

PCR testing can reveal genotype info useful for treatment. There are 6 known genotypes and more than 50 subtypes of HCV, and genotype information is helpful in defining the epidemiology of hepatitis C. Patients w/ genotypes 2 and 3 are almost three times more likely than patients with genotype 1 to respond to alpha interferon or combination Tx (alpha interferon and ribavirin).

The presence of Anti-HCV in the blood does not tell whether the infection is new (acute), chronic (long-term) or no longer present. Anti-HCV (antibodies) can be found in 7 out of 10 persons when symptoms begin and in about 9 out of 10 persons within 3 months after symptoms begin.

At the same time as these first tests, it would be wise to get a metabolic panel to assess the patient's liver enzyme levels. An elevated ALT in conjuntion with a positive Anti-HCV suggests liver inflammation. It is possible to have high or fluctuating ALT in conjunction with chronic Hep C. The primary organ of concern is the liver, though should liver function fail all the other organs are subject to compromise.

Another test which is essential at this stage is HIV. Co-infection is common and will affect treatment choices. Further followup tests include qualitative tests to detect presence or absence of herpes virus (HCV RNA), and quantitative tests to detect amount (titer) of virus (HCV RNA). A single positive PCR test indicates infection with HCV. A single negative test does not prove that a person is not infected. Virus may be present in the blood and just not found by PCR. Also, a person infected in the past who has recovered may have a negative test. When hepatitis C is suspected and PCR is negative, PCR should be repeated. False positives and false negatives occur in this testing. False negatives occur the early part of infection when antibody levels have not yet elevated, or when immune response is reduced. PCR is most reliable, yielding a positive test for HCV within 1 to 2 weeks after being infected with the virus.

To reduce the chance of transmission, the infected individual should abstain from donating blood, abstain from IV drugs and sharing needles, and abstain from unprotected sex. Any exchange of bodily fluids is to be avoided. Prior infection does not prevent infection with different genotypes, so he may not exchange fluids with another hepatitis C infected individual without incurring additional risk. Any spilled blood needs to be immediately cleaned up and disinfected using 1:10 bleach solution.

YES I would recommend that he cease and desist from smoking cigarettes, but alcohol is far more important for him to avoid. ...So do what you can. I would recommend that he get vaccinated against the other strains of Hep if he has any liver damage or continuing risk factors. He may end up needing a liver transplant.



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