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Q1 Female, 24 years of age, 10 weeks pregnant, kindergarten teacher. Some kids in her class were diagnosed this week with Parvovirus B19 aka "Fifths Disease". She wants to avoid getting it or infecting her baby. Describe treatment and coaching for "two new patients" today and over next several months.

Fifths Disease is also known as Human Parvovirus B19 or erythema infectiousum or "slapped cheek syndrome". It is important for this woman to understand that Parvovirus B19 is a low risk infection, even during her pregnancy. My first responsibility will be to impart to her a sense of the actual risks involved to herself and to her unborn child. She needs to know that approximately half of adults have been exposed and are already immune to this virus. Because she works with kindergarten children, this woman has a higher than average chance of having been exposed. If she was infected, there is a 20% chance that she did not have any symptoms. If she is already immune then there is zero risk to her fetus. If she is not immune, the risk is low.

This virus is contagious before the rash appears, but not contagious once the rash is apparent (as opposed to measles which is contagious when rash is expressed). The incubation period is 4 to 20 days after transmission, which usually occurs by respiratory droplets. The best way to prevent transmission is by frequent and thorough handwashing.

According to the CDC there are usually no serious complications for pregnant women. The disease is usually mild for a mother and for an unborn baby. Less than 5% of the time parvovirus B19 infection causes severe anemia in the unborn baby, and the woman may miscarry. This risk is most common in the 1st half of the pregnancy, and she is already at 10 weeks. There is no evidence that B19 infx causes birth defects or retardation

She may opt to test her blood for antibodies. A positive blood test for antibodies can show 1) that she is immune to parvovirus B19 and has no sign of recent infection, 2) that she is not immune and have not yet been infected, or 3) that she has had a recent infection. If she is immune she has no worries. If she is not infected she can attempt to avoid exposure by not going to work until after she is past the 1st half of her pregnancy. She will certainly be exposed if she goes to work. She might be reassured to know that the CDC does not recommend that pregnant women be excluded from a workplace where a fifth disease outbreak is occurring. If she is already infected I would provide immune system support and watch her carefully. Ultrasound and additional blood tests will not treat the illness, but if the woman needs additional medical reassurance, these are options.

Additionally I would coach her on the common signs and symptoms of infection in children and adults so that she would be aware. S/Sx in children: infectious before the rash appears, the early symptoms are nondescript and include low grade fever, malaise or cold symptoms. The rash mild, "slapped-cheek" in appearance on the face and a lacy red rash on the trunk and limbs, occasionally itchy. The rash generally resolves in 7-10 days. Adult symptoms are slightly different, as the rash is less common, and adults may experience bilateral joint pain or swelling. Discomfort is most common in the hands, wrists, and knees and usually resolves in a week or two but can last for months.

Q2: Describe how Slapped Cheek Syndrome (Erythema Infectiosum) and the red cheeks of scarlet fever (Strep pyogenes) can be differentially diagnosed emphasizing symptoms, onset, and clinical diagnostic tests you would use.

It is very important to distinguish between these two infections because the first, which is Parvovirus B19 as described in the previous question, is a mild illness that resolves on its own and complications are unusual. Streptococcus pyogenes on the other hand causes scarlet fever and strep throat, but more severely can result in acute glomerular nephritis and rheumatic fever. Strep pyo must be treated appropriately to avoid the possibility of lifelong consequence. The two tests to perform would include a blood test for the antibodies to Parvovirus, which will inform the decision only partly. The more important antibody test is from a throat swab to check for group A strep, aka an ISO titer. A further clue to distinguish the two may be had from the differing incubation periods. B19 incubates for 4-20 days, whereas Strep pyo intoxication become evident in 2-4 days after infection. The rashes also have different appearances. The rash of Strep pyo begins on the chest and stomach but can spread to the entire body, and is comprised of tiny red bumps. The slapped cheek rash is not raised, and begins on the face. The strep rash lasts about 2-7 days, and after it is gone the tips of the fingers and toes peel. The strep rash also includes a "slapped cheek" phase that includes a flushed face with a pale area around the lips. More strep symptoms include a red and sore throat can have white or yellow patches, swollen lymph glands in neck, whitish coating on tongue. Less commonly the infected individual may experienc nausea, vomiting, headache, body aches. Strep pyogenes requires antibiotics to treat, whereas B19 resolves on its own.

Q3
A mom wants advice on whether to immunize her 11 year old daughter for HPV using Gardasil from Merck. Describe my next steps for treating and coaching my new patient, the 11 year old daughter.

First of all, the decision lies in the hands of the guardians of the child. I will make my recommendation clearly and give my reasons, but also share the other side of the debate with the mother, and send her home with a lot to think about. Regardless of the mother's decision, the 11 year old girl needs to learn about sex and about the risks involved with sex. The timing and specifics of this education depend more on the parents than they do on me. This vaccination will not protect her from all the risks of sexuality, so safe sex practices will need to be communicated to the child at the appropriate time. In my opinion, 11 years of age is old enough to comprehend much, but certainly not all of the concerns regarding sexuality. But this also depends on the intelligences and maturity level of the child. In fact, so much depends on the parents and the child that I cannot actually describe my treatment/coaching because it depends on the details of the situation. As you may guess I am biased against vaccines except in a few cases, when the vaccine's efficacy and the public health need are clear and powerful. In the case of an STD, there is no need to vaccinate against it unless the patient will be having unsafe sex. Tis much safer in my view to avoid STD's via sexual precautions. There are no guarantees that a girl who accepts this vaccination will not get cervical cancer.

To clarify my own position, I am not against ALL vaccines. It depends on the case, and on the public health benefits. I remain suspicious of the pharmaceutical corporations who place profit highest among their values. Small pox, measles, mumps, rubella, polio, diphtheria, and whooping cough (Bordetella pertussis) have all proven useful for limiting outbreaks, and as the vaccines formulas are revised to be less toxic, I will feel better about recommending them. New vaccines may well arise that are worth the risk of a small injection. These will need to be judged as always on a case by case basis.

Q4: A 60 year old woman comes to my office. She had adenocarcinoma of her colon and it was surgically removed. She bled substantially during the sugery and received several blood transfusions. Three weeks after the surgery she developed fever, diarrhea and vomiting. Blood and stool cultures are negative for bacter, negative for clostridium difficile and negative for Hep B surface antigen. Liver biopsy reveals multinucleated giant cells with intranuclear niclusions. Negative for cysts resembling Entamoeba histolytical. What virus do I suspect and why?

Initially I suspected CMV, cytomegalovirus. She may have contracted it from the blood transfusions because it inhabits the nuclei of leukocytes. It causes swollen "giant" cells with multiple nuclei with inclusion bodies. Ninety percent of the population has antibodies to CMV but are asymptomatic, so it is probably present in many blood samples. The reason that this woman presented as she did is that she just had colon cancer and is probably undergoing chemotherapy and radiation as followup to her colonectomy. These therapies induce immuno-deficiency, and CMV presents very differently in this population. CMV tends to infect people when their T cell numbers get under 50-100/cc. CMV can cause retinitis and pneumonia, but more commonly causes recurring diarrhea due to colitis. She doesn't have a colon anymore, so it is probably affecting her remaining bowel in an increasingly destructive way. If disseminates it kills rapidly.

The two criteria by which CMV does not fit the case is the onset and the vomiting.

I do not suspect EBV because there is no mention of atypical mononuclear cells int he blood, but I would want to confirm that. Could it be Human Herpes Virus 6, 7 or 8? Probably not due to symptom mismatch, but remain open to all possibilities until a diagnosis is confirmed.

HEPATITIS C is also an option.

Transmission, High Risk Populations:
--spread by contact with blood of infected person
--current risk from blood transfusion is less than 1 chance per 2 million units transfused.
--drug injection, no matter how long ago
--treatment for clotting problems with a blood product made before 1987
--blood transfusions from a person who later tested positive for hep c
--blood transfusion or solid organ transplant before July 1992
--long-term hemodialysis patients
--S/Sx of liver disease (e.g., abnormal liver enzyme tests)
--healthcare workers after exposures (e.g., needle sticks or splashes to the eye)
--children born to HCV-positive women (4:100 are infected, no way to prevent, if coinfected with HIV transmission rate is closer to 19%)
--sexual transmission is rare, oral sex transmission not documented

S/Sx:
--many people are asymptomatic
--evidence of liver disease (e.g., persistently abnormal ALT levels)
--a few pts develop extrahepatic conditions incl: glomerulonephritis, essential mixed cryoglobulinemia, and porphyria cutanea tarda

General:
--no vaccine
--if infected you may not donate blood
--there are 6 known genotypes and more than 50 subtypes of HCV, and genotype information is helpful in defining the epidemiology of hepatitis C
--pts 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)
--prior infection does not prevent infection with different genotypes
--needle stick risk for healthcare workers: 1.8%
--Risks per 100 persons with Hep C:
75-85 long-term infection
60-70 chronic liver disease
5-20 cirrhosis over a period of 20 to 30 years
1-5 death

Dx: (blood tests)
1)--Anti-HCV (antibody to HCV. EIA (enzyme immunoassay) or CIA (enhanced chemiluminescence immunoassay) Test is usually done first.
--If positive, confirm using RIBA (recombinant immunoblot assay).
--Anti-HCV does not tell whether the infection is new (acute), chronic (long-term) or is 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
--if positive anti-HCV test-->get ALT measurement, if elevated then liver inflam
--it is possible to have high or fluctuating ALT and still have chronic hep C
2)--Qualitative tests to detect presence or absence of virus (HCV RNA)
3)--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 are possible. Commonest in persons w/ low risk.
--FALSE NEGATIVES also possible, esp in early part of infection because antibody levels are still low, or when immune response is reduced. Use PCR to reduce this risk.
--PCR yields a positive test for HCV within 1 to 2 weeks after being infected with the virus.

PREVENTION:
--clean surfaces w/ blood using 1:10 bleach solution, wear gloves
--avoid risk behaviors (IV drug use, unprotected sex, etc)

Tx:
--moderate exercise, healthy diet, zero alcohol, rest
--Get vaccinated against hepatitis A if liver damage is present.
--get vaccinated against hep B if you're in a high risk group
--liver transplant if cirrhosis is progressed (Hep C is the leading cause)
--combination therapy with pegylated interferon and ribavirin-->sustained response rates of 40%-80%. (up to 50% for patients infected with the most common genotype found in the U.S. [genotype 1] and up to 80% for patients infected with genotypes 2 or 3)
--interferon monotherapy reserved for pts in whom ribavirin is contraindicated. Ribavirin, when used alone, does not work. Combination therapy using interferon and ribavirin is now FDA approved for the use in children aged 3-17 years.
--side effects of interferon therapy: flu-like symptoms (fever, chills, headache, muscle and joint aches, fast heart rate) early in treatment, lessening, later: tiredness, hair loss, low blood count, trouble with thinking, moodiness, and depression. RARE SE's: thyroid disease, depression with suicidal thoughts, seizures, acute heart or kidney failure, eye and lung problems, hearing loss, and blood infection
--death is usu due to cirrhosis
--side effects of combination (ribavirin + interferon) treatment: in addition to interferon SE's, anemia, birth defects.
--treatment is expensive, numerous social programs exist to help people get treated

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