The University of Arizona

Case 5: A Mother's Day Gift That Keeps On Giving

Monkey pox story 2003 - Child*
5/11, Mothers’ Day, Two prairie dogs from pet swap meet in Wausau given to Mother in Dorchester, WI.
5/13 Prairie dog bites 3 1/2 year old daughter on right index finger and dorsal left hand.
5/15 Prairie dog seen by veterinarian due to skin lesions and discharge from nose and eyes. Prairie dog bites veterinary technician.
5/16 Child get fevers, wounds are red.
5/20 Child seen by primary care physician. Lesions are raised and whitish and child has URI [upper respiratory infection]-like symptoms. Augmentin and Zithromax [antibiotics] are started. Prairie dog dies. Head sent by veterinarian to Madison for rabies check, negative. Enlarged submandibular [under jaw] lymph gland harvested and sent to Marshfield Joint Venture Laboratory for cultures.
5/22 Child hospitalized because of festering wounds, fevers, sweats, right eye discharge, swelling around the right eye (from rubbing with wounded hands?), and new skin lesions, including scalp, perineum and extremities. Multiple IV antibiotics given including ciprofloxacin.


5/25 Dermatology consult obtained because of persistent fevers and new skin lesions. Primary inoculation sites on on right index finger and dorsal left hand have central hemorrhagic crusts with pustular borders. Disseminated papulovesicles and pustules have erythematous flares with central umbilication and/or hemorrhagic crusts. Lesions biopsied for aerobic culture and histology 12:30 AM. By 9 PM, histology report of extensive epidermal necrosis [cell death], cells with cytoplasmic inclusions and possible multinucleated cells. Stains for HSV [Herpes Simplex Virus] I & II negative. Intravenous acyclovir started.

Monkey pox story 2003 - Mother
5/27 28 year old mother gets vesiculation around cat scratch on dorsal right hand. Biopsies taken for viral culture, electron microscopy, and histology. Swab sent for aerobic culture. Mother has had drenching sweats, malaise, sore throat and does not feel well.
5/28 Mother has disseminated skin lesions. Has had more sweats, but feels better. Afebrile [no fever] by oral temp.
5/29 Mother’s primary lesion is re-biopsied. Disseminated lesion on right forearm biopsied. Mother feels better, but throat still sore, tonsils enlarged. Acute serum obtained. WBC 6.2 (23% bands, 39% segs, 24% lymph, 5% activated lymphs, 8% monos), CRP [C-Reactive Protein] =5.3, chemistries normal. Throat culture negative Valacyclovir 1 gram tid. Mother kept out of work. Child discharged on ciprofloxacin.
5/30 Orthopox virus seen on mothers initial biopsy. Valacyclovir stopped. Orthopox virus cultured from skin.

Monkey pox story 2003 - Father
5/31-6/1 38 year old father gets sweats, malaise and develops multiple skin lesions.
6/2 Primary care physician reports 12-15 disseminated skin lesions on all extremities, trunk and head. Father now feeling well but kept out of work.
6/5 Family seen in clinic. All feeling well. Primary lesions are crusted ulcerations. Mother’s tonsils are smaller and she has no adenopathy [swollen lymph nodes]. Father has at least two lesions that are still vesiculated and some axillary adenopathy. Acute serum and viral cultures obtain from Father. Mother and Father told to stay out of work.
6/6 Family’s 13 cats, 20 dogs, 7 horses, 4 goats, 3 donkeys and one recovering prairie dog are kept in quarantine.
Orthopox virus cultured from prairie dog lymph node.

* Cases from CDC http://www.cdc.gov/ncidod/monkeypox/index.htm Go to Related Links and then Electron Microscopy Images of the Virus. Cases in Wisconsin May 2003.

Monkeypox is an Orthopox Virus, a close relative of smallpox. It is an enveloped DNA virus that replicates in skin epithelial cells. Cell death and the resulting immune response results in raised fluid-filled blisters on the skin. Monkeypox was first identified in monkeys and later in rats in Africa. As of June 18, 87 cases had been reported to the CDC from Wisconsin, Indiana, Illinois, Ohio, Kansas and Missouri (MMWR 52: 561-564, June 20, 2003). The majority of infected people had direct or close contact with prairie dogs or other wild or exotic mammals sold as pets. The CDC confirmed twenty of the cases by finding monkeypox DNA in lesions by PCR.

Monkeypox causes a less severe disease in humans than does smallpox. Twenty of the 87 infected people were hospitalized. Many of those were not seriously ill but were hospitalized to prevent spread of the disease. Smallpox vaccination protects against monkeypox and has been recommended for health care workers and other healthy people exposed to monkeypox. The smallpox vaccine is a live attenuated viral vaccine of the Vaccinia (cowpox) virus.

1. List the immune system effector cells and molecules that would be involved in the immune response to monkeypox. For each, give its location and effector function (phagocytose and kill virus, opsonize or neutralize virus, etc.)

2. Describe where and how a mature naïve CD8 T cell specific for monkeypox would be activated to produce a clone of monkeypox-specific cytotoxic T cells (CTL). Include the most likely APC, the co-stimulatory signals (what they do and why they are necessary), and a key T cell cytokine that in required for proliferation.

3. Describe where and how an activated CTL specific for monkeypox would find and kill infected epithelial cells. Include how the CTL recognizes an infected cell and the ways in which that cell is killed.

4. Tell me about how T cells navigate around the body, how and where they enter the lymph nodes and how and where they enter infected tissues.

5. What immune effectors are causing the skin rash and how?

6. What memory cells would be generated by the smallpox vaccine that would protect against monkeypox infection? How would a vaccine to one virus protect against another virus?

Answer the questions with as much detail as possible and save as a Word document entitled YourNameCase5.doc. Send to jdecker@u.arizona.edu as an attachment by 9 AM Tuesday June 22. Make sure your name is in the document as well as in the title.

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Supplementary Materials :TCMI, Cytokines