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varicella - Grand Rounds Andy Chien MD PhD University of...

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Unformatted text preview: Grand Rounds Andy Chien, MD, PhD University of Washington Division of Dermatology Andy’s previous grand rounds 10 20 30 40 50 60 70 80 90 Time (min) Sweet’s Stem cells Eosinophils Today (projected) 85 75 70 60? Andy’s previous grand rounds • Total time for three grand rounds: 230 min. • Average per grand rounds: 77 min. (9:02 am) • Total time over so far: 50 min. varicella diminutive of variola (medieval Latin): “pustule” varius (Latin): “various, mottled” variare (Latin): “to vary or change” chicken pox gican (Old English): “to itch” chiche-pois (French): “chick-pea” ? ? pokkes (Middle English) pocc (Old English) beu (hypothetical Indo-European root): “to swell” herpes zoster herpes (Greek): “creeping” zoster (Greek): “belt, girdle” shingles schingles (medieval Latin) cingulum (Latin): “belt, girdle” Varicella zoster virus • Herpes family double-stranded DNA virus (smallest genome of herpesviruses) • Produces two clinically distinct syndromes • Acquired by inhalation or contact, with primary infection of conjunctiva or upper airway mucosa Primary varicella • Days 2-4: initial viral replication in regional lymph nodes • Days 4-6: primary viremia • Subsequent second round of viral replication in liver, spleen, other organs • Secondary viremia seeds capillaries and then epidermis by day 14-16 Herpes zoster • VZV spreads from skin/mucosa into sensory nerve endings • Virus travels to dorsal root ganglion and becomes latent • Reactivation occurs with decreased cell- mediated immunity • Initial replication occurs in affected DRG after reactivation Herpes zoster • Ganglionitis ensues, with inflammation and neuronal necrosis • Pain ensues with travel of the virus down the sensory nerve Great moments in varicella history • 1767 - Heberden distinguishes chickenpox and herpes zoster • 1875 - Steiner innoculates volunteers with fluid from varicella blister, demonstrating infectious transmission • 1888 - von Bokay notices that chickenpox developed in susceptible children following exposure to a patient with herpes zoster (pub. 1892) Great moments in varicella history • 1932 - Bruusgarrd (and earlier Kundratiz in 1922) innoculate children with zoster vesicle fluid; the children get chickenpox • 1942 - Garland hypothesizes that zoster was the result of reactivation of VZV acquired earlier in life • 1953 - Weller isolates VZV from primary varicella and zoster (confirmed in 1984 using restriction endonucleases by Straus et al.) Great moments in varicella history • 1970s - Takahashi and colleagues in Japan develop attenuated “Oka” strain of VZV for vaccination (genetic basis of attenuation remains unknown today) • 1986 - Davison and Scott publish the complete DNA sequence of VZV Great moments in varicella history • 1987 - Lowe et al. design first genetically-engineered strain of VZV • 1995 - VZV vaccine becomes available in the United States Chickenpox versus smallpox...
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varicella - Grand Rounds Andy Chien MD PhD University of...

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