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Smallpox, a potential problem Julia Higgins MSc Molecular Medical Microbiology Contents • • • • • Introduction and History Epidemiology and Transmission Microbiology and Pathogenesis Clinical Features Methods to counteract pre-exposure and postexposure • Potential as a Bioterrorist Weapon • Conclusion Introduction and History Introduction • Smallpox (Variola) feared most devastating of all infectious diseases • WHO declared smallpox extinct 1980 • Consequently no further need for immunisation programs History • Smallpox illness of humans 3,000 years • Edward Jenner, father of smallpox vaccination 1798 • Smallpox largely eradicated early 20th Century Epidemiology & Transmission • Only officially exists in two laboratories in World: CDC Atlanta USA & Koltsovo former USSR • Transmission mainly via airborne route • Only person to person, no animal reservoir or insect vector • Can be via direct contact of vesicle fluid, saliva and respiratory secretions • Contaminated linen and clothing Microbiology & Pathogenesis • • • • Microbiology Member of genus Orthopoxvirus Double-stranded DNA virus Virion brick-shaped structure ~200nm diameter Uses host enzymes for replication • • • • Pathogenesis Infective dose believed to be only few virions Migration & multiplication in lymph nodes Asymptomatic viremia 20 viremia followed by fever Clinical Features • Incubation period ~ 12 days • Flu-like symptoms • Lesions to macules to papules to vesicles to pustules • Scabbing of pustules Table 1: Comparison in onset, symptoms and rates of fatality in variations of Smallpox Infections Type Infection Incubation Period Diagnostic Symptoms Rate of Fatality Variola Minor (alastrim) 12 days Sparse rash < 1% Variola Major (90% cases) 12 days Maculopapular rash 30% Malignant Variant Abrupt onset Confluent lesions Frequently fatal Hemorrhagic Variant Considerably less than minor and major variants Dusky erythema followed by petechiae Uniformly fatal Smallpox lesions on skin of trunk. Picture taken in Bangladesh, 1973. Public Health Images Library (PHIL) ID # 284. Source: CDC/James Hicks A Practical treatise on smallpox : illustrated by coloured photographs from life / by George Henry Fox ; with the collaboration of S.D. Hubbard, S. Pollitzer, and J.H. Huddleston. Philadelphia : Lippincott, c1902 Figure 1. Typical Temperature Chart of Patient With Smallpox Infection Temperature 0C 40.5 40 Rash _ _ _ _ _ Scabbing 39.5 39 38.5 38 37.5 37 10 12 14 16 18 20 22 24 26 28 30 32 Days of Infectivity Chart adapted from JAMA June 9th 1999 Measures to counteract preexposure and post-exposure • • • • Pre-exposure Natural immunity from previous exposure to virus Routine vaccination – Completely stopped in 1979 as recommended by WHO. Vaccination only effective for 10 years Previous vaccination reduces effects of virus • • • • Post-exposure Vaccine up to 4 days after exposure to virus No Antiviral therapy except treatment of symptoms Compounds cidofovir and adefovir Cidofovir evidence of promising results Potential as a Bioterrorist Weapon • Widespread immunity no longer in population • Increase in immune disorders results in increased fatality • Only 90 million vaccines readily available worldwide (15.4 million USA alone) • Rate of transmission estimated at 10-20 new infections per infected person • Reports from Ken Alibek of successful programs to produce smallpox in large quantities Conclusion • Worldwide need to produce sufficient supply of vaccines to combat potential deliberate release • Worldwide need to mass produce bifurcated needle to administer vaccines • Merck & Company to mass produce vaccines for USA • Research to develop antiviral drugs to treat virus • Because of the lack of immunity all the above need to be addressed post haste in the event of an intentional release • As it stands the release of smallpox would pose a potential danger