1. Reemerging of Corynebacterium Diphtheria Case Study Number Four Table #6 Emerita Arias Ofili Okolonwamu Romelene Juban

2. Patient Evaluation Patient is a 42 year old female Living in US but born in Russia Returned to Moscow for a visit on Nov. 22 Dec. 6, experienced onset of fever and sore throat Hospitalized on Dec. 7 Physical examination revealed a pharyngeal membrane Lab examination of membrane revealed gram positive rods Patient’s vaccination history is unknown

3. Pharyngeal Membrane

4. Possible Causes of Patient’s Distress that Need to be Ruled Out: Severe streptococcal sore throat Infectious mononucleosis Vincent’s angina Pharyngitis Tonsillitis Influenza

5. Lab Tests Need to Support an Accurate Diagnosis: Strept test CBC Monospot Test Throat and nares swab test Culture of pharyngeal membrane Also, the collection of patient’s data indispensable: Patient details, clinical details, contact list, and traveling history.

6. Toxigenic Corynebacterum diphtheria biotype gravis was isolated from the pharyngeal culture received on Dec. 9

7. Patient’s Antitoxin Level by Neutralization Assay Measured at >5 IU/mL Interpretation of antitoxin levels by in vitro neutralization assay Antitoxin level (IU/mlInterpretation <0.01Susceptible 0.01Lowest level of antitoxin/some protection 0.01-0.09Levels of antitoxin/some protection 0.1Protecting Level of antitoxin >1.0Level of antitoxin /long term protection

8. ELISA (EIA) Level for Specific Human Antibodies was <0.03 IU/ml Titer (enzyme immunoassay) revealed that patient had immune response showing a level of long term protection- level due to immune response Although vaccination history was unknown, neutralization assay helped determined that patient was immunize at certain point

9. Why Did Patient Contracted Disease Traveling to an endemic area Moscow has a high incidence of diphtheria Diphtheria is very contagious, transmitted by air droplets, physical contact, even by a hand shaking Patient not having current booster shot Inadequately immunized-not fully protected

10. What Accounts for C. diphtheria Capable of Producing Toxins Gram positive, fermentative, pleomorphic rod Four biotypes: var gravis, var mitis, var intermedius, and var belfanti All biotypes, except var belfanti produce lethal exotoxins. Pathogenesis based upon two determinants

11. Determinants of C. diphtheria pathogenesis Ability to colonize the nasopharyngeal cavity or the skin Ability to produce diphtheria toxins Determinants involved in colonization of host-encoded by the bacteria Toxin-encoded by corynebacteriophages

12. Corynebacteriophage (Beta phage) that carries the tox gene

13. Toxin Relative Potencies ToxinPower Ratio Cyanide1 Curare20 Alfatoxin25 Snake Venom167 Diphtheria Toxin10 8 Botulinum A Toxin3.3 x 10 8

14. Patient’s Treatment and Prognosis ¤Patient received 40,000 IU of diphtheria antitoxin ¤ Penicillin G for six days ¤ Roxithromycin, same as erythromycin in US, for several days ¤ Delay in treatment can result in death or long term disease ¤ Patient fully recovered with no complications ¤ May continue to harbor the bacteria in nose, or throat ¤ Patient’s family and contacts to be checked to prevent possible recurrences

15. Could an Epidemic of Diphtheria Occur in United States? 1990-1994 Outbreak in Russian Federation; >157,000 cases and 5,000 deaths Diphtheria can cause epidemic disease in developed countries like U.S. despite high vaccination coverage rate in children Prevalence studies in U.S. show 30% -60% adults with antitoxin levels below protection levels Last cases of diphtheria in U.S.- drug and alcohol abusers Diphtheria remains endemic in developing countries-potential source of entry into the U.S.

17. References http://www.astdhppe.org/infect/dip.html http://www.cdc.gov./ncidod/eid/vol5nos/ http://gsbs.utmb.edu/microbook/ch032.htm http://www.intmed.mcw.edu/ITC/Diphthe riaRussia.htm http://www.intmed.mcw.edu/ITC/Diphthe http://ncid.dcd.gov/travel/yb/utils/ybGet Lebofe J. Michael. “A Photographic Atlas for the 3 rd Edition Microbiology Laboratory.” Englewood, Colorado:Morton Publishing Company, Copyright 2005 Sanford, P. Jay M.D. “The Sanford Guide to Antimicrobial Therapy 2006 36 th Edition.” VA:Antimicrobial Therapy, Inc. 1969