Reemerging of Corynebacterium DiphtheriaCase Study Number FourTable #6Emerita AriasOfili OkolonwamuRomelene Juban

Patient Evaluation

Patient is a 42 year old femaleLiving in US but born in RussiaReturned to Moscow for a visit on Nov. 22Dec. 6, experienced onset of fever and sore throatHospitalized on Dec. 7Physical examination revealed a pharyngeal

membraneLab examination of membrane revealed gram

positive rodsPatient’s vaccination history is unknown

Pharyngeal Membrane

Possible Causes of Patient’s Distress

that Need to be Ruled Out: Severe streptococcal sore throatInfectious mononucleosisVincent’s anginaPharyngitisTonsillitisInfluenza

Lab Tests Need to Support an Accurate Diagnosis:Strept testCBCMonospot TestThroat and nares swab testCulture of pharyngeal membraneAlso, the collection of patient’s data

indispensable:Patient details, clinical details, contact list, and

traveling history.

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

Patient’s Antitoxin Level by Neutralization Assay Measured at >5 IU/mLInterpretation of antitoxin levels by in vitro neutralization

assay

 

Antitoxin level (IU/ml Interpretation

<0.01 Susceptible

0.01 Lowest level of antitoxin/some protection

0.01-0.09 Levels of antitoxin/some protection

0.1 Protecting Level of antitoxin

>1.0 Level of antitoxin /long term protection

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

Why Did Patient Contracted Disease

Traveling to an endemic areaMoscow has a high incidence of diphtheriaDiphtheria is very contagious, transmitted by

air droplets, physical contact, even by a hand shaking

Patient not having current booster shotInadequately immunized-not fully protected

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

Determinants of C. diphtheria pathogenesis

Ability to colonize the nasopharyngeal cavity or the skin

Ability to produce diphtheria toxinsDeterminants involved in colonization of

host-encoded by the bacteriaToxin-encoded by corynebacteriophages

Corynebacteriophage (Beta phage) that carries the tox gene

Toxin Relative Potencies

Toxin Power RatioCyanide 1

Curare 20

Alfatoxin 25

Snake Venom 167

Diphtheria Toxin 108

Botulinum A Toxin 3.3 x 108

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

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.

Referenceshttp://www.astdhppe.org/infect/dip.htmlhttp://www.cdc.gov./ncidod/eid/vol5nos/http://gsbs.utmb.edu/microbook/ch032.htmhttp://www.intmed.mcw.edu/ITC/Diphthe

riaRussia.htmhttp://ncid.dcd.gov/travel/yb/utils/ybGetLebofe J. Michael. “A Photographic Atlas for

the 3rd Edition Microbiology Laboratory.” Englewood, Colorado:Morton Publishing Company, Copyright 2005

Sanford, P. Jay M.D. “The Sanford Guide to Antimicrobial Therapy 2006 36th Edition.” VA:Antimicrobial Therapy, Inc. 1969