This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis.ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B3), since this is one of the reactions end products, and high amounts drive the reaction in the opposite direction. Diagnosis
The current clinical case definition of diphtheria used by the United States Centers for Disease Control and Prevention  is based on both laboratory and clinical criteria. Laboratory criteria
Isolation of C. diphtheriae from a Gram stain or throat culture from a clinical specimen,
Histopathologic diagnosis of diphtheria by Alberts stain

Toxin demonstration
In vivo tests (guinea pig inoculation): Subcutaneous and intracutaneous tests
In vitro test: Eleks gel precipitation test, detection of tox gene by PCR, ELISA, ICA

Clinical criteria
Upper respiratory tract illness with sore throat
Low-grade fever (above 39 °C (102 °F) is rare)
An adherent, dense, grey pseudomembrane covering the posterior aspect of the pharynx: in severe cases, it can extend to cover the entire tracheobronchial tree. Case classification
Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a laboratory-confirmed case
Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a laboratory-confirmed caseEmpirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
By contrast, in 1990, only 1,211 cases were reported.In early May 2010, a case of diphtheria was diagnosed in Port-au-Prince, Haiti, after the devastating 2010 Haiti earthquake. The 15-year-old male patient died while workers searched for antitoxin.In 2013, three children died of diphtheria in Hyderabad, India.In early June 2015, a case of diphtheria was diagnosed at Vall dHebron University Hospital in Barcelona, Spain. The 6-year-old child who died of the illness had not been previously vaccinated due to parental opposition to vaccination. It was the first case of diphtheria in the country since 1986 as reported by "El Mundo" or from 1998, as reported by WHO.In March 2016, a 3-year-old girl died of diphtheria in the University Hospital of Antwerp, Belgium.In June 2016, a 3-year-old, 5-year-old, and 7-year-old girl died of diphtheria in Kedah, Malacca, and Sabah, Malaysia.In January 2017, more than 300 cases were recorded in Venezuela.In 2017, outbreaks occurred in a Rohingya refugee camp in Bangladesh, and in children unvaccinated due to the Yemeni Civil War.In November and December 2017, an outbreak of diphtheria occurred in Indonesia with more than 600 cases found and 38 fatalities.In November 2019, two cases of diphtheria occurred in the Lothian area of Scotland. Additionally, in November 2019 an unvaccinated 8-year-old boy died of diphtheria in Athens, Greece.In July 2022, two cases of diphtheria occurred in northern New South Wales, Australia. References
Further reading
Holmes, R .K. (2005). "Diphtheria and other corynebacterial infections". In Kasper;  et al. (eds.). Harrisons Principles of Internal Medicine (16th ed.). New York: McGraw-Hill. ISBN 978-0-07-139140-5.