Biochemistry
The overall reaction is

4 Fe2+ – cytochrome c + 4 H+ + O2 → 4 Fe3+ – cytochrome c + 2 H2O                ΔfGo = - 218 kJ/molTwo electrons are passed from two cytochrome cs, through the CuA and cytochrome a sites to the cytochrome a3–CuB binuclear center, reducing the metals to the Fe2+ form and Cu+. The hydroxide ligand is protonated and lost as water, creating a void between the metals that is filled by O2. The oxygen is rapidly reduced, with two electrons coming from the Fe2+-cytochrome a3, which is converted to the ferryl oxo form (Fe4+=O). The oxygen atom close to CuB picks up one electron from Cu+, and a second electron and a proton from the hydroxyl of Tyr(244), which becomes a tyrosyl radical. The second oxygen is converted to a hydroxide ion by picking up two electrons and a proton. A third electron from another cytochrome c is passed through the first two electron carriers to the cytochrome a3–CuB binuclear center, and this electron and two protons convert the tyrosyl radical back to Tyr, and the hydroxide bound to CuB2+ to a water molecule.
Similar outbreaks were reported in Singapore (more than 2,600 cases as of April 20, 2008), Vietnam (2,300 cases, 11 deaths), Mongolia (1,600 cases), and Brunei (1053 cases from June–August 2008)
In 2009 17 children died in an outbreak during March and April 2009 in Chinas eastern Shandong Province, and 18 children died in the neighboring Henan Province. Out of 115,000 reported cases in China from January to April, 773 were severe and 50 were fatal. In 2010 in China, an outbreak occurred in southern Chinas Guangxi Autonomous Region as well as Guangdong, Henan, Hebei and Shandong provinces. Until March, 70,756 children were infected and 40 died from the disease. By June, the peak season for the disease, 537 had died. The World Health Organization reporting between January to October 2011 (1,340,259) states the number of cases in China had dropped by approx 300,000 from 2010 (1,654,866) cases, with new cases peaking in June. There were 437 deaths, down from 2010 (537 deaths). In December 2011, the California Department of Public Health identified a strong form of the virus, coxsackievirus A6 (CVA6), where nail loss in children is common. In 2012 in Alabama, United States there was an outbreak of an unusual type of the disease. It occurred in a season when it is not usually seen and affected teenagers and older adults. There were some hospitalizations due to the disease but no reported deaths.