1885. it soon replaced tracheostomy as the emergency diphtheric intubation method. in 1888, emile roux and alexandre yersin showed that a substance produced by c. diphtheriae caused symptoms of diphtheria in animals. in 1890, shibasaburō kitasato and emil von behring immunized guinea pigs with heat-treated diphtheria toxin. they also immunized goats and horses in the same way and showed that an "antitoxin" made from serum of immunized animals could cure the disease in non-immunized animals. behring used this antitoxin (now known to consist of antibodies that neutralize the toxin produced by c. diphtheriae) for human trials in 1891, but they were unsuccessful. successful treatment of human patients with horse-derived antitoxin began in 1894, after production and quantification of antitoxin had been optimized. von behring won the first nobel prize in medicine in 1901 for his work on diphtheria. in 1895, h. k. mulford company of philadelphia started production and testing of diphtheria antitoxin in the united states. park and biggs described the method for producing serum from horses for use in diphtheria treatment. in 1897, paul ehrlich developed a standardized unit of measure for diphtheria antitoxin. this was the first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines. in 1901, 10 of 11 inoculated st. louis children died from contaminated diphtheria antitoxin. the horse from which the antitoxin was derived died of tetanus. this incident, coupled with a tetanus outbreak in camden, new jersey, played an important part in initiating federal regulation of biologic products. on 7 january 1904, ruth cleveland died of diphtheria at the age of 12 years in princeton, new jersey. ruth was the eldest daughter of former president grover cleveland and the former first lady frances folsom. in 1905, franklin royer, from philadelphia's municipal hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin. in 1906, clemens pirquet and béla schick described serum sickness in children receiving large quantities of horse-derived antitoxin. between 1910 and 1911, béla schick developed the schick test to detect pre-existing immunity to diphtheria in an exposed person. only those who had not been exposed to diphtheria were vaccinated. a massive, five-year campaign was coordinated by dr. schick. as a part of the campaign, 85 million pieces of literature were distributed by the metropolitan life insurance company with an appeal to parents to "save your child from diphtheria." a vaccine was developed in the next decade, and deaths began declining significantly in 1924. a poster from the united kingdom advertising diphtheria immunization (published prior to 1962) in 1919, in dallas, texas, 10 children were killed and 60 others made seriously ill by toxic antitoxin which had passed the tests of the new york state health department. mulford company of philadelphia (manufacturers) paid damages in every case. in the 1920s, each year an estimated 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the united states. children represented a large majority of these cases and fatalities. one of the most infamous outbreaks of diphtheria occurred in 1925, in nome, alaska; the "great race of mercy" to deliver diphtheria antitoxin is now celebrated by the iditarod trail sled dog race. in 1926, alexander thomas glenny increased the effectiveness of diphtheria toxoid (a modified version of the toxin used for vaccination) by treating it with aluminum salts. vaccination with toxoid was not widely used until the early 1930s. in 1939, dr. nora wattie principal medical officer (maternity and child welfare) introduced immunisation clinics across glasgow, and promoted mother and child health education, resulting in virtual eradication of the infection in the city. widespread vaccination pushed cases in the united states down from 4.4 per 100,000 inhabitants in 1932 to 2.0 in 1937. in nazi germany, where authorities preferred treatment and isolation over vaccination (until about 1939–1941), cases rose over the same period from 6.1 to 9.6 per 100,000 inhabitants. between june 1942 and february 1943, 714 cases of diphtheria were recorded at sham shui po barracks, resulting in 112 deaths because the imperial japanese army did not release supplies of anti-diphtheria serum. in 1943, diphtheria outbreaks accompanied war and disruption in europe. the 1 million cases in europe resulted in 50,000 deaths. in kyoto during 1948, 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid. in 1974, the world health organization included dpt vaccine in their expanded programme on immunization for developing countries. in 1975, an outbreak of cutaneous diphtheria in seattle, washington, was reported. after the breakup of the former soviet union in 1991, vaccination rates in its constituent countries fell so low that an explosion of diphtheria cases occurred. in 1991, 2,000 cases of diphtheria occurred in the ussr. between 1991 and 1998 as many as 200,000 cases in the commonwealth of independent states were reported, with 5,000 deaths. in 1994, the russian federation had 39,703 diphtheria cases. 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 d'hebron university hospital in barcelona, spain. the six-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 three-year-old girl died of diphtheria in the university hospital of antwerp, belgium. in june 2016, a three-year-old, five-year-old, and seven-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. in october 2022 there was an outbreak of diphtheria at the former manston airfield, a former mod site in kent, england, which had been converted to an asylum seeker processing centre. the capacity of the processing centre was 1,000 people, though about 3,000 were living at the site with some accommodated in tents. the home office, the government department responsible for asylum seekers, refused to confirm the number of cases.