Icterohaemorrhagiae (serovar), Ictero No. 1 (reference strain), 1915 (year of valid description)
The serovar name icterohaemorrhagiae was first used by the Japanese workers Inada and Ido (1915, a and b), when they reported the isolation of the first leptospire from man in February, 1915. They called it Spirochaeta icterohaemorrhagiae (japonica). Since it was published earlier it takes priority over the name icterogenes that was used in the original publication of Uhlenhuth and Fromme (1916) in their description of the organism that they had isolated and believed to be aetiological agent of Weil's disease which they called Spirochaeta icterogenes.
A Japanese and the German isolate were later designated Ictero No. 1 and RGA, respectively Both strains could have been attached to this serovar as reference strain. Because of doubt on the authenticity of strain Ictero No. 1, strain RGA was designated many years a reference strain (TSC 1966 and 1986), notwithstanding the fact that the latter was published a year later.
Only after the recent detailed publication on the history of strain Ictero No. I (Yamamoto and Yanagawa, 1990) it was decided at the TSC meeting (Osaka 1990) to recognize the authenticity of this strain. Because Ictero No. 1 was isolated earlier than RGA the TSC agreed at the same meeting to replace RGA by Ictero No. 1 as reference strain of serovar Icterohaemorrhagiae and as neotype strain of the species L. interrogans. A historical description of both strains will now be given.
Naming:
In the original Japanese publications (Inada and Ido, 1915, a and b, and Inada et al, 1917) no mention is made of the strain name Ictero No. 1. The authors only recorded the isolation of four strains, Nishimura, Yamasaki, Matsumoto and Sakamoto, through serial guinea-pig passages. In an other publication of 1915 (in Japanese) Inado and Ido use the notation "No. 1" in combination with the Yamasaki strain. However, they do so in one table only without any further explanation in the text.
The first publication with a more explicit reference to the name Ictero No. 1 is from Kitaoka (1937), who describes the strain as "Icteroh. Nr 1" (in combination with "Menschlicher Stamm Nr 1 "). He claims this strain to be the original decent of the Yamasaki strain. Much later (1968) Babudieri and Smith made the same reference to this strain but under the name "Ictero No I". Also in correspondence between Yamamoto and Borg-Petersen, dated May 3, 1968, this strain name is mentioned. In this correspondence and in the publication of Babudieri et al. (1968) it is stated that according to Yamamoto, strain Ictero No. 1 corresponds to the original Yamasaki strain that was recorded by Inada et al. (1915, a and b, and 1917).
History:
In the original Japanese publications (see above) it is stated that the Yamasaki strain was isolated from a guinea-pig inoculated on November 23, 1914, with blood from a sick 59 years old rice-handler, who was suffering from Weil's disease and admitted to the Kyushu University Hospital in Fukuoka. The strain was maintained by many serial guinea-pig passages (Inada et al., 1917). On May 13, 1915, after 24 passages through guinea-pigs, the strain was cultured in Noguchi's medium (Inada et al., 1916).
On the further history of the strain, different papers (correspondence between BorgPetersen and Yamamoto, 1968, Babudieri et al., 1968, TSC report to ICNB, 1971, and Yamamoto et al., 1990) provide identical information, all based on the same source (Prof. Yamamoto). The papers indicate that Inada maintained the strain in the laboratory of Kyushu University until 1918. Then he moved to the Faculty of Medicine, Tokyo University, where the strain was maintained by him and by his successor Professor Sakaguchi. In 1940, Dr. Kubo, who worked in the same laboratory, sent a culture of the strain to Professor Yamamoto at the Tokyo Institute of Veterinary Pathology. He referred to it as Ictero No. I and stated that it corresponds to the strain Yamasaki, which Inada and Ido isolated from a patient of that name (Inada at al., 1917). In 1945, this culture of strain Ictero No. I was found to be contaminated by fungi. Yamamoto purified the culture by intraperitoneal inoculation of splenectomized mice and by culturing their heart blood ten minutes later. Unfortunately, the mice were not examined on a concurrent leptospiral infection before the decontamination procedure was started. Nevertheless both before and after mouse passage the strain was found to be antigenically identical with another Japanese strain of human origin, Akasawa, isolated in 1933 by Numata in Ibaraki. "It seems therefore unlikely that the purified strain was other than the original strain Ictero No. 1" (Babudieri and Smith, 1968).
After World War II, no information was obtained on the existence of strain Ictero No. 1. According to the Report (1962-1966) of the TSC, Kitaoka informed the Subcommittee that he "understood that the original strain of Inada and Ido (Strain No. 1) had been lost". The same report mentions that as a result of a following circular letter "Yamamoto claimed to have a culture of strain No. I" and subsequently he gives its history as from 1940 as mentioned above.
In the "Statements and Recommendations" of the TSC meeting - Moscow, 1966, it is reported that "Strain RGA was unanimously accepted as authentic and well documented. It was preferred to the Japanese strain because the authenticity of the strain is now doubtful". This view continued until the recent review on the strain's history by Yamamoto and Yanagawa (1990). The TSC then decided during its meeting in Osaka (1990) to recognize the authenticity of strain Ictero No. 1. As Ictero No. I is earlier isolated and published than strain RGA the TSC decided at the same meeting to replace RGA by Ictero No. 1 as reference strain of serovar icterohaemorrhagiae and as neotype strain of the species interrogans, notwithstanding its serological difference from strain RGA.
No comparative typing studies had been carried out on strains RGA and Ictero No. I until those of Babudieri and Smith (1968), which revealed serological differences. Lately this was confirmed by Yamamoto (1990). Borg-Petersen (1971) and Kmety (1972) considered these differences to be due to the presence in Ictero No. I of a thermolabile antigen, designated as Vi, which was not present in strain RGA. Kmety suggested subdividing serovar icterohaemorrhagiae into two varieties, Vi+ and Vi-, with Ictero No. 1 being the reference strain of Vi+ variety and RGA the reference strain of Vi- variety. However, over the years the stability of the Vi antigen became questionable.
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* Inada R., Ido Y. The discovery of a new kind of spirochetes as agents of Weil's disease (Jap.). Tokyo Ijishinshi no. 1908, 1915, 351-360.
* Inada R., Ido Y. The pure cultivation of Spirochaeta icterohaemorrhagiae japonica (in Japanese). Saikingaku Zasshi no. 239, Sept. 10, 1915, 621-632.
* Uhlenhuth P., Fromme W.: Zur Aethiologie der sogenannten Weilschen Krankheit. Berl. Klin. Wschr. 53, 1916, 269-273.
* Uhlenhuth P., Fromme W. Untersuchungen uber die Aethiologie, Immunitat and spezifische Behandlung der Weilschen Krankheit (Icterus infectiosus). Z. Immun. Forsch. 25, 1916, 217-483.
* Inada. Mitteilungen aus der med. Klinik der Kaiserlichen Universitat, Kyushu zu Fukuoka, Japan 1917, 1-17 and Kitasato Arch. Exp. Med. 1, 1917, 53-156.
* Kitaoka M.: Ueber die Typenfrage der Rattenstamme von Leptospira icterohaemorrhagiae in Japan. Zbl. Bakt. I. Org. 138, 1937, 163-178.
* Babudieri B., Smith D.J.W.: A serological study of the Leptospira strain Ictero No. l of Inada et al. 1916. Trop. Geogr. Med. 20, 1968, 379-384.
* Inada R., Ido Y., Hoki R., Kaneko R, Ito H.: The etiology, mode of infection, and specific therapy of Weil's disease (Spirochaetosis icterohaemorrhagiae). J. Exp. Med. 23, 1916, 377.
* TSC meeting, 1966, Moscow: Minutes. Int. J. Syst. Bacteriol. 21, 1971, 138-139.
* TSC: Report (1962-1966) to the International Committee on Nomenclature of Bacteria. Int. J. Syst. Bacteriol. 21, 1971, 140-141.
* TSC meeting, 1986, Manchester: Minutes. Int. J. Syst. Bacteriol. 37, 1987, 472-473.
* TSC meeting, 1990, Osaka: Minutes. Int. J. Syst. Bacteriol. 42, 1992, 330-334.
* Borg-Petersen Ch.: A thermo-labile Antigen in the Leptospira strain Ictero No. l. Trop. Geogr. Med. 23, 1971, 282-285.
* Kmety E.: Uber ein Vi-Antigen bei Leptospiren. Zbl. Bakt. Hyg. I. Abt. Orig. A., 221, 1972, 343-351.
* Yamamoto S., Yanagawa R. On strain Ictero No. 1, which was the First Causal Agent of Weil's Disease isolated by Inada and Ido. Proc. Japan Acad. 66 (B), 6, 1990, 1116-11120.
Icterohaemorrhagiae (serovar), RGA (reference strain), 1916 (year of valid description)
The designation RGA is an abbreviation of the Reichsgesundheitsamt in Berlin, where the strain was first cultured in vitro.
During World War I, in November 1915, strain RGA was isolated by Uhlenhuth and Fromme through guinea-pig inoculation-with blood from a soldier in Belgium. They considered it to be the aethiological agent of Weil's disease. In the original publication (Uhlenhuth and Fromme, 1916) the organism is described as Spirochaeta icterogenes. According to a letter of Borg-Petersen to the secretary of the TSC, dated January 1969, the infected guinea-pigs were sent to the Robert Koch Institute (Prof. Otto) and thence to the laboratory of the Reichsgesundheitsamt. There the strain was cultured in vivo in February 1916. The strain originally named "Berlin" and "original strain from Uhlenhuth and Fromme" was successfully maintained and in 1924 a subculture was sent by Manteufel from the Reichsgesundheitsamt to Schüffner in Amsterdam (Institute of Tropical Hygiene) under the designation RGA (Gispen and Schüffner, 1939).
Strain RGA appeared already on the list of Wolff and Broom (1954) as the reference strain of serovar icterohaemorrhagiae and still did when the last WHO list was published in 1967 (WHO, Tech. Rep. No. 380, 1967). This was in accordance with the recommendations of the TSC at the meeting in Moscow in 1966, reading that, "the oldest surviving authentic strain, RGA should be accepted as the neotype strain of the species interrogans". This was approved again at the Manchester meeting of the TSC in 1986.
However after recognizing by the TSC (Osaka, 1990), the authenticity of the strain Ictero No. I, they consequently decided to replace RGA by Ictero No. 1 as reference strain of the serovar and as a neotype strain of the species interrogans in spite of the serological difference between the two strains (for details see Ictero No. 1).
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* Uhlenhuth P., Fromme W. Zur Aethiologie der sogenannten Weilschen Krankheit. Berl. Klin. Wschr. 53, 1916, 269-273.
* Wolff J.W., Broom J.C. The Genus Leptospira Noguchi 1917, Problems of Classification and Suggested System Based on Antigenic Analysis. Doc. Med. Geogr. Trop. 6, 1954, 78-95.
* Gispen R., Schuffner W. Die Spaltung der klassischen L. icterohaemorrhagiae in zwei Biotypen. Zbl. Bakt. I. Abt. Orig. 144, 1939, 427-434.
* WHO: Current Problems in Leptospirosis Research. Wld. Hlth. Org. Tech. Rep. Ser. No. 380, Geneva 1967, p.32.
* TSC meeting, 1986, Manchester: Minutes. Int. J. Syst. Bacteriol. 37, 1987, 472-473.
* TSC meeting, 1990, Osaka: Minutes. Int. J. Syst. Bacteriol. 42, 1992, 330-334.