![](https://webarchive.library.unt.edu/web/20090117142703im_/http://www.cdc.gov/ncidod/eid/images/spacer.gif)
|
![](https://webarchive.library.unt.edu/web/20090117142703im_/http://www.cdc.gov/ncidod/eid/images/spacer.gif) |
Letter
Reemerging Murine Typhus,
Japan
Satoshi Sakaguchi,* Ichiki Sato,† Hiroaki Muguruma,* Hiroaki Kawano,*
Yoshito Kusuhara,* Seiji Yano,* Saburo Sone,* and Tsuneo Uchiyama*![Comments](https://webarchive.library.unt.edu/web/20090117142703im_/http://www.cdc.gov/ncidod/eid/images/email.gif)
*The University of Tokushima Graduate School of Medicine, Tokushima, Japan;
and †Sato Clinic, Tokushima, Japan
Suggested citation
for this article:
Sakaguchi S, Sato I, Muguruma H, Kawano H, Kusuhara Y, Yano S, et al.
Murine typhus, Japan. Emerg Infect Dis [serial on the Internet] 2004
May [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no5/03-0697.htm
To the Editor: Murine typhus is an arthropod-borne infectious
disease caused by Rickettsia typhi, which is distributed widely
around the world (1–4). In Japan, tsutsugamushi disease
occurs most frequently in persons infected with rickettsioses (5).
Spotted fever caused by R. japonica also occurs in the southwestern
part of Japan (6,7). In the 1940s and 1950s, many murine
typhus cases were reported in Japan. These diagnoses were made according
to the clinical features of the illness and the reactivity of the serum
samples to OX19 in Weil-Felix tests. A few cases were diagnosed on the
basis of symptoms exhibited by animals infected with isolated rickettsiae
and complement fixation tests, in addition to results of the Weil-Felix
tests. The Weil-Felix test is useful for preliminary screening of rickettsiosis;
however, the reaction could indicate epidemic typhus or spotted fever
in some cases. Since 1958, only three murine typhus cases have been reported
in Japan (8). In these cases, no serologic tests for
epidemic typhus were conducted. Serum sample from patients with epidemic
typhus and murine typhus frequently possess serologic cross-reactivity
to R. typhi and R. prowazekii, respectively (9).
Thus, the possibility of epidemic typhus could not be excluded definitively
in these cases.
On May 4, 2003, a 56-year-old man living in Tokushima, Japan, sought
medical care; he had a temperature of 39.1°C and exanthema on the
trunk and the upper limbs. No surface lymph nodes were palpable. He was
treated with lincomycin and cefditoren pivoxil with no improvement. On
day 3, the patient informed caregivers that he had been in a bamboo grove
on days 1 and 11 before the onset of symptoms. C-reactive protein of the
serum sample collected on day 3 was positive (= 7.6 mg/dL). From this
finding, spotted fever was suspected; the disease is endemic in Tokushima.
On day 4, the exanthema had spread systemically, and treatment with minocycline
was started, which led to a gradual decrease in fever and rashes. The
patient was admitted to the Tokushima University Hospital on day 6 of
the illness for diagnosis and further treatment.
Serum samples were collected from the patient on days 5, 6, 9, 20, and
34. Indirect immunoperoxidase tests on the serum samples for tsutsugamushi
disease, spotted fever, murine typhus, and Q fever on day 5 of the illness
were negative for immunoglobulin (Ig) G and IgM antibodies (<1:40).
Weil-Felix tests on the serum samples on days 5 and 9 of the illness were
negative for OX2, OX19, and OXK. Indirect immunofluorescence of the serum
samples on days 6, 9, 20, and 34 of the illness was conducted by using
strains 18 and Wilmington of R. typhi, and the strain Breinl of
R. prowazekii as typhus group rickettsiae; and the strain YH of
R. japonica, the strain Malish 7 of R. conorii, and the
strain Tick of R. montanensis as the spotted fever group rickettsiae.
All serum samples tested for the rickettsiae showed an IgM titer of 1:20.
On the other hand, the IgM titers of these serum samples, to the Orientia
tsutsugamushi were <1:20. For the IgG antibodies of these serum,
spotted fever group rickettsiae were negative (<1:20). However, the
typhus group rickettsiae were positive for IgG antibodies. Among the typhus
group rickettsiae, strain 18 of R. typhi had the highest elevated
titers. The titers to the sera on days 6, 9, 20, and 34 of illness were
1:80, 1:160, 1:160, and 1:80, respectively. Another strain of R. typhi,
the strain Wilmington, had lower titers of 1:40, 1:80, 1:80, and 1:40,
on days 6, 9, 20, and 34 of the illness, respectively. This could have
occurred because strain 18 may be a closer antigenic relation of the causative
agent than is the strain Wilmington. R. prowazekii demonstrated
the lowest IgG titers among typhus group rickettsiae for these serum samples,
<1:20, 1:20, 1:40, and 1:20, on days 6, 9, 20, and 34 of the illness,
respectively. These results suggested that the disease was murine typhus.
To demonstrate more detailed antigenic reactivity, Western immunoblotting
of rickettsiae was conducted by using a serum specimen from day 20. All
of the rickettsiae were reactive to the serum to various extents. The
serum reacted to the ladder-like lipopolysaccharide of R. typhi
and R. prowazekii; the antigenicity of rickettsial lipopolysaccharide
is group-specific. As expected from the immunofluorescence data, no reaction
was demonstrated to the lipopolysaccharide of spotted fever group rickettsiae,
R. japonica and R. montanensis, although trace cross-reactivity,
mainly to rOmpB, was shown. Thus, typhus group rickettsiosis was suspected
for this case on the basis of these data. Compared to the trace reaction
of spotted fever group rickettsiae to rOmpB, a stronger, but still weak,
reaction was detected to the heat-labile state of rOmpB of R. prowazekii,
and an extremely strong reaction was demonstrated to the heat-labile and
heat-stable states of rOmpB of R. typhi. These results strongly
suggested that the disease was murine typhus.
To confirm this diagnosis, we conducted absorption tests as described
previously (10). The patient serum collected on day 20
showed complete absorption by the homologous antigen, the purified R.
typhi strain 18, demonstrating no reaction to R. typhi or to
R. prowazekii by immunofluorescence. However, the serum showed
incomplete absorption by the heterologous antigen, the purified R.
prowazekii, demonstrating no reactivity to R. prowazekii but
some reactivity to R. typhi. These tests confirmed the diagnosis
of murine typhus.
Murine typhus has never been reported in Japan after the 1950s, except
for the three suspected cases and this case. Although other undiagnosed
cases may have occurred, they appear to be few; many febrile cases of
exanthema have been examined for various rickettsioses, especially after
spotted fever was diagnosed in Japan in 1984. Murine typhus may have reemerged
because of the recent increase of black rats, Rattus rattus, in
Japan. This patient mentioned that he had captured a rat and disposed
of the carcass about a week before the onset of symptoms. Infection could
have resulted at that time from contamination with feces of infected fleas
such as the oriental rat flea, Xenopsylla cheopis. Historical review
indicates that this is the first complete serologic diagnosis of a murine
typhus case in Japan.
Acknowledgment
We thank Akio Adachi
for his valuable suggestions.
References
- Parola P, Vogelaers D, Roure C, Janbon, Raoult D.
Murine
typhus in travelers returning from Indonesia. Emerg Infect Dis 1998;4:677–80.
- Azad AF, Beard CB. Rickettsial
pathogens and their arthropod vectors. Emerg Infect Dis 1998;4:179–86.
- Walker DH. Advances in understanding of typhus group rickettsial infections.
In: Kazar J, Toman R, editors. Rickettsiae and rickettsial diseases.
Bratislava, Slovak Republic: VEDA Press; 1996. p.16–25.
- Azad AF, Radulovic S, Higgins JA, Noden BH, Troyer MJ. Flea-borne
rickettsioses: some ecological considerations. Emerg Infect Dis
1997;3:319–28.
- Kawamura A Jr, Nogami S. Seasonal prevalence of the disease in Japan.
In: Kawamura A Jr, Tanaka H, Tamura A, editors. Tsutsugamushi disease.
Tokyo, Japan: University of Tokyo Press; 1995. p.10–20.
- Mahara F, Koga K, Sawada T, Taniguchi F, Shigemi T, Suto Y, et al.
The
first report of rickettsial infections of spotted fever group in Japan;
three clinical cases. Kansenshogaku Zasshi 1985;59:1165–72. [in
Japanese]
- Uchida T, Uchiyama T, Kumano K, Walker DH. Rickettsia
japonica sp. nov., the etiological agent of spotted fever group
rickettsiosis in Japan. Int J Syst Bacteriol 1992;42:303–5.
- Takagi K, Iwasaki H, Kishi S, Nakamura T, Takada N, Ueda T. Murine
typhus infected in Oku-etsu area, Fukui Prefecture. Kansenshogaku
Zasshi 2001;75:341–4. [in Japanese]
- La Scola B, Raoult D. Laboratory
diagnosis of rickettsioses: current approaches to diagnosis of old and
new rickettsial diseases. J Clin Microbiol 1997;35:2715–27.
- La Scola B, Rydkina L, Ndihokubwayo JB, Vene S, Raoult D. Serological
differentiation of murine typhus and epidemic typhus using cross-adsorption
and Western blotting. Clin Diagn Lab Immunol 2000;7:612–6.
|