Tick paralysis by Ixodes holocyclus in a Japanese traveler returning from Australia

Tick Paralysis by Ixodes holocyclus in a Japanese Traveler Returning from Australia Associated with Rickettsia helvetica Infection Hisashi Inokuma, Hiroaki Takahata, Pierre-Edouard Fournier, Philippe Brouqui, Didier Raoult, Masaru Okuda,Takafumi Onishi, Kazue Nishioka, and Masato Tsukahara Ixodes holocyclus is a tick species that is widely distributed in the east coast from Queensland to Victoria, in Australia. The tick produces neurotoxin that causes paralysis to host animals.1 In Australia, there have been sporadic human cases of Ix. holocyclus paralysis.2 Ix. holocyclus is also known as a vector of the Queensland tick typhus pathogen, Rickettsia australis and also a suspected vector of Lyme borreliosis.3,4 Although several tick paralysis cases by Ix. holocyclus have been reported, little is known about the infection with tickborne pathogens in such cases. In the present report, we describe a traveler returning from Australia who developed a tick paralysis by Ix. holocyclus. Tickborne pathogens were investigated, because the patient also had fever, erythema, and enlargement of mandibular lymph nodes. A 59-year-old man who lives in Yamaguchi Prefecture, Japan, with a previous history of emphysema, traveled to the Gold Coast area in Australia from December 1 through 14, 2000, and stayed at a farm to experience some farm activities. On the December 4, he felt something tight on his scalp, then sore throat and nasal discharge were started from December 6. He noticed a reddish skin region around the small mass on his scalp on December 7. He developed a fever on December 9 that was soon alleviated. After returning home to Japan,

he had a fever of more than 39.0°C on the night of December 15, and he removed a semi-engorged female tick (7.8
4.5 mm) by himself on December 17. The tick was identified as a semi-engorged female of Ix. holocyclus by morphologic features, of the palp, hypostome, scutum, and coxal (Fig. 1).5 On the following day, he went to a hospital with complaints of erythema, paralysis, and tick infestation on his scalp, lethargy, and a fever. On examination, erythema and sensory loss around a small eschar on the scalp and enlargement of mandibular lymph nodes were observed. Two days of administration of minocycline was not effective for the symptoms. Fever had continued; edema and sensory loss around the eschar on his scalp had become worse; lymph nodes had

Hisashi Inokuma, DVM, PhD: Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan; Hiroaki Takahata, MD: Department of Dermatology, Yamaguchi Red Cross Hospital, Yamaguchi, Japan; Pierre-Edouard Fournier, MD, PhD, Didier Raoult, MD, PhD, Masaru Okuda, DVM, PhD: Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan; Takafumi Onishi, DVM, PhD: Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan; Kazue Nishioka, MD, PhD: Department of Dermatology, Yamaguchi Red Cross Hospital, Yamaguchi, Japan; Masato Tsukahara, MD, PhD: Faculty of Medicine, Yamaguchi University, Yamaguchi, Japan.

A

B

The authors had no financial or other conflicts of interest to disclose.

C

Figure 1 Ixodes holocyclus, which was taken from the patient. A, A dorsal view of nearly fully engorged female of I. holocyclus. Length
wide = 7.8
4.5 mm. B, A ventral view of hypostome that has dentition 3/3. C, The coxa I has a huge external spur.

Correspondence: Hisashi Inokuma, DVM, PhD, Faculty of Agriculture, Yamaguchi University, 753-8515 Yamaguchi, Japan. J Travel Med 2003 ; 10:61–63.

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J o u r n a l o f Tr a v e l M e d i c i n e , Vo l u m e 10 , N u m b e r 1

A

B

Figure 2 On December 20, 2000, A, the patient still showed erythema around a small eschar on the scalp and B, enlargement of mandibular lymphnodes were also observed.

been enlarged and headache had begun (Fig. 2). He was hospitalized on December 20. On admission, the body temperature was 38.6°C, and narrowing of the visual field of the right eye caused by paralysis of the ocular muscles and weakness of oscillating sense in the right leg were observed. Routine laboratory studies, including hematology, biochemical blood examination, and spinal fluid analysis, showed no abnormalities. Bacterial culture from the eschar region was negative. Neutrophils and eosinophils infiltration and edema were observed as pathologic findings of the eschar region. After hospitalization, a combination of minocycline, ciprofloxacin, amoxicillin, and d-chlorpheniramine maleate was started. Fever was alleviated from December 21, and the signs of paralysis disappeared gradually. Although a slight sensory loss around the eschar remained, he left the hospital on December 29. In addition to the symptoms of typical tick paralysis, he also had uncommon findings, including a fever, erythema around an eschar on the scalp, and enlargement of mandibular lymph nodes,2,6 suggesting possible concomitant infection with tickborne pathogens. The

presence of antibodies to Rickettsia, Orientia, Bartonella, and Borrelia was assessed in both acute phase (December 18) and convalescent sera (January 10, 2001). The indirect immunofluorescence assay (IFA) revealed that the patient’s acute serum had low antibody titers to Rickettsia helvetica (1:32 for immunoglobulin G and 1:16 for immunoglobulin M), Rickettsia conorii (1:32 and 1:8), Rickettsia slovaca (1:32 and < 1:4), and Rickettsia australis, Rickettsia honei and Rickettsia japonica (1:16 and < 1:4). The convalescent serum also showed low antibody titers to R. helvetica (1:32 and 1:16), R. conorii, and R. slovaca (1:32 and < 1:4), and R. australis, R. honei, and R. japonica (1:16 and < 1:4). Additional western blot analysis showed reactivity of the serum against the high molecular weight outer membrane proteins that are species-specific for R. helvetica.7 The IFA titer of R. helvetica was too low to allow cross-adsorption test for the patient serum. The Weil-Felix reaction, the antibodies against Orientia tsutsugamushi (Gilliam, Karp and Kato8), Bartonella henselae, and Borrelia garini were all negative. Additionally, the Ix. holocyclus tick removed from the patient was examined for Rickettsia by polymerase chain

I n o k u m a e t a l . , T i ck Pa r a l y s i s b y I x o d e s h o l o c y c l u s

reaction with 2 genus specific primer sets, CS877/ CS1273R9 and Rr190.70p/190–701,10 but yielded negative results. In general, children aged 1 to 5 years are the most commonly affected with the tick paralysis by I. holocyclus, and lethargy, loss of appetite, unsteadiness in walking, ataxia, voice change, weakness of bulbar, facial, and ocular muscles, and occasional death from respiratory failure are the symptoms,2 although it is many years since the last fatal case. In older children and adults, the clinical signs found in patients with tick paralysis by Ix. holocyclus include diplopia, photophobia, dilation of the pupils, transient squinting, darting movements of the eyes, or a sluggish reaction to light. Adults usually suffer from dizziness, headache, and a general weakness and lethargy.2 The present patient was a rare adult case of tick paralysis caused by Ix. holocyclus in a Japanese traveler returning from Australia, and typical symptoms of the tick paralysis were observed. View constriction of the right eye caused by paralysis of ocular muscles, headache, general weakness, and lethargy were recorded as typical signs of the tick paralysis. Unsteadiness in walking, sensory loss around the eschar on his scalp, and weakness of oscillating sense in the right leg were also observed in the patient. All these signs can be explained by the neurotoxin produced by Ix. holocyclus. Rarer complications of tick paralysis, such as myocarditis or myositis, were not found in this patient. Worsening of paralysis after tick removal was also recorded. Deterioration despite removal of the tick and slow recovery are important features differentiating paralysis by Ix. holocyclus from that of other tick paralysis.2 Since the treatment for the tick paralysis is limited, removal of the tick is the most recommended treatment method.2 A broad spectrum antiserum is now available, which reduces the risk of serum sickness; however, tick paralysis has been improved in the patient, without any special therapy after tick removal. Results of the IFA and the western blot analysis for Rickettsia revealed the existence of weak but specific antibodies against R. helvetica in the patient suggesting that this patient had been in contact with R. helvetica in the past. R. helvetica is widely distributed in Europe,7,11 and this is the first detection of antibodies against R. helvetica outside Europe. As the patient had traveled to Europe, including the United Kingdom and France where the vector tick Ixodes ricinus exists, the origin of the infection is unknown. With the fact that the patient often enjoys hunting and had been bitten by ticks in Japan, the present result also suggests the possibility of the existence of the agent in Japan or Australia. More epidemiologic

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studies are required to investigate the distribution of R. helvetica in both countries. Acknowledgment The authors would like to acknowledge the technical expertise of Dr. T. Masuzawa, University of Shizuoka, Japan, for the examination of Borrelia antibodies of the patient. We also thank Dr. D. H. Kemp, CSIRO, Australia, for helping with the tick identification and English correction. This work was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science. References 1. Stone BF. Tick paralysis, particularly involving Ixodes holocyclus and other Ixodes species. In: Harris KF, ed. Advances in disease vector research. Vol. 5. New York: Springer-Verlag, 1988:61–85. 2. Grattan-Smith PJ, Morris JG, Johnston HM, et al. Clinical and neurophysiological features of tick paralysis. Brain 1997; 120:1975–1987. 3. Baird RW, Stenos J, Stewart R, et al. Genetic variation in Australian spotted fever group rickettsiae. J Clin Microbiol 1996; 34:1526–1530. 4. Piesman J, Stone BF. Vector competence of the Australian paralysis tick, Ixodes holocyclus, for the Lyme disease spirochete Borrelia burgdorferi. Int J Parasitol 1991; 121:109–111. 5. Roberts FHS. A systematic study of the Australian species of the genus Ixodes (Acarina: Ixodidae). Aust J Zool 1960; 8: 392–485. 6. Felz MW, Smith CD, Swift TR. A six-year-old girl with tick paralysis. N Engl J Med 2000; 342:90–94. 7. Fournier P-E, Grunnenberger F, Jaulhac B, et al. Evidence of Rickettsia helvetica infection in humans, Eastern France. Emerg Infect Dis 2000; 6:389–392. 8. Shishido A, Kono S, Hikita M, et al. Complement fixation and direct immunofluorescence for typing of tsutsugamushi disease rickettsia. Acta Med Biol (N gata); 1967; 15:87–95. 9. Roux V, Rudkina E, Eremeeva M, Raoult D. Citrate synthase gene comparison, a new tool for phylogenetic analysis, and its application for the rickettsiae. Int J Syst Bact 1997; 47: 252–261. 10. Roux V, Fournier P-E, Raoult D. Differentiation of spotted fever group rickettsiae by sequencing and analysis of restriction fragment length polymorphism of PCR amplified DNA of the gene encoding the protein rOmpA. J Clin Microbiol 1996; 34:2058–65. 10. Raoult D, Olson JG. Emerging rickettsioses. In: Scheld WM, Craig WA, Hughes JM, eds. Emerging infection. Washington, DC: ASM Press, 1999:17–35.