The First Imported Case of Rabies Into Japan in 36 Years: A Forgotten Life‐Threatening Disease

Shungo Yamamoto MD, Chihiro Iwasaki MD, Hiroshi Oono MD, Kiyoshi Ninomiya MD, FJSIM, Tadashi Matsumura MD, FCCP
DOI: http://dx.doi.org/10.1111/j.1708-8305.2008.00241.x 372-374 First published online: 1 September 2008

Abstract

A domestic case of rabies has not been reported in Japan since 1957. The last case of rabies reported in Japan was an imported case from Nepal in 1970. We recently experienced a new case imported from the Philippines, the first case in Japan in 36 years. Although Japanese people are about to forget the dangers of rabies, this case should serve as a warning to those Japanese who are planning a trip abroad.

Case report

A 69‐year‐old Japanese man with a history of diabetes mellitus was admitted to Rakuwakai Otowa Hospital on November 13, 2006, because of fever and hallucinations. He traveled regularly between Japan and the Philippines, several times a year, to see his family in the Philippines. He spent 2 weeks in the Philippines for about 10 weeks, and again about 4 weeks, prior to admission. Seven days before the admission, he developed fever, cough, a runny nose, and numbness in his left hand. Cough medicine, prescribed by a local hospital, did not improve his condition. Three days before admission, the patient began to experience difficulty swallowing water. One day before admission, he visited the emergency department of our hospital because of continuous fever. He received intravenous fluids for dehydration and was sent home. He returned on the following day, visually hallucinating insects and was admitted to our hospital. On the day of admission, he presented various phobias. He was unable to wash his hands after using the bathroom as he was terrified of the water. He was also extremely uncomfortable when the air conditioning blew on him, or even when someone walked by him.

On physical examination, the patient seemed alert and oriented to time, place, and person, but appeared somewhat confused. His temperature was 38°C, heart rate 135 beats per minute, blood pressure 205/118 mm Hg, and respiratory rate 30 breaths per minute. He was sweating profusely. He had slight redness over the pharynx and dry mouth. No bite marks were found. The remainder of the examination was normal.

Laboratory studies revealed the following: white blood cell count, 15,100/μL; hemoglobin level, 19.1 g/dL; hematocrit, 52.1%; platelet count, 16.9 × 104/μL; aspartate aminotransferase level, 48 U/L; alanine aminotransferase level, 28 U/L; creatine phosphokinase level, 2,032 U/L; urea nitrogen level, 35.7 mg/dL; creatinine level, 1.3 mg/dL; sodium level, 150 mEq/L; potassium level, 3.7 mEq/L; and blood glucose level, 286 mg/dL. These findings were consistent with severe dehydration.

Given the symptoms consisting with hydrophobia and aerophobia, we initially suspected rabies. However, as the patient denied having any contact with animals in the Philippines, we had to discard the possibility. We considered alcohol withdrawal syndrome instead, given the typical symptoms that included fever, sweating, tachycardia, tremors, hallucinations like seeing insects, and his history of alcohol intake. The patient received fluid replacement and benzodiazepine, which improved his symptoms slightly. However, around midnight on the day of admission, his condition deteriorated suddenly. He became excitable, he started to pull down the bars of his bed, and spit at the nurses. Following a convulsion, he suffered cardiopulmonary arrest. Immediate resuscitation recovered a pulse, and he was intubated and sent to the intensive care unit for additional care.

The following day, we contacted his family who confirmed that the patient had actually been bitten by a dog on his left hand 10 weeks earlier while in Isabela, Philippines, and that he had not received any pre‐ or postexposure prophylaxis against rabies. Although his family noticed the dog bite and advised him to see a doctor, the patient did not care because the wound was shallow and the dog was a family dog, not a wild one. The dog that bit him died of unknown cause after that. Then, we strongly reconsidered the diagnosis of rabies. To prevent secondary infection, the patient was isolated and we started a contact precaution. The National Institute of Infectious Diseases, Japan, was asked to conduct tests using saliva, blood, urine, and biopsy specimens of the skin of the nuchal region. The polymerase chain reaction for saliva samples detected a viral gene similar to the Philippine strain of rabies (Figure 1), and the immunostaining of the neural tissue at the nuchal hair roots was also positive for the rabies virus antigens, resulting in a definitive diagnosis of rabies. Despite the use of various anticonvulsants including phenytoin, phenobarbital, midazolam, and thiamylal, the patient’s status epilepticus was difficult to control. Rhabdomyolysis developed, and he died from multiple organ failure on the fifth hospital day.

Figure 1

Polymerase chain reaction findings.

The autopsy revealed mild inflammatory infiltrates around vessels in the brain stem and cytoplasmic inclusions consistent with Negri bodies in the cerebral cortex. Intracytoplasmic rabies virus antigens were detected on immunohistochemical staining in neurons from multiple areas of the central nervous system, in cranial nerves, and in peripheral nerves. The virus antigens were identified in nerve plexuses of salivary glands but not in either acini or ducts.

Discussion

No domestic case of rabies has been reported in Japan since 1957, and there was only one imported case from Nepal reported in 1970. 1 This extremely low incidence is due to the vaccination of dogs and quarantine of animals under the “Rabies Prevention Law” enacted in 1950. Because no case of rabies has been reported for a long time in Japan, Japanese people are about to forget the dangers of rabies. The vaccination rate for domestic dogs has been decreasing. In addition, the concept of travel medicine is not so widely accepted in Japan. It had been considered unavoidable among experts that a case would enter Japan in face of the recent increase in people and animals traveling internationally. 2 In these circumstances, it could be considered surprising that there has been no case of rabies for 36 years. One week following our report, there was another case of rabies diagnosed in a Japanese person, returning from the Philippines. 3 It suggests the possibility that more cases of rabies might have occurred in Japan in the past but simply have been overlooked.

Antemortem diagnosis of rabies remains difficult. Even in developed countries, there are reports of cases in which rabies was transmitted via transplanted organs or corneal transplants from donors who experienced animal bites. 4,5 In our case, because the patient himself denied having any contact with an animal when abroad, it was difficult to diagnose rabies at first. Even though he seemed alert, his mental status must have been already altered enough to give erroneous information. History of exposure is often not obtainable from the patient, and one should not eliminate rabies in the differential diagnosis in such patient. It is crucially important to contact the family or relatives, or even a third party, to confirm the patient’s history of animal contact.

Although most patients present with furious rabies, with the symptoms of hydrophobia or aerophobia, up to one third of patients may present symptoms of the paralytic type, which lacks such characteristic symptoms. The latter type is extremely difficult to diagnose clinically and may be confused with Guillain–Barre syndrome. 6 To avoid missing the diagnosis, it is essential to consider rabies in the differential diagnosis for any encephalitic patient presenting with a history of travel to a rabies‐endemic country.

A report from the United States in 2004 of an unvaccinated teenager, who survived rabies by combination therapy with ketamine, midazolam, ribavirin, and amantadine, evoked quite a sensation. 7 In our patient, the disease progression was too rapid to try this new treatment.

While this potential new treatment of rabies has been reported, to date, there has been no other report of survival. Prevention is still undoubtedly of critical importance. Greater awareness of travel medicine is needed in Japan. This case of ours should serve as a reminder and warning to those Japanese travelers who are planning a trip abroad.

Declaration of interests

The authors state that they have no conflicts of interest.

Acknowledgments

We thank the patient’s family for permission to publish this case; we are also grateful to the following people from the National Institute of Infectious Diseases, Japan, for their help and technical assistance: Akio Yamada, Satoshi Inoue, Akira Noguchi, Yoshihiro Kaku, Akiko Okutani (Department of Veterinary Science), Ichiro Kurane, Kazuo Nakamichi, Mutsuyo Ito (Department of Virology 1), Tetsutaro Sata, Hideki Hasegawa, Minoru Tobiume, and Yuko Sato (Department of Pathology).

References

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