Concept
  Cholera is an acute gastroenteritis elicited by a toxigenic strain of the Vibrio cholerae serotypes 01 and 0139. In typical cases, the disease begins abruptly with watery diarrhea and vomiting after an incubation period of usually 2~3 days. The patient develops rapidly dehydration and acidosis due to the loss of fluids and electrolytes. There is no abdominal pain, and the body temperature drops. The white watery diarrhea occurs, and the loss of body fluids exceeds one liter per hour. The patient presents with dehydration symptoms, such as "cholera face", laundress, hoarse voice, spasms of the calf muscles, consciousness disorders, convulsions, etc. This leads to acute circulation insufficiency and acute renal failure. Since there is no abdominal pain and fever, consultation to a doctor tends to be delayed. In Japan, although the symptoms are mild in most cases, they tend to aggravate in elderly subjects, young children, persons having undergone gastrectomy, and also in subjects on antacids and anti-ulcer medication due to anacidity and hypoacidity. The few fatality cases encountered in Japan consist made up of such patients. Laboratory test data show an elevation of hematocrit, hemoglobin (Hb), serum total protein (TP), urea nitrogen (BUN) and creatinine (CRN) and metabolic acidosis due to severe dehydration. The white blood cell (WBC) count increases, but CRP does not rise. Basically the treatment consists of improving the patient's general condition and eradicating bacteria through transfusion and administration of antibiotics and preventing secondary infections. Although the priority is on transfusion, antibiotics are efficacious for shortening the duration of diarrhea and stopping early bacterial excretion. There are almost no cases of person-to-person transmission in Japan. Cholera being a communicable disease to be quarantined, countries where this disease is prevalent are under the obligation of notification to the WHO. In Japan, cholera has been classified as an infectious disease of Category 2 under the Law on Infectious Diseases revised in 1999. Although it is necessary to notify this disease to public health centers, hospitalization is not mandatory in the absence of symptoms, and treatment on an outpatient basis is possible.
Present status of cholera in Japan
  The annual number of cholera cases notified from 1999 is 30~80. Presently these are imported infection cases of which at least 80% were contracted abroad. In Japan foreign infection cases contracted notably in South East Asia. However, there are also cases are contracted in domestic, probably originating from imported food products. Four cases of food intoxication and nineteen patients have been notified since 1999. As far as the age distribution is concerned, whereas the distribution is almost equal in a wide bracket of years with a peak in the 20s in foreign countries, cases of cholera in Japan are concentrated in subjects aged 41 and over (Figure 1). The number of infected cases in the Philippines increased in 2002 (Figure 2)
Presentation of cases
1) African male in 30s
The subject arrived at Yokohama on January 29 to take up a job. At around 8 PM, he developed nausea, vomiting and watery diarrhea. He was carried by ambulance to our hospital at 1 AM on January 30. His body temperature at admission was 35.6C and his blood pressure was not felt. He presented with cholera face and laundness'hands. The patient complained of sever muscular pain and his stools were watery and transparent. Laboratory test data showed a WBC count of 22,000/ul, Hb 20.4 g/dl, TP 13.4 g/dl, CRN 3.4 mg/dl. BUN 30.1 mg/dl, CRP 3.9 mg/dl, pH 7.292; in the stools Na + was 143 mEq/l, K+ 12.7 mEq/l, C-126 mEq/l. He was diagnosed with acute dehydration and he received intravenously a large volume of lactated Ringer's solution. He excreted the stools every 30 minutes to one hour, reaching approximately 15 L per day. He was given a transfusion of 12 L per day for three days, and dehydration abated. Vibrio cholerae serotype O1 was detected from feces culture at the time of admission. The administration of 300 mg of Levofloxin for three days was initiated. In the evening of that day, laboratory tests commissioned to the Yokohama Health Research Center showed that the organism was biotype El Tor producing cholera toxin. The case was notified to the public health center. The bacterium turned negative from February 1, diarrhea disappeared from February 5, and the patient was discharged on February 7.
2) Japanese male in 50s
The subject was on treatment for diabetes. He traveled to the Philippines for business from June 14 to 17. He consumed raw fish in a Japanese restaurant on June 16. From the night of June 17, he vomited and had diarrhea 6~7 times. He experienced weakness of the lower extremities and muscular pain from around midnight on June 18. He received a transfusion in a night emergency hospital. Then he was transferred to hospital because he was suspected of having cholera since he could not urinate and he had low blood pressure. His body temperature was 35.7C and his blood pressure was 74/54. The laboratory test data were as follows: WBC 19700,Hb 18.8, TP 10.7, CRN 4.1, BUN 24.1, CRP 3.1, blood glucose 354 mg/dl. He had watery diarrhea exceeding 1 L each time. He was intravenously administered a massive volume of lactated Ringer's solution, reaching 20 L during the first 24 hours. The treatment was initiated in the evening of that day with 300 mg of Levoflaxin for three days. Remission of diarrhea was noted on June 21, and the patient was discharged on June 25. The detected organism was serotype El Tor Ogawa, and it was positive for cholera toxin. The patient said he had eaten raw fish in the Philippines in a restaurant reputed to be clean.
3) Japanese female in 20s
The subject traveled to Phuket, Thailand, from April 12 to19. Her activities were swimming and snorkeling. She ate raw oysters on the April 17. She passed 5~6 times watery diarrhea from the April 19. She had nausea and vomited 3~4 times. After seeing a nearby doctor, she was hospitalized. Her body weight decreased from 50 kg to 41 kg. Her condition improved after she received lactated Ringer's solution and 300 mg of Levoflaxin for three days. She was discharged from the hospital on the April 24. The detected organism was serotype El Tor Inaba; it was positive for cholera toxin and negative for norovirus. The patient said she ate raw oysters without suspecting anything wrong, since people in the same restaurant were also consuming them.
4) Japanese male in 50s
That person had no history of traveling abroad. He went out for dinner with his company's coworkers on April 27 and he consumed raw fish. He passed watery diarrhea more than 20 times from the night of April 30. He did not vomit and had no abdominal pain. In spite of treatment at his home, his condition did not improve. He was examined by a nearby doctor on May 2 and he received a transfusion and a phosphomycin instillation. On May 6, he had 2~3 times diarrhea. Since Vibrio cholerae was detected in his stool culture on the May 7, he was referred to our hospital for examination. The strain was positive for cholera toxin serotype El Tor Ogawa. Since remission of the diarrhea was observed, the subject was treated on an outpatient basis with 300 mg of Levofloxacin during three days. Feces cultures on May 14 and 15 after termination of the treatment were confirmed to be negative for Vibrio cholerae, and we made a report to the public health. Suspecting food intoxication, an epidemiological study was performed, but the source of infection was unclear.
Treatment
  Transfusion is the first priority when treating cholera. If the patient is examined promptly in a medical institution even in the presence of dehydration symptoms, he or she will be able to receive adequate treatment, given the current level of health care in Japan. Transfusion in excess of 3 L is rare in routine treatment. However, some cases require 5~10 L or even more in case of cholera. There exist guidelines for transfusion in case of cholera established by the WHO. When dehydration is severe, a transfusion of lactated Ringer's solution is given for three hours (100 ml/kg) (six hours in children under one year of age). A maintenance transfusion is administered until dehydration disappears. Oral rehydration solution (ORS) is recommended in case of dehydration. This simple and convenient method is widely employed in developed countries, where its effectiveness has been recognized. The electrolytes used are Na+ 90 mEq, K+ 20 mEq, Cl-80 mEq and HC03-30 mEq. This approach is not popular in Japan. Sports drinks suffice in case of mild symptoms. Presently 2 L/day of oral rehydration solution is recommended in children aged ten or more even in the absence of dehydration.
  The recommended antimicrobacterial agents are tetracycline (TC), sulphamethoxazole-trimethropim combined agent (ST), and erythromycin in children. In Japan new quinolone drugs are primarily the choice. The reasons are that 1)these agents are also effective against TC and ST resistant organisms, which have been occasionally observed in recent years, 2)they are widely used in travelers' diarrhea, 3)they are often administered for the confirmation of diagnosis, and 4)TC is not generally given in the treatment of diarrhea in Japan. Re-excretion of the organism is virtually not observed. If two successive stool cultures performed 48 hours after termination of the treatment with microbial agents at an interval of 24 hours of more turn out to be negative, it means that the causative agent is not present. In other words, the patient is considered to have recovered.