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Resistant Typhoid Fever Outbreak in Travelers Returning from Bangladesh

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Resistant Typhoid Fever Outbreak in Travelers Returning from Bangladesh LETTERS Multidrug- Although the proportion of enter- that date until April 28, there were 6 ic fever cases related to international confi rmed and 2 probable typhoid fe- Resistant Typhoid travel has increased in industrialized ver cases reported in the 13 tour par- Fever Outbreak in countries, few outbreaks of enteric ticipants, resulting in an attack rate of Travelers Returning fever have been reported in travel- 62%. The median age of the patients ers (6,7). We describe an outbreak was 17 years (range 12–28 years); 5 from Bangladesh of MDR and NAR typhoid fever in patients were female. No other cases To the Editor: Enteric fever young Japanese travelers returning of typhoid fever were reported in that (typhoid and paratyphoid fever) is a from Bangladesh. This outbreak high- period in Japan. systemic infection caused by several lights the need for standard treatments All 6 S. Typhi isolates were Vi- Salmonella enterica serotypes includ- for MDR and NAR enteric fever. phage type E9. These isolates were ing S. Typhi and S. Paratyphi A. The Ten Japanese junior and senior also MDR and NAR, and the MIC Indian subcontinent, which has the high school students living in the To- for ciprofl oxacin for the 6 isolates highest incidence of the disease world- kyo metropolitan area took part in a was 0.38 μg/mL. It was strongly sus- wide, is also an epicenter of enteric 9-day study tour to Dhaka in March– pected that a single-point exposure to fever caused by multidrug-resistant April, 2004. They were escorted by 2 S. Typhi occurred in the tour partici- (MDR; resistant to chloramphenicol, Japanese college students and a 28- pants during their stay in Bangladesh ampicillin, and trimethoprim-sulfa- year-old Japanese instructor. The 13 and caused this exceptional outbreak. methoxazole) and nalidixic acid–re- participants returned to Japan on April None of the participants had received sistant (NAR) strains, i.e., strains with 4, 2004. The purpose of the study tour a typhoid vaccination. decreased susceptibility to ciprofl oxa- was to acquire knowledge about street The 8 patients were admitted to cin (1–3). A total of 57% of S. Typhi children in Dhaka. The students stayed 5 hospitals in the Tokyo metropolitan strains isolated at a referral center in at a guesthouse and visited orphanag- area. Four different antimicrobial drug Dhaka, Bangladesh, in 2005 were es in the city. The itinerary included a regimens were used on the basis of the MDR and NAR (4). visit to a local home, where the family age of the patients and the hospital in More than 80% of 442 enteric served them a meal. They shared all which each patient was hospitalized fever cases reported in Japan dur- their meals during the tour. (Table). Four patients at 2 hospitals ing 2001–2004 were imported (5). Fever and diarrhea developed in who received fl uoroquinolone mono- Most Japanese persons, especially the 2 participants on April 3 and 5, and therapies were given other regimens younger generation, are not immune these symptoms were later shown to on days 4–6 of treatment because of to enteric fever as are persons living in be caused by shigellosis. On April 19, concern of treatment failure. The me- other industrialized countries. the index patient became febrile. From dian fever clearance time was 6 days Table. Characteristics of 8 case-patients with typhoid fever, Bangladesh, 2004* Case- Age, y/ Date of Vi-phage Ciprofloxacin Cefotaxime MIC, patient† sex onset type MIC, μg/mL μg/mL Treatment‡ FCT, d 1C 28/F Apr 19 E9 0.38 0.094 Ciprofloxacin 500 mg 2× a day for 3 d, 4§ cefotaxime 1 g every 12 h + tosulfoxacin 300 mg 2× a day for 11 d 2C 17/F Apr 20 E9 0.38 0.094 Levofloxacin 200 mg 2× a day for 14 d 6 3C 17/F Apr 21 E9 0.38 0.094 Ciprofloxacin 500 mg 2× a day for 3 d, 3 cefotaxime 1 g every 12 h + tosulfoxacin 300 mg 2× a day for 11 d 4P 19/F Apr 21 NA NA NA Levofloxacin 200 mg 2× a day for 3 d, 12 cefotaxime 1 g every 12 h + tosulfoxacin 300 mg 2× a day for 13 d 5C 12/M Apr 22 E9 0.38 0.094 Azithromycin 1 g for 1 d, 500 mg a day for 7 2 d; norfloxacin 250 mg 3× a day for 11 d 6C 16/F Apr 23 E9 0.38 0.094 Levofloxacin 500 mg a day for 14 d 5 7C 19/M Apr 23 E9 0.38 0.064 Ciprofloxacin 500 mg 2× a day for 5 d, 6 ceftriaxone 2 g every 12 h for 16 d 8P 15/M Apr 28 NA NA NA Levofloxacin 200 mg 2× a day for 18 d 7 *MICs were determined by E-test (AB Biodisk, Solna, Sweden). MICs of chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, and nalidixic acid were >256 μg/mL, >256 μg/mL, >32 μg/mL, and >256 μg/mL, respectively. FCT, fever clearance time (time from the start of treatment until the body temperature reached 37.5°C and remained at 37.5°C for 48 h); NA:, not available. †C, confirmed case, i.e., a patient with fever (>38°C) for >3 d and a laboratory-confirmed positive blood culture for Salmonella enterica serotype Typhi; P, probable case, i.e., a patient with fever (>38°C) for >3 d without isolation of S. Typhi. ‡All fluoroquinolones were given orally. Tosufloxacin is a fluoroquinolone with properties similar to those of levofloxacin. §Fever relapsed 15 d after completion of treatment. Retreatment with tosufloxacin, 600 mg/d for 23 d, was successful. 1954 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 12, December 2007 LETTERS (range 3–12 days). No complications Yasuyuki Kato,*1 8. Parry CM, Ho VA, Phuong le T, Bay occurred during any of the treatment Makiko Fukayama,†2 PV, Lanh MN, Tung le T, et al. Random- 3 ized controlled comparison of ofl oxacin, regimens. Although a relapse occurred Takuya Adachi,‡ azithromycin, and an ofl oxacin-azithro- 15 days after completion of treatment Akifumi Imamura,§ mycin combination for treatment of multi- in the oldest patient, who had received Takafumi Tsunoda,¶ drug-resistant and nalidixic acid–resistant cefotaxime and oral tosufl oxacin, re- Naohide Takayama,§ typhoid fever. Antimicrob Agents Che- mother. 2007;51:819–25. treatment cured the infection without Masayoshi Negishi,§4 fecal carriage. Kenji Ohnishi,* Address for correspondence: Yasuyuki Kato, The high attack rate may refl ect and Hiroko Sagara‡ Disease Control and Prevention Center, the high sensitivity of adolescents to *Tokyo Metropolitan Bokutoh Hospital, To- International Medical Center of Japan, Toyama typhoid fever and the high level of kyo, Japan; †Tokyo Metropolitan Toshima 1-21-1, Shinjuku-ku, Tokyo 162-8655, Japan, bacterial contamination in food the Hospital, Tokyo, Japan; ‡Yokohama Munic- email: [email protected] participants had eaten during travel ipal Citizen’s Hospital, Yokohama, Japan; (2). Although the meal at the private §Tokyo Metropolitan Komagome Hospital, home was suspected as the source of Tokyo, Japan; and ¶Tokyo Metropolitan infection, we could not determine the Ebara Hospital, Tokyo, Japan exact cause of this outbreak. The optimum treatment for MDR References and NAR enteric fever has not yet Human Rabies been established. A third-generation 1. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. Cluster Following cephalosporin or high doses of fl uoro- 2002;347:1770–82. quinolones (e.g., ciprofl oxacin, 20 mg/ 2. Bhan MK, Bahl R, Bhatnagar S. Ty- Badger Bites, kg/day or levofl oxacin, 10 mg/kg/day) phoid and paratyphoid fever. Lancet. People’s Republic for 10–14 days are the drugs of choice 2005;366:749–62. 3. Crump JA, Barrett TJ, Nelson JT, Angulo of China (1,2). Azithromycin is also a promising FJ. Reevaluating fl uoroquinolone break- agent (8). However, for any of the reg- points for Salmonella enterica serotype To the Editor: From February imens, the mean fever clearance times Typhi and for non-Typhi salmonellae. Clin 2002 to April 2004, 7 rural residents of are relatively long (≈7 days), and the Infect Dis. 2003;37:75–81. 4. Ahmed D, D’Costa LT, Alam K, Nair GB, Coteau County (population 450,000) relapse rates are high (1). Although all Hossain MA. Multidrug-resistant Salmo- in western Zhejiang Province in east- 6 isolates showed reduced susceptibil- nella enterica serover Typhi isolates with ern People’s Republic of China died of ity to ciprofl oxacin, a long course (14 high-level resistance to ciprofl oxacin in rabies following badger bites (Figure). days) of fl uoroquinolones was still ef- Dhaka, Bangladesh. Antimicrob Agents Chemother. 2006;50:3516–7. In this county, 89% of residents are 2 fective in this outbreak. However, cli- 5. National Institute of Infectious Diseases farmers. The county covers 4,475 km , nicians should be aware of treatment and Ministry of Health, Labour and Wel- and the terrain is mountainous. No failure in MDR and NAR enteric fever fare. Typhoid fever and paratyphoid fever other cases of human rabies had been (3). The combination therapy of cefo- in Japan, 2001–2004. Infectious Agents Surveillance Report. 2005;26:87–88 [cited reported from this county since 1986. taxime and a fl uoroquinolone used in 2007 Sep 25]. Available from http://idsc. We investigated the cluster to ascertain 3 patients has not shown greater ef- nih.go.jp/iasr/26/302/tpc302.html characteristics of these exposures. fi cacy than monotherapies.
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