Inoue Shingo

Khanal Santa Raj

Kurane Ichiro

Miyazaki Isao

Morita Kouichi

Ogawa Tetsuro

Pandey Basu Dev

Takasaki Tomohiko

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LETTERS10.  Wininger DA, Fass RJ. Antibiotic ce-ment and beads for orthopedic infections. Antimicrob Agents Chemother. 1996;40:2675–9.Address for correspondence: Jason J. Schafer, UPMC St. Margaret, Department of Pharmacy, 815 Freeport Rd, Pittsburgh, PA 15215, USA; email: schaferjj@upmc.eduDengue Virus, NepalTo the Editor: Dengue virus be-longs to the genus Flavivirus, family Flaviviridae. It has 4 serotypes: den-gue virus type 1 (DENV-1), dengue virus type 2 (DENV-2), dengue virus type 3 (DENV-3), and dengue virus type 4 (DENV-4). Dengue virus is maintained in a cycle between humans and Aedes aegypti, domestic day-bit-ing mosquitoes. Dengue virus induces clinical illness, which ranges from a nonspecifi c viral syndrome (dengue fever [DF]) to severe and fatal hem-orrhagic disease (dengue hemorrhagic fever [DHF]). DF/DHF occurs primar-ily in tropical and subtropical areas of the world. Domestic dengue virus in-fection occurs in >100 countries; >2.5 billion persons live in these areas. Ap-proximately 100 million cases of DF, 500,000 cases of DHF, and several thousand deaths occur annually world-wide (1). During the past decades, dengue virus has emerged in south-ern Asia; DF/DHF epidemics have occurred in Bhutan, India, Maldives, Bangladesh, and Pakistan (2–4).From August through November 2006, the number of febrile patients increased in 4 major hospitals in the Terai region of Nepal: Nepalgunj Medical College, Bheri Zonal Hospi-tal in Nepalgunj, Tribhuban Hospital in Dang, and Narayani subregional hospital in Birgunj. Patients with se-vere symptoms were referred to Sukr-araj Tropical and Infectious Disease Hospital, Kathmandu, for diagnosis and treatment. The clinical features in most patients were consistent with signs of DF, but some patients showed signs (high fever, rash, ecchymosis, epistaxis, positive tourniquet test, liv-er dysfunction, and thrombocytopenia [platelet count <100,000/mm3]) con-sistent with the World Health Organi-zation (WHO) defi nition of DHF. As-cites and plural effusion developed in 2 patients. Blood specimens were col-lected from all patients at the time of admission to the local hospitals. Par-ticle agglutination (PA) assay (Pentax Ltd, Tokyo, Japan) (5) and immuno-globulin (Ig) M–capture ELISA (Den-gue/JE IgM Combo ELISA kit, Panbio Ltd, Brisbane, Queensland, Australia) were performed. Dengue virus–specif-ic IgM was detected in 11 patients who had fever, headache, and rash (Table). Each of these patients had negative 514 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 3, March 2008Table. Clinical and laboratory data for 11 patients admitted to hospitals and diagnosed with dengue fever or dengue hemorrhagicfever, Nepal, 2006* Patientage, y/SexMonthadmitted LocationInitialdiagnosisTravelhistoryClinical signs and symptoms Selected laboratory and other test results 20/M Sep Kathmandu DF Yes Fever, headache, nauseaHb 15.4 g/dL; TLC 10,500/mm3;Plt 185,000/mm3; blood culture for salmonellae negative; ALT 38 IU/L 27/F Sep Bardiya Viral fever No Fever, headache, vomitingTLC 5,600/mm3; blood culture for salmonellae negative 3/M Sep Salayan Encephalitis No Fever, vomiting, convulsionsWidal negative; TLC 4,700/mm313/M Oct Sindhuli Typhoid feverNo Fever, headache Widal negative; TLC 4,500/mm3; blood culture for salmonellae negative; Brucellaantigen negative; chest radiograph normal 22/M Oct Birgunj DHF No Fever, headache, vomiting, ascites Bil 0.8 mg/dL; ALT 80 IU/L; Plt 22,000/mm3;chest radiograph normal 55/F Oct Dang DF No Fever, headache, muscular pain Plt 51,000/mm3; TLC 7,600/mm3; MP negative; ESR 20 mm/h; Bil 0.7 mg/dL 22/F Oct Birgunj Viral fever No Fever, headache,  body ache Brucella negative; Widal negative;TLC 5,600/mm313/M Nov Dang DF No Fever, headache, rashesPlt 95,000/mm3; TLC 4,700/mm3;Hb 13.1 g%; Bil 0.8mg/dL; ALT 26 IU/L 35/F Nov Birgunj DHF No Fever, headache, bruises; tourniquet: positiveBil 0.81mg/dL; Plt 31,000/mm3;PT 2 min 30 s (control 14) 40/M Nov Birgunj DF No Fever, headache, rashesALT 127IU/L; Plt 110,000 /mm3;PCV 38.8%;TLC 5,500/mm3;ultrasonography liver size, 16.8 cm 42/M Nov Dang DF No Fever, headache, rashesBil 0.7 mg/dL; Widal test negative;TLC 6,800/mm3; Plt 164,000/mm3*Blood specimens were collected at time of hospital admission. Diagnosis was confirmed by using immunoglobulin M–capture ELISA. DF, dengue fever; Hb, hemoglobulin;TLC, total leukocyte count; Plt, platelets; ALT, alanine aminotransferase; DHF, dengue hemorrhagic fever Bil, bilirubin; MP, malaria parasites; ESR, erythrocyte sedimentation rate; PT, prothrombin time; PCV, packed cell volume. LETTERSresults for Japanese encephalitis vi-rus–specifi c IgM. Of the 11 patients, 10 had no history of travel to India or other dengue-endemic countries. DF or DHF was initially diagnosed for 7 pa-tients, and viral encephalitis, typhoid fever, or viral fever was diagnosed for others without serologic tests. Reverse transcription–PCR and virus isolation were performed at Institute of Tropi-cal Medicine, Nagasaki University, Nagasaki, Japan, but the dengue virus genome was not detected, and no virus was isolated, likely because sample collection was delayed and the sample was transported to Japan in a deterio-rated condition.DF/DHF have been considered to be a possible public health threat to Nepal because DF/DHF epidemics have occurred recently in India and Pakistan, which reported several thou-sand cases and >100 deaths (6). The fi rst DF case in Nepal was reported in 2004 (7). Further, the fi rst DENV-2 strain of Nepal origin was isolated from a Japanese traveler who visited Nepal and in which DF developed af-ter the patient returned to Japan. The isolated DENV-2 (GenBank accession no. AB194882) was 98% homologous with DENV-2 isolated in India (8). The prevalence of dengue virus antibody was reported to be 10.4% in the south-western region of Nepal (9). These reports suggest that dengue virus has been circulating in Nepal for several years. Thus, DF/DHF has likely been misdiagnosed and illness caused by dengue virus underestimated in Ne-pal. In contrast, Japanese encephali-tis has been a public health problem in southwestern region of Nepal, and large epidemics have occurred almost every year since 1978 (10). Nepal has no dengue surveillance programs, and health professionals do not usually consider dengue as a differential diag-nosis.The emergence occurred in the lowland Terai belt region, which bor-ders the state of Bihar, India. The Ae-des mosquito is known to persist in this region. The emerging DENV-2 is likely to have been introduced into Nepal from India.Basu Dev Pandey,* Kouichi Morita,† Santa Raj Khanal,‡ Tomohiko Takasaki,§ Isao Miyazaki,¶ Tetsuro Ogawa,¶ Shingo Inoue,† and Ichiro Kurane§*Tropical and Infectious Disease Hospital, Kathmandu, Nepal; †Nagasaki University, Nagasaki, Japan; ‡Tribhuban University, Kathmandu, Nepal; §National Institute of Infectious Diseases, Tokyo, Japan; and ¶Pentax Company Limited, Tokyo, JapanReferences  1.  World Health Organization. Dengue and dengue haemorrhagic fever. Fact sheet no.117; revised 2002 Apr [cited 2006 Oct 31]. Available from http://www.who.int/mediacentre/factsheets/fs117/en  2.  World Health Organization. Dengue out-break in Bhutan. Communicable Disease Newsletter. 2007;4(1).  3.  Islam MA, Ahmed M, Begum N, Choud-hury N, Khan A, Parquet C, et al. Molecu-lar characterization and clinical evaluation of dengue outbreak in 2002 in Bangladesh. Jpn J Infect Dis. 2006;59:85–91.  4.  Jamil B, Hasan R, Zafar A, Bewley K, Chamberlain J, Mioulet V, et al. Dengue virus serotype, Karachi, Pakistan. Emerg Infect Dis. 2007;13:182-3.  5.  Pandey B, Yamamoto A, Morita K, Kuro-sawa Y, Rai S, Adhikari S, et al. Serodi-agnosis of Japanese encephalitis among Nepalese patients by the particle aggluti-nation assay. Epidemiol Infect. 2003;131:881–5 .  6.  Gupta E, Dar L, Kapoor G, Broor S. The changing epidemiology of dengue in Del-hi. Virol J. 2006;3:92.  7.  Pandey BD, Rai SK, Morita K, Kurane I. First case of dengue in Nepal. Nepal Med Coll J. 2004;6:157–9.  8.  Takasaki T, Kotaki A, Nishimura K, Sato Y , Tokuda A, Lim C, et al. Dengue virus type 2 from an imported dengue patient in Japan. First isolation of dengue virus from Nepal. J Travel Med. 2007;14:445–8  9.  Sherchand JB, Pandey BD, Haruki K, Jimba M. Sero-diagnosis of Japanese en-cephalitis and dengue virus infection from clinically suspected patients of Nepal. J Inst Med. 2001;23:25–31. 10.  Epidemiology and Disease Control Divi-sion, Ministry of Health Nepal. The annual report of malaria, Kala-azar and Japanese encephalitis in Nepal, 2005. Kathmandu, Nepal: Ministry of Health; 2006. Address for correspondence: Basu Dev Pandey, Tropical and Infectious Disease Hospital, Teku Road, GPO Box 9045, Kathmandu, Nepal; email: basupandey@wlink.com.npHuman Tuberculosis Caused by Mycobacterium bovis, Taiwan To the Editor: Mycobacterium bovis is one of the causative agents of tuberculosis (TB) in humans and animals. Drinking unpasteurized milk, eating undercooked meat, and close contact with infected animals are the main sources of infection for humans. Currently, 119 M. bovis spoligotypes are contained in the fourth internation-al spoligotyping database (SpolDB 4) and are categorized into 3 main sublin-eages corresponding to ST prototypes 482, 683, and 479 (1). Although an M. bovis surveillance program for farm animals has been implemented by the Taiwan Council of Agriculture, no surveillance system exists for human TB cases caused by M. bovis. To monitor the epidemiol-ogy of M. bovis in domestic animals, a regular tuberculin skin test (TST) is compulsory for cattle and sheep and optional for deer in Taiwan (2). In 2005, screening of Mycobacterium spp. infections by TST was performed for 111,412 cattle and 73,396 caprint and ovine herds, of which 188 (0.17%) and 148 (0.2%), respectively, were positive (2). We used spacer oligo-nucleotide typing (spoligotyping) and  Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 3, March 2008 515 

Dengue virus, Nepal

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Dengue virus, Nepal

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