今日の臨床サポート

デング熱・デング出血熱

著者: 忽那賢志 国立国際医療研究センター病院 国際感染症センター

監修: 山本舜悟 京都市立病院 感染症科/京都大学 医療疫学(非常勤講師) 

著者校正/監修レビュー済:2019/07/09
参考ガイドライン:
蚊媒介感染症の診療ガイドライン(第5版)
Dengue: guidelines for diagnosis, treatment, prevention and control- new edition. Geneva :World Health Organization, 2009.
患者向け説明資料

概要・推奨   

  1. 少なくとも中等症のデング出血熱の患者では、輸液管理に細胞外液を用いることが推奨される(推奨度2)
  1. デングショック症候群の患者にステロイドを投与することは推奨されない(推奨度3)
  1. デング熱は1度目よりも2度目に罹患したときのほうが重症化しやすいため注意が必要である。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
忽那賢志 : 講演料(Yahoo!JAPAN),研究費・助成金など(武田薬品,株式会社キアゲン)[2021年]
監修:山本舜悟 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 疫学情報のアップデート
  1. デングワクチンに関するアップデート

病態・疫学・診察

疾患情報(疫学・病態)  
  1. デング出血熱はフラビウイルス属に属するデングウイルスによる感染症であり、ネッタイシマカやヒトスジシマカが媒介する。
  1. デングウイルスによる臨床像は、無症候性感染や非致死性のデング熱から重症型のデング出血熱やデングショック症候群まで幅広い。デング熱が1週間程度で自然軽快するのに対し、デング出血熱は解熱の時期に血漿漏出や血小板減少による出血傾向に基づく症状が出現し、死に至ることもある。
  1. 発生動向調査によると、わが国におけるデング熱の患者報告数は20092018年の10年間で2,180例であるが、近年増加傾向であり2016年には343例もの輸入例の報告があった。
  1. デング熱の輸入症例は年々増加傾向にあり、夏季休暇の時期に最も多くみられる。
  1. 現在WHOはデングの分類をデング熱と重症デング熱に分けており、デング出血熱という分類名はなくなっている。わが国の感染症法では依然としてデング出血熱という名称が用いられており届出基準が定められている。
  1. 2014年に海外渡航歴のないデング熱症例が計162名報告された。2015年以降は国内例は報告されていないが、今後は輸入感染症としてだけでなく、国内での感染症としても考慮する必要がある。
 
  1. デング熱の輸入症例は年々増加傾向にあり、夏季休暇の時期に最も多くみられる。
  1. まとめ:1942~45年の間、デング熱のアウトブレイクが日本でもみられていたが、それ以降は国内発症例はない。しかし、輸入感染症としてのデング熱は年々増加傾向にある。感染症法に従って1999~2010年までの間に868例のデング熱症例の届け出が行われている。また、2003~10年の間には768例の疑い例のうち406例が国立感染症研究所での検査にて確定例と診断されている。406例の確定診断例の年齢層は20歳代、30歳代、40歳代がそれぞれ142例(35.6%)、103例(25.8%)、62例(15.5%)であった。感染したウイルスのタイプは1型が98例(35%)、3型が78例(28%)、2型が72例(26%)、4型が32例(11%)であった。デング熱症例の60%がわが国の夏季休暇の時期である7~9月に最も多かった[1]
 
  1. 今後も日本国内でデング熱の流行が起こりうる。
  1. まとめ:2014年に日本国内でデング熱の流行が起こった。代々木公園で曝露した症例が多く、合計で162名の感染者がみられた。本報告は国立国際医療研究センター病院で診断された19例の疫学的・臨床的なデータをまとめたものである[2]
 
  1. 注意すべき蚊媒介感染症としてデング熱、チクングニア熱、ジカ熱が挙げられる。
  1. 蚊媒介感染症の診療ガイドライン(第5版)[3]
  1. わが国における蚊媒介感染症のガイドラインであり、主にデング熱、チクングニア熱、ジカ熱について記載されている。
問診・診察のポイント  
ポイント:
  1. 問診として一番大事なのは海外渡航歴である。他に、デング熱の所見を確認する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Tomohiko Takasaki
雑誌名: Trop Med Health. 2011 Dec;39(4 Suppl):13-5. doi: 10.2149/tmh.2011-S07. Epub 2011 Oct 12.
Abstract/Text Several dengue outbreaks occurred in Japan from 1942 to 1945. Dengue fever emerged in Nagasaki in August 1942 and soon spread to other cities such as Sasebo, Hiroshima, Kobe and Osaka, recurring every summer until 1945 and constituting the greatest outbreak in the temperate zone. Domestic outbreaks have not been reported in Japan since then. However, the number of imported dengue cases has increased year by year: 868 imported cases were reported in Japan between 1999 and 2010 according to the Infectious Diseases Control Law. Moreover, 406 imported cases were confirmed to be dengue virus infection among 768 dengue suspected cases received at NIID from 2003 to 2010. A total of 142 cases (35.6%), 103 cases (25.8%) and 62 cases (15.5%) were noted in the 20-29, 30-39 and 40-49 age groups, respectively. Infecting dengue virus serotypes were determined for 280 of the 406 cases. The number of cases infected with each of the 4 serotypes was 98 (35%) with type 1, 78 (28%) with type 3, 72 (26%) with type 2, and 32 (11%) with type 4. Sixty percent of dengue cases were imported from July to October, the summer vacation season in Japan.

PMID 22500132  Trop Med Health. 2011 Dec;39(4 Suppl):13-5. doi: 10.214・・・
著者: Satoshi Kutsuna, Yasuyuki Kato, Meng Ling Moi, Akira Kotaki, Masayuki Ota, Koh Shinohara, Tetsuro Kobayashi, Kei Yamamoto, Yoshihiro Fujiya, Momoko Mawatari, Tastuya Sato, Junwa Kunimatsu, Nozomi Takeshita, Kayoko Hayakawa, Shuzo Kanagawa, Tomohiko Takasaki, Norio Ohmagari
雑誌名: Emerg Infect Dis. 2015 Mar;21(3):517-20. doi: 10.3201/eid2103/141662.
Abstract/Text After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August-September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.

PMID 25695200  Emerg Infect Dis. 2015 Mar;21(3):517-20. doi: 10.3201/e・・・
著者: T Jelinek, N Mühlberger, G Harms, M Corachán, M P Grobusch, J Knobloch, U Bronner, H Laferl, A Kapaun, Z Bisoffi, J Clerinx, S Puente, G Fry, M Schulze, U Hellgren, I Gjørup, P Chalupa, C Hatz, A Matteelli, M Schmid, L N Nielsen, S da Cunha, J Atouguia, B Myrvang, K Fleischer, European Network on Imported Infectious Disease Surveillance
雑誌名: Clin Infect Dis. 2002 Nov 1;35(9):1047-52. doi: 10.1086/342906. Epub 2002 Oct 10.
Abstract/Text Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

PMID 12384837  Clin Infect Dis. 2002 Nov 1;35(9):1047-52. doi: 10.1086・・・
著者: Satoshi Kutsuna, Kayoko Hayakawa, Yasuyuki Kato, Yoshihiro Fujiya, Momoko Mawatari, Nozomi Takeshita, Shuzo Kanagawa, Norio Ohmagari
雑誌名: J Infect Chemother. 2015 Apr;21(4):272-6. doi: 10.1016/j.jiac.2014.12.004. Epub 2014 Dec 18.
Abstract/Text BACKGROUND: Without specific symptoms, diagnosis of febrile illness in returning travelers is challenging. Dengue, malaria, and enteric fever are common causes of fever in returning travelers and timely and appropriate treatment is important. However, differentiation is difficult without specific diagnostic tests.
METHODS: A retrospective study was conducted at the National Centre for Global Health and Medicine (NCGM) from April 2005 to March 2013. Febrile travelers returning from overseas who were diagnosed with dengue, malaria, or enteric fever were included in this study. Clinical characteristics and laboratory findings were compared for each diagnosis.
RESULTS: During the study period, 86 malaria, 85 dengue, and 31 enteric fever cases were identified. The mean age of the study cohort was 33.1 ± 12 years and 134 (66.3%) study participants were male. Asia was the most common area visited by returning travelers with fevers (89% of dengue, 18.6% of malaria, and 100% of enteric fever cases), followed by Africa (1.2% of dengue and 70.9% of malaria cases). Clinical characteristics and laboratory findings were significantly different among each group with each diagnosis. Decision tree models revealed that returning from Africa and CRP levels <10 mg/L were factors specific for diagnosis of malaria and dengue fever, respectively.
CONCLUSION: Clinical manifestations, simple laboratory test results, and regions of travel are helpful to distinguish between dengue, malaria, and enteric fever in febrile returning travelers with non-specific symptoms.

Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 25592811  J Infect Chemother. 2015 Apr;21(4):272-6. doi: 10.1016/・・・
著者: David O Freedman, Leisa H Weld, Phyllis E Kozarsky, Tamara Fisk, Rachel Robins, Frank von Sonnenburg, Jay S Keystone, Prativa Pandey, Martin S Cetron, GeoSentinel Surveillance Network
雑誌名: N Engl J Med. 2006 Jan 12;354(2):119-30. doi: 10.1056/NEJMoa051331.
Abstract/Text BACKGROUND: Approximately 8 percent of travelers to the developing world require medical care during or after travel. Current understanding of morbidity profiles among ill returned travelers is based on limited data from the 1980s.
METHODS: Thirty GeoSentinel sites, which are specialized travel or tropical-medicine clinics on six continents, contributed clinician-based sentinel surveillance data for 17,353 ill returned travelers. We compared the frequency of occurrence of each diagnosis among travelers returning from six developing regions of the world.
RESULTS: Significant regional differences in proportionate morbidity were detected in 16 of 21 broad syndromic categories. Among travelers presenting to GeoSentinel sites, systemic febrile illness without localizing findings occurred disproportionately among those returning from sub-Saharan Africa or Southeast Asia, acute diarrhea among those returning from south central Asia, and dermatologic problems among those returning from the Caribbean or Central or South America. With respect to specific diagnoses, malaria was one of the three most frequent causes of systemic febrile illness among travelers from every region, although travelers from every region except sub-Saharan Africa and Central America had confirmed or probable dengue more frequently than malaria. Among travelers returning from sub-Saharan Africa, rickettsial infection, primarily tick-borne spotted fever, occurred more frequently than typhoid or dengue. Travelers from all regions except Southeast Asia presented with parasite-induced diarrhea more often than with bacterial diarrhea.
CONCLUSIONS: When patients present to specialized clinics after travel to the developing world, travel destinations are associated with the probability of the diagnosis of certain diseases. Diagnostic approaches and empiric therapies can be guided by these destination-specific differences.

Copyright 2006 Massachusetts Medical Society.
PMID 16407507  N Engl J Med. 2006 Jan 12;354(2):119-30. doi: 10.1056/N・・・
著者: Anon Srikiatkhachorn, Anchalee Krautrachue, Warangkana Ratanaprakarn, Lawan Wongtapradit, Narong Nithipanya, Siripen Kalayanarooj, Ananda Nisalak, Stephen J Thomas, Robert V Gibbons, Mammen P Mammen, Daniel H Libraty, Francis A Ennis, Alan L Rothman, Sharone Green
雑誌名: Pediatr Infect Dis J. 2007 Apr;26(4):283-90; discussion 291-2. doi: 10.1097/01.inf.0000258612.26743.10.
Abstract/Text BACKGROUND: Although plasma leakage is the major cause of mortality and morbidity in patients with dengue hemorrhagic fever (DHF), a detailed assessment of the natural course of this process is still lacking. We employed serial ultrasound examination to delineate the locations and the timing of plasma leakage and to evaluate the usefulness of ultrasound in detecting plasma leakage in DHF.
METHOD: Daily ultrasound examinations of the abdomen and right thorax were performed in 158 suspected dengue cases to detect ascites, thickened gall bladder wall and pleural effusions. Cases were classified into dengue fever (DF), DHF or other febrile illness (OFI) based on serology and evidence of plasma leakage including hemoconcentration and pleural effusion detected by chest radiograph.
RESULTS: Ultrasonographic evidence of plasma leakage was detected in DHF cases starting from 2 days before defervescence and was detected in some cases within 3 days after fever onset. Pleural effusion was the most common ultrasonographic sign of plasma leakage (62% of DHF cases one day after defervescence). Thickening of the gallbladder wall and ascites were detected less frequently (43% and 52% of DHF cases respectively) and resolved more rapidly than pleural effusions. The size of pleural effusions, ascites and gall bladder wall thickness in DHF grade I and II were smaller than those of grade III patients. Ultrasound detected plasma leakage in 12 of 17 DHF cases who did not meet the criteria for significant hemoconcentration.
CONCLUSIONS: Ultrasound examinations detected plasma leakage in multiple body compartments around the time of defervescence. Ultrasonographic signs of plasma leakage were detectable before changes in hematocrits. Ultrasound is a useful tool for detecting plasma leakage in dengue infection.

PMID 17414388  Pediatr Infect Dis J. 2007 Apr;26(4):283-90; discussion・・・
著者: Stuart D Blacksell, Paul N Newton, David Bell, James Kelley, Mammen P Mammen, David W Vaughn, Vanaporn Wuthiekanun, Amornwadee Sungkakum, Ananda Nisalak, Nicholas P J Day
雑誌名: Clin Infect Dis. 2006 Apr 15;42(8):1127-34. doi: 10.1086/501358. Epub 2006 Mar 8.
Abstract/Text BACKGROUND: The serological diagnosis of acute dengue virus infection relies on the detection of dengue-specific immunoglobulin M (IgM) antibodies. Immunochromatographic tests are rapid diagnostic tests (RDTs) that can be performed at the bedside, but they have not been fully validated for diagnosis of dengue infection.
METHODS: More than 20 RDTs for diagnosis of acute dengue infection are commercially available. Of these, 8 were selected for evaluation of performance by use of characterized dengue and nondengue serum specimens, and results were compared with those of a previously published dengue IgM/IgG enzyme-linked immunosorbent assay in conjunction with dengue virus serotyping by reverse-transcriptase polymerase chain reaction.
RESULTS: Assay sensitivities were low, ranging from 6.4% (95% confidence interval [CI], 4.0%-9.7%) to 65.3% (95% CI, 59.9%-70.5%), and specificities ranged from 69.1% (95% CI, 61.4%-76.0%) to 100% (95% CI, 97.8%-100%). Of the 8 tests, only 2 had sensitivities of >50%, the level considered to be clinically useful, and, of these, 1 had relatively low specificity (69.1%). Samples collected early in the infection were less likely to test positive than those collected later. A thermal stability study demonstrated a loss in performance of some RDTs when they were stored at a high ambient temperature for 3 months.
CONCLUSIONS: Users of RDTs for dengue should be aware that many of these tests have a diagnostic accuracy that falls well below the manufacturers' claims. If an acute specimen yields a negative result, a convalescent serum sample should be tested to confirm the result. No RDT adequately differentiated primary and secondary dengue infections, and the tests should not be used for this purpose.

PMID 16575730  Clin Infect Dis. 2006 Apr 15;42(8):1127-34. doi: 10.108・・・
著者: Vianney Tricou, Hang T T Vu, Nhu V N Quynh, Chau V V Nguyen, Hien T Tran, Jeremy Farrar, Bridget Wills, Cameron P Simmons
雑誌名: BMC Infect Dis. 2010 May 28;10:142. doi: 10.1186/1471-2334-10-142. Epub 2010 May 28.
Abstract/Text BACKGROUND: Dengue is a major public health problem in tropical and subtropical countries. Rapid and easy diagnosis of dengue can assist patient triage and care-management. The detection of DENV NS1 on rapid lateral flow tests offers a fast route to a presumptive dengue diagnosis but careful evaluations are urgently needed as more and more people use them.
METHODS: The sensitivity and specificity of the Bio-Rad NS1 Ag Strip and SD Dengue Duo (NS1/IgM/IgG) lateral flow rapid tests were evaluated in a panel of plasma samples from 245 Vietnamese patients with RT-PCR confirmed dengue and 47 with other febrile illnesses.
RESULTS: The NS1 rapid tests had similar diagnostic sensitivities (respectively 61.6% and 62.4%) in confirmed dengue cases but were 100% specific. When IgM/IgG results from the SD Dengue Duo were included in the test interpretation, the sensitivity improved significantly from 62.4% with NS1 alone to 75.5% when NS1 and/or IgM was positive and 83.7% when NS1 and/or IgM and/or IgG was positive. Both NS1 assays were significantly more sensitive for primary than secondary dengue. NS1 positivity was associated with the underlying viraemia as NS1-positive samples had a significantly higher viraemia than NS1-negative samples.
CONCLUSIONS: These data suggest that the NS1 test component of these assays are highly specific and have similar levels of sensitivity. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. The SD Dengue Duo lateral flow rapid test deserves further prospective evaluation in dengue endemic settings.

PMID 20509940  BMC Infect Dis. 2010 May 28;10:142. doi: 10.1186/1471-2・・・
著者: C Cobra, J G Rigau-Pérez, G Kuno, V Vorndam
雑誌名: Am J Epidemiol. 1995 Dec 1;142(11):1204-11.
Abstract/Text The authors investigated the role of secondary immunologic response, virus serotype, age, and sex on the clinical manifestations of dengue fever in Puerto Rico. From surveillance data for 1990 and 1991, this study identified 3,926 laboratory-positive cases, including 889 for whom dengue immunologic status and symptoms could be ascertained. Of those, 622 cases were virologically confirmed, and 267 cases were serologically confirmed. More than 50% of all positive patients reported fever, chills, headache, eye pain, body pains, joint pains, nausea, vomiting, or skin rash. The frequency of reporting signs, symptoms, and hospitalization was significantly higher among persons with secondary infections diagnosed by serological methods. Only rash was more common among those with primary infections. Symptom reporting increased with age; body pains, joint pains, and rash were significantly more frequently reported by female patients. No significant difference in symptom frequency was found among the virologically confirmed cases, comparing primary and secondary cases or infections due to different serotypes. The data for serologically confirmed cases suggest that in Puerto Rico the manifestations of dengue fever are, as with dengue hemorrhagic fever in Asia, more prominent among those who are experiencing secondary infections, and this effect may be more marked in the younger age groups.

PMID 7485067  Am J Epidemiol. 1995 Dec 1;142(11):1204-11.
著者: M G Guzmán, G Kourí, E Martínez, J Bravo, R Riverón, M Soler, S Vázquez, L Morier
雑誌名: Bull Pan Am Health Organ. 1987;21(3):270-9.
Abstract/Text
PMID 3442718  Bull Pan Am Health Organ. 1987;21(3):270-9.
著者: A Díaz, G Kourí, M G Guzmán, L Lobaina, J Bravo, A Ruiz, A Ramos, R Martínez
雑誌名: Bull Pan Am Health Organ. 1988;22(2):133-44.
Abstract/Text
PMID 3167282  Bull Pan Am Health Organ. 1988;22(2):133-44.
著者: R Panpanich, P Sornchai, K Kanjanaratanakorn
雑誌名: Cochrane Database Syst Rev. 2006 Jul 19;(3):CD003488. doi: 10.1002/14651858.CD003488.pub2. Epub 2006 Jul 19.
Abstract/Text BACKGROUND: Dengue shock syndrome is the most severe from of dengue haemorrhagic fever, one of the leading causes of death in children. Observational studies have suggested corticosteroids may benefit people with dengue shock syndrome.
OBJECTIVES: To compare corticosteroids with placebo or no corticosteroids for treating dengue shock syndrome.
SEARCH STRATEGY: We searched the Cochrane Infectious Disease Group Specialized Register (January 2006), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to January 2006), EMBASE, (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted researchers.
SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing corticosteroids with no corticosteroids or placebo in people diagnosed with dengue shock syndrome.
DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria, extracted data, and assessed methodological quality. We calculated the relative risk (RR) for dichotomous data and weighted mean difference for continuous data, and presented them with 95% confidence intervals (CI).
MAIN RESULTS: Four trials involving 284 participants met the inclusion criteria. Corticosteroids were no more effective than placebo or no treatment for reducing the number of deaths (RR 0.68, 95% CI 0.42 to 1.11; 284 participants, 4 trials), the need for blood transfusion (RR 1.08, 0.52 to 2.24; 89 participants, 2 trials), or the number of serious complications (convulsions and pulmonary haemorrhage) as reported in one trial (63 participants).
AUTHORS' CONCLUSIONS: There is insufficient evidence to justify the use of corticosteroids in managing dengue shock syndrome. As corticosteroids can potentially do harm, clinicians should not use them unless they are participating in a randomized controlled trial comparing corticosteroids with placebo.

PMID 16856011  Cochrane Database Syst Rev. 2006 Jul 19;(3):CD003488. d・・・
著者: Vianney Tricou, Nguyet Nguyen Minh, Toi Pham Van, Sue J Lee, Jeremy Farrar, Bridget Wills, Hien Tinh Tran, Cameron P Simmons
雑誌名: PLoS Negl Trop Dis. 2010 Aug 10;4(8):e785. doi: 10.1371/journal.pntd.0000785. Epub 2010 Aug 10.
Abstract/Text BACKGROUND: There is currently no licensed antiviral drug for treatment of dengue. Chloroquine (CQ) inhibits the replication of dengue virus (DENV) in vitro.
METHODS AND FINDINGS: A double-blind, randomized, placebo-controlled trial of CQ in 307 adults hospitalized for suspected DENV infection was conducted at the Hospital for Tropical Diseases (Ho Chi Minh City, Vietnam) between May 2007 and July 2008. Patients with illness histories of 72 hours or less were randomized to a 3-day course of CQ (n = 153) or placebo (n = 154). Laboratory-confirmation of DENV infection was made in 257 (84%) patients. The primary endpoints were time to resolution of DENV viraemia and time to resolution of DENV NS1 antigenaemia. In patients treated with CQ there was a trend toward a longer duration of DENV viraemia (hazard ratio (HR) = 0.80, 95% CI 0.62-1.05), but we did not find any difference for the time to resolution of NS1 antigenaemia (HR = 1.07, 95% CI 0.76-1.51). Interestingly, CQ was associated with a significant reduction in fever clearance time in the intention-to-treat population (HR = 1.37, 95% CI 1.08-1.74) but not in the per-protocol population. There was also a trend towards a lower incidence of dengue hemorrhagic fever (odds ratio = 0.60, PP 95% CI 0.34-1.04) in patients treated with CQ. Differences in levels of T cell activation or pro- or anti-inflammatory plasma cytokine concentrations between CQ- and placebo-treated patients did not explain the trend towards less dengue hemorrhagic fever in the CQ arm. CQ was associated with significantly more adverse events, primarily vomiting.
CONCLUSIONS: CQ does not reduce the durations of viraemia and NS1 antigenaemia in dengue patients. Further trials, with appropriate endpoints, would be required to determine if CQ treatment has any clinical benefit in dengue.
TRIAL REGISTRATION: Current Controlled Trials number ISRCTN38002730.

PMID 20706626  PLoS Negl Trop Dis. 2010 Aug 10;4(8):e785. doi: 10.1371・・・
著者: Bridget A Wills, M Dung Nguyen, T Loan Ha, T H Tam Dong, T N Thuy Tran, T T Minh Le, V Diet Tran, T Hao Nguyen, V Chau Nguyen, Kasia Stepniewska, Nicholas J White, Jeremy J Farrar
雑誌名: N Engl J Med. 2005 Sep 1;353(9):877-89. doi: 10.1056/NEJMoa044057.
Abstract/Text BACKGROUND: Dengue shock syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based.
METHODS: We performed a double-blind, randomized comparison of three fluids for initial resuscitation of Vietnamese children with dengue shock syndrome. We randomly assigned 383 children with moderately severe shock to receive Ringer's lactate, 6 percent dextran 70 (a colloid), or 6 percent hydroxyethyl starch (a colloid) and 129 children with severe shock to receive one of the colloids. The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid.
RESULTS: Only one patient died (<0.2 percent mortality). The primary outcome measure--requirement for rescue colloid--was similar for the different fluids in the two severity groups. The relative risk of requirement for rescue colloid was 1.08 (95 percent confidence interval, 0.78 to 1.47; P=0.65) among children with moderate shock who received Ringer's lactate as compared with either of the colloid solutions, 1.13 (95 percent confidence interval, 0.74 to 1.74; P=0.59) among children who received dextran as compared with starch in the group with severe shock, and 0.88 (95 percent confidence interval, 0.66 to 1.17; P=0.38) among children who received dextran as compared with starch in the combined analysis. Although treatment with Ringer's lactate resulted in less rapid improvement in the hematocrit and a marginally longer time to initial recovery than did treatment with either of the colloid solutions, there were no differences in all other measures of treatment response. Only minor differences in efficacy were detected between the two colloids, but significantly more recipients of dextran than of starch had adverse reactions. Bleeding manifestations, coagulation derangements, and severity of fluid overload were similar for all fluid-treatment groups.
CONCLUSIONS: Initial resuscitation with Ringer's lactate is indicated for children with moderately severe dengue shock syndrome. Dextran 70 and 6 percent hydroxyethyl starch perform similarly in children with severe shock, but given the adverse reactions associated with the use of dextran, starch may be preferable for this group.

Copyright 2005 Massachusetts Medical Society.
PMID 16135832  N Engl J Med. 2005 Sep 1;353(9):877-89. doi: 10.1056/NE・・・
著者: N T Ngo, X T Cao, R Kneen, B Wills, V M Nguyen, T Q Nguyen, V T Chu, T T Nguyen, J A Simpson, T Solomon, N J White, J Farrar
雑誌名: Clin Infect Dis. 2001 Jan 15;32(2):204-13. doi: 10.1086/318479. Epub 2001 Jan 15.
Abstract/Text Dengue hemorrhagic fever is an important cause of morbidity among Asian children, and the more severe dengue shock syndrome (DSS) causes a significant number of childhood deaths. DSS is characterized by a massive increase in systemic capillary permeability with consequent hypovolemia. Fluid resuscitation is critical, but as yet there have been no large trials to determine the optimal fluid regimen. We undertook a randomized blinded comparison of 4 fluids (dextran, gelatin, lactated Ringer's, and "normal" saline) for initial resuscitation of 230 Vietnamese children with DSS. All the children survived, and there was no clear advantage to using any of the 4 fluids, but the longest recovery times occurred in the lactated Ringer's group. The most significant factor determining clinical response was the pulse pressure at presentation. A comparison of the colloid and crystalloid groups suggested benefits in children presenting with lower pulse pressures who received one of the colloids. Further large-scale studies, stratified for admission pulse pressure, are indicated.

PMID 11170909  Clin Infect Dis. 2001 Jan 15;32(2):204-13. doi: 10.1086・・・
著者: N M Dung, N P Day, D T Tam, H T Loan, H T Chau, L N Minh, T V Diet, D B Bethell, R Kneen, T T Hien, N J White, J J Farrar
雑誌名: Clin Infect Dis. 1999 Oct;29(4):787-94. doi: 10.1086/520435.
Abstract/Text Dengue hemorrhagic fever and dengue shock syndrome (DSS) are major causes of childhood morbidity and mortality in many tropical countries. Increased intravascular permeability leading to shock is the cardinal feature of DSS. Fluid resuscitation to counteract massive plasma leakage is the mainstay of treatment. A double-blind, randomized trial comparing four intravenous-fluid regimens for acute resuscitation of 50 children with DSS was conducted. Colloids (dextran 70 or the protein digest gelafundin 35,000) restored cardiac index and blood pressure and normalized hematocrit more rapidly than crystalloids (Ringer's lactate or 0.9%-weight/volume saline). Dextran 70 provided the most rapid normalization of the hematocrit and restoration of the cardiac index, without adverse effects, and may be the preferred solution for acute resuscitation in DSS. Further large-scale double-blind trials are required to provide an evidence-based approach to the management of DSS.

PMID 10589889  Clin Infect Dis. 1999 Oct;29(4):787-94. doi: 10.1086/52・・・
著者: Mark S Fradin, John F Day
雑誌名: N Engl J Med. 2002 Jul 4;347(1):13-8. doi: 10.1056/NEJMoa011699.
Abstract/Text BACKGROUND: The worldwide threat of arthropod-transmitted diseases, with their associated morbidity and mortality, underscores the need for effective insect repellents. Multiple chemical, botanical, and "alternative" repellent products are marketed to consumers. We sought to determine which products available in the United States provide reliable and prolonged complete protection from mosquito bites.
METHODS: We conducted studies involving 15 volunteers to test the relative efficacy of seven botanical insect repellents; four products containing N,N-diethyl-m-toluamide, now called N,N-diethyl-3-methylbenzamide (DEET); a repellent containing IR3535 (ethyl butylacetylaminopropionate); three repellent-impregnated wristbands; and a moisturizer that is commonly claimed to have repellent effects. These products were tested in a controlled laboratory environment in which the species of the mosquitoes, their age, their degree of hunger, the humidity, the temperature, and the light-dark cycle were all kept constant.
RESULTS: DEET-based products provided complete protection for the longest duration. Higher concentrations of DEET provided longer-lasting protection. A formulation containing 23.8 percent DEET had a mean complete-protection time of 301.5 minutes. A soybean-oil-based repellent protected against mosquito bites for an average of 94.6 minutes. The IR3535-based repellent protected for an average of 22.9 minutes. All other botanical repellents we tested provided protection for a mean duration of less than 20 minutes. Repellent-impregnated wristbands offered no protection.
CONCLUSIONS: Currently available non-DEET repellents do not provide protection for durations similar to those of DEET-based repellents and cannot be relied on to provide prolonged protection in environments where mosquito-borne diseases are a substantial threat.

PMID 12097535  N Engl J Med. 2002 Jul 4;347(1):13-8. doi: 10.1056/NEJM・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから