今日の臨床サポート

渡航者健康管理と予防接種

著者: 氏家 無限 国立国際医療研究センター 国際感染症センター

監修: 大曲貴夫 国立国際医療研究センター

著者校正/監修レビュー済:2020/07/03
患者向け説明資料

概要・推奨   

  1. 新型コロナウイルス感染症の流行状況については外務省の海外安全ホームページ等で最新の情報を確認する。
  1. 海外渡航者における新型コロナウイルスへの対応:
  1. 海外渡航時には健康問題を生じるリスクが高くなるため、注意を要する(推奨度2)。
  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。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
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  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。閲覧にはご契約が必要となります。閲覧にはご契約が
  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。閲覧にはご契約が必要となります。閲
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  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。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  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。閲覧にはご契約が必要となりま
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  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
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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:
氏家 無限 : 特に申告事項無し[2021年]
監修:大曲貴夫 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、改訂に伴う図表の更新、新たなワクチンの承認に基づく情報の記載、疫学情報の更新等を行った。
  1. 海外渡航者における新型コロナウイルスへの対応: >詳細情報 を追加した。

病態・疫学・診察

渡航者健康管理  
  1. 渡航には様々な形態があり、必要な健康管理は個々の渡航者により異なる。
  1. 渡航前には健康診断や歯科検診などにより健康状態を確認し、基礎疾患があれば英文の診断書を作成、海外旅行保険への加入などの準備を行うことが望ましい。
  1. 渡航前に現地で流行している疾患や医療システムなどの医療情報を収集しておくことが重要である。
  1. 一般的な現地渡航情報は外務省 世界の医療事情[1]厚生労働省検疫所FORTH[2]の他、米国疾病対策センター(CDC)のTraveler’s Health[3]、最新の流行情報はHealthMap[4]などのウェブサイトが参考になる。
  1. 新型コロナウイルス感染症の流行状況については外務省の海外安全ホームページ等で最新の情報を確認する。
  1. 海外渡航者における新型コロナウイルスへの対応: >詳細情報 
  1. 渡航の期間、場所、目的などに注目して渡航によるリスクを評価し、リスクに応じて必要なワクチン接種や予防内服の適応を決める。
  1. 熱帯地域から帰国後1カ月以内の急な発熱では、マラリアなどの重症疾患を考慮し、必要に応じ診断検査を実施する、または専門医療機関を紹介する。
 
  1. 長時間の移動により静脈血栓症のリスクが高まるため注意を促す必要がある。
  1. 渡航に関連した静脈血栓症のリスクを評価したメタ解析において、静脈血栓症4,055例を含む14の研究を評価した[5]。静脈血栓症の精査のために紹介された対照群を除いて調整すると、渡航者では非渡航者と比較して静脈血栓症の相対リスクが2.8倍高かった(95%CI 2.2-3.7)。また、2時間以上の移動において静脈血栓症のリスクは18%上昇(P=0.010)、2時間以上の航空機の搭乗において静脈血栓症のリスクは26%上昇した(P=0.005)。
問診・診察のポイント  
  1. 通院中の疾患があるかどうか、服薬している薬剤があるかどうかを確認する。

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」。
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文献 

著者: Divay Chandra, Emilio Parisini, Dariush Mozaffarian
雑誌名: Ann Intern Med. 2009 Aug 4;151(3):180-90. Epub 2009 Jul 6.
Abstract/Text BACKGROUND: The potential risk for travel-related venous thromboembolism (VTE) has become an important public health concern because of rapid increases in long-distance travel; however, previous studies on this relationship are surprisingly contradictory.
PURPOSE: To estimate the risk for VTE in travelers, determine whether a dose-response relationship exists, and identify reasons for the contradictory results of previous studies.
DATA SOURCES: MEDLINE, EMBASE, BIOSIS, CINAHL, grey-literature sources, contact with investigators, and reference lists of studies, without language restrictions.
STUDY SELECTION: Reports were selected if they investigated the association between travel and VTE for persons who used any mode of transportation and if nontraveling persons were included for comparison.
DATA EXTRACTION: Data on study and patient characteristics, risk estimates, and quality were independently extracted by 2 investigators. Pooled effect estimates were obtained by using random-effect meta-analysis.
DATA SYNTHESIS: Of 1560 identified abstracts, 14 studies (11 case-control, 2 cohort, and 1 case-crossover) met inclusion criteria, including 4055 cases of VTE. Compared with nontravelers, the overall pooled relative risk for VTE in travelers was 2.0 (95% CI, 1.5 to 2.7). Significant heterogeneity was present because of the method for selecting control participants (P = 0.008): whether the studies used control participants who had been referred for VTE evaluation or nonreferred control participants. When the studies that used referred control participants were excluded, the pooled relative risk for VTE in travelers was 2.8 (CI, 2.2 to 3.7), without significant heterogeneity. A dose-response relationship was identified, with an 18% higher risk for VTE for each 2-hour increase in duration of travel by any mode (P = 0.010) and a 26% higher risk for every 2 hours of air travel (P = 0.005).
LIMITATION: All available studies were from Western countries; generalizability to non-Western populations is expected but needs confirmation.
CONCLUSION: Travel is associated with a nearly 3-fold higher risk for VTE, with a dose-response relationship of 18% higher risk for each 2-hour increase in travel duration. Heterogeneity in results of previous studies was due to selection bias toward the null from use of referred control participants.

PMID 19581633  Ann Intern Med. 2009 Aug 4;151(3):180-90. Epub 2009 Jul・・・
著者: Susan L Hills, Anne C Griggs, Marc Fischer
雑誌名: Am J Trop Med Hyg. 2010 May;82(5):930-6. doi: 10.4269/ajtmh.2010.09-0676.
Abstract/Text Japanese encephalitis (JE) is a severe disease and a risk for travelers who visit JE-endemic countries. We reviewed all published JE cases in travelers from non-endemic areas from 1973 through 2008, and assessed factors related to risk of infection. There were 55 cases that occurred in citizens of 17 countries. Age range of case-patients was 1-91 years (median = 34 years). Ten (18%) persons died and 24 (44%) had mild to severe sequelae. In a detailed risk assessment of 37 case-patients, 24 (65%) had spent > or = 1 month in JE-endemic areas, and most had factors identified that may have increased infection risk. The estimate of overall JE risk was low, < 1 case/1 million travelers to JE-endemic countries. Nonetheless, for each traveler, a careful assessment of itinerary and activities, a decision on vaccination, and information on mosquito precautions are needed to reduce the risk of this disease.

PMID 20439978  Am J Trop Med Hyg. 2010 May;82(5):930-6. doi: 10.4269/a・・・
著者: Alessandro Remo Zanetti, Andrea Mariano, Luisa Romanò, Raffaele D'Amelio, Maria Chironna, Rosa Cristina Coppola, Mario Cuccia, Rossana Mangione, Fosca Marrone, Francesco Saverio Negrone, Antonino Parlato, Emanuela Zamparo, Carla Zotti, Tommaso Stroffolini, Alfonso Mele, Study Group
雑誌名: Lancet. 2005 Oct 15-21;366(9494):1379-84. doi: 10.1016/S0140-6736(05)67568-X.
Abstract/Text BACKGROUND: Universal anti-hepatitis-B vaccination of infants and adolescents was implemented in Italy in 1991. We undertook a multicentre study in previously vaccinated individuals to assess the duration of immunity and need for booster, over 10 years after vaccination.
METHODS: In 1212 children and 446 Italian Air Force recruits vaccinated as infants and adolescents, respectively, we measured the concentrations of antibodies to hepatitis-B surface antigen (anti-HBs) and the presence of antibodies to hepatitis-B core antigen (anti-HBc) at enrollment; postimmunisation values were not available. Individuals positive for anti-HBc were tested for hepatitis B surface antigen (HBsAg) and hepatitis B viral DNA. Individuals with anti-HBs concentrations at 10 IU/L or more were regarded as protected; those with antibody less than 10 IU/L were given a booster dose and retested 2 weeks later. Individuals showing postbooster anti-HBs concentrations of less than 10 IU/L were offered two additional vaccine doses and retested 1 month after the third dose.
FINDINGS: Protective anti-HBs concentrations were retained in 779 (64%, 95% CI 61.6-67) children and 398 (89%, 86.4-92.1) recruits. We recorded antibody amounts of less than 10 IU/L in 433 children (36%, 33-38.4) and 48 (11%, 7.9-13.6) recruits. One child and four recruits were positive for anti-HBc, but negative for HBsAg and hepatitis B viral DNA. Antibody concentrations were higher in recruits than in children (geometric mean titre 234.8 IU/L vs 32.1 IU/L, p=0.0001). 332 (97%) of 342 children and 46 (96%) of 48 recruits who received a booster showed an anamnestic response, whereas ten (3%) children and two (4%) recruits remained negative for anti-HBs or had antibody concentrations of less than 10 IU/L. Prebooster and postbooster antibody titres were strongly correlated with each other in both groups. All individuals given two additional vaccine doses (eight children and two recruits) showed anti-HBs amounts of more than 10 IU/L at 1 month after vaccination.
INTERPRETATION: Strong immunological memory persists more than 10 years after immunisation of infants and adolescents with a primary course of vaccination. Booster doses of vaccine do not seem necessary to ensure long-term protection.

PMID 16226616  Lancet. 2005 Oct 15-21;366(9494):1379-84. doi: 10.1016/・・・
著者: Robert Steffen, Isis Amitirigala, Margot Mutsch
雑誌名: J Travel Med. 2008 May-Jun;15(3):145-6. doi: 10.1111/j.1708-8305.2008.00198.x.
Abstract/Text
PMID 18494690  J Travel Med. 2008 May-Jun;15(3):145-6. doi: 10.1111/j.・・・
著者: K C Kain, G D Shanks, J S Keystone
雑誌名: Clin Infect Dis. 2001 Jul 15;33(2):226-34. doi: 10.1086/321817. Epub 2001 Jun 14.
Abstract/Text As international travel becomes increasingly common and resistance to antimalarial drugs escalates, a growing number of travelers are at risk for contracting malaria. Parasite resistance to chloroquine and proguanil and real or perceived intolerance among patients to standard prophylactic agents such as mefloquine have highlighted the need for new antimalarial drugs. Promising new regimens include atovaquone and proguanil, in combination; primaquine; and a related 8-aminoquinoline, tafenoquine. These agents are active against the liver stage of the malaria parasite and therefore can be discontinued shortly after the traveler leaves an area where malaria is endemic, which encourages adherence to the treatment regimen. Part 1 of this series reviews currently recommended chemoprophylactic drug regimens, and part 2 will focus on 8-aminoquinoline drugs.

PMID 11418883  Clin Infect Dis. 2001 Jul 15;33(2):226-34. doi: 10.1086・・・
著者: Patricia Schlagenhauf, Miriam Adamcova, Loredana Regep, Martin T Schaerer, Hans-Georg Rhein
雑誌名: Malar J. 2010 Dec 9;9:357. doi: 10.1186/1475-2875-9-357. Epub 2010 Dec 9.
Abstract/Text BACKGROUND: Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis.
METHODS: A literature search to update the status of mefloquine as a malaria chemoprophylaxis.
RESULTS: Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerability of mefloquine and the use of this medication by groups at high risk of malaria.
DISCUSSION: Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors.
CONCLUSION: The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline.

PMID 21143906  Malar J. 2010 Dec 9;9:357. doi: 10.1186/1475-2875-9-357・・・
著者: Lin H Chen, Mary E Wilson, Patricia Schlagenhauf
雑誌名: JAMA. 2006 Nov 8;296(18):2234-44. doi: 10.1001/jama.296.18.2234.
Abstract/Text CONTEXT: Long-term travelers, defined here as those traveling for periods of 6 months or longer, face particular challenges regarding malaria prevention. Current guidelines for malaria prevention primarily address prevention of Plasmodium falciparum infections in short-term travelers.
OBJECTIVES: To examine the risk of malaria in long-term travelers, recent developments in personal protective measures, and the safety and tolerability of malaria chemoprophylaxis during long-term use and to consider prevention strategies including continuous chemoprophylaxis, stand-by emergency self-treatment, seasonal prophylaxis, and strategies to prevent primary infection and relapses from P vivax malaria.
EVIDENCE ACQUISITION: Comprehensive search of scientific publications including MEDLINE via both OVID and PubMED for relevant studies and articles with a cutoff date of July 2006, using the search terms long-term travel and malaria prevention, long-term malaria chemoprophylaxis, and insect repellent and malaria. Additional references were obtained from searching the bibliographies of the selected articles, from dissertations, and from the proceedings of relevant conferences on travel medicine. There were no language restrictions.
EVIDENCE SYNTHESIS: Long-term travelers have a higher risk of malaria than short-term travelers. Long-term travelers underuse personal protective measures and adhere poorly to continuous chemoprophylaxis regimens. A number of strategies are used during long-term stays: discontinuation of chemoprophylaxis after the initial period, sequential regimens with different medications for chemoprophylaxis, stand-by emergency self-treatment, and seasonal chemoprophylaxis targeting high-incidence periods or locations. All strategies have advantages and drawbacks. Counterfeit drugs sold in countries endemic for malaria pose serious concern for long-term travelers who purchase their medications overseas. Vivax malaria causes significant illness in travelers, but relapses of vivax malaria are not prevented with the current first-line chemoprophylaxis regimens. Consensus guidelines are needed for prevention of malaria in long-term travelers.
CONCLUSIONS: Prevention of malaria in long-term travelers is a complex issue and requires expert advice from travel medicine specialists. Recommendations for prevention of malaria in long-term travelers must be individualized.

PMID 17090770  JAMA. 2006 Nov 8;296(18):2234-44. doi: 10.1001/jama.296・・・
著者: Frederique A Jacquerioz, Ashley M Croft
雑誌名: Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006491. doi: 10.1002/14651858.CD006491.pub2. Epub 2009 Oct 7.
Abstract/Text BACKGROUND: Malaria infects 10,000 to 30,000 international travellers each year. It can be prevented through anti-mosquito measures and drug prophylaxis. However, antimalaria drugs have adverse effects which are sometimes serious.
OBJECTIVES: To compare the effects of currently used antimalaria drugs when given as prophylaxis to non-immune adult and child travellers who are travelling to regions with Plasmodium falciparum resistance to chloroquine. Specifically, to assess the efficacy, safety, and tolerability of atovaquone-proguanil, doxycycline, and mefloquine compared to each other, and also when compared to chloroquine-proguanil and to primaquine.
SEARCH STRATEGY: In August 2009 we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 4), MEDLINE, EMBASE, LILACS, BIOSIS, mRCT, and reference lists. We handsearched conference proceedings and one specialist journal, and contacted researchers and drug companies. We searched PubMed for drug-related deaths.
SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of any antimalaria drug regimen currently used by non-immune international travellers.
DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed eligibility and risk of bias using a standardized data collection form. We resolved any disagreement through discussion. We combined dichotomous outcomes using risk ratio (RR) and continuous data using mean difference (MD), presenting both with 95% confidence intervals (CI).
MAIN RESULTS: Eight trials (4240 participants) met the inclusion criteria. Evidence on comparative efficacy from head-to-head comparisons was limited. Atovaquone-proguanil compared to doxycycline had similar adverse events reported. Compared to mefloquine, atovaquone-proguanil users had fewer reports of any adverse effect (RR 0.72, 95% CI 0.6 to 0.85), gastrointestinal adverse effects (RR 0.54, 95% CI 0.42 to 0.7), neuropsychiatric adverse events (RR 0.86, 95% CI 0.75 to 0.99), and neuropsychiatric adverse effects (RR 0.49, 95% CI 0.38 to 0.63), besides a better total mood disturbance score (MD -7.20, 95% CI -10.79 to -3.61). Similarly, doxycycline users had fewer reported neuropsychiatric events than mefloquine users (RR 0.84, 95% CI 0.73 to 0.96). We also examined these three regimens against chloroquine-proguanil; this latter regimen had more reports of any adverse effect (RR 0.84, 95% CI 0.73 to 0.96) and of gastrointestinal adverse effects (RR 0.71, 95% CI 0.6 to 0.85).
AUTHORS' CONCLUSIONS: Atovaquone-proguanil and doxycycline are the best tolerated regimens, and mefloquine is associated with adverse neuropsychiatric outcomes.

PMID 19821371  Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006491. do・・・
著者: Karin Leder, Jim Black, Dan O'Brien, Zoe Greenwood, Kevin C Kain, Eli Schwartz, Graham Brown, Joseph Torresi
雑誌名: Clin Infect Dis. 2004 Oct 15;39(8):1104-12. doi: 10.1086/424510. Epub 2004 Sep 27.
Abstract/Text BACKGROUND: Malaria is a common and important infection in travelers.
METHODS: We have examined data reported to the GeoSentinel surveillance network to highlight characteristics of malaria in travelers.
RESULTS: A total of 1140 malaria cases were reported (60% of cases were due to Plasmodium falciparum, 24% were due to Plasmodium vivax). Male subjects constituted 69% of the study population. The median duration of travel was 34 days; however, 37% of subjects had a travel duration of < or =4 weeks. The majority of travellers did not have a pretravel encounter with a health care provider. Most cases occurred in travelers (39%) or immigrants/refugees (38%). The most common reasons for travel were to visit friends/relatives (35%) or for tourism (26%). Three-quarters of infections were acquired in sub-Saharan Africa. Severe and/or complicated malaria occurred in 33 cases, with 3 deaths. Compared with others in the GeoSentinel database, patients with malaria had traveled to sub-Saharan Africa more often, were more commonly visiting friends/relatives, had traveled for longer periods, presented sooner after return, were more likely to have a fever at presentation, and were less likely to have had a pretravel encounter. In contrast to immigrants and visitors of friends or relatives, a higher proportion (73%) of the missionary/volunteer group who developed malaria had a pretravel encounter with a health care provider. Travel to sub-Saharan Africa and Oceania was associated with the greatest relative risk of acquiring malaria.
CONCLUSIONS: We have used a global database to identify patient and travel characteristics associated with malaria acquisition and characterized differences in patient type, destinations visited, travel duration, and malaria species acquired.

PMID 15486832  Clin Infect Dis. 2004 Oct 15;39(8):1104-12. doi: 10.108・・・
著者: R Steffen, E Fuchs, J Schildknecht, U Naef, M Funk, P Schlagenhauf, P Phillips-Howard, C Nevill, D Stürchler
雑誌名: Lancet. 1993 May 22;341(8856):1299-303.
Abstract/Text There is much confusion over which malaria chemoprophylaxis should be used in areas such as East Africa. We did two consecutive studies between 1985 and 1991 to assess the efficacy and side-effects of malaria chemoprophylaxis in short-term travellers to East Africa. All passengers returning from Kenya to Europe received an in-flight questionnaire and a second one three months later. Any report of documented malaria or of admission to hospital for possible side-effects was verified with the physician. 145 003 travellers completed questionnaires. Among the 139 164 who stayed in East Africa for less than one year, 296 cases of confirmed malaria were reported (275 due to P falciparum). In people who used no chemoprophylaxis, the incidence of falciparum malaria was 1.2% per month. Prophylactic effectiveness was 91% (95% Cl 85 to 94) for mefloquine, 82% (71 to 89) for pyrimethamine and sulfadoxine, 72% (56 to 82) for chloroquine plus proguanil, and 10 to 42% for chloroquine at various doses. Rates of side-effects, which were usually mild, were 18.8% for mefloquine users, 17.1% and 18.6% for chloroquine 300 mg and 600 mg base per week, respectively, 30.1% for chloroquine plus proguanil, and 11.7% for sulfadoxine and pyrimethamine. Mefloquine is significantly more effective than chloroquine plus proguanil for malaria prophylaxis in short-term tourists visiting East Africa and has a tolerance similar to that of chloroquine used alone.

PMID 8098447  Lancet. 1993 May 22;341(8856):1299-303.
著者: Patricia Schlagenhauf, Alois Tschopp, Richard Johnson, Hans D Nothdurft, Bernhard Beck, Eli Schwartz, Markus Herold, Bjarne Krebs, Olivia Veit, Regina Allwinn, Robert Steffen
雑誌名: BMJ. 2003 Nov 8;327(7423):1078. doi: 10.1136/bmj.327.7423.1078.
Abstract/Text OBJECTIVE: To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers.
DESIGN: Randomised, double blind, study with placebo run-in phase.
SETTING: Travel clinics in Switzerland, Germany, and Israel.
MAIN OUTCOME MEASURE: Proportion of participants in each treatment arm with subjectively moderate or severe adverse events.
PARTICIPANTS: 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil.
RESULTS: A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013).
CONCLUSIONS: Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.

PMID 14604928  BMJ. 2003 Nov 8;327(7423):1078. doi: 10.1136/bmj.327.74・・・
著者: Pamela Rendi-Wagner, Herwig Kollaritsch
雑誌名: Clin Infect Dis. 2002 Mar 1;34(5):628-33. doi: 10.1086/338640. Epub 2002 Jan 16.
Abstract/Text Travelers' diarrhea is the most common health impairment in persons visiting developing countries, affecting 20% to >50% of tourists. Although it is usually benign, travelers' diarrhea represents a considerable socioeconomic burden for both the traveler and the host country. The most common enteropathogens are enterotoxigenic and enteroaggregative Escherichia coli. Travelers' compliance with dietary precautionary measures is poor. Despite the excellent protection rates provided by antibiotics, routine administration of prophylaxis is currently not recommended because of potential adverse reactions. Of the various antibiotics that have been tested, quinolones are considered to be the first choice worldwide; however, quinolone-resistant pathogens are increasingly being isolated. Because it is frequently administered and provides only moderate protection, bismuth subsalicylate is not considered a recommendable option for prophylaxis in Europe, where it is rarely available anyhow. To date, no probiotic has been able to demonstrate clinically relevant protection worldwide. In conclusion, there is no satisfactory prophylactic option, and worldwide monitoring of antimicrobial susceptibility patterns and the search for novel antimicrobial agents, such as nonabsorbed antibiotics, and nonantibiotic medications should continue.

PMID 11803509  Clin Infect Dis. 2002 Mar 1;34(5):628-33. doi: 10.1086/・・・
著者: Seif S Al-Abri, Nick J Beeching, Fred J Nye
雑誌名: Lancet Infect Dis. 2005 Jun;5(6):349-60. doi: 10.1016/S1473-3099(05)70139-0.
Abstract/Text Traveller's diarrhoea affects over 50% of travellers to some destinations and can disrupt holidays and business trips. This review examines the main causes and epidemiology of the syndrome, which is associated with poor public health infrastructure and hygiene practices, particularly in warmer climates. Although travellers may be given common sense advice on avoidance of high-risk foods and other measures to prevent traveller's diarrhoea, adherence to such advice is sometimes difficult and the evidence for its effectiveness is contradictory. However, non-antimicrobial means for prevention of traveller's diarrhoea are favoured in most settings. A simple stepwise approach to the management of traveller's diarrhoea includes single doses or 3-day courses of antimicrobials, often self administered. The antibiotics of choice are currently fluoroquinolones or azithromycin, with an emerging role for rifaximin. In the long term, there will be greater benefit and effect on the health of local inhabitants and travellers from improving public health and hygiene standards at tourist destinations.

PMID 15919621  Lancet Infect Dis. 2005 Jun;5(6):349-60. doi: 10.1016/S・・・
著者: Zoe Greenwood, James Black, Leisa Weld, Daniel O'Brien, Karin Leder, Frank Von Sonnenburg, Prativa Pandey, Eli Schwartz, Bradley A Connor, Graham Brown, David O Freedman, Joseph Torresi, GeoSentinel Surveillance Network
雑誌名: J Travel Med. 2008 Jul-Aug;15(4):221-8. doi: 10.1111/j.1708-8305.2008.00203.x.
Abstract/Text BACKGROUND: Data on relative rates of acquisition of gastrointestinal infections by travelers are incomplete. The objective of this study was to analyze infections associated with oral ingestion of pathogens in international travelers in relation to place of exposure.
METHODS: We performed a multicenter, retrospective observational analysis of 6,086 travelers ill enough with any gastrointestinal infection to seek medical care at a GeoSentinel clinic after completion of travel during 2000 to 2005. We determined regional and country-specific reporting rate ratios (RRRs) in comparison to risk in northern and western Europe.
RESULTS: Travel to sub-Saharan Africa (RRR = 282), South America (RRR = 203), and South Asia (RRR = 890) was associated with the greatest rate of gastrointestinal infections. RRRs were moderate (25-142) for travel to Oceania, the Middle East, North Africa, Central America, the Caribbean, and Southeast Asia. RRRs were least (<28) following travel to southern, central, and eastern Europe; North America; Northeast Asia; and Australasia. Income level of the country visited was inversely proportional to the RRR for gastrointestinal infection. For bacterial and parasitic infections examined separately, the regions group in the same way. RRRs could be estimated for 28 individual countries and together with regional data were used to derive a global RRR map for travel-related gastrointestinal infection.
CONCLUSIONS: This analysis of morbidity associated with oral ingestion of pathogens abroad determines which parts of the world currently are high-risk destinations.

PMID 18666921  J Travel Med. 2008 Jul-Aug;15(4):221-8. doi: 10.1111/j.・・・
著者: David R Hill, Edward T Ryan
雑誌名: BMJ. 2008 Oct 6;337:a1746. Epub 2008 Oct 6.
Abstract/Text
PMID 18838421  BMJ. 2008 Oct 6;337:a1746. Epub 2008 Oct 6.
著者: R Steffen, F Collard, N Tornieporth, S Campbell-Forrester, D Ashley, S Thompson, J J Mathewson, E Maes, B Stephenson, H L DuPont, F von Sonnenburg
雑誌名: JAMA. 1999 Mar 3;281(9):811-7.
Abstract/Text CONTEXT: Traveler's diarrhea (TD) can incapacitate travelers. Characteristics of TD could be helpful in identifying individuals who might benefit from a vaccine against TD.
OBJECTIVE: To determine epidemiology, etiology, and impact of TD in Jamaica. Design Two-armed, cross-sectional survey conducted between March 1996 and May 1997.
SETTING: Sangster International Airport and 10 hotels in Montego Bay area, Jamaica.
SUBJECTS: To investigate epidemiology and impact, 30369 short-term visitors completed a questionnaire just before boarding their homebound aircrafts. To investigate etiology, 322 patients (hotel guests) with TD provided stool samples.
MAIN OUTCOME MEASURES: Attack and incidence rates of reported diarrhea and of classically defined TD (> or =3 unformed stool samples in 24 hours and > or =1 accompanying symptom), incapacity, risk factors, and etiology.
RESULTS: The attack rate for diarrhea was 23.6% overall, with 11.7% having classically defined TD. For a mean duration of stay of 4 to 7 days, the incidence rate was 20.9% (all TD) and 10.0% (classic TD). Among airport respondents, the incapacity lasted a mean of 11.6 hours. Less than 3% of all travelers avoided potentially high-risk food and beverages. The most frequently detected pathogens were enterotoxigenic Escherichia coli, Rotavirus, and Salmonella species.
CONCLUSIONS: A realistic plan for reducing TD is needed. Preventive measures such as the improvement of hygienic conditions at the destination, and/or the development of vaccines against the most frequent pathogens associated with TD may contribute toward achieving this goal.

PMID 10071002  JAMA. 1999 Mar 3;281(9):811-7.
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: Juliette Morgan, Shari L Bornstein, Adam M Karpati, Michael Bruce, Carole A Bolin, Constance C Austin, Christopher W Woods, Jairam Lingappa, Carl Langkop, Belinda Davis, Donald R Graham, Mary Proctor, David A Ashford, Mary Bajani, Sandra L Bragg, Kathleen Shutt, Bradley A Perkins, Jordan W Tappero, Leptospirosis Working Group
雑誌名: Clin Infect Dis. 2002 Jun 15;34(12):1593-9. doi: 10.1086/340615. Epub 2002 May 24.
Abstract/Text We investigated an outbreak of leptospirosis among athletes and community residents after a triathlon was held in Springfield, Illinois. A telephone survey was conducted to collect clinical information and data on possible risk factors, community surveillance was established, and animal specimens and lake water samples were collected to determine the source of the leptospiral contamination. A total of 834 of 876 triathletes were contacted; 98 (12%) reported being ill. Serum samples obtained from 474 athletes were tested; 52 of these samples (11%) tested positive for leptospirosis. Fourteen (6%) of 248 symptomatic community residents tested positive for leptospirosis. Heavy rains that preceded the triathlon are likely to have increased leptospiral contamination of Lake Springfield. Among athletes, ingestion of 1 or more swallows of lake water was a predominant risk factor for illness. This is the largest outbreak of leptospirosis that has been reported in the United States. Health care providers and occupational and recreational users of bodies of freshwater in the United States should be aware of the risk of contracting leptospirosis, particularly after heavy rains.

PMID 12032894  Clin Infect Dis. 2002 Jun 15;34(12):1593-9. doi: 10.108・・・
著者: Stefan Brockmann, Isolde Piechotowski, Oswinde Bock-Hensley, Christian Winter, Rainer Oehme, Stefan Zimmermann, Katrin Hartelt, Enno Luge, Karsten Nöckler, Thomas Schneider, Klaus Stark, Andreas Jansen
雑誌名: BMC Infect Dis. 2010 Apr 10;10:91. doi: 10.1186/1471-2334-10-91. Epub 2010 Apr 10.
Abstract/Text BACKGROUND: In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infection an epidemiological investigation was performed.
METHODS: Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A confirmed case patient was defined as a clinical case (i.e. fever and at least one additional symptom suggestive for leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscopic agglutination testing. Rainfall and temperature records were obtained.
RESULTS: A total of 142 of 507 triathletes were contacted; among these, five confirmed leptospirosis cases were found. Open wounds were identified as the only significant risk factor for illness (p = 0.02). Heavy rains that preceded the swimming event likely increased leptospiral contamination of the Neckar River.
DISCUSSION: This is the first outbreak of leptospirosis related to a competitive sports event in Germany. Among people with contact to freshwater, the risk of contracting leptospirosis should be considered by health care providers also in temperate countries, particularly in the summer after heavy rains.

PMID 20380736  BMC Infect Dis. 2010 Apr 10;10:91. doi: 10.1186/1471-23・・・
著者: Christoph Radl, Maria Müller, Sandra Revilla-Fernandez, Stefanie Karner-Zuser, Alfred de Martin, Ulrike Schauer, Franz Karner, Gerold Stanek, Peter Balcke, Andreas Hallas, Herbert Frank, Albert Fürnschlief, Friedrich Erhart, Franz Allerberger
雑誌名: Wien Klin Wochenschr. 2011 Dec;123(23-24):751-5. doi: 10.1007/s00508-011-0100-2. Epub 2011 Nov 24.
Abstract/Text We report on the first documented outbreak of leptospirosis in Austria. In July 2010, four cases of serologically confirmed leptospirosis occurred in athletes after a triathlon held in Langau. Heavy rains preceded the triathlon (rainfall: 22 mm). The index case (Patient A) was a 41-year-old previously healthy male, who was admitted to hospital A on July 8 with a four-day history of fever up to 40°C that began 14 days after attending the triathlon event. On July 7, patient B, a 42-year-old male, was admitted to the same hospital, with signs and symptoms of kidney failure. Hemodialysis was performed every other day for 3 weeks. While the serum drawn on the day of admission was negative for antibodies against Leptospira, a specimen from July 28 tested positive with Leptospira interrogans. On July 11, patient C, a 40-year-old male, was admitted to hospital B for nephritis. On July 14, patient D, a 44-year-old male, was admitted to hospital C with a ten days history of intermittent fever, mild dry cough and headache. Our report underlines that in Austria recreational users of bodies of freshwater must be aware of an existing risk of contracting leptospirosis, particularly after heavy rains. The suppressive influence of a triathlon on the immune system is well documented and therefore an outbreak in this population group can be seen as a sensitive indicator concerning possible risk for the general population.

PMID 22105111  Wien Klin Wochenschr. 2011 Dec;123(23-24):751-5. doi: 1・・・
著者: Eyal Meltzer, Galit Artom, Esther Marva, Marc Victor Assous, Galia Rahav, Eli Schwartzt
雑誌名: Emerg Infect Dis. 2006 Nov;12(11):1696-700. doi: 10.3201/eid1211.060340.
Abstract/Text Schistosomiasis is increasingly encountered among travelers returning from the tropics; signs and symptoms of travelers may differ from those of local populations. During 1993-2005, schistosomiasis was diagnosed in 137 Israeli travelers, most of whom were infected while in sub-Saharan Africa. Clinical findings compatible with acute schistosomiasis were recorded for 75 (66.4%) patients and included fever (71.3%), respiratory symptoms (42.9%), and cutaneous symptoms (45.2%). At time of physical examination, 42 patients (37.1%) still had symptoms of acute schistosomiasis, chronic schistosomiasis had developed in 23 (20.4%), and 48 (42.5%) were asymptomatic. Of patients who were initially asymptomatic, chronic schistosomiasis developed in 26%. Diagnosis was confirmed by serologic testing for 87.6% of patients, but schistosome ova were found in only 25.6%. We conclude that acute schistosomiasis is a major clinical problem among travelers, diagnostic and therapeutic options for acute schistosomiasis are limited, and asymptomatic travelers returning from schistosomiasis-endemic areas should be screened and treated.

PMID 17283619  Emerg Infect Dis. 2006 Nov;12(11):1696-700. doi: 10.320・・・
著者: Andrew M Luks, Paul S Auerbach, Luanne Freer, Colin K Grissom, Linda E Keyes, Scott E McIntosh, George W Rodway, Robert B Schoene, Ken Zafren, Peter H Hackett
雑誌名: Wilderness Environ Med. 2019 Dec;30(4S):S3-S18. doi: 10.1016/j.wem.2019.04.006. Epub 2019 Jun 24.
Abstract/Text To provide guidance to clinicians about best preventive and therapeutic practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each form of acute altitude illness that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2010 and subsequently updated as the WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness in 2014.

Copyright © 2019 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.
PMID 31248818  Wilderness Environ Med. 2019 Dec;30(4S):S3-S18. doi: 10・・・
著者: Martha C Tissot van Patot, Guy Leadbetter, Linda E Keyes, Kirsten M Maakestad, Sheryl Olson, Peter H Hackett
雑誌名: High Alt Med Biol. 2008 Winter;9(4):289-93. doi: 10.1089/ham.2008.1029.
Abstract/Text Previous studies have shown low-dose acetazolamide to be effective in preventing AMS in persons already at high altitude and then moving higher, a relatively low risk situation. We wished to evaluate prophylactic administration of low-dose acetazolamide for reducing the incidence and severity of AMS in a high-risk setting: rapid ascent from 1600 to 4300 m. We performed a double-blind, randomized, placebo-controlled study with human subjects (n=44) exposed to 4300 m for 24 h. Subjects were treated for 3 days prior to ascent to 4300 m and during day 1 at altitude with placebo (n=22) or acetazolamide 250 mg/day (125 mg bid, n=22). AMS diagnosis required both an AMS-C score from the Environmental Symptom Questionnaire-III>or=0.7 and a Lake Louise Symptom (LLS) questionnaire score>or=3 plus headache. Acetazolamide reduced the incidence of AMS compared to placebo-treated subjects (14% vs. 45%, respectively, p=0.02), and the number needed to treat was 3. The AMS-C and LLS scores were lower in acetazolamide-treated subjects, indicating less severe AMS. Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting.

PMID 19115912  High Alt Med Biol. 2008 Winter;9(4):289-93. doi: 10.108・・・

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