今日の臨床サポート

マラリア

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:2021/07/28
参考ガイドライン:
  1. 熱帯病治療薬研究班: 「寄生虫症薬物治療の手引き」2020年8月改訂版
  1. World Health Organization(WHO): Guidelines for the treatment of malaria - Third edition
  1. Centers for Disease Control and Prevention(CDC): Treatment of Malaria: Guidelines for Clinicians (United States)
  1. Public Health England Advisory Committee on Malaria Prevention in UK Travellers: UK malaria treatment guidelines 2016
患者向け説明資料

概要・推奨   

  1. 高齢者ではマラリアが重症化しやすく致命率が高い(推奨度2)
  1. サハラ砂漠以南ではマラリアの罹患リスクが最も高い(推奨度2)
  1. 発熱や脾腫の身体所見、高ビリルビン血症や血小板低下の検査所見はマラリアを疑うために有用な所見である(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
  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
  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
  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
  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。
  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
  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
  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
  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
  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
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、国内承認により使用可能となった薬剤(リアメット、プリマキン)の情報更新、薬剤耐性マラリアの情報追加、国内承認された検査機器の情報追加、海外で新規承認された抗マラリア薬の情報追加を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. マラリアは、マラリア原虫(Plasmodium spp.)を運ぶ雌のハマダラカ(Anopheles spp.)の吸血で感染する発熱性の疾患である。
 
マラリア原虫の生活環

ハマダラカが吸血することで体内に侵入する(スポロゾイト)。マラリア原虫はまず肝臓に感染し、潜伏期間を経て成長し(シゾント)、血液中に数千の娘細胞(メロゾイト)を放出する(マラリアが発症する)。赤血球に寄生した娘細胞(トロフォゾイト)は赤血球内で成長して破裂し、娘細胞の放出を繰り返す。これにより、赤血球のマラリア原虫寄生率が高くなり、重症化する。血液中のマラリア原虫の一部(ガメトサイト)は蚊に吸血されることで再び蚊に感染、蚊の中で成長して、蚊の刺咬により人に感染できる状態となる。

 
吸血するハマダラカ

マラリアを媒介するハマダラカは吸血時に臀部を上を向ける特徴がある。

 
  1. 蚊を介して人と人の間で感染するマラリアは熱帯熱マラリア原虫(P. falciparum)、三日熱マラリア原虫(P. vivax)、四日熱マラリア原虫(P. malariae)、卵形マラリア原虫(P. ovale)の4種類がある。近年はこれに東南アジアのサルマラリア原虫(P. knowlesi)を加えて、5種類とすることもある。
 
赤血球に感染した熱帯熱マラリア原虫

マラリア原虫が感染した赤血球から破裂して複数のメロゾイトが放出される

 
  1. 特に熱帯熱マラリアは発症後短期間で重症化しやすく、多臓器不全や死亡などの転帰をたどることがある。
  1. 熱帯熱マラリアの流行はサハラ砂漠以南の西アフリカ、ドミニカ共和国、ハイチで多く認める。
  1. 三日熱マラリアはメキシコ、中米、中東、北アフリカで多く認める。
  1. 熱帯熱マラリアと三日熱マラリアのどちらの流行も認める地域は、インド、インド亜大陸、南米、中米、東南アジア、オセアニア、パプアニューギニアなどである。
  1. 四日熱マラリアの流行は、まれではあるがほとんどの地域で認める(特に中央アフリカ、西アフリカ)。
  1. 卵形マラリアの流行は主に西アフリカで認める。
  1. 一般にマラリア流行国は社会経済状態の低い国に多い。
  1. WHOによる報告[1]によると2019年にマラリアは熱帯・亜熱帯地域の87カ国での流行を認め<図表>、2019年に推定で年間2億2900万人がマラリアに感染、40.9万人が死亡しているとされる。
  1. 人にも感染するサルマラリアの一種として注目されているP. knowlesiは、1965年にマレーシアで人への自然感染が報告されて以降、死亡例を含めて東南アジアでの感染報告が続き、米国、フランス、日本などへの輸入感染報告も認められる[2][3][4]
 
渡航者におけるマラリア罹患のリスク地域

マラリアの流行地域は熱帯地域に広がっているが、熱帯熱マラリア(上図)は特に西アフリカ、中央アフリカで感染のリスクが高い。三日熱マラリア(下図)

 
  1. 世界における死亡例の5歳未満の小児割合は2000年には84%を占めたが、2019年には67%まで減少した[1]
  1. 日本国内においても、かつて三日熱マラリアは土着の感染症であり、南西諸島では熱帯熱マラリアも認めた。
  1. 1900年頃には年間1,000人を超えるマラリアによる死亡数が報告されたが、大正期よりマラリア症例は減少した[5]
  1. 終戦後に帰還兵による国内のマラリア症例数が増加したものの、その後国内発生数は急速に減少し、1962年以降にシナハマダラカを介した国内のマラリア伝播の報告はない[6]
  1. 過去10年間では、国内では輸入マラリアとして年間40~78症例[7]の報告がされている。
  1. 非流行地域の輸入マラリアによる致命率は、英国において1987~2006年までに報告された熱帯熱マラリアでは0.73%(184/25,054)とされる[8]
  1. 三日熱マラリア、卵形マラリアでは、急性期の感染治療の後、数カ月~数年以内(多くは3~45週間)[4]に肝細胞に潜伏する休眠原虫(ヒプノゾイト)による再発を認めることがある。
  1. マラリアの罹患を予防するためには、抗マラリア薬を用いた予防内服やDEET(ディート)やicaridin(イカリジン、別名:picaridin ピカリジン)などの忌避剤の使用が有効である。
  1. 2020年時点で、マラリアワクチン(RTS,S/AS01)の臨床第Ⅲ相パイロット試験がケニア、マラウィ、ガーナで実施されているが、正式に承認されたマラリアワクチンはない。
問診・診察のポイント  
  1. 現在、マラリアは国内での感染を認めず、発熱患者に対して渡航歴を聴取することが診断に重要である。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
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: Anu Kantele, T Sakari Jokiranta
雑誌名: Clin Infect Dis. 2011 Jun;52(11):1356-62. doi: 10.1093/cid/cir180.
Abstract/Text Human malaria has been known to be caused by 4 Plasmodium species, with Plasmodium falciparum causing the most-severe disease. Recently, numerous reports have described human malaria caused by a fifth Plasmodium species, Plasmodium knowlesi, which usually infects macaque monkeys. Hundreds of human cases have been reported from Malaysia, several cases have been reported in other Southeast Asian countries, and a few cases have been reported in travelers visiting these areas. Similarly to P. falciparum, P. knowlesi can cause severe and even fatal cases of disease that are more severe than those caused by the other Plasmodium species. Polymerase chain reaction is of value for diagnosis because P. knowlesi infection is easily misdiagnosed as less dangerous Plasmodium malariae infection with conventional microscopy. P. knowlesi infection should be suspected in patients who are infected with malaria in Southeast Asia. If human-mosquito-human transmission were to occur, the disease could spread to new areas where the mosquito vectors live, such as the popular tourist areas in western India.

PMID 21596677  Clin Infect Dis. 2011 Jun;52(11):1356-62. doi: 10.1093/・・・
著者: Antoine Berry, Xavier Iriart, Nathalie Wilhelm, Alexis Valentin, Sophie Cassaing, Benoit Witkowski, Françoise Benoit-Vical, Sandie Menard, David Olagnier, Judith Fillaux, Stephane Sire, Alain Le Coustumier, Jean-François Magnaval
雑誌名: Am J Trop Med Hyg. 2011 Apr;84(4):535-8. doi: 10.4269/ajtmh.2011.10-0622.
Abstract/Text We report a case of imported Plasmodium knowlesi malaria in a French tourist following a vacation in Thailand. This case shows, first, tourists may contract knowlesi malaria even only staying on the beach and second, the diagnosis remains difficult, even with polymerase chain reaction methods.

PMID 21460005  Am J Trop Med Hyg. 2011 Apr;84(4):535-8. doi: 10.4269/a・・・
著者: Anna M Checkley, Adrian Smith, Valerie Smith, Marie Blaze, David Bradley, Peter L Chiodini, Christopher J M Whitty
雑誌名: BMJ. 2012 Mar 27;344:e2116. Epub 2012 Mar 27.
Abstract/Text OBJECTIVES: To determine which travellers with malaria are at greatest risk of dying, highlighting factors which can be used to target health messages to travellers.
DESIGN: Observational study based on 20 years of UK national data.
SETTING: National register of malaria cases.
PARTICIPANTS: 25,054 patients notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and 2006.
MAIN OUTCOME MEASURES: Comparison between those with falciparum malaria who died and non-fatal cases, including age, reason for travel, country of birth, time of year diagnosed, malaria prophylaxis used.
RESULTS: Mortality increased steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65 years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001 compared with 18-35 year olds. There were no deaths in the ≤ 5 year age group. Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to 13.3), P<0.001). Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds ratio 4.6 (3.1 to 9.9), P<0.001). Case fatality was particularly high from the Gambia. There was an inverse correlation in mortality between region of presentation and number of cases seen in the region (R(2) = 0.72, P<0.001). Most delay in fatal cases was in seeking care.
CONCLUSIONS: Most travellers acquiring malaria are of African heritage visiting friends and relatives. In contrast the risks of dying from malaria once acquired are highest in the elderly, tourists, and those presenting in areas in which malaria is seldom seen. Doctors often do not think of these as high risk groups for malaria; for this reason they are important groups to target in pre-travel advice.

PMID 22454091  BMJ. 2012 Mar 27;344:e2116. Epub 2012 Mar 27.
著者: J Whitworth, D Morgan, M Quigley, A Smith, B Mayanja, H Eotu, N Omoding, M Okongo, S Malamba, A Ojwiya
雑誌名: Lancet. 2000 Sep 23;356(9235):1051-6. doi: 10.1016/S0140-6736(00)02727-6.
Abstract/Text BACKGROUND: An association between HIV-1 and malaria is expected in theory, but has not been convincingly shown in practice. We studied the effects of HIV-1 infection and advancing immunosuppression on falciparum parasitaemia and clinical malaria.
METHODS: HIV-1-positive and HIV-1-negative adults selected from a population-based cohort in rural Uganda were invited to attend a clinic every 3 months (routine visits) and whenever they were sick (interim visits). At each visit, information was collected on recent fever, body temperature, and malaria parasites. Participants were assigned a clinical stage at each routine visit and had regular CD4-cell measurements.
FINDINGS: 484 participants made 7220 routine clinic visits between 1990 and 1998. Parasitaemia was more common at visits by HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001). At HIV-1-positive visits, lower CD4-cell counts were associated with higher parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%] vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024). Participants made 3377 interim visits. The risk of clinical malaria was significantly higher at visits by HIV-1-positive individuals than HIV-1-negative individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to increase with falling CD4-cell counts (p=0.052).
INTERPRETATION: HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia. This association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.

PMID 11009139  Lancet. 2000 Sep 23;356(9235):1051-6. doi: 10.1016/S014・・・
著者: Cheryl Cohen, Alan Karstaedt, John Frean, Juno Thomas, Nelesh Govender, Elizabeth Prentice, Leigh Dini, Jacky Galpin, Heather Crewe-Brown
雑誌名: Clin Infect Dis. 2005 Dec 1;41(11):1631-7. doi: 10.1086/498023. Epub 2005 Oct 26.
Abstract/Text BACKGROUND: Conflicting reports exist regarding the impact of human immunodeficiency virus (HIV) infection on the risk of severe malaria. We aimed to assess the effect of HIV infection status, advancing immunosuppression, and antimalarial immunity on the severity of malaria.
METHODS: A prospective cohort study was conducted. Consecutive hospitalized adult patients with falciparum malaria were tested for HIV antibodies and to determine CD4+ T cell count. Immunity to malaria was assessed by obtaining a history of childhood residence in an area where malaria is endemic. Patients were assessed for features of severe malaria.
RESULTS: Three hundred thirty-six patients were enrolled in the study, of whom 32 (10%) had severe malaria. The prevalence of HIV infection was 33%, and 111 patients (33%) were nonimmune to malaria. HIV-infected patients complained more frequently about respiratory and abdominal symptoms and less frequently about rigors and headache. Risk factors for severe malaria determined by multivariate analysis included being nonimmune to malaria, having a positive HIV serostatus, having an elevated parasite count, and having an increased white blood cell count. Risk of severe malaria was increased in HIV-infected patients with a CD4+ T cell count of < 200 x 10(6) cells/L (P < or = .001). Nonimmune HIV-infected patients were significantly more likely to have severe malaria (13 [36%] of 36 patients) than were nonimmune non-HIV-infected patients (9 [12%] of 75 patients; odds ratio, 4.15 [95% confidence interval, 1.57-10.97]; P = .003). HIV serostatus did not affect risk of severe malaria in the group from an area with endemicity (5 [7%] of 74 HIV-infected patients had severe malaria, and 5 [3%] of 151 non-HIV-infected patients had malaria; P = .248).
CONCLUSIONS: HIV-infected nonimmune adults are at increased risk of severe malaria. This risk is associated with a low CD4+ T cell count. This interaction is of great public health importance.

PMID 16267737  Clin Infect Dis. 2005 Dec 1;41(11):1631-7. doi: 10.1086・・・
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: 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: Steve M Taylor, Malcolm E Molyneux, David L Simel, Steven R Meshnick, Jonathan J Juliano
雑誌名: JAMA. 2010 Nov 10;304(18):2048-56. doi: 10.1001/jama.2010.1578. Epub 2010 Nov 5.
Abstract/Text CONTEXT: Malaria commonly infects residents of and travelers to tropical regions. The clinical features of infection are notoriously nonspecific but have not been comprehensively evaluated.
OBJECTIVE: To systematically review and synthesize data related to the predictive value of clinical findings for the diagnosis of malaria in endemic areas and in travelers returning from endemic areas.
DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: The databases of MEDLINE and EMBASE (1950-July 2010) were searched to identify studies published in the English language of endemic and "imported" (acquired during travel) malaria. Additional studies were identified from reference lists. Studies were included that had patients suspected of having acute malaria (usually because of fever) and compared the presence or absence of clinical findings with blood smear confirmation. Two authors independently identified studies, appraised study quality, and extracted data on the patient population, outcome assessment, and clinical findings. Differences between reviewers were resolved by consensus.
DATA SYNTHESIS: Fourteen studies for endemic malaria were identified that met review criteria. Individual symptoms are of limited diagnostic utility but presence of splenomegaly (summary likelihood ratio [LR], 3.3; 95% confidence interval [CI], 2.0-4.7) or hepatomegaly (summary LR, 2.4; 95% CI, 1.6-3.6) make malaria more likely. Combinations of findings can affect the likelihood of malaria, but their performance varies by setting. Seven studies of imported malaria were identified. The presence of fever (LR, 5.1; 95% CI, 4.9-5.3), splenomegaly (summary LR, 6.5; 95% CI, 3.9-11.0), hyperbilirubinemia (LR, 7.3; 95% CI, 5.5-9.6), or thrombocytopenia (summary LR, 5.6; 95% CI, 4.1-7.5) make malaria more likely.
CONCLUSIONS: In endemic areas, the likelihood of malaria is increased by the presence of splenomegaly and hepatomegaly but individual findings are of limited utility and cannot reliably exclude malaria; combinations of findings may be useful to stratify risk in patients. In returning travelers, the clinical assessment can provide substantial diagnostic benefit, although all patients still require laboratory testing because malaria can be rapidly fatal.

PMID 21057136  JAMA. 2010 Nov 10;304(18):2048-56. doi: 10.1001/jama.20・・・
著者: Aubrey J Cunnington, J Brian de Souza, Michael Walther, Eleanor M Riley
雑誌名: Nat Med. 2011 Dec 18;18(1):120-7. doi: 10.1038/nm.2601. Epub 2011 Dec 18.
Abstract/Text In sub-Saharan Africa, invasive nontyphoid Salmonella (NTS) infection is a common and often fatal complication of Plasmodium falciparum infection. Induction of heme oxygenase-1 (HO-1) mediates tolerance to the cytotoxic effects of heme during malarial hemolysis but might impair resistance to NTS by limiting production of bactericidal reactive oxygen species. We show that co-infection of mice with Plasmodium yoelii 17XNL (Py17XNL) and Salmonella enterica serovar Typhimurium 12023 (Salmonella typhimurium) causes acute, fatal bacteremia with high bacterial load, features reproduced by phenylhydrazine-induced hemolysis or hemin administration. S. typhimurium localized predominantly in granulocytes. Py17XNL, phenylhydrazine and hemin caused premature mobilization of granulocytes from bone marrow with a quantitative defect in the oxidative burst. Inhibition of HO by tin protoporphyrin abrogated the impairment of resistance to S. typhimurium by hemolysis. Thus, a mechanism of tolerance to one infection, malaria, impairs resistance to another, NTS. Furthermore, HO inhibitors may be useful adjunctive therapy for NTS infection in the context of hemolysis.

PMID 22179318  Nat Med. 2011 Dec 18;18(1):120-7. doi: 10.1038/nm.2601.・・・
著者: Elizabeth A Reddy, Andrea V Shaw, John A Crump
雑誌名: Lancet Infect Dis. 2010 Jun;10(6):417-32. doi: 10.1016/S1473-3099(10)70072-4.
Abstract/Text Data on the prevalence and causes of community-acquired bloodstream infections in Africa are scarce. We searched three databases for studies that prospectively studied patients admitted to hospital with at least a blood culture, and found 22 eligible studies describing 58 296 patients, of whom 2051 (13.5%) of 15 166 adults and 3527 (8.2%) of 43 130 children had bloodstream infections. 1643 (29.1%) non-malaria bloodstream infections were due to Salmonella enterica (58.4% of these non-typhoidal Salmonella), the most prevalent isolate overall and in adults, and 1031 (18.3% overall) were due to Streptococcus pneumoniae, the most common isolate in children. Other common isolates included Staphylococcus aureus (531 infections; 9.5%) and Escherichia coli (412; 7.3%). Mycobacterium tuberculosis complex accounted for 166 (30.7%) of 539 isolates in seven studies that used mycobacterial culture techniques. HIV infection was associated with any bloodstream infection, particularly with S enterica and M tuberculosis complex bacteraemia. Where recorded, patients with bloodstream infections had an in-hospital case fatality of 18.1%. Our results show that bloodstream infections are common and associated with high mortality. Improved clinical microbiology services and reassessment of empirical treatment guidelines that account for the epidemiology of bloodstream infections might contribute to better outcomes.

2010 Elsevier Ltd. All rights reserved.
PMID 20510282  Lancet Infect Dis. 2010 Jun;10(6):417-32. doi: 10.1016/・・・
著者: Meghna Desai, Feiko O ter Kuile, François Nosten, Rose McGready, Kwame Asamoa, Bernard Brabin, Robert D Newman
雑誌名: Lancet Infect Dis. 2007 Feb;7(2):93-104. doi: 10.1016/S1473-3099(07)70021-X.
Abstract/Text We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100,000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.

PMID 17251080  Lancet Infect Dis. 2007 Feb;7(2):93-104. doi: 10.1016/S・・・
著者: Bertrand Lell, Peter G Kremsner
雑誌名: Antimicrob Agents Chemother. 2002 Aug;46(8):2315-20.
Abstract/Text
PMID 12121898  Antimicrob Agents Chemother. 2002 Aug;46(8):2315-20.
著者: R N Brogden, T M Speight, G S Avery
雑誌名: Drugs. 1975;9(4):251-91.
Abstract/Text Minocycline is a semi-synthetic tetracycline derivative which is well absorbed and distributed in body tissues and is suitable for twice daily administration. It appears to be as generally effective as other tetracyclines and analogues, but also to be effective in infections due to tetracycline-resistant staphylococci. Side-effects are typical of those of other tetracyclines, but minocycline has been associated with a high incidence of vertigo in some studies. On the other hand, minocycline appears to have little or no photosensitising potential. It is not yet clear whether minocycline can be safely used in patients with moderate or severe impairment of renal function, but if used in renal failure, the plasma urea concentration should be monitored.

PMID 1173232  Drugs. 1975;9(4):251-91.
著者: David G Lalloo, Delane Shingadia, Geoffrey Pasvol, Peter L Chiodini, Christopher J Whitty, Nicholas J Beeching, David R Hill, David A Warrell, Barbara A Bannister, HPA Advisory Committee on Malaria Prevention in UK Travellers
雑誌名: J Infect. 2007 Feb;54(2):111-21. doi: 10.1016/j.jinf.2006.12.003. Epub 2007 Jan 9.
Abstract/Text Malaria is the tropical disease most commonly imported into the UK, with 1500-2000 cases reported each year, and 10-20 deaths. Approximately three-quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other two species of Plasmodium: Plasmodium ovale or Plasmodium malariae. Mixed infections with more than 1 species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until 3 blood specimens have been examined by an experienced microscopist. There are no typical clinical features of malaria, even fever is not invariably present. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites; P. falciparum malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens or enzymes, although RDTs for other Plasmodium species are not as reliable. The treatment of choice for non-falciparum malaria is a 3-day course of oral chloroquine, to which only a limited proportion of P. vivax strains have gained resistance. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine. This must be avoided or given with caution under expert supervision in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. Uncomplicated P. falciparum malaria can be treated orally with quinine, atovaquone plus proguanil (Malarone) or co-artemether (Riamet); quinine is highly effective but poorly tolerated in prolonged dosage and is always supplemented by additional treatment, usually with oral doxycycline. ALL patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h, since patients can deteriorate suddenly, especially early in the course of treatment. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized), should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. In the UK, the treatment of choice for severe or complicated malaria is currently an infusion of intravenous quinine. This may exacerbate hypoglycaemia that can occur in malaria; patients treated with intravenous quinine therefore require careful monitoring. Intravenous artesunate reduces high parasite loads more rapidly than quinine and is more effective in treating severe malaria in selected situations. It can also be used in patients with contra-indications to quinine. Intravenous artesunate is unlicensed in the EU. Assistance in obtaining artesunate may be sought from specialist tropical medicine centres, on consultation, for named patients. Patients with severe or complicated malaria should be managed in a high dependency or intensive care environment. They may require haemodynamic support and management of acute respiratory distress syndrome, disseminated intravascular coagulation, renal impairment/failure, seizures, and severe intercurrent infections including gram-negative bacteraemia/septicaemia. Falciparum malaria in pregnancy is more likely to be severe and complicated: the placenta contains high levels of parasites. Stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. The treatment of choice for falciparum malaria in pregnancy is quinine; doxycycline is contraindicated in pregnancy but clindamycin can be substituted for it, and is equally effective. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy; after treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery when hypnozoite eradication can be considered. Children are over-represented in the incidence of malaria in the UK, probably because completely susceptible UK-born children accompany their overseas-born parents on visits to family and friends in endemic areas. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints; the diagnosis must always be sought in a feverish or very sick child who has visited malaria-endemic areas. Children can be treated with most of the antimalarial regimens which are effective in adults, with appropriate dosage adjustment. Doxycycline plus quinine should not be given to children under 12 years as doxycycline is contraindicated in this age group, but clindamycin can be substituted for doxycycline, and pyrimethamine-sulfadoxine (Fansidar) may also be an effective substitute. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas.

PMID 17215045  J Infect. 2007 Feb;54(2):111-21. doi: 10.1016/j.jinf.20・・・
著者: Klara Sondén, Katja Wyss, Irina Jovel, Antero Vieira da Silva, Anton Pohanka, Muhammad Asghar, Manijeh Vafa Homann, Lars L Gustafsson, Urban Hellgren, Anna Färnert
雑誌名: Clin Infect Dis. 2017 Jan 15;64(2):199-206. doi: 10.1093/cid/ciw710. Epub 2016 Oct 24.
Abstract/Text BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment of Plasmodium falciparum malaria. Since the introduction of artemether-lumefantrine (AL) for treatment of uncomplicated malaria in Sweden, treatment failures have been reported in adults.
METHODS: A retrospective comparative analysis of treatment regimen for P. falciparum malaria in adults in Stockholm during 2000-2015 was performed to evaluate the effectiveness of AL. Parasite genotyping and drug concentrations were investigated in the AL treatment failures.
RESULTS: Among the total 397 P. falciparum episodes, 310 were treated with oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were administered initial intravenous therapy (38 artesunate and 49 quinine) followed by oral treatments. Five late treatment failures were detected after AL and one slow response to AP. The effectiveness of AL alone was 94.7% (95% confidence interval [CI], 88.1%-98.3%), compared with 99.5% for other oral regimens (P = .003). All AL failures occurred in European men and the effectiveness in this group was only 73.7% (95% CI, 48.8%-90.0%). Genotyping confirmed recrudescence of the initial parasite populations and drug resistance markers revealed no clinically significant resistance patterns. Lumefantrine concentrations suggested subtherapeutic concentrations in at least 2 cases.
CONCLUSIONS: Our findings indicate a high rate of symptomatic late treatment failures after 6-dose AL regime in nonimmune adults, especially in men. Our report warrants the need to establish optimal dosing of AL in adults and to alert clinicians about the importance of informing patients regarding the risk of parasites reappearing weeks after AL treatment.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID 27986683  Clin Infect Dis. 2017 Jan 15;64(2):199-206. doi: 10.109・・・
著者: Elizabeth A Ashley, Mehul Dhorda, Rick M Fairhurst, Chanaki Amaratunga, Parath Lim, Seila Suon, Sokunthea Sreng, Jennifer M Anderson, Sivanna Mao, Baramey Sam, Chantha Sopha, Char Meng Chuor, Chea Nguon, Siv Sovannaroth, Sasithon Pukrittayakamee, Podjanee Jittamala, Kesinee Chotivanich, Kitipumi Chutasmit, Chaiyaporn Suchatsoonthorn, Ratchadaporn Runcharoen, Tran Tinh Hien, Nguyen Thanh Thuy-Nhien, Ngo Viet Thanh, Nguyen Hoan Phu, Ye Htut, Kay-Thwe Han, Kyin Hla Aye, Olugbenga A Mokuolu, Rasaq R Olaosebikan, Olaleke O Folaranmi, Mayfong Mayxay, Maniphone Khanthavong, Bouasy Hongvanthong, Paul N Newton, Marie A Onyamboko, Caterina I Fanello, Antoinette K Tshefu, Neelima Mishra, Neena Valecha, Aung Pyae Phyo, Francois Nosten, Poravuth Yi, Rupam Tripura, Steffen Borrmann, Mahfudh Bashraheil, Judy Peshu, M Abul Faiz, Aniruddha Ghose, M Amir Hossain, Rasheda Samad, M Ridwanur Rahman, M Mahtabuddin Hasan, Akhterul Islam, Olivo Miotto, Roberto Amato, Bronwyn MacInnis, Jim Stalker, Dominic P Kwiatkowski, Zbynek Bozdech, Atthanee Jeeyapant, Phaik Yeong Cheah, Tharisara Sakulthaew, Jeremy Chalk, Benjamas Intharabut, Kamolrat Silamut, Sue J Lee, Benchawan Vihokhern, Chanon Kunasol, Mallika Imwong, Joel Tarning, Walter J Taylor, Shunmay Yeung, Charles J Woodrow, Jennifer A Flegg, Debashish Das, Jeffery Smith, Meera Venkatesan, Christopher V Plowe, Kasia Stepniewska, Philippe J Guerin, Arjen M Dondorp, Nicholas P Day, Nicholas J White, Tracking Resistance to Artemisinin Collaboration (TRAC)
雑誌名: N Engl J Med. 2014 Jul 31;371(5):411-23. doi: 10.1056/NEJMoa1314981.
Abstract/Text BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies.
METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined.
RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days.
CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).

PMID 25075834  N Engl J Med. 2014 Jul 31;371(5):411-23. doi: 10.1056/N・・・
著者: S Looareesuwan, P Wilairatana, K Chalermarut, Y Rattanapong, C J Canfield, D B Hutchinson
雑誌名: Am J Trop Med Hyg. 1999 Apr;60(4):526-32.
Abstract/Text The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P < 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in < 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.

PMID 10348224  Am J Trop Med Hyg. 1999 Apr;60(4):526-32.
著者: T H Nguyen, N P Day, V C Ly, D Waller, N T Mai, D B Bethell, T H Tran, N J White
雑誌名: Lancet. 1996 Oct 5;348(9032):917-21.
Abstract/Text BACKGROUND: Neurological signs and symptoms are common in malaria, but observations in Vietnam and Thailand have pointed to a discrete transient neurological syndrome after recovery from severe infections.
METHODS: A prospective study of the post-malaria neurological syndrome (PMNS) was conducted at two centres in Vietnam over four years. Criteria for inclusion were recent symptomatic malaria infection with parasites cleared from blood (and in cases of cerebral malaria full recovery of consciousness), and development of neurological or psychiatric symptoms within two months after the acute illness. Half of the patients with severe falciparum malaria had been taking part in a randomised trial of antimalarials.
FINDINGS: Of 18,124 patients with falciparum malaria treated (1176 of whom had severe infections) 19 adults and three children had subsequent PMNS; in one patient it followed uncomplicated malaria and in 21 it followed severe malaria. The overall incidence (95% confidence interval) of PMNS after falciparum malaria at the main study centre was 1.2 per 1000 (0.7 to 1.8 per 1000) and relative risk (95% CI) for developing PMNS after severe versus uncomplicated falciparum malaria was 299 (40 to 2223). 13 patients had an acute confusional state or psychosis, six had one or more generalised convulsions, two had generalised convulsions followed by a long period of acute confusion, and one developed a fine tremor. At the time of PMNS diagnosis all patients were aparasitaemic. The syndrome was self-limiting, median duration 60 h (range 24-240). PMNS was associated with the use of oral mefloquine. In the randomised trial 4.4% (10/228) of patients with severe malaria who received mefloquine after parenteral treatment developed PMNS compared with 0.5% (1/210) of those who received quinine; relative risk 9.2 (95% CI 1.2 to 71.3, p = 0.012).
INTERPRETATION: Mefloquine is not the only risk factor for PMNS but it is a strong one. Where an effective alternative drug is available, mefloquine should not be used after treatment of severe malaria.

PMID 8843810  Lancet. 1996 Oct 5;348(9032):917-21.
著者: C Luxemburger, F O ter Kuile, F Nosten, G Dolan, J H Bradol, L Phaipun, T Chongsuphajaisiddhi, N J White
雑誌名: Trans R Soc Trop Med Hyg. 1994 Mar-Apr;88(2):213-7.
Abstract/Text The therapeutic efficacy and toxicity of a combination of low dose mefloquine (15 mg/kg) plus artesunate 10 mg/kg in one day (MA) was compared with the currently used regimen of high dose mefloquine (25 mg/kg) (MQ) in 552 patients with uncomplicated falciparum malaria in an area of multi-drug resistance on the Thai-Burmese border. MA gave faster clinical and parasitological responses and prevented early treatment failure; 15 patients in the MQ group (6%) were early failures (< 9 d) compared with none receiving MA (P = 0.0001). Overall failure rates by day 28 were 19% in the MA group and 24% in with MQ group (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.54-1.12). In the subgroup of patients who required re-treatment, MA proved significantly more effective than MQ; failure rates were 25% and 52% respectively (RR = 0.49, 95% CI = 0.29-0.83). Treatment failures were associated with mefloquine treatment in the previous month (RR = 1.72, 95% CI = 1.09-2.70) and diarrhoea (RR = 1.55, 95% CI = 1.05-2.28). Gastrointestinal side-effects and dizziness were more likely in the MQ group. There was no evident adverse effect associated with artesunate. A single day's treatment with artesunate augments the antimalarial efficacy of mefloquine.

PMID 8036679  Trans R Soc Trop Med Hyg. 1994 Mar-Apr;88(2):213-7.
著者: Jason D Maguire, Krisin, Hariyani Marwoto, Thomas L Richie, David J Fryauff, J Kevin Baird
雑誌名: Clin Infect Dis. 2006 Apr 15;42(8):1067-72. doi: 10.1086/501357. Epub 2006 Mar 13.
Abstract/Text BACKGROUND: During the period of 1996-1999, we prospectively monitored 243 Javanese adults and children after arriving in Papua, Indonesia, and microscopically documented each new case of malaria by active surveillance.
METHODS: In a randomized, open-label, comparative malaria treatment trial, 72 adults and 50 children received chloroquine for each incident case of malaria, and 74 adults and 47 children received mefloquine.
RESULTS: Among 975 primary treatment courses, the cumulative 28-day curative efficacies were 26% and 82% for chloroquine against Plasmodium falciparum malaria and Plasmodium vivax malaria, respectively. Mefloquine cure rates were far superior (96% against P. falciparum malaria and 99.6% against P. vivax malaria).
CONCLUSIONS: Mefloquine is a useful alternative treatment for P. vivax malaria and P. falciparum malaria in areas such as Papua, where chloroquine is still recommended as the first-line therapeutic agent.

PMID 16575721  Clin Infect Dis. 2006 Apr 15;42(8):1067-72. doi: 10.108・・・
著者: G N L Galappaththy, A A A Omari, P Tharyan
雑誌名: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004389. doi: 10.1002/14651858.CD004389.pub2. Epub 2007 Jan 24.
Abstract/Text BACKGROUND: Plasmodium vivax infections contribute to a significant proportion of the malaria infections in many countries. Primaquine is the most widely used drug for treating the dormant liver stage. Different primaquine dosing regimens are in use.
OBJECTIVES: To compare primaquine regimens for preventing relapses in people with P. vivax malaria.
SEARCH STRATEGY: In 2006, we searched the Cochrane Infectious Diseases Group's Specialized Register (January), CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE (October), EMBASE (January), LILACS (January). We also checked conference proceedings and reference lists, and contacted researchers, the World Health Organization (WHO), malaria mailing lists, and pharmaceutical companies.
SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing primaquine plus chloroquine with chloroquine alone, and the standard primaquine regimen (15 mg/day for 14 days) with other primaquine-containing regimens in people with vivax malaria.
DATA COLLECTION AND ANALYSIS: All authors independently assessed trial eligibility and quality, and extracted data. We calculated odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model if there was significant heterogeneity.
MAIN RESULTS: Nine trials (3423 participants) met the inclusion criteria. Compared with chloroquine alone, five-day primaquine plus chloroquine was no better at preventing relapses (OR 1.04, 95% CI 0.64 to 1.69, random-effects model; 2104 participants; 3 trials), while 14-day primaquine plus chloroquine was significantly better (OR 0.24, 95% CI 0.12 to 0.45, random-effects model; 1071 participants, 6 trials). Limited data suggest the advantage for the 14-day primaquine regimen persisted for over six months (OR 0.41, 95% CI 0.29 to 0.60; 585 participants, 2 trials). Direct comparisons of the 14-day and five-day primaquine plus chloroquine regimens also confirm the superiority of the longer course (OR 13.33, 95% CI 3.45 to 51.44; 186 participants, 2 trials). Adverse effects were poorly reported, with three trials reporting skin rash, vertigo, headache, abdominal pain and/or nausea, and two trials reporting that primaquine was well tolerated.
AUTHORS' CONCLUSIONS: Primaquine (15 mg/kg/day for 14 days) plus chloroquine is more effective than chloroquine alone or primaquine (15 mg/kg for 5 days) plus chloroquine in preventing relapses of vivax malaria. Primaquine (five days) plus chloroquine appears no better than chloroquine. Countries should follow the WHO's recommendation for 14-day primaquine plus chloroquine regimen. Alternative regimens need to be evaluated in randomized controlled trials, which should also consider variations in regional P. vivax strains and the possibility of primaquine resistance, reinfection, and adherence in those who relapse.

PMID 17253504  Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004389. d・・・
著者: Nicola Townell, David Looke, David McDougall, James S McCarthy
雑誌名: Malar J. 2012 Jun 22;11:214. doi: 10.1186/1475-2875-11-214. Epub 2012 Jun 22.
Abstract/Text BACKGROUND: Relapsing Plasmodium vivax infection results in significant morbidity for the individual and is a key factor in transmission. Primaquine remains the only licensed drug for prevention of relapse. To minimize relapse rates, treatment guidelines have recently been revised to recommend an increased primaquine dose, aiming to achieve a cumulative dose of ≥6 mg/kg, i.e. ≥420 mg in a 70 kg patient. The aims of this study were to characterize the epidemiology of P. vivax infection imported into Queensland Australia, to determine the rates of relapse, to investigate the use of primaquine therapy, and its efficacy in the prevention of relapse.
METHODS: A retrospective study was undertaken of laboratory confirmed P. vivax infection presenting to the two major tertiary hospitals in Queensland, Australia between January 1999 and January 2011.Primaquine dosing was classified as no dose, low dose (<420 mg), high dose (≥420 mg), or unknown. The dose of primaquine prescribed to patients who subsequently relapsed that prescribed to patients who did not relapse.
RESULTS: Twenty relapses occurred following 151 primary episodes of P. vivax infection (13.2%). Relapses were confirmed among 3/21 (14.2%), 9/50 (18.0%), 1/54 (1.9%) and 7/18 (38.9%) of patients administered no dose, low dose, high dose and unknown primaquine dose respectively. High dose primaquine therapy was associated with a significantly lower rate of relapse compared to patients who were prescribed low dose therapy (OR 11.6, 95% CI 1.5-519, p = 0.005).
CONCLUSIONS: Relapse of P. vivax infection is more likely in patients who received low dose primaquine therapy. This study supports the recommendations that high dose primaquine therapy is necessary to minimize relapse of P. vivax malaria.

PMID 22727113  Malar J. 2012 Jun 22;11:214. doi: 10.1186/1475-2875-11-・・・
著者: Jane Achan, James K Tibenderana, Daniel Kyabayinze, Fred Wabwire Mangen, Moses R Kamya, Grant Dorsey, Umberto D'Alessandro, Philip J Rosenthal, Ambrose O Talisuna
雑誌名: BMJ. 2009 Jul 21;339:b2763. Epub 2009 Jul 21.
Abstract/Text OBJECTIVE: To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children.
DESIGN: Randomised, open label effectiveness study.
SETTING: Outpatient clinic of Uganda's national referral hospital in Kampala.
PARTICIPANTS: 175 children aged 6 to 59 months with uncomplicated malaria.
INTERVENTIONS: Participants were randomised to receive oral quinine or artemether-lumefantrine administered by care givers at home.
MAIN OUTCOME MEASURES: Primary outcomes were parasitological cure rates after 28 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections. Secondary outcomes were adherence to study drug, presence of gametocytes, recovery of haemoglobin concentration from baseline at day 28, and safety profiles.
RESULTS: Using survival analysis the cure rate unadjusted by genotyping was 96% for the artemether-lumefantrine group compared with 64% for the quinine group (hazard ratio 10.7, 95% confidence interval 3.3 to 35.5, P=0.001). In the quinine group 69% (18/26) of parasitological failures were due to recrudescence compared with none in the artemether-lumefantrine group. The mean adherence to artemether-lumefantrine was 94.5% compared with 85.4% to quinine (P=0.0008). Having adherence levels of 80% or more was associated with a decreased risk of treatment failure (0.44, 0.19 to 1.02, P=0.06). Adverse events did not differ between the two groups.
CONCLUSIONS: The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ugandan children was significantly lower than that of artemether-lumefantrine. These findings question the advisability of the recommendation for quinine therapy for uncomplicated malaria in Africa.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00540202.

PMID 19622553  BMJ. 2009 Jul 21;339:b2763. Epub 2009 Jul 21.
著者: David Sinclair, Sarah Donegan, Rachel Isba, David G Lalloo
雑誌名: Cochrane Database Syst Rev. 2012 Jun 13;6:CD005967. doi: 10.1002/14651858.CD005967.pub4. Epub 2012 Jun 13.
Abstract/Text BACKGROUND: Severe malaria results in over a million deaths every year, most of them in children aged under five years and living in sub-Saharan Africa. This review examines whether treatment with artesunate, instead of the standard treatment quinine, would result in fewer deaths and better treatment outcomes.
OBJECTIVES: To compare artesunate with quinine for treating severe malaria.
SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, ISI Web of Science, the metaRegister of Controlled trials (mRCT), conference proceedings, and reference lists of articles to November 2010.
SELECTION CRITERIA: Randomized controlled trials comparing intravenous, intramuscular, or rectal artesunate with intravenous or intramuscular quinine for treating adults and children with severe malaria who are unable to take medication by mouth.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility and risk of bias of trials, and extracted and analysed data. The primary outcome was all-cause death. Dichotomous outcomes were summarized using risk ratios (RR) and continuous outcomes by mean differences (MD). Where appropriate, we combined data in meta-analyses.
MAIN RESULTS: Eight trials enrolling 1664 adults and 5765 children are included in this review.Treatment with artesunate significantly reduced the risk of death both in adults (RR 0.61, 95% Confidence Interval (CI) 0.50 to 0.75; 1664 participants, five trials) and children (RR 0.76, 95% CI 0.65 to 0.90; 5765 participants, four trials)In children, treatment with artesunate increased the incidence of neurological sequelae at the time of hospital discharge. The majority of these sequelae were transient and no significant difference between treatments was seen at later follow up.
AUTHORS' CONCLUSIONS: The evidence clearly supports the superiority of parenteral artesunate over quinine for the treatment of severe malaria in both adults and children and in different regions of the world.

PMID 22696354  Cochrane Database Syst Rev. 2012 Jun 13;6:CD005967. doi・・・
著者: F Bruneel, B Gachot, M Wolff, B Régnier, M Danis, F Vachon, Corresponding Group
雑誌名: Clin Infect Dis. 2001 Apr 15;32(8):1133-40. doi: 10.1086/319743. Epub 2001 Apr 2.
Abstract/Text Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically exposed to Plasmodium falciparum and irregularly taking quinine. BWF virtually disappeared after 1950, when chloroquine superseded quinine. We report 21 cases of BWF seen in France from 1990 through 1999 in European expatriates who lived in sub-Saharan Africa. All patients had macroscopic hemoglobinuria, jaundice, and anemia. Acute renal failure occurred in 15 patients (71%), 7 of whom required dialysis. The presumed triggers of BWF were halofantrine (38%), quinine (24%), mefloquine (24%), and halofantrine or quinine (14%). Glucose-6-phosphate dehydrogenase (G6PD) activity was normal in the 14 patients who underwent this test. Low-level P. falciparum parasitemia was found in 8 patients. All 21 patients survived. Our data and 13 cases reported in the literature suggest a resurgence of classic BWF among Europeans living in Africa and a need to discuss attendant therapeutic implications.

PMID 11283802  Clin Infect Dis. 2001 Apr 15;32(8):1133-40. doi: 10.108・・・
著者: Victor Mung'Ala-Odera, Robert W Snow, Charles R J C Newton
雑誌名: Am J Trop Med Hyg. 2004 Aug;71(2 Suppl):64-70.
Abstract/Text The burden of Plasmodium falciparum malaria has been estimated traditionally in terms of infections and mortality. Neurocognitive sequelae have recently been identified that add to the burden caused by this parasite. We have attempted to provide estimates of the neurocognitive burden based upon more recent estimates of the population at risk and a detailed review of published studies in sub-Saharan Africa. There is little data on which to estimate the burden, and considerable limitations in extracting the data from the published studies to provide these estimates. However, we estimate that at least 1,300-7,800 children will have neurologic sequelae following cerebral malaria in stable endemic areas per year. The figure is likely to be considerably higher, since these estimates do not include neurocognitive impairment following non-cerebral malaria in children or adults in stable endemic areas, or populations in low stable or epidemic areas.

Copyright 2004 The American Society of Tropical Medicine and Hygiene
PMID 15331820  Am J Trop Med Hyg. 2004 Aug;71(2 Suppl):64-70.
著者: Mark S Riddle, Jeffrey L Jackson, John W Sanders, David L Blazes
雑誌名: Clin Infect Dis. 2002 May 1;34(9):1192-8. doi: 10.1086/339810. Epub 2002 Apr 3.
Abstract/Text The efficacy of exchange transfusion as an adjunct treatment for severe falciparum malaria is controversial. No sufficiently powered, randomized, controlled study has been reported. We analyzed 8 studies that compared survival rates associated with adjunct exchange transfusion with those associated with antimalarial chemotherapy alone. Exchange transfusion was not associated with a higher survival rate than was antimalarial chemotherapy alone (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.7-2.1). However, patients who received transfusions had higher levels of parasitemia and more-severe malaria. Sensitivity analysis found that survival rates were higher among patients with partial immunity to malaria (OR, 0.5; 95% CI, 0.2-1.2) than they were among patients with no immunity (OR, 2.1; 95% CI, 0.9-4.8; P=.007). Exchange transfusion does not appear to increase the survival rate; however, there were significant problems with the comparability of treatment groups in the studies reviewed, and a randomized controlled trial is necessary to determine whether exchange transfusion is beneficial.

PMID 11941545  Clin Infect Dis. 2002 May 1;34(9):1192-8. doi: 10.1086/・・・
著者: Jung-Yeon Kim, Jeong-Su Kim, Mi-Hyun Park, Young-A Kang, Jun-Wook Kwon, Shin-Hyeong Cho, Byeong-Chul Lee, Tong-Soo Kim, Jong-Koo Lee
雑誌名: Korean J Parasitol. 2009 Sep;47(3):269-73. doi: 10.3347/kjp.2009.47.3.269. Epub 2009 Aug 28.
Abstract/Text A 57-year old man who was admitted to an emergency room of a tertiary hospital with hemoptysis developed malarial fever 19 days later and then died from severe falciparum malaria 2 days later. He had not traveled outside of Korea for over 30 years. Through intensive interviews and epidemiological surveys, we found that a foreign patient with a recent history of travel to Africa was transferred to the same hospital with severe falciparum malaria. We confirmed through molecular genotyping of the MSP-1 gene that Plasmodium falciparum genotypes of the 2 patients were identical. It is suggested that a breach of standard infection control precautions resulted in this P. falciparum transmission between 2 patients in a hospital environment. This is the first report of a nosocomial transmission of falciparum malaria in Korea.

PMID 19724701  Korean J Parasitol. 2009 Sep;47(3):269-73. doi: 10.3347・・・
著者: Sanjay K Jain, Deborah Persaud, Trish M Perl, Margaret A Pass, Kathleen M Murphy, John M Pisciotta, Peter F Scholl, James F Casella, David J Sullivan
雑誌名: Emerg Infect Dis. 2005 Jul;11(7):1097-9. doi: 10.3201/eid1107.050092.
Abstract/Text An investigation of malaria in a US patient without recent travel established Plasmodium falciparum molecular genotype identity in 2 patients who shared a hospital room. P. falciparum can be transmitted in a hospital environment from patient to patient by blood inoculum if standard precautions are breached.

PMID 16022788  Emerg Infect Dis. 2005 Jul;11(7):1097-9. doi: 10.3201/e・・・
著者: H A Abulrahi, E A Bohlega, R E Fontaine, S M al-Seghayer, A A al-Ruwais
雑誌名: Lancet. 1997 Jan 4;349(9044):23-5.
Abstract/Text BACKGROUND: After a community investigation had implicated hospital admission as a shared feature of a cluster of acute Plasmodium falciparum malaria (AFM) cases in Riyadh, Saudi Arabia, we began an in-hospital investigation to determine the method of transmission.
METHODS: We investigated all AFM patients admitted to one paediatric hospital for any reason from December, 1991, to April, 1992. We classified AFM as locally acquired (LAFM) if during the month before AFM onset the patient had not visited a malarious area, and as hospital acquired (HAFM) if the LAFM patient had been admitted to hospital during that month. We compared exposures of HAFM cases with those of other patients sampled from the same wards. We observed nursing practices and investigated by anonymous questionnaire how nurses administered parenteral drugs.
FINDINGS: Of 21 LAFM cases, 20 (95%) had a previous hospital admission (exposure admission) compared with 15 (25%) of 61 other patients (p < 0.001; chi 2 test). During the exposure admission, all HAFM patients had occupied the same room as, or a room adjacent to, an AFM patient; 14 (23%) of 60 other patients occupied the same room or rooms adjacent to an AFM patient (p < 0.001, chi 2). 90% of HAFM patients received infusions through a heparin lock during the exposure admission, compared with 49% of 120 general patients (p < 0.001, chi 2). 10% of nurses admitted to using one syringe for more than one heparin lock and 50% filled syringes with enough heparin for three to ten heparin locks.
INTERPRETATION: P falciparum was transmitted between patients when single syringes were used on heparin locks of sequential patients. This practice would easily transmit other blood-borne agents.

PMID 8988119  Lancet. 1997 Jan 4;349(9044):23-5.

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