{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:02:37Z","timestamp":1788433357776,"version":"build-2803163510"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Giardiasis failing nitroimidazole first-line treatment is an emerging problem in returning European travelers. We present data on the efficacy and tolerability of 2 second-line treatment regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This prospective, open-label, multicenter study assessed the efficacy and tolerability of quinacrine monotherapy (100 mg 3 times per day for 5 days) and albendazole plus chloroquine combination therapy (400 mg twice daily plus 155 mg twice daily for 5 days) in nitroimidazole-refractory giardiasis. The defined end points were the clinical outcome, assessed at week 5 after treatment and the parasitological outcome, assessed using microscopy of 2 stool samples, \u22652 to \u22645 weeks after treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 106 patients were included in the study. Quinacrine achieved clinical and parasitological cure in 81% (59\/73) and 100% (56\/56), respectively. Albendazole plus chloroquine achieved clinical and parasitological cure in 36% (12\/33) and 48% (12\/25), respectively. All patients (9\/9) who clinically and parasitologically failed albendazole plus chloroquine treatment and opted for retreatment with quinacrine achieved clinical cure. Mild to moderate treatment-related adverse events were reported by 45% and 30% of patients treated with quinacrine and albendazole plus chloroquine, respectively. One patient treated with quinacrine developed severe neuropsychiatric side effects. The majority of nitroimidazole-refractory Giardia infections (57%) were acquired in India.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Quinacrine was a highly effective treatment in nitroimidazole-refractory giardiasis, but patients should be cautioned on the low risk of severe neuropsychiatric adverse event. Albendazole plus chloroquine had a low cure rate in nitroimidazole-refractory giardiasis. Nitroimidazole-refractory giardiasis was primarily seen in travelers returning from India.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab513","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T20:19:00Z","timestamp":1622665140000},"page":"1517-1523","source":"Crossref","is-referenced-by-count":22,"title":["Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: A TropNet Study"],"prefix":"10.1093","volume":"73","author":[{"given":"Andreas","family":"Neumayr","sequence":"first","affiliation":[{"name":"Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"},{"name":"Department of Public Health and Tropical Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Schunk","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-University Hospital Centre, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Theunissen","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Van Esbroeck","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Mechain","sequence":"additional","affiliation":[{"name":"Section Tropical Medicine and Clinical International Health, Division of Infectious and Tropical Diseases, Department of Medicine, University Hospital Centre, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hatz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"M\u00f8rch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Norwegian National Advisory Unit on Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Jes\u00fas","family":"Soriano P\u00e9rez","sequence":"additional","affiliation":[{"name":"Tropical Medicine Unit, Department of Internal Medicine, Hospital de Poniente, El Ejido, Almer\u00eda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Sydow","sequence":"additional","affiliation":[{"name":"Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sothmann","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-University Hospital Centre, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Kuenzli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Rothe","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-University Hospital Centre, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Bottieau","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"2021102017443308100_CIT0001","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jinf.2009.05.008","article-title":"A global study of pathogens and host risk factors associated with infectious gastrointestinal disease in returned international travellers","volume":"59","author":"Swaminathan","year":"2009","journal-title":"J Infect"},{"key":"2021102017443308100_CIT0002","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.mib.2016.07.019","article-title":"An up-date on Giardia and giardiasis","volume":"34","author":"Einarsson","year":"2016","journal-title":"Curr Opin Microbiol"},{"key":"2021102017443308100_CIT0003","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1128\/CMR.8.3.427","article-title":"Human antiprotozoal therapy: past, present, and future","volume":"8","author":"Khaw","year":"1995","journal-title":"Clin Microbiol Rev"},{"key":"2021102017443308100_CIT0004","first-page":"1181","article-title":"La lambliase et son traitement par l\u2019atebrine","volume":"67","author":"Galli Verlio","year":"1937","journal-title":"Schweiz Med Wochenschr"},{"key":"2021102017443308100_CIT0005","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1128\/CMR.14.1.114-128.2001","article-title":"Treatment of giardiasis","volume":"14","author":"Gardner","year":"2001","journal-title":"Clin Microbiol Rev"},{"key":"2021102017443308100_CIT0006","first-page":"84","article-title":"[Treatment of giardiasis (lambliasis) by metronidazole]","volume":"54","author":"Schneider","year":"1961","journal-title":"Bull Soc Pathol Exot Filiales"},{"key":"2021102017443308100_CIT0007","first-page":"15","article-title":"[Treatment of giardiasis (lambliasis) with metronidazole. Apropos of 100 cases]","volume":"70","author":"Darbon","year":"1962","journal-title":"Presse Med"},{"key":"2021102017443308100_CIT0008","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.2174\/1568026618666181002095314","article-title":"Giardiasis: characteristics, pathogenesis and new insights about treatment","volume":"18","author":"Vivancos","year":"2018","journal-title":"Curr Top Med Chem"},{"key":"2021102017443308100_CIT0009","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4269\/ajtmh.1979.28.19","article-title":"Giardiasis in infancy and childhood: a prospective study of 160 cases with comparison of quinacrine (Atabrine) and metronidazole (Flagyl)","volume":"28","author":"Kavousi","year":"1979","journal-title":"Am J Trop Med Hyg"},{"key":"2021102017443308100_CIT0010","first-page":"280","article-title":"Treatment of giardiasis in children with quinacrine, metronidazole, tinidazole and ornidazole","volume":"11","author":"Sabchareon","year":"1980","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"2021102017443308100_CIT0011","doi-asserted-by":"crossref","first-page":"O135","DOI":"10.1111\/1469-0691.12327","article-title":"A family cluster of giardiasis with variable treatment responses: refractory giardiasis in a family after a trip to India","volume":"20","author":"Requena-M\u00e9ndez","year":"2014","journal-title":"Clin Microbiol Infect"},{"key":"2021102017443308100_CIT0012","doi-asserted-by":"crossref","first-page":"791e6","DOI":"10.1016\/j.cmi.2015.04.019","article-title":"Increased incidence of nitroimidazole-refractory giardiasis at the Hospital for Tropical Diseases, London, 2008-2013","volume":"21","author":"Nabarro","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"2021102017443308100_CIT0013","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/infdis\/jix066","article-title":"The use of quinacrine in nitroimidazole-resistant Giardia duodenalis: an old drug for an emerging problem","volume":"215","author":"Requena-M\u00e9ndez","year":"2017","journal-title":"J Infect Dis"},{"key":"2021102017443308100_CIT0014","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3201\/eid2010.140073","article-title":"Treatment of giardiasis after nonresponse to nitroimidazole","volume":"20","author":"Meltzer","year":"2014","journal-title":"Emerg Infect Dis"},{"key":"2021102017443308100_CIT0015","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cmi.2017.05.028","article-title":"Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions","volume":"24","author":"Carter","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2021102017443308100_CIT0016","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/jac\/dkg150","article-title":"Isolation, excystation and axenization of Giardia lamblia isolates: in vitro susceptibility to metronidazole and albendazole","volume":"51","author":"Cruz","year":"2003","journal-title":"J Antimicrob Chemother"},{"key":"2021102017443308100_CIT0017","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.pt.2009.11.010","article-title":"Giardiasis\u2014why do the symptoms sometimes never stop?","volume":"26","author":"Robertson","year":"2010","journal-title":"Trends Parasitol"},{"key":"2021102017443308100_CIT0018","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/0020-7519(90)90196-T","article-title":"Drug resistance in Giardia intestinalis","volume":"20","author":"Upcroft","year":"1990","journal-title":"Int J Parasitol"},{"key":"2021102017443308100_CIT0019","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.tmaid.2012.10.004","article-title":"Refractory giardiasis in Spanish travellers","volume":"11","author":"Mu\u00f1oz Guti\u00e9rrez","year":"2013","journal-title":"Travel Med Infect Dis"},{"key":"2021102017443308100_CIT0020","doi-asserted-by":"crossref","first-page":"e682","DOI":"10.1371\/journal.pntd.0000682","article-title":"A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis","volume":"4","author":"Solaymani-Mohammadi","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"2021102017443308100_CIT0021","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1046\/j.1365-2036.2001.01066.x","article-title":"Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from northern Peru","volume":"15","author":"Ortiz","year":"2001","journal-title":"Aliment Pharmacol Ther"},{"key":"2021102017443308100_CIT0022","first-page":"607","article-title":"A randomized, controlled, open-label trial evaluating the efficacy and safety of chloroquine in the treatment of giardiasis in children","volume":"59","author":"Ca\u00f1ete","year":"2010","journal-title":"West Indian Med J"},{"key":"2021102017443308100_CIT0023","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1179\/000349803235002290","article-title":"Comparison of chloroquine, albendazole and tinidazole in the treatment of children with giardiasis","volume":"97","author":"Escobedo","year":"2003","journal-title":"Ann Trop Med Parasitol"},{"key":"2021102017443308100_CIT0024","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.actatropica.2016.06.026","article-title":"Combination therapy in the management of giardiasis: what laboratory and clinical studies tell us, so far","volume":"162","author":"Escobedo","year":"2016","journal-title":"Acta Trop"},{"key":"2021102017443308100_CIT0025","first-page":"63","article-title":"Toxic psychoses following atabrine","volume":"86","author":"Gaskill","year":"1945","journal-title":"Bull US Army M Dept"},{"key":"2021102017443308100_CIT0026","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1001\/archneurpsyc.1946.02300200041003","article-title":"Toxicity of quinacrine (atabrine) for the central nervous system; an experimental study on human subjects","volume":"56","author":"Lidz","year":"1946","journal-title":"Arch Neurol Psychiatry"},{"key":"2021102017443308100_CIT0027","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1001\/archneurpsyc.1947.02300320088005","article-title":"Effect of quinacrine (atabrine) on the central nervous system; clinical and electroencephalographic studies","volume":"58","author":"Engel","year":"1947","journal-title":"Arch Neurol Psychiatry"},{"key":"2021102017443308100_CIT0028","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1086\/320886","article-title":"Treatment of patients with refractory giardiasis","volume":"33","author":"Nash","year":"2001","journal-title":"Clin Infect Dis"},{"key":"2021102017443308100_CIT0029","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1445-5994.1978.tb04908.x","article-title":"Histopathology in giardiasis: a correlation with diarrhoea","volume":"8","author":"Duncombe","year":"1978","journal-title":"Aust N Z J Med"},{"key":"2021102017443308100_CIT0030","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/QCO.0000000000000668","article-title":"Giardiasis treatment: an update with a focus on refractory disease","volume":"33","author":"M\u00f8rch","year":"2020","journal-title":"Curr Opin Infect Dis"},{"key":"2021102017443308100_CIT0031","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jinf.2008.01.013","article-title":"Treatment-ladder and genetic characterisation of parasites in refractory giardiasis after an outbreak in Norway","volume":"56","author":"M\u00f8rch","year":"2008","journal-title":"J Infect"},{"key":"2021102017443308100_CIT0032","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1001\/jama.1964.03060180059026","article-title":"Toxic psychosis due to quinacrine and chloroquine","volume":"187","author":"SAPP","year":"1964","journal-title":"JAMA"},{"key":"2021102017443308100_CIT0033","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1176\/ajp.124.9.1257","article-title":"Psychiatric complications with chloroquine and quinacrine","volume":"124","author":"Rockwell","year":"1968","journal-title":"Am J Psychiatry"},{"key":"2021102017443308100_CIT0034","volume-title":"The Sanford guide to antimicrobial therapy","author":"David","year":"2020"},{"key":"2021102017443308100_CIT0035","author":"Bartelt"},{"key":"2021102017443308100_CIT0036","volume-title":"Antiparasitic treatment recommendations","author":"Neumayr","year":"2018","edition":"2"},{"key":"2021102017443308100_CIT0037","first-page":"379","article-title":"Treatment of refractory paediatric giardiasis using secnidazole plus albendazole: a case series","volume":"26","author":"Escobedo","year":"2018","journal-title":"Infez Med"},{"key":"2021102017443308100_CIT0038","first-page":"761","article-title":"[Synergic effect of albendazole plus metronidazole association in the treatment of metronidazole-resistant giardiasis]","volume":"146","author":"Cacopardo","year":"1995","journal-title":"Clin Ter"},{"key":"2021102017443308100_CIT0039","doi-asserted-by":"crossref","first-page":"1092.e1","DOI":"10.1016\/j.cmi.2019.12.017","article-title":"5-Nitroimidazole refractory giardiasis is common in Matanzas, Cuba and effectively treated by secnidazole plus high-dose mebendazole or quinacrine: a prospective observational cohort study","volume":"26","author":"Ca\u00f1ete","year":"2020","journal-title":"Clin Microbiol Infect"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciab513\/39068619\/ciab513.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/73\/8\/1517\/40786369\/ciab513.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/73\/8\/1517\/40786369\/ciab513.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T01:01:29Z","timestamp":1634778089000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/73\/8\/1517\/6296769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,6,11]]},"published-print":{"date-parts":[[2021,10,20]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciab513","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,15]]},"published":{"date-parts":[[2021,6,11]]}}}