Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: A TropNet Study

Abstract

Background Giardiasis failing nitroimidazole first-line treatment is an emerging clinical problem in returning European travelers. We present data on the efficacy and tolerability of two second-line treatment regimens. Methods Prospective, open-label, multi-center study assessing the efficacy and tolerability of quinacrine monotherapy (100mg TID for 5 days) and albendazole plus chloroquine combination therapy (400mg BID plus 155mg BID for 5 days) in nitroimidazole-refractory giardiasis, defined as cases with persisting or relapsing infection despite single or repeated courses of nitroimidazole treatment. The defined endpoints were the clinical outcome, assessed by a questionnaire, at week 5 after treatment and the parasitological outcome, assessed by microscopy of 2 stool samples, ≥2–≤5 weeks after treatment. Result 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 re-treatment 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. Conclusion 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.

Systematic Review of Psychiatric Adverse Effects Induced by Chloroquine and Hydroxychloroquine: Case Reports and Population Studies

“…27,39,40 In less frequency, studies also mentioned that patients developed psychosis, 7,17,21 agitation, 7,40 disturbed/strange thoughts, 7,14 depressive psychosis, 7 manic psychosis, 7 restlessness, 7 irritable mood, 7 panic attack, 17 confusion, 16 post-traumatic stress disorder (PTSD), 22 delirium, 27 and emotional lability. 39 Case reports. The most common psychiatric adverse effects among the case reports were decreased need for sleep/insomnia, increased psychomotor activity, excessive talking and talking irrelevantly, and auditory hallucinations (Supplemental Table S1).…”

“…Most populational studies do not specify the dose in which individuals ingested CQ, especially survey-based and retrospective studies. The studies that addressed how much CQ was ingested reported a mean of 443 mg, ranging from 250 to 2700 mg. 7,11,16,19,26,39,80 Ursing et al 20 and Saint-Gerons et al 40 reported a more detailed dose, in which patients took 10 mg/kg on days 0 and 1 and 2 doses of 5 mg/kg on day 2, and 10 mg/kg on day 1 and 7.5 mg/kg on days 2 and 3, respectively.…”

Parasiten – wichtige endemische und importierte Erreger

“…Aufgrund einer insbesondere bei Infektionen aus Indien zunehmenden Resistenz gegenüber Metronidazol kommt es inzwischen häufig zum Therapieversagen [7]. Eine erneute Monotherapie mit einem Nitroimidazol-Präparat ist meist erfolglos und auch Kombinationstherapien mit Medikamenten anderer Substanzklassen führen häufig nicht zum Therapieerfolg [7,8]. Bei Therapieversagen der Zweitlinientherapie kann ein Therapieversuch mit Quinacrin (Synonym: Mepacrin) erwogen werden.…”

“…Hierbei handelt es sich um ein in den 1930ern entwickeltes Medikament gegen Malaria, wel-ches aktuell in Deutschland nicht zugelassen ist, es kann jedoch über internationale Apotheken bezogen werden. Ältere Fallserien [9] und eine aktuelle multizentrische Studie [8] konnten eine Erfolgsrate von bis zu 100 % bei therapierefraktären Infektionen mit Giardia lamblia nachweisen.…”

Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy

“…A substantial number of clinical giardiasis cases are resistant to these nitro drug treatments ( 3 , 4 ). Other potential therapeutics, like quinacrine, are effective in treating metronidazole-resistant giardiasis but have been withdrawn from the U.S. market due to poor tolerability ( 5 – 7 ). Even with increasing emphasis on new approaches to expand treatment options, development of new drugs against Giardia lamblia is limited ( 8 ).…”