Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

Bouchaud, Olivier; Mühlberger, Nikolai; Parola, Philippe; Calleri, Guido; Matteelli, Alberto; Peyerl‐Hoffmann, Gabriele; Méchaï, F.; Clerinx, Jan; Kremsner, Peter G.; Jelı́nek, Tomáš; Kaiser, Annette; Beltrame, Anna; Schmid, Matthias; Kern, Peter; Probst, Meike; Bartoloni, Alessandro; Weinke, Thomas; Grobusch, Martin P.

doi:10.1186/1475-2875-11-212

Cited by 33 publications

(26 citation statements)

References 39 publications

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“…The 57 GeoSentinel sites in 24 countries consist of travel and tropical medicine clinics that actively monitor travel-related morbidity. TropNet is a European travel and tropical medicine research and surveillance network [15]. Together, these networks encompass >110 travel and tropical medicine sites and >225 participating affiliated sites worldwide.…”

Section: Methodsmentioning

confidence: 99%

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

Esposito

Stich

Epelboin

et al. 2014

Clinical Infectious Diseases

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Background Through 2 international traveler-focused surveillance networks (GeoSentinel and TropNet), we identified and investigated a large outbreak of acute muscular sarcocystosis (AMS), a rarely reported zoonosis caused by a protozoan parasite of the genus Sarcocystis, associated with travel to Tioman Island, Malaysia, during 2011–2012. Methods Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology. Case confirmation required histologic observation of sarcocysts or isolation of Sarcocystis species DNA from muscle biopsy. Results Sixty-eight patients met the case definition (62 probable and 6 confirmed). All but 2 resided in Europe; all were tourists and traveled mostly during the summer months. The most frequent symptoms reported were myalgia (100%), fatigue (91%), fever (82%), headache (59%), and arthralgia (29%); onset clustered during 2 distinct periods: “early” during the second and “late” during the sixth week after departure from the island. Blood eosinophilia and elevated serum creatinine phosphokinase (CPK) levels were observed beginning during the fifth week after departure. Sarcocystis nesbitti DNA was recovered from 1 muscle biopsy. Conclusions Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS, noting the apparent biphasic aspect of the disease, the later onset of elevated CPK and eosinophilia, and the possibility for relapses. The exact source of infection among travelers to Tioman Island remains unclear but needs to be determined to prevent future illnesses.

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Section: Methodsmentioning

confidence: 99%

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

Esposito

Stich

Epelboin

et al. 2014

Clinical Infectious Diseases

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“…Hipoalbuminemi bağlı olmayan ilaç düzeyinde artışa yol açarak metabolik klirenste artışa yol açabilir (23). Avrupa'da yapılan bir çalışmada ilaç toleransındaki kötü verilere bağlı olarak hastanede kalış süresinin uzamasına yol açması, ilk seçenek tedavide kininlerin tercih edilmemesi belirtilmektedir (24). Olgu bazlı yapılan bildirilerde bazı Avrupa ve Uzakdoğu ülkelerinde lümefantrinli kombinasyonların-da tedavi başarızlığından da söz edilmektedir.…”

Section: Olgu Sunumuunclassified

The Management of Therapeutic Failure in a Falciparum Malaria Patient under Oral Arthemether-Lumefantrine Therapy

Ülçay

Karaahmetoğlu²,

Turhan³

et al. 2014

TurkiyeParazitolDerg

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ÖZET Sıtma, ateş, anemi ve splenomegali ile seyreden, akut dönemde tedavi edilmediği taktirde kronikleşme eğilimi gösteren paraziter bir infeksiyondur. Falsiparum sıtması, kıtalar arası seyahat imkanlarının artışına paralel olarak ülkemizde import vakalar olarak görülebilen ve erken tedaviye başlanmaması halinde ciddi morbidite ve mortalite ile sonuçlanan bir durumdur. Uganda'da altı aylık ikametinden sonra ülkemize dönüş yapan ve sıtma profilaksisine uyum göstermediği anlaşılan bir olguya falsiparum sıtması tanısı konulmuştur. Başlangıçta kanda yüksek düzey parazitemisi artemisin ve lümefantrin kombinasyonu ile kaybolan ancak tedavi bitiminden yaklaşık 18 gün sonra tekrar parazitemi ve ateş atakları ile başvuran bu import vakada kinin ve tetrasiklin tedavisiyle kür sağlanmış olup uygun artemisin kombinasyon tedavisine rağmen rekürrens durumu dikkati çekmiştir. Ülkemizde falciparum sıtmasına bağlı vakalar olmamasına rağmen bu hastalık yurtdışına seyahat öyküsü olan ve ateş ile müracaat eden hastalarda enfeksiyon acilleri arasında düşünülmesi gereken bir durumdur. Dünya Sağlık Örgütü'nün (DSÖ) de önerdiği şekilde tanısı konulduktan sonra başlangıç tedavisi olarak hızlı parazitemi klirensi ve semptomların dramatik kaybomasını sağlayan artemisinli kombinasyonlara hemen başvurulmalıdır. Artemisin bazlı preparatlardan artemether-lümefantrin kombinasyonu ülkemizde de sık tercih edilen rejimdir. Ancak özellikle kanda yüksek parazit yükü olan olgularda uygun artemeter kombinasyonu uygulamasından sonraki takiplerde rekürrens (reinfeksiyon veya rekrudesens) olasılığı açısından hastaların yakından takibi önemlidir. (Turkiye Parazitol Derg 2014; 38: 61- ABSTRACT Malaria is a parasitic infection characterized by anemia, splenomegaly and periodic fever. This infection has a tendency to cause serious complications. Falciparum malaria could occur in our country as an imported case due to increasing intercontinental travel opportunities. The World Health Organisation (WHO) recommends arthemether combination treatment as a first line choice. Here we report a Turkish case admitted to the hospital with high fever, sweating and fatigue. He had been in Uganda for 6 months without prophylaxis. Plasmodium falciparum with an intense parasitic load was diagnosed. We started arthemether-lumefantrine combination therapy immediately. 18 days after his discharge he was readmitted with the same complaints and parasitemia was detected once again. This time, we treated him with the quinine-tetracycline combination regime for 7 days. Within 48 hours the patient was afebrile and the blood smear was negative. Falciparum malaria must be considered in infection emergencies for febrile patients especially with any travel history. For an initial therapy, arthemetherlumefantrine combination is a successful choice of treatment. Even with adequate treatment of arthemether-lumefantrine combination, the problems of recurrence (recrudescence or reinfection) could occur due to treatment failure. For the possibility of recurrence, close monitoring of patients...

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“…Artemether-lumefantrine (AL) is one of the most widely used ACTs in the world and adopted in 48 countries as first line therapy for uncomplicated falciparum malaria, including patients with HIV co-infection 10 . True treatment failure (recrudescence) is uncommon with multiple studies showing the drug is effective 11–13 . However, for patients within whom pharmacokinetic (PK) exposure to AL may be reduced (e.g.…”

Section: Introductionmentioning

confidence: 99%

Concomitant Efavirenz Reduces Pharmacokinetic Exposure to the Antimalarial Drug Artemether–Lumefantrine in Healthy Volunteers

Huang

Parikh

Rosenthal

et al. 2012

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background The antiretroviral drug efavirenz (EFV) and the antimalarial artemisinin-based combination therapy (ACT) artemether-lumefantrine (AL) are commonly co-administered to treat HIV and malaria. EFV is a known inducer of cytochrome P450 3A4, which converts artemether to dihydroartemisinin (DHA) that is also active and metabolizes longer acting lumefantrine (LR). A study in healthy volunteers was completed to address the concern that EFV impacts AL pharmacokinetics (PK). Methods Adults received AL (80/480 mg BID) for 3-days prior to and during EFV co-administration (600 mg daily for 26-days) with intensive PK for artemether, DHA, and LR conducted after the last AL dose for each period. EFV PK was evaluated with and without AL. PK parameters were estimated using non-compartmental methods. Results Twelve subjects completed the two-period study. PK exposure for artemether, DHA, and LR [as estimated by the area under the concentration time curve (AUClast)] decreased or trended toward decrease with EFV, compared to when administered alone [−51% (p=0.084), −46% (p=0.005), and −21% (p=0.102), respectively]. Day 7 LR levels, previously deemed predictive of treatment success, were 46% lower (p=0.002) with EFV, but the LR half-life was unchanged. EFV PK exposure was minimally altered following AL co-administration [AUC0–24h decreased by 17% (p=0.034)]. Conclusions Exposure to DHA, but not LR, was significantly lower during EFV-AL co-administration compared to that during administration of AL alone. These findings may have implications for the treatment efficacy of AL, particularly in children. However, the observed modest changes probably do not warrant dosage adjustment during co-administration of AL with EFV.

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Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

Cited by 33 publications

References 39 publications

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

The Management of Therapeutic Failure in a Falciparum Malaria Patient under Oral Arthemether-Lumefantrine Therapy

Concomitant Efavirenz Reduces Pharmacokinetic Exposure to the Antimalarial Drug Artemether–Lumefantrine in Healthy Volunteers

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