Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Malaria by Plasmodium Falciparum
Condition: Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this study was to evaluate the effectiveness of the fixed combination of
      artesunate+mefloquine in the treatment of uncomplicated malaria caused by Plasmodium
      falciparum in the municipality of Cruzeiro do Sul, Juruá Valley, Brazil, where it was being
      used as specific first-line drug.
    

Detailed description: 
      -  Objectives: To evaluate the efficacy of the fixed combination of artesunate + mefloquine
           in the treatment of uncomplicated malaria caused by Plasmodium falciparum, in the county
           (municipality) of Cruzeiro do Sul, Juruá Valley, State of Acre (AC), Brazil, where it
           was being used as specific first-line drug.

        -  Selection Criteria : Persons aged between 6 months and 70 years with history of fever in
           the last 48 hours that had a confirmed diagnosis of mono-infection by Plasmodium
           falciparum (F or F+Fg) with parasitemia of 250 to 100000 parasites/μl and absence of
           signs of severe malaria, malnutrition or another severe disease. Pregnant women were not
           included.

        -  Intervention: Three days of supervised treatment with the fixed combination of
           artesunate+mefloquine (ASMQ-Farmanguinhos/Fiocruz) in accordance with the scheme
           recommended by the Ministry of Health, respecting four age and weight groups based on
           the target dose of each drug (artesunate -4 mg/kg/dose and 12 mg/kg of total dose,
           mefloquine- 8 mg/kg/dose and 24 mg/kg of total dose). Patients in the range of 5 to <18
           kg (6 months to 5 years old) received the combination in pediatric presentation (ASMQ 25
           + 50mg) and subjects with 18 kg or more (6 years or more years old) received the
           presentation ASMQ 100 + 200mg.

        -  Main Outcomes: The proportion of subjects who had experienced treatment failure during
           the following 42 days is used to estimate the effectiveness of the antimalarial
           combination in this study. Adverse events and speed of resolution of the clinical and
           infectious status are described. The phenotype of multidrug resistance (MDR) was
           investigated in the population of P. falciparum present in the subjects of the study.

        -  Methods: A therapeutic trial of a single "arm" for prospective evaluation of clinical
           and parasitological response of at least 100 individuals with uncomplicated malaria by
           P. falciparum treated with artesunate+mefloquine combination for three days and
           monitored for 42 days. The follow-up was done with assessments in the first four days
           and then once a week until the day 42. During the visits, subjects were submitted to an
           interview, clinical examination, temperature measurement and collection of venous (D0,
           D3 and D42) or capillar (all visits) blood samples for hemogram (D0, D3 and D42) and
           parasitological exam (all visits). The parasitological evaluation was done by microscopy
           (immediately with review later) and real time PCR (qPCR) in order to confirm the
           infecting specie of Plasmodium, to detect gametocytes and to measure the parasitemia
           (parasites/μl). ). The blood samples of D0 (before the treatment) was used to evaluate
           the phenotype of multidrug resistance (MDR) in the population of P. falciparum.

        -  Potential risks to participants: The action proposed does not add risks beyond those
           inherent to the treatment and course of illness, since the fixed combination artesunate
           + mefloquine was being used as the first line treatment of uncomplicated malaria caused
           by Plasmodium falciparum in the Valley Juruá since 2006 and still is recognized by the
           Ministry of Health as an alternative to the combination of artemether + lumefantrine in
           Brazil. If necessary, the study subjects could be admitted to the General Hospital Juruá
           seat of outpatient malaria. Medical and laboratory support was guaranteed free of charge
           to all study subjects and for all health problems that have been present during the
           follow-up.

        -  What the study adds to knowledge in public health? : This study offers a crucial
           knowledge to guide the development of policies to antimalarial drugs in endemic areas.
    

Intervention name(s): artesunate & mefloquine combination
Intervention type(s): Drug
Intervention description(s): A therapeutic trial of a single arm for prospective evaluation of responses of individuals with uncomplicated malaria by P. falciparum treated with combination artesunate + mefloquine for three days and monitored clinically and biochemically for 42 days.
Other intervention name(s): ASMQ
Intervention MeSH terms: Artesunate; Mefloquine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: malaria; Plasmodium falciparum; artesunate and mefloquine combination (ASMQ); treatment; Juruá Valley; Brazil; multidrug resistance 1 gene of Plasmodium falciparum -Pfmdr1