Efficacy of Antimalarial Drugs Used for the Treatment of Uncomplicated Malaria, Plasmodium Falciparum, at the Agadez, Gaya and Tessaoua Sentinel Sites
Condition: MALARIA
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 4

Summary: 
      In Niger, malaria is a major public health problem. It is the main cause of morbidity and
      mortality among children. The management of malaria cases is based on the principle of early
      diagnosis and rapid treatment with effective drugs. It is confronted with the appearance of
      strains resistant to antimalarial drugs, hence the need to monitor antimalarial drug
      sensitivity.

      The study was conducted in three regions representing epidemiological strata of the country:
      Agadez (Centre de santé Intégré of Dagamanet in the Health district of Agadez), Maradi
      (Centre de santé intégré of Guindaoua in Tessaoua) and Dosso (Centre de santé Intégré centre
      in Gaya). The protocol used is the WHO standardized protocol of 2009. Artemether/Lumefantrine
      (AL) was administered with a 28-day follow-up in children aged 3 months to 15 years. A
      Polymerase Chain Reaction (PCR) correction is planned to differentiate between treatment
      failure and re-infestation as well as a study of genes responsible for resistance on the main
      drugs used.
    

Detailed description: 
      The study took place from September 1 to October 31, 2020 at the time of peak malaria
      transmission. It took place at three sentinel sites of the National Malaria Control Program
      (NMCP). These were in the regions of i) Agadez at the Centre de Santé Intégré (CSI) of
      Dagamanet in the Agadez district, ii) Dosso at the CSI centre in the health district (HD) of
      Gaya iii) Maradi at the CSI Guindaoua in the HD of Tessaoua. These sites were identified by
      the NMCP because of their high attendance rate and belong to 3 different malaria
      epidemiological strata.

      As the treatment failure rate of artemether lumefantrine (AL) in the regions is unknown, 5%
      was chosen. With a confidence level of 95% and a precision around the estimate of 5%, a
      minimum of 73 patients were included. The number of patients was increased by 20% to account
      for possible dropouts and withdrawals during the 28/42 day follow-up period, 88 patients were
      included in the study per site.

      The study drug is oral AL. It is one of the four antimalarial drugs selected by the Niger's
      NMCP for the management of malaria. The product consists of blister packs of 6 tablets, box
      of 30 of lot number K U142 with an expiration date of January 2022 and blister packs of 12
      tablets, box of 30 of lot number K U456 with an expiration date of January 2022.

      The AL combination was administered at a dose of 4 mg artemether and 24 mg lumefantrine per
      kg for three days. The AL was provided by the NMCP.

      The different prescriptions were as follows:

        -  5 to 15 Kg: 1 tablet, twice a day for three days.

        -  15 to 25 Kg: 2 tablets, twice a day for three days.

        -  25 to 35 kg: 3 tablets, twice a day for three days.

        -  Over 35 kg: 4 tablets, twice a day for three days.

      The first day's intake was done under direct observation and possible side effects were
      noted. Any patient who persistently vomited after taking the medication was excluded from the
      study and treated with artesunate. Patients were followed up regularly until Day 28 and
      received a clinical examination with thick drop control and axillary temperature taking at
      Day 0, Day 1, Day 2, Day 3, Day 7, Day 14, Day 21, and Day 28. Capillary blood on filtered
      paper (Wattman) was routinely collected from all patients on the day of inclusion ( Day 0)
      and during follow-up for molecular analysis. For follow-up, the density of asexual parasite
      forms was assessed on the basis of 8 000 leukocytes per microliter of blood. All slides were
      read by two microscopists to ensure control. At the end of the follow-up, the response to
      treatment was classified according to clinical and parasitological criteria
    

Intervention name(s): Artemether-lumefantrine
Intervention type(s): Drug
Intervention description(s): Efficacy of artemether lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in three sentinel sites in Niger (Agadez, Gaya and Tessaoua) in 2020
Intervention MeSH terms: Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination
Intervention model: Single Group Assignment
Intervention model description: This surveillance study is a prospective one-arm evaluation of clinical and parasitological responses to treatment of uncomplicated malaria with direct observation of treatment. Individuals with uncomplicated malaria, who meet the study inclusion criteria, will be recruited and treated at the sites by AL. They will be monitored for 28 days. Follow-up will consist of a series of fixed-date monitoring visits and corresponding clinical examinations and laboratory tests. Based on the results of these assessments, patients will be classified as having treatment failure (early or late) or adequate response. The proportion of patients with treatment failure during follow-up will be used to assess the efficacy of the study drugs.
PCR analysis will be used to distinguish between true recrudescence due to treatment failure and episodes of re-infestation. A proportion of 10% of the slides read in the field will be submitted for quality control.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Malaria; Efficacy; Arthemeter; Lumefantrine; Niger