Artemisinin-resistant Malaria in Cambodia
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Observational

Summary: 
      Background:

      - Artemisinin-based combination therapies (ACTs) are the first-line treatments for malaria.
      ACTs are highly effective, but malaria caused by the Plasmodium falciparum parasite is
      becoming resistant to some ACTs. ACT-resistant malaria has shown up in some parts of
      Cambodia, but not yet in other parts of the country. This has been shown by treating patients
      with ACTs, checking the amount of parasites in the patient s blood every 6 hours, and
      calculating the rate of parasite clearance. The parasite clearance rate in response to ACTs
      is getting slower in western Cambodia and may be the first sign of ACT resistance.
      Researchers want to study how effective ACTs are in different regions of Cambodia. This study
      will look at the extent of ACT resistance and how widespread ACT-resistant malaria has
      become.

      Objectives:

      - To compare the prevalence of ACT-resistant malaria in western, northern and eastern
      Cambodia.

      Eligibility:

      - Individuals between 2 and 65 years of age who have uncomplicated Plasmodium falciparum
      malaria and have not taken any antimalarial drugs for their symptoms in the previous 7 days.

      Design:

        -  Participants will be recruited from clinics and hospitals in three Cambodian provinces.

        -  Participants will be informed about the study and their consent to participate in the
           study will be obtained.

        -  A venous blood sample will be obtained from patients before treatment and used for
           laboratory experiments to measure parasite and patient factors that might affect the
           parasite clearance rate.

        -  Participants with malaria will be treated with dihydroartemisinin-piperaquine (DHA-PPQ),
           the standard first-line treatment for malaria in Cambodia.

        -  Treatment will be monitored with frequent blood samples obtained from a finger prick.
           The amount of malaria parasites in each blood sample will be counted and followed until
           they are no longer detectable.

        -  Participants will have weekly follow-up visits for up to 9 weeks. Finger-prick blood
           samples will be taken at each visit to see if the parasites reappear after treatment
           with ACT.
    

Detailed description: 
      Artemisinin-based combination therapies (ACTs) are the first-line treatments for Plasmodium
      falciparum malaria worldwide. In Western Cambodia,artemisinin resistance has been defined as
      a long half-life of parasite clearance (T1/2) in response to an artemisinin, given orally for
      uncomplicated malaria. We hypothesize that this artemisinin resistance phenotype compromises
      the efficacy of ACTs. The primary objective of this study is to compare P. falciparum
      recrudescence rates in Western, Northern and Eastern Cambodia, following
      dihydroartemisinin-piperaquine (DHA-PPQ) treatment. The secondary objective of this study is
      to determine whether parasite recrudescence is associated with long T1/2. In the Parasite
      Recrudescence Study, patients with uncomplicated malaria will receive directly-observed
      treatment with DHA-PPQ over 3 days. We will follow these patients weekly for 9 weeks to
      identify those with recurrent parasitemia and use genotyping methods to distinguish
      recrudescences from reinfections. We will enroll a subset of these patients who have an
      initial parasite density greater than or equal to 10,000/microL in the Parasite Clearance
      Rate Study and follow their parasite densities more intensively by examining 6-hourly finger
      prick blood samples until parasites are undetectable by microscopy. With these data we will
      calculate and compare T1/2 values from patients with and without recrudescent parasitemia.
      Using various laboratory assays, we will also explore the contribution of host factors to
      T1/2 variation, and whether naturally-acquired immunity reduces the risk of drug-resistant
      parasite recrudescence.
    

Time perspective: Prospective
Keywords: Artemisinin-based Combination Therapies; Recrudescence; DHA-PPQ; Parasite Clearance Rate