Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pyronaridine-artesunate and Artemether-lumefantrine for the Treatment of Paediatric Uncomplicated Falciparum Malaria in Western Kenya
Brief Summary: The purpose of this study is to determine the efficacy of pyronaridine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children.


Options:
A: Inclusion Criteria:

* Children \>5yrs and adults presenting with acute falciparum malaria (N=40) to Pailin hospital will be eligible for inclusion in this study provided that

  * They or their parents/guardians give fully informed consent.
  * They are not pregnant.
  * They have not received antimalarial drugs in the previous 48 hours.
  * P.falciparum parasitaemia exceeds 10,000/uL

Exclusion Criteria:

* Mixed infection (such as vivax malaria), history of allergy to artesunate or mefloquine, any sign of severe disease according to WHO criteria
B: Inclusion Criteria:

* Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations:

  * Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children.
  * Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear). analysis).
* Weight ≥5 kg - \< 20 kg (granules); ≥20 kg (tablets).
* Ability to take an oral medication.
* Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country.
* The patient has to comply with all scheduled follow-up visits.

Exclusion Criteria:

* Patients with clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4).
* Known allergy to artemisinin and/or to pyronaridine.
* Known pregnancy.
* Lactating women should be excluded if other anti-malarial treatments are available.
* Complicated malaria as per WHO definition (Annex 2)
* Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study.
* Patients having been treated with Pyramax in the previous 28 days.
C: Inclusion Criteria:

* Adults and children ≥ 20 kg
* Symptomatic of malaria infection, i.e. history of fever within 24 hours and/or presence of fever \>37.5°c.
* Microscopic confirmation of asexual stages of P. falciparum (P. falciparum and mixed infection in Pailin only)
* Capability of taking an oral medication
* Written informed consent given to participate in the trial
* Willingness and ability to adhere to follow-up visit schedule

Exclusion Criteria:

* Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age, that is 18 to 45 y/o)
* Female aged 12-18y
* Parasitemia \> 150 000/µL).
* Signs or symptoms indicative of severe malaria:

  * Impaired consciousness (Blantyre Coma Score \<5)
  * Severe anaemia (Hct\<15%)
  * Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites
  * Respiratory distress
  * Severe jaundice
* Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or to pyronaridine
* History of splenectomy
* Known history or evidence of clinically significant disorders, such as:

  * Known active Hepatitis A, e.g. by detection of anti HAV-IgM.
  * Known hepatitis B surface antigen (HBsAg) carrier.
  * Known hepatitis C antibody (HCV Ab).
  * Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range.
D: Inclusion Criteria:

* Children between 6 months and 12 years old, with a body weight of ≥5 kg;
* Living in the catchment area of the study (within a radius of \~10 km from St. Jude's Clinic, Mbita, Kenya);
* Having microscopically confirmed P. falciparum mono-infection (asexual parasite density 1,000-200,000 µL-1).

Exclusion Criteria:

* Signs and symptoms of severe malaria (according to WHO criteria for severe malaria, (WHO 2012)) or any other severe illness necessitating parenteral treatment;
* Mixed Plasmodium infection;
* Clinically suspected (oedema, jaundice and/or ascites) or reported hepatic and/or renal impairment (any cause, as reported by parents/guardians and/or evident from medical history);
* Having anaemia with an Hb \<6 g/dL;
* Evidence of severe malnutrition (severe wasting: z-score weight for age \<-3 and severe stunting: z-score height for age \<-3 (WHO 2009b));
* Having received anti-malarial therapy in the previous two weeks;
* Known history of hypersensitivity, allergic or adverse reactions to artesunate, artemether-lumefantrine or other artemisinins;
* Participating in other anti-malarial drug intervention studies;
* Previous participation in the PAAL study, e.g. in the previous transmission season (each individual child can only take part in this study once);
* Not being available for follow-up.

Answer: D