Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Investigator-Blinded, Multicenter, Parallel-Group Study to Compare Efficacy, Safety and Tolerability of Arthemeter/ Lumefantrine Dispersible Tablet Formulation vs. Artemether/ Lumefantrine 6-Dose Crushed Tablet in the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Infants and Children.
Brief Summary: This study will evaluate the safety and efficacy of artemether-lumefantrine against uncomplicated malaria caused P. falciparum in children of 5-35 kg bodyweight.


Options:
A: Inclusion Criteria:

1. Male or female patients ≤12 years of age.
2. Body weight ≥ 5 kg and \< 25 kg with no clinical evidence of severe malnutrition (defined as a child whose weight-for-height is below -3 standard deviations or \<70% of the median of the NCHS/WHO normalised reference values).
3. Presence of acute uncomplicated P. falciparum mono-infection confirmed by:

   1. Fever, as defined by axillary temperature ≥37.5°C or oral/tympanic/rectal temperature ≥38°C, or documented history of fever in the previous 24 hours and,
   2. Positive microscopy of P. falciparum with parasite density between 1,000 and 200,000 asexual parasite count/µl of blood.
4. Written informed consent, in accordance with local practice, provided by parent/guardian. If the parent/guardian is unable to write, witnessed consent is permitted according to local ethical considerations. Where possible, patient assent will be sought.
5. Ability to swallow whole volume of liquid in which medication is suspended.
6. Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
7. Ability and willingness to participate based on information given to parent or guardian and access to health facility. The patient is to comply with all scheduled follow up visits until D42.

Exclusion Criteria:

1. Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2000 \[Attachment 3\].
2. Mixed Plasmodium infection.
3. Severe vomiting, defined as \>3 times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as ≥3 watery stools per day.
4. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval ≥450 milliseconds), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including recent head trauma).
5. Presence of significant anaemia, as defined by Hb \<8 g/dL.
6. Presence of febrile conditions caused by diseases other than malaria.
7. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, lumefantrine or artesunate or other artemisinins.
8. Patients with known disturbances of electrolytes balance, e.g. hypokalaemia or hypomagnesaemia.
9. Use of any other antimalarial agent within 2 weeks prior to start of the study as evidenced by reported patient history.
10. Pregnant or breastfeeding.
11. Patients taking any drug which is metabolised by the cytochrome enzyme CYP2D6 (flecainide, metoprol, imipramine, amitriptyline, clomipramine).
12. Received an investigational drug within the past 4 weeks.
13. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
14. Known positive for HIV antibody.
15. Liver function tests \[ASAT/ALAT levels\] \>2.5 times upper limit of normal range.
16. Known significant renal impairment as indicated by serum creatinine of \>1.4 mg/dL.
17. Previous participation in any clinical study with pyronaridine artesunate.
B: Inclusion Criteria:

* male or female infants and children ≤12 years of age
* body weight of ≥5 kg and \<35 kg,
* with a confirmed diagnosis of uncomplicated malaria caused by the P. falciparum parasite

Exclusion Criteria:

* complicated malaria
* persistent vomiting
* malaria due to parasites other than P. falciparum
* antimalarial treatment received in the past 2 weeks
* known chronic disease e.g. positive HIV status, severe cardiac, renal, or hepatic disease
C: 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.
D: Inclusion Criteria:

* Patient is a child between 6 to 59 months
* Visiting health facility for treatment of fever
* Do not have signs of severe disease
* Are not being referred to another health facility
* Living within a defined distance from the health facility (\<8 km/ 5 miles)
* Have not taken part in the study already or are not part of a household that has already taken part in the study
* Responsible caretakers/parents provide additional informed consent

Exclusion Criteria:

-

Answer: B