Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3a: Efficacy, Safety, and Tolerability of Dihydroartemisinin/Piperaquine (Artekin®) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Peruvian Amazon Region
Brief Summary: In Peru, Mefloquine plus Artesunate (MAS3), is the current first line treatment for P. falciparum malaria in the Amazonian Region, and has proved its efficacy against multi-resistant P. falciparum parasites, but several side effects have been reported. Dihydroartemisinin-piperaquine (DHA-PPQ) is a new co-formulated and well tolerated ACT, increasingly used in Southeast Asia where it has proved to be highly effective against Plasmodium falciparum malaria. We tested the efficacy, safety and tolerability of DHA-PPQ in patients with uncomplicated P. falciparum malaria. A RCT to evaluate DHA-PPQ was carried out, between 2003 and 2005. Patients with uncomplicated P. falciparum malaria were randomly allocated to receive either DHA-PPQ or MAS3 with a 63-day follow-up period. Five hundred twenty two patients were included in the analysis, 262 were allocated to receive DHA-PPQ, and 260 to receive MAS3. The two groups were comparable at baseline in demographic and clinical characteristics. The mean time for parasite clearance into the DHA-PPQ group was 32.0 hours and 35.5 hours in the MAS3 group. Twenty-four hours after the first dose, the proportions of patients whose cleared parasitaemia were 67.2% in the DHA-PPQ group, and 58.1% in the MAS3 group (RR 1.25, \[95% CI 1.03-1.52\], p = 0.017). All patients were able to clear parasites within 72 hours after the first dose. The mean time for fever clearance was 28.0 and 29.5 hours in DHA-PPQ and MAS3 group respectively. (P= 0.69). Twenty-four hours after the first dose, 85.5% and 83.1% of patients cleared fever in the DHA-PPQ and MAS3 group respectively (p\>0.05). The Adequate Clinical and Parasitological Response (ACPR), PCR adjusted, were 97.7% and 99,2% for the DHA-PPQ and MAS3 group respectively, (RR 0.99, 95% CI \[0.86-1.13\], P = 0.88). No Early Treatments Failures were reported in any group. In the DHA-PPQ group, according to the PCR adjusted results, 6 subjects had Late treatment Failures. In the MAS3 group, two Late Treatment Failures was reported. The frequency of adverse events was significantly lower in patients treated with DHA-PPQ than in those treated with MAS3.

DHA-PPQ proved to be a highly effective antimalarial drug for the treatment of P. falciparum malaria and suitable for use in the Peruvian Amazon region. It also has the advantage of being better tolerated. In terms of cost, DHA-PPQ is cheaper and more affordable than MAS3 and should be considered for the National Antimalarial Drug Policy in Perú.


Options:
A: Inclusion Criteria:

* Males and Females aged between 6 months and 59 months inclusive. In the sites where CDA is tested all recruited children will be aged between 12 months and 59 months inclusive (this arm was discontinued on 17th February 2008). This criterion applies only for the recruitment in the first follow up. For the second follow up, children having been included in the first follow up are eligible, regardless of their age.
* Body weight of 5 Kg and above.
* Microscopically confirmed, monoinfection of Plasmodium falciparum (parasitaemia ≥ 2,000/μL to 200,000/μL).
* Fever (axillary temperature at ≥ 37.5°C) or history of fever in the previous 24 hours.
* Haemoglobin value ≥ 7.0 g/dl;
* Signed (or thumb-printed whenever parents/guardians are illiterate) informed consent by the parents or guardians. Note the informed consent will be asked only at recruitment and will cover the whole period of the study, including second active follow up and passive case detection.
* Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the trial.

Exclusion Criteria:

* Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
* Known hypersensitivity to the study drugs.
* Severe malaria.
* Danger signs: not able to drink or breast-feed, vomiting (\> twice in 24hours), recent history of convulsions (\>1 in 24h), unconscious state, unable to sit or stand.
* Presence of intercurrent illness or any condition (cardiac, renal, hepatic diseases) which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency.
* Severe malnutrition (defined as weight for height \<70% of the median NCHS/WHO reference).
* Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carinii pneumonia in children born to HIV+ women.
B: Inclusion criteria

* Age over 6 months and
* Weight ≥ 5 kg, and
* Slide-confirmed infection with Plasmodium falciparum (including mixed infections), and
* Asexual parasite density between 500 and 200,000/µl of blood, and
* Informed consent from a parent or guardian aged at least 18 years.

Exclusion criteria

* General danger signs according to the WHO definition or
* Signs of severe/complicated malaria according to the WHO definition or
* Severe anaemia (haemoglobin \< 5 g/dL), or
* Known history of hypersensitivity to any of the study drugs, or
* Severe malnutrition (as defined by a weight-for-height below 70% of median and/or symmetrical oedemas involving at least the feet), or
* Concomitant febrile illness due to causes other than malaria with the potential to confound study outcome (measles, acute lower tract respiratory infection, otitis media, tonsillitis, abscesses, severe diarrhoea with dehydration, etc.; mild flu should not lead to exclusion) or
* History of psychiatric diseases, or
* Having received a full course treatment including MQ in the preceding 9 weeks or
* Having received any other antimalarials in the previous 48 hours.
C: Inclusion Criteria:

1. Age 6 weeks to 9 months
2. Documented HIV-1 status of mother and child
3. Agreement to come to the study clinic for any febrile episode or other illness
4. Agreement to avoid medications administered outside the study protocol
5. Guardian age 18 years or older (no age limit for parents)
6. Parent or guardian willing to provide informed consent
7. Residence within a 30 km radius of the study clinic

Exclusion Criteria:

1. HIV-exposed infants who have already stopped receiving TMP/SMX as a result of having stopped breastfeeding and having been tested HIV-negative before screening
2. Intention to move more than 30 km from the study clinic during the follow-up period
3. History of allergy or sensitivity to AL or DP or TMP/SMX
4. Active medical problem requiring in-patient evaluation at the time of screening
D: Inclusion Criteria:

* Age: 5 - 60 years old
* Fever (axillary temperature equal or higher than 37,5 °C) or history of fever in the previous 24 hours
* Monoinfection with P. falciparum, with parasitic density between 1,000 and 200,000 par/µl
* Informed consent provided by patient or parent or legal tutor

  • Exclusion criteria:
* Mixed malaria infection
* Pregnancy or breastfeeding to child ≤ 6 months of age
* One or more danger signs or any sign of severe or complicated malaria
* A concomitant severe disease
* History of treatment with mefloquine in the last 60 days or chloroquine, primaquine or quinine within the 14 days before the present episode
* History of neuropsychiatric disease
* History of hypersensitivity reactions to artemisinins or mefloquine
* History of splenectomy

Answer: D