Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: Artemisinin combination therapy (ACT) with artemether lumefantrine (AL) is currently the first line treatment policy in Tanzania. AL is an efficacious drug that also has the capacity to reduce malaria transmission to mosquitoes. Nevertheless, there is concern about the development of parasite resistance against AL and there have been very few clinical trials that compared different ACT regimens. A recent clinical trial shows that the combination of dihydroartemisinin-piperaquine (DP) may be more efficacious than AL and may have a more pronounced beneficial effect on post-treatment malaria transmission. Screening for molecular markers that are related to parasite susceptibility to ACT drugs and to post-ACT treatment malaria transmission can assist in preventing the development and spread of ACT resistance.

In the current study, the investigators compared AL and DP for the treatment of uncomplicated malaria. The investigators endpoints are

* clinical efficacy
* post-treatment gametocytaemia by molecular techniques
* post-treatment malaria transmission.


Options:
A: 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
B: 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.
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 6 months - 10 years
* Residents of research area (5 km around the clinic)
* Willingness to come for complete scheduled follow-up.
* Uncomplicated malaria with P. falciparum mono-infection
* Parasitaemia of 1000-200,000 parasites/ul
* Temperature \> 37.5°C and \< 39.5°C, or history of fever in previous 24 hours.
* No history of adverse reactions to AL
* Understanding of the procedures of the study by parent or guardian and willing to participate by signing informed consent forms.

Exclusion Criteria:

* General signs of severe malaria
* Haemoglobin concentration \< 5g/dl
* Presence of disease other than malaria causing febrile conditions
* Mixed infection with P. malariae or other non-falciparum malaria species
* Unwilling to participate and sign informed consent forms.

Answer: D