Please select the eligibility criteria that correspond to the clinical trial below.
Title: Artemisinin-resistant Plasmodium Falciparum Malaria in Cambodia
Brief 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.


Options:
A: Inclusion Criteria:

1. Viable pregnancy assessed by Doppler
2. Gestational age 16 to 32 weeks (inclusive) by fundal height
3. No history of IPTp use during this pregnancy
4. Willing to participate and complete the study schedule
5. Willing to sign or thumb print informed consent
6. Resident of study area and intending to stay in the area for the duration of the follow-up
7. Willing to deliver in the labor ward of the study clinic or hospital
8. HIV negative at enrolment

Exclusion Criteria:

1. HIV positive or unknown
2. Residence outside study area or planning to move out in the 12 months following enrolment
3. High risk pregnancy, including any pre-existing illness likely to cause complication of pregnancy (hypertension, diabetes, asthma, epilepsy, renal disease, liver disease, fistula repair, leg or spine deformity)
4. Severe anemia requiring blood transfusion (Hb ≤ 7.0 g/dL) at enrolment
5. Known allergy or previous adverse reaction to any of the study drugs
6. Unable to give informed consent (for example due to mental disability)
7. Previous inclusion in the same study
8. Gestational age \>32 weeks
9. Previous IPTp during the current pregnancy
10. Participating in other malaria intervention studies
11. Known or suspected cardiac disease
12. Patients taking drugs in any of the following classes: antiarrhythmic agents, neuroleptics, macrolides, and certain antimalarial drugs such as mefloquine, chloroquine, halofantrine and lumefantrine.
B: * INCLUSION CRITERIA (Parasite Recrudescence Study):

  1. Age 2 to 65 years, inclusive
  2. Uncomplicated P. falciparum malaria
  3. Temperature greater than or equal to 37.5 degrees Celsius or history of fever within the last 24 h
  4. P. falciparum asexual parasite density less than or equal to 200,000/microL
  5. Willingness to allow the storage of blood samples collected as part of the study
  6. Willingness and ability of patients/guardians to comply with the protocol for the duration of the study.

EXCLUSION CRITERIA (Parasite Recrudescence Study):

1. Severe malaria: diminished consciousness, respiratory distress, severe prostration, anuria, jaundice, hemoglobinuria, repetitive vomiting, or cessation of eating and drinking
2. Non-malaria etiology of febrile illness (e.g., respiratory tract infection) evident by history and physical examination
3. Hematocrit \<25%
4. Treatment of present symptoms with an antimalarial drug within the previous 7 days
5. Pregnancy or breastfeeding
6. History of allergy or known contraindication to artemisinins or MQ
7. Splenectomy
8. P. vivax parasitemia

INCLUSION CRITERIA (Peripheral Blood Collection Study):

1. Healthy-appearing adults greater than or equal to 18 years old
2. Residence in Pursat province
3. Willingness to participate in the study as evidenced by informed consent

EXCLUSION CRITERIA (Peripheral Blood Collection Study):

1. Pregnancy
2. Hematocrit \<25%
C: Inclusion Criteria:

1. Age 4 -5 months
2. Confirmed HIV status of biological mother
3. Negative HIV DNA PCR test at time of enrollment for infants born to HIV-infected mothers
4. Infants born to HIV-infected mothers must be breastfeeding
5. Residency within 30km of the study clinic
6. Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol
7. Provision of informed consent by parent/guardian

Exclusion Criteria:

1. History of allergy or sensitivity to TS, SP, or DP
2. Active medical problem requiring in-patient evaluation at the time of screening
3. Intention of moving more that 30km from the study clinic during the follow-up period
4. Chronic medical condition (i.e. malignancy) requiring frequent medical attention
5. Living in the same household as a previously enrolled study participant
6. QTc interval \> 450 msec
7. Other clinically significant ECG abnormalities such as arrhythmia, ischemia, or evidence of heart failure
8. Family history of Long QT syndrome
9. Current use of drugs that prolong the QT interval
D: Inclusion Criteria:

* 3 months old living in the aera for the next 2 years, exlusive use of the study health facilities

Exclusion Criteria:

* Known chronic illness, e.g. TB, diabetes, renal failure severe malnutrition (weight-for-age (WAZ) \< 60% percentile) severe anaemia (Hb \< 5 g/dl), or permanent disability, that prevents or impedes study participation

Answer: B