Prevalence Survey of Antimalarial Drug Resistance Markers
Prevalence Survey of Antimalarial Drug Resistance Markers
Study is cross-sectional and observational with one-time dried-blood spot sample collection
 from persons with laboratory-confirmed uncomplicated Plasmodium falciparum malaria (mixed or
 monoinfection). Samples will be analysed for the presence of molecular markers of resistance
 to ACT partner drugs (gene amplifications and/or other mutations in pfmdr1, gene
 amplifications of pfpm2, and additional mutations which may be identified during the course
 of the trial) in the first instance. Testing to detect additional markers of antimalarial
 drug resistance will also be performed where feasible. Prevalence of mutations will be
 summarized and mapped to provide intelligence on antimalarial drug resistance in the region
 of interest.
Malaria Malaria is caused by a mosquito-borne, protozoan parasite belonging to the genus
 Plasmodium. Of the five species of Plasmodium that infect humans, Plasmodium falciparum is
 the most deadly and is responsible for the majority of malaria disease and death. Every year,
 falciparum malaria causes disease in hundreds of millions of people living in the tropics and
 subtropics, killing a million or more according to some estimates. The vast majority of these
 deaths occur in sub-Saharan Africa, mostly among young children and infants. When treated
 with effective antimalarial drugs, malaria can be cured completely.

 Antimalarial drug resistance The emergence in Southeast Asia and the subsequent global spread
 of drug resistant malaria was a major factor contributing to the failure of the first global
 malaria eradication campaign in the mid-20th century (1). The widespread implementation of
 highly effective artemisinin-based combination therapy (ACT) for malaria has contributed to
 significant gains in global control and elimination efforts and has brought malaria
 eradication back on the agenda, 40 years after the first global malaria eradication campaign
 was abandoned (2). However the gains seen in the past decade are now at risk as parasite
 resistance to artemisinin compounds has been confirmed in Southeast Asia and threatens Africa
 once again (3-8). In the absence of effective vaccines, it is critical to prolong the usable
 life of antimalarial drugs by judicious implementation of treatment strategies.

 Primary Objective To measure prevalence of established and candidate molecular markers of
 drug resistant malaria in Greater Mekong Subregion

 Secondary Objective To map the geographical and temporal changes in prevalence of molecular
 markers of antimalarial drug resistance in Greater Mekong Subregion
Inclusion Criteria:

 -  Patients (6 months - 75 years) with confirmed uncomplicated P. falciparum infection

 -  Written informed consent obtained (by parents/guardian in case of children less than
 18 years old)

 Exclusion Criteria:

 Patients presenting signs of severe malaria* will be excluded from the survey to prevent
 any delay in the management of the patient.

 *Guideline for the treatment of Malaria-3rd edition, WHO (27) Severe falciparum malaria is
 defined as one or more of the following, occurring in the absence of an identified
 alternative cause and in the presence of P.falciparum asexual parasitaemia.

 -  Impaired consciousness: A Glasgow comma score < 11 in adults or Blantyre coma score <
 3 in children

 -  Prostration: Generalized weakness so that the person is unable to sit, stand or walk
 without assistance.

 -  Multiple convulsions: More than two episodes within 24 h

 -  Acidosis: A base deficit of > 8 mEq/L or, if not available a plasma bicarbonate level
 of < 15 mmol/L or venous plasma lactate ≥ 5 mmol/L. Severe acidosis manifests
 clinically as respiratory distress (rapid, deep, laboured breathing).

 -  Hypoglycaemia: Blood or plasma glucose < 2.2 mmol/L (<40 mg/dL)

 -  Severe malarial anaemia: Haemoglobin concentration ≤ 5 g/dL or a haematocrit of ≤ 15%
 in children < 12 years of age (< 7 g/dL and < 20%, respectively, in adults) with a
 parasite count > 10,000/µL

 -  Renal impairment: Plasma or serum creatinine > 265 µmol/L (3 mg/dL) or blood urea > 20
 mmol/L

 -  Jaundice: Plasma or serum bilirubin > 50 µmol/L (3 mg/dL) with a parasite count >
 100,000/ µL

 -  Pulmonary oedema: Radiologically confirmed or oxygen saturation < 92% on room air with
 a respiratory rate > 30/min, often with chest indrawing and crepitations on
 auscultation

 -  Significant bleeding: Including recurrent or prolonged bleeding from the nose, gums or
 venepuncture site; haematemesis or melaena

 -  Shock: Compensated shock is defined as capillary refill ≥ 3 s or temperature gradient
 on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as
 systolic blood pressure < 70 mm Hg in children or < 80 mm Hg in adults, with evidence
 of impaired perfusion (cool peripheries or prolonged capillary refill)

 -  Hyperparasitaemia: P.falciparum parasitaemia > 10%