Plasmodium Falciparum Clearance Rates in Response to Artesunate in Eastern Cambodia
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria
Phase: N/A
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Rick M Fairhurst, M.D., Principal Investigator, Affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
Summary
Plasmodium falciparum parasite clearance rates (PCRs) after oral artesunate treatment of
patients with uncomplicated malaria were recently found to be significantly slower in Pailin
(Western Cambodia) compared to Wang Pha (Eastern Thailand). This difference in PCRs has been
attributed to different histories of artesunate drug pressure in the two areas. In Pailin,
artesunate monotherapy has been used inappropriately for 30 years and is hypothesized to
have selected for artemisinin-resistant parasites (slow PCRs). To investigate the potential
contribution of human factors to the artemisinin resistance phenotype, we have identified a
study site in Eastern Cambodia where artemisinin-resistant parasites are not believed to be
present. The main aims of this study are to 1) determine whether the artemisinin resistance
phenotype (i. e., a half-life longer than the 2-hour half-life observed in Wang Pha) is
present in Eastern Cambodia, 2) determine whether hemoglobin E affects parasite clearance
rates in vivo, 3) determine whether age-associated acquired immunity affects parasite
clearance rates in vivo, and 4) identify parasite-heritable traits that are associated with
slow parasite clearance rates in vivo. To meet these aims, we are conducting a prospective,
longitudinal study to recruit Cambodian residents of Lumphat District in Ratanakiri Province
who complain of fever and/or symptoms of malaria. Patients diagnosed with uncomplicated
malaria will be treated with weight-based doses of artesunate given orally each day for 3
days followed by mefloquine given orally for 2 days. During this time, finger prick blood
smears will be obtained every 6 hours until parasite density is zero. From these data, we
will estimate parasite clearance rates using a half-life parameter. We will also collect
parasitized red blood cell samples from malaria patients prior to antimalarial drug
administration. These parasites will be tested in short-term in vitro culture experiments to
determine their susceptibility to artemisinins and other antimalarial drugs....
Clinical Details
Official title: Plasmodium Falciparum Clearance Rates in Response to Artesunate in Eastern Cambodia
Study design: Time Perspective: Prospective
Detailed description:
Plasmodium falciparum parasite clearance rates (PCRs) after oral artesunate treatment of
patients with uncomplicated malaria were recently found to be significantly slower in Pailin
(Western Cambodia) compared to Wang Pha (Eastern Thailand). This difference in PCRs has been
attributed to different histories of artesunate drug pressure in the two areas. In Pailin,
artesunate monotherapy has been used inappropriately for 30 years and is hypothesized to
have selected for artemisinin-resistant parasites (slow PCRs). To investigate the potential
contribution of human factors to the artemisinin resistance phenotype, we have identified a
study site in Eastern Cambodia where artemisinin-resistant parasites are not believed to be
present. The main aims of this study are to 1) determine whether the artemisinin resistance
phenotype (i. e., a half-life longer than the 2-hour half-life observed in Wang Pha) is
present in Eastern Cambodia, 2) determine whether hemoglobin E affects parasite clearance
rates in vivo, 3) determine whether age-associated acquired immunity affects parasite
clearance rates in vivo, and 4) identify parasite-heritable traits that are associated with
slow parasite clearance rates in vivo. To meet these aims, we are conducting a prospective,
longitudinal study to recruit Cambodian residents of Lumphat District in Ratanakiri Province
who complain of fever and/or symptoms of malaria. Patients diagnosed with uncomplicated
malaria will be treated with weight-based doses of artesunate given orally each day for 3
days followed by mefloquine given orally for 2 days. During this time, finger prick blood
smears will be obtained every 6 hours until parasite density is zero. From these data, we
will estimate parasite clearance rates using a half-life parameter. We will also collect
parasitized red blood cell samples from malaria patients prior to antimalarial drug
administration. These parasites will be tested in short-term in vitro culture experiments to
determine their susceptibility to artemisinins and other antimalarial drugs.
Eligibility
Minimum age: 1 Year.
Maximum age: N/A.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
Age 2 to 65 years, inclusive
Uncomplicated P. falciparum malaria.
Tympanic temperature greater than or equal to 37. 5 degree C or history of fever within the
last 24 h.
P. calciparum asexual parasite density 10,000 200,000/microL, Inclusive.
Willingness to allow the storage of blood samples collected as part of the study.
Willingness and ability of the patient/guardians to comply with the protocol for the
duration of the study.
EXCLUSION CRITERIA:
Severe malaria: diminished consciousness, respiratory distress, severe prostration,
anuria, jaundice, hemoglobinuria, repetitive vomiting, or cessation of eating and
drinking.
Non-malaria etiology of febrile illness (e. g., respiratory tract infection) evident on
clinical examination.
Hematocrit < 25 percent
Treatment of present symptoms with an artemisinin compound or artemisinin-based
combination therapy within the previous 7 days.
Pregnancy or breastfeeding
History or allergy or known contraindication to artemisinins or piperaquine
Splenectomy.
Locations and Contacts
National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H, Phnom Penh, Cambodia
Additional Information
Starting date: October 2010
Last updated: October 23, 2014
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