- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00663546
Malaria Studies in Cambodia
Studies of P. Vivax and P. Falciparum Malaria in Cambodia
This study, conducted by the National Center for Parasitology, Entomology and Malaria Control of Cambodia s Ministry of Health and the National Institute of Allergy and Infectious Diseases, will explore whether the following factors confer protection against malaria and associated anemia: certain blood groups, the hemoglobin E variant, G6PD-deficiency and alpha-thalassemia. Malaria is caused by parasites (P. falciparum and P. vivax) that are transmitted to humans through mosquito bites. This protocol includes two studies, a cohort study and a P. vivax collection study.
Individuals are eligible for enrollment in the studies as follows:
Cohort study:
Residents of all ages of Kandal, Ekapheap and Sangkumthmey villages (Thmar Da commune) who plan to remain in Thmar Da commune for the next 5 years.
P. vivax collection study:
2 years of age and older
Participating in NIAID protocol 05-I- N210 ( Severe Malaria and Anti-malarial Drug Resistance in Cambodia ) and diagnosed with P. vivax malaria
Participants undergo the following procedures:
Cohort study:
Baseline evaluation, including the following:
- Collection of demographic information
- Malaria history, temperature measurement and review of current symptoms, if any
- Blood draw of 300 microliters
- Additional blood draw of 10 milliliters in selected adults 18 years of age and older
Treatment with artesunate-piperaquine at a commune health post for subjects who develop malaria
Contact once a year for 5 years to determine continued residency in Thmar Da commune
P. vivax collection study:
- Medical history and physical examination
- Hemoglobin level measurement
- Blood draw
- Treatment with chloroquine
- Blood draw 3 to 5 weeks after treatment in some patients 18 years of age or older
Study Overview
Status
Conditions
Detailed Description
Cohort study. Hemoglobin (Hb) and red blood cell (RBC) polymorphisms that give rise to HbE, alpha-thalassemia, G6PD-deficiency, and ABO blood groups occur at high frequency along the Thailand-Cambodia border, where Plasmodium vivax and P. falciparum have been and continue to be transmitted. To determine whether these Hb/RBC polymorphisms have been naturally selected because they confer protection against malaria and malaria-associated anemia, we will conduct a cohort study of ethnic Khmer in Cambodia. Approximately 1000 individuals of all ages will be genotyped for the four polymorphisms listed above and then followed for 5 years to determine the mean incidence rates for both P. vivax and P. falciparum malaria, stratified by genotype. Incidence rate ratios (IRRs) will be calculated for each polymorphism relative to the wildtype genotype. Differences between Hb levels during acute episodes of malaria and Hb levels at baseline will also be calculated to determine if Hb/RBC polymorphisms influence the degree of malaria-associated anemia.
P. vivax collection study. Unlike P. falciparum, P. vivax cannot be efficiently cultivated in vitro. Improved cultivation methods are needed to make progress on nearly all aspects of P. vivax malariology, including pathogenesis, naturally-acquired immunity, vaccination, and antimalarial drug resistance. We plan to improve both short- and long-term cultivation methods in order to test various hypotheses of P. vivax pathogenesis and protection. Using freshly obtained parasite isolates from individuals with P. vivax malaria, we will test whether Hb/RBC polymorphisms influence potentially pathogenic properties of P. vivax parasites, such as their ability to bind non-infected RBCs and other host cells. It is believed that P. vivax selectively invades reticutocytes. This tropism has frustrated attempts at long-term cultivation of this parasite, which requires a constant source of reticulocyte-rich blood not easily obtained even in developed countries. The host reticulocyte receptor that mediates the highly selective tropism of P. vivax has not been identified. Fresh P. vivax parasites will also be used in in vitro experiments to identify the putative receptor that defines reticulocyte tropism. Any P. vivax ligand that bound selectively to a reticulocyte receptor will then be discovered and worked up as a promising vaccine candidate.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Phnom Penh, Cambodia
- National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H
-
Preah Vihear Province, Cambodia
- Preah Vihear Referral Hospital
-
Ratanakiri Province, Cambodia
- Ratanakiri Referral Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA: (Cohort Study)
Resident of Kandal, Ekapheap, and Sangkumthmey villages (Thmar Da commune), and no plans to leave the Thmar Da commune for the next 5 years.
Willingness to participate in the study as evidenced by informed consent of subjects or his/her parent or guardian, and willingness to come to commune health posts if he/she develops fever or other symptoms of malaria.
Individuals of all ages will be enrolled.
EXCLUSION CRITERIA: (Cohort Study)
Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS).
INCLUSION CRITERIA: (P. vivax Collection Study)
P. vivax malaria (mono-infection).
Willingness to participate in the study as evidenced by informed consent of subjects or his/her parent or guardian.
Age greater than or equal to 2.
Hematocrit greater than or equal to 25%.
EXCLUSION CRITERIA: (P. vivax Collection Study)
Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS).
Pregnancy.
Prior use of antimalarials during the past 2 months.
INCLUSION CRITERIA: (Cord and Peripheral Blood Collection Study)
Healthy male or female adults greater than or equal to 18 years old or healthy pregnant female adults greater than or equal to 18 years old.
Willingness to participate in the study as evidenced by informed consent.
EXCLUSION CRITERIA: (Cord and Peripheral Blood Collection Study)
Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric disease).
Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS).
INCLUSION CRITERIA: (Collection of peripheral blood for identifying and isolating memory B cells)
Healthy male or non- pregnant female adults greater than or equal to 18 years old.
Previous enrollment on the P. vivax collection study.
Willingness to participate in the study as evidenced by written informed consent.
EXCLUSION CRITERIA: (Collection of peripheral blood for identifying and isolating memory B cells)
For the follow-up blood draw (250 mL), symptomatic parasitemia with any species of Plasmodium.
For the follow-up blood draw (250 mL), hemoglobin level <9 g/dL.
For the follow-up blood draw (250 mL), weight <45 kg.
Any condition that in the opinion of the investigator would render the subject unable to comply with the protocol (e.g., psychiatric illness).
Any health condition that in the opinion of the investigator would confound data analysis or pose unnecessary exposure risks to study personnel (e.g., individuals who are known to be HIV-infected or to have AIDS).
Study Plan
How is the study designed?
Design Details
Collaborators and Investigators
Publications and helpful links
General Publications
- Frischer H, Bowman J. Hemoglobin E, an oxidatively unstable mutation. J Lab Clin Med. 1975 Apr;85(4):531-9.
- Lachant NA, Tanaka KR. Impaired antioxidant defense in hemoglobin E-containing erythrocytes: a mechanism protective against malaria? Am J Hematol. 1987 Nov;26(3):211-9. doi: 10.1002/ajh.2830260302.
- Hill AV. Molecular epidemiology of the thalassaemias (including haemoglobin E). Baillieres Clin Haematol. 1992 Jan;5(1):209-38. doi: 10.1016/s0950-3536(11)80042-9.
- Hostetler JB, Sharma S, Bartholdson SJ, Wright GJ, Fairhurst RM, Rayner JC. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. PLoS Negl Trop Dis. 2015 Dec 23;9(12):e0004264. doi: 10.1371/journal.pntd.0004264. eCollection 2015 Dec.
- Amaratunga C, Sreng S, Mao S, Tullo GS, Anderson JM, Chuor CM, Suon S, Fairhurst RM. Chloroquine remains effective for treating Plasmodium vivax malaria in Pursat province, Western Cambodia. Antimicrob Agents Chemother. 2014 Oct;58(10):6270-2. doi: 10.1128/AAC.03026-14. Epub 2014 Jul 21.
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 999908094
- 08-I-N094
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria