MalariaNCT00663546
Malaria Studies in Cambodia
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in Cambodia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages Up to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- How many people
- 1,978 participants
- Where
- 3 sitesCambodia
- Study dates
- 24 Mar 2008to 5 Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
- 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%.
Who cannot join
- 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).
- 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.
Show all 22Show fewer
- 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).
Trial locations and contacts
3 sites in 1 country.
Cambodia3 sites
National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H
Phnom Penh
Preah Vihear Referral Hospital
Preah Vihear Province
Ratanakiri Referral Hospital
Ratanakiri Province
About this study
Official title: 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:
Read more
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.
- 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
- 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
Read the 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.
- 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.
- Conditions
- Malaria
- Keywords
- Malaria, Plasmodium, Hemoglobin E, Alpha-thalssemia, G6PD Deficiency
- Medical subject headings
- Malaria, Glucosephosphate Dehydrogenase Deficiency
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2008 (estimated)
- Study start24 Mar 2008
- Study completion5 Dec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 1,978 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Rick M Fairhurst, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00663546
- Sponsor's protocol ID
- 999908094
- Other IDs
- 08-I-N094
- Status last verified
- 5 Dec 2013
- First submitted
- 19 Apr 2008
- Last updated
- 20 Aug 2018
- Results posted
- No
Publications
Frischer H, Bowman J. Hemoglobin E, an oxidatively unstable mutation. J Lab Clin Med. 1975 Apr;85(4):531-9.
PubMed 1120926Lachant 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.
PubMed 3674003Hill 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.
PubMed 1596592Fantin RF, Coelho CH, Berhe AD, Magalhaes LMD, Pereira DB, Salinas ND, Tolia NH, Amaratunga C, Suon S, Sagara I, Narum DL, Fujiwara RT, Abejon C, Campos-Neto A, Duffy PE, Bueno LL. Immunological characterization of a VIR protein family member (VIR-14) in Plasmodium vivax-infected subjects from different epidemiological regions in Africa and South America. PLoS Negl Trop Dis. 2023 Apr 7;17(4):e0011229. doi: 10.1371/journal.pntd.0011229. eCollection 2023 Apr.
PubMed 37027391Hostetler 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.
PubMed 26701602Amaratunga 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.
PubMed 25049249
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of P. Vivax and P. Falciparum Malaria in Cambodia
- ClinicalTrials.gov ID
- NCT00663546
- Acronym / sponsor ID
- 999908094
- Conditions
- Malaria
- Keywords
- Malaria, Plasmodium, Hemoglobin E, Alpha-thalssemia, G6PD Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,978 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 24 Mar 2008
- Study completion
- 5 Dec 2013
- First posted
- 22 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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
- 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
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.
- 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 design
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- vivax malaria (mono-infection).
- Willingness to participate in the study as evidenced by informed consent of subjects or his/her parent or guardian.
Key exclusion criteria (22 listed)
- 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).
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2018.
- Background: PubMed 1120926Frischer H, Bowman J. Hemoglobin E, an oxidatively unstable mutation. J Lab Clin Med. 1975 Apr;85(4):531-9.
- Background: PubMed 3674003Lachant 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.
- Background: PubMed 1596592Hill 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.
- Derived from this study: PubMed 37027391Fantin RF, Coelho CH, Berhe AD, Magalhaes LMD, Pereira DB, Salinas ND, Tolia NH, Amaratunga C, Suon S, Sagara I, Narum DL, Fujiwara RT, Abejon C, Campos-Neto A, Duffy PE, Bueno LL. Immunological characterization of a VIR protein family member (VIR-14) in Plasmodium vivax-infected subjects from different epidemiological regions in Africa and South America. PLoS Negl Trop Dis. 2023 Apr 7;17(4):e0011229. doi: 10.1371/journal.pntd.0011229. eCollection 2023 Apr.
- Derived from this study: PubMed 26701602Hostetler 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.
- Derived from this study: PubMed 25049249Amaratunga 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rick M Fairhurst, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in Cambodia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Cambodia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00663546, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2018.