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
Studieoversikt
Status
Forhold
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Kontakter og plasseringer
Studiesteder
-
-
-
Phnom Penh, Kambodsja
- National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H
-
Preah Vihear Province, Kambodsja
- Preah Vihear Referral Hospital
-
Ratanakiri Province, Kambodsja
- Ratanakiri Referral Hospital
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
- 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).
Studieplan
Hvordan er studiet utformet?
Designdetaljer
Samarbeidspartnere og etterforskere
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Studiet fullført
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 999908094
- 08-I-N094
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .