Artemisinin-resistant Malaria in Cambodia

NCT01736319 | Completed

• 2 other identifiers: 99991216312-I-N163
• Study Type: observational
• Target: 561
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Artemisinin-based combination therapies (ACTs) are the first-line treatments for malaria. ACTs are highly effective, but malaria caused by the Plasmodium falciparum parasite is becoming resistant to some ACTs. ACT-resistant malaria has shown up in some parts of Cambodia, but not yet in other parts of the country. This has been shown by treating patients with ACTs, checking the amount of parasites in the patient s blood every 6 hours, and calculating the rate of parasite clearance. The parasite clearance rate in response to ACTs is getting slower in western Cambodia and may be the first sign of ACT resistance. Researchers want to study how effective ACTs are in different regions of Cambodia. This study will look at the extent of ACT resistance and how widespread ACT-resistant malaria has become. Objectives: \- To compare the prevalence of ACT-resistant malaria in western, northern and eastern Cambodia. Eligibility: \- Individuals between 2 and 65 years of age who have uncomplicated Plasmodium falciparum malaria and have not taken any antimalarial drugs for their symptoms in the previous 7 days. Design:

• Participants will be recruited from clinics and hospitals in three Cambodian provinces.
• Participants will be informed about the study and their consent to participate in the study will be obtained.
• A venous blood sample will be obtained from patients before treatment and used for laboratory experiments to measure parasite and patient factors that might affect the parasite clearance rate.
• Participants with malaria will be treated with dihydroartemisinin-piperaquine (DHA-PPQ), the standard first-line treatment for malaria in Cambodia.
• Treatment will be monitored with frequent blood samples obtained from a finger prick. The amount of malaria parasites in each blood sample will be counted and followed until they are no longer detectable.
• Participants will have weekly follow-up visits for up to 9 weeks. Finger-prick blood samples will be taken at each visit to see if the parasites reappear after treatment with ACT.

Conditions

Plasmodium Falciparum Malaria

Keywords

Artemisinin-based Combination Therapies; Recrudescence; DHA-PPQ; Parasite Clearance Rate

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 2 to 65 years, inclusive
• Uncomplicated P. falciparum malaria
• Temperature greater than or equal to 37.5 degrees Celsius or history of fever within the last 24 h
• P. falciparum asexual parasite density less than or equal to 200,000/microL
• Willingness to allow the storage of blood samples collected as part of the study
• Willingness and ability of patients/guardians to comply with the protocol for the duration of the study.

You may not qualify if:

• 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 by history and physical examination
• Hematocrit \<25%
• Treatment of present symptoms with an antimalarial drug within the previous 7 days
• Pregnancy or breastfeeding
• History of allergy or known contraindication to artemisinins or MQ
• Splenectomy
• P. vivax parasitemia
• Healthy-appearing adults greater than or equal to 18 years old
• Residence in Pursat province
• Willingness to participate in the study as evidenced by informed consent
• Pregnancy
• Hematocrit \<25%

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H

Phnom Penh, Cambodia

Location

Related Publications (5)

• Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.

  PMID: 19641202 BACKGROUND

• Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, ler Moo C, Al-Saai S, Dondorp AM, Lwin KM, Singhasivanon P, Day NP, White NJ, Anderson TJ, Nosten F. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet. 2012 May 26;379(9830):1960-6. doi: 10.1016/S0140-6736(12)60484-X. Epub 2012 Apr 5.

  PMID: 22484134 BACKGROUND

• White NJ. The parasite clearance curve. Malar J. 2011 Sep 22;10:278. doi: 10.1186/1475-2875-10-278.

  PMID: 21939506 BACKGROUND

• Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, Sam B, Dek D, Try V, Amato R, Blessborn D, Song L, Tullo GS, Fay MP, Anderson JM, Tarning J, Fairhurst RM. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis. 2016 Mar;16(3):357-65. doi: 10.1016/S1473-3099(15)00487-9. Epub 2016 Jan 8.

  PMID: 26774243 DERIVED

• Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, Lim P, Mao S, Sopha C, Sam B, Anderson JM, Duong S, Chuor CM, Taylor WR, Suon S, Mercereau-Puijalon O, Fairhurst RM, Menard D. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis. 2013 Dec;13(12):1043-9. doi: 10.1016/S1473-3099(13)70252-4. Epub 2013 Sep 11.

  PMID: 24035558 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Recurrence

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rick M Fairhurst, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: November 29, 2012
• Study Start: June 26, 2012
• Study Completion: April 6, 2016
• Last Updated: June 1, 2018

Record last verified: 2016-04-06

Locations

CA (1)