Artemisinin-resistant Malaria in Cambodia - Full Text View

Purpose

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.

Condition
Plasmodium Falciparum Malaria


Study Type:	Observational
Study Design:	Time Perspective: Prospective
Official Title:	Artemisinin-resistant Plasmodium Falciparum Malaria in Cambodia

Resource links provided by NLM:

MedlinePlus related topics: Malaria

Genetic and Rare Diseases Information Center resources: Malaria

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):


Estimated Enrollment:	860
Study Start Date:	June 26, 2012
Estimated Study Completion Date:	April 6, 2016

Detailed Description:

Artemisinin-based combination therapies (ACTs) are the first-line treatments for Plasmodium falciparum malaria worldwide. In Western Cambodia,artemisinin resistance has been defined as a long half-life of parasite clearance (T1/2) in response to an artemisinin, given orally for uncomplicated malaria. We hypothesize that this artemisinin resistance phenotype compromises the efficacy of ACTs. The primary objective of this study is to compare P. falciparum recrudescence rates in Western, Northern and Eastern Cambodia, following dihydroartemisinin-piperaquine (DHA-PPQ) treatment. The secondary objective of this study is to determine whether parasite recrudescence is associated with long T1/2. In the Parasite Recrudescence Study, patients with uncomplicated malaria will receive directly-observed treatment with DHA-PPQ over 3 days. We will follow these patients weekly for 9 weeks to identify those with recurrent parasitemia and use genotyping methods to distinguish recrudescences from reinfections. We will enroll a subset of these patients who have an initial parasite density greater than or equal to 10,000/microL in the Parasite Clearance Rate Study and follow their parasite densities more intensively by examining 6-hourly finger prick blood samples until parasites are undetectable by microscopy. With these data we will calculate and compare T1/2 values from patients with and without recrudescent parasitemia. Using various laboratory assays, we will also explore the contribution of host factors to T1/2 variation, and whether naturally-acquired immunity reduces the risk of drug-resistant parasite recrudescence.

Eligibility


Ages Eligible for Study:	2 Years to 65 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

INCLUSION CRITERIA (Parasite Recrudescence Study):
1. Age 2 to 65 years, inclusive
2. Uncomplicated P. falciparum malaria
3. Temperature greater than or equal to 37.5 degrees Celsius or history of fever within the last 24 h
4. P. falciparum asexual parasite density less than or equal to 200,000/microL
5. Willingness to allow the storage of blood samples collected as part of the study
6. Willingness and ability of patients/guardians to comply with the protocol for the duration of the study.

EXCLUSION CRITERIA (Parasite Recrudescence Study):

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

INCLUSION CRITERIA (Peripheral Blood Collection Study):

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

EXCLUSION CRITERIA (Peripheral Blood Collection Study):

Pregnancy
Hematocrit <25%

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736319

Locations


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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Principal Investigator:	Rick M Fairhurst, M.D.	National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Publications:

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. Erratum in: N Engl J Med. 2009 Oct 22;361(17):1714.

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.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01736319 History of Changes
Other Study ID Numbers:	999912163 12-I-N163
Study First Received:	November 27, 2012
Last Updated:	June 30, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):


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

Additional relevant MeSH terms:


Malaria Malaria, Falciparum Protozoan Infections Parasitic Diseases Artemisinins	Artemisinine Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on July 17, 2017