Defining the Micro-epidemiology and Elimination Strategy of Falciparum Malaria in Areas of Artemisinin Resistance (TME)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Oxford
Sponsor:
Collaborators:
Mahidol Oxford Tropical Medicine Research Unit, Thailand
Shoklo Malaria Research Unit, Thailand
National Centre for Parasitology Entomology and Malaria Control, Cambodia
Family Health International, Cambodia
Oxford University Clinical Research Unit, Vietnam
National Malaria Control Program, Vietnam
Mahidol Oxford Clinical Research Unit, Myanmar
National Malaria Control Program, Myanmar
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01872702
First received: June 4, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

The overall aim of this study is two fold:

  1. to pilot targeted chemo-elimination of plasmodium falciparum malaria in known areas of artemisinin resistance in South East Asia.
  2. to understand the micro-epidemiology of malaria in these areas; chiefly, the prevalence and importance to on-going transmission of sub-clinical p.f malaria infections.

Condition Intervention
Plasmodium Falciparum Malaria
Drug: malaria elimination using DP and low-dose primaquine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Defining the Micro-epidemiology and Elimination Strategy of Falciparum Malaria in Areas of Artemisinin Resistance: Targeted Chemo-elimination to Eradicate Malaria in Areas of Suspected or Proven Artemisinin Resistance in Southeast Asia

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • prevalence of falciparum malaria measured by qPCR (quantitative real time polymerase chain reaction), 12 months after the first administration of treatment with dihydroartemisinin-piperaquine and primaquine. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Percentage falls in asymptomatic malaria prevalence in the intervention villages vs control villages, as determined by highly sensitive qPCR, 12 months after the first administration of treatment with dihydroartemisinin-piperaquine and primaquine.


Secondary Outcome Measures:
  • Safety and acceptability of targeted malaria elimination [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Safety and acceptability of targeted malaria elimination with dihydroartemisinin-piperaquine and low dose primaquine, evaluated by questionnaires filled out by participants or care givers.


Other Outcome Measures:
  • Effect on gametocyte carriage by targeted malaria elimination [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Effect on gametocyte carriage by targeted malaria elimination, measured by the proportions of gametocyte carriers over the 12 month period

  • Characterize parasite carriage using highly sensitive techniques in four geographically separate sites where resistance to artemisinin has been documented [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Characterize parasite carriage using by molecular analysis of parasite genotypes, markers of resistance and parasite population genetic structure


Estimated Enrollment: 8000
Study Start Date: April 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: malaria elimination using DP and low-dose primaquine
Two villages randomly allocated to intervention (chemo-elimination) at each of the 4 sites (population approximately 500 people in each village). In these villages the entire population will be invited to receive three, monthly rounds of treatment with dihydroartemisinin-piperaquine and primaqunine to kill malaria parasites. The micro-epidemiology of malaria will be studied and prevalence and patterns of transmission used for comparison. NB, in Cambodia there will be no intervention villages and all four villages will be used to study the micro-epidemiology of malaria transmission in the absence of malaria elimination.
Drug: malaria elimination using DP and low-dose primaquine
Treatment of all persons resident in the intervention villages including those who do not have malaria parasites as detected by rapid diagnostic test. This is to interrupt p.f malaria transmission by removing the reservoir of all potentially infectious people from the area.
Other Names:
  • Three monthly rounds of:
  • Dihydroartemisinin-piperaquine
  • Low-dose primaquine
No Intervention: Control villages
Two villages randomly allocated to control (no chemo-elimination) at each of the 4 sites (population approximately 500 people in each village). In these villages only the micro-epidemiology of malaria will be studied and prevalence and patterns of transmission used for comparison. NB, in Cambodia there will be no intervention villages and all four villages will be used to study the micro-epidemiology of malaria transmission in the absence of malaria elimination.

Detailed Description:

The spread of artemisinin resistance in Plasmodium falciparum, which compromises the therapeutic efficacy of artemisinin combination treatments (ACTs), is the greatest threat to current global initiatives to control and eliminate malaria and is considered the highest priority of the WHO Global Malaria Programme. If not eliminated, resistant parasites could spread across Asia to Africa, as happened with resistance to other antimalarials in the past.

Conventional descriptions of the epidemiology of malaria in low transmission settings suggest that malaria prevalences are low (<10%) and heterogeneous. Most or all infections are thought to be symptomatic so the focus of malaria control activities is on the identification and treatment of symptomatic individuals. We and others have shown recently that artemisinin resistant P. falciparum is prevalent in Western Cambodia, and that it is now also found along the Thailand-Myanmar border and Vietnam. We have recently developed highly sensitive quantitative PCR (qPCR) methods for parasite detection using >1mL of blood which are 5,000 times more sensitive than conventional microscopy, and 100 times more sensitive than currently used PCR.

We have studied villages along the Thai-Myanmar border which are typical for the region and are classified by conventional epidemiological techniques as low-transmission (5-20% malaria prevalence). Our studies suggest that the majority of the population is infected. In Pailin, Western Cambodia, in areas where the National Malaria Control Programme and WHO believe that malaria has been all but eliminated, we have also found very high rates (>80%) of sub-microscopic parasitaemia in patients with fever or history of fever who are RDT negative. Thus, there is a lot more asymptomatic malaria in low transmission settings than previously thought, suggesting that control and elimination activities need to be rethought.

This study is designed to conduct and evaluate the efficacy of pilot implementation of targeted chemo-elimination in selected areas with the goal of eliminating malaria in these regions. This differs from mass drug administration (MDA); it is a strategy used to identify specific areas where mass treatment is necessary, in this case to eliminate all malaria parasites. Elimination will be targeted at communities with significant levels of subclinical infection and transmission which will be identifiable in the future by comparing rates of positivity by RDT or microscopy from new population samples against our qPCR data, which shows the true falciparum prevalence.

The study will assess the feasibility, safety and acceptability of this strategy and its impact on the transmission of malaria and the progression of artemisinin resistance. In addition it will evaluate the contribution of low parasitaemia carriage to transmission of artemisinin resistant malaria. These pilot studies are a necessary prelude to future scale up and policy implementation.

Dihydroartemisinin-piperaquine (DP) is a highly efficacious and inexpensive ACT which is well tolerated by all age groups when used to treat uncomplicated multi-drug resistant falciparum malaria in South East Asia. Monthly DP treatments have proved highly effective and well tolerated. When used as part of a MDA strategy, the addition of a gametocytocidal drug contributes towards the goal of malaria elimination by adding a strong transmission blocking activity to the regimen. Primaquine (PQ), the only currently licensed 8-aminoquinoline, is relatively safe and very effective when used at a dose of 0.25 mg base/kg, and does not require G6PD screening. Thus, we propose to evaluate the potential of this strategy to eliminatie malaria focally in areas where artemisinin resistance in P. falciparum is prevalent using DP plus PQ.

  Eligibility

Ages Eligible for Study:   6 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • willingness to comply with study protocol
  • no known allergy to study drugs
  • informed consent obtained

Exclusion Criteria:

  • unwillingness to comply with study protocol
  • known allergy to study drugs
  • informed consent not obtained
  • exclusive breastfeeding
  • pregnancy
  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: NCT01872702

Contacts
Contact: Nicholas J White, PhD +66 (0)22036333 nickwdt@tropmedres.ac
Contact: Arjen Dondorp, PhD +66 (0)22036333 arjen@tropmedres.ac

Locations
Cambodia
National Centre for Parasitology, Entomology and Malaria Control Active, not recruiting
Phnom Penh, Cambodia, 372
Myanmar
Mahidol Oxford Clincal Research Unit, Myanmar Active, not recruiting
Rangoon, Myanmar
Thailand
Shoklo Malaria Research Unit Recruiting
Mae Sot, Tak, Thailand
Contact: Francois Nosten, PhD       francois@tropmedres.ac   
Contact: Khin M Lwin, MD         
Principal Investigator: Francois Nosten, PhD         
Vietnam
Oxford University Clinical Research Unit - Vietnam Recruiting
Ho Chi Minh city, Vietnam, Ward 1, District 5
Contact: Tran Tinh Hien, PhD    +84 (8) 3923 7954    hientt@oucru.org   
Principal Investigator: Tran T Hien, PhD         
Sponsors and Collaborators
University of Oxford
Mahidol Oxford Tropical Medicine Research Unit, Thailand
Shoklo Malaria Research Unit, Thailand
National Centre for Parasitology Entomology and Malaria Control, Cambodia
Family Health International, Cambodia
Oxford University Clinical Research Unit, Vietnam
National Malaria Control Program, Vietnam
Mahidol Oxford Clinical Research Unit, Myanmar
National Malaria Control Program, Myanmar
Investigators
Principal Investigator: Nicholas J White, PhD University of Oxford
  More Information

Additional Information:
Publications:

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01872702     History of Changes
Other Study ID Numbers: BAKMAL1305
Study First Received: June 4, 2013
Last Updated: July 21, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Malaria elimination
Chemotherapy
Epidemiology
South East Asia
Artemisinin resistance
Dihydroartemisinin piperaquine
Primaquine

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Piperaquine
Primaquine
Artemisinins
Dihydroartemisinin
Artemisinine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014