Targeted Chemo-elimination (TCE) to Eradicate Malaria in Areas of Suspected or Proven Artemisinin Resistance in Southeast Asia and South Asia

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. Previous research has shown that artemisinin-resistant P. falciparum is prevalent in Western Cambodia and that it is now also found along the Thailand-Myanmar border and Vietnam.

Recently, highly sensitive quantitative PCR (uPCR) methods have been developed 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.

Villages along the Thai-Myanmar border are typical for the region and are classified by conventional epidemiological techniques as low-transmission (5-20% malaria prevalence). 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, very high rates (>80%) of sub-microscopic parasitaemia have been found 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.

Highly sensitive quantitative PCR (uPCR) requires a venous blood sample, a laboratory which can perform vacuum DNA extraction, and on average four weeks for processing. A rapid highly sensitive diagnostic test which can be performed at the point of care would be a technological breakthrough. Screening with highly sensitive RDTs and treating of asymptomatic carriers will have a range of public health applications. Such tests are becoming available in 2017 and will be evaluated side by side with uPCR.

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 an 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, the project proposes to evaluate the potential of this strategy to eliminate malaria focally in areas where artemisinin resistance in P. falciparum is prevalent using DP plus PQ.

• Clinicaltrials.gov ID: NCT01872702

Type: Interventional
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Primary purpose: Treatment

Targeted Chemo-elimination (TCE) of Malaria (TME)Bill & Melinda Gates Foundation, Grants

Drug-based Strategies

Apr 2013 — Jul 2017

$13.56M

Cambodia
Lao PDR
Myanmar
Vietnam

Mass Drug Administration (MDA)