Containment of Artemisinin Resistance in Eastern Myanmar

A retailer in rural Myanmar offers a customer a package of Supa Arte, a high-quality antimalarial medication which was procured and subsidized by Population Services International to help slow the spread of drug-resistant malaria. (Photo courtesy of PSI)

Note: This page was created using content published by Good Ventures and GiveWell, the organizations that created the Open Philanthropy Project, before this website was launched. Uses of “we” and “our” on this page may therefore refer to Good Ventures or GiveWell, but they still represent the work of the Open Philanthropy Project.

Good Ventures awarded a $1 million grant to Population Services International in August 2012 to support a project aimed at slowing the spread of drug resistance to the highly effective antimalarial artemisinin in Myanmar. The project was recommended to us by the Gates Foundation and is the first project we’re co-funding with another foundation. We expect this grant to help us learn how a major funder like the Gates Foundation monitors the progress and asseses the impact of a large-scale global health project.

The purpose of the project is to prevent the emergence of drug-resistant malarial parasites in Myanmar by replacing artemisinin monotherapies (AMTs) with artemisinin combination therapies (ACTs) as the primary mode of treatment available for individuals to purchase in the private sector, and by promoting the proper diagnosis and treatment of malaria. The project was estimated to cost $35 million over three years, with approximately $27.5 million previously committed by the Gates Foundation and the UK Department for International Development.

The goal of co-funding with other foundations is twofold: to support promising projects and, most importantly, to learn how experienced foundations find, monitor and assess the impact of projects. Read more about our rationale for co-funding and how we selected this project.

We’ve published updates on this project in April 2013 and November 2013.

About the project

PSI aims to improve malaria treatment in Myanmar with the primary aim of preventing the spread of drug resistance to the highly effective antimalarial drug artemisinin. PSI states that drug resistance is minimized when patients complete full treatment regimens and when treatment regimens contain combinations of drugs that attack the parasite in multiple ways.1 PSI’s project focuses on replacing therapies that contain a single antimalarial drug (artemisinin monotherapies, or AMTs) with therapies that contain artemisinin in combination with other antimalarials (artemisinin combination therapies, or ACTs),2 and on ensuring that malaria patients receive and complete a full course of ACT and that only patients with malaria receive antimalarials.3

The project will include the following primary activities:4

  • Subsidizing ACTs sold through the private sector. To date, PSI has agreed to work with a single supplier that provides over 70% of the AMT delivered through private sector suppliers in Myanmar.5 PSI aims to provide a subsidy that results in the price of a full course of ACT being equal to what patients previously paid to treat malaria with AMT (which in many cases was only part of a recommended course).6 PSI has budgeted $14.4 million to purchase ACTs over three years, $12.5 million of which will treat adult patients.7
  • Advocating to drug providers to improve prescription practices. PSI will use mass media, targeted media, and visits to providers (pharmaceutical detailing) to promote use of ACTs and rapid diagnostic tests and to encourage providers to prescribe recommended drug regimens.8
  • Advocating to the national government for legal restrictions on selling AMTs. As of mid-2012, the government had agreed to institute an importation and marketing ban on AMTs by the end of 2012.9
  • Promoting PSI-branded ACTs and other behavior change communications. PSI will launch a campaign to promote demand for high-quality ACTs, prompt treatment seeking, use of diagnostic tests, and completion of full treatment courses.10
  • Training informal drug providers in the use of rapid diagnostic tests (RDTs), and supplying RDTs to these providers. In order to reduce the number of patients receiving antimalarials for fevers not caused by malaria, PSI aims to motivate drug providers to conduct regular testing of patients for malaria before prescribing drugs.11

The project is expected to have national reach with a particular focus on a high-risk area in the eastern part of the country.12

Potential project impact

PSI’s project, if it succeeds in helping to stop the spread of artemisinin resistance, has the potential to have a very high impact. A World Health Organization report states that artemisinin is the most effective antimalarial and that “there is currently no practical alternative treatment” for P. falciparum,13 the most deadly form of malaria.14 Artemisinin resistance has been found in countries neighboring Myanmar in the Greater Mekong region,15 and signs of resistance have been detected near Thailand’s border with Myanmar.16

There is an extensive history of the development and spread of drug resistance to other classes of antimalarial drugs. This, in turn, is thought to have led to rising child mortality rates as available drugs became ineffective.17 In particular, resistance to two types of antimalarial drugs emerged in the Greater Mekong region and likely spread from there to Africa,18 where the malaria burden is highest.19 Myanmar has by far the highest malaria burden in the region, and therefore, resistance, once in Myanmar, may be more likely to spread quickly.20 PSI reports that a high proportion of malaria treatments in Myanmar are supplied through the private sector,21 and over 70% of private sector treatments are supplied through a supplier that has agreed to work with PSI.22 A recent household survey conducted in regions at high risk of drug resistance, found that 30-47% reported that they used a private healthcare provider for their most recent case of fever.23

The project is also high risk, as the development and spread of drug resistance is not well understood and the project is has not been tried and tested previously.24

Risks to the success of the project

As discussed above, this is a high-risk project because it is an unproven approach to a problem that is not well understood. In addition to the risk of PSI’s project being an ineffective approach, there are risks that could prevent PSI from executing the project as planned. These include:

  • Operating environment: The government of Myanmar has in the past restricted the movement and activities of charitable organizations. It has recently begun to ease these restrictions.25
  • Targeting of subsidies: PSI will subsidize ACTs through a national supplier and will not have direct control over the supply chain of the drugs.26 There is therefore a risk that the price reduction will not reach consumers and will instead be captured by suppliers or retailers. There is also a risk of the subsidized drugs being misappropriated by the government, military, or other powerful interests.27
  • Patient compliance with full treatment course of ACT: The success of the project will be dependent on patients choosing to buy and complete a full course of ACT. PSI believes that patients are often highly sensitive to price, and many purchase partial courses of AMT. If they chose to purchase partial courses of ACT, as they do AMT, or to continue to purchase AMTs, the project is likely to have a smaller impact on controlling drug resistance. Helping to mitigate this risk, the ACT treatment course PSI plans to use is only three days long, compared to seven days for a full course of AMT. Also, PSI aims to keep the price of a full course of ACT at approximately the same price patients pay for a typical partial course of AMT.28
  • Partnership with large supplier: A single supplier provides over 70% of AMT treatments nationwide. The success of the project is highly dependent on a successful partnership with this single supplier.
  • Inherent challenges of behavior change: many of PSI’s planned interventions revolve around advocacy to change behavior; this sort of work seems inherently difficult to us. However, we note that this project, unlike behavior change projects that rely exclusively on communications, aims to increase the use of an inexpensive, high-quality product by subsidizing that product, and the country has agreed to ban the product it aims to replace. Therefore, this project relies less on convincing people to behave in a way that causes them to incur costs in the near term (as campaigns to exercise more or use condoms do, for example).

Monitoring and evaluation

PSI plans to use the following tools to monitor and evaluate the program:

  1. Private outlet surveys: PSI will randomly select areas in which to conduct the surveys and will visit all private antimalarial providers and sellers in the area (government-run facilities will not be surveyed). During the visits, PSI will directly observe availability of different types of antimalarials, as well as rapid diagnostic tests, and interview the provider to collect information on prices, sales volume, and knowledge of correct prescription practices.29 PSI has provided details of the survey methodology,30 and plans to conduct the surveys annually throughout the project.31 PSI has completed a baseline outlet survey and shared preliminary results.32
  2. Household surveys: PSI will conduct nationally-representative baseline and three-year follow up surveys to question households33 on their access to and use of different antimalarials. PSI will also ask households about the prices they paid for the medicines and test their basic knowledge about malaria and its treatment.34 PSI has provided details of the survey methodology.35
  3. Baseline supply chain assessment: PSI will conduct interviews with suppliers and key informants to map the supply chain for antimalarials in the country and determine the pricing structure.36 PSI also plans to conduct “routine monitoring of the supply chain to ensure consistent availability of stock at all levels.”37
  4. Mystery client surveys, exit interviews, and focus group discussions: PSI will “use actors who pretend to seek treatment for fever at a variety of outlets” to check drug providers prescription practices. Mystery client surveys will be conducted on an annual basis and ad hoc basis during the year.38 It will also interview patients after they visit drug sellers “to find out what advice they were given, what they bought and their views of the experience.”39
  5. Monthly sales data of subsidized antimalarials.

PSI has used this set of tools to collect data on anti-malarial markets in seven countries in Africa and Asia as part of an initiative called “ACTwatch.”40

In addition, the World Health Organization collects data on parasite clearance rates, a measure of the prevalence of drug resistance.41 We have not seen details of where or when this data will be collected in Myanmar. PSI notes, “the project contributes to, but wouldn’t be solely responsible for, any goal-level impact observed. Lastly, many aspects determining the nature of artemisinin resistance spread remain unclear, thus further complicating evaluation of impact at this level.”42

Use of additional funding and room for more funding

The project is projected to cost about $35 million over three years. The UK’s Department for International Development (DFID) and the Bill and Melinda Gates Foundation have committed approximately $27.5 million to the project.43

PSI told us, “At current levels of funding, PSI will conduct the planned surveys, run social mobilization campaigns, and purchase some commodities. The additional $7.5 million would allow for the purchase of additional ACTs and malaria diagnostic tests, and therefore scale up the replacement program more quickly.”44

Assuming that non-drug costs do not vary with the quantity of drugs sold (this is an aggressive assumption that likely understates the full costs of providing additional drugs),45 the cost to PSI of an average ACT treatment46 is about $1.78, which includes the cost of drugs and packaging.47 PSI estimates the cost of an additional RDT, including packaging, at $0.74.48 Thus an additional $1 million donation purchases up to 561,000 ACT treatments or 1.3 million RDTs, or a combination of the two.

Good Ventures has committed an additional $1 million for the project, leaving a funding gap of about $6.5 million. PSI hopes to secure the remaining funding for the project through new donors by the end of 2012; it does not believe that existing donors will fill the gap.49

Sources