Anti-malaria drug resistance: a threat to global health security

In this guest post, S. Patrick Kachur, MD, MPH, FACPM—chief of the Malaria Branch in the Division of Parasitic Diseases and Malaria at the Center for Disease Control and Prevention’s (CDC) Center for Global Health—and Larry Slutsker, MD, MPH—director of the Division of Parasitic Diseases and Malaria at CDC’s Center for Global Health—write about the emerging global security threat of anti-malaria drug resistance and CDC’s efforts to prevent, detect, and respond to this growing threat.

Malaria starts with a small bite from a mosquito and can quickly turn into a life threatening illness. The President’s Malaria Initiative (PMI), Global Fund to Fight AIDS, Tuberculosis, and Malaria, and other global efforts have made remarkable progress to help control malaria, saving an estimated 3.3 million lives since 2000 according to the World Health Organization’s (WHO) 2013 World Malaria Report. Key interventions that contributed to this success include insecticide treated bed nets (ITNs), indoor residual spraying (IRS), rapid diagnosis and treatment with artemisinin-containing combination therapies (ACTs), and intermittent preventative treatment during pregnancy (IPTp).

However, to sustain momentum and move toward elimination of malaria, new tools and technologies will be required. While ITNs remain a highly effective tool and should continue to be used, we must acknowledge that ITNs are not perfect given the challenges of adequate coverage, personal use, durability, daytime biting, and insecticide resistance. Of additional concern, there is evidence in Southeast Asia that the malaria parasite may be developing resistance to artemisinin drugs—the last remaining class of antimalarial drugs and the basis for treatment around the world. Reasons for this resistance are multifactorial, including poor treatment practices, inadequate patient adherence to treatment, and widespread availability of monotherapies, counterfeits, and substandard forms of the drug.

Given the mobility of human populations, this resistance could easily spread. We have witnessed the spread of resistance to antimalarial drugs (chloroquine) before, beginning in Southeast Asia and then quickly spreading globally; it would be a devastating setback for child survival and a threat to global health security if artemisinin drug resistance followed this same pattern and reached Africa, where most malaria occurs. Understanding this resistance phenomenon, containing its current focus of transmission, and remaining vigilant for resistance in other parts of the world align well with the Global Health Security Agenda to prevent, detect, and respond to potential threats.

Prevent

One way to actively prevent or mitigate resistance is to limit the inappropriate use of antimalarial drugs. For generations, health workers and consumers used malaria drugs without confirming the diagnosis of malaria. In the last decade, new rapid diagnostic tests made it possible to detect the parasites before giving treatment. Used consistently, this approach could reduce the unnecessary use of antimalarial drugs and improve the detection and treatment of other illnesses. Another approach to prevent drug resistance relies on identifying and removing counterfeit and substandard antimalarials from the market. These medications, similar to substandard doses of antibiotics, can contribute to increased resistance. The US government—CDC, the Food and Drug Administration, the US Agency for International Development, and PMI—are using novel technologies to easily detect counterfeit and substandard drugs with the touch of a button, outside of a specially equipped laboratory. Additional efforts will be needed to ensure these medications are removed from the market.

Another way to help prevent resistance from worsening is to ensure a wide spectrum of tools exist to prevent and control malaria, especially where drug-resistant parasites are present. CDC, as part of PMI, is working with partners to develop and evaluate newer interventions and approaches such as durable wall linings or spatial repellants to aid in mosquito control, and promising vaccines which have been shown to reduce the number of malaria cases in vaccinated children and young infants.

Detect

Enhanced surveillance is critical to track how, where, and how fast the resistance is spreading. Through PMI, the US government supports and provides financial and technical assistance to countries for antimalarial drug resistance monitoring. Furthermore, rapid and accurate detection of resistant malaria parasites are critical for the prevention, treatment, and containment or elimination of infections, and will drive reduction of unnecessary antimicrobial use.

As part of its efforts to monitor malaria domestically, CDC is working to characterize the drug resistance profile of malaria infections diagnosed in the U.S. This provides an early warning of spreading resistance and helps to monitor the situation more accurately. The use of genetic sequencing can also help quickly determine when a person is infected with drug resistant malaria parasites, so that clinicians can provide the best treatment. This information also guides CDC’s recommendation for medications taken for malaria prevention for people traveling to an area where resistance is detected.

Respond

Containment efforts are underway in all areas with suspected or confirmed artemisinin resistance in affected countries. PMI supports containment of artemisinin-resistant malaria in the Greater Mekong sub-region in Southeast Asia. In higher transmission areas, efforts focus on limiting the risk of spread by lowering the malaria burden through intensified malaria control, by increasing access to diagnosis and appropriate treatment, and by scaling up provision of health care services to migrant and mobile populations. In addition to containment efforts, CDC and partners actively contribute to global policy discussions on antimalarial drug resistance, helping provide recommendations for action that are based on the best available data.

The ability to respond quickly and accurately also requires building global capacity and developing a cadre of trained and experienced staff. The call under the Global Health Security Agenda is to create and strengthen real-time networks of information systems to detect outbreaks and up-to-date rapid diagnostic tests enabling in-country laboratories to conduct at least five of 10 core tests for high-risk and high-priority diseases—malaria being one of them.

The public health investments made through the Global Health Security Agenda will not just benefit a few target diseases. Instead, the increased capacity to prevent, detect, and respond through current and newly developed evidence based interventions, improved surveillance systems, accurate real-time rapid diagnostic testing, and an available cadre of trained people will benefit all known and emerging infectious disease threats, including resistant malaria parasites.