Malaria in the Amazon Region

Malaria began to reemerge in the Amazon region of South America in the 1990s. A number of factors were associated with this increase:

• The migration of large numbers of nonimmune persons into malaria-endemic areas;
• Establishment of highly competent malaria-transmitting mosquitoes, e.g., Anopheles darlingi;
• Climatic fluctuations, such as seen with El Niño;
• Low levels of funding for malaria control programs; and
• Presence of strains of P. falciparum resistant to chloroquine and sulfadoxine-pyrimethamine.

AMI/RAVREDA: Response to Malaria’s Reemergence

In 2001, eight countries established a surveillance network to address antimalarial drug resistance: the Amazon Malaria Initiative / Red Amazónica para la Vigilancia de la Resistencia a las Drogas Antimaláricas (Amazon Network for the Surveillance of Antimalarial Drug Resistance) (AMI/RAVREDA). Funding has been provided by the United States Agency for International Development (USAID), and CDC has provided technical assistance.

After the network had been active for several years investigating resistance and changing national antimalarial drug policies accordingly, the number of cases of P. falciparum malaria dropped significantly.

Graph used with permission of Dr. Keith Carter, PAHO.

A young girl in Iquitos, Peru, has a blood smear taken by medical technician to determine if she has malaria. Courtesy: RAVREDA

Brief History of AMI/RAVREDA

In 1998, an expert meeting was held in Manaus, Brazil, to adapt the World Health Organization’s standardized in vivo malaria drug efficacy protocol for the Americas. At the meeting, researchers interested in antimalarial drug resistance in the Americas formed an information network. Later that year, researchers from the Instituto Nacional de Salud in Peru, in collaboration with malariologists from CDC, embarked on a series of drug studies to assess different drug combinations containing artemisinin derivatives for uncomplicated P. falciparum malaria.

In early 2001, the Pan American Health Organization (PAHO) convened a meeting in Salvador, Brazil, on drug resistance in the Amazon region, and participating countries agreed to use the adapted, standardized in vivo protocol within a newly created regional network to monitor antimalarial drug resistance, AMI/RAVREDA.

(Courtesy: Gabriel Ponce de Leon)

AMI/RAVREDA Objectives, Members, Partners, and Coordinating Agencies

AMI/RAVREDA’s stated objectives are to:

• Collect reliable and standardized malaria drug efficacy information in the Amazon region;
• Develop evaluation tools that allow countries to improve their malaria control programs;
• Enhance partnerships to improve malaria control in the Amazon region.

Initially there were eight members: Bolivia, Brazil, Colombia, Ecuador, Guyana, Peru, Suriname, and Venezuela. Venezuela was a member of AMI through 2008.

Five partners provide technical assistance: CDC www.cdc.gov/malaria, Rational Pharmaceutical Management Plus/Management Sciences for Health www.msh.org/projects/rpmplus/index.html*, Links Media http://www.linksmedia.net*, Research Triangle Institute International , www.rti.org*, and the United States Pharmacopoeia www.usp.org*.

USAID www.usaid.gov and PAHO www.paho.org serve as coordinating agencies.

AMI/RAVREDA Accomplishments to Date

• All AMI countries have collected reliable information about the efficacy of their first-line antimalarial treatments.
• All AMI countries have changed their national treatment guidelines to highly efficacious artemisinin-based combination therapy.
• Members have begun regular ongoing insecticide resistance training to support active insecticide resistance surveillance.
• Suriname implemented artemether-lumefantrine (an artemesinin-based combination therapy) as first-line therapy for uncomplicated P. falciparum malaria and then field-tested a protocol to assess patients’ adherence to this drug combination.
• Member countries improved their drug management systems and strategies to evaluate the quality of their drugs.

After initial in vivo efficacy studies were completed and most member countries had changed their antimalarial drug policies, countries began to evaluate other components of their national malaria control programs.

A young boy is interviewed by a health-care worker as part of CDC activities in Iquitos, Peru. Courtesy: RAVREDA

CDC Contributions

In the first few years after AMI/RAVREDA was established (2001-05), CDC provided technical assistance primarily in the areas of antimalarial drug efficacy and effectiveness that would help support conduct of individual country’s in vivo efficacy studies, as well as in mosquito control.

In addition, CDC, along with other technical AMI/RAVREDA partners, shared its expertise by conducting workshops, participating in studies, providing training at CDC/Atlanta for AMI/RAVREDA member personnel, and conducting evaluations on several topics, including:

• Patient adherence to antimalarial regimens
• Vector control strategies, including evaluation of insecticide-treated mosquito net efficacy and insecticide resistance
• Burden of malaria in pregnancy
• Quality of care provided at health facilities
• Laboratory capacity in molecular epidemiology as well as laboratory techniques for detection of antimalarial drug levels in blood.

Since 2005, CDC has continued to share its malaria expertise with member countries in these areas:

• Provided malaria diagnostic and training support.
• Adapted and validated methods for chloroquine and mefloquine analysis in blood using simpler techniques and evaluation of insecticide levels on insecticide-treated bednets using a simple colorimetric method.
• Trained laboratory personnel how to use the bottle bioassay to measure resistance for vector insecticide susceptibility surveillance (VISS). Supported investigation of entomologic effects of use of ITNs in the region using experimental houses. Helped coordinate monitoring and evaluation of vector control activities. CDC had developed manuals and standard operating guidelines to support VISS.
• Continued to assist in monitoring and evaluation of in vivo antimalarial drug efficacy trials. Discussions are underway to help support malaria control in Haiti, Central America, and Mexico.
• Developed standards for genotyping of P. vivax to adjust findings of in vivo drug efficacy trials. Molecular surveillance has been utilized and promoted by CDC and partner countries to evaluate the prevalence of sulfadoxine-pyramethamine, chloroquine, and other drug-resistant genotypes as an effort to predict changes in clinical efficacy.
• CDC encourages and supports direct collaboration among partner countries, as well as sustainability of malaria control activities and helps build capacity through activities such as those outlined above. CDC envisions continued collaboration with AMI/RAVREDA partners to strengthen malaria control activities and reduce the burden of malaria in the region.