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The Evolution of Public Health Research: Malaria, Part 2

Posted by Amy Brankin on Jan 5, 2017 10:25:35 AM

Malaria Elimination vs. Eradication, and Genetic Diversity vs. “Freezer Epidemiology”

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It is because of its historic mission to eliminate malaria that the CDC is in Atlanta, Georgia. The agency is still deeply involved with the control of malaria, by providing technical assistance around the world, and continuing to protect the US population from the parasite. The CDC estimates that 1,500 people in the USA annually are infected with malaria while traveling, and the CDC tracks these cases and advises the medical community on accurate diagnosis and treatment.

It was the challenge of malaria that required a new distinction between “elimination” and “eradication.” The term "elimination" is used when malaria transmission is no longer occurring in a specific geographic area. "Eradication" is used to describe elimination of malaria transmission worldwide.

Initiatives of multiple global and national organizations, including the World Health Organization, the CDC, the US Agency for International Development, and many individual National Malaria Control Programs (NMCPs) are showing results. Between 2000 and 2016, large-scale malaria prevention and treatment interventions saved approximately 6.2 million lives globally, and death rates in Africa were cut by more than half. However, malaria remains a major public health problem, even though it is both preventable and treatable.

The control and eventual eradication of malaria is occurring on three fronts:  Prevention, treatment, and vector control. Each of these efforts faces complications. 

Mosquito_Zika_Image.jpgVector Control.  Malaria was eliminated in the US by draining wetlands and with widespread application of DDT, before the toxic effects of the chemical were known.  DDT was applied to interior surfaces as well as outdoors—even from aircraft—to kill mosquitoes. The effectiveness of DDT led to a reduction in numerous insect-related diseases in people, livestock, and crops, in addition to malaria. However, given the toxicity of DDT, the US program cannot be used as a model for eliminating malaria elsewhere.   

Vector control generally consists of draining standing water where possible, and use of a chemical larvacide where it is not. Vector control includes sleeping beneath pesticide-treated netting and indoor residual spraying (IRS) of pyrethrins, which is the only class of pesticide currently recommended for anti-malaria programs. Both these methods take advantage of the mosquito’s habit of feeding at night, and the fact that it will alight on a wall or other interior surface while indoors, especially after a meal. Spraying of indoor surfaces with insecticide ensures the mosquito will, literally, not leave the house alive and transmit the parasite elsewhere. The downside is that the mosquito may already have infected any resident not sleeping under a net.  Vector control thus depends on the individual to use netting, as well as participation of the entire community in IRS, which must be used in at least 80 percent of households to have an effect.  Resistance to pyrethrins is also being reported in certain locations.

Treatment to prevent transmission.  Although treatments for malaria have been known for a long time, Artesunate is not widely available outside the Far East (it can only be acquired for US patients through the CDC). GMP manufacturing is a primary issue.  Quinine has side effects that often interfere with compliance.  And although individuals can be cleared of the parasite, an infected individual can transmit malaria via mosquito bite before symptoms develop. We do not yet have the diagnostic tools to detect either pre-symptomatic infections, or dormant forms residing in the liver.

Chemoprevention. WHO recommends intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnant women and infants where infection rates warrant.  WHO also recommends chemoprevention during the high-transmission season for children younger than age five.

The ultimate tool against malaria would be a vaccine, but there is only one vaccine on the horizon, GSK’s  RTS,S/AS01. The GSK candidate vaccine was evaluated in phase 2 studies in 15,000 children in multiple countries in Africa between 2009 and 2013. The vaccine confers modest (“sieve”) protection against specific strains of malaria, reducing the overall occurrence of that strain. The protection provided by the vaccine appears to fade over time, although use of the vaccine has been recommended in a limited number of countries in sub-Sahara Africa.

And this is where biobanking plays a part. In supporting the clinical trial, sample collection was relatively simple—blood samples from participants consisted of dried blood spots on Whatman FTA sample cards that were used for DNA extraction, PCR amplification, and sequencing.

The development of the vaccine, however, offers a different perspective. A commentary on vaccine-resistant malaria in the November 19, 2015 issue of the New England Journal of Medicine noted that virtually all vaccines against P. falciparum, including RTS,S/AS01, have used genetic sequences derived from a single reference strain, known as 3D7.  Given the great diversity of malaria parasites, could this “freezer epidemiology” approach be one of the reasons we do not yet have an effective vaccine against malaria?  Vaccine development and efficacy testing is in need of integration from biobanking, molecular epidemiology, population genetics, and immunology in order to design a more broadly protective, next generation vaccine if we hope to eradicate Malaria.

We recently published an eBook on Controlling Preanalytical Variability in Biospecimen Collections. This is an issue that must be thoroughly addressed in public health research – the possibility that the handling of specimens prior to laboratory testing has skewed results.  To read more, download our eBook below.

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References:

Neafsey, D. E.; Juraska, M.; Bedford, T.; Benkeser, D.; & Valim, C. et al. (20150. Genetic diversity and protective efficacy of the RTS,S/AS01 malaria vaccine. New England Journal of Medicine, 373, 2025–2037. DOI: 10.1056/NEJMoa1505819.

Plowe, C.V. (2015).Editorial:  Vaccine-resistant malaria.  New England Journal of Medicine, 373, 2082–2083. DOI: 10.1056/NEJMoa1505819.

World Health Organization. (2015) Control and elimination of plasmodium vivax malaria: a technical brief. WHO.

World Health Organization. (2015) World Malaria Report. WHO. http://www.who.int/malaria/visual-refresh/en/