Current and Future Research
CDC’s research extends from basic research and development in the field and laboratory to strategic and applied research aimed at controlling or eliminating malaria worldwide.
CDC’s malaria research goals are to
Optimize the mix of current interventions for malaria control
Identify opportunities to integrate efforts with other initiatives
Optimize Mix of Current Interventions
Proven tools for malaria control include early treatment of malaria illness with artemisinin-containing combination treatments (ACTs), intermittent preventive treatment for pregnant women (IPTp), and measures that reduce the risk of infection such as indoor residual spraying (IRS) or insecticide-treated nets (ITNs). Each of these has been shown to be effective at contributing to malaria control on its own.
As effective control programs expand these interventions, it is becoming increasingly important to understand how they can be deployed optimally alongside one another and on a large scale. Prevention through widespread use of ITNs or IRS, for example, might reduce the level of malaria transmission to the point that pregnant women are no longer at measureable risk of asymptomatic malaria, suggesting that IPTp interventions may no longer be needed. Scaled-up prevention of malaria transmission can also affect decisions about how best to deliver treatment for malaria illness.
It is critical to understand the interaction of IRS and ITNs, two of our core transmission reduction interventions. Understanding whether IRS, with the addition of universal ITN coverage, results in lower malaria burden, or, alternatively, whether high ITN coverage can help to reduce the number of IRS rounds needed for sustained transmission reduction can help us to invest our resources more strategically.
While both long-lasting insecticide-treated nets (LLINs) and IRS have similar efficacy in preventing malaria, it is unclear how best to integrate these interventions in a coherent malaria prevention strategy. A major question is whether LLINs and IRS have an additive effect on malaria transmission and malaria-related illness and death. CDC is currently studying the combined impact of LLINs plus IRS in comparison to LLINs alone in reducing the incidence of new malaria infections and the burden of malaria. Rachuonyo District in western Kenya, an area with high perennial transmission, was sprayed in July-September of 2008 under the President's Malaria Initiative. In December 2008, a cohort of approximately 1,000 persons was recruited from areas surrounding 3 health facilities within Rachuonyo District. A similar cohort was recruited from areas surrounding 3 health facilities in a neighboring district that was not sprayed. All enrolled participants were provided LLINs and then visited monthly to assess the incidence of new infections. Rachuonyo District was sprayed again in April 2009 and the follow-up of study participants was completed in October 2009. Before the start of the program and once after each round of IRS, three cross-sectional surveys were conducted in Rachuonyo District and a neighboring community, to estimate the impact on malaria morbidity in the community. The data are currently being analyzed and are are expected to provide critical information to malaria control programs on how best to integrate IRS and LLINs for the prevention of malaria.
In Indonesia, CDC is working in three sites where the transmission of malaria ranges from near elimination to hyperendemic to try to determine the optimal interventions for each epidemiologic context. Among the interventions being evaluated are ACTs, preventive treatment during pregnancy, community-based larval interventions including larvicides, and environmental management and IRS.
Establish and Integrate New or Revisited Interventions
Along with scaling up proven interventions for malaria control, researchers are contemplating new interventions or updating previously used malaria control interventions. These include new drugs and vaccines for treatment and prevention, new diagnostic tests, innovative insecticide-treated materials, and revised systems for delivering and evaluating malaria control. Understanding how these new or revisited interventions will operate under field conditions; proving their efficacy, effectiveness and safety; and demonstrating their interaction with existing malaria control efforts will be crucial to advising endemic countries and global donors about when and where to introduce them.
Rapid malaria diagnostic tests have made it possible to expand laboratory diagnosis of malaria beyond health facilities with functioning microscopes to more outlying locations, even beyond the walls of remote health posts into endemic communities. Understanding the performance limitations of the current generation of rapid tests can help us decide how to deploy them most efficiently and may provide experience and evidence that can shape the next generation of diagnostic tools. Evaluating strategies based on mass screening and treatment of healthy populations could suggest how diagnosis and treatment might be used to respond to localized outbreaks of malaria transmission in settings where effective control has been achieved and may ultimately contribute to elimination.
The use of insecticides has evolved, along with development of long-lasting wash-resistant applications for bed nets and new formulations for use in indoor residual spraying (IRS). We are evaluating novel uses for these materials, including the use of insecticide-treated materials to cover eaves where mosquitoes often enter houses and wall coverings. We are looking at the durability of the net fabric to determine the impact of holes on the protective efficacy of nets and how to make nets more durable. Paints with insecticides are also being evaluated as an alternative to IRS.
Identify Opportunities to Integrate Efforts with other Initiatives
In addition to new resources for malaria control, many endemic countries are simultaneously rolling out programs to combat HIV/ AIDS and neglected tropical diseases, enhance health information systems and supplies management, and reinforce maternal and child health. For each of these to operate at its potential will require careful planning and collaboration, especially at the most peripheral level where most of the tasks fall to the same few health workers. Examining how interventions can be delivered and managed in integrated ways will be key to achieving sustainable progress across multiple health conditions.
In many parts of the malaria-endemic world, mosquito vectors also transmit other viral and parasitic diseases. Coordinating an integrated vector management policy could effectively reduce both malaria and other illnesses like lymphatic filariasis or dengue. Like malaria control programs, many other health initiatives evaluate their effectiveness through regular population surveys or routine health facility reporting. Identifying opportunities to develop integrated evaluation tools and reporting systems that may lead to broader gains for malaria control and across the public health spectrum.
In many parts of Africa and the South Pacific, lymphatic filariasis is transmitted by the same mosquitoes that transmit malaria. While filariasis elimination strategies are based on mass drug administration with a combination of drugs, studies have shown that vector control can accelerate the elimination of filariasis and limit the potential reintroduction of this parasitic disease to areas where it has been eliminated.
Conduct Research and Development in the Laboratory and the Field
Field-based investigations provide insights into mechanisms and dynamics of malaria parasite transmission, emerging trends such as drug resistance and the range and type of host immune and pathological responses to malaria. They often yield valuable specimens that provide critical information when studied further through cutting-edge bench research in well-equipped laboratories in the United States and overseas. CDC’s laboratories (augmented by state-of-the-art insectaries and animal facilities) conduct more basic and applied studies, whose findings can in turn be verified or expanded during field investigations and lead to improved or new interventions for control and prevention.
Investigate Immune Responses and Immunity
CDC, through its field-based studies and laboratory investigations, has unique biological samples available from malaria cohort studies designed to investigate the role of antibodies, cytokines, and innate immune factors in protection against both uncomplicated malaria and severe malaria with anemia and cerebral involvement. These studies include birth cohort studies conducted in Kenya and ongoing cohort studies in India, which include both Plasmodium vivax and P. falciparum infections.
Collectively, these studies allow investigation of why manifestations of severe disease outcomes differ in various endemic settings (intense transmission versus seasonal transmission), how transmission pressure affects development of immune responses, and, importantly what factors determine the acquisition of clinical and parasitological immunity. These questions are being addressed using various immunologic assays and the latest molecular tools. The malaria research community is in the process of developing vaccines effective against malaria parasites in order to provide new interventions that will help control and eliminate malaria. Understanding which immune responses are active in malaria and how they are destructive to parasites is important to the rational development of vaccines. CDC investigators have undertaken ongoing field- and laboratory-based studies in this area to define the correlates of immunity for candidate vaccine antigens, which are critically important for guiding and efficiently furthering malaria vaccine development.
Characterize Genetic Contribution to Drug Resistance, Immunity, and Disease
CDC conducts ongoing investigations into the genetic complexity of malaria parasites and how this complexity and selection affects drug resistance, immunity, and disease.
The CDC malaria laboratories engaged in this malaria research are developing molecular tools and networks in the field in South America, Africa, and Southeast Asia that will monitor emergence of drug-resistant malaria parasites globally. The laboratories collect and maintain malaria parasite isolates with a wide array of defined drug-resistant properties in order to identify and characterize the molecular and biological markers of drug resistance and, also, the mechanisms by which drug resistance develops in these malaria parasites. These in vivo and in vitro adapted strains are archived and made available to qualified malaria researchers around the world. As well, CDC’s malaria program offers training to investigators in endemic countries on using molecular markers to detect and track drug-resistant parasites and in vitro methods of testing parasites for drug susceptibility.
CDC is also characterizing the genetic diversity in important malaria vaccine candidate antigens. Detection of molecular diversity in candidate vaccine antigens is elemental to the development of vaccines effective against malaria and to the determination of the best and least variable antigens that can serve as stable targets of immunity and for vaccine development.
A person’s genetic factors can influence dramatically the development and outcomes of severe disease states in malaria infections as well as the acquisition of immune status. We are taking advantage of our laboratory facilities and materials from our field-based cohort studies to identify potential host genetic factors associated with susceptibility to or protection from severe malarial anemia and cerebral malaria or with protection from infection. Recent advances in human genome research have opened up new opportunities for identifying host genetic factors associated with severe disease outcomes and innate resistance factors that protect against morbidity and mortality due to malaria infections.
These studies in parasite and human genetics also help to develop suitable molecular markers that could be used for tracking parasite populations associated with severe disease outcomes.
Development and Evaluation of Vaccines, Host-Parasite Biology, and Nonhuman Primate Models
The development of an effective malaria vaccine faces major challenges. Most vaccine development efforts are targeted against Plasmodium falciparum, the most serious and deadly malaria parasite. These vaccine efforts must take into account the genetic diversity of both the parasite and the human host and strive to provide effective immunity against the different stages of the life cycle. With a growing call for greater efforts to tackle malaria elimination, efforts are increasing to produce vaccines that target P. vivax, which must take into consideration features such as relapses and hypnozoite stages.
CDC scientists have an ongoing malaria vaccine development and evaluation program that develops models of human malaria in small New World monkeys and uses these nonhuman primate models to investigate the immunogenicity and protective efficacy of malaria vaccine candidates developed by CDC and other scientific groups globally. These primate malaria models are the only methods available to test the potential efficacy of human malaria vaccines prior to expensive human clinical trials.
Other studies of the biology of the malaria parasites using these nonhuman primate models and bench research
aim to gain a better understanding of the relationships between malaria parasites, mosquito vectors, and vertebrate hosts, in order to improve or facilitate the development of new methods to combat malaria such as vaccines or new drugs.
allow the modeling of parasite-host relationships with regard to immunity, pathology, and response and susceptibility to old and newly developed antimalarial drugs.
New isolates and strains of malaria parasites are collected, adapted to laboratory culture or nonhuman primates, and tested using the latest available treatments. These nonhuman primate hosts of human malarias and of the simian malaria parasites also offer faithful models to investigate mechanisms and treatments for severe pathology associated with malaria infections such as anemia, cerebral malaria, and malaria in pregnancy.
Rapid Diagnostic Tests
The malaria laboratories at CDC in conjunction with WHO and the Foundation for Innovative New Diagnostics (FIND) conduct extensive laboratory-based evaluations on the performance of commercial RDTs on the global market as well as investigation into a variety of other issues connected with the development and deployment of these new diagnostic tests.
More on: Rapid Diagnostic Tests.
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