Date Published: January 25, 2011
Publisher: Public Library of Science
Abstract: The Malaria Eradication Research Agenda (malERA) Consultative Group on Vector Control outline the research needed to ensure vector control at every stage of malaria eradication.
Partial Text: The overarching goal of malaria vector control is to reduce the vectorial capacity of local vector populations below the critical threshold needed to achieve a malaria reproduction rate (R0, the expected number of human cases that arise from each human case in a population) of less than 1. Because of the long extrinsic incubation time of Plasmodium in its Anopheles vectors, the most effective vector control strategies in use today rely on insecticide interventions like indoor residual insecticide sprays (IRSs) and long-lasting insecticide-treated nets (LLINs) that reduce vector daily survival rates . For many malaria-endemic regions, these tools can make substantial contributions to malaria control and may be sufficient for local malaria elimination. These were the only regions considered by the recent Malaria Elimination Group (MEG). Regions where existing interventions will not be sufficiently effective include those where high rates of transmission occur. For example, in much of sub-Saharan Africa, where the entomological inoculation rates (EIRs) can reach levels approaching 1,000 infective bites per person per year ,, the best use of existing interventions can only help to reduce annual inoculation rates by approximately an order of magnitude. Additional interventions will clearly be required, however, both for regions with extremely high rates of transmission and for regions where the major vectors are not susceptible to current control tools .
The key goal of the malERA Consultative Group on Vector Control was to help define the research and development agenda that will be required to sustain and improve the effectiveness of currently available tools like LLINs and IRS and to develop new vector-targeted tools that can be used to interrupt transmission in environments or at intensities that these existing tools cannot reach. It is clear that new technology will be required in very high transmission areas to reduce vectorial capacity and achieve even effective control, let alone elimination. The main aim of this paper is to define a research and development agenda that focuses on those new research questions and knowledge gaps that arise specifically in response to the call for malaria eradication, and that would not otherwise be at the top of the agenda (Table 1). It is particularly important to recognize that this operationally specified goal significantly limits the scope of research and development under consideration, and this document should not be the basis for all vector research related to malaria. Our article does, however, describe the challenges for vector control methodology in the elimination phase, for detecting and monitoring areas of persistent transmission, and for detecting and monitoring nonrandom transmission leading to outbreaks. We also discuss the requirements for rapid and urgent intervention when outbreaks occur (see also ).
The malaria eradication agenda would clearly be advanced by the development of a formalized analytical framework that facilitates the collection, analysis, and central presentation of relevant information (Figure 1). Such a framework could significantly help elimination/eradication programs optimize the use of current vector control tools. In addition, when available tools are properly deployed and transmission persists, such a framework could also highlight the knowledge gaps that currently limit accurate development of clear target product profiles (TPPs) for new tools. The generation and sharing of information from systematic assessments of the results of malaria elimination programs across different epidemiological settings will help drive the development of new technologies that will be needed to achieve elimination in more intransigent transmission settings.
The obvious major threat to current vector-targeted interventions is insecticide resistance, and addressing this problem will be both an important near-term research concern and a continuing, long-term concern as new insecticide formulations and ingredients are developed and used. Furthermore, this problem is critical for control efforts as well as for elimination and eradication efforts. Pyrethroids are the only insecticides currently used operationally on LLINs and are also the dominant insecticide class in IRS, but resistance to this insecticide class is now widespread, with multiple resistance mechanisms spreading in the two major African malaria vectors ,. Although the operational impact of these resistance indicators remains to be established, multiple studies have demonstrated the direct association of resistance measures with entomological indicators such as mosquito mortality, biting rates, and blood feeding success.
Malaria is transmitted in diverse epidemiological situations by a wide range of potential combinations of “primary” and “secondary” vectors. Moreover, most widely recognized vector species are members of cryptic species complexes  and even within currently recognized complexes, further heterogeneities may exist in vector population structure that can limit the effectiveness of control tools . The present vector control tools (LLINs and IRS) were developed to reduce transmission in areas where the primary vectors feed and/or rest indoors. When these interventions are implemented under optimal programmatic conditions, diligent monitoring will identify areas where there are limitations in their effectiveness.
In order to establish TPPs for novel vector control products, particularly for products that target outdoor feeding or resting mosquitoes, we need to establish the critical points in the life cycle of these mosquitoes where they congregate in numbers, are susceptible to attraction by external stimuli, or come into contact with their human hosts. Better sampling methods that continuously track mosquito movement in space and time, rather than current methods that sample at known fixed points of interaction, are therefore needed. Moreover, methods that generate representative samples of mosquitoes in areas with intensive vector control activity are needed for accurate monitoring and evaluation of insecticide resistance and infection rates.
On the basis of its deliberations, the malERA Consultative Group on Vector Controls proposes a research and development agenda for vector control (Box 1). The first of these agenda items—the development of an analytical framework to facilitate decision making—is achievable in the next 12–18 months. The other areas need to be rapidly progressed over the next decade. It will be up to everyone involved in malaria elimination/eradication to work together to ensure that all the needs and goals highlighted in this agenda are achieved as efficiently as possible. Importantly, however, our proposed agenda provides a starting point only for the research and development needs associated with vector control. This agenda must not be set in stone; it must continue to evolve as the elimination/eradication program progresses.