This Funding Opportunity Announcement (FOA) solicits
applications to participate in an International Centers of Excellence for
Malaria Research (ICEMR) program that will provide a multidisciplinary
research approach to malaria control and prevention through the integration
of findings from clinical and field research. The overarching goal of
the ICEMR program is to establish research centers in malaria-endemic
settings that will provide the necessary knowledge, tools, and evidence-based
strategies for use by government organizations and health care institutions
to control and treat malaria. This program is not intended to support
research which can be conducted primarily in U.S. institutions.
Although malaria has been eliminated from many parts of the
globe, over 40% of the world’s population still lives in areas where they are
at risk for contracting the disease. Control efforts have not been sustainable
in many locations and have been associated with the emergence and spread of
both parasite resistance to antimalarial drugs and vector resistance to
insecticides. Currently, there are no point-of-care diagnostic tools available
to monitor emerging drug resistance to malaria. A malaria vaccine has not yet
been licensed, and although a number of promising candidates are in
development, a highly effective malaria vaccine for all age groups may not be
available for years to come. Although various efforts to curb malaria have
been launched, it has become increasingly clear that sustainable and effective
malaria control requires an improved understanding of the complex interactions
among the parasite, the mosquito vector, and the human host in local clinical
and field settings. Furthermore, novel drugs, diagnostics, and vaccines, as
well as vector management strategies, will need to be developed, evaluated and
ultimately utilized in malaria-endemic locations (http://www.who.int/malaria/publications/world_malaria_report_2014/report/en/).
Thus, a multidisciplinary research approach is urgently needed to address these
complex interactions at the molecular, cellular, organismic, population and
field levels in malaria-endemic areas in order to provide the knowledge base
necessary for improved clinical and field management of malaria, as well as to
guide the development of new tools and interventions.
Research Objectives and Scope
The objective of this Funding Opportunity Announcement (FOA)
is to recompete the National Institute of Allergy and Infectious Diseases’
(NIAID) International Centers of Excellence for Malaria Research program
comprised of a network of research centers in malaria endemic regions. In 2010
the NIAID established the International Centers of Excellence for Malaria
Research (ICEMR) program to support multidisciplinary research in diverse
epidemiologic settings spanning all representative malaria endemic regions of
the world. Research projects were designed to capture and track changes in the
complex interactions between the human host, malaria parasites and the mosquito
vectors in different eco-epidemiologic settings. Unlike routine surveillance
and intervention evaluation programs, the Centers are mandated both to adopt an
integrated approach to malaria research, and to apply molecular epidemiology
and genomics to study transmission and disease in the context of dynamic
changes in disease prevalence and incidence. The research objective of each Center
will focus on the design and conduct of multidisciplinary research on the
epidemiology, transmission, and pathogenesis of malaria in endemic geographic
regions, and the design and conduct of special projects to capitalize on new
opportunities and emerging public health needs, and to assist in understanding,
controlling and eliminating malaria. Integral to accomplishing the goals of
each Center is the inclusion of milestones, which will be used to measure the
progress of the individual projects and cores as well as the Center as a
whole.
The majority of Center research projects must be conducted
within malaria-endemic geographic regions and must provide for significant
involvement of local/regional researchers in study design, development and
execution. It is important to note that the ICEMR program is not intended to
support research that can be conducted primarily in the U.S. and countries
where malaria is not endemic. In addition, each Center must develop and
maintain affiliations with local/regional government agencies and established
institutions in the endemic countries to ensure necessary coordination of
research activities with ongoing malaria control/intervention programs and to
facilitate access to relevant study populations and treatment centers.
Location of Field Sites: Center research activities should
include a minimum of three field sites which could be in the same or different
countries at distances that provide for potential variability in the
epidemiology and transmission across field sites. The application should
describe the epidemiology of malaria at each of the sites to show that there is
variability in transmission of malaria. Alternatively, Center research activities
should include a minimum of three field sites in different malaria endemic
regions but with similar malaria transmission characteristics. Examples of
these include persistent low level transmission, seasonal transmission, and
hyper-endemic perennial transmission. Applications with sites in
malaria-endemic areas where there is a paucity of research and surveillance
data are encouraged.
ICEMR Program Components
Each application in response to this FOA must include: (1) an
Administrative Core; (2) a Data Management and Biostatistics Core; and (3) three
or more Research Projects. In addition, the application may include optional
Shared Resources Cores that support the work within the ICEMR.
Administrative
Core
The ICEMR Administrative Core will be responsible for
managing, coordinating, and supervising the entire range of Center activities,
monitoring progress, and ensuring that the project milestones are being met and
are being implemented effectively within the proposed timelines. The
Administrative Core will also be responsible for the management and
administration of the Special Projects Program which will be designed to
capitalize on opportunities and needs resulting from (1) changing
epidemiological conditions, (2) implementation of malaria control programs and
resulting public health needs, and/or (3) emerging scientific developments and
associated research needs.
Data
Management and Biostatistics Core
All applications must include a Data Management and
Biostatistics Core providing for the data management and statistical support of
the overall center. The Data Management system must collect and manage data
from all the participating study sites ensuring uniformity of procedures and
high quality data. The Data Management Core will be responsible for the rapid
release to the broader scientific community of datasets, analysis tools,
reagents, and other resources generated under the grant in adherence to the
requirements and timelines described in the NIAID Data and Reagents Sharing and
Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx)
and the NIH Genomic Data Sharing (GDS) Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html).
Shared
Resource Cores
Shared Resource Cores are optional Cores that provide
scientific and/or clinical services or resources to at least two research
projects. Shared Resources Cores must be well justified and clearly
non-duplicative of other services or facilities available to ICEMR
investigators. Examples of services provided by a shared scientific core are
laboratory support, monoclonal antibody production, peptide synthesis,
microbiology laboratory services, insectary or vector biology laboratory, and
immunology/molecular biology support. Shared clinical cores could provide a
source of patients and healthy volunteers, clinical specimens or represent a
facility for procedures that require health care personnel supervision.
Research
Projects
The three research projects must address one question in
Research Area A - Epidemiology, and two or more projects in Research Area B –
Transmission and/or Research Area C – Pathogenesis and Diagnosis. Research Area
A – Epidemiology should be a multi-site project involving at least three of the
field sites proposed by the Center. The design of the Research Projects should reflect
a multidisciplinary approach that integrates clinical and field aspects with
laboratory, molecular and genomic methods, and be capable of adapting to a
changing landscape based on epidemiological malaria research.
Examples
of research activities that are responsive to this FOA include, but are not
limited to, the following:
1. Research
Area A – Epidemiology
- Research and Impact Analysis (e.g., cost-effectiveness analysis) to assess the optimal combination of standard public health interventions in an integrated manner to reduce the burden of disease due to malaria. Examples of such interventions include use of rapid diagnostics, larviciding, bed-net use, indoor residual spraying, and treatment or prevention of malaria which are in routine public health use in accordance with the country’s Ministry of Health (MOH) guidelines;
- Immuno-epidemiology evaluating prevalence of antibodies, innate and adaptive responses associated with protection;
- Assessment of the degree of parasite population diversity and structure and its relevance to interventions;
- Multidisciplinary research approaches to discover, identify, validate, evaluate, and optimize interventional tools and strategies;
- Studies that encourage the merging of laboratory research and field research such as use of molecular tools and/or immune responses to explain linkage between epidemiologic, pathologic and ecologic phenomena;
- Development of mathematical models based on emerging field data that will help guide product development and optimize the combinations of interventions;
- Evaluation of novel diagnostics (until a new diagnostic receives regulatory approval, results should not impact clinical management of malaria cases);
- Factors, biomarkers, or combination of indicators associated with recurrent malaria infections and/or recrudescence.
2. Research
Area B – Transmission
- Research on vector biology and ecology;
- Impact of emerging resistance to current drugs and insecticides on transmission;
- Impact of vector management or control strategies on disease transmission;
- Evaluation of novel transmission reduction strategies, e.g., combination of existing vector control methods;
- Study of asymptomatic carriers and their contribution to disease transmission;
- Assessment and evaluation of monitoring tools and surveillance methods when malaria transmission is at low levels or to detect onset of epidemics.
3. Research
Area C – Pathogenesis and Diagnosis
-
Identification and characterization of :
- host susceptibility and parasite virulence factors contributing to changes in the spectrum of disease severity, changes in pathological manifestation(s), evasion of protective host responses, or increased transmissibility;
- host factors and immune responses that are associated with resistance to infection and/or disease, or with reduced transmission;
- host factors associated with carriage of hypnozoites;
- serological markers and diagnostic tools for identification of carriers of hypnozoites;
- factors associated with persistence or clearance of gametocytes;
- Identification, development and testing of diagnostics for human and mosquito infections, as well as drug and insecticide resistance;
-
Development and evaluation of:
- rapid diagnostic tools that can evaluate the quality of antimalarial drugs;
- field deployable genomic surveillance tools for parasites and vectors.
- Development or adaptation of robust genomic tools for analysis of field derived host, parasite and vector specimens.
Applications
proposing the following studies will be considered not responsive and will not
be reviewed:
- Research on malaria parasites that do not infect humans;
- Animal model research or the development of new/improved animal models;
- Research that does not require access to human subjects or specimens from malaria-endemic sites;
- Stand-alone basic research projects; stand-alone basic research not requiring access to malaria endemic field sites or samples from such field sites is funded through other mechanisms, including investigator-initiated research grants;
- Construction and major renovations other than minimal alterations of existing facilities to conform to Good Laboratory Practices (GLP) and Good Clinical Practices (GCP) guidelines; or adapted to an alternative use to meet a specific scientific requirement;
- Clinical trials, including interventional clinical trials of investigational products;
- Research on pathogens other than malaria except in the context of co-infections or non-malaria outcomes as a result of anti-malarial interventions;
- Research on vectors other than those that transmit malaria;
- Operations and Health Systems research, and outreach and care delivery that is not linked to one or more of the research areas (A, B, or C) identified above;
- Research on HIV and/or AIDS
Scientific
Advisory Group (SAG)
Applicants, in collaboration with NIAID, will establish,
plan and coordinate the activities of a Scientific Advisory Group (SAG)
beginning in the second year. The SAG will review Center progress and provide
scientific advice with respect to the scientific direction of the Center,
progress and performance of ongoing research projects, and proposed Special
Projects. The SAG will also make recommendations regarding the continuation or
re-direction of projects on an ongoing basis and in consultation with the NIAID
staff.
Applicants
should not contact nor identify individuals who might be invited to serve on
the SAG for their ICEMR program.
Annual
Workshops
Each Center will be responsible for hosting one 2-3 day
workshop during the life of the grant that will have the participation of all
of the ICEMR program Centers. The workshops are intended to identify areas of
collaboration among the Centers, including methods to share expertise, facilities,
and other resources of the Centers and identifying opportunities for clinical
research involving participating sites from more than one ICEMR.
Eligible Applicants
Eligible Organizations
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
