TROPICAL DISEASE RESEARCH UNITS

Release Date:  February 20, 1998

RFA:  AI-98-004

P.T.

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  March 31, 1998
Application Receipt Date:  June 17, 1998

APPLICATIONS IN RESPONSE TO THIS REQUEST FOR APPLICATIONS (RFA) MUST BE PREPARED
USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR
COMPLETING THE APPLICATION ARE IN AN NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR
APPLICATIONS FOR MULTI-PROJECT AWARDS."

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH), invites applications for program project (P01) grants
to conduct multidisciplinary research leading to the development and evaluation
of new strategies to prevent and control diseases caused by protozoan and
helminth parasites.  Programs will focus on one of the following areas: (1)
development of vaccines for infection and disease; (2) discovery of drug targets
and development of new chemotherapeutic agents for treating and preventing
parasitic infections; or (3) development of new approaches for interruption of
the parasite life cycle at the level of the invertebrate (vector) host.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, Tropical Disease Research Units
(TDRUs), is related to the priority area(s) of immunization and infectious
diseases.  Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Research grant applications may be submitted by domestic for-profit and non-
profit organizations, public and private institutions, such as universities,
colleges, hospitals, laboratories, units of State and local governments, and
eligible agencies of the Federal government.  Foreign organizations are not
eligible to apply.  Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

The mechanism of support will be the program project (P01) grant.  This type of
award supports broadly based multidisciplinary research programs that have a
well-defined central research focus or objective.  An important feature is that
the interrelationships among the individual scientifically meritorious projects
will result in a greater contribution to the overall program goals than if each
project was pursued individually.  The program project grant consists of a
minimum of three interrelated individual research projects that contribute to the
program objective.  The award also can provide support for certain common
resources termed cores.  Such resources should be utilized by two or more
projects within the award.

Responsibility for the planning, direction, and execution of the proposed
projects will be solely that of the applicant.  The total project period may not
exceed five years.  At this time, the NIAID is administratively limiting the
duration of P01 grants to four years; this administrative limitation may change
in the future.  The earliest anticipated award date is May 1999.

FUNDS AVAILABLE

The estimated total funds (direct and indirect) available for the first year of
support for this RFA will be $2.5 million.  In fiscal year 1999, the NIAID plans
to make four awards related to this RFA.  This level of support is dependent on
the receipt of a sufficient number of applications of high scientific merit. 
Applications may not request budgets in excess of $625,000 in total (direct and
indirect) costs in the first year.  The usual PHS policies governing grants
administration and management will apply.  Although this program is provided for
in the financial plans of the NIAID, awards pursuant to this RFA are contingent
upon the availability of funds for this purpose.  Funding beyond the first and
subsequent years of the grant will be contingent upon satisfactory progress
during the preceding years and availability of funds.  At this time, the NIAID
has not determined whether or how this solicitation will be continued beyond the
present RFA.

RESEARCH OBJECTIVES

Background

Parasitic diseases continue to represent tremendous public health problems,
especially for people living in the tropics where they are responsible for deaths
and impaired growth and development among children as well as for debilitating,
chronic diseases among adults.  Additionally, parasitic infections have been
recognized with increasing frequency as responsible for diseases in the United
States and other industrialized countries.  Of special interest to clinicians and
public health workers in developed nations is the occurrence of severe disease
in individuals who acquired their infection congenitally or as a result of
immunosuppression.

Prevention and treatment of parasitic diseases remain problematic.  In many
cases, currently available drugs exhibit either excessive toxicity and/or
inadequate efficacy.  Moreover, several previously useful compounds are no longer
effective due to the spread of drug resistant parasite variants.  Vaccines do not
exist for any human parasitic infection.  Environmental changes, notably those
associated with land and water management practices, have led to the emergence
or re-emergence of parasitic diseases, especially those that are vector-borne.

Currently parasitology research supported by the DMID, NIAID, is largely
conducted under investigator initiated research project grants focusing on the
biology (molecular and cellular biology, immunology, and biochemistry) of the
medically important protozoa and helminths as well as on the biology of
invertebrate vectors.  Research reagents in support of schistosomiasis,
filariasis and malaria research are available through repository contracts funded
by NIAID (http://www.niaid.nih.gov/reposit/default.htm).  In addition, the
Institute also supports several special programs for studies on parasitic and
other tropical diseases. The International Centers for Tropical Disease Research
(ICTDR) network serves to coordinate many of the Institute's activities in the
area of tropical infectious diseases.  Within the ICTDR network, studies in areas
endemic for tropical parasitic diseases are funded through its International
Collaboration in Infectious Disease Research (ICIDR) and Tropical Medicine
Research Center (TMRC) programs.  Available resources in endemic areas supported
by the ICIDR and TMRC programs may provide opportunities for field testing of new
intervention strategies as they arise.  In addition, NIAID is developing a
network of clinical trial sites in endemic areas for evaluation of malaria
vaccines or therapies.

This RFA represents a continuation of another major component of NIAID's ICTDR
network, the Tropical Disease Research Units (TDRUs) program which was initiated
in 1980 and was originally designed to stimulate advanced biomedical research on
the five parasitic diseases (filariasis, leishmaniasis, malaria, schistosomiasis
and trypanosomiasis) that form the basis of the World Health Organization's
Special Programme for Research and Training in Tropical Diseases (TDR).  Since
the inception of the TDRU program, much has been learned about the biology of
these and other parasites as a result of the dramatic advances in molecular and
cellular biology and in immunology. Recent advances in our understanding of the
basic biology of parasites and of host-parasite interactions have created unique
opportunities for discovering and evaluating new means of controlling the
mortality and morbidity associated with parasitic infections.  Recognizing that
substantial advances have been made in the understanding of many parasitic
diseases of significant global public health impact, in 1995 NIAID expanded the
scope of the TDRU program to encompass all medically important human parasitic
diseases.

Under the current renewal, TDRUs will be expected to provide a resource for
concerted efforts in the development and preclinical testing of new intervention
strategies for parasitic diseases.  Components of the TDRU program will have the
opportunity to work with other members of the ICTDR network to move promising
vaccination, chemotherapeutic or vector control strategies toward clinical or
field trials.

Research Objectives and Scope

The NIAID wishes to support multidisciplinary, state of the art biomedical
research units focused on development and preclinical testing of new intervention
strategies to control the public health impact of diseases caused by protozoa and
helminths.  For the purpose of this RFA, intervention strategies to be considered
are: i) vaccines to prevent infection and/or disease; ii) chemotherapeutic agents
to prevent and/or treat infection; and iii) methods to control invertebrate
vectors or to interrupt the parasite's life cycle in the vector.

The entire program project grant, consisting of three or more projects as well
as cores, must address the development of one of these intervention strategies. 
In addition to being limited to a single intervention strategy, the program
project must focus on a single parasitic infection.  Within this focus, studies
on human pathogens are preferred but studies on animal pathogens that are
recognized to provide relevant models of human disease will also be acceptable.

The entire program project should be designed to address the common goal in a
cohesive manner.  Thus, responsive programs would be those in which each project
provides information necessary for further development of the single intervention
strategy chosen as the overall program objective and/or evaluation of its utility
in an appropriate in vitro or in vivo system.  Each application must clearly
define the mechanisms to be used to ensure integration and information exchange
among the different projects of the program in pursuit of this single goal.

Studies relevant to this program include, but are not restricted to, the
following:

identification of structures, pathways or functions in medically relevant
protozoa or helminth pathogens, that could serve as new  targets for
chemotherapeutic or immunologic intervention, and development of methods to
evaluate their utility;

o  identification of host-pathogen interactions involved in protective immunity
or immunopathogenesis, leading to development and testing of experimental
vaccines/immunotherapies;

o  use of improved methods for antigen delivery/presentation or enhancement of
protective immunity to design anti-parasite vaccines;

o  identification of mechanisms of susceptibility and resistance to antiparasitic
agents (including structural biological studies of essential parasite enzymes and
pathways) and development of novel methods to reverse or bypass this process;

o  identification of methods to interrupt parasite transmission in invertebrate
vectors of human parasitic infections.

Each application must provide an experimental plan which details the methods that
will be used to validate the utility of the chosen approach.  The experimental
plans must indicate, by use of a schedule or time table, when the appropriate
validation strategy will be applied for evaluating the chosen approach as an
intervention method.  Examples of validation strategies include:

o  use of site-directed mutagenesis, gene knockouts, testing of specific
inhibitors or antisense technology to establish the essential nature of a drug
target in programs seeking to discover and develop new anti-parasitic agents,

o  examination of the inhibition of infection or of documented correlates of
pathology in in vitro or in vivo model systems in programs seeking to develop
vaccines or therapeutic agents,

o  examination of the reduction in vectorial capacity for parasite transmission
in programs seeking to develop control programs targeted at the level of the
invertebrate vector.

Programs may involve collaboration among investigators at several institutions. 
For example, programs involving more developmental aspects of the proposed
studies may benefit from resources available through collaborative arrangements
with private industry.  Consortium arrangements should follow the NIH Guide
outline in "Guidelines for Establishing & Operating Consortium Grants, January,
1989."  These are available from the individuals listed under INQUIRIES, below.

SPECIAL REQUIREMENTS

Institutions receiving TDRU awards are considered as Centers in the NIAID ICTDR
network, and TDRU program directors are designated as Center Directors in this
network.  A further description of the network available on the NIAID Website at
http://www.niaid.nih.gov/ictdr.  The application should budget appropriate funds
to allow the TDRU program director to attend the annual meeting of the network
which is generally held in Bethesda in Spring.  Attendance of other key personnel
is encouraged.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and their
subpopulations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification are provided that inclusion is inappropriate with
respect to the health of the subjects of the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research", which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11,
March 18, 1994.

Investigators may obtain copies from these sources or from Dr. Gottlieb (listed
in INQUIRIES below) who may also provide additional relevant information
concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 31, 1998, a letter of intent
that includes a descriptive title of the overall proposed research, the name,
address and telephone number of the Principal Investigator, and the number and
title of this RFA.  Although the letter of intent is not required, is not
binding, does not commit the sender to submit an application, and does not enter
into the review of subsequent applications, the information that it contains
allows NIAID staff to estimate the potential review workload and to avoid
conflict of interest in the review.  The letter of intent is to be sent to Dr.
Madelon Halula at the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applicants for P01 grants must follow special application guidelines in the 
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS
(September 1997); this brochure is available from NIAID staff listed in 
INQUIRIES below an via the WWW at: http://www.niaid.nih.gov/ncn/grants/
multibron.htm

Applications are to be submitted on the standard research grant application form
PHS 398 (rev. 5/95).  Application kits are available at most institutional
offices of sponsored research and may be obtained from the Division of Extramural
Outreach and Information, National Institutes of Health, 6701 Rockledge Drive,
MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, email:
asknih@od.nih.gov.

For purposes of identification and processing, item 2 on the face page of the
application must be marked "YES" and the RFA number "AI-98-004" and the words
"Tropical Disease Research Units" must be typed in.

Applications must be received by June 17,1998.  Applications that are not
received as a single package on the receipt date or that do not conform to the
instructions contained in PHS 398 (rev. 5/95) Application Kit (as modified in,
and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR
MULTI-PROJECT AWARDS"), will be judged non-responsive and will be returned to the
applicant.  The RFA label available in the application form PHS 398 must be
affixed to the bottom of the face page.  Failure to use this label could result
in delayed processing of the application such that it may not reach the review
committee in time for review.

Applicants from institutions that have a General Clinical Research Center (GCRC)
funded by the NIH National Center for Research Resources may wish to identify the
GCRC as a resource for conducting the proposed research.  If so, a letter of
agreement from either the GCRC program director or principal investigator could
be included with the application.

It is highly recommended that the appropriate NIAID program contact be consulted
before submitting the letter of intent and during the early stages of preparation
of the application.  (See program contact under INQUIRIES).

Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040 - MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express mail or courier service)

At the time of submission, two additional exact copies of the grant application
and all five sets of any appendix material must be sent to Dr. Halula at the
address listed under INQUIRIES.

Concurrent submission of an R01 and a Component Project of a  Multi-project
Application:  Current NIH policy permits a component research project of a multi-
project grant application to be concurrently submitted as a traditional
individual research project (R01) application.  If, following review, both the
multi-project application and the R01 application are found to be in the fundable
range, the investigator must relinquish the R01 and will not have the option to
withdraw from the multi-project grant.  This is an NIH policy intended to
preserve the scientific integrity of a multi-project grant, which may be
seriously compromised if a strong component project(s) is removed from the
program.  Investigators wishing to participate in a multi-project grant must be
aware of this policy before making a commitment to the Principal Investigator and
awarding institution.

SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA

Applicants for P01 grants must follow special application guidelines in the NIAID
Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS
(September 1997); this brochure is available via the WWW at:
http://www.niaid.nih.gov/ncn/grants/multibron.htm.

The brochure presents specific instructions for sections of the PHS 398 (rev.
5/95) application form that should be completed differently than usual.  For all
other items in the application, follow the usual instructions on pages 5-20 of
the PHS 398 booklet.

REVIEW CONSIDERATIONS

Review Procedures

Upon receipt, applications will be reviewed for completeness by the NIH Center
for Scientific Review and for responsiveness by NIAID staff.  Incomplete and/or
non-responsive applications will be returned to the applicant without further
consideration.

Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the NIAID in accordance with the review criteria stated below.  As part of the
initial merit review, a process (triage) may be used by the initial review group
in which applications will be determined to be competitive or non-competitive
based on their scientific merit relative to other applications received in
response to the RFA.

Applications judged to be competitive will be discussed and be assigned a
priority score.  Applications determined to be non-competitive will be withdrawn
from further consideration and the Principal Investigator and the official
signing for the applicant organization will be notified.  The second level of
review will be provided by the National Advisory Allergy and Infectious Diseases
Council.

Review Criteria

The general criteria for P01 grant applications are presented in the NIAID
brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS
(September 1997).  Additional review criteria specific to this RFA are:

o  The project is centered around a well-focused goal related to development and
preclinical testing of an intervention strategy to control the public health
impact of a parasitic disease; each project contributes to that goal.

o  The project addresses the development of one such intervention strategy, and
focuses on a single parasitic infection

AWARD CRITERIA

Funding decisions will be made on the basis of scientific and technical merit as
determined by peer review, program balance, and the availability of funds.  The
totality of the awarded projects will reflect the diversity of medically relevant
protozoan and helminth parasites, as well as the diversity of possible
intervention approaches.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.  The
opportunity to clarify any issues or questions from potential applicants is
welcome.

Requests for the NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS" as well as inquiries regarding programmatic (eligibility and research
scope) issues, may be directed to:

Michael Gottlieb, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 3A-12
Bethesda, MD  20892-7630
Telephone:  (301) 496-2544
FAX:  (301) 402-0659
Email:  mg35s@nih.gov

Direct inquiries regarding preparation of the application and review issues, and
address the letter of intent to, and mail two copies of the application and all
five sets of appendices to:

Dr. Madelon Halula
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4C-16
Bethesda, MD  20892-7610
Telephone:  (301)402-2636
FAX:  (301) 402-2638
Email:  mh30x@nih.gov

Direct inquiries regarding fiscal matters to:

Mr. Todd Ball
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B-35
Bethesda, MD  20892-7610
Telephone:  (301) 496-7075
Email:  tb22j@nih.gov

Schedule

Letter of Intent Receipt Date:   March 31, 1998
Application Receipt Date:        June 17,1998
Scientific Review Date:          October 1, 1998
Advisory Council Date:           January 25, 1999
Earliest Date of Award:          May 1, 1999

AUTHORITY AND REGULATIONS

This program is supported under authorization of the Public Health Service Act,
Sec. 301 (c), Public Law 78-410, as amended.  The Catalogue of Federal Domestic
Assistance Citation is Sec. 93.856, Microbiology and Infectious Diseases
Research.  Awards will be administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74.  This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or Health
Systems review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.


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