[Federal Register Volume 62, Number 130 (Tuesday, July 8, 1997)]
[Notices]
[Pages 36533-36541]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-17703]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
[Announcement Number 778]
Extraumural Applied Research Program in Emerging Infections;
Novel Methods for Identification of Emerging Infections
Introduction
The Centers for Disease Control and Prevention (CDC) announces the
availability of fiscal year (FY) 1997 funds for competitive cooperative
agreements and/or grants to support applied research on emerging
infections.
The CDC is committed to achieving the health promotion and disease
prevention objectives of Healthy People 2000, a national activity to
reduce morbidity and mortality and improve the quality of life. This
announcement is related to the priority area of Immunization and
Infectious Diseases. (For ordering a copy of Healthy People 2000, see
the section WHERE TO OBTAIN ADDITIONAL INFORMATION.)
Authority
This program is authorized under Sections 301 and 317 of the Public
Health Service Act, as amended (42 U.S.C. 241 and 247b).
Smoke-Free Workplace
CDC strongly encourages all grant recipients to provide a smoke-
free workplace and to promote the non-use of all tobacco products, and
Public Law 103-227, the Pro-Children's Act of 1994, prohibits smoking
in certain facilities that receive Federal funds in which education,
library, day care, health care and early childhood development services
are provided to children.
Eligible Applicants
Applications may be submitted by public and private non-profit
organizations and governments and their agencies. Thus, universities,
colleges, research institutions, hospitals, other public and private
organizations, including State and local governments or their bona fide
agents, federally recognized Indian tribal governments, Indian tribes
or Indian tribal organizations, and small, minority- and/or women-owned
businesses are eligible to apply.
Note: An organization described in section 501(c)(4) of the
Internal Revenue Code of 1986 which engages in lobbying activities
shall not be eligible to receive Federal funds constituting an
award, grant, contract, loan, or any other form.
Availability of Funds
Approximately $1,205,000 is available in FY 1997 to fund 7 to 11
awards in six specific focus areas as follows:
Focus Area #1
Evaluating Algorithms to Diagnose Emerging Causes of Infectious
Diarrhea: Approximately $480,000 is available to make 2-3 awards with a
maximum project period of 3 years.
Focus Area #2
Rapid Identification of Emerging and Unusual Pathogenic Bacteria by
Partial 16S rRNA Sequencing: Approximately $60,000 is available to make
one award with a maximum project period of 3 years.
Focus Area #3
Development and Evaluation of Improved Tests for Malaria Diagnosis
in the United States: Approximately $100,000 is available to make 1-2
awards with a maximum project period of 2 years.
Focus Area #4
Development of Improved Diagnostic Tests for Leishmaniasis:
Approximately $150,000 is available to make 1-2 awards with a maximum
project period of 2 years.
Focus Area #5
Identification of Unrecognized Etiologic Agents in Idiopathic
Sexually Transmitted Disease Syndromes: Approximately $300,000 is
available to make one to two awards with a maximum project period of 2
years.
[[Page 36534]]
Focus Area #6
Development of Non-culture Molecular Epidemiologic Detection/Typing
Methods for Treponema pallidum or Haemophilus ducreyi: Approximately
$115,000 is available to make one award for a maximum project period of
2 years.
For Focus Areas 2 and 3, only cooperative agreement applications
will be accepted. For Focus Areas 1, 4, 5, and 6, either grant or
cooperative agreement applications will be accepted.
Applicants must specify the type of award for which they are
applying, either grant or cooperative agreement. CDC will review all
applications in accordance with the Evaluation Criteria section of this
announcement. Before issuing awards, CDC will determine whether a grant
or cooperative agreement is the appropriate instrument based upon the
need for substantial CDC involvement in the project.
It is expected that awards will begin on or about August 30, 1997,
and will be made for a 12-month budget period within a project period
of up to three years (maximum project period varies by Focus Area--see
above). Funding estimates may vary and are subject to change.
Continuation awards within the project period will be made on the
basis of satisfactory progress and availability of funds.
Use of Funds
Restrictions on Lobbying
Applicants should be aware of restrictions on the use of Department
of Health and Human Services (HHS) funds for lobbying of Federal or
State legislative bodies. Under the provisions of 31 U.S.C. Section
1352 (which has been in effect since December 23, 1989), recipients
(and their subtier contractors) are prohibited from using appropriated
Federal funds (other than profits from a Federal contract) for lobbying
Congress or any Federal agency in connection with the award of a
particular contract, grant, cooperative agreement, or loan. This
includes grants/cooperative agreements that, in whole or in part,
involve conferences for which Federal funds cannot be used directly or
indirectly to encourage participants to lobby or to instruct
participants on how to lobby.
In addition, the FY 1997 Departments of Labor, HHS, and Education,
and Related Agencies Appropriations Act, which became effective October
1, 1996, expressly prohibits the use of 1997 appropriated funds for
indirect or ``grass roots'' lobbying efforts that are designed to
support or defeat legislation pending before State legislatures.
Section 503 of this new law, as enacted by the Omnibus Consolidated
Appropriations Act, 1997, Division A, Title I, Section 101(e), Pub. L.
No. 104-208, (September 30, 1996), provides as follows:
Sec. 503(a) No part of any appropriation contained in this Act
shall be used, other than for normal and recognized executive-
legislative relationships, for publicity or propaganda purposes, for
the preparation, distribution, or use of any kit, pamphlet, booklet,
publication, radio, television, or video presentation designed to
support or defeat legislation pending before the Congress, * * * except
in presentation to the Congress or any State legislative body itself.
(b) No part of any appropriation contained in this Act shall be
used to pay the salary or expenses of any grant or contract recipient,
or agent acting for such recipient, related to any activity designed to
influence legislation or appropriations pending before the Congress or
any State legislature.
Background
Once expected to be eliminated as a public health problem,
infectious diseases remain the leading cause of death worldwide. In the
United States and elsewhere, infectious diseases increasingly threaten
public health and contribute significantly to the escalating costs of
health care.
In 1992, the Institute of Medicine of the National Academy of
Sciences published a report entitled Emerging Infections, Microbial
Threats to Health in the United States highlighting the threat of
emerging infections and making specific recommendations to address the
threat. This report emphasized a critical leadership role for CDC in a
national effort to detect and control infectious disease threats.
In partnership with other Federal agencies, State and local health
departments, academic institutions, and others, CDC has developed a
plan for revitalizing the nation's ability to identify, contain, and
prevent illness from emerging infectious diseases. The plan, Addressing
Emerging Infectious Disease Threats; A Prevention Strategy for the
United States, identifies objectives in four major areas: surveillance,
applied research, prevention and control, and infrastructure.
Under the objective for applied research, the plan proposes to
integrate laboratory science and epidemiology to optimize public health
practice in the United States. One component of these efforts is to
implement an extramural program for research in emerging infectious
disease surveillance, epidemiology, and prevention, which will fill the
gaps in existing support for such research. In FY 1996, CDC initiated
the Extramural Applied Research Program in Emerging Infections (EARP)
and made competitive grant and cooperative agreement awards to seven
institutions for projects in the areas of antimicrobial resistance and
tickborne diseases. In FY 1997, CDC will make additional competitive
grant and/or cooperative agreement awards in two areas: hepatitis C
virus infection and novel methods for identification of emerging
infections. This announcement specifically addresses novel methods for
identification of emerging infections and solicits applications in the
following six specific focus areas:
Focus Area #1: Evaluating Algorithms To Diagnose Emerging Causes of
Infectious Diarrhea
Without specific diagnostic algorithms, health professionals and
laboratories do not know when to test for many emerging diarrheal
disease pathogens. CDC will assist in the development of guidelines for
health professionals that recommend when to order specific diagnostic
tests for patients with diarrheal diseases, and for diagnostic
laboratories that recommend what diangostic tests to perform. Lack of
guidelines such as these severely limits the ability of laboratories to
adequately detect and report cases of infectious diarrhea caused by
emerging pathogens such as Cyclospora cayetanensis, Cryptosporidium
parvum, Escherichia coli 0157:H7, and common viral agents. Health
professionals may consider tests to identify diarrheal pathogens to be
too expensive and of low yield. Laboratories are reluctant to conduct
routine surveillance for many emerging pathogens, since to do so would
require expensive additional testing procedures. It might be cost-
effective, however, for health professionals and laboratories to test
for these and other pathogens under specific circumstances once
guidelines are available.
For example, during the waterborne outbreak of cryptosporidiosis in
Milwaukee in 1993, CDC scientists discovered that a simple 3-component
screening algorithm would increase the positive predictive value that a
stool specimen contained detectable C. parvum oocysts from 27 percent
to 63 percent. Another recent CDC study of the diagnosis of C. parvum
reported that laboratories in Connecticut that tested for C. parvum
only upon physician request reported a positivity rate of 2.8
[[Page 36535]]
percent compared with a rate of 5.2 percent for laboratories that used
multiple critiera. In a large multi-center study the rate of isolation
of E. coli 0157:H7 from patients with diarrhea increases from 0.4
percent among all patients to 7.8 percent among patients with visibly
bloody stools.
In addition to factors that are present for all health care
providers under capitated managed care where health care providers
receive a flat fee per patient seen, there are additional incentives to
reduce the number of disgnostic tests performed unless they can be
shown clearly as cost-beneficial. Current data are inadequate, however,
to calculate the cost or the benefit of performing specific diagnostic
tests or starting empiric treatment for specific clinical
presentations. As increasing proportions of the population receive
their health care under systems of capitated managed care, we are
likely to see more empiric treatment of diarrhea with no confirmatory
tests for the etiology of the illness.
Focus Area #2--Rapid Identification of Emerging and Unusual Pathogenic
Bacteria by Partial 16S rRNA Sequencing
Standard batteries of biochemical tests are no longer adequate to
identify a growing number of emerging and unusual bacterial pathogens.
Specialized procedures are necessary for identification of emerging and
unusual pathogenic strains that are difficult or impossible to identify
in the average clinical laboratory. 16S rRNA sequencing is one
specialized procedure that has the potential to allow for rapid
molecular identification of pathogens. Many species of bacteria could
be identified on the basis of their full 16S rRNA sequence. Sequences
of many unusual and emerging bacterial pathogens, as well as their
presumed non-pathogenic relatives, need to be determined and entered
into sequence databases. It should then be possible to rapidly identify
most pathogenic species on the basis of a unique partial sequence, and
to use this methodology to largely replace routine identification
methods.
Focus Area #3--Development and Evaluation of Improved Tests for Malaria
Diagnosis in the United States
Every year, approximately 1,000 cases of malaria are reported in
the United States (U.S.). Nineteen deaths due to malaria were recorded
in the U.S. during the period 1992-1994. Of particular concern, cases
of locally transmitted malaria have been reported practically on an
annual basis in densely populated areas (New York City, Houston, and
Palm Beach County, Florida). The substantial U.S. public health impact
of malaria is very likely to increase in the future due to increased
international travel combined with a worldwide resurgence of malaria.
This resurgence is attributable to factors such as inadequate control
programs, increasing drug and insecticide resistance, and global
warming.
This situation must be addressed by vigilant surveillance and
prompt clinical management of all cases of malaria occurring in the
U.S. Both strategies require a timely and correct diagnosis of the
disease. However, available information indicates that malaria
diagnosis is not optimally performed in the U.S. In a recent survey of
samples sent to CDC's National Malaria Reference Laboratory (NMRL) by
various health institutions (including State health departments,
hospitals, and commercial laboratories), the diagnosis made by the NMRL
differed from that made at the health institution in 21 percent of the
samples. This is due mainly to the fact that the international accepted
method for diagnosing malaria (the microscopic examination of a Giemsa-
stained blood smear) requires a degree of microscopy experience that
most clinical laboratorians in the U.S. lack due to their infrequent
contact with malaria samples.
One solution to this problem would be a diagnostic test that
depends, not on the experience and skills of a microscopist, but on
more objective, quantifiable criteria. Several malaria diagnostic tests
that follow this approach are currently on the market or in various
development phases. Such tests identify malaria parasites by nucleic
acid fluorescence or by detecting parasite-specific antigens or
enzymes. However, none of these tests satisfy all desirable criteria
for a malaria diagnostic tool applicable to clinical laboratory
practice in the U.S. Such criteria include: (a) sensitivity at least
equal to that of microscopy (4) parasites per ul. of blood), (b)
detection of all 4 known species of human malaria parasites, (c)
specificity above 95 percent, (d) simplicity of performance, and (e)
rapidity of execution (results available in less than 1 hour). In
addition, none of these tests have been adequately evaluated under
strictly controlled conditions in U.S. health facilities.
Focus Area #4--Development of Improved Diagnostic Tests for
Leishmaniasis
Leishmaniasis, a parasitic infection caused by several species of
protozoa in the genus Leishmania, can cause serious, sometimes fatal,
disease in humans. Leishmaniasis is considered by the World Health
Organization to be one of the top five parasitic infections afflicting
mankind today. The infection is transmitted through the bite of
infected sandflies and occurs in several forms: cutaneous, mucosal, and
visceral leishmaniasis. The mucosal form can result in disfiguring
destruction of the nose and mouth, while the visceral form, as
indicated by the name, localizes in the viscera and bone marrow and
results in severe and life-threatening infection. Leishmaniasis in its
various forms occurs throughout the tropical areas of Central and South
America, in countries around the Mediterranean Sea, and in the Middle
East, Africa, and portions of South East Asia. The disease is currently
viewed as being epidemic in India and Sudan. U.S. citizens traveling to
endemic areas, especially Central and South America, are exposed and
frequently acquire infection.
Currently available serologic assays for viscerotrophic
leishmaniasis have unacceptable sensitivity and specificity levels,
both for the species of Leishmania causing the infection as well as for
determining whether the person has an active infection or past
exposure. Diagnostic laboratories have not been able to adequately
resolve this issue because of poor assay performance. The U.S. Congress
and the Department of Defense have been concerned about the possibility
that leishmaniasis accounts for symptoms in some individuals with Gulf
War Syndrome, and the need for better diagnostic tests is repeatedly
raised in Congressional hearings. Since currently available tests have
unacceptable sensitivity and/or specificity levels or are highly
invasive with a significant false negative rate, there is a clear need
for improved diagnostic capabilities related to leishmaniasis,
especially the viscerotrophic form thought to occur in the Gulf War
Syndrome. The development of a suitably formatted assay to detect
Leishmania infections would allow diagnostic laboratories to be able to
distinguish current infections from past exposure and to begin to
differentiate the causative agents.
Suspected cases of cutaneous leishmaniasis are routinely diagnosed
through microscopic examination of stained histologic sections taken
from the lesion site. In some instances, the number of organisms is
high and the infection can be diagnosed microscopically with little
difficulty. However, in many instances there are few organisms and
microscopic
[[Page 36536]]
examination does not permit confirmation of infection. Immunohistologic
staining with appropriate monoclonal/polyclonal antibodies or molecular
based probes might provide much more sensitive approaches.
Focus Area #5--Identification of Unrecognized Etiologic Agents in
Idiopathic Sexually Transmitted Disease Syndromes
For a significant proportion of clinical cases of male unrethritis
and pelvic inflammatory disease (PID) in women, no demonstrated
etiology can be found. It is likely that other unidentified sexually
transmitted organisms have yet to be identified in these syndromes. In
the U.S., urethritis in men is a common sexually transmitted infection;
over 200,000 cases of gonorrhea were reported to CDC and over 250,000
cases of non-specific urethritis were seen by private physicians in
1995. Besides Neisseria gonorrhoeae, urethritis in men can be caused by
Chlamydia trachomatis, Trichomonas vaginalis, Herpes Simplex Virus
(HSV), Mycoplasma genitalium, and Ureaplasma species; however, no
etiologic agent can be identified in nearly 25 percent of cases. Among
women with PID, C. trachomatis, N. gonorrhoeae, and vaginal anaerobes
are recognized etiologic agents, yet in 25-50 percent of cases, no
causal organisms can be identified.
Potentially unidentified agents could emerge and become significant
public health problems as gonorrhea and chlamydial infections are
successfully controlled. There is suggestive evidence that this is
occurring. For example, in Seattle where gonorrhea and chlamydial
infections have been controlled, approximately 70 percent of the
urethritis in local men has no known etiology. It is likely that
similar agents are involved in PID. The identification of additional
agents for urethritis in men, which may also be associated with PID in
women, will help develop better prevention strategies for this costly
and serious complication. Available data strongly suggest that there
are unidentified sexually transmitted organisms associated with
idiopathic syndromes such as urethrities in men and PID.
Focus Area #6--Development of Nonculture Molecular Epidemiologic
Detection/Typing Methods for Treponema pallidum or Haemophilus ducreyi
Most genital ulcer disease (GUD) is caused by one or more of three
sexually transmitted agents; Haemophilus ducreyi, Treponema pallidum,
and HSV. GUD caused by the bacterial agents H. ducreyi and T. pallidum
accounts for approximately 17,000 cases each year in the U.S. Bacterial
GUD infections also occur frequently in developing countries and
several out-breaks of chancroid (H. ducreyi) in the U.S. have been
directly traced to importation of strains from overseas. Along with the
morbidity associated with primary infections with these organisms, a
serious potential sequelae is the development of syphilis, including
neuro- and congential syphilis.
Bacterial GUDs may be easily cured with antimicrobial agents if the
etiologic agents are accurately diagnosed (although antimicrobial
resistance is emerging in H. ducreyi). Examination of ulcers with
microbiologic and research polymerase chain reaction (PCR) detection
methods indicate that it is not possible to accurately determine the
etiology of infections by the physical appearance of the ulcers. The
diagnosis of these agents is further complicated by the fact that T.
pallidum cannot be cultured in vitro and H. ducreyi may be recovered
from fewer than 50 percent of specimens from infected patients.
Development of non-culture methods for detecting and typing strains of
T. pallidum and H. ducreyi in ulcer specimens would allow medical
practitioners to more quickly determine the etiology of and effectively
treat GUDs. It would also allow researchers to determine the molecular
epidemiology of these infections, identify strain type associated with
antimicrobial resistance, and devise and monitor targeted control
methods to eliminate GUD.
Purpose
The purpose of the Extramural Applied Research Program in Emerging
Infections (EARP) is to provide financial and technical assistance for
applied research projects on emerging infections in the U.S. As a
component of EARP, the purpose of this grant/cooperative agreement
announcement is to provide assistance for projects addressing novel
methods for identification of emerging infections. Specifically,
applications are solicited for projects addressing any of the following
six focus areas:
Focus Area #1
Evaluating Algorithms to Diagnose Emerging Causes of Infectious
Diarrhea. The objective is to determine the costs and effectiveness of
different diagnostic algorithms for emerging agents of infectious
diarrhea.
Focus Area #2
Rapid Identification of Emerging and Unusual Pathogenic Bacteria by
Partial 16S rRNA Sequencing. The objective is to develop a rapid
identification system using 16S rRNA sequencing for emerging, atypical,
and unclassified pathogenic bacteria.
Focus Area #3
Development and Evaluation of Improved Tests for Malaria Diagnosis
in the U.S. The objective is to develop and evaluate a malaria
diagnostic test that does not require microscopic examination of blood
smears and: (a) is at least as sensitive as microscopy (4 parasites per
ul. of blood), (b) can detect all 4 known species of human malaria
parasites, (c) has a specificity of at least 95 percent, (d) is simple
to perform, and (e) can provide results in less than 1 hour.
Focus Area #4
Development of Improved Diagnostic Tests for Leishmaniasis. The
objective is to develop improved diagnostic assays for viscerotrophic
and cutaneous forms of leishmaniasis that are formatted using modern
immunologic and molecular tools. The assays would be formatted in such
a way that they would be readily transferable to laboratories, provide
acceptable sensitivity and specificity for the detection and diagnosis
of Leishmania infections in humans, and when performed under
appropriate conditions, provide the degree of accuracy necessary so
that specific medical treatments can be safely initiated.
Focus Area #5
Identification of Unrecognized Etiologic Agents in Idiopathic
Sexually Transmitted Disease Syndromes.
Focus Area #6
Development of Non-culture Molecular Epidemiologic Detection/Typing
Methods for Treponema pallidum or Haemophilus ducreyi.
Applicants may submit separate applications for projects in one or
more focus areas. (See section on APPLICATION for detailed
instructions.)
Program Requirements
In conducting activities to achieve the purpose of this program,
the recipient will be responsible for the activities under A.
(Recipient Activities), and CDC will be responsible for conducting
activities under B. (CDC Activities):
[[Page 36537]]
A. Recipient Activities
Focus Area #1
1. Evaluate Algorithms to Diagnose Emerging Causes of Infectious
Diarrhea:
a. Identify a patient population where health professionals will be
encouraged to collect stool specimens on all patients presenting with
diarrhea.
b. Determine the etiology of infectious diarrhea in patients who
seek medical care for diarrhea by collecting and testing clinical
specimens for bacterial enteric pathogens such as Salmonella, Shigella,
Campylobacter, Escherichia coli 0157, Listeria monocytogenes, and
Yersinia, viral pathogens such as rotovirus, enteric adenovirus and
astrovirus, and parasitic pathogens such as Cyclospora cayetanesis and
Cryptosporidium parvum.
c. Collect information on patients for whom stool specimens are
ordered such as specific signs and symptoms reported by patients at
their first medical encounter, prior treatment, and epidemiologic
exposures such as a history of foreign travel.
d. Develop diagnostic algorithms using clinical characteristics
associated with identification of pathogens in stool specimens to
increase the positive predictive value of diagnostic tests.
e. Determine the cost-effectiveness of the diagnostic algorithms.
f. Publish and/or otherwise disseminate the study findings.
Focus Area #2
1. Perform Rapid Identification of Emerging and Unusual Pathogenic
Bacteria by Partial 16S rRNA Sequencing:
a. Identify appropriate known pathogenic and control bacterial
strains and design and conduct a blinded comparison study to determine
the utility of 16S rRNA sequencing for the rapid identification of
pathogenic bacterial strains.
(1) Fully sequence 16S rRNA of selected strains to update the
database of sequences.
(2) Retrospectively identify by partial 16S sequencing, strains
that have been previously biochemically identified.
(3) Prospectively identify by partial 16S rRNA sequencing all
strains received as unknowns in the CDC Special Bacteriology Reference
Laboratory (CDC will perform standard biochemical identification tests
and cell wall fatty acid analyses on the same strains.). Compare
accuracy, time, and cost of each method. Where there are disagreements,
identify strains by the gold standard of DNA relatedness.
(4) Conduct comparative sequencing studies on selected strains to
determine reproducibility, accuracy, and variability of sequencing and
of identification.
b. Publish and/or otherwise disseminate the study findings.
Focus Area #3
1. Develop and Evaluate Improved Tests for Malaria Diagnosis in the
United States:
a. Develop a new diagnostic test or improve currently available
test(s) that: (a) are at least as sensitive as microscopy (4 parasites
per ul. of blood), (b) able to detect all 4 known species of human
malaria parasites, (c) have a specificity of at least 95 percent, (d)
are simple to perform, and (e) can provide results in less than 1 hour.
Field-robustness and distinctive diagnostic reaction (e.g., color
change) are desirable characteristics.
b. Conduct a first phase of evaluation of the new or improved
test(s). This should involve testing clinical samples for malaria under
blinded conditions and using mainly samples collected from non-human
primates experimentally infected with human malaria parasites and
malaria-infected human blood samples, both of which can be made
available by CDC.
c. Conduct field evaluations of the test(s) in endemic countries
(e.g., a large-scale assessment in a short time period where n>=500)
and in U.S. facilities. The actual U.S. field testing will likely
require a longer time period due to low frequency of malaria, and
should involve collaboration with State health departments, hospitals,
and commercial laboratories.
d. Publish and/or otherwise disseminate results.
Focus Area # 4
1. Develop an Improved Diagnostic Test for Leishmaniasis:
a. Develop new or improved assay(s) for viscerotrophic or cutaneous
leishmaniasis that provide significantly better sensitivity and
specificity than currently available assays.
b. Evaluate the assay(s) (e.g., through blinded evaluation of
selected panels of sera). CDC can provide limited assistance in
preparing serum panels, parasite isolates, animal model support, and
outlets to the field.
c. Publish and/or otherwise disseminate results.
Focus Area # 5
1. Identify Unrecognized Etiologic Agents in Idiopathic Sexually-
Transmitted Disease Syndromes:
a. Obtain swab specimens from 18 to 39 year old sexually active men
with urethritis attending sexually transmitted disease clinics. In
those samples for which no etiology can be identified either by
traditional laboratory methods (e.g., culture) or specific DNA
amplification methods (polymerase chain reaction or ligase chain
reaction for N. gonorrhoeae, C. trachomatis and M. genitalium), use
molecular biological tools to identify causative infectious agents. One
example of an appropriate approach would be: Extract DNA, amplify 16S
rRNA-specific DNA by polymerase chain reaction (PCR) using several sets
of universal bacterial primers, and sequence the amplified DNA directly
with an automated sequencer. Clone the amplified material into
Escherichia coli, and sequence the inserts using automated sequencing.
Use the sequences to search existing Genbank files for relatedness with
known organisms. This approach has been used successfully to identify
the agents of cat scratch fever, bacillary angiomatosis, Whipple's
disease, and the putative agent of Kaposi's sarcoma. Although this
approach will identify only new bacterial etiologies, the favorable
response of idiopathic urethritis and PID to antibiotic therapy
suggests bacterial causation.
b. Publish and/or otherwise disseminate results.
Focus Area #6
1. Develop Non-culture Molecular Epidemiologic Detection/Typing
Methods for Treponema pallidum or Haemophilus ducreyi:
a. Develop comprehensive methods for detecting and typing strains
of T. pallidum and/or H. ducreyi in ulcer specimens with the vitro
materials. In the case of T. pallidum, the method(s) developed should
be able to differentiate between the T. pallidum subspecies pallidum,
pertenue, and endemicum.
b. Determine if the methods developed can be used to detect/type
strains in ulcer specimens.
c. In the event that previously untyped strains are identified in
the evaluation phase, expand the typing system to include new types.
d. Publish and/or otherwise disseminate results.
B. CDC Activities
1. Research Project Grants (Focus areas 1, 4, 5, and 6 only)
A research project grant is one in which substantial programmatic
involvement by CDC is not anticipated by the recipient during the
project period. Applicants for grants must demonstrate the ability to
conduct the proposed research with minimal
[[Page 36538]]
assistance, other than financial support, from CDC. This includes
possessing sufficient resources for clinical, laboratory, and data
management services and level of scientific expertise to achieve the
objectives described in their research proposal without substantial
technical assistance from CDC.
2. Cooperative Agreements
In a cooperative agreement, CDC is available to assist recipients
in conducting the proposed research. The application should be
presented in a manner that demonstrates the applicant's ability to
address the research problem in a collaborative manner with CDC. In
addition to the financial support provided, CDC may collaborate by: (a)
providing technical assistance in the design and conduct of the
research, (b) performing selected laboratory tests as appropriate and
necessary, (c) participating in data management, the analysis of
research data, and the interpretation and presentation of research
findings, and (d) providing biological materials (e.g., strains,
reagents, etc.) as necessary for studies.
Technical Reporting Requirements
An original and two copies of a narrative progress reports are
required semiannually. The first semiannual report is required with
each year's non-competing continuation application and should cover
program activities from date of the previous report (or date of award
for reporting in the first year of the project).
An original and two copies of the second semiannual progress and
Financial Status Report (FSR) are due 90 days after the end of each
budget period and should cover activities from the date of previous
report. Progress reports should address the status of specific project
objectives and should include copies of any publications resulting from
the project.
The final performance report and FSR are required no later than 90
days after the end of the project period. All reports should be
directed to the CDC Grants Management Officer at the address referenced
in the following section.
Application Process
Notification of Intent To Apply
In order to assist CDC in planning and executing the evaluation of
applications submitted under this Program Announcement, all parties
intending to submit application(s) are requested to inform CDC of their
intention to do so as soon as possible but not later than 10 business
days prior to the application due date. Notification should include:
(1) name and address of institution; (2) name, address, and phone
number of contact person, and (3) which focus area(s) application(s)
will be submitted for.
Notification can be provided by facsimile, postal mail, or
electronic mail (E-mail) to Sharron Orum, Grants Management Officer,
Grants Management Branch, Procurement and Grants Office, Centers for
Disease Control and Prevention (CDC), 255 East Paces Ferry Road, NE.,
Room 300, Mailstop E-18, Atlanta, Georgia 30305, facsimile: (404) 842-
6513, Internet: SP02@cdc.gov.
Application
Applicants may apply for assistance for projects in one or more of
the six separate focus areas identified under PURPOSE and PROGRAM
REQUIREMENTS section above. IF APPLICANT IS APPLYING FOR ASSISTANCE FOR
MORE THAN ONE FOCUS AREA, A SEPARATE AND COMPLETE APPLICATION MUST BE
SUBMITTED FOR EACH FOCUS AREA.
All applicants must develop their application(s) in accordance with
PHS Form 398, information contained in this grant/cooperative agreement
announcement, and the instructions outlined below. In order to ensure
an objective, impartial, and prompt review, applications must conform
to the following instructions:
General Instructions
Due to the need to reproduce copies of the applications for the
reviewers, ALL pages of each application MUST be in the following
format:
1. The original and two (2) copies of the application must be
UNSTAPLED and UNBOUND.
2. All pages must be clearly numbered, and a complete index to the
application and its appendices must be included.
3. All materials must be typewritten, single-spaced, using a font
no smaller than size 12, and on 8\1/2\'' by 11'' white paper.
4. Any reprints, brochures, or other enclosures must be copied onto
8\1/2\'' by 11'' white paper by the applicant. NO BOUND MATERIALS WILL
BE ACCEPTED in the narrative or appendices.
5. All pages must be printed on ONE side only, with at least 1''
margins, headers, and footers.
Special Instructions
The application narrative for each application/focus area must not
exceed 10 pages (excluding budget and appendices). Unless indicated
otherwise, all information requested below must appear in the
narrative. Materials or information that should be part of the
narrative will not be accepted if placed in the appendices. The
application narrative must contain the following sections in the order
presented below. (REMINDER: If proposing projects under multiple focus
areas, submit a separate and complete application for each project):
1. Abstract:
Provide a brief (two pages maximum) abstract of the project.
Clearly identify the specific focus area being addressed and the
project period proposed (not to exceed maximum as indicated in
AVAILABILITY OF FUNDS section). Clearly identify the types of award
that is being applied for--grant or cooperative agreement.
2. Background and Need:
Discuss the background and need for the proposed project.
Demonstrate a clear understanding of the purpose and objectives of the
focus area.
3. Capacity and Personnel:
Describe applicant's past experience in conducting activities
similar to that being proposed. Describe applicant's resources,
facilities, and professional personnel that will be involved in
conducting the project. Include, in an appendix, curriculum vitae for
all professional personnel involved with the project. Describe plans
for administration of the project and identify administrative
resources/personnel that will be assigned to the project. Provide, in
an appendix, letters of support from all key participating non-
applicant organizations, individuals, etc. (if any), which clearly
indicate their commitment to participate as described in the
operational plan. Do not include letters of support from CDC personnel.
Letters of support from CDC will not be accepted. Award of a grant or
cooperative agreement implies CDC participation as outlined in the
PROGRAM REQUIREMENTS section of this announcement.
4. Objectives and Technical Approach:
Present specific objectives for the proposed project which are
measurable and time-phased and are consistent with the PURPOSE and
RECIPIENT ACTIVITIES sections for the specific focus area. Present a
detailed operational plan for initiating and conducting the project
which clearly and appropriately addresses these objectives (if
proposing a multi-year project, provide a detailed description of
first-year activities and a brief overview of subsequent-year
activities).
[[Page 36539]]
Clearly identify specific assigned responsibilities for all key
professional personnel. Include a clear description of applicant's
technical approach/methods which are directly relevant to the above
objectives. Describe specific study protocols or plans for the
development of study protocols. Describe the nature and extent of
collaboration with CDC (if proposing a cooperative agreement) and/or
others during various phases of the project. Describe in detail a plan
for evaluating progress toward achieving process and outcome project
objectives.
5. Budget:
Provide a line-item budget and accompanying detailed, line-by-line
justification that demonstrates the request is consistent with the
purpose and objectives of this program. If requesting funds for any
contracts, provide the following information for each proposed
contract: (1) Name of proposed contractor, (2) breakdown and
justification for estimated costs, (3) description and scope of
activities to be performed by contractor, (4) period of performance,
and (5) method of contractor selection (e.g., sole-source or
competitive solicitation). (See sample budget included in application
package.)
Note: If indirect costs are requested from CDC on a new or
continuation application, a copy of the organization's current
negotiated Federal indirect cost rate agreement or cost allocation
plan must be provided.
6. Human Subjects:
Whether or not exempt from DHHS regulations, if the proposed
project involves human subjects, describe adequate procedures for the
protection of human subjects. Also, ensure that women, racial and
ethnic minority populations are appropriately represented in
applications for research involving human subjects.
Evaluation Criteria
The applications will be reviewed and evaluated according to the
following criteria:
1. Background and Need (10 points)
Extent to which applicant demonstrates a clear understanding of the
background, purpose, and objectives of the focus area being addressed.
2. Capacity (45 points)
Extent to which applicant describes adequate resources and
facilities (both technical and administrative) for conducting the
project. Extent to which applicant documents that professional
personnel involved in the project are qualified and have past
experience and achievements in research related to that proposed as
evidenced by curriculum vitae, publications, etc. If applicable, extent
to which applicant includes letters of support from non-applicant
organizations, individuals, etc., and the extent to which such letters
clearly indicate the author's commitment to participate as described in
the operational plan.
3. Objectives and Technical Approach (45 points total)
a. Extent to which applicant describes objectives of the proposed
project which are consistent with the purpose of the focus area being
addressed and which are measurable and time-phased. (10 points)
b. Extent to which applicant presents a detailed operational plan
for initiating and conducting the project which clearly and
appropriately addresses all Recipient Activities for the specific
programmatic focus area being addressed. Extent to which applicant
clearly identifies specific assigned responsibilities of all key
professional personnel. Extent to which the plan clearly describes
applicant's technical approach/methods for conducting the proposed
studies and extent to which the approach/methods are appropriate and
adequate to accomplish the objectives. Extent to which applicant
describes specific study protocols or plans for the development of
study protocols that are appropriate for achieving project objectives.
Extent to which applicant meets CDC requirements regarding the
inclusion of women, racial and ethnic minority populations are
appropriately represented in applications involving human research.
Extent to which applicant describes adequate and appropriate
collaboration with CDC (if proposing a cooperative agreement) and/or
others during various phases of the project. (30 points)
c. Extent to which applicant provides a detailed and adequate plan
for evaluating progress toward achieving project process and outcome
objectives. If the proposed project involves notifiable conditions, the
degree to which applicant describes an adequate process for providing
necessary information to appropriate State and/or local health
departments. (5 points)
4. Budget (not scored)
Extent to which the proposed budget is reasonable, clearly
justifiable, and consistent with the intended use of grant/cooperative
agreement funds.
5. Human Subjects (not scored)
If the proposed project involves human subjects, whether or not
exempt from the Department of Health and Human Services (DHHS)
regulations, the extent to which adequate procedures are described for
the protection of human subjects. Note: Objective Review Group (ORG)
recommendations on the adequacy of protections include: (1) protections
appear adequate and there are no comments to make or concerns to raise,
(2) protections appear adequate, but there are comments regarding the
protocol, (3) protections appear inadequate and the ORG has concerns
related to human subjects, or (4) disapproval of the application is
recommended because the research risks are sufficiently serious and
protection against the risks are inadequate as to make the entire
application unacceptable.
Executive Order 12372 Review
This program is not subject to Executive Order 12372 Review.
Public Health System Reporting Requirements
This program is not subject to the Public Health System Reporting
Requirements.
Catalog of Federal Domestic Assistance Number
The Catalog of Federal Domestic Assistance Number is 93.283.
Other Requirements
Paperwork Reduction Act
Projects that involve the collection of information from ten or
more individuals and funded by the grant/cooperative agreement will be
subject to review and by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act.
Human Subjects
If the proposed project involves research on human subjects, the
applicant must comply with the Department of Health and Human Services
Regulations (45 CFR Part 46) regarding the protection of human
subjects. Assurance must be provided to demonstrate that the project
will be subject to initial and continuing review by an appropriate
institutional review committee. The applicant will be responsible for
providing evidence of this assurance in accordance with the appropriate
guidelines and form provided in the application kit.
In addition to other applicable committees, Indian Health Service
(IHS) institutional review committees also must review the project if
any component of IHS will be involved or will support the research. If
American Indian community is involved, its tribal
[[Page 36540]]
government must also approve that portion of the project applicable to
it.
Women, Racial and Ethnic Minorities
It is the policy of the Centers for Disease Control and Prevention
(CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR)
to ensure that individuals of both sexes and the various racial and
ethnic groups will be included in CDC/ATSDR-supported research projects
involving human subjects, whenever feasible and appropriate. Racial and
ethnic groups are those defined in OMB Directive No. 15 and include
American Indian, Alaskan Native, Asian, Pacific Islander, Black and
Hispanic. Applicants shall ensure that women, racial and ethnic
minority populations are appropriately represented in applications for
research involving human subjects. Where clear and compelling rationale
exist that inclusion is inappropriate or not feasible, this situation
must be explained as part of the application. This policy does not
apply to research studies when the investigator cannot control the
race, ethnicity and/or sex of subjects. Further guidance to this policy
is contained in the Federal Register, Vol. 60, No. 179, pages 47947-
47951, dated Friday, September 15, 1995.
Animal Subjects
If the proposed project involves research on animal subjects, the
applicant must comply with the ``PHS Policy on Humane Care and Use of
Laboratory Animals by Awardee Institutions.'' An applicant organization
proposing to use vertebrate animals in supported activities must file
an Animal Welfare Assurance with the Office for Protection from
Research Risks at the National Institutes of Health.
Application Submission and Deadline
The original and five copies of each application PHS Form 398 must
be submitted to Sharron Orum, Grants Management Officer, Grants
Management Branch, Procurement and Grants Office, Centers for Disease
Control and Prevention (CDC), 255 East Paces Ferry Road, NE., Room 300,
Mailstop E-18, Atlanta, Georgia 30305, on or before August 8, 1997.
1. Deadline: Applications shall be considered as meeting the
deadline if they are either:
(a) Received on or before the deadline date; or
(b) Sent on or before the deadline date and received in time for
submission to the objective review group. (Applicants must request a
legibly dated U.S. Postal Service postmark or obtain a legibly dated
receipt from a commercial carrier or U.S. Postal Service. Private
metered postmarks shall not be acceptable as proof of timely mailing.)
2. Late Applications: Applications which do not meet the criteria
in 1(a) or 1(b) above are considered late applications. Late
applications will not be considered and will be returned to the
applicant.
Where To Obtain Additional Information
To receive additional written information call (404) 332-4561. You
will be asked to leave your name, address, and telephone number and
will need to refer to Announcement 778. You will receive a complete
program description, information on application procedures, and
application forms.
If you have questions after reviewing the contents of all the
documents, business management technical assistance may be obtained
from Oppie M. Byrd, Grants Management Specialist, Grants Management
Branch, Procurement and Grants Office, Centers for Disease Control and
Prevention (CDC), 255 East Paces Ferry Road, NE., Room 314, Mailstop E-
18, Atlanta, Georgia 30305, telephone (404) 842-6546, facsimile (404)
842-6513, E-mail oxb3@cdc.gov.
Programmatic technical assistance may be obtained from the
following individuals:
Focus Area #1
Evaluating Algorithms to Diagnose Emerging Causes of Infectious
Diarrhea: Robert V. Tauxe, M.D., M.P.H., or David L. Swerdlow, M.D.,
National Center for Infectious Diseases, Division of Bacterial and
Mycotic Diseases, Centers for Disease Control and Prevention (CDC),
1600 Clifton Road, NE., Mailstop A-38, Atlanta, Georgia 30333, (for Dr.
Tauxe) telephone (404) 639-2206, E-mail address rvt1@cdc.gov, (for Dr.
Swerdlow) telephone (404) 639-3234, E-mail address dls3@cdc.gov.
Focus Area #2
Rapid Identification of Emerging and Unusual Pathogenic Bacteria by
Partial 16S rRNA Sequencing: Don J. Brenner, Ph.D, National Center for
Infectious Diseases, Division of Bacterial and Mycotic Diseases,
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road,
NE., Mailstop D-11, Atlanta, Georgia 30333, telephone (404) 639-2841,
E-mail address djb3@cdc.gov.
Focus Area #3
Development and Evaluation of Improved Tests for Malaria Diagnosis
in the United States: Phuc P. Nguyen-Dinh, M.D., National Center for
Infectious Diseases, Division of Parasitic Diseases, Centers for
Disease Control and Prevention (CDC), 1600 Clifton Road, NE., Mailstop
F-13, Atlanta, Georgia 30333, telephone (770) 488-4435, E-mail address
ppn1@cdc.gov.
Focus Area #4
Development of Diagnostic Tests for Leishmaniasis: Mark L.
Eberhard, Ph.D., or Marianna Wilson, M.S., National Center for
Infectious Diseases, Division of Parasitic Diseases, Centers for
Disease Control and Prevention (CDC), 1600 Clifton Road, NE., Mailstop
F-13, Atlanta, Georgia 30333, (for Dr. Eberhard) telephone (770) 488-
4419, E-mail address mle1@cdc.gov, (for Ms. Wilson) telephone (770)
488-4431, E-mail address myw1@cdc.gov.
Focus Area #5
Identification of Unrecognized Etiologic Agents in Idiopathic
Sexually Transmitted Disease Syndromes: Consuelo Beck-Sague, M.D., or
Cheng-Yen Chen, Ph.D., National Center for Infectious Diseases,
Division of AIDS/HIV, STD, and TB Laboratory Research, Centers for
Disease Control and Prevention (CDC), 1600 Clifton Road, NE., Mailstop
C-12 (Dr. Beck-Sague) or G-39 (Dr. Chen), Atlanta, Georgia 30333, (for
Dr. Beck-Sague) telephone (404) 639-3467, E-mail cmb1@cdc.gov, (for Dr.
Chen) telephone (404) 639-1535, E-mail address cyc1@cdc.gov.
Focus Area #6
Development of Non-culture Molecular Epidemiologic Detection/Typing
Methods for Treponema pallidum or Haemophilus ducreyi: Victoria Pope,
Ph.D., or David L. Trees, Ph.D., National Center for Infectious
Diseases, Division of AIDS/HIV, STD, and TB Laboratory Research,
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road,
NE., Mailstop D-13, Atlanta, Georgia 30333, (for Dr. Pope) telephone
(404) 639-3224, E-mail address vxp1@cdc.gov, (for Dr. Trees) telephone
(404) 639-2134, E-mail address dlt1@cdc.gov.
Please refer to Announcement Number 778 when requesting information
regarding this program.
You may also obtain this announcement from one of two Internet
sites on the actual publication date: CDC's homepage at http://
www.cdc.gov or at the Government Printing Office homepage (including
free on-line access to the Federal Register at http://
www.access.gpo.gov).
Potential applicants may obtain a copy of Healthy People 2000 (Full
Report, Stock No. 017-001-00474-0) or Healthy People 2000 (Summary
Report,
[[Page 36541]]
Stock No. 017-001-00473-1) referenced in the INTRODUCTION through the
Superintendent of Documents, Government Printing Office, Washington,
D.C. 20402-9325, telephone (202) 512-1800.
Dated: July 1, 1997.
Joseph R. Carter,
Acting Associate Director for Management and Operations Centers for
Disease Control and Prevention (CDC).
[FR Doc. 97-17703 Filed 7-7-97; 8:45 am]
BILLING CODE 4163-18-M
