[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]


-----------------------------------------------------------------------

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: SP[email protected].

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 [email protected].
    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 [email protected], (for Dr. 
Swerdlow) telephone (404) 639-3234, E-mail address [email protected].

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 [email protected].

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 
[email protected].

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 [email protected], (for Ms. Wilson) telephone (770) 
488-4431, E-mail address [email protected].

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 [email protected], (for Dr. 
Chen) telephone (404) 639-1535, E-mail address [email protected].

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 [email protected], (for Dr. Trees) telephone 
(404) 639-2134, E-mail address [email protected].
    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