Applied Research Program in Emerging Infections Correlation of Environmental Monitoring of Microbial Agents With Disease Control; Notice of Availability of Funds for Fiscal Year 1999

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Announcement Number 99005]

Applied Research Program in Emerging Infections Correlation of

Environmental Monitoring of Microbial Agents With Disease Control;

Notice of Availability of Funds for Fiscal Year 1999

Introduction

The Centers for Disease Control and Prevention (CDC) announces the

availability of fiscal year (FY) 1999 funds for competitive grants and/

or cooperative agreements to support applied research on emerging

infections. This announcement specifically addresses the correlation of

environmental monitoring of microbial agents with disease control.

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(a) and 317(k)(2) of

the Public Health Service Act, as amended [42 U.S.C. 241(a) and

247b(k)(2)].

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 nonprofit

organizations and governments and their agencies. Thus, universities,

colleges, research institutions, hospitals, other public and private

nonprofit organizations, including State and local governments or their

bona fide agents 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.

Only one application will be accepted from any single applicant,

organization, government, or agency.

Availability of Funds

Approximately $500,000 is available in FY 1999 to fund one to three

awards, ranging from $100,000 to $500,000. It is expected the award(s)

will begin on or about March 1, 1999, and will be made for a 12-month

budget period within a project period of up to three years. (The

funding amounts listed above are for the first 12-month budget period

and include both direct and indirect costs.) Funding estimates may vary

and are subject to change.

Continuation awards within an approved project period will be made

on the basis of satisfactory progress and availability of funds.

[[Page 36916]]

Determination of Which Instrument to Use

Applicants must specify the type of award for which they are

applying, either grant or cooperative agreement. CDC will review the

applications in accordance with the evaluation criteria. 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.

To assist applicants in making a determination as to which type of

award to apply for, the following information is provided:

1. Grants

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 an ability to

conduct the proposed research with minimal assistance, other than

financial support, from CDC. This would include possessing sufficient

resources for clinical, laboratory, and data management services and a

level of scientific expertise to achieve the objectives described in

their research proposal without substantial technical assistance from

CDC.

2. Cooperative Agreements

A research project cooperative agreement is one in which CDC will

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.

Use of Funds

Restrictions on Lobbying

Applicants should be aware of restrictions on the use of 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 1998 ``Department of Labor, Health and Human

Services, and Education, and Related Agencies Appropriations Act''

(Public Law 105-78) states in Section 503 (a) and (b) that no part of

any appropriation contained in this Act shall be used, other than for

normal and recognized executive-legislative relations, 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 or any State legislature, except in presentation to the

Congress or any State legislature itself. 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 (U.S.) 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, includes applied research as a major objective,

stressing the importance of integrating laboratory science and

epidemiology to optimize public health practice in the U.S. CDC has

developed an Extramural Applied Research Program in Emerging Infections

(EARP) designed to fill gaps in existing support for research in

emerging infectious disease surveillance, epidemiology, and prevention.

This announcement specifically addresses the correlation of

environmental monitoring of microbial agents with disease control.

The microorganisms present in the environment have played a role in

the transmission of infectious diseases. Legionella, Cryptosporidia,

Cyclospora, Aspergillus, and vancomycin-resistant enterococci are just

a few examples of agents with public health significance. There are

very few situations where the results of environmental monitoring have

been correlated with disease control. A good example of a situation

where correlation has been done is the microbial quality of water and

dialysate in hemodialysis units. Here it has long been established that

once bacteria (and in some instances endotoxin) go above certain

concentrations (2,000 CFU/ml in dialysate, 200 CFU/ml in water, or 5

EU/ml in water used to reprocess hemodialyzers) the risk of patients

developing bacteremia or a ``pyrogenic'' reaction during dialysis

increases substantially. However, the correlation of environmental

monitoring of microbial agents with disease control in other situations

is unclear.

Legionnaires' disease (LD) occurs when an aerosol of water

containing Legionella spp. is inhaled. There are 8,000-18,000 cases of

LD that occur each year in the U.S., and 23 percent of case-patients

reported to the CDC appear to have acquired the infection in a health-

care facility. Recent investigations have demonstrated that nosocomial

transmission from colonized hot water systems can occur for years or

even decades unless the illness is recognized and the organism is

eradicated. Case-fatality rates among patients with nosocomial LD may

reach > 30 percent, particularly in immunocompromised individuals. In

1997, a survey of 253 National Nosocomial Infections Surveillance

System (NNIS) hospitals indicated that 31 percent have identified cases

of nosocomial LD since 1990 and in 41 percent of hospitals legionellae

were recovered from the potable water systems. However, many hospitals

with cases had done little to reduce colonization and prevent further

transmission. Current CDC guidelines only state that an environmental

investigation and intervention should be done after nosocomial cases

are identified.

Vancomycin-resistant enterococci (VRE) were first reported in 1989

and have increased rapidly in incidence and prevalence in the interim.

At 189 hospitals reporting to the NNIS system, the percentage of

enterococcal isolates from all body sites that were resistant to

vancomycin increased from 0.3 percent in 1989 to 10.5 percent in 1995.

[[Page 36917]]

Numerous hospital VRE outbreaks have been reported and contamination of

environmental surfaces (e.g., bed rails, countertops) with VRE has been

documented. Since VRE may survive routine cleaning and disinfection

procedures, contamination of environmental surfaces may contribute to

nosocomial transmission of VRE. There is a need to document the extent

of environmental contamination with this organism, the extent to which

such contamination contributes to nosocomial transmission, and the

cleaning/disinfection procedures necessary to remove VRE.

Invasive aspergillosis is a threat to patients with compromised

macrophage or neutrophil function (i.e., patients with neutropenia,

receiving high-dose corticosteroid therapy) or with underlying chronic

lung disease. Aspergillus spp., are ubiquitous and are routinely

isolated from tap water, soil, decaying vegetation, wet paint, food,

dust, and even sanitizing agents used in hospitals. Several outbreaks

of aspergillosis have occurred during periods of construction in and

around hospitals. Current recommendations are directed at controlling

the production of aerosols during these periods. Additionally, there is

evidence that higher aspergillosis spore counts contribute to higher

rates of invasive disease among immunocompromised patients. However,

there is not consensus about whether there should be a benchmark spore

count or on the best methods to purify air.

Outbreaks of child-care-associated illness may be caused by many

different agents and involve several different modes of transmission.

The environment can play an important role in these outbreaks. Most

environmental studies in child care settings have focused on enteric

diseases. Toys and surfaces become contaminated either directly or

indirectly by feces and body secretions from ill children. The

incidence of diarrhea has been associated with isolation of fecal

coliforms from hands of children and staff and from various

environmental surfaces in child-care centers. Levels of environmental

fecal coliforms have also been linked with diaper type and the use of

over clothing in classes of non-toilet-trained children in child-care

centers. Cytomegalovirus has also been isolated from hands and toys in

a classroom with a high prevalence of infected children. Although

respiratory infections account for the majority of illness episodes

among children in child-care facilities, relatively little work has

been done on the environmental aspects of these infections.

The relationship between results of environmental monitoring of

microbial agents and the risk of infection from these agents in the

environment remains largely undefined. In addressing this issue, it is

necessary to consider the following requirements for environmental

transmission of disease to take place: (1) presence of a microbial

agent in the environment, (2) the organism must have sufficient

virulence, (3) relatively high numbers of organisms, (4) mechanism of

transmission from the environment to the host, (5) a successful portal

of entry, and (6) a susceptible host.

Purpose

The purpose of the 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 one or more

projects addressing the correlation of environmental monitoring of

microbial agents with disease control. Environmental monitoring may

play an important role in infectious disease control. However,

additional studies are needed to correlate results of environmental

monitoring with human disease. Examples of areas needing attention

include, but are not limited to, Legionella and Cryptosporidia in

water, Aspergillus spores in air, vancomycin-resistant enterococci and

other agents in hospital and child-care environments. Where

appropriate, projects proposed may include interventions to evaluate

detection methods.

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) under cooperative agreements:

A. Recipient Activities

1. Identify a microbial agent of increasing public health

importance that has a known environmental reservoir (air, water, etc).

2. Conduct surveillance for human infections in a particular

setting, e.g., child-care facilities, health-care facilities

(hospitals, clinics, long-term care facilities), etc.

3. Define the relationship between finding the target organism in

the environment and the risk of human disease in the target setting.

4. If feasible, determine the cost effectiveness of different

options for microbial detection and disease control; determine

interventions where appropriate.

5. Publish and/or otherwise disseminate study findings.

B. CDC Activities (Cooperative Agreements)

1. Provide technical assistance in the design and conduct of the

research.

2. Perform selected laboratory tests, as appropriate and necessary.

3. Participate in data management, the analysis of research data,

and the interpretation and presentation of research findings.

4. Provide biological materials (e.g., strains, reagents, etc.) as

necessary for studies.

Technical Reporting Requirements

Narrative progress reports are required semiannually. The first

semiannual report is required with the first noncompeting continuation

application and should cover program activities from date of award. The

second semiannual report is due 90 days after the end of each budget

period and should cover activities from the date of previous report.

Progress reports should summarize tasks completed, problems

encountered, and plans for continued research activities. Reports

should also include copies of any publications resulting from the

project.

An original and two copies of a Financial Status Report (FSR) are

required not later than 90 days after the end of each budget period.

A final performance report and FSR are due not later than 90 days

after the end of the project period. All reports are to be submitted to

the Grants Management Branch, CDC.

Application

1. Pre-application Letter-of-Intent

In order to enable CDC to plan the review 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 30 business days prior to the

application due date. Notification should include: (1) this program

announcement number (99005), (2) name and address of institution, and

(3) name, address, and phone number of contact person. Notification can

be provided by Facsimile, postal mail, or electronic mail (E-mail) to:

Matthew Arduino, Dr. P.H., National Center for Infectious Diseases,

Centers for Disease Control and Prevention (CDC) 1600

[[Page 36918]]

Clifton Road, NE., Mailstop C-1, Atlanta, GA 30333, Facsimile (404)

639-3822, E-mail [email protected].

2. Application Content

Applicants are strongly encouraged to develop applications in

accordance with PHS Form 398 information contained in this grant/

cooperative agreement announcement, and the instructions outlined

below.

The original and five (5) complete copies of the application must

be UNSTAPLED and UNBOUND. ALL pages must be clearly numbered, and a

complete index to the application and its appendices must be included.

All typewritten materials must be single-spaced, using a font no

smaller than size 12. All supplemental pages of the application (i.e.,

in addition to the 398 forms) must be on the 8\1/2\'' by 11'' white

paper. All pages must be printed on ONE side only, with at least 1''

margins, headers, and footers.

The application narrative must not exceed 12 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:

a. Abstract

Provide a brief (two pages maximum) abstract of the project.

Clearly identify the project period proposed (not to exceed maximum of

3 years as indicated in Availability of Funds Section). Clearly

identify the type of award that is being applied for, grant or

cooperative agreement.

b. Background and Need

Discuss the background and need for the proposed project.

Demonstrate a clear understanding of the purpose and objectives of this

program announcement. Discuss and demonstrate how the proposed project

addresses an important gap which is of public health importance.

c. 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. Clearly identify specific assigned

responsibilities for all key professional personnel. 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--they will not be accepted.)

d. Objectives and Technical Approach

Present specific objectives for the proposed project which are

measurable and time-phased and are consistent with the Purpose and

Program Requirements (Recipient Activities) sections of this

announcement. 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). 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. If the project will employ a particular research subject

population, describe characteristics of the patient population and how

research in this subject group will yield generalizable information.

Describe contingency plans which acknowledge how the project will

address likely obstacles and assure that the proposed task(s) can still

be completed. Include sample size calculations where appropriate to

assure that measurable objectives can be evaluated.

e. Budget

Provide a line-item budget and accompanying detailed, line-by-line

justification for the first year of the project that demonstrates the

request is consistent with the purpose and objectives of this program.

If requesting a multi-year project, provide estimated total budget

(direct plus indirect) for subsequent years. 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).

f. Human Subjects

Whether or not exempt from DHHS regulations, if the proposed

project involves human subjects, describe in an appendix 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

Applications will be reviewed and evaluated according to the

following criteria:

1. Background and Need (15 Points)

Extent to which applicant demonstrates a clear understanding of the

background, purpose, and objectives of the project and the extent to

which the proposed project addresses an area of public health

importance not adequately addressed in ongoing programs.

2. Capacity (30 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. Extent to which

applicant clearly identifies specific assigned responsibilities of all

key professional personnel. 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 (55 Points Total)

a. Extent to which applicant describes objectives of the proposed

project which are consistent with the purpose of this announcement and

which are measurable and time-phased. (15 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. 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

[[Page 36919]]

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 describes adequate and appropriate collaboration with CDC (if

proposing a cooperative agreement) and/or others during various phases

of the project. If the proposed project involves human subjects,

whether or not exempt from the HHS regulations, the extent to which

adequate procedures are described for the protection of human subjects,

and the extent that women, racial and ethnic minority populations are

appropriately represented in applications involving human research. (35

points)

c. Extent to which applicant provides a detailed and adequate plan

for evaluating progress toward achieving project process and outcome

objectives. (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.

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 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

the Native American community is involved, its tribal government must

also approve that portion of the project applicable to it.

Women, Racial and Ethnic Minorities

It is the policy of the 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 or Alaska Native, Asian,

Black or African American, Hispanic or Latino, Native Hawaiian or Other

Pacific Islander. 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, and 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 PHS-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 complete copies of each application PHS Form

398 must be submitted to Sharron P. 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, GA 30305, on or before October 1,

1998.

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 and to request an

application kit, call 1-888-GRANTS (1-888 472-6874). You will be asked

to leave your name and address and will be instructed to identify the

announcement number of interest. (Please refer to Announcement Number

99005.) 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, GA 30305, telephone (404) 842-6546, Facsimile (404) 842-

6513, Internet [email protected].

Programmatic technical assistance may be obtained from Matthew J.

Arduino, M.S., Dr.P.H., National Center for Infectious Diseases,

Hospital Infections Program, Centers for Disease Control and Prevention

(CDC), 1600 Clifton Road, NE., Mailstop C-01, Atlanta, GA 30333,

telephone (404) 639-2318, Internet [email protected].

You may 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).

[[Page 36920]]

Potential applicants may obtain a copy of Healthy People 2000 (Full

Report, Stock No. 017-001-00474-0) or Healthy People 2000 (Summary

Report, 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, 1998.

Joseph R. Carter,

Acting Associate Director for Management and Operations, Centers for

Disease Control and Prevention (CDC).

[FR Doc. 98-18017 Filed 7-7-98; 8:45 am]

BILLING CODE 4163-18-P