Year-Long Estimation of the Frequency of Bacterial Contamination of Blood Products in the United States

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Announcement Number 733]

Year-Long Estimation of the Frequency of Bacterial Contamination

of Blood Products in the United States

Introduction

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

availability of funds in fiscal year (FY) 1997 for a cooperative

agreement program to conduct a year-long study to estimate the

frequency of bacterial contamination of blood and blood products in the

United States (U.S.).

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 areas of Immunization and

Infectious Diseases and HIV Infection. (For ordering a copy of Healthy

People 2000, see the section Where to Obtain Additional Information.)

In addition, the Public Health Service (PHS) in Addressing Emerging

Infectious Disease Threats: A Prevention Strategy for the United

States, emphasizes the need for identification and prevention of new

and emerging infections. Some of these newly identified infections have

been associated with the transfusion of blood and blood products. This

announcement is related to the national identification of bacterially

contaminated blood products in the U.S. blood supply and to ensuring

the safety of the U.S. blood supply.

Authority

This program is authorized by Section 301(a) of the Public Health

Service Act, as amended [42 U.S.C. 241(a)]. Applicable program

regulations are found in 42 CFR Part 52, Grants for Research Projects.

Smoke-Free Workplace

CDC strongly encourages all grant recipients to provide a smoke-

free workplace and to promote the nonuse of all tobacco products, and

Public Law 103-227, the Pro-Children 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

Assistance will be provided only to national nonprofit

organizations that coordinate multiple blood collection sites for the

purpose of collecting and distributing blood and blood products

nationwide. Status as a national organization will be determined if the

organization coordinates blood collection sites in a majority of the

States in the U.S. The applicant must indicate the number of States in

which they coordinate blood collection sites. For nonprofit

organizations, 501(c)(3) status is required. For-profit organizations

are not eligible for this program.

Only national nonprofit organizations that coordinate the

collection and distribution blood and blood products nationwide will be

considered eligible applicants because of the need to generalize data

to the entire nation and to ensure that no duplication of data occur.

Only these organizations have the capability to initiate a nationwide

study to develop standardized definitions of adverse transfusion

reactions, to increase clinical nursing and medical staff awareness of

these reactions and of bacterial contamination as a mechanism for these

reactions, and to prospectively determine the rates of bacterial

contamination of blood products (RBC, whole blood, and platelets) in

the U.S.

Note: Effective January 1, 1996, Public Law 104-65 states that

an organization described in section 501(c)(4) of the Internal

Revenue Code of 1986 which engages in Lobbying activities shall not

be eligible for the receipt of Federal funds constituting an award,

grant (cooperative agreement), contract, loan, or any other form.

Availability of Funds

Approximately $150,000 will be available in FY 1997 to fund

approximately two to three awards. It is expected that awards will

range from $40,000 to $75,000 with an average award of $50,000. It is

expected that awards will begin on or about August 1, 1997, and will be

made for a 12-month budget period within a one year project period.

Funding estimates may vary and are subject to change. No specific

matching funds are required.

Use of Funds

Cooperative agreement funds shall not be used for the collection or

delivery of blood or blood products. They will be used for developing:

(1) educational materials, and (2) data collection materials and

systems.

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 1997 HHS 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. This new law, Section 503 of Pub. L. No. 104-208,

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.

Department of Labor, Health and Human Services, and Education, and

Related Agencies Appropriations Act, 1997, as enacted by the Omnibus

Consolidated Appropriations Act, 1997, Division A, Title I, Section

101(e), Pub. L. No. 104-208 (September 30, 1996).

Background

Each year over 20 million units of blood products are transfused in

the United States. Although safety has improved through improved donor

screening and testing by the blood product industry in response to the

human immunodeficiency virus (HIV)

[[Page 22953]]

epidemic, residual risk remains for the transmission of HIV and other

emerging infectious pathogens. Some of these transfusion-associated

pathogens and affected blood products include the transmission of

Trypanosoma cruzi, the cause of Chagas' disease, by red blood cell

(RBC) transfusion and hepatitis C virus by intravenous immunoglobulin

product. Other emerging infectious pathogens, i.e., bacteria, also have

been associated with transfusions and adverse reactions.

Approximately one death per million units transfused occurs due to

transfusion-associated sepsis, a newly recognized and emerging problem

(CDC, unpublished data). From 1986 through 1991, 16 percent (29/182) of

transfusion-associated fatalities reported to the FDA were associated

with bacterial contamination of blood products, including red blood

cells (RBCs), whole blood, and platelets. Reports of sepsis and death

after transfusion of blood products, platelets, and RBCs contaminated

by bacteria have been increasing over the past decade. Since 1987, CDC

has received anecdotal reports, from community sources and

conversations with transfusion service personnel and clinical nursing

and medical staff, regarding the bacterial contamination of blood

products. These reports include 20 episodes of Yersinia enterocolitica-

contaminated red blood cells (RBCs), including 12 deaths.

The Code of Federal Regulations (Title 21, Section 606.170[b])

requires only that fatal complications of blood collection or

transfusion be reported to the Food and Drug Administration (FDA);

thus, when non-fatal events are considered, the true incidence of

infectious complications associated with the receipt of blood and blood

products may be substantially underestimated. Lack of knowledge

concerning the mechanisms of adverse transfusion reactions and

transfusion-associated bacterial infection may be another reason for

under-reporting. If blood products are not cultured after an adverse

reaction, bacterial contamination of the product as a cause of the

reaction cannot be definitely established. After a cluster of bacterial

contamination of platelets occurred at one university hospital, medical

staff were educated about adverse transfusion reactions and active

surveillance for bacterial contamination of platelets was initiated;

subsequently the number of platelet transfusion reactions reported

monthly and the reported rate of bacterial contamination of platelets

increased 31 (2.3/1000 to 72.4/1000 platelet pools) and 23 (0.3% to

7.7%) fold, respectively, in the following 22 month period.

A recent study from Germany estimated RBC bacterial contamination

at approximately 0.5 percent and random donor platelet contamination at

approximately 2.5 percent. Since the rates of bacterial contamination

of different blood products in the U.S. is unknown, how the German

rates compare with the bacterial contamination rates of blood products

in the U.S. is unclear.

The existence of a significant number of transfusion-associated

bacterial infectious events reported to CDC, the lack of known

incidence of bacterial contamination of blood products in the U.S., and

likely current underestimation of morbidity and mortality from these

events, demonstrate the need to determine the incidence of transfusion-

associated bacterial contamination of blood and blood products in the

U.S. Therefore, this cooperative agreement is being established to

initiate a study to develop standardized definitions of adverse

transfusion reactions, to increase clinical nursing and medical staff

awareness of these reactions and of bacterial contamination as a

mechanism for these reactions, and to prospectively determine the rates

of bacterial contamination of blood products (RBC, whole blood, and

platelets) in the U.S. These results will aid in the study of the

etiologic agents, risk factors, and outcomes associated with

transfusion-associated bacterial contamination.

Purpose

The purpose of this cooperative agreement is to develop a pilot

study with the national non-profit organizations that coordinate

multiple blood collection sites to: (1) Determine the bacterial

contamination rate of blood products; (2) identify donor risk factors

for bacterial contamination of these blood products; and (3) determine

the impact of transfusion of these bacterially contaminated blood

products on the recipients.

The objectives of the cooperative agreement are:

1. To determine the rates of bacterial contamination of blood

products, i.e., RBCs, pooled and apheresis platelets, and whole blood.

2. To describe risk factors of donors of bacterially contaminated

blood products, i.e., prior or past medical history and prior exposures

significantly associated with bacteremia at time of donation.

3. To determine health outcomes in recipients receiving bacterially

contaminated blood products.

4. To describe underlying medical conditions of recipients that are

significantly associated with death following receipt of bacterially

contaminated blood products.

Program Requirements

In conducting activities to achieve the purpose of this program,

the recipients will be responsible for the activities under A., below,

and CDC will be responsible for conducting activities under B., below:

A. Recipient Activities

1. Coordinate the collection of denominator data to include the

number and types of blood products collected by the transfusion

services, the number and types of blood products distributed by

transfusion services, the number and types of blood products

subsequently transfused.

2. Develop standardized definitions to include a microbiologic

description of bacterially contaminated blood products and the clinical

indicators to differentiate significant and insignificant transfusion

reactions.

3. Collect numerator data to determine the bacterial contamination

rate of blood products, to identify donor risk factors for bacterial

contamination of these products; and, to determine the impact of

transfusion of these bacterially contaminated blood products on the

recipients.

4. Develop educational materials to increase clinical nursing and

medical staff awareness of transfusion reactions.

5. Publish the study outcomes.

B. CDC Activities

1. Assist in the conduct of the study, including:

a. Collaboration in the development of study design.

b. Support recipients as a reference laboratory in confirmation of

contaminating organisms, endotoxin and antibody testing.

2. Assist in the development of data management systems.

3. Collaborate in the coordination of data analysis, dissemination,

and presentation of aggregated data from all recipients.

4. Collaborate in the publication of the study outcomes.

Technical Reporting Requirements

A narrative progress report is required semiannually. An original

and two copies of all progress reports are due within 30 days after

each semiannual reporting period. Progress reports should address the

status of projects and progress toward project objectives and the goals

of this cooperative agreement

[[Page 22954]]

as represented in the Purpose and Recipient Activities sections of this

announcement.

An original and two copies of the financial status report (FSR) are

required no later than 90 days after the end of the budget period. A

final FSR is due no later than 90 days after the end of the project

period. All reports are submitted to the Grants Management Branch,

Procurement and Grants Office, CDC. Please address all reports or other

correspondence 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., Mailstop

E-18, Room 300, Atlanta, Georgia 30305.

Application Content

Format

Pages must be clearly numbered, and a complete index to the

application and its appendices must be included. Please begin each

separate section on a new page. The original and each copy of the

application set must be submitted unstapled and unbound. All material

must be typewritten, single-spaced, with unreduced type on 8\1/2\'' by

11'' paper, with at least 1'' margins, headings and footers, and

printed on one side only.

Application Narrative

All applicants must develop their applications in accordance with

the PHS Form 5161-1 (revised 7/92, OMB Number 0937-0189), information

contained in this announcement, and the instructions outlined below.

Also, the narrative must be limited to 10 pages excluding appendices

and should include the following:

1. The background and feasibility, need for funding, and

willingness to collaborate with CDC in the conduct of the study.

2. The objectives of the proposed study which are consistent with

the purposes of the cooperative agreement and are measurable and time-

phased. The applicant should establish a specific and realistic plan of

operation and timetable for all activities including development of

methodology, development and dissemination of educational material,

development and implementation of data collection instruments,

collection of potentially contaminated blood products, laboratory

identification of bacterial contamination of blood products, and data

analysis.

3. The methods which will be used to accomplish the objectives of

the study. Describe activities and methods already in place or planned,

including capacity and experience to coordinate study efforts; assess

quality of the project coordinators, facilities, and supporting

resources; plan, coordinate, and maintain data collection and analysis;

and disseminate information.

4. A budget which is reasonable and consistent with the purpose and

objectives of the cooperative agreement funds. Please use standard form

424A, ``Budget Information'', provided with the PHS 5161-1 application.

All budget categories should be itemized and individually justified.

5. A description of the project's principal investigator's role and

responsibilities.

6. Documentation of eligibility status including: the number of

States in which blood collection sites are coordinated; and, 501(c)(3)

documentation of nonprofit status.

7. Establish a specific and realistic plan of operation and

timetable for all activities.

8. Any other information that will support the request for

technical and funding assistance.

9. Human Subjects: Whether or not exempt from the Department of

Health and Human Services (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

Applications will be reviewed and evaluated according to the

following criteria: (Total 100 points)

1. The applicant's understanding of the purpose and objectives of

the cooperative agreement and willingness to cooperate with CDC in the

design, implementation, and analysis of the project. (20 Points)

2. The quality of the plans to coordinate and conduct the project

with multiple blood collection sites, including a description of

techniques for educational material, data collection, and data

management. (20 Points)

3. The quality and feasibility of methods to accomplish objectives

and required activities, including the provision of numerator and

denominator data for the generalization of results nationally. The

degree to which the applicant has met CDC requirements regarding the

inclusion of women, ethnic, and racial groups in the proposed research.

This includes: (a) The proposed plan for inclusion of both sexes and

racial and ethnic minority populations for appropriate representation.

(b) The proposed justification when representation is limited or

absent. (c) A statement as to whether the design of the study is

adequate to measure differences when warranted. (d) A statement as to

whether the plans for recruitment and outreach for study participants

include the process of establishing partnerships with community(ies)

and recognition of mutual benefits will be documented. (30 Points)

4. How the study will be administered, including duties and

responsibilities and time allocation of the proposed staff; and a

schedule for accomplishing the program activities, including time

frames. (15 Points)

5. A statement of the applicant's demonstrated capabilities and

experience in conducting such a project. (15 Points)

6. The extent to which the budget is reasonable, clearly

justifiable, and consistent with the intended use of cooperative

agreement funds. (Not scored)

7. Human Subjects (not scored): If the proposed project involves

human subjects, whether or not exempt from the DHHS regulations, the

extent to which adequate procedures are described for the protection of

human subjects. Recommendations on the adequacy of protections include:

(a) Protections appear adequate and there are no comments to make or

concerns to raise, (b) protections appear adequate, but there are

comments regarding the protocol, (c) protections appear inadequate and

the ORG has concerns related to human subjects, (d) 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, or (e) protections appear adequate

that women, racial and ethnic minority populations are appropriately

represented in applications involving human research.

Executive Order 12372 Review

This program is not subject to review by Executive Order 12372.

Public Health Systems 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,

Centers for

[[Page 22955]]

Disease Control and Prevention (CDC)--Investigations and Technical

Assistance.

Other Requirements

Paperwork Reduction Act

Projects that involve the collection of information from 10 or more

individuals and funded by cooperative agreements 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.

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.

Application Submission and Deadline

The original and two copies of the completed application PHS Form

5161-1 (revised 7/92, OMB Number 0937-0189) 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., Mailstop E-18, Room

300, Atlanta, Georgia 30305, on or before May 30, 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 will not be acceptable as proof of timely mailings.)

2. Late Applications

Applications which do not meet the criteria in either 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

A complete program description, information on application

procedures, an application package, and business management technical

assistance may be obtained from Locke Thompson, Grants Management

Specialist, Grants Management Branch, Procurement and Grants Office,

Centers for Disease Control and Prevention (CDC), 255 East Paces Ferry

Road, NE., Mailstop E-18, Room 300, Atlanta, GA 30305, telephone (404)

842-6595 or through the Internet or CDC WONDER electronic mail at:

[email protected]. Programmatic technical assistance may be obtained from

Matthew J. Kuehnert, M.D. or Marsha A. Jones, Hospital Infections

Program, National Center for Infectious Diseases, Centers for Disease

Control and Prevention (CDC), Mailstop E-69, Atlanta, GA 30333,

telephone (404) 639-6413 or through the Internet or CDC WONDER

electronic mail at: [email protected].

You may obtain this announcement from one of two Internet sites:

CDC's homepage at: http://www.cdc.gov or the Government Printing Office

homepage (including free on-line access to the Federal Register) at:

http://www.access.gpo.gov.

Please refer to Announcement Number 733 when requesting information

and submitting an application.

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, DC 20402-9325, telephone (202) 512-1800.

Dated: April 22, 1997.

Joseph R. Carter,

Acting Associate Director for Management and Operations, Centers for

Disease Control and Prevention (CDC).

[FR Doc. 97-10829 Filed 4-25-97; 8:45 am]

BILLING CODE 4163-18-P