INFECTIOUS CAUSES OF DIARRHEA OR WASTING SYNDROME IN PEOPLE WITH AIDS NIH GUIDE, Volume 22, Number 45, December 17, 1993 PA NUMBER: PA-94-019 P.T. 34 Keywords: Digestive Diseases & Disorders AIDS 0715151 National Institute of Allergy and Infectious Diseases PURPOSE The purpose of this Program Announcement (PA) is to solicit investigator-initiated applications to identify and determine the role of opportunistic pathogens as putative causative agents of diarrhea or wasting syndrome in people with AIDS and to develop methods for targeted drug discovery against those pathogens. The research scope will be limited to studies on parasitic protozoa and mycobacteria (excluding M. tuberculosis) as causative infectious agents. No clinical trials will be supported. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This PA, Infectious Causes of Diarrhea or Wasting Syndrome in People with AIDS, is related to the priority area of HIV infection. 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. 017-001-00474-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications may be submitted from one institution or may include arrangements with several institutions if appropriate. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applications from or involving minority institutions, individuals, and women are encouraged. MECHANISM OF SUPPORT Support for this program will be by the investigator-initiated research project grant (R01) and First Independent Research Support and Transition (FIRST) award (R29). RESEARCH OBJECTIVES Background Wasting syndrome, a condition that commonly includes chronic diarrhea, is one of the most frequent AIDS-defining conditions among adults and adolescents reported to the Centers for Diseases Control and Prevention. Although the true incidence of this condition is unknown, this clinical presentation occurs in a high proportion of patients with AIDS during the course of the disease. Severe diarrhea and weight loss associated with intestinal damage and malabsorption contribute to malnutrition, poor drug absorption, and diminished quality of life. Although diarrhea can often be attributed to infections with one or more enteric pathogens, no causative agent can be conclusively identified in up to 50 percent of AIDS patients with diarrhea. Intestinal protozoa often associated with AIDS include coccidian parasites causing protracted diarrhea (e.g., Cryptosporidium parvum and Isospora belli) and microsporidia (particularly Enterocytozoon bieneusi, causing intestinal microsporidiosis). Successful management of AIDS-associated diarrhea is confounded by the lack of reproducibly effective therapies; lack of convenient, standardized diagnostic procedures other than microscopy; lack of quantifiable assessments of infectious organisms to determine clinical response to therapy; presence of other concomitant opportunistic infections; and emergence of new etiologic agents. Recently, additional microorganisms have been associated with diarrhea and wasting such as Cyclospora cayetanensis, a coccidian protozoan causing intractable diarrhea; Septata intestinalis, an obligate intracellular microsporidian associated with chronic diarrhea; and Mycobacterium genavense, an acid-fast bacillus isolated from AIDS patients exhibiting diarrhea, weight loss and fevers. Wasting syndrome, in the absence of diarrhea or gastrointestinal pathogens, is poorly understood, but may involve decreased nutrient absorption, metabolic disturbances, and excess production of tumor necrosis factor (TNF) or other immune effectors. Objectives and scope The objective of this PA is to stimulate drug discovery through original and innovative research focused on key metabolic and pathophysiologic features of infectious organisms contributing to diarrhea or wasting syndrome. Applications based on sound scientific rationale to improve growth and detection techniques in order to evaluate therapies against newly recognized pathogens are encouraged. The research scope will focus on parasitic protozoa and mycobacteria potentially responsible for causing diarrhea or wasting syndrome. This includes, but is not limited to, Cryptosporidium, the Microsporidia species associated with AIDS (Enterocytozoon sp., Septata intestinalis), Mycobacterium avium complex, and newly identified organisms such as Cyclospora cayetanensis, and Mycobacterium genavense. Areas of research may include studies designed to: o Develop in vitro (culture) and in vivo (animal model) systems for drug testing. o Develop rapid, noninvasive diagostic methods for the specific and quantifiable detection of the infectious organism. o Determine the interrelation between the etiologic agent and host factors (e.g., cytokines) contributing to diarrhea or wasting syndrome. o Identify and characterize biochemical, metabolic and molecular properties of the infectious organism which may serve as targets for chemotherapy. o Discover new therapeutic agents or prophylactic approaches (chemo-, immuno- or gene-based therapies) through exploitation of biochemical, metabolic or molecular differences between pathogen and host. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders, and conditions that disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in the Research Plan Sections 1-4 AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, African Americans, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders, or conditions. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in the priority score assigned to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the receipt dates for applications for AIDS-related research: January 2, May 1, and September 1. Application kits are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 710-0267. Each application must be identified by checking "YES" on line 2a of the PHS 398 face page, citing this announcement number. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** FIRST (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. REVIEW CONSIDERATIONS Upon receipt, applications and supporting material will be examined by the Division of Research Grants for completeness. Incomplete applications will be returned without further consideration. Applications will be assigned on the basis of established Public Health Service Referral Guidelines. Applications will be reviewed independently for scientific and technical merit by study sections of the Division of Research Grants, NIH in accordance with the standard NIH peer review procedures. Review criteria will include: o Significance and originality of the research and methodological approaches. o Feasibility of the research and adequacy of the experimental design. o Training, experience, research competence and commitment of the investigator(s). o Adequacy of the facilities and resources. o Provisions for the protection of human subjects, the humane care of animals, and biosafety conditions. Following scientific and technical merit review, applications will receive a second level review by the appropriate National Advisory Council(s). AWARD CRITERIA Applications will compete for available funds with all other applications found to have significant and substantial merit. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues either to: Dr. Chris Lambros Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C04 Bethesda, MD 20892 Telephone: (301) 402-0135 FAX: (301) 402-3211 E-mail: cbl@exec.niaid.pc.niaid.nih.gov Dr. Michael Gottlieb Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A03 Bethesda, MD 20892 Telephone: (301) 496-7115 FAX: (301) 402-0804 E-mail: mog@exec.niaid.pc.niaid.nih.gov Direct inquiries regarding fiscal matters to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No 93.856, Microbiology and Infectious Diseases Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. .
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |