Notice of Special Interest (NOSI): Advancing Rheumatic Heart Disease Research (R01)
Notice Number:

Key Dates

Release Date:

September 13, 2023

First Available Due Date:
February 05, 2024
Expiration Date:
January 08, 2027

Related Announcements

  • May 10, 2022 - Dissemination and Implementation Research in Health (R01 Clinical Trial Optional). See NOFO PAR-22-105
  • May 5, 2020 - Research Project Grant (Parent R01 Clinical Trial Required). See NOFO PA-20-183.
  • May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

Issued by

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Allergy and Infectious Diseases (NIAID)



This Notice of Special Interest (NOSI) seeks to advance Rheumatic Heart Disease (RHD) research. There is a critical need to reduce RHD burden within low- and middle-income countries and low-resource settings in high-income countries. The NOSI calls for research proposals across the translational science spectrum (e.g., basic science, clinical research, and implementation and dissemination studies) within endemic settings to improve health outcomes.


RHD is one of the most neglected yet preventable chronic disorders, with low- and middle-income countries (LMICs) and endemic populations in high-income countries (HICs) (e.g., low-resource settings and indigenous populations) carrying the heaviest burden. The disease is initially caused by Group A streptococcus (GAS) infections that induce subsequent autoimmune Acute Rheumatic Fever (ARF) episodes, leading to the permanent condition RHD. It is estimated that over 40 million individuals suffer from the disease globally, claiming over 300,000 lives each year. HICs have made significant strides to reduce RHD burden through advocacy/support for improved living conditions, targeted outreach, and access to appropriate care. Moreover, evidence-based interventions (EBIs) and guidelines have been developed to support prevention and care. Unfortunately, these RHD advances in HICs do not easily translate across settings. There is a critical need for innovative methods and strategies to support the eradication of RHD, which remains endemic in LMICs and low-resource settings. 

This NOSI targets three notices of funding opportunity (NOFOs) to build robust evidence for prevention, detection, intervention, and implementation of evidence for limiting the burden of RHD. For example NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185) would support basic/discovery science research and longitudinal studies meant to gain a better understanding of GAS/ARF/RHD pathogenesis and progression in LMICs and low-resource settings. The Research Project Grant NOFO (Parent R01 Clinical Trial Required) (PA-20-183), would support mechanistic clinical trials to understand the biological or behavioral process, the pathophysiology of GAS/ARF/RHD, or the mechanism of action of an intervention. The Dissemination and Implementation Research in Health NOFO (R01 Clinical Trial Optional) (PAR-22-105) would support the contextual adaptation of EBIs in collaboration with communities to ensure their feasibility, acceptability and sustainability. Please see NIH Institute/Center/Office-specific language about other eligible activity codes.

Areas of interest include:

  1. Primordial prevention proposals assessing modifiable social determinants of health impacting RHD burden and the development/testing of GAS vaccines
  2. Primary prevention proposals to study the pathophysiology, diagnosis, and treatment of GAS infections and subsequent ARF episodes
  3. Secondary prevention proposals to study the pathophysiology, diagnosis, and management of persons with established RHD to prevent disease progression (including long-term penicillin prophylaxis)
  4. Tertiary care proposals focused on the management of complications of RHD, including surgery and palliative care

In addition, ancillary studies can also be proposed to address research questions for which the parent study can provide participants, infrastructure, and data. These ancillary studies should include: the collection of new information, compatible timelines (e.g., the timeline of the parent study would need to be compatible with the timeline of the ancillary study), Letters of Support, and a clear research strategy aimed at increasing the knowledge base related to GAS/ARF/RHD. Applications proposing studies taking place in LMICs and low-resource settings experiencing high burden of GAS/ARF/RHD would also be responsive.

Specific criteria for implementation and dissemination research responsiveness (PAR-22-105): Applications responsive to this NOSI may propose pure dissemination and implementation (D&I) studies as well as all hybrid approaches to advance RHD research. If effectiveness-implementation hybrid approaches are proposed, Hybrid Type 2 or 3 approaches are preferred in which Type 2 has a dual focus on testing clinical interventions and implementation strategies and Type 3 focuses primarily on testing the impact of D&I interventions/strategies. Lower in priority are Type 1 approaches in which the focus is on testing clinical effectiveness of an intervention while simultaneously exploring implementation factors. D&I studies utilizing multidisciplinary/multi-sector partnerships (e.g., Ministry of Health), community engagement, and multilevel approaches (e.g., organizational, provider level, community and patient) are strongly encouraged. D&I applications not including these components would be of lower programmatic priority.

Research topics of interest within the scope of this NOSI may include, but are not limited to:

  • Research assessing the pathophysiology and development of GAS/ARF/RHD and related complications
  • Longitudinal and follow-up studies evaluating GAS/ARF/RHD  disease progression in endemic settings
  • Research to develop and test novel vaccines and/or vaccine platforms for broad protection against GAS infections
  • Research identifying correlates of protection in appropriate preclinical models and/or human specimens
  • Research to develop innovative, early and economic point of care (POC) diagnostics and therapeutics that are contextually appropriate and feasible to improve health outcomes in endemic settings
  • Research to improve the dissemination and uptake of evidence-based GAS/ARF/RHD prevention, screening, early detection, and diagnostic interventions, as well as effective treatments, clinical procedures, or guidelines in real world settings (e.g., antenatal care screening programs, school-based programs and oral health programs)
  • Research to identify and evaluate appropriate evidence-based screening tools to support active case finding in endemic settings
  • Research to identify or develop methods to support the contextual adaptation of existing diagnostic, therapeutic and management guidelines for GAS/ARF/RHD in endemic settings
  • Studies evaluating mechanisms influencing medication adherence or proposing implementation strategies to increase adoption
  • Research to identify and develop strategies to address modifiable determinants of GAS/ARF/RHD progression, including poor housing, overcrowding, and reduced access to care in LMICs and low-resource settings
  • Cost-effectiveness evaluation related to the implementation of evidence-based interventions in endemic settings
  • Research to decipher facilitators and barriers to care impacting the integration of GAS/ARF/RHD care model within health services and community-based programs
  • Research to ascertain innovative decentralized approaches to support GAS/ARF/RHD patient care and access for high-risk groups in endemic settings
  • Research to identify and evaluate feasible implementation strategies to support the integration and/or scaling of available GAS/ARF/RHD evidence based interventions in endemic settings

National Heart, Lung, and Blood Institute (NHLBI)

The National Heart, Lung, and Blood Institute (NHLBI) provides global leadership for a research, training, and education program to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives. Responsive applications would include proposals that address primordial prevention (measures to improve social determinants of health); primary prevention (diagnosis and treatment of ARF sequelae); secondary prevention (diagnosis and management of persons with established RHD  to prevent disease progression, including long-term penicillin prophylaxis); and tertiary care (diagnosis and management of complications of RHD, including surgery and palliative care). Applications that would not be responsive to the NHLBI include those that (1) seek to evaluate and test GAS  vaccines or (2) assess the pathophysiology, diagnosis, or treatment of GAS  (independent of ARF sequelae).

Note: Clinical Trial applications to the NHLBI must be mechanistic. See NOT-HL-19-690.

National Institute of Allergy and Infectious Diseases (NIAID)

The mission of NIAID is to conduct and support basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. The research areas of interest to NIAID include, but are not limited to, studies that (1) seek to evaluate and test novel GAS vaccines, (2) assess the pathophysiology, natural history, diagnosis, or treatment of GAS infections (independent of ARF sequelae, or (3) study vaccine related host immune mechanisms and responses. NIAID is only interested in applications focused on GAS; other research topics, e.g., HIV/AIDS, are nonresponsive. 

Application and Submission Information

This notice applies to due dates on or after February 5, 2024 and subsequent receipt dates through January 7, 2027. 

Submit applications for this initiative using one of the following notice of funding opportunity (NOFO) or any reissues of these announcements through the expiration date of this notice. This NOSI expires on January 8, 2027; thus no applications will be accepted on or after January 8, 2027. 

  • PAR-22-105 - Dissemination and Implementation Research in Health (R01 Clinical Trial Optional)
  • PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

NOTE: NHLBI will only accept mechanistic clinical trials in response to PA-20-183, in accordance with NOT-HL-19-690. Applicants wishing to propose non-mechanistic clinical trials may consider applying to one of the NHLBI clinical trial mechanisms described at Non-mechanistic clinical trials submitted in response to this NOSI via PA-20-183 will be withdrawn.

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-HL-23-106” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Mary Masterson PhD, MS
National Heart, Lung, and Blood Institute (NHLBI)
Center for Translation Research and Implementation Science (CTRIS)
Telephone: 301-827-6113  

Xin-Xing Gu, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Division of Microbiology & Infectious Diseases 
Telephone: 240-627-3265

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Shaheed Michael Ziyout
National Heart, Lung, And Blood Institute (NHLBI)
T hone: 301-827-8152
E mail:

Samuel Ashe
National Institute of Allergy and Infectious Diseases (NIAID)
Telep hone: 301-435-4799
E mail: