https://www.ssmri.org/chagas-delphi-panel/
Chagas Delphi Panel
Chagas Delphi Panel Summary Report
Introduction
A Delphi Panel was convened to help SWEMRI rapidly develop an unbiased overview of the impact of Chagas disease in both Latin America and the United States. This Delphi Panel was also tasked with identifying strategic research opportunities where SWEMRI funding might advance programs designed to reduce Chagas morbidity and/or mortality or reduce Chagas disease incidence and/or progression. Seven researchers and clinicians, representing U.S. government and academic institutions, with expertise ranging from etymology to immunology, drug discovery to vaccine development, and parasitology to public health, were invited to participate in a Chagas Delphi Panel (CDP). All invited experts agreed to participate; they were awarded a small honorarium as compensation for their time and effort. The Delphi Panel operated for approximately 6 months, completing its work in March, 2014.
The Chagas Delphi Panel operated anonymously. Panelists had no direct contact with each other and did not know each other’s identity. All communications occurred between panelists and SWEMRI staff. Panelists initially responded via email to a list of questions and provided both quantitative and qualitative responses to each question. Responses where collated by SWEMRI staff and summary statistics calculated for each question. All responses and statistics for each question were returned to the panelists for consideration, and revised responses collected. Three rounds of this process were performed in an attempt to develop a consensus, if possible, around common responses. However, no responses were discarded during each round of responses and the final report expresses the range of responses and the enthusiasm expressed by the panelists for the responses.
Chagas Delphi Panel (CDP)
Our Delphi Panel included the following Chagas disease experts.
- Igor Almeida, PhD (vaccines)
Professor, Dept. of Biological Sciences
The Border Biomedical Research Center
University of Texas at El Paso
- Fred Buckner, MD (treatments)
Professor, University of Washington
- Patricia L. Dorn, PhD (T. cruzi epidemiology)
William and Audrey Hutchinson Distinguished Professor
Loyola University New Orleans
- Nisha Garg, PhD (vaccines)
Professor, Department of Microbiology & Immunology
University of Texas Medical Branch
- Sarah Hamer PhD, DVM (vector distribution)
Assistant Professor, Department of Veterinary Integrative Biosciences
Texas A&M University
- W. David Nes, PhD (drug discovery)
Paul Whitfield Horn Professor of Chemistry and Biochemistry
Director, Center for Chemical Biology
Texas Tech University
- Rick L. Tarleton, PhD
UGAAA Distinguished Professor of Biological Sciences
Center for Tropical & Emerging Global Diseases
University of Georgia
Questions and responses (both consensus and dissenting) produced by the Delphi Panel.
1) What is the health burden of Chagas disease relative to other infectious diseases in Latin (South and Central) America?
There was strong agreement amongst the Chagas Delphi Panel (CDP) that it is not possible to reliably estimate the Chagas health burden due to lack of accurate epidemiological data. The large majority of the CDP agreed that the limited data suggest Chagas disease may be a large contributor to the health burden of infectious diseases in Latin America because it is a chronic disease with infected individuals impacted for many years. There was agreement that the “traditional killers” of diarrheal and respiratory disease likely remain the largest infectious disease health burdens in Latin America.
Note: data from the Global Burden of Disease Study 2010 was used to provide an initial estimate of the relative DALYs (disability-adjusted life years) from infectious diseases and neglected tropical diseases as: cryptosporidiosis (8.4M), cholera (4.5 M), leishmaniasis (3.3M), schistosomiasis (3.3M), hookworm (3.2M), fungal skin disease (2.3 M), amebiasis (2.2 M), rabies (1.5M), dengue (0.8M), Chagas disease (0.6M), trichuriasis (0.6M) (Hotez et al, PLoS Negl Trop Dis, 2014). This selected list does not include all diseases caused by infectious agents.
2) What is the health burden of Chagas disease relative to other infectious diseases in Texas, USA?
There was uniform agreement amongst the CDP that no reliable data (e.g., large-scale seroscreening) exists to estimate Chagas disease burden or prevalence in Texas. Thus, the health and economic burden of Chagas disease in Texas is still undefined. There was agreement that the burden of Chagas disease in Texas will likely not approach that of Latin America, although the number of cases of Chagas disease will be diagnosed more frequently over the next decade likely due to more screening. It is likely locally-acquired T. cruzi infections will remain low.
On January 1, 2013, Texas became one of 4 US states in which Chagas was reportable in humans. Moreover, Chagas is a reportable disease for veterinarians in Texas. Unfortunately, not all veterinarians (and presumably doctors) are aware of this requirement or know to include Chagas disease within their index of suspicion. The CDP was in uniform agreement that mandatory reporting should help assess Chagas disease impact and determine how to allocate limited health care resources. There was general agreement amongst the CDP that a better estimate of T. cruzi prevalence in the Texas population was needed. There was general agreement that reporting of T. cruzi infection in humans and animals should be a nation-wide requirement.
A 2008 study (Kjos et al, 2008) reported that ~20% of tested domestic dogs in Texas tested positive for T. cruzi infection. However, this study used samples selectively sent to the Texas Veterinary Medical Diagnostic Laboratory (TAMU, College Station, Texas) for serological evaluation and thus cannot be considered an unbiased representation of T. cruzi prevalence in domestic dogs in Texas. A recent study (Tenney et al, 2014) reported ~9% of dogs randomly sampled from canine shelters across Texas were T. cruzi seropositive.
3A) Has the health impact of Chagas disease in Latin America changed in the past decade? If so, what might be responsible for this change?
The CDP was in general agreement that in the past 10-20 years, the health impact of Chagas has been reduced in most Latin America countries following widespread vector control efforts. In Central America, reduced transmission has been attributed to the near eradication of the vector Rhodnius prolixus, possibly due to intensive (and expensive) spraying with residual pesticides and roof improvements in domestic housing. However, many spraying efforts have been dismantled and insecticidal resistance is being increasingly detected.
There was strong agreement on the CDP that any decreased burden of Chagas disease in Latin American countries was not due to increased treatment of patients. improved patient follow-up care, or improved blood screening.
3B) Has the health impact of Chagas disease in Texas (or the US) changed in the past decade? If so, what might be responsible for this change?
There was uniform agreement in the CDP that any growing health impact of Chagas in the US results largely from more widespread diagnostic testing, public awareness efforts, and increased recognition. Moreover, the CDP generally agreed that the health impact of Chagas in nonendemic regions (e.g., Europe) has been increasing in recent years in large part from immigration of chronically infected (but, unaware) individuals from endemic countries. Immigration simply determines where infected individuals are located; immigration in and of itself does not increase the transmission or spread of Chagas in nonendemic areas.
There was general agreement that it is not possible to definitively determine if the health impact of Chagas in Texas has changed in the past decade since the data required to make this determination does not exist. It was noted by a panelist that without appropriate data, the case for Chagas importance in the U.S. should not be overblown or this will only serve to further deepen the mistrust of science by the public.
4A) What will be the most effective strategy(ies) to reduce the health burden of Chagas disease in Latin America during the next 10 years?
There was general agreement in the CDP that T cruzi transmission could be reduced by vector control, which would involve insecticide spraying along with efforts to improve housing conditions (e.g., Ecohealth approach). These efforts could be aided by development of more effective and less toxic insecticides.
There was strong agreement on the CDP that T. cruzi vertical transmission could be reduced by universal screening of pregnant woman and T. cruzi transfusion spread could be reduced by screening of blood and solid organ transplant tissue. Careful monitoring and drug treatment of people identified as T. cruzi positive should then occur.
The CDP was divided as to whether a protective vaccine for humans would be an effective strategy to reduce transmission. Similarly, the panel was divided as to whether developing a therapeutic vaccine to cure the disease in infected individuals was an effective strategy to reduce disease progression. Panelists that were not enthusiastic regarding vaccine strategies cited concerns of cost, time, and feasibility.
There was general agreement on the CDP that disease progression could be reduced by identifying infected individuals and treating them with therapeutic drugs to clear or reduce parasite load. Identifying infected individuals would be greatly aided by rapid, sensitive, specific, and inexpensive diagnostic tests that could be used in remote clinical and point-of-care settings.
4B) What might be the most effective strategy(ies) to realistically reduce the health burden of Chagas disease in Texas during the next 10 years?
There was general agreement in the CDP that it would be beneficial to better understand if or how human transmission of T. cruzi occurs in Texas. There was agreement that horizontal transmission could be limited by continuing (and expanding) current widespread screening of blood donations for the presence of T. cruzi infection. However, several panelists noted that the benefits of universal screening must be balanced with the costs and that targeted screening makes more sense
since current data does not suggest universal screening.
There was strong agreement in the CDP that identifying infected individuals for treatment with therapeutic drugs to clear or reduce parasite load would provide near-term health benefits. Screening at-risk pregnant women and their new-born babies, and initiating treatment of vertically-infected infants, would provide additional near-term benefits. However, front-line therapeutics (i.e., benznidazole, nifurtimox) are not readily available in the US for human use; neither drug is approved in the United States, but both can be obtained from the CDC and used under investigational protocols. Thus, efforts must be made to increase access to Chagas medications, including obtaining FDA approval for therapeutic use.
5) What research priorities offer the greatest opportunities to reduce the health burden of Chagas disease?
There was wide-spread agreement in the CDP that the following opportunities should be the highest research priorities:
- Better therapeutic treatment regimens (e.g., new formulations, drug combinations, dosing schedules) for current T. cruzi drugs, including regimens appropriate for use by children and pregnant women.
- Chagas therapeutics that are more effective and/or less harmful than current drugs.
- An accurate and practical “test of cure” assay for use in clinical settings.
- Effective public outreach and human/veterinary medical awareness campaigns to increase awareness of Chagas disease especially in areas like the US
Items cited by the CDP as being of lessor priority were:
- Improved insecticides to use in cost-effective vector control programs.
- Predictive transmission risk maps, based on comprehensive epidemiological studies and mathematical modeling of well-established risk factors including environmental/ecological parameters and socio-economic conditions.
- Improved vector control strategies.
- Novel Chagas therapeutics for veterinarian use.
Research priorities that were viewed by the CDP as having lowest priority in terms of reducing the Chagas health burden were:
- Development of a prophylactic (i.e., protective) vaccine for humans. This was recognized as a beneficial approach, but was viewed as a high-risk endeavor which resulted in the CDP assigning it a low priority research opportunity.
- Chagas protective vaccines for veterinarian use.
6) What are the main basic research gaps that need to be addressed to implement effective strategies to reduce Chagas health burden?
The CDP identified several knowledge gaps that were impeding the development of more effective anti-Chagas strategies. The CDP largely agreed that the following research areas could be ranked from highest to lowest priority as:
- Understanding T. cruzi's biochemistry, physiology, and behavior in its different hosts (human, insect).
- Understanding the mechanisms (molecular, cellular, etc.) that lead to cardiomyopathy.
- Understanding the relationship between parasite burden and clinical disease, namely determining if reduced parasite load or parasitological cure is sufficient to prevent disease development.
- Accumulating basic prevalence information in the US (especially in marginalized populations) and many areas of Mexico.
- Understanding the mechanisms of immunomodulation in relation to T. cruzi infection so as to stimulate the host immune response to clear T. cruzi infection.
- Understanding the basic ecology and distribution of T. cruzi strain.
- Understanding how T. cruzi resists clearance in an immune host.
7) What approaches/technologies/treatments/strategies/policies could be better utilized today to reduce the incidence of Chagas disease (either by reducing infection or progression to chronic Chagas disease)? These responses overlap responses generated to Question 4.
The approaches that could be better utilized to reduce Chagas disease incidence are listed below in order (highest to lowest) of expected effectiveness:
- Continue or restart vector control initiatives in Latin America since they have provided some demonstrated measure of reducing disease incidence.
- Screen pregnant women in or from endemic areas to identify females at risk of transmitting T. cruzi to their infants; these newborn children could be targeted for further screening and treatment.
- Guarantee the availability of existing drugs for use in treatment of infected indivudals.
- Raise awareness among physicians, veterinarians, and medical students even in “non-endemic” countries to kissing bug distributions and clinical presentations of Chagas disease so that diagnosis can be recommended and treatment established if needed. This would include making Chagas disease a reportable indication in all states of the U.S. with vectors and/or large Hispanic populations to better monitor disease patterns.
- Expand screening for T. cruzi infected individuals in blood banks and in hospitals/clinics in endemic areas, with centralized reporting of results to identify infected individuals for treatment and to prevent transfusion-associated transmission.
- Encourage government policies to enable all T. cruzi infected individuals to be treated, irrespective of age or length of infection.
- Undertake systematic epidemiological studies to identify at risk populations.
- Increase awareness of Chagas disease on the national level in the US.
Panelists felt that the above approaches would be most effective if implemented as part of an integrated control strategy.
8) What approaches/technologies/treatments/strategies/policies could be better utilized today to reduce morbidity and mortality from chronic Chagas disease?
The approaches that could be better utilized to reduce Chagas disease morbidity and mortality are listed below in order (highest to lowest) of expected effectiveness:
- Expanded availability and use of therapeutics, since it has been suggested that >98% of people with chronic Chagas infection have not received anti-trypanosomal treatment.
The next three (3) approaches were viewed as producing essentially equivalent effectiveness:
- Implement systematic screening to identify at risk populations, followed by treatment of infected individuals and education about local measures to eliminate reduviid bugs and mammalian hosts that serve as reservoirs.
- Screen pregnant women in or from endemic areas to identify females at risk of transmitting T. cruzi to their infants; then target at-risk newborn children for screening and, if necessary, treatment.
- Improve (guarantee) the availability of existing drugs for use in treatment.
- Encourage government policies to state that all T. cruzi infected individuals should be treated, irrespective of age or length of infection.
- Complete the BENEFIT trial, which is testing the effectiveness of benznidazole (anti-parasite drug) in chronic patients. This would likely provide an indication whether (and when) chronically infected individuals should be treated to prevent parasite-induced cardiac damage.