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Background: Group visits have the potential to help patients identify their health care values and engage in the emotionally and cognitively challenging task of advance care planning (ACP) in a resource-efficient manner by providing a forum for social learning and social support. Objective: To evaluate the feasibility and acceptability of disease-specific group visits for patients with heart failure and their caregivers. Design: Feasibility trial of a 90-minute group visit held for 10 separate groups and led by a trained facilitator using the video-based PREPARE for Your Care ACP tool. Setting:/Subjects: Older adults with recent hospitalization for heart failure (n = 36; median age, 74 years) and their caregivers (n = 21). Measurements: Pre- and post-visit surveys and a postvisit telephone interview assessing perceived value and acceptability; structured nonparticipant observations to assess process and feasibility. Results: Mean scores from the postgroup visit evaluation showed that participants reported that they felt comfortable discussing ACP in a group (4.59), understood the information covered (4.70), and were able to identify and clarify their health care values (4.43). Interview and observation data demonstrated that participants were able to identify and clarify their preferences by listening and learning from a diverse range of perspectives in the group and that the disease-focused nature of the group visit created a supportive space for participants to share their experiences. Conclusions: Disease-focused ACP group visits were feasible to conduct and acceptable to participants, underscoring their value as an efficient intervention to engage patients and caregivers in the otherwise time- and resource-intensive task of ACP.

One in six community-dwelling older adults experience elder abuse yearly, and persons with dementia are especially at risk. Although many risk factors for elder abuse have been identified, there are still knowledge gaps concerning risk and protective factors. This cross-sectional survey among Norwegian informal caregivers (ICGs) aimed to find individual, relational, and community factors associated with psychological and physical abuse of home-dwelling persons with dementia. This study involved 540 ICGs and was conducted from May to December 2021. Statistical analysis using penalized logistic regression with lasso was performed to find covariates associated with psychological and physical elder abuse. The most prominent risk factor for both subtypes of abuse was the caregiver being a spouse. In addition, risk factors for psychological abuse were having a higher caregiver burden, experiencing psychological aggression from the person with dementia, and the person with dementia being followed up by their general practitioner. For physical abuse, the protective factors were the ICG being female and having an assigned personal municipal health service contact, while the risk factors were the ICG attending a caregiver training program and experiencing physical aggression from the person with dementia and the person with dementia having a higher degree of disability. These findings add to the existing knowledge of risk and protective factors in elder abuse among home-dwelling persons with dementia. This study provides relevant knowledge for healthcare personnel working with persons with dementia and their caregivers and for the development of interventions to prevent elder abuse.

Despite higher prevalence of dementing illnesses in Latina/o populations, detection is lower compared to white populations, compounding racial/ethnic and economic disparities. Undetected illness compromises effective delivery of primary care and impedes linkages to much needed services. Development of robust detection and culturally sensitive management of cognitive impairment is critical for adequate care of this population. The Geriatric Workforce Enhancement Program at the University of Southern California (USC) partnered with Eisner Health, a Federally Qualified Health Center, serving a primarily immigrant, Spanish-speaking, uneducated, urban older adult population, to help achieve their goal of becoming an Age-Friendly Health System to prioritize identification and management of cognitive impairment. Over 14 months, a sustainable clinic workflow was developed and implemented to detect, evaluate, diagnose, and develop care plans for patients and their care partners. Staff and provider education was delivered through didactics, workshops, case reviews, and at-elbow training. Additional efforts focused on EHR optimization and alignment of existing clinical resources. Frequency data was extracted using i2iTracks software reflecting pre and post-implementation. Results show a higher percentage of patients diagnosed with cognitive impairment in the post-implementation period (7.35%) compared to pre-implementation (4.05%). Detailed data tracking the volume of patients engaged at each step of the workflow supports meaningful analysis of barriers and opportunities for optimization, such as how and where additional resources and efforts will yield the greatest effects. Data-driven strategies such as these, strengthen efficiency and effectiveness of the collaborative process and result in sustainable outcomes for this underserved population.

Universal screening of older adults in emergency departments (ED) effectively improves identification of elder mistreatment (EM). To realize improved response, collaboration between ED providers and staff and local Adult Protective Services (APS) is essential. Qualitative data was derived from transcribed and coded key informant interviews with 10 APS workers and 5 ED clinical providers from 6 states. Results indicate each entity approaches EM from a different global perspective which informs key strategies to build effective response. ED providers focus on acute medical needs while APS focuses on long-term psychosocial needs. Assignment of specific individuals in both entities to be liaisons between ED and APS would support improved communication and collaboration. Education should focus on 1) capabilities and limitations in EM response and 2) clarity regarding bilateral sharing of information. Both entities report participation in multidisciplinary teams is valuable to foster collaboration on effective interventions in EM cases.

During the COVID-19 pandemic, many older adults were not receiving primary care services because they could not negotiate the technology for telehealth visits. Coupled with persisting pandemic physical distancing, increased social isolation in older adults was- and continues to be a significant problem. To combat these issues, we aimed to 1) prepare older adults for longitudinal isolation by encouraging social connectedness, and 2) enable older adults to safely access remote primary care services during the pandemic. We paired older adults from 9 housing sites in Los Angeles, CA with health professions graduate students from 9 programs at USC (N = 88 dyads) and provided iPhones to participants without a smartphone. Students educated and supported older adults about the use of technology to access primary care services and to socially connect with family/friends. When requested, 3 additional students provided enhanced 1:1 technology support. Among the 45 participating older adults who received iPhones (51.1%), 22 requests were made for enhanced technology assistance during the 6-month program. Most requests related to initial setup/navigation of iPhone (81.8%) or video calls (27.3%), where others requested help with Wi-Fi (13.6%), composing emails (4.5%), and adding language/translation features (4.5%). Nineteen (83%) technology support requests were successfully resolved; the remaining were unresolved due to loss to follow-up. Our findings demonstrate that older adults can successfully cross the digital divide when technology support is provided. Additionally, pairing older adults with health professions students is an effective strategy to enable access to remote primary care and social connectedness.

Objective Advance care planning (ACP) is critically important for heart failure patients, yet important challenges exist. Group visits can be a helpful way to engage patients and caregivers in identifying values and preferences for future care in a resource-efficient way. We sought to evaluate the impact of group visits for ACP among older adults with heart failure and their caregivers on ACP-related outcomes. Methods We conducted a mixed-methods pilot study evaluating the impact of an ACP group visit for older adults with heart failure and their caregivers on ACP-related outcomes including readiness and self-efficacy. The evidence-based PREPARE for Your Care video-based intervention was used to guide the group visits. Twenty patients and 10 caregivers attended one of the five 90-min group visits led by a trained facilitator. Group visit participants completed pre-, post-, and 1-month follow-up surveys using validated 5-point ACP readiness and self-efficacy scales. Qualitative feedback obtained within 3 days of a group visit was analyzed using a directed content analysis. Results Patient participants had a median age of 78 years. Approximately half were female while caregiver participants were mostly female. Participants were predominantly white. Patient readiness scores improved significantly pre-to-post (+0.53; p = 0.002) but was not sustained at 1-month follow-up. Patient and caregiver self-efficacy showed some improvement pre-to-post but was also not sustained at follow-up. Interviews revealed positive impacts of group visits across the three themes: encouraging reviewing or revisiting prior ACP activities, motivating patients to take direct steps towards ACP, and serving as a "wake-up" call to action. Conclusions Disease-focused group visits may have a short-term effect on ACP outcomes but ongoing touchpoints are likely necessary to sustain ACP over time. The results highlight a need for follow-up ACP conversations after a single group visit. Timing for follow-ups and the ideal person to follow-up ACP conversations needs to be explored.

There are few structured methods to assess a client's decisional ability, and none have been evaluated for use by Adult Protective Services (APS) workers. As part of a larger randomized-controlled trial to test the California APS Interview for Decisional Ability (IDA 3.0-CA), we sought to determine the reliability of the instrument. We assessed the extent to which trained APS personnel reached similar conclusions about a client’s decisional ability (i.e., inter-rater reliability) when presented with a client vignette and a completed IDA 3.0-CA form. First, we developed 12 client vignettes based on common client risks. Consideration was given to diversity in gender, race/ethnicity, socioeconomic status, and geography. Second, five content experts familiar with development of the tool reviewed completed IDA 3.0-CA forms for each case. Based on reported case difficulty and level of agreement between experts, eight cases were selected to formally test the instrument’s reliability. Third, 39 APS personnel, who had trained to use the IDA 3.0-CA, reviewed completed IDA 3.0-CA forms and answered questions about the clients’ decisional ability for two randomly-assigned cases. For each case, we calculated the percent correct and inter-rater reliability (Cohen’s Kappa). The percent correct ranged from 67% to 100%, with an average of 87%. The inter-rater reliability for cases ranged from -0.01 to 1.00, with the average across cases of 0.66 (i.e., substantial inter-rater reliability). The results suggest that APS personnel using the IDA 3.0-CA have a high likelihood of reaching similar conclusions about a client’s decisional ability when provided the same client responses.

Background: Advance care planning (ACP) is critical for older adults with heart failure; however, patient-level and clinician-level barriers exist. Although a group visit (GV) approach to engage patients in ACP has proven effective among general geriatric populations, little is known about clinician perceptions/likelihood of referral. Methods: Qualitative study to understand clinician perspectives on GVs for ACP among older adult patients with heart failure and caregivers. Twenty physicians and advance practice providers participated in telephone-based interviews guided by a semistructured research protocol. Transcripts were analyzed using a grounded theory approach. Results: Results highlight variability in clinician engagement in ACP but greater agreement around the factors that prompt discussions. Qualitative themes included (1) inherent properties of GVs (characteristics that make GVs ideal for most but less ideal for some, risk-to-benefit ratio); (2) purpose of GVs (general education, “priming the pump” for subsequent discussions, providing tools for action); and (3) format and procedures for GVs (inclusion/exclusion considerations, organizing by unifying characteristic, link back to clinicians). Conclusions: This is the first study to gain clinician insights into ACP GVs specific to patients and caregivers affected by heart failure. Results shed light on an important topic and suggest key considerations for conducting GVs for ACP.

© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society Ten percent of older adults experience elder mistreatment, and it is much more common in older adults with dementia. It is associated with higher rates of psychological distress, hospitalization, and death and, in the United States, costs billions of dollars each year. Although elder mistreatment is relatively common and costly, it is estimated that fewer than 10% of instances of elder mistreatment are reported. Given these data, there is a great need for research on interventions to mitigate elder mistreatment and for a practical model or framework to use in approaching such interventions. Although many theories have been proposed, adapted, and applied to understand elder mistreatment, there has not been a simple, coherent framework of known risk factors of the victim, perpetrator, and environment that applies to all types of abuse. This article presents a new model to examine the multidimensional and complex relationships between risk factors. Theories of elder mistreatment, research on risk factors for elder mistreatment, and 10 years of experience of faculty and staff at an Elder Abuse Forensics Center who have investigated more than 1,000 cases of elder mistreatment inform this model. It is hoped that this model, the Abuse Intervention Model, will be used to study and intervene in elder mistreatment.

As our country increases our capacity to provide quality interprofessional geriatric medical care to older adults, we find challenges that are unique to the setting. Many older adults receive care in Federally Qualified Healthcare Centers where implementing Age-Friendly Care is critical. Implementing the 4M’s in this setting has specific challenges including lack of geriatric trained staff, staff turnover, leadership engagement and financial sustainability. When implementing Age-Friendly Care within a large-scale complex academic health system, equally difficult challenges surface. With less nimble infrastructures, changes in one service area can have a domino effect and create larger barriers in other parts of the system. Instituting the 4M’s in an academic health system environment requires a careful strategic approach and support from many areas of organizational leadership. This talk will focus on strategies to anticipate and adapt implementation plans to best address barriers that are unique to the setting.

Throughout the country, access to professional capacity assessments is inconsistent. Capacity assessments are often a critical factor in case management of elder abuse investigations. This unmet need for many Adult Protective Services (APS) programs hampers their ability to protect older adults from mistreatment and preserve self-determination when appropriate. In June 2019, electronic surveys regarding access to capacity assessments were sent to APS leadership in all 58 California counties. A similar survey is planned for each US state in June 2020. In California, with 100% response rate, 53% of counties had no access to assessments and 56.1% had no funding for assessments. Most assessments were completed by physicians or psychologists. Seventy-three percent of counties reported that primary care physicians complete requests for capacity declarations less than half the time. Physicians decline to complete capacity declarations because they don’t know how to do the assessments (22.4%) and are concerned about being called into court (28.5%). Findings from the national survey will be presented along with maps illustrating capacity assessment accessibility. Factors that appear to influence accessibility positively (forensic centers) and negatively (lack of funding and lack of trained evaluators) will be discussed along with policy implications.

By U.S. Centers for Disease Control and Prevention estimates, the number of older adults with Alzheimer’s Disease and related dementias (ADRD) is expected to increase 278% by 2060 to affect approximately 13.9 million individuals. Research is needed to not only improve understanding and treatment of ADRD but to also study its effect on the physical, emotional, and psychological well-being of persons with dementia (PWD) and their care partners (CP). However, due to the diminishing cognitive and functional capacities of PWDs associated with the progression of ADRD over time, research efforts are sometimes hampered by a plethora of potential scientific, logistical, ethical, and emotional barriers. This session will introduce an educational approach used to train students who are interested in conducting in-home research among PWDs and their CPs and share lessons learned through the program’s pilot training of undergraduate and graduate students (N=6). Through didactic training, role-playing exercises, and experiential learning processes, trainees are equipped to accompany research project interviewers into the homes of PWD and assist in implementing research protocols. Students receive extensive training in the disease trajectories of ADRD, the impacts of disease on PWDs and their CPs, ways to communicate and interact with PWDs, best practices in promoting the protection and autonomy of human subjects with dementia, and approaches to obtaining quality data for research.

Elder abuse is a significant societal and public health concern that has been associated with a loss of financial independence, reduced overall well-being, and higher rates of mortality. Dementia and cognitive impairment are the most salient risk factors for elder abuse. Clinical neuropsychologists may be the first clinical providers that are able to determine whether an older adult is being abused or at risk of being abused and thus have a unique opportunity to intervene and address this devastating problem. To this end, this chapter will describe the various forms that elder abuse may take, provide recommendations for elder abuse screening specifically within the context of the neuropsychological evaluation, and provide guidelines for reporting of elder abuse that will maximize the chances of having a positive outcome for the patient.

The National Collaboratory to Address Elder Mistreatment developed a streamlined care model for addressing elder mistreatment in emergency department settings. This presentation will describe the core elements of the care model as well as present methods and findings related to prototyping and feasibility testing. The care model was developed based on findings from an environmental scan and formative research interviews to promote triaging older patients based on their level of risk. Tools developed to facilitate improved practices include an emergency department assessment profile, a training curriculum, as well as guidelines for screening, intervention, follow-up and collaboration with community resources. The authors used results from feasibility testing of the core elements with community partners to refine the elements and revealed key considerations for implementation. Authors will discuss the development of the core elements, including results from prototype testing and clinical partner feedback.

Elder mistreatment (EM) is a public health problem that is rarely recognized or addressed in emergency departments (ED) where a lack of evidence-based protocols leave clinicians to rely on intuition and inconsistent action plans. In this presentation we will share findings from focus groups and online surveys with ED clinicians and administrators to evaluate the perceived value and likelihood of adopting the National Collaboratory’s third core element: the EM Screening and Response Protocol (EM-SAR). Results indicated a strong support for the EM-SAR tool in general and highlighted specific considerations for refining the tool. Considerations include resistance to adding to the ED workload, need to clarify roles and responsibilities for administering the tool, hesitancy to rely on clinical judgement to assess EM, concerns over Adult Protective Services’ ability to respond to increased reports, and a desire for cross-training and cooperation. These findings and implications for ongoing feasibility testing will be discussed.

The aging population requires a health care workforce that is trained to meet the varying needs of this population. Competency in gerontology and geriatrics is now required in all accredited health professional training programs. Patient-centered and team care are two core concepts for the care of older adults. Interprofessional education (IPE), where students learn together, is essential for developing improved communication between health professionals and better care outcome for older adults. Thus, IPE is an ideal training vehicle for improving health care for older adults. Three separate IPE programs – Student Senior Partnership Program (SSSP), Interprofessional Geriatric Curriculum (IPGC) and Geriatric Assessment Program (GAP) that involve students from up to 8 health professional programs (dentistry, occupational therapy, medicine, PA, pharmacy, physical therapy, psychology and social work) at one university that focus on care of older adults will be described. Similarities and differences in the older adult population and the curriculum content of each program will be presented. Outcomes from common measures used to assess changes in knowledge and attitude about aging and about team care among students participating in each program and across multiple program experiences have been positive. Lessons learned in the course of development and refinement of each program, limitations of current assessment tools and potential measures to address these as the programs evolve and improve will be discussed.

Adult Protective Services (APS) workers assess clients for abuse and neglect and are asked to determine the client’s understanding of risks they face. Yet, APS workers have little structured training in how to make such judgements. The Interview for Decisional Abilities (IDA 3.0-CA) is a tool designed for use by APS workers to assess the ability of suspected victims of elder mistreatment to make decisions about the risks they face. This study evaluates the impact of training and use of this tool on the knowledge, experiences and ability of APS workers to determine decisional ability. APS workers and supervisors were recruited from central and northern California APS programs and randomized into either control (n=94) or IDA 3.0-CA training groups (n= 95). Baseline surveys measure knowledge of, and experiences with, assessing decisional ability and determining next steps for case management. Additionally, respondents determine the decisional ability of three case scenarios. Three months post-training, controls and trained subjects complete the same survey with a new set of cases. Preliminary results at baseline indicate there were no statistically-significant differences between trained subjects (n=42) and controls (n=50) in their knowledge scores (78.6% correct vs. 81.0%, p=0.6641) or performance assessing decisional ability in the case scenarios (60.1% correct vs. 63.3%, p=0.3497). Reported experiences assessing decisional ability and determining next steps in case management were also similar for trained subjects and controls. Complete results will be presented regarding change in knowledge scores, experiences, and assessing decisional ability in case scenarios compared across trained subjects and controls.

Multidisciplinary teams are a cornerstone intervention in the elder abuse field, but the prevalence and effectiveness of different MDT models in the U.S remains unknown. In this study, we surveyed 508 elder abuse-related professionals across the country on their knowledge of existing elder abuse MDTs and networks. Preliminary findings show that elder abuse MDTs focus most on financial exploitation (90.8% of teams), followed by physical abuse (83.58%) and neglect by other (81.59%). The most common perceived barrier to MDTs was funding/resources (35.8% of teams), followed by time commitment (30.56%) and agency engagement (22.84%). As the first study to identify the prevalence and perceptions of different elder abuse MDT models, this research can be used to inform policy makers on effective elder abuse interventions and identify gaps to be filled through policy action.

This article describes the clinical work that three sets of geriatricians and psychologists provided in three elder abuse forensic centers in California. After a brief history of how the clinical services in each program developed, the contributions of geriatricians and psychologists within these elder abuse teams are detailed through the use of several case anecdotes. Beyond providing physical and psychological evaluations, geriatricians and psychologists provide consultations and education to other professionals and to elder abuse victims and their caregivers. These clinical teams emphasize the importance of conducting home visits and functional assessments, working with interdisciplinary team members, and providing expert testimony.

Exhaled breath condensate (EBC) analyses promise simple and noninvasive methods to measure airway biomarkers but pose considerable methodological challenges. We utilized mass spectrometry to measure EBC purine biomarkers adenosine and AMP plus urea to control for dilutional variability in two studies: 1) a cross-sectional analysis of 28 healthy, 40 cystic fibrosis (CF), and 11 asthmatic children; and 2) a longitudinal analysis of 26 CF children before and after treatment of a pulmonary exacerbation. EBC adenosine, AMP, and urea were readily detected and quantified by mass spectrometry, and analysis suggested significant dilutional variability. Using biomarker-to-urea ratios to control for dilution, the EBC AMP-to-urea ratio was elevated in CF [median 1.3, interquartile range (IQR) 0.7–2.3] vs. control (median 0.75, IQR 0.3–1.4; P < 0.05), and the adenosine-to-urea ratio was elevated in asthma (median 1.5, IQR 0.9–2.9) vs. control (median 0.4, IQR 0.2–1.6; P < 0.05). Changes in EBC purine-to-urea ratios correlated with changes in percent predicted forced expiratory volume in 1 s (FEV1) ( r = −0.53 AMP/urea, r = −0.55 adenosine/urea; P < 0.01 for both) after CF exacerbation treatment. Similar results were observed using dilution factors calculated from serum-to-EBC urea ratios or EBC electrolytes, and the comparable ratios of EBC electrolytes to urea in CF and control (median 3.2, IQR 1.6–6.0 CF; median 5.5, IQR 1.4–7.7 control) validated use of airway urea as an EBC dilution marker. These results show that mass spectrometric analyses can be applied to measurement of purines in EBC and demonstrate that EBC adenosine-to-urea and AMP-to-urea ratios are potential noninvasive biomarkers of airways disease.

Resisting the bactericidal activity of naturally occurring antibodies and complement of normal human serum is an important element in the evasion of innate immunity by bacteria. In the gram-negative mucosal pathogen Haemophilus ducreyi , serum resistance is mediated primarily by the trimeric autotransporter DsrA. DsrA also functions as an adhesin for the extracellular matrix proteins fibronectin and vitronectin and mediates attachment of H. ducreyi to keratinocytes. We sought to determine the domain(s) of the 236-residue DsrA protein required for serum resistance and extracellular matrix protein binding. A 140-amino-acid truncated protein containing only the C-terminal portion of the passenger domain and the entire translocator domain of DsrA exhibited binding to fibronectin and vitronectin and conferred serum resistance to an H. ducreyi serum-sensitive strain. A shorter DsrA construct consisting of only 128 amino acids was unable to bind to extracellular matrix proteins but was serum resistant. We concluded that neither fibronectin binding nor vitronectin binding is required for high-level serum resistance in H. ducreyi .

Chancroid, caused by the gram-negative bacterium Haemophilus ducreyi (for reviews, see references 2, 47, and 60), is one of the sexually transmitted genital ulcer diseases. Although outbreaks are more prevalent in developing countries, sporadic outbreaks have occurred in the United States. Up to 50% of patients visiting sexually transmitted disease clinics in sub-Saharan Africa may have chancroid (12, 23). Additionally, it is an independent risk factor for the heterosexual transmission of human immunodeficiency virus (HIV) (34; F. A. Plummer, M. A. Wainberg, P. Plourde, P. Jessamine, L. J. DCosta, I. A. Wamola, and A. R. Ronald, Letter, J. Infect. Dis. 161:810-811, 1990); therefore, the interest in chancroid has recently intensified. In the last 10 years, several laboratories have begun to define the molecular biology of this pathogen. The study of virulence factors, the body's immune response to infection, and potential vaccines for H. ducreyi have all made significant contributions to the understanding of this bacterium (3-10, 13-16, 22, 24, 26-28, 32, 33, 36, 38, 39, 46, 50, 53, 54, 59, 61, 64). With the genome sequence completed, the process of annotation will, undoubtedly, further accelerate progress on this strictly human pathogen (www.microbial-pathogenesis.org). At present, there are several laboratory methods for the diagnosis of chancroid, including Gram stain, culture, and PCR. Various rates of sensitivity have been reported for the Gram stain, all approximating 50% (51, 57). The presence of other organisms in the polymicrobial chancroid ulcer reduces the specificity of the Gram stain, as these bacteria may be confused with H. ducreyi morphologically, especially by inexperienced personnel. Thus, the Gram stain has little clinical utility in the diagnosis of chancroid. Before the advent of reliable PCR methods, culture was the widely accepted standard of laboratory diagnosis (43, 57). H. ducreyi is a fastidious bacterium that has an absolute requirement for heme because it lacks a heme biosynthetic pathway (60); therefore, use of a special medium is required. Many strains require the addition of fetal bovine serum for growth. Furthermore, H. ducreyi requires a CO2 or microaerophilic atmosphere, and its optimal growth temperature (33°C) is lower than those of most human pathogens, mandating an additional dedicated incubator if it is to be routinely cultured. On primary isolation, small colonies of H. ducreyi usually appear after 2 to 3 days of incubation. Because ulcers are often secondarily contaminated with other more rapidly growing bacteria, cultures can be lost due to contamination (41). Culture is relatively insensitive, with the sensitivity ranging between 56 and 84% (25). The use of more than one primary isolation medium improves isolation rates, but not substantially (25). Culture is thought to be 100% specific; however, traditional biochemical identification of a presumptive H. ducreyi isolate is problematic due to its relative biochemical inertness. Furthermore, H. ducreyi fails to grow on standard biochemical media used to test other bacteria. Thus, for culturing, optimum sensitivity and specificity require microbiologists with specific training and experience with H. ducreyi. Such personnel are lacking both in underdeveloped areas where the organism is endemic and in developed countries such as the United States where it is not endemic. Two advantages that culture offers are the abilities to perform sensitivity testing of isolates and strain typing for epidemiological studies. Despite its limitations, culture will remain a valuable tool in the future. As technology has improved, PCR has become the most sensitive method for the diagnosis of chancroid (19, 40, 44, 58; K. A. Orle et al., Abstr. 94th Gen. Meet. Am. Soc. Microbiol. 1995, abstr. C-247, p. 43, 1995). It has a sensitivity approaching 100%. Although some surmise that false-positive results occur, this has been very difficult to prove. To date, PCR studies are done in laboratories remote from the clinic setting and therefore are not useful for establishing a diagnosis in a time frame that would benefit patient treatment. At present, multiplex PCR is not available for commercial use; rather, it is used for limited research purposes only. The need to maintain trained personnel to perform and interpret cultures and PCR in the resource-poor settings where chancroid is endemic makes these tests economically prohibitive. Furthermore, the costs of media, equipment, and reagents for culture and PCR are considerable. Because of these limitations, culture and PCR in their current formats are not suitable for on-site, immediate detection of H. ducreyi in clinical specimens in areas where the organism is endemic. Therefore, a stable, inexpensive, and rapid test that is simple to perform and interpret at the bedside would be a valuable tool in chancroid control, so long as it maintains its sensitivity and specificity. The immunochromatography (IC) test described in this report is based on novel monoclonal antibodies (MAbs) to the hemoglobin receptor, HgbA, which is an abundant outer membrane protein (OMP) that is required for the acquisition of heme from hemoglobin (26, 27; C. Elkins, unpublished data, 1999). The ability of H. ducreyi to obtain heme from hemoglobin is required for pustule formation. An isogenic hgbA mutant which is unable to utilize hemoglobin was unable to form pustules in a human experimental model of infection (5). As HgbA is conserved in geographically diverse isolates, we developed an IC test based on these MAbs to this protein. In the present report, we describe progress in the initial development of a rapid diagnostic test for H. ducreyi.

The Administration for Community Living awarded five cooperative agreements to support elder abuse prevention initiatives. This symposium describes findings from four of those agreements.

Haemophilus ducreyi is unable to synthesize heme and must acquire it from its only known host, humans. We cloned and sequenced a gene encoding an outer membrane receptor for heme. It was designated tdhA (for TonB-dependent heme receptor A) since it was related by sequence homology to the family of TonB-dependent receptors. TdhA was strikingly similar to open reading frame HI0113 from the genome of Haemophilus influenzae Rd and also shared homology with five other heme receptors, including HxuC, HemR, HmuR, ChuA, and ShuA, from gram-negative bacteria. An Escherichia coli hemA tonB mutant strongly expressing H. ducreyi tdhA grew on low levels of heme as a source of heme only when an intact H. ducreyi Ton system plasmid was present, formally demonstrating functional TonB dependence. tdhA was expressed poorly in vitro by H. ducreyi and only under conditions of heme limitation. A survey of H. ducreyi revealed that all tested strains but one synthesized small amounts of TdhA in vitro under heme-limiting conditions. Surprisingly, an isogenic mutant of tdhA as well as its parent, 35000, both required the same high levels of heme for growth (50 μg/ml [77 μM] on agar medium). This result, together with previous findings, suggests that in vitro, the uptake of heme by H. ducreyi is mediated by a TonB- and TdhA-independent mechanism, possibly diffusion.

Measurement of exhaled breath condensate (EBC) biomarkers offers a noninvasive means to assess airway disease, but the ability of EBC biomarkers to track longitudinal changes in disease severity remains unproven. EBC was collected from pediatric patients with cystic fibrosis (CF) during regular clinic visits over 1 yr. EBC biomarkers urea, adenosine (Ado), and phenylalanine (Phe) were measured by mass spectrometry, and biomarker ratios were used to control for variable dilution of airway secretions. EBC biomarker ratios were assessed relative to lung function in longitudinal, multivariate models and compared with sputum inflammatory markers and quality of life assessment (CFQ-R). EBC was successfully analyzed from 51 subjects during 184 visits (3.6 ± 0.9 visits per subject). EBC Ado/urea ratio was reproducible in duplicate samples ( r = 0.62, P < 0.01, n = 20) and correlated with sputum neutrophil elastase (β = 2.5, P < 0.05). EBC Ado/urea correlated with the percentage predicted of forced expiratory volume in 1 s in longitudinal, multivariate models (β = −2.9, P < 0.01); EBC Ado/Phe performed similarly (β = −2.1, P < 0.05). In contrast, IL-8 and elastase measured in spontaneously expectorated sputum ( n = 57 samples from 25 subjects) and the CFQ-R respiratory scale ( n = 90 tests from 47 subjects) were not significantly correlated with lung function. EBC was readily collected in a clinic setting from a wide range of subjects. EBC Ado tracked longitudinal changes in lung function in CF, with results similar to or better than established measures.

HgbA is the sole TonB-dependent receptor for hemoglobin (Hb) acquisition of Haemophilus ducreyi . Binding of Hb to HgbA is the initial step in heme acquisition from Hb. To better understand this step, we mutagenized hgbA by deletion of each of the 11 putative surface-exposed loops and expressed each of the mutant proteins in trans in host strain H . ducreyi FX547 hgbA . All mutant proteins were expressed, exported, and detected on the surface by anti-HgbA immunoglobulin G (IgG). Deletion of sequences in loops 5 and 7 of HgbA abolished Hb binding in two different formats. In contrast, HgbA proteins containing deletions in the other nine loops retained the ability to bind Hb. None of the clones expressing mutant proteins were able to grow on plates containing low concentrations of Hb. Previously we demonstrated in a swine model of chancroid infection that an HgbA vaccine conferred complete protection from a challenge infection. Using anti-HgbA IgG from this study and the above deletion mutants, we show that loops 4, 5, and 7 of HgbA were immunogenic and surface exposed and that IgG directed against loops 4 and 5 blocked Hb binding. Furthermore, loop 6 was cleaved by protease on intact H . ducreyi , suggesting surface exposure. These data implicate a central domain of HgbA (in respect to the primary amino acid sequence) as important in Hb binding and suggest that this region of the molecule might have potential as a subunit vaccine.

We have identified an 85-kDa outer membrane protein that is expressed by all tested strains ofHaemophilus ducreyi. Studies of related proteins from other pathogenic bacteria, includingHaemophilus influenzae, Pasteurella multocida, Neisseria gonorrhoeae, Neisseria meningitidis, andShigella dysenteriae, suggested a role for these proteins in pathogenesis and immunity. In keeping with the first such described protein fromHaemophilus influenzaetype B, we termed theH. ducreyiprotein D15. The gene encoding theH. ducreyiD15 protein was cloned and sequenced, and the deduced amino acid sequence was found to be most similar to sequences of the D15-related proteins from otherPasteurellaspp. The arrangement of the flanking genes was similar to that ofH. influenzaeRd and suggested that D15 was part of a multigene operon. Attempts to make a null mutation of the D15 gene were unsuccessful, paralleling results in other D15 gene studies. Overexpression ofH. ducreyiD15 inEscherichia coliresulted in a source of recombinant D15 (rD15) from which it was readily purified. rD15 was immunogenic, and it was found that immunization of rabbits with an rD15 vaccine preparation conferred partial protection against a virulent challenge infection. Antisera to an N-terminal peptide recognized all tested strains ofH. ducreyi.

We developed a new enzyme immunoassay (rpEIA) for use in determining the seroprevalence of chancroid. Three highly conserved outer membrane proteins from Haemophilus ducreyi strain 35000 were cloned, overexpressed, and purified from Escherichia coli for use as antigens in the rpEIA. Serum specimens from patients with and without chancroid were assayed to determine optimum sensitivity and specificity and to establish cutoff values. On the basis of these data, rpEIA was found to be both sensitive and specific when used to test a variety of serum specimens from patients with genital ulcers and urethritis and from healthy blood donors.

By cloning into Escherichia coli and construction of isogenic mutants of Haemophilus ducreyi , we showed that the hemoglobin receptor (HgbA) is TonB dependent. An E. coli hemA tonB mutant expressing H. ducreyi hgbA grew on low levels of hemoglobin as a source of heme only when an intact H. ducreyi Ton system plasmid was present. In contrast, growth on heme by the E. coli hemA tonB mutant expressing hgbA was observed only at high concentrations of heme, was TonB independent, and demonstrated that H. ducreyi HgbA was not sufficient to function as a typical TonB-dependent heme receptor in E. coli . Allelic replacement of the wild-type H. ducreyi exbB , exbD , and tonB loci with the exbB , exbD , and tonB deletion resulted in an H. ducreyi isogenic mutant unable to utilize hemoglobin but able to utilize hemin at the same levels as the parent strain to fulfill its heme requirement. This finding confirms the TonB dependence of HgbA-mediated hemoglobin utilization and suggests that uptake of hemin in H. ducreyi is TonB independent. Additionally, the H. ducreyi Ton system mutant synthesized increased amounts of HgbA and other heme-regulated outer membrane proteins, consistent with derepression of these proteins due to lower intracellular heme and/or iron concentrations in the mutant. Sequencing of the Ton system genes revealed that the arrangement of the genes was exbB exbD tonB . The proximity and structure of these genes suggested that they are transcribed as an operon. This arrangement, as well as the DNA and deduced amino acid sequences of these H. ducreyi genes, was most similar to those from other pasteurellae.