Urinary Antigen Assay Research Articles

Histoplasma capsulatum urinary antigen detection in a kidney transplant recipient with acute paracoccidioidomycosis: Case study and literature review.

Paracoccidioidomycosis (PCM) and histoplasmosis are endemic fungal diseases in South America. Both can lead to lung involvement with fungal dissemination progressing to systemic and severe clinical manifestations, especially in immunosuppressed hosts. As the population of immunosuppressed individuals has been rising, a higher occurrence of fungal infections is predicted in this setting. This poses challenges regarding the differential diagnosis due to overlapping clinical and laboratorial findings, hampering the management of cases. In this study, the authors discuss the occurrence of a false-positive Histoplasma urinary antigen detection in a kidney transplant recipient with acute PCM. Given the scarce information about this subject, a review on literature data is provided. A comprehensive literature search was conducted to investigate previous studies that found cross-reactivity between Histoplasma urinary antigen assays in human patients with confirmed diagnosis of PCM. Additionally, an update of PCM in transplant recipients is provided. The included studies reported 120 samples from patients with PCM tested for Histoplasma antigen, presenting an overall cross-reactivity of 51.67% and 17 cases of PCM in transplant recipients. CONCLUSIONS: The galactomannan urinary antigen developed to diagnose histoplasmosis can cross react with PCM, which may represent a concern in countries where both mycoses overlap.

Comparison of a Urine Antigen Assay and Multiple Examinations with the Formalin-Ethyl Acetate Concentration Technique for Diagnosis of Opisthorchiasis.

Detection of worm antigen in urine is a sensitive diagnostic method for opisthorchiasis, particularly for light-intensity infections; however, the presence of eggs in feces is essential for validating results from the antigen assay. To address the issue of low sensitivity of fecal examination, we modified the protocol for the formalin-ethyl acetate concentration technique (FECT) and compared it against urine antigen measurements for detection of the parasite Opisthorchis viverrini. First, we optimized the FECT protocol by increasing the number of drops for examinations from the standard two drops to a maximum of eight. We were able to detect additional cases after examination of ≥ 3 drops, and the prevalence of O. viverrini saturated after examination of ≥ 5 drops. We then compared the optimized FECT protocol (examining five drops of suspension) against urine antigen detection for the diagnosis of opisthorchiasis in field-collected samples. The optimized FECT protocol detected O. viverrini eggs in 25 of 82 individuals (30.5%) who had positive urine antigen tests but were fecal egg negative by the standard FECT protocol. The optimized protocol also retrieved O. viverrini eggs in 2 of 80 antigen-negative cases (2.5%). In comparison with the composite reference standard (combined FECT and urine antigen detection), the diagnostic sensitivity of examining two and five drops of FECT and the urine assay was 58.2, 67, and 98.8%, respectively. Our results show that multiple examinations of fecal sediment increase the diagnostic sensitivity of FECT and thus provide further support for the reliability and utility of the antigen assay for diagnosis and screening of opisthorchiasis.

Radiographically confirmed community-acquired pneumonia in hospitalized adults due to pneumococcal vaccine serotypes in Sweden, 2016-2018-The ECAPS study.

In Sweden, pneumococcal serotype distribution in adults with community-acquired pneumonia (CAP) and potential coverage of currently licensed pneumococcal conjugate vaccines (PCVs) is unknown. During 2016-2018, patients aged ≥18 years hospitalized with radiologically confirmed (RAD+) CAP were enrolled at Skåne University Hospital in a study on the etiology of CAP in Sweden (ECAPS). Urine samples and blood cultures were collected per-protocol. Streptococcus pneumoniae (Spn) culture isolates were serotyped and urine samples tested for the pan-pneumococcal urinary antigen (PUAT) and multiplex urine antigen detection (UAD) assay, detecting 24 serotypes. Analyses included 518 participants with RAD+CAP; 67.4% were ≥65 years of age, 73.4% were either immunocompromised or had an underlying chronic medical condition. The proportion of CAP due to Spn identified by any method was 24.3% of which 9.3% was detected by UAD alone. The most frequently identified serotypes were 3 (26 cases, 5.0% of all CAP), and 8, 11A and 19A (10 cases each, 1.9%). In individuals aged 18-64 and ≥65 years, respectively, PCV20 serotypes contributed to 35 of 169 (20.7%) and 53 of 349 cases of all CAP (15.2%), and PCV13 serotypes caused 21 of 169 (12.4%) and 35 of 349 (10.0%) cases. PCV15 coverage was 23 of 169 (13.6%) and 42 of 349 (12.0%) in individuals aged 18-64 and ≥65 years, respectively. Overall, PCV20 increases the coverage of all CAP from 10.8% (PCV13) to 17.0%. Compared to earlier pneumococcal vaccines, PCV20 expands the coverage of all-cause CAP. Routine diagnostic tests underestimate the proportion of CAP caused by Spn.

Synopsis.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer worldwide. Despite the severity of the disease and its impact on individuals, families, and communities, there remains an overall lack of awareness and interest in this disease. The information contained in the chapters of this book shows that this is indeed a significant public health and socioeconomic problem with varying levels of country-specific awareness. In Southeast Asia liver fluke, O. viverrini related CCA is endemic with the highest incidence worldwide in northeast Thailand, yet it is treatable and preventable. The chapters highlight significant advances in our knowledge of the biology and epidemiology of the O. viverrini species complex, intermediate hosts, systematics, population genetics, and the complexity of the three-host life cycle. A comprehensive conceptual framework has been developed to assist in understanding the complexity of molecular mechanisms of CCA carcinogenesis and cancer development which can result in improvement of targeted CCA therapy. There have been many advances in understanding the pathology of CCA in the biliary tract, including advances in prognosis and molecular pathogenesis. The development of different modalities and their advantages for diagnosis have increased diagnostic accuracy, providing reliable information allowing appropriate treatment and management programs to be selected for each patient. Particularly exciting is the recent development of a urine antigen assay which has revolutionized the diagnostic approach of opisthorchiasis due to its simplicity, the non-invasive nature of sample collection, and its ease of use in field settings. Significant in-roads and advances have been made in the surgical and systemic treatment of CCA patients. Additionally, a sophisticated data collection and analysis system, the Isan Cohort, has been developed and established for the treatment and control of CCA. Importantly, a greater understanding has been made of the social, community, religious, and anthropological issues initiating and sustaining the eating behavior of raw, partially cooked, and/or fermented fresh water fish. Specially designed education programs/curricula, based on currently available multidisciplinary hard data targeting school children, have been introduced since the inception of the Cholangiocarcinoma Screening and Care Program (CASCAP) and the subsequent strategic Fluke Free Thailand Model. The education program is being expanded to other provinces in Thailand and in the near future to other Southeast Asian countries, initially to Lao PDR, where the Fluke Free Lao PDR program has already been implemented. Despite advances that have been made in many disciplines focused on O. viverrini related CCA, raising awareness of CCA at all levels, particularly across endemic regions, is still needed, as is raising the awareness of CCA globally. As parasites and parasite related diseases have no borders, it is critical that an effective common strategic plan is instigated and established between all countries where liver fluke, O. viverrini related CCA is a significant public health problem, thereby increasing the quality of life and life expectancy of millions of people who suffer from this insidious disease.

Diagnostic Performance of Streptococcus pneumoniae Urinary Antigen Assay: A Cross-sectional Study on Comparative Analysis of Bacterial Culture and Molecular Detection in Pneumococcal Infections

Introduction: Pneumonia is the most prevalent infection worldwide, leading to hospitalisation and contributing to mortality rates. Among the bacterial agents associated with CommunityAcquired Pneumonia (CAP), Streptococcus pneumoniae remains the most common. Conventional microbiological diagnostic tests have various limitations, including issues with sample collection, prior antibiotic administration, and delayed specimen transport. Urinary Antigen Testing (UAT) shows promise in rapidly identifying the causative agent of CAP, allowing for targeted therapy. Aim: To evaluate the diagnostic accuracy of the pneumococcal UAT in identifying CAP. Materials and Methods: A cross-sectional analytical study was conducted over a period of one year from June 2022 to May 2023 at SRM Medical College Hospital and Research Centre, Kattankulathur, Chengalpattu, Tamil Nadu, India. A total of 38 patients (>18 years of age) with clinically suspected CAP and who satisfied the clinical criteria for CAP were recruited for the study. Respiratory specimens were subjected to bacterial culture, real-time Polymerase Chain Reaction (PCR), and UAT using the Fluorescent Immunoassay (FIA) to detect Streptococcus pneumoniae. The sensitivity, specificity, positive and negative predictive values, and accuracy of the pneumococcal UAT for detecting CAP were assessed. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software, version 21.0. Results: The study revealed a female predominance 22 (57.89%). Bacterial culture and real-time PCR identified 7 (18.42%) of patients with S. pneumoniae, while the UAT only detected 1 (2.63%). The pneumococcal UAT showed low sensitivity (14.29%), high specificity (100%), and satisfactory accuracy (84.21%). Conclusion: The pneumococcal UAT, with its straightforward technology, ease of use, rapid results, non invasive approach, cost-effectiveness, and high specificity and accuracy, could be favoured over bacterial culture and molecular techniques for ruling out CAP.

2175. Diagnostic Utility of Pneumococcal Urinary Antigen Assay in Clinical Practice: a Retrospective Study in a Community Hospital in Evanston, Illinois

Abstract Background While the pneumococcal urine antigen test (PUAT) is a validated tool for diagnosing pneumonia, recent evidence suggested lower sensitivity than expected (approximately 60-65%) and limited impact on clinical outcomes. A lack of clinical indicators for a positive test result and the absence of clear recommendations based on high-quality evidence create grounds for potential test misuse in real practice. Methods We performed a Workbench report to retrieve individual orders of Streptococcus pneumoniae urine antigen test (BinaxNOWTM) from our community hospital in Evanston, Illinois, between January 1, 2011, and December 31, 2021. We then identified patients with or without clinical pneumonia based on McGeer criteria: new infiltrates on chest x-ray plus cough, shortness of breath, oxygen saturation < 94%, or respiratory rate ≥ 25 plus fever, leukocytosis, or altered mental status. Results Among 8,110 individuals tested for PUAT, only 273 positive results were identified (3.36%); of those, 83 (30.4%) did not meet criteria for clinical pneumonia (Figure 1). The median age of patients in a group with clinical pneumonia and without was 67 and 69 years, respectively. The prevalence of diabetes mellitus, COPD/asthma, and immunosuppression was not statistically significant between groups (Table 1). The signs and symptoms are presented in Table 2.S. pneumoniae was cultured in only 13.9% of cases in patients with clinical pneumonia, which correlates with the known sensitivities of this test (Table 3). More ICU admissions and NIPPV use were noted in patients with clinical pneumonia (p = 0.04 each). However, there was no difference in the use of antibacterial therapy among the two groups (p = 0.83), mechanical ventilation rates (p = 0.2), and length of hospital stay (p = 0.2) (Table 4). The positive predictive value of PUAT was 69% in our study (Table 5). Conclusion Our study demonstrated a low positivity rate of PUAT despite a large sample size and a significant proportion of positive test results in patients without clinical pneumonia. The widespread use of PUAT should be carefully reconsidered and applied only to a selected category of patients. Such a strategy will reduce the discrepancy between current guidelines and real-world care patterns and provide an additional benefit of cost-effectiveness. Disclosures All Authors: No reported disclosures.

Effects of day-to-day variation of Opisthorchis viverrini antigen in urine on the accuracy of diagnosing opisthorchiasis in Northeast Thailand.

Antigen detection in urine using an enzyme-linked immunosorbent assay (ELISA) is more sensitive than fecal examination for diagnosis of opisthorchiasis and for assessment of the effects of drug treatment. It is not known whether day-to-day variation of urine composition, including levels of Opisthorchis viverrini antigen, influences the urine assay. We investigated this topic with the cooperation of participants from two localities in Northeast Thailand. Project participants were screened for parasite infections for three consecutive days using the quantitative formalin-ethyl acetate concentration technique (FECT) to detect O. viverrini eggs and the urine ELISA for detection of O. viverrini antigen. A subset of participants (n = 801) with matched fecal and urine samples were analyzed for comparison of inter-day prevalence estimates and the performance of the urine assay compared against FECT for diagnosis of opisthorchiasis. The daily prevalence measured by the urine assay ranged between 29.0%-30.2% while those by FECT ranged between 11.9%-20.2%. The cumulative three-day prevalence estimate determined by the urine antigen assay was 30.3%, which was significantly higher than that by FECT (20.2%, p < 0.05). A significant positive correlation was found between the concentration of antigen in urine and fecal egg counts (p < 0.001). Overall, the urine assay had better diagnostic performance for opisthorchiasis than fecal examination by FECT. The high sensitivity plus negligible daily variation of O. viverrini antigen in urine indicates the utility of the urine assay for diagnosis, as well as population screening, of opisthorchiasis.

Application of Urine and Copro Antigen Assays after Primary Infection and Drug Treatment in an Experimental Opisthorchiasis Animal Model.

Infection by Opisthorchis viverrini causes significant health problems, including cholangiocarcinoma (CCA); thus control and elimination of this trematode is an important strategy for the reduction of CCA. Currently, urine and copro antigen detection is more sensitive than parasitological examination of the feces for the diagnosis of opisthorchiasis. Given limitations in human studies, we used an animal model to quantify the parasite antigen profiles in urine and feces in O. viverrine-infected hamsters, and postdrug treatment. The positive detections of O. viverrini antigen began from week 1 in urine and week 2 in feces after infection until week 28 of the study. The recoveries of O. viverrini worms were detected starting from week 1 and eggs of O. viverrini were detected in feces from week 3 after infection and remained detectable throughout the study period. There was a significant positive correlation of urine and copro antigen levels with the number of fecal egg counts (P < 0.01) and worm recovery (P < 0.01). In the drug-treatment experiment, treatment of infected hamsters with praziquantel significantly reduced worm burden, fecal egg output, and antigen in urine and feces compared with the untreated controls (P < 0.001). At 4 weeks posttreatment, the egg and worm reduction rates were 100% and 95.5%, respectively. The positive antigen detections in urine and feces corresponded with partial worm clearance from praziquantel treatment. This study demonstrated a direct link of urine and copro antigen tests with worms infecting the liver thereby reaffirming the reliability of urine and copro antigen assay in opisthorchiasis diagnosis.

A CASE OF MEDIASTINAL ABSCESS AS A COMPLICATION OF ENDOBRONCHIAL ULTRASOUND TRANSBRONCHIAL NEEDLE ASPIRATION

SESSION TITLE: Medical Student/Resident Procedures Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Limited literature is available regarding the clinical presentation and management of EBUS-TBNA’s complications. We report a case of mediastinal abscess post-EBUS-TBNA and discuss its management. CASE PRESENTATION: A 44 years old woman presented in 2018 with a history of chest pain radiating to her back. She immigrated to Canada in 2015 from Mauritania. She was a former smoker of 4 pack-years. Her HIV serology was negative, and she was not immunocompromised nor previously exposed to tuberculosis. Chest CT-scan revealed a 1.5cm right lower paratracheal lymphadenopathy. EBUS-TBNA was performed on April 11th, 2019. Lymph node #4R was punctured 9 times. The immediate post-procedure period was uneventful, and the patient was discharged the same day. Histopathology revealed necrotic granulomas with 3 to 5 µm yeast-like organisms on Grocott stain. No neoplastic cells were seen. Auramine, Ziehl-Nielsen and PAS diastase stains and direct M. tuberculosis PCR were negative. A presumptive diagnosis of Histoplasma lymphadenitis was made. Serum and urinary Histoplasma antigen assays sampled 2 weeks later were positive. Antifungal treatment was omitted given the spontaneous improvement in symptoms. Seven days post-procedure, the patient complained of fatigue, chills, chest pain and dyspnea. She came to the emergency department on April 26th with persistent fever (39,4°C), and odynophagia. A chest CT scan revealed an enlarged #4R node (42X26mm) with a heterogeneous content and necrotic material. Mediastinal abscess was suspected and IV piperacillin-tazobactam was initiated. She had little improvement in her chest pain at 48 hours of therapy and remained febrile. Therefore, a mediastinoscopy was done on April 28th. Peri-operative findings consisted of enlarged lymph nodes and frank mediastinal pus, which were sampled, debrided and thoroughly washed. Bacterial cultures were positive for Streptococcus anginosus and oxacillin-susceptible S. epidermidis and negative for fungi. The patient completed a 28 days regimen of piperacillin-tazobactam 4.5g IV q8h. A chest CT scan made on June 14th showed a regression of the mediastinal nodes. As of January 2020, no recurrence of mediastinitis was observed. DISCUSSION: We sought to report post-EBUS-TBNA mediastinal abscess in the context of Histoplasma lymphadenitis. Although rare, one must be aware of the presentation of post-EBUS mediastinitis which can occur from 5 days (2) up to 32 days(3) post procedure. Once mediastinal abscess is diagnosed, a treatment of IV antibiotics can be considered for mild cases but mediastinal drainage should be considered for more severe ones. CONCLUSIONS: In conclusion, we reported a case of post-EBUS-TBNA mediastinal abscess in the context of Histoplasma lymphadenitis. The combination of mediastinal drainage and IV antibiotics led to clinical remission. Reference #1: Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2007 Oct 1;45(7):807-25. Reference #2: Dai JH, Chen LL, Li H, Miao LY, Li R, Gao L, Meng FQ, Cai HR. Severe mediastinal abscess after endobronchial ultrasound with transbronchial needle aspiration. Chinese Medical Journal. 2018 Feb 5;131(3):357-58. Reference #3: Kouskov OS, Almeida FA, Eapen GA, Uzbeck M, Deffebach M. Mediastinal infection after ultrasound-guided needle aspiration. Journal of Bronchology & Interventional Pulmonology. 2010 Oct 1;17(4):338-41. DISCLOSURES: No relevant relationships by Mario Dugas, source=Web Response No relevant relationships by Sebastien Nguyen, source=Web Response No relevant relationships by Bich Nguyen, source=Web Response No relevant relationships by Marc-André Smith, source=Web Response No relevant relationships by Alexandre Tayler-Gomez, source=Web Response

Application of urine antigen assay to evaluate outcomes of praziquantel treatment and reinfection in opisthorchiasis in northeast Thailand.

A urine antigen assay was applied to evaluate chemotherapeutic outcomes and reinfection patterns of opisthorchiasis in Thailand. We used a prospective study design by following opisthorchiasis subjects at baseline and post-treatment using a urine antigen assay and faecal examination by the formalin-ethyl acetate concentration technique (FECT). The antigen of Opisthorchis viverrini in urine diminished within 4weeks after praziquantel treatment. Concurrent faecal examinations by FECT showed that faecal eggs were negative at 4weeks after treatment. In a subsequent study, reinfection rates and intensity patterns of O. viverrini were evaluated at 48weeks after praziquantel treatment. Within a group of subjects with curative treatment (n=137), 16.8% became reinfected according to FECT and 27.7% according to the urine antigen assay (p<0.05). There were significant correlations in intensity of infection between pretreatment and at 48weeks post-treatment in both faecal egg counts and antigen levels in urine. The results suggested that in addition to screening, the urine antigen assay is an efficient tool for monitoring outcomes of drug treatment and reinfection in opisthorchiasis. Due to the ease of urine sample collection and handling, the urine assay becomes an alternative method to faecal examination for diagnosis and monitoring of opisthorchiasis.

Urine Antigen Testing is Equally Sensitive to B. dermatitidis and B. gilchristii Infections.

Blastomycosis is endemic in Wisconsin with Blastomyces dermatitidis and B. gilchristii responsible for infections. Urine antigen testing is a non-invasive diagnostic method for blastomycosis with up to 93% test sensitivity. However, the test's sensitivity has not been evaluated with relationship to B. gilchristii infections. We aimed to assess physician use of the urine antigen assay and its sensitivity to B. gilchristii and B. dermatitidis infections in a retrospective study. Culture confirmed clinical cases of blastomycosis from 2008-2016 were identified within Marshfield Clinic Health System (MCHS) and UW Hospital and Clinics (UWHC) medical records. Clinical data were abstracted from each medical record and included the following: patient demographics, presence of immune compromising and underlying medical conditions, treatment drugs, presence of isolated pulmonary or disseminated disease, death, urine antigen testing, timeframe of testing, and quantitative test values (EIA units or ng/mL). A total of 140 blastomycosis cases were included in this study, with MCHS contributing 114 cases to the study and UWHC contributing 26 cases. The majority of UWHC cases (n=22; 85%) were caused by B. dermatitidis and the majority of MCHS cases (n=73; 64%) were caused by B. gilchristii. UWHC physicians were significantly more likely to treat with multiple drugs during the course of infection and were more likely to prescribe amphotericin B and voriconazole. Urine antigen testing was more frequently used at UWHC (n=24; 92%) than MCHS (n=51; 45%; P < 0.00001). In this study, the urine antigen assay demonstrated 79% sensitivity. Sensitivity was significantly associated with the timeframe of testing (P < 0.05), with most true positive urine antigen tests (83%) being performed ≤ 7 days from diagnosis. In this study, the urine antigen assay was capable of detecting both B. dermatitidis and B. gilchristii at about equal sensitivity. Urine antigen concentration (ng/mL) trended higher in B. dermatitidis infections. This study found that the urine antigen assay is capable of detecting both species of Blastomyces at about the same sensitivity. We recommend continued use of the urine antigen assay for diagnosis of blastomycosis and recommend that the assay be used early in the diagnostic process to minimize the chance of false negative results.

Diagnosis and long-term management of blastomycosis in two ferrets (Mustela putorius furo)

Abstract Background - Blastomycosis is an uncommon fungal infection endemic to certain parts of Eastern North America. Blastomycosis has been reported twice before in ferrets, but both cases died shortly after diagnosis. Case description - Two male neutered ferrets ( Mustela putorius furo ) from the same household, 4 and 1½-years of age, presented for respiratory signs. The diagnostic work-up included thoracic radiographs and ultrasound, advanced imaging, and cytology of a pulmonary mass, which led to a diagnosis of pulmonary blastomycosis in both cases. Both ferrets developed central nervous system (CNS) clinical signs. Ferret 1 developed signs referable to CNS lesions 3 months after initial presentation, and the second ferret 27 months after initial presentation. An MRI study and CSF analysis were performed on the first case. Both ferrets were treated with combinations of antifungal therapy and short-term prednisolone with a total follow-up period of 35 and 31 months respectively. Both cases responded favorably to antifungal therapy and supportive care. Response to therapy and the dynamics of infection were monitored with serial urinary Blastomyces antigen assays, thoracic radiographs, and routine bloodwork. The first ferret was euthanized three years after diagnosis due to an abdominal neoplasia. An exocrine pancreatic carcinoma, a cervical chordoma, and pulmonary blastomycosis were diagnosed on histopathology. Conclusions and case relevance - This report constitutes the first to document CNS blastomycosis in ferrets, long-term medical management of both pulmonary and suspected CNS blastomycosis in ferrets, and the use of serial urinary Blastomyces antigen assays to monitor disease progression in this species.

Comparison of Urine Antigen Assays for the Diagnosis of Histoplasma capsulatum Infection.

Urine antigen testing is a rapid sensitive method for detecting active infection with the endemic fungi Histoplasma capsulatum and Blastomyces dermatitidis. Herein, we compared the performance of the MiraVista Diagnostics (MVista) Histoplasma urine antigen assay with the Niche Diagnostics (ND) Histoplasma urine antigen assay for the detection of histoplasmosis and blastomycosis. Two hundred fifty urine samples from 234 patients previously tested by the MVista Histoplasma urine antigen assay as part of routine care were tested by the ND Histoplasma and Blastomyces urine antigen assays. The electronic medical records of all patients whose samples were tested were retrospectively reviewed to identify patients with a clinical diagnosis of and/or treatment for histoplasmosis or blastomycosis, and the diagnostic workup undertaken to support these diagnoses. The MVista and ND Histoplasma urine antigen assays were highly concordant, showing 99% overall agreement (90.5% positive agreement and 99.6% negative agreement). Three specimens collected after antifungal therapy returned discrepant results, with the MVista assay positive in 2 of these and the ND assay positive in 1; in each case, the antigen concentration was near the lower quantification limit. Both Histoplasma assays were positive in all patients with culture-proven blastomycosis (n = 3). The MVista and ND Histoplasma urine antigen assays performed similarly in identifying histoplasmosis cases encountered in routine clinical practice, with discrepancies affecting posttreatment specimens. Given the paucity of Blastomyces-positive samples, further studies are needed to better compare the utility of the MVista and ND Histoplasma urine antigen assays in diagnosing blastomycosis.

396. Clinical Features of Proven and Probable Cases of Histoplasmosis and the Role of Urinary Histoplasma Antigen Testing: A Case Series From India

BackgroundHistoplasmosis is considered uncommon in India, and the diagnosis usually depends on invasive tissue sampling. The histoplasma urinary antigen assay is a non-invasive test that has been recently introduced in India.MethodsThis was a single-centre retrospective study done from January 2013 till February 2018. Case records of patients with proven (confirmed by demonstrating intra-cellular yeast like organisms on histopathology or culture) and probable (presence of antigenuria—done by IMMY Alpha Histoplasma enzyme immunoassay) histoplasmosis were analysed.ResultsA total of 37 patients (18 proven and 19 probable) with mean age of 51.59 ± 11.17 years were studied. Diabetes was the most common co-morbidity (15 patients) followed by HIV (6), whereas no co-morbidity was found in 10 patients. Adrenals (29%), lungs (27%), lymph nodes (27%), and skin and oral mucosa (24.3%) were the most common organs involved (Figure 1). Anti-tubercular therapy based on granulomatous inflammation was given to 10 patients prior to the diagnosis. Raised GGTP and ALP (54%) and hyperglobulinemia (40%) were the common laboratory features. Most patients (83.7%) came from endemic areas (North-Eastern states, West Bengal, and Bangladesh) whereas all six cases from non-endemic areas were classified as probable (Figure 2). All-cause mortality rate was 10.8%, with 27 cases (72.9%) showing improvement at a median follow-up of 6 months. Comparison of proven and probable cases revealed that the following features were significantly higher in theprobable group: female sex (P = 0.001), coming from nonendemic areas (P = 0.009), requiring in-patient care (P = 0.001), leucocytosis (P = 0.043), absence of skin and oral mucosal findings (P = 0.002), simultaneous alternate diagnosis (P = 0.039), and death (P = 0.039).ConclusionThis study emphasises that histoplasmosis is an under recognised entity in India. Histoplasma antigenuria does help in making the diagnosis easily and needs to be more extensively utilized by clinicians. However, it can yield false-positive results in patients belonging to nonendemic areas and lacking typical clinical features of histoplasmosis. Further studies are needed to determine the utility of the antigen test in Indian settings.Figure 1.Distribution of involved organs.Figure 2.Distribution of cases in the study across Indian states.Disclosures All authors: No reported disclosures.

Recent Advances in the Diagnosis and Detection of Opisthorchis viverrini Sensu Lato in Human and Intermediate Hosts for Use in Control and Elimination Programs.

Opisthorchiasis is a neglected tropical disease, caused by infection with the fish-borne trematode Opisthorchis viverrini sensu lato that afflicts more than 10million people in Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The disease is characterized by a chronic infection that induces hepatobiliary inflammation, especially periductal fibrosis, which can be detected by ultrasonography. This chronic inflammation eventually leads to cholangiocarcinoma (CCA), a usually fatal bile duct cancer that develops in approximately 1% of O. viverrini-infected individuals. In Thailand alone, CCA kills up to 20,000 people every year and is therefore of substantial public health importance. Its socioeconomic impacts on impoverished families and communities are considerable. To reduce O. viverrini-associated morbidity and CCA, the primary intervention measures focus on opisthorchiasis control and elimination. Accurate diagnoses of O. viverrini infection, in both mammalian, snail and fish intermediate hosts, are important for achieving these goals. Despite extensive efforts over several decades to find sensitive and specific diagnostics for opisthorchiasis, a simple and robust diagnostic method is still required. Here we review earlier and current developments in the search for new diagnostics for opisthorchiasis, with practical applications in the research laboratory, the clinic and the field. Of the methods currently available, the urine antigen assay shows considerable potential for the diagnosis and screening of opisthorchiasis. Nevertheless, these new assays require validation, determination of their cost-effectiveness when applied for mass screening in an endemic setting in support of policy decisions for national public health programs aimed at the control and elimination of opisthorchiasis.

Community-acquired Legionnaires' disease at a medical center in northern Taiwan.

Legionella pneumophila had been recognized as an important pathogen for community-acquired pneumonia. We aimed to investigate clinical features and outcomes of patients with Legionnaires' disease at a tertiary medical center in northern Taiwan. From June 2012 to February 2017, a retrospective review of adult community-acquired. Legionnaires' disease at a medical center was conducted. All Legionella infections were confirmed by positive urinary Legionella antigen assay, sera indirect immunofluorescence assay, or sputum culture for Legionella. Literature review of Legionnaires' disease from Medline and PubMED websites was performed. A total of 32 cases of Legionnaires' disease were identified. Their mean age was 64.3 years, with male predominance (27 cases, 84.3%). The underlying diseases were varied and most were attributed to chronic disorders, such as diabetes mellitus (31%) and cigarette smoking (40.6%). The most common symptoms were cough (68%) and fever (59.3%). More than half of patients (18, 56.2%) with Legionnaires' disease could initially present with extrapulmonary manifestations. Sixteen (50%) patients had delay in initiation of appropriate antibiotic therapy. Patients without adequately initiation of appropriate antibiotic therapy had higher proportion (11 of 16, 68.7%) of intensive care unit admission than patients with adequate initiation (5 of 16, 31.2%). Our results inferred that a delay in treatment might result in worsening of disease severity and the need for more intensive management. Overall mortality rate was 21.8%. Development of vasopressor requirement is an independent risk factor associated with mortality. Legionnaires' disease in Taiwan frequently present with extrapulmonary manifestations. Patients with hemodynamic instability that need vasopressor therapy associated with mortality.

Population Pharmacokinetics and Pharmacodynamics of Praziquantel in Ugandan Children with Intestinal Schistosomiasis: Higher Dosages Are Required for Maximal Efficacy.

ABSTRACTEach year, millions of African children receive praziquantel (PZQ) by mass drug administration (MDA) to treat schistosomiasis at a standard single dose of 40 mg/kg of body weight, a direct extrapolation from studies of adults. A higher dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patent Schistosoma mansoni received PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of PZQ racemate and enantiomers (R and S) were quantified. PD outcomes were assessed by standard fecal egg counts and novel schistosome-specific serum (circulating anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen assays. Population PK and PD analyses were performed to estimate drug exposure in individual children, and the relationship between drug exposure and parasitological cure was estimated using logistic regression. Monte Carlo simulations were performed to identify better, future dosing regimens. There was marked PK variability between children, but the area under the concentration-time curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR). Although no child achieved antigenic cure, which is suggestive of an important residual adult worm burden, higher AUC was associated with greater CAA antigenic decline at 24 days. To optimize the performance of PZQ, analysis of our simulations suggest that higher doses (>60 mg/kg) are needed, particularly in smaller children.

Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

BackgroundChallenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed.Methods and findingsA prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection.ConclusionsThe interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.

Legionella spp. in UK composts—a potential public health issue?

Over the past 5 years, a number of cases of legionellosis in Scotland have been associated with compost use; however, studies investigating sources of infection other than water systems remain limited. This study delivers the first comprehensive survey of composts commonly available in the UK for the presence of Legionella species. Twenty-two store-bought composts, one green-waste compost and one home-made compost were tested for Legionella by culture methods on BCYE-α medium, and the findings were confirmed by macrophage infectivity potentiator (mip) speciation. Twenty-two of the samples were retested after an enrichment period of 8 weeks. In total, 15 of 24 composts tested positive for Legionella species, a higher level of contamination than previously seen in Europe. Two isolates of Legionella pneumophila were identified, and Legionella longbeachae serogroup 1 was found to be one of the most commonly isolated species. L. longbeachae infection would not be detected by routine Legionella urinary antigen assay, so such testing should not be used as the sole diagnostic technique in atypical pneumonia cases, particularly where there is an association with compost use. The occurrence of Legionella in over half of the samples tested indicates that compost could pose a public health risk. The addition of general hygiene warnings to compost packages may be beneficial in protecting public health.

Clinical evaluation of urine Histoplasma capsulatum antigen measurement in cats with suspected disseminated histoplasmosis.

Diagnosis of Histoplasma capsulatum infection in cats traditionally relies upon identification of organisms in circulating monocytes or in tissue specimens from affected organs. In this retrospective study, results of a urine antigen assay were compared with standard diagnostic methods in cats with clinical signs suggestive of histoplasmosis. Antigenuria was detected in 17/18 cats with a histopathologic or cytopathologic diagnosis of histoplasmosis. This preliminary evaluation of the Histoplasma urine antigen test suggests it may be a useful aid in diagnosing this disease in cats.