Surveillance Plan Research Articles

Pathogen prioritisation for wastewater surveillance ahead of the Paris 2024 Olympic and Paralympic Games, France.

BackgroundWastewater surveillance is an effective approach to monitor population health, as exemplified by its role throughout the COVID-19 pandemic.AimThis study explores the possibility of extending wastewater surveillance to the Paris 2024 Olympic and Paralympic Games, focusing on identifying priority pathogen targets that are relevant and feasible to monitor in wastewater for these events.MethodsA list of 60 pathogens of interest for general public health surveillance for the Games was compiled. Each pathogen was evaluated against three inclusion criteria: (A) analytical feasibility; (B) relevance, i.e. with regards to the specificities of the event and the characteristics of the pathogen; and (C) added value to inform public health decision-making. Analytical feasibility was assessed through evidence from peer-reviewed publications demonstrating the detectability of pathogens in sewage, refining the initial list to 25 pathogens. Criteria B and C were evaluated via expert opinion using the Delphi method. The panel consisting of some 30 experts proposed five additional pathogens meeting criterion A, totalling 30 pathogens assessed throughout the three-round iterative questionnaire. Pathogens failing to reach 70% group consensus threshold underwent further deliberation by a subgroup of experts.ResultsSix priority targets suitable for wastewater surveillance during the Games were successfully identified: poliovirus, influenza A virus, influenza B virus, mpox virus, SARS-CoV-2 and measles virus.ConclusionThis study introduced a model framework for identifying context-specific wastewater surveillance targets for a mass gathering. Successful implementation of a wastewater surveillance plan for Paris 2024 could incentivise similar monitoring efforts for other mass gatherings globally.

The "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) Project: An Expert Panel Opinion.

Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation. Significant immunosuppression is a risk factor for the development of AK and subsequent lesion progression to squamous cell carcinoma. Immunocompromised patients (ICPs), particularly organ transplant recipients, often have more advanced or complex AK presentations and an increased risk of skin carcinomas versus non-ICPs with AK, making lesions more difficult to treat and resulting in worse treatment outcomes. The recent "Personalising Actinic Keratosis Treatment" (PAKT) consensus reported that delivering patient-centric care may play a role in supporting better clinical outcomes and patient satisfaction with treatments for chronic dermatologic conditions such as AK, which require repeated cycles of treatment. Additionally, currently published guidance and recommendations were considered by the PAKT panel to be overly broad for managing ICPs with their unique and complex needs. Therefore, the "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) panel was established to build upon general recommendations from the PAKT consensus. The panel identified current gaps in guidance for AK care in ICPs, offered practical care approaches based on typical ICP scenarios, and highlighted the need to adapt AK management to optimize care and improve treatment outcomes in ICPs. In particular, dermatologists should establish collaborative and transparent relationships with patients' multidisciplinary teams to enhance overall care for patients' comorbidities: given their increased risk of progression to malignancy, earlier assessments/interventions and frequent follow-ups are vital.The panel also developed a novel "triage" tool outlining effective treatment follow-up and disease surveillance plans tailored to patients' risk profiles, guided by current clinical presentation and relevant medical history. Additionally, we present the panel's expert opinion on three fictional ICP scenarios to explain their decision-making process for assessing and managing typical ICPs that they may encounter in clinical practice.

Predicting chronic wasting disease in white-tailed deer at the county scale using machine learning

Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/.

Evaluation of Multiple RNA Extraction Protocols for Chikungunya Virus Screening in Aedes aegypti Mosquitoes.

Chikungunya virus (Togaviridae, Alphavirus; CHIKV) is a mosquito-borne global health threat. The main urban vector of CHIKV is the Aedes aegypti mosquito, which is found throughout Brazil. Therefore, it is important to carry out laboratory tests to assist in the virus's diagnosis and surveillance. Most molecular biology methodologies use nucleic acid extraction as the first step and require quality RNA for their execution. In this context, four RNA extraction protocols were evaluated in Ae. aegypti experimentally infected with CHIKV. Six pools were tested in triplicates (n = 18), each containing 1, 5, 10, 20, 30, or 40 mosquitoes per pool (72 tests). Four commercial kits were compared: QIAamp®, Maxwell®, PureLink®, and PureLink® with TRIzol®. The QIAamp® and PureLink® with TRIzol® kits had greater sensitivity. Two negative correlations were observed: as the number of mosquitoes per pool increases, the Ct value decreases, with a higher viral load. Significant differences were found when comparing the purity and concentration of RNA. The QIAamp® protocol performed better when it came to lower Ct values and higher RNA purity and concentration. These results may provide help in CHIKV entomovirological surveillance planning.

Germline Predisposition in Hematologic Malignancies: Testing, Management, and Implications.

Although numerous barriers for clinical germline cancer predisposition testing exist, the increasing recognition of deleterious germline DNA variants contributing to myeloid malignancy risk is yielding steady improvements in referrals for testing and testing availability. Many germline predisposition alleles are common in populations, and the increasing number of recognized disorders makes inherited myeloid malignancy risk an entity worthy of consideration for all patients regardless of age at diagnosis. Germline testing is facilitated by obtaining DNA from cultured skin fibroblasts or hair bulbs, and cascade testing is easily performed via buccal swab, saliva, or blood. Increasingly as diagnostic criteria and clinical management guidelines include germline myeloid malignancy predisposition, insurance companies recognize the value of testing and provide coverage. Once an individual is recognized to have a deleterious germline variant that confers risk for myeloid malignancies, a personalized cancer surveillance plan can be developed that incorporates screening for other cancer risk outside of the hematopoietic system and/or other organ pathology. The future may also include monitoring the development of clonal hematopoiesis, which is common for many of these cancer risk disorders and/or inclusion of strategies to delay or prevent progression to overt myeloid malignancy. As research continues to identify new myeloid predisposition disorders, we may soon recommend testing for these conditions for all patients diagnosed with a myeloid predisposition condition.

Communicating cardiovascular health information and improving coordination with primary care: A Childhood Cancer Survivor Study randomized trial.

10011 Background: Childhood cancer survivors are at risk of early cardiovascular disease (CVD). We conducted a survivorship care plan (SCP)-based counseling intervention to improve CVD risk factor control in adult-aged survivors. Methods: Randomized (1:1) trial of survivors at high CVD risk based on history of anthracycline or chest radiotherapy exposures with undertreated hypertension (≥130/80 mmHg), dyslipidemia (LDL ≥160 mg/dL or triglyceride ≥200 mg/dL), and/or glucose intolerance (threshold varied if history of pre-diabetes or diabetes) based on in-home testing. Approximating a survivorship clinic visit, the intervention consisted of a remotely delivered session with an advanced practice provider to review results, a SCP with personalized CVD risk information, and an action plan to help manage CVD risk factors. A remote booster session was provided 4 months later with the action plan updated. Control participants only received a copy of their in-home results with abnormalities noted and written encouragement to follow-up with their primary care provider (PCP). Blood pressure, lipid profile, and glucose tolerance were retested after 1y. For both groups, all participant materials were sent to PCPs throughout the study, and PCP medical records were abstracted at study completion. Logistic regression assessed the odds ratio (OR) for undertreatment at 1y associated with the intervention, adjusting for pre-specified variables (sex, current age, time since cancer, insurance status, recent history of survivorship clinic visit, and undertreated CVD risk factor). Results: Among 644 survivors who completed in-home testing, 347 met inclusion criteria and were randomized (175 intervention; overall 52% male, mean age 40y, 31y since cancer diagnosis); 264 with 1y follow-up (126 intervention). At baseline, rates of hypertension, dyslipidemia, and glucose intolerance were 53%, 52%, and 49%, respectively; 43% had > 1 undertreated condition. Although the intervention achieved > 95% satisfaction, it was not associated with reduced undertreatment vs control (OR 0.9, 95% CI 0.7-1.3). Notably, 48% of intervention and 44% of control participants had less undertreatment after 1y. In secondary analysis, greater internal locus of control was associated with less undertreatment at 1y (OR 0.7, 95% CI 0.6-0.9). The intervention group was more likely than controls to have CVD risk (+10 vs -1%), SCP (+17 vs -2%), and some late effects surveillance plan (+8 vs +2%) documented within PCP records at 1y vs baseline (p < 0.05 for all). Conclusions: While a remotely delivered counseling intervention did not reduce CVD risk factor undertreatment compared with provision of test results alone, both study arms had > 40% reduction in undertreatment. These results suggest that simply providing a formal CVD risk assessment to high-risk cancer survivors and their PCPs may be effective. Clinical trial information: NCT03104543 .

Emerging role of carbon fiber-reinforced polyetheretherketone instrumentation in spinal oncology: A systematic review

Spinal metastases are increasing in incidence with affected patients experiencing significant pain and disability. Continuous research and innovation in the field of spinal oncology have given rise to an increase in personalized treatment based on tumor characteristics and various patient-specific factors. Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) instrumentation has gained popularity as an alternative to titanium-based implants primarily due to their ability to minimize imaging artifact. A literature search was performed to find articles that examined the use of CFR-PEEK screws in spinal fusion procedures in oncologic patients. Data from each study were compiled to compare complication rates, durability, and effects on postoperative imaging in patients treated with CFR-PEEK instrumentation to those treated with traditional titanium implants. Overall, CFR-PEEK-based products were similar to titanium hardware in terms of durability and complication rates while CFR-PEEK allows for improved postoperative tumor surveillance and radiosurgical planning.

Mātauranga Māori framework for surveillance of plant pathogens

Faced with growing biosecurity risks and threats, countries worldwide seek to protect their biodiversity from ecosystem degradation and loss. Biosecurity surveillance of plant pathogens and the diseases they cause is fundamental for management and eradication of these risks. To date, the surveillance systems in Aotearoa New Zealand have reflected empirical scientific principles and have been largely devoid of mātauranga and te ao Māori, which have seldom been regarded as valid or relevant knowledge systems to inform biosecurity. Because of this, mana whenua themselves have been disconnected from these systems. The inclusion of mana whenua and their mātauranga is important, not only to recognise their role and rights as indigenous peoples of Aotearoa New Zealand, but because it is through place-based approaches that better biodiversity and environmental outcomes can be achieved. Here, we describe a mātauranga Māori framework for surveillance (MMFS) of plant pathogens, which introduces the principles and methodologies that aim to elevate mana whenua and mātauranga research into the biosecurity and science systems. The MMFS facilitates the co-existence of mātauranga and empirical scientific knowledge without the need for inter-dependent validation, on the assumption that this will lead to better research and operational outcomes. It addresses issues around data ownership and sovereignty, informed consent, and cultural licence. We present a case study where the MMFS has been applied to research initiatives aimed at addressing myrtle rust and kauri dieback in Aotearoa New Zealand. The MMFS informed the development of a data storage platform, which anchors data to the place of origin, recognising its provenance and giving effect to Māori data sovereignty. This process ensures mana whenua have timely access and use of existing and emergent data. Following the principles of the MMFS, we developed and used a “proof of pathogen absence” tool to co-design with mātauranga environmental experts a risk-based surveillance plan for the purpose of demonstrating freedom from disease in areas where a pathogen has not been detected. The MMFS provides a way of planning and implementing environmental surveillance that can be applied to the full range of environmental problems internationally where indigenous populations are involved.

Cost of controlling the dengue vector Aedes aegypti in the Peruvian amazon.

Motivation for the study. Dengue prevention and control is based on the control of its vector. This study was conducted because of the need to know the costs associated with Aedes aegypti control in a region that carries out planned vector control activities. Main findings. The costs incurred in dengue vector control in the Loreto region in 2017 and 2018 amounted to PEN 4,066,380.25 and PEN 3,807,858.73, respectively. Implications. Knowing the cost of vector control activities will allow us to better plan these activities and have a basis for cost-effectiveness studies with other methods of prevention and control of dengue. To estimate the costs incurred in the control of Aedes aegypti in the Loreto region, during the years 2017 and 2018. We conducted a partial retrospective economic evaluation of the costs of Aedes aegypti control of the Regional Health Directorate Loreto, during the implementation of the Regional Plan for Surveillance and Control of Aedes aegypti. Documentation such as plans, intervention reports and payment slips were reviewed, and interviews were conducted with professional personnel involved in vector control, on the costs of control interventions. We found that the costs incurred in dengue vector control in the Loreto Region in the two years were: PEN 3,807,858 and PEN 4,066,380 during 2017 and 2018, respectively (USD 1,175,264 and USD 1,1210,232 at the 2017 and 2018 exchange rate). However, the effect of control activities is short-lived. The high cost involved in vector control with the methods currently used and the short duration of its effect make it unsustainable. Studies should be conducted in order to find other more efficient methods for dengue control.

Distribution and ecological aspects of sand fly species from Kousseri, an endemic focus of visceral leishmaniasis in Northern Cameroon

IntroductionKousseri in the Far North Region of Cameroon has long been known as an endemic focus of visceral leishmaniasis (VL), although the study on sand flies in this focus is scarce. The present study investigates the spatial distribution, seasonality, and ecological aspects of sand flies from Kousseri. This study is based on the need to optimize the effectiveness of leishmaniasis control programs in the northern part of the country. MethodsSand flies were sampled monthly over 12 months in five selected sites using CDC light traps. Only captured females were morphologically identified at species level based on valid keys. Results and discussionOverall, 4,214 sand fly specimens were collected during 360 trapping nights. The male/female sex ratio slightly favored females (1:1.04). The eudominant Sergentomyia antennata followed by both dominant Sergentomyia schwetzi and Sergentomyia squamipleuris were the most common and abundant species, accounting for 76.1% of the collection. Phlebotomus duboscqi, the confirmed vector of cutaneous leishmaniasis (CL) in West African foci, although rare in the collection, was found in four of the five surveyed sites. This sand fly species with Se. schwetzi abounded in peri-urban areas and, respectively, in animal shed and in uninhabited house biotopes, while Se. antennata and Se. squamipleuris prevailed in rural areas and, respectively, in animal shelter biotopes and outside dwellings. All caught sand fly species except Se. schwetzi, Sergentomyia clydei, Sergentomyia inermis, and Sergentomyia adleri prevailed during the dry season. The highest Shannon–Wiener index of sand flies due to the maximal richness and evenness was found in the urban area, in outdoor biotopes, and during the rainy season (H′ = 1.68, 1.80, and 1.74, respectively). These data provide evidence that less urbanized areas, animal shelters around the compounds, and the absence of precipitation (dry season) favored the dispersion of abundant sand fly species in Kousseri. Based on previous reports on Leishmania transmission, a surveillance plan is required to prevent an outbreak of VL or an establishment of CL or canine leishmaniasis (CnL) in this focus. Further research identifying the blood meal source and the Leishmania parasites in these insects is critical for providing insightful data to fight leishmaniasis in Northern Cameroon.

Use of the 31-Gene Expression Profile Test to Aid in the Decision of Adjuvant Treatment of Cutaneous Melanoma

Melanoma is the fifth most common cancer in the United States, with over 7,000 deaths annually. Although most patients diagnosed with early-stage (stage I or II) disease have an excellent prognosis, two out of three patients who die from melanoma were initially diagnosed in early stages. Thus, additional methods to identify which patients are at risk of poor outcomes are needed. DecisionDx-Melanoma is a 31-gene expression profile (31-GEP) molecular risk stratification test that predicts an individual’s risk of recurrence or metastasis in patients with cutaneous melanoma (CM). Here, we describe a 61-year-old man who presented with a spot on his upper scalp. A biopsy confirmed malignant melanoma measuring > 3.87 mm, with ulceration and mitotic rate 2 to 3/mm2. CT, PET, and MRI scans did not reveal metastasis. Following wide local excision and sentinel lymph node biopsy, he was diagnosed with stage IIB CM. Due to the presence of high-risk features, 31-GEP testing was ordered, which revealed Class 2B (high-risk) CM. Due to the high-risk 31-GEP result, the patient was treated off-label with nivolumab for 1 year and received follow-up surveillance scans every 3 months for 3 years. At his last follow-up in April 2022, scans continued to show no recurrent or metastatic disease. The patient continues dermatologic screening every 6 months. The 31-GEP test provides valuable additional information to help clinicians make personalized, risk-based treatment and surveillance plans for patients with CM.

Equine Infectious Anaemia: The Active Surveillance of an Entire Equid Population Reduces the Occurrence of the Infection

Equine infectious anaemia (EIA) is a life-long viral infection affecting equids, transmitted mechanically by biting flies and iatrogenic means. Despite its global distribution, active surveillance is limited, with passive clinical surveillance or control of specific equine sectors prevailing. In Italy, a national surveillance plan in horse, donkey, and mule populations has been established and includes mandatory passive and active surveillance through annual serological tests. During 2007–2010, the agar gel immunodiffusion (AGID) test served as both screening and confirmatory tests. Since 2011, a three-tier diagnostic pathway was introduced, utilizing the ELISA test for screening, AGID as the confirmatory test, and the immunoblot test for cases where ELISA was positive and AGID was negative. From a total equid population of 406,000 animals, 1,337,899 samples were analysed during 2007–2012, with 2,348 (0.18%) testing positive. EIA seroprevalence significantly decreased across all the species/hybrids during the study period. EIA occurrence was higher in mules (IRR = 48.90) and lower in donkeys (IRR = 0.56) compared to horses. The holding seroprevalence was 1.15%. Spatial analysis revealed clusters of infection in central Italy. These findings demonstrate that active systematic surveillance effectively reduces EIA prevalence in equid populations. Mules and working horses in wooded areas appeared to be at higher risk of infection and act as EIA reservoirs. Surveillance and control should be maintained and strengthened in these species/hybrids and in these areas to effectively control EIA. Passive surveillance alone is insufficient to eradicate the disease, and EIA remains a constant threat for the equine industry if active control is not implemented.

Foot-and-mouth disease seroprevalence is higher in young female crossbred sheep and goats compared to their counterparts in the border area between Pakistan and Afghanistan.

Foot-and-mouth disease (FMD) is a highly contagious disease in ruminants that causes significant economic losses worldwide. However, the prevalence of FMD virus (FMDV) in small ruminants has been overlooked in Pakistan. This study aimed to determine the prevalence of FMD in sheep and goats in the border area between Pakistan and Afghanistan. 800 sheep and goats belongs to age groups of 6 month to > 2 years. A total of 800 serum samples were collected from sheep (n = 424) and goats (n = 376) and subjected to structural protein (SP) and 3ABC non-SP (NSP) ELISAs for the detection of antibodies against SP and NSP of the FMDV. For NSP, 340/800 (42.5%) of samples were positive, while SP analysis revealed that serotype O (44.5%) was the most common in sheep and goats, followed by Asia-1 (42%) and A (32%) serotypes. Sheep (39%; 95% CI, 34 to 44) had a higher (P < .05) prevalence of FMD than goats (46%; 95% CI, 41 to 51). Statistically significant (P < .05) differences in the seroprevalence of FMD-SP and FMD-NSPs were observed between various agencies (areas) of the study area. Risk factors such as age, sex, breed, season, flock size, body condition, animal movement, and production system were significantly (P < .05) associated with FMDV prevalence. This study showed that FMD is highly prevalent in sheep and goats in the border areas of Pakistan and Afghanistan. Therefore, outbreak investigation teams should be arranged at the border level to develop FMD risk-based surveillance and control plans for small ruminants in order to mitigate infection risks.

Synergizing IoT-Based Gender-Responsive Security Surveillance to Gauge ICT Infrastructure Maturity

Effective planning and implementation of smart security surveillance ensures campus protection for all genders. Thus, the integration of a reliable ICT infrastructure as the core foundation for the security and privacy of the institutions leads to a substantial transformation in the way individuals interact, increasing the confidentiality of the stakeholders. Hence, the study aims to assess the current state of ICT infrastructure and identify the parameters in the design of an IoT-based gender-responsive security surveillance system for Colegio de San Juan de Letran Manaoag. The study implemented a comprehensive review of related literature about maturity models and their capabilities. A focus group discussion was assembled to administer a semi-structured interview on the current state of the ICT infrastructure and conducted an online survey for the assessment of the ICT infrastructure among the administrators and staff of the MIS Department in identifying the strengths and weaknesses of the current ICT infrastructure. Employing the IT Infrastructure Maturity Model (ITI-MM) as a tool in determining the maturity levels of its capabilities. Based on the results, the ITI-MM model determined the current state of the ICT infrastructure, which is currently operating at maturity level 2, and identified the gaps in achieving the requirements between Level 1 and Level 2. In conclusion, the study indicated that measuring of the maturity level is applicable in integrating the proposed system for developing an IoT-based gender-responsive security surveillance system to enhance the security measures of the institution.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Recurrence morbidity of olfactory neuroblastoma.

With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence. A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses. A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p<0.001), overall stage (p<0.001), and modified Kadish scores (p<0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio=5.62; p=0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence. Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.

A Case of Multidrug-Resistant Tuberculosis in an Active Duty Military Health Care Worker.

Cases of active tuberculosis (TB) in the U.S. Military have fallen over the last century in large part due to improved screening and treatment options. The subset of multidrug-resistant TB (MDR-TB) is almost nonexistent within the U.S. Military. We present a case of MDR-TB in an active duty U.S. Military health care worker and discuss several considerations for treatment that may present challenges for U.S. Military medical practitioners. A 30-year-old active duty Soldier was referred to Army public health services after a bronchoscopy sample was positive for Mycobacterium tuberculosis complex. Sputum smears were negative for acid-fast bacilli, suggesting lower risk for community spread. One month after initiation of the standard 4-drug regimen for active TB, genetic susceptibility testing found the patient's M. tuberculosis isolate to be resistant to rifampin, isoniazid, and pyrazinamide. Contact investigation efforts among co-workers and family members fortunately found no new interferon-gamma release assay conversions. Coordination of public health assets to ensure a successful treatment regimen occurred across varied local, state, and federal agencies. Atypical medications required coordination with the FDA for procurement. An extensive surveillance plan for medication adverse effects was required. Finally, questions of public health authority versus patient autonomy arose requiring multidisciplinary input and ethical discussions.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada

ObjectivesHealth administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. Study Design and SettingData from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1–5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). ResultsAlgorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. ConclusionValidated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

Abstract 6198: TP53 mutational clusters stratify the Li-Fraumeni syndrome spectrum

Abstract Li-Fraumeni syndrome (LFS) is a highly penetrant cancer predisposition disorder caused by germline variants in the TP53 tumor suppressor gene. LFS has recently been redefined as a ‘spectrum’ disorder to reflect the highly variable cancer types with largely unpredictable ages-of-onset and disease severity. The broad functional gradient associated with different TP53 variants is thought to contribute to LFS heterogeneity, although it is still poorly understood and there is an unmet clinical need for risk stratification strategies to improve variant interpretation and patient care. Here, we performed an unsupervised cluster analysis leveraging p53 mutagenesis datasets (Kato et al., 2003 &amp; Giacomelli et al., 2018) that revealed five TP53 mutational clusters with unique mutation patterns, structural features, and functional consequences. Stratifying germline carriers based on the five clusters exposed important clinical characteristics to consider for patient management, such as ages-of-onset, tumor type development, and survival outcomes. In particular, we discovered an osteosarcoma-prone subgroup comprised of monomeric mutant p53 carriers with aggressive cancer phenotypes. We also identified a cluster of TP53 variants found more often in non-cancer and healthy older populations, and carriers of these variants that developed cancer had less “LFS-like” phenotypes including an older age-of-onset and a significantly higher frequency of colorectal cancers. Remarkably, our TP53 variant clustering strategy could also stratify breast cancer survival among germline carriers. This work provides a new framework to delineate the LFS spectrum toward the development of machine learning-based approaches for personalized cancer surveillance plans. Citation Format: Nicholas W. Fischer, Brianne Laverty, Ran Kafri, Kara N. Maxwell, Emma R. Woodward, Christian Kratz, David Malkin. TP53 mutational clusters stratify the Li-Fraumeni syndrome spectrum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6198.

Multiple-Drug Resistant Shiga Toxin-Producing E. coli in Raw Milk of Dairy Bovine.

Raw milk may contain pathogenic microorganisms harmful to humans, e.g., multidrug-resistant Escherichia coli non-O157:H7, which can cause severe colitis, hemolytic uremia, and meningitis in children. No studies are available on the prevalence of Shiga toxin-producing E. coli (STEC O157:H7) in sick or healthy dairy animals in the Khyber Pakhtunkhwa Province of Pakistan. This study aimed to isolate, characterize, and detect antibiotic resistance in STEC non-O157:H7 from unpasteurized milk of dairy bovines in this province. We collected raw milk samples (n = 800) from dairy farms, street vendors, and milk shops from different parts of the Khyber Pakhtunkhwa Province. E. coli was isolated from these samples followed by latex agglutination tests for serotyping. The detection of STEC was conducted phenotypically and confirmed by the detection of virulence genes genotypically. An antibiogram of STEC isolates was performed against 12 antibiotics using the disc diffusion method. A total of 321 (40.12%) samples were found to be positive for E. coli in this study. These samples were processed for the presence of four virulence genes (Stx1, Stx2, ehxA, eae). Forty samples (5.0%) were STEC-positive. Of these, 38%, 25%, 19%, and 18% were positive for Stx1, Stx2, ehxA, and eae, respectively. Genotypically, we found that 1.37% of STEC isolates produced extended-spectrum beta-lactamase (ESBL) and contained the blaCTX M gene. Resistance to various antibiotics ranged from 18% to 77%. This study highlights the risk of virulent and multidrug-resistant STEC non-O157:H7 in raw milk and the need for proper quality surveillance and assurance plans to mitigate the potential public health threat.