True Burden Research Articles

Pooled Prevalence of Byssinosis in India: A Systematic Review and Meta-analysis

Abstract Byssinosis is an occupational lung disease affecting textile workers exposed to cotton, jute and hemp dust. It causes symptoms like cough, breathlessness, and wheezing which is more during Mondays. Diagnosis is mainly clinical. The true burden of byssinosis in India remains unknown, and this systematic review and meta-analysis (SR-MA) aims to estimate its prevalence among textile industry workers in India. This study was registered in PROSPERO. The search spanned from January 2000 to September 2023, focusing on observational studies that met specific criteria. Two independent reviewers screened the literature, extracted relevant data, and assessed the risk of bias. Statistical analysis included a random effects model, assessment of heterogeneity and publication bias. Eighteen studies (5678 individuals) were included in the analysis. Byssinosis diagnosis was based on Schilling’s criteria in the majority of studies. Seven studies had low risk of bias, three had high risk, and the rest were moderate. There was no significant publication bias. The pooled prevalence of byssinosis was 24% (95% CI = 13%-36%) with high heterogeneity (I 2 = 99.02%). Sub-group analysis of studies with low risk of bias showed a prevalence of 20% (95% CI = 11% - 29%). Extrapolation of these findings to India suggests that about 10 million people are affected by byssinosis. The authors recommend development and practice of tailored health surveillance guidelines and the promotion of respiratory protective equipment (RPE) among those employed in textile industries.

Epidemiological signatures and surveillance bias in cancer

Surveillance bias occurs when variations in cancer incidence are the result of changes in screening or diagnostic practices rather than increases in the true occurrence of cancer. This bias is linked to the issue of overdiagnosis and can be apprehended by looking at epidemiological signatures of cancer. We explain the concept of epidemiological signatures using the examples of melanoma and of lung and prostate cancer. Accounting for surveillance bias is particularly important for assessing the true burden of cancer and for accurately communicating cancer information to the population and decision-makers.

Estimating the true number of people with acute rheumatic fever and rheumatic heart disease from two data sources using capture-recapture methodology.

ObjectiveIn Australia, accurate case ascertainment of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) diagnoses for disease surveillance and control purposes requires the use of multiple data sources, including RHD registers and hospitalisation records. Despite drawing on multiple data sources, the true burden of ARF/RHD is likely to be underestimated.MethodsThis study used capture-recapture methods to quantify the missing number of ARF/RHD cases in data from hospitals and jurisdictional RHD registers. Linked datasets comprised reported cases of ARF/RHD in register records and administrative hospital data.ResultsCapture-recapture analyses indicated the total number of new ARF/RHD cases in three Australian jurisdictions (Queensland, South Australia and Western Australia), among people aged 3-54years, was 3480 (95% CI=3366-3600) during 2011-2016. This included 894 (25.7%) individuals who were not listed in either the hospital or register datasets. Non-Indigenous, urban and older people with ARF/RHD were least likely to be identified in either the hospital or register data sources.ConclusionsThe 894 likely ARF/RHD cases our analyses detected that are not included in the routine surveillance datasets are concerning and quantify the magnitude and characteristics of under-notification to RHD registers in Australia, especially for groups that are not typically at high risk of ARF.

Serological Investigation of Japanese Encephalitis Virus Infection in Commercially Reared Pigs, Southwestern Nigeria.

Japanese encephalitis virus (JEV) is a zoonotic arbovirus that causes abortion, stillbirth, and congenital defects in pigs, and epidemic encephalitis in humans. Currently, there is scarcity of information on JEV infection in pigs in Nigeria. Since the Culex tritaeniorhynchus vector of JEV is present in Nigeria and considering recent anecdotal reports of abortions and birth of weak piglets in some pig farms in southwestern Nigeria, there is a need for studies on the presence of the virus and its true burden among pig populations in the country. Serum samples (n=368) obtained from farm-reared pigs in four States of southwestern Nigeria were screened for JEV-specific IgG antibodies using a commercial ELISA kit. An overall JEV seropositivity of 35.1% (95% CI: 30.18 - 39.93%) was obtained, with detectable antibodies in pigs of all age groups, breeds, sex, and locations. Our results suggest natural exposure of these unvaccinated intensively reared pigs to JEV circulating silently in the swine population with significant association of the seropositivity with location (state/community in which the pig farms exist) and breed of the pigs studied. This first report of detection of anti-JEV antibodies in pigs in Nigeria indicates that JEV circulated among these pigs and underscores the need for active surveillance for JEV in humans, pigs, and mosquitoes to provide valuable epidemiological data for the design of effective control strategies against the virus, thus forestalling potential future outbreaks of the infection.

Socio-ecological determinants of malaria transmission risk among population residing in an endemic area of southern province of Karnataka, India

BackgroundIndia accounts for 79% of global malaria burden. With progress towards malaria elimination, assessment of true disease burden and determinants of its transmission risk is critical. The present study aimed to estimate the burden of malaria and identify socioecological factors determining the disease prevalence. MethodsA community-based cross-sectional study was carried out among 839 households covering 2910 individuals residing in Udupi taluk. A representative sample from urban, rural tribal and migrant communities were recruited and a questionnaire was used to collect information on socio-demographic, housing & behavioral factors. Data was collected using Epi-info mobile application version 7.2.4 and analyzed using SPSS version 16.0. ResultsAmong the population covered a total of 15 participants had a history of malaria in the past. Advancing age (AOR = 3.60; 95% CI: 2.14–6.04), illiteracy (AOR = 2.28; 95% CI:1.35–3.85), (AOR = 1.96; 95% CI:1.24–3.11) and rural (AOR = 1.96; 95% CI:1.39–2.74), tribal (AOR = 2.38; 95% CI:1.49–3.79), migrant (AOR = 4.28; 95% CI:2.30–7.98) localities were found to be independent predictors of disease awareness. With respect to malaria prevention practices, households from middle (AOR = 0.73; 95% CI: 0.49–1.09) & low SES (AOR = 0.30; 95% CI: 0.19–0.46) and those from migrant localities (AOR = 0.66; 95% CI: 0.38–1.14) were less likely to have poor practices. ConclusionAge, education, socioeconomic status, and locality were found to be significantly associated with knowledge and practice towards malaria prevention. Creating awareness regarding malaria and its prevention with enhanced community participation in control activities jointly with local authority is further emphasized.

Chronic kidney disease of unknown aetiology in Africa: A review of the literature.

During the last two decades, an epidemic of a severe form of chronic kidney disease (CKD) unrelated to traditional risk factors (diabetes and hypertension) has been recognized in low- to middle-income countries. CKD of unknown aetiology (CKDu) mainly affects young working-age adults, and has become as an important and devastating public health issue. CKDu is a multifactorial disease with associated genetic and environmental risk factors. This review summarizes the current epidemiological evidence on the burden of CKDu and its probable environmental risk factors contributing to CKD in Africa. PubMed/Medline and the African Journals Online databases were searched to identify relevant population-based studies published in the last two decades. In the general population, the burden of CKD attributable to CKDu varied from 19.4% to 79%. Epidemiologic studies have established that environmental factors, including genetics, infectious agents, rural residence, low socioeconomic status, malnutrition, agricultural practise and exposure to agrochemicals, heavy metals, use of traditional herbs, and contaminated water sources or food contribute to the burden of CKD in the region. There is a great need for epidemiological studies exploring the true burden of CKDu and unique geographical distribution, and the role of environmental factors in the development of CKD/CKDu.

Prevalence of chronic pulmonary aspergillosis along the continuum of pulmonary tuberculosis care: A protocol for a living systematic review and meta-analysis

Introduction Chronic pulmonary aspergillosis (CPA) is a debilitating disease estimated to affect over 3 million people worldwide. Pulmonary tuberculosis (PTB) is the most significant risk factor for CPA. However, the true burden of CPA at the time of PTB diagnosis, during, and after PTB treatment remains unknown. In this paper, we present a protocol for a living systematic review aimed at estimating the current burden of CPA along the continuum of PTB care. Materials and methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines to formulate this protocol, which is registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023453900). We will identify primary literature through various electronic databases, including CINAHL, Ovid MEDLINE, MEDLINE (PubMed), EMBASE, Google Scholar, Cochrane Database of Systematic Reviews, and African Journal Online. The search will encompass articles from inception to December 31st, 2023, using medical subject heading search terms "pulmonary tuberculosis" AND "chronic pulmonary aspergillosis". Two reviewers will independently assess titles, abstracts, and full texts for eligibility using the Covidence web-based software. The eligible studies will comprise original observational research that reports on the prevalence of CPA diagnosed in individuals with PTB, based on established criteria, without language or geographic restriction. We intend to exclude single case reports and case series with fewer than 10 participants, as well as review articles, guidelines, and letters to the editors. Cochrane Risk of Bias Tools (ROB2 and ROBINS-I) will used to assess study quality and risk of bias and the quality of the evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Our data syntheses will encompass meta-analysis and meta-regression, conducted using STATA version 18 and R- Studio version 4.0.2. This systematic review will be updated every 3–5 years as more data emerges. Conclusions The findings of this proposed systematic review will summarize the available evidence on the occurrence of CPA, at the time of PTB diagnosis, during and after PTB treatment. The study results have the potential to guide healthcare policies regarding screening for CPA, enhance clinical decision-making, and catalyse further research into understanding the interplay between PTB and CPA. By shedding light on the current burden of CPA along the continuum of PTB care, we aspire to contribute to the betterment of patient care, disease management, and global health outcomes. PROSPERO registration CRD42023453900.

One hundred malaria attacks since birth. A longitudinal study of African children and young adults exposed to high malaria transmission

Despite significant progress in malaria control over the past twenty years, malaria remains a leading cause of child morbidity and mortality in Tropical Africa. As most patients do not consult any health facility much uncertainty persists about the true burden of the disease and the range of individual differences in susceptibility to malaria. Over a 25-years period, from 1990 to 2015, the inhabitants of Dielmo village, Senegal, an area of intense malaria transmission, have been monitored daily for their presence in the village and the occurrence of diseases. In case of fever thick blood films were systematically examined through microscopy for malaria parasites and patients received prompt diagnosis and treatment. We analysed data collected in 111 children and young adults monitored for at least 10 years (mean 17.3 years, maximum 25 years) enrolled either at birth (95 persons) or during the two first years of life. A total of 11,599 episodes of fever were documented, including 5268 malaria attacks. The maximum number of malaria attacks in a single person was 112. Three other persons suffered one hundred or more malaria attacks during follow-up. The minimum number of malaria attacks in a single person was 11. The mean numbers of malaria attacks in children reaching their 4th, 7th, and 10th birthdays were 23.0, 37.7, and 43.6 attacks since birth, respectively. Sixteen children (14.4%) suffered ten or more malaria attacks each year at ages 1-3 years, and six children (5.4%) each year at age 4-6 years. Long-term close monitoring shows that in highly endemic areas the malaria burden is higher than expected. Susceptibility to the disease may vary up to 10-fold, and for most children childhood is an endless history of malaria fever episodes. No other parasitic, bacterial or viral infection in human populations has such an impact on health. The Pasteur Institutes of Dakar and Paris, the Institut de Recherche pour le Développement, and the French Ministry of Cooperation provided funding.

Acute kidney injury surveillance in the high-risk neonatal population following implementation of creatinine screening protocol.

Acute kidney injury (AKI) in neonates is associated with longer hospital stays and higher mortality rates. However, there is significant variability in prevalence rates of AKI and the true burden is incompletely understood. In November 2020, the University of Iowa Stead Family Children's Hospital Neonatal Intensive Care Unit implemented a creatinine screening protocol to enhance kidney function monitoring. We sought to evaluate adherence to the protocol to determine if increased surveillance led to increased detection of AKI events. A retrospective chart review was conducted for neonates born at <30 weeks' gestation admitted between 2015 and 2020. We reviewed 100 charts in both the pre (2015-2016) and post (2020-2021) implementation era of the AKI surveillance protocol. AKI was defined according to neonatal modified KDIGO criteria. Following implementation of the protocol, neonates were significantly more likely to have creatinine checked (p < 0.001). Serum creatinine was drawn according to protocol guidelines 68% of the time, and 42% of patients (34/82) had an 80% or higher adherence to the protocol. There was a significant increase in detection of AKI in the post-protocol cohort (13/82, incidence of 16%) compared to the pre-protocol cohort (5/83, incidence of 6%), (p = 0.047). The implementation of a serum creatinine screening protocol increased the frequency of creatinine draws and detection of AKI.

Evidence of tick-borne encephalitis virus neutralizing antibodies in Serbian individuals exposed to tick bites.

Tick-borne encephalitis (TBE) is an emerging vector-borne and food-borne disease caused by the tick-borne encephalitis virus (TBEV; Orthoflavivirus encephalitidis), with a distribution spanning the Eurasian continent. Despite its significant public health impact in various European regions, TBE remains largely underdiagnosed in Serbia due to limited awareness and diagnostic challenges. In response to this, our study aimed to comprehensively assess TBEV exposure in individuals infested with ticks and to identify potential TBEV foci within Serbia. From 2019 to 2021, we conducted an observational study involving 450 patients who reported tick infestations. Our demographic analysis revealed a median age of 38 years, with a slight male predominance among the participants. We documented tick infestations in 38 municipalities across 14 districts of Serbia, with a notable concentration in proximity to Fruška Gora Mountain. The ticks most frequently removed were Ixodes ricinus, with nymphs and adult females being the predominant stages. On average, nymphs were removed after about 27.1 hours of feeding, while adult females remained attached for approximately 44.4 hours. Notably, we found age as a significant predictor of infestation time for both nymphs and adult females. Furthermore, we detected TBEV-neutralizing antibodies in 0.66% of the serum samples, shedding light on potential TBEV foci, particularly in Fruška Gora Mountain and other regions of Serbia. Our study emphasizes the urgent need for active TBE surveillance programs, especially in areas suspected of hosting TBEV foci, in order to assess the true TBE burden, identify at-risk populations, and implement effective preventive measures.

Changing patterns in the epidemiology of drug allergy.

Drug allergy (DA) remains a complex and unaddressed problem worldwide that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. Underdiagnosis and overdiagnosis are common and due to the lack of standardized definitions and biomarkers. The true burden of DA is unknown, and recent efforts in data gathering through electronic medical records are starting to provide emerging patterns around the world. Ten percent of the general population engaged in health care claim to have a DA, and the most common label is penicillin allergy. Up to 20% of emergency room visits for anaphylaxis are due to DA and 15%-20% of hospitalized patients report DA. It is estimated that DA will increase based on the availability and use of new and targeted antibiotics, vaccines, chemotherapies, biologicals, and small molecules, which are aimed at improving patient's options and quality of life. Global and regional variations in the prevalence of diseases such as human immunodeficiency virus and mycobacterial diseases, and the drugs used to treat these infections have an impact on DA. The aim of this review is to provide an update on the global impact of DA by presenting emerging data on drug epidemiology in adult and pediatric populations.

Riding high: seroprevalence of SARS-CoV-2 after 4 pandemic waves in Manitoba, Canada, April 2020–February 2022

BackgroundCanada is emerging from the largest SARS-CoV-2 Omicron wave to date, with over 3.3 million confirmed cases. Unfortunately, PCR confirmed cases illuminate only a small portion of infections in the community and underestimate true disease burden. Population based seroprevalence studies, which measure antibody levels against a virus can more accurately estimate infection rates in the community and identify geographical and epidemiological trends to inform public health responses.MethodsThe Manitoba COVID-19 Seroprevalence (MCS) study is a population-based cross-sectional study to assess the prevalence of SARS-CoV-2 antibodies across the province. Residual convenience specimens (n = 14,901) were tested for anti-SARS-CoV-2 nucleocapsid and spike IgG antibodies from April 1, 2020 to February 31, 2022. We estimated the monthly and cumulative prevalence using an exponential decay model, accounting for population demographics, sensitivity/specificity, and antibody waning. This approach generated estimates of natural infection as well as total antibody including vaccine-induced immunity within the community.FindingsAfter four waves of the pandemic, 60.1% (95%CI-56.6–63.7) of Manitobans have generated SARS-CoV-2 antibodies due to natural exposure independent of vaccination. Geographical analysis indicates a large portion of provincial prevalence stems from increased transmission in the Northern (92.3%) and Southern (71.8%) regional health authorities. Despite the high mortality rates reported by Manitoba, infection fatality ratios (IFR) peaked at 0.67% and declined to 0.20% following the Omicron wave, indicating parity with other national and international jurisdictions. Manitoba has achieved 93.4% (95%CI- 91.5–95.1) total antibody when including vaccination.InterpretationOur data shows that more than 3 in 5 Manitobans have been infected by SARS-CoV-2 after four waves of the pandemic. This study also identifies key geographical and age specific prevalence rates that have contributed greatly to the overall severity of the pandemic in Manitoba and will inform jurisdictions considering reduction of public health measures.

Refinement of a Preliminary Case Definition for Use in Traumatic Brain Injury Surveillance.

Current methods used to measure incidence of traumatic brain injury (TBI) underestimate its true public health burden. The use of self-report surveys may be an approach to improve these estimates. An important step in public health surveillance is to define a public health problem using a case definition. The purpose of this article is to outline the process that the Centers for Disease Control and Prevention undertook to refine a TBI case definition to be used in surveillance using a self-report survey. Survey. A total of 10 030 adults participated via a random digit-dial telephone survey from September 2018 to September 2019. Respondents were asked whether they had sustained a hit to the head in the preceding 12 months and whether they experienced a series of 12 signs and symptoms as a result of this injury. Head injuries with 1 or more signs/symptoms reported were initially categorized into a 3-tiered TBI case definition (probable TBI, possible TBI, and delayed possible TBI), corresponding to the level of certainty that a TBI occurred. Placement in a tier was compared with a range of severity measures (whether medical evaluation was sought, time to symptom resolution, self-rated social and work functioning); case definition tiers were then modified in a stepwise fashion to maximize differences in severity between tiers. There were statistically significant differences in the severity measure between cases in the probable and possible TBI tiers but not between other tiers. Timing of symptom onset did not meaningfully differentiate between cases on severity measures; therefore, the delayed possible tier was eliminated, resulting in 2 tiers: probable and possible TBI. The 2-tiered TBI case definition that was derived from this analysis can be used in future surveillance efforts to differentiate cases by certainty and from noncases for the purpose of reporting TBI prevalence and incidence estimates. The refined case definition can help researchers increase the confidence they have in reporting survey respondents' self-reported TBIs as well as provide them with the flexibility to report an expansive (probable + possible TBI) or more conservative (probable TBI only) estimate of TBI prevalence.

Geographic variation of prevalence of Alzheimer’s Disease and related dementias in the Central Appalachian region of the United States

AbstractBackgroundAreas within the Appalachian region may have a greater burden of under diagnosed Alzheimer’s disease and related dementias (ADRD). As rural areas have lower reported ADRD prevalence compared to urban areas in spite of lower educational attainment (which should lead to higher ADRD prevalence) this argues that the true burden of ADRD is likely underestimated in areas without adequate detection resources. There is need to understand if ADRD prevalence is truly lower in rural areas, or if this is a disease detection difference. The objective of this proposal is to assess the burden of ADRD in Central Appalachia.MethodsCenters for Medicare and Medicaid Services Public Use Files from 2015‐2018 were used to estimate county‐level ADRD prevalence among all fee‐for‐service beneficiaries in Central Appalachia (Kentucky, North Carolina, Ohio, Tennessee, Virginia, and West Virginia). Negative binomial regression was used to estimate prevalence overall, by Appalachian Regional Commission’s Appalachian/non‐Appalachian designation, and by rural/urban (Rural‐Urban Continuum Codes) classification. Models were then adjusted for county‐level demographics including age, gender, Medicaid eligibility, and comorbidities (atrial fibrillation, chronic kidney disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, ischemic heart disease, schizophrenia/other psychotic disorders, and stroke).ResultsThe prevalence of ADRD did not vary over the time period but was higher for Appalachian counties both overall (12.0% vs. 11.6%; p = 0.001; Figure 1) and among both urban (p&lt;0.001) and rural counties (p = 0.024; Figure 2). Urban Appalachian counties had 2‐4% higher prevalence compared to urban non‐Appalachian counties with this difference reaching statistical significance in 2017 and 2018. While a similar trend was observed in rural counties (Appalachian counties having 1‐3% higher prevalence), these yearly ratios did not reach statistical significance. After adjustment, the associations attenuated in urban counties, but over the entire study period, rural Appalachian counties had 2.2% higher prevalence than rural non‐Appalachian counties (Figure 3).ConclusionThere is a consistent difference between Appalachian and non‐Appalachian counties, demonstrated overall and by rural status, with Appalachian counties having ADRD prevalence in the range of 1.0‐4.5% higher than non‐Appalachian counties. However, while county‐level demographics and comorbidities explained the difference in urban counties, the elevated prevalence in rural‐Appalachian counties persisted.

1743. Health Care Resource Utilisation (HCRU) Due to Respiratory Syncytial Virus (RSV) Before the Age of Two in England

Abstract Background RSV is responsible for 33 million lower respiratory tract infections (LRTI) worldwide. The highest burden occurs in infants &amp;lt; 1 year of age during RSV season, which is from October to February in England. Due to lack of routine laboratory testing, its true disease burden is unknown. This study aimed to estimate the respiratory related primary and secondary care healthcare resource utilisation (HCRU) of RSV admissions before the age two in England. Methods This retrospective cohort study used Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked data to establish a birth cohort of all infants born between 01/03/2015 and 28/02/2017 (n=449,591). Case cohorts included infants under two with a hospital admission of: 1) confirmed RSV (n=4,813), 2) bronchiolitis (n=22,913), 3) any RTI (n=56,871). Each case cohort was compared with all birth cohort infants without the corresponding admission (comparative cohorts). Respiratory related HCRU (primary care, outpatient, accident and emergency [A&amp;E], and inpatient admissions) were estimated in the month prior to and up to 24 months following the first admission in each cohort. Results The RSV-coded cohort had the highest HCRU overall, mean (SD) of 5.1 (4.8) admissions vs. 1.5 (2.4) in its comparative cohort (71% difference). This difference was largely due to A&amp;E and inpatient admissions. Comparable results were found for bronchiolitis-coded and RTI-coded cohorts. The highest rates of inpatient admissions were observed for the RSV-coded case cohort, and these occurred during the calendar months of November and December. Inpatient admissions were largely among infants up to 12 months of age and included infants that were born both before and during the season (Figure 1). Conclusion Infants with an RSV admission had higher HCRU than infants without. Most hospitalisations occurred in November and December when services are at their most stretched. During the first year of life, the HCRU rates observed for infants born before and in the season were equally very high, emphasizing the need for preventative strategies to all infants entering their first RSV season. Funding: This research was funded by collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease. Disclosures Maria João Fonseca, n/a, Sanofi: Advisor/Consultant Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds Richard Hudson, n/a, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds

1506. Prevalence of Histoplasma Antigenuria among an outpatient Advanced HIV cohort in Kampala,Uganda

Abstract Background Histoplasmosis is a major cause of mortality in persons with advanced HIV disease (CD4&amp;lt; 200 cells/mcL) and areas of endemicity are evolving. Presenting symptoms of histoplasmosis may overlap with that of tuberculosis (TB). The true burden of histoplasmosis remains unknown in persons with advanced HIV disease, in part due to poor diagnostic capacity. We sought to evaluate the prevalence of Histoplasma antigenuria among outpatients with advanced HIV disease in Kampala, Uganda. Methods This prospective cohort study of outpatients with advanced HIV in Kampala, Uganda was nested within the ongoing ENCORE trial evaluating preemptive therapy and prophylaxis among outpatients with advanced HIV disease. Urine samples were obtained from participants at the time of enrollment and a Histoplasma galactomannan enzyme immunoassay (EIA) (Immy, Norman OK) was run on urine per manufacturer’s instructions. We obtained baseline characteristics and laboratory values, a statistical comparison by antigen status was not done due to a low number of positives. We calculated the prevalence of histoplasmosis in our cohort using EIA results. We obtained information on symptoms, TB diagnostics, and TB treatment for those with Histoplasma antigenuria. Results We tested 388 urine samples among participants with advanced HIV disease. Four samples were positive for Histoplasma antigen (1%). Baseline characteristics of participants are summarized in Table 1. Histoplasma antigen prevalence among participants with CD4&amp;lt; 100 cells/mcL was 2.5% (4/158). Of those that tested positive for histoplasmosis, the median CD4 count was 39 cells/mcL (interquartile range (IQR): 16–54), and median CRP was elevated at 29 (IQR 14-46). All four participants with Histoplasma antigenuria had a positive TB urine lipoarabinomannan (LAM, AlereLAM, Abbott, Palatine, IL, USA), though only two of four participants reported symptoms of cough, weight loss, and/or physical weakness. Three of four participants with positive Histoplasma antigen were started on anti-TB treatment. Patient symptoms resolved with no intervention. Conclusion Among outpatients with severe advanced HIV disease with CD4&amp;lt; 100 cells/mcL in Kampala, Uganda Histoplasma antigen prevalence was 2.5%. Disclosures All Authors: No reported disclosures

Novel PVC detection algorithm in an implantable cardiac monitor for longitudinal risk monitoring

Abstract Background Guideline therapy is recommended in patients with frequent premature ventricular contractions (PVCs). Longitudinal monitoring of the PVC burden can effectively guide treatment options, stratify patient risk, and manage HF progression. Implantable cardiac monitors (ICMs) may provide a suitable long-term diagnostic tool to monitor PVC burden and guide clinical therapy. Objective Quantify the performance of a novel QRS morphology and timing-based PVC detection algorithm as implemented for an ICM. Methods The algorithm utilizes self-adapting timing-based ectopy detection and dynamic measures of QRS morphology to identify unifocal and multifocal PVCs. The training dataset consisted of 200 sECG episodes recorded in implanted BIOMONITOR (BM) devices, collected from 48 patients. The algorithm was then evaluated on 227 sixty-second duration sECG episodes from 79 BM patients in the CERTITUDE registry. Each beat was adjudicated as normal, PVC, or PAC by at least two clinical experts. In a total of 22,433 beats, 756 true PVCs were assessed (3.4% PVC prevalence). Overall, patient averaged, and generalized estimating equation (GEE) estimates for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated, as well as patient-specific PVC burden (PVCs/Total Beats). Results Patient-averaged PVC detection sensitivity was 73.8%, with a PPV of 89.2%, specificity of 99.6%, and NPV of 99.1%. Using a GEE model to adjust for multiple episodes per patient, the algorithm achieved detection sensitivity of 66.6±9.8% (95% CI) and PPV of 86.6±6.5%, with specificity of 99.5±0.4% and NPV of 99.0±0.5%. The main reasons for missed PVC detections were morphological similarities to normal beats, insufficient prematurity, or lack of a compensatory pause. Additionally, the algorithm faithfully represented the PVC burden, with a median difference of -0.24% between the PVC burden calculated by the detection algorithm and the adjudicated burden. Algorithm burden was highly correlated with the true PVC burden for each patient, with a Pearson correlation coefficient of 0.80 (p &amp;lt; 0.0001). Conclusions The PVC detection algorithm was highly specific, achieving a specificity of 99.6% and a sensitivity of 73.8%, and accurately representing the overall PVC burden for each patient. This PVC detection algorithm would provide a valuable clinical diagnostic marker to monitor PVC burden trends to guide therapy as well as assess the longitudinal risk of HF. Measurement of PVC burden combined with the 5.5-year longevity of the BIOMONITOR ICM could provide an innovative approach to optimize clinical management of patients.Example PVCs detected by the algorithm

Prevalence and Associated Factors of Dengue Virus Circulation in the Rural Community, Handeni District in Tanga, Tanzania.

Dengue virus is among the most important re-emerging arbovirus that causes global public health attention. Dengue has historically been thought of as an urban disease that frequently occurs in rapidly urbanized settings. However, dengue has become more widespread in rural regions in recent years. Understanding the changing dengue epidemiology in different geographical settings is important for targeted intervention. In Tanzania, dengue fever is not frequently reported because of the poor surveillance infrastructure, underestimation, and a lack of consideration of dengue as a priority. Therefore, the true burden as well as the risk factors for increased transmission has not been fully ascertained, particularly in rural areas. A cross-sectional community-based study was conducted in June 2021, involving a total of 362 participants of all age groups. We investigated the prevalence of acute dengue infection, seroprevalence, and associated factors among the community in three villages of the rural Handeni district. The prevalence of acute dengue infection (based on PCR) was 2.2% (8/362). Dengue-specific IgM and IgG antibodies were detected in 3.3% (12/362) and 5.2% (19/362) of the participants, respectively. Adult participants who were having vegetation around their houses were more likely to be DENV seropositive (AOR = 2.4, CI = 1.88-4.18, p value = 0.05). Children living in houses with garbage pit around their households were less likely to be DENV seropositive (AOR = 0.13, CI = 0.03-0.56, p value <0.01). DENV continues to circulate in rural Tanzania, causes an alarming situation, and necessitates prompt public health action to enhance vector surveillance and control in rural communities.

Abstract 13214: Arrhythmic Burden After Bruton's Tyrosine Kinase Inhibitor Initiation and Major Cardiovascular Events

Background: Bruton’s tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B cell malignancies. BTKi’s also cause cardiotoxic arrhythmias, including atrial fibrillation (AF) and ventricular arrhythmias (VA). Yet, the true burden and long term effects of arrhythmias after BTKi therapy are unknown. Research Question: In patients with suspected BTKi related arrhythmias, what is the relative AF burden? Does it prognosticate future events? Methods: Leveraging a cohort of consecutive B cell malignancy patients initiated on BTKi from 2009-2020, we identified patients with available ambulatory rhythm monitors. The primary outcome was AF burden after BTKi initiation. Secondary outcomes included VA burden, conduction blocks, and other arrhythmias of probable or definite BTKi association. Observed incident AF rates and burden with next generation BTKi’s were compared to ibrutinib. Multivariable regression and survival analysis were used to define factors associated with AF related hospitalizations and major adverse cardiac events (MACE), as well as the relationship between AF burden and mortality. Outcomes were stratified by high (≥5%) vs low (&lt;5%) AF burden. Results: Of 890 BTKi treated patients, 98 wore ambulatory rhythm monitors, including 38 on next generation BTKi’s [age 67.7 years, 24.2% prior AF]. Median duration BTKi use was 34 months. Among next generation BTKi treated patients, 8.7% developed incident AF compared to 25.5% with ibrutinib ( P =0.048). Ten patients (26.3%) developed symptomatic or &gt;1% PVCs, at a mean burden of 7.1% compared to eight patients (13.3%) with mean burden 9.4% on ibrutinib. In a multivariable model accounting for traditional CV risk factors, prior AF associated with increased post BTKi AF burden. In follow up, high AF burden associated with increased MACE (HR 3.49, P =0.001) and mortality (HR 3.2, P =0.002); Figure . Conclusions: In BTKi treated patients, cardiotoxic AF burden prognosticates future MACE and mortality.

Abstract 15939: Site of Origin Associated With Differences in Day-to-Day Variability of Premature Ventricular Contractions

Background Premature ventricular contractions (PVC) from the ventricular outflow tracts are well characterized, but there is limited literature to describe how other sites of origin (SOO) correlate with clinical and electrophysiologic characteristics. Methods We analyzed single lead ambulatory loop monitors (Zio, iRhythm, San Francisco, CA) from 1/2017-3/2020 (n=581) at a single institution. All included subjects had a PVC burden &gt;1% and monitoring period of &gt;72 hours. Twelve-lead ECG of the PVC for each subject was reviewed by an electrophysiologist to identify the SOO. Demographic information, clinical presentation, and cardiac testing results were collected from the electronic medical record. Those without a PVC captured on ECG or with atrial fibrillation or flutter were excluded. Analysis was performed via calculation of odds ratios for presence of dichotomous characteristics and two-tailed t-tests for comparison of means, stratified by outflow tract (OT) versus non-OT SOO and perivalvular (PV) versus non-PV SOO. Results Of 39 subjects who met criteria for inclusion, stratified by SOO (analysis 1: OT (n=18), non-OT (n=21), analysis 2: PV (n=30), non-PV (n=9)), there were no significant differences in the odds of developing certain symptoms or exhibiting certain PVC characteristics. PVCs from OT vs. non-OT and PV vs. non-PV locations had similar burden and numbers of single PVCs, couplets, and triplets. Odds of reporting symptoms were higher with OT than non-OT PVCs (OR 1.49, 95% CI 0.86 - 2.58) and with PV than non-PV PVCs (OR 1.70, 95% CI 0.85 - 3.41). PVC-Native QRS Duration index was no different between SOO groups. Day-to-day variability of PVC burden was higher in OT vs. non-OT SOO (p=0.08), with no difference in PV vs. non-PV SOO (p=0.90). Odds of RV dysfunction were higher in PV vs. non-PV SOO (OR 8, 95% CI 1.54 - 41.64). Coupling interval was longer in non-PV PVCs vs. PV PVCs (n=29, p=0.02). Discussion Electrophysiologic characteristics of PVCs from different sites of origin were similar, suggesting common mechanisms. OT PVCs exhibited more day-to-day variability, emphasizing the need for extended monitoring to characterize true PVC burden. Exploratory analysis by SOO suggests more frequent symptoms with OT PVCs, and RV dysfunction with non-PV SOO.