True Burden Research Articles

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<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 < 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&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&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< 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< 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< 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 < 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.

Abstract 15856: Genetics, Pathologic Characteristics, and Burden of Lethal Hypertrophic Cardiomyopathy Among Countywide Sudden Deaths

Background: Annual incidence of sudden cardiac death (SCD) is reported at 1% in cohorts with known hypertrophic cardiomyopathy (HCM), but these estimates presume arrhythmic cause and miss occult cases dying before diagnosis. Hypothesis: Prospective surveillance and postmortem investigation of community sudden deaths will uncover the true burden of presumed SCD (pSCD) and arrhythmic death (SAD) attributable to HCM. Objectives: Determine characteristics and precise contribution of HCM to population pSCD and SAD. Methods: POST SCD (POstmortem SysTematic Investigation of Sudden Cardiac Death) is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (potentially rescuable with implantable defibrillator) or non-arrhythmic (e.g., tamponade, overdose) causes among pSCDs 0-90 years in San Francisco County. We included all incident cases from 2/1/11-3/1/14 (n=525) and approximately every 3rd day from 3/1/14-9/1/22 (n=497). We identified HCM victims via 3 parallel approaches: 1) pathology criteria; 2) echocardiogram (TTE) review; 3) genetic analysis. Results: Of 1022 pSCDs in the 11-year study period, we identified 13 cases with HCM, yielding a 2% contribution to arrhythmic death burden: 10 met pathology criteria; 2 via review of 203 TTEs (missed on initial report); 1 with pathogenic ALPK3 mutation. Only 2 of 13 (15%) pSCDs with HCM had premortem diagnosis. A greater proportion of pSCDs with HCM had autopsy-confirmed arrhythmic cause than pSCDs without HCM (11/13 [85%] vs. 547/1009 [54%], p=0.03). HCM contribution to pSCD burden decreased with age (p=0.003), highest among victims &lt;35 years, accounting for 7.1% (6/84) of pSCDs and 9.4% (3/32) of SADs. Genetic testing of 317 consented pSCDs (5/12 meeting pathologic or TTE HCM criteria) yielded pathogenic mutations in 40% (2/5), and identified 1 additional case without clinical phenotype. Conclusions: In this 11-year countywide postmortem study, HCM meeting pathologic, clinical, or genetic criteria was associated with autopsy-confirmed arrhythmic cause of sudden death, accounting for 2% of SADs, highest in cases &lt;35 years. As 85% of cases were undiagnosed before pSCD, the true burden of HCM-related sudden death may be substantially underestimated.

Seroprevalence and factors associated with SARS-CoV-2 infection among healthcare workers: cross-sectional study

BackgroundHealthcare workers (HCWs) are at a higher risk of contracting COVID-19 due to their close contact with infected patients. However, the true burden of COVID-19 among HCWs in Yemen is unknown due to the inadequate availability of healthcare and the subclinical nature of the disease. This study aims to estimate the seroprevalence of SARS-CoV-2 infection among HCWs in two Yemeni governorates and identify associated factors using a cross-sectional design.MethodA total of 404 HCWs were surveyed from June 2022 to September 2022 in Lahj and AL-Dhalea hospitals. A self-administered questionnaire collected demographic data, COVID-19 infection history, and vaccination status. A total of 404 human sera were tested using a specific electrochemiluminescence immunoassay assay. Association analysis was conducted to identify associations between antibody prevalence and demographic and vaccine-related variables.ResultThe median age of the HCWs was 31 (Range 20–64) years, with 65.0% being male and 35.0% female. Of all HCWs, 94% were SARS-CoV-2 seropositive and 77.0% had no confirmed test of COVID-19-related symptoms. There was no significant association between seropositivity and demographic factors such as age, gender, occupation, or COVID-19 vaccination (P > 0.05).ConclusionThe seroprevalence of SARS-CoV-2 was high among HCWs in Yemen, primarily due to natural infection rather than vaccination. Compliance with infection prevention and control measures did not significantly affect seropositivity. This study highlights the need for improved healthcare systems and resources to reduce the burden of COVID-19 and promote infection prevention and control (IPC) measures among HCWs in Yemen.

Substantial Burden of Nonmedically Attended RSV Infection in Healthy-Term Infants: An International Prospective Birth Cohort Study.

During the first year of life, 1 in 4 infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV therefore underrepresents the true societal burden of RSV. We assessed the burden of nonmedically attended RSV infections and compared with medically attended RSV. We performed active RSV surveillance until the age of 1 year in a cohort (n = 993) nested within the Respiratory Syncytial Virus Consortium in EUrope (RESCEU) prospective birth cohort study enrolling healthy term-born infants in 5 European countries. Symptoms, medication use, wheezing, and impact on family life were analyzed. For 97 of 120 (80.1%) nonmedically attended RSV episodes, sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97) of episodes; worries, 75.3% (73/97); anxiety, 34.0% (33/97); and work absenteeism, 10.8% (10/93). Compared with medically attended RSV (n = 102, 9 hospital admissions), Respiratory Syncytial Virus NETwork (ReSViNET) severity scores were lower (3.5 vs 4.6, P < .001), whereas duration of respiratory symptoms and was comparable. Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families, and society. These findings are important for policy makers when considering the implementation of RSV immunization. Clinical Trials Registration. ClinicalTrials.gov (NCT03627572).

La Crosse virus neuroinvasive disease: the kids are not alright.

La Crosse virus (LACV) is the most common cause of neuroinvasive mosquito-borne disease in children within the United States. Despite more than 50 years of recognized endemicity in the United States, the true burden of LACV disease is grossly underappreciated, and there remain severe knowledge gaps that inhibit public health interventions to reduce morbidity and mortality. Long-standing deficiencies in disease surveillance, clinical diagnostics and therapeutics, actionable entomologic and environmental risk indices, case response capacity, public awareness, and availability of community support groups clearly frame LACV disease as neglected. Here we synthesize salient prior research and contextualize our findings as an assessment of current gaps and opportunities to develop a framework to prevent, detect, and respond to LACV disease. The persistent burdens of LACV disease clearly require renewed public health attention, policy, and action.

Vaccine value profile for cytomegalovirus

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85–90 %) have asymptomatic infection and are not identified. However, about 7–11 % of those with asymptomatic infection will develop SNHL throughout early childhood.Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden.This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study.

Three years into the pandemic, there remains significant uncertainty about the true infection and mortality burden of COVID-19 in the World Health Organization Africa region. High quality, population-representative studies in Africa are rare and tend to be conducted in national capitals or large cities, leaving a substantial gap in our understanding of the impact of COVID-19 in rural, low-resource settings. Here, we estimated the spatio-temporal morbidity and mortality burden associated with COVID-19 in a rural health district of Madagascar until the first half of 2021. We integrated a nested seroprevalence study within a pre-existing longitudinal cohort conducted in a representative sample of 1600 households in Ifanadiana District, Madagascar. Socio-demographic and health information was collected in combination with dried blood spots for about 6500 individuals of all ages, which were analysed to detect IgG and IgM antibodies against four specific proteins of SARS-CoV-2 in a bead-based multiplex immunoassay. We evaluated spatio-temporal patterns in COVID-19 infection history and its associations with several geographic, socio-economic and demographic factors via logistic regressions. Eighteen percent of people had been infected by April-June 2021, with seroprevalence increasing with individuals' age. COVID-19 primarily spread along the only paved road and in major towns during the first epidemic wave, subsequently spreading along secondary roads during the second wave to more remote areas. Wealthier individuals and those with occupations such as commerce and formal employment were at higher risk of being infected in the first wave. Adult mortality increased in 2020, particularly for older men for whom it nearly doubled up to nearly 40 deaths per 1000. Less than 10% of mortality in this period would be directly attributed to COVID-19 deaths if known infection fatality ratios are applied to observed seroprevalence in the district. Our study provides a very granular understanding on COVID-19 transmission and mortality in a rural population of sub-Saharan Africa and suggests that the disease burden in these areas may have been substantially underestimated.

Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review

Traditionally, within dose-finding clinical trials, treatment toxicity and tolerability are assessed by clinicians. Research has shown that clinician reporting may have inadequate inter-rater reliability, poor correlation with patient reported outcomes, and under capture the true toxicity burden. The introduction of patient-reported outcomes (PROs), where the patient can assess their own symptomatic adverse events or quality of life, has potential to complement current practice to aid dose optimisation. There are no international recommendations offering guidance for the inclusion of PROs in dose-finding trial design and analysis. Our review aimed to identify and describe current statistical methods and data visualisation techniques employed to analyse and visualise PRO data in published early phase dose-finding oncology trials (DFOTs). DFOTs published from June 2016-December 2022, which presented PRO analysis methods, were included in this methodological review. We extracted 35 eligible papers indexed in PubMed. Study characteristics extracted included: PRO objectives, PRO measures, statistical analysis and visualisation techniques, and whether the PRO was involved in interim and final dose selection decisions. Most papers (30, 85.7%) did not include clear PRO objectives. 20 (57.1%) papers used inferential statistical techniques to analyse PROs, including survival analysis and mixed-effect models. One trial used PROs to classify a clinicians' assessed dose-limiting toxicities (DLTs). Three (8.6%) trials used PROs to confirm the tolerability of the recommended dose. 25 trial reports visually presented PRO data within a figure or table within their publication, of which 12 papers presented PRO score longitudinally. This review highlighted that the statistical methods and reporting of PRO analysis in DFOTs are often poorly described and inconsistent. Many trials had PRO objectives which were not clearly described, making it challenging to evaluate the appropriateness of the statistical techniques used. Drawing conclusions based on DFOTs which are not powered for PROs may be misleading. With no guidance and standardisation of analysis methods for PROs in early phase DFOTs, it is challenging to compare study findings across trials. Therefore, there is a crucial need to establish international guidance to enhance statistical methods and graphical presentation for PRO analysis in the dose-finding setting. EA has been supported to undertake this work as part of a PhD studentship from the Institute of Cancer Research within the MRC/NIHR Trials Methodology Research Partnership. AM is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust, the Institute of Cancer Research and Imperial College.

Estimating the burden of severe malarial anaemia and access to hospital care in East Africa

Severe malarial anaemia can be fatal if not promptly treated. Hospital studies may under-represent the true burden because cases often occur in settings with poor access to healthcare. We estimate the relationship of community prevalence of malaria infection and severe malarial anaemia with the incidence of severe malarial anaemia cases in hospital, using survey data from 21 countries and hospital data from Kenya, Tanzania and Uganda. The estimated percentage of severe malarial anaemia cases that were hospitalised is low and consistent for Kenya (21% (95% CrI: 7%, 47%)), Tanzania (18% (95% CrI: 5%, 52%)) and Uganda (23% (95% CrI: 9%, 48%)). The majority of severe malarial anaemia cases remain in the community, with the consequent public health burden being contingent upon the severity of these cases. Alongside health system strengthening, research to better understand the spectrum of disease associated with severe malarial anaemia cases in the community is a priority.

A cost-of-illness analysis of the economic burden of obsessive-compulsive disorder in the United Kingdom

ObjectivesObsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition, with diagnosed patients typically experiencing moderate or severe symptoms. This study evaluated the cost-of-illness (CoI) of OCD in the UK, capturing the annual costs accrued to the National Health Service (NHS) and Personal Social Services (PSS), people with OCD, caregivers and society. MethodsThe UK OCD population was estimated and stratified by age group (children, adults, elderly), symptom severity (mild, moderate, severe) and treatment received (including no treatment). Costs for each subpopulation were estimated through a prevalence-based approach. Cost inputs were sourced from national databases, while additional inputs were informed by literature searches or expert clinician opinion. Scenario analyses explored other factors including comorbid depression treatment and presenteeism. ResultsThe base-case analysis estimated a total annual CoI of £378,356,004 to the NHS, rising to £5,095,759,464 when a societal perspective was considered. The annual cost of care per person with OCD increased with severity (mild: £174; moderate: £365; severe: £902) due to increasing healthcare resource utilisation. The largest contributor to healthcare costs was cognitive behavioural therapy, while societal costs were driven by lost productivity through absenteeism. The base-case results likely underestimated the true economic burden of OCD; including comorbid depression led to a 132% increase in treatment costs, while presenteeism in people with OCD and lost productivity in caregivers amplified indirect costs. ConclusionsThe economic burden of OCD in the UK is substantial and extends beyond direct treatment costs, highlighting a need for research into alternative treatments with greater efficacy.

Using Wastewater Surveillance to Monitor Gastrointestinal Pathogen Infections in the State of Oklahoma.

During the COVID-19 pandemic, wastewater surveillance was widely used to monitor temporal and geographical infection trends. Using this as a foundation, a statewide program for routine wastewater monitoring of gastrointestinal pathogens was established in Oklahoma. The results from 18 months of surveillance showed that wastewater concentrations of Salmonella, Campylobacter, and norovirus exhibit similar seasonal patterns to those observed in reported human cases (F = 4-29, p < 0.05) and that wastewater can serve as an early warning tool for increases in cases, offering between one- and two-weeks lead time. Approximately one third of outbreak alerts in wastewater correlated in time with confirmed outbreaks of Salmonella or Campylobacter and our results further indicated that several outbreaks are likely to go undetected through the traditional surveillance approach currently in place. Better understanding of the true distribution and burden of gastrointestinal infections ultimately facilitates better disease prevention and control and reduces the overall socioeconomic and healthcare related impact of these pathogens. In this respect, wastewater represents a unique opportunity for monitoring infections in real-time, without the need for individual human testing. With increasing demands for sustainable and low-cost disease surveillance, the usefulness of wastewater as a long-term method for tracking infectious disease transmission is likely to become even more pronounced.

A 4-Year Retrospective Study Of Dengue And Chikungunya In Tertiary-Care Hospital Of East Delhi

Backgound&#x0D; Dengue is a vector-borne disease caused by the dengue virus (DENV, 1–4 serotypes), an arbovirus from flaviviridae family and chikungunya virus is an alphavirus.&#x0D; Material and Methods&#x0D; A 4 year retrospective study was conducted from January 2017 to December 2020 to determine the prevalence of the disease among in-patients and OPD patients. NS1 ELISA for invitro diagnostic kit was used to detect anti-dengue immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies from 2017-2018. Bio-Rad Dengue NS1 Ag ELISA kit was employed for 2019-2020.&#x0D; Results&#x0D; There were 5110 samples were received of which 1269 (24.8%) were laboratory-confirmed as DEN infections. The most common affected age group was 21-40 years old. In terms of gender distribution females were more affected with both dengue and chikungunya as compared to males. Results showed that 28.74% of patients were seropositive in 2017. The maximum seropositivity was observed in 2018 with 36.97% and minimum seropositivity observed in 2020 with 3.43%.&#x0D; Conclusion&#x0D; Further epidemiological studies are required to determine the true burden of these infections.