Last data update: May 13, 2024. (Total: 46773 publications since 2009)
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Integrating 'undetectable equals untransmittable' into HIV counselling in South Africa: the development of locally acceptable communication tools using intervention mapping
Sineke T , Bor J , King R , Mokhele I , Dukashe M , Bokaba D , Inglis R , Kgowedi S , Richman B , Kinker C , Blandford J , Ruiter RAC , Onoya D . BMC Public Health 2024 24 (1) 1052 BACKGROUND: The global campaign for "Undetectable equals Untransmittable" (U = U) seeks to spread awareness of HIV treatment as prevention, aiming to enhance psychological well-being and diminish stigma. Despite its potential benefits, U = U faces challenges in Sub-Saharan Africa, with low awareness and hesitancy to endorse it. We sought to develop a U = U communications intervention to support HIV counselling in primary healthcare settings in South Africa. METHODS: We used Intervention Mapping (IM), a theory-based framework to develop the "Undetectable and You" intervention for the South African context. The six steps of the IM protocol were systematically applied to develop the intervention including a needs assessment consisting of a systematic review and qualitative research including focus group discussions (FGD) and key informant (KI) interviews. Program objectives and target population were determined before designing the intervention components and implementation plan. RESULTS: The needs assessment indicated low global U = U awareness, especially in Africa, and scepticism about its effectiveness. Lay counsellors and clinic managers stressed the need for a simple and standardized presentation of U = U addressing both patients' needs for encouragement and modelling of U = U success but also clear guidance toward ART adherence behaviour. Findings from each step of the process informed successive steps. Our final intervention consisted of personal testimonials of PLHIV role models and their partners, organized as an App to deliver U = U information to patients in primary healthcare settings. CONCLUSIONS: We outline an intervention development strategy, currently in evaluation stage, utilizing IM with formative research and input from key U = U stakeholders and people living with HIV (PLHIV). |
First trimester plasma per- and polyfluoroalkyl substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnanacy
Burdeau JA , Stephenson BJK , Aris IM , Preston EV , Hivert MF , Oken E , Mahalingaiah S , Chavarro JE , Calafat AM , Rifas-Shiman SL , Zota AR , James-Todd T . Environ Int 2024 186 108628 BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother. |
The real-world foundation of adapting clinical guidelines for the digital age
Michaels M , Jakhmola P , Lubin IM , Fochtmann LJ , Casey DE Jr , Opelka FG , Skapik J , Larsen K , Tailor A , Matson-Koffman D . Am J Med Qual 2024 39 (2) 89-90 |
Historical reconstruction of inaccessibility status in Local Government Areas (LGAs) of Borno and Yobe States, Nigeria, 2010-2020
Forbi JC , Musa MS , Salawu M , Idris JM , Ba'aba AI , Higgins J , Musa AI , Bashir B , Shettima A , Njeakor N , Uzoma I , Mshelia H , Nganda GW , Mohammed KI , Bomoi IM , Chiroma U , Kovacs SD , Biya O , Waziri NE , Aina M , Adamu US , Shuaib F , Bolu O , Franka R , Wiesen E . Pan Afr Med J 2023 45 7 INTRODUCTION: ultimately detected in 2016, wild poliovirus (WPV) transmission continued undetected after 2011 in Northeast Nigeria Borno and Yobe States in security-compromised areas, inaccessible due to armed insurgency. Varying inaccessibility prevented children aged <5 years in these areas from polio vaccination interventions and surveillance, while massive population displacements occurred. We examined progress in access over time to provide data supporting a very low probability of undetected WPV circulation within remaining trapped populations after 2016. METHODS: to assess the extent of inaccessibility in security-compromised areas, we obtained empirical historical data in 2020 on a quarterly and annual basis from relevant polio eradication staff for the period 2010-2020. The extent of access to areas for immunization by recall was compared to geospatial data from vaccinator tracking. Population estimates over time in security-compromised areas were extracted from satellite imagery. We compared the historical access data from staff with tracking and population esimates. RESULTS: access varied during 2010-2020, with inaccessibility peaking during 2014-2016. We observed concurrent patterns between historical recalled data on inaccessibility and contemporaneous satellite imagery on population displacements, which increased confidence in the quality of recalled data. CONCLUSION: staff-recalled access was consistent with vaccinator tracking and satellite imagery of population displacments. Despite variability in inaccessibility over time, innovative immunization initiatives were implemented as access allowed and surveillance initiatives were initiated to search for poliovirus transmission. Along with escape and liberation of residents by the military in some geographic areas, these initiatives resulted in a massive reduction in the size of the unvaccinated population remaining resident. |
Newborn screening: from Guthrie to whole genome sequencing.
Caggana M , Jones EA , Shahied SI , Tanksley S , Hermerath CA , Lubin IM . Public Health Rep 2013 128 Suppl 2 14-9 Newborn screening (NBS), a comprehensive system that includes testing, diagnosis, follow-up, treatment, education, and evaluation, was recently named one of the Top 10 Great Public Health Achievements by the Centers for Disease Control and Prevention (CDC).1 Each year, approximately 10,000 infants are identified with NBS conditions, which frequently go unnoticed at birth.2 NBS is administered by state public health programs across the country and provides for early identification of newborns with certain congenital, metabolic, endocrine, hematologic, and other genetic conditions. Early identification of these conditions in newborns facilitates timely interventions that result in significant decreases in morbidity, mortality, and disability.1 | | Screening begins by pricking a newborn's heel to get enough blood to fill a few circles on a filter paper card. The specimen, referred to as a dried blood spot, is collected by a health-care provider—typically at the birthing facility—during the first 24–48 hours of life. Some states are required to collect two specimens, in which case the second specimen is collected between seven and 15 days of life. The specimens are then sent to a state-designated NBS laboratory for analysis. When a test result is out of normal range, laboratory or follow-up personnel contact the birthing facility and the newborn's physician to ensure the child receives the appropriate diagnostic work-up and treatment. NBS goes beyond blood-spot screening to include point-of-care testing for hearing and, in some states, critical congenital heart disease. These tests are performed at the hospital shortly after birth, and the state NBS program performs follow-up testing. Although there is some variability in protocols among states, most NBS programs have similar components, including specimen collection, laboratory testing, follow-up, education of providers and the public, verification of a diagnosis, treatment, and ongoing program evaluation.3 |
Effective communication of molecular genetic test results to primary care providers.
Scheuner MT , Edelen MO , Hilborne LH , Lubin IM . Genet Med 2013 15 (6) 444-9 PURPOSE: We evaluated a template for molecular genetic test reports that was developed as a strategy to reduce communication errors between the laboratory and ordering clinician. METHODS: We surveyed 1,600 primary care physicians to assess satisfaction, ease of use, and effectiveness of genetic test reports developed using our template and reports developed by clinical laboratories. Mean score differences of responses between the reports were compared using t-tests. Two-way analysis of variance evaluated the effect of template versus standard reports and the influence of physician characteristics. RESULTS: There were 396 (24%) respondents. Template reports had higher scores than the standard reports for each survey item. The gender and specialty of the physician did not influence scores; however, younger physicians gave higher scores regardless of report type. There was significant interaction between report type and whether physicians ordered or reviewed any genetic tests (none versus at least one) in the past year, P = 0.005. CONCLUSION: For each survey item assessing satisfaction, ease of use, and effectiveness, physicians gave higher ratings to genetic test reports developed with the template than standard reports used by clinical laboratories. Physicians least familiar with genetic test reports, and possibly having the greatest need for better communication, were best served by the template reports. |
Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.
Bayer DK , Martinez CA , Sorte HS , Forbes LR , Demmler-Harrison GJ , Hanson IC , Pearson NM , Noroski LM , Zaki SR , Bellini WJ , Leduc MS , Yang Y , Eng CM , Patel A , Rodningen OK , Muzny DM , Gibbs RA , Campbell IM , Shaw CA , Baker MW , Zhang V , Lupski JR , Orange JS , Seeborg FO , Stray-Pedersen A . Clin Exp Immunol 2014 178 (3) 459-69 In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients. |
Fostering governance and information partnerships for chronic disease surveillance: The Multi-State EHR-Based Network for Disease Surveillance
Kraus EM , Saintus L , Martinez AK , Brand B , Begley E , Merritt RK , Hamilton A , Rubin R , Sullivan A , Karras BT , Grannis S , Brooks IM , Mui JY , Carton TW , Hohman KH , Klompas M , Dixon BE . J Public Health Manag Pract 2024 30 (2) 244-254 CONTEXT: Electronic health records (EHRs) are an emerging chronic disease surveillance data source and facilitating this data sharing is complex. PROGRAM: Using the experience of the Multi-State EHR-Based Network for Disease Surveillance (MENDS), this article describes implementation of a governance framework that aligns technical, statutory, and organizational requirements to facilitate EHR data sharing for chronic disease surveillance. IMPLEMENTATION: MENDS governance was cocreated with data contributors and health departments representing Texas, New Orleans, Louisiana, Chicago, Washington, and Indiana through engagement from 2020 to 2022. MENDS convened a governance body, executed data-sharing agreements, and developed a master governance document to codify policies and procedures. RESULTS: The MENDS governance committee meets regularly to develop policies and procedures on data use and access, timeliness and quality, validation, representativeness, analytics, security, small cell suppression, software implementation and maintenance, and privacy. Resultant policies are codified in a master governance document. DISCUSSION: The MENDS governance approach resulted in a transparent governance framework that cultivates trust across the network. MENDS's experience highlights the time and resources needed by EHR-based public health surveillance networks to establish effective governance. |
Rapid identification of enteric bacteria from whole genome sequences using average nucleotide identity metrics
Lindsey RL , Gladney LM , Huang AD , Griswold T , Katz LS , Dinsmore BA , Im MS , Kucerova Z , Smith PA , Lane C , Carleton HA . Front Microbiol 2023 14 1225207 Identification of enteric bacteria species by whole genome sequence (WGS) analysis requires a rapid and an easily standardized approach. We leveraged the principles of average nucleotide identity using MUMmer (ANIm) software, which calculates the percent bases aligned between two bacterial genomes and their corresponding ANI values, to set threshold values for determining species consistent with the conventional identification methods of known species. The performance of species identification was evaluated using two datasets: the Reference Genome Dataset v2 (RGDv2), consisting of 43 enteric genome assemblies representing 32 species, and the Test Genome Dataset (TGDv1), comprising 454 genome assemblies which is designed to represent all species needed to query for identification, as well as rare and closely related species. The RGDv2 contains six Campylobacter spp., three Escherichia/Shigella spp., one Grimontia hollisae, six Listeria spp., one Photobacterium damselae, two Salmonella spp., and thirteen Vibrio spp., while the TGDv1 contains 454 enteric bacterial genomes representing 42 different species. The analysis showed that, when a standard minimum of 70% genome bases alignment existed, the ANI threshold values determined for these species were ≥95 for Escherichia/Shigella and Vibrio species, ≥93% for Salmonella species, and ≥92% for Campylobacter and Listeria species. Using these metrics, the RGDv2 accurately classified all validation strains in TGDv1 at the species level, which is consistent with the classification based on previous gold standard methods. |
Seroprevalence to schistosoma soluble egg antigen among nomadic pastoralists residing in Northern Senegal
Seck MC , Badiane AS , Thwing J , Ndiaye M , Diongue K , Ndiaye IM , Diallo MA , Sy M , Gomis JF , Ndiaye T , Gaye A , Lee YM , Secor WE , Ndiaye D , Rogier E . J Parasitol 2023 109 (6) 580-587 Urinary and intestinal schistosomiasis are endemic in Senegal, with prevalence heterogeneous throughout the country. Because of their way of life, nomadic pastoralists are not typically included in epidemiological surveys, and data on the prevalence of schistosomiasis in Senegalese nomadic populations are largely non-existent. The purpose of this study was to determine the seroprevalence of schistosomiasis in Senegalese nomadic pastoralists. A modified snowball sampling survey was conducted among 1,467 nomadic pastoralists aged 6 mo and older in 5 districts in northern Senegal. Dried blood spots from participants of all ages and data regarding demographics were collected to assess IgG antibody responses against Schistosoma mansoni soluble egg antigen (SEA) using a bead-based multiplex assay. Out of 1,467 study subjects, 1,464 (99.8%) provided IgG serological data that cleared quality assurance. Of the participants with appropriate data, 56.6% were male, the median age was 22 yr, and 31.6% were under 15 yr of age. The overall anti-SEA IgG seroprevalence was 19.1% (95% confidence interval [CI]: 17.1-21.1%) with the highest estimates observed in Dagana (35.9%) and the lowest observed in Podor nomadic groups (3.4%). Antibody responses increased significantly with age except for the oldest age groups (>40 yr of age), which saw lower levels of antibody response compared to younger adults. When controlling for age and location by multivariate regression, the male sex was associated with a 2-fold greater odds of anti-SEA IgG seropositivity (aPOR: 2.0; 95% CI: 1.5-2.7). Serosurveys for anti-SEA IgG among nomadic peoples in northern Senegal found a substantial percentage of individuals with evidence for current or previous Schistosoma spp. infection with the highest levels of exposure in the district adjacent to the Diama dam along the Senegal River. With IgG prevalence increased by age except in the older adults, and the male sex significantly associated with seropositivity, these data point toward sex-associated behavioral practices and human environmental modification as risk factors for Schistosoma exposure. |
Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal
Schaffner SF , Badiane A , Khorgade A , Ndiop M , Gomis J , Wong W , Ndiaye YD , Diedhiou Y , Thwing J , Seck MC , Early A , Sy M , Deme A , Diallo MA , Sy N , Sene A , Ndiaye T , Sow D , Dieye B , Ndiaye IM , Gaye A , Ndiaye A , Battle KE , Proctor JL , Bever C , Fall FB , Diallo I , Gaye S , Sene D , Hartl DL , Wirth DF , MacInnis B , Ndiaye D , Volkman SK . Nat Commun 2023 14 (1) 7268 We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure. |
Evaluation of whole and core genome multilocus sequence typing allele schemes for Salmonella enterica outbreak detection in a national surveillance network, PulseNet USA
Leeper MM , Tolar BM , Griswold T , Vidyaprakash E , Hise KB , Williams GM , Im SB , Chen JC , Pouseele H , Carleton HA . Front Microbiol 2023 14 1254777 Salmonella enterica is a leading cause of bacterial foodborne and zoonotic illnesses in the United States. For this study, we applied four different whole genome sequencing (WGS)-based subtyping methods: high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multilocus sequence typing using either all loci [wgMLST (all loci)] and only chromosome-associated loci [wgMLST (chrom)], and core genome multilocus sequence typing (cgMLST) to a dataset of isolate sequences from 9 well-characterized Salmonella outbreaks. For each outbreak, we evaluated the genomic and epidemiologic concordance between hqSNP and allele-based methods. We first compared pairwise genomic differences using all four methods. We observed discrepancies in allele difference ranges when using wgMLST (all loci), likely caused by inflated genetic variation due to loci found on plasmids and/or other mobile genetic elements in the accessory genome. Therefore, we excluded wgMLST (all loci) results from any further comparisons in the study. Then, we created linear regression models and phylogenetic tanglegrams using the remaining three methods. K-means analysis using the silhouette method was applied to compare the ability of the three methods to partition outbreak and sporadic isolate sequences. Our results showed that pairwise hqSNP differences had high concordance with cgMLST and wgMLST (chrom) allele differences. The slopes of the regressions for hqSNP vs. allele pairwise differences were 0.58 (cgMLST) and 0.74 [wgMLST (chrom)], and the slope of the regression was 0.77 for cgMLST vs. wgMLST (chrom) pairwise differences. Tanglegrams showed high clustering concordance between methods using two statistical measures, the Baker's gamma index (BGI) and cophenetic correlation coefficient (CCC), where 9/9 (100%) of outbreaks yielded BGI values ≥ 0.60 and CCCs were ≥ 0.97 across all nine outbreaks and all three methods. K-means analysis showed separation of outbreak and sporadic isolate groups with average silhouette widths ≥ 0.87 for outbreak groups and ≥ 0.16 for sporadic groups. This study demonstrates that Salmonella isolates clustered in concordance with epidemiologic data using three WGS-based subtyping methods and supports using cgMLST as the primary method for national surveillance of Salmonella outbreak clusters. |
Changes in provider perceptions and practices regarding dosing units for oral liquid medications
Lind JN , Lovegrove MC , Paul IM , Shonna Yin H , Budnitz DS . Acad Pediatr 2023 OBJECTIVE: A 2015 survey of primary care providers (PCPs) found that while many believed that milliliter (mL)-only dosing was safest for oral liquid medications, few would use mL alone in dosing instructions. Since 2015, many recommendations have promoted "mL-only" dosing. In 2019, a follow-up survey was conducted to assess if PCP perceptions and practices have changed. METHODS: Pediatricians, family medicine physicians, nurse practitioners, and internists participating in the 2015 and 2019 DocStyles cross-sectional, web-based surveys were asked about their perceptions and practices regarding dosing units for oral liquid medications. RESULTS: In 2019, among 1392 respondents, the proportion of PCPs who reported they believed using mL-only is the safest dosing instruction ranged from 55.1% of internists to 80.8% of pediatricians. While fewer PCPs believed patients/caregivers prefer dosing instructions in mL-only (23.9% of nurse practitioners to 48.4% of pediatricians), more held this belief in 2019 compared to 2015; pediatricians had the greatest absolute increase (+14.4%) and family medicine physicians had the smallest increase (+1.3%). While 61.6% of pediatricians reported they would use mL-only dosing, only 36.0% of internists, 36.6% of nurse practitioners, and 42.5% of family medicine physicians reported they would do so. After controlling for age, gender, region, and specialty, 2019 PCP survey participants were more likely to report that they would use mL-only dosing compared to 2015 participants (adjusted odds ratio 1.51, 95% confidence interval 1.29-1.77). CONCLUSIONS: Broader educational efforts may be necessary to reach non-pediatricians, to encourage prescribing and communication with patients/caregivers using mL-only dosing. |
An integrated process for co-developing and implementing written and computable clinical practice guidelines
Matson-Koffman DM , Robinson SJ , Jakhmola P , Fochtmann LJ , Willett D , Lubin IM , Burton MM , Tailor A , Pitts DL , Casey DE Jr , Opelka FG , Mullins R , Elder R , Michaels M . Am J Med Qual 2023 38 S12-s34 The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes. |
An evaluation framework for a novel process to codevelop written and computable guidelines
Tailor A , Robinson SJ , Matson-Koffman DM , Michaels M , Burton MM , Lubin IM . Am J Med Qual 2023 38 S35-s45 Clinical practice guidelines (CPGs) support individual and population health by translating new, evidence-based knowledge into recommendations for health practice. CPGs can be provided as computable, machine-readable guidelines that support the translation of recommendations into shareable, interoperable clinical decision support and other digital tools (eg, quality measures, case reports, care plans). Interdisciplinary collaboration among guideline developers and health information technology experts can facilitate the translation of written guidelines into computable ones. The benefits of interdisciplinary work include a focus on the needs of end-users who apply guidelines in practice through clinic decision support systems as part of the Centers for Disease Control and Prevention's (CDC's) Adapting Clinical Guidelines for the Digital Age (ACG) initiative, a group of interdisciplinary experts proposed a process to facilitate the codevelopment of written and computable CPGs, referred to as the "integrated process (IP)."1 This paper presents a framework for evaluating the IP based on a combination of vetted evaluation models and expert opinions. This framework combines 3 types of evaluations: process, product, and outcomes. These evaluations assess the value of interdisciplinary expert collaboration in carrying out the IP, the quality, usefulness, timeliness, and acceptance of the guideline, and the guideline's health impact, respectively. A case study is presented that illustrates application of the framework. |
Population analysis of Vibrio cholerae in aquatic reservoirs reveals a novel sister species (Vibrio paracholerae sp. nov.) with a history of association with human infections (preprint)
Islam MT , Nasreen T , Kirchberger P , Liang KYH , Orata FD , Johura FT , Im MS , Tarr CL , Alam M , Boucher YF . bioRxiv 2021 2021.05.05.442690 Most efforts to understand the biology of Vibrio cholerae have focused on a single group, the pandemic-generating lineage harbouring the strains responsible for all known cholera pandemics. Consequently, little is known about the diversity of this species in its native aquatic environment. To understand the differences in the V. cholerae populations inhabiting in regions with varying history of cholera cases and how that might influence the abundance of pandemic strains, a comparative analysis of population composition was performed. Little overlap was found in lineage compositions between those in Dhaka (cholera endemic) located in the Ganges delta, and of Falmouth (no known history of cholera), a small coastal town on the US East Coast. The most striking difference was the presence of a group of related lineages at high abundance in Dhaka which was completely absent from Falmouth. Phylogenomic analysis revealed that these lineages form a cluster at the base of the phylogeny of V. cholerae species, sufficiently differentiated genetically and phenotypically to form a novel species. Strains from this species have been anecdotally isolated from around the world and were isolated as early as 1916 from a British soldier in Egypt suffering from choleraic diarrhoea. In 1935 Gardner and Venkatraman unofficially referred to a member of this group as Vibrio paracholerae. In recognition of this earlier designation, we propose the name Vibrio paracholerae, sp. nov. for this bacterium. Genomic analysis suggests a link with human populations for this novel species and substantial interaction with its better-known sister species.Importance Cholera continues to remain a major public health threat around the globe. Understanding the ecology, evolution and environmental adaptation of the causative agent Vibrio cholerae and tracking the emergence of novel lineages with pathogenic potential are essential to combat the problem. In this study, we investigated the population dynamics of Vibrio cholerae in an inland locality which is known as endemic for cholera and compared with that of a cholera free coastal location. We found the consistent presence of the pandemic generating V. cholerae in cholera-endemic Dhaka and an exclusive presence of a lineage phylogenetically distinct from other V. cholerae. Our study suggests that this lineage represents a novel species having pathogenic potential and a human link to its environmental abundance. The possible association with human population, co-existence and interaction with toxigenic V. cholerae in the natural environment make this potential human pathogen an important subject for future studies.Competing Interest StatementThe authors have declared no competing interest. |
Creation of an Expert Curated Variant List for Clinical Genomic Test Development and Validation: A ClinGen and GeT-RM Collaborative Project (preprint)
Wilcox E , Harrison SM , Lockhart E , Voelkerding K , Lubin IM , Rehm HL , Kalman L , Funke B . medRxiv 2021 2021.06.09.21258594 Modern genomic sequencing tests often interrogate large numbers of genes. Identification of appropriate reference materials for development, validation studies, and quality assurance of these tests poses a significant challenge for laboratories. It is difficult to develop and maintain expert knowledge to identify all variants that must be validated to assure analytic and clinical validity. Additionally, it is usually not possible to procure appropriate and characterized genomic DNA reference materials containing the number and scope of variants required. To address these challenges, the Centers for Disease Control and Prevention’s Genetic Testing Reference Material Program (GeT-RM) has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated, clinically important variants. ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease associated genes, including common pathogenic and difficult to detect variants. Variant types nominated included 346 SNVs, 104 deletions, 37 CNVs, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 in difficult to sequence regions, and 2 fusions. This expert-curated variant list is a resource that provides a foundation for designing comprehensive validation studies and for creating in silico reference materials for clinical genomic test development and validation.Competing Interest StatementThe authors have declared no competing interest.Funding StatementClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study did not involve human subjects and therefore no IRB was required.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data is included in the figures, tables and supplement included in the manuscript. |
Guiding Vaccine Efficacy Trial Design During Public Health Emergencies: An interactive web-based decision support tool (preprint)
Bellan SE , Eggo RM , Gsell PS , Kucharski AJ , Dean NE , Donohue R , Zook M , Odhiambo F , Longini IM Jr , Brisson M , Mahon BE , Henao-Restrepo AM . bioRxiv 2018 252783 The design and execution of rigorous, fast, and ethical vaccine efficacy trials can be challenging during epidemics of emerging pathogens, such as the 2014-2016 Ebola virus and 2015-2016 Zika virus epidemics. Response to an urgent public health crisis requires accelerated research even as emerging epidemics themselves change rapidly and are inherently less well understood than well-established diseases. As part of the World Health Organization Research and Development Blueprint, we designed a web-based interactive decision support system (InterVax-Tool) to help diverse stakeholders navigate the epidemiological, logistical, and ethical decisions involved in designing a vaccine efficacy trial during a public health emergency. In contrast to existing literature on trial design, InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of 1) the Primary Endpoint, (2) the Target Population, (3) Randomization, and (4) the Comparator. Guidance is provided on how each of fourteen key considerations–grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural–should be used to inform each decision in the trial design process. The tool is not intended to provide a black box decision framework for identifying an optimal trial design, but rather to facilitate transparent, collaborative and comprehensive discussion of the relevant decisions, while recording the decision process. The tool can also assist capacity building by providing a cross-disciplinary picture of trial design using concepts from epidemiology, study design, vaccinology, biostatistics, mathematical modeling and clinical research ethics. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.One Sentence Summary An interactive web-based decision support tool was developed to assist in the design of vaccine efficacy trials during emerging outbreaks. |
Integrated SARS-CoV-2 serological and virological screening across an acute fever surveillance platform to monitor temporal changes in anti-spike antibody levels and risk of infection during sequential waves of variant transmission - Dominican Republic, March 2021 to August 2022 (preprint)
Nilles EJ , Aubin MDSt , Dumas D , Duke W , Etienne MC , Abdalla G , Jarolim P , Oasan T , Garnier S , Iihoshi N , Lopez B , de la Cruz L , Puello YC , Baldwin M , Roberts KW , Pena F , Durski K , Sanchez IM , Gunter SM , Kneubehl AR , Murray KO , Lino A , Strobel S , Baez AA , Lau CL , Kucharski A , Gutierrez EZ , Skewes-Ramm R , Vasquez M , Paulino CT . medRxiv 2022 26 The global SARS-CoV-2 immune landscape and population protection against emerging variants is largely unknown. We assessed SARS-CoV-2 antibody changes in the Dominican Republic and implications for immunological protection against variants of concern. Between March 2021 and August 2022, 2,300 patients with undifferentiated febrile illnesses were prospectively enrolled. Sera was tested for total anti-spike antibodies and simultaneously collected nasopharyngeal samples for acute SARSCoV-2 infection with RT-PCR. Geometric mean anti-spike titers increased from 6.6 BAU/ml (95% CI 5.1-8.7) to 1,332 BAU/ml (1055-1,682). Multivariable binomial odds ratios for acute SARS-CoV-2 infection were 0.55 (0.40-0.74), 0.38 (0.27-0.55), and 0.27 (0.18-0.40) for the second, third, and fourth versus the first anti-S quartile, with similar findings by viral strain. Integrated serological and virological screening can leverage existing acute fever surveillance platforms to monitor population-level immunological markers and concurrently characterize implications for emergent variant transmission in near real-time. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention (preprint)
Ndiaye YD , Wong W , Thwing J , Schaffner SS , Tine A , Diallo MA , Deme A , Sy M , Bei AK , Thiaw AB , Daniels R , Ndiaye T , Gaye A , Ndiaye IM , Toure M , Gadiaga N , Sene A , Sow D , Garba MN , Yade MS , Dieye B , Diongue K , Zoumarou D , Ndiaye A , Gomis J , Fall FB , Ndiop M , Diallo I , Sene D , Macinnis B , Seck MC , Ndiaye M , Badiane AS , Hartl DL , Volkman SK , Wirth DF , Ndiaye D . medRxiv 2023 26 Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase in Pfcrt K76T and decline in Pfdhps A437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Knowledge of COVID-19 Symptoms, Transmission, and Prevention: Evidence from Health and Demographic Surveillance in Southern Mozambique (preprint)
Nhacolo AQ , Madewell ZJ , Muir JA , Sacoor CN , Xerinda EG , Matsena T , Bassat Q , Whitney CG , Mandomando IM , Cunningham SA . medRxiv 2023 03 Over 230,000 COVID-19 cases and over 2,200 deaths have been reported in Mozambique though May 2023. Understanding community members' knowledge of SARS-CoV-2 transmission and prevention is essential for directing public health interventions to reduce disease spread and improve vaccination coverage. Here, we describe knowledge of COVID-19 transmission, prevention, and symptoms among community residents in Mozambique. We conducted a cross-sectional survey among 33,087 households in a Health and Demographic Surveillance System in Manhica, Mozambique. Participants were recruited at the tail end of the Delta variant wave in September 2021 to the peak of Omicron cases in January 2022. Principal components analysis was used to create scores representing knowledge of COVID-19 symptoms, transmission, and prevention. Multiple imputation and quasi-Poisson regression were used to examine associations between demographic characteristics and sources of COVID-19 information, and knowledge of COVID-19 symptoms, transmission, and prevention. We examined whether sources of COVID-19 information mediated the relationship between educational attainment and knowledge of symptoms, transmission, and prevention. Across this rural community, 98.2%, 97.0%, and 85.1% of respondents reported knowing how COVID-19 could be prevented, that SARS-CoV-2 can cause disease, and how SARS-CoV-2 is transmitted, respectively. Most cited symptoms were cough (51.2%), headaches (44.9%), and fever (44.5%); transmission mechanisms were droplets (50.5%) or aerosol (<5 microm diameter) (46.9%) from an infected person; and prevention measures were handwashing (91.9%) and mask-wearing (91.8%). Characteristics associated with greater knowledge of symptoms, transmission, and prevention included having at least primary education, older age, employment, higher wealth, and Christian religion. Respondents who had had COVID-19 symptoms were also more likely to have knowledge of symptoms, transmission, and prevention. Gathering information from TV, WhatsApp, radio, and hospital mediated the relationship between educational attainment and knowledge scores. These findings support the need for outreach and for community-engaged messaging to promote prevention measures, particularly among people with low education. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Vibrio tarriae sp. nov., a novel member of the Cholerae clade isolated from across the United States (preprint)
Islam MT , Liang K , Orata FD , Im MS , Alam M , Lee CC , Boucher YF . bioRxiv 2022 17 A number of bacteria with close resemblance to Vibrio cholerae has been isolated over the years by the Centers for Disease Control and Prevention (CDC), which could not be assigned a proper taxonomic designation based on preliminary identification methods. Nine such isolates have been found to share 16S rRNA gene identity exceeding 99% with V. cholerae, yet DNA-DNA hybridization (60.4-62.1%) and average nucleotide identity values (94.4-95.1%) were below the species cut-off, indicating a potentially novel species. Phylogenetic analysis of core genomes places this group of isolates in a monophyletic clade, within the "Cholerae clade," but distinct from any other species. Extensive phenotypic characterization reveals unique biochemical properties that distinguish this novel species from V. cholerae. Comparative genomic analysis reveals a unique set of siderophore genes, suggesting that iron acquisition strategies could be vital for the divergence of the novel species from a common ancestor with V. cholerae. Based on genetic, phylogenetic, and phenotypic differences observed, we propose these isolates represent a novel species of the genus Vibrio, for which the name Vibrio tarriae sp. nov. is proposed. Strain 2521-89 (= DSM 112461 = CCUG 75318), isolated from lake water, is the type strain. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal (preprint)
Schaffner SF , Badiane A , Khorgade A , Ndiop M , Gomis J , Wong W , Ndiaye YD , Diedhiou Y , Thwing J , Seck MC , Early A , Sy M , Deme A , Diallo MA , Sy N , Sene A , Ndiaye T , Sow D , Dieye B , Ndiaye IM , Gaye A , Ndiaye A , Battle KE , Proctor JL , Bever C , Fall FB , Diallo I , Gaye S , Sene D , Hartl DL , Wirth DF , MacInnis B , Ndiaye D , Volkman SK . medRxiv 2023 17 Parasite genetic surveillance has the potential to play an important role in malaria control. We describe here an analysis of data from the first year of an ongoing, nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal, intended to provide actionable information for malaria control efforts. Looking for a good proxy for local malaria incidence, we found that the best predictor was the proportion of polygenomic infections (those with multiple genetically distinct parasites), although that relationship broke down at very low incidence. The proportion of closely related parasites in a site was more weakly correlated with incidence while the local genetic diversity was uninformative. Study of related parasites indicated their potential for discriminating local transmission patterns: two nearby study areas had similarly high fractions of relatives, but one area was dominated by clones and the other by outcrossed relatives. Throughout the country, most related parasites proved to belong to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci as well as at one novel locus, reflective of ongoing selection pressure. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Estimates of SARS-CoV-2 seroprevalence and incidence of primary SARS-CoV-2 infections among blood donors, by COVID-19 vaccination status - United States, April 2021-September 2022
Jones JM , Manrique IM , Stone MS , Grebe E , Saa P , Germanio CD , Spencer BR , Notari E , Bravo M , Lanteri MC , Green V , Briggs-Hagen M , Coughlin MM , Stramer SL , Opsomer J , Busch MP . MMWR Morb Mortal Wkly Rep 2023 72 (22) 601-605 Changes in testing behaviors and reporting requirements have hampered the ability to estimate the U.S. SARS-CoV-2 incidence (1). Hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone (2). To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies (or both), data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 (April-June), an estimated 68.4% of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including 47.5% from vaccination alone, 12.0% from infection alone, and 8.9% from both. By the third quarter of 2022 (July-September), 96.4% had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years (36.9%), the group with the highest risk for severe disease if infected, and was highest among those aged 16-29 years (59.6%). Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*(,)(†). |
Characterization of a nonagglutinating toxigenic vibrio cholerae isolate
Gladney LM , Griswold T , Turnsek M , Im MS , Parsons MMB , Katz LS , Tarr CL , Lee CC . Microbiol Spectr 2023 11 (3) e0018223 Toxigenic Vibrio cholerae serogroup O1 is the etiologic agent of the disease cholera, and strains of this serogroup are responsible for pandemics. A few other serogroups have been found to carry cholera toxin genes-most notably, O139, O75, and O141-and public health surveillance in the United States is focused on these four serogroups. A toxigenic isolate was recovered from a case of vibriosis from Texas in 2008. This isolate did not agglutinate with any of the four different serogroups' antisera (O1, O139, O75, or O141) routinely used in phenotypic testing and did not display a rough phenotype. We investigated several hypotheses that might explain the recovery of this potential nonagglutinating (NAG) strain using whole-genome sequencing analysis and phylogenetic methods. The NAG strain formed a monophyletic cluster with O141 strains in a whole-genome phylogeny. Furthermore, a phylogeny of ctxAB and tcpA sequences revealed that the sequences from the NAG strain also formed a monophyletic cluster with toxigenic U.S. Gulf Coast (USGC) strains (O1, O75, and O141) that were recovered from vibriosis cases associated with exposures to Gulf Coast waters. A comparison of the NAG whole-genome sequence showed that the O-antigen-determining region of the NAG strain was closely related to those of O141 strains, and specific mutations were likely responsible for the inability to agglutinate. This work shows the utility of whole-genome sequence analysis tools for characterization of an atypical clinical isolate of V. cholerae originating from a USGC state. IMPORTANCE Clinical cases of vibriosis are on the rise due to climate events and ocean warming (1, 2), and increased surveillance of toxigenic Vibrio cholerae strains is now more crucial than ever. While traditional phenotyping using antisera against O1 and O139 is useful for monitoring currently circulating strains with pandemic or epidemic potential, reagents are limited for non-O1/non-O139 strains. With the increased use of next-generation sequencing technologies, analysis of less well-characterized strains and O-antigen regions is possible. The framework for advanced molecular analysis of O-antigen-determining regions presented herein will be useful in the absence of reagents for serotyping. Furthermore, molecular analyses based on whole-genome sequence data and using phylogenetic methods will help characterize both historical and novel strains of clinical importance. Closely monitoring emerging mutations and trends will improve our understanding of the epidemic potential of Vibrio cholerae to anticipate and rapidly respond to future public health emergencies. |
Hepatitis B vaccine delivered by microneedle patch: Immunogenicity in mice and rhesus macaques
Choi Y , Lee GS , Li S , Lee JW , Mixson-Hayden T , Woo J , Xia D , Prausnitz MR , Kamili S , Purdy MA , Tohme RA . Vaccine 2023 41 (24) 3663-3672 Vaccination against hepatitis B using a dissolving microneedle patch (dMNP) could increase access to the birth dose by reducing expertise needed for vaccine administration, refrigerated storage, and safe disposal of biohazardous sharps waste. In this study, we developed a dMNP to administer hepatitis B surface antigen (HBsAg) adjuvant-free monovalent vaccine (AFV) at doses of 5 µg, 10 µg, and 20 µg, and compared its immunogenicity to vaccination with 10 µg of standard monovalent HBsAg delivered by intramuscular (IM) injection either in an AFV format or as aluminum-adjuvanted vaccine (AAV). Vaccination was performed on a three dose schedule of 0, 3, and 9 weeks in mice and 0, 4, and 24 weeks in rhesus macaques. Vaccination by dMNP induced protective levels of anti-HBs antibody responses (≥10 mIU/ml) in mice and rhesus macaques at all three HBsAg doses studied. HBsAg delivered by dMNP induced higher anti-HBsAg antibody (anti-HBs) responses than the 10 µg IM AFV, but lower responses than 10 µg IM AAV, in mice and rhesus macaques. HBsAg-specific CD4+ and CD8+ T cell responses were detected in all vaccine groups. Furthermore, we analyzed differential gene expression profiles related to each vaccine delivery group and found that tissue stress, T cell receptor signaling, and NFκB signaling pathways were activated in all groups. These results suggest that HBsAg delivered by dMNP, IM AFV, and IM AAV have similar signaling pathways to induce innate and adaptive immune responses. We further demonstrated that dMNP was stable at room temperature (20 °C-25 °C) for 6 months, maintaining 67 ± 6 % HBsAg potency. This study provides evidence that delivery of 10 µg (birth dose) AFV by dMNP induced protective levels of antibody responses in mice and rhesus macaques. The dMNPs developed in this study could be used to improve hepatitis B birth dose vaccination coverage levels in resource limited regions to achieve and maintain hepatitis B elimination. |
Response to Editorial
Bruce MG , Miernyk K , Sacco F , Thomas T , McMahon B , Hennessy T . Helicobacter 2019 24 (2) e12558 We read with interest the editorial by Lee et al1 | that highlighted | the challenge of elevated rates of H pylori‐associated gastric can‐ | cer among Alaska Native people and recognized our ongoing work | in Alaska to document and address this health disparity. As health | practitioners in Alaska, we share their concerns about the elevated | gastric cancer rates and would welcome increased efforts to reduce | the health threats associated with H pylori infection; however, some | of their points require a response. The authors posit that H pylori | eradication programs and pilot studies used in Japan and Taiwan | should be applied to Alaska. While such studies offer an intriguing | approach, early results have not completely answered the question | of how to prevent gastric cancer. The absence of evidence‐based | guidelines and the lack of national or professional society recom‐ | mendations supporting population‐level H pylori eradication are a | strong indication that this approach is not yet proven. There are im‐ | portant unanswered questions about the risks and benefits of such | an eradication program. These risks include, but are not limited to, | the potential to develop worsening antimicrobial resistance among | H pylori and antimicrobial resistance among non‐targeted commen‐ | sal or pathogenic organisms, and the risk of causing harm by giving | antibiotics to healthy persons who may not be at risk for gastric can‐ | cer (eg, allergic responses, drug‐drug interactions, Clostridium diffi‐ | cile infections). Additional unanswered questions relevant for Alaska | include the effectiveness and feasibility of a population‐level H pylori | eradication program in a remote population with high rates of H py‐ | lori reinfection, a high proportion of H pylori isolates demonstrating | antimicrobial resistance, and documented high rates of treatment | failure. Even if the health benefit of a population‐based eradication | effort were to be established, concerns about funding, logistical op‐ | erations, and the relative value of such a program compared with | other high priority health concerns would need to be considered. In | Alaska, such concerns are magnified, where our ~200 rural commu‐ | nities are dispersed over a mostly roadless area larger than Texas, | Taiwan, and Japan combined |
Evaluation of core genome and whole genome multilocus sequence typing schemes for Campylobacter jejuni and Campylobacter coli outbreak detection in the USA
Joseph LA , Griswold T , Vidyaprakash E , Im SB , Williams GM , Pouseele HA , Hise KB , Carleton HA . Microb Genom 2023 9 (5) Campylobacter is a leading causing of bacterial foodborne and zoonotic illnesses in the USA. Pulsed-field gene electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST) have been historically used to differentiate sporadic from outbreak Campylobacter isolates. Whole genome sequencing (WGS) has been shown to provide superior resolution and concordance with epidemiological data when compared with PFGE and 7-gene MLST during outbreak investigations. In this study, we evaluated epidemiological concordance for high-quality SNP (hqSNP), core genome (cg)MLST and whole genome (wg)MLST to cluster or differentiate outbreak-associated and sporadic Campylobacter jejuni and Campylobacter coli isolates. Phylogenetic hqSNP, cgMLST and wgMLST analyses were also compared using Baker's gamma index (BGI) and cophenetic correlation coefficients. Pairwise distances comparing all three analysis methods were compared using linear regression models. Our results showed that 68/73 sporadic C. jejuni and C. coli isolates were differentiated from outbreak-associated isolates using all three methods. There was a high correlation between cgMLST and wgMLST analyses of the isolates; the BGI, cophenetic correlation coefficient, linear regression model R (2) and Pearson correlation coefficients were >0.90. The correlation was sometimes lower comparing hqSNP analysis to the MLST-based methods; the linear regression model R (2) and Pearson correlation coefficients were between 0.60 and 0.86, and the BGI and cophenetic correlation coefficient were between 0.63 and 0.86 for some outbreak isolates. We demonstrated that C. jejuni and C. coli isolates clustered in concordance with epidemiological data using WGS-based analysis methods. Discrepancies between allele and SNP-based approaches may reflect the differences between how genomic variation (SNPs and indels) are captured between the two methods. Since cgMLST examines allele differences in genes that are common in most isolates being compared, it is well suited to surveillance: searching large genomic databases for similar isolates is easily and efficiently done using allelic profiles. On the other hand, use of an hqSNP approach is much more computer intensive and not scalable to large sets of genomes. If further resolution between potential outbreak isolates is needed, wgMLST or hqSNP analysis can be used. |
The clinical laboratory is an integral component to health care delivery : An expanded representation of the total testing process
Lubin IM , Astles JR , Bunn JD , Cornish NE , Lazaro G , Marshall AA , Stang HL , De Jesús VR . Am J Clin Pathol 2023 160 (2) 124-129 OBJECTIVES: Developing an expanded representation of the total testing process that includes contemporary elements of laboratory practice can be useful to understanding and optimizing testing workflows across clinical laboratory and patient care settings. METHODS: Published literature and meeting reports were used by the coauthors to inform the development of the expanded representation of the total testing process and relevant examples describing its uses. RESULTS: A visual representation of the total testing process was developed and contextualized to patient care scenarios using a number of examples covering the detection of blood culture contamination, use of next-generation sequencing, and pharmacogenetic testing. CONCLUSIONS: The expanded representation of the total testing process can serve as a model and framework to document and improve the use of clinical testing within the broader context of health care delivery. This representation recognizes increased engagement among clinical laboratory professionals with patients and other health care providers as essential to making informed decisions. The increasing use of data is highlighted as important to ensuring quality, appropriate test utilization, and sustaining an efficient workflow across clinical laboratory and patient care settings. Maintaining a properly resourced and competent workforce is also featured as an essential component to the testing process. |
Monitoring temporal changes in SARS-CoV-2 spike antibody levels and variant-specific risk for infection, Dominican Republic, March 2021-August 2022
Nilles EJ , de St Aubin M , Dumas D , Duke W , Etienne MC , Abdalla G , Jarolim P , Oasan T , Garnier S , Iihoshi N , Lopez B , de la Cruz L , Puello YC , Baldwin M , Roberts KW , Peña F , Durski K , Sanchez IM , Gunter SM , Kneubehl AR , Murray KO , Lino A , Strobel S , Baez AA , Lau CL , Kucharski A , Gutiérrez EZ , Skewes-Ramm R , Vasquez M , Paulino CT . Emerg Infect Dis 2023 29 (4) 723-733 To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission. |
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