Last data update: Sep 30, 2024. (Total: 47785 publications since 2009)
Records 1-30 (of 6141 Records) |
Query Trace: precision health[original query] |
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Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States
Perofsky AC , Huddleston J , Hansen CL , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Lewis N , Whittaker L , Ermetal B , Harvey R , Galiano M , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Sullivan SG , Barr IG , Subbarao K , Krammer F , Bedford T , Viboud C . Elife 2024 13 Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity. | Seasonal influenza (flu) viruses cause outbreaks every winter. People infected with influenza typically develop mild respiratory symptoms. But flu infections can cause serious illness in young children, older adults and people with chronic medical conditions. Infected or vaccinated individuals develop some immunity, but the viruses evolve quickly to evade these defenses in a process called antigenic drift. As the viruses change, they can re-infect previously immune people. Scientists update the flu vaccine yearly to keep up with this antigenic drift. The immune system fights flu infections by recognizing two proteins, known as antigens, on the virus’s surface, called hemagglutinin (HA) and neuraminidase (NA). However, mutations in the genes encoding these proteins can make them unrecognizable, letting the virus slip past the immune system. Scientists would like to know how these changes affect the size, severity and timing of annual influenza outbreaks. Perofsky et al. show that tracking genetic changes in HA and NA may help improve flu season predictions. The experiments compared the severity of 22 flu seasons caused by the A(H3N2) subtype in the United States with how much HA and NA had evolved since the previous year. The A(H3N2) subtype experiences the fastest rates of antigenic drift and causes more cases and deaths than other seasonal flu viruses. Genetic changes in HA and NA were a better predictor of A(H3N2) outbreak severity than the blood tests for protective antibodies that epidemiologists traditionally use to track flu evolution. However, the prevalence of another subtype of influenza A circulating in the population, called A(H1N1), was an even better predictor of how severe A(H3N2) outbreaks would be. Perofsky et al. are the first to show that genetic changes in NA contribute to the severity of flu seasons. Previous studies suggested a link between genetic changes in HA and flu season severity, and flu vaccines include the HA protein to help the body recognize new influenza strains. The results suggest that adding the NA protein to flu vaccines may improve their effectiveness. In the future, flu forecasters may want to analyze genetic changes in both NA and HA to make their outbreak predictions. Tracking how much of the A(H1N1) subtype is circulating may also be useful for predicting the severity of A(H3N2) outbreaks. | eng |
Notes from the field: Support for wastewater monitoring and influence on protective behavioral intentions among adults - United States, July 2024
Soelaeman RH , Kleven D , Losch J , Vega M , Fehrenbach SN , Ricaldi JN , Valencia D , Santibañez S . MMWR Morb Mortal Wkly Rep 2024 73 (37) 825-827 In 2020, during the COVID-19 pandemic, CDC established the National Wastewater Surveillance System and later expanded it to include mpox and influenza A data dashboards.(†) Wastewater utility partners have cited community health benefits as a motivating factor for participating in wastewater surveillance; a lack of public support for wastewater surveillance activities might lead utility partners to cease participation (1,2). However, little is known about public support for wastewater monitoring and its influence on protective health behaviors. As innovative surveillance strategies such as wastewater surveillance evolve, ethical considerations, including understanding public perceptions regarding support for these activities and potential risks to communities, are essential (3). |
Infectious disease physicians' knowledge and practices regarding wastewater surveillance, United States, 2024
Adams C , Horter L , Beekmann SE , Polgreen PM , Ricaldi JN , Louis S , Santibañez S . Emerg Infect Dis 2024 30 (10) 2222-2223 A survey of US infectious disease physicians indicated that few regularly reviewed wastewater surveillance (WWS) data but many reported examples of how WWS has affected or could affect their clinical practice. WWS data can be useful for physicians, but increased communication between public health professionals and physicians regarding WWS could improve its utility. |
Challenges and opportunities for wastewater monitoring of influenza viruses during the multistate outbreak of highly pathogenic avian influenza A(H5N1) virus in dairy cattle and poultry
Honein MA , Olsen SJ , Jernigan DB , Daskalakis DC . Am J Public Health 2024 e1-e4 |
Wastewater surveillance for influenza A virus and H5 subtype concurrent with the highly pathogenic avian influenza A(H5N1) virus outbreak in cattle and poultry and associated human cases - United States, May 12-July 13, 2024
Louis S , Mark-Carew M , Biggerstaff M , Yoder J , Boehm AB , Wolfe MK , Flood M , Peters S , Stobierski MG , Coyle J , Leslie MT , Sinner M , Nims D , Salinas V , Lustri L , Bojes H , Shetty V , Burnor E , Rabe A , Ellison-Giles G , Yu AT , Bell A , Meyer S , Lynfield R , Sutton M , Scholz R , Falender R , Matzinger S , Wheeler A , Ahmed FS , Anderson J , Harris K , Walkins A , Bohra S , O'Dell V , Guidry VT , Christensen A , Moore Z , Wilson E , Clayton JL , Parsons H , Kniss K , Budd A , Mercante JW , Reese HE , Welton M , Bias M , Webb J , Cornforth D , Santibañez S , Soelaeman RH , Kaur M , Kirby AE , Barnes JR , Fehrenbach N , Olsen SJ , Honein MA . MMWR Morb Mortal Wkly Rep 2024 73 (37) 804-809 As part of the response to the highly pathogenic avian influenza A(H5N1) virus outbreak in U.S. cattle and poultry and the associated human cases, CDC and partners are monitoring influenza A virus levels and detection of the H5 subtype in wastewater. Among 48 states and the District of Columbia that performed influenza A testing of wastewater during May 12-July 13, 2024, a weekly average of 309 sites in 38 states had sufficient data for analysis, and 11 sites in four states reported high levels of influenza A virus. H5 subtype testing was conducted at 203 sites in 41 states, with H5 detections at 24 sites in nine states. For each detection or high level, CDC and state and local health departments evaluated data from other influenza surveillance systems and partnered with wastewater utilities and agriculture departments to investigate potential sources. Among the four states with high influenza A virus levels detected in wastewater, three states had corresponding evidence of human influenza activity from other influenza surveillance systems. Among the 24 sites with H5 detections, 15 identified animal sources within the sewershed or adjacent county, including eight milk-processing inputs. Data from these early investigations can help health officials optimize the use of wastewater surveillance during the upcoming respiratory illness season. |
Conditional expression of flagellar motility, curli fimbriae, and biofilms in Shiga toxin- producing Escherichia albertii
Carter MQ , Carychao D , Lindsey RL . Front Microbiol 2024 15 1456637 Escherichia albertii is an emerging foodborne pathogen. We previously reported that some avian Shiga toxin-producing E. albertii strains exhibited higher or comparable cytotoxicity in Vero-d2EGFP cells with several enterohemorrhagic E. coli (EHEC) outbreak strains. To better understand the environmental persistence of this pathogen, comparative genomics and phenotypic assays were applied to assess adhesion capability, motility, and biofilm formation in E. albertii. Among the 108 adherence-related genes, those involved in biogenesis of curli fimbriae, hemorrhagic E. coli pilus, type 1 fimbriae, and Sfm fimbriae were conserved in E. albertii. All 20 E. albertii strains carried a complete set of primary flagellar genes that were organized into four gene clusters, while five strains possessed genes related to the secondary flagella, also known as lateral flagella. Compared to EHEC strain EDL933, the eight chemotaxis genes located within the primary flagellar gene clusters were deleted in E. albertii. Additional deletion of motility genes flhABCD and motBC was identified in several E. albertii strains. Swimming motility was detected in three strains when grown in LB medium, however, when grown in 5% TSB or in the pond water-supplemented with 10% pigeon droppings, an additional four strains became motile. Although all E. albertii strains carried curli genes, curli fimbriae were detected only in four, eight, and nine strains following 24, 48, and 120 h incubation, respectively. Type 1 fimbriae were undetectable in any of the strains grown at 37°C or 28°C. Strong biofilms were detected in strains that produced curli fimbriae and in a chicken isolate that was curli fimbriae negative but carried genes encoding adhesive fimbriae K88, a signature of enterotoxigenic E. coli strains causing neonatal diarrhea in piglets. In all phenotypic traits examined, no correlation was revealed between the strains isolated from different sources, or between the strains with and without Shiga toxin genes. The phenotypic variations could not be explained solely by the genetic diversity or the difference in adherence genes repertoire, implying complex regulation in expression of various adhesins. Strains that exhibited a high level of cytotoxicity and were also proficient in biofilm production, may have potential to emerge into high-risk pathogens. |
Assessing attitudes and knowledge of mpox vaccine among unvaccinated men who have sex with men
Green CJ , Hall GC , Kachur R , Finley E , Furness BW , Merritt M , Lewis FMT . Sex Transm Dis 2024 BACKGROUND: The 2022 mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBMSM). Mpox cases continue to be reported nationally. Vaccination is a tool to prevent the spread of and serious disease from mpox. To understand mpox vaccine uptake and hesitancy, a virtual focus group with unvaccinated GBMSM was conducted. METHODS: In November 2022, a 60-minute, virtual focus group was conducted within an artificial intelligence (AI) platform that engages participants in chat-based conversation. The AI system uses machine learning and natural language processing to analyze and provide results immediately to the moderator. Descriptive frequencies, cross-tabulations and qualitative themes were analyzed. RESULTS: Fifty-one GBMSM ages 18-55 participated, of whom 12 had attempted to get the mpox vaccine. The top barriers in accessing the vaccine included challenges in scheduling appointments (4/12), available vaccine locations (3/12), and transportation (2/12). Nine participants reported not wanting the vaccine and 22 were undecided; Of these, 15 (4/9 and 11/22, respectively) said they did not think they needed the vaccine due to low perceived risk or monogamy.. Among the undecided, after receiving health messaging about mpox, 12/22 said the messaging made them reconsider getting the vaccine. CONCLUSION: During an outbreak, many unvaccinated GBMSM who may be at increased risk for mpox either wanted the vaccine or, with appropriate health messaging, may be open to getting the vaccine. Messaging about mpox vaccine efficacy, potential side effects, and how to access the vaccine may improve vaccine uptake especially as cases continue to occur. |
Estimation of vaccine effectiveness against SARS-CoV-2-associated hospitalization using sentinel surveillance in South Africa
Chiwandire N , Walaza S , von Gottberg A , Wolter N , Du Plessis M , Moosa F , Groome MJ , Nel J , Variava E , Dawood H , Makhasi M , Feldstein LR , Marcenac P , Lafond KE , Samuels AM , Cohen C . Int J Epidemiol 2024 53 (5) BACKGROUND: COVID-19 vaccine effectiveness (VE) studies leveraging systematic surveillance in sub-Saharan Africa are limited. We assessed the effectiveness of two vaccines (Pfizer BNT162b2 and Johnson & Johnson Ad26.COV2.S) against SARS-CoV-2-associated hospitalization in South African adults aged ≥18 years. METHODS: We conducted a test-negative case-control study using pneumonia surveillance data in South Africa. Inpatients with physician-diagnosed lower respiratory tract infection or suspected COVID-19, testing SARS-CoV-2 positive or negative from June 2021-March 2022, were cases or controls, respectively. Fully vaccinated individuals received one Ad26.COV2.S dose or two BNT162b2 doses ≥14-days before enrollment. VE was estimated using multivariable logistic regression for Delta- and Omicron BA.1/BA.2-predominant periods, stratified by age and HIV status. RESULTS: The study included 925 cases and 1890 controls; 38 (4%) cases and 186 (10%) controls were fully vaccinated with BNT162b2, and 30 (3%) cases and 94 (5%) controls with Ad26.COV2.S. The vaccine effectiveness of BNT162b2 against SARS-CoV-2-associated hospitalization over Delta and Omicron BA.1/BA.2 periods was 91% (95% CI: 52%, 98%) and 33% (-16%, 86%), respectively. The vaccine effectiveness of Ad26.COV2.S against hospitalization over Delta and Omicron BA.1/BA.2 periods was 72% (-36% ,94%), and -19% (-130%, 39%), respectively. The vaccine effectiveness of BNT162b2 against hospitalization over the Delta period was 94% (50%, 99%) and 89% (27%, 98%) among adults aged ≥60 years and HIV-uninfected, respectively. CONCLUSIONS: The BNT162b2 vaccine was effective against SARS-CoV-2-associated hospitalization during the Delta period for adults aged ≥18 years, ≥60 years and those HIV-uninfected. VE for Ad26.COV2.S was inconclusive, potentially due to limited sample size or residual confounding. These findings highlight the utility of sentinel surveillance for estimating VE. |
Modernizing public health data systems and workforce capacity: The Centers for Disease Control and Prevention's Public Health Informatics Fellowship Program
Kirkcaldy RD , Biggers B , Bonney W , Gordon J , Yassine B , Crawford B , Papagari-Sangareddy S , Franzke L , Bernstein KT . J Public Health Manag Pract 2024 CONTEXT: The COVID-19 pandemic exposed governmental public health's outdated information technology and insufficient data science and informatics workforce capacity. The Centers for Disease Control and Prevention's Public Health Informatics Fellowship Program (PHIFP) is well positioned to strengthen public health data science and informatics workforce capacity. PROGRAM: Established in 1996, PHIFP is a 2-year, full-time, on-the-job training program. PHIFP includes a didactic curriculum, applied learning through informatics projects completed at the assigned host site, short-term technical assistance projects, and a final capstone project. EVALUATION: Fellows have learned from and bolstered host site informatics capacity through the development or enhancement of information systems, evaluations, data integration, data visualization, and analysis. Among recent graduates, 54% are employed at Centers for Disease Control and Prevention and 16% are employed at other public health organizations, including local health departments. DISCUSSION: Fellowships such as PHIFP, which recruit and train promising scientists in public health informatics, are important components of efforts to strengthen public health workforce capacity. |
Promotion of order Bunyavirales to class Bunyaviricetes to accommodate a rapidly increasing number of related polyploviricotine viruses
Kuhn JH , Brown K , Adkins S , de la Torre JC , Digiaro M , Ergünay K , Firth AE , Hughes HR , Junglen S , Lambert AJ , Maes P , Marklewitz M , Palacios G , Sasaya T , Shi M , Zhang YZ , Wolf YI , Turina M . J Virol 2024 e0106924 Prior to 2017, the family Bunyaviridae included five genera of arthropod and rodent viruses with tri-segmented negative-sense RNA genomes related to the Bunyamwera virus. In 2017, the International Committee on Taxonomy of Viruses (ICTV) promoted the family to order Bunyavirales and subsequently greatly expanded its composition by adding multiple families for non-segmented to polysegmented viruses of animals, fungi, plants, and protists. The continued and accelerated discovery of bunyavirals highlighted that an order would not suffice to depict the evolutionary relationships of these viruses. Thus, in April 2024, the order was promoted to class Bunyaviricetes. This class currently includes two major orders, Elliovirales (Cruliviridae, Fimoviridae, Hantaviridae, Peribunyaviridae, Phasmaviridae, Tospoviridae, and Tulasviridae) and Hareavirales (Arenaviridae, Discoviridae, Konkoviridae, Leishbuviridae, Mypoviridae, Nairoviridae, Phenuiviridae, and Wupedeviridae), for hundreds of viruses, many of which are pathogenic for humans and other animals, plants, and fungi. |
Beyond bacteria: the growing threat of antifungal resistance
van Rhijn N , Arikan-Akdagli S , Beardsley J , Bongomin F , Chakrabarti A , Chen SC , Chiller T , Lopes Colombo A , Govender NP , Alastruey-Izquierdo A , Kidd SE , Lackner M , Li R , Hagen F . Lancet 2024 404 (10457) 1017-1018 |
Impact of COVID-19 on myalgic encephalomyelitis/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey
Wood MS , Halmer N , Bertolli J , Amsden LB , Nugent JR , Lin JS , Rothrock G , Nadle J , Chai SJ , Cope JR , Champsi JH , Yang J , Unger ER , Skarbinski J . PLoS One 2024 19 (9) e0309810 BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can be triggered by infectious agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the impact of the coronavirus disease 2019 (COVID-19) pandemic on ME/CFS prevalence is not well characterized. METHODS: In this population-based cross-sectional study, we enrolled a stratified random sample of 9,825 adult participants in the Kaiser Permanente Northern California (KPNC) integrated health system from July to October 2022 to assess overall ME/CFS-like illness prevalence and the proportion that were identified following COVID-19 illness. We used medical record and survey data to estimate the prevalence of ME/CFS-like illness based on self-reported symptoms congruent with the 2015 Institute of Medicine ME/CFS criteria. History of COVID-19 was based on a positive SARS-CoV-2 nucleic acid amplification test or ICD-10 diagnosis code in the medical record, or self-report of prior COVID-19 on a survey. RESULTS: Of 2,745,374 adults in the eligible population, an estimated 45,892 (95% confidence interval [CI]: 32,869, 58,914) or 1.67% (CI 1.20%, 2.15%) had ME/CFS-like illness. Among those with ME/CFS-like illness, an estimated 14.12% (CI 3.64%, 24.6%) developed the illness after COVID-19. Among persons who had COVID-19, those with ME/CFS-like illness after COVID-19 were more likely to be unvaccinated and to have had COVID-19 before June 1, 2021. All persons with ME/CFS-like illness had significant impairment in physical, mental, emotional, social, and occupational functioning compared to persons without ME/CFS-like illness. CONCLUSIONS: In a large, integrated health system, 1.67% of adults had ME/CFS-like illness and 14.12% of all persons with ME/CFS-like illness developed it after COVID-19. Though COVID-19 did not substantially increase ME/CFS-like illness in the KPNC population during the study time period, ME/CFS-like illness nevertheless affects a notable portion of this population and is consistent with estimates of ME/CFS prevalence in other populations. Additional attention is needed to improve awareness, diagnosis, and treatment of ME/CFS. |
An outbreak investigation of Salmonella Weltevreden illnesses in the United States linked to frozen precooked shrimp imported from India - 2021
Jenkins E , Cripe J , Whitney BM , Greenlee T , Schneider B , Nguyen TA , Pightling A , Manetas J , Abraham A , Fox T , Mickelsen N , Priddy C , McMullen S , Crosby A , Viazis S . J Food Prot 2024 100360 In 2021, the U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and state partners investigated a multi-state sample-initiated retrospective outbreak investigation (SIROI) consisting of a cluster of nine Salmonella Weltevreden illnesses associated with frozen, pre-cooked shrimp imported from India. Import surveillance testing identified Salmonella Weltevreden recovered from a cooked shrimp sample from Supplier B. In total, nine patients with clinical isolates highly related via whole genome sequencing were reported in four states with illness onset dates between February 26 and July 17, 2021. Epidemiologic data was gathered by state partners for seven patients, whom all reported exposure to shrimp. Five patients reported consuming shrimp cocktail from the same retailer. A traceback investigation for five of the six patients converged on Supplier B. This evidence demonstrated that the outbreak of Salmonella Weltevreden illnesses was caused by the consumption of cooked, ready-to-eat shrimp manufactured by Supplier B. At the time of the investigation, outbreak and recall information was shared with Indian competent authorities. In March 2022, a follow up inspection of Supplier B's facility in India was conducted, and insanitary conditions and practices were observed. This outbreak investigation highlighted the importance of multidisciplinary national and international public health partnerships. The lessons learned from this investigation should continue to inform investigational activities and food safety guidance for industry. |
Progress toward poliomyelitis eradication - Pakistan, January 2023-June 2024
Mbaeyi C , Ul Haq A , Safdar RM , Khan Z , Corkum M , Henderson E , Wadood ZM , Alam MM , Franka R . MMWR Morb Mortal Wkly Rep 2024 73 (36) 788-792 Since its launch in 1988, the Global Polio Eradication Initiative has made substantial progress toward the eradication of wild poliovirus (WPV), including eradicating two of the three serotypes, and reducing the countries with ongoing endemic transmission of WPV type 1 (WPV1) to just Afghanistan and Pakistan. Both countries are considered a single epidemiologic block. Despite the occurrence of only a single confirmed WPV1 case during the first half of 2023, Pakistan experienced widespread circulation of WPV1 over the subsequent 12 months, specifically in the historical reservoirs of the cities of Karachi, Peshawar, and Quetta. As of June 30, 2024, eight WPV1 cases had been reported in Pakistan in 2024, compared with six reported during all of 2023. These cases, along with more than 300 WPV1-positive environmental surveillance (sewage) samples reported during 2023-2024, indicate that Pakistan is not on track to interrupt WPV1 transmission. The country's complex sociopolitical and security environment continues to pose formidable challenges to poliovirus elimination. To interrupt WPV1 transmission, sustained political commitment to polio eradication, including increased accountability at all levels, would be vital for the polio program. Efforts to systematically track and vaccinate children who are continually missed during polio vaccination activities should be enhanced by better addressing operational issues and the underlying reasons for community resistance to vaccination and vaccine hesitancy. |
A microRNA diagnostic biomarker for amyotrophic lateral sclerosis
Banack SA , Dunlop RA , Mehta P , Mitsumoto H , Wood SP , Han M , Cox PA . Brain Commun 2024 6 (5) fcae268 Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson's disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal-Wallis test was used to assess differences in plasma microRNAs followed by post hoc Mann-Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis. |
Deep humoral profiling coupled to interpretable machine learning unveils diagnostic markers and pathophysiology of schistosomiasis
Saha A , Chakraborty T , Rahimikollu J , Xiao H , de Oliveira LBP , Hand TW , Handali S , Secor WE , AOFraga L , Fairley JK , Das J , Sarkar A . Sci Transl Med 2024 16 (765) eadk7832 Schistosomiasis, a highly prevalent parasitic disease, affects more than 200 million people worldwide. Current diagnostics based on parasite egg detection in stool detect infection only at a late stage, and current antibody-based tests cannot distinguish past from current infection. Here, we developed and used a multiplexed antibody profiling platform to obtain a comprehensive repertoire of antihelminth humoral profiles including isotype, subclass, Fc receptor (FcR) binding, and glycosylation profiles of antigen-specific antibodies. Using Essential Regression (ER) and SLIDE, interpretable machine learning methods, we identified latent factors (context-specific groups) that move beyond biomarkers and provide insights into the pathophysiology of different stages of schistosome infection. By comparing profiles of infected and healthy individuals, we identified modules with unique humoral signatures of active disease, including hallmark signatures of parasitic infection such as elevated immunoglobulin G4 (IgG4). However, we also captured previously uncharacterized humoral responses including elevated FcR binding and specific antibody glycoforms in patients with active infection, helping distinguish them from those without active infection but with equivalent antibody titers. This signature was validated in an independent cohort. Our approach also uncovered two distinct endotypes, nonpatent infection and prior infection, in those who were not actively infected. Higher amounts of IgG1 and FcR1/FcR3A binding were also found to be likely protective of the transition from nonpatent to active infection. Overall, we unveiled markers for antibody-based diagnostics and latent factors underlying the pathogenesis of schistosome infection. Our results suggest that selective antigen targeting could be useful in early detection, thus controlling infection severity. |
The TIRS trial: Enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico
Earnest JT , Kirstein OD , Mendoza AC , Barrera-Fuentes GA , Puerta-Guardo H , Parra-Cardeña M , Yam-Trujillo K , Collins MH , Pavia-Ruz N , Ayora-Talavera G , Gonzalez-Olvera G , Medina-Barreiro A , Bibiano-Marin W , Lenhart A , Halloran ME , Longini I , Dean N , Waller LA , Crisp AM , Correa-Morales F , Palacio-Vargas J , Granja-Perez P , Villanueva S , Delfın-Gonzalez H , Gomez-Dantes H , Manrique-Saide P , Vazquez-Prokopec GM . PLoS One 2024 19 (9) e0310480 Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks. |
An update on highly pathogenic avian influenza A(H5N1) virus, clade 2.3.4.4b
Webby RJ , Uyeki TM . J Infect Dis 2024 Since the resurgence of highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b, during 2021, these viruses have spread widely among birds worldwide, causing poultry outbreaks and infections of a wide range of terrestrial and marine mammal species. During 2024, HPAI A(H5N1) virus, clade 2.3.4.4b, was detected in dairy cattle for the first time and caused an ongoing multistate outbreak, with high levels of virus documented in raw cow milk. Human infections with clade 2.3.4.4b viruses from exposures to infected poultry or dairy cattle have resulted in a wide spectrum of illness severity, from conjunctivitis or mild respiratory illness to severe and fatal pneumonia in different countries. Vigilance, and stronger global virologic surveillance among birds, poultry, terrestrial and marine mammals, and humans, with virus characterization and rapid data sharing, is needed to inform the threat of clade 2.3.4.4b viruses, as they continue to evolve, to public health. |
Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis
Hassoun Y , Aptekmann AA , Keniya MV , Gomez RY , Alayo N , Novi G , Quinteros C , Kaya F , Zimmerman M , Caceres DH , Chow NA , Perlin DS , Shor E . PLoS Pathog 2024 20 (9) e1012521 Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata. |
Increased proportions of invasive pneumococcal disease cases amongs adults experiencing homelessness sets stage for new serotype 4 capsular-switch recombinant
Beall B , Chochua S , Metcalf B , Lin W , Tran T , Li Z , Li Y , Bentz ML , Sheth M , Osis G , McGee L . J Infect Dis 2024 BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant. |
Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in the Democratic Republic of the Congo: a case report study
Mukadi-Bamuleka D , Edidi-Atani F , Morales-Betoulle ME , Legand A , Nkuba-Ndaye A , Bulabula-Penge J , Mbala-Kingebeni P , Crozier I , Mambu-Mbika F , Whitmer S , Tshiani Mbaya O , Hensley LE , Kitenge-Omasumbu R , Davey R , Mulangu S , Fonjungo PN , Wiley MR , Klena JD , Peeters M , Delaporte E , van Griensven J , Ariën KK , Pratt C , Montgomery JM , Formenty P , Muyembe-Tamfum JJ , Ahuka-Mundeke S . Lancet Microbe 2024 100905 BACKGROUND: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence. METHODS: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques. FINDINGS: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2. INTERPRETATION: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence. FUNDING: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, French National Research Institute for Development, and WHO. |
Widespread geographic distribution of Aedes aegypti (Diptera: Culicidae) kdr variants in Panama
García J , Chong M , Rojas AL , McMillan WO , Bennett KL , Lenhart AE , Chaves LF , Loaiza JR . J Med Entomol 2024 We searched for evidence of knockdown resistance (kdr) mutations in the voltage-gated sodium channel gene of Aedes aegypti (Linnaeus) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) mosquitoes from Panama. Conventional PCR was performed on 469 Ae. aegypti and 349 Ae. albopictus. We did not discover kdr mutations in Ae. albopictus, but 2 nonsynonymous kdr mutations, V1016I (found in 101 mosquitoes) and F1534C (found in 29 of the mosquitoes with the V1016I), were detected in Ae. aegypti. These kdr mutations were present in all specimens that were successfully sequenced for both IIS5-S6 and IIIS6 regions, which included samples collected from 8 of the 10 provinces of Panama. No other kdr mutations were found in Ae. aegypti, including V1016G, which has already been reported in Panama. Findings suggest that the V1016I-F1534C variant is prevalent in Panama, which might be related to the introduction and passive movement of mosquitoes as part of the used-tire trade. However, we cannot rule out the possibility that selection on de novo replacement of kdr mutations also partially explains the widespread distribution pattern of these mutations. These 2 ecological and evolutionary processes are not mutually exclusive, though, as they can occur in tandem. Research in Panama needs to calculate the genotypic and allelic frequencies of kdr alleles in local Ae. aegypti populations and to test whether some combinations confer phenotypic resistance or not. Finally, future studies will have to track the introduction and spreading of new kdr mutations in both Aedes species. |
The 2023 South Sudanese outbreak of Hepatitis E emphasizes ongoing circulation of genotype 1 in North, Central, and East Africa
Orf GS , Bbosa N , Berg MG , Downing R , Weiss SL , Ssemwanga D , Ssekagiri A , Ashraf S , da Silva Filipe A , Kiiza R , Buule J , Namagembe HS , Nabirye SE , Kayiwa J , Deng LL , Wani G , Maror JA , Baguma A , Mogga JJH , Kamili S , Thomson EC , Kaleebu P , Cloherty GA . Infect Genet Evol 2024 105667 In April 2023, an outbreak of acute hepatitis was reported in the Nazareth internally displaced persons camp in South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis. |
Rotavirus vaccine effectiveness against severe acute gastroenteritis: 2009-2022
Diallo AO , Wikswo ME , Sulemana I , Sahni LC , Boom JA , Ramani S , Selvarangan R , Moffatt ME , Harrison CJ , Halasa N , Chappell J , Stewart L , Staat MA , Schlaudecker E , Quigley C , Klein EJ , Englund JA , Zerr DM , Weinberg GA , Szilagyi PG , Albertin C , Johnston SH , Williams JV , Michaels MG , Hickey RW , Curns AT , Honeywood M , Mijatovic-Rustempasic S , Esona MD , Bowen MD , Parashar UD , Gautam R , Mirza SA , Tate JE . Pediatrics 2024 BACKGROUND: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). METHODS: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. RESULTS: Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. CONCLUSIONS: Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children. |
Monovalent rotavirus vaccine effectiveness and long-term impact among children <5 years old in Antananarivo, Madagascar, 2010-2022
Raboba JL , Rahajamanana VL , Rakotojoelimaria HE , Masembe YV , Martin PR , Weldegebriel GG , Diallo AO , Burnett E , Tate JE , Parashar UD , Mwenda JM , Seheri M , Magagula N , Mphahlele J , Robinson AL . Vaccine 2024 42 (26) 126321 BACKGROUND: Monovalent rotavirus vaccine substantially reduced rotavirus disease burden after introduction (May 2014) in Madagascar. We examined the effectiveness and long-term impact on acute watery diarrhea and rotavirus-related hospitalizations among children <5 years old at two hospitals in Antananarivo, Madagascar (2010-2022). METHODS: We used a test-negative case-control design to estimate monovalent rotavirus vaccine effectiveness (VE) against laboratory-confirmed rotavirus hospitalizations among children age 6-23 months with documented vaccination status adjusted for year of symptom onset, rotavirus season, age group, nutritional status, and clinical severity. To evaluate the impact, we expanded to children age 0-59 months with acute watery diarrhea. First, we used admission logbook data to compare the proportion of all hospitalizations attributed to diarrhea in the pre-vaccine (January 2010-December 2013), transition period (January 2014-December 2014), and post-vaccine (January 2015-December 2022) periods. Second, we used active surveillance data (June 2013-May 2022) to describe rotavirus positivity and detected genotypes by vaccine introduction period and surveillance year (1 June-31 May). RESULT: Adjusted VE of at least one dose against hospitalization due to rotavirus diarrhea among children age 6-23 months was 61 % (95 % CI: -39 %-89 %). The annual median proportion of hospitalizations attributed to diarrhea declined from 28 % in the pre-vaccine to 10 % in the post-vaccine period. Rotavirus positivity among hospitalized children age 0-59 months with acute watery diarrhea was substantially higher during the pre-vaccine (59 %) than the post-vaccine (23 %) period. In the pre-vaccine period, G3P[8] (76 %) and G2P[4] (12 %) were the dominant genotypes detected. Although genotypes varied by surveillance year, G1P[8] and G2P[4] represented >50 % of the genotypes detected post-introduction. CONCLUSIONS: Rotavirus vaccine has been successfully implemented in Madagascar's routine childhood immunization program and had a large impact on rotavirus disease burden, supporting continued use of rotavirus vaccines in Madagascar. |
Machine learning to attribute the source of Campylobacter infections in the United States: a retrospective analysis of national surveillance data
Pascoe B , Futcher G , Pensar J , Bayliss SC , Mourkas E , Calland JK , Hitchings MD , Joseph LA , Lane CG , Greenlee T , Arning N , Wilson DJ , Jolley KA , Corander J , Maiden MCJ , Parker CT , Cooper KK , Rose EB , Hiett K , Bruce BB , Sheppard SK . J Infect 2024 106265 OBJECTIVES: Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern and there is an urgent need to quantify the main routes to human infection. METHODS: During routine US national surveillance (2009-2019), 8,856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs. RESULTS: Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens. CONCLUSIONS: National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US. DATA AVAILABILITY: All sequence reads were uploaded and shared on NCBI's Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli). |
Fasten: a toolkit for streaming operations on FASTQ files
Katz LS , Phan J , den Bakker HC . J Open Source Softw 2024 9 (94) 6030 |
A vision to the future: value-based laboratory medicine
Plebani M , Cadamuro J , Vermeersch P , Jovičić S , Ozben T , Trenti T , McMillan B , Lowe CR , Lennerz J , Macintyre E , Gabelli C , Sandberg S , Padoan A , Wiencek JR , Banfi G , Lubin IM , Orth M , Carobene A , Zima T , Cobbaert CM , van Schaik RHN , Lippi G . Clin Chem Lab Med 2024 The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future. |
Epidemiology of pediatric astrovirus gastroenteritis in a Nicaraguan Birth Cohort
Rubinstein RJ , Gutiérrez L , Toval-Ruíz C , Hammond K , Bode L , Vinjé J , Vilchez S , Becker-Dreps S , Bucardo F , Vielot NA , Reyes Y . Open Forum Infect Dis 2024 11 (9) ofae465 BACKGROUND: Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low- and middle-income countries. METHODS: We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections, and time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. RESULTS: Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. CONCLUSIONS: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity. |
Human keratinocyte response to 4,4'-methylene diphenyl diisocyanate-glutathione conjugate exposure
Law BF , Lin CC , Hettick JM . Xenobiotica 2024 1-16 Workplace exposure to diisocyanates like 4,4'-methylene diphenyl diisocyanate can cause occupational asthma (MDI-OA), and the underlying biological pathways are still being researched.Although uncertainty remains, evidence supports the hypothesis that dermal exposure to MDI plays an important role in the development of MDI-OA.Gene expression, proteomics, and informatics tools were utilized to characterize changes in expression of RNA and protein in cultured human HEKa keratinocyte cells following exposure to conjugates of MDI with glutathione (MDI-GSH).RT-qPCR analysis using a panel of 39 candidate primers demonstrated 9 candidate genes upregulated and 30 unchanged.HPLC-MS/MS analysis of HEKa cell lysate identified 18,540 proteins across all samples Sixty proteins demonstrate statistically significant differential expression in exposed cells, some of which suggest activation of immune and inflammatory pathways.The results support the hypothesis that dermal exposures have the potential to play an important role in the development of MDI-OA. Furthermore, proteomic and gene expression data suggest multiple immune (adaptive and innate) and inflammatory pathways may be involved in the development of MDI-OA. |
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