Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
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Exploring the potential of introducing an electronic death registration system in South Africa
Sant Fruchtman C , Kallis N , Govender S , Bradshaw D , Cobos D , Morof D , Groenewald P . Health Res Policy Syst 2024 22 (1) 177 ![]() BACKGROUND: Despite South Africa's well-established Civil Registration and Vital Statistics system (CRVS) and good completeness of death registration, challenges persist in terms of the quality of cause of death information and the delayed availability of mortality statistics. The introduction of an electronic medical certification of cause of death (eMCCD) system may offer opportunities to improve both the quality and timeliness of this information. METHODS: This study used an exploratory mixed methods design to investigate perceptions surrounding an electronic solution for registering deaths in South Africa. We conducted 14 key informant interviews from 23 key informants invited, surveyed 208 out of 250 targeted health workers and engaged with more than 500 South African health professionals in a participatory workshop about the acceptability of introducing an eMCCD. Mentimeter was used to obtain feedback from the participants. Rapid qualitative analysis methods were used to analyse the key informant interviews and descriptive statistics for the survey and workshop data. During the interpretation phase, qualitative and quantitative data were integrated according to key themes that emerged from the data. RESULTS: During the qualitative interviews, the underlying factors mentioned as contributing to inadequate mortality data quality included insufficient MCCD training, diseases subjected to stigma, limited access to and quality of patient health information, and a significant proportion of deaths occurring outside medical facilities. More than 80.8% of the surveyed health professionals (168/208) rated the importance of mortality statistics as high, but the current quality was rated as low or very low by 29.3% (61/208). An eMCCD appeared to be acceptable to most workshop participants who registered on Mentimeter and was perceived as a means to strengthen the timeliness of mortality information. However, 43.0% (68/158) of the workshop participants who responded to this question on Mentimeter saw poor internet use as the main barrier to introducing an online system. CONCLUSIONS: Our results shed light on critical aspects surrounding cause of death information in South Africa, as well as the challenges faced in maintaining the quality of such data. The findings suggest that the implementation of an eMCCD system could provide opportunities to strengthen the cause of death information in South Africa if it is designed to integrate into the current system and provide supplementary functionalities. |
Description of school outcomes among children with traumatic brain injuries, Centers for Disease Control and Prevention's National Concussion Surveillance System Pilot
Waltzman D , Peterson AB , Chang D , Daugherty J . J Sch Health 2024 BACKGROUND: Traumatic brain injury (TBI) is a common injury in children. Though research on youth TBI has largely focused on high school students, this study describes selected school outcomes after TBI in the past 12 months among children aged 5-17 years. METHODS: Data from parent-proxy respondents from the pilot administration of the National Concussion Surveillance System (a random-digit-dial telephone survey with over 10,000 adult respondents) were examined. Descriptive statistics of demographic and injury characteristics of children who sustained a TBI were calculated. The association between TBI signs/symptoms and selected school outcomes were determined by multinomial logistic regressions. RESULTS: Among the 3557 children sampled via parent-proxy-reporting, 9.9% sustained a TBI in the past year. Changes in sleep or being more tired than usual, trouble concentrating, sensitivity to light or noise, and difficulty learning or remembering new things were associated with a greater risk of worse school outcomes following a TBI. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: To promote a positive return to learn (RTL) experience among children following TBI, school districts may prioritize accommodations (e.g., breaks in learning, extra time for assignments) and implement existing ascending levels of academic support where warranted. CONCLUSION: These findings may inform stakeholders seeking to enhance RTL and provide needed support or services for school-aged children who sustain a TBI. |
Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study
Park J , Bartzoka F , von Beck T , Li ZN , Mishina M , Hebert LS , Kain J , Liu F , Sharma S , Cao W , Eddins DJ , Kumar A , Kim JE , Lee JS , Wang Y , Schwartz EA , Brilot AF , Satterwhite E , Towers DM , McKnight E , Pohl J , Thompson MG , Gaglani M , Dawood FS , Naleway AL , Stevens J , Kennedy RB , Jacob J , Lavinder JJ , Levine MZ , Gangappa S , Ippolito GC , Sambhara S , Georgiou G . Lancet Microbe 2024 100935 BACKGROUND: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response. METHODS: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16-0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography-mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain-variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins. FINDINGS: During September and October of the 2018-19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88-99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16-0019/2016 HA: 0·037 μg/mL [95% CI 0·012-0·12] for RIV4; 4·43 μg/mL [0·030-100·0] for eIIV4; and 18·50 μg/mL [0·99-100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017-0·32] for RIV4; 1·10 μg/mL [0·045-100] for eIIV4; and 12·6 μg/mL [1·8-100] for ccIIV4). Comparison of B-cell receptor sequencing repertoires on day 7 showed that eIIV4 increased the median frequency of canonical egg glycan-targeting B cells (0·20% [95% CI 0·067-0·37] for eIIV4; 0·058% [0·050-0·11] for RIV4; and 0·035% [0-0·062] for ccIIV4), whereas RIV4 vaccination decreased the median frequency of B-cell receptors displaying stereotypical features associated with membrane proximal anchor-targeting antibodies (0·062% [95% CI 0-0·084] for RIV4; 0·12% [0·066-0·16] for eIIV4; and 0·18% [0·016-0·20] for ccIIV4). In exploratory analysis, we characterised the structure of a highly abundant monoclonal antibody that binds to both group 1 and 2 HAs and recognises the HA trimer interface, despite its sequence resembling the stereotypical sequence motif found in membrane-proximal anchor binding antibodies. INTERPRETATION: Although all three licensed seasonal influenza vaccines elicit serological antibody repertoires with indistinguishable features shaped by heavy imprinting, the RIV4 vaccine selectively boosts higher affinity monoclonal antibodies to contemporary strains and elicits greater serum binding potency and breadth, possibly as a consequence of the multivalent structural features of the HA immunogen in this vaccine formulation. Collectively, our findings show advantages of RIV4 vaccines and more generally highlight the benefits of multivalent HA immunogens in promoting higher affinity serum antibody responses. FUNDING: Centers for Disease Control and Prevention, National Institutes of Health, and Bill & Melinda Gates Foundation. |
A label-free optical biosensor-based point-of-care test for the rapid detection of Monkeypox virus
Aslan M , Seymour E , Brickner H , Clark AE , Celebi I , Townsend MB , Satheshkumar PS , Riley M , Carlin AF , Ünlü MS , Ray P . Biosens Bioelectron 2024 269 116932 ![]() ![]() Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation In our latest work, we have further improved our previous 'Single-Particle' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, 'Pixel-Diversity' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/mL (∼3.3 aM). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface. |
Genomic epidemiology of early SARS-CoV-2 transmission dynamics in Bangladesh
Carnegie L , McCrone JT , du Plessis L , Hasan M , Ali MZ , Begum R , Hassan MZ , Islam S , Rahman MH , Uddin ASM , Sarker MS , Das T , Hossain M , Khan M , Razu MH , Akram A , Arina S , Hoque E , Molla MMA , Nafisaa T , Angra P , Rambaut A , Pullan ST , Osman KL , Hoque MA , Biswas P , Flora MS , Raghwani J , Fournié G , Samad MA , Hill SC . Virol J 2024 21 (1) 291 ![]() ![]() BACKGROUND: Genomic epidemiology has helped reconstruct the global and regional movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is still a lack of understanding of SARS-CoV-2 spread in some of the world's least developed countries (LDCs). METHODS: To begin to address this disparity, we studied the transmission dynamics of the virus in Bangladesh during the country's first COVID-19 wave by analysing case reports and whole-genome sequences from all eight divisions of the country. RESULTS: We detected > 50 virus introductions to the country during the period, including during a period of national lockdown. Additionally, through discrete phylogeographic analyses, we identified that geographical distance and population -density and/or -size influenced virus spatial dispersal in Bangladesh. CONCLUSIONS: Overall, this study expands our knowledge of SARS-CoV-2 genomic epidemiology in Bangladesh, shedding light on crucial transmission characteristics within the country, while also acknowledging resemblances and differences to patterns observed in other nations. |
Human monoclonal antibody cloning and expression with overlap extension PCR and short DNA fragments
Ende Z , Mishina M , Kauffman RC , Kumar A , Kumari R , Knight PR , Sambhara S . J Immunol Methods 2024 113768 ![]() ![]() Monoclonal antibodies are powerful therapeutic, diagnostic, and research tools. Methods utilized to generate monoclonal antibodies are evolving rapidly. We created a transfectable linear antibody expression cassette from a 2-h high-fidelity overlapping PCR reaction from synthesized DNA fragments. We coupled heavy and light chains into a single linear sequence with a promoter, self-cleaving peptide, and poly(A) signal to increase the flexibility of swapping variable regions from any sequence available in silico. Transfection of the linear cassette tended to generate similar levels to the two-plasmid system and generated an average of 47 μg (14-98 μg) after 5 days in 2 mL cultures with 15 unique antibody sequences. The levels of antibodies produced were sufficient for most downstream applications in less than a week. The method presented here reduces the time, cost, and complexity of cloning steps. |
A public, cross-reactive glycoprotein epitope confounds Ebola virus serology
Kainulainen MH , Harmon JR , Karaaslan E , Kyondo J , Whitesell A , Twongyeirwe S , Malenfant JH , Baluku J , Kofman A , Bergeron É , Waltenburg MA , Nyakarahuka L , Balinandi S , Cossaboom CM , Choi MJ , Shoemaker TR , Montgomery JM , Spiropoulou CF . J Med Virol 2024 96 (10) e29946 ![]() ![]() Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human-to-human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B-cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross-reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross-reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology. |
Laboratory maintenance and care of Rhodnius prolixus (Hemiptera: Reduviidae) and other Triatominae
Sutcliffe AC , Dotson EM . J Med Entomol 2024 Triatomines (Hemiptera: Reduviidae) are hematophagous insects that transmit Trypanosoma cruzi, the etiological agent for Chagas disease, to humans and other mammals. As medically important vectors, species such as Rhodnius prolixus (Hemiptera: Reduviidae) have long been used as a model organism for physiological studies. Laboratory rearing of triatomines is needed to support vector and parasite research. Many environmental conditions, such as suitable housing containers, light source and duration, temperature, humidity, and density, must be addressed when adapting triatomines from a natural habitat for artificial rearing to create conditions for optimal growth and survival. Food source is also an important factor, as triatomines are considered the obligate blood feeders. Parasites and pathogens present risks not only for triatomines but also for the laboratorians handling them. Equipping an insectary space should apply best practices to ensure community, personnel, and insect health. Various triatomine colonies have been maintained in the Centers for Disease Control and Prevention (CDC) Entomology Branch insectary for over 25 years and have more recently been made available to the research community through the Biodefense and Emerging Infections Research Resources Repository (BEI Resources). The CDC Rhodnius prolixus genome has been characterized and thus represents an opportunity for continued model organism research. In addition to fulfilling requests for live triatomines, inquiries are received for support in establishing new and troubleshooting existing laboratory colonies. To accompany the extensive MR4 manual, Methods in Anopheles Research, procedures for triatomine husbandry have been developed and are shared here to address the aforementioned topics. |
ATP-based assessments of recent cleaning and disinfection for high-touch surfaces in low-resource shared toilets
Prentice-Mott G , Maru L , Kossik A , Mugambi EM , Ombok C , Odinoh R , Mwikali F , Rosenberg R , Ngere I , Murphy J , Berendes D . npj Clean Water 2024 7 (1) Quality improvements and reduction of disease risk for low-resource shared sanitation facilities require cleanliness assessment approaches that are both rigorous and practical. Using Adenosine Triphosphate (ATP) bioluminescence testing, we assessed contamination on high-touch (HT) surfaces (inner door handles) at 32 shared toilet sites in Kisumu, Kenya. In public toilets, contamination was lowest after cleaning and disinfection (C&D) with 0.5% chlorine solution (adjusted difference in mean log10 Relative Light Units per 100 cm2 (aDiff): −1.61; CI: −2.43, −0.59), followed by C&D with 0.1% chlorine solution (aDiff: −1.16; CI: −1.77, −0.55). ATP levels were not associated with overall observable toilet cleanliness and had poor agreement with visually assessed HT surface cleanliness. Our findings demonstrate the utility of this field-feasible method for detecting the impact of recent C&D in low-resource shared toilets, a novel setting for ATP cleanliness testing, while also highlighting the importance of using effective C&D procedures and addressing HT surfaces within cleaning protocols. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024. |
Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation: Technical report
Bhutani VK , Wong RJ , Turkewitz D , Rauch DA , Mowitz ME , Barfield WD . Pediatrics 2024 OBJECTIVE: To summarize the principles and application of phototherapy consistent with the current 2022 American Academy of Pediatrics "Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation." METHODS: Relevant literature was reviewed regarding phototherapy devices in the United States, specifically those that incorporate blue to blue-green light-emitting diode, fluorescent, halogen, or fiberoptic light sources, and their currently marketed indications. RESULTS: The efficacy of phototherapy devices varies widely because of nonstandardized use of light sources and configurations and irradiance meters. In summary, the most effective and safest devices have the following characteristics: (1) incorporation of narrow band blue-to-green light-emitting diode lamps (∼460-490 nm wavelength range; 478 nm optimal) that would best overlap the bilirubin absorption spectrum; (2) emission of irradiance of at least 30 µW/cm2/nm (in term infants); and (3) illumination of the exposed maximal body surface area of an infant (35% to 80%). Furthermore, accurate irradiance measurements should be performed using the appropriate irradiance meter calibrated for the wavelength range delivered by the phototherapy device. CONCLUSIONS: With proper administration of effective phototherapy to an infant without concurrent hemolysis, total serum or plasma bilirubin concentrations will decrease within the first 4 to 6 hours of initiation safely and effectively. |
Prevalence of Post-COVID conditions among Mexican COVID-19 survivors: a nationwide cross-sectional study
Ramírez-Toscano Y , Torres-Ibarra L , Carnalla M , Basto-Abreu A , Vidaña-Perez D , Colchero MA , Bautista-Arredondo S , Saydah S , Barrientos-Gutiérrez T . BMC Public Health 2024 24 (1) 1729 BACKGROUND: There are limited population-representative data that describe the potential burden of Post-COVID conditions (PCC) in Mexico. We estimated the prevalence of PCC overall and by sociodemographic characteristics among a representative sample of adults previously diagnosed with COVID-19 in Mexico. We additionally, characterized the PCC symptoms, and estimated the association between diagnosed type-2 diabetes and hypertension with PCC. METHODS: We used data from the 2021 National Health and Nutrition Survey in Mexico, a nationally and regionally representative survey, from August 1st to October 31st, 2021. Using the WHO definition, we estimated the prevalence of PCC by sociodemographics and prevalence of PCC symptoms. We fit multivariable log-binomial regression models to estimate the associations. RESULTS: The prevalence of PCC was 37.0%. The most common persistent symptoms were fatigue (56.8%), myalgia or arthralgia (47.5%), respiratory distress and dyspnea (42.7%), headache (34.0%), and cough (25.7%). The prevalence was higher in older people, women, and individuals with low socioeconomic status. There was no significant association between hypertension and PCC or diabetes and PCC prevalence. CONCLUSIONS: About one-third of the adult Mexican population who had COVID-19 in 2021 had Post-COVID conditions. Our population-based estimates can help assess potential priorities for PCC-related health services, which is critical in light of our weak health system and limited funding. |
Predicting the environmental suitability and identifying climate and sociodemographic correlates of Guinea worm (Dracunculus Medinensis) in chad
Eneanya OA , Delea MG , Cano J , Tchindebet PO , Richards RL , Zhao Y , Meftuh A , Unterwegner K , Guagliardo SAJ , Hopkins DR , Weiss A . Am J Trop Med Hyg 2024 ![]() ![]() A comprehensive understanding of the spatial distribution and correlates of infection are key for the planning of disease control programs and assessing the feasibility of elimination and/or eradication. In this work, we used species distribution modeling to predict the environmental suitability of the Guinea worm (Dracunculus medinensis) and identify important climatic and sociodemographic risk factors. Using Guinea worm surveillance data collected by the Chad Guinea Worm Eradication Program (CGWEP) from 2010 to 2022 in combination with remotely sensed climate and sociodemographic correlates of infection within an ensemble machine learning framework, we mapped the environmental suitability of Guinea worm infection in Chad. The same analytical framework was also used to ascertain the contribution and influence of the identified climatic risk factors. Spatial distribution maps showed predominant clustering around the southern regions and along the Chari River. We also identified areas predicted to be environmentally suitable for infection. Of note are districts near the western border with Cameroon and southeastern border with Central African Republic. Key environmental correlates of infection as identified by the model were proximity to permanent rivers and inland lakes, farmlands, land surface temperature, and precipitation. This work provides a comprehensive model of the spatial distribution of Guinea worm infections in Chad 2010-2022 and sheds light on potential environmental correlates of infection. As the CGWEP moves toward elimination, the methods and results in this study will inform surveillance activities and help optimize the allocation of intervention resources. |
Detection of SARS-CoC-2 in a squirrel monkey (Saimiri sciureus): A One Health investigation and response
Yaglom HD , Roth A , Alvarez C , Corbus E , Ghai RR , Ferguson S , Ritter JM , Hecht G , Rekant S , Engelthaler DM , Venkat H , Tygielski S . J Zoo Wildl Med 2024 55 (2) 471-478 ![]() Through collaborative efforts, One Health partners have responded to outbreaks of COVID-19 among animals, including those in human care at zoos. Zoos have been faced with numerous challenges, including the susceptibility of many mammalian species, and therefore the need to heighten biosecurity measures rapidly. Robust One Health collaborations already exist in Arizona to address endemic and emerging zoonoses, but these have rarely included zoos. The pandemic shed light on this, and Arizona subsequently expanded its SARS-CoV-2 surveillance efforts to include zoo animals. Testing and epidemiologic support was provided to expedite the detection of and response to zoonotic SARS-CoV-2 infection in zoo animals, as well as to understand possible transmission events. Resulting from this program, SARS-CoV-2 was detected from a rectal swab collected from an 8-yr-old squirrel monkey (Saimiri sciureus) from a zoo in Southern Arizona. The animal had rapidly become ill with nonrespiratory symptoms and died in July 2022. Genomic sequencing from the swab revealed mutations consistent with the Omicron (BA.2) lineage. An epidemiologic investigation identified an animal caretaker in close proximity to the affected squirrel monkey who tested positive for COVID-19 the same day the squirrel monkey died. Critical One Health partners provided support to the zoo through engagement of local, state, and federal agencies. Necropsy and pathologic evaluation showed significant necrotizing colitis; the overall clinical and histopathological findings did not implicate SARS-CoV-2 infection alone as a causal or contributing factor in the squirrel monkey's illness and death. This report documents the first identification of SARS-CoV-2 in a squirrel monkey and highlights a successful and timely One Health investigation conducted through multisectoral collaboration. |
U.S. preparedness and response to increasing clade I mpox cases in the Democratic Republic of the Congo - United States, 2024
McQuiston JH , Luce R , Kazadi DM , Bwangandu CN , Mbala-Kingebeni P , Anderson M , Prasher JM , Williams IT , Phan A , Shelus V , Bratcher A , Soke GN , Fonjungo PN , Kabamba J , McCollum AM , Perry R , Rao AK , Doty J , Christensen B , Fuller JA , Baird N , Chaitram J , Brown CK , Kirby AE , Fitter D , Folster JM , Dualeh M , Hartman R , Bart SM , Hughes CM , Nakazawa Y , Sims E , Christie A , Hutson CL . MMWR Morb Mortal Wkly Rep 2024 73 (19) 435-440 ![]() ![]() Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies. |
An In-Field Assessment of the P.ALP Device in Four Different Real Working Conditions: A Performance Evaluation in Particulate Matter Monitoring
Fanti G , Borghi F , Campagnolo D , Rovelli S , Carminati A , Zellino C , Cattaneo A , Cauda E , Spinazzè A , Cavallo DM . Toxics 2024 12 (4) This study aimed to assess the performance, in terms of precision and accuracy, of a prototype (called "P.ALP"-Ph.D. Air Quality Low-cost Project) developed for monitoring PM(2.5) concentration levels. Four prototypes were co-located with reference instrumentation in four different microenvironments simulating real-world and working conditions, namely (i) office, (ii) home, (iii) outdoor, and (iv) occupational environments. The devices were evaluated for a total of 20 monitoring days (approximately 168 h) under a wide range of PM(2.5) concentrations. The performances of the prototypes (based on the light-scattering working principle) were tested through different statistical methods. After the data acquisition and data cleaning processes, a linear regression analysis was performed to assess the precision (by comparing all possible pairs of devices) and the accuracy (by comparing the prototypes against the reference instrumentation) of the P.ALP. Moreover, the United States Environmental Protection Agency (US EPA) criteria were applied to assess the possible usage of this instrumentation, and to evaluate the eventual error trends of the P.ALP in the data storage process, Bland-Altman plots were also adopted. The outcomes of this study underlined that the P.ALP performed differently depending on the microenvironment in which it was tested and, consequently, on the PM(2.5) concentrations. The device can monitor PM(2.5) variations with acceptable results, but the performance cannot be considered satisfactory at extremely low and remarkably high PM(2.5) concentrations. Thanks to modular components and open-source software, the tested device has the potential to be customized and adapted to better fit specific study design needs, but it must be implemented with ad hoc calibration factors depending on the application before being used in field. |
Comparison of different trapping methods to collect malaria vectors indoors and outdoors in western Kenya
Kosgei J , Gimnig JE , Moshi V , Omondi S , McDermott DP , Donnelly MJ , Ouma C , Abong'o B , Ochomo E . Malar J 2024 23 (1) 81 BACKGROUND: Vector surveillance is among the World Health Organization global vector control response (2017-2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors. METHODS: Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R. RESULTS: Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P < 0.001) then UV-LT (mean = 3.70; RR = 3.97, P < 0.001) and CDC-LT (mean = 1.74; RR = 1.89, P = 0.03) compared to HLC. UV-LT and CDC-LT indoors captured averagely 0.18 An. arabiensis RR = 5.75, P = 0.028 and RR = 5.87, P = 0.028 respectively. Outdoors, UV-LT collected significantly higher Anopheles mosquitoes compared to HLC (An. funestus: RR = 5.18, P < 0.001; An. arabiensis: RR = 15.64, P = 0.009; An. coustani: RR = 11.65, P < 0.001). Anopheles funestus hourly biting indoors in UV-LT and CDC-LT indicated different peaks compared to HLC. CONCLUSIONS: Anopheles funestus remains the predominant mosquito species. More mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs. The varied trends observed at different times of the night suggest that these methods collect mosquitoes with diverse activities and care must be taken when interpreting the results. |
Evaluation of CHROMagar Candida Plus for the detection of C. auris with a panel of 206 fungal isolates and 83 colonization screening skin-swabs
Bentz ML , Le N , Min B , Nunnally NS , Sullivan V , Tran M , Lockhart SR , Litvintseva A , Berkow EL , Sexton DJ . Microbiol Spectr 2024 e0356423 CHROMagar Candida Plus is a new formulation of chromogenic media designed for the detection and differentiation of major clinical Candida species, including Candida auris. The objective of this study is to evaluate CHROMagar Candida Plus when used according to manufacturer's instructions with a panel of 206 fungal isolates and 83 skin-swab specimens originally collected for C. auris colonization screening. Of the 68 C. auris isolates tested, 66/68 displayed the expected light-blue colony morphology and blue halo within 48 h. None of the remaining 138 non-auris isolates appeared similar to C. auris. CHROMagarCandida Plus was, therefore, inclusive to 97% of 68 C. auris isolates tested and supported visual exclusion of 100% of the 138 non-C. auris isolates tested. For the 83 colonization screening specimens, direct plating onto CHROMagarCandida Plus was 60% sensitive and 100% specific when compared to the enrichment broth gold-standard reference method. In sum, these findings demonstrate the utility of this media when working with isolates but also notable limitations when working with primary skin-swabs specimens when competing yeast species are present.IMPORTANCECandida auris is an emerging fungal pathogen of public health concern. As it continues to spread, it is important to publish evaluations of new diagnostic tools. In this study, we share our experience with a new chromogenic media which can help distinguish C. auris from related species. |
A naturally occurring HA-stabilizing amino acid (HA1-Y17) in an A(H9N2) low-pathogenic influenza virus contributes to airborne transmission
Sun X , Belser JA , Pulit-Penaloza JA , Brock N , Kieran TJ , Zeng H , Pappas C , Tumpey TM , Maines TR . mBio 2023 e0295723 ![]() Despite the accumulation of evidence showing that airborne transmissible influenza A virus (IAV) typically has a lower pH threshold for hemagglutinin (HA) fusion activation, the underlying mechanism for such a link remains unclear. In our study, by using a pair of isogenic recombinant A(H9N2) viruses with a phenotypical difference in virus airborne transmission in a ferret model due to an acid-destabilizing mutation (HA1-Y17H) in the HA, we demonstrate that an acid-stable A(H9N2) virus possesses a multitude of advantages over its less stable counterpart, including better fitness in the ferret respiratory tract, more effective aerosol emission from infected animals, and improved host susceptibility. Our study provides supporting evidence for the requirement of acid stability in efficient airborne transmission of IAV and sheds light on fundamental mechanisms for virus airborne transmission. |
Reply to Gonzales-Luna et al
Gargis AS , Karlsson M , Kamile Rasheed J , Kent AG , McKay SL , Paulick AL , Anderson KF , Adamczyk M , Campbell D , Korhonen LC , McAllister G , Vlachos N , Halpin AL , Lutgring JD , Guh AY , Clifford McDonald L , Elkins CA . Clin Infect Dis 2023 76 (11) 2039-2041 We thank Gonzales-Luna and colleagues [1] for their comments. We agree that laboratories must have access to accurate and standardized methods for antimicrobial susceptibility testing (AST) results to be clinically meaningful. The reference method for performing Clostridioides difficile AST is agar dilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines [2]. The CLSI method for performing AST for anaerobic bacteria recommends that 5 μg/mL of hemin be incorporated into agar dilution plates and that the hemin stock solution should be protected from light and stored at 4°C–8°C for no longer than 1 month [2]. The susceptibility testing done by Gargis et al [3] was performed according to these guidelines, and the hemin stock solution was protected from light. | | Nevertheless, we read with interest the research in recent years [4–6] related to heme-dependent metronidazole resistance, including the reported association between isolates characterized as heme dependent and metronidazole resistant and the presence of a T to G mutation (PnimBG) in the −10 promoter region of the nitroimidazole reductase gene, nimB [5]. While Olaitan et al [5] found that not all heme-dependent metronidazole-resistant isolates contained the PnimBG mutation, Olaitan et al [5] indicate that most do; therefore, the presence of PnimBG may be predictive of resistance. We determined that the nimB mutation was present in 20% of our study isolates (116 of 593), of which 99% (115 of 116) belonged to RT027 (Table 1). The remaining isolate was RT014, the only RT014 isolate containing the PnimBG mutation among the 65 evaluated. |
Round bodies detected by treponema pallidum immunohistochemical stain in two cases of cutaneous syphilitic gummata
Birmingham SW , Saeed L , Thurlow CM , Vilfort K , Pillay A , Rojek NW , Doan LT , Lee BA . Am J Dermatopathol 2023 46 (1) 31-35 Tertiary syphilis may present a diagnostic challenge due to negative nontreponemal serologies in up to 30% of cases and frequent lack of identifiable spirochetes on histopathology or other direct detection tests. We report 2 cases of round bodies staining with Treponema pallidum immunohistochemistry by light microscopy in biopsies from cutaneous syphilitic gummata. In 1 case, the finding was validated 3 times by 2 independent laboratories; in the other case, T. pallidum was detected by polymerase chain reaction in the biopsy sample. Spirochete round bodies have previously been reported in the setting of electron microscopy and fluorography, but to the best of our knowledge, have not been reported by light microscopy in a routine skin biopsy. Although the clinical implications are unclear, this may represent a helpful new paradigm for the diagnosis of tertiary syphilis. |
Sleep deprivation, sleep disorders, and chronic disease
Ramos AR , Wheaton AG , Johnson DA . Prev Chronic Dis 2023 20 E77 This editorial aims to highlight the complex interplay among sleep, mental health, and chronic disease, emphasizing the critical role that sleep plays in health outcomes and overall well-being. With the mounting evidence linking sleep to numerous health problems — from mental health disorders to chronic diseases — it is paramount that we shift our focus toward understanding sleep not as a passive state but as a vital process for brain restoration and regulation. Recognizing and addressing sleep disturbances and disorders, along with promoting comprehensive strategies for improving sleep health, is a national imperative with far-reaching economic and health implications. | | The articles in this collection in Preventing Chronic Disease (PCD) — Sleep Deprivation, Sleep Disorders, and Chronic Disease — provide valuable insights into the bidirectional relationships between sleep, mental health, and chronic disease throughout the lifespan. Furthermore, the articles shed light on key themes — starting from childhood to young adulthood — while considering the role of parents and sociodemographic factors, the effect of sleep health on various racial and ethnic groups, and the geographic variation in the prevalence of short sleep duration. |
Stillbirths and neonatal deaths caused by group B streptococcus in Africa and South Asia identified through Child Health and Mortality Prevention Surveillance (CHAMPS)
Mahtab S , Madewell ZJ , Madhi SA , Wise A , Swart PJ , Velaphi S , Mandomando I , Bramugy J , Mabunda R , Xerinda E , Scott AG , Assefa N , Madrid L , Bweihun M , Temesgen F , Onyango D , Akelo V , Oliech R , Otieno P , Verani JR , Arifeen SE , Gurley ES , Alam M , Rahman A , Hossain MZ , Sow S , Kotloff K , Tapia M , Keita AM , Sanogo D , Ogbuanu I , Ojulong J , Lako S , Ita O , Kaluma E , Wilson T , Mutevedzi P , Barr BAT , Whitney CG , Blau DM , Bassat Q . Open Forum Infect Dis 2023 10 (9) ofad356 BACKGROUND: Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). METHODS: Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. RESULTS: We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). CONCLUSIONS: Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs. |
Food insecurity and the risk of HIV acquisition: Findings from population-based surveys in six sub-Saharan African countries (2016-2017) (preprint)
Low A , Gummerson E , Schwitters A , Bonifacio R , Teferi M , Mutenda N , Ayton S , Juma J , Ahpoe C , Ginindza C , Patel H , Biraro S , Sachathep K , Hakim AJ , Barradas D , Hassani AS , Kirungi W , Jackson K , Goeke L , Philips N , Mulenga L , Ward J , Hong S , Rutherford G , Findley S . medRxiv 2021 2021.09.27.21263917 Introduction Food insecurity has a bidirectional relationship with HIV infection, with hunger driving compensatory risk behaviors, while infection can increase poverty. We used a laboratory recency assay to estimate the timing of HIV infection vis-à-vis the timing of severe food insecurity (SFI).Methods Data from population-based surveys in Zambia, Eswatini, Lesotho, Uganda, and Tanzania and Namibia were used. We defined SFI as having no food ≥three times in the past month. Recent HIV infection was identified using the HIV-1 LAg avidity assay, with a viral load (>1000 copies/ml) and no detectable antiretrovirals indicating an infection in the past 6 months. Logistic regression was conducted to assess correlates of SFI. Poisson regression was conducted on pooled data, adjusted by country to determine the association of SFI with recent HIV infection and risk behaviors, with effect heterogeneity evaluated for each country. All analyses were done using weighted data.Results Of 112,955 participants aged 15-59, 10.3% lived in households reporting SFI. SFI was most common in urban, woman-headed households. Among women and not men, SFI was associated with a two-fold increase in risk of recent HIV infection (adjusted relative risk [aRR] 2.08, 95% CI 1.09-3.97), with lower risk in high prevalence countries (Eswatini and Lesotho). SFI was associated with transactional sex (aRR 1.28, 95% CI 1.17-1.41), a history of forced sex (aRR 1.36, 95% CI 1.11-1.66), and condom-less sex with a partner of unknown or positive HIV status (aRR 1.08, 95% CI 1.02-1.14) in all women, and intergenerational sex (partner ≥10 years older) in women aged 15-24 (aRR 1.23, 95% CI 1.03-1.46), although this was heterogeneous. Recent receipt of food support was protective (aRR 0.36, 95% CI 0.14-0.88).Conclusion SFI increased risk for HIV acquisition in women by two-fold. Worsening food scarcity due to climactic extremes could imperil HIV epidemic control.What is already knownThe link between food insecurity and the adoption of high-risk sexual behaviors as a coping mechanism has been shown in several settings.HIV infection can also drive food insecurity due to debilitating illness reducing productivity, the costs of treatment diverting money from supplies, and potentially reduced labor migration.Food insecurity has been associated with chronic HIV infection, but it has not been linked with HIV acquisition.What are the new findingsThis study of 112,955 adults across six countries in sub-Saharan Africa provides unique information on the association between acute food insecurity and recent HIV infection in women, as well as the potential behavioral and biological mediators, including community viremia as a measure of infectiousness.The data enabled a comprehensive analysis of factors associated with risk of infection, and how these factors differed by country and gender. Women living in food insecure households had a two-fold higher risk of recent HIV acquisition, and reported higher rates of transactional sex, early sexual debut, forced sex, intergenerational sex and sex without a condom with someone of unknown or positive HIV status. This pattern was not seen in men.This study is also the first to demonstrate a protective association for food support, which was associated with a lower risk of recent HIV infection in women.What do the new findings implyIn light of worsening food insecurity due to climate change and the recent COVID-19 pandemic, our results support further exploration of gender-specific pathways of response to acute food insecurity, particularly how women’s changes in sexual behavior heighten their risk of HIV acquisition.These and other data support the inclusion of food insecurity in HIV risk assessments for women, as well as the exploration of provision of food support to those households at highest risk based on geographic and individual factors.Competing Interest StatementThe authors have declared no competing interest.Clinical Protocols https://phia.icap.columbia.edu/ Funding StatementThis project has been supported by the Presid nt Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of cooperative agreement #U2GGH001226.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:The PHIA protocol and data collection tools were approved by national ethics committees for each country, and the institutional review boards at Columbia University Irving Medical Center, the US Centers for Disease Control and Prevention (CDC) and the University of California, San Francisco in the case of Namibia. Due to the inclusion of six countries and the multiple ethical boards involved, we are providing the protocol numbers for the Columbia University Irving Medical Center, which approved all protocols (AAAQ0753, AAAQ7860, AAAQ8408, AAAQ8537, AAAR2051, AAAQ889). 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 used in this manuscript are publicly available at https://phia-data.icap.columbia.edu/. https://phia-data.icap.columbia.edu/ |
Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin (preprint)
Joseph SJ , Thomas Iv JC , Schmerer MW , Cartee J , St Cyr S , Schlanger K , Kersh EN , Raphael BH , Gernert KM . bioRxiv 2021 2021.08.05.455198 Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009-2011 and again during the 2012-2013 time, facilitating the clonal expansion of this genogroup with AZMrs in the U.S. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the U.S. and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers.Competing Interest StatementThe authors have declared no competing interest. |
Competition is a determinant of multidrug resistant plasmid acquisition in Salmonella (preprint)
Oladeinde A , Abdo Z , Zwirzitz B , Woyda R , Lakin SM , Press MO , Cook K , Cox NA , Thomas JCIV , Looft T , Rothrock MJJr , Zock G , Plumblee Lawrence J , Cudnik D , Ritz C , Aggrey SE . bioRxiv 2021 2021.04.02.438293 Host microbiome homeostasis ensures that gut conditions are unfavorable to an invading pathogen such as Salmonella enterica. Consequently, fostering a “balanced” gut microbiome through the administration of microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known on how competitive exclusion affects the transfer of antibiotic resistance. To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter – a complex environment comprising of decomposing pine shavings, feces, uric acid, feathers, and feed, with Salmonella Heidelberg (S. Heidelberg), a model pathogen. We show that chicks raised on reused litter carried lower abundance of Salmonella and harbored a more uniform and diverse microbiome comprising of bacterial species that are known to provide colonization resistance towards Salmonella compared to chicks raised on fresh bedding composed of pine shavings. Additionally, these bacterial species were associated with a lower horizontal transfer of multidrug resistance genes to S. Heidelberg. Using in vitro competition experiments, we confirmed that conjugation between S. Heidelberg and E. coli strains from chicks raised on fresh litter resulted in the acquisition of multidrug resistant plasmids. Contrastingly, bacteriophage-mediated recombination between S. Heidelberg and E. coli strains made the acquisition of plasmid-mediated β-lactamase gene (blaCMY-2) possible. Collectively, this study demonstrates that competitive exclusion can reduce the transfer of antibiotic resistance and provides information on the bacterial species that can be explored for their benefits to reduce antibiotic resistance transfer.Importance/Significance Antimicrobial resistance spread is a worldwide health challenge, stemming in large part, from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organization have adopted a one health approach to curtail the proliferation of antibiotic resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how antimicrobial resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we demonstrate that commensal bacteria play a key role in reducing the horizontal transfer of antibiotic resistance to Salmonella and provide the identity and characteristics of the bacterial species that performs this function in broiler chickens. |
Under pressure: phenotypic divergence and convergence associated with microhabitat adaptations in Triatominae (preprint)
Abad-Franch F , Monteiro FA , Pavan MG , Patterson JS , Bargues MD , Zuriaga MÁ , Aguilar M , Beard CB , Mas-Coma S , Miles MA . bioRxiv 2020 2020.07.28.224535 ![]() Background Triatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. When these blood-sucking bugs adapt to new microhabitats, their phenotypes may change. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood.Methods/Findings We combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrial cytb and nuclear ITS2 DNA-sequence analyses to study Rhodnius ecuadoriensis populations from across the species’ range. We found three major, naked-eye phenotypic variants. Southern-Andean bugs (SW Ecuador/NW Peru) from house and vertebrate-nest microhabitats are typical, light-colored, small bugs with short heads/wings. Northern-Andean bugs (W Ecuador wet-forest palms) are dark, large bugs with long heads/wings. Finally, northern-lowland bugs (coastal Ecuador dry-forest palms) are light-colored and medium-sized. Wing and (size-free) head shapes are similar across Ecuadorian populations, regardless of habitat or naked-eye phenotype, but distinct in Peruvian bugs. Bayesian phylogenetic and multispecies-coalescent DNA-sequence analyses strongly suggest that Ecuadorian and Peruvian populations are two independently-evolving lineages, with little within-lineage structuring/differentiation.Conclusions We report sharp naked-eye phenotypic divergence of genetically similar Ecuadorian R. ecuadoriensis (house/nest southern-Andean vs. palm-dwelling northern bugs; and palm-dwelling Andean vs. lowland); and sharp naked-eye phenotypic similarity of typical, yet genetically distinct, southern-Andean bugs from house and nest (but not palm) microhabitats (SW Ecuador vs. NW Peru). This remarkable phenotypic diversity within a single nominal species likely stems from microhabitat adaptations possibly involving predator-driven selective pressure (yielding substrate-matching camouflage coloration) and a shift from palm-crown to vertebrate-nest microhabitats (yielding smaller bodies and shorter heads and wings). These findings shed new light on the origins of phenotypic diversity in triatomines, warn against excess reliance on phenotype-based triatomine-bug taxonomy, and confirm the Triatominae as an informative model-system for the study of phenotypic change under ecological pressure.Author summary Triatomine bugs feed on the blood of vertebrates including humans and transmit the parasite that causes Chagas disease. The bugs, of which 150+ species are known, are highly diverse in size, shape, and color. Some species look so similar that they are commonly confused, whereas a few same-species populations look so different that they were thought to be separate species. Despite the crucial role of naked-eye phenotypes in triatomine-bug identification and classification (which are essential for vector control-surveillance), the origins of this variation remain unclear. Here, we describe a striking case of phenotypic divergence, with genetically similar bugs looking very different from one another, and phenotypic convergence, with bugs from two genetically distinct populations (likely on their way to speciation) looking very similar – and all within a single nominal species, Rhodnius ecuadoriensis. Phenotypically divergent populations occupy different ecological regions (wet vs. dry) and microhabitats (palm-crowns vs. vertebrate nests), whereas convergent populations occupy man-made and nest (but not palm) microhabitats. These findings suggest that triatomines can ‘respond’ to ecological novelty by changing their external, naked-eye phenotypes as they adapt to new microhabitats. We therefore warn that phenotypic traits such as overall size or color may confound triatomine-bug species identification and classification. |
Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit (preprint)
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . medRxiv 2020 2020.12.11.20236919 Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe shortages of personal protective equipment (PPE) necessary to protect front-line healthcare personnel. These shortages underscore the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed PPE enabling safe reuse of masks and respirators. Efficient decontamination must be available not only in low-resourced settings, but also in well-resourced settings affected by PPE shortages. Methylene blue (MB) photochemical treatment, hitherto with many clinical applications including those used to inactivate virus in plasma, presents a novel approach for widely applicable PPE decontamination. Dry heat (DH) treatment is another potential low-cost decontamination method.Methods MB and light (MBL) and DH treatments were used to inactivate coronavirus on respirator and mask material. We tested three N95 filtering facepiece respirators (FFRs), two medical masks (MMs), and one cloth community mask (CM). FFR/MM/CM materials were inoculated with SARS-CoV-2 (a Betacoronavirus), murine hepatitis virus (MHV) (a Betacoronavirus), or porcine respiratory coronavirus (PRCV) (an Alphacoronavirus), and treated with 10 µM MB followed by 50,000 lux of broad-spectrum light or 12,500 lux of red light for 30 minutes, or with 75°C DH for 60 minutes. In parallel, we tested respirator and mask integrity using several standard methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. Intact FFRs/MMs/CM were subjected to five cycles of decontamination (5CD) to assess integrity using International Standardization Organization (ISO), American Society for Testing and Materials (ASTM) International, National Institute for Occupational Safety and Health (NIOSH), and Occupational Safety and Health Administration (OSHA) test methods.Findings Overall, MBL robustly and consistently inactivated all three coronaviruses with at least a 4-log reduction. DH yielded similar results, with the exception of MHV, which was only reduced by 2-log after treatment. FFR/MM integrity was maintained for 5 cycles of MBL or DH treatment, whereas one FFR failed after 5 cycles of VHP+O3. Baseline performance for the CM was variable, but reduction of integrity was minimal.Interpretation Methylene blue with light and DH treatment decontaminated masks and respirators by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination of masks is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. These attractive features support the utilization and continued development of this novel PPE decontamination method.Competing Interest StatementAuthors Thomas S. Lendvay, James Chen are Co-Founders and equity owners of Singletto, Inc. (Seattle, WA, USA) Authors Yi Cui and Steven Chu are Co-Founders and equity owners of 4C Air, Inc. (Sunnyvale, CA)Funding StatementThis study was funded by Open Philanthropy; Amazon Inc./University of Washington Catalyst Award; University of Liege (Belgium) and the Walloon Region, Belgium; Li Ka Shing Institute; Alberta Health Services; and an Anonymous donor to the University of Washington, Department of Urology.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:Stanford University and Alberta Health Services/University of Calgary were exempt from IRB as the human fit testing was considered Quality Improvement. ERB for clinical specimen use: A clinical saliva specimen with a SARS-CoV-2 was provided by Dr. John Conly from Calgary, Alberta with Calgary ERB approval (ID# Pro00099761).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 inte ventional 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.YesData will be freely shared post publication on reasonable request by contacting the corresponding author of the study. |
An assessment of adult mosquito collection techniques for studying species abundance and diversity in Maferinyah, Guinea (preprint)
Cansado-Utrilla C , Jeffries CL , Kristan M , Brugman VA , Heard P , Camara G , Sylla M , Beavogui AH , Messenger LA , Walker T . bioRxiv 2019 772822 Background Guinea is a West African country with a high prevalence of vector-borne diseases where few entomological studies have been undertaken. Although several mosquito collection methods are routinely used for surveillance in vector control programmes, they target different behaviours causing bias in species diversity and abundance. Given the paucity of mosquito trap data in West Africa, we compared the performance of five trap-lure combinations and Human Landing Catches (HLCs) in Guinea.Methods Five mosquito traps were compared in a 5×5 Latin Square design for 15 days in three villages in Guinea between June and July 2018. CDC light traps, BG sentinel 2 traps (with BG and MB5 lures), gravid traps and Stealth traps were deployed for 24-hour intervals with mosquitoes collected every 12 hours (day and night collections). HLCs were also performed for 15 nights. A Generalised Linear Mixed Model was applied to compare the effect of the traps, sites and collection times on the mosquito abundance. Species identification was confirmed using PCR-based analysis and Sanger sequencing.Results In total, 10,610 mosquitoes were captured across all five traps. Significantly more mosquitoes (P<0.005) were collected by Stealth traps (7,096) compared to the rest of the traps. Stealth traps and BG sentinel 2 traps were the best at capturing An. gambiae and Ae. aegypti mosquitoes respectively. HLCs captured predominantly An. coluzzii (41%) and hybrids of An. gambiae s.s. / An. coluzzii (36%) in contrast to the five adult traps, which captured predominantly An. melas (83%). Senguelen (rural) presented the highest abundance of mosquitoes and overall diversity in comparison with Fandie (semi-rural) and Maferinyah Centre One (semi-urban). To our knowledge, four species are reported for the first time in Guinea.Conclusions Stealth traps presented the best performance overall, suggesting that this trap may play an important role for mosquito surveillance in Guinea and similar sites in West Africa. We recommend the incorporation of molecular tools in entomological studies since it has helped to reveal, together with morphological identification, the presence of 25 mosquito species in this area.BG2BG sentinel 2 trapBG2-BGBG sentinel 2 trap with BG lureBG2-MB5BG sentinel 2 trap with MB5 lureGLMMgeneralized linear mixed modelGTGravid trapHLCHuman Landing CatchLTCDC light trapSTStealth trap |
Peripheral blood DNA methylation and autism spectrum disorder (preprint)
Andrews SV , Sheppard B , Windham GC , Schieve LA , Schendel DE , Croen LA , Chopra P , Alisch RS , Newschaffer CJ , Warren ST , Feinberg AP , Fallin MD , Ladd-Acosta C . bioRxiv 2018 320622 BackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size, and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12×10−7. Seven CpGs showed differences at p < 1×10−5 and 48 at 1×10−4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpGs hits, which was consistent across EWAS and meQTL discovery p-value thresholds.ConclusionsWe report the largest case-control EWAS study of ASD to date. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the 7 sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. |
Fast estimation of genetic relatedness between members of heterogeneous populations of closely related genomic variants (preprint)
Tsyvina V , Campo DS , Sims S , Zelikovsky A , Khudyakov Y , Skums P . bioRxiv 2018 324418 Many biological analysis tasks require extraction of families of genetically similar sequences from large datasets produced by Next-generation Sequencing (NGS). Such tasks include detection of viral transmissions by analysis of all genetically close pairs of sequences from viral datasets sampled from infected individuals or studying of evolution of viruses or immune repertoires by analysis of network of intra-host viral variants or antibody clonotypes formed by genetically close sequences. The most obvious naϊeve algorithms to extract such sequence families are impractical in light of the massive size of modern NGS datasets. In this paper, we present fast and scalable k-mer-based framework to perform such sequence similarity queries efficiently, which specifically targets data produced by deep sequencing of heterogeneous populations such as viruses. The tool is freely available for download at https://github.com/vyacheslav-tsivina/signature-sj |
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