Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 266 Records) |
Query Trace: Silva L [original query] |
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ORF virus causes tumor-promoting inflammation in sheep and goats
Pintus D , Cancedda MG , Puggioni G , Scivoli R , Rocchigiani AM , Maestrale C , Coradduzza E , Bechere R , Silva-Flannery L , Bullock HA , Macciocu S , Montesu MA , Marras V , Dore S , Ritter JM , Ligios C . Vet Pathol 2024 3009858241241794 ORF virus (ORFV) causes contagious ecthyma ("ORF"), a disease of sheep and goats characterized by lesions ranging from vesicles and pustules to atypical papilloma-like and angiomatous lesions in the skin and mucosae. The authors investigated the molecular factors leading to the ORF-associated atypical tumor-like changes. Fifteen lambs, 15 kids, and an adult ram clinically affected by natural ORFV infection were enrolled in the study and examined by several methods. ORFV was detected by viral culture or real-time polymerase chain reaction (RT-PCR) in the lesioned tissues and in the blood of the clinically affected sheep and goats. Surprisingly, ORFV was also detected in the blood of healthy goats from an affected herd. Microscopically, they found a pseudo-papillomatous proliferation of the epithelium, while the dermis and lamina propria were expanded by a proliferating neovascular component that highly expressed the viral vascular endothelial growth factor (vVEGF) and its host receptor vascular endothelial growth factor receptor 2 (VEGFR2). Immunohistochemistry, immunofluorescence, and in situ hybridization for mRNA showed that epidermal growth factor receptor (EGFR) was expressed in the fibrovascular component, in the infiltrating CD163+ macrophages, and in the basal stratum of the epidermis. Confocal immunofluorescence microscopy demonstrated that CD163+ macrophages were associated with VEGF and VEGFR2. Finally, they found by quantitative RT-PCR the overexpression of the interleukin-6 and VEGFR2 genes in the lesioned tissues. These findings suggest that ORFV activates an inflammatory reaction characterized by CD163+ macrophages expressing EGFR and VEGFR2, which might play an oncogenic role through synergistic action with vVEGF signaling. |
Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014.
Cassemiro KM , Burlandy FM , Barbosa MR , Chen Q , Jorba J , Hachich EM , Sato MI , Burns CC , da Silva EE . PLoS One 2016 11 (3) e0152251 A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication. |
Xylazine use among people who inject drugs, Philadelphia 2022
Tan M , Nassau T , Kuncio D , Higgins D , Teixeira da Silva D , Tomlinson D , Brady KA . J Addict Med 2024 OBJECTIVES: Xylazine is commonly mixed with illicit opioids in Philadelphia, and potential associations with wound issues, infectious diseases, and overdoses are of public health concern. We used data from the National HIV Behavioral Surveillance Survey among persons who inject drugs (PWIDs) in Philadelphia to better identify individuals at risk and inform patients and clinicians about xylazine risk factors. METHODS: We compared characteristics of participants who reported using xylazine to those who reported not using xylazine in the past 12 months. Among those who reported xylazine use, we compared characteristics between people who prefer and did not prefer to use xylazine. RESULTS: In this sample of PWIDs, most prefer not to use xylazine, yet use is common. Compared with PWIDs not using xylazine, PWIDs who use xylazine were more likely to have recent homelessness, polysubstance use, overdose history, and hepatitis C virus infection (P < 0.05 for all comparisons). Compared with concordant xylazine use, discordant xylazine use was associated with lower preference for fentanyl, heroin as the primary injection drug, and lower use of syringe service programs (P < 0.05 for all comparisons). CONCLUSIONS: Public health entities should prioritize studying the use and health effects of xylazine in their jurisdictions and consider supporting point-of-care and drug-checking surveillance in addition to raising awareness of xylazine in the drug supply. |
Pathology and monkeypox virus localization in tissues from immunocompromised patients with severe or fatal mpox
Ritter JM , Martines RB , Bhatnagar J , Rao AK , Villalba JA , Silva-Flannery L , Lee E , Bullock HA , Hutson CL , Cederroth T , Harris CK , Hord K , Xu Y , Brown CA , Guccione JP , Miller M , Paddock CD , Reagan-Steiner S . J Infect Dis 2024 BACKGROUND: Pathology and monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5/16 (31%) biopsy and 4/6 (67%) autopsy cases. DISCUSSION: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings. |
Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance
Ko ER , Reller ME , Tillekeratne LG , Bodinayake CK , Miller C , Burke TW , Henao R , McClain MT , Suchindran S , Nicholson B , Blatt A , Petzold E , Tsalik EL , Nagahawatte A , Devasiri V , Rubach MP , Maro VP , Lwezaula BF , Kodikara-Arachichi W , Kurukulasooriya R , De Silva AD , Clark DV , Schully KL , Madut D , Dumler JS , Kato C , Galloway R , Crump JA , Ginsburg GS , Minogue TD , Woods CW . Sci Rep 2023 13 (1) 22554 Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76-0.90) with overall accuracy of 81.6% (95% CI 72.7-88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens. |
Substantial Diversity in Cocirculating Omicron Lineages in Hospital Setting, Porto Alegre, Brazil
Andreis TF , Cantarelli VV , da Silva MB , Helfer MS , Brust FR , Zavascki AP , GAIHN-HAI Team , Westercamp M , Tashayev V , Donadel M , Magleby R , Petersen E , Mahon G . Emerg Infect Dis 2023 29 (12) 2583-2586 We describe substantial variant diversity among 23 detected SARS-CoV-2 Omicron lineage viruses cocirculating among healthcare workers and inpatients (272 sequenced samples) from Porto Alegre, Brazil, during November 2022-January 2023. BQ.1 and related lineages (61.4%) were most common, followed by BE.9 (19.1%), first described in November 2022 in the Amazon region. |
Clinical features, etiologies, and outcomes of central nervous system infections in intensive care: A multicentric retrospective study in a large Brazilian metropolitan area
Andrade HB , da Silva IRF , Espinoza R , Ferreira MT , da Silva MST , Theodoro PHN , Detepo PJT , Varela MC , Ramos GV , da Silva AR , Soares J , Belay ED , Sejvar JJ , Bozza FA , Cerbino-Neto J , Japiassú AM . J Crit Care 2023 79 154451 PURPOSE: The goal of this study was to investigate severe central nervous system infections (CNSI) in adults admitted to the intensive care unit (ICU). We analyzed the clinical presentation, causes, and outcomes of these infections, while also identifying factors linked to higher in-hospital mortality rates. MATERIALS AND METHODS: We conducted a retrospective multicenter study in Rio de Janeiro, Brazil, from 2012 to 2019. Using a prediction tool, we selected ICU patients suspected of having CNSI and reviewed their medical records. Multivariate analyses identified variables associated with in-hospital mortality. RESULTS: In a cohort of 451 CNSI patients, 69 (15.3%) died after a median 11-day hospitalization (5-25 IQR). The distribution of cases was as follows: 29 (6.4%) had brain abscess, 161 (35.7%) had encephalitis, and 261 (57.8%) had meningitis. Characteristics: median age 41 years (27-53 IQR), 260 (58%) male, and 77 (17%) HIV positive. The independent mortality predictors for encephalitis were AIDS (OR = 4.3, p = 0.01), ECOG functional capacity limitation (OR = 4.0, p < 0.01), ICU admission from ward (OR = 4.0, p < 0.01), mechanical ventilation ≥10 days (OR = 6.1, p = 0.04), SAPS 3 ≥ 55 points (OR = 3.2, p = 0.02). Meningitis: Age > 60 years (OR = 234.2, p = 0.04), delay >3 days for treatment (OR = 2.9, p = 0.04), mechanical ventilation ≥10 days (OR = 254.3, p = 0.04), SOFA >3 points (OR = 2.7, p = 0.03). Brain abscess: No associated factors found in multivariate regression. CONCLUSIONS: Patients' overall health, prompt treatment, infection severity, and prolonged respiratory support in the ICU all significantly affect in-hospital mortality rates. Additionally, the implementation of CNSI surveillance with the used prediction tool could enhance public health policies. |
Assessing the association between food environment and dietary inflammation by community type: a cross-sectional REGARDS study
Algur Y , Rummo PE , McAlexander TP , De Silva SSA , Lovasi GS , Judd SE , Ryan V , Malla G , Koyama AK , Lee DC , Thorpe LE , McClure LA . Int J Health Geogr 2023 22 (1) 24 BACKGROUND: Communities in the United States (US) exist on a continuum of urbanicity, which may inform how individuals interact with their food environment, and thus modify the relationship between food access and dietary behaviors. OBJECTIVE: This cross-sectional study aims to examine the modifying effect of community type in the association between the relative availability of food outlets and dietary inflammation across the US. METHODS: Using baseline data from the REasons for Geographic and Racial Differences in Stroke study (2003-2007), we calculated participants' dietary inflammation score (DIS). Higher DIS indicates greater pro-inflammatory exposure. We defined our exposures as the relative availability of supermarkets and fast-food restaurants (percentage of food outlet type out of all food stores or restaurants, respectively) using street-network buffers around the population-weighted centroid of each participant's census tract. We used 1-, 2-, 6-, and 10-mile (~ 2-, 3-, 10-, and 16 km) buffer sizes for higher density urban, lower density urban, suburban/small town, and rural community types, respectively. Using generalized estimating equations, we estimated the association between relative food outlet availability and DIS, controlling for individual and neighborhood socio-demographics and total food outlets. The percentage of supermarkets and fast-food restaurants were modeled together. RESULTS: Participants (n = 20,322) were distributed across all community types: higher density urban (16.7%), lower density urban (39.8%), suburban/small town (19.3%), and rural (24.2%). Across all community types, mean DIS was - 0.004 (SD = 2.5; min = - 14.2, max = 9.9). DIS was associated with relative availability of fast-food restaurants, but not supermarkets. Association between fast-food restaurants and DIS varied by community type (P for interaction = 0.02). Increases in the relative availability of fast-food restaurants were associated with higher DIS in suburban/small towns and lower density urban areas (p-values < 0.01); no significant associations were present in higher density urban or rural areas. CONCLUSIONS: The relative availability of fast-food restaurants was associated with higher DIS among participants residing in suburban/small town and lower density urban community types, suggesting that these communities might benefit most from interventions and policies that either promote restaurant diversity or expand healthier food options. |
Healthcare personnel in 2016-2019 prospective cohort infrequently got vaccinated, worked while ill, and frequently used antibiotics rather than antivirals against viral influenza illnesses
Azziz-Baumgartner E , Neyra J , Yau TS , Soto G , Owusu D , Zhang C , Romero C , Yoo YM , Gonzales M , Tinoco Y , Silva M , Bravo E , Serrano NR , Matos E , Chavez-Perez V , Castro JC , Esther Castillo M , Porter R , Munayco C , Rodriguez A , Levine MZ , Prouty M , Thompson MG , Arriola CS . Influenza Other Respir Viruses 2023 17 (9) e13189 BACKGROUND: Uncertainty about risk of illness and the value of influenza vaccines negatively affects vaccine uptake among persons targeted for influenza vaccination. METHODS: During 2016-2019, we followed a cohort of healthcare personnel (HCP) targeted for free-of-charge influenza vaccination in five Lima hospitals to quantify risk of influenza, workplace presenteeism (coming to work despite illness), and absenteeism (taking time off from work because of illness). The HCP who developed acute respiratory illnesses (ARI) (≥1 of acute cough, runny nose, body aches, or feverishness) were tested for influenza using reverse-transcription polymerase chain reaction (rt-PCR). FINDINGS: The cohort (2968 HCP) contributed 950,888 person-days. Only 36 (6%) of 605 HCP who participated every year were vaccinated. The HCP had 5750 ARI and 147 rt-PCR-confirmed influenza illnesses. The weighted incidence of laboratory-confirmed influenza was 10.0/100 person-years; 37% used antibiotics, and 0.7% used antivirals to treat these illnesses. The HCP with laboratory-confirmed influenza were present at work while ill for a cumulative 1187 hours. INTERPRETATION: HCP were frequently ill and often worked rather than stayed at home while ill. Our findings suggest the need for continuing medical education about the risk of influenza and benefits of vaccination and stay-at-home-while-ill policies. |
Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Carey ME , Dyson ZA , Ingle DJ , Amir A , Aworh MK , Chattaway MA , Chew KL , Crump JA , Feasey NA , Howden BP , Keddy KH , Maes M , Parry CM , Van Puyvelde S , Webb HE , Afolayan AO , Alexander AP , Anandan S , Andrews JR , Ashton PM , Basnyat B , Bavdekar A , Bogoch II , Clemens JD , da Silva KE , De A , de Ligt J , Diaz Guevara PL , Dolecek C , Dutta S , Ehlers MM , Francois Watkins L , Garrett DO , Godbole G , Gordon MA , Greenhill AR , Griffin C , Gupta M , Hendriksen RS , Heyderman RS , Hooda Y , Hormazabal JC , Ikhimiukor OO , Iqbal J , Jacob JJ , Jenkins C , Jinka DR , John J , Kang G , Kanteh A , Kapil A , Karkey A , Kariuki S , Kingsley RA , Koshy RM , Lauer AC , Levine MM , Lingegowda RK , Luby SP , Mackenzie GA , Mashe T , Msefula C , Mutreja A , Nagaraj G , Nagaraj S , Nair S , Naseri TK , Nimarota-Brown S , Njamkepo E , Okeke IN , Perumal SPB , Pollard AJ , Pragasam AK , Qadri F , Qamar FN , Rahman SIA , Rambocus SD , Rasko DA , Ray P , Robins-Browne R , Rongsen-Chandola T , Rutanga JP , Saha SK , Saha S , Saigal K , Sajib MSI , Seidman JC , Shakya J , Shamanna V , Shastri J , Shrestha R , Sia S , Sikorski MJ , Singh A , Smith AM , Tagg KA , Tamrakar D , Tanmoy AM , Thomas M , Thomas MS , Thomsen R , Thomson NR , Tupua S , Vaidya K , Valcanis M , Veeraraghavan B , Weill FX , Wright J , Dougan G , Argimón S , Keane JA , Aanensen DM , Baker S , Holt KE . Elife 2023 12 BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng |
Sporozoite immunization: Innovative Translational Science to Support the Fight against malaria
Richie TL , Church LWP , Murshedkar T , Billingsley PF , James ER , Chen MC , Abebe Y , Natasha Kc , Chakravarty S , Dolberg D , Healy SA , Diawara H , Sissoko MS , Sagara I , Cook DM , Epstein JE , Mordmüller B , Kapulu M , Kreidenweiss A , Franke-Fayard B , Agnandji ST , López Mikue MA , McCall MBB , Steinhardt L , Oneko M , Olotu A , Vaughan AM , Kublin JG , Murphy SC , Jongo S , Tanner M , Sirima SB , Laurens MB , Daubenberger C , Silva JC , Lyke KE , Janse CJ , Roestenberg M , Sauerwein RW , Abdulla S , Dicko A , Kappe SHI , Sim BKL , Duffy PE , Kremsner PG , Hoffman SL . Expert Rev Vaccines 2023 22 (1) 964-1007 INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection. This review describes > 30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives. |
Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: Report of an investigation
Gould CV , Free RJ , Bhatnagar J , Soto RA , Royer TL , Maley WR , Moss S , Berk MA , Craig-Shapiro R , Kodiyanplakkal RPL , Westblade LF , Muthukumar T , Puius YA , Raina A , Hadi A , Gyure KA , Trief D , Pereira M , Kuehnert MJ , Ballen V , Kessler DA , Dailey K , Omura C , Doan T , Miller S , Wilson MR , Lehman JA , Ritter JM , Lee E , Silva-Flannery L , Reagan-Steiner S , Velez JO , Laven JJ , Fitzpatrick KA , Panella A , Davis EH , Hughes HR , Brault AC , St George K , Dean AB , Ackelsberg J , Basavaraju SV , Chiu CY , Staples JE . Lancet Microbe 2023 4 (9) e711-e721 BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases. |
Population structure and antimicrobial resistance patterns of Salmonella Typhi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India
da Silva KE , Date K , Hirani N , LeBoa C , Jayaprasad N , Borhade P , Warren J , Shimpi R , Hoffman SA , Mikoleit M , Bhatnagar P , Cao Y , Haldar P , Harvey P , Zhang C , Daruwalla S , Dharmapalan D , Gavhane J , Joshi S , Rai R , Rathod V , Shetty K , Warrier DS , Yadav S , Chakraborty D , Bahl S , Katkar A , Kunwar A , Yewale V , Dutta S , Luby SP , Andrews JR . mBio 2023 14 (4) e0117923 We performed whole-genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing bla(SHV-12), associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among S. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal Salmonella spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of S. Typhi and S. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of S. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant S. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies. |
Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America
Erchick DJ , Subedi S , Verhulst A , Guillot M , Adair LS , Barros AJD , Chasekwa B , Christian P , da Silva BGC , Silveira MF , Hallal PC , Humphrey JH , Huybregts L , Kariuki S , Khatry SK , Lachat C , Matijasevich A , McElroy PD , Menezes AMB , Mullany LC , Perez TLL , Phillips-Howard PA , Roberfroid D , Santos IS , Ter Kuile FO , Ravilla TD , Tielsch JM , Wu LSF , Katz J . Popul Health Metr 2023 21 (1) 10 INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly. |
Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant (preprint)
Coutinho RM , Marquitti FMD , Ferreira LS , Borges ME , da Silva RLP , Canton O , Portella TP , Poloni S , Franco C , Plucinski MM , Lessa FC , da Silva AAM , Kraenkel RA , de Sousa Mascena Veras MA , Prado PI . medRxiv 2021 2021.03.03.21252706 The variant of concern (VOC) P.1 emerged in the Amazonas state (Brazil) in November-2020. It contains a constellation of mutations, ten of them in the spike protein. Consequences of these specific mutations at the population level have been little studied so far, despite the detection of P.1 variant in 26 countries, with local transmission in at least four other countries in the Americas and Europe. Here, we estimate P.1’s transmissibility and reinfection using a model-based approach, by fitting data from the Brazilian national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December 2020 to February 2021, when the city was devastated by four times more cases than in the previous peak (April 2020). The new variant was found to be about 2.6 times more transmissible (95% Confidence Interval (CI): 2.4–2.8) than previous circulating variant(s). The city already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus (estimated as 78%, CI:73–83%), and the fitted model attributed 28% of the cases during the period to reinfections by the variant P.1. Our estimates rank P.1 as the most transmissible among the current identified SARS-CoV-2 VOCs, posing a serious threat and requiring urgent measures to control its global spread.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialEthics approval was not necessary because this study analysed only publicly available data, not including identifiable information.Funding StatementThis work was supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (Finance Code 001 to FMDM, LSF and TPP), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil (grant number: 315854/2020-0 to MEB, 141698/2018-7 to RLPS, 313055/2020-3 to PIP, 312559/2020-8 to MASMV, 311832/2017-2 to RAK, 305703/2019-6 to AAMS) and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil (grant number: 2019/26310-2 and 2017/26770-8 to CF, 2018/26512-1 to OC, 2018/24037-4 to SPL and contract number: 2016/01343-7 to RAK). 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:Ethics approval was not necessary because this study analysed only publicly available data, not including identifiable information.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 are publicly available. The data sources are described in the manuscript and in supplementary file. |
A Collaborative Multi-Model Ensemble for Real-Time Influenza Season Forecasting in the U.S (preprint)
Reich NG , McGowan CJ , Yamana TK , Tushar A , Ray EL , Osthus D , Kandula S , Brooks LC , Crawford-Crudell W , Gibson GC , Moore E , Silva R , Biggerstaff M , Johansson MA , Rosenfeld R , Shaman J . bioRxiv 2019 566604 Seasonal influenza results in substantial annual morbidity and mortality in the United States and worldwide. Accurate forecasts of key features of influenza epidemics, such as the timing and severity of the peak incidence in a given season, can inform public health response to outbreaks. As part of ongoing efforts to incorporate data and advanced analytical methods into public health decision-making, the United States Centers for Disease Control and Prevention (CDC) has organized seasonal influenza forecasting challenges since the 2013/2014 season. In the 2017/2018 season, 22 teams participated. A subset of four teams created a research consortium called the FluSight Network in early 2017. During the 2017/2018 season they worked together to produce a collaborative multi-model ensemble that combined 21 separate component models into a single model using a machine learning technique called stacking. This approach creates a weighted average of predictive densities where the weight for each component is based on that component’s forecast accuracy in past seasons. In the 2017/2018 influenza season, one of the largest seasonal outbreaks in the last 15 years, this multi-model ensemble performed better on average than all individual component models and placed second overall in the CDC challenge. It also outperformed the baseline multi-model ensemble created by the CDC that took a simple average of all models submitted to the forecasting challenge. This project shows that collaborative efforts between research teams to develop ensemble forecasting approaches can bring measurable improvements in forecast accuracy and important reductions in the variability of performance from year to year. Efforts such as this, that emphasize real-time testing and evaluation of forecasting models and facilitate the close collaboration between public health officials and modeling researchers, are essential to improving our understanding of how best to use forecasts to improve public health response to seasonal and emerging epidemic threats. |
Reemergence of Dengue Virus Serotype 3, Brazil, 2023
Naveca FG , Santiago GA , Maito RM , Ribeiro Meneses CA , do Nascimento VA , de Souza VC , do Nascimento FO , Silva D , Mejía M , Gonçalves L , de Figueiredo RMP , Ribeiro Cruz AC , Diniz Nunes BT , Presibella MM , Quallio Marques NF , Riediger IN , de Mendonça MCL , de Bruycker-Nogueira F , Sequeira PC , de Filippis AMB , Resende P , Campos T , Wallau GL , Gräf T , Delatorre E , Kopp E , Morrison A , Muñoz-Jordán JL , Bello G . Emerg Infect Dis 2023 29 (7) 1482-1484 We characterized 3 autochthonous dengue virus serotype 3 cases and 1 imported case from 2 states in the North and South Regions of Brazil, 15 years after Brazil's last outbreak involving this serotype. We also identified a new Asian lineage recently introduced into the Americas, raising concerns about future outbreaks. |
Reemergence of Dengue Virus Serotype 3, Brazil, 2023 (preprint)
Naveca FG , Santiago GA , Maito RM , Meneses CAR , do Nascimento VA , de Souza VC , do Nascimento FO , Silva D , Mejia M , Goncalves L , de Figueiredo RMP , Cruz ACR , Nunes BTD , Presibella MM , Marques NFQ , Riediger IN , de Mendonca MCL , de Bruycker-Nogueira F , Sequeira PC , de Filippis AMB , Resende P , Campos T , Wallau GL , Graf T , Delatorre E , Kopp E , Morrison A , Munoz-Jordan JL , Bello G . medRxiv 2023 05 (7) 1482-1484 In 2023, three autochthonous DENV-3 cases were detected in Roraima and one imported case in Parana, fifteen years after the last DENV-3 outbreak in Brazil. Phylogenetic analyses confirmed all belonging to a new Asian lineage recently introduced in the Americas, raising concerns about future large dengue outbreaks in this region. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Population structure and antimicrobial resistance patterns of Salmonella Typhi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India (preprint)
Da Silva KE , Date K , Hirani N , LeBoa C , Jayaprasad N , Borhade P , Warren J , Shimpi R , Hoffman SASS , Mikoleit M , Bhatnagar P , Cao Y , Dutta S , Luby SP , Andrews JR . medRxiv 2023 28 We performed whole genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective and retrospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patters of emergence and spread of antimicrobial resistance. Additionally, we evaluated the relationship between the spatial distance between households and genetic clustering of isolates using hierarchical Bayesian models. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing >=3 mutations in the quinolone resistance determining region, conferring high-level resistance. Two H58 isolates carried an IncX3 resistance plasmid containing bla<inf>SHV-12</inf>, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant S. Typhi isolates from India have evolved independently on multiple occasions. Among S. Typhi isolates, we identified two main clades circulating in Navi Mumbai (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (OR 0.72 per km; 95% CrI: 0.66-0.79). This effect was seen for distances up to 5 km (OR 0.65 per km; 95% CrI: 0.59-0.73) but was not seen for distances beyond 5 km (OR 1.02 per km; 95% CrI: 0.83-1.26). Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial-genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Human-aided dispersal facilitates parasitism escape in the most invasive mosquito species (preprint)
Girard M , Martin E , Vallon L , Van VT , Da Silva Carvalho C , Sacks J , Bontemps Z , Balteneck J , Colin F , Duval P , Malassigne S , Swanson J , Hennessee I , Jiang S , Vizcaino L , Romer Y , Dada N , Huynh Kim KL , Thi Thuy TH , Bellet C , Lambert G , Raharimalala FN , Jupatanakul N , Goubert C , Boulesteix M , Mavingui P , Desouhant E , Luis P , Cazabet R , Hay AE , Moro CV , Minard G . bioRxiv 2023 20 Human-aided invasion of alien species across the world sometimes leads to economic, health or environmental burdens. During invasion process, species encounter new environments and partially escape some ecological constrains they faced in their native range, while they face new ones. The Asian tiger mosquito Aedes albopictus is one of the most iconic invasive species that was introduced in every inhabited continent over a short period of time due to international trade. It has also been shown to be infected by a prevalent and yet disregarded gregarine entomoparasite Ascogregarina taiwanensis. In this study, we aimed at deciphering the global dynamics of As. taiwanensis infection in natural Ae. albopictus populations and we further explored factors shaping its distribution. We showed that Ae. albopictus populations are highly colonized by several As. taiwanesis genotypes but recently introduced ones are escaping the parasite. We further performed experiments to explain such pattern. First, we hypothesized that founder effects (i.e. population establishment by a small number of individuals) may influence the parasite dynamics. This was confirmed since experimental increase in mosquitoes' density improves the parasite horizontal transmission to larvae. Furthermore, Ae. albopictus larvae do not exhibit density dependent prophylaxis to control the parasite meaning that infection is not mitigated when larval density increases. Secondly, we hypothesized that unparasitized mosquitoes were more prompt to found new populations through active flight dispersal. This was, however, unlikely since parasitized mosquitoes tend to be more active than their unparasitized relatives. Finally, we hypothesized that mosquito passive dispersal (i.e. often mediated by human-aided transportation of dried eggs) affects the parasite infectiveness. Our results support this hypothesis since parasite infection decreases over time when dry eggs are stored. This study highlights the importance of global trade on parasitism escape in one of the most invasive vector species on earth. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Profiling and benchmarking central nervous system infections in an infectious diseases intensive care unit
Andrade HB , Rocha Ferreira da Silva I , Espinoza R , da Silva MST , Theodoro PHN , Ferreira MT , Soares J , Belay ED , Sejvar JJ , Bozza FA , Cerbino-Neto J , Japiassú AM . J Intensive Care Med 2023 39 (1) 8850666231188665 BACKGROUND: There is little information comparing the performance of community acquired central nervous system infections (CNSI) treatment by intensive care units (ICUs) specialized in infectious diseases with treatment at other ICUs. Our objective was to reduce these gaps, creating bases for benchmarking and future case-mix classification. METHODS: This is a retrospective observational cohort of 785 admissions with 82 cases of CNSI admitted to the ICU of an important Brazilian referral center for infectious diseases (INI) between January 2012 and January 2019. Comparisons were made to data retrospectively collected from the 303,500 intensive care admissions from the Brazilian state health care system included in the Epimed Monitor database. Clinical, epidemiologic, and performance indicators: the standardized mortality rate (SMR) and the standardized resource use rate per ICU surviving patient (SRU) were collected. RESULTS: Case-mix infections profile and SMR/SRU data. SUS Mixed medical/surgical ICUs: SMR = 1.26, SRU = 1.59; SUS Neurological ICUs: SMR = 1.17, SRU = 2.23; INI ICU: SMR = 1.1, SRU = 1.1; INI ICU CNSI patients: SMR = 0.95, SRU = 1.01. CONCLUSIONS: Severe patients with CNSI can be efficiently and effectively treated in an ICU specialized in infectious diseases when compared to mixed medical/surgical and neurological ICUs from the public health system. At the same time, we provided profiling and a case-mix that can help and encourage benchmarking by other institutions and other countries. |
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination -United States, December 2020-August 2021 (preprint)
Calamari LE , Weintraub WS , Santos R , Gibbs M , Bertoni AG , Ward LM , Saydah S , Plumb ID , Runyon MS , Wierzba TF , Sanders JW , Herrington D , Espeland MA , Williamson J , Mongraw-Chaffin M , Bertoni A , Alexander-Miller MA , Castri P , Mathews A , Munawar I , Seals AL , Ostasiewski B , Ballard CAP , Gurcan M , Ivanov A , Zapata GM , Westcott M , Blinson K , Blinson L , Mistysyn M , Davis D , Doomy L , Henderson P , Jessup A , Lane K , Levine B , McCanless J , McDaniel S , Melius K , O'Neill C , Pack A , Rathee R , Rushing S , Sheets J , Soots S , Wall M , Wheeler S , White J , Wilkerson L , Wilson R , Wilson K , Burcombe D , Saylor G , Lunn M , Ordonez K , O'Steen A , Wagner L , McCurdy LH , Gibbs MA , Taylor YJ , Calamari L , Tapp H , Ahmed A , Brennan M , Munn L , Dantuluri KL , Hetherington T , Lu LC , Dunn C , Hogg M , Price A , Leonidas M , Manning M , Rossman W , Gohs FX , Harris A , Priem JS , Tochiki P , Wellinsky N , Silva C , Ludden T , Hernandez J , Spencer K , McAlister L , Weintraub W , Miller K , Washington C , Moses A , Dolman S , Zelaya-Portillo J , Erkus J , Blumenthal J , Romero Barrientos RE , Bennett S , Shah S , Mathur S , Boxley C , Kolm P , Franklin E , Ahmed N , Larsen M , Oberhelman R , Keating J , Kissinger P , Schieffelin J , Yukich J , Beron A , Teigen J , Kotloff K , Chen WH , Friedman-Klabanoff D , Berry AA , Powell H , Roane L , Datar R , Correa A , Navalkele B , Min YI , Castillo A , Ward L , Santos RP , Anugu P , Gao Y , Green J , Sandlin R , Moore D , Drake L , Horton D , Johnson KL , Stover M , Lagarde WH , Daniel L , Maguire PD , Hanlon CL , McFayden L , Rigo I , Hines K , Smith L , Harris M , Lissor B , Cook V , Eversole M , Herrin T , Murphy D , Kinney L , Diehl P , Abromitis N , Pierre TSt , Heckman B , Evans D , March J , Whitlock B , Moore W , Arthur S , Conway J , Gallaher TR , Johanson M , Brown S , Dixon T , Reavis M , Henderson S , Zimmer M , Oliver D , Jackson K , Menon M , Bishop B , Roeth R , King-Thiele R , Hamrick TS , Ihmeidan A , Hinkelman A , Okafor C , Bray Brown RB , Brewster A , Bouyi D , Lamont K , Yoshinaga K , Vinod P , Peela AS , Denbel G , Lo J , Mayet-Khan M , Mittal A , Motwani R , Raafat M , Schultz E , Joseph A , Parkeh A , Patel D , Afridi B , Uschner D , Edelstein SL , Santacatterina M , Strylewicz G , Burke B , Gunaratne M , Turney M , Zhou SQ , Tjaden AH , Fette L , Buahin A , Bott M , Graziani S , Soni A , Mores C , Porzucek A , Laborde R , Acharya P , Guill L , Lamphier D , Schaefer A , Satterwhite WM , McKeague A , Ward J , Naranjo DP , Darko N , Castellon K , Brink R , Shehzad H , Kuprianov D , McGlasson D , Hayes D , Edwards S , Daphnis S , Todd B , Goodwin A , Berkelman R , Hanson K , Zeger S , Hopkins J , Reilly C , Edwards K , Gayle H , Redd S . medRxiv 2022 10 Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Effectiveness of whole virus COVID-19 vaccine at protecting health care personnel against SARS-CoV-2 infections in Lima, Peru (preprint)
Arriola CS , Soto G , Westercamp M , Bollinger S , Espinoza A , Grogl M , Llanos-Cuentas A , Matos E , Romero C , Silva M , Smith R , Olson N , Prouty M , Azziz-Baumgartner E , Lessa FC . medRxiv 2022 18 In February 2021, Peru launched a vaccination campaign among healthcare personnel using BBIBP-CorV inactivated whole virus (BBIBP-CorV) COVID-19 vaccine. Two doses of BBIBP-CorV vaccine are recommended, 21 days apart. Data on BBIBP-CorV vaccine effectiveness will inform the use and acceptance of vaccination with BBIBP-CorV vaccine. We evaluated BBIBP-CorV vaccine effectiveness among an existing multi-year influenza cohort at two hospitals in Lima. We analyzed data on 290 participants followed between February and May 2021. Participants completed a baseline questionnaire and provided weekly self-collected anterior nasal swabs tested for SARS-CoV-2 by rRT-PCR for sixteen weeks. We performed multivariable logistic regression models adjusting for pre-selected characteristics (age, sex, exposure to COVID-19 patients, work in intensive care unit or emergency department, BMI, and exposure time in days). BBIBP-CorV vaccine effectiveness was calculated after the two-week post-vaccination period as (1-Odds Ratio for testing SARS-CoV-2 positive)x100%. SARS-CoV-2 was detected by rRT-PCR among 25 (9%) participants during follow-up (February-May 2021). Follow-up period ranged 1-11 weeks (median: 2 weeks). Among cohort participants who were fully vaccinated the adjusted vaccine effectiveness against SARS-CoV-2 infection was estimated as 95% (95% CI: 70%, 99%) and 100% (95% CI: 88%, 100%) for those partially vaccinated. During the study period, vaccination of healthcare personnel with BBIBP-CorV vaccine was effective at reducing SARS-CoV-2 infections in the weeks immediately following vaccination. This information can be used to support vaccination efforts in the region, especially among those who could be concerned about their effectiveness. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Biologically synthesized zinc and copper oxide nanoparticles using Cannabis sativa L. enhance soybean (Glycine max) defense against fusarium virguliforme
Karmous I , Vaidya S , Dimkpa C , Zuverza-Mena N , da Silva W , Barroso KA , Milagres J , Bharadwaj A , Abdelraheem W , White JC , Elmer WH . Pestic Biochem Physiol 2023 194 105486 In this study, zinc and copper oxide nanoparticles (NPs) were synthesized using hemp (Cannabis sativa L.) leaves (ZnONP-HL and CuONP-HL), and their antifungal potential was assessed against Fusarium virguliforme in soybean (Glycine max L.). Hemp was selected because it is known to contain large quantities of secondary metabolites that can potentially enhance the reactivity of NPs through surface property modification. Synthesizing NPs with biologically derived materials allows to avoid the use of harsh and expensive synthetic reducing and capping agents. The ZnONP-HL and CuONP-HL showed average grain/crystallite size of 13.51 nm and 7.36 nm, respectively. The biologically synthesized NPs compared well with their chemically synthesized counterparts (ZnONP chem, and CuONP chem; 18.75 nm and 10.05 nm, respectively), confirming the stabilizing role of hemp-derived biomolecules. Analysis of the hemp leaf extract and functional groups that were associated with ZnONP-HL and CuONP-HL confirmed the presence of terpenes, flavonoids, and phenolic compounds. Biosynthesized NPs were applied on soybeans as bio-nano-fungicides against F. virguliforme via foliar treatments. ZnONP-HL and CuONP-HL at 200 μg/mL significantly (p < 0.05) increased (∼ 50%) soybean growth, compared to diseased controls. The NPs improved the nutrient (e.g., K, Ca, P) content and enhanced photosynthetic indicators of the plants by 100–200%. A 300% increase in the expression of soybean pathogenesis related GmPR genes encoding antifungal and defense proteins confirmed that the biosynthesized NPs enhanced disease resistance against the fungal phytopathogen. The findings from this study provide novel evidence of systemic suppression of fungal disease by nanobiopesticides, via promoting plant defense mechanisms. © 2023 Elsevier Inc. |
Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique
da Silva C , Boene S , Datta D , Rovira-Vallbona E , Aranda-Díaz A , Cisteró P , Hathaway N , Tessema S , Chidimatembue A , Matambisso G , Nhama A , Macete E , Pujol A , Nhamussua L , Galatas B , Guinovart C , Enosse S , De Carvalho E , Rogier E , Plucinski MM , Colborn J , Zulliger R , Saifodine A , Alonso PL , Candrinho B , Greenhouse B , Aide P , Saute F , Mayor A . Commun Biol 2023 6 (1) 619 Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys. |
Single high-dose of liposomal amphotericin B in HIV/AIDS-related disseminated histoplasmosis: A randomized trial
Pasqualotto AC , Dalla Lana D , Godoy CSM , Leitão Tdmjs , Bay MB , Damasceno LS , Soares RBA , Kist R , Silva LR , Wiltgen D , Melo M , Guimarães TF , Guimarães MR , Vechi HT , de Mesquita JRL , Monteiro GRG , Adenis A , Bahr NC , Spec A , Boulware DR , Israelski D , Chiller T , Falci DR . Clin Infect Dis 2023 77 (8) 1126-1132 BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of one or two-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) Single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomizedMedian CD4+ counts and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for Single-dose L-AmB, 69% Two-dose L-AmB, and 74% Control arm (p=0.69). Overall survival on D14 was 89.0% (34/38) for Single-dose L-AmB, 78.0% (29/37) for Two-dose L-AmB, and 92.1% (35/38) for Control arm (p=0.82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access. |
Improving connections to early childhood systems of care via a universal home visiting program in Massachusetts
Kotake C , Fauth RC , Stetler K , Goldberg JL , Silva CF , Manning SE . Child Youth Serv Rev 2023 150 Welcome Family is a universal, short-term nurse home visiting program designed to promote optimal maternal and infant physical and mental well-being and provide an entry point into the early childhood system of care to all families with newborns up to 8 weeks old living in defined communities in Massachusetts. The present study examines whether: 1) Welcome Family meets its goal of successfully connecting families to two early childhood programs—evidence-based home visiting (EBHV) and early intervention (EI)—relative to families with similar background experiences who do not participate in Welcome Family, and 2) whether these impacts are conditional on families’ race and ethnicity and their primary language—two characteristics that are related to structural racism and health inequities. The study used coarsened exact matching (CEM) based on birth certificate data to match Welcome Family participants who enrolled during 2013–2017 to mothers and their infants living in the home visiting catchment areas who did not receive home visiting during the study period. Primary study outcomes included enrollment in any EBHV program supported by the Massachusetts Maternal, Infant, and Early Childhood Home Visiting (MA MIECHV) program up to age 1 year, measured using MA MIECHV home visiting program data, and EI service receipt for children aged up to age 3 years, measured using EI program data. Impacts were assessed by fitting weighted regression models adjusted for preterm birth, maternal depression, and substance use. Mothers’ race, ethnicity, and language were included in the model as moderators of Welcome Family impacts on enrollment in EBHV and EI. Welcome Family participants (n = 3,866) had more than double the odds of EBHV enrollments up to age 1 and had 1.39 greater odds of receiving EI individualized family service plans (IFSPs) up to age 3 relative to the comparison group (n = 46,561). Mothers’ primary language moderated Welcome Family impacts on EBHV enrollments. Universal, short-term programs such as Welcome Family may be an effective method of ensuring families who could benefit from more intensive early childhood services are identified, engaged, and enrolled. © 2023 Elsevier Ltd |
A novel subtype of sporadic Creutzfeldt-Jakob disease with PRNP codon 129MM genotype and PrP plaques
Bayazid R , Orru C , Aslam R , Cohen Y , Silva-Rohwer A , Lee SK , Occhipinti R , Kong Q , Shetty S , Cohen ML , Caughey B , Schonberger LB , Appleby BS , Cali I . Acta Neuropathol 2023 1-23 The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt-Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP(D) type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrP(D) T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (p(GM)) or the white matter (p(WM)) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of p(GM)- and p(WM)-CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of p(WM)- and p(GM)-CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in p(GM)-CJD, but were ubiquitous in p(WM)-CJD. Typing of resPrP(D) T1 showed an unglycosylated fragment of ~ 20 kDa (T1(20)) in p(GM)-CJD and sCJDMM1 patients, while a doublet of ~ 21-20 kDa (T1(21-20)) was a molecular signature of p(WM)-CJD in subcortical regions. In addition, conformational characteristics of p(WM)-CJD resPrP(D) T1 differed from those of p(GM)-CJD and sCJDMM1. Inoculation of p(WM)-CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with p(WM)-CJD. Furthermore, T1(20) of p(WM)-CJD, but not T1(21), was propagated in mice. These data suggest that T1(21) and T1(20) of p(WM)-CJD, and T1(20) of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T1(20) of the novel p(GM)-CJD subtype. |
Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant.
Coutinho RM , Marquitti FMD , Ferreira LS , Borges ME , da Silva RLP , Canton O , Portella TP , Poloni S , Franco C , Plucinski MM , Lessa FC , da Silva AAM , Kraenkel RA , de Sousa Mascena Veras MA , Prado PI . Commun Med (Lond) 2021 1 48 BACKGROUND: The SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant). METHODS: We estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021. RESULTS: Here we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4-2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city. CONCLUSIONS: Our estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread. |
Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study.
Peñataro Yori P , Paredes Olórtegui M , Schiaffino F , Colston JM , Pinedo Vasquez T , Garcia Bardales PF , Shapiama Lopez V , Zegarra Paredes LF , Perez K , Curico G , Flynn T , Zhang J , Ramal Asayag C , Meza Sanchez G , Silva Delgado H , Casapia Morales M , Casanova W , Jiu B , Oberhelman R , Munayco Escate C , Silver R , Henao O , Cooper KK , Liu J , Houpt ER , Kosek MN . BMC Public Health 2023 23 (1) 674 BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú. |
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