Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 117 Records) |
Query Trace: da Silva J[original query] |
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Performance of conditional random forest and regression models at predicting human fecal contamination of produce irrigation ponds in the southeastern United States
Hofstetter J , Holcomb DA , Kahler AM , Rodrigues C , da Silva ALBR , Mattioli MC . ACS EST 2024 ![]() Irrigating fresh produce with contaminated water contributes to the burden of foodborne illness. Identifying fecal contamination of irrigation waters and characterizing fecal sources and associated environmental factors can help inform fresh produce safety and health hazard management. Using two previously collected data sets, we developed and evaluated the performance of logistic regression and conditional random forest models for predicting general and human-specific fecal contamination of ponds in southwest Georgia used for fresh produce irrigation. Generic Escherichia coli served as a general fecal indicator, and human-associated Bacteroides (HF183), crAssphage, and F+ coliphage genogroup II were used as indicators of human fecal contamination. Increased rainfall in the previous 7 days and the presence of a building within 152 m (a proxy for proximity to septic systems) were associated with increased odds of human fecal contamination in the training data set. However, the models did not accurately predict the presence of human-associated fecal indicators in a second data set collected from nearby irrigation ponds in different years. Predictive statistical models should be used with caution to assess produce irrigation water quality as models may not reliably predict fecal contamination at other locations and times, even within the same growing region. © 2024 American Chemical Society. |
The 2023 South Sudanese outbreak of Hepatitis E emphasizes ongoing circulation of genotype 1 in North, Central, and East Africa
Orf GS , Bbosa N , Berg MG , Downing R , Weiss SL , Ssemwanga D , Ssekagiri A , Ashraf S , da Silva Filipe A , Kiiza R , Buule J , Namagembe HS , Nabirye SE , Kayiwa J , Deng LL , Wani G , Maror JA , Baguma A , Mogga JJH , Kamili S , Thomson EC , Kaleebu P , Cloherty GA . Infect Genet Evol 2024 105667 ![]() ![]() ![]() In April 2023, an outbreak of acute hepatitis was reported in the Nazareth internally displaced persons camp in South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis. |
HIV-1 pretreatment and acquired antiretroviral drug resistance before tenofovir/ /lamivudine /dolutegravir (TLD) roll-out in Mozambique
Ismael N , Gemusse H , Mahumane I , Laurindo O , Magul C , Baxter C , Wilkinson E , Hofstra LM , Wagar N , Bila D , Mabunda N , da Silva J , Oliveira T , Raizes E , Preiser W , Manuel P , Ramos A , Vúbil A . BMC Infect Dis 2024 24 (1) 748 ![]() ![]() BACKGROUND: The World Health Organization (WHO) recommends that HIV treatment scale-up is accompanied by a robust assessment of drug resistance emergence and transmission. The WHO HIV Drug Resistance (HIVDR) monitoring and surveillance strategy includes HIVDR testing in adults both initiating and receiving antiretroviral therapy (ART). Due to limited information about HIVDR in Mozambique, we conducted two nationally representative surveys of adults initiating and receiving first-line ART regimes to better inform the HIV program. METHODS: We carried out a cross-sectional study between March 2017 and December 2019. Adults (older than 15 years) living with HIV (PLHIV) initiating ART or receiving first-line ART for between 9-15 months at 25 health facilities across all eleven provinces in Mozambique were included. Genotypic HIVDR was assessed on dried blood spots (DBS) when viral loads were ≥ 1000 copies/ml. Genotypic resistance for non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was determined using the Stanford HIV database algorithm 9.5 and calibrated population resistance tool 8.1. RESULTS: Of 828 participants -enrolled, viral load (VL) testing was performed on 408 initiators and 409 ART experienced. Unsuppressed VL was found in 68.1% 419 initiators and 18.8% (77/409) of the ART experienced. Of the 278 initiators and 70 ART experienced who underwent sequencing, 51.7% (144/278) and 75.7% (53/70) were sequenced successfully. Among the new initiators, pretreatment drug resistance (PDR) for NNRTI and PI was found in 16.0% (23/144) and 1.4% (2/144) of the participants, respectively. Acquired drug resistance (ADR) was found in 56.5% (30/53) of the ART-experienced participants of whom 24.5% (13/53) were resistant to both NRTI and NNRTI. CONCLUSION: High rates of PDR and ADR for NNRTI and ADR for NRTI were observed in our study. These findings support the replacement of NNRTIs with dolutegravir (DTG) but high levels of NRTI resistance in highly treatment-experienced individuals still require attention when transitioning to new regimens. Moreover, the study underlines the need for routine VL testing and HIVDR surveillance to improve treatment management strategies. |
Prevalence, risk factors, and impact of long COVID in a socially vulnerable community in Brazil: a prospective cohort study
Azambuja P , Bastos LSL , Batista-da-Silva AA , Ramos GV , Kurtz P , Dias CMC , da Silva EP , Arouca LE , Soares J , Sejvar JJ , Sigfrid L , Ranzani OT , Hamacher S , Bozza FA . Lancet Reg Health - Am 2024 37 Background: Long COVID is an emerging global public health issue. Socially vulnerable communities in low- and-middle-income countries were severely impacted by the pandemic and are underrepresented in research. This prospective study aimed to determine the prevalence of long COVID, its impact on health, and associated risk factors in one such community in Rio de Janeiro, Brazil. Methods: A total of 710 individuals aged 18 and older, with confirmed SARS-CoV-2 infection at least three months prior, were enrolled between November 25, 2021, and May 5, 2022. Participants were assessed via telephone or in person using a standardized questionnaire to evaluate their perception of recovery, symptoms, quality of life, and functional status. Findings: Twenty percent of participants did not feel fully recovered, 22% experienced new or persistent symptoms, 26% had worsened functional status, 18% had increased dyspnoea, and 32% reported a worse quality of life. Persistent symptoms included headache, cough, fatigue, muscle pain, and shortness of breath. Dyspnoea during the acute phase was the strongest independent predictor of worsening outcomes. Females and individuals with comorbidities were more likely to report worse recovery, functioning, dyspnoea, and quality of life. Interpretation: Our findings reveal a high burden of severe and persistent physical and mental health sequelae in a socially vulnerable community following COVID-19. Funding: UK Foreign, Commonwealth and Development Office and Wellcome Trust Grant (222048/Z/20/Z), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro ( FAPERJ), and the Centers for Disease Control and Prevention (CDC). © 2024 |
High viral suppression rates among PLHIV on dolutegravir who had an initial episode of viral non-suppression in Uganda September 2020-July 2021
Namayanja GA , Da Silva JF , Elur B , Nasirumbi PM , Raizes E , Ssempiira J , Nazziwa E , Nabukenya M , Sewanyana I , Balaba J , Ntale J , Calnan J , Birabwa E , Akao J , Mwangi C , Naluguza M , Ahimbisibwe A , Katureebe C , Nabadda S , Nelson L , Dirlikov E . PLoS One 2024 19 (6) e0305129 BACKGROUND: In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According to the 2018 Uganda's HIV treatment guidelines, patients with viral non-suppression (≥1,000 copies/mL) should receive intensive adherence counseling (IAC) with repeat viral load (VL) within 6 months. This analysis focused on the prevalence and factors associated with viral suppression following IAC among PLHIV on DTG-based regimens (DBRs) with an initial episode of viral non-suppression (VNS) in Uganda. METHODS: We conducted a retrospective analysis for PLHIV on DBRs with an initial episode of VNS (≥1,000 copies/mL) in Uganda during October 2019-September 2020 who had a follow up VL test result during September 2020-July 2021. Data were abstracted from the Central Public Health Laboratory (CPHL) database, including patient demographics and VL results. Viral non-suppression (VNS) was defined as a VL test result of ≥1,000 copies/mL. We characterized PLHIV on DBRs and used logistic regression models to determine factors associated with VL suppression after an initial episode of VNS. RESULTS: A total of 564 PLHIV on DBRs with an initial episode of VNS were followed up and 43 were excluded due to missing data. Of the 521, 220 (42.2%) were children (<15 years) and 231 (44.3%) were female. Median age was 28 years (interquartile range [IQR]: 12-43 years), and median duration on DBRs was 12 months (IQR: 6-15 months). Overall, 80.8% (421/521) PLHIV had a suppressed viral load at first follow up testing (children = 74.5% [164/220]; adults = 85.4% [257/301]). Children with initial VL results ≥5,000 copies/mL were less likely to achieve viral suppression at follow up testing compared to those with <5,000 copies/mL (AOR: 0.38; 95% CI: 0.20-0.71; p = 0.002). CONCLUSIONS: In a programmatic setting, most adults and children suppressed following an initial episode of VNS on DBRs. High rates of suppression after VNS suggest adherence challenges, rather than drug resistance. Continuation of DBRs should be considered before regimen switch. |
Sources and prevalence of Cyclospora cayetanensis in southeastern U.S. Growing environments
Kahler AM , Hofstetter J , Arrowood M , Peterson A , Jacobson D , Barratt J , Luiz Biscaia Ribeiro da Silva A , Rodrigues C , Mattioli MC . J Food Prot 2024 100309 ![]() ![]() Recent cyclosporiasis outbreaks associated with fresh produce grown in the United States highlight the need to better understand C. cayetanensis prevalence in U.S. agricultural environments. In this study, C. cayetanensis occurrence was assessed in municipal wastewater sludge, on-farm portable toilets, irrigation pond water, and spent packing house dump tank water in a Southeastern Georgia growing region over two years. Detection of the C. cayetanensis 18S rRNA qPCR gene target in pond samples was 0%, 28%, and 42% (N=217) depending on the detection definition used, and ≤ 1% in dump tank samples (N=46). However, no qPCR detections were confirmed by sequencing, suggesting false detection occurred due to cross-reactions. C. cayetanensis qPCR detections were confirmed in 9% of wastewater sludge samples (N=76). The human-specific fecal markers HF183 and crAssphage were detected in 33% and 6% of pond samples, respectively and 4% and 0% of dump tank samples, respectively. Despite community Cyclospora shedding and evidence of human fecal contamination in irrigation water, there was no correlation between C. cayetanensis and HF183 qPCR detections, further supporting that 18S gene target qPCR amplifications were due to cross reactions. When evaluating C. cayetanensis qPCR environmental detection data, the impact of assay specificity and detection criteria should be considered. Moreover, additional sequence-based testing may be needed to appropriately interpret Cyclospora qPCR environmental data. |
A diagnostic algorithm for detection of leishmania spp. In human fresh and fixed tissue samples
Silva-Flannery LM , de Almeida ME , da Silva AJ , Bollweg BC , Fair PS , Ritter JM , Paddock CD , Martines RB , Zaki SR . Am J Trop Med Hyg 2024 Leishmaniasis is an important travel-related parasitic infection in the United States. Treatment regimens vary by Leishmania species and require an accurate diagnosis. The sensitivity and specificity of diagnostic methods depend on the type and condition of specimen analyzed. To identify the best algorithm for detection of parasites in fresh and fixed tissue samples, we evaluated parasite cultures, two PCR methods, and Leishmania immunohistochemistry (IHC) in samples received by the CDC from 2012 through 2019. The sensitivity and specificity of IHC assays were evaluated in fresh specimens tested. Diagnostic accuracy for formalin-fixed tissue was evaluated by using PCR-based methods and IHC. Of 100 suspected cases with fresh tissue available, Leishmania spp. infection was identified by PCR in 56% (56/100) of specimens; from these, 80% (45/56) were positive by parasite culture and 59% (33/56) by IHC. Of 420 possible cases where only fixed specimens were available, 58% (244/420) were positive by IHC and/or PCR. Of these, 96% (235/420) were positive by IHC and 84% (204/420) by PCR-based methods. Overall parasite detection using all methodologies was similar for fresh and formalin-fixed tissue specimens (56% versus 58%, respectively). Although PCR-based methods were superior for diagnosis of leishmaniasis and species identification in fresh samples, IHC in combination with PCR increased the accuracy for Leishmania spp. detection in fixed samples. In conclusion, PCR is the most effective method for detecting Leishmania infection in fresh tissue samples, whereas for formalin-fixed samples, IHC and PCR-based methods should be used in combination. |
Human-aided dispersal and population bottlenecks facilitate parasitism escape in the most invasive mosquito species
Girard M , Martin E , Vallon L , Tran Van V , Da Silva Carvalho C , Sack J , Bontemps Z , Balteneck J , Colin F , Duval P , Malassigné S , Hennessee I , Vizcaino L , Romer Y , Dada N , Ly Huynh Kim K , Huynh Thi Thuy T , Bellet C , Lambert G , Nantenaina Raharimalala F , Jupatanakul N , Goubert C , Boulesteix M , Mavingui P , Desouhant E , Luis P , Cazabet R , Hay AE , Valiente Moro C , Minard G . PNAS Nexus 2024 3 (5) pgae175 During biological invasion process, species encounter new environments and partially escape some ecological constraints 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 introduced in every inhabited continent due to international trade. It has also been shown to be infected by a prevalent yet disregarded microbial entomoparasite Ascogregarina taiwanensis. In this study, we aimed at deciphering the factors that shape the global dynamics of A. taiwanensis infection in natural A. albopictus populations. We showed that A. albopictus populations are highly colonized by several parasite genotypes but recently introduced ones are escaping it. We further performed experiments based on the invasion process to explain such pattern. To that end, we hypothesized that (i) mosquito passive dispersal (i.e. human-aided egg transportation) may affect the parasite infectiveness, (ii) founder effects (i.e. population establishment by a small number of mosquitoes) may influence the parasite dynamics, and (iii) unparasitized mosquitoes are more prompt to found new populations through active flight dispersal. The two first hypotheses were supported as we showed that parasite infection decreases over time when dry eggs are stored and that experimental increase in mosquitoes' density improves the parasite horizontal transmission to larvae. Surprisingly, parasitized mosquitoes tend to be more active than their unparasitized relatives. Finally, this study highlights the importance of global trade as a driver of biological invasion of the most invasive arthropod vector species. |
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. |
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. |
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 |
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. |
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. |
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. |
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. |
Severity of influenza illness by seasonal influenza vaccination status among hospitalised patients in four South American countries, 2013-19: a surveillance-based cohort study
Regan AK , Arriola CS , Couto P , Duca L , Loayza S , Nogareda F , de Almeida WAF , Antman J , Araya S , Avendaño Vigueras MA , Battaglia Paredes SC , Brstilo IF , Bustos P , Fandiño ME , Fasce R , Giovacchini CM , González Caro CI , von Horoch M , Del Valle Juarez M , Katz N , Olivares MF , da Silva DA , da Silva ET , Sotomayor V , Vergara N , Azziz-Baumgartner E , Ropero AM . Lancet Infect Dis 2022 23 (2) 222-232 BACKGROUND: Although several studies have reported attenuated influenza illness following influenza vaccination, results have been inconsistent and have focused predominantly on adults in the USA. This study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of influenza vaccine target groups across multiple South American countries. METHODS: We analysed data from four South American countries (Argentina, Brazil, Chile, and Paraguay) participating in REVELAC-i, a multicentre, test-negative design, vaccine effectiveness network including 41 sentinel hospitals. Individuals hospitalised at one of these centres with severe acute respiratory infection were tested for influenza by real-time RT-PCR, and were included in the analysis if they had complete information about their vaccination status and outcomes of their hospital stay. We used multivariable logistic regression weighted by inverse probability of vaccination and adjusted for antiviral use, duration of illness before admission, and calendar week, to calculate the adjusted odds ratios (aORs) of intensive care unit (ICU) admission and in-hospital death (and combinations of these outcomes) among influenza-positive patients by vaccination status for three target groups: young children (aged 6-24 months), adults (aged 18-64 years) with pre-existing health conditions, and older adults (aged ≥65 years). Survival curves were used to compare length of hospital stay by vaccination status in each target group. FINDINGS: 2747 patients hospitalised with PCR-confirmed influenza virus infection between Jan 1, 2013, and Dec 8, 2019, were included in the study: 649 children (70 [10·8%] fully vaccinated, 193 [29·7%] partially vaccinated) of whom 87 (13·4%) were admitted to ICU and 12 (1·8%) died in hospital; 520 adults with pre-existing medical conditions (118 [22·7%] vaccinated), of whom 139 (26·7%) were admitted to ICU and 55 (10·6%) died in hospital; and 1578 older adults (609 [38·6%] vaccinated), of whom 271 (17·2%) were admitted to ICU and 220 (13·9%) died in hospital. We observed earlier discharge among partially vaccinated children (adjusted hazard ratio 1·14 [95% CI 1·01-1·29]), fully vaccinated children (1·24 [1·04-1·47]), and vaccinated adults with pre-existing medical conditions (1·78 [1·18-2·69]) compared with their unvaccinated counterparts, but not among vaccinated older adults (0·82 [0·65-1·04]). Compared with unvaccinated individuals, lower odds of ICU admission were found for partially vaccinated children (aOR 0·64 [95% CI 0·44-0·92]) and fully vaccinated children (0·52 [0·28-0·98]), but not for adults with pre-existing conditions (1·25 [0·93-1·67]) or older adults (0·88 [0·72-1·08]). Lower odds of in-hospital death (0·62 [0·50-0·78]) were found in vaccinated versus unvaccinated older adults, with or without ICU admission, but did not differ significantly in partially vaccinated (1·35 [0·57-3·20]) or fully vaccinated young children (0·88 [0·16-4·82]) or adults with pre-existing medical conditions (1·09 [0·73-1·63]) compared with the respective unvaccinated patient groups. INTERPRETATION: Influenza vaccination was associated with illness attenuation among those hospitalised with influenza, although results differed by vaccine target group. These findings might suggest that attenuation of disease severity might be specific to certain target groups, seasons, or settings. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section. |
Emergence of dengue virus serotype 2 cosmopolitan genotype, Brazil
Giovanetti M , Pereira LA , Santiago GA , Fonseca V , Mendoza MPG , de Oliveira C , de Moraes L , Xavier J , Tosta S , Fristch H , de Castro Barbosa E , Rodrigues ES , Figueroa-Romero D , Padilla-Rojas C , Cáceres-Rey O , Mendonça AF , de Bruycker Nogueira F , Venancio da Cunha R , de Filippis AMB , Freitas C , Peterka CRL , de Albuquerque CFC , Franco L , Méndez Rico JA , Muñoz-Jordán JL , Lemes da Silva V , Alcantara LCJ . Emerg Infect Dis 2022 28 (8) 1725-1727 We used nanopore sequencing and phylogenetic analyses to identify a cosmopolitan genotype of dengue virus serotype 2 that was isolated from a 56-year-old male patient from the state of Goiás in Brazil. The emergence of a cosmopolitan genotype in Brazil will require risk assessment and surveillance to reduce epidemic potential. |
Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.
Singh B , Lant S , Cividini S , Cattrall JWS , Goodwin LC , Benjamin L , Michael BD , Khawaja A , Matos AMB , Alkeridy W , Pilotto A , Lahiri D , Rawlinson R , Mhlanga S , Lopez EC , Sargent BF , Somasundaran A , Tamborska A , Webb G , Younas K , Al Sami Y , Babu H , Banks T , Cavallieri F , Cohen M , Davies E , Dhar S , Fajardo Modol A , Farooq H , Harte J , Hey S , Joseph A , Karthikappallil D , Kassahun D , Lipunga G , Mason R , Minton T , Mond G , Poxon J , Rabas S , Soothill G , Zedde M , Yenkoyan K , Brew B , Contini E , Cysique L , Zhang X , Maggi P , van Pesch V , Lechien J , Saussez S , Heyse A , Brito Ferreira ML , Soares CN , Elicer I , Eugenín-von Bernhardi L , Ñancupil Reyes W , Yin R , Azab MA , Abd-Allah F , Elkady A , Escalard S , Corvol JC , Delorme C , Tattevin P , Bigaut K , Lorenz N , Hornuss D , Hosp J , Rieg S , Wagner D , Knier B , Lingor P , Winkler AS , Sharifi-Razavi A , Moein ST , SeyedAlinaghi S , JamaliMoghadamSiahkali S , Morassi M , Padovani A , Giunta M , Libri I , Beretta S , Ravaglia S , Foschi M , Calabresi P , Primiano G , Servidei S , Biagio Mercuri N , Liguori C , Pierantozzi M , Sarmati L , Boso F , Garazzino S , Mariotto S , Patrick KN , Costache O , Pincherle A , Klok FA , Meza R , Cabreira V , Valdoleiros SR , Oliveira V , Kaimovsky I , Guekht A , Koh J , Fernández Díaz E , Barrios-López JM , Guijarro-Castro C , Beltrán-Corbellini Á , Martínez-Poles J , Diezma-Martín AM , Morales-Casado MI , García García S , Breville G , Coen M , Uginet M , Bernard-Valnet R , Du Pasquier R , Kaya Y , Abdelnour LH , Rice C , Morrison H , Defres S , Huda S , Enright N , Hassell J , D'Anna L , Benger M , Sztriha L , Raith E , Chinthapalli K , Nortley R , Paterson R , Chandratheva A , Werring DJ , Dervisevic S , Harkness K , Pinto A , Jillella D , Beach S , Gunasekaran K , Rocha Ferreira Da Silva I , Nalleballe K , Santoro J , Scullen T , Kahn L , Kim CY , Thakur KT , Jain R , Umapathi T , Nicholson TR , Sejvar JJ , Hodel EM , Tudur Smith C , Solomon T . PLoS One 2022 17 (6) e0263595 BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission. |
Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study
Nabity SA , Mponda K , Gutreuter S , Surie D , Zimba SB , Chisuwo L , Moffitt A , Williams AM , Sharma AJ , Marshall RE , Chiwaula MJ , da Silva R , Kumwenda T , Chilikutali L , Mwamale S , Nagoli E , Mwenyeheri G , Ngongonda D , Kaunda E , Mtoto F , Mhango V , Mbewe K , Melgar M , Odo M , Jahn A , Buono N , Maida A , Girma B , Kalua T , Nyirenda R , Sunguti J , Woelk G , Gunde LJ , Mekonnen TF , Maphosa T , Kim EJ , Auld AF , Muula AS , Oeltmann JE . Lancet Glob Health 2022 10 (5) e705-e714 BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173. |
Risk-Factors for Exposure Associated With SARS-CoV-2 Detection After Recent Known or Potential COVID-19 Exposures Among Patients Seeking Medical Care at a Large Urban, Public Hospital in Fulton County, Georgia - A Cross-Sectional Investigation.
Smith-Jeffcoat SE , Sleweon S , Koh M , Khalil GM , Schechter MC , Rebolledo PA , Kasinathan V , Hoffman A , Rossetti R , Shragai T , O'Laughlin K , Espinosa CC , Bankamp B , Bowen MD , Paulick A , Gargis AS , Folster JM , da Silva J , Biedron C , Stewart RJ , Wang YF , Kirking HL , Tate JE . Front Public Health 2022 10 809356 We aimed to describe frequency of COVID-19 exposure risk factors among patients presenting for medical care at an urban, public hospital serving mostly uninsured/Medicare/Medicaid clients and risk factors associated with SARS-CoV-2 infection. Consenting, adult patients seeking care at a public hospital from August to November 2020 were enrolled in this cross-sectional investigation. Saliva, anterior nasal and nasopharyngeal swabs were collected and tested for SARS-CoV-2 using RT-PCR. Participant demographics, close contact, and activities ≤14 days prior to enrollment were collected through interview. Logistic regression was used to identify risk factors associated with testing positive for SARS-CoV-2. Among 1,078 participants, 51.8% were male, 57.0% were aged ≥50 years, 81.3% were non-Hispanic Black, and 7.6% had positive SARS-CoV-2 tests. Only 2.7% reported COVID-19 close contact ≤14 days before enrollment; this group had 6.79 adjusted odds of testing positive (95%CI = 2.78-16.62) than those without a reported exposure. Among participants who did not report COVID-19 close contact, working in proximity to ≥10 people (adjusted OR = 2.17; 95%CI = 1.03-4.55), choir practice (adjusted OR = 11.85; 95%CI = 1.44-97.91), traveling on a plane (adjusted OR = 5.78; 95%CI = 1.70-19.68), and not participating in an essential indoor activity (i.e., grocery shopping, public transit use, or visiting a healthcare facility; adjusted OR = 2.15; 95%CI = 1.07-4.30) were associated with increased odds of testing positive. Among this population of mostly Black, non-Hispanic participants seeking care at a public hospital, we found several activities associated with testing positive for SARS-CoV-2 infection in addition to close contact with a case. Understanding high-risk activities for SARS-CoV-2 infection among different communities is important for issuing awareness and prevention strategies. |
Drug resistance and use of long-acting ART.
daSilva J , Siedner M , McCluskey S , Chandiwana N , Venter F , Raizes E . Lancet HIV 2022 9 (6) e374-e375 ![]() ![]() The approval, in 2021, of long-acting cabotegravir plus rilpivirine as the first long-term antiretroviral therapy (ART) has engendered enthusiasm for its use among patients with adherence challenges, given its potential to address stigma and other challenges associated with daily pill intake. Several factors could prevent the implementation of long-acting cabotegravir plus rilpivirine in resource-poor settings, such as cold chain requirement; inactivity of long-acting cabotegravir plus rilpivirine against hepatitis B; and the requirement for dosing once a month or every 2 months, which conflicts with differentiated service delivery models that allow patients to attend clinics every 6 months. However, the greatest challenge to implementation of long-acting cabotegravir plus rilpivirine in sub-Saharan Africa involves its efficacy in the face of widespread non-nucleoside reverse-transcriptase inhibitor resistance (NNRTI). |
Specimen self-collection for SARS-CoV-2 testing: Patient performance and preferences-Atlanta, Georgia, August-October 2020.
O'Laughlin K , Espinosa CC , Smith-Jeffcoat SE , Koh M , Khalil GM , Hoffman A , Rebolledo PA , Schechter MC , Stewart RJ , da Silva J , Biedron C , Bankamp B , Folster J , Gargis AS , Bowen MD , Paulick A , Wang YF , Tate JE , Kirking HL . PLoS One 2022 17 (3) e0264085 Self-collected specimens can expand access to SARS-CoV-2 testing. At a large inner-city hospital 1,082 participants self-collected saliva and anterior nasal swab (ANS) samples before healthcare workers collected nasopharyngeal swab (NPS) samples on the same day. To characterize patient preferences for self-collection, this investigation explored ability, comfort, and ease of ANS and saliva self-collection for SARS-CoV-2 testing along with associated patient characteristics, including medical history and symptoms of COVID-19. With nearly all participants successfully submitting a specimen, favorable ratings from most participants (at least >79% in ease and comfort), and equivocal preference between saliva and ANS, self-collection is a viable SARS-CoV-2 testing option. |
Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package.
Griffiths EJ , Timme RE , Mendes CI , Page AJ , Alikhan NF , Fornika D , Maguire F , Campos J , Park D , Olawoye IB , Oluniyi PE , Anderson D , Christoffels A , da Silva AG , Cameron R , Dooley D , Katz LS , Black A , Karsch-Mizrachi I , Barrett T , Johnston A , Connor TR , Nicholls SM , Witney AA , Tyson GH , Tausch SH , Raphenya AR , Alcock B , Aanensen DM , Hodcroft E , Hsiao WWL , Vasconcelos ATR , MacCannell DR . Gigascience 2022 11 ![]() ![]() BACKGROUND: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. RESULTS: As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. CONCLUSIONS: Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI's BioSample database. |
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