Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 102 Records) |
Query Trace: Garrett BE[original query] |
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Characteristics of hard tick relapsing fever caused by borrelia miyamotoi, United States, 2013-2019
McCormick DW , Brown CM , Bjork J , Cervantes K , Esponda-Morrison B , Garrett J , Kwit N , Mathewson A , McGinnis C , Notarangelo M , Osborn R , Schiffman E , Sohail H , Schwartz AM , Hinckley AF , Kugeler KJ . Emerg Infect Dis 2023 29 (9) 1719-29 Borrelia miyamotoi, transmitted by Ixodes spp. ticks, was recognized as an agent of hard tick relapsing fever in the United States in 2013. Nine state health departments in the Northeast and Midwest have conducted public health surveillance for this emerging condition by using a shared, working surveillance case definition. During 2013-2019, a total of 300 cases were identified through surveillance; 166 (55%) were classified as confirmed and 134 (45%) as possible. Median age of case-patients was 52 years (range 1-86 years); 52% were male. Most cases (70%) occurred during June-September, with a peak in August. Fever and headache were common symptoms; 28% of case-patients reported recurring fevers, 55% had arthralgia, and 16% had a rash. Thirteen percent of patients were hospitalized, and no deaths were reported. Ongoing surveillance will improve understanding of the incidence and clinical severity of this emerging disease. |
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 |
Estimating typhoid incidence from community-based serosurveys: A multicohort study in Bangladesh, Nepal, Pakistan and Ghana (preprint)
Aiemjoy K , Seidman JC , Saha S , Munira SJ , Islam Sajib MS , Sium SMA , Sarkar A , Alam N , Zahan FN , Kabir MS , Tamrakar D , Vaidya K , Shrestha R , Shakya J , Katuwal N , Shrestha S , Yousafzai MT , Iqbal J , Dehraj IF , Ladak Y , Maria N , Adnan M , Pervaiz S , Carter AS , Longley AT , Fraser C , Ryan ET , Nodoushani A , Fasano A , Leonard MM , Kenyon V , Bogoch II , Jeon HJ , Haselbeck A , Park SE , Zellweger RM , Marks F , Owusu-Dabo E , Adu-Sarkodie Y , Owusu M , Teunis P , Luby SP , Garrett DO , Qamar FN , Saha SK , Charles RC , Andrews JR . medRxiv 2022 2021.10.20.21265277 Background The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae, is largely unknown in regions lacking blood culture surveillance. New serologic markers have proven accurate in diagnosing enteric fever, but whether they could be used to reliably estimate population-level incidence is unknown.Methods We collected longitudinal blood samples from blood culture-confirmed enteric fever cases enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to Hemolysin E (HlyE) and S. Typhi lipopolysaccharide (LPS). We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titers and decay rate to estimate population-level incidence rates from cross-sectional serosurveys.Findings The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children <5 years ranged between 58.5 per 100 person-years (95% CI: 42.1 - 81.4) in Dhaka, Bangladesh to 6.6 (95% CI: 4.3-9.9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates.Interpretation The approach described here has the potential to expand the geographic scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographic regions and time.Funding This work was supported by the Bill and Melinda Gates Foundation (INV-000572).Evidence before this study Previous studies have identified serologic responses to two antigens (Hemolysin E [HlyE] and Salmonella lipopolysaccharide [LPS]) as promising diagnostic markers of acute typhoidal Salmonella infection. We reviewed the evidence for seroepidemiology tools for enteric fever available as of November 01, 2021, by searching the National Library of Medicine article database and medRxiv for preprint publications, published in English, using the terms “enteric fever”, “typhoid fever”, “Salmonella Typhi”, “Salmonella Paratyphi”, “typhoidal Salmonella”, “Hemolysin E”, “Salmonella lipopolysaccharide”, “seroconversion”, “serosurveillance”, “seroepidemiology”, “seroprevalence” and “seropositivity.” We found no studies using HlyE or LPS as markers to measure the incidence or prevalence of enteric fever in a population. Anti-Vi IgG responses were used as a marker of population seroprevalence in cross-sectional studies conducted in South Africa, Fiji, and Nepal, but were not used to calculate population-based incidence estimates.Added value of this study We developed and validated a method to estimate typhoidal Salmonella incidence in cross-sectional population samples using antibody responses measured from dried blood spots. First, using longitudinal dried blood spots collected from over 1400 blood culture-confirmed cases in four countries, we modeled the longitudinal dynamics of antibody responses for up to two years following infection, accounting for heterogeneity in antibody responses and age-dependence. We found that longitudinal antibody responses were highly consistent across four countries on two continents and did not differ by clinical severity. We then used these antibody kinetic parameters to estimate incidence in population-based samples in six communities across the four countries, where concomitant population-based incidence was measured using blood cultures. Seroincidence estimates were much higher than blood-culture-based case estimates across all six sites, suggestive of a high incidence of asymptomatic or unrecognized infections. Still, the rank order of seroincidence and culture-based incidence rates were the same, with the highest rates in Bangladesh and lowest in Ghana.Implications of all the available evidence Many a -risk low- and middle-income countries lack data on typhoid incidence needed to inform and evaluate vaccine introduction. Even in countries where incidence estimates are available, data are typically geographically and temporally sparse due to the resources necessary to initiate and sustain blood culture surveillance. We found that typhoidal Salmonella infection incidence can be estimated from community-based serosurveys using dried blood spots, representing an efficient and scalable approach for generating the typhoid burden data needed to inform typhoid control programs in resource-constrained settings.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by th eBill and Melinda Gates Foundation (grant INV-000572)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:Institutional Review Boards in the United States (Centers for Disease Control and Prevention; Stanford University Institutional Review Board), Bangladesh (Bangladesh Institute of Child Health Ethical Review Committee), Nepal (Nepal Health Research Council Ethical Review Board), Pakistan (AKU Ethic Review Committee and Pakistan National Bioethics Committee), Korea (International Vaccine Institute IRB), Belgium (Institute of Tropical Medicine Antwerp Institutional Review Board) and Ghana (Komfo Anokye Teaching Hospital, Committee on Human Research, Publication and Ethics) approved the study forms and protocols.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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 produced in the present study are available upon reasonable request to the authors |
Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet (preprint)
Block JP , Marsolo KA , Nagavedu K , Bailey LC , Boehmer TK , Fearrington J , Harris AM , Garrett N , Goodman AB , Gundlapalli AV , Kaushal R , Kho A , McTigue KM , Nair VP , Puro J , Shenkman E , Weiner MG , Williams N , Carton TW . medRxiv 2023 18 Background: Prior studies have documented differences in the age, racial, and ethnic characteristics among patients with SARS-CoV-2 infection. However, little is known about how these characteristics changed over time during the pandemic and whether racial, ethnic, and age disparities evident early in the pandemic were persistent over time. This study reports on trends in SARS-CoV-2 infections among U.S. adults from March 1, 2020 to January, 31 2022, using data from electronic health records. Methods and Findings: We captured repeated cross-sectional information from 43 large healthcare systems in 52 U.S. States and territories, participating in PCORnet, the National Patient-Centered Clinical Research Network. Using distributed queries executed at each participating institution, we acquired information for all patients >= 20 years of age who were tested for SARS-CoV-2 (both positive and negative results), including care setting, age, sex, race, and ethnicity by month as well as comorbidities (assessed with diagnostic codes). During this time period, 1,325,563 patients had positive (13% inpatient) and 6,705,868 patients had negative (25% inpatient) viral tests for SARS-CoV-2. Disparities in testing positive were present across racial and ethnic groups, especially in the inpatient setting. Compared to White patients, Black or African American and other race patients had relative risks for testing positive of 1.5 or greater in the inpatient setting for 12 of the 23-month study period. Compared to non-Hispanic patients, Hispanic patients had relative risks for testing positive in the inpatient setting of 1.5 or greater for 16 of 23. Ethnic and racial differences were present in emergency department and ambulatory settings but were less common across time than in inpatient settings. Trends in infections by age group demonstrated higher test positivity for older patients in the inpatient setting only for most months, except for June and July of 2020, April to August 2021, and January 2022. Comorbidities were common, with much higher rates among those hospitalized; hypertension (38% of patients SARS-CoV-2 positive vs. 29% for those negative) and type 2 diabetes mellitus (22% vs. 13%) were the most common. Conclusion and Relevance: Racial and ethnic disparities changed over time among persons infected with SARS-CoV-2. These trends highlight potential underlying mechanisms, such as poor access to care and differential vaccination rates, that may have contributed to greater disparities, especially early in the pandemic. Monitoring data on characteristics of patients testing positive in real time could allow public health officials and policymakers to tailor interventions to ensure that patients and communities most in need are receiving adequate testing, mitigation strategies, and treatment. 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. |
Implementing strategies to prevent infections in acute-care settings
Trivedi KK , Schaffzin JK , Deloney VM , Aureden K , Carrico R , Garcia-Houchins S , Garrett JH Jr , Glowicz J , Lee GM , Maragakis LL , Moody J , Pettis AM , Saint S , Schweizer ML , Yokoe DS , Berenholtz S . Infect Control Hosp Epidemiol 2023 44 (8) 1-15 This document introduces and explains common implementation concepts and frameworks relevant to healthcare epidemiology and infection prevention and control and can serve as a stand-alone guide or be paired with the "SHEA/IDSA/APIC Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2022 Updates," which contain technical implementation guidance for specific healthcare-associated infections. This Compendium article focuses on broad behavioral and socio-adaptive concepts and suggests ways that infection prevention and control teams, healthcare epidemiologists, infection preventionists, and specialty groups may utilize them to deliver high-quality care. Implementation concepts, frameworks, and models can help bridge the "knowing-doing" gap, a term used to describe why practices in healthcare may diverge from those recommended according to evidence. It aims to guide the reader to think about implementation and to find resources suited for a specific setting and circumstances by describing strategies for implementation, including determinants and measurement, as well as the conceptual models and frameworks: 4Es, Behavior Change Wheel, CUSP, European and Mixed Methods, Getting to Outcomes, Model for Improvement, RE-AIM, REP, and Theoretical Domains. |
Infection Prevention and Control Core Practices: A Roadmap for Nursing Practice
Carrico RM , Garrett H , Balcom D , Glowicz JB . Nursing 2018 48 (8) 28-29 In 2017, the CDC released a set of Core Practices focusing on infection prevention and control relevant for care delivered in all settings. These eight Core Practices address foundational elements of practice and should be embedded into every aspect of nursing care and part of every nurse's professional development plan. |
Notes From the Field: First evidence of locally acquired dengue virus infection - Maricopa County, Arizona, November 2022
Kretschmer M , Collins J , Dale AP , Garrett B , Koski L , Zabel K , Staab RN , Turnbow K , Nativio J , Andrews K , Smith WE , Townsend J , Busser N , Will J , Burr K , Jones FK , Santiago GA , Fitzpatrick KA , Ruberto I , Fitzpatrick K , White JR , Adams L , Sunenshine RH . MMWR Morb Mortal Wkly Rep 2023 72 (11) 290-291 On November 7, 2022, dengue virus (DENV), which is not endemic in the continental United States (1), was identified in a Maricopa County, Arizona resident by reverse transcription–polymerase chain reaction (RT-PCR) testing at Arizona State Public Health Laboratory (ASPHL). The patient (patient A) was admitted to a hospital on October 19 for a dengue-like illness, 7 days after traveling to and remaining in Mexicali, Mexico for <4 hours. Patient A was hospitalized for 3 days and subsequently recovered. Maricopa County Environmental Services Department (MCESD) conducted retrospective testing for DENV in samples collected from 21 mosquito pools located within 5 miles (8 km) of patient A’s residence during October 1–November 3. A sample collected from one mosquito pool (pool A) on October 5 was positive for DENV. Whole genome sequencing by CDC’s Dengue Branch later revealed that closely related DENV-3 strains not known to be circulating in the patient’s travel region were identified in both patient A and pool A, suggesting local DENV transmission. |
Application of a universal parasite diagnostic test to biological specimens collected from animals.
Lane M , Kashani M , Barratt JL , Qvarnstrom Y , Yabsley MJ , Garrett KB , Bradbury RS . Int J Parasitol Parasites Wildl 2023 20 20-30 A previously described universal parasite diagnostic (nUPDx) based on PCR amplification of the 18S rDNA and deep-amplicon sequencing, can detect human blood parasites with a sensitivity comparable to real-time PCR. To date, the efficacy of this assay has only been assessed on human blood. This study assessed the utility of nUPDx for the detection of parasitic infections in animals using blood, tissues, and other biological sample types from mammals, birds, and reptiles, known to be infected with helminth, apicomplexan, or pentastomid parasites (confirmed by microscopy or PCR), as well as negative samples. nUPDx confirmed apicomplexan and/or nematode infections in 24 of 32 parasite-positive mammals, while also identifying several undetected coinfections. nUPDx detected infections in 6 of 13 positive bird and 1 of 2 positive reptile samples. When applied to 10 whole parasite specimens (worms and arthropods), nUPDx identified all to the genus or family level, and detected one incorrect identification made by morphology. Babesia sp. infections were detected in 5 of the 13 samples that were negative by other diagnostic approaches. While nUPDx did not detect PCR/microscopy-confirmed trichomonads or amoebae in cloacal swabs/tissue from 8 birds and 2 reptiles due to primer template mismatches, 4 previously undetected apicomplexans were detected in these samples. Future efforts to improve the utility of the assay should focus on validation against a larger panel of tissue types and animal species. Overall, nUPDx shows promise for use in both veterinary diagnostics and wildlife surveillance, especially because species-specific PCRs can miss unknown or unexpected pathogens. |
Concussion education for youth athletes using Pre-Game Safety Huddles: a cluster-randomised controlled trial
Kroshus E , Chrisman SPD , Glang A , Hunt T , Hays R , Lowry S , Peterson A , Garrett K , Ramshaw D , Hafferty K , Kinney E , Manzueta M , Steiner MK , Bollinger BJ , Chiampas G , Rivara FP . Inj Prev 2022 29 (1) 22-28 OBJECTIVES: Determine whether Pre-Game Safety Huddles, a novel and low-resource approach to concussion education, increase the expected likelihood of concussion reporting for youth athletes. METHODS: A cluster-randomised trial compared Safety Huddles to usual care. Safety Huddles bring together athletes and coaches from both teams before the start of each game for coaches to briefly affirm the importance of speaking up if a concussion is suspected. Participants were athletes from 22 competitive community-based American football and girls and boys soccer teams (ages 9-14), and randomisation into intervention or control occurred at the level of the bracket (group of teams that compete against each other during the regular season). The primary outcome was expected likelihood of reporting concussion symptoms to the coach, measured via validated athlete survey at the beginning and end of the season. RESULTS: Of 343 eligible participants, 339 (99%) completed baseline surveys and 303 (88%) completed surveys at season end. The mean (SD) age was 11.4 (1.1) years, 26% were female soccer athletes, 27% were male soccer athletes and 47% were football athletes. In adjusted analyses accounting for baseline values and clustering by sport and team via random effects, expected likelihood of concussion reporting at the end of the season was significantly higher in the intervention group compared to controls (mean difference=0.49, 95% CI 0.11 to 0.88; Cohen's d=0.35). CONCLUSIONS AND RELEVANCE: Pre-Game Safety Huddles increased the expected likelihood of athletes reporting concussion symptoms. While further study is warranted, sport organisations should consider this approach a promising low-resource option for improving concussion safety in their setting. TRIAL REGISTRATION NUMBER: NCT04099329. |
Estimating typhoid incidence from community-based serosurveys: a multicohort study
Aiemjoy K , Seidman JC , Saha S , Munira SJ , Islam Sajib MS , Sium SMA , Sarkar A , Alam N , Zahan FN , Kabir MS , Tamrakar D , Vaidya K , Shrestha R , Shakya J , Katuwal N , Shrestha S , Yousafzai MT , Iqbal J , Dehraj IF , Ladak Y , Maria N , Adnan M , Pervaiz S , Carter AS , Longley AT , Fraser C , Ryan ET , Nodoushani A , Fasano A , Leonard MM , Kenyon V , Bogoch II , Jeon HJ , Haselbeck A , Park SE , Zellweger RM , Marks F , Owusu-Dabo E , Adu-Sarkodie Y , Owusu M , Teunis P , Luby SP , Garrett DO , Qamar FN , Saha SK , Charles RC , Andrews JR . Lancet Microbe 2022 3 (8) e578-e587 BACKGROUND: The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae (Salmonella enterica serovars Typhi and Paratyphi), is largely unknown in regions without blood culture surveillance. The aim of this study was to evaluate whether new diagnostic serological markers for typhoidal Salmonella can reliably estimate population-level incidence. METHODS: We collected longitudinal blood samples from patients with blood culture-confirmed enteric fever enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana between 2016 and 2021 and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to hemolysin E and S Typhi lipopolysaccharide. We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titres and decay rate to estimate population-level incidence rates from cross-sectional serosurveys. FINDINGS: The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children younger than 5 years ranged between 58·5 per 100 person-years (95% CI 42·1-81·4) in Dhaka, Bangladesh, to 6·6 per 100 person-years (4·3-9·9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates. INTERPRETATION: The approach described here has the potential to expand the geographical scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographical regions and time. FUNDING: Bill & Melinda Gates Foundation. TRANSLATIONS: For the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section. |
Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project
Garrett DO , Longley AT , Aiemjoy K , Yousafzai MT , Hemlock C , Yu AT , Vaidya K , Tamrakar D , Saha S , Bogoch II , Date K , Saha S , Islam MS , Sayeed KMI , Bern C , Shakoor S , Dehraj IF , Mehmood J , Sajib MSI , Islam M , Thobani RS , Hotwani A , Rahman N , Irfan S , Naga SR , Memon AM , Pradhan S , Iqbal K , Shrestha R , Rahman H , Hasan MM , Qazi SH , Kazi AM , Saddal NS , Jamal R , Hunzai MJ , Hossain T , Marks F , Carter AS , Seidman JC , Qamar FN , Saha SK , Andrews JR , Luby SP . Lancet Glob Health 2022 10 (7) e978-e988 BACKGROUND: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies. METHODS: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 days; inpatients with suspected or confirmed enteric fever; patients with blood culture-confirmed enteric fever from the hospital laboratories not captured by inpatient or outpatient enrolment and cases from the laboratory network; and patients with non-traumatic ileal perforation under surgical care. We used a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of health-care use. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. We additionally calculated incidence of hospitalisation due to typhoid and paratyphoid. FINDINGS: A total of 34 747 patients were enrolled across 23 facilitates (six tertiary hospitals, surgical wards of two additional hospitals, and 15 laboratory network sites) during the study period. Of the 34 303 blood cultures performed on enrolled patients, 8705 (26%) were positive for typhoidal Salmonella. Adjusted incidence rates of enteric fever considered patients in the six tertiary hospitals. Adjusted incidence of S Typhi, expressed per 100 000 person-years, was 913 (95% CI 765-1095) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (230-480) in Kathmandu and 268 (202-362) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 176 (144-216) and 103 (85-126). The adjusted incidence rates of paratyphoid (of which all included cases were due to S Paratyphi A) were 128 (107-154) in Bangladesh, 46 (34-62) and 81 (56-118) in the Nepal sites, and 23 (19-29) and 1 (1-1) in the Pakistan sites. Adjusted incidence of hospitalisation was high across sites, and overall, 2804 (32%) of 8705 patients with blood culture-confirmed enteric fever were hospitalised. INTERPRETATION: Across diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for "high burden" of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines. FUNDING: Bill & Melinda Gates Foundation. |
Stakeholder-engaged development of a theory-driven, feasible, and acceptable approach to concussion education
Kroshus E , Chrisman SPD , Hunt T , Hays R , Garrett K , Peterson A , Rivara FP , Chiampas G , Ramshaw Ba D , Glang A . Health Educ Behav 2022 10901981221099886 Concussion education is widely mandated and largely ineffective. Recent consensus guidance on concussion education asserts the importance of (1) theory-driven programming that targets the team as a system and (2) working with end users throughout the development process, and considering issues such as feasibility, acceptability, and sustainability. Consistent with this guidance, and in collaboration with youth sport stakeholders in two regions of the United States, we developed a novel approach to concussion education: Pre-game safety huddles. Safety huddles have the following two core components: (1) athletes, coaches, and other stakeholders come together before the start of each game and (2) opinion leaders (coaches, referees) affirm the importance of care seeking for suspected concussion. The aim of this article is to provide an overview of the collaborative process through which we refined the safety huddle concept into an acceptable and feasible intervention with potential for sustainable implementation in diverse youth sports settings with minimal resource demands. In describing our process and discussing challenges and opportunities, we hope to provide an example for others seeking to develop and implement injury prevention interventions in youth sports settings. |
Investigation of A SARS-CoV-2 Delta (B.1.617.2) Variant Outbreak Among Residents of a Skilled Nursing Facility and Vaccine Effectiveness Analysis - Maricopa County, Arizona, June-July 2021.
Dale AP , Almendares O , Howard B , Burnett E , Prasai S , Arons M , Collins J , Duffy N , Pandit U , Brady S , White J , Garrett B , Kirking HL , Sunenshine R , Tate JE , Scott SE . Clin Infect Dis 2022 75 (1) e20-e26 BACKGROUND: Short-term rehabilitation units present unique infection control challenges due to high turnover and medically complex residents. In June 2021, Maricopa County Department of Public Health (MCDPH) was notified of a SARS-CoV-2 Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE). METHODS: Facility electronic medical records were reviewed for residents who spent >1 night on the affected unit between June 10-July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. COVID-19 VE estimates using Cox proportional hazards models were calculated. RESULTS: Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2 positive case-patients were mostly male (58%) and white (78%) with a median age of 65 (range: 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases; 32 non-cases) received 2-doses and 9% (4 cases, 6 non-cases) received 1-dose of mRNA vaccine. Among non-immunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% CI: 15, 95). More cases were hospitalized (33%) or died (38%) than non-cases (10% hospitalized; 16% died). CONCLUSIONS: In this large SARS-CoV-2 Delta outbreak in a high-turnover short term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in non-immunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks. |
Investigating flubendazole as an anthelmintic treatment for Guinea worm (Dracunculus medinensis): Clinical trials in laboratory-reared ferrets and domestic dogs in Chad
Cleveland CA , Garrett KB , Box EK , Thompson AT , Haynes EK , Elder DL , Richards RL , Majewska AA , Guagliardo SAJ , Wiegand RE , Bryan Ii JA , Torres-Velez F , Unterwegner K , Romero M , Zirimwabagabo H , Sidouin M , Oaukou PT , Ada MM , Ngandolo BNR , Mackenzie CD , Geary TG , Weiss AJ , Yabsley MJ . Am J Trop Med Hyg 2022 106 (5) 1456-65 Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in domestic dog GW infections highlight the need for novel approaches. We conducted two clinical trials evaluating the efficacy of subcutaneously injected flubendazole (FBZ) as a treatment of GW infection. The first trial was conducted administering FBZ to experimentally infected ferrets; the second trial involved administering FBZ or a placebo to domestic dogs in the Republic of Tchad (Chad). We found contrasting results between the two trials. When adult gravid female GW were recovered from ferrets treated with FBZ, larvae presented in poor condition, with low to no motility, and an inability to infect copepods. Histopathology results indicated a disruption to morulae development within uteri of worms from treated animals. Results from the trial in Chadian dogs failed to indicate significant treatment of or prevention against GW infection. However, the difference in treatment intervals (1 month for ferrets and 6 months for dogs) or the timing of treatment (ferrets were treated later in the GW life-cycle than dogs) could explain different responses to the subcutaneous FBZ injections. Both trials provided valuable data guiding the use of FBZ in future trials (such as decreasing treatment intervals or increasing the dose of FBZ in dogs to increase exposure), and highlighted important lessons learned during the implementation of a field-based, double-blinded randomized control trial in Chadian dogs. |
SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant results.
Miller EM , Law EA , Ajeen R , Karasik J , Mendoza C , Abernathy H , Garrett H , King E , Wallace J , Zelek M , Edwards JK , Xiong K , Beatty C , Fleischauer AT , Ciccone EJ , Shook-Sa BE , Aiello AE , Boyce RM . PLoS One 2021 16 (10) e0259070 Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics. |
The Childhood Obesity Data Initiative: A case study in implementing clinical-community infrastructure enhancements to support health services research and public health
King RJ , Heisey-Grove DM , Garrett N , Scott KA , Daley MF , Haemer MA , Podila P , Block JP , Carton T , Gregorowicz AJ , Mork KP , Porter RM , Chudnov DL , Jellison J , Kraus EM , Harrison MR , Sucosky MS , Armstrong S , Goodman AB . J Public Health Manag Pract 2021 28 (2) E430-E440 CONTEXT: We describe a participatory framework that enhanced and implemented innovative changes to an existing distributed health data network (DHDN) infrastructure to support linkage across sectors and systems. Our processes and lessons learned provide a potential framework for other multidisciplinary infrastructure development projects that engage in a participatory decision-making process. PROGRAM: The Childhood Obesity Data Initiative (CODI) provides a potential framework for local and national stakeholders with public health, clinical, health services research, community intervention, and information technology expertise to collaboratively develop a DHDN infrastructure that enhances data capacity for patient-centered outcomes research and public health surveillance. CODI utilizes a participatory approach to guide decision making among clinical and community partners. IMPLEMENTATION: CODI's multidisciplinary group of public health and clinical scientists and information technology experts collectively defined key components of CODI's infrastructure and selected and enhanced existing tools and data models. We conducted a pilot implementation with 3 health care systems and 2 community partners in the greater Denver Metro Area during 2018-2020. EVALUATION: We developed an evaluation plan based primarily on the Good Evaluation Practice in Health Informatics guideline. An independent third party implemented the evaluation plan for the CODI development phase by conducting interviews to identify lessons learned from the participatory decision-making processes. DISCUSSION: We demonstrate the feasibility of rapid innovation based upon an iterative and collaborative process and existing infrastructure. Collaborative engagement of stakeholders early and iteratively was critical to ensure a common understanding of the research and project objectives, current state of technological capacity, intended use, and the desired future state of CODI architecture. Integration of community partners' data with clinical data may require the use of a trusted third party's infrastructure. Lessons learned from our process may help others develop or improve similar DHDNs. |
A governance framework to integrate longitudinal clinical and community data in a distributed data network: The Childhood Obesity Data Initiative
Kraus EM , Scott KA , Zucker R , Heisey-Grove D , King RJ , Carton TW , Daley MF , Deakyne Davies SJ , Block JP , Haemer M , Goodman AB , Garrett N , Davidson AJ . J Public Health Manag Pract 2021 28 (2) E421-E429 CONTEXT: Integrating longitudinal data from community-based organizations (eg, physical activity programs) with electronic health record information can improve capacity for childhood obesity research. OBJECTIVE: A governance framework that protects individual privacy, accommodates organizational data stewardship requirements, and complies with laws and regulations was developed and implemented to support the harmonization of data from disparate clinical and community information systems. PARTICIPANTS AND SETTING: Through the Childhood Obesity Data Initiative (CODI), 5 Colorado-based organizations collaborated to expand an existing distributed health data network (DHDN) to include community-generated data and assemble longitudinal patient records for research. DESIGN: A governance work group expanded an existing DHDN governance infrastructure with CODI-specific data use and exchange policies and procedures that were codified in a governance plan and a delegated-authority, multiparty, reciprocal agreement. RESULTS: A CODI governance work group met from January 2019 to March 2020 to conceive an approach, develop documentation, and coordinate activities. Governance requirements were synthesized from the CODI use case, and a customized governance approach was constructed to address governance gaps in record linkage, a procedure to request data, and harmonizing community and clinical data. A Master Sharing and Use Agreement (MSUA) and Memorandum of Understanding were drafted and executed to support creation of linked longitudinal records of clinical- and community-derived childhood obesity data. Furthermore, a multiparty infrastructure protocol was approved by the local institutional review board (IRB) to expedite future CODI research by simplifying IRB research applications. CONCLUSION: CODI implemented a clinical-community governance strategy that built trust between organizations and allowed efficient data exchange within a DHDN. A thorough discovery process allowed CODI stakeholders to assess governance capacity and reveal regulatory and organizational obstacles so that the governance infrastructure could effectively leverage existing knowledge and address challenges. The MSUA and complementary governance documents can inform similar efforts. |
Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis.
Sumner JA , Maihofer AX , Michopoulos V , Rothbaum AO , Almli LM , Andreassen OA , Ashley-Koch AE , Baker DG , Beckham JC , Bradley B , Breen G , Coleman JRI , Dale AM , Dennis MF , Feeny NC , Franz CE , Garrett ME , Gillespie CF , Guffanti G , Hauser MA , Hemmings SMJ , Jovanovic T , Kimbrel NA , Kremen WS , Lawford BR , Logue MW , Lori A , Lyons MJ , Maples-Keller J , Mavissakalian MR , McGlinchey RE , Mehta D , Mellor R , Milberg W , Miller MW , Morris CP , Panizzon MS , Ressler KJ , Risbrough VB , Rothbaum BO , Roy-Byrne P , Seedat S , Smith AK , Stevens JS , van den Heuvel LL , Voisey J , Young RM , Zoellner LA , Nievergelt CM , Wolf EJ . Front Neurosci 2021 15 678503 Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk. |
SARS-CoV-2 Infection and Mitigation Efforts among Office Workers, Washington, DC, USA.
Sami S , Vuong N , Miller H , Priestley R , Payne M , Licata-Portentoso G , Drobeniuc J , Petersen LR . Emerg Infect Dis 2021 27 (2) 669-672 Despite mitigation efforts, 2 coronavirus disease outbreaks were identified among office workers in Washington, DC. Moderate adherence to workplace mitigation efforts was reported in a serologic survey; activities outside of the workplace were associated with infection. Adherence to safety measures are critical for returning to work during the pandemic. |
Diagnostic value of clinical features to distinguish enteric fever from other febrile illnesses in Bangladesh, Nepal, and Pakistan
Aiemjoy K , Tamrakar D , Saha S , Naga SR , Yu AT , Longley A , Date K , Hemlock C , Qamar FN , Saha SK , Luby SP , Garrett DO , Andrews JR , Bogoch II . Clin Infect Dis 2020 71 S257-s265 BACKGROUND: Enteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan. METHODS: Outpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients. RESULTS: We enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0-74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6-65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8-77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4-95.5) and specificity of 13.6% (95% CI, 9.8-17.5). CONCLUSIONS: Clinical features do not accurately distinguish blood culture-confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity. |
Healthcare utilization patterns for acute febrile illness in Bangladesh, Nepal, and Pakistan: Results from the Surveillance for Enteric Fever in Asia Project
Andrews JR , Vaidya K , Saha S , Yousafzai MT , Hemlock C , Longley A , Aiemjoy K , Yu AT , Bogoch II , Tamrakar D , Date K , Saha SK , Garrett DO , Luby SP , Qamar F . Clin Infect Dis 2020 71 S248-s256 BACKGROUND: Characterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data. METHODS: We used a hybrid model in the Surveillance for Enteric Fever in Asia Project (SEAP) to assess incidence of enteric fever at 6 study hospitals in 3 countries. We recruited individuals presenting to the hospitals and obtained blood cultures to evaluate for enteric fever. For this analysis, we undertook cluster random household surveys in Dhaka, Bangladesh (2 sites); Karachi, Pakistan; Kathmandu, Nepal; and Kavrepalanchok, Nepal between January 2017 and February 2019, to ascertain care-seeking behavior for individuals with 1) fever for ≥3 consecutive days within the past 8 weeks; or 2) fever resulting in hospitalization within the past year. We also collected data about disease severity and household demographics and assets. We used mixed-effect multivariable logistic regression models to identify determinants of healthcare seeking at study hospitals and determinants of culture-confirmed enteric fever. RESULTS: We enrolled 31 841 households (53 926 children) in Bangladesh, 25 510 households (84 196 children and adults) in Nepal, and 21 310 households (108 031 children and adults) in Pakistan. Children <5 years were most likely to be taken to the study hospitals for febrile illness at all sites. Household wealth was positively correlated with healthcare seeking in 4 of 5 study sites, and at least one marker of disease severity was positively associated with healthcare seeking in 3 of 5 catchment areas. Wealth and disease severity were variably predictive of blood culture-confirmed enteric fever. CONCLUSIONS: Age, household wealth, and disease severity are important determinants of healthcare seeking for acute febrile illness and enteric fever risk in these communities, and should be incorporated into estimation models for enteric fever incidence. |
Utilization of blood culture in South Asia for the diagnosis and treatment of febrile illness
Hemlock C , Luby SP , Saha S , Qamar F , Andrews JR , Saha SK , Tamrakar D , Date K , Longley AT , Garrett DO , Bogoch II . Clin Infect Dis 2020 71 S266-s275 BACKGROUND: Blood culture is the current standard for diagnosing bacteremic illnesses, yet it is not clear how physicians in many low- and middle-income countries utilize blood culture for diagnostic purposes and to inform treatment decisions. METHODS: We screened suspected enteric fever cases from 6 hospitals in Bangladesh, Nepal, and Pakistan, and enrolled patients if blood culture was prescribed by the treating physician. We used generalized additive regression models to analyze the probability of receiving blood culture by age, and linear regression models to analyze changes by month to the proportion of febrile cases prescribed a blood culture compared with the burden of febrile illness, stratified by hospital. We used logistic regression to analyze predictors for receiving antibiotics empirically. We descriptively reviewed changes in antibiotic therapy by susceptibility patterns and coverage, stratified by country. RESULTS: We screened 30 809 outpatients resulting in 1819 enteric fever cases; 1935 additional cases were enrolled from other hospital locations. Younger outpatients were less likely to receive a blood culture. The association between the number of febrile outpatients and the proportion prescribed blood culture varied by hospital. Antibiotics prescribed empirically were associated with severity and provisional diagnoses, but 31% (1147/3754) of enteric fever cases were not covered by initial therapy; this was highest in Pakistan (50%) as many isolates were resistant to cephalosporins, which were commonly prescribed empirically. CONCLUSIONS: Understanding hospital-level communication between laboratories and physicians may improve patient care and timeliness of appropriate antibiotics, which is important considering the rise of antimicrobial resistance. |
Illness severity and outcomes among enteric fever cases from Bangladesh, Nepal, and Pakistan: Data from the Surveillance for Enteric Fever in Asia Project, 2016-2019
Longley AT , Hemlock C , Date K , Luby SP , Andrews JR , Saha SK , Bogoch II , Yousafzai MT , Garrett DO , Qamar FN . Clin Infect Dis 2020 71 S222-s231 BACKGROUND: Enteric fever can lead to prolonged hospital stays, clinical complications, and death. The Surveillance for Enteric Fever in Asia Project (SEAP), a prospective surveillance study, characterized the burden of enteric fever, including illness severity, in selected settings in Bangladesh, Nepal, and Pakistan. We assessed disease severity, including hospitalization, clinical complications, and death among SEAP participants. METHODS: We analyzed clinical and laboratory data from blood culture-confirmed enteric fever cases enrolled in SEAP hospitals and associated network laboratories from September 2016 to September 2019. We used hospitalization and duration of hospital stay as proxies for severity. We conducted a follow-up interview 6 weeks after enrollment to ascertain final outcomes. RESULTS: Of the 8705 blood culture-confirmed enteric fever cases enrolled, we identified 6 deaths (case-fatality ratio, .07%; 95% CI, .01-.13%), 2 from Nepal, 4 from Pakistan, and none from Bangladesh. Overall, 1.7% (90/5205) of patients recruited from SEAP hospitals experienced a clinical complication (Bangladesh, 0.6% [18/3032]; Nepal, 2.3% [12/531]; Pakistan, 3.7% [60/1642]). The most identified complications were hepatitis (n = 36), septic shock (n = 22), and pulmonary complications/pneumonia (n = 13). Across countries, 32% (2804/8669) of patients with hospitalization data available were hospitalized (Bangladesh, 27% [1295/4868]; Nepal, 29% [455/1595]; Pakistan, 48% [1054/2206]), with a median hospital stay of 5 days (IQR, 3-7). CONCLUSIONS: While defined clinical complications and deaths were uncommon at the SEAP sites, the high proportion of hospitalizations and prolonged hospital stays highlight illness severity and the need for enteric fever control measures, including the use of typhoid conjugate vaccines. |
Typhoid and paratyphoid cost of illness in Nepal: Patient and health facility costs from the Surveillance for Enteric Fever in Asia Project II
Mejia N , Abimbola T , Andrews JR , Vaidya K , Tamrakar D , Pradhan S , Shakya R , Garrett DO , Date K , Pallas SW . Clin Infect Dis 2020 71 S306-s318 BACKGROUND: Enteric fever is endemic in Nepal and its economic burden is unknown. The objective of this study was to estimate the cost of illness due to enteric fever (typhoid and paratyphoid) at selected sites in Nepal. METHODS: We implemented a study at 2 hospitals in Nepal to estimate the cost per case of enteric fever from the perspectives of patients, caregivers, and healthcare providers. We collected direct medical, nonmedical, and indirect costs per blood culture-confirmed case incurred by patients and their caregivers from illness onset until after enrollment and 6 weeks later. We estimated healthcare provider direct medical economic costs based on quantities and prices of resources used to diagnose and treat enteric fever, and procedure frequencies received at these facilities by enrolled patients. We collected costs in Nepalese rupees and converted them into 2018 US dollars. RESULTS: We collected patient and caregiver cost of illness information for 395 patients, with a median cost of illness per case of $59.99 (IQR, $24.04-$151.23). Median direct medical and nonmedical costs per case represented ~3.5% of annual individual labor income. From the healthcare provider perspective, the average direct medical economic cost per case was $79.80 (range, $71.54 [hospital B], $93.43 [hospital A]). CONCLUSIONS: Enteric fever can impose a considerable economic burden on patients, caregivers, and health facilities in Nepal. These new estimates of enteric fever cost of illness can improve evaluation and modeling of the costs and benefits of enteric fever-prevention measures. |
Typhoid and paratyphoid cost of illness in Bangladesh: Patient and health facility costs from the Surveillance for Enteric Fever in Asia Project II
Mejia N , Pallas SW , Saha S , Udin J , Sayeed KMI , Garrett DO , Date K , Abimbola T . Clin Infect Dis 2020 71 S293-s305 BACKGROUND: We conducted a cost of illness study to assess the economic burden of pediatric enteric fever (typhoid and paratyphoid) in Bangladesh. Results can inform public health policies to prevent enteric fever. METHODS: The study was conducted at 2 pediatric health facilities in Dhaka. For the patient and caregiver's perspective, we administered questionnaires on costs incurred from illness onset until the survey dates to caregivers of patients with blood culture positive cases at enrollment and 6 weeks later to estimate the direct medical, direct nonmedical, and indirect costs. From the perspective of the health care provider, we collected data on quantities and prices of resources used by the 2 hospitals to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Bangladeshi takas and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: Among the 1772 patients from whom we collected information, the median cost of illness per case of enteric fever from the patient and caregiver perspective was US $64.03 (IQR: US $33.90 -$173.48). Median direct medical and nonmedical costs per case were 3% of annual labor income across the sample. From the perspective of the healthcare provider, the average direct medical cost per case was US $58.64 (range: US $37.25 at Hospital B, US $73.27 at Hospital A). CONCLUSIONS: Our results show substantial economic burden of enteric fever in Bangladesh, with higher costs for patients receiving inpatient care. As antimicrobial resistance increases globally, the cost of illness could increase, due to more expensive and potent drugs required for treatment. |
Typhoid and paratyphoid cost of illness in Pakistan: Patient and health facility costs from the Surveillance for Enteric Fever in Asia Project II
Mejia N , Qamar F , Yousafzai MT , Raza J , Garrett DO , Date K , Abimbola T , Pallas SW . Clin Infect Dis 2020 71 S319-s335 BACKGROUND: The objective of this study was to estimate the cost of illness from enteric fever (typhoid and paratyphoid) at selected sites in Pakistan. METHODS: We implemented a cost-of-illness study in 4 hospitals as part of the Surveillance for Enteric Fever in Asia Project (SEAP) II in Pakistan. From the patient and caregiver perspective, we collected direct medical, nonmedical, and indirect costs per case of enteric fever incurred since illness onset by phone after enrollment and 6 weeks later. From the health care provider perspective, we collected data on quantities and prices of resources used at 3 of the hospitals, to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Pakistani rupees and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: We collected patient and caregiver information for 1029 patients with blood culture-confirmed enteric fever or with a nontraumatic terminal ileal perforation, with a median cost of illness per case of US $196.37 (IQR, US $72.89-496.40). The median direct medical and nonmedical costs represented 8.2% of the annual labor income. From the health care provider perspective, the estimated average direct medical cost per case was US $50.88 at Hospital A, US $52.24 at Hospital B, and US $11.73 at Hospital C. CONCLUSIONS: Enteric fever can impose a considerable economic burden in Pakistan. These new estimates of the cost of illness of enteric fever can improve evaluation and modeling of the costs and benefits of enteric fever prevention and control measures, including typhoid conjugate vaccines. |
Antimicrobial resistance in typhoidal Salmonella: Surveillance for enteric fever in Asia Project, 2016-2019
Qamar FN , Yousafzai MT , Dehraj IF , Shakoor S , Irfan S , Hotwani A , Hunzai MJ , Thobani RS , Rahman N , Mehmood J , Hemlock C , Memon AM , Andrews JR , Luby SP , Garrett DO , Longley AT , Date K , Saha SK . Clin Infect Dis 2020 71 S276-s284 BACKGROUND: Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan. METHODS: From September 2016-September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric fever. Antimicrobial resistance of isolates was determined by disc diffusion using Clinical and Laboratory Standard Institute cut-off points. We reported the frequency of multidrug resistance (MDR)(resistance to ampicillin, cotrimoxazole, and chloramphenicol), extensive drug resistance (XDR) (MDR plus non-susceptible to fluoroquinolone and any 3rd generation cephalosporins), and fluoroquinolone (FQ) and azithromycin non-susceptibility. RESULTS: We enrolled 8,705 blood culture confirmed enteric fever cases: 4,873 (56%) from Bangladesh, 1,602 (18%) from Nepal and 2,230 (26%) from Pakistan. Of these, 7,591 (87%) were Salmonella Typhi and 1114 (13%) were S. Paratyphi. MDR S. Typhi was identified in 17% (701/4065) of isolates in Bangladesh, and 1% (19/1342) in Nepal. In Pakistan, 16 % (331/2084) of S. Typhi isolates were MDR, and 64% (1319/2074) were XDR. FQ nonsusceptibility among S. Typhi isolates was 98% in Bangladesh, 87% in Nepal, and 95% in Pakistan. Azithromycin non-susceptibility was detected in 77 (2%) in Bangladesh, 9 (.67%) in Nepal and 9 (.59%) isolates in Pakistan. In Pakistan, three (2%) S. Paratyphi isolates were MDR; no MDR S. Paratyphi was reported from Bangladesh or Nepal. CONCLUSIONS: Although AMR against S. Paratyphi was low across the three countries, there was widespread drug resistance among S. Typhi, including FQ non-susceptibility and the emergence of XDR S. Typhi in Pakistan, limiting treatment options. As typhoid conjugate vaccine (TCV) is rolled out, surveillance should continue to monitor changes in AMR to inform policies and to monitor drug resistance in S. Paratyphi, for which there is no vaccine. |
Spatial heterogeneity of enteric fever in 2 diverse communities in Nepal
Tamrakar D , Vaidya K , Yu AT , Aiemjoy K , Naga SR , Cao Y , Bern C , Shrestha R , Karmacharya BM , Pradhan S , Qamar FN , Saha S , Date K , Longley AT , Hemlock C , Luby S , Garrett DO , Bogoch II , Andrews JR . Clin Infect Dis 2020 71 S205-s213 BACKGROUND: Typhoid fever is endemic in the urban Kathmandu Valley of Nepal; however, there have been no population-based studies of typhoid outside of this community in the past 3 decades. Whether typhoid immunization should be prioritized in periurban and rural communities has been unclear. METHODS: We performed population-based surveillance for enteric fever in 1 urban catchment (Kathmandu) and 1 periurban and rural catchment (Kavrepalanchok) as part of the Surveillance for Enteric Fever in Asia Project (SEAP). We recruited individuals presenting to outpatient and emergency departments at 2 study hospitals with suspected enteric fever and performed blood cultures. Additionally, we conducted a household survey in each catchment area to characterize care seeking for febrile illness. We evaluated spatial heterogeneity in febrile illness, care seeking, and enteric fever incidence. RESULTS: Between September 2016 and September 2019, we enrolled 5736 participants with suspected enteric fever at 2 study hospitals. Among these, 304 (5.3%) were culture positive for Salmonella Typhi (249 [81.9%]) or Paratyphi A (55 [18.1%]). Adjusted typhoid incidence in Kathmandu was 484 per 100 000 person-years and in Kavrepalanchok was 615 per 100 000 person-years. While all geographic areas for which estimates could be made had incidence >200 per 100 000 person-years, we observed spatial heterogeneity with up to 10-fold variation in incidence between communities. CONCLUSIONS: In urban, periurban, and rural communities in and around Kathmandu, we measured a high but heterogenous incidence of typhoid. These findings provide some support for the introduction of conjugate vaccines in Nepal, including outside urban areas, alongside other measures to prevent enteric fever. |
Antibiotic use prior to hospital presentation among individuals with suspected enteric fever in Nepal, Bangladesh, and Pakistan
Vaidya K , Aiemjoy K , Qamar FN , Saha SK , Tamrakar D , Naga SR , Saha S , Hemlock C , Longley AT , Date K , Bogoch II , Garrett DO , Luby SP , Andrews JR . Clin Infect Dis 2020 71 S285-s292 BACKGROUND: Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity. METHODS: Between November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity. RESULTS: We enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant (prevalence ratio, 1.22 [95% confidence interval, .99-1.50]). CONCLUSIONS: The reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use. |
A cluster-based, spatial-sampling method for assessing household healthcare utilization patterns in resource-limited settings
Yu AT , Shakya R , Adhikari B , Tamrakar D , Vaidya K , Maples S , Date K , Bogoch II , Bern C , Qamar F , Yousafzai MT , Garrett DO , Longley AT , Hemlock C , Luby S , Aiemjoy K , Andrews JR . Clin Infect Dis 2020 71 S239-s247 BACKGROUND: Implementation of population-based surveys is resource intensive and logistically demanding, especially in areas with rapidly changing demographics and incomplete or no enumeration of the underlying population and their residences. To remove the need for pre-enumeration and to simplify field logistics for the population healthcare utilization survey used for the Surveillance for Enteric Fever in Asia Project in Nepal, we incorporated a geographic information system-based geosurvey and field mapping system into a single-stage cluster sampling approach. METHODS: A survey was administered to ascertain healthcare-seeking behavior in individuals with recent suspected enteric fever. Catchment areas were based on residential addresses of enteric fever patients using study facilities; clusters were randomly selected from digitally created grids using available satellite images and all households within clusters were offered enrollment. A tablet-compatible geosurvey and mapping system that allowed for data-syncing and use in areas without cellular data was created using the ArcGIS suite of software. RESULTS: Between January 2017 and November 2018, we surveyed 25 521 households in Nepal (16 769 in urban Kathmandu and 8752 in periurban Kavrepalanchok), representing 84 202 individuals. Overall, the survey participation rate was 90.9%, with geographic heterogeneity in participation rates within each catchment area. Areas with higher average household wealth had lower participation rates. CONCLUSION: A geographic information system-based geosurvey and field mapping system allowed creation of a virtual household map at the same time as survey administration, enabling a single-stage cluster sampling method to assess healthcare utilization in Nepal for the Surveillance for Enteric Fever in Asia Project . This system removed the need for pre-enumeration of households in sampling areas, simplified logistics and could be replicated in future community surveys. |
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