Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 50 Records) |
Query Trace: Abraham H[original query] |
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Molecular detection of Bartonella species in ticks from Peru.
Billeter SA , Cáceres AG , Gonzales-Hidalgo J , Luna-Caypo D , Kosoy MY . J Med Entomol 2011 48 (6) 1257-60 A total of 103 ticks, collected from canines, horses, donkeys, and snakes from Peru, were screened for the presence of Bartonella DNA by polymerase chain reaction analysis. Bartonella DNA was detected in two ticks using Bartonella 16S-23S intergenic spacer region primers and in an additional two ticks using Bartonella NADH dehydrogenase gamma subunit gene (nuoG) primers. Bartonella rochalimae Eremeeva et al., B. quintana Schmincke, and B. elizabethae Daly et al. DNA was detected in a Rhipicephalus sanguineus Latreille (Acari: Ixodidae) female tick removed from a dog and B. quintana DNA was present in a Dermacentor nitens Neumann (Acari: Ixodidae) pool of five larvae, one nymph, and one adult male tick collected from donkeys. This is the first study to report the detection of B. rochalimae, B. quintana, and B. elizabethae DNA in ticks from Peru. Further investigations must be performed to decipher the role ticks may play in the transmission of Bartonella species. |
Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA
Go LHT , Rose CS , Zell-Baran LM , Almberg KS , Iwaniuk C , Clingerman S , Richardson DL , Abraham JL , Cool CD , Franko AD , Green FHY , Hubbs AF , Murray J , Orandle MS , Sanyal S , Vorajee NI , Sarver EA , Petsonk EL , Cohen RA . Occup Environ Med 2023 80 (8) 425-430 BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners. |
Evaluation of Sampling and Concentration Methods for Salmonella enterica Serovar Typhi Detection from Wastewater
Zhou N , Ong A , Fagnant-Sperati C , Harrison J , Kossik A , Beck N , Shirai J , Burnor E , Swanstrom R , Demeke B , Patel S , Scott Meschke J , Kang G , Giri S , Raghava V , Abraham D , Moe C , Kapoor R , Wang Y , Liu P , Feasey N , Rigby J , Dines Y , Elviss N , Alm E , Moniz K , Xiao A , Karmacharya D , Napit R , Poudel A , Muhammad S , Ashraf Z , Boyle D , Andrews J , Aiemjoy K , LeBoa C , Tamrakar D , Shrestha S , Shakya J , Murphy JL , Narayanan J , Brown TW , Taniuchi M , Islam Md O , Blake I . Am J Trop Med Hyg 2023 108 (3) 482-491 Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with 12 variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on its ability to detect Salmonella Typhi and its feasibility. Salmonella Typhi strains Ty21a and Ty2 were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via quantitative polymerase chain reaction (qPCR). Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses, including the Salmonella Typhi concentration it is best suited for, with a range of positive detections observed as low as 0.1-0.001 colony-forming units (CFU) Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned. |
Evaluation of sampling and concentration methods for Salmonella enterica serovar Typhi detection from wastewater (preprint)
Zhou NA , Ong AQW , Fagnant-Sperati CS , Harrison JC , Kossik AL , Beck NK , Shirai JH , Burnor E , Swanstrom R , Demeke B , Patel S , Meschke JS , Kang G , Giri S , Raghava V , Abraham D , Moe C , Kapoor R , Wang Y , Liu P , Feasey N , Rigby J , Dines Y , Elviss N , Alm E , Moniz K , Xiao A , Karmacharya D , Napit R , Poudel A , Muhammad S , Ashraf Z , Boyle D , Andrews J , Aiemjoy K , LeBoa C , Tamrakar D , Shrestha S , Shakya J , Murphy JL , Narayanan J , Brown TW , Taniuchi M , Islam Md O , Blake I . medRxiv 2022 08 Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of Typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens, and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with twelve variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on their ability to detect Salmonella Typhi and feasibility. Salmonella Typhi strains, Ty21a and Ty2, were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via qPCR. Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses including the Salmonella Typhi concentrations they are best suited for with a range of positive detections observed as low as 0.1-0.001 CFU Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned. 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. |
When to update COVID-19 vaccine composition.
Grant R , Sacks JA , Abraham P , Chunsuttiwat S , Cohen C , Figueroa JP , Fleming T , Fine P , Goldblatt D , Hasegawa H , MacIntrye CR , Memish ZA , Miller E , Nishioka S , Sall AA , Sow S , Tomori O , Wang Y , Van Kerkhove MD , Wambo MA , Cohen HA , Mesfin S , Otieno JR , Subissi L , Briand S , Wentworth DE , Subbarao K . Nat Med 2023 29 (4) 776-780 Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy. | | Entering the fourth year of the COVID-19 pandemic, index virus-based1 vaccines across several different platforms continue to provide high levels of protection against severe disease caused by all variants of SARS-CoV-2, including Omicron2. However, there has been continuous and substantial evolution of SARS-CoV-2 since the virus emerged, posing challenges to the ongoing public health response, including ensuring that vaccines continue to provide protection. In September 2021, the World Health Organization (WHO) established the Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC)3 to assess the public health implications of emerging SARS-CoV-2 variants of concern (VOC) on the performance of COVID-19 vaccines and to issue timely recommendations on proposed modifications to vaccine antigen composition. The TAG-CO-VAC has evaluated evidence to inform its advice on COVID-19 vaccine composition so far, but there remain challenges and evidence gaps that the scientific community needs to address to enable future, timely decisions on modifications to COVID-19 vaccine antigen composition. |
Mining tenure and job duties differ among contemporary and historic underground coal miners with progressive massive fibrosis
Zell-Baran L , Go LHT , Sarver E , Almberg KS , Iwaniuk C , Green FHY , Abraham JL , Cool C , Franko A , Hubbs AF , Murray J , Orandle MS , Sanyal S , Vorajee N , Cohen RA , Rose CS . J Occup Environ Med 2022 65 (4) 315-320 OBJECTIVE: To characterize differences in mining jobs and tenure between contemporary (born 1930+, working primarily with modern mining technologies) and historic coal miners with progressive massive fibrosis (PMF). METHODS: We classified jobs as designated occupations (DOs) and non-DOs based on regulatory sampling requirements. Demographic, occupational characteristics, and histopathological PMF type were compared between groups. RESULTS: Contemporary miners (n = 33) had significantly shorter mean total (30.4 years vs. 37.1 years, p = 0.0006) and underground (28.8 years vs. 35.8 years, p = 0.001) mining tenure compared to historic miners (n = 289). Silica-type PMF was significantly more common among miners in non-DOs (30.1% vs. 15.8%, p = 0.03) and contemporary miners (58.1% vs. 15.2%, p < 0.0001). CONCLUSIONS: Primary jobs changed over time with the introduction of modern mining technologies and likely changed exposures for workers. Elevated crystalline silica exposures are likely in non-DOs and require attention. |
Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network
Cohen AL , Platts-Mills JA , Nakamura T , Operario DJ , Antoni S , Mwenda JM , Weldegebriel G , Rey-Benito G , deOliveira LH , Ortiz C , Daniels DS , Videbaek D , Singh S , Njambe E , Sharifuzzaman M , Grabovac V , Nyambat B , Logronio J , Armah G , Dennis FE , Seheri ML , Magagula N , Mphahlele J , Fumian TM , Maciel ITA , GagliardiLeite JP , Esona MD , Bowen MD , Samoilovich E , Semeiko G , Abraham D , Giri S , Praharaj I , Kang G , Thomas S , Bines J , Liu N , Kyu HH , Doxey M , RogawskiMcQuade ET , McMurry TL , Liu J , Houpt ER , Tate JE , Parashar UD , Serhan F . BMJ Glob Health 2022 7 (9) INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality. |
Refractory, fatal autoimmune hemolytic anemia due to ineffective thymic-derived T-cell reconstitution following allogeneic hematopoietic cell transplantation for hypomorphic RAG1 deficiency
Yonkof JR , Basu A , Redmond MT , Dobbs AK , Perelygina L , Notarangelo LD , Abraham RS , Rangarajan HG . Pediatr Blood Cancer 2022 70 (5) e30183 Pathogenic recombination-activating gene 1 (RAG1) variants cause a phenotypic spectrum ranging from severe combined immunodeficiency (SCID) to combined immunodeficiency with granulomas and autoimmunity (CID-G/A), depending on residual recombinase activity.1-4 Our patient, a 12-year-old African American female with hypogammaglobulinemia and T-, B-cell lymphopenia, was diagnosed with CID at 5 years of age, with a history of recurrent herpes simplex virus (HSV) gingivostomatitis, bacterial pneumonia, and cutaneous abscess. She tolerated two doses of live measles–mumps–rubella (MMR) vaccine. She was referred to our facility for steroid-refractory sterile non-caseating cutaneous granulomas (Figure S1) affecting posterior thigh and midface, appearing at 9 years and with progressive lymphopenia (Figure 1A) concerning for a CID. Next-generation sequencing identified compound heterozygous pathogenic RAG1 variants, c.1187G>A, p.Arg396His and c.1566G>T, p.Trp522Cys (NM_000448.2). Residual recombinase activity is estimated at 40%–50% for RAG1-Trp522Cys and less than 5%–30% for RAG1-Arg396His.2, 5, 6 |
Pathology and mineralogy demonstrate respirable crystalline silica is a major cause of severe pneumoconiosis in US coal miners
Cohen RA , Rose CS , Go LHT , Zell-Baran LM , Almberg KS , Sarver EA , Lowers HA , Iwaniuk C , Clingerman SM , Richardson DL , Abraham JL , Cool CD , Franko AD , Hubbs AF , Murray J , Orandle MS , Sanyal S , Vorajee NI , Petsonk EL , Zulfikar R , Green FHY . Ann Am Thorac Soc 2022 19 (9) 1469-1478 RATIONALE: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States (US) are not yet fully understood. OBJECTIVE: To compare the pathologic and mineralogic features of contemporary coal miners suffering severe pneumoconiosis to their historical counterparts. METHODS: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) to those born in or after 1930 (contemporary). RESULTS: We found a significantly higher proportion of silica-type PMF (57% vs. 18%, p<0.001) among contemporary miners compared to their historical counterparts. Mineral dust alveolar proteinosis (MDAP) was also more common in contemporary miners compared to their historical counterparts (70% vs. 37%, p<0.01). In situ mineralogic analysis showed the percentage (26.1% vs. 17.8%, p<0.01) and concentration (47.3 x 108 vs. 25.8 X 108 particles/cm3, p=0.036) of silica particles was significantly greater in specimens from contemporary miners compared to their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, MDAP, silicotic nodules, or immature silicotic nodules were present (p<0.05). CONCLUSIONS: Exposure to respirable crystalline silica appears causal in the unexpected surge in severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure in order to prevent the disabling and untreatable adverse health effects afflicting US coal miners. Primary Source of Funding: Alpha Foundation for the Improvement of Mine Safety and Health, Inc. |
Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity.
Perelygina L , Faisthalab R , Abernathy E , Chen MH , Hao L , Bercovitch L , Bayer DK , Noroski LM , Lam MT , Cicalese MP , Al-Herz W , Nanda A , Hajjar J , Vanden Driessche K , Schroven S , Leysen J , Rosenbach M , Peters P , Raedler J , Albert MH , Abraham RS , Rangarjan HG , Buchbinder D , Kobrynski L , Pham-Huy A , Dhossche J , Cunningham Rundles C , Meyer AK , Theos A , Atkinson TP , Musiek A , Adeli M , Derichs U , Walz C , Krüger R , von Bernuth H , Klein C , Icenogle J , Hauck F , Sullivan KE . Front Immunol 2021 12 796065 Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions. |
'Hybrid Survey' approach to non-communicable disease surveillance in the US-Affiliated Pacific Islands
Cash HL , De Jesus S , Durand AM , Tin STW , Shelton D , Robles R , Mendiola AR , Brikul S , Ipil M , Murphy M , Hunt LSS , Nielsen Lesa F , Sigrah CA , Waguk R , Abraham D , Kapiriel SF , Camacho J , Chutaro E . BMJ Glob Health 2021 6 (10) In 2010 the US-Affiliated Pacific Islands (USAPI) declared a regional state of health emergency due to the epidemic of non-communicable disease (NCD) and an NCD monitoring and surveillance framework was developed that includes adult NCD risk factor and disease prevalence indicators to be collected every 5 years using a population-based survey. On evaluation of existing data from adult population-based NCD surveys, it was found that there was a lack of valid, available and consistently collected data. Therefore, a new model was developed to combine various indicators and survey tools from different partner agencies into one survey. After the report was endorsed by local health leadership, a dissemination workshop was conducted. In 2015 (baseline for Hybrid Survey implementation), three out of nine jurisdictions (33.3%) had completed a population-based survey in the past 5 years. Four (44.4%) had no adult prevalence data at all, two (22.2%) had data sets from their surveys and four (44.4%) had at least two surveys ever collected that could be used for comparison. As of 2020, all nine jurisdictions have, or are in the process of completing an adult population-based survey. Eight (88.9%) have data sets from their surveys, and five (55.6%) have at least two surveys collected that can be used for comparison. This Hybrid Survey model has helped to improve adult NCD surveillance in the USAPI by more efficiently using limited resources. This model could be considered in other small island nations, or rural areas where adult NCD surveillance is challenging. |
Evidence for environmental-human microbiota transfer at a manufacturing facility with novel work-related respiratory disease
Wu BG , Kapoor B , Cummings KJ , Stanton ML , Nett RJ , Kreiss K , Abraham JL , Colby TV , Franko AD , Green FHY , Sanyal S , Clemente JC , Gao Z , Coffre M , Meyn P , Heguy A , Li Y , Sulaiman I , Borbet TC , Koralov SB , Tallaksen RJ , Wendland D , Bachelder VD , Boylstein RJ , Park JH , Cox-Ganser JM , Virji MA , Crawford JA , Edwards NT , Veillette M , Duchaine C , Warren K , Lundeen S , Blaser MJ , Segal LN . Am J Respir Crit Care Med 2020 202 (12) 1678-1688 INTRODUCTION: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. As part of a public health investigation of a manufacturing facility, we performed paired environmental and human sampling to evaluate cross-pollination of microbes between environment and host and possible effects on lung pathology present among workers. METHODS: Workplace environmental microbiota was evaluated in air and MWF samples. Human microbiota was evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, lung tissue controls, and in skin, nasal and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B-cells were assessed. RESULTS: Increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared to controls. Among workers in different locations within the facility, those that worked in machine shop area had skin, nasal and oral microbiota more closely related to the microbiota present in MWF samples. Lung samples from four index cases, and skin and nasal samples from workers in machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in pathology of index cases. CONCLUSIONS: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard. |
An open challenge to advance probabilistic forecasting for dengue epidemics.
Johansson MA , Apfeldorf KM , Dobson S , Devita J , Buczak AL , Baugher B , Moniz LJ , Bagley T , Babin SM , Guven E , Yamana TK , Shaman J , Moschou T , Lothian N , Lane A , Osborne G , Jiang G , Brooks LC , Farrow DC , Hyun S , Tibshirani RJ , Rosenfeld R , Lessler J , Reich NG , Cummings DAT , Lauer SA , Moore SM , Clapham HE , Lowe R , Bailey TC , Garcia-Diez M , Carvalho MS , Rodo X , Sardar T , Paul R , Ray EL , Sakrejda K , Brown AC , Meng X , Osoba O , Vardavas R , Manheim D , Moore M , Rao DM , Porco TC , Ackley S , Liu F , Worden L , Convertino M , Liu Y , Reddy A , Ortiz E , Rivero J , Brito H , Juarrero A , Johnson LR , Gramacy RB , Cohen JM , Mordecai EA , Murdock CC , Rohr JR , Ryan SJ , Stewart-Ibarra AM , Weikel DP , Jutla A , Khan R , Poultney M , Colwell RR , Rivera-Garcia B , Barker CM , Bell JE , Biggerstaff M , Swerdlow D , Mier YTeran-Romero L , Forshey BM , Trtanj J , Asher J , Clay M , Margolis HS , Hebbeler AM , George D , Chretien JP . Proc Natl Acad Sci U S A 2019 116 (48) 24268-24274 A wide range of research has promised new tools for forecasting infectious disease dynamics, but little of that research is currently being applied in practice, because tools do not address key public health needs, do not produce probabilistic forecasts, have not been evaluated on external data, or do not provide sufficient forecast skill to be useful. We developed an open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem. Sixteen teams used a variety of methods and data to generate forecasts for 3 epidemiological targets (peak incidence, the week of the peak, and total incidence) over 8 dengue seasons in Iquitos, Peru and San Juan, Puerto Rico. Forecast skill was highly variable across teams and targets. While numerous forecasts showed high skill for midseason situational awareness, early season skill was low, and skill was generally lowest for high incidence seasons, those for which forecasts would be most valuable. A comparison of modeling approaches revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts. Leveraging these insights, data, and the forecasting framework will be critical to improve forecast skill and the application of forecasts in real time for epidemic preparedness and response. Moreover, key components of this project-integration with public health needs, a common forecasting framework, shared and standardized data, and open participation-can help advance infectious disease forecasting beyond dengue. |
Severe lung disease characterized by lymphocytic bronchiolitis, alveolar ductitis, and emphysema (BADE) in industrial machine-manufacturing workers
Cummings KJ , Stanton ML , Nett RJ , Segal LN , Kreiss K , Abraham JL , Colby TV , Franko AD , Green FHY , Sanyal S , Tallaksen RJ , Wendland D , Bachelder VD , Boylstein RJ , Park JH , Cox-Ganser JM , Virji MA , Crawford JA , Green BJ , LeBouf RF , Blaser MJ , Weissman DN . Am J Ind Med 2019 62 (11) 927-937 BACKGROUND: A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures. METHODS: Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing. RESULTS: Five previously healthy male never-smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV1 = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B-cell follicles lacking germinal centers, and significant emphysema for never-smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities. CONCLUSION: This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never-smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention. |
The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.
Commons RJ , Simpson JA , Thriemer K , Chu CS , Douglas NM , Abreha T , Alemu SG , Anez A , Anstey NM , Aseffa A , Assefa A , Awab GR , Baird JK , Barber BE , Borghini-Fuhrer I , D'Alessandro U , Dahal P , Daher A , de Vries PJ , Erhart A , Gomes MSM , Grigg MJ , Hwang J , Kager PA , Ketema T , Khan WA , Lacerda MVG , Leslie T , Ley B , Lidia K , Monteiro WM , Pereira DB , Phan GT , Phyo AP , Rowland M , Saravu K , Sibley CH , Siqueira AM , Stepniewska K , Taylor WRJ , Thwaites G , Tran BQ , Hien TT , Vieira JLF , Wangchuk S , Watson J , William T , Woodrow CJ , Nosten F , Guerin PJ , White NJ , Price RN . BMC Med 2019 17 (1) 151 BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016. |
Amyotrophic lateral sclerosis among patients with a Medicare Advantage prescription drug plan; prevalence, survival and patient characteristics
Bhattacharya R , Harvey RA , Abraham K , Rosen J , Mehta P . Amyotroph Lateral Scler Frontotemporal Degener 2019 20 1-9 OBJECTIVE: To estimate amyotrophic lateral sclerosis (ALS) prevalence, 5-year survival, and explore factors associated with survival in a Medicare population. METHODS: A validated administrative claims algorithm was used to classify individual's ages 18-89 years at index date (first claim with a diagnosis of motor neuron disease or ALS between 1 January 2007 and 31 December 2011) with Medicare Advantage prescription drug coverage into mutually exclusive categories: ALS, no ALS, and possible ALS. Crude prevalence and cumulative survival from index date to the date of death, disenrollment or end of the study were calculated. Cox-proportional hazards were used to estimate and explore factors associated with survival. RESULTS: Of 2631 eligible individuals, the algorithm identified 1271 (48 %), 1157 (44 %), 203 (8 %) as ALS, no ALS and possible ALS, respectively. The 5-year period prevalence and the 2011 point prevalence of ALS were 20.5 and 11.8 per 100,000, respectively. Evidence of death was documented in 81%, 35%, and 1.6% of the ALS, no ALS or possible ALS groups, respectively. Unadjusted median survival time was 388, 542 and 1473 days for the ALS, no ALS and possible ALS groups, respectively. Seeing a psychiatrist or neurologist at the index visit, having respiratory or genitourinary comorbidities, and the number of pre-index acute inpatient admissions were associated with shorter survival. CONCLUSIONS: Surveillance data from a Medicare population demonstrated a higher prevalence of ALS. Results highlight the need for effective ALS treatment options and resources for patients with ALS who will likely face limited therapeutic choices and care options at the end of life. |
Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum
Patton JB , Bennuru S , Eberhard ML , Hess JA , Torigian A , Lustigman S , Nutman TB , Abraham D . PLoS Negl Trop Dis 2018 12 (12) e0006977 BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus. |
The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa.
Park SE , Pham DT , Boinett C , Wong VK , Pak GD , Panzner U , Espinoza LMC , von Kalckreuth V , Im J , Schutt-Gerowitt H , Crump JA , Breiman RF , Adu-Sarkodie Y , Owusu-Dabo E , Rakotozandrindrainy R , Soura AB , Aseffa A , Gasmelseed N , Keddy KH , May J , Sow AG , Aaby P , Biggs HM , Hertz JT , Montgomery JM , Cosmas L , Fields B , Sarpong N , Razafindrabe TJL , Raminosoa TM , Kabore LP , Sampo E , Teferi M , Yeshitela B , El Tayeb MA , Sooka A , Meyer CG , Krumkamp R , Dekker DM , Jaeger A , Poppert S , Tall A , Niang A , Bjerregaard-Andersen M , Valborg Løfberg S , Seo HJ , Jeon HJ , Deerin JF , Park J , Konings F , Ali M , Clemens JD , Hughes P , Sendagala JN , Vudriko T , Downing R , Ikumapayi UN , Mackenzie GA , Obaro S , Argimon S , Aanensen DM , Page A , Keane JA , Duchene S , Dyson Z , Holt KE , Dougan G , Marks F , Baker S . Nat Commun 2018 9 (1) 5094 There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa. |
The Amblyomma maculatum Koch, 1844 (Acari: Ixodidae) group of ticks: phenotypic plasticity or incipient speciation?
Lado P , Nava S , Mendoza-Uribe L , Caceres AG , Delgado-de la Mora J , Licona-Enriquez JD , Delgado-de la Mora D , Labruna MB , Durden LA , Allerdice MEJ , Paddock CD , Szabo MPJ , Venzal JM , Guglielmone AA , Beati L . Parasit Vectors 2018 11 (1) 610 BACKGROUND: The goal of this study was to reassess the taxonomic status of A. maculatum, A. triste and A. tigrinum by phylogenetic analysis of five molecular markers [four mitochondrial: 12S rDNA, 16S rDNA, the control region (DL) and cytochrome c oxidase 1 (cox1), and one nuclear: ribosomal intergenic transcribed spacer 2 (ITS2)]. In addition, the phenotypic diversity of adult ticks identified as A. maculatum and A. triste from geographically distinct populations was thoroughly re-examined. RESULTS: Microscopic examination identified four putative morphotypes distinguishable by disjunct geographical ranges, but very scant fixed characters. Analysis of the separated mitochondrial datasets mostly resulted in conflicting tree topologies. Nuclear gene sequences were almost identical throughout the geographical ranges of the two species, suggesting a very recent, almost explosive radiation of the terminal operational taxonomic units. Analysis of concatenated molecular datasets was more informative and indicated that, although genetically very close to the A. maculatum - A. triste lineage, A. tigrinum was a monophyletic separate entity. Within the A. maculatum - A. triste cluster, three main clades were supported. The two morphotypes, corresponding to the western North American and eastern North American populations, consistently grouped in a single monophyletic clade with many shared mitochondrial sequences among ticks of the two areas. Ticks from the two remaining morphotypes, south-eastern South America and Peruvian, corresponded to two distinct clades. CONCLUSIONS: Given the paucity of morphological characters, the minimal genetic distance separating morphotypes, and more importantly the fact that two morphotypes are genetically indistinguishable, our data suggest that A. maculatum and A. triste should be synonymized and that morphological differences merely reflect very recent local adaptation to distinct environments in taxa that might be undergoing the first steps of speciation but have yet to complete lineage sorting. Nonetheless, future investigations using more sensitive nuclear markers and/or crossbreeding experiments might reveal the occurrence of very rapid speciation events in this group of taxa. Tentative node dating revealed that the A. tigrinum and A. maculatum - A. triste clades split about 2 Mya, while the A. maculatum - A.triste cluster radiated no earlier than 700,000 years ago. |
Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study
Saha SK , Schrag SJ , El Arifeen S , Mullany LC , Shahidul Islam M , Shang N , Qazi SA , Zaidi AKM , Bhutta ZA , Bose A , Panigrahi P , Soofi SB , Connor NE , Mitra DK , Isaac R , Winchell JM , Arvay ML , Islam M , Shafiq Y , Nisar I , Baloch B , Kabir F , Ali M , Diaz MH , Satpathy R , Nanda P , Padhi BK , Parida S , Hotwani A , Hasanuzzaman M , Ahmed S , Belal Hossain M , Ariff S , Ahmed I , Ibne Moin SM , Mahmud A , Waller JL , Rafiqullah I , Quaiyum MA , Begum N , Balaji V , Halen J , Nawshad Uddin Ahmed ASM , Weber MW , Hamer DH , Hibberd PL , Sadeq-Ur Rahman Q , Mogan VR , Hossain T , McGee L , Anandan S , Liu A , Panigrahi K , Abraham AM , Baqui AH . Lancet 2018 392 (10142) 145-159 BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95.4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13.2 (95% credible interval [CrI] 11.2-15.6) per 1000 livebirths and of viral infections was 10.1 (9.4-11.6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5.4, 95% CrI 4.8-6.3 episodes per 1000 livebirths), followed by Ureaplasma spp (2.4, 1.6-3.2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation. |
Methylprednisolone acetate induces, and Delta7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice
Patton JB , Bonne-Annee S , Deckman J , Hess JA , Torigian A , Nolan TJ , Wang Z , Kliewer SA , Durham AC , Lee JJ , Eberhard ML , Mangelsdorf DJ , Lok JB , Abraham D . Proc Natl Acad Sci U S A 2017 115 (1) 204-209 Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Delta7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection. |
Multimorbidity Among Persons Living with Human Immunodeficiency Virus in the United States
Wong C , Gange SJ , Moore RD , Justice AC , Buchacz K , Abraham AG , Rebeiro PF , Koethe JR , Martin JN , Horberg MA , Boyd CM , Kitahata MM , Crane HM , Gebo KA , Gill MJ , Silverberg MJ , Palella FJ , Patel P , Samji H , Thorne J , Rabkin CS , Mayor A , Althoff KN . Clin Infect Dis 2017 Background: Age-associated conditions are increasingly common among persons living with HIV. A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among persons living with HIV receiving clinical care, and differences in their prevalence by demographic subgroup. Methods: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy-exposed persons living with HIV and receiving clinical care (i.e., having ≥1 CD4 T-cell lymphocyte lab) in the U.S. during 2000-2009. Multimorbidity was irreversible, defined as having ≥2 of: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non-AIDS-related cancer. Adjusted prevalence ratios and 95% confidence intervals comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. Results: Among 22,969 adults, 79% were male, 36% black, and median baseline age was 40 years (IQR: 34-46). Between 2000-2009, multimorbidity prevalence increased from 8.2% to 22.4% (p-trend<0.001). Adjusting for age, this trend was still significant (p<0.001). There was no difference by sex, however, blacks were less likely to have multimorbidity compared to whites (aPR=0.87 [0.77,0.99]). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR=1.16 [1.01,1.34]). Hypertension and hypercholesterolemia most commonly co-occurred. Conclusions: Multimorbidity prevalence has increased among persons living with HIV. Comorbidity prevention and multi-subspecialty management of increasingly complex healthcare needs will be vital to ensuring they receive needed care. |
The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants
Lazarus RP , John J , Shanmugasundaram E , Rajan AK , Thiagarajan S , Giri S , Babji S , Sarkar R , Kaliappan PS , Venugopal S , Praharaj I , Raman U , Paranjpe M , Grassly NC , Parker EPK , Parashar UD , Tate JE , Fleming JA , Steele AD , Muliyil J , Abraham AM , Kang G . Vaccine 2017 36 (2) 273-279 BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix(R), GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677). |
Cancer-attributable mortality among people with treated human immunodeficiency virus infection in North America
Engels EA , Yanik EL , Wheeler W , Gill MJ , Shiels MS , Dubrow R , Althoff KN , Silverberg MJ , Brooks JT , Kitahata MM , Goedert JJ , Grover S , Mayor AM , Moore RD , Park LS , Rachlis A , Sigel K , Sterling TR , Thorne JE , Pfeiffer RM , Benson CA , Bosch RJ , Kirk GD , Boswell S , Mayer KH , Grasso C , Hogg RS , Harrigan PR , Montaner JSG , Yip B , Zhu J , Salters K , Gabler K , Buchacz K , Gebo KA , Carey JT , Rodriguez B , Horberg MA , Rabkin C , Jacobson LP , D'Souza G , Klein MB , Rourke SB , Rachlis AR , Globerman J , Kopansky-Giles M , Hunter-Mellado RF , Deeks SG , Martin JN , Patel P , Saag MS , Mugavero MJ , Willig J , Eron JJ , Napravnik S , Crane HM , Drozd DR , Haas D , Rebeiro P , Turner M , Bebawy S , Rogers B , Justice AC , Fiellin D , Gange SJ , Anastos K , McKaig RG , Freeman AM , Lent C , Van Rompaey SE , Morton L , McReynolds J , Lober WB , Abraham AG , Lau B , Zhang J , Jing J , Modur S , Wong C , Hogan B , Desir F , Liu B , You B . Clin Infect Dis 2017 65 (4) 636-643 Background Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. Methods We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load. Results There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts <100 cells/mm 3. PAFs for NADCs increased during 1995-2009, reaching 10.1% in 2006-2009. Conclusions Approximately 10% of deaths in PWHIV prescribed ART during 1995-2009 were attributable to cancer, but this fraction increased over time. A large proportion of cancer-attributable deaths were associated with non-Hodgkin lymphoma, lung cancer, and liver cancer. Deaths due to NADCs will likely grow in importance as AIDS mortality declines and PWHIV age. |
A Flow-Based Model of the HIV Care Continuum in the United States
Gonsalves GS , Paltiel AD , Cleary PD , Gill MJ , Kitahata MM , Rebeiro PF , Silverberg MJ , Horberg M , Abraham AG , Althoff KN , Moore R , Bosch RJ , Tang T , Hall HI , Kaplan EH . J Acquir Immune Defic Syndr 2017 75 (5) 548-553 BACKGROUND: Understanding the flow of patients through the continuum of HIV care is critical to determine how best to intervene so that the proportion of HIV-infected persons who are on antiretroviral treatment and virally suppressed is as large as possible. METHODS: Using immunological and virological data from the Centers for Disease Control and Prevention and the North American AIDS Cohort Collaboration on Research and Design from 2009 to 2012, we estimated the distribution of time spent in and dropout probability from each stage in the continuum of HIV care. We used these estimates to develop a queueing model for the expected number of patients found in each stage of the cascade. RESULTS: HIV-infected individuals spend an average of about 3.1 months after HIV diagnosis before being linked to care, or dropping out of that stage of the continuum with a probability of 8%. Those who link to care wait an additional 3.7 months on average before getting their second set of laboratory results (indicating engagement in care) or dropping out of care with probability of almost 6%. Those engaged in care spent an average of almost 1 year before achieving viral suppression on antiretroviral therapy or dropping out with average probability 13%. For patients who achieved viral suppression, the average time suppressed on antiretroviral therapy was an average of 4.5 years. CONCLUSIONS: Interventions should be targeted to more rapidly identifying newly infected individuals, and increasing the fraction of those engaged in care that achieves viral suppression. |
Sex, race, and HIV risk disparities in discontinuity of HIV care after antiretroviral therapy initiation in the United States and Canada
Rebeiro PF , Abraham AG , Horberg MA , Althoff KN , Yehia BR , Buchacz K , Lau BM , Sterling TR , Gange SJ . AIDS Patient Care STDS 2017 31 (3) 129-144 Disruption of continuous retention in care (discontinuity) is associated with HIV disease progression. We examined sex, race, and HIV risk disparities in discontinuity after antiretroviral therapy (ART) initiation among patients in North America. Adults (≥18 years of age) initiating ART from 2000 to 2010 were included. Discontinuity was defined as first disruption of continuous retention (≥2 visits separated by >90 days in the calendar year). Relative hazard ratio (HR) and times from ART initiation until discontinuity by race, sex, and HIV risk were assessed by modeling of the cumulative incidence function (CIF) in the presence of the competing risk of death. Models were adjusted for cohort site, baseline age, and CD4+ cell count within 1 year before ART initiation; nadir CD4+ cell count after ART, but before a study event, was assessed as a mediator. Among 17,171 adults initiating ART, median follow-up time was 3.97 years, and 49% were observed to have ≥1 discontinuity of care. In adjusted regression models, the hazard of discontinuity for patients was lower for females versus males [HR: 0.84; 95% confidence interval (CI): 0.79-0.89] and higher for blacks versus nonblacks (HR: 1.17; 95% CI: 1.12-1.23) and persons with injection drug use (IDU) versus non-IDU risk (HR: 1.33; 95% CI: 1.25-1.41). Sex, racial, and HIV risk differences in clinical retention exist, even accounting for access to care and known competing risks for discontinuity. These results point to vulnerable populations at greatest risk for discontinuity in need of improved outreach to prevent disruptions of HIV care. |
Effects of overburden characteristics on dynamic failure in underground coal mining
Lawson HE , Tesarik D , Larson MK , Abraham H . Int J Min Sci Technol 2016 27 (1) 121-129 Dynamic failures, or bumps, remain an imperative safety concern in underground coal mining, despite significant advancements in engineering controls. The presence of spatially discrete, stiff roof units are one feature that has been linked to these events. However, an empirical stratigraphic review indicates that no significant difference exists in the relative commonality of discrete units between bumping and non-bumping deposits. Instead an apparent relationship exists between reportable bumping and the overall stiffness of the host rock. However, this initial study is too simplistic to be conclusive; to weight the relative impact of changes in a single variable, such as the thickness or location of sandstone members, it must be examined in isolation-i.e., in a setting where all other variables are held constant. Numerical modelling provides this setting, and the effects of variability in a stiff discrete member in a hypothetical longwall mining scenario are investigated within the context of three stratigraphic types, Compliant, Intermediate and Stiff. A modelling experiment examines changes in rupture potential in stiff roof units for each stratigraphic type as discrete unit thickness and location are manipulated through a range of values. Results suggest that the stiff-to-compliant ratio of the host rock has an impact on the relative stress-inducing effects of discrete stiff members. In other words, it is necessary to consider both the thickness and the distance to the seam, within the context of the host rock, to accurately anticipate areas of elevated rupture-induced hazard; acknowledging the presence of a discrete unit within the overburden in general terms is an insufficient indicator of risk. This finding helps to refine our understanding of the role of individual stiff, strong roof members in bumping phenomena, and suggests that a holistic view of overburden lithology and site-specific numerical modelling may be necessary to improve miner safety. |
First occurrence of diabetes, chronic kidney disease, and hypertension among North American HIV-infected adults, 2000-2013
Wong C , Gange SJ , Buchacz K , Moore RD , Justice AC , Horberg MA , Gill MJ , Koethe JR , Rebeiro PF , Silverberg MJ , Palella FJ , Patel P , Kitahata MM , Crane HM , Abraham AG , Samji H , Napravnik S , Ahmed T , Thorne JE , Bosch RJ , Mayor AM , Althoff KN . Clin Infect Dis 2016 64 (4) 459-467 BACKGROUND: There remains concern regarding the occurrence of non-communicable diseases (NCDs) among individuals aging with HIV but few studies have described whether disparities between demographic subgroups are present among individuals on antiretroviral therapy (ART) with access to care. METHODS: We assessed the first documented occurrence of type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and treated hypertension (HTN) by age, sex, and race within the North American AIDS Cohort Collaboration on Research and Design. HIV-infected adults (≥18 years) who initiated ART were observed for first NCD occurrence between 1 January 2000 - 31 December 2013. Cumulative incidences as of age 70 were estimated accounting for the competing risk of death; Poisson regression was used to compare rates of NCD occurrence by demographic subgroup. RESULTS: We included >50,000 persons with >250,000 person-years (PY) of follow-up. Median follow-up was 4.7 years (interquartile range (IQR): 2.4-8.1). Rates of first occurrence (per 100 PY) were: 1.2 for DM, 0.6 for CKD, and 2.6 for HTN. Relative to non-black women, the cumulative incidences were increased in black women (68% vs. 51% for HTN, 52% vs. 41% for DM, and 38% vs. 35% for CKD; all p<0.001); this disparity was also found among men (73% vs. 60% for HTN, 44% vs. 34% for DM, and 30% vs. 25% for CKD; all p<0.001). CONCLUSIONS: Racial disparities in the occurrence of DM, CKD, and HTN emphasize the need for prevention and treatment options for these HIV populations receiving care in North America. |
Update on incidence of herpes zoster among children and adolescents after implementation of varicella vaccination, Antelope Valley, CA, 2000 to 2010
Civen R , Marin M , Zhang J , Abraham A , Harpaz R , Mascola L , Bialek SR . Pediatr Infect Dis J 2016 35 (10) 1132-6 BACKGROUND: Changes in herpes zoster (HZ) epidemiology are expected with childhood varicella vaccination. We reported previously that during 2000 to 2006 HZ incidence decreased 55% in children <10 years of age, while among 10- to 19-year olds it increased by 63%. We update the analysis with 4 additional years of data. METHODS: Population-based active surveillance was conducted for HZ in Antelope Valley, California. Structured telephone interviews and medical chart reviews collected data on demographics, varicella vaccinations, disease histories and clinical information. We calculated HZ incidence for 2007 to 2010 and assessed trends since 2000. RESULTS: Among children <10 years of age, HZ incidence continued the decreasing trend previously reported. During 2007 to 2010, the average incidence was 12.8 cases/100,000 children compared with 41.6 cases/100,000 children during 2000 to 2006, a 69% decline (P < 0.0001). For the 10- to 19-year olds, during 2007 to 2010 HZ incidence did not continue the increasing trend reported from 2000 to 2006; lower rates than in 2006 were observed in 3 of the 4 additional years evaluated. During 2007 to 2010 the average incidence was 78.2 cases/100,000 children compared with 68.0 cases/100,000 children during 2000 to 2006, a 13% increase (P = 0.123), with substantial fluctuation in annual rates throughout the 11 years of surveillance. CONCLUSIONS: During the mature varicella vaccination program, declines in HZ incidence among children <10 years of age continued through 2010. Among the 10- to 19-year olds, the increase reported through 2006 did not continue further and lower rates than in 2006 were observed through 2010. Widespread use of varicella vaccine could reduce HZ incidence among vaccinated populations. Ongoing monitoring of HZ incidence is needed to detect and understand changes in HZ epidemiology in the varicella vaccine era. |
Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000-2010
Buchacz K , Lau B , Jing Y , Bosch R , Abraham AG , Gill MJ , Silverberg MJ , Goedert JJ , Sterling TR , Althoff KN , Martin JN , Burkholder G , Gandhi N , Samji H , Patel P , Rachlis A , Thorne JE , Napravnik S , Henry K , Mayor A , Gebo K , Gange SJ , Moore RD , Brooks JT . J Infect Dis 2016 214 (6) 862-72 BACKGROUND: There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada. METHODS: We studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010. RESULTS: A total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend<.001); the rates of most individual OIs decreased as well. During 2008-2010, the leading OIs included Pneumocystis jiroveci pneumonia, esophageal candidiasis, and disseminated Mycobacterium avium complex or Mycobacterium kansasii infection. CONCLUSIONS: For HIV-infected persons in care during 2000-2010, rates of first OI were relatively low and generally declined over this time. |
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