Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
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Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America
Erchick DJ , Subedi S , Verhulst A , Guillot M , Adair LS , Barros AJD , Chasekwa B , Christian P , da Silva BGC , Silveira MF , Hallal PC , Humphrey JH , Huybregts L , Kariuki S , Khatry SK , Lachat C , Matijasevich A , McElroy PD , Menezes AMB , Mullany LC , Perez TLL , Phillips-Howard PA , Roberfroid D , Santos IS , Ter Kuile FO , Ravilla TD , Tielsch JM , Wu LSF , Katz J . Popul Health Metr 2023 21 (1) 10 INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data
Badr HS , Colston JM , Nguyen NH , Chen YT , Burnett E , Ali SA , Rayamajhi A , Satter SM , Van Trang N , Eibach D , Krumkamp R , May J , Adegnika AA , Manouana GP , Kremsner PG , Chilengi R , Hatyoka L , Debes AK , Ateudjieu J , Faruque ASG , Hossain MJ , Kanungo S , Kotloff KL , Mandomando I , Nisar MI , Omore R , Sow SO , Zaidi AKM , Lambrecht N , Adu B , Page N , Platts-Mills JA , Mavacala Freitas C , Pelkonen T , Ashorn P , Maleta K , Ahmed T , Bessong P , Bhutta ZA , Mason C , Mduma E , Olortegui MP , Peñataro Yori P , Lima AAM , Kang G , Humphrey J , Ntozini R , Prendergast AJ , Okada K , Wongboot W , Langeland N , Moyo SJ , Gaensbauer J , Melgar M , Freeman M , Chard AN , Thongpaseuth V , Houpt E , Zaitchik BF , Kosek MN . Lancet Glob Health 2023 11 (3) e373-e384 BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation. |
MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques.
DeBarry JD , Nural MV , Pakala SB , Nayak V , Warrenfeltz S , Humphrey J , Lapp SA , Cabrera-Mora M , Brito CFA , Jiang J , Saney CL , Hankus A , Stealey HM , DeBarry MB , Lackman N , Legall N , Lee K , Tang Y , Gupta A , Trippe ED , Bridger RR , Weatherly DB , Peterson MS , Jiang X , Tran V , Uppal K , Fonseca LL , Joyner CJ , Karpuzoglu E , Cordy RJ , Meyer EVS , Wells LL , Ory DS , Lee FE , Tirouvanziam R , Gutiérrez JB , Ibegbu C , Lamb TJ , Pohl J , Pruett ST , Jones DP , Styczynski MP , Voit EO , Moreno A , Galinski MR , Kissinger JC . Sci Data 2022 9 (1) 722 Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades. |
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Schiabor Barrett KM , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . Nature 2022 609 (7925) 101-108 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases(1-3). SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing(4,5). Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.
Colston JM , Zaitchik BF , Badr HS , Burnett E , Ali SA , Rayamajhi A , Satter SM , Eibach D , Krumkamp R , May J , Chilengi R , Howard LM , Sow SO , JahangirHossain M , Saha D , ImranNisar M , Zaidi AKM , Kanungo S , Mandomando I , Faruque ASG , Kotloff KL , Levine MM , Breiman RF , Omore R , Page N , Platts-Mills JA , Ashorn U , Fan YM , Shrestha PS , Ahmed T , Mduma E , Yori PP , Bhutta Z , Bessong P , Olortegui MP , Lima AAM , Kang G , Humphrey J , Prendergast AJ , Ntozini R , Okada K , Wongboot W , Gaensbauer J , Melgar MT , Pelkonen T , Freitas CM , Kosek MN . Geohealth 2022 6 (1) e2021GH000452 Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes. |
A One Health approach to child stunting: Evidence and research agenda
Gharpure R , Mor S , Viney M , Hodobo T , Lello J , Siwila J , Dube K , Robertson RC , Mutasa K , Berger CN , Hirai M , Brown T , Ntozini R , Evans C , Hoto P , Smith LE , Tavengwa NV , Joyeux M , Humphrey JH , Berendes D , Prendergast AJ . Am J Trop Med Hyg 2021 104 (5) 1620-1624 Stunting (low height for age) affects approximately one-quarter of children aged < 5 years worldwide. Given the limited impact of current interventions for stunting, new multisectoral evidence-based approaches are needed to decrease the burden of stunting in low- and middle-income countries (LMICs). Recognizing that the health of people, animals, and the environment are connected, we present the rationale and research agenda for considering a One Health approach to child stunting. We contend that a One Health strategy may uncover new approaches to tackling child stunting by addressing several interdependent factors that prevent children from thriving in LMICs, and that coordinated interventions among humans, animals, and environmental health sectors may have a synergistic effect in stunting reduction. |
Putting the "A" into WaSH: a call for integrated management of water, animals, sanitation, and hygiene
Prendergast AJ , Gharpure R , Mor S , Viney M , Dube K , Lello J , Berger C , Siwila J , Joyeux M , Hodobo T , Hurt L , Brown T , Hoto P , Tavengwa N , Mutasa K , Craddock S , Chasekwa B , Robertson RC , Evans C , Chidhanguro D , Mutasa B , Majo F , Smith LE , Hirai M , Ntozini R , Humphrey JH , Berendes D . Lancet Planet Health 2019 3 (8) e336-e337 Water, sanitation, and hygiene (WaSH) are foundational public health interventions for infectious disease control. Renewed efforts to end open defecation and provide universal access to safe drinking water, sanitation, and hygiene by 2030 are being enacted through the Sustainable Development Goals. However, results from clinical trials1, 2, 3 question the efficacy of conventional rural WaSH approaches in low-income and middle-income countries (LMICs). Randomised trials in Bangladesh,1 Kenya,2 and Zimbabwe,3 which introduced household pit latrines, hand-washing with soap, and point-of-use water chlorination, found no effect on child growth, and two of the three trials found no reductions in diarrhoea in children. We have, therefore, called for transformative WaSH approaches,4 to more effectively reduce pathogen burden and promote child health and growth in LMICs. However, currently, it remains uncertain what transformative WaSH entails. |
Contribution of maternal ART and breastfeeding to 24-month survival in HIV-exposed uninfected children: an individual pooled analysis of African and Asian studies
Arikawa S , Rollins N , Jourdain G , Humphrey J , Kourtis AP , Hoffman I , Essex M , Farley T , Coovadia HM , Gray G , Kuhn L , Shapiro R , Leroy V , Bollinger RC , Onyango-Makumbi C , Lockman S , Marquez C , Doherty T , Dabis F , Mandelbrot L , Le Coeur S , Rolland M , Joly P , Newell ML , Becquet R . Clin Infect Dis 2017 66 (11) 1668-1677 Background: Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children. Results: Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months. Conclusion: Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates. |
Estimates of burden and consequences of infants born small for gestational age in low and middle income countries with INTERGROWTH-21st standard: analysis of CHERG datasets
Lee AC , Kozuki N , Cousens S , Stevens GA , Blencowe H , Silveira MF , Sania A , Rosen HE , Schmiegelow C , Adair LS , Baqui AH , Barros FC , Bhutta ZA , Caulfield LE , Christian P , Clarke SE , Fawzi W , Gonzalez R , Humphrey J , Huybregts L , Kariuki S , Kolsteren P , Lusingu J , Manandhar D , Mongkolchati A , Mullany LC , Ndyomugyenyi R , Nien JK , Roberfroid D , Saville N , Terlouw DJ , Tielsch JM , Victora CG , Velaphi SC , Watson-Jones D , Willey BA , Ezzati M , Lawn JE , Black RE , Katz J . BMJ 2017 358 j3677 Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard.Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated.Setting CHERG birth cohorts from 14 population based sites in low and middle income countries.Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%.Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700).Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries. |
Heightened HIV antibody responses in postpartum women as exemplified by recent infection assays: implications for incidence estimates
Hargrove J , van Schalkwyk C , Humphrey J , Mutasa K , Ntozini R , Owen M , Masciotra S , Parekh B , Duong YT , Dobbs T , Kilmarx P , Gonese E . AIDS Res Hum Retroviruses 2017 33 (9) 902-904 BACKGROUND: Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. METHODS: We determined MDRIs for BED-CEIA, LAg and BRAI assays for 101 seroconverting postpartum women, recruited in Harare in 1997- 2000 during the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) Trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first nine months, or at later stages, postpartum. RESULTS: At cut-offs (C) of 0.8 for BED, 1.5 for LAg and 40% for BRAI, estimated MDRIs for postpartum mothers, were 192, 104 and 144 days, 33%, 32-41% and 52% lower than published estimates of 287, 152-177 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7 - 19% shorter for women who seroconverted in the first 9- months postpartum, compared with those seroconverting later. CONCLUSIONS: MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunologic activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states. |
High-Quality Genome Assembly and Annotation for Plasmodium coatneyi, Generated Using Single-Molecule Real-Time PacBio Technology.
Chien JT , Pakala SB , Geraldo JA , Lapp SA , Humphrey JC , Barnwell JW , Kissinger JC , Galinski MR . Genome Announc 2016 4 (5) Plasmodium coatneyi is a protozoan parasite species that causes simian malaria and is an excellent model for studying disease caused by the human malaria parasite, P. falciparum Here we report the complete (nontelomeric) genome sequence of P. coatneyi Hackeri generated by the application of only Pacific Biosciences RS II (PacBio RS II) single-molecule real-time (SMRT) high-resolution sequence technology and assembly using the Hierarchical Genome Assembly Process (HGAP). This is the first Plasmodium genome sequence reported to use only PacBio technology. This approach has proven to be superior to short-read only approaches for this species. |
Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.
Feasey NA , Hadfield J , Keddy KH , Dallman TJ , Jacobs J , Deng X , Wigley P , Barquist Barquist L , Langridge GC , Feltwell T , Harris SR , Mather AE , Fookes M , Aslett M , Msefula C , Kariuki S , Maclennan CA , Onsare RS , Weill FX , Le Hello S , Smith AM , McClelland M , Desai P , Parry CM , Cheesbrough J , French N , Campos J , Chabalgoity JA , Betancor L , Hopkins KL , Nair S , Humphrey TJ , Lunguya O , Cogan TA , Tapia MD , Sow SO , Tennant SM , Bornstein K , Levine MM , Lacharme-Lora L , Everett DB , Kingsley RA , Parkhill J , Heyderman RS , Dougan G , Gordon MA , Thomson NR . Nat Genet 2016 48 (10) 1211-1217 An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa. |
Aggregation of adenovirus 2 in source water and impacts on disinfection by chlorine
Kahler AM , Cromeans TL , Metcalfe MG , Humphrey CD , Hill VR . Food Environ Virol 2016 8 (2) 148-55 It is generally accepted that viral particles in source water are likely to be found as aggregates attached to other particles. For this reason, it is important to investigate the disinfection efficacy of chlorine on aggregated viruses. A method to produce adenovirus particle aggregation was developed for this study. Negative stain electron microscopy was used to measure aggregation before and after addition of virus particles to surface water at different pH and specific conductance levels. The impact of aggregation on the efficacy of chlorine disinfection was also examined. Disinfection experiments with human adenovirus 2 (HAdV2) in source water were conducted using 0.2 mg/L free chlorine at 5 degrees C. Aggregation of HAdV2 in source water (≥3 aggregated particles) remained higher at higher specific conductance and pH levels. However, aggregation was highly variable, with the percentage of particles present in aggregates ranging from 43 to 71 %. Upon addition into source water, the aggregation percentage dropped dramatically. On average, chlorination CT values (chlorine concentration in mg/L x time in min) for 3-log10 inactivation of aggregated HAdV2 were up to three times higher than those for dispersed HAdV2, indicating that aggregation reduced the disinfection rate. This information can be used by water utilities and regulators to guide decision making regarding disinfection of viruses in water. |
Identification of Source of Brucella suis Infection in Human by Using Whole-Genome Sequencing, United States and Tonga.
Quance C , Robbe-Austerman S , Stuber T , Brignole T , DeBess EE , Boyd L , LeaMaster B , Tiller R , Draper J , Humphrey S , Erdman MM . Emerg Infect Dis 2016 22 (1) 79-82 Brucella suis infection was diagnosed in a man from Tonga, Polynesia, who had butchered swine in Oregon, USA. Although the US commercial swine herd is designated brucellosis-free, exposure history suggested infection from commercial pigs. We used whole-genome sequencing to determine that the man was infected in Tonga, averting a field investigation. |
Fate and transport of enteric microbes from septic systems in a coastal watershed
Schneeberger CL , O'Driscoll M , Humphrey C , Henry K , Deal N , Seiber K , Hill VR , Zarate-Bermudez M . J Environ Health 2015 77 (9) 22-30 Onsite wastewater treatment systems (OWTS) are commonly used in coastal areas to treat household wastewater. These systems represent potential sources of fecal pollution of groundwater and nearby surface water. OWTS are expected to reduce microbial concentrations in wastewater; however, system and environmental factors can affect treatment efficiency and impacts on ground and surface water. In the study of OWTS described in this article, the authors sampled septic tanks and groundwater at two households in coastal North Carolina between October 2009 and October 2011. Samples were tested for the fecal indicator microbes E. coli, enterococci, and Clostridium perfringens. Microbial source tracking was also performed in year two. Results showed that enteric microbe concentrations in groundwater significantly decreased with distance from the OWTS. Human markers of fecal contamination were also detected in the OWTS and downgradient groundwater, indicating that OWTS can impact the microbial quality of shallow groundwater. |
Meteorological influences on nitrogen dynamics of a coastal onsite wastewater treatment system
O'Driscoll MA , Humphrey CP , Deal NE , Lindbo DL , Zarate-Bermudez MA . J Environ Qual 2014 43 (6) 1873-1885 On-site wastewater treatment systems (OWTS) can contribute nitrogen (N) to coastal waters. In coastal areas with shallow groundwater, OWTS are likely affected by meteorological events. However, the meteorological influences on temporal variability of N exports from OWTS are not well documented. Hydrogeological characterization and seasonal monitoring of wastewater and groundwater quality were conducted at a residence adjacent to the Pamlico River Estuary, North Carolina, during a 2-yr field study (October 2009-2011). Rainfall was elevated during the first study year, relative to the annual mean. In the second year, drought was followed by extreme precipitation from Hurricane Irene. Recent meteorological conditions influenced N speciation and concentrations in groundwater. Groundwater total dissolved nitrogen (TDN) beneath the OWTS drainfield was dominated by nitrate during the drought; during wetter periods, ammonium and organic N were common. Effective precipitation (precipitation [P] minus evapotranspiration [ET]) affected OWTS TDN exports because of its influence on groundwater recharge and discharge. Groundwater nitrate-N concentrations beneath the drainfield were typically higher than 10 mg/L when total biweekly precipitation was less than evapotranspiration (precipitation deficit: P < ET). Overall, groundwater TDN concentrations were elevated above background concentrations at distances > 15 m downgradient of the drainfield. Although OWTS nitrate inputs caused elevated groundwater nitrate concentrations between the drainfield and the estuary, the majority of nitrate was attenuated via denitrification between the OWTS and 48 m to the estuary. However, DON originating from the OWTS was mobile and contributed to elevated TDN concentrations along the groundwater flowpath to the estuary. |
Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children.
Conrad MD , LeClair N , Arinaitwe E , Wanzira H , Kakuru A , Bigira V , Muhindo M , Kamya MR , Tappero JW , Greenhouse B , Dorsey G , Rosenthal PJ . J Infect Dis 2014 210 (3) 344-53 BACKGROUND: Artemisinin-based combination therapies, including artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), are recommended to treat uncomplicated falciparum malaria. Sensitivities to components of AL and DP are impacted by polymorphisms in pfmdr1 and pfcrt. We monitored changes in prevalences of polymorphisms in Tororo, Uganda, from 2008 to 2012. METHODS: Polymorphic loci in pfmdr1 and pfcrt were characterized in samples from 312 children randomized to AL or DP for each episode of uncomplicated malaria (50 samples per arm for each 3-month interval) utilizing a fluorescent microsphere assay. Treatment outcomes and impacts of prior therapies were also characterized. RESULTS: Prevalence increased significantly over time for pfmdr1 N86 (AL: odds ratio [OR], 2.08 [95% confidence interval {CI}, 1.83-2.38]; DP: 1.41 [95% CI, 1.25-1.57]), pfmdr1 D1246 (AL: 1.46 [95% CI, 1.29-1.64]; DP: 1.36 [95% CI, 1.23-1.50]), and pfcrt K76 (AL: 3.37 [95% CI, 1.85-6.16]; DP: 5.84 [95% CI, 1.94-17.53], and decreased for pfmdr1 Y184 (AL: 0.78 [95% CI, .70-.86]; DP: 0.84 [95% CI, .76-1.50]); changes were consistently greater in the AL arm. Recent AL treatment selected for pfmdr1 N86, D1246, and 184F in subsequent episodes; DP selected for the opposite alleles. CONCLUSIONS: Genotypes with decreased sensitivity to AL components increased over time. This increase was greater in children receiving AL, suggesting that the choice of treatment regimen can profoundly influence parasite genetics and drug sensitivity. CLINICAL TRIALS REGISTRATION: NCT00527800. |
An unusual case of influenza-like illness after yellow fever vaccination
Lamson DM , Ramani R , Kleabonas M , Metcalfe M , Humphrey C , St George K . J Clin Virol 2014 60 (1) 67-9 Yellow fever (YF) is an important public health concern in areas where the disease is endemic. For more than 60 years a highly effective live attenuated vaccine has been available, its widespread use resulting in a dramatic decrease in the number of cases. On rare occasions, YF vaccine can cause mild to severe disease and rare adverse vaccine-associated events have been reported. Additionally, an average viremia of 3-5 days after administration of the YF vaccine has been published. Here we present a case where YF vaccine was isolated in cell culture from a respiratory swab collected from a patient presenting with influenza-like illness. To the best of our knowledge, this is the first report finding replicating YF vaccine in the respiratory sample of a post inoculated individual. |
Onsite wastewater system nitrogen contributions to groundwater in coastal North Carolina
Humphrey Jr C , O'Driscoll M; , Deal N , Lindbo D , Thieme S , Zarate-Bermudez M . J Environ Health 2013 76 (5) 16-22 The objective of the study described in this article was | to evaluate the nitrogen contributions from two onsite wastewater systems (sites 1 and 2) to groundwater and adjacent surface waters in coastal Beaufort County, North Carolina. Groundwater levels and water quality parameters including total nitrogen, nitrogen species, temperature, and pH were monitored from October 2009 to May 2010. Nitrogen was also tested in groundwater from deeper irrigation or drinking water wells from the two sites and six additional neighboring residences. Mean total nitrogen concentrations | in groundwater beneath onsite wastewater systems 1 and 2 were | 34.3 ± 16.7 mg/L and 12.2 ± 2.9 mg/L, respectively, and significantly higher than background groundwater concentrations (<1 mg/L). Groundwater in the deeper wells appeared not to be influenced by the onsite systems. Groundwater nitrogen concentrations typically decreased with distance down-gradient from the systems, but were still elevated relative to background conditions more than 15 m from the systems and near the estuary. This was a pioneering effort to better understand the link of onsite systems, the fate of nitrogen in the environment, and public health. |
Safe lists for medications in pregnancy: inadequate evidence base and inconsistent guidance from Web-based information, 2011
Peters SL , Lind JN , Humphrey JR , Friedman JM , Honein MA , Tassinari MS , Moore CA , Mathis LL , Broussard CS . Pharmacoepidemiol Drug Saf 2013 22 (3) 324-8 PURPOSE: Medication use during pregnancy is common and increasing. Women are also increasingly getting healthcare information from sources other than their physicians. METHODS: This report summarizes an environmental scan that identified 25 active Internet sites that list medications reported to be safe for use in pregnancy and highlights the inadequate evidence base and inconsistent guidance provided by these sites. RESULTS: These lists included 245 different products, of which 103 unique components had been previously evaluated in terms of fetal risk by the Teratogen Information System (TERIS), a resource that assesses risk of birth defects after exposure under usual conditions by consensus of clinical teratology experts. For 43 (42%) of the 103 components that were listed as 'safe' on one or more of the Internet sites surveyed, the TERIS experts were unable to determine the fetal risk based on published scientific literature. For 40 (93%) of these 43, either no data were available to assess human fetal risk or the available data were limited. CONCLUSIONS: Women who see a medication on one of these 'safe' lists would be led to believe that there is no increased risk of birth defects resulting from exposure. Thus, women are being reassured that fetal exposure to these medications is safe even though a sufficient evidence base to determine the relative safety or risk does not exist. (Copyright (c) 2013 John Wiley & Sons, Ltd.) |
Evaluation of on-site wastewater system Escherichia coli contributions to shallow groundwater in coastal North Carolina
Humphrey Jr CP , O'Driscoll MA , Zarate MA . Water Sci Technol 2011 63 (4) 789-95 The study goal was to determine if on-site wastewater systems (OSWWS) installed in coastal areas were effective at reducing indicator bacteria densities before discharge to groundwater. Groundwater Escherichia coli (E. coli) densities and groundwater levels adjacent to 16 OSWWS in three different soil groups (sand, sandy loam, and sandy clay loam) were monitored and compared to background groundwater conditions on four occasions between March 2007 and February 2008 in coastal North Carolina. Groundwater beneath OSWWS had significantly (p≤0.05) lower densities of E. coli than septic tank effluent, but significantly higher densities of E. coli than background conditions for each soil type. Twenty three percent of all groundwater samples near OSWWS had E. coli densities that exceeded the EPA freshwater contact standards (single sample 235 cfu/100 mL) for surface waters. Groundwater E. coli densities near OSWWS were highest during shallow water table periods. The results indicate that increasing the required vertical separation distance from drainfield trenches to seasonal high water table could improve shallow groundwater quality. |
The methodology of visual field testing with frequency doubling technology in the National Health and Nutrition Examination Survey, 2005-2006
Terry AL , Paulose-Ram R , Tilert TJ , Johnson CA , Zhang X , Lee PP , Saaddine JB . Ophthalmic Epidemiol 2010 17 (6) 411-21 PURPOSE: To describe the frequency doubling technology (FDT) methodology to measure visual field loss in the National Health and Nutrition Examination Survey and to evaluate data reliability. METHODS: Participants aged 40 years and older were eligible (n = 2,529) for 2 visual field tests per eye performed with the Humphrey Matrix N-30-5 screening test. Visual field loss was determined using a 2-2-1 algorithm requiring 2 complete tests per eye, with at least 2 abnormal field results in each test, and 1 common abnormal field. RESULTS: Response rate was 86.2%. Time constraints were the main reason for no exam (55.6%). Median times were: single test, 37 seconds; entire exam, 9.1 minutes. When defining reliability based on ≤ 1/3 blind spots, ≤ 1/3 false positive tests, and technician noted proper fixation, 80.1% of examined adults had 2 reliable tests for both eyes; an additional 13.4% had 2 reliable tests for 1 eye. Increasing age, decreasing visual acuity, and the presence of self-reported glaucoma resulted in decreased examination rates, increased test times, and decreased data reliability. Sensitivity and specificity to detect persons with glaucoma was 54.8% and 91.9%, respectively. CONCLUSIONS: FDT is a feasible, fast, and reliable method for visual field loss screening in a population-based U.S. study, with an 86.2% response rate, median exam time ~9 minutes, and nearly 95% of examined participants having complete, reliable results in 1 or both eyes. |
2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States
Shieh WJ , Blau DM , Denison AM , Deleon-Carnes M , Adem P , Bhatnagar J , Sumner J , Liu L , Patel M , Batten B , Greer P , Jones T , Smith C , Bartlett J , Montague J , White E , Rollin D , Gao R , Seales C , Jost H , Metcalfe M , Goldsmith CS , Humphrey C , Schmitz A , Drew C , Paddock C , Uyeki TM , Zaki SR . Am J Pathol 2010 177 (1) 166-75 In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection. |
First detection of group C rotavirus in children with acute gastroenteritis in South Korea.
Moon S , Humphrey CD , Kim JS , Baek LJ , Song JW , Song KJ , Jiang B . Clin Microbiol Infect 2010 17 (2) 244-7 Group C rotavirus (GpC RV) causes sporadic cases and outbreaks of acute diarrhea in humans worldwide, but has not been detected among children in South Korea. The aims of the present study were to detect GpC RV among children hospitalized with gastroenteritis in South Korea and perform molecular characterization of GpC RV strains. From November 2003 to January 2006, 434 fecal samples were collected from children < 10 years of age who were hospitalized for treatment of acute diarrhea and screened for group C and A rotaviruses by EIA. GpC RV strains were characterized by sequence and phylogenetic analysis.Of the 434 samples screened, two were positive for GpC RV and one had a mixed GpC and GpA RV infection. One of the strains, Icheon, shared high sequence conservation in VP4, VP6 and VP7 genes with other published GpC RV. This is the first report describing the molecular characteristics of GpC RV among children in South Korea, more surveillance is needed to determine the burden of GpC RV diarrhea. |
Identification of adenoviruses in fecal specimens from wild chimpanzees (Pan trogylodytes schweinfurthii) in western Tanzania
Tong S , Singh J , Ruone S , Humphrey C , Yip CC , Lau SK , Anderson LJ , Kaur T . Am J Trop Med Hyg 2010 82 (5) 967-70 DNA of two distinctive adenoviruses was detected in wild chimpanzees in western Tanzania that showed clinical signs of acute, upper respiratory disease, notably coughing. The amplified sequences from part of the capsid hexon gene suggests that one virus is a novel adenovirus serotype candidate and the other virus is a species C adenovirus most closely related to recent isolates from captive chimpanzees in the United States, Simian AdV 37 with 86% nucleic acid identity and Simian AdV 40 with 95% nucleic acid identity, respectively. The species C adenovirus sequences suggest possible recombination with a human adenovirus. The source of these viruses and disease association is not known. |
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