A novel platform for isotype-specific testing of autoantibodies.

The objective of this study was to test if a novel platform could be used for isotype-specific autoantibody testing in humans. Further, we evaluated if testing with this novel platform enables earlier detection of insulin autoantibodies in individuals that have first-degree relatives with type-1 diabetes than currently used approaches. Longitudinal serum samples from participants were collected before and after they converted to become positive for insulin autoantibodies by the current standardly used assays. Using a novel plasmonic gold chip platform, we tested these samples for IgM isotype-specific autoantibodies. Serial serum samples from individuals without diabetes were also tested as a comparison control cohort. Our results demonstrate proof-of-concept that a plasmonic gold chip can specifically detect the IgM insulin autoantibody. Five out of the six individuals that converted to being positive for insulin autoantibodies by standard testing had significant IgM autoantibodies on the plasmonic chip platform. The plasmonic chip platform detected IgM autoantibodies earlier than standard testing by up to 4 years. Our results indicate that the plasmonic gold platform can specifically detect the IgM isotype autoantibodies and suggest that combining isotype-specific testing with currently used approaches enables earlier detection of insulin autoantibodies in individuals that have first-degree relatives with type 1 diabetes

Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case–control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was43.1% (95% CI: 26.8-74.5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1

Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case–control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was43.1% (95% CI: 26.8-74.5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1

Enterovirus D68 and other enterovirus serotypes identified in South African patients with severe acute respiratory illness, 2009-2011

BACKGROUND : Human enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa. OBJECTIVES : We aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009-2011. PATIENTS/METHODS : Study samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay. RESULTS : 8.2% (842/10 260) of SARI cases tested positive for enterovirus; 16% (7/45) were species EV-A, 44% (20/45) EV-B, 18% (8/45) EV-C and 22% (10/45) EV-D. Seventeen different EV serotypes were identified within EV-A to EV-D, of which EV-D68 (22%; 10/45) and Echovirus 3 (11%; 5/45) were the most prevalent. CONCLUSIONS : EV-D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains.The United States Centers for Disease Control and Prevention, Atlanta, Georgia, USA (co-operative agreement number: 5U51IP000155).http://www.wileyonlinelibrary.com/journal/irvhttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1750-2659am2018Medical Virolog

The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa, 2012-2015

BACKGROUND : Viruses detected in patients with acute respiratory infections may be the cause of illness or colonizers. METHODS : We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1, 2, and 3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012-2015 in South Africa. We estimated the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses. RESULTS : We enrolled 1959 SARI, 3784 ILI and 1793 controls. Influenza virus (AF: 86.3%; 95%CI: 77.7%-91.6%), hMPV (AF: 85.6%%; 95%CI: 72.0%-92.6%), and RSV (AF: 83.7%; 95%CI: 77.5%-88.2%) infections were highly associated with severe disease, while rhinovirus (AF: 46.9%; 95%CI: 37.6%-56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6%-49.0%) were only moderately associated. The estimated detection rate associated with severe disease was: 20.2% for rhinovirus, 16.7% for RSV, 7.0% for adenovirus, 4.9% for influenza virus and 3.8% for hMPV. Similar patterns were observed for patients with ILI. CONCLUSIONS : Influenza, RSV and hMPV can be considered likely pathogens if detected in patients with ILI and SARI while rhinovirus and adenovirus were commonly identified also among controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, given their high estimated detection rate attributable to illness, they may be important contributors to disease.Co-operative agreement 5U51/IP000155 with the Centers for Disease Control and Prevention, Atlanta, Georgia, USA.http://www.elsevier.com/locate/jcv2017-02-28hb2016Medical Virolog

Development of a respiratory severity score for hospitalized adults in a high HIV-prevalence setting—South Africa, 2010-2011

BACKGROUND : Acute lower respiratory tract infections (LRTI) are a frequent cause of hospitalization and mortality in South Africa; however, existing respiratory severity scores may underestimate mortality risk in HIV-infected adults in resource limited settings. A simple predictive clinical score for low-resource settings could aid healthcare providers in the management of patients hospitalized with LRTI. METHODS : We analyzed 1,356 LRTI hospitalizations in adults aged ≥18 years enrolled in Severe Acute Respiratory Illness (SARI) surveillance in three South African hospitals from January 2010 to December 2011. Using demographic and clinical data at admission, we evaluated potential risk factors for in-hospital mortality. We evaluated three existing respiratory severity scores, CURB-65, CRB-65, and Classification Tree Analysis (CTA) Score assessing for discrimination and calibration. We then developed a new respiratory severity score using a multivariable logistic regression model for in-hospital mortality and assigned points to risk factors based on the coefficients in the multivariable model. Finally we evaluated the model statistically using bootstrap resampling techniques. RESULTS : Of the 1,356 patients hospitalized with LRTI, 101 (7.4%) died while hospitalized. The CURB-65, CRB-65, and CTA scores had poor calibration and demonstrated low discrimination with c-statistics of 0.594, 0.548, and 0.569 respectively. Significant risk factors for in-hospital mortality included age ≥ 45 years (A), confusion on admission (C), HIV-infection (H), and serum blood urea nitrogen >7 mmol/L (U), which were used to create the seven-point ACHU clinical predictor score. In-hospital mortality, stratified by ACHU score was: score ≤1, 2.4%, score 2, 6.4%, score 3, 11. 9%, and score ≥ 4, 29.3%. Final models showed good discrimination (c-statistic 0.789) and calibration (chi-square 1.6, Hosmer-Lemeshow goodness-of-fit p-value = 0.904) and discriminated well in the bootstrap sample (average optimism of 0.003). CONCLUSIONS : Existing clinical predictive scores underestimated mortality in a low resource setting with a high HIV burden. The ACHU score incorporates a simple set a risk factors that can accurately stratify patients ≥18 years of age with LRTI by in-hospital mortality risk. This score can quantify in-hospital mortality risk in an HIV-endemic, resource-limited setting with limited clinical information and if used to facilitate timely treatment may improve clinical outcomes.Additional file 1: BMC Pulmonary_Severity Score Data.xlsx. Severity Score Dataset. Dataset generated and used for analysis and creation of the ACHU score. Two tabs are included 1) includes the data used for the analysis 2) includes important notes related to the analytical methods and definitions for several composite variables.Additional file 2: Table S1. CURB-65, CRB-65, Classification Tree Analysis (CTA) severity scores. Table S2. Predicted and observed risk of mortality based on CURB-65, CRB-65, Classification Tree Analysis (CTA), and CURB-45 severity scores among hospitalized adults with lower respiratory tract infections, South Africa, 2010–2011. Table S3. Predicted and observed risk of mortality based by ACHU (Age, confusion, HIV, urea) respiratory severity score among hospitalized adults with lower respiratory tract infections, South Africa, 2010–2011.The Centers for Disease Control and Preventionhttp://www.biomedcentral.com/bmccom/plementalternmedam2017Medical Virolog

Household transmission of seasonal influenza from HIV-infected and HIV-uninfected individuals in South Africa, 2013-2014

BACKGROUND : We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases. METHODS : Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every 4 days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. RESULTS : We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio [OR] 0.2; 95% confidence interval [CI], 0.1–0.6; SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1–4 years (OR 3.6; 95% CI, 1.2–11.3) and 25–44 years (OR 8.0; 95% CI, 1.8–36.7), and contact age group 1–4 years (OR 3.5; 95% CI, 1.2–10.3) compared to 5–14 years, and sleeping with index case (OR 2.7; 95% CI, 1.3–5.5). HIV infection of index case was not associated with SI. CONCLUSIONS : HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission.The National Institute for Communicable Diseases of the National Health Laboratory Service and the US Centers for Disease Control and Prevention [co-operative agreement number: 5U51IP000155.https://academic.oup.com/jid2020-05-15hj2019Medical Virolog

Genetic diversity and molecular epidemiology of human rhinoviruses in South Africa

BACKGROUND Rhinoviruses (RV) are a well-established cause of respiratory illness. RV-C has been associated with more severe illness. We aimed to characterize and compare the clinical presentations and disease severity of different RV type circulating in South Africa. METHOD We performed two analyses of RV-positive specimens identified through surveillance in South Africa across all age groups. First, RV-positive specimens identified through severe acute respiratory illness (SARI) surveillance in four provinces was randomly selected from 2009 to 2010 for molecular characterization. Second, RV-positive specimens identified through SARI, influenzalike illness (ILI) and control surveillance at hospitals and outpatient clinics in during 2012–2013 were used to determine the association of RV type with severe disease. Selected specimens were sequenced, and phylogenetic analysis was performed. RESULTS Among the 599 sequenced specimens from 2009 to 2010 and 2012 to 2013, RV-A (285, 48%) and RV-C (247, 41%) were more commonly identified than RV-B (67, 11%), with no seasonality and a high genetic diversity. A higher prevalence of RV infection was identified in cases with SARI [515/962 (26%); aRRR = 1 6; 95% CI 1 21; 2 2] and ILI [356/962 (28%); aRRR = 1 9; 95% CI 1 37; 2 6] compared with asymptomatic controls (91/962, 22%). There was no difference in disease severity between the different type when comparing SARI, ILI and controls. CONCLUSION All three type of RV were identified in South Africa, although RV-A and RV-C were more common than RV-B. RV was associated with symptomatic respiratory illness; however, there was no association between RV type and disease severity.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1750-2659http://www.influenzajournal.comam201

The role of human immunodeficiency virus in influenza- and respiratory syncytial virus-associated hospitalizations in South African children, 2011-2016

BACKGROUND : Data describing influenza– or respiratory syncytial virus (RSV)–associated hospitalized illness in children aged <5 years in Africa are limited. METHODS : During 2011–2016, we conducted surveillance for severe respiratory illness (SRI) in children aged <5 years in 3 South African hospitals. Nasopharyngeal aspirates were tested for influenza and RSV using real-time reverse transcription polymerase chain reaction. We estimated rates of influenza- and RSV-associated hospitalized SRI by human immunodeficiency virus (HIV) status and compared children who tested positive for influenza vs RSV using multivariable penalized logistic regression. RESULTS : Among 3650 hospitalized children, 203 (5.6%) tested positive for influenza viruses, 874 (23.9%) for RSV, and 19 (0.5%) for both. The median age of children hospitalized with influenza was 13.9 months vs 4.4 months for RSV (P < .01). Annual influenza-associated hospitalization rates per 100000 were highest among infants aged 6–11 months (545; 95% confidence interval [CI], 409–703), while RSV-associated hospitalization rates were highest in infants aged 0–2 months (6593; 95% CI, 5947–7217). HIV exposure was associated with increased incidence of influenza- and RSV-associated hospitalization in infants aged 0–5 months, with relative risk (RR) 2.2 (95% CI, 1.4–3.4) and 1.4 (95% CI, 1.3–1.6), respectively. HIV infection was associated with increased incidence of influenza- and RSV-associated hospitalization in all age groups; RR 2.7 (95% CI, 2.0–3.5) and 3.8 (95% CI, 3.1–4.8), respectively. CONCLUSIONS : Influenza- and RSV-associated hospitalizations are common among South African infants. HIV infection and HIV exposure in infants increase risk of influenza- and RSV-associated hospitalization.The CDC through a cooperative agreement with the National Institute for Communicable Diseases, South Africa (5U01IP001048).http://cid.oxfordjournals.orghj2019Medical Virolog

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives