The Infectious Disease Ontology in the Age of COVID-19

The Infectious Disease Ontology (IDO) is a suite of interoperable ontology modules that aims to provide coverage of all aspects of the infectious disease domain, including biomedical research, clinical care, and public health. IDO Core is designed to be a disease and pathogen neutral ontology, covering just those types of entities and relations that are relevant to infectious diseases generally. IDO Core is then extended by a collection of ontology modules focusing on specific diseases and pathogens. In this paper we present applications of IDO Core within various areas of infectious disease research, together with an overview of all IDO extension ontologies and the methodology on the basis of which they are built. We also survey recent developments involving IDO, including the creation of IDO Virus; the Coronaviruses Infectious Disease Ontology (CIDO); and an extension of CIDO focused on COVID-19 (IDO-CovID-19).We also discuss how these ontologies might assist in information-driven efforts to deal with the ongoing COVID-19 pandemic, to accelerate data discovery in the early stages of future pandemics, and to promote reproducibility of infectious disease research

Schistosoma mansoni extracellular vesicles: immunobiology and vaccine efficacy

Desalegn Kifle characterized the molecular composition of extracellular vesicles secreted by Schistosoma mansoni parasites. He demonstrated their role in host-parasite communication via host cell gene regulation, as well as their vaccine potential. His findings could have potential impact on our understanding of schistosome biology and the wider field of molecular parasitology

Diagnostic Markers for Schistosome-Mediated Liver Disease

Chronic schistosomiasis presents with either a moderate or a severe form, termed intestinal (INT) or hepatosplenic (HS) schistosomiasis, respectively. The Schistosoma mansoni-associated hepatomegaly is estimated in 8.5 million people and ultimately results from liver granulomas induced by trapped parasitic eggs. The CBA/J mouse model replicates these two human disease forms and was used to understand the progressive pathology that leads to HS and to identify potential biomarkers. In this model 20% of infected mice spontaneously develop hypersplenomegaly syndrome (HSS) by 20 weeks of infection while the remaining 80% develop moderate splenomegaly syndrome (MSS). Using this model, we compared the liver protein patterns of control mice and mice infected for 6, 8, 12, or 20 (MSS and HSS) weeks. Two-dimensional differential in gel electrophoresis (2D-DIGE) was used to identify protein pattern variations and protein spots were identified using matrix adsorption laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry. In the first experiment, we found 124 protein spot unique changes for MSS and HSS compared to control mice of which 80 were identified and 35 changes were specific for HSS. In the second experiment, comparison between various time points with control mice revealed 76 significant protein spot changes of which 44 were identified using MALDI-TOF mass spectrometry. Importantly, we found that the abundance of liver keratin D, transferrin isoforms, collagen isoforms, hydroxyproline and Schistosoma mansoni-phosphoenolpyruvate carboxykinase increased while epoxide hydrolase isoforms, peroxiredoxin 6 and major urinary protein (MUP) isoforms decreased significantly with infection. To verify the changes in the liver 2D-DIGE analysis, candidate liver protein markers were measured in mouse serum using targeted biochemical assays. The mouse serum analysis showed MUP levels were decreased, while transferrin, connective tissue growth factor (CTGF), keratin D, hydroxyproline were increased in HSS mice compared to control mice or MSS mice supporting the liver 2D-DIGE analysis. Using targeted assays, serum samples from INT and HS patients were tested for the candidate liver protein markers: keratin D, CTGF, hydroxyproline and transferrin. The human serum analysis showed keratin D levels increased for HS compared to INT and normal sera. The CTGF levels were high in INT compared to HS and normal sera, while transferrin remained unchanged in INT and HS similar to normal sera. Additionally, in severe HS disease, serum hydroxyproline emerged as a strong indicator of fibrosis. We believe that these findings will have direct value in the development of diagnostic tools for early detection of hepatosplenic schistosomiasis in humans

Development of a nanobody-based amperometric immunocapturing assay for sensitive and specific detection of Toxocara canis excretory-secretory antigen

Introduction Human Toxocariasis (HT) is a zoonosis that, despite of its wide distribution around the world, remains poorly diagnosed. The identification of specific IgG immunoglobulins against the Toxocara canis Excretory-Secretory antigen (TES), a mix of glycoproteins that the parasite releases during its migration to the target organs in infected patients, is currently the only laboratory tool to detect the disease. The main drawbacks of this test are the inability to distinguish past and active infections together with lack of specificity. These factors seriously hamper the diagnosis, follow-up and control of the disease. Aim To develop an amperometric immunocapturing diagnostic assay based on single domain immunoglobulins from camelids (nanobodies) for specific and sensitive detection of TES. Methods After immunization of an alpaca (Vicugna pacos) with TES, RNA from peripheral blood lymphocytes was used as template for cDNA amplification with oligo dT primers and library construction. Isolation and screening of TES-specific nanobodies were carried out by biopanning and the resulting nanobodies were expressed in Escherichia coli. Two-epitopes amperometric immunocapturing assay was designed using paramagnetic beads coated with streptavidin and bivalent nanobodies. Detection of the system was carried out with nanobodies chemically coupled to horseradish peroxidase. The reaction was measured by amperometry and the limit of detection (LOD) was compared to conventional sandwich ELISA. Results We obtained three nanobodies that specifically recognize TES with no-cross reactivity to antigens of Ascaris lumbricoides and A. suum. The LOD of the assay using PBST20 0.05% as diluent was 100 pg/ml, 10 times more sensitive than sandwich ELISA. Conclusion Sensitive and specific detection of TES for discrimination of active and past infections is one of the most difficult challenges of T. canis diagnosis. The main advantage of our system is the use of two different nanobodies that specifically recognize two different epitopes in TES with a highly sensitive and straightforward readout. Considering that the amounts of TES available for detection in clinical samples are in the range of picograms or a few nanograms maximum, the LOD found in our experiments suggests that the test is potentially useful for the detection of clinically relevant cases of HT

Automatic classification of registered clinical trials towards the Global Burden of Diseases taxonomy of diseases and injuries

Includes details on the implementation of MetaMap and IntraMap, prioritization rules, the test set of clinical trials and the classification of the external test set according to the 171 GBD categories. Dataset S1: Expert-based enrichment database for the classification according to the 28 GBD categories. Manual classification of 503 UMLS concepts that could not be mapped to any of the 28 GBD categories. Dataset S2: Expert-based enrichment database for the classification according to the 171 GBD categories. Manual classification of 655 UMLS concepts that could not be mapped to any of the 171 GBD categories, among which 108 could be projected to candidate GBD categories. Table S1: Excluded residual GBD categories for the grouping of the GBD cause list in 171 GBD categories. A grouping of 193 GBD categories was defined during the GBD 2010 study to inform policy makers about the main health problems per country. From these 193 GBD categories, we excluded the 22 residual categories listed in the Table. We developed a classifier for the remaining 171 GBD categories. Among these residual categories, the unique excluded categories in the grouping of 28 GBD categories were “Other infectious diseases” and “Other endocrine, nutritional, blood, and immune disorders”. Table S2: Per-category evaluation of performance of the classifier for the 171 GBD categories plus the “No GBD” category. Number of trials per GBD category from the test set of 2,763 clinical trials. Sensitivities, specificities (in %) and likelihood ratios for each of the 171 GBD categories plus the “No GBD” category for the classifier using the Word Sense Disambiguation server, the expert-based enrichment database and the priority to the health condition field. Table S3: Performance of the 8 versions of the classifier for the 171 GBD categories. Exact-matching and weighted averaged sensitivities and specificities for 8 versions of the classifier for the 171 GBD categories. Exact-matching corresponds to the proportion (in %) of trials for which the automatic GBD classification is correct. Exact-matching was estimated over all trials (N = 2,763), trials concerning a unique GBD category (N = 2,092), trials concerning 2 or more GBD categories (N = 187), and trials not relevant for the GBD (N = 484). The weighted averaged sensitivity and specificity corresponds to the weighted average across GBD categories of the sensitivities and specificities for each GBD category plus the “No GBD” category (in %). The 8 versions correspond to the combinations of the use or not of the Word Sense Disambiguation server during the text annotation, the expert-based enrichment database, and the priority to the health condition field as a prioritization rule. Table S4: Per-category evaluation of the performance of the baseline for the 28 GBD categories plus the “No GBD” category. Number of trials per GBD category from the test set of 2,763 clinical trials. Sensitivities and specificities (in %) of the 28 GBD categories plus the “No GBD” category for the classification of clinical trial records towards GBD categories without using the UMLS knowledge source but based on the recognition in free text of the names of diseases defining in each GBD category only. For the baseline a clinical trial records was classified with a GBD category if at least one of the 291 disease names from the GBD cause list defining that GBD category appeared verbatim in the condition field, the public or scientific titles, separately, or in at least one of these three text fields. (DOCX 84 kb

An assessment of the social impacts of water pollution on children in informal settlement : the case of Kliptown informal settlement, Soweto, Johannesburg

The study investigated the causes of water pollution in Kliptown, an informal settlement 17km south of Johannesburg. The study further examined the impact of water pollution, sanitation and inadequate and low quality water provision on children’s social life, health and well-being in informal settlements. The subject of water pollution due to inadequate water supply and sanitation is one that brings a lot of debate, due to the overwhelming impacts it has on children’s social life as well as their health. In informal settlements, social impacts arising from inadequate water supply and sanitation such as the prevalence of water-related diseases like diarrhoea, skin rashes and eye infections have become a permanent feature. This study aimed at assessing the social impacts of water pollution in Kliptown’s Tamatievlei, Mandela View and Valentine Village informal settlements. It also looked at the factors that contribute to the social impacts of water pollution and propose recommendations on how to minimise the social impacts of water pollution on children in Kliptown’s informal settlements. The study applied a mixed method approach, utilising exploratory and descriptive questions to extrapolate both qualitative and quantitative data, which was also presented in quality and quantity form. Outcomes of the investigation indicated that diarrhoea is a major waterborne disease that affects children, mostly under-five years of age, in the informal settlements and that children sometimes missed school due to their being treated for diarrhoea and other water-related illnesses. It was also found that children lived in unhygienic conditions with smelling bucket system toilets and rotting garbage. The study established that children congregated for water at water points for long periods and in the process, they were deprived of time to take part in other social activities. The study recommends mitigating inadequate, low quality water supply, water pollution and sanitation in an integrated manner to gradually eliminate the negative social impacts on children’s social life, health and well-being in Kliptown informal settlement.Environmental ScienceM.Sc. (Environmental Management

Ultrasensitive detection of toxocara canis excretory-secretory antigens by a nanobody electrochemical magnetosensor assay.

peer reviewedHuman Toxocariasis (HT) is a zoonotic disease caused by the migration of the larval stage of the roundworm Toxocara canis in the human host. Despite of being the most cosmopolitan helminthiasis worldwide, its diagnosis is elusive. Currently, the detection of specific immunoglobulins IgG against the Toxocara Excretory-Secretory Antigens (TES), combined with clinical and epidemiological criteria is the only strategy to diagnose HT. Cross-reactivity with other parasites and the inability to distinguish between past and active infections are the main limitations of this approach. Here, we present a sensitive and specific novel strategy to detect and quantify TES, aiming to identify active cases of HT. High specificity is achieved by making use of nanobodies (Nbs), recombinant single variable domain antibodies obtained from camelids, that due to their small molecular size (15kDa) can recognize hidden epitopes not accessible to conventional antibodies. High sensitivity is attained by the design of an electrochemical magnetosensor with an amperometric readout with all components of the assay mixed in one single step. Through this strategy, 10-fold higher sensitivity than a conventional sandwich ELISA was achieved. The assay reached a limit of detection of 2 and15 pg/ml in PBST20 0.05% or serum, spiked with TES, respectively. These limits of detection are sufficient to detect clinically relevant toxocaral infections. Furthermore, our nanobodies showed no cross-reactivity with antigens from Ascaris lumbricoides or Ascaris suum. This is to our knowledge, the most sensitive method to detect and quantify TES so far, and has great potential to significantly improve diagnosis of HT. Moreover, the characteristics of our electrochemical assay are promising for the development of point of care diagnostic systems using nanobodies as a versatile and innovative alternative to antibodies. The next step will be the validation of the assay in clinical and epidemiological contexts