scholarly journals Multimodal biomarker discovery for active Onchocerca volvulus infection

2021 ◽  
Vol 15 (11) ◽  
pp. e0009999
Author(s):  
Ole Lagatie ◽  
Emmanuel Njumbe Ediage ◽  
Dirk Van Roosbroeck ◽  
Stijn Van Asten ◽  
Ann Verheyen ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Onchocerca Volvulus ◽  
Plasma Metabolites ◽  
Full Potential ◽  
River Blindness ◽  
Filarial Infection ◽  
Drug Candidates ◽  
Endemic Population ◽  
Transmission Studies ◽  
Urine Metabolite

The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated.

Nematodes (roundworms)

2017 ◽  
Author(s):  
Philippa C. Matthews
Keyword(s):  
Lymphatic Filariasis ◽  
Onchocerca Volvulus ◽  
River Blindness ◽  
Loa Loa ◽  
Filarial Infection ◽  
Guinea Worm ◽  
Treatment And Prevention ◽  
Clinical Syndromes

This chapter consists of short notes, diagrams, maps, and tables to summarize human nematode (‘roundworm’) infections, starting with a classification of relevant organisms. The chapter then goes on to cover Ascaris, Trichinella, Enterobius (‘pin worm’), Trichuris (‘whip worm’), Necator and Ancylostoma (‘hook worms’), and Strongyloides (‘thread worm’). The chapter concludes with a section dedicated to filarial infection, including lymphatic filariasis, Loa Loa (‘eye worm’), Onchocerca volvulus (‘river blindness’), and Dracunculus (‘Guinea worm’). For ease of reference, each topic is broken down into sections, including classification, epidemiology, microbiology, pathophysiology, clinical syndromes, diagnosis, treatment and prevention.

scholarly journals Feasibility of Localized Metabolomics in the Study of Pancreatic Islets and Diabetes

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 207 ◽  
Author(s):  
Oscar Alcazar ◽  
Luis F. Hernandez ◽  
Ashley Tschiggfrie ◽  
Michael J. Muehlbauer ◽  
James R. Bain ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Aqueous Humor ◽  
General Circulation ◽  
Biomarker Discovery ◽  
Nod Mice ◽  
Health Condition ◽  
Plasma Metabolites ◽  
Islet Transplant ◽  
Metabolic Biomarkers ◽  
Longitudinal Dataset

(1) Background: Disruption of insulin production by native or transplanted pancreatic islets caused by auto/allo-immunity leads to hyperglycemia, a serious health condition and important therapeutic challenge due to the lifelong need for exogeneous insulin administration. Early metabolic biomarkers can prompt timely interventions to preserve islet function, but reliable biomarkers are currently lacking. We explored the feasibility of “localized metabolomics” where initial biomarker discovery is made in aqueous humor samples for further validation in the circulation. (2) Methods: We conducted non-targeted metabolomic studies in parallel aqueous humor and plasma samples from diabetic and nondiabetic mice. Metabolite levels and associated pathways were compared in both compartments as well as to an earlier longitudinal dataset in hyperglycemia-progressor versus non-progressor non-obese diabetic (NOD) mice. (3) Results: We confirmed that aqueous humor samples can be used to assess metabolite levels. About half of the identified metabolites had well-correlated levels in the aqueous humor and plasma. Several plasma metabolites were significantly different between diabetic and nondiabetic animals and between males and females, and many of them were correlated with the aqueous humor. (4) Conclusions: This study provides proof-of-concept evidence that aqueous humor samples enriched with islet-related metabolites and representative of the immediate islet microenvironment following intraocular islet transplant can be used to assess metabolic changes that could otherwise be overlooked in the general circulation. The findings support localized metabolomics, with and without intraocular islet transplant, to identify biomarkers associated with diabetes and islet allograft rejection.

scholarly journals Wolbachia- and Onchocerca volvulus-Induced Keratitis (River Blindness) Is Dependent on Myeloid Differentiation Factor 88

2006 ◽  
Vol 74 (4) ◽  
pp. 2442-2445 ◽  
Author(s):  
Illona Gillette-Ferguson ◽  
Amy G. Hise ◽  
Yan Sun ◽  
Eugenia Diaconu ◽  
Helen F. McGarry ◽  
...  
Keyword(s):  
Essential Role ◽  
Onchocerca Volvulus ◽  
Filarial Nematode ◽  
Myeloid Differentiation ◽  
River Blindness ◽  
Corneal Inflammation ◽  
Differentiation Factor ◽  
Myeloid Differentiation Factor 88 ◽  
Myeloid Differentiation Factor

ABSTRACT Endosymbiotic Wolbachia bacteria that infect the filarial nematode Onchocerca volvulus were previously found to have an essential role in the pathogenesis of river blindness. The current study demonstrates that corneal inflammation induced by Wolbachia or O. volvulus antigens containing Wolbachia is completely dependent on expression of myeloid differentiation factor 88.

scholarly journals A metabolite-based machine learning approach to diagnose Alzheimer’s-type dementia in blood: Results from the European Medical Information Framework for Alzheimer’s Disease biomarker discovery cohort

2019 ◽  
Author(s):  
Daniel Stamate ◽  
Min Kim ◽  
Petroula Proitsi ◽  
Sarah Westwood ◽  
Alison Baird ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medical Information ◽  
Biomarker Discovery ◽  
Gradient Boosting ◽  
Plasma Metabolites ◽  
Csf Biomarkers ◽  
Extreme Gradient Boosting ◽  
And Gender

AbstractINTRODUCTIONMachine learning (ML) may harbor the potential to capture the metabolic complexity in Alzheimer’s Disease (AD). Here we set out to test the performance of metabolites in blood to categorise AD when compared to CSF biomarkers.METHODSThis study analysed samples from 242 cognitively normal (CN) people and 115 with AD-type dementia utilizing plasma metabolites (n=883). Deep Learning (DL), Extreme Gradient Boosting (XGBoost) and Random Forest (RF) were used to differentiate AD from CN. These models were internally validated using Nested Cross Validation (NCV).RESULTSOn the test data, DL produced the AUC of 0.85 (0.80-0.89), XGBoost produced 0.88 (0.86-0.89) and RF produced 0.85 (0.83-0.87). By comparison, CSF measures of amyloid, p-tau and t-tau (together with age and gender) produced with XGBoost the AUC values of 0.78, 0.83 and 0.87, respectively.DISCUSSIONThis study showed that plasma metabolites have the potential to match the AUC of well-established AD CSF biomarkers in a relatively small cohort. Further studies in independent cohorts are needed to validate whether this specific panel of blood metabolites can separate AD from controls, and how specific it is for AD as compared with other neurodegenerative disorders

scholarly journals Sex-Specific Metabolic Pathways Were Associated with Alzheimer’s Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1610
Author(s):  
Jin Xu ◽  
Rebecca Green ◽  
Min Kim ◽  
Jodie Lord ◽  
Amera Ebshiana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Pathways ◽  
Medical Information ◽  
Biomarker Discovery ◽  
Plasma Metabolites ◽  
Csf Biomarkers ◽  
Tryptophan Pathway ◽  
Personalised Treatment ◽  
Information Framework

Background: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives. Methods: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites’ discriminatory performance in AD. Results: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046). Conclusions: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment.

scholarly journals Beginning of the end of Onchocerciasis in the Americas

2013 ◽  
pp. 132-133
Author(s):  
Gloria Ines Palma ◽  
Sofía Duque Bernal ◽  
Ruben Santiago Nicholls
Keyword(s):  
West Africa ◽  
20Th Century ◽  
Slave Trade ◽  
Onchocerca Volvulus ◽  
Parasitic Disease ◽  
Black Flies ◽  
River Blindness ◽  
Vector Borne ◽  
Single Focus ◽  
Transmission Foci

Onchocerciasis, also known as River Blindness, is a parasitic disease caused by the nematode Onchocerca volvulus and transmitted by black flies of the genus Simulium. It is endemic in Africa, where an estimated 37 million people are infected. It is almost certain that the slave trade in the 17th and 18th centuries brought onchocerciasis from West Africa to the Americas (1), where transmission foci where established in six countries: Mexico, Guatemala, Venezuela, Brazil, Ecuador and Colombia. Since the beginning of the 20th century it was suspected that this vector borne disease was present in Colombia but the first confirmed case was not reported until 1965. The exact location of the single focus in the country was confirmed almost thirty years later in the locality of Naicioná, on the stream that bears the same name

scholarly journals Biomarkers: Delivering on the expectation of molecularly driven, quantitative health

2017 ◽  
Vol 243 (3) ◽  
pp. 313-322 ◽  
Author(s):  
Jennifer L Wilson ◽  
Russ B Altman
Keyword(s):  
Precision Medicine ◽  
Human Disease ◽  
Biomarker Discovery ◽  
Disease Diagnosis ◽  
Full Potential ◽  
The Status ◽  
The Many ◽  
The Impact ◽  
The Internet Of Things ◽  
Precision Health

Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health. Here we review themes of biomarker discovery, current implementations of biomarkers for precision health, and future opportunities and challenges for biomarker discovery. Impact statement Precision medicine evolved because of the understanding that human disease is molecularly driven and is highly variable across patients. This understanding has made biomarkers, a diverse class of biological measurements, more relevant for disease diagnosis, monitoring, and selection of treatment strategy. Biomarkers’ impact on precision medicine can be seen in cancer, pharmacogenomics, and safety. The successes in these cases suggest many more applications for biomarkers and a greater impact for precision medicine across the spectrum of human disease. The authors assess the status of biomarker-guided medical practice by analyzing themes for biomarker discovery, reviewing the impact of these markers in the clinic, and highlight future and ongoing challenges for biomarker discovery. This work is timely and relevant, as the molecular, quantitative approach of precision medicine is spreading to many disease indications.

Chemoprophylaxis of Onchocerca infections: in a controlled, prospective study ivermectin prevents calves becoming infected with O. ochengi

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 195-199 ◽  
Author(s):  
V. L. TCHAKOUTÉ ◽  
M. BRONSVOORT ◽  
V. TANYA ◽  
A. RENZ ◽  
A. J. TREES
Keyword(s):  
Public Health ◽  
West Africa ◽  
Prospective Study ◽  
Adult Worm ◽  
Control Strategies ◽  
Onchocerca Volvulus ◽  
River Blindness ◽  
Public Health Importance ◽  
Therapeutic Benefits ◽  
Northern Cameroon

Onchocerciasis (‘River Blindness’), caused by the filarial nematode Onchocerca volvulus is of major public health importance in West Africa. Ivermectin, a drug originally developed for veterinary use, is now being incorporated in control strategies but whilst it has potent efficacy against L1 larvae (microfilariae), ivermectin is not lethal to adult (L5) O. volvulus, nor to adults of the related cattle parasite O. ochengi. We have exploited this model to determine if ivermectin has prophylactic activity against naturally transmitted, O. ochengi infections in a controlled, prospective study in northern Cameroon. Calves were treated monthly with ivermectin at either 200 μg/kg or 500 μg/kg for 21 months. None of 15 treated calves developed adult worm infection, whereas 5/6 untreated controls became infected (P<0·001) with a total of 54 O. ochengi nodules, and all 5 developed patent microfilaridermia. These results have significant implications for the use of ivermectin in humans, and suggest that strategic chemotherapy at times of maximal transmission will confer prophylactic as well as therapeutic benefits.

Sign in / Sign up

Export Citation Format

Share Document