FeverTracker app – an example of big data science that can improve health outcomes in India

Big Data has been in the news for some time now. The COVID-19 pandemic has highlighted its uses in healthcare at the popular level when simple mobile apps have been used to collect large amounts of public data quickly, allowing scientists to advise governments on the best methods for tackling this health emergency. Jyoti Chibber-Goel describes another similar effort in a remote region of India where technology and Big Data are helping to fight the scourge of malaria that took more than half-a-million lives around the world in 2020

A perspective on SARS-CoV-2 and community transmission in the top COVID-19 affected nations

In most countries, during the initial months of the COVID-19 outbreak resources were directed to mitigation measures that prevented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from symptomatic individuals. The coverage of the pre-symptomatic and asymptomatic individuals' testing required intensive clinical sampling along with rigorous symptom-based screening. Based on the SARS-CoV-2 transmission, the disease outbreak across nations was divided into four distinct stages: (i) epidemic, (ii) community transmission, (iii) local transmission, and (iv) imported cases. Here we discuss the COVID-19 community transmission stage for the top ten COVID-19 affected nations. Epidemic dynamics and policies implemented to contain the spread of SARS-CoV-2 infection varied globally. Further, the mitigation strategies and related health policies for dealing with the pandemic were based on the stages of transmission of the disease. We suggest that correctly identifying the transmission stage during a pandemic ensures the implementation of mitigation strategies. Thus prompt analysis of the status of COVID-19 transmission stage(s) in any nation seems crucial to direct health policies accordingly

The profiles of first and second SARS-CoV-2 waves in the top ten COVID-19 affected countries

In March 2020, the World Health Organization (WHO) acknowledged the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a "public health emergency of international concern." Within a month, coronavirus disease 2019 (COVID-19) was declared a pandemic. As of 21 July 2021, 192.8 million cases and 4.13 million deaths have been attributed to COVID-19 worldwide. Here we discuss the data from top ten COVID-19 affected countries, with an emphasis on the average strolling period of 6 to 8 months between first and second wave in these nations. Our study ascertains that analysis of the data from countries temporally ahead of others during the pandemic gives policymakers the chance to strategize and postpone or mitigate subsequent COVID-19 waves. With governments throughout the globe continuing their immunisation efforts, a study of the key indicators of COVID-19 waves from the top ten countries is critical to preparing the healthcare system to save millions of lives

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 (Campylobacter rectus, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations

Engagement Rules That Underpin DBL-DARC Interactions for Ingress of Plasmodium knowlesi and Plasmodium vivax Into Human Erythrocytes

Malaria parasite erythrocytic stages comprise of repeated bursts of parasites via cyclical invasion of host erythrocytes using dedicated receptor-ligand interactions. A family of erythrocyte-binding proteins from Plasmodium knowlesi (Pk) and Plasmodium vivax (Pv) attach to human Duffy antigen receptor for chemokines (DARC) via their Duffy binding-like domains (DBLs) for invasion. Here we provide a novel, testable and overarching interaction model that rationalizes even contradictory pieces of evidence that have so far existed in the literature on Pk/Pv-DBL/DARC binding determinants. We further address the conundrum of how parasite-encoded Pk/Pv-DBLs recognize human DARC and collate evidence for two distinct DARC integration sites on Pk/Pv-DBLs

The metabolite trimethylamine-N-oxide is an emergent biomarker of human health

Trimethylamine-N-oxide (TMAO) is a low molecular weight metabolite whose production is dependent on metabolism of its precursors choline, carnitine, creatinine, betaine or lecithin by host gut microbes resulting in the synthesis of trimethylamine (TMA), which is subsequently oxidized to TMAO via hepatic flavin monooxygenase (FMO). TMAO is associated with microbial dysbiosis and is being studied for its linkage with cardiovascular disorders. In addition, dysregulated levels of TMAO have been linked with renal diseases, neurological disorders and cancer. Here we discuss the enzymatic and metabolic landscape that results in TMAO production, and in addition, collate data from numerous clinical studies that have assessed TMAO as a biomarker for various disease conditions. We also summarize the interaction of TMAO with modern and traditional drugs that together affect circulating TMAO levels in the human body

The complex metabolism of trimethylamine in humans: Endogenous and exogenous sources

Trimethylamine (TMA) is a tertiary amine with a characteristic fishy odour. It is synthesised from dietary constituents, including choline, L-carnitine, betaine and lecithin by the action of microbial enzymes during both healthy and diseased conditions in humans. Trimethylaminuria (TMAU) is a disease typified by its association with the characteristic fishy odour because of decreased TMA metabolism and excessive TMA excretion. Besides TMAU, a number of other diseases are associated with abnormal levels of TMA, including renal disorders, cancer, obesity, diabetes, cardiovascular diseases and neuropsychiatric disorders. Aside from its role in pathobiology, TMA is a precursor of trimethylamine-N-oxide that has been associated with an increased risk of athero-thrombogenesis. Additionally, TMA is a major air pollutant originating from vehicular exhaust, food waste and animal husbandry industry. The adverse effects of TMA need to be monitored given its ubiquitous presence in air and easy absorption through human skin. In this review, we highlight multifaceted attributes of TMA with an emphasis on its physiological, pathological and environmental impacts. We propose a clinical surveillance of human TMA levels that can fully assess its role as a potential marker of microbial dysbiosis-based diseases

Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis.

The prolyl-tRNA synthetase (PRS) is a validated drug target for febrifugine and its synthetic analog halofuginone (HFG) against multiple apicomplexan parasites including Plasmodium falciparum and Toxoplasma gondii. Here, a novel ATP-mimetic centered on 1-(pyridin-4-yl) pyrrolidin-2-one (PPL) scaffold has been validated to bind to Toxoplasma gondii PRS and kill toxoplasma parasites. PPL series exhibited potent inhibition at the cellular (T. gondii parasites) and enzymatic (TgPRS) levels compared to the human counterparts. Cell-based chemical mutagenesis was employed to determine the mechanism of action via a forward genetic screen. Tg-resistant parasites were analyzed with wild-type strain by RNA-seq to identify mutations in the coding sequence conferring drug resistance by computational analysis of variants. DNA sequencing established two mutations, T477A and T592S, proximal to terminals of the PPL scaffold and not directly in the ATP, tRNA, or L-pro sites, as supported by the structural data from high-resolution crystal structures of drug-bound enzyme complexes. These data provide an avenue for structure-based activity enhancement of this chemical series as anti-infectives