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Objectives: Due to large sample sizes, electronic medical records (EMR) databases have the potential to provide pivotal insights into patients diagnosed with rare, orphan, or emerging diseases. This study aimed to explore the patient profile of African and American trypanosomiasis, both vector-borne parasitic diseases, pre-and post the COVID-19 pandemic using the TriNetX Network. Method(s): From Jan 1, 2018 - Nov 30, 2019 (pre-COVID) and Jan 1, 2020 - Nov 30, 2021 (post-COVID) patients were queried from the TriNetX Global health research network, inclusive of 88 million patients from the United States (US), Europe, the Middle East, Africa, Latin America, and Asia Pacific. Eligible patients with an ICD-10 diagnosis code of African trypanosomiasis or American trypanosomiasis were identified (2280 patients on 22-Dec-2022) and analyzed separately, pre- and post-COVID. Result(s): We identified 340 patients pre- and 960 patients post-COVID with African trypanosomiasis and 960 patients pre- and 190 patients post-COVID with American trypanosomiasis. Most patients resided in the US. Pre-COVID African trypanosomiasis patients had a mean age of 38 and were 59% female while post-COVID patients had a mean age of 34 and were 57% female. Pre-COVID American trypanosomiasis patients had a mean age of 49 and were 57% female while post-COVID patients had a mean age of 49 and were 53% female. Top co-diagnoses included diseases of the respiratory (85%, 84%) and nervous systems (82%, 79%) for patients with African trypanosomiasis and diseases of the digestive (69%, 54%) and circulatory systems (68%, 61%) for patients with American trypanosomiasis in both the pre- and post-COVID cohorts, respectively. Conclusion(s): Using real-world EMR data we were able to obtain patient profiles for a rare disease (African trypanosomiasis) and a common, emerging disease (American trypanosomiasis). This informationsupportsutilizing EMR data for describing patient populations in rare, orphan, or emerging diseases, which may aid drug development for these indications.Copyright © 2023
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These proceedings contains 30 articles that covered various topics related to immunology and related fields. The conference papers presented focused on investigating the role of genetics, microbiome, and immunological pathways in disease pathogenesis and treatment. Studies presented at the conference explored the genetic factors associated with obesity in Brazilian children, the role of flavonoids in reprogramming microglia towards a neuroprotective inflammatory profile, the gut microbiome in asthmatic individuals, and the involvement of the MTOR gene and its variants in the severity of COVID-19. Other studies evaluated the immunodiagnostic potential of a protein exclusive to Corynebacterium pseudotuberculosis, genetic markers associated with alcohol dependence and asthma, and the effects of nicotine on glial cells in Parkinson's disease. The conference also presented research on the molecular mechanisms associated with the anti-glioma and immunomodulatory effects of flavonoids, the influence of Trypanosoma cruzi co-infection on the immune response and clinical outcome of patients with cutaneous leishmaniasis, and the association of metalloproteinase gene variants with periodontitis. Furthermore, the papers presented discussed the production of Zika virus singular peptide for the development of serological immunassays, and the role of genetic polymorphisms in the IL1B and IL6 genes in periodontitis. Lastly, the conference included research on the immunological response of broiler chickens fed with diet supplemented with zinc, and the modulatory effects of Agatis flavone on the glial response in an ex vivo model of brain trauma.
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Background: African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The continued lack of new trypanocides has precipitated drug misuse and overuse, thus contributing to the development of the AATr phenotype. In this study, we investigated the threat associated with AATr by using the major globally available chemotherapeutical agents. Methods: A total of seven electronic databases were screened for an article on trypanocide resistance in AATr by using keywords on preclinical and clinical trials with the number of animals with treatment relapse, days taken to relapse, and resistant gene markers using the PRISMA checklist. Data were cleaned using the SR deduplicator and covidence and analyzed using Cochrane RevMan®. Dichotomous outputs were presented using risk ratio (RR), while continuous data were presented using the standardized mean difference (SMD) at a 95% confidence interval. Results: A total of eight publications in which diminazene aceturate (DA), isometamidium chloride (ISM), and homidium chloride/bromide (HB) were identified as the major trypanocides were used. In all preclinical studies, the development of resistance was in the order of HB > ISM > DA. DA vs. ISM (SMD = 0.15, 95% CI: -0.54, 0.83; I 2 = 46%, P = 0.05), DA vs. HB (SMD = 0.96, 95% CI: 0.47, 1.45; I 2 = 0%, P = 0.86), and HB vs. ISM (SMD = -0.41, 95% CI: -0.96, 0.14; I 2 = 5%, P = 0.38) showed multiple cross-resistance. Clinical studies also showed evidence of multi-drug resistance on DA and ISM (RR = 1.01, 95% CI: 0.71-1.43; I 2 = 46%, P = 0.16). To address resistance, most preclinical studies increased the dosage and the treatment time, and this failed to improve the patient's prognosis. Major markers of resistance explored include TbAT1, P1/P2 transporters, folate transporters, such as F-I, F-II, F-III, and polyamine biosynthesis inhibitors. In addition, immunosuppressed hosts favor the development of AATr. Conclusion: AATr is a threat that requires a shift in the current disease control strategies in most developing nations due to inter-species transmission. Multi-drug cross-resistance against the only accessible trypanocides is a major public health risk, justifying the need to revise the policy in developing countries to promote control of African trypanosomiasis.
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The year 2019 is a outbreak year during which the whole globe has suffered from Covid19 pandemic which has been spotted initially in China and later spread to the whole world;as a result of this viral disease, the whole world had shut down affecting billions of people but till today the Covid battle is on and people are suffering not only from this disease but also in terms of economy, starving being jobless etc. This paper briefs about Corona virus, its types, and structure;the replication and spreading of this virus, Covid19 detection methods, research on vaccination developed across the world to curb this virus;virus impact on various sectors, precautions to be taken to stay away from this virus and Ayurvedic remedy for it. The waves of corona had taken many lives on the globe & have its effect on life style of people. To curb this virus, prevention vaccination has to be found and we people must change in a way so that we could avoid future consequences for the upcoming generation. Keywords.
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We analyzed epidemiologic characteristics and distribution of 492 deaths related to Chagas disease and coronavirus disease (COVID-19) co-infection in Brazil during MarchâDecember 2020. Cumulative co-infected death rates were highest among advanced age groups, persons of Afro-Brazilian ethnicity and with low education levels, and geographically distributed mainly in major Chagas diseaseâendemic areas.
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COVID-19 , Chagas Disease , Coinfection , Humans , Brazil/epidemiology , Coinfection/epidemiology , Chagas Disease/epidemiologyABSTRACT
Scientists in Africa, Asia and Europe from a range of disciplines have been researching these diseases of poverty as part of Zoonoses and Emerging Livestock Systems (ZELS), a United Kingdom Department for International Development (DFID) and UK Research and Innovation funded programme. Managing zoonoses A finding that treating cattle with insecticides to combat ticks and tsetse flies can contain the risk of sleeping sickness in people offers the possibility of simple and cost-effective disease-management strategies. Discovering that the majority of schistosomiasis transmission and sickness in Senegal and Niger is driven not by a human schistosome species, as had been previously assumed, but through schistosome species from people and their livestock combining to form highly transmissible viable parasitic hybrids, has helped ensure the WHO embraces a One Health approach to eliminating of a disease that infects more than 240 million people globally.
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Infections by protozoa can cause some of the most serious human diseases, particularly in tropical regions. However, the number of available drugs used to treat such diseases tends to be limited with relatively high toxicity, and the vast majority of such drugs were developed in the 1920s to 1970s. The development of antiprotozoal drugs has been hindered owing in part to: (1) the highly complicated life cycles of such organisms and their ability to avoid innate immune defences;(2) challenges associated with culturing such organisms particularly in different phases of their growth and amplification;and (3) a lack of investment in biomedical research aimed at developing treatments for tropical diseases that do not tend to affect more affluent countries. Indeed, only three new drugs have entered into clinical trials in recent times, highlighting the tremendous gap in knowledge that should be bridged to more effectively treat protozoal infections.
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Human African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas disease) are vector-borne neglected tropical diseases, caused by the protozoan parasites Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases were circumscribed to South American and African countries in the past. However, human migration, military interventions, and climate changes have had an important effect on their worldwide propagation, particularly Chagas disease. Currently, the treatment of trypanosomiasis is not ideal, becoming a challenge in poor populations with limited resources. Exploring natural products from higher plants remains a valuable approach to find new hits and enlarge the pipeline of new drugs against protozoal human infections. This review covers the recent studies (2016-2021) on plant terpenoids, and their semi-synthetic derivatives, which have shown promising in vitro and in vivo activities against Trypanosoma parasites.
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BACKGROUND: In recent years, a programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections led to a rapid decline in cases in the Mandoul focus of Chad. To represent the biology of transmission between humans and tsetse, we previously developed a mechanistic transmission model, fitted to data between 2000 and 2013 which suggested that transmission was interrupted by 2015. The present study outlines refinements to the model to: (1) Assess whether elimination of transmission has already been achieved despite low-level case reporting; (2) quantify the role of intensified interventions in transmission reduction; and (3) predict the trajectory of gHAT in Mandoul for the next decade under different strategies. METHOD: Our previous gHAT transmission model for Mandoul was updated using human case data (2000-2019) and a series of model refinements. These include how diagnostic specificity is incorporated into the model and improvements to the fitting method (increased variance in observed case reporting and how underreporting and improvements to passive screening are captured). A side-by-side comparison of fitting to case data was performed between the models. RESULTS: We estimated that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (95% credible interval (CI) 99.9-100%, Specificity = 99.9%), the high screening and low infection levels mean that some recently reported cases with no parasitological confirmation might be false positives. We also find that the focus-wide tsetse reduction estimated through model fitting (95% CI 96.1-99.6%, Reduction = 99.1%) is comparable to the reduction previously measured by the decline in tsetse catches from monitoring traps. In line with previous results, the model suggests that transmission was interrupted in 2015 due to intensified interventions. CONCLUSIONS: We recommend that additional confirmatory testing is performed in Mandoul to ensure the endgame can be carefully monitored. More specific measurement of cases, would better inform when it is safe to stop active screening and vector control, provided there is a strong passive surveillance system in place.
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Trypanosomiasis, African , Animals , Chad/epidemiology , Humans , Mass Screening , Trypanosoma brucei gambiense , Trypanosomiasis, African/diagnosis , Trypanosomiasis, African/epidemiology , Trypanosomiasis, African/prevention & controlABSTRACT
Objective: To explore the pharmacological mechanism of Xuanbai Qingfei Jiedu Decoction in the treatment of coronavirus disease 2019 (COVID-19) on account of network pharmacology.
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Filovirus ebolavirus (ZE; Zaire ebolavirus, Bundibugyo ebolavirus), Neisseria meningitidis (NM), and Trypanosoma brucei (Tb) are serious infectious pathogens, spanning viruses, bacteria and protists and all may target the blood and central nervous system during their life cycle. NM and Tb are extracellular pathogens while ZE is obligatory intracellular, targetting immune privileged sites. By using interactomics and comparative evolutionary analysis we studied whether conserved human proteins are targeted by these pathogens. We examined 2797 unique pathogen-targeted human proteins. The information derived from orthology searches of experimentally validated protein-protein interactions (PPIs) resulted both in unique and shared PPIs for each pathogen. Comparing and analyzing conserved and pathogen-specific infection pathways for NM, TB and ZE, we identified human proteins predicted to be targeted in at least two of the compared host-pathogen networks. However, four proteins were common to all three host-pathogen interactomes: the elongation factor 1-alpha 1 (EEF1A1), the SWI/SNF complex subunit SMARCC2 (matrix-associated actin-dependent regulator of chromatin subfamily C), the dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1 (RPN1), and the tubulin beta-5 chain (TUBB). These four human proteins all are also involved in cytoskeleton and its regulation and are often addressed by various human pathogens. Specifically, we found (i) 56 human pathogenic bacteria and viruses that target these four proteins, (ii) the well researched new pandemic pathogen SARS-CoV-2 targets two of these four human proteins and (iii) nine human pathogenic fungi (yet another evolutionary distant organism group) target three of the conserved proteins by 130 high confidence interactions.
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OBJECTIVES: One Health is transiting from multidisciplinary to transdisciplinary concepts and its viewpoints should move from 'proxy for zoonoses', to include other topics (climate change, nutrition and food safety, policy and planning, welfare and well-being, antimicrobial resistance (AMR), vector-borne diseases, toxicosis and pesticides issues) and thematic fields (social sciences, geography and economics). This work was conducted to map the One Health landscape in Africa. METHODS: An assessment of existing One Health initiatives in Sub-Saharan African (SSA) countries was conducted among selected stakeholders using a multi-method approach. Strengths, weaknesses, opportunities and threats to One Health initiatives were identified, and their influence, interest and impacts were semi-quantitatively evaluated using literature reviews, questionnaire survey and statistical analysis. RESULTS: One Health Networks and identified initiatives were spatiotemporally spread across SSA and identified stakeholders were classified into four quadrants. It was observed that imbalance in stakeholders' representations led to hesitation in buying-in into One Health approach by stakeholders who are outside the main networks like stakeholders from the policy, budgeting, geography and sometimes, the environment sectors. CONCLUSION: Inclusion of theory of change, monitoring and evaluation frameworks, and tools for standardized evaluation of One Health policies are needed for a sustained future of One Health and future engagements should be outputs- and outcomes-driven and not activity-driven. National roadmaps for One Health implementation and institutionalization are necessary, and proofs of concepts in One Health should be validated and scaled-up. Dependence on external funding is unsustainable and must be addressed in the medium to long-term. Necessary policy and legal instruments to support One Health nationally and sub-nationally should be implemented taking cognizance of contemporary issues like urbanization, endemic poverty and other emerging issues. The utilization of current technologies and One Health approach in addressing the ongoing pandemic of COVID-19 and other emerging diseases are desirable. Finally, One Health implementation should be anticipatory and preemptive, and not reactive in containing disease outbreaks, especially those from the animal sources or the environment before the risk of spillover to human.
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BACKGROUND: Riverine species of tsetse (Glossina) transmit Trypanosoma brucei gambiense, which causes Gambian human African trypanosomiasis (gHAT), a neglected tropical disease. Uganda aims to eliminate gHAT as a public health problem through detection and treatment of human cases and vector control. The latter is being achieved through the deployment of 'Tiny Targets', insecticide-impregnated panels of material which attract and kill tsetse. We analysed the spatial and temporal distribution of cases of gHAT in Uganda during the period 2010-2019 to assess whether Tiny Targets have had an impact on disease incidence. METHODS: To quantify the deployment of Tiny Targets, we mapped the rivers and their associated watersheds in the intervention area. We then categorised each of these on a scale of 0-3 according to whether Tiny Targets were absent (0), present only in neighbouring watersheds (1), present in the watersheds but not all neighbours (2), or present in the watershed and all neighbours (3). We overlaid all cases that were diagnosed between 2000 and 2020 and assessed whether the probability of finding cases in a watershed changed following the deployment of targets. We also estimated the number of cases averted through tsetse control. RESULTS: We found that following the deployment of Tiny Targets in a watershed, there were fewer cases of HAT, with a sampled error probability of 0.007. We estimate that during the intervention period 2012-2019 we should have expected 48 cases (95% confidence intervals = 40-57) compared to the 36 cases observed. The results are robust to a range of sensitivity analyses. CONCLUSIONS: Tiny Targets have reduced the incidence of gHAT by 25% in north-western Uganda.
Subject(s)
Insect Control/methods , Insect Vectors/drug effects , Insecticides/pharmacology , Public Health/standards , Trypanosoma brucei gambiense/pathogenicity , Trypanosomiasis, African/epidemiology , Trypanosomiasis, African/prevention & control , Tsetse Flies/drug effects , Animals , Gambia , Humans , Incidence , Insect Vectors/parasitology , Public Health/methods , Tsetse Flies/parasitology , Uganda/epidemiologyABSTRACT
Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite-host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.
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Many control programmes against neglected tropical diseases have been interrupted due to the coronavirus disease 2019 (COVID-19) pandemic, including those that rely on active case finding. In this study we focus on gambiense human African trypanosomiasis (gHAT), where active screening was suspended in the Democratic Republic of Congo (DRC) due to the pandemic. We use two independent mathematical models to predict the impact of COVID-19 interruptions on transmission and reporting and achievement of the 2030 elimination of transmission (EOT) goal for gHAT in two moderate-risk regions of the DRC. We consider different interruption scenarios, including reduced passive surveillance in fixed health facilities, and whether this suspension lasts until the end of 2020 or 2021. Our models predict an increase in the number of new infections in the interruption period only if both active screening and passive surveillance were suspended, and with a slowed reduction-but no increase-if passive surveillance remains fully functional. In all scenarios, the EOT may be slightly pushed back if no mitigation, such as increased screening coverage, is put in place. However, we emphasise that the biggest challenge will remain in the higher-prevalence regions where EOT is already predicted to be behind schedule without interruptions unless interventions are bolstered.
Subject(s)
COVID-19/epidemiology , Communicable Disease Control/organization & administration , Trypanosomiasis, African/epidemiology , Trypanosomiasis, African/prevention & control , Democratic Republic of the Congo/epidemiology , Humans , Models, Theoretical , Neglected Diseases/epidemiology , Neglected Diseases/prevention & control , Pandemics , Population Surveillance , SARS-CoV-2 , Trypanosoma brucei gambienseABSTRACT
The global disruptions caused by the coronavirus disease 2019 crisis posed a threat to the momentum the vector control team at the Liverpool School of Tropical Medicine (LSTM) and the Programme National de Lutte contre la Tryaponosomiase Humaine Africaine (PNLTHA) had built in their efforts to control tsetse fly populations in the Democratic Republic of Congo. But despite the pandemic and global lockdown, field activities did continue and the same impressive results in tsetse fly reduction were observed and the team followed this by completing a round of 'tiny target' deployment without any external presence. Such a success was possible due to the investment in vector control capacity strengthening undertaken by the LSTM and PNLTHA.