scholarly journals Supplemented nutrition increases immunity and drug efficacy in a natural host-helminth system

2019 ◽  
Author(s):  
Amy R. Sweeny ◽  
Melanie Clerc ◽  
Paulina A. Pontifes ◽  
Saudamini Venkatesan ◽  
Simon A. Babayan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Drug Efficacy ◽  
Natural Host ◽  
Chronic Infections ◽  
Gastrointestinal Helminths ◽  
Transmission Potential ◽  
Wood Mice ◽  
Balanced Diet ◽  
Helminth Infections ◽  
The World

AbstractGastrointestinal helminths are common parasites of humans, wildlife, and livestock, leading to chronic infections in large parts of the world. In humans, there is also an overlap in the incidence of malnutrition and helminth infections which can predispose individuals to higher infection burdens and reduced anthelmintic efficacy due to compromised immunity. This relationship has been well-studied in laboratory models by testing for the impact of dramatic reductions of specific nutrients on infection outcomes. However, much less is known about the benefits of whole-diet supplementation in natural host-helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) and measured resistance to the gastrointestinal nematode Heligmosomoides polygyrus and anthelmintic treatment efficacy in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, supplemented nutrition in conjunction with anthelminthic treatment significantly reduced H. polygyrus transmission potential. These large-scale improvements in condition and immunity of supplemented nutrition found in controlled and wild environments show the rapid and extensive benefits of a well-balanced diet and have important implications for using diet interventions to improve disease control programmes.Author SummaryGastrointestinal helminths are ubiquitous parasites which cause chronic infections and debilitating symptoms worldwide for human and animal populations alike. Efforts to control helminth infections rely primarily on deworming drugs. However, despite high availability and low cost of these drugs, reinfection is common and helminths remain a substantial problem in many areas of the world. One factor which contributes to the persistence of helminth infections is co-occurrence of malnutrition. Extensive work in model laboratory systems has shown that deficiencies in both macro- and micronutrients can impair host immune responses to helminth infections, but how this relationship translates to natural host-helminth systems and drug efficacy is still poorly understood. Here, we used a combination of experimental nutrition supplementation and deworming treatment in paired wood mouse populations in both wild and captive environments to determine the role of a well-balanced diet for infection control in a natural host-helminth system. We found that mice on a supplemented diet had lower burden of infection and increased drug efficacy, body condition, and immune responses. We also found that supplementation lowered transmission potential of hosts. These broad and rapid effects of increased nutrition quality have important implications for the benefits of diet interventions alongside deworming drugs.

scholarly journals Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host–helminth system

2021 ◽  
Vol 288 (1943) ◽  
pp. 20202722
Author(s):  
Amy R. Sweeny ◽  
Melanie Clerc ◽  
Paulina A. Pontifes ◽  
Saudamini Venkatesan ◽  
Simon A. Babayan ◽  
...  
Keyword(s):  
Drug Efficacy ◽  
Natural Host ◽  
Anthelmintic Treatment ◽  
Chronic Infections ◽  
Heligmosomoides Polygyrus ◽  
Transmission Potential ◽  
Wood Mice ◽  
Susceptibility To Infection ◽  
Balanced Diet ◽  
Measured Resistance

Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual's immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice ( Apodemus sylvaticus ) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus . To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.

scholarly journals Basophils and Eosinophils in Nematode Infections

2020 ◽  
Vol 11 ◽  
Author(s):  
Kazushige Obata-Ninomiya ◽  
Phillip P. Domeier ◽  
Steven F. Ziegler
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Cell Surfaces ◽  
Effector Functions ◽  
Therapeutic Drugs ◽  
Helminth Infections ◽  
The World

Helminths remain one of the most prolific pathogens in the world. Following infection helminths interact with various epithelial cell surfaces, including skin, lung, and gut. Recent works have shown that epithelial cells produce a series of cytokines such as TSLP, IL-33, and IL-25 that lead to the induction of innate and acquired type 2 immune responses, which we named Type 2 epithelial cytokines. Although basophils and eosinophils are relatively rare granulocytes under normal conditions (0.5% and 5% in peripheral blood, respectively), both are found with increased frequency in type 2 immunity, including allergy and helminth infections. Recent reports showed that basophils and eosinophils not only express effector functions in type 2 immune reactions, but also manipulate the response toward helminths. Furthermore, basophils and eosinophils play non-redundant roles in distinct responses against various nematodes, providing the potential to intervene at different stages of nematode infection. These findings would be helpful to establish vaccination or therapeutic drugs against nematode infections.

ADDRESSING THE ISSUE OF СOVID-19, SARS-COV-2 VIRUS AND THE DISEASE

2020 ◽  
Vol 99 (6) ◽  
pp. 15-31
Author(s):  
A.A. Korenkova ◽  
◽  
E.M. Mayorova ◽  
V.V. Bahmetjev ◽  
M.V. Tretyak ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Herd Immunity ◽  
Significant Problem ◽  
Prevention Measures ◽  
Optimal Therapy ◽  
The World ◽  
Public Health Challenge ◽  
Coronavirus Infection

The new coronavirus infection has posed a major public health challenge around the world, but new data on the disease raises more questions than answers. The lack of optimal therapy is a significant problem. The article examines the molecular mechanisms of SARS-CoV-2 infection and the pathogenesis of COVID-19, special attention is paid to features of pathological processes and immune responses in children. COVID-19 leads to a wide diversity of negative outcomes, many of which can persist for at least months. Many of the consequences have yet to be identified. SARS-CoV-2 may provoke autoimmune reactions. Reinfection, herd immunity, vaccines and other prevention measures are also discussed in this review.

scholarly journals Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Low Income ◽  
Controlled Trial ◽  
Interferon Γ ◽  
Population Differences ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Helminth Infections ◽  
Registration Number ◽  
Randomised Controlled

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.

Vaccination today and tomorrow

1995 ◽  
Vol 15 (6) ◽  
pp. 493-502 ◽  
Author(s):  
F. Brown
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Molecular Level ◽  
Critical Issue ◽  
Natural Host ◽  
Increasing Knowledge ◽  
Empirical Approaches

The vaccines against infectious diseases in use today are, with few exceptions, prepared from the causal agents themselves, either by inactivating them with a chemical such as formaldehyde or by attenuating them so that they grow and thus evoke an immune response in the natural host but cause no disease. These empirical approaches have produced many highly successful vaccines. Increasing knowledge at the molecular level of the agents and of the immune response to protein antigent is now providing us with the opportunity to design vaccines that will elicit protective responses without the need to use the agents themselves. The critical issue is to identify the immune responses that correlate with protection.

Putrescine and its metabolic precursor arginine promote biofilm and c-di-GMP synthesis in Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Zhexian Liu ◽  
Sarzana S. Hossain ◽  
Zayda Morales Moreira ◽  
Cara H. Haney
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune Responses ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Bacterial Pathogen ◽  
Guanosine Monophosphate ◽  
Genetic Approach ◽  
Chronic Infections ◽  
Host Immune Responses ◽  
Primary Mechanism

Pseudomonas aeruginosa , an opportunistic bacterial pathogen can synthesize and catabolize a number of small cationic molecules known as polyamines. In several clades of bacteria polyamines regulate biofilm formation, a lifestyle-switching process that confers resistance to environmental stress. The polyamine putrescine and its biosynthetic precursors, L-arginine and agmatine, promote biofilm formation in Pseudomonas spp. However, it remains unclear whether the effect is a direct effect of polyamines or through a metabolic derivative. Here we used a genetic approach to demonstrate that putrescine accumulation, either through disruption of the spermidine biosynthesis pathway or the catabolic putrescine aminotransferase pathway, promoted biofilm formation in P. aeruginosa . Consistent with this observation, exogenous putrescine robustly induced biofilm formation in P. aeruginosa that was dependent on putrescine uptake and biosynthesis pathways. Additionally, we show that L-arginine, the biosynthetic precursor of putrescine, also promoted biofilm formation, but via a mechanism independent of putrescine or agmatine conversion. We found that both putrescine and L-arginine induced a significant increase in the intracellular level of bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) (c-di-GMP), a bacterial second messenger widely found in Proteobacteria that upregulates biofilm formation. Collectively these data show that putrescine and its metabolic precursor arginine promote biofilm and c-di-GMP synthesis in P. aeruginosa . Importance: Biofilm formation allows bacteria to physically attach to a surface, confers tolerance to antimicrobial agents, and promotes resistance to host immune responses. As a result, regulation of biofilm is often crucial for bacterial pathogens to establish chronic infections. A primary mechanism of biofilm promotion in bacteria is the molecule c-di-GMP, which promotes biofilm formation. The level of c-di-GMP is tightly regulated by bacterial enzymes. In this study, we found that putrescine, a small molecule ubiquitously found in eukaryotic cells, robustly enhances P. aeruginosa biofilm and c-di-GMP. We propose that P. aeruginosa may sense putrescine as a host-associated signal that triggers a lifestyle switching that favors chronic infection.

Clinical Management Updates for Novel Corona Virus (COVID-19)

2021 ◽  
Vol 14 (3) ◽  
pp. 5449-5456
Author(s):  
Yogesh Chand Yadav ◽  
Ramakant Yadav ◽  
Sushant Kumar
Keyword(s):  
Clinical Management ◽  
Respiratory Illness ◽  
Symptomatic Treatment ◽  
Structural Features ◽  
Therapeutic Agents ◽  
Human Coronavirus ◽  
Transmission Potential ◽  
The World ◽  
Severe Respiratory Illness ◽  
Droplet Transmission

The SARS-CoV-2 virus was first detected in Wuhan, China in December 2019 and was known to produce acute severe respiratory illness in humans which rapidly spread almost throughout the world within a few months. This human coronavirus has seven strains and they commonly produce illness in the nervous system, respiratory system and hepato- intestinal systems. This present review is an attempt to illustrate recent reports pertaining to the management of SARS-CoV-2. Further, it also highlights the diagnosis and clinical management of COVID-19. Various search engines like Scopus, Pubmed and WHO databases were accessed and literature on current advances about COVID-19 including structural features, replication, possible pathogenic, symptoms, diagnosis, prognosis, methods of prevention and possible therapeutic agents used for treatment of patients was reviewed. Current studies indicate that COVID-19 is very infectious with droplet transmission potential. The key modalities to prevent the infection is by keeping social distancing, respiratory/hand hygiene, detection of infection and subsequent quarantine of the infected persons. Presently, either no vaccine for prevention or specific treatments available, however, COVID-19 patients may be managed by using some repositioned drugs and symptomatic treatment.

scholarly journals Analysis of Structures and Epitopes of Surface Antigen Glycoproteins Expressed in Bradyzoites ofToxoplasma gondii

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hua Cong ◽  
Min Zhang ◽  
Qingli Zhang ◽  
Jing Gong ◽  
Haizi Cong ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Surface Antigen ◽  
Protein Sequence ◽  
Protozoan Parasite ◽  
3D Models ◽  
Chronic Infections ◽  
Homologous Proteins ◽  
Protein Sequence Alignment

Toxoplasma gondiiis a protozoan parasite capable of infecting humans and animals. Surface antigen glycoproteins, SAG2C, -2D, -2X, and -2Y, are expressed on the surface of bradyzoites. These antigens have been shown to protect bradyzoites against immune responses during chronic infections. We studied structures of SAG2C, -2D, -2X, and -2Y proteins using bioinformatics methods. The protein sequence alignment was performed by T-Coffee method. Secondary structural and functional domains were predicted using software PSIPRED v3.0 and SMART software, and 3D models of proteins were constructed and compared using the I-TASSER server, VMD, and SWISS-spdbv. Our results showed that SAG2C, -2D, -2X, and -2Y are highly homologous proteins. They share the same conserved peptides and HLA-I restricted epitopes. The similarity in structure and domains indicated putative common functions that might stimulate similar immune response in hosts. The conserved peptides and HLA-restricted epitopes could provide important insights on vaccine study and the diagnosis of this disease.

scholarly journals Early epidemiological assessment of the transmission potential and virulence of coronavirus disease 2019 (COVID-19) in Wuhan City: China, January-February, 2020

2020 ◽  
Author(s):  
Kenji Mizumoto ◽  
Katsushi Kagaya ◽  
Gerardo Chowell
Keyword(s):  
Basic Reproduction Number ◽  
Reproduction Number ◽  
Public Health Intervention ◽  
Ecological Modelling ◽  
The Novel ◽  
Wuhan City ◽  
Transmission Potential ◽  
The World ◽  
Novel Coronavirus ◽  
Epidemiological Parameters

AbstractBackgroundSince the first cluster of cases was identified in Wuhan City, China, in December, 2019, coronavirus disease 2019 (COVID-19) rapidly spread around the world. Despite the scarcity of publicly available data, scientists around the world have made strides in estimating the magnitude of the epidemic, the basic reproduction number, and transmission patterns. Accumulating evidence suggests that a substantial fraction of the infected individuals with the novel coronavirus show little if any symptoms, which highlights the need to reassess the transmission potential of this emerging disease. In this study, we derive estimates of the transmissibility and virulence of COVID-19 in Wuhan City, China, by reconstructing the underlying transmission dynamics using multiple data sources.MethodsWe employ statistical methods and publicly available epidemiological datasets to jointly derive estimates of transmissibility and severity associated with the novel coronavirus. For this purpose, the daily series of laboratory–confirmed COVID-19 cases and deaths in Wuhan City together with epidemiological data of Japanese repatriated from Wuhan City on board government–chartered flights were integrated into our analysis.ResultsOur posterior estimates of basic reproduction number (R) in Wuhan City, China in 2019–2020 reached values at 3.49 (95%CrI: 3.39–3.62) with a mean serial interval of 6.0 days, and the enhanced public health intervention after January 23rd in 2020 was associated with a significantly reduced R at 0.84 (95%CrI: 0.81–0.88), with the total number of infections (i.e. cumulative infections) estimated at 1906634 (95%CrI: 1373500–2651124) in Wuhan City, elevating the overall proportion of infected individuals to 19.1% (95%CrI: 13.5–26.6%). We also estimated the most recent crude infection fatality ratio (IFR) and time–delay adjusted IFR at 0.04% (95% CrI: 0.03%–0.06%) and 0.12% (95%CrI: 0.08–0.17%), respectively, estimates that are several orders of magnitude smaller than the crude CFR estimated at 4.06%ConclusionsWe have estimated key epidemiological parameters of the transmissibility and virulence of COVID-19 in Wuhan, China during January-February, 2020 using an ecological modelling approach. The power of this approach lies in the ability to infer epidemiological parameters with quantified uncertainty from partial observations collected by surveillance systems.

scholarly journals Clinical efficacy and safety of alemtuzumab in postmarketing practice

2019 ◽  
pp. 56-62
Author(s):  
N. V. Khachanova
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Drug Efficacy ◽  
Safety Monitoring ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Treatment Benefit ◽  
Dosing Schedule ◽  
The World ◽  
Multiple Sclerosis Treatment

Clinical trials confirm alemtuzumab efficacy for multiple sclerosis treatment in terms of both conventional measures and combined criteria such as NEDA (no evidence of disease activity). However, established drug efficacy and convenient dosing schedule are balanced by the risk of serious adverse events. Therefore, it is necessary to inform physicians about the benefits of alemtuzumab therapy along with the pattern of its safety profile.The present review provides the analysis of alemtuzumab real-world studies in Europe, USA and other parts of the world. The information obtained can help physicians to prescribe and administer the drug properly and to perform effective safety monitoring for early detection of adverse events and saving the maximum treatment benefit for the patient.

Sign in / Sign up

Export Citation Format

Share Document