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At least 19 records

Bioactive peptoids against vector-borne parasitic diseases

Protozoan parasites represent a severe threat to global human health as they are responsible for infection in Malaria, and a range of Neglected Tropical Diseases (NTDs) including Chagas disease, leishmaniasis and African sleeping sickness. Often treatments for protozan parasites are limited in their efficacy and drug resistance is an emerging problem. The current efforts to develop new treatments for the aforementioned diseases have been met with limited success and as such novel compound classes for development are being actively sought. Peptoids are peptidomimetics that have showed promise as antimicrobial agents but their application in the field of vector-borne parasitic diseases is highly underdeveloped. Herein, a library of over 50 peptoids containing a wide variety of chemical functionalities has been prepared and biologically evaluated against a range of protozoan parasitic targets. Selected members of the peptoid library were found to have potent anti-parasitic activity and good selectivity indices (SI). For example, peptoid 29 [NamyNspeNspe)(NhArgNspeNspe)]2 had an IC50 of 0.05 μM against Plasmodium falciparum and a SI > 100.

Antiparasitic↗

Public health applications of remote sensing of vector borne and parasitic diseases

Results of an investigation of the potential application of remote sensing to various fields of public health are presented. Specific topics discussed include: detection of snail habitats in connection with the epidemiology of schistosomiasis; the detection of certain Anopheles breeding sites, and location of transient human populations, both in connection with malaria eradication programs; and detection of overwintering population sites for the primary screwworm (Cochliomyia americana). Emphasis was placed on the determination of ground truth data on the biological, chemical, and physical characteristics of ground waters which would or would not support the growth of significant populations of mosquitoes.

Source record↗

HI-STAR. Health Improvements through Space Technologies and Resources: Executive Summary

Our mission is to develop and promote a global strategy to help combat malaria using space technology. Like the tiny yet powerful mosquito, HI-STAR (Health Improvements Through Space Technologies and Resources) is a small program that aspires to make a difference. Timely detection of malaria danger zones is essential to help health authorities and policy makers make decisions about how to manage limited resources for combating malaria. In 2001, the technical support network for prevention and control of malaria epidemics published a study. HI-STAR focuses on malaria because it is the most common and deadly of the vector-borne diseases. Malaria also shares many commonalities with other diseases, which means the global strategy developed here may also be applicable to other parasitic diseases. HI-STAR would like to contribute to the many malaria groups already making great strides in the fight against malaria. Some examples include: Roll Back Malaria, The Special Program for Research and Training in Tropical Diseases (TDR) and the Multilateral Initiative on Malaria (MIM). Other important groups that are among the first to include space technologies in their model include: The Center for Health Application of Aerospace Related Technologies (CHAART) and Mapping Malaria Risk in Africa (MARA). Malaria is a complex and multi-faceted disease. Combating it must therefore be equally versatile. HI-STAR incorporates an interdisciplinary, international, intercultural approach.called 'Malaria Early Warning Systems; Concepts, Indicators and Partners.' This study, funded by Roll Back Malaria, a World Health Organization initiative, offers a framework for a monitoring and early warning system. HI-STAR seeks to build on this proposal and enhance the space elements of the suggested framework. It is the work of fifty-three professionals and students from the International Space University's 2002 Summer Session Program held in California, USA.

Finarelli, Margaret G.↗

Biochemical basis for the regulation of biosynthesis of antiparasitics by bacterial hormones

Diffusible small molecule microbial hormones drastically alter the expression profiles of antibiotics and other drugs in actinobacteria. For example, avenolide (a butenolide) regulates the production of avermectin, derivatives of which are used in the treatment of river blindness and other parasitic diseases. Butenolides and γ-butyrolactones control the production of pharmaceutically important secondary metabolites by binding to TetR family transcriptional repressors. Here, we describe a concise, 22-step synthetic strategy for the production of avenolide. We present crystal structures of the butenolide receptor AvaR1 in isolation and in complex with avenolide, as well as those of AvaR1 bound to an oligonucleotide derived from its operator. Biochemical studies guided by the co-crystal structures enable the identification of 90 new actinobacteria that may be regulated by butenolides, two of which are experimentally verified. These studies provide a foundation for understanding the regulation of microbial secondary metabolite production, which may be exploited for the discovery and production of novel medicines.

59 BASIC BIOLOGICAL SCIENCES↗

TOMS as a monitor of the ultraviolet radiation environment: Applications to photobiology

The flux of biologically relevant ultraviolet radiation that reaches the surface of the Earth varies with the ozone amount, surface reflectivity, and cloudcover. The Total Ozone Mapping Spectrometer (TOMS) provides information relevant to all three items. A recent application of satellite-based ozone measurements has been to develop climatologies of the biologically significant UV-B radiation reaching the Earth's surface. A growing body of research suggests that UV-B radiation tends to suppress the immune system of laboratory mice. At tropical latitudes, it is likely that parasitical diseases develop most readily in people who have experienced immune system suppression from UV-B exposure. The computed distribution of surface radiation combined with information on disease incidence may clarify the role of UV-B as a suppressor of the human immune system. TOMS used in conjunction with radiative transfer calculations can provide information of relevance in photobiology.

Frederick, John E.↗

Biodiversity and disease risk in an algal biofuel system: An experimental test in outdoor ponds using a before-after-control-impact (BACI) design

For outdoor cultivation of algal feedstocks to become a commercially viable and sustainable option for biofuel production, algal cultivation must maintain high yields and temporal stability in environmentally variable outdoor ponds. One of the main challenges is mitigating disease outbreaks that leads to culture crashes. Drawing on predictions from the ‘dilution effect’ hypothesis, in which increased biodiversity is thought to reduce disease risk in a community, a teste of whether algal polycultures would reduce disease risk and improve feedstock production efficiencies compared to monocultures was performed. While the positive benefits of biodiversity on disease risk have been demonstrated in various systems, to the best of our knowledge this is the first test in an algal biofuel system. Here, the results a before-after-control-impact (BACI) experimental design to compare mean monoculture (control) and polyculture (impact) yield, stability, and productivity before and after fungal infection when grown in 400-L outdoor raceway ponds are presented. It has been found that polycultures did not experience a reduction in disease risk compared to monocultures or differ in production efficiencies throughout the course of the 43-day experiment. These results show that polyculture feedstocks can maintain similar levels of productivity, stability, and disease resistance to that of a monoculture. Determining whether these results are generalizable or represent one case study requires additional outdoor experiments using a larger variety of host and pathogen species.

09 BIOMASS FUELS↗

Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum -Infected Erythrocytes

While there is ample evidence suggesting that carriers of heterozygous hemoglobin S and C are protected from life-threatening malaria, little is known about the underlying biochemical mechanisms at the single cell level. In this work, using nanofocused scanning X-ray fluorescence microscopy, we quantify the spatial distribution of individual elements in subcellular compartments, including Fe, S, P, Zn, and Cu, in Plasmodium falciparum -infected ( P. falciparum -infected) erythrocytes carrying the wild type or variant hemoglobins. Our data indicate that heterozygous hemoglobin S and C significantly modulate biochemical reactions in parasitized erythrocytes, such as aberrant hemozoin mineralization and a delay in hemoglobin degradation. The label-free scanning X-ray fluorescence imaging has great potential to quantify the spatial distribution of elements in subcellular compartments of P. falciparum -infected erythrocytes and unravel the biochemical mechanisms underpinning disease and protective traits.

59 BASIC BIOLOGICAL SCIENCES↗

Improving Decision-Making Activities for Meningitis and Malaria

Public health professionals are increasingly concerned about the potential impact that climate variability and change can have on infectious disease. The International Research Institute for Climate and Society (IRI) is developing new products to increase the public health community's capacity to understand, use and demand the appropriate climate data and climate information to mitigate the public health impacts of climate on infectious disease, in particular meningitis and malaria. In this paper, we present the new and improved products that have been developed for: (i) estimating dust aerosol for forecasting risks of meningitis and (ii) for monitoring temperature and rainfall and integrating them into a vectorial capacity model for forecasting risks of malaria epidemics. We also present how the products have been integrated into a knowledge system (IRI Data Library Map Room, SERVIR) to support the use of climate and environmental information in climate-sensitive health decision-making.

parasitic diseases↗

Linking Climate to Incidence of Zoonotic Cutaneous Leishmaniasis (L. major) in Pre-Saharan North Africa

Shifts in surface climate may have changed the dynamic of zoonotic cutaneous leishmaniasis (ZCL) in the pre-Saharan zones of North Africa. Caused by Leishmania major, this form multiplies in the body of rodents serving as reservoirs of the disease. The parasite is then transmitted to human hosts by the bite of a Phlebotomine sand fly (Diptera: Psychodidae) that was previously fed by biting an infected reservoir. We examine the seasonal and interannual dynamics of the incidence of this ZCL as a function of surface climate indicators in two regions covering a large area of the semi-arid Pre-Saharan North Africa. Results suggest that in this area, changes in climate may have initiated a trophic cascade that resulted in an increase in ZCL incidence. We find the correlation between the rainy season precipitation and the same year Normalized Difference Vegetation Index (NDVI) to be strong for both regions while the number of cases of ZCL incidence lags the precipitation and NDVI by 2 years. The zoonotic cutaneous leishmaniasis seasonal dynamic appears to be controlled by minimum temperatures and presents a 2-month lag between the reported infection date and the presumed date when the infection actually occurred. The decadal increase in the number of ZCL occurrence in the region suggests that changes in climate increased minimum temperatures sufficiently and created conditions suitable for endemicity that did not previously exist. We also find that temperatures above a critical range suppress ZCL incidence by limiting the vector's reproductive activity.

NDIV↗

A non-traditional crystal-based compound screening method targeting the ATP binding site of Plasmodium falciparum GRP78 for identification of novel nucleoside analogues

Drug resistance to front-line malarial treatments represents an ongoing threat to control malaria, a vector borne infectious disease. The malarial parasite, Plasmodium falciparum has developed genetic variants, conferring resistance to the current standard therapeutic artemisinin and its derivatives commonly referred to as artemisinin-combination therapies (ACTs). Emergence of multi-drug resistance parasite genotypes is a warning of potential treatment failure, reaffirming the urgent and critical need to find and validate alternate drug targets to prevent the spread of disease. An attractive and novel drug target includes glucose-regulated protein 78 kDa (GRP78, or BiP), an essential molecular chaperone protein involved in the unfolded protein response that is upregulated in ACT treated P. falciparum parasites. We have shown that both sequence and structure are closely related to human GRP78 (hGRP78), a chaperone belonging to the HSP70 class of ATPase proteins, which is often upregulated in cellular stress responses and cancer. By screening a library of nucleoside analogues, we identified eight ‘hit’ compounds binding at the active site of the ATP binding domain of P. falciparum GRP78 using a high-throughput ligand soaking screen using x-ray crystallography. These compounds were further evaluated using protein thermal shift assays to assess target binding activity. The nucleoside analogues identified from our screen provide a starting point for the development of more potent and selective antimalarial inhibitors. In addition, we have established a well-defined, high-throughput crystal-based screening approach that can be applied to many crystallizable P. falciparum proteins for generating anti-Plasmodium specific compounds.

59 BASIC BIOLOGICAL SCIENCES↗

Moving With Parasites: Relationships Between Animal Movement and Infectious Disease Across Systems and Scales

Animal movement patterns are important for ecological processes such as population dynamics and infectious disease transmission. Because animals move in response to environmental cues like temperature and precipitation, changes to the environment – whether they are seasonal, interannual, or long-term – can change these processes, leading to changes in population sizes or infectious disease prevalence across space and time. My work uses a combination of simulation modeling and data analysis at multiple spatial and temporal scales to understand the environment-movement-disease connection in diverse animal taxa and environments. In this seminar, I will highlight the diverse ways that the environment can influence infectious disease dynamics via changes to animal movement patterns, including through a global study of migration in ungulate populations, a study of American White Ibis adapting to urban environments in South Florida, and examples of avian influenza prevalence in wild waterfowl. Together, these examples highlight that understanding environment-movement interactions can help predict how infectious disease dynamics might change in the future, as changes to climate, land use, and habitats alter animal movement patterns.

Animal movement↗

A scoping review of zoonotic parasites and pathogens associated with abattoirs in Eastern Africa and recommendations for abattoirs as disease surveillance sites

Abattoirs are facilities where livestock are slaughtered and are an important aspect in the food production chain. There are several types of abattoirs, which differ in infrastructure and facilities, sanitation and PPE practices, and adherence to regulations. In each abattoir facility, worker exposure to animals and animal products increases their risk of infection from zoonotic pathogens. Backyard abattoirs and slaughter slabs have the highest risk of pathogen transmission because of substandard hygiene practices and minimal infrastructure. These abattoir conditions can often contribute to environmental contamination and may play a significant role in disease outbreaks within communities. To assess further the risk of disease, we conducted a scoping review of parasites and pathogens among livestock and human workers in abattoirs across 13 Eastern African countries, which are hotspots for zoonoses. Our search results (n = 104 articles) showed the presence of bacteria, viruses, fungi, and macroparasites (nematodes, cestodes, etc.) in cattle, goats, sheep, pigs, camels, and poultry. Most articles reported results from cattle, and the most frequent pathogen detected was Mycobacterium bovis, which causes bovine tuberculosis. Some articles included worker survey and questionnaires that suggested how the use of PPE along with proper worker training and safe animal handling practices could reduce disease risk. Based on these findings, we discuss ways to improve abattoir biosafety and increase biosurveillance for disease control and mitigation. Abattoirs are a ‘catch all’ for pathogens, and by surveying animals at abattoirs, health officials can determine which diseases are prevalent in different regions and which pathogens are most likely transmitted from wildlife to livestock. We suggest a regional approach to biosurveillance, which will improve testing and data gathering for enhanced disease risk mapping and forecasting. Next generation sequencing will be key in identifying a wide range of pathogens, rather than a targeted approach.

60 APPLIED LIFE SCIENCES↗

Development of a Colorimetric Loop-Mediated Isothermal Amplification Assay for the Detection of Trypanosoma cruzi in Low-Resource Settings

Chagas disease is an inflammatory parasitic infection caused by Trypanosoma cruzi (T. cruzi). Early diagnosis is crucial in guiding treatment and slowing disease progression; however, current diagnostic methods have insufficient detection limits and often require skilled technicians. Molecular tests, especially isothermal nucleic acid assays, are advantageous due to their excellent sensitivity, specificity, speed, and simplicity. Here, we optimized a colorimetric loop-mediated isothermal amplification (LAMP) assay for T. cruzi. We can detect as few as 2 genomic copies/reaction using three different T. cruzi strains. We examined selectivity using other parasitic protozoans and successfully detected T. cruzi DNA extracted from parasites in human whole blood down to 1.2 parasite equivalents/reaction. We also performed a blinded study using canine blood samples and established a 100% sensitivity, specificity, and accuracy for the colorimetric LAMP assay. Finally, we used a heated 3D printer bed and an insulated thermos cup to demonstrate that the LAMP incubation step could be performed with accessible, low-cost materials. Altogether, we have developed a high-performing assay for T. cruzi with a simple colorimetric output that would be ideal for rapid, low-cost screening at the point of use.

60 APPLIED LIFE SCIENCES↗

Identifying Geographic Areas at Risk of Soil-transmitted Helminthes Infection Using Remote Sensing and Geographical Information Systems: Boaco, Nicaragua as a Case Study

Several types of intestinal nematodes, that can infect humans and specially school-age children living in poverty, develop part of their life cycle in soil. Presence and survival of these parasites in the soil depend on given environmental characteristics like temperature and moisture that can be inferred with remote sensing (RS) technology. Prevalence of diseases caused by these parasitic worms can be controlled and even eradicated with anthelmintic drug treatments and sanitation improvement. Reliable and updated identification of geographic areas at risk is required to implement effective public health programs; to calculate amount of drug required and to distribute funding for sanitation projects. RS technology and geographical information systems (GIS) will be used to analyze for associations between in situ prevalence and remotely sensed data in order to establish RS proxies of environmental parameters that indicate the presence of these parasits. In situ data on helminthisasis will be overlaid over an ecological map derived from RS data using ARC Map 9.3 (ESRI). Temperature, vegetation, and distance to bodies of water will be inferred using data from Moderate-Resolution Imaging Spectroradiometer (MODIS) and Landsat TM and ETM+. Elevation will be estimated with data from The Shuttle Radar Topography Mission (SRTM). Prevalence and intensity of infections are determined by parasitological survey (Kato Katz) of children enrolled in rural schools in Boaco, Nicaragua, in the communities of El Roblar, Cumaica Norte, Malacatoya 1, and Malacatoya 2). This study will demonstrate the importance of an integrated GIS/RS approach to define clusters and areas at risk. Such information will help to the implementation of time and cost efficient control programs and sanitation efforts.

Moreno, Max J.↗

Effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum and ileum in broiler chickens

Coccidiosis, an intestinal disease caused by Eimeria parasites, is responsible for major losses in the poultry industry by impacting chicken health. The gut microbiota is associated with health factors, such as nutrient exchange and immune system modulation, requiring understanding on the effects of Eimeria infection on the gut microbiota. This study aimed to determine the effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum (CeL and CeM) and ileum (IlL and IlM) at multiple time points (days 3, 5, 7, 10, and 14) post-infection. E. acervulina infection decreased evenness in CeL microbiota at day 10, increased richness in CeM microbiota at day 3 before decreasing richness at day 14, and decreased richness in IlL microbiota from day 3 to 10. CeL, CeM, and IlL microbiota differed between infected and control birds based on beta diversity at varying time points. Infection reduced relative abundance of bacterial taxa and some predicted metabolic pathways known for short-chain fatty acid production in CeL, CeM, and IlL microbiota, but further understanding of metabolic function is required. Despite E. acervulina primarily targeting the duodenum, our findings demonstrate the infection can impact bacterial diversity and abundance in the cecal and ileal microbiota.

59 BASIC BIOLOGICAL SCIENCES↗

Surface, Water and Air Biocharacterization - A Comprehensive Characterization of Microorganisms and Allergens in Spacecraft Environment

A Comprehensive Characterization of Microorganisms and Allergens in Spacecraft (SWAB) will use advanced molecular techniques to comprehensively evaluate microbes on board the space station, including pathogens (organisms that may cause disease). It also will track changes in the microbial community as spacecraft visit the station and new station modules are added. This study will allow an assessment of the risk of microbes to the crew and the spacecraft. Research Summary: Previous microbial analysis of spacecraft only identify microorganisms that will grow in culture, omitting greater than 90% of all microorganisms including pathogens such as Legionella (the bacterium which causes Legionnaires' disease) and Cryptosporidium (a parasite common in contaminated water) The incidence of potent allergens, such as dust mites, has never been systematically studied in spacecraft environments and microbial toxins have not been previously monitored. This study will use modern molecular techniques to identify microorganisms and allergens. Direct sampling of the ISS allows identification of the microbial communities present, and determination of whether these change or mutate over time. SWAB complements the nominal ISS environmental monitoring by providing a comparison of analyses from current media-based and advanced molecular-based technologies.

Pierson, Duane L.↗