Journal: Pathogens and global health
Free-living amoebae (FLA) are potential reservoirs of Legionella in aquatic environments. However, the parasitic relationship between various Legionella and amoebae remains unclear. In this study, surface water samples were gathered from two rivers for evaluating parasitic Legionella. Warmer water temperature is critical to the existence of Legionella. This result suggests that amoebae may be helpful in maintaining Legionella in natural environments because warmer temperatures could enhance parasitisation of Legionella in amoebae. We next used immunomagnetic separation (IMS) to identify extracellular Legionella and remove most free Legionella before detecting the parasitic ones in selectively enriched amoebae. Legionella pneumophila was detected in all the approaches, confirming that the pathogen is a facultative amoebae parasite. By contrast, two obligate amoebae parasites, Legionella-like amoebal pathogens (LLAPs) 8 and 9, were detected only in enriched amoebae. However, several uncultured Legionella were detected only in the extracellular samples. Because the presence of potential hosts, namely Vermamoeba vermiformis, Acanthamoeba spp. and Naegleria gruberi, was confirmed in the samples that contained intracellular Legionella, uncultured Legionella may survive independently of amoebae. Immunomagnetic separation and amoebae enrichment may have referential value for detecting parasitic Legionella in surface waters.
Policy prescriptions for combating dengue fever tend to focus on addressing environmental and social conditions of poverty. However, while poverty has long been considered a determinant of dengue, the research evidence for such a relationship is not well established. Results of a systematic review of the research literature designed to identify and assess the current state of the empirical evidence for the dengue-poverty link reveal a mixed story. Of 260 peer-reviewed articles referencing dengue-poverty relationships, only 12 English-language studies empirically assessed these relationships. Our analysis covering various social and economic conditions of poverty showed no clear associations with dengue rates. While nine of the 12 studies demonstrated some positive associations between measures of dengue and poverty (measured inconsistently through income, education, structural housing condition, overcrowding, and socioeconomic status), nine also presented null results and five with negative results. Of the five studies relating to access to water and sanitation, four reported null associations. Income and physical housing conditions were more consistently correlated with dengue outcomes than other poverty indicators. The small size of this sample, and the heterogeneity of measures and scales used to capture conditions of poverty, make it difficult to assess the strength and consistency of associations between various poverty indicators and dengue outcomes. At present, the global body of eligible English-language peer-reviewed literature investigating dengue-poverty relationships is too small to support a definitive relationship. We conclude that more research, particularly using standardized measures of both outcomes and indicators, is needed to support evidence-informed policies and approaches.
Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified. Brazilian strains clustered all together and closely related to the French Polynesia isolates. A strong presence of a negatively selected site in the envelope gene (Env) protein was evidenced, suggesting a probable purging of deleterious polymorphisms in functionally important genes. Our results show relative conservancy of ZIKV sequences when envelope and other non-structural proteins (NS3 and NS5) are analyzed by homology modeling. However, some regions within the consensus sequence of NS5 protein and to a lesser extent in the envelope protein, show localized high mutation frequency corresponding to a considerable alteration in protein stability. In terms of viral immune escape, envelope protein is under a higher selective pressure than NS5 and NS3 proteins for HLA class I and II molecules. Moreover, envelope mutations that are not strictly related to T-cell immune responses are mostly located on the surface of the protein in putative B-cell epitopes, suggesting an important contribution of B cells in the immune response as well.
Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa’s poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions. Although the recent increase in LF case reports is likely due to improved surveillance, recent studies suggest that future socio-ecological changes in West Africa may drive increases in LF burden. Future research should focus on the geographical distribution and disease burden of LF, in order to improve its integration into public policy and disease control strategies.
As the most recent outbreak of Ebola virus disease (EVD) in West Africa continues to grow since its initial recognition as a Public Health Emergency of International Concern, an unanswered question is what is the cost of a case of Ebola? Understanding this cost will help decision makers better understand the impact of each case of EVD, benchmark this against that of other diseases, prioritize which cases may require response, and begin to estimate the cost of Ebola outbreaks. To date, the scientific literature has not characterized this cost per case. Therefore, we developed a mathematical model to estimate the cost of an EVD case from the provider and societal perspectives in the three most affected countries of Guinea, Liberia, and Sierra Leone. Our model estimates the total societal cost of an EVD case with full recovery ranges from $480 to $912, while that of an EVD case not surviving ranges from $5929 to $18 929, varying by age and country. Therefore, as of 10 December 2014, the estimated total societal costs of all reported EVD cases in these three countries range from $82 to potentially over $356 million.
It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials.
This study aimed to explore geographic distribution and molecular characterization of cutaneous leishmaniasis (CL) species by amplifying two popular markers in kinetoplast DNA and internal transcribed spacer 1 loci by nested-PCR, and characterized by sequencing and phylogenetic analyses. Findings demonstrated that two species co-existed in the province: L. tropica (88.5%) and L. major (11.5%). All gender and age groups were equally infected, although males, 21-30 years old, exhibited a significantly higher infection. Sequencing and phylogenetic analyses of 34 randomly selected samples showed that L. tropica isolates exhibited some degree of heterogeneity. Both anthroponotic CL and zoonotic CL are present in south-eastern Iran with predominance of L. tropica species. Some level of heterogeneity was observed in L. tropica isolates which possibly reflects different colonies in the area. Implementation of diagnostic tools directly from clinical samples could be an important strategic approach for exploration of spatial distribution, molecular characterization and phylogenetic analyses.
Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.
The GPI (Glycosylphosphatidylinositol) biosynthetic pathway is a multistep conserved pathway in eukaryotes that culminates in the generation of GPI glycolipid which in turn anchors many proteins (GPI-APs) to the cell surface. In spite of the overall conservation of the pathway, there still exist subtle differences in the GPI pathway of mammals and other eukaryotes which holds a great promise so far as the development of drugs/inhibitors against specific targets in the GPI pathway of pathogens is concerned. Many of the GPI structures and their anchored proteins in pathogenic protozoans and fungi act as pathogenicity factors. Notable examples include GPI-anchored variant surface glycoprotein (VSG) in Trypanosoma brucei, GPI-anchored merozoite surface protein 1 (MSP1) and MSP2 in Plasmodium falciparum, protein-free GPI related molecules like lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) in Leishmania spp., GPI-anchored Gal/GalNAc lectin and proteophosphoglycans in Entamoeba histolytica or the GPI-anchored mannoproteins in pathogenic fungi like Candida albicans. Research in this active area has already yielded encouraging results in Trypanosoma brucei by the development of parasite-specific inhibitors of GlcNCONH2-β-PI, GlcNCONH2-(2-O-octyl)-PI and salicylic hydroxamic acid (SHAM) targeting trypanosomal GlcNAc-PI de-N-acetylase as well as the development of antifungal inhibitors like BIQ/E1210/gepinacin/G365/G884 and YW3548/M743/M720 targeting the GPI specific fungal inositol acyltransferase (Gwt1) and the phosphoethanolamine transferase-I (Mcd4), respectively. These confirm the fact that the GPI pathway continues to be the focus of researchers, given its implications for the betterment of human life.
The Brazilian municipality of Rondonópolis is an emerging urban focus of intense transmission of visceral leishmaniasis (VL), where few investigations have addressed canine reservoirs. This study assessed the seroprevalence and spatial distribution of canine visceral leishmaniasis (CVL) in the urban area of Rondonópolis. A CVL serosurvey was conducted between October 2016 and February 2017 using an immunochromatographic rapid test and enzyme-linked immunosorbent assay. Domestic dogs were sampled from 25 heterogeneous regions previously defined by the Spatial ‘K'luster Analysis by Tree Edge Removal algorithm, which considered the socioeconomic and environmental features from the last demographic census. The CVL spatial distribution was analyzed by kernel density estimation (KDE) and spatial scan statistic. All the autochthonous human VL cases reported between 2014 and 2016 were georeferenced. Of the 600 dogs tested, 115 were seropositive in both tests. The overall CVL prevalence was 19.2% (95%CI: 16.1-22.3%), which varied widely among the evaluated regions (0.0-35.1%). Almost 25% of the sampled households (n = 405) had at least one infected dog. KDE demonstrated that positive CVL households were concentrated in the peripheral areas of the city. Spatial scan statistics detected a spatial cluster with significantly low CVL prevalence in the central region (relative risk = 0.37; p = 0.04), where only one human VL case was reported. Thus, we demonstrated a high prevalence of CVL in domestic dogs from diverse socioeconomic and environmental urban contexts in Rondonópolis. The CVL cases were peripherally distributed and occurred more frequently in areas that had reported human VL.