Zika virus infections can cause a range of neurologic disorders including congenital microcephaly. However, while Zika infections have been notified across all regions in Brazil, there has been an ...unusual number of congenital microcephaly case notifications concentrated in the Northeast of the country. To address this observation, we investigated epidemiological data (2014-2016) on arbovirus co-distribution, environmental and socio-economic factors for each region in Brazil. Data on arbovirus reported cases and microcephaly were collected from several Brazilian Ministry of Health databases for each Federal unit. These were complemented by environmental management, social economic and Aedes aegypti infestation index data, extracted from multiple databases. Spatial time "ecological" analysis on the number of arboviruses transmitted by Aedes mosquitoes in Brazil show that the distribution of dengue and Zika was widespread in the whole country, with higher incidence in the West-Central region. However, reported chikungunya cases were higher in the Northeast, the region also with the highest number of microcephaly cases registered. Social economic factors (human development index and poverty index) and environmental management (water supply/storage and solid waste management) pointed the Northeast as the less wealthy region. The Northeast is also the region with the highest risk of Aedes aegypti house infestation due to the man-made larval habitats. In summary, the results of our ecological analysis support the hypothesis that the unusual distribution of microcephaly might not be due to Zika infection alone and could be accentuated by poverty and previous or co-infection with other pathogens. Our study reinforces the link between poverty and the risk of disease and the need to understand the effect on pathogenesis of sequential exposure to arboviruses and co-viral infections. Comprehensive large-scale cohort studies are required to corroborate our findings. We recommend that the list of infectious diseases screened, particularly during pregnancy, be regularly updated to include and effectively differentiate all viruses from ongoing outbreaks.
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress ...syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS. Mice developing ALI/ARDS showed greater neutrophil accumulation in the lungs compared with mice that did not develop pulmonary complications. In addition, mice with ALI/ARDS produced more neutrophil-attracting chemokines, myeloperoxidase and reactive oxygen species. We also observed that the parasites Plasmodium falciparum and PbA induced the formation of neutrophil extracellular traps (NETs) ex vivo, which were associated with inflammation and tissue injury. The depletion of neutrophils, treatment with AMD3100 (a CXCR4 antagonist), Pulmozyme (human recombinant DNase) or Sivelestat (inhibitor of neutrophil elastase) decreased the development of malaria-associated ALI/ARDS and significantly increased mouse survival. This study implicates neutrophils and NETs in the genesis of experimentally induced malaria-associated ALI/ARDS and proposes a new therapeutic approach to improve the prognosis of severe malaria.
Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug ...susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax (n = 558) establishes South Asian isolates (n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps, and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b. Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic diversity, and genetic evidence of recent directional selection in this important human pathogen.
Although Plasmodium vivax parasites are the predominant cause of malaria outside of sub-Saharan Africa, they not always prioritised by elimination programmes. P. vivax is resilient and poses ...challenges through its ability to re-emerge from dormancy in the human liver. With observed growing drug-resistance and the increasing reports of life-threatening infections, new tools to inform elimination efforts are needed. In order to halt transmission, we need to better understand the dynamics of transmission, the movement of parasites, and the reservoirs of infection in order to design targeted interventions. The use of molecular genetics and epidemiology for tracking and studying malaria parasite populations has been applied successfully in P. falciparum species and here we sought to develop a molecular genetic tool for P. vivax. By assembling the largest set of P. vivax whole genome sequences (n = 433) spanning 17 countries, and applying a machine learning approach, we created a 71 SNP barcode with high predictive ability to identify geographic origin (91.4%). Further, due to the inclusion of markers for within population variability, the barcode may also distinguish local transmission networks. By using P. vivax data from a low-transmission setting in Malaysia, we demonstrate the potential ability to infer outbreak events. By characterising the barcoding SNP genotypes in P. vivax DNA sourced from UK travellers (n = 132) to ten malaria endemic countries predominantly not used in the barcode construction, we correctly predicted the geographic region of infection origin. Overall, the 71 SNP barcode outperforms previously published genotyping methods and when rolled-out within new portable platforms, is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.
A taxonomic review of Copella is presented based on the analysis of the type material of all nominal species and extensive material from South American drainages. Six out of ten nominal species are ...recognized as valid: Copella arnoldi, C. callolepis, C. compta, C. eigenmanni, C. nattereri, and C. vilmae. Copella carsevennensis is a junior synonym of C. arnoldi, C. nigrofasciata and 'Nannostomus' stigmasemion are junior synonyms of C. callolepis, C. metae is junior synonym of C. eigenmanni, and C. meinkeni is junior synonym of C. nattereri. Species of Copella occur in the rio Amazonas and Orinoco basins, and coastal drainages of Guyana, French Guiana, Surinam, and Venezuela. An identification key is provided.
Knodus nuptialis n. sp. is described from the Rio Curuá drainage, Rio Xingu basin, Brazil. It can be diagnosed from its congeners by having dentary teeth decreasing gradually in size posteriorly, ...outer premaxillary teeth row with five cusps, 12-15 branched anal-fin rays and a single humeral spot. The species presents notable sexual dimorphism consisting of densely concentrated nuptial tubercles on head, body, and fins, gill-gland, and bony hooks in the anal fin of mature males. It was found that these sexually dimorphic features are useful and functional in males of the new species only during the reproductive season and after this period, they become atrophied, and eventually disappear. The list of characiform species presenting breeding tubercles is updated and nine species and two genera of the Characidae, Deuterodon and Bryconacidnus, are for the first time reported to have breeding tubercles.
Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth ...retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities.
The treatment for both leishmaniasis and trypanosomiasis, which are severe human infections caused by trypanosomatids belonging to Leishmania and Trypanosoma genera, respectively, is extremely ...limited because of concerns of toxicity and efficacy with the available anti-protozoan drugs, as well as the emergence of drug resistance. Consequently, the urgency for the discovery of new trypanosomatid targets and novel bioactive compounds is particularly necessary. In this context, the investigation of changes in parasite gene expression between drug resistant/sensitive strains and in the up-regulation of virulence-related genes in infective forms has brought to the fore the involvement of calpain-like proteins in several crucial pathophysiological processes performed by trypanosomatids. These studies were encouraged by the publication of the complete genome sequences of three human pathogenic trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, which allowed in silico analyses that in turn directed the identification of numerous genes with interesting chemotherapeutic characteristics, including a large family of calpain-related proteins, in which to date 23 genes were assigned as calpains in T. brucei, 40 in T. cruzi and 33 in L. braziliensis. In the present review, we intend to add to these biochemical/biological reports the investigations performed upon the inhibitory capability of calpain inhibitors against human pathogenic trypanosomatids.
Histopathology is the study of how disease alters human and animal tissue and is based on the microscopic examination of stained tissue sections. To maintain tissue integrity, preserving it from ...degradation, it is initially fixed, primarily with formalin, before being treated with alcohol and organic solvents, allowing the infiltration of paraffin wax. The tissue can then be embedded in a mold and sectioned, usually at a thickness between 3 and 5 μm, before staining with dyes or antibodies to demonstrate specific components.
As the paraffin wax is insoluble in water, it is necessary to remove it from the tissue section before applying any aqueous or water-based dye solution, to allow the tissue to successfully interact with the stain. This deparaffinization/hydration step is normally carried out using xylene, an organic solvent, followed by hydration using graded alcohols.
However, this use of xylene has been shown to have detrimental effects on acid-fast stains (AFS), such as those employed to demonstrate Mycobacterium, including the causative agent of tuberculosis (TB), as the integrity of the lipid-rich wall present in these bacteria may be compromised using xylene.
A simple, novel method, Projected Hot Air Deparaffinization (PHAD) removes the solid paraffin from the tissue section without the use of any solvents, which produces significantly improved staining results using AFS. PHAD relies on the projection of hot air onto the histological section to melt and remove paraffin from the tissue, which can be achieved using a common hairdryer.
•PHAD relies on the projection of hot air onto the histological section which can be achieved using a common hairdryer.•The blowing force is such that melted paraffin is removed from the tissue in 20 min.•Subsequent hydration allows for using aqueous histological stains with success, such as the fluorescent auramine O acid-fast-stain.
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