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Update on the Geographic Distribution of the Intermediate Host Snails of Schistosoma mansoni on St. Lucia: A Step Toward Confirming the Interruption of Transmission of Human Schistosomiasis.

ABSTRACT: To provide information to guide considerations of declaring interruption of transmission of human schistosomiasis due to Schistosoma mansoni on St. Lucia, we undertook an island-wide survey in June-July 2022 to determine the presence of Biomphalaria snails, the intermediate hosts of S. mansoni, and their infection status. Snail surveys were carried out at 58 habitats to determine presence of Biomphalaria snails followed by examination of the collected snails for evidence of infection with S. mansoni. Furthermore, water samples were collected at the snail habitats and screened for presence of S. mansoni DNA using an eDNA approach. We found B. glabrata present in one habitat (Cul de Sac) where it was abundant. Specimens provisionally identified as Biomphalaria kuhniana were recovered from 10 habitats. None of the Biomphalaria specimens recovered were positive for S. mansoni. None of the eDNA water samples screened were positive for S. mansoni. Experimental exposures of both field-derived and laboratory-reared St. Lucian B. glabrata and B. kuhniana to Puerto Rican and Kenyan-derived S. mansoni strains revealed B. glabrata to be susceptible to both and B. kuhniana proved refractory from histological and snail shedding results. We conclude, given the current rarity of B. glabrata on the island and lack of evidence for the presence of S. mansoni, that transmission is unlikely to be ongoing. Coupled with negative results from recent human serological surveys, and implementation of improved sanitation and provision of safe water supplies, St. Lucia should be considered a candidate for declaration of interruption of human schistosomiasis transmission.

SUBMITTER: Mukaratirwa S

PROVIDER: S-EPMC10551094 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Update on the Geographic Distribution of the Intermediate Host Snails of Schistosoma mansoni on St. Lucia: A Step Toward Confirming the Interruption of Transmission of Human Schistosomiasis.

Mukaratirwa Samson S Laidemitt Martina R MR Hewitt Reynold R Sengupta Mita E ME Marchi Silvia S Polius Consortia C Belmar Sharon S Scholte Ronaldo G C RGC Perez Freddy F Stensgaard Anna-Sofie AS Vennervald Birgitte J BJ Willingham Arve L AL Loker Eric S ES

The American journal of tropical medicine and hygiene 20230814 4

To provide information to guide considerations of declaring interruption of transmission of human schistosomiasis due to Schistosoma mansoni on St. Lucia, we undertook an island-wide survey in June-July 2022 to determine the presence of Biomphalaria snails, the intermediate hosts of S. mansoni, and their infection status. Snail surveys were carried out at 58 habitats to determine presence of Biomphalaria snails followed by examination of the collected snails for evidence of infection with S. man ...[more]

PMID: 37580035

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Project description:Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.

Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs. The perfused adult female worms were incubated with cold RNAlater solution (Ambion) and kept at 4 0C until RNA extraction. Total RNA was extracted using Trizol reagent (Invitrogen) according to the manufacture's instructions. RNA was quantified using Nanodrop ND-1000 UV/Vis spectrophotometer and its quality was assured with Agilent 2100 Bioanalyzer, a micro fluidics-based electrophoresis platform. 1 Î¼g total RNA from each sample was amplified using the T7-RNA polymerase based SuperScript Indirect RNA amplification system (Invitrogen) and subsequently 3 Î¼g of aminoallyl-modified amplified RNA was labeled using Cy3 or Cy5 by indirect labeling (General Electric). Amplification and labeling were done according to manufacturer specifications. The Cy3 and Cy5 labeled samples were then combined, dried and re-suspended in hybridization buffer (50 % formamide, 25 % RNase free water and 25 % Microarray Hybridization buffer 4x) (General Electric). Pools of RNA from worms treated with QN were hybridized against RNA from control worms. In order to ensure the uniformity of data, all experiments were performed using slides from the same printing batch and dyes from the same lot. The same washing protocol was used and immediately after washing we scanned the slides using the same parameters. Technical and biological replicates were performed. Dye swap was employed in order to account for dye biases. A total of eight different replicated data values were obtained for each probe on the array. The samples were hybridized overnight to cDNA microarray slides containing 4,000 elements in duplicate (GEO accession: GPL3929) using ASP hybridization chambers (GE, USA) at 42 Â°C. Slides were washed once for 3 minutes in low stringency wash solution at 45 Â°C (1 x SSC + 0.2 % SDS), followed by one wash for 5 minutes in medium stringency wash solution (0.1 x SSC + 0.2%SDS) and one wash of 1 minute in high stringency wash solution (0.1 x SSC). Moreover, slides were air dried and scanned using a microarray dual channel laser scanner (GenePix 4000B, Molecular Devices, USA) at 5 Î¼m resolution, 100 % laser power and PMT levels were adjusted in order to obtain similar average intensities of red and green signal. Data were extracted using Array Vision 8.0 program. To correct for systematic biases on the data originated from small differences in the labeling and/or detection efficiencies between the fluorescent dyes, expression ratios were logged (base 2) and normalized using a locally weighted linear regression (LOWESS) algorithm [60]. Normalized log2 (ratios) were further analyzed with the Significance Analysis of Microarrays tool (SAM) [61] using a 0.1 % false discovery rate (FDR) to find differentially expressed genes. The genes identified in the previous step were filtered using a 1.7 fold change cut-off in at least 4 out of the 8 data points. This step is critical in identifying more biological relevant changes. It is important to stress that the fold change filter was used after the identification of differentially expressed genes, and our results are not influenced by the potentially misleading effects caused by the use of arbitrary thresholds to trim data sets before significance testing .

Dataset Information

Update on the Geographic Distribution of the Intermediate Host Snails of Schistosoma mansoni on St. Lucia: A Step Toward Confirming the Interruption of Transmission of Human Schistosomiasis.

Publications

Update on the Geographic Distribution of the Intermediate Host Snails of Schistosoma mansoni on St. Lucia: A Step Toward Confirming the Interruption of Transmission of Human Schistosomiasis.

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