248 results found
Parsons DAJ, Walker AJ, Emery AM, et al., 2023, Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum., Parasit Vectors, Vol: 16
BACKGROUND: Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host's immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated. METHODS: SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity. RESULTS: Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, fu
Gabain IL, Ramsteijn AS, Webster JP, 2023, Parasites and childhood stunting - a mechanistic interplay with nutrition, anaemia, gut health, microbiota, and epigenetics., Trends Parasitol, Vol: 39, Pages: 167-180
Globally, stunting affects approximately 149.2 million children under 5 years of age. The underlying aetiology and pathophysiological mechanisms leading to stunting remain elusive, and therefore few effective treatment and prevention strategies exist. Crucial evidence directly linking parasites to stunting is often lacking - in part due to the complex nature of stunting, as well as a lack of critical multidisciplinary research amongst key age groups. Here, based on available studies, we present potential mechanistic pathways by which parasitic infection of mother and/or infant may lead to childhood stunting. We highlight the need for future multidisciplinary longitudinal studies and clinical trials aimed at elucidating the most influential factors, and synergies therein, that can lead to stunting, and ultimately towards finding solutions to successfully mitigate against it.
Milne GC, Webster JP, Walker M, 2023, Is the incidence of congenital toxoplasmosis declining?, Trends in Parasitology, Vol: 39, Pages: 26-37, ISSN: 0169-4758
Prenatal infection with the protozoan parasite Toxoplasma gondii can cause congenital toxoplasmosis (CT), an often fatal or lifelong-disabling condition. Several studies of human populations have reported temporal decreases in seroprevalence, suggesting declining CT incidence. However, the consistency of this trend among diverse populations remains unclear, as does its implication for prenatal screening programmes, the major intervention against CT. Using temporally resolved data on the seroprevalence of T. gondii in various countries, we discuss how the parasite's changing epidemiology may affect trends in CT incidence in varying and counterintuitive ways. We argue that parasite stage-specific serology could be helpful for understanding underlying causes of secular changes in seroprevalence. Furthermore, we highlight the importance of updating cost-effectiveness estimates of screening programmes, accounting for neuropsychiatric sequelae.
Wang N, Peng H-Q, Gao C-Z, et al., 2022, In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice., Int J Parasitol Drugs Drug Resist, Vol: 20, Pages: 129-134
Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.
Li Y, Bletsa M, Zisi Z, et al., 2022, Endogenous Viral Elements in Shrew Genomes Provide Insights into Pestivirus Ancient History., Mol Biol Evol, Vol: 39
As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral-host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive in silico screening of a large data set of available mammalian genomes for EVEs deriving from members of the viral family Flaviviridae, an important group of viruses including well-known human pathogens, such as Zika, dengue, or hepatitis C viruses. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (Crocidura indochinensis). Homologs of these novel EVEs were subsequently detected in vivo by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily on different continents. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and Flaviviridae in general. Moreover, we provide the first description of Flaviviridae-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known Pestivirus host range and provide novel insight into the ancient evolutionary history of pestiviruses and the Flaviviridae family in general.
Pennance T, Neves MI, Webster BL, et al., 2022, Potential drivers for schistosomiasis persistence: Population genetic analyses from a cluster-randomized urogenital schistosomiasis elimination trial across the Zanzibar islands., PLoS Negl Trop Dis, Vol: 16
The World Health Organization's revised NTD Roadmap and the newly launched Guidelines target elimination of schistosomiasis as a public health problem in all endemic areas by 2030. Key to meeting this goal is elucidating how selective pressures imposed by interventions shape parasite populations. Our aim was to identify any differential impact of a unique cluster-randomized tri-armed elimination intervention (biannual mass drug administration (MDA) applied alone or in association with either mollusciciding (snail control) or behavioural change interventions) across two Zanzibarian islands (Pemba and Unguja) on the population genetic composition of Schistosoma haematobium over space and time. Fifteen microsatellite loci were used to analyse individual miracidia collected from infected individuals across islands and intervention arms at the start (2012 baseline: 1,522 miracidia from 176 children; 303 from 43 adults; age-range 6-75, mean 12.7 years) and at year 5 (2016: 1,486 miracidia from 146 children; 214 from 25 adults; age-range 9-46, mean 12.4 years). Measures of genetic diversity included allelic richness (Ar), Expected (He) and Observed heterozygosity (Ho), inbreeding coefficient (FST), parentage analysis, estimated worm burden, worm fecundity, and genetic sub-structuring. There was little evidence of differential selective pressures on population genetic diversity, inbreeding or estimated worm burdens by treatment arm, with only the MDA+snail control arm within Unguja showing trends towards reduced diversity and altered inbreeding over time. The greatest differences overall, both in terms of parasite fecundity and genetic sub-structuring, were observed between the islands, consistent with Pemba's persistently higher mean infection intensities compared to neighbouring Unguja, and within islands in terms of infection hotspots (across three definitions). These findings highlight the important contribution of population genetic analyses to elucidate extensive gene
Berger DJ, Leger E, Sankaranarayanan G, et al., 2022, Genomic evidence of contemporary hybridization between Schistosoma species, PLOS PATHOGENS, Vol: 18, ISSN: 1553-7366
Lo NC, Bezerra FSM, Colley DG, et al., 2022, Review of 2022 WHO guidelines on the control and elimination of schistosomiasis., Lancet Infectious Diseases, ISSN: 1473-3099
Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.
Liang S, Ponpetch K, Zhou Y-B, et al., 2022, Diagnosis of Schistosoma infection in non-human animal hosts: A systematic review and meta-analysis., PLoS Negl Trop Dis, Vol: 16
BACKGROUND: Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 19 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FEA-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animal hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03-0.48) with FEA-SD showing highest sensitivity (0.89, 95% CI: 0.65-1.00). CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the parasitologic technique FEA-SD and the molecular technique qPCR are the most promising techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.
Marsh KJ, Raulo AM, Brouard M, et al., 2022, Synchronous Seasonality in the Gut Microbiota of Wild Mouse Populations, FRONTIERS IN MICROBIOLOGY, Vol: 13
- Author Web Link
- Citations: 1
Raj E, Calvo-Urbano B, Heffernan C, et al., 2022, Systematic review to evaluate a potential association between helminth infection and physical stunting in children, PARASITES & VECTORS, Vol: 15, ISSN: 1756-3305
- Author Web Link
- Citations: 1
Adeyemo P, Leger E, Hollenberg E, et al., 2022, Estimating the financial impact of livestock schistosomiasis on traditional subsistence and transhumance farmers keeping cattle, sheep and goats in northern Senegal, PARASITES & VECTORS, Vol: 15, ISSN: 1756-3305
Platt RN, Le Clec'h W, Chevalier FD, et al., 2022, Genomic analysis of a parasite invasion: Colonization of the Americas by the blood fluke Schistosoma mansoni, MOLECULAR ECOLOGY, Vol: 31, Pages: 2242-2263, ISSN: 0962-1083
- Author Web Link
- Citations: 2
Li YQ, Bletsa M, Zisi Z, et al., 2022, Discovery of Flaviviridae-derived endogenous viral elements in shrew genomes provide novel insights into <i>Pestivirus</i> ancient history
<jats:title>Abstract</jats:title><jats:p>As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral-host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive <jats:italic>in silico</jats:italic> screening of a large dataset of available mammalian genomes for EVEs deriving from members of the viral family <jats:italic>Flaviviridae</jats:italic>, an important group of viruses including well-known human pathogens. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (<jats:italic>Crocidura indochinensis</jats:italic>). Homologs of these novel EVEs were subsequently detected <jats:italic>in vivo</jats:italic> by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and <jats:italic>Flaviviridae</jats:italic> in general. Moreover, we provide the first description of <jats:italic>Flaviviridae</jats:italic>-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members, including major human pathogens such as Zika, dengue, or hepatitis C viruses. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known <jats:italic>Pestivirus</jats:italic> host range and provide novel insight into the ancient evolutionary history of pestiviruses and the <jats:italic>Flaviviridae
Walker M, Freitas LT, Halder JB, et al., 2022, Improving anthelmintic treatment for schistosomiasis and soil-transmitted helminthiases through sharing and reuse of individual participant data., Wellcome Open Res, Vol: 7, ISSN: 2398-502X
The Infectious Diseases Data Observatory (IDDO, https://www.iddo.org) has launched a clinical data platform for the collation, curation, standardisation and reuse of individual participant data (IPD) on treatments for two of the most globally important neglected tropical diseases (NTDs), schistosomiasis (SCH) and soil-transmitted helminthiases (STHs). This initiative aims to harness the power of data-sharing by facilitating collaborative joint analyses of pooled datasets to generate robust evidence on the efficacy and safety of anthelminthic treatment regimens. A crucial component of this endeavour has been the development of a Research Agenda to promote engagement with the SCH and STH research and disease control communities by highlighting key questions that could be tackled using data shared through the IDDO platform. Here, we give a contextual overview of the priority research themes articulated in the Research Agenda-a 'living' document hosted on the IDDO website-and describe the three-stage consultation process behind its development. We also discuss the sustainability and future directions of the platform, emphasising throughout the power and promise of ethical and equitable sharing and reuse of clinical data to support the elimination of NTDs.
Le Clec'h W, Chevalier FD, Mattos ACA, et al., 2021, Genetic analysis of praziquantel response in schistosome parasites implicates a transient receptor potential channel, SCIENCE TRANSLATIONAL MEDICINE, Vol: 13, ISSN: 1946-6234
- Author Web Link
- Citations: 13
Díaz AV, Walker M, Webster JP, 2021, Surveillance and control of SARS-CoV-2 in mustelids: An evolutionary perspective., Evolutionary Applications: evolutionary approaches to environmental, biomedical and socio-economic issues, Vol: 14, Pages: 2715-2725, ISSN: 1752-4563
The relevance of mustelids in SARS-CoV-2 transmission has become increasingly evident. Alongside experimental demonstration of airborne transmission among ferrets, the major animal model for human respiratory diseases, transmission of SARS-CoV-2 within- and/or between-commercial mink farms has occurred and continues to occur. The number of mink reared for the luxury fur trade is approximately 60.5 million, across 36 mustelid-farming countries. By July 2021, SARS-CoV-2 outbreaks have been reported in 12 of these countries, at 412 European and 20 North American mink farms. Reverse zoonotic transmission events (from humans to mink) have introduced the virus to farms with subsequent extensive mink-to-mink transmission as well as further zoonotic (mink-to-human) transmission events generating cases among both farm workers and the broader community. Overcrowded housing conditions inherent within intensive mink farms, often combined with poor sanitation and welfare, both guarantee spread of SARS-CoV-2 and facilitate opportunities for viral variants, thereby effectively representing biotic hubs for viral transmission and evolution of virulence. Adequate preventative, surveillance and control measures within the mink industry are imperative both for the control of the current global pandemic and to mitigate against future outbreaks.
Platt RN, Le Clech W, Chevalier FD, et al., 2021, Genomic analysis of a parasite invasion: colonization of the Americas by the blood fluke, <i>Schistosoma mansoni</i>
<jats:title>Abstract</jats:title><jats:p><jats:italic>Schistosoma mansoni,</jats:italic> a snail-vectored, blood fluke that infects humans, was introduced into the Americas from Africa during the Trans-Atlantic slave trade. As this parasite shows strong specificity to the snail intermediate host, we expected that adaptation to S. American <jats:italic>Biomphalaria</jats:italic> spp. snails would result in population bottlenecks and strong signatures of selection. We scored 475,081 single nucleotide variants (SNVs) in 143 <jats:italic>S. mansoni</jats:italic> from the Americas (Brazil, Guadeloupe, and Puerto Rico) and Africa (Cameroon, Niger, Senegal, Tanzania, and Uganda), and used these data to ask: (i) Was there a population bottleneck during colonization? (ii) Can we identify signatures of selection associated with colonization? And (iii) what were the source populations for colonizing parasites? We found a 2.4-2.9-fold reduction in diversity and much slower decay in linkage disequilibrium (LD) in parasites from East to West Africa. However, we observed similar nuclear diversity and LD in West Africa and Brazil, suggesting no strong bottlenecks and limited barriers to colonization. We identified five genome regions showing selection in the Americas, compared with three in West Africa and none in East Africa, which we speculate may reflect adaptation during colonization. Finally, we infer that unsampled African populations from central African regions between Benin and Angola, with contributions from Niger, are likely the major source(s) for Brazilian <jats:italic>S. mansoni</jats:italic>. The absence of a bottleneck suggests that this is a rare case of a serendipitous invasion, where <jats:italic>S. mansoni</jats:italic> parasites were preadapted to the Americas and were able to establish with relative ease.</jats:p>
Marsh KJ, Raulo AM, Brouard M, et al., 2021, Synchronous seasonality in the gut microbiota of wild wood mouse populations
<jats:title>Abstract</jats:title><jats:p><jats:list list-type="order"><jats:list-item><jats:p>The gut microbiome performs many important functions in mammalian hosts, with community composition shaping its functional role. However, what factors drive individual microbiota variation in wild animals and to what extent these are predictable or idiosyncratic across populations remains poorly understood.</jats:p></jats:list-item><jats:list-item><jats:p>Here, we use a multi-population dataset from a common rodent species (the wood mouse,<jats:italic>Apodemus sylvaticus</jats:italic>), to test whether a consistent set of ‘core’ gut microbes is identifiable in this species, and to what extent the predictors of microbiota variation are consistent across populations.</jats:p></jats:list-item><jats:list-item><jats:p>Between 2014 and 2018 we used capture-mark-recapture and 16S rRNA profiling to intensively monitor two wild UK mouse populations and their gut microbiota, as well as characterising the microbiota from a laboratory-housed colony of the same species.</jats:p></jats:list-item><jats:list-item><jats:p>Although broadly similar at high taxonomic levels and despite being only 50km apart, the two wild populations did not share a single bacterial amplicon sequence variant (ASV). Meanwhile, the laboratory-housed colony shared many ASVs with one of the wild populations from which it is thought to have been founded decades ago. Despite strong taxonomic divergence in the microbiota, the factors predicting compositional variation in each wild population were remarkably similar. We identified a strong and consistent pattern of seasonal microbiota restructuring that occurred at both sites, in all years, and within individual mice. While the microbiota was highly individualised, seasonal convergence in the gut microbiota among individuals occu
Borlase A, Rudge JW, Leger E, et al., 2021, Spillover, hybridization, and persistence in schistosome transmission dynamics at the human-animal interface, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 118, ISSN: 0027-8424
- Author Web Link
- Citations: 6
Behnke JM, Stewart A, Smales L, et al., 2021, Parasitic nematodes of the genus Syphacia Seurat, 1916 infecting Cricetidae in the British Isles: the enigmatic status of Syphacia nigeriana, PARASITOLOGY, Vol: 149, Pages: 76-94, ISSN: 0031-1820
Lu D-B, Yu Q-F, Zhang J-Y, et al., 2021, Extended survival and reproductive potential of single-sex male and female Schistosoma japonicum within definitive hosts, INTERNATIONAL JOURNAL FOR PARASITOLOGY, Vol: 51, Pages: 887-891, ISSN: 0020-7519
- Author Web Link
- Citations: 5
Fall CB, Lambert S, Leger E, et al., 2021, Hybridized zoonotic schistosoma infections result in hybridized morbidity profiles: a clinical morbidity study amongst co-infected human populations of Senegal, Microorganisms, Vol: 9, Pages: 1-18, ISSN: 2076-2607
Hybridization of infectious agents is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, and control. Whilst evidence of the extent of hybridization amongst parasites is increasing, their impact on morbidity remains largely unknown. This may be predicted to be particularly pertinent where parasites of animals with contrasting pathogenicity viably hybridize with human parasites. Recent research has revealed that viable zoonotic hybrids between human urogenital Schistosoma haematobium with intestinal Schistosoma species of livestock, notably Schistosoma bovis, can be highly prevalent across Africa and beyond. Examining human populations in Senegal, we found increased hepatic but decreased urogenital morbidity, and reduced improvement following treatment with praziquantel, in those infected with zoonotic hybrids compared to non-hybrids. Our results have implications for effective monitoring and evaluation of control programmes, and demonstrate for the first time the potential impact of parasite hybridizations on host morbidity.
Berger DJ, Crellen T, Lamberton PHL, et al., 2021, Whole-genome sequencing of Schistosoma mansoni reveals extensive diversity with limited selection despite mass drug administration, NATURE COMMUNICATIONS, Vol: 12
- Author Web Link
- Citations: 11
Yu Q-F, Zhang J-Y, Sun M-T, et al., 2021, In vivo praziquantel efficacy of Schistosoma japonicum over time: A systematic review and meta-analysis, ACTA TROPICA, Vol: 222, ISSN: 0001-706X
- Author Web Link
- Citations: 4
Le Clech W, Chevalier FD, Mattos ACA, et al., 2021, Genetic analysis of praziquantel response in schistosome parasites implicates a Transient Receptor Potential channel
<jats:title>Abstract</jats:title><jats:p>Mass treatment with praziquantel (PZQ) monotherapy is the mainstay for schistosomiasis treatment. This drug shows imperfect cure rates in the field and parasites showing reduced PZQ response can be selected in the laboratory, but the extent of resistance in <jats:italic>Schistosoma mansoni</jats:italic> populations is unknown. We examined the genetic basis of variation in PZQ response in a <jats:italic>S. mansoni</jats:italic> population (SmLE-PZQ-R) selected with PZQ in the laboratory: 35% of these worms survive high dose (73 µg/mL) PZQ treatment. We used genome wide association to map loci underlying PZQ response. The major chr. 3 peak contains a transient receptor potential (<jats:italic>Sm.TRPM<jats:sub>PZQ</jats:sub></jats:italic>) channel (Smp_246790), activated by nanomolar concentrations of PZQ. PZQ response shows recessive inheritance and marker-assisted selection of parasites at a single <jats:italic>Sm.TRPM<jats:sub>PZQ</jats:sub></jats:italic> SNP enriched populations of PZQ-resistant (PZQ-ER) and sensitive (PZQ-ES) parasites showing >377 fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents better than PZQ-ES. Resistant parasites show 2.25-fold lower expression of <jats:italic>Sm.TRPM<jats:sub>PZQ</jats:sub></jats:italic> than sensitive parasites. Specific chemical blockers of <jats:italic>Sm.TRPM<jats:sub>PZQ</jats:sub></jats:italic> enhanced PZQ resistance, while <jats:italic>Sm.TRPM<jats:sub>PZQ</jats:sub></jats:italic> activators increased sensitivity. A single SNP in <jats:italic>Sm.TRPM<jats:sub>PZQ</jats:sub></jats:italic> differentiated PZQ-ER and PZQ-ES lines, but mutagenesis showed this was not involved in PZQ-response, suggesting linked regulatory changes. We surveyed <jats:
Neves MI, Gower CM, Webster JP, et al., 2021, Revisiting density-dependent fecundity in schistosomes using sibship reconstruction., PLoS Neglected Tropical Diseases, Vol: 15, Pages: 1-16, ISSN: 1935-2727
The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.
Mawa PA, Kincaid-Smith J, Tukahebwa EM, et al., 2021, Schistosomiasis morbidity hotspots: roles of the human host, the parasite and their interface in the Development of severe morbidity, Frontiers in Immunology, Vol: 12, ISSN: 1664-3224
Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities. For urogenital schistosomiasis, severe morbidity manifests as pathology throughout the urinary system and genitals, and is a definitive cause of squamous cell bladder carcinoma. Preventative chemotherapy (PC) programmes, delivered through mass drug administration (MDA) of praziquantel (PZQ), have been at the forefront of schistosomiasis control programmes in sub-Saharan Africa since their commencement in Uganda in 2003. However, despite many successes, 'biological hotspots' (as distinct from 'operational hotspots') of both persistent high transmission and morbidity remain. In some areas, this failure to gain control of schistosomiasis has devastating consequences, with not only persistently high infection intensities, but both "subtle" and severe morbidity remaining prevalent. These hotspots highlight the requirement to revisit research into severe morbidity and its mechanisms, a topic that has been out of favor during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and the morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review evidence of potential unique parasite factors, host factors, and their gene-environmental interactions in terms of explaining differential morbidity profiles in the human host. We then take the situation of schistosomiasis mansoni within the Albertin
Jones BP, Norman BF, Borrett HE, et al., 2021, Author Correction: Divergence across mitochondrial genomes of sympatric members of the Schistosoma indicum group and clues into the evolution of Schistosoma spindale., Sci Rep, Vol: 11
Levecke B, Vlaminck J, Andriamaro L, et al., 2020, Evaluation of the therapeutic efficacy of praziquantel against schistosomes in seven countries with ongoing large-scale deworming programs, INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, Vol: 14, Pages: 183-187, ISSN: 2211-3207
- Author Web Link
- Citations: 8
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