The effects of subcurative praziquantel treatment on life-history traits and trade-offs in drug-resistant Schistosoma mansoni

Natural selection acts on all organisms, including parasites, to maximise reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian State-Space Models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma may be limited by life-history costs not present in susceptible counterparts. Schistosoma mansoni parasites from a praziquantel–susceptible (S), a praziquantel–resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by praziquantel treatment in the R line, could limit the spread of R parasites under praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond

Parasites and childhood stunting – a mechanistic interplay with nutrition, anaemia, gut health, microbiota, and epigenetics

Funding Information: We are very grateful to the Bloomsbury Colleges grant to I.G. ( VPR.1924 ), and the Global Challenges Research Fund (A.S.R. and J.P.W.: Ref MR/S01313X/1 ) for funding. Figures created with BioRender.com .Peer reviewedPublisher PD

Reduced efficacy of praziquantel against Schistosoma mansoni associated with multiple-rounds of mass drug administration

The efficacy of praziquantel against Schistosoma mansoni was significantly lower in Ugandan schools that had received more prior rounds of mass drug administration, as determined by fitting a statistical model to parasite egg counts before and after treatment

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity.

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 Albertine region of Uganda as a case study in terms of elucidating the factors behind the severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot)

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity.

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 Albertine region of Uganda as a case study in terms of elucidating the factors behind the severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot)

Contrasting reservoirs for Schistosoma japonicum between marshland and hilly regions in Anhui, China--a two-year longitudinal parasitological survey.

Schistosoma japonicum remains highly endemic in many counties in China and has recently re-emerged, to a large extent, in previously controlled areas. To test the hypothesis that small rodents and less agriculturally important domestic animals such as dogs and cats may play an important role in the transmission and potential re-emergence of this disease, an annual investigation of S. japonicum among humans, domestic animals and rodents, combined with detailed surveys of the snail intermediate host, was performed across 3 marshland villages and 3 hilly villages in Anhui province of China over 2 consecutive years. The highest infection prevalence and intensity observed across all mammals was in rodents in the hilly region; while in the marshland, bovines were suspected as the main reservoirs. However, relatively high infection prevalence levels were also found in dogs and cats in both regions. Such results may have implications for the current human- and bovine-oriented control policy for this medically and veterinarily important disease, particularly within the hilly regions of mainland China

Epidemiological Interactions between Urogenital and Intestinal Human Schistosomiasis in the Context of Praziquantel Treatment across Three West African Countries

© 2015 Knowles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era

Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/ or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples fromboth human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control. This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'