Advances in Parasitology最新文献

African protected areas strive to conserve the continent's great biodiversity with a targeted focus on the flagship 'Big Five' megafauna. Though often not considered, this biodiversity protection also extends to the lesser-known microbes and parasites that are maintained in these diverse ecosystems, often in a silent and endemically stable state. Climate and anthropogenic change, and associated diversity loss, however, are altering these dynamics leading to shifts in ecological interactions and pathogen spill over into new niches and hosts. As many African protected areas are bordered by game and livestock farms, as well as villages, they provide an ideal study system to assess infection dynamics at the human-livestock-wildlife interface. Here we review five zoonotic, multi-host diseases (bovine tuberculosis, brucellosis, Rift Valley fever, schistosomiasis and cryptosporidiosis)-the 'Microscopic Five'-and discuss the biotic and abiotic drivers of parasite transmission using the iconic Kruger National Park, South Africa, as a case study. We identify knowledge gaps regarding the impact of the 'Microscopic Five' on wildlife within parks and highlight the need for more empirical data, particularly for neglected (schistosomiasis) and newly emerging (cryptosporidiosis) diseases, as well as zoonotic disease risk from the rising bush meat trade and game farm industry. As protected areas strive to become further embedded in the socio-economic systems that surround them, providing benefits to local communities, One Health approaches can help maintain the ecological integrity of ecosystems, while protecting local communities and economies from the negative impacts of disease.

Schistosomiasis is a poverty-associated tropical disease caused by blood dwelling trematodes that threaten approximately 10% of the world population. Praziquantel, the sole drug currently available for treatment, is insufficient to eliminate the disease and the clinical drug development pipeline is empty. Here, we review the characteristics of the patent Schistosoma mansoni mouse model used for in vivo antischistosomal drug discovery, highlighting differences in the experimental set-up across research groups and their potential influence on experimental results. We explore the pharmacokinetic/pharmacodynamic relationship of selected drug candidates, showcasing opportunities to improve the drug profile to accelerate the transition from the early drug discovery phase to new clinical candidates.

The predominant clonal evolution (PCE) model of pathogenic microorganisms postulates that the impact of genetic recombination in those pathogens' natural populations is not enough to erase a persistent phylogenetic signal at all evolutionary scales from microevolution till geological times in the whole ecogeographical range of the species considered. We have tested this model with a set of representative parasitic protozoa, yeasts and bacteria in the light of the most recent genomic data. All surveyed species, including those that were considered as highly recombining, exhibit similar PCE patterns above and under the species level, from macro- to micro-evolutionary scales (Russian doll pattern), suggesting gradual evolution. To our knowledge, it is the first time that such a strong common evolutionary feature among very diverse pathogens has been evidenced. The implications of this model for basic biology and applied research are exposed. These implications include our knowledge on the pathogens' reproductive mode, their population structure, the possibility to type strain and to follow up epidemics (molecular epidemiology) and to revisit pathogens' taxonomy through a flexible use of the phylogenetic species concept (Cracraft, 1983).

Defence mechanisms of fish can be divided into specific and non-specific that act in concert and are often interdependent. Most fish in both wild and cultured populations are vulnerable to metazoan parasites. Endoparasitic helminths include several species of digeneans, cestodes, nematodes, and acanthocephalans. Although they may occur in large numbers, helminth infections rarely result in fish mortality. Conversely, some ectoparasites cause mass mortality in farmed fish. Given the importance of fish innate immunity, this review addresses non-specific defence mechanisms of fish against metazoan parasites, with emphasis on granulocyte responses involving mast cells, neutrophils, macrophages, rodlet cells, and mucous cells. Metazoan parasites are important disease agents that affect wild and farmed fish and can induce high economic loss and, as pathogen organisms, deserve considerable attention. The paper will provide our light and transmission electron microscopy data on metazoan parasites-fish innate immune and neuroendocrine systems. Insights about the structure and functions of the cell types listed above and a brief account of the effects and harms of each metazoan taxon to specific fish apparati/organs will be presented.

Human parasitic infections-including malaria, and many neglected tropical diseases (NTDs)-have long represented a Gordian knot in global public health: ancient, persistent, and exceedingly difficult to control. With the coronavirus disease (Covid-19) pandemic substantially interrupting control programmes worldwide, there are now mounting fears that decades of progress in controlling global parasitic infections will be undone. With Covid-19 moreover exposing deep vulnerabilities in the global health system, the current moment presents a watershed opportunity to plan future efforts to reduce the global morbidity and mortality associated with human parasitic infections. In this chapter, we first provide a brief epidemiologic overview of the progress that has been made towards the control of parasitic diseases between 1990 and 2019, contrasting these fragile gains with the anticipated losses as a result of Covid-19. We then argue that the complementary aspirations of the United Nations Sustainable Development Goals (SDGs) and the World Health Organization (WHO)'s 2030 targets for parasitic disease control may be achieved by aligning programme objectives within the One Health paradigm, recognizing the interdependence between humans, animals, and the environment. In so doing, we note that while the WHO remains the preeminent international institution to address some of these transdisciplinary concerns, its underlying challenges with funding, authority, and capacity are likely to reverberate if left unaddressed. To this end, we conclude by reimagining how models of multisectoral global health governance-combining the WHO's normative and technical leadership with greater support in allied policy-making areas-can help sustain future malaria and NTD elimination efforts.

Molecular epidemiology has been central to uncovering P. knowlesi as an important cause of human malaria in Southeast Asia, and to understanding the complex nature of this zoonosis. Species-specific parasite detection and characterization of sequences were vital to show that P. knowlesi was distinct from the human parasite species that had been presumed to cause all malaria. With established sensitive and specific molecular detection tools, surveys subsequently indicated the distribution of P. knowlesi infections in humans, wild primate reservoir host species, and mosquito vector species. The importance of studying P. knowlesi genetic polymorphism was indicated initially by analysing a few nuclear gene loci as well as the mitochondrial genome, and subsequently by multi-locus microsatellite analyses and whole-genome sequencing. Different human infections generally have unrelated P. knowlesi genotypes, acquired from the diverse local parasite reservoirs in macaques. However, individual human infections are usually less genetically complex than those of wild macaques which experience more frequent superinfection with different P. knowlesi genotypes. Multi-locus analyses have revealed deep population subdivisions within P. knowlesi, which are structured both geographically and in relation to different macaque reservoir host species. Simplified genotypic discrimination assays now enable efficient large-scale surveillance of the sympatric P. knowlesi subpopulations within Malaysian Borneo. The whole-genome sequence analyses have also identified loci under recent positive natural selection in the P. knowlesi genome, with evidence that different loci are affected in different populations. These provide a foundation to understand recent adaptation of the zoonotic parasite populations, and to track and interpret future changes as they emerge.

Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use change. With a 24-h asexual life cycle in humans, high parasite counts are possible, but most clinical cases of knowlesi malaria are uncomplicated with low parasitaemia. In co-endemic areas, median parasitaemia in knowlesi malaria is lower than that seen in vivax and falciparum malaria, suggesting a lower fever threshold. Severe malaria occurs in 6-9% of symptomatic adults. Manifestations of severe malaria from P. knowlesi are similar to those seen with falciparum malaria, with the notable absence of coma. Age, parasitaemia, cardiovascular comorbidities and delayed diagnosis are risk factors for severe disease and death, which are only seen in adults. Thrombocytopenia is near-universal in adults, likely related to platelet-red cell binding and clearance. Mechanisms underlying the microvascular sludging seen in fatal disease in non-natural primate hosts and the microvascular accumulation of parasites in fatal human disease are not clear. Marked reductions in deformability of both infected and uninfected red blood cells are associated with disease severity in both humans and other non-natural primate hosts, likely contributing to impaired microvascular perfusion and organ dysfunction. Endothelial activation, endothelial dysfunction, glycocalyx degradation and haemolysis are also associated with, and likely contribute to, severe disease and organ dysfunction, particularly acute kidney injury.

The zoonotic parasite Plasmodium knowlesi has emerged as an important cause of human malaria in parts of Southeast Asia. The parasite is indistinguishable by microscopy from the more benign P. malariae, but can result in high parasitaemias with multiorgan failure, and deaths have been reported. Recognition of severe knowlesi malaria, and prompt initiation of effective therapy is therefore essential to prevent adverse outcomes. Here we review all studies reporting treatment of uncomplicated and severe knowlesi malaria. We report that although chloroquine is effective for the treatment of uncomplicated knowlesi malaria, artemisinin combination treatment is associated with faster parasite clearance times and lower rates of anaemia during follow-up, and should be considered the treatment of choice, particularly given the risk of administering chloroquine to drug-resistant P. vivax or P. falciparum misdiagnosed as P. knowlesi malaria in co-endemic areas. For severe knowlesi malaria, intravenous artesunate has been shown to be highly effective and associated with reduced case-fatality rates, and should be commenced without delay. Regular paracetamol may also be considered for patients with severe knowlesi malaria or for those with acute kidney injury, to attenuate the renal damage resulting from haemolysis-induced lipid peroxidation.