Advances in Parasitology最新文献

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.

Onchocerciasis (also known as 'river blindness'), is a neglected tropical disease (NTD) caused by the (Simulium-transmitted) filarial nematode Onchocerca volvulus. The occurrence of 'blinding' (savannah) and non-blinding (forest) parasite strains and the existence of corresponding, locally adapted Onchocerca-Simulium complexes were postulated to explain greater blindness prevalence in savannah than in forest foci. As a result, the World Health Organization (WHO) Onchocerciasis Control Programme in West Africa (OCP) focused anti-vectorial and anti-parasitic interventions in savannah endemic areas. In this paper, village-level data on blindness prevalence, microfilarial prevalence, and transmission intensity (measured by the annual transmission potential, the number of infective, L3, larvae per person per year) were extracted from 16 West-Central Africa-based publications, and analysed according to habitat (forest, forest-savannah mosaic, savannah) to test the dichotomous strain hypothesis in relation to blindness. When adjusting for sample size, there were no statistically significant differences in blindness prevalence between the habitats (one-way ANOVA, P=0.68, mean prevalence for forest=1.76±0.37 (SE); mosaic=1.49±0.38; savannah=1.89±0.26). The well-known relationship between blindness prevalence and annual transmission potential for savannah habitats was confirmed and shown to hold for (but not to be statistically different from) forest foci (excluding data from southern Côte d'Ivoire, in which blindness prevalence was significantly lower than in other West African forest communities, but which had been the focus of studies leading to the strain-blindness hypothesis that was accepted by OCP planners). We conclude that the evidence for a savannah blinding onchocerciasis strain in simple contrast with a non-blinding forest strain is equivocal. A re-appraisal of the strain hypothesis to explain patterns of ocular disease is needed to improve understanding of onchocerciasis epidemiology and disease burden estimates in the light of the WHO 2030 goals for onchocerciasis.

Infection with the pork tapeworm (Taenia solium) is responsible for a substantial global burden of disease, not only restricted to its impact on human health, but also resulting in a considerable economic burden to smallholder pig farmers due to pig cysticercosis infection. The life-cycle, parasitology and immunology of T. solium are complex, involving pigs (the intermediate host, harbouring the larval metacestode stage), humans (the definitive host, harbouring the adult tapeworm, in addition to acting as accidental intermediate hosts) and the environment (the source of infection with eggs/proglottids). We review the parasitology, immunology, and epidemiology of the infection associated with each of the T. solium life-cycle stages, including the pre-adult/adult tapeworm responsible for human taeniasis; post-oncosphere and cysticercus associated with porcine and human cysticercosis, and the biological characteristics of eggs in the environment. We discuss the burden associated, in endemic settings, with neurocysticercosis (NCC) in humans, and the broader cross-sectoral economic impact associated both with NCC and porcine cysticercosis, the latter impacting food-value chains. Existing tools for diagnostics and control interventions that target different stages of the T. solium transmission cycle are reviewed and their limitations discussed. Currently, no national T. solium control programmes have been established in endemic areas, with further work required to identify optimal strategies according to epidemiological setting. There is increasing evidence suggesting that cross-sectoral interventions which target the parasite in both the human and pig host provide the most effective approaches for achieving control and ultimately elimination. We discuss future avenues for research on T. solium to support the attainment of the goals proposed in the revised World Health Organisation neglected tropical diseases roadmap for 2021-2030 adopted at the 73rd World Health Assembly in November 2020.

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.

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.

Within the overlapping geographical ranges of P. knowlesi monkey hosts and vectors in Southeast Asia, an estimated 1.5 billion people are considered at risk of infection. P. knowlesi can cause severe disease and death, the latter associated with delayed treatment occurring from misdiagnosis. Although microscopy is a sufficiently sensitive first-line tool for P. knowlesi detection for most low-level symptomatic infections, misdiagnosis as other Plasmodium species is common, and the majority of asymptomatic infections remain undetected. Current point-of-care rapid diagnostic tests demonstrate insufficient sensitivity and poor specificity for differentiating P. knowlesi from other Plasmodium species. Molecular tools including nested, real-time, and single-step PCR, and loop-mediated isothermal amplification (LAMP), are sensitive for P. knowlesi detection. However, higher cost and inability to provide the timely point-of-care diagnosis needed to guide appropriate clinical management has limited their routine use in most endemic clinical settings. P. knowlesi is likely underdiagnosed across the region, and improved diagnostic and surveillance tools are required. Reference laboratory molecular testing of malaria cases for both zoonotic and non-zoonotic Plasmodium species needs to be more widely implemented by National Malaria Control Programs across Southeast Asia to accurately identify the burden of zoonotic malaria and more precisely monitor the success of human-only malaria elimination programs. The implementation of specific serological tools for P. knowlesi would assist in determining the prevalence and distribution of asymptomatic and submicroscopic infections, the absence of transmission in certain areas, and associations with underlying land use change for future spatially targeted interventions.

Ticks and tick-borne diseases (TTBDs) substantially affect the health and production of ruminants, particularly in resource-poor, small-scale farming systems worldwide. However, to date, there has been no critical appraisal of the current state of knowledge of TTBDs in such farming systems. In this article, we systematically reviewed the situation in Pakistan-as an example of a country that is highly reliant on agriculture to sustain its economy, particularly smallholder livestock farms, which are continually faced with challenges associated with TTBDs. The main aims of this review were to gain improved insights into the current status of TTBDs in small-scale farming systems, and to identify knowledge gaps, through the systematic evaluation of published literature on this topic from Pakistan, and to recommend future research directions. We searched publicly available literature from three databases (i.e. Web of Science, Google Scholar, and PubMed) on bovine TTBDs in Pakistan. Of 11,224 published studies identified, 185 were eligible for inclusion; these studies were published between August 1947 and June 2021. A critical analysis of these 185 studies revealed that the diagnosis of ticks and tick-borne pathogens (TBPs) in Pakistan has been based largely on the use of traditional methods (i.e. 'morpho-taxonomy'). At least 54 species of tick have been recorded, most of which belong to the genera Haemaphysalis, Hyalomma and Rhipicephalus. The prevalence of ticks was higher, particularly in young, exotic and crossbred female cattle, during the summer season. Major TBPs include species of Anaplasma, Babesia and Theileria, with prevalences being higher in cattle than buffaloes. Additionally, pathogens of zoonotic potential, including species of Anaplasma, Borrelia, the Crimean-Congo haemorrhagic fever virus, Coxiella, Ehrlichia and Rickettsia, have been recorded in both tick and bovine populations. Information on risk factors, spatial-temporal distribution, genetic diversity, and control of ticks and TBPs is limited, the vector potential of ticks and the distribution patterns of ticks and TBPs in relation to climate remains largely unexplored. Future research should focus on addressing these knowledge gaps and the key challenges of poverty, food security and disease outbreaks in a small-scale livestock farming context in order to provide sustainable, environment-friendly control measures for TTBDs.