Advances in Parasitology最新文献

Strongyloidiasis and HTLV-I (human T-lymphotropic virus-1) are important infections that are endemic in many countries around the world with an estimated 370 million infected with Strongyloides stercoralis alone, and 5-10 million with HTVL-I. Co-infections with these pathogens are associated with significant morbidity and can be fatal. HTLV-I infects T-cells thus causing dysregulation of the immune system which has been linked to dissemination and hyperinfection of S. stercoralis leading to bacterial sepsis which can result in death. Both of these pathogens are endemic in Australia primarily in remote communities in Queensland, the Northern Territory, and Western Australia. Other cases in Australia have occurred in immigrants and refugees, returned travellers, and Australian Defence Force personnel. HTLV-I infection is lifelong with no known cure. Strongyloidiasis is a long-term chronic disease that can remain latent for decades, as shown by infections diagnosed in prisoners of war from World War II and the Vietnam War testing positive decades after they returned from these conflicts. This review aims to shed light on concomitant infections of HTLV-I with S. stercoralis primarily in Australia but in the global context as well.

Widespread resistance to currently-used anthelmintics represents a major obstacle to controlling parasitic nematodes of livestock animals. Given the reliance on anthelmintics in many control regimens, there is a need for the continued discovery and development of new nematocides. Enabling such a focus are: (i) the major chemical diversity of natural products; (ii) the availability of curated, drug-like extract-, fraction- and/or compound-libraries from natural sources; (iii) the utility and practicality of well-established whole-worm bioassays for Haemonchus contortus-an important parasitic nematodes of livestock-to screen natural product libraries; and (iv) the availability of advanced chromatographic (HPLC), spectroscopic (NMR) and spectrometric (MS) techniques for bioassay-guided fractionation and structural elucidation. This context provides a sound basis for the identification and characterisation of anthelmintic candidates from natural sources. This chapter provides a background on the importance and impact of helminth infections/diseases, parasite control and aspects of drug discovery, and reviews recent work focused on (i) screening well-defined compound libraries to establish the methods needed for large-scale screening of natural extract libraries; (ii) discovering plant and marine extracts with nematocidal or nematostatic activity, and purifying bioactive compounds and assessing their potential for further development; and (iii) synthesising analogues of selected purified natural compounds for the identification of possible 'lead' candidates. The chapter describes some lessons learned from this work and proposes future areas of focus for drug discovery. Collectively, the findings from this recent work show potential for selected natural product scaffolds as candidates for future development. Developing such candidates via future chemical optimisation, efficacy and safety evaluations, broad spectrum activity assessments, and target identification represents an exciting prospect and, if successful, could pave the way to subsequent pre-clinical and clinical evaluations.

There is only limited scientific literature on trial methodology, trial procedures and mitigation strategies to overcome challenges faced during clinical research taking place in resource constrained healthcare environments. Organisational, cultural, infrastructural and ethical challenges may vary between settings although conduct of clinical trials for the same disease (in our case soil-transmitted helminth (STH) infections) share similar risks for implementation. We use the example of a phase III randomised controlled trial, conducted between 2018 and 2020 in Côte d'Ivoire, Lao PDR and Pemba Island (Tanzania), to share challenges faced and mitigation strategies to guide future planning of studies in similar settings. We describe the planning, screening, enrolment and implementation phases in each of the three settings. Our findings indicate that involvement of local staff and close collaboration are essential factors for successful trial preparation and implementation. A strategic plan adapted to each setting with a distinct focus on community engagement and workforce is crucial to proceed efficiently. Mutual trust between the trial population and the trial team is of utmost importance and allows for early reaction and adaption to emerging issues.

The broad fish tapeworm, Dibothriocephalus latus (Diphyllobothriidea), is the most frequent causative agent of diphyllobothriosis, a fish-borne zoonosis, in Europe. Diphyllobothriosis is characterized by the transmission of D. latus larvae to humans via the consumption of raw, marinated, smoked or inadequately cooked fish products. The most important European foci of diphyllobothriosis have been Fennoscandia, the Baltic region, the Alpine lakes region, the Danube River region, and several endemic regions in Russia. This review provides basic data on the biology, life cycle, host specificity, methods of identification of D. latus, and a detailed summary of its occurrence in intermediate and definitive hosts in Fennoscandia and the Baltic, Alpine, and Danube regions during the last 120 years (1900-2020). Deeper insight into the unique pattern of distribution of D. latus in endemic regions is provided. The numbers of records are associated with several milestones of particular time periods. The first milestone (historical), which influenced studies on D. latus in Europe, was the period during and after World War II (1941-1950). The second milestone (epidemiological) was the decade 1981-1990, when previous massive health campaigns led to a marked decline of diphyllobothriosis in Europe and less published data on D. latus. Based on recent data, the broad fish tapeworm is either absent or present at very low prevalences in Fennoscandia and the Baltic and Danube regions, but the Alpine lakes region represents a continuous ongoing circulation of the parasite in the natural environment and humans.

Plasmodium knowlesi, a simian malaria parasite of great public health concern has been reported from most countries in Southeast Asia and exported to various countries around the world. Currently P. knowlesi is the predominant species infecting humans in Malaysia. Besides this species, other simian malaria parasites such as P. cynomolgi and P. inui are also infecting humans in the region. The vectors of P. knowlesi and other Asian simian malarias belong to the Leucosphyrus Group of Anopheles mosquitoes which are generally forest dwelling species. Continual deforestation has resulted in these species moving into forest fringes, farms, plantations and human settlements along with their macaque hosts. Limited studies have shown that mosquito vectors are attracted to both humans and macaque hosts, preferring to bite outdoors and in the early part of the night. We here review the current status of simian malaria vectors and their parasites, knowledge of vector competence from experimental infections and discuss possible vector control measures. The challenges encountered in simian malaria elimination are also discussed. We highlight key knowledge gaps on vector distribution and ecology that may impede effective control strategies.

Enterocytozoon bieneusi is a microsporidian microorganism that causes intestinal disease in animals including humans. E. bieneusi is an obligate intracellular pathogen, typically causing severe or chronic diarrhoea, malabsorption and/or wasting. Currently, E. bieneusi is recognised as a fungus, although its exact classification remains contentious. The transmission of E. bieneusi can occur from person to person and/or animals to people. Transmission is usually via the faecal-oral route through E. bieneusi spore-contaminated water, environment or food, or direct contact with infected individuals. Enterocytozoon bieneusi genotypes are usually identified and classified by PCR-based sequencing of the internal transcribed spacer region (ITS) of nuclear ribosomal DNA. To date, ~600 distinct genotypes of E. bieneusi have been recorded in ~170 species of animals, including various orders of mammals and reptiles as well as insects in >40 countries. Moreover, E. bieneusi has also been found in recreational water, irrigation water, and treated raw- and waste-waters. Although many studies have been conducted on the epidemiology of E. bieneusi, prevalence surveys of animals and humans are scant in some countries, such as Australia, and transmission routes of individual genotypes and related risk factors are poorly understood. This article/chapter reviews aspects of the taxonomy, biology and epidemiology of E. bieneusi; the diagnosis, treatment and prevention of microsporidiosis; critically appraises the naming system for E. bieneusi genotypes as well as the phylogenetic relationships of these genotypes; provides new insights into the prevalence and genetic composition of E. bieneusi populations in animals in parts of Australia using molecular epidemiological tools; and proposes some areas for future research in the E. bieneusi/microsporidiosis field.