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Antiparasitic, Insecticidal, and Larvicidal Activities of Seaweeds and their Extracts
Published in Leonel Pereira, Therapeutic and Nutritional Uses of Algae, 2018
Leishmaniasis (or leishmaniosis) is a vector-borne disease caused by obligate protozoan parasites from the genus Leishmania (kingdom Protozoa, infrakingdom Excavata, order Trypanosomatida, family Trypanosomatidae), and is transmitted to humans by the bite of infected female phlebotomine (Nyssomyia spp., and other species) sandflies (Pinto et al. 2011, Torres et al. 2014). Leishmaniasis is endemic in large areas of the tropics, subtropics, and the Mediterranean basin, including more than 98 countries, where there are a total of 350 million people at risk and 12 million cases of infection. Canine leishmaniasis is a serious problem, and it is estimated that 2.5 million dogs are infected in the Mediterranean basin itself (Moreno and Alvar 2002, WHO 2017).
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Leishmaniasis provides a particularly striking example. The factors that determine the outcome of infection with Leishmania are complex and depend in large part on the species of parasite involved. Host factors also play an important part in disease progression. L. mexicana and L. tropica, for instance, generally cause a relatively benign form of the disease called localized cutaneous leishmaniasis (Figure 4.16). In this case, infected macrophages do not move far beyond the initial site of inoculation and the lesions that form are typically self-healing. However, on occasion the disease can progress to a far more serious disseminated cutaneous leishmaniasis. This condition is characterized by numerous disfiguring lesions over a wide area, caused by the dissemination of infected macrophages. In patients who respond with a primarily cell-mediated, Th-1 response, localized cutaneous leishmaniasis is the rule. Activated Th-1 cells release abundant IFN-γ, which enhances the ability of macrophages to kill parasites, effectively terminating the infection and allowing healing to commence. There is also increased activation of cytotoxic T cells, which are able to identify and kill infected cells. Few antibodies are observed. In individuals in whom the response is primarily humoral, although antibody titers are high, there is little or no effect on these intracellular parasites. Consequently, parasites continue to survive and replicate and, as infected macrophages disseminate away from the original site of infection, the gross tissue damage associated with the disseminated form of the disease is observed. The same general pattern is observed in canine leishmaniasis (canL), caused by Leishmania infantum. Historically associated with the Mediterranean region, this veterinary disease is now established in North America, with cases first being reported in 2000. It is especially well known in Texas and Oklahoma. Dogs vary considerably in terms of disease severity. As in humans, less serious symptoms are associated with a strong cell-mediated response. Interestingly, different breeds appear to respond differently, with some more susceptible to infection than others. The Ibizan hound, for instance, a breed that is native to the Mediterranean, is highly resistant to canL and its resistance has been attributed to the robust cell-mediated response with which it confronts the parasite. Boxers, German shepherds and especially fox hounds, on the other hand, are particularly susceptible, in part because their immune response is skewed toward a more humoral, less protective response.
The enemy at home: leishmaniasis in the Mediterranean basin, Italy on the focus
Published in Expert Review of Anti-infective Therapy, 2020
Elena Gianchecchi, Emanuele Montomoli
In Albania, VL has been identified since 1938 and usually it is recognized to be a childhood disease [169]. Although it is an infection that must be reported, few data regarding its incidence is available. The group of Petrela [170] conducted a retrospective analysis including 1,210 hospitalized VL patients admitted to the University Hospital of Tirana during the period 1995–2009. Despite the fact that the investigation suffered critical limitations, such as the availability of a low standard laboratory diagnostic methodology and the use of presumptive treatments, the study highlights that pediatric VL in Albania has a specific pattern, different from the neighboring developed Mediterranean countries. In fact, although common Leishmania agents, reservoir and vectors are shared by the Mediterranean countries, the noteworthy elevated incidence of VL in Albania in childhood as well as the frequency of co-morbidities, such as bronco-pneumonia, reflect the typical features of a poverty-related disease [171]. All the areas of this country are affected, although with elevated differences in case distribution. More specifically, 74% of VL cases resided in urbanized areas, and only 26% in rural areas of coastal or lake territories [170]. In any case, it has been hypothesized that the number of cases might be higher due to the presence of an underdeveloped surveillance system. A limited number of investigations regarding canine leishmaniasis prevalence indicate that it is widespread and, in some areas, including the capital, it reaches 16–17% [170].
From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection
Published in Expert Review of Vaccines, 2021
Greta Volpedo, Ryan H Huston, Erin A Holcomb, Thalia Pacheco-Fernandez, Sreenivas Gannavaram, Parna Bhattacharya, Hira L Nakhasi, Abhay R Satoskar
Animal reservoirs are another factor affecting disease emergence and transmission. Dogs remain the main reservoir for many forms of leishmaniasis, although other animals such as carnivores, rodents, and cattle can also be affected [110,111]. The seroprevalence of Leishmania in dogs ranges from 3 to 50% depending on the endemic areas, although PCR-based diagnostic methods suggest this percentage might be even higher [112]. Culling seropositive dogs is recommended in many endemic countries, as treatment could lead to the development of drug resistance in Leishmania. However, culling has not been shown to be particularly effective to reduce incidence of human leishmaniasis, and it presents economic and ethical concerns [113,114]. Furthermore, almost half of all infected dogs do not present clinical symptoms, while the other half presents a wide range of nonspecific symptoms, making surveillance and diagnosis very difficult [115]. Developing strategies to prevent and control canine leishmaniasis is not only a veterinary issue, but also a public health goal, as dogs can facilitate transmission to humans in endemic as well as Leishmania-free areas [116]. This has been a particular problem in the Mediterranean region and South America [112]. Although no vaccine has yet been approved for human use several vaccines are available for canine leishmaniasis, such as CaniLeish® and LetiFend® in Europe, and Leishmune® (withdrawn in 2014) and Leish-Tec® in Brazil. Safety and efficacy of these vaccines are reviewed in this reference [117]. These observations suggest that improving surveillance and treatment of the disease might not be enough to significantly slow down the spread of leishmaniasis, and that there is a critical need for a strong campaign of prevention in the future decades.
Vaccines against leishmaniasis: using controlled human infection models to accelerate development
Published in Expert Review of Vaccines, 2021
Vivak Parkash, Paul M. Kaye, Alison M Layton, Charles J Lacey
The early part of the 20th century bought with it an abundance of small experiments in quick succession that improved the understanding of the disease, the parasite and mode of transmission. The first documented experimental transmission to humans was in 1907, using subcutaneous inoculation [40]. Further work suggested the association of the Leishmania parasite with the sand fly [41]. The role of the sand fly in transmission of the parasite was then confirmed in experiments on human participants, although these early investigations did not expose humans directly to sandflies [42]. The first documented human exposure to sand flies in an experimental setting involved xenodiagnosis to confirm transmission to non-infected sand flies from infected human participants [43]. Further pioneering work by Adler and Theodor in the early 20th century successfully confirmed the transmission of Leishmania from phlebotomine sand flies directly to humans and this has been reproduced since, as well as many experimental human infections using parenteral methods [44–51]. This early work elucidated the life cycle of the Leishmania parasite in the sand fly and the finding of transmission via sand fly bite was made. It was also demonstrated that artificial feeding on infected tissue was comparable to transmission from human to sand fly [52,53]. Subsequent studies demonstrated transmission using different sand fly and Leishmania species [54–56]. Inoculation of Leishmania infantum, causing canine leishmaniasis, into human participants, which demonstrated the ability for similar Leishmania species to infect and manifest similar disease phenotypes across mammalian species, confirmed the suggestions of an infectious reservoir across species with relevance to human disease [57].