Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniases, which affect millions of people worldwide. Cutaneous leishmaniasis (CL), caused by L. major, is one the most common forms of the disease in the Old World. There is no preventive or therapeutic human vaccine available for L. major CL, and existing drug treatments are expensive, have toxic side effects, and resistant parasite strains have been reported. Hence, further therapeutic interventions against the disease are necessary. Terminal, non-reducing, and linear α-galactopyranosyl (α-Gal) epitopes are abundantly found on the plasma membrane glycolipids of L. major known as glycoinositolphospholipids. The absence of these α-Gal epitopes in human cells makes these glycans highly immunogenic and thus potential targets for vaccine development against CL.
Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.
The authors report the results of parasitological analyses of stool samples in N'Djamena (Chad) since 1963 and in Garoua (North Cameroon) since 1990. The number of positive stool examinations has fallen, with a significant decline in helminthiases, although the level of protozoan infections has remained essentially the same.
The flagellate protozoan parasite, Giardia intestinalis, is widely distributed throughout the world with a high prevalence in developing countries in the tropics and subtropics, including Malaysia. Approximately 200 million people are infected with the parasite globally, with 500,000 new cases reported annually. This cross-sectional study was conducted among three tribes of Orang Asli communities in Selangor, Perak and Pahang states of Malaysia. The main objective was to determine the prevalence of and risk factors for giardiasis. Stool samples were collected from 500 individuals aged between 2 and 74years (males=219, females=281). The samples were examined with formalin-ether sedimentation and trichrome staining techniques. Socioeconomic data were collected through a pre-tested questionnaire. The overall prevalence of giardiasis was 20.0% with the highest prevalence in the Proto-Malays (33.3%) followed by Negritos (20.1%) and Senois (10.4%). The positive cases showed a decrease with increasing age and most of the positive cases were observed in individuals less than 24years old. Males had significantly higher prevalence than females (χ(2)=5.283, P=0.022). Logistic regression analysis of the overall population studied and the Senoi tribe confirmed that being a child aged less than 15years, being male, the consumption of raw vegetables and the presence of other family members infected with G. intestinalis were the main risk factors for giardiasis. The presence of other family members infected with G. intestinalis was the only risk factor highlighted in the Proto-Malay and Negrito tribes. Diarrhoea was significantly associated with giardiasis. However, the cause and effect relationship has yet to be determined. Thus, screening family members and treating the infected individuals are the main strategies that should be adopted by the public health authority in combating this infection in Orang Asli communities as well as health education regarding good personal and food hygiene practises.
A retrospective study of the pathologic findings in weedy (Phyllopteryx taeniolatus) and leafy (Phycodurus eques) seadragons was performed on specimens submitted to 2 reference laboratories from 1994 to 2012 to determine the range and occurrence of diseases affecting aquarium-held populations. One hundred two and 94 total diagnoses were recorded in weedy and leafy seadragons, respectively. Two of the more common etiologic diagnoses in both species were mycobacteriosis and scuticociliatosis, whereas myxozoanosis was common in weedy seadragons. Metazoan parasite infections were less common etiologic diagnoses. There were no correlations between mycobacteriosis and ciliate protozoan infections in either species. Myxozoanosis was usually found in combination with other diseases and, except for 1 case, was restricted to weedy seadragons. Phaeohyphomycosis, nonmycobacterial bacterial infections, and trauma were also important but less frequent diagnoses. Intestinal coccidiosis was found in weedy but not leafy seadragons. Mineralization of the swim bladder was detected in 26 of 197 leafy seadragons and only 2 of 257 weedy seadragons. Although weedy and leafy seadragons share certain diseases of significance to exhibit populations, there are diseases unique to each species about which the veterinary pathologist, clinician, or diagnostician should be aware.
Tetrahymena rostrata, which is characterized by a particular encystment-excystment cycle involving autogamy, has been recently found infecting the kidney of edible Helix aspersa snails under farming conditions. In this work, the effects of several factors on its encystment/excystment behaviour and the occurrence of different serotypes were investigated. The encystment/excystment response under starvation conditions was seriously affected by temperature. While a peak of encystment at 48 h followed by a progressive spontaneous excystment was observed at 18 and 25 °C, the encystment response was practically inhibited at 5 °C and clearly slowed down at 10 °C. At 30 °C, most of surviving ciliates remained encysted throughout the experiment, with spontaneous excystment being detected only after switching the temperature to 18 °C. Soil components also affected the encystment/excystment behaviour at 18 °C, with spontaneous excystment occurring in the presence of a sterile-filtered soil extract or mineral water but being strongly minimized with a non-filtered soil extract. Resting cysts formed in the latter extract exhibited a 3-4 times thicker and ultrastructurally more complex wall than that formed in mineral water and retained the excystment ability for about 4 weeks. Incomplete desiccation did not affect significantly the encystment response, while the mucus and kidney extracts from snails as well as a ciliate extract strongly stimulated a rapid excystment. Finally, two different serotypes infecting H. aspersa in heliciculture farms of Galicia (NW Spain) were identified, but no differences were observed between the encystment/excystment responses exhibited by two isolates belonging to each serotype.
Leishmania (Leishmania) amazonensis is an intracellular protozoan parasite responsible for the cutaneous leishmaniasis. The parasite replicates inside mammalian macrophage to establish infection. Host-pathogen interactions result in microRNA-mediated post-transcriptional regulation of host genes involved in inflammatory immune response. We analyzed macrophage miRNA profiles during L. (L.) amazonensis infection. The regulation of macrophage miRNA expression by the parasite correlates with/depends on parasite arginase activity during infection. L. (L.) amazonensis (La-WT) presented significant miRNA profile alteration (27%) compared to L. (L.) amazonensis arginase knockout (La-arg(-)) (~40%) in relation to uninfected-macrophages. We observed that 78% of the altered miRNAs were up-regulated in La-WT infection, while only 32% were up-regulated in La-arg(-)-infected macrophages. In contrast to La-WT, the lack of L. (L.) amazonensis arginase led to the inhibition of miR-294 and miR-721 expression. The expression of miR-294 and miR-721 was recovered to levels similar to La-WT in La-arg(-) addback mutant. The inhibition of miR-294/Nos2 and miR721/Nos2 interactions increased NOS2 expression and NO production, and reduced L. (L.) amazonensis infectivity, confirming Nos2 as target of these miRNAs. The role of miR-294 and miR-721 in the regulation of NOS2 expression during Leishmania replication in infected macrophages pointing these miRNAs as potential new targets for drug development.
Visceral leishmaniasis (VL) is a potentially lethal, sand fly-borne disease caused by protozoan parasites belonging to the Leishmania donovani species complex. There are several adequate methods for diagnosing VL, but the majority of infected individuals remain asymptomatic, comprising potential parasite reservoirs for transmission of the disease. The gold standard for assessing host infectiousness to biting vector insects is xenodiagnosis (i.e. scoring infection rates among insectary-reared insects that had fed on humans suspected of being infected). However, when it comes to sand flies and leishmaniasis, xenodiagnosis is an intricate operation burdened by logistical hurdles and ethical concerns that prevent its effective application for mass screening of widely dispersed communities, particularly in rural regions of underdeveloped countries. Minimally invasive microbiopsy (MB) devices were designed to penetrate the skin to a depth of ∼200 µm and absorb blood as well as skin cell lysates, mimicking the mode by which phlebotomine sand flies acquire blood meals, as well as their composition. MBs taken from 137 of 262 volunteers, living in endemic VL foci in Ethiopia, detected Leishmania parasites that could potentially be imbibed by feeding sand flies. Although the volume of MBs was 10-fold smaller than finger-prick blood samples, Leishmania DNA detection rates from MBs were significantly higher, implying that skin, more often than blood, was the source of parasites. Volunteers with histories of VL were almost as likely as healthy volunteers to test positive by MBs (southern Ethiopian focus: 95% CI: 0.35 - 2.59, P = 1.0. northern Ethiopian focus 0.87: 95% CI: 0.22 - 3.76, P = 1), suggesting the importance of asymptomatic patients as reservoirs of L. donovani. Minimally invasive, painless MBs should be considered for reliably and efficiently evaluating both L. donovani infection rates among large numbers of asymptomatic carriers and their infectiousness to blood-feeding sand flies.
Parasitic protozoan infections represent a major health burden in the developing world and contribute significantly to morbidity and mortality. These infections are often associated with considerable variability in clinical presentation. An emerging body of work suggests that the intestinal microbiota may help to explain some of these differences in disease expression. The objective of this minireview is to synthesize recent progress in this rapidly advancing field. Studies in humans, animal models and in vitro concerning the contribution of the intestinal microbiota to infectious disease will be discussed. We hope to provide an understanding of the human-protozoal pathogen-microbiome interaction and to speculate on how that might be leveraged for treatment.
Deep hypersaline anoxic basins (DHABs) are isolated habitats at the bottom of the eastern Mediterranean Sea, which originate from the ancient dissolution of Messinian evaporites. The different basins have recruited their original biota from the same source, but their geological evolution eventually constituted sharp environmental barriers, restricting genetic exchange between the individual basins. Therefore, DHABs are unique model systems to assess the effect of geological events and environmental conditions on the evolution and diversification of protistan plankton. Here, we examine evidence for isolated evolution of unicellular eukaryote protistan plankton communities driven by geological separation and environmental selection. We specifically focused on ciliated protists as a major component of protistan DHAB plankton by pyrosequencing the hypervariable V4 fragment of the small subunit ribosomal RNA. Geospatial distributions and responses of marine ciliates to differential hydrochemistries suggest strong physical and chemical barriers to dispersal that influence the evolution of this plankton group.