Major Human Parasitic Diseases Research Articles

Benign-by-Design SAHA Analogues for Human and Animal Vector-Borne Parasitic Diseases.

The search for new drugs fulfilling One Health and Green Chemistry requirements is an urgent call. Here, for the first time, we envisaged developing SAHA analogues by starting from the cashew nutshell liquid (CNSL) agro-industrial waste and employing a metathesis approach. This sustainable combination (comprising principles #7 and #9) allowed a straightforward synthesis of compounds 13-20. All of them were found to not be toxic on HepG2, IMR-32, and L929 cell lines. Then, their potential against major human and animal vector-borne parasitic diseases (VBPDs) was assessed. Compound 13 emerged as a green hit against the trypomastigote forms of T. b. brucei. In silico studies showed that the T. b. brucei HDAC (TbDAC) catalytic pocket could be occupied with a similar binding mode by both SAHA and 13, providing a putative explanation for its antiparasitic mechanism of action (13, EC50 = 0.7 ± 0.2 μM).

Temporal trends in disease burden of major human parasitic diseases in China from 1990 to 2019

To analysize the temporal trends in the disease burden of major human parasitic diseases in China from 1990 to 2019, so as to provide the evidence for improving the parasitic disease control strategy in China. The disability-adjusted life years (DALYs) of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis in China from 1990 to 2019 were captured from the Global Burden of Disease Study 2019 (GBD 2019), and age- and gender-specific DALYs of parasitic diseases were estimated. The temporal trends in DALYs of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis were evaluated in China from 1990 to 2019 using average annual percent change (AAPC) with Joinpoint regression analysis. The DALYs were 643 836.42 person-years due to food-borne trematodiases, 156 853.03 person-years due to cysticercosis, 79 764.62 person-years due to schistosomiasis, 70 989.73 person-years due to intestinal nematode infections, 4 258.61 person-years due to echinococcosis and 264.86 person-years due to malaria in China in 2019, respectively. The overall DALYs of six parasitic diseases were higher among men (546 441.93 person-years) than among women (409 525.33 person-years), and were greater among adults at ages of 14 to 65 years (684 780.84 person-years) than among children at 14 years and lower (35 437.38 person-years) and the elderly at ages of 65 years and older (235 749.04 person-years). During the period from 1990 to 2019, food-borne trematodiases were the leading cause of DALYs among the six parasitic diseases, and cysticercosis shifted from the fourth leading cause in 1990 to the second leading cause of DALYs in China in 2019, while intestinal nematode infections shifted from the second leading cause in 1990 to the fourth leading cause of DALYs in 2019. The DALYs of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with the fastest drop seen in DALYs due to malaria (AAPC = -19.6%, P = 0.003), followed by due to intestinal nematode infections (AAPC = -8.2%, P < 0.001) and schistosomiasis (AAPC = -3.1%, P < 0.001), and a slow decline was seen in the DALYs of food-borne trematodiases (AAPC = -1.0%, P < 0.001), while there were no significant decrease in the DALYs of echinococcosis (AAPC = -0.5%, P = 0.264) and the DALYs of cysticercosis appeared a tendency towards a rise (AAPC = 0.7%, P < 0.001). The disease burden of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with a high disease burden seen due to food-borne parasitic diseases, no remarkable reduction seen in echinococcosis, and a tendency towards a rise seen in cysticercosis. It is recommended to focus on echinococcosis control, and continue to consolidate the control achievements of other major human parasitic diseases in China; meanwhile, the surveillance and prevention of food-borne parasitic diseases should be reinforced.

Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections.

Vaccines against parasites have lagged centuries behind those against viral and bacterial infections, despite the devastating morbidity and widespread effects of parasitic diseases across the globe. One of the greatest hurdles to parasite vaccine development has been the lack of vaccine strategies able to elicit the complex and multifaceted immune responses needed to abrogate parasitic persistence. Viral vectors, especially adenovirus (AdV) vectors, have emerged as a potential solution for complex disease targets, including HIV, tuberculosis, and parasitic diseases, to name a few. AdVs are highly immunogenic and are uniquely able to drive CD8+ T cell responses, which are known to be correlates of immunity in infections with most protozoan and some helminthic parasites. This review presents recent developments in AdV-vectored vaccines targeting five major human parasitic diseases: malaria, Chagas disease, schistosomiasis, leishmaniasis, and toxoplasmosis. Many AdV-vectored vaccines have been developed for these diseases, utilizing a wide variety of vectors, antigens, and modes of delivery. AdV-vectored vaccines are a promising approach for the historically challenging target of human parasitic diseases.

A Multimedia Active Learning Approach to Introducing Human Parasitic Diseases in an Undergraduate Parasitology Course †

Introducing undergraduate students to major human diseases is a key focus of many parasitology courses. Here I present a multifaceted active learning technique that familiarizes students with major human parasitic diseases while simultaneously exposing students to a range of important medical, biological, and ecological concepts.

Prevalence of soil - borne nematode infections among residents living in urban/town areas of China in 2015

To understand the prevalence of soil-borne nematode infections among residents living in urban/town areas of China, so as to provide insights into the control and elimination of soil-borne nematodiasis. A total of 5 epidemic areas were classified in China according to the prevalence of human Clonorchis sinensis infections captured from the 2014-2015 national survey on major human parasitic diseases in China, and the total sample size was estimated according to the binomial distribution and Poisson's distribution. Then, the total sample size was allocated proportionally to each province (autonomous region, municipality) of China based on the percentage of residents living in urban and town areas, and the number of survey sites in each province (autonomous region, municipality) was proportionally assigned according to the percentages of residents living in urban and town areas. Then, stratified sampling was performed at county, township and community levels according to the number of sampling sites in each province (autonomous region, municipality), and the survey site (community) was defined as the smallest sampling unit. All permanent residents in the survey sites were selected as the study subjects, and their stool samples were collected for identification and counting of parasite egg using a Kato-Katz technique. The prevalence and intensity of each parasite species were calculated. From 2014 to 2015, among the 133 231 residents detected in 31 provinces (autonomous regions, municipalities) of China, the overall prevalence of soil-borne nematode infections was 1.23% (1 636/133 231), and the prevalence rates of hookworm, Ascaris lumbricoides and Trichuris trichiura infections were 0.77% (1 032/133 231), 0.32% (426/133 231) and 0.17% (224/133 231), respectively. The highest prevalence of soil-borne nematode infections was seen in Jiangxi (4.03%, 82/2 034) and Chongqing (4.03%, 524/13 012), followed by in Hainan (3.47%, 72/2 075). The prevalence of soilborne nematode infections was 1.07% (662/62 139) in men and 1.37% (974/71 092) in women, and the greatest prevalence was found in residents at ages of 65 to 70 years (2.56%, 219/8 569). With regard to occupations and education levels, herdsmen (2.47%, 2/81) and illiterate residents (3.33%, 226/6 795) were found to have the highest prevalence of soil-borne nematode infections, respectively. In addition, mild infections were predominantly identified in hookworm-, A. lumbricoides- and T. trichiura-infected individuals (all > 90%). The overall prevalence of soil-borne nematodiasis remains low in urban and town areas of China; however, human infections are widespread. According to the epidemiological features, health education combined with deworming are recommended to reduce the prevalence of soil-borne nematode infections among residents living in urban and town areas of China.

Prevalence and influencing factors of intestinal parasitic diseases among rural children in Henan Province

To understand the epidemic status and influencing factors of intestinal parasitic diseases among rural children in Henan Province. According to the Scheme for The National Survey on Current Status of Major Human Parasitic Diseases in China, the survey counties were selected based on the ecological zones and economic levels in Henan Province between 2014 and 2015. Then, the included counties were stratified according to the topography and economic levels. A township was randomly sampled from each stratum, and a village was randomly sampled from each township as the study site. Finally, a total of 104 study sites from 35 counties were enrolled for the survey of intestinal parasitic diseases in children. At least 250 fresh stool samples were collected from each study site for detection of intestinal helminth eggs with the Kato-Katz technique, for the identification of Necator americanus and Ancylostoma duodenale with the fecal culture method, and for the detection of intestinal protozoa trophozoite and cyst with the physiological saline smear and iodine staining techniques. In addition, the Enterobius vermicularis and tapeworm eggs were detected in children aged 3 to 6 years using the adhesive cellophane-tape perianal swab method. The overall prevalence of intestinal parasitic infections was 3.21% (214/6 671) among rural children in Henan Province, and the prevalence of intestinal helminthes (2.62%, 175/6 671) was higher than that of intestinal protozoa (0.60%, 40/6 671). A total of 12 species of intestinal parasites were found, including 4 nematodes species, one trematode species, and 7 protozoa species, and the highest infection was seen in E. vermicularis (2.47%, 161/6 671). Among the four ecological zones in Henan Province, the greatest prevalence of intestinal parasitic infections was detected among children in the Qinba Mountain Ecological Zone (5.85%, 90/1 538). There was no gender-specific difference in the prevalence of intestinal parasitic infections in children (P > 0.05); however, there were age- (χ2 = 32.762, P < 0.05) and education level-specific differences in the prevalence of intestinal parasitic infections in children (χ2 = 67.507, P < 0.05), with the greatest prevalence of E. vermicularis infection seen in all species of intestinal parasites in children at all age groups. Multivariate non-conditional logistic regression analysis showed that high education level, high coverage of harmless toilets, drinking tap water and deworming were protective factors for intestinal parasitic infections in children in Henan Province. The overall prevalence of intestinal parasitic infections appeared a tendency towards a gradual decline among children in Henan Province as compared to the previous two surveys. The overall prevalence of intestinal parasitic infections shows a tendency towards a remarkable decline among children in Henan Province. E. vermicularis infection should be given a priority for future parasitic disease control activities among rural children in Henan Province.

Cytological and Wet Mount Microscopic Observations Made in Urine of Schistosoma haematobium-Infected Children: Hint of the Implication in Bladder Cancer.

Background Schistosomiasis is the second major human parasitic disease next to malaria, in terms of socioeconomic and public health consequences, especially in sub-Saharan Africa. Schistosoma haematobium (S. haematobium) is a trematode and one of the species of Schistosoma that cause urogenital schistosomiasis (urinary schistosomiasis). Although the knowledge of this disease has improved over the years, there are still endemic areas, with most of the reported cases in Africa, including Ghana. Not much has been done in Ghana to investigate cytological abnormalities in individuals within endemic communities, although there are epidemiologic evidences linking S. haematobium infection with carcinoma of the bladder. Aim The aim of this study was to identify microscopic and cytological abnormalities in the urine deposits of S. haematobium-infected children. Methodology Three hundred and sixty-seven (367) urine samples were collected from school children in Zenu and Weija communities. All the samples were examined microscopically for the presence of S. haematobium eggs, after which the infected samples and controls were processed for cytological investigation. Results S. haematobium ova were present in 66 (18.0%) out of the 367 urine samples. Inflammatory cells (82%, 54/66), hyperkeratosis (47%, 31/66), and squamous cell metaplasia (24%, 16/66) were the main observations made during the cytological examination of the S. haematobium-infected urine samples. Conclusion Cytological abnormalities in S. haematobium-infected children may play an important role in the severity of the disease, leading to the possible development of bladder cancer in later years, if early attention is not given. Therefore, routine cytological screening for urogenital schistosomiasis patients (especially children) at hospitals in S. haematobium-endemic locations is recommended.

Investigation on human intestinal parasitic diseases in ecological regions of Qinba Mountains in Henan Province in 2015

To understand and analyze the epidemic status of human intestinal parasitic diseases in the ecological region of the Qinba Mountains in Henan Province, so as to provide the evidence for the control of the diseases in this region. According to the methods of National Survey Scheme on Major Human Parasitic Diseases, 26 survey spots were selected in 8 counties (cities) in ecological regions of Qinba Mountains in Henan Province in 2015. After collecting the human fecal samples, the eggs of intestinal helminthes were detected with the modified Kato-Katz thick smear method, the species of Ancylostoma of the hookworm egg-positive samples were identified with the tube fecal culture method, the eggs of Enterobius vermicularis were detected by using the adhesive tape method in children aged 3 to 6 years, and the cyst and trophozoite of intestinal protozoa were examined by iodine staining. The infections of intestinal parasites in different populations and the related influencing factors were analyzed. Totally 6 706 residents were recruited in this study, 8 kinds of parasites were found including 3 species of helminthes and 5 species of protozoans. The overall infection rate of intestinal parasites was 3.39%, covering 2.92% for helminthes and 0.49% for protozoans. The infection rate of E. vermicularis in children aged 3 to 6 years was 3.93%. The 3 identified helminthes were Ascaris lumbricoides, E. vermicularis, and Dicrocoelium dendriticum, with the highest infection rate of E. vermicularis (2.68%, χ2 = 306.362, P < 0.05). The 5 identified protozoans were Entamoeba hartmani, E. coli, Endolimax nana, Giardia lamblia, and Blastocystis hominis, and the infection rate of E. nana was the highest (χ2 = 23.842, P < 0.05). Among the 8 counties (cities), the highest infection rate of helminthes, mainly with Enterobius infection, existed in Ruyang County, and the infection rate of protozoans in Xin'an County was the highest, mainly with E. nana infection. There was a significant difference in the infection rates of helminthes and protozoans among the 8 counties (cities) (helminthes: χ2 = 357.525, P < 0.05; protozoans: χ2 = 38.795, P < 0.05). There was no significant difference in the helminth infection rate between males and females ( χ2 = 0.034, P > 0.05), but the protozoan infection rate of the males was higher than that of the females ( χ2 = 12.946, P < 0.05). The helminth infection rate of the 0-9 years old group was the highest ( χ2 = 62.600, P < 0.05), up to 6.60%, mainly with E. vermicularis infection. There was no significant difference in the infection rate of intestinal parasites among nationalities ( χ2 = 0.212, P > 0.05). The helminth infection rate of preschool children was the highest and up to 8.43%, mainly with E. vermicularis infection. The infection of A. lumbricoides was mainly happened among farmers, with the infection rate of 0.31%. There was a significant difference in the helminth infection rate among different occupations (χ2 = 84.333, P < 0.05). The intestinal parasites infection rate of the illiterate population was the highest and up to 7.63%, there was a significant difference among the populations with different educational levels (χ2 = 72.013, P < 0.05). The helminth infection rate of plain areas was higher than that of valley and hill ( χ2 = 11.690, P < 0.05). The helminth infection rate of people with low-income was the highest and up to 10.32% (χ2 = 244.999, P < 0.05). The protozoan infection rate of people with middle-income was the highest, who had the annual per capita net income of 6 000 to 7 999 Yuan ( χ2 = 24.749, P < 0.05). The helminth infection rate of people drinking well water was much higher than that of people drinking tap water (χ2 = 62.255, P < 0.05). The protozoan infection rate of people without insect repellent was higher than that of people with insect repellent (χ2 = 5.235, P < 0.05). The infection rates of human intestinal parasites in the ecological region of the Qinba Mountains in Henan Province have decreased sharply. E. vermicularis infection in children should be the main point of prevention and treatment of parasitic diseases in the future.

Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents.

Schistosomiasis is a major human parasitic disease afflicting more than 250 million people, historically treated with chemotherapies praziquantel or oxamniquine. Since oxamniquine is species-specific, killing Schistosoma mansoni but not other schistosome species (S. haematobium or S. japonicum) and evidence for drug resistant strains is growing, research efforts have focused on identifying novel approaches. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust structure-activity relationship (SAR) program that identified several new lead compounds with effective worm killing. These studies culminated in the discovery of compound 12a, which demonstrated broad-species activity in killing S. mansoni (75%), S. haematobium (40%), and S. japonicum (83%).

Stratified sampling survey of major human parasitic diseases in Henan province

Objective: To understand the prevalence of major human parasitic diseases and related factors in Henan province. Methods: This stratified sampling survey was carried out according to the requirement of national survey protocol of major human parasitic diseases, 2014-2015. The prevalence of soil-transmitted helminths infection, taeniasis and intestinal protozoiasis were surveyed in 104 sites selected from 35 counties (districts) and the prevalence of clonorchiasis was surveyed in 62 sites selected from 37 townships. In each survey spot, 250 persons were surveyed. A total of 26 866 persons and 15 893 persons were surveyed. Modified Kato-Katz thick smear was used to detect the eggs of intestinal helminthes. Tube fecal culture was used to identify the species of hookworm. The Enterobius eggs were detected in children aged 3 to 6 years by using adhesive tape. The cyst and trophozoite of intestinal protozoa were examined with physiological saline direct smear method and iodine stain method. Results: The overall infestation rate of intestinal parasites was2.02% in Henan, and the worm infection rate was higher than protozoa infection rate. Fourteen kinds of intestinal parasites were found, including nematode (5 species), trematode (2 species), and protozoan (7 species). The infection rate of Enterobius vermicularis was highest, and Qinba Mountain ecological area had the highest infestation rate of intestinal parasites in 4 ecological areas of Henan. There was no significant difference in intestinal parasite infection rate between males and females (χ(2)=3.630, P=0.057), and the differences in intestinal parasite infection rate among different age groups had significance (χ(2)=124.783, P=0.000 1). The infection rate reached the peak in age group ≤9 years and the major parasite was Enterobius vermicularis. Furthermore the overall human infection rate of parasite showed a downward trend with the increase of educational level of the people (χ(2)=70.969, P=0.000 1), the differences had significance (χ(2)=120.118, P=0.000 1). For different populations, the infection rate of intestinal parasites was highest among preschool children. The infection of intestinal helminth was mainly mild, only 2 severe cases were detected. The infection rate of Clonorchis sinensis in urban residents was only 0.006%. Logistic regression analysis showed that being preschool children (χ(2)=15.765, P=0.000 1) and drinking well water (χ(2)=45.589, P=0.000 1) were the risk factors for intestinal parasite infection, and annual income per capita of farmers was the protective factor against intestinal parasite infection. The infection rates of protozoa and intestinal parasites decreased sharply compared with the results of previous two surveys, and the rate of intestinal helminth infection also dropped sharply compared with the second survey. The numbers of protozoa, helminth and intestinal parasites detected in this survey were all less than the numbers found in the previous two surveys. Conclusions: Compared the results of three surveys in Henan, the infection rate of protozoa and intestinal parasites showed a downward trend. The prevention and treatment of Enterobius vermicularis infection in children should be the key point of parasitic disease control in the future.

Survey and analysis of major human parasitic diseases in Chongqing City

To investigate the epidemic of major human parasitic diseases in Chongqing City, so as to provide a reference for developing prevention and control strategies. According to the unified methods formulated by the national investigation scheme and stratified cluster random sampling, 36 rural pilots and 50 urban pilots were selected in Chongqing City. The number of the objects investigated in individual pilot was defined over 250. Totally 22 263 residents were detected. The overall infection rate of intestinal parasites was 5.41%. The infection rates of Ascaris lumbricoides, hookworm, Trichuris trichiura, and Enterobius vermicularis were 1.20%, 4.23%, 0.13% and 0.47% respectively. Only 0.22% of the infections were co-infections. The infection rate of overall intestinal parasites was statistically higher in the females than that in the males (χ2 = 15.19, P < 0.05), and the infection rates were significantly different among various age groups, occupations, education levels, and regions (χ2 = 15.19, 396.72, 421.07, 347.79, all P < 0.05). The infection rates of major human parasites in Chongqing show an obviously decreasing tendency compared with the rates of the past twice of national surveys. In the future, the controlling practices are obliged to focus on reducing the infection rates of soil-borne parasites.

Parasite Carbohydrate Vaccines.

Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases—malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma, and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development.

Co-endemicity of Pulmonary Tuberculosis and Intestinal Helminth Infection in the People's Republic of China.

Both pulmonary tuberculosis (PTB) and intestinal helminth infection (IHI) affect millions of individuals every year in China. However, the national-scale estimation of prevalence predictors and prevalence maps for these diseases, as well as co-endemic relative risk (RR) maps of both diseases’ prevalence are not well developed. There are co-endemic, high prevalence areas of both diseases, whose delimitation is essential for devising effective control strategies. Bayesian geostatistical logistic regression models including socio-economic, climatic, geographical and environmental predictors were fitted separately for active PTB and IHI based on data from the national surveys for PTB and major human parasitic diseases that were completed in 2010 and 2004, respectively. Prevalence maps and co-endemic RR maps were constructed for both diseases by means of Bayesian Kriging model and Bayesian shared component model capable of appraising the fraction of variance of spatial RRs shared by both diseases, and those specific for each one, under an assumption that there are unobserved covariates common to both diseases. Our results indicate that gross domestic product (GDP) per capita had a negative association, while rural regions, the arid and polar zones and elevation had positive association with active PTB prevalence; for the IHI prevalence, GDP per capita and distance to water bodies had a negative association, the equatorial and warm zones and the normalized difference vegetation index had a positive association. Moderate to high prevalence of active PTB and low prevalence of IHI were predicted in western regions, low to moderate prevalence of active PTB and low prevalence of IHI were predicted in north-central regions and the southeast coastal regions, and moderate to high prevalence of active PTB and high prevalence of IHI were predicted in the south-western regions. Thus, co-endemic areas of active PTB and IHI were located in the south-western regions of China, which might be determined by socio-economic factors, such as GDP per capita.

Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition.

Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.

Expressions of P53 and CD68 in mouse liver withSchistosoma mansoniinfection and the protective role of silymarin

Schistosomiasis is one of the major human parasitic diseases in many developing countries and is one of the causes of morbidity and mortality in the human population. The present work has been planned to study the histopathological and immunohistochemical expression of P53 and CD68 in mouse liver tissues experimentally infected with Schistosoma mansoni, in addition to the ameliorating role of silymarin. A total of 50 adult male mice were divided into 5 groups (10 animals each). Groups 1 and 2 were the control and silymarin groups, respectively, while group 3 was the infected group in which the mice were infected with S. mansoni live cercariae for 6weeks. Groups 4 and 5 were the cotreated and posttreated groups, respectively, in which mice were infected with cercariae of S. mansoni and treated with silymarin during and after Schistosoma infection, respectively. The major histopathological lesions were variable numbers of perioval granulomas, diffuse infiltration of inflammatory cells, mainly eosinophils and small mononuclear cells, and fibrosis of portal areas and interlobular septa. Treatment with silymarin led to a significant reduction in granuloma area in all treated infected mice compared with nontreated infected mice. Immunohistochemical observations of the liver tissues showed a significant increase in the apoptotic proteins P53 and CD68 after the infection with the cercariae of Schistosoma, compared with the control group. The expression of the cytoplasmic P53 and CD68 was very low in the control liver sections. A significant decrease in the expression of the cytoplasmic P53 and CD68 was observed after silymarin treatment.

HDAC inhibitors in parasitic diseases

Parasitic diseases cause significant global morbidity and mortality, particularly in underdeveloped regions of the world. Malaria alone causes ~800000 deaths each year, with children and pregnant women being at highest risk. There is no licensed vaccine available for any human parasitic disease and drug resistance is compromising the efficacy of many available anti-parasitic drugs. This is driving drug discovery research on new agents with novel modes of action. Histone deacetylase (HDAC) inhibitors are being investigated as drugs for a range of diseases, including cancers and infectious diseases such as HIV/AIDS, and several parasitic diseases. This review focuses on the current state of knowledge of HDAC inhibitors targeted to the major human parasitic diseases malaria, schistosomiasis, trypanosomiasis, toxoplasmosis and leishmaniasis. Insights are provided into the unique challenges that will need to be considered if HDAC inhibitors are to be progressed towards clinical development as potential new anti-parasitic drugs.

Schistosoma mansoni worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN

In schistosomiasis, a major human parasitic disease caused by helminths, different life-stages of the parasite contribute to the developing host immune response. To increase our understanding of the mechanisms that play a role in shaping the host immune responses, we have investigated the effects of schistosome glycoconjugates on the phenotype of dendritic cells (DCs), which form a crucial link between the innate and the adaptive immunity. We show here that Schistosoma mansoni worm glycolipids induce DC activation as indicated by upregulation of the maturation markers CD80, CD86 and MHC-II, as well as the production of the cytokines interleukin-12 p40 (IL-12 p40), IL-10, IL-1β, IL-6, IL-8 and tumor necrosis factor-α (TNF-α). Co-culture of glycolipid-primed DCs with naïve T cells results in skewing of the T cell response towards a Th1 profile. Remarkably, the DC activation is dependent on fucosylated glycan moieties of the glycolipids. On the DCs, the C-type lectin DC-SIGN and TLR4 are both critically involved in the induced activation, as was demonstrated by using monoclonal antibodies that block interaction of these receptors with the glycolipids. Furthermore, whereas the worm glycolipids were not able to activate HEK 293 cells expressing TLR4, they did show TLR4 activation after introduction of DC-SIGN in the HEK 293-TLR4 cells. Our data provide evidence for a novel function of DC-SIGN as an essential co-receptor for TLR4-induced activation of human DCs. This mechanism of TLR4 activation by worm glycolipids may contribute to eliciting Th1 immune responses in schistosome infection.

Gene sequencing, modelling and immunolocalization of the protein disulfide isomerase from Plasmodium chabaudi

Malaria remains one of the major human parasitic diseases, particularly in subtropical regions. Most of the fatal cases are caused by Plasmodium falciparum. The rodent parasite Plasmodium chabaudi has been the model of choice in research due to its similarities to human malaria, including developmental cycle, preferential invasion of mature erythrocytes, synchrony of asexual development, antigenic variation, gene sinteny as well as similar resistance mechanisms. Protein disulfide isomerase (PDI) is an essential catalyst of the endoplasmic reticulum in different biological systems with folding and chaperone activities. Most of the proteins exported by parasites have to pass through the endoplasmic reticulum before reaching their final destination and their correct folding is critical for parasite survival. PDI constitutes a potential target for the development of alternative therapy strategies based on the inhibition of folding and chaperoning of exported proteins. We here describe the sequencing of the gene coding for the PDI from P. chabaudi and analyse the relationship to its counterpart enzymes, particularly with the PDI from other Plasmodium species. The model constructed, based on the recent model deduced from the crystallographic structure 2B5E, was compared with the previous theoretical model for the whole PDI molecule constructed by threading. A recombinant PDI from P. chabaudi was also produced and used as an antigen for monoclonal antibody production for application in PDI immunolocalization.

The Use of Anticancer Drugs in Antiparasitic Chemotherapy

Many similarities exist between cancer cells and parasites. A potentially lucrative starting point for the discovery of novel drugs to combat parasites is to examine available compounds developed against cancer for antiparasitic properties. Here, we review the use of current and promising anticancer agents for treating major human parasitic diseases.

Meager genetic variability of the human malaria agent Plasmodium vivax.

Malaria is a major human parasitic disease caused by four species of Plasmodium protozoa. Plasmodium vivax, the most widespread, affects millions of people across Africa, Asia, the Middle East, and Central and South America. We have studied the genetic variability of 13 microsatellite loci in 108 samples from 8 localities in Asia, Africa, South America, and New Guinea. Only one locus is polymorphic; nine are completely monomorphic, and the remaining three are monomorphic in all but one or two populations, which have a rare second allele. In contrast, Plasmodium falciparum displays extensive microsatellite polymorphism within and among populations. We further have analyzed, in 96 samples from the same 8 localities, 8 tandem repeats (TRs) located on a 100-kb contiguous chromosome segment described as highly polymorphic. Each locus exhibits 2-10 alleles in the whole sample but little intrapopulation polymorphism (1-5 alleles with a prevailing allele in most cases). Eight microsatellite loci monomorphic in P. vivax are polymorphic in three of five Plasmodium species related to P. vivax (two to seven individuals sampled). Plasmodium simium, a parasite of New World monkeys, is genetically indistinguishable from P. vivax. At 13 microsatellite loci and at 7 of the 8 TRs, both species share the same (or most common) allele. Scarce microsatellite polymorphism may reflect selective sweeps or population bottlenecks in recent evolutionary history of P. vivax; the differential variability of the TRs may reflect selective processes acting on particular regions of the genome. We infer that the world expansion of P. vivax as a human parasite occurred recently, perhaps <10,000 years ago.