Major Parasitic Disease 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).

Bioactivity of synthetic peptides from Ecuadorian frog skin secretions against Leishmania mexicana, Plasmodium falciparum, and Trypanosoma cruzi.

Chagas disease, leishmaniasis, and malaria are major parasitic diseases disproportionately affecting the underprivileged population in developing nations. Finding new, alternative anti-parasitic compounds to treat these diseases is crucial because of the limited number of options currently available, the side effects they cause, the need for long treatment courses, and the emergence of drug-resistant parasites. Anti-microbial peptides (AMPs) derived from amphibian skin secretions are small bioactive molecules capable of lysing the cell membrane of pathogens while having low toxicity against human cells. Here, we report the anti-parasitic activity of five AMPs derived from skin secretions of three Ecuadorian frogs: cruzioseptin-1, cruzioseptin-4 (CZS-4), and cruzioseptin-16 from Cruziohyla calcarifer; dermaseptin-SP2 from Agalychnis spurrelli; and pictuseptin-1 from Boana picturata. These five AMPs were chemically synthesized. Initially, the hemolytic activity of CZS-4 and its minimal inhibitory concentration against Escherichia coli, Staphylococcus aureus, and Candida albicans were determined. Subsequently, the cytotoxicity of the synthetic AMPs against mammalian cells and their anti-parasitic activity against Leishmania mexicana promastigotes, erythrocytic stages of Plasmodium falciparum and mammalian stages of Trypanosoma cruzi were evaluated in vitro. The five AMPs displayed activity against the pathogens studied, with different levels of cytotoxicity against mammalian cells. In silico molecular docking analysis suggests this bioactivity may occur via pore formation in the plasma membrane, resulting in microbial lysis. CZS-4 displayed anti-bacterial, anti-fungal, and anti-parasitic activities with low cytotoxicity against mammalian cells. Further studies about this promising AMP are required to gain a better understanding of its activity.IMPORTANCEChagas disease, malaria, and leishmaniasis are major tropical diseases that cause extensive morbidity and mortality, for which available treatment options are unsatisfactory because of limited efficacy and side effects. Frog skin secretions contain molecules with anti-microbial properties known as anti-microbial peptides. We synthesized five peptides derived from the skin secretions of different species of tropical frogs and tested them against cultures of the causative agents of these three diseases, parasites known as Trypanosoma cruzi, Plasmodium falciparum, and Leishmania mexicana. All the different synthetic peptides studied showed activity against one of more of the parasites. Peptide cruzioseptin-4 is of special interest since it displayed intense activity against parasites while being innocuous against cultured mammalian cells, which indicates it does not simply hold general toxic properties; rather, its activity is specific against the parasites.

Construction and mouse antibody response evaluation of juvenile stage-specific chimeric protein from Fasciola gigantica

Fasciolosis, caused by the liver fluke Fasciola gigantica, is a major parasitic disease that affects livestock and therefore causes significant economic losses in tropical countries. Although anthelminthic drugs can kill the parasite, drug-resistant liver fluke populations are increasing. In this study, a recombinant F. gigantica chimeric protein (rFgCHI) consisting of cathepsin L1H (FgCL1H), cathepsin B3 (FgCB3), and Saposin-like protein 1 (FgSAP1) was designed and expressed in Escherichia coli (BL21). The molecular weight of rFgCHI was 61 kDa. To study the antibody response, male BALB/c mice were immunized via the subcutaneous injection of rFgCHI combined with Quil A. Immunization with rFgCHI showed the induction of IgG1 and IgG2a with a higher IgG1 isotype level, indicating the potential of mixed Th1/Th2 immune responses, with Th2 predominating. However, the results showed high levels of IgG against the single proteins, except for rFgSAP1. Through Western blotting, mouse anti-rFgCHI polyclonal antibodies could be detected to the native proteins obtained from the parasite at all stages. Immunolocalization also revealed that the anti-rFgCHI antibodies could detect targeted antigens in the cecal epithelium of the parasite. These results demonstrated that rFgCHI is immunogenic to the mouse immune system and may potentially be a protein candidate for the development of a fasciolosis vaccine.

Distribution of Scabies Infestations in Stray Dogs in Bursa Province.

Scabies infestation is a major parasitic disease affecting both human and animal health worldwide. This study aimed to determine the distribution of scabies infestation in stray dogs in Bursa province. The study material was obtained from stray dogs suspected of mange kept in a municipal shelter in Bursa between June 2020 and February 2022. Samples from stray dogs were examined in a laboratory, and dogs with scabies were determined. During the study, samples were collected from 205 (115 males, 90 females) scabies-suspected stray dogs, 58 (28.29%) of which had scabies. Demodex spp. were detected in 35 of the positive dogs (60.34%) (D. canis, D. injae), 19 (32.76%) Sarcoptes scabiei canis, 2 (3.44%) mixed infestation (Sarcoptes and Demodex), and 2 (3.44%) Otodectes cynotis agents. It was determined that 32 (55.17%) of 58 scabies-positive dogs were male and 26 (44.83%) were female. The association of infestations with age, season, and sex has not been found to be statistically meaningful. This study identified scabies agents and their prevalence rate in stray dogs of Bursa province, Türkiye.

Cloning, expression, and functional identification of aquaporin genes from Eimeria tenella

Avian coccidiosis, caused by Eimeria spp., is one of the major parasitic diseases in chicken. Aquaporins (AQP) are essential mediators of water regulation and nutritional intake in parasites, and it may be a suitable molecule for chemotherapeutic target and vaccine candidate. We identified two aquaporin genes in Eimeria tenella (EtAQP1 and EtAQP2) with their full sequence, and the expression profiles were analyzed across different stages of E. tenella life cycle. The expression of EtAQP1 and EtAQP2 in Xenopus oocytes renders them highly permeable for both water and glycerol. Sugar alcohols up to five carbons and urea pass the pore. The immunohistochemical analysis confirms the restriction of antiserum staining to the surface of transfected Xenopus oocytes. Like other AQP family, EtAQPs are transmembrane proteins that are likely important molecules that facilitate solute uptake for parasite intracellular growth and therapeutic targets.

Integrated application of transcriptomics and metabolomics provides insight into the mechanism of Eimeria tenella resistance to maduramycin

Avian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.

Accelerating the Control and Elimination of Major Parasitic Diseases in China - On World NTD Day 2024.

Accelerating the Control and Elimination of Major Parasitic Diseases in China - On World NTD Day 2024.

English

Coccidiosis is one of the major parasitic diseases infecting almost all ruminants, including cows, buffalo, sheep, and goats. Coccidiosis is caused by the genus Eimeria, which are host-specific obligate intestinal parasites. These are found almost all over the world and cause infections leading to mortalities and morbidities. Coccidiosis is usually treated by ionophores and synthetic chemicals of various classes including ionophores and synthetic chemical drugs. These drugs have been effective against coccidiosis but emerging issues of anthelmintic resistance, public health concerns, and consumer demand for organic products are leading to minimizing the use of these drugs. Vaccination is also being used, but vaccine failure and high cost limit their use. Among alternatives, herbal medicines are promising replacements because of their complex formulations, multiple modes of action, easy availability, and cost-effectiveness. Various plants, their parts, various formulations like herbal preparations, and the active compounds found in them are being searched to control ruminant coccidiosis. Multiple groups of botanical formulations, i.e., Flavonoids, alkaloids, tannins, terpenes, sulfur compounds, etc. have been proven to be effective against the ruminant coccidiosis-causing agents. They can control various stages of Eimeria directly and indirectly by antioxidant and immunomodulatory actions. Further research is needed to determine the most suitable herbal preparations and their pharmacological interactions for the effective and sustainable control of coccidiosis in ruminants. This review highlights the significance of ruminant coccidiosis, botanical compounds used against ruminant coccidiosis their mechanisms of action, and reasons and benefits of herbal compounds.

Assessing risk factors for malaria and schistosomiasis among children in Misungwi, Tanzania, an area of co-endemicity: A mixed methods study.

Malaria and schistosomiasis are two major parasitic vector-borne diseases that are a particular threat to young children in Sub-Saharan Africa. In the present study, we investigated factors that are associated with malaria, schistosomiasis, and co-infection among school-aged children, using an explanatory sequential mixed-methods approach. A cross-sectional study was conducted in January 2022 in Misungwi, Tanzania, that sampled 1,122 children aged 5 to 14 years old for malaria and schistosomiasis infection. Mixed-effect logistic regression models were used to assess the association between infection prevalence or seroprevalence, and environmental determinants that create favorable conditions for vectors and parasites and social determinants that relate to disease exposure. Community mapping combined with direct field observations were conducted in August 2022 in three selected villages from the cross-sectional study to understand specific water use behaviors and to identify potential malaria mosquito larval breeding sites and freshwater snail habitat. The prevalence of malaria, seroprevalence of schistosomiasis, and co-infection in this study were 40.4%, 94.3%, and 38.1%, respectively. Individual-level factors emerged as the primary determinants driving the association with infection, with age (every one-year increase in age) and sex (boys vs girls) being statistically and positively associated with malaria, schistosomiasis, and co-infection (P<0.05 for all). Community maps identified many unimproved water sources in all three villages that were used by humans, cattle, or both. We found that children primarily fetched water, and that unprotected wells were dedicated for drinking water whereas ponds were dedicated for other domestic uses and cattle. Although not identified in the community maps, we found hand pumps in all three villages were not in use because of unpleasant taste and high cost. This study improves our understanding of individual, social and environmental factors that are associated with malaria, schistosomiasis, and co-infection, which can inform potential entry points for integrated disease prevention and control.

Past and present seroprevalence and disease burden estimates of Toxoplasma gondii infections in Germany: An appreciation of the role of serodiagnostics

Toxoplasmosis is one of the major foodborne parasitic diseases in Germany, with 49% of its population chronically infected with its causative agent, Toxoplasma gondii. Although the acute disease is usually benign in immunocompetent individuals, it is a threat for immunocompromised patients as well as for fetuses of seronegative mothers. As a result of infection, congenital and ocular toxoplasmosis can have serious lifelong consequences. Here I will highlight the epidemiologic situation, from its past in the two separate parts of Germany, to its unification 30 years ago and up to the present day. The main identified risk factor for infection in Germany is thought to be the consumption of undercooked or raw meat or sausages. However, the relative impact of this risky eating habit as well as that of other risk factors are changing and are discussed and compared to the situation in the Netherlands. Finally, the importance of robust and efficient high-throughput serological assays for obtaining reliable epidemiological data, on which public health decisions can be made, is highlighted. The potential of bead-based multiplex assays, which allow the incorporation of multiple antigens with different analytical properties and thus yield additional information, are described in this context. It illustrates the interdependence of new analytic assay developments and sound epidemiology, a foundation that decades-old data from Germany did not have.

Dietary citric acid decreased the theront number of Cryptocaryon irritans (Ciliata) in seawater-adapted tilapia (Oreochromis niloticus).

Cryptocaryoniasis remains a major parasitic disease and economic challenge for marine aquaculture. Cryptocaryoniasis in marine fish is caused by Cryptocaryon irritans (Ciliata). A theront is a motile, free-swimming stage in the life cycle of C. irritans, which is typically the infective stage that actively seeks out a host to initiate infection. Population density and growth rate of theronts were investigated in Nile tilapia, Oreochromis niloticus fed with citric acid-supplemented feed. The experiment involved feeding three diets with graded levels of citric acid (0, control diet, 0.5, 1 and 1.5 g kg-1 diet), to seawater-adapted Nile tilapia (O. niloticus) juveniles for 21 days. The results showed that citric acid in the fish feed had an impact on the theront number of C. irritans in a manner of dose-dependent. In the experimental cohort administered a diet supplemented with 1.5 g kg-1 citric acid, the population density of theronts was observed to be significantly reduced, measured at 29 ± 3.34, as opposed to 473.34 ± 16.48 in the control group at the culmination of the experiment. The observed population growth rate of theronts was significantly higher in the control group than in the group administered the citric acid feed (p < .005). The growth rate (r d-1 ) was 0.12 in control, 0.05 in 0.5 g kg-1 , 0.031 in 1 g kg-1 , and - 0.031 in 1.5 g kg-1 citric acid-supplemented groups. Fish growth and feed conversion ratio were not affected by the citric acid in the feed. In conclusion, the findings of this investigation provide a valuable addition to our understanding of the potential protective effects of citric acid supplementation for fish against the C. irritans parasite. This is evidenced by the observed reduction in theronts present in the water.

In vitro screening of natural product-based compounds for leishmanicidal activity.

Leishmaniasis is one of the major parasitic diseases, caused by obligate intracellular protozoa Leishmania, having high mortality as well as morbidity rate. As there is no human licensed vaccine available against leishmaniasis, chemotherapy remains the major way of combating this disease. Many disadvantages are known to be associated with the current drug regime including severe side effects and toxicity, long duration and expensive treatment, and the emergence of resistance. An alternative approach is being utilized to search for active molecules using natural sources, rather than relying on synthetic drugs. Many plant-derived secondary metabolites like phenolic compounds, steroids, quinones, etc. are being extensively investigated for their anti-leishmanial potential. One such group of complex phenolic compounds are diarylheptanoids. These compounds have been shown to exhibit anti-inflammatory, anti-parasitic, anti-fungal, and other pharmacological activities. In the present study, a set of sixteen tetrahydropyran derivatives including three natural products were obtained in lyophilized form. These compounds with trans-2,6-disubstituted tetrahydropyrans, Diospongin A, Diospongin B (isolated from Dioscorea spongiosa) and Centrolobine (Centrolobium sclerophyllum) as parent compounds were synthesized by the reaction of 1-phenyl-1-triemthylsiloxyethylene with six-membered cyclic hemiacetals in the presence of iodine as a catalyst. All the sixteen synthesized tetrahydropyran derivatives were used for toxicity analysis against L. donovani promastigotes, amastigotes and THP-1-derived human macrophages. IC50 values and selectivity index were calculated for all the compounds. Out of these sixteen, five compounds showed the best effect in vitro in terms of both leishmanicidal activity and non-toxicity to human macrophages.

A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments.

Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches.

A Quinquennial Review on Recent Advancements and Developments in Search of Anti-malarial Agents.

Malaria has been a major parasitic disease in tropical and subtropical regions and is estimated to kill between one and two million people (mainly children) every year. Novel anti-malarial agents are urgently needed to combat the malarial parasites enduring resistance to the current medications, leading to increased morbidity and mortality. The heterocycles, holding a prominent position in chemistry and found in both natural and synthetic sources, have shown several biological activities including anti-malarial activity. Towards this goal, several research groups have reported the design and development of novel and potential anti-malarial agents like artemisinin, benzimidazole, benzothiazole, chalcone, cyclopeptide, fosmidomycin, furan, indole oxadiazole, 2-oxindoles, peroxides, pyrazole, pyrazolines, pyridines, pyrimidine, pyrrolidine, quinazoline, quinazolinone, quinolone, quinoline, thiazole, triazole and other scaffolds acting against newly emerging anti-malarial targets. The present work reports the complete quinquennial coverage of anti-malarial agents reported during 2016-2020 with a view of providing the merits and demerits of reported anti-malarial scaffolds, structure-activity relationship, along with their in vitro/ in vivo/ in silico profiles to the medicinal chemists working in the field of design and discovery of novel anti-malarial agents.

Trypanocidal effects of Balanites aegyptiaca Del. (Zygophyllaceae) Leaf ‎Extract and Suramin on Trypanosoma evansi Experimental Infection in ‎Albino rat

TTrypanosoma evansi, is one among several species of Trypanosomes responsible for a major protozoan parasitic disease of domestic animals. The current study aimed to investigate the trypanocidal effects of aqueous and methanolic leaf extracts of Balanites aegyptiacaDel (Zygophyllaceae) and suramin on albino rats infected with Trypanosoma evansi. In total, 35 Swiss albino rats randomly separated into seven (7) groups (A- G) of 5 rats each were intraperitoneally infected with 0.5 ml of blood containing 1.0 × 106trypanosomes and treated with the extracts and suramin for 7 days and single dose respectively by day 12 post infection (p.i). Clinical parameters and haematological indices were evaluated. Preliminary phytochemical screening revealed that Balanitesaegyptiaca contained the following metabolites: flavonoids, tannin, saponins, alkaloids, glycosides, steroids and volatile oils. There was marked initial reduction in Packed Cell Volume (PCV), Haemoglobin (Hb) and Red Blood Cells (RBCs) counts in the infected/untreated group (Group A) but following treatment with B. aegyptiaca leaf aqueous and methanolic extracts, these values were reversed. Furthermore, there was reversion of leukopenia after treatment of the rats individually with methanolic leaf extracts (150 mg/kg of B. aegyptiaca; Group B) from 3.47±1.49 × 103/mm3 by day 12 p.i. to 9.03±2.18 by day 40 p.i., similar to the pre-infection value. In conclusion, the infection caused clinical and haematological changes that were ameliorated following treatment with methanolic and aqueous leaf extract of B. aegyptiaca

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.

Development of an enzyme linked immunosorbent assay using recombinant cathepsin B5 antigen for sero-surveillance of bovine tropical fasciolosis

Bovine tropical fasciolosis, caused by Fasciola gigantica, is a major parasitic disease in tropical countries responsible for significant production losses in animal husbandry practices. The disease is transmitted by the Radix sp. snails. In the early developmental stage of the parasite, the juveniles and immature flukes cause considerable damage to the liver parenchyma of the bovine host while migrating through the liver. The cathepsin (cat) B5 is a cysteine protease that is present in the excretory-secretory product of the fluke both in immature and adult stages. The early detection of fasciolosis is very critical in effective disease management. In this study, the cathepsin B5 gene from newly excysted juveniles were cloned, sequenced and analyzed. The phylogenetic analysis revealed existence of two distinct clades. The clade I includes cat B 1 to B3 whereas clade II consist of cat B4 to B7. Further, the present study was aimed to develop an enzyme linked immuno sorbent assay (ELISA) using recombinant cat B5 antigen. The developed enzyme immuno assay showed 95.3 % sensitivity and 92.4 % specificity with a cut-off of 60 % percent positive. It revealed weighted Kappa value as 0.768 (95 % CI 0.648–0.889) when compared with ELISA using native cathepsin protein. Hence, the developed assay can be exploited as a potent tool in the diagnosis and sero-surveillance of bovine tropical fasciolosis.

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.

Preparation of polyclonal anti-Schistosoma mansoni cysteine protease antibodies for early diagnosis

In many parts of the tropics, schistosomiasis is a major parasitic disease second only to malaria as a cause of morbidity and mortality. Diagnostic approaches include microscopic sampling of excreta such as the Kato-Katz method, radiography, and serology. Due to their vital role in many stages of the parasitic life cycle, proteases have been under investigation as targets of immunological or chemotherapeutic anti-Schistosoma agents. Five major classes of protease have been identified on the basis of the peptide hydrolysis mechanism: serine, cysteine, aspartic, threonine, and metalloproteases. Proteases of all five catalytic classes have been identified from S. mansoni through proteomic or genetic analysis. The study aimed to produce polyclonal antibodies (pAbs) against schistosomal cysteine proteases (CP) to be used in the diagnosis of schistosomiasis. This study was conducted on S. mansoni-infected patients from highly endemic areas and from outpatients’ clinic and hospitals and other patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids). In this study, the produced polyclonal antibodies against S. mansoni cysteine protease antigens were labeled with horseradish peroxidase (HRP) conjugate and used to detect CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA. The study involved 200 S. mansoni-infected patients (diagnosed by finding characteristic eggs in the collected stool samples), 100 patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids), and 100 individuals who served as parasite-free healthy negative control. The prepared pAb succeeded in detecting CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA with a sensitivity of 98.5% and 98.0% respectively. A positive correlation was observed between S. mansoni egg counts and both stool and serum antigen concentrations. Purified 27.5 kDa CP could be introduced as a suitable candidate antigen for early immunodiagnosis using sandwich ELISA for antigen detection.Key points• Detection of cysteine protease antigens can replace parasitological examination.• Sandwich ELISA has a higher sensitivity than microscopic examination of eggs.• Identification of antigens is important for the goal of obtaining diagnostic tools.

New frontiers in host-parasite interactions, from cell to organism.

New frontiers in host-parasite interactions, from cell to organism.