Preliminary investigations of parasite contamination of water sources in Armenia.

The intestinal protozoan parasites, Cryptosporidium and Giardia, are known to have a global distribution, infecting and causing disease in a range of hosts, including people, livestock, pets, and wildlife. However, data from some regions is very sparse. In Armenia, in the Caucasus region of West Asia, only scanty data are available, with just a few surveys on Cryptosporidium infections in livestock, and no available data on human infections or environmental contamination. As part of implementation of water analysis methods for these parasites in Armenia, 24 raw water samples and two sediment samples were analysed for these parasites using a range of approaches, including modified Ziehl-Neelsen, Lugol stain, immunofluorescent antibody test (IFAT), qPCR and, on sediment samples, immunomagnetic separation and IFAT. Results suggest substantial contamination of raw water sources and indicate the need for further targeted studies using appropriate methods and collecting data on host infections in catchment areas.

Global epidemiology and spatial distribution of Toxoplasma gondii in goats: Protocol for a systematic review and Bayesian hierarchical meta-analysis.

BACKGROUND: Toxoplasma gondii, a cosmopolitan protozoan parasite causes toxoplasmosis in humans and many species of domestic and wild animals. T. gondii instigates significant economic losses in sheep and goat farming industry and can lead to abortion, stillbirth, congenital malformations and neonatal losses. The objective of this protocol is to evaluate worldwide seroprevalence of T. gondii exposure in goats using Bayesian hierarchical meta-analysis and geographic information system (GIS). METHODS: A comprehensive literature search will be conducted using search engines, including Web of Science, ScienceDirect, Scopus, PubMed, ProQuest, EMBASE, PROSPERO Register and, Google Scholar without date and language restrictions. The authors search for cross-sectional studies that determine the seroprevalence of T. gondii in goats. Two reviewers will independently screen, selected studies; also, they will extract data, and assess the risk of bias. In case(s) of disagreement, a consensus will be reached with the help of a third author. The Bayesian hierarchical meta-analysis will use to estimate country and worldwide true seroprevalence of T. gondii, which is consist of the sensitivity and specificity of the applied serological assays. The obtained data will be used to identify country-level risk factors associated with T. gondii exposure using GIS in the ArcGIS software. DISCUSSION: The systematic review produced from this protocol will provide the true prevalence rate and spatial distribution T. gondii exposure in goats both regionally and globally using Bayesian hierarchical and GIS analysis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020107928.

Phylogenomics revealed migration routes and adaptive radiation timing of Holarctic malaria mosquito species of the Maculipennis Group.

BACKGROUND: Phylogenetic analyses of closely related species of mosquitoes are important for better understanding the evolution of traits contributing to transmission of vector-borne diseases. Six out of 41 dominant malaria vectors of the genus Anopheles in the world belong to the Maculipennis Group, which is subdivided into two Nearctic subgroups (Freeborni and Quadrimaculatus) and one Palearctic (Maculipennis) subgroup. Although previous studies considered the Nearctic subgroups as ancestral, details about their relationship with the Palearctic subgroup, and their migration times and routes from North America to Eurasia remain controversial. The Palearctic species An. beklemishevi is currently included in the Nearctic Quadrimaculatus subgroup adding to the uncertainties in mosquito systematics. RESULTS: To reconstruct historic relationships in the Maculipennis Group, we conducted a phylogenomic analysis of 11 Palearctic and 2 Nearctic species based on sequences of 1271 orthologous genes. The analysis indicated that the Palearctic species An. beklemishevi clusters together with other Eurasian species and represents a basal lineage among them. Also, An. beklemishevi is related more closely to An. freeborni, which inhabits the Western United States, rather than to An. quadrimaculatus, a species from the Eastern United States. The time-calibrated tree suggests a migration of mosquitoes in the Maculipennis Group from North America to Eurasia about 20-25 million years ago through the Bering Land Bridge. A Hybridcheck analysis demonstrated highly significant signatures of introgression events between allopatric species An. labranchiae and An. beklemishevi. The analysis also identified ancestral introgression events between An. sacharovi and its Nearctic relative An. freeborni despite their current geographic isolation. The reconstructed phylogeny suggests that vector competence and the ability to enter complete diapause during winter evolved independently in different lineages of the Maculipennis Group. CONCLUSIONS: Our phylogenomic analyses reveal migration routes and adaptive radiation timing of Holarctic malaria vectors and strongly support the inclusion of An. beklemishevi into the Maculipennis Subgroup. Detailed knowledge of the evolutionary history of the Maculipennis Subgroup provides a framework for examining the genomic changes related to ecological adaptation and susceptibility to human pathogens. These genomic variations may inform researchers about similar changes in the future providing insights into the patterns of disease transmission in Eurasia.

An updated list of mosquito species in Armenia and Transcaucasian region responsible for Dirofilaria transmission: A review.

Canine dirofilariasis is a world-wide distributed mosquito-borne helminthiasis that has a potential zoonotic impact. This disease is a serious problem in Southern Caucasus region, including Armenia. Average extensity of Dirofilaria infection in canids in Armenia is 26.9%. At present, 77 mosquito species (Diptera: Culicidae) are presumed to have a role in the transmission of dirofilariasis. 80 species of Culicidae family mosquitoes are registered in Southern Caucasus Region, and 31 of them are described in Armenia. The following species of Culicidae can serve as vectors of Dirofilaria spp. in Armenia: Aedes vexans, Ae. caspius, Ae. albopictus, Ae. geniculatus, Culex pipiens, Cx. theileri, Cx. modestus, Anopheles maculipennis s.s., An. claviger, An. hyrcanus, An. superpictus, Coquillettidia richardi, Culiseta annulata and Uranotaenia unguiculta. We see a risk of transmission in active foci of dirofilariasis, as well as for human infection in Armenia. Comprehensive research should be conducted on detection of microfilariae in the target mosquito species and in target localities.

Chromosome-scale Echinococcus granulosus (genotype G1) genome reveals the Eg95 gene family and conservation of the EG95-vaccine molecule.

Cystic echinococcosis is a socioeconomically important parasitic disease caused by the larval stage of the canid tapeworm Echinococcus granulosus, afflicting millions of humans and animals worldwide. The development of a vaccine (called EG95) has been the most notable translational advance in the fight against this disease in animals. However, almost nothing is known about the genomic organisation/location of the family of genes encoding EG95 and related molecules, the extent of their conservation or their functions. The lack of a complete reference genome for E. granulosus genotype G1 has been a major obstacle to addressing these areas. Here, we assembled a chromosomal-scale genome for this genotype by scaffolding to a high quality genome for the congener E. multilocularis, localised Eg95 gene family members in this genome, and evaluated the conservation of the EG95 vaccine molecule. These results have marked implications for future explorations of aspects such as developmentally-regulated gene transcription/expression (using replicate samples) for all E. granulosus stages; structural and functional roles of non-coding genome regions; molecular 'cross-talk' between oncosphere and the immune system; and defining the precise function(s) of EG95. Applied aspects should include developing improved tools for the diagnosis and chemotherapy of cystic echinococcosis of humans.

Low MSP-1 haplotype diversity in the West Palearctic population of the avian malaria parasite Plasmodium relictum.

BACKGROUND: Although avian Plasmodium species are widespread and common across the globe, limited data exist on how genetically variable their populations are. Here, the hypothesis that the avian blood parasite Plasmodium relictum exhibits very low genetic diversity in its Western Palearctic transmission area (from Morocco to Sweden in the north and Transcaucasia in the east) was tested. METHODS: The genetic diversity of Plasmodium relictum was investigated by sequencing a portion (block 14) of the fast-evolving merozoite surface protein 1 (MSP1) gene in 75 different P. relictum infections from 36 host species. Furthermore, the full-length MSP1 sequences representing the common block 14 allele was sequenced in order to investigate if additional variation could be found outside block 14. RESULTS: The majority (72 of 75) of the sequenced infections shared the same MSP1 allele. This common allele has previously been found to be the dominant allele transmitted in Europe. CONCLUSION: The results corroborate earlier findings derived from a limited dataset that the globally transmitted malaria parasite P. relictum exhibits very low genetic diversity in its Western Palearctic transmission area. This is likely the result of a recent introduction event or a selective sweep.

Burden of Ischemic Heart Disease in Central Asian Countries, 1990-2017.

BACKGROUND: The burden of ischemic heart disease (IHD) is high. There is limited information on the burden of IHD in identified high risk areas like Central Asia (CA) which is comprised of Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Turkmenistan, Mongolia, Uzbekistan and Tajikistan. This study addresses the burden of IHD in CA at the regional and country levels. METHODS: Using data from the latest iteration of the Global Burden of Disease Study (GBD), this study provides age-adjusted mortality, prevalence, and Disability Adjusted Life Years (DALYs) of IHD by sex in the CA region, and national levels for countries in this region from 1990 to 2017. RESULTS: The CA region has a higher IHD burden than the rest of the world over the studied period. Amongst the countries within this region, age-standardized mortality and DALY rates in Uzbekistan are the highest not only in CA but worldwide, while Armenia consistently has the lowest IHD burden in CA. Unhealthy diet, high systolic blood pressure and LDL-cholesterol are the risk factors with the highest attributable IHD DALYs. CONCLUSION: Increasing burden of IHD over time in CA can be partially explained by the economic crisis in the 1990s. There is considerable variation in IHD DALY rates among countries in the CA region. The reasons for such differences are likely multifactorial such as differences in risk factors distribution, health care effectiveness, political, social and economic factors.

The First Report of Trichinella britovi in Armenia.

BACKGROUND: More than a hundred species of mammals, birds, and reptiles are infected by nematodes of the Trichinella genus worldwide. Although, Trichinella spp. are widely distributed in neighboring countries including Georgia, Azerbaijan, Turkey and Iran, no study was conducted in Armenia since 1980's. METHODS: In 2017-2018, five muscle samples belonging to Armenian lynx, otter, wild boar, fox and wolf were tested for Trichinella spp. and recovered larvae were identified by multiplex PCR technique. RESULTS: Twenty-six larvae/gram and one larva/gram were found in lynx and fox samples respectively. They were identified as T. britovi. CONCLUSION: So far only two species were identified in Armenia, T. spiralis and T. pseudospiralis, and this is the first time that T. britovi is reported in Armenia.

Genetic characterization of Toxoplasma gondii in Iranian HIV positive patients using multilocus nested-PCR-RFLP method.

The aim of the present study was to investigate the prevalence and genotyping of Toxoplasma gondii in Iranian human immunodeficiency virus (HIV)-positive patients using multilocus-nested polymerase chain reaction restriction fragment length polymorphism (Mn-PCR-RFLP). A total of 102 serum samples obtained from infected patients were collected from the laboratory centres in northern Iran. Anti-T. gondii antibodies and deoxyribonucleic acid (DNA) detection were accomplished by an enzyme-linked immunosorbent assay and PCR. The Mn-PCR-RFLP method was used for the genotyping of T. gondii. Overall, 68.6% (70/102) and 11.7% (12/102) of the individuals were tested positive for anti-T. gondii immunoglobulin G and T. gondii DNA, respectively. Complete genotyping was performed on 10/12 (83.3%) PCR-positive samples. Accordingly, the samples were classified as genotype #1 (type II clonal; n = 3, 30%), genotype #2 (type III clonal; n = 2, 20%), genotype #10 (type I clonal; n = 2, 20%), genotype #27 (type I variant; n = 1, 10%), genotype #35 (type I variant; n = 1, 10%) and genotype #48 (type III variant; n = 1, 10%). The results were indicative of the high frequency of the type I and type I variant of T. gondii strains in HIV-positive patients in northern Iran. Given the high prevalence of T. gondii and frequency of pathogenic types (pathogen in laboratory mice) in the patients, special measures should be taken to prevent the possible increased incidence of encephalitis by T. gondii.

A systematic review of Toxoplasma gondii genotypes and feline: Geographical distribution trends.

Toxoplasma gondii (T. gondii) is well known for its ability to virtually infect all warm-blooded vertebrates. Although felines as the definitive hosts have an important role in the epidemiology of toxoplasmosis, there are few descriptions of genetic diversity in the world. The present review study aimed to describe the population structure of T. gondii in these animal species. For the purpose of the study, five English language databases reporting data on T. gondii genotyping in cats were searched within March-June 2019. This study is registered on the site of CAMARADES-NC3Rs (15-Jan-2018). The searching process resulted in the inclusion of 50 reports published from 1992 to June 2019. The data revealed that 47,390 samples were genotyped into 662 T. gondii DNA/isolates. Globally, atypical genotypes were predominant (47.7%, n = 316); in addition, Type II clonal strains were the second most common genotype (37%, n = 244). These results suggested an epidemic population structure in America and Asia, and a clonal population structure in Europe and Africa. Genotype #3 was found to be dominant in Africa, Europe and Oceania continents. Furthermore, genotypes #9 and #5 were prevalent in Asia and America, respectively. Additionally, genotypes #2, #3, #5 and #20 were common genotypes in domestic and sylvatic cycles from family Felidae. Collectively, this systematic review indicated a large degree of genetic diversity and circulation of mouse-virulent T. gondii strains in this family. However, further studies are necessary to better understand the population structure of T. gondii in these animal species and determine the significance of their features.

Is Toxoplasma gondii a potential risk factor for Alzheimer's disease? A systematic review and meta-analysis.

Toxoplasmosis is a major public health concern due to neurotropic nature and role in the development of mental and behavioral disorders. Alzheimer's disease (AD) is an important nervous disease that results in the reduction of the amount of beta-amyloid plaque deposition and irreversible loss of neurons in the brain. Although a few studies evaluated the association between AD and toxoplasmosis, the present study as a systematic review and meta-analysis of published studies investigated the possible association between Toxoplasma gondii (T. gondii) and AD. A systematic literature search was conducted using seven electronic databases from the inception to 25th of November 2018 with no restriction of language that looked at toxoplasmosis (as an exposure) and AD (as a disease). The random effect model was used to determine the total odds ratio (OR) and total p-value. Generally, eight studies containing 3239 subjects (360 patients and 2879 controls) met the eligibility criteria. Then, eight articles were used for meta-analysis with respect to inclusion and exclusion criteria. The results of the meta-analysis (random effect model) showed a common OR of 1.53 (95% CI: 1.07-2.18). Despite the fact that there was no evidence of publication bias (P = 0.079) using formal statistical test, the visual inspection of the funnel graph suggested that the observed effect was fueled mainly by three studies with large effects (and large standard errors). Moreover, the file-drawer effect (i.e. publishing mainly studies with positive results) might play a role in the phenomenon. Results of this meta-analytic study suggested that T. gondii can be considered a risk factor for the development of AD and exacerbation of its symptoms. However, the number of published relevant studies is still relatively low, and the risk of the presence of publication bias is relatively high. Therefore, the investigation of the clinically important question of the possible association between toxoplasmosis and AD definitively deserves further attention.

Infection of parthenogenetic lizards by blood parasites does not support the "Red Queen hypothesis" but reveals the costs of sex.

Sexual organisms should be better suited than asexual ones in a context of continuous evolution in response to opposite organisms in changing environments ("Red Queen" hypothesis of sex). However, sex also carries costs associated with the maintenance of males and mating (sex cost hypothesis). Here, both non-mutually excluding hypotheses are tested by analysing the infestation by haemogregarines of mixed communities of Darevskia rock lizards composed of parthenogens generated by hybridisation and their bisexual relatives. Prevalence and intensity were recorded from 339 adult lizards belonging to six species from five syntopic localities and analysed using Generalized Mixed-Models (GLMM). Both infestation parameters depended on host-size (like due to longer exposure with age), sex and, for intensity, species. Once accounting for locality and species, males were more parasitized than conspecific females with bisexual species, but no signal of reproductive mode itself on parasitization was recovered. Essentially, male-male interactions increased haemogregarine intensity while females either sexual or asexual had similar reproductive costs when in the same conditions. These findings deviate from the predictions from "Red Queen" dynamics while asymmetric gender costs are here confirmed. Thus, increased parasitization pressure on males adds to other costs, such as higher social interactions and lower fecundity, to explain why parthenogenetic lizards apparently prevail in the short-term evolutionary scale. How this is translated in the long-term requires further phylogenetic analysis.

Evidence of Crimean-Congo Haemorrhagic Fever Virus Occurrence in Ixodidae Ticks of Armenia.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) causes serious health problems in humans. Though ticks of the genera Hyalomma play a significant role in the CCHF virus transmission it was also found in 31 other tick species. METHODS: Totally, 1412 ticks from 8 remote sites in Armenia during 2016 were sampled, pooled (3-5 ticks per pool) and tested for the presence of CCHFV antigen using ELISA test. RESULTS: From 359 tick pools, 132 were CCHF virus antigen-positive. From 6 tick species, four species (Rhipicephalus sanguineus, R. annulatus, R. bursa, Hyalomma marginatum) were positive for the virus antigen and R. sanguineus was the most prevalent (37.9%). Dermacentor marginatus and Ixodes ricinus revealed no positive pools, but both revealed delectable but very low virus antigen titers. The highest infection rate (50%) was observed in R. sanguineus, whereas H. marginatus rate of infection was 1 out of 17 pools. CONCLUSION: For the first time in the last four decades CCHF virus antigen was detected in Ixodid ticks of Armenia. This finding substantiates the role of R. sanguineus in the disease epidemiology; however, the role of H. marginatum in the CCHF virus circulation in the country could not be excluded.

Is there any association between Toxoplasma gondii infection and depression? A systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental disorders; however, the relationship between T. gondii infection and depressive disorder is unclear. Regarding this, the present systematic review and meta-analysis was conducted to investigate the scientific evidence regarding the potential association between major depression disorder (MDD) and Toxoplasma infection. METHODS: For the purpose of the study, the articles related to the subject of interest were systematically searched in seven electronic databases. Special attention was given to the studies examining T. gondii seropositivity level in depressed patients and controls. RESULTS: The search process resulted in the identification of a total of 30 publications meeting the inclusion criteria and published up to April 2018 for the systematic review. Furthermore, 29 studies met the inclusion criteria to be entered into meta-analysis. Our meta-analysis involved the review of cross-sectional studies including 1657 depressed patients and 19565 individuals as controls and case-control studies entailing 1311 depressed cases and 6015 controls without depression. 1582 depressed people participated in cross-sectional studies whose results were reported as odds ratio (OR). In addition, the total number of participants was 15068 in this type of studies. Statistical analysis indicated that the pooled OR of the risk of anti-T. gondii IgG antibody in depressed individuals in case-control and cross-sectional studies was 1.15 (95% confidence interval (CI): 0.95-1.39). CONCLUSIONS: As the findings of the reviewed articles indicated, toxoplasmosis is not a risk factor for MDD. However, it is necessary to perform further research to clarify the detailed association between T. gondii and dysthymia or mild and moderate depression. Furthermore, it is recommended to better investigate the effect of antibody titers on the relationship between depression and T. gondii infection.

Seroprevalence of Toxoplasma gondii infection in cancer patients: A systematic review and meta-analysis.

Toxoplasmosis, caused by Toxoplasma gondii, is a great public health concern in cancer patients, which can induce serious pathological effects. This systematic review and meta-analysis was performed to evaluate the worldwide seroprevalence rate of T. gondii infection among cancer patients. A search was conducted on five electronic databases that reported data on T. gondii seroprevalence in cancer patients. The searching process resulted in the inclusion of 57 studies. The results showed that T. gondii had the pooled prevalence of 30.8% in cancer patients using a random-effect model (95% CI: 26.3-35.6). Cancer patients had a higher overall prevalence of T. gondii infection, compared to those without cancer. Furthermore, the odds ratio of toxoplasmosis in cancer patients was 3.1 times, compared to that of controls (95% CI: 2.5-3.8, P < 0.0001). Toxoplasmosis had a higher prevalence in females (40%) than in males (33%). Furthermore, the age group of upper 40 years had the highest prevalence infection rate (30%). In addition, a significant association was also observed between toxoplasmosis infection and year (P < 0.001), type of cancer (P < 0.001), country (P < 0.001), gender (P < 0.001), age (P = 0.006) and diagnostic method (P < 0.001) in cancer patients. Considering the high prevalence of T. gondii infection in cancer patients and its serious outcomes, the researchers are suggested to carry out further studies to prevent and control toxoplasmosis among this population.

Geographic patterns of mtDNA and Z-linked sequence variation in the Common Chiffchaff and the 'chiffchaff complex'.

The Common Chiffchaff Phylloscopus collybita is an abundant, polytypic Palearctic bird. Validity of some of its subspecies is controversial and birds from some parts of the species range remain unclassified taxonomically. The relationships among populations from different geographic areas have not been sufficiently explored with molecular data. In this study we analyzed the relationships among the four species in the 'chiffchaff complex' (Common Chiffchaff, Iberian Chiffchaff P. ibericus, Canary Islands Chiffchaff P. canariensis and Mountain Chiffchaff P. sindianus), and the patterns of intraspecific geographic variation in the mtDNA ND2 gene and intron 9 of the Z-linked aconitase gene (ACO1I9) across the Common Chiffchaff range, including a recently discovered population breeding on Mt. Hermon (Anti-Lebanon mountains). Our data supported the monophyly of the chiffchaff complex and its current systematics at the species level. Within the Common Chiffchaff, the Siberian race P. c. tristis was the most differentiated subspecies and may represent a separate or incipient species. Other Common Chiffchaff subspecies also were differentiated in their mtDNA, however, lineages of neighboring subspecies formed wide zones of introgression. The Mt. Hermon population was of mixed genetic origin but contained some birds with novel unique lineage that could not be assigned to known subspecies. All Common Chiffchaff lineages diverged at the end of the Ionian stage of Pleistocene. Lineage sorting of ACO1I9 alleles was not as complete as that of mtDNA. Chiffchaff species were mostly distinct at ACO1I9, except the Common and Canary Islands Chiffchaffs that shared multiple alleles. An AMOVA identified geographic structure in Common Chiffchaff ACO1I9 variation that was broadly consistent with that of mtDNA ND2 gene. The genetic and other data suggest the chiffchaff complex to be a group of evolutionarily young taxa that represent a paradigm of 'species evolution in action' from intergrading subspecies through to apparently complete biological speciation.

Aetiology of livestock fetal mortality in Mazandaran province, Iran.

In the farming industry, the productivity of livestock herds depends on the fertility efficiency of animals. The accurate diagnosis of a broad range of aetiological agents causing fetal death is often difficult. Our aim was to assess the prevalence rates of Toxoplasma gondii, Neospora caninum, and Brucella spp. infections in ruminant abortion using bacteriological culture and molecular techniques in Mazandaran Province, northern Iran. Samples were collected from 70 aborted sheep, goat, and cattle fetuses between September 2014 and December 2015. Necropsy was performed on all the received samples, and brain tissue and abomasal content were obtained from the aborted fetuses. Protozoan infections were detected by specific polymerase chain reaction (PCR) and bacterial agents using bacteriological examinations and PCR assay. Infectious pathogens were detected in 22 out of 70 (31.4%) examined fetuses. Moreover, T. gondii, N. caninum, and B. melitensis were verified in 13 (18.6%), four (5.7%), and two (2.85%) samples, respectively. Our results showed that infection with the mentioned pathogenic agents may lead to fetal mortality, which can be a major cause of economic loss. The listed pathogens could be considered important etiological agents of fetal loss in Mazandaran Province, for which appropriate control measures such as vaccination and biosecurity can be implemented to prevent infection and reduce reproductive loss in livestock farms.

A systematic review on efficiency of microneme proteins to induce protective immunity against Toxoplasma gondii.

Toxoplasma gondii is an intracellular parasite infecting almost all warm-blooded animals. Many studies on vaccination have been performed previously, and micronemal proteins (MICs) have crucial importance in this regard. The current review aims to reveal the efficiency of MICs as target antigen, adjuvants, animal models (species/strain), T. gondii strains for challenge infection, and routes of vaccine to prevent Toxoplasma infection. A comprehensive literature search was performed on April 18, 2018, in several known databases. Studies were included when evaluating vaccines based on MIC against T. gondii compared to that of a control group. Two independent researchers done the search process, study choice, and data extraction. A total of 28 articles published were selected for further analysis. Among them, 57.03% of the studies focused on MIC3 and its epitopes. SAG1 was further used in cocktail vaccines compared to other antigens. GM-CSF and Freund's complete were the predominant adjuvants used. BALB/c mice have been introduced as a proper model for lethal challenge. Virulent T. gondii (RH) was utilized more than other strains for challenge. Among MICs, the results of vaccination with MIC1-4, MIC6, and PLP1 demonstrated significantly strong humoral and cellular immunity, increased survival time, and reduced cyst burden in the mice. This review summarizes the latest results on MIC-based vaccines and presents that the most effective vaccination procedure is the administration of the cocktail vaccines. Our survey can serve as a basis for further studies to develop more efficient novel vaccines against T. gondii for animals and humans.

A systematic review of Toxoplasma gondii antigens to find the best vaccine candidates for immunization.

At present, there is not any available accepted vaccine for prevention of Toxoplasma gondii (T. gondii) in human and animals. We conducted literature search through English (Google Scholar, PubMed, Science Direct, Scopus, EBSCO, ISI Web of Science) scientific paper databases to find the best vaccine candidates against toxoplasmosis among T. gondii antigens. Articles with information on infective stage, pathogenicity, immunogenicity and characterization of antigens were selected. We considered that the ideal and significant vaccines should include different antigens and been expressed in all infective stages of the parasite with a high pathogenicity and immunogenicity. Evaluation within this systematic review indicates that MIC 3, 4, 13, ROP 2, RON 5, GRA 1, 6, 8, 14 are expressed in all three infective stages and have pathogenicity and immunogenicity. MIC 5, ROM 4, GRA 2, 4, 15, ROP 5, 16, 17, 38, RON 4, MIC 1, GRA 10, 12, 16, SAG 3 are expressed in only tachyzoites and bradyzoites stages of T. gondii with pathogenicity/immunogenicity. Some antigens appeared to be expressed in a single stage (tachyzoites) but have high pathogenicity and induce immune response. They include enolase2 (ENO2), SAG 1, SAG5D, HSP 70, ROM 1, ROM 5, AMA 1, ROP 18, RON2 and GRA 24. In conclusion, current vaccination against T. gondii infection is not satisfactory, and with the increasing number of high-risk individuals, the development of an effective and safe specific vaccine is greatly valuable for toxoplasmosis prevention. This systematic review reveals prepare candidates for immunization studies.

Drug Resistance in Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is a global protozoan parasite infecting up to one-third of the world population. Pyrimethamine (PYR) and sulfadiazine (SDZ) are the most widely used drugs for treatment of toxoplasmosis; however, several failure cases have been recorded as well; suggesting the existence of drug resistant strains. This review aims to give a systematic and comprehensive understanding of drug resistance in T. gondii including mechanisms of resistance and sites of drug action in parasite. Analogous amino acid substitutions in the Toxoplasma enzyme were identified to confer PYR resistance. Moreover, resistance to clindamycin, spiramycin, and azithromycin is encoded in the rRNA genes of T. gondii. However, T. gondii SDZ resistance mechanism has not been proved yet. Recently there has been a slight increase in SDZ resistance. That is why the majority of studies were carried out using SDZ. Six strains resistant to SDZ were found in clinical cases between 2013 and 2017 which among Brazilian T. gondii isolates, TgCTBr11, Ck3, and Pg1 were identified in human toxoplasmosis, as well as in livestock intended for human consumption. In conclusion, recent experimental studies in clinical cases have clearly shown that drug resistance in Toxoplasma is ongoing. Thus, establishing a more effective therapeutic scheme in the treatment of toxoplasmosis is critically needed. The emergence of T. gondii strains resistant to current drugs, reviewed here, represents a concern not only for treatment failure but also for increased clinical severity in immunocompromised patients. To improve the therapeutic outcome in patients, a greater understanding of the exact mechanisms of drug resistance in T. gondii should be developed. Thus, monitoring the presence of resistant parasites, in food products, would seem a prudent public health program.