Rhomboid antigens are promising targets in the vaccine development against Toxoplasma gondii

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite with worldwide distribution. It is estimated that near one-third of the people around the globe are latently seropositive for the parasite. Since the current common drugs are incapable in the elimination of parasites within tissue cysts, the development of an effective vaccine has high priority for researchers to limit the infection. During recent years, non-stop efforts of scientists have made great progress in the identification and development of T. gondii candidate vaccines. However, there is a lack of a commercially licensed vaccine for human application yet. Rhomboid proteases (ROMs) are a class of serine proteases that have an important role in the invasion of the parasites that can be considered as a new target for vaccine strategy. They also play critical roles in mitochondrial fusion and growth factor signaling, allowing the parasite to completely enter into the host cell. In the current review, we have summarized the recent progress regarding the development of ROM-based vaccines against acute and chronic T. gondii infection in animal models

Expression of Plasmid Encoded GRA4 Gene of Toxoplasma gondii RH Strain in CHO Eukaryotic Cells

Background: Toxoplasmosis is a common infection all around the world. During pregnancy; it may lead to congenital disorders or abortion in human and animals. Severe damage of toxoplasmosis indicates to require effective vaccine. One of dense granules antigen is GRA4 that secrete from tachyzoite and bradyzoite. GRA4 genome is unique without intron and is one of the major immunogenic proteins from Toxoplasma gondii. Methods: We confirmed the cloning of GRA4 gene into pcDNA3 by restriction enzyme and PCR of GRA4 gene with pcGRA4 plasmids as template. Then with using calcium- phosphate method we transfected the pcGRA4 into CHO (Chinesehamster ovary) cells. The yielded protein was separated by SDS-PAGE and moved by electroblotting to nitrocellulose paper. Results: Result of SDS-PAGE analysis showed the appearance of band approximately 42 kDa which was absent in the negative control, that was able to identify toxoplasmosis antibody IgM+ serum in western blot analysis. Conclusion: pcGRA4 plasmid is able to synthesis of antigenic protein in CHO cells. The ability of pcGRA4 for induction of protective immune response against toxoplasmosis will be evaluated in mouse model

Prevalence and Risk Factors of Toxoplasma gondii Infection among Pregnant Women in Hormozgan Province, South of Iran

Background: Toxoplasmosis can cause miscarriage or complications in the fetus. Diagnosis and treatment of this disease by anti-parasitic drugs especially in early pregnancy can help to prevent fetal infection and its complications. This study aimed to determine T. gondii infection in pregnant women, evaluate risk factors in the transmission of the disease and congenital toxoplasmosis. Methods: Overall, 360 sera of pregnant women from 5 cities in the Hormozgan Province in southern Iran with different climate were evaluated from 2015-2016 for T. gondii infection by using ELISA method and positive cases of IgM and IgG were tested again using Avidity IgG ELISA. All cases were evaluated according to climate, acute and chronic of toxoplasmosis, number of pregnancy and abortion, epidemiological factors and food habits. Results: Among 360 specimens T. gondii IgG + IgM antibodies were found positive in 0. 8% subjects and also 27% of samples had IgG seropositivity. A significant relationship was observed between age, sampling place, consumption of raw and half cooked meat, history of contact with cats, abortion history, number of children, and parity with IgG positive. In Avidity IgG ELISA test, 13 people with low avidity, 3 people with borderline avidity were reported. Conclusion: 72. 2% of the population had no antibody against the disease that this could be a warning to the people and requires education of preventive and prenatal care and routine screening of women at childbearing age

In Vitro Antiparasitic and Apoptotic Effects of Antimony Sulfide Nanoparticles on Leishmania infantum

Visceral leishmaniasis is one of the most important sever diseases in tropical and subtropical countries. In the present study the effects of antimony sulfide nanoparticles on Leishmania infantum in vitro were evaluated. Antimony sulfide NPs (Sb2S5) were synthesized by biologicalmethod fromSerratia marcescens bacteria. Then the cytotoxicity effects of different concentrations (5, 10, 25, 50, and 100 μg/mL) of this nanoparticle were assessed on promastigote and amastigote stages of L. infantum. MTTmethodwas used for verification results of promastigote assay. Finally, the percentages of apoptotic, necrotic, and viable cells were determined by flow cytometry. The results indicated the positive effectiveness of antimony sulfide NPs on proliferation of promastigote form. The IC50 (50% inhibitory concentration) of antimony sulfide NPs on promastigotes was calculated 50 μg/mL. The cytotoxicity effect was dose-dependent means by increasing the concentration of antimony sulfide NPs, the cytotoxicity curve was raised and the viability curve of the parasite dropped simultaneously. Moreover, the IC50 of antimony sulfide NPs on amastigote stage was calculated 25 μg/mL. On the other hand, however, antimony sulfide NPs have a low cytotoxicity effect on uninfected macrophages but it can induce apoptosis in promastigote stage at 3 of 4 concentrations

Avidez do IgG pelo Western Blot usando o r GRA-7 do Toxoplasma gondii clonado de nucleotídeos 39-711 para sorodiagnóstico de toxoplasmose aguda

Toxoplasmosis is an important cause of congenital infection. The present study was performed to evaluate the usefulness of recombinant (r) GRA-7 cloned from nucleotides (n) 39-711 in discriminating between acute and chronic toxoplasmosis. First, commercial IgM, IgG and IgG avidity ELISAs were used to determine the serological profile of the sera. Serum samples were from 20 symptomatic patients with acute infection (low IgG avidity, IgM positive), 10 with chronic infection (high IgG avidity, IgM negative) and 10 with indeterminate IgG avidity (IgM positive) which were tested for IgG avidity status with an in-house developed IgG avidity Western blot using the rGRA-7 recombinant antigen. All 20 sera from cases of probable acute infection showed bands which either faded out completely or reduced significantly in intensity after treatment with 8 M urea, whereas the band intensities of the 10 serum samples from chronic cases remained the same. Of the 10 sera with indeterminate IgG avidity status, after treatment with 8 M urea the band intensities with six sera remained the same, two sera had completely faded bands and another two sera had significantly reduced band intensities. Discrimination between acute and chronic toxoplasmosis was successfully performed by the in-house IgG avidity Western blot.Toxoplasmose é uma causa importante de infecção congênita. O presente estudo foi feito para avaliar o uso do recombinante (r) GRA-7 clonado de nucleotídeos (n) 30-711 para discriminar entre toxoplasmose aguda e crônica. Inicialmente IgM, IgG e ELISA avidez IgG comerciais foram usados para determinar o perfil sorológico do soro. Amostras de soro de 20 pacientes sintomáticos com infecção aguda (IgG avidez baixa, IgM positivo), 10 com infecção crônica (alta avidez IgG, IgM negativo) e 10 com avidez IgG indeterminada (IgM positivo) que foram testados para o status de avidez IgG com um doméstico Western Blot desenvolvendo avidez IgG usando o rGRA-7 antígeno recombinante. Todos os 20 soros de provável infecção aguda mostraram bandas que ou se apagaram completamente ou tiveram a sua intensidade significantemente reduzida após tratamento com uréia 8 M, enquanto as intensidades das bandas das 10 amostras de soros de casos crônicos permaneceram iguais. Dos 10 soros com status indeterminado de avidez de IgG, após tratamento com uréia 8 M a intensidade das bandas em seis soros permaneceram iguais, dois soros tiveram bandas apagadas completamente e dois outros tiveram significante redução da intensidade das bandas. Discriminação entre toxoplasmose aguda e crônica foi feita com sucesso através do IgG avidez Western blot doméstico

Efficacy of biogenic selenium nanoparticles against Leishmania major: In vitro andin vivo studies

Project: This study investigated the in vitro and in vivo effectiveness of biogenic selenium nanoparticles(Se NPs), biosynthesized by Bacillus sp. MSh-1, against Leishmania major (MRHO/IR/75/ER). Procedure:The 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to evaluatethe cytotoxicity effects of the biogenic Se NPs against both promastigote and amastigote forms of L.major. In a separate in vivo experiment, we also determined the preventive and therapeutic effects ofbiogenic Se NPs in BALB/c mice following subcutaneous infected with L. major. Results: The MTT assaysshowed that the highest toxicity occurred after 72 h against both promastigote and amastigote formsof L. major. The cytotoxicity of Se NPs was higher at all incubation times (24, 48, and 72 h) against thepromastigote than the amastigote form (p < 0.05). The 50% inhibitory concentrations (IC50) of the Se NPswere 1.62 ± 0.6 and 4.4 ± 0.6 �g ml−1against the promastigote and amastigote forms, respectively, aftera 72-h incubation period. Apoptosis assays showed DNA fragmentation in promastigotes treated with SeNPs. In an animal challenge, prophylactic doses of biogenic Se NPs delayed the development of localizedcutaneous lesions. Moreover, daily administration of Se NPs (5 or 10 mg kg−1day−1) in similarly infectedBALB/c mice that had not received prophylactic doses of Se NPs also abolished the localized lesions after14 days. Conclusion: Based on these in vitro and in vivo studies, biogenic Se NPs can be considered as anovel therapeutic agent for treatment of the localized lesions typical of cutaneous leishmaniasis

The prevalence of human trichuriasis in Asia: a systematic review and meta‑analysis

Trichuriasis is one of the most common soil-transmitted helminth (STH) infections, affecting populations globally. The condition is particularly prevalent in tropical and subtropical areas with low levels of sanitation and poor living conditions. The objective of this systematic review and meta-analysis was to evaluate the prevalence of Trichuris trichiura infection in Asia at the country and region level. Multiple databases/academic search engines (Web of Science, PubMed, ProQuest, Scopus, and Google Scholar) were searched for literature on T. trichiura prevalence in Asia published through January 2021. Pooled prevalence was determined using the meta-package in R (version 3.6.1). Out of 13,836 articles, 226 studies (5,439,500 individuals) from 26 countries met the inclusion criteria. Of the 226 studies, 151 were community-based studies that included individuals across the age spectrum, while 75 studies focused on school children (typically in the 5–16 years age range). The overall T. trichiura pooled prevalence was 15.3% (95% CI: 12.4–19.1%), with a pooled prevalence of 13.3% (95% CI: 10.0–17.1%) for the community studies and 20.9% (95% CI: 14.7–27.9%) for the studies only including school children. For studies including all age groups, individuals in the 1–15 years age group had the highest pooled prevalence at 23.4% (95% CI: 1.7–49.4%). There was a significant difference found in overall pooled prevalence by sex (p < 0.001) and community type (rural versus urban) (p < 0.001). Although prevalence appears to be decreasing, study findings suggest that T. trichiura infection continues to be a public health problem in Asia. Therefore, control programs focused on at-risk individuals in endemic areas are needed

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens