Effects of diverse Types of Toxoplasma gondii on the outcome of Alzheimer's disease in the rat model.

Toxoplasma gondii has lifelong persistence in the brain and its cysts can affect gene expression and change diverse biological functions of neurons. Many studies indicated T. gondii infection as a risk factor for the development of behavioral changes and neurodegenerative diseases such as Alzheimer's disease (AD), although the etiopathogenetic link between them has not been exactly elucidated. The current study aimed to examine the effects of chronic toxoplasmosis infection with Types I, II, and III strains (RH, PRU, and VEG) alone and in combination on cognitive impairments and neuronal death in the Aß1-42-induced rat model of Alzheimer's disease. In the chronic toxoplasmosis phase, Alzheimer's induction was conducted by injecting Aß1-42 oligomers into the rat brain hippocampus. Behavioral tests were conducted 10 days after the AD induction. Real-time PCR was performed to evaluate T. gondii parasite burden by amplification of the B1 gene. Cytokines IL-1ß, TNF-α, and IL-10 were assayed in brain tissue supernatant using ELISA. Also, histopathological examinations were conducted to calculate inflammatory changes and neuronal death in the brain. Our findings showed that chronic toxoplasmosis infection with PRU reduces cognitive disorders, while the RH strain of T. gondii plays a destructive role and aggravates cognitive impairments in AD. Also, infection with a combination of PRU and VEG strains significantly improved spatial learning and memory impairments in Alzheimer's rat model. Histopathological findings also confirmed the results of behavioral tests, so that in AßPRU and AßPRU + VEG groups, neuronal death and infiltration of inflammatory cells were negligible and significantly less than in Alzheimer's and AßRH groups. Our findings indicate that chronic toxoplasmosis infection with PRU strain alone, also in combination with VEG strain can significantly improve cognitive disorders in AD rats, while RH strain plays a destructive role in AD pathogenesis.

Genetic diversity of Toxoplasma gondii isolates from birds in the world: A systematic review.

Toxoplasma gondii (T. gondii) is one of the most important foodborne pathogens that infects a large number of vertebrate species and has a cosmopolitan distribution. Birds as intermediate hosts are very important in the life cycle of T. gondii and they can be a main source of infection for humans and felids, as well as other animals. Most species of birds feed from the ground and are the best indicator for soil contamination with T. gondii oocysts. Hence, T. gondii strains isolated from birds can represent different genotypes circulating in the environment and their main predators and consumers. The recent systematic review tries to represent the population structure of T. gondii in birds around the world. Six English language databases were searched from 1990 to 2020 to find the related studies and overall, 1275 isolates of T. gondii were separated from the analyzed samples in birds. The results of our study revealed that atypical genotypes were predominant (58.8%, 750 out of 1275). Types II, III, and I had less frequency with prevalence rates of 23.4%, 13.8%, and 2%, respectively. No isolates of Type I were reported from Africa. Summarizing ToxoDB genotypes circulating in birds around the world manifested that ToxoDB #2 was the most common (101/875), followed by ToxoDB #1 (80/875), and #3 (63/875). Totally, the results of our review represented the high genetic diversity of T. gondii with circulating non-clonal strains in birds from South and North America, while clonal parasites with low genetic diversity were predominant in Europe, Asia, and Africa.

Enhancement of immune responses by vaccine potential of three antigens, including ROP18, MIC4, and SAG1 against acute toxoplasmosis in mice.

Toxoplasma gondii (T. gondii) causes considerable financial losses in the livestock industry and can present serious threats to pregnant women, as well as immunocompromised patients. Therefore, it is required to design and produce an efficient vaccine for controlling toxoplasmosis. The present study aimed to evaluate the protective immunity induced by RMS protein (ROP18, MIC4, and SAG1) with Freund adjuvant, calcium phosphate nanoparticles (CaPNs), and chitosan nanoparticles (CNs) in BALB/c mice. The RMS protein was expressed in Escherichia coli (E. coli) and purified using a HisTrap HP column. Thereafter, cellular and humoral immunity was assessed by injecting RMS protein on days 0, 21, and 35 into four groups [RMS, RMS-chitosan nanoparticles (RMS-CNs), RMS-calcium phosphate nanoparticles (RMS-CaPNs), and RMS-Freund]. Phosphate buffered saline (PBS), CNs, CaPNs, and Freund served as the four control groups. The results displayed that vaccination with RMS protein and adjuvants significantly elicited the levels of specific IgG antibodies and cytokines against toxoplasmosis. There were high levels of total IgG, IgG2a, and IFN-γ in vaccinated mice, compared to those in the control groups, especially in the RMS-Freund, indicating a Th-1 type response. The vaccinated and control mice were challenged intraperitoneally with 1 × 103 tachyzoites of the T. gondii RH strain four weeks after the last injection, and in RMS-Freund and RMS-CaPNs groups, the highest increase in survival time was observed (15 days). The RMS can significantly increase Th1 and Th2 responses; moreover, multi-epitope vaccines with adjuvants can be a promising strategy for the production of a vaccine against toxoplasmosis.

Identification and multilocus genotyping of Toxoplasma gondii isolates from congenital infection in north of Iran.

Congenital toxoplasmosis can cause severe consequences in the fetus, such as spontaneous abortion which is affected by parasite strain. Also, recent studies revealed the high genetic diversity of Toxoplasma gondii. This study aims to investigate the serological status of T. gondii in pregnant women, multilocus genotyping in aborted fetuses' tissue, and archived formalin-fixed paraffin-embedded placenta. This study was performed on 100 pregnant women with spontaneous abortion and their aborted fetuses, and 250 of the archived placentae in Iran. The blood and tissue were examined for seroprevalence and genotype determination of T. gondii using ELISA and multilocus nested-PCR-RFLP, respectively. Anti-T. gondii IgG and IgM were detected in 68 samples (68%) and 1 (1%) out of 100 serums. Toxoplasma DNA was identified in 1 (1%) aborted fetuses' tissue and 32 (12.8%) placenta samples. Overall, ten positive DNA samples were successfully genotyped, and five genotypes were recognized (ToxoDB#1, #2, #10, #27, and #48). The obtained results indicated congenital toxoplasmosis is a severe risk in this region. As type I is highly pathogen and can lead to severe complications, the prevention of the infection should be considered in seronegative pregnant women.

Evaluation of anti-parasitic activities of new quinolones containing nitrofuran moiety against Toxoplasma gondii.

Toxoplasmosis is a disease with a worldwide prevalence that is caused by Toxoplasma gondii. Pyrimethamine and sulfadiazine are two pharmacological agents commonly used to treat of this infection. However, they are accompanied by some side effects. Therefore, the identifying of new drugs with low toxocytosis seems to be a matter of vital importance. Quinolones are DNA replication inhibitors, exerting inhibitory effects against many pathogens, including bacteria, mycoplasma, and protozoa. Given the importance of quinolones and their efficacy, the present in vitro study was conducted to investigate the antiparasitic activities of new quinolones (NFQ-2, NFQ-5, and NFQ-6) containing nitrofuran moiety against T. gondii. To this end, Vero cells were incubated with various concentrations of new quinolones and pyrimethamine (positive control) to determine their viability. Subsequently, they were infected with T. gondii (RH strain) and then subjected to drug treatment. The obtained IC50 values were 3.60, 4.84, 5.59, 3.44 and 2.75 µg/mL for NFQ-2, NFQ-5, NFQ-6, ciprofloxacin and pyrimethamine, respectively. The CC50 values for the NFQ-2, NFQ-5, and NFQ-6 were 25.20, 29.89, and 28.43 µg/mL, indicating the selectivity indexes more than 5 for these compounds. The anti-Toxoplasma efficiency was determined by evaluating infection index, number and size of plaques, and T. gondii intracellular proliferation. As the results indicated, the administration of new quinolone derivatives resulted in the reduction of intracellular proliferation, infection index, and the number and size of plaques in comparison to uninfected treated cells (P < 0.05). The results were indicative of a considerable synergetic effect when each of the derivatives was used in combination with pyrimethamine, compared to when used alone. Based on our results, the nitrofuran-derived quinolones can be considered as new leads for the design of new anti-Toxoplasma agents.

Toxoplasmosis: Targeting neurotransmitter systems in psychiatric disorders.

The most common form of the disease caused by Toxoplasma gondii (T. gondii) is latent toxoplasmosis due to the formation of tissue cysts in various organs, such as the brain. Latent toxoplasmosis is probably a risk factor in the development of some neuropsychiatric disorders. Behavioral changes after infection are caused by the host immune response, manipulation by the parasite, central nervous system (CNS) inflammation, as well as changes in hormonal and neuromodulator relationships. The present review focused on the exact mechanisms of T. gondii effect on the alteration of behavior and neurotransmitter levels, their catabolites and metabolites, as well as the interaction between immune responses and this parasite in the etiopathogenesis of psychiatric disorders. The dysfunction of neurotransmitters in the neural transmission is associated with several neuropsychiatric disorders. However, further intensive studies are required to determine the effect of this parasite on altering the level of neurotransmitters and the role of neurotransmitters in the etiology of host behavioral changes.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Protective efficacy by a novel multi-epitope vaccine, including MIC3, ROP8, and SAG1, against acute Toxoplasma gondii infection in BALB/c mice.

Toxoplasma gondii is an intracellular apicomplexan parasite, which can cause a serious infectious disease in pregnant women and immunocompromised individuals. Therefore, the development of a polyvalent vaccine consisting of all stages of the parasite life cycle using the epitopes from tachyzoites, bradyzoites, and sporozoites is likely to be required for complete protective immunity. In this study, we designed protein vaccine candidate based on the prediction of specific epitopes (i.e., B cell and T cell) from three Toxoplasma gondii antigens. The MRS protein (MIC3: 30-180, ROP8: 85-185, and SAG1: 85-235) was expressed in Escherichia coli, and purification was performed using a HisTrap HP column and then we evaluated immunogenicity and protective property in BALB/c mice. Seventy-two mice were randomly divided into six groups, including three vaccinations (i.e., MRS, MRS-Freund, and MRS-Calcium Phosphate Nanoparticles (MRS-CaPNs)) and three control (i.e., Phosphate-buffered saline, Freund, and CaPNs) groups. All groups were immunized three times via subcutaneous injection within three-week intervals. In the vaccination groups, the BALB/c mice were injected with 20 µg of MRS protein for the first time and 10 µg of MRS for the next two times. Antibodies, cytokines, and splenocytes proliferation in the immunized mice were assayed using the enzyme-linked immunosorbent assay. Protective efficacy was analyzed by challenging the immunized mice with T. gondii of RH strain. Antibody, cytokine, and lymphocyte proliferation assays showed that the mice immunized with MRS induced stronger humoral and T helper type 1 cell-mediated immune responses, compared to the control mice. However, co-immunization with adjuvants (i.e., Freund and CaNPs) resulted in impaired immune responses. Effective protection against the parasite achieved an increase in survival time in the immunized mice, especially in the MRS-CaNPs group. The obtained results of the present study demonstrated that multi-epitope protein vaccination, MRS, is a potential strategy against toxoplasmosis infection. In addition, the vaccine co-delivered with CaPNs could provide an important key for vaccine candidate to control T. gondii infection.

Toxoplasma gondii in mollusks and cold-blooded animals: a systematic review.

Toxoplasma gondii (T. gondii) is known for its ability to infect warm-blooded vertebrates. Although T. gondii does not appear to parasitize cold-blooded animals, the occurrence of T. gondii infection in marine mammals raises concerns that cold-blooded animals (frogs, toad, turtles, crocodiles, snakes, and fish) and shellfish are potential sources of T. gondii. Therefore, this systematic review aimed to determine the prevalence of T. gondii in mollusks and cold-blooded animals worldwide. We searched PubMed, ScienceDirect, ProQuest, Scopus, and Web of Science from inception to 1 August 2020 for eligible papers in the English language and identified 26 articles that reported the prevalence of T. gondii in mollusks and cold-blooded animals. These articles were subsequently reviewed and data extracted using a standard form. In total, 26 studies [involving 9 cross-sectional studies including 2988 samples of cold-blooded animals (129 positive cases for T. gondii) and 18 cross-sectional studies entailing 13 447 samples of shellfish (692 positive cases for T. gondii)] were included in this study. Although this study showed that shellfish and cold-blooded animals could be potential sources of T. gondii for humans and other hosts that feed on them, further investigations are recommended to determine the prevalence of T. gondii in shellfish and cold-blooded animals.

The global status and genetic characterization of hydatidosis in camels (Camelus dromedarius): a systematic literature review with meta-analysis based on published papers.

Hydatidosis is a potential zoonotic helminthic disease affecting a broad spectrum of mammals, including humans, worldwide. The current review was conducted to investigate the genotypic status and prevalence of hydatid disease in camels across the world. For the purpose of the study, the articles addressing the worldwide prevalence of hydatidosis in camels were searched in several English language databases. The search process resulted in the inclusion of 122 papers. Based on the data presented in the reviewed articles, the pooled prevalence of hydatid disease in camels across the world was measured at 23.75% (95% CI 20.15-27.55). Moreover, the subgroup analysis demonstrated significant differences in the overall prevalence of hydatidosis among camels based on year, geographic area, climate parameters, camel population, gender, infected organ, fertility rate of the cyst and laboratory diagnostic technique. Furthermore, the Echinococcus granulosus genotypes identified in camels with hydatidosis included G1, G2, G3, G1-G3, G5, G6, G7, G6-G7 and G6-G10, with G6 being the most common genotype throughout the world. The data obtained from the current study are central to the better conceptualization of the biological and epidemiological characteristics of E. granulosus s.l. genotypes around the world, which can be helpful in the planning and adoption of more comprehensive control strategies.

The global seroprevalence of Toxoplasma gondii infection in bovines: a systematic review and meta-analysis.

Bovines, especially cattle, are considered as one of the main sources of Toxoplasma gondii infection for humans. A more comprehensive understanding of the occurrence of T. gondii is needed to provide a global perspective on the prevalence of T. gondii in bovines. Here, we present the results of the first systematic review and meta-analysis on the global T. gondii seroprevalence in bovines. Six databases (PubMed, ScienceDirect, Web of Science, Scopus, ProQuest and Google Scholar) were comprehensively searched for relevant studies published between 1 January 1967 and 30 May 2019. Among 7691 publications searched, 178 studies (from 50 countries) with 193 datasets were included in the meta-analysis. The global pooled and weighted seroprevalence of T. gondii among bovines was 17.91% [95% confidence interval (CI): 15.32­20.6]. Weighted prevalence based on the host was as follows: cattle 16.94% (95% CI: 14.25­19.81), buffalo 22.26% (95% CI: 16.8­29), yak 23% (95% CI: 14­33) and bison 8.1% (95% CI: 3.9­13.7). Continued monitoring on the status of T. gondii seroprevalence in bovines is essential. Study on the prevalence of T. gondii in the products of bovines such as milk, meat, etc., which are considered as the source of transmission of infection to humans, is recommended.

Relationship between toxoplasmosis and autism: A systematic review and meta-analysis.

Toxoplasma gondii (T. gondii) is a foodborne parasite that is investigated in many psychiatric diseases, such as autism spectrum disorders (ASD). Therefore, a systematic literature review was conducted searching seven electronic databases on the prevalence of T. gondii antibodies among autism patients. The current study involved sensitivity analysis, meta-regression, subgroup analysis, publication bias test, and quality assessment of studies. On the basis of the findings, the odds ratio (OR) of latent Toxoplasma infection 1.93 (95% confidence intervals (CI): 1.01-3.66) was associated with ASD risk. However, there was no relationship between acute infection and ASD 0.39 (95% CI: 0.18-0.87). The obtained results of Begg's and Egger's tests showed no publication bias (P = 0.851 and P = 0.297, respectively). The sensitivity analysis confirmed robust and stable estimates with a significant level of heterogeneity (I2 = 78.1%, P < 0.000). Of the investigated patients' characteristics, only the gender variable was analyzed, indicating the combined ORs of 2.63 (95% CI: 0.29-23.63) in females and 2.62 (95% CI: 0.94-7.30) in male participants. This study showed that toxoplasmosis plays an important role as a risk factor for autism. However, further prospective investigations are highly recommended to illuminate the developmental pathways to this disorder and provide new strategies for the prevention and treatment of this disease.

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.

Morphometric, genetic diversity and phylogenetic analysis of Taenia hydatigena (Pallas, 1766) larval stage in Iranian livestock.

Cysticercus tenuicollis as metacestode of Taenia hydatigena is the most prevalent taeniid species in livestock. Eighty-eight C. tenuicollis samples were collected from sheep (n = 44) and goats (n = 44) of the northern Iran from 2015 to 2016. The isolated parasites were characterized by morphometric keys. The DNA of the larval stage was extracted, amplified and sequenced targeting mitochondrial 12S rRNA and Cox 1 markers. A significant difference in larval rostellar hook length was observed in 12S rRNA haplotypes. Analysis of molecular variance of 12S rRNA indicated a moderate genetic diversity in the C. tenuicollis isolates. The pairwise sequence distance of C. tenuicollis showed an intra-species diversity of 0.3-0.5% and identity of 99.5-100%. Using the 12S rRNA sequence data we found a moderate genetic difference (Fst; 0.05421) in C. tenucollis isolates collected from livestock of the northern and southeastern regions of Iran. We concluded that the genetic variants of C. tenuicollis are being undoubtedly distributing mostly in different parts of Iran. Further studies with a larger number of T. hydatigena isolates collected from various intermediate and definitive hosts are needed to study this evolutionary assumption and also to determine the apparent genetic differences observed in the studied regions.

A serological investigation and genotyping of Toxoplasma gondii among Iranian blood donors indicates threat to health of blood recipients.

BACKGROUND: Toxoplasmosis is a zoonotic disease in animals and human caused by the intracellular obligatory protozoan named Toxoplasma gondii. The purpose of this study was to evaluate the sero-molecular prevalence and genotyping T. gondii among healthy blood donors in north of Iran. METHODS: In this cross-sectional study, 400 blood donors participated from all Blood Transfusion Organization (BTO) in Mazandaran province during October and November 2014. The blood samples were investigated for seroprevalence, DNA detection and genotyping of T. gondii using ELISA, nested-PCR, and Multilocus nested-PCR-RFLP methods respectively. RESULTS: Among all of blood donors, 294 (73.5 %) and 9 (2.2 %) cases were seropositive for anti-T. gondii IgG and IgM antibodies. T. gondii DNA was detected in 7 samples. Four genotype of T. gondii were identified in blood donors samples (Genotype ToxoDB#1, #2, #10 and #27), which 50 % of T. gondii strains were highly pathogenic. CONCLUSIONS: Taking into account survive T. gondii in blood transfusion bag, the high prevalence of T. gondii and existence of pathogenic genotypes in Iranian blood donors, it seems that T. gondii screening should be performed at the BTO to prevent complications of toxoplasmosis in blood recipients.

Synthesis and in vitro anti-Toxoplasma gondii activity of a new series of aryloxyacetophenone thiosemicarbazones.

A new series of aryloxyacetophenone thiosemicarbazones 4a-q have been synthesized as anti-Toxoplasma gondii agents. All compounds showed significant inhibitory activity against T. gondii-infected cells (IC50 values 1.09-25.19 µg/mL). The 4-fluorophenoxy derivative (4l) was the most potent compound with the highest selectivity toward host cells (SI = 19), being better than standard drug pyrimethamine. SAR study indicated that the concurrence of proper substituents on both aryl ring of phenoxyacetophenone is important for potency and safety profile. Further in vitro experiments with the representative compounds 4l and 4p revealed that these compounds at the concentration of 5 µg/mL can significantly reduce the viability of T. gondii tachyzoites, as well as their infectivity rate and intracellular proliferation, comparable to those of pyrimethamine.

Global trends of hand and wrist trauma: a systematic analysis of fracture and digit amputation using the Global Burden of Disease 2017 Study.

BACKGROUND: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. RESULTS: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. CONCLUSIONS: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study.

BACKGROUND: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. METHODS: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. RESULTS: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. CONCLUSIONS: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.

Epidemiology of facial fractures: incidence, prevalence and years lived with disability estimates from the Global Burden of Disease 2017 study.

BACKGROUND: The Global Burden of Disease Study (GBD) has historically produced estimates of causes of injury such as falls but not the resulting types of injuries that occur. The objective of this study was to estimate the global incidence, prevalence and years lived with disability (YLDs) due to facial fractures and to estimate the leading injurious causes of facial fracture. METHODS: We obtained results from GBD 2017. First, the study estimated the incidence from each injury cause (eg, falls), and then the proportion of each cause that would result in facial fracture being the most disabling injury. Incidence, prevalence and YLDs of facial fractures are then calculated across causes. RESULTS: Globally, in 2017, there were 7 538 663 (95% uncertainty interval 6 116 489 to 9 493 113) new cases, 1 819 732 (1 609 419 to 2 091 618) prevalent cases, and 117 402 (73 266 to 169 689) YLDs due to facial fractures. In terms of age-standardised incidence, prevalence and YLDs, the global rates were 98 (80 to 123) per 100 000, 23 (20 to 27) per 100 000, and 2 (1 to 2) per 100 000, respectively. Facial fractures were most concentrated in Central Europe. Falls were the predominant cause in most regions. CONCLUSIONS: Facial fractures are predominantly caused by falls and occur worldwide. Healthcare systems and public health agencies should investigate methods of all injury prevention. It is important for healthcare systems in every part of the world to ensure access to treatment resources.

Epidemiology of injuries from fire, heat and hot substances: global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study.

BACKGROUND: Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. METHODS: We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. RESULTS: Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). CONCLUSIONS: The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.