Lactate Dehydrogenase in Toxoplasma Gondii Controls Virulence, Bradyzoite Differentiation, and Chronic Infection

In the asexual stages, Toxoplasma gondii stage converts between acute phase rapidly replicating tachyzoites and chronic phase slowly dividing bradyzoites. Correspondingly, T. gondii differentially expresses two distinct genes and isoforms of the lactate dehydrogenase enzyme, expressing LDH1 exclusively in the tachyzoite stage and LDH2 preferentially in the bradyzoite stage. LDH catalyzes the interconversion of pyruvate and lactate in anaerobic growth conditions and is utilized for energy supply, however, the precise role of LDH1 and LDH2 in parasite biology in the asexual stages is still unclear. Here, we investigated the biological role of LDH1 and LDH2 in the asexual stages, and the vaccine strain potential of deletion mutants lacking LDH1, LDH2, or both genes (Δldh1, Δldh2 and Δldh1/2). Deletion of LDH1 reduced acute parasite virulence, impaired bradyzoite differentiation in vitro, and markedly reduced chronic stage cyst burdens in vivo. In contrast, deletion of LDH2 impaired chronic stage cyst burdens without affecting virulence or bradyzoite differentiation. Deletion of both LDH1 and LDH2 induced a more severe defect in chronic stage cyst burdens. These LDH mutant phenotypes were not associated with any growth defect. Vaccination of mice with a low dose of mutants deleted for LDH elicited effective protective immunity to lethal challenge infection, demonstrating the vaccine potential of LDH deletion mutants. These results suggest that lactate dehydrogenase in T. gondii controls virulence, bradyzoite differentiation, and chronic infection and reveals the potential of LDH mutants as vaccine strains

Perception of Ticks and Tick-Borne Diseases Worldwide

In this comprehensive review study, we addressed the challenge posed by ticks and tick-borne diseases (TBDs) with growing incidence affecting human and animal health worldwide. Data and perspectives were collected from different countries and regions worldwide, including America, Europe, Africa, Asia, and Oceania. The results updated the current situation with ticks and TBD and how it is perceived by society with information bias and gaps. The study reinforces the importance of multidisciplinary and international collaborations to advance in the surveillance, communication and proposed future directions to address these challenges

Comparative physiological, morphological, histological, and AQP2 immunohistochemical analysis of the Arabian camels (Camelus dromedarius) and oxen kidney: Effects of adaptation to arid environments

Compared to other mammals, Arabian camels are ideal models for exploring the structural adaptations that enable camels to survive in arid environments. Thus, this study aimed to explore how evolutionary adaptation to arid conditions modifies the characteristics of the kidneys in Arabian camels (Camelus dromedarius) compared to oxen. Urine samples were physically and chemically analyzed. Harvested kidneys were subjected to topographical and fast spin echo magnetic resonance (FSE-MR) imaging. Histology, histomorphometry, and Aquaporin-2 (AQP2) expression by immunohistochemistry were also performed. Here, in dromedaries, sodium and potassium values in the urine were much higher (p=0.001, for both), whereas chloride was much lower (p=0.004) than the values of oxen. Compared with oxen, the level of the hormone aldosterone in serum was significantly lower (p=0.002), whereas creatinine and urea were significantly higher (p=0.005 and p=0.001, respectively). Uric acid in dromedaries and oxen did not differ significantly (p=0.349). Like sodium levels (p=0.001) in dromedary serum, chloride was also much higher (p=0.002) than in oxen. The average value of potassium was much lower (p=0.009) than that of oxen. Morphologically, anatomical and FSE MRI studies revealed that minor and major calyces were not found in dromedary kidneys. The renal pelvis was not found in oxen, and the major calyx was directly connected to the ureter. The dromedary kidney contained a wider medullary portion as well as increased diameters for renal corpuscles (RCs), proximal convoluted tubules (PCTs), and collecting tubules (CTs, p<0.05) compared with the oxen. We also noted that AQP2 was significantly expressed in dromedary nephron components, except for RCs, compared with oxen as shown by immunohistochemistry. Overall, these data strongly suggest that the dromedary has a greater ability to adapt to harsh desert conditions in terms of producing highly concentrated urine than oxen

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

An overview of Neem (Azadirachta indica) and its potential impact on health

Global health and medical practice seek to merge alternative medicine with evidence-based medicine for a better understanding of the metabolic process and its effects in the human body. An example is the use of complementary medicine like phytotherapy. Azadirachta indica (Neem), a tree originally from India and Myanmar, called by many “The village pharmacy” or “Divine tree” because of its many health properties. In recent times, Neem-derived extracts have been shown to work from anywhere from insect repellent, to supplements to lower inflammation, diabetic control, and even to combat cancer. Herein, we state the health benefits found in diverse compounds and extracts derived from Neem, highlighting the mechanisms and pathways in which Neem compounds produce their effects, while warning that the improper and unstandardized conditions to produce extracts can lead to health issues, particularly certain compounds might have damaging effects on the liver and kidneys

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Cross-sectional study for determining the prevalence of Q fever in small ruminants and humans at El Minya Governorate, Egypt

Abstract Objective Q fever is a febrile illness caused by the bacterial pathogen Coxiella burnetii (C. burnetii) and is transmitted to humans from small ruminants via contaminated secreta and excreta of infected animals. This pathogen threatens public health; however, little is known regarding Q fever prevalence in humans and small ruminants. Therefore, we employed a cross-sectional design to determine the Q fever seroprevalence and the associated risk factors in small ruminants and their owners in El Minya Governorate, Egypt between August 2016 and January 2017. Results The seroprevalence of C. burnetii IgG antibodies was 25.68% (28 of 109), 28.20% (11 of 39) and 25.71% (9 of 35) in sheep, goats, and humans, respectively. None of the studied variables in small ruminants differed significantly between the seropositive and seronegative animals. There was a significantly higher prevalence (P = 0.0435) and increased odds of exposure was also observed among women (odds ratio, OR = 5.43 (95% CI 1.058–27.84) when compared to men; nevertheless, no significant difference was noted between the infection rate in small ruminants and humans. This study clearly points out that Q fever may be emerging in the area which lay the foundation for early prediction and better management of possible future outbreaks