Infectious Diseases

Background Plasmodium vivax is the main cause of malaria in Nepal. Relapse patterns have not been characterized previously. Methods Patients with P. vivax malaria were randomized to receive chloroquine (CQ; 25 mg base/kg given over 3 days) alone or together with primaquine (PQ; 0.25 mg base/kg/day for 14 days) and followed intensively for 1 month, then at 1- to 2-month intervals for 1 year. Parasite isolates were genotyped. Results One hundred and one (49%) patients received CQ and 105 (51%) received CQ + PQ. In the CQ + PQ arm, there were 3 (4.1%) recurrences in the 73 patients who completed 1 year of follow-up compared with 22 of 78 (28.2%) in the CQ-only arm (risk ratio, 0.146 [95% confidence interval, .046–.467]; P < .0001). Microsatellite genotyping showed relatively high P. vivax genetic diversity (mean heterozygosity, 0.843 [range 0.570–0.989] with low multiplicity of infection (mean, 1.05) reflecting a low transmission preelimination setting. Of the 12 genetically homolog...

X&Y chromosomal aneuploidies are among the most common human whole-chromosomal copy number changes, but the population-based incidence and prevalence in the childbearing population is unclear. This retrospective analysis of prospectively collected data leveraged a routine non-invasive prenatal test (NIPT) using parental genotyping to estimate the population-based incidence of X&Y chromosome variations in this population referred for NIPT (generally due to advanced maternal age). From 141,916 women and 29,336 men, 119 X&Y chromosomal abnormalities (prevalence: 1 in 1,439) were identified. Maternal findings include: 43 cases of 45,X (40 mosaic); 30 cases of 47,XXX (12 mosaic); 3 cases of 46,XX uniparental disomy; 2 cases of 46,XY/46, XX; 23 cases of mosaicism of unknown type; 2 cases of 47,XX,i(X)(q10). Paternal findings include: 2 cases of 47,XXY (1 mosaic); 10 cases of 47,XYY (1 mosaic); 4 partial Y deletions. Single chromosome aneuploidy was present in one of every 1,439 individuals considered in this study, showing 47,XXX; 47,XX,i(X)(q10); 47,XYY; 47,XXY, partial Y deletions, and a high level of mosaicism for 45,X. This expands significantly our understanding of X&Y chromosomal variations and fertility issues, and is critical for families and adults affected by

Tuberculosis continues to be one of the most devastating global health problem. Its diagnosis will benefit in timely initiation of the treatment, cure and therefore reduction in the transmission of the disease. Tests are available, but none can be comprehensively relied on for its diagnosis; especially in TB-endemic zones. PhoP is a key player in Mycobacterium tuberculosis virulence but nothing has been known about its role in the diagnosis of TB. We monitored the presence of anti-PhoP antibodies in the healthy, patients and their contacts. In addition, we also measured antibodies against early secretory antigens ESAT-6 and CFP-10, and latency associated antigen Acr-1 to include proteins that are associated with the different stages of disease progression. Healthy subjects showed high antibody titer against PhoP than patients and their contacts. In addition, a distinct pattern in the ratio of Acr-1/ PhoP was observed among all cohorts. This study for the first time demonstrates a novel role of anti-PhoP antibodies, as a possible marker for the diagnosis of TB and therefore will contribute in the appropriate action and management of the disease.

Tuberculosis continues to be one of the most devastating global health problem. Its diagnosis will benefit in timely initiation of the treatment, cure and therefore reduction in the transmission of the disease. Tests are available, but none can be comprehensively relied on for its diagnosis; especially in TB-endemic zones. PhoP is a key player in Mycobacterium tuberculosis virulence but nothing has been known about its role in the diagnosis of TB. We monitored the presence of anti-PhoP antibodies in the healthy, patients and their contacts. In addition, we also measured antibodies against early secretory antigens ESAT-6 and CFP-10, and latency associated antigen Acr-1 to include proteins that are associated with the different stages of disease progression. Healthy subjects showed high antibody titer against PhoP than patients and their contacts. In addition, a distinct pattern in the ratio of Acr-1/PhoP was observed among all cohorts. This study for the first time demonstrates a nov...

The present study describes a novel and simple vaccination strategy that involves the culturing of live Mycobacterium tuberculosis and Salmonella typhimurium in syngeneic, allogeneic, and xenogeneic macrophages, followed by drug treatment and gamma irradiation, to kill the bacteria. Notable observations were that the lymphocytes obtained from the vaccinated mice proliferated and secreted mainly interferon-g and IgG2a, but not interleukin-4 and IgG1. The enumeration of viability of M. tuberculosis indicated a significant level of protection in the vaccinated mice after challenge with live M. tuberculosis. This vaccination strategy worked successfully for tuberculosis but also showed a significant decrease in mortality of mice challenged with live S. typhimurium. Approximately 100 million newborns and children received bacille-Calmette Gue ´rin (BCG) in 1992 through the World Health Organization (WHO)/United Nations Children's Emergency Fund (UNICEF) Expanded Program for Immunization . Despite the fact that more people have been vaccinated with BCG than any other vaccine, tuberculosis continues to kill some 3 million people annually, and ∼2 billion people worldwide are infected with Mycobacterium tuberculosis . Thus, the protective efficacy of the BCG vaccine remains doubtful. The wide spread of tuberculosis has been further compounded by the emergence of multidrug-resistant strains of mycobacteria and the AIDS pandemic . Therefore, there is an urgent need to develop an effective vaccine for the control of the disease. Approximately one-third of the world population is infected with M. tuberculosis, but only 5%-10% contract

The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology. This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017. 15 of 22 laboratories were able to share their isolates, and the first 22•5% of isolates from each year were requested. We used whole genome sequencing to infer the population structure (PopPUNK), and we investigated the clade composition of the dominant multidrug resistant clonal complex (CC)131 using genetic markers previously reported for sequence type (ST)131, effective population size (BEAST), and presence of determinants of antimicrobial resistance (ARIBA, PointFinder, and ResFinder databases) over time. We compared these features between the 2002-10 and 2011-17 time periods. We also compared our results with those of a longitudinal study from the UK done between 2001 and 2011. Findings Of the 3500 isolates requested from the participating laboratories, 3397 (97•1%) were received, of which 3254 (95•8%) were successfully sequenced and included in the analysis. A significant increase in the number of multidrug resistant CC131 isolates from 71 (5•6%) of 1277 in 2002-10 to 207 (10•5%) of 1977 in 2011-17 (p<0•0001), was the largest clonal expansion. CC131 was the most common clone in extended-spectrum β-lactamase (ESBL)-positive isolates (75 [58•6%] of 128) and fluoroquinolone non-susceptible isolates (148 [39•2%] of 378). Within CC131, clade A increased in prevalence from 2002, whereas the global multidrug resistant clade C2 was not observed until 2007. Multiple de-novo acquisitions of both bla CTX-M ESBL-encoding genes in clades A and C1 and gain of phenotypic fluoroquinolone non-susceptibility across the clade A phylogeny were observed. We estimated that exponential increases in the effective population sizes of clades A, C1, and C2 occurred in the mid-2000s, and in clade B a decade earlier. The rate of increase in the estimated effective population size of clade A (N e =3147) was nearly ten-times that of C2 (N e =345), with clade A over-represented in Norwegian CC131 isolates (75 [27•0%] of 278) compared with the UK study (8 [5•4%] of 147 isolates). Interpretation The early and sustained establishment of predominantly antimicrobial susceptible CC131 clade A isolates, relative to multidrug resistant clade C2 isolates, suggests that resistance is not necessary for clonal success. However, even in the low antibiotic use setting of Norway, resistance to important antimicrobial classes has rapidly been selected for in CC131 clade A isolates. This study shows the importance of genomic surveillance in uncovering the complex ecology underlying multidrug resistance dissemination and competition, which have implications for the design of strategies and interventions to control the spread of high-risk multidrug resistant clones.

To assess the cost of varicella in young children in France, a prospective study was done in day care centers. Children (1263), who were 3 months to 3 years old and attending day care, were followed over a varicella season. For every child who developed varicella (n Å 200), detailed information was obtained by use of parental questionnaires. Questions concerned medical care, days missed from work for parents, and the need for extra baby-sitting. On average, each sick child had one consultation with a physician and received three medications. In half of the families (52%), at least 1 parent had to miss work an average of 4.5 days to care for a sick child. Total costs to society were estimated to be US$352 per family, with medical costs accounting for 22% of the cost. The average eventual cost to parents was $89 per family, including $80 of non-medical costs. This study emphasizes the important socioeconomic impact of varicella in the day care setting in France. teered their participation before the study began were included. For a DCC to be eligible for the study, children had to attend the on the cost-effectiveness of vaccination programs [1 -4]. Howparticipating center for the entire working day and for at least 4 ever, data on the cost of varicella are sparse and usually based days a week, and about half of the children attending the center on hospitalizations or outpatient contacts [5 -7]. Very few studhad to be still susceptible to varicella, as assessed by a brief interies have attempted to assess varicella costs using a populationview with the parents. All children attending a participating DCC based approach [8,. Moreover, most published data regarding were enrolled in the study and followed for varicella-zoster virus healthy children are from the United States and may not apply (VZV) infection from January to June 1995. to other countries. Since the cost of varicella is likely to depend Informed consent was obtained from parents to participate in this observavaricella occurred from 1 month before to 1 month after the index tional study. child's illness. Financial support: Pasteur Me ´rieux Connaught. Diagnostic assessment of varicella during the study was based P.S. and S.A.P. are professionally affiliated with Pasteur Me ´rieux Connaught.

Three water-soluble Ru(II) chiral heteroleptic coordination compounds [Ru(en)(pdto)]Cl2 (1), [Ru(gly)(pdto)]Cl (2), and [Ru(acac)(pdto)]Cl (3), where pdto = 2,2&#39;-[1,2-ethanediylbis-(sulfanediyl-2,1-ethanediyl)]dipyridine, en = ethylendiamine, gly = glycinate, and acac = acetylacetonate, have been synthezised and fully characterized. The crystal structures of compounds 1-3 are described. The IC50 values for compounds 1-3 are within nanomolar range (14, 12, and 6 nM, respectively). The cytotoxicity for human peripheral blood lymphocytes is extremely low (&gt;100 μM). Selectivity indexes for Ru(II) compounds are in the range 700-1300. Trophozoites exposed to Ru(II) compounds die through an apoptotic pathway triggered by ROS production. The orally administration to infected mice induces a total elimination of the parasite charge in mice faeces 1-2-fold faster than metronidazole. Besides, all compounds inhibit the trophozoite proliferation in amoebic liver abscess induced in hamster....

The human population is aging at an astonishing rate. The aim of this study is to capture a situation snapshot revealing the proportion of individuals aged 65 years and over among inpatients in healthcare institutions in Turkey and the prevalence and type of infections in this patient group in order to draw a road map. Materials and Methods: Hospitalized patients over 65 years at any of the 62 hospitals in 29 cities across Turkey on February 9, 2017 were included in the study. Web-based SurveyMonkey was used for data recording and evaluation system. Results: Of 17,351 patients 5871 (33.8%) were !65 years old. The mean age was 75.1 AE7.2 years; 3075 (52.4%) patients were male. Infection was reason for admission for 1556 (26.5%) patients. Pneumonia was the most common infection. The median length of hospital stay was 5 days (IQR: 2-11 days). The Antibiotic therapy was initiated for 2917 (49.7%) patients at the time of admission, and 23% of the antibiotics prescribed were inappropriate. Healthcare-associated infections developed in 1059 (18%) patients. Urinary catheters were placed in 2388 (40.7%) patients with 7.5% invalid indication. This study used real data to reveal the proportion of elderly patients in hospital admissions. The interventions done, infections developed during hospitalization, length of hospital stay, and excessive drug load emphasize the significant impact on health costs and illustrate the importance of preventive medicine in this group of patients.

Long-term functional stability of isolated membrane proteins is crucial for many in vitro applications used to elucidate molecular mechanisms, and used for drug screening platforms in modern pharmaceutical industry. Compared to soluble proteins, the understanding at the molecular level of membrane proteins remains a challenge. This is partly due to the difficulty to isolate and simultaneously maintain their structural and functional stability, because of their hydrophobic nature. Here we show, how scintillation proximity assay can be used to analyze time-resolved high-affinity ligand binding to membrane proteins solubilized in various environments. The assay was used to establish conditions that preserved the biological function of isolated human kappa opioid receptor. In detergent solution the receptor lost high-affinity ligand binding to a radiolabelled ligand within minutes at room temperature. After reconstitution in Nanodiscs made of phospholipid bilayer the half-life of high-affinity ligand binding to the majority of receptors increased 70-fold compared to detergent solubilized receptors-a level of stability that is appropriate for further downstream applications. Time-resolved scintillation proximity assay has the potential to screen numerous conditions in parallel to obtain high levels of stable and active membrane proteins, which are intrinsically unstable in detergent solution, and with minimum material consumption.

Long-term functional stability of isolated membrane proteins is crucial for many in vitro applications used to elucidate molecular mechanisms, and used for drug screening platforms in modern pharmaceutical industry. Compared to soluble proteins, the understanding at the molecular level of membrane proteins remains a challenge. This is partly due to the difficulty to isolate and simultaneously maintain their structural and functional stability, because of their hydrophobic nature. Here we show, how scintillation proximity assay can be used to analyze time-resolved high-affinity ligand binding to membrane proteins solubilized in various environments. The assay was used to establish conditions that preserved the biological function of isolated human kappa opioid receptor. In detergent solution the receptor lost high-affinity ligand binding to a radiolabelled ligand within minutes at room temperature. After reconstitution in Nanodiscs made of phospholipid bilayer the half-life of high-affinity ligand binding to the majority of receptors increased 70-fold compared to detergent solubilized receptors-a level of stability that is appropriate for further downstream applications. Time-resolved scintillation proximity assay has the potential to screen numerous conditions in parallel to obtain high levels of stable and active membrane proteins, which are intrinsically unstable in detergent solution, and with minimum material consumption.

Tuberculosis (TB) remains one of the most deadly infections with approximately a quarter of cases not being identified and/or treated mainly due to a lack of resources. Rapid detection of TB or drug-resistant TB enables timely adequate treatment and is a cornerstone of effective TB management. We evaluated the analytical performance of a single-tube assay for multidrug-resistant TB (MDR-TB) on an experimental platform utilising RT-PCR and melting curve analysis that could potentially be operated as a point-of-care (PoC) test in resource-constrained settings with a high burden of TB. Firstly, we developed and evaluated the prototype MDR-TB assay using specimens extracted from well-characterised TB isolates with a variety of distinct rifampicin and isoniazid resistance conferring mutations and nontuberculous Mycobacteria (NTM) strains. Secondly, we validated the experimental platform using 98 clinical sputum samples from pulmonary TB patients collected in high MDR-TB settings. The sen...

Rabies continues to pose a significant public health challenge in the Philippines, particularly in regions like San Fernando, Pampanga. This study aimed to evaluate the knowledge, attitudes, and practices (KAP) regarding rabies prevention and management among residents of San Fernando. This study utilized a quantitative descriptive correlational research design. This study employed a stratified random sampling technique to ensure a representative sample of the population. The participants, aged 18 to 59 years, were systematically selected to gather a total of 400 respondents from the city of San Fernando located in the province of Pampanga. The results revealed significant gaps in knowledge and varying attitudes and practices towards rabies prevention. The results indicate a low level of knowledge on rabies, high level of attitude on rabies, and fair to high level of practices in addition, the association of these variables with that of their sociodemographic factors and KAP level was measured by Kruskal Wallis Test and Wilcoxon Rank Sum Test to explore the correlations between sociodemographic factors and KAP levels. The study's results underscored the need for targeted educational campaigns and community-based interventions to enhance rabies prevention efforts. These findings provide crucial insights for public health policymakers and practitioners aiming to reduce rabies incidence in San Fernando and similar settings.

Introduction: Among beta-hemolytic streptococci, Streptococcus pyogenes causes a wide variety of human disease including pharyngitis, necrotizing fasciitis and streptococcal toxic syndrome. Group A Streptococcus (GAS) uses a variety of virulence traits to colonize and then cause damage to the host; others species of beta-hemolytic streptococci are considered as emerging pathogens for humans. Despite its recognized virulence, only few studies have investigated virulence factors of GAS strains isolated in Mexico. Methodology: We conducted an epidemiological study to investigate the prevalence of GAS strains in child illnesses in Chiapas Mexico. Virulence genes encoding proteases, DNases, superantigens, as well as susceptibility to antibiotics were investigated. Results: During 2010, 2013 and 2014, beta-hemolytic streptococci (N=12) were isolated from cases of bacterial infections including pharyngitis and bacteremia, with a prevalence of 0.42, 0.04 and 0.20%, respectively. S. pyogenes...

Introduction of pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes substantially decreased invasive (IPD) and non-invasive pneumococcal diseases (NIPD) but it was accompanied by non-vaccine type replacement disease. After 9 years of introduction of PCV in Mexico, we analyze the evidence of the indirect effects on IPD and NIPD serotype distribution among groups not targeted to receive the vaccine. From January 2000 to December 2014, pneumococcal strains isolated from IPD and NIPD cases from patients ≥5 years of age from participant hospitals of the SIREVA II (Sistema Regional de Vacunas) network were serotyped. A regression analysis was performed considering year and proportion of serotypes included in the different vaccine formulations (PCV7, PCV10 and PCV13). The slope was obtained for each regression line and their correspondent p-value. The proportion of each serotype in the pre-PCV7 and post-PCV7 periods was evaluated by χ2 test. From a total of...

Recently, three distinct groups of C. parapsilosis (groups I, II, and III) were described as new species, i.e., C. parapsilosis sensu stricto , C. orthopsilosis , and C. metapsilosis , respectively . The importance of C. orthopsilosis and C. metapsilosis as human pathogens remains unknown; however, studies point to their signifi cant involvement in human candidiasis [5 -8]. Interestingly, the incidence of C. orthopsilosis and C. metapsilosis infections may have increased since 2004 [6], with prevalence rates ranging from 2.3 -9% and 0.9 -6.9%, respectively, depending on the geographical area and clinical specimens analyzed. In our hospital, as reported by the Infection Control Committee, C. parapsilosis became the second most common Candida species isolated from blood samples

Nontyphoidal Salmonella is a major contributor to the global burden of foodborne disease, with invasive infections contributing substantially to illnesses and deaths. We analyzed notifiable disease surveillance data for invasive nontyphoidal Salmonella disease (iNTS) in Queensland, Australia. We used Poisson regression to estimate incidence rate ratios by gender, age group, and geographical area over 2007-2016. There were 995 iNTS cases, with 945 (92%) confirmed by blood culture. Salmonella Virchow accounted for 254 (25%) of 1,001 unique iNTS isolates. Invasive NTS disease notification rates peaked among infants, during the summer months, and in outback Queensland where the notification rate (95% CI) was 17.3 (14.5-20.1) cases per 100,000 population. Overall, there was a 6,5% annual increase (p<0.001) in iNTS disease incidence. In conclusion, high iNTS rates among males, infants, and the elderly require investigation of household level risk factors for NTS infection. Controlling Salmonella Virchow infections is a public health priority.

Din punct de vedere economic, indicatorii de greutate au fost clar în declin. La sfârşitul perioadei de experiment, s-a înregistrat un minus de 26 kg şi patru purcei morţi. In concluzie, utilizarea comparativă în terapie a Dimetridazolului şi Tiamutinului, preparate cu efect consacrat in dizenteria treponemica, a indicat că ambele au efecte terapeutice certe dar Tiamutinul s-a dovedit de departe a fi cel mai eficient. Rezultatele vin să confirme şi alte studii care atestă eficacitatea superioară a Tiamutinului asupra lui Brachyspira hyodysenteriae în terapia preventivă şi curativă a dizenteriei.

Hematopoietic stem cell transplant (HSCT) recipients have severe impairment in cell-mediated immunity as a result of the conditioning regimen used, immunosuppressive therapy, and graftversus-host disease (GVHD). 1,2 Accordingly, they are susceptible to bacterial, viral, and fungal infections. Mycobacterial infections can also occur in these patients, although the incidence is not high, even in countries where tuberculosis (TB) is common. 2 Data from the USA show that the incidence of Mycobacterium infection among HSCT recipients ranges from 0.0014% to 3%. Countries in which the prevalence of TB in the general population is higher than in the USA have reported incidences varying from 1.6% in Spain 6 and Turkey, 7 to 8.57% in Hong Kong and Taiwan and 16% in Pakistan. We describe herein a case of pulmonary and probable pericarditis TB in a patient who underwent HSCT, and review the English language literature on this subject. An extensive PubMed and Ovid search was performed using the search terms 'Mycobacterium tuberculosis' or 'tuberculosis', in combination with 'hematopoietic stem cell transplantation' or 'bone marrow transplantation', and 'allogeneic and autologous transplant'. A specific search for 'pericarditis due to Mycobacterium tuberculosis' and 'hematopoietic stem cell transplantation' or 'bone marrow transplantation' was performed. Studies that focused on stem cell transplantation for other diseases, such as autoimmune or solid tumor, were excluded.

Human antimicrobial RNases, which belong to the vertebrate RNase A superfamily and are secreted upon infection, display a wide spectrum of antipathogen activities. In this work, we examined the antifungal activity of the eosinophil RNase 3 and the skin-derived RNase 7, two proteins expressed by innate cell types that are directly involved in the host defense against fungal infection. Candida albicans has been selected as a suitable working model for testing RNase activities toward a eukaryotic pathogen. We explored the distinct levels of action of both RNases on yeast by combining cell viability and membrane model assays together with protein labeling and confocal microscopy. Site-directed mutagenesis was applied to ablate either the protein active site or the key anchoring region for cell binding. This is the first integrated study that highlights the RNases&#39; dual mechanism of action. Along with an overall membrane-destabilization process, the RNases could internalize and targe...

Preparations of CdTe quantum platelets, magic-size (CdTe) 13 nanoclusters, and CdTe quantum wires are described using (Me 2 N) 3 PTe (with (Me 2 N) 3 P) as a Te precursor. The (Me 2 N) 3 PTe/(Me 2 N) 3 P precursor mixture is shown to be more reactive than mixtures of trialkylphosphine tellurides and the corresponding trialkylphosphines, R 3 PTe/R 3 P, which are commonly employed in nanocrystal syntheses. For syntheses conducted in primary amine solvents, (Me 2 N) 3 PTe and (Me 2 N) 3 P undergo a transamination reaction, affording (Me 2 N) x (RHN) 3-x PTe and (Me 2 N) x (RHN) 3-x P (R = n-octyl or oleyl). The transaminated (Me 2 N) x (RHN) 3-x PTe derivatives are shown to be the likely Te precursors under those conditions. The enhanced reactivities of the tris(amino)phosphine tellurides are ascribed to increased nucleophilicity due to the amino-N lone pairs.

Preparations of CdTe quantum platelets, magic-size (CdTe) 13 nanoclusters, and CdTe quantum wires are described using (Me 2 N) 3 PTe (with (Me 2 N) 3 P) as a Te precursor. The (Me 2 N) 3 PTe/(Me 2 N) 3 P precursor mixture is shown to be more reactive than mixtures of trialkylphosphine tellurides and the corresponding trialkylphosphines, R 3 PTe/R 3 P, which are commonly employed in nanocrystal syntheses. For syntheses conducted in primary amine solvents, (Me 2 N) 3 PTe and (Me 2 N) 3 P undergo a transamination reaction, affording (Me 2 N) x (RHN) 3-x PTe and (Me 2 N) x (RHN) 3-x P (R = n-octyl or oleyl). The transaminated (Me 2 N) x (RHN) 3-x PTe derivatives are shown to be the likely Te precursors under those conditions. The enhanced reactivities of the tris(amino)phosphine tellurides are ascribed to increased nucleophilicity due to the amino-N lone pairs.

Mice carrying a defective leptin receptor gene (db/db mice) are metabolically challenged and upon infection with Trypanosoma cruzi (Brazil strain) suffer high mortality. In genetically modified db/db mice, (NSE-Rb db/ db mice), central leptin signaling is reconstituted only in the brain, which is sufficient to correct the metabolic defects. NSE-Rb db/db mice were infected with T. cruzi to determine the impact of the lack of leptin signaling on infection in the absence of metabolic dysregulation. Parasitemia levels, mortality rates, and tissue parasitism were statistically significantly increased in infected db/db mice compared with those in infected NSE-Rb db/ db and FVB wild-type mice. There was a reduction in fat mass and blood glucose level in infected db/db mice. Plasma levels of several cytokines and chemokines were statistically significantly increased in infected db/db mice compared with those in infected FVB and NSE-Rb db/db mice. These findings suggest that leptin resistance in individuals with obesity and diabetes mellitus may have adverse consequences in T. cruzi infection. Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic in Mexico, Central America, and South America . In recent years, there has been an influx of immigrants into North America and Europe from areas where Chagas disease is endemic. Some

Single-chain polymer nanoparticles (SCNPs) are protein-inspired materials based on intramolecularly cross-linked polymer chains. We report here the development of SCNPs as uniquely sized nanocarriers that are capable of drug encapsulation independent of the polarity of the employed medium. Synthetic routes are presented for SCNP preparation in both organic and aqueous environments. Importantly, the SCNPs in organic media were successfully rendered water soluble, resulting in two complementary pathways toward water-soluble SCNPs with comparable resultant physicochemical characteristics. The solvatochromic dye Nile red was successfully encapsulated inside the SCNPs following both pathways, enabling probing of the SCNP interior. Moreover, the antibiotic rifampicin was encapsulated in organic medium, the loaded nanocarriers were rendered water soluble, and a controlled release of rifampicin was evidenced. The absence of discernible cytotoxic effects and promising cellular uptake behavio...

Peer education (PE) interventions may help improve knowledge and appropriate use of antibiotics in young adults. In this feasibility study, health-care students were trained to educate 16–18 years old biology students, who then educated their non-biology peers, using e-Bug antibiotic lessons. Knowledge was assessed by questionnaires, and antibiotic use by questionnaire, SMS messaging and GP record searches. Five of 17 schools approached participated (3 PE and 2 control (usual lessons)). 59% (10/17) of university students and 28% (15/54) of biology students volunteered as peer-educators. PE was well-received; 30% (38/127) intervention students and 55% (66/120) control students completed all questionnaires. Antibiotic use from GP medical records (54/136, 40% of students’ data available), student SMS (69/136, 51% replied) and questionnaire (109/136, 80% completed) data showed good agreement between GP and SMS (kappa = 0.72), but poor agreement between GP and questionnaires (kappa = 0.0...

Objectives: Staphylococcus aureus (S. aureus) is regarded as an important aetiological agent of various human infections. Fluoroquinolones are routinely used in the chemotherapeutic management of these infections; nonetheless, in recent years, a growing rate of resistance to these drugs has been reported worldwide. The aims of this study were to isolate and discover the prevalence of plasmid-mediated (qnrA, qnrB, and qnrS) genes among the quinolone-resistant clinical S. aureus isolates in Bayelsa State, Nigeria. Methods: A total of 25 (31.25%) clinical isolates of S. aureus were collected from hospitalized patients. The bacterial isolates were identified through standard laboratory protocols and further confirmed using the API Staph system (bioMérieux, France) test strips. The antimicrobial susceptibility and minimum inhibitory concentration (MIC) were determined by the standard disk diffusion and serial dilutions methods respectively. Polymerase chain reaction (PCR) was used for de...

The Fibrosis-4 Index (FIB-4), developed to predict fibrosis in liver disease, was used to identify patients with coronavirus disease 2019 who will require ventilator support as well as those associated with 30-day mortality. Multivariate analysis found obesity (odds ratio [OR], 4.5), diabetes mellitus (OR, 2.55), and FIB-4 ≥2.67 (OR, 3.09) independently associated with need for mechanical ventilation. When controlling for ventilator use, sex, and comorbid conditions, FIB-4 ≥2.67 was also associated with increased 30-day mortality (OR, 8.4 [95% confidence interval, 2.23–31.7]). Although it may not be measuring hepatic fibrosis, its components suggest that increases in FIB-4 may be reflecting systemic inflammation associated with poor outcomes.

Background: Tuberculosis is the oldest infectious disease and it is still the leading cause of morbidity and mortality worldwide. Even though several primary studies have been conducted on the incidence of tuberculosis among HIV-infected individuals in Ethiopia, national-level tuberculosis incidence is unknown. Therefore, this study is aimed to assess the TB incidence rate and its predictors among HIV-infected individuals after the initiation of ART in Ethiopia. We conducted an extensive search of literature as indicated in the guideline of reporting systematic review and meta-analysis (PRISMA). The databases used were PubMed, Google Scholar, and HINARI literature. We used the Joanna Briggs Institute (JBI) Meta-Analysis of Statistics Assessment and Review Instrument for critical appraisal of studies. The meta-analysis and Meta regressions were conducted using STATA 14 software. Met-analysis and meta-regression were computed to present the pooled incidence rate and predictors of tuberculosis among HIV-infected patients after initiation of ART with a 95% confidence interval. Results: Among a total of 189 studies, 11 studies were included in this analysis. The estimated pooled incidence rate of TB per 100-person year observation (PYO) among HIV-infected patients after initiation of ART therapy was 4.8(95% CI 3.69-5.83). In subgroup analysis, the estimated pooled incidence of tuberculosis showed a slight difference between adults and children after initiation of ART treatment, which was 4.3 (95% CI 2.96, 5.71) and 5.0 (95% CI 3.51, 6.50), respectively. Significantly pooled estimates of predictors of TB incidence by a meta-analysis were being anemic (2.30, 95% CI 1.75, 3.02); on clinical stages III and IV (2.26, 95% CI 1.70, 3.02); and not on cotrimoxazole preventive therapy (CPT) (2.16, 95% CI 1.23, 3.72). Besides, a meta-regression revealed that CD4 <200 cells/mm 3 (2.12, 95% CI 1.17, 3.86) was a positive significant predictor of TB among HIV patients after the initiation of ART.

The urinary tract infection (UTI) which affects any part of the urinary tract is one of the most common paediatric infections that may cause permanent kidney damage. The most common causative organisms are bowel flora. Schistosomiasis, a neglected parasitic tropical disease is one of the major public health problems facing developing countries. School-aged children are at the greatest risk of acquiring Schistosomiasis. The complexity of Schistosomiasis morbidity is associated with its co-infection with bacteriuria. Against this background, current information on the prevalence of urinary Schistosomiasis, as well as associated bacteriuria co-infection is necessary for effective control of the disease. We therefore investigated the current prevalence of urinary Schistosomiasis and co-infection with bacteriuria in Ishara in order to provide information for public health action. 280urine samples were collected and cultured on the appropriate media. Urinalysis and microscopy were also co...

Background: India is endemic for viral hepatitis A (HAV) infection with 66% of states reporting at least one outbreak from 2011 to 2013. Following media reports in January 2015, we investigated a jaundice outbreak in Kangra town of Himachal Pradesh Valley with the following objectives: (1) assess the magnitude, (2) identify the source, and (3) initiate preventive measures. Methods & Materials: An active case search was done in Kangra to identify case-patients who had acute onset of jaundice during 1 st November 2014 to 23 rd January 2015. We conducted a 1:1 case-control study; data on exposures were collected using a structured questionnaire. Serum specimens from five cases were tested for IgM anti-HAV and IgM anti-hepatitis E virus. End-point water specimens from households of case-patients were tested for faecal coliforms using most probable number method. Results: The overall attack rate was 1.6 (149/ 9528). There were no deaths. Illness began on November 3 rd , 2014 and persisted through January 21 st , 2015. Among 149 patients, 62% were in 5-14 age-group with no gender differences. All five serum samples tested positive only for IgM anti-HAV; no contamination was detected in water samples. Contact with jaundice patients in previous two weeks (OR 1.6; 95% CI 1.03-2.6; p<0.01), drawing water by dipping ladle in storage containers (3.2; 95% CI 2-5.2; p<0.001), storing drinking water in narrow necked containers (16.9; 95% CI 7.7-36.9; p<0.001), past history of jaundice (OR 15.3; 95% CI 1.9-118; p<0.001) and not washing hands with soap before meals (OR 3.8; 95% CI 2.0-7.1; p<0.001) were associated with illness. The findings suggested that this was an outbreak of hepatitis A. Promotion of personal hygiene and sanitation among residents of Kangra was recommended.

The aim of this study was to assess knowledge regarding cataract and associated factors among adults in Gondar town Northwest Ethiopia. A community-based cross-sectional study was conducted on 836 adults age �18years, using multi-stage systematic random sampling technique, in Gondar town Northwest Ethiopia from April 15-May 7, 2017. Data were collected using pre-tested structured questionnaires through face to face interview. The collected data was entered to Epi info version 7 and analyzed using SPSS version 20. Binary logistic regression was used to identify associated factors. Those variables with p-value <0.05 and confidence interval 6 ¼ 1 in multivariable logistic regression were considered as statistically significant factors for knowledge regarding cataract. Among 845 eligible adults, 98.9% (836) of them were fully participated. The median age of participants was 28 years with an interquartile range of 17 years. Of the total participants, 67.2% (562) of them had awareness about cataract [95% CI,]. Among 562 participants, 61.7% of them had good knowledge about cataract [95% CI, 57.5-66.00]. It was also found that higher level of education [AOR = 2.86, 95%CI: 1.37-5.96], higher family monthly income [AOR = 1.92, 95%CI: 1.03-3.57], having previous eye examination [AOR = 1.53, 95% CI: 1.02-2.31] and positive family history of cataract [AOR = 1.76, 95%CI: 1.03-3.01] were positively associated with good knowledge. Significant portion of the participants had good knowledge about cataract, which was positively associated with higher level of education, higher family monthly income, presence of

Re su men. En el pre sen te tra ba jo, es tu dia mos la ex pre sión ex vivo e in vitro de los re cep to res CD95/Fas y CD127 en lin fo ci tos T CD8+ to ta les, vír genes y de me mo ria de pa cien tes in fec ta dos con VIH con di fe ren tes con cen tracio nes san guí neas de lin fo ci tos T CD4+. Ade más, a es tas cé lu las se les de termi nó la apop to sis es pon tá nea e in du ci da por an tí ge nos vi ra les (Env) y su capa ci dad pro li fe ra ti va es pe cí fi ca. Los re sul ta dos mos tra ron que los pa cien tes con una baja den si dad de lin fo ci tos T CD4 san guí neos (CD4 < 250/µL), ma nifes ta ban ex vivo una alta ex pre sión de CD95/Fas y una baja ex pre sión de CD127 en to das las sub po bla cio nes de lin fo ci tos T CD8+ en re la ción a los pacien tes con una den si dad ma yor de lin fo ci tos T CD4+ en san gre (CD4 > 250/µL). En en sa yos in vi tro usan do el an tí ge no Env, los lin fo ci tos T CD8+ to ta les pre sen ta ron una ex pre sión si mi lar de am bos re cep to res con una ma yor in ci den cia de apop to sis es pon tá nea y una dis mi nui da ca pa ci dad pro li fe ra ti va en re la ción a los con tro les. Estos re sul ta dos se ña lan como el de sa rro llo progre si vo de la in fec ción por VIH en pa cien tes no tra ta dos está aso cia do con una dis mi nu ción de lin fo ci tos T CD8+ san guí neos, ca rac te ri za dos por fa llas en su ca pa ci dad pro li fe ra ti va y en la fre cuen cia de apop to sis, lo cual se evi den cia por una ex pre sión al te ra da de CD127 y CD95/Fas.

Staphylococcus aureus is a leading cause of pneumonia. We show here that the ClpXP protease involved in protein turnover is important for pathogenesis in a murine model of acute pneumonia. Staphylococcus aureus lacking this protease is attenuated in vivo, being rapidly cleared from the airway and leading to decreased immune cell influx and inflammation. Characterization of defined mutations in vitro identified defects in intracellular survival and protection against neutrophil killing. Our results further expand on what is known about ClpXP in the pathogenesis of S. aureus to include the respiratory tract.

Two series of star-shaped discotic compounds (A and B) were studied to establish the relationship between their molecular structure and mesogenity. Series A included 19 three-arm compounds with known mesomorphism. Series B consisted of 132 new compounds with unknown mesomorphism: pyromellitic and cyanuric acid derivatives, 5,5 0 -azo-bisisophthalic and 4,4 0 -azodiphthalic acids and triphenylene derivatives. The columnar mesomorphism prediction data for both series were obtained using the original program E;C ChemCard. The prediction data for series A are in good agreement with the experimental results and the reliability of the prediction was estimated to be 89.5%. The same method was applied for series B. The prediction results were approved by the synthesis of individual representatives of series B. A good correlation of the prediction with the experimental data was revealed.

Schistosomiasis is a water-based disease transmitted by trematodes belonging to the genus Schistosoma. The aim of this study was to assess the relationship between the prevalence of schistosomiasis and access to water, sanitation and hygiene (WASH) and environmental and socioeconomic factors in the city of Korhogo, northern Côte d&#39;Ivoire. A cross-sectional study including 728 randomly selected households was conducted in Korhogo in March 2015. The heads of the households were interviewed about access to WASH and environmental and socioeconomic factors. All children abed between 5 and 15 years living in the households were selected to provide stool and urine samples for parasitological diagnosis of Schistosoma mansoni and Schistosoma haematobium infection. The relationship between infection with S. mansoni and potential risk factors was analysed by a mixed logistic regression model with &#39;household&#39; as a random factor. Likelihood ratio tests were used to identify factors t...

Bats are considered important reservoirs of rabies virus, which is paramount in the study of the pathogenesis of this zoonosis disease, through the use of sensitive systems. The presence of viral antigen in these species shows that non-neuronal viral spread is efficient in different organs that participate effectively in the elimination of rabies virus, such as, salivary glands and bladder. This study aimed to investigate the presence of rabies virus in samples of bats submitted for laboratory diagnosis, as well as, to study the pathogenesis of the disease through the use of laboratory animals. 3,930 routine diagnostic specimens of bats were processed during the period between January 2011 and May 2012 by direct immunofluorescence (DIF) and viral isolation on murine neuroblastoma cells (VICC) techniques. 58 samples were diagnosed rabies positive from 37 bats in 2011 and 21 samples were diagnosis rabies positive in 2012, representing a positivity rate of 1.80%. We randomly selected 2...

Background: Urinary tract infection (UTI) is one of the most common bacterial infections in the world, and uropathogenic Escherichia Coli (UPEC) is the principal pathogen of UTI. Escherichia coli (E. coli) outer membrane protease T (OmpT), a member of the omptin family with high substrate specificity, is supposed to be involved in the pathogenesis of E.coli. Methods: In order to explore the role of OmpT in UPEC-induced UTI, an ompT gene deletion mutant of UPEC strain CFT073 was constructed by using the RED recombineering, then its biological properties were analyzed with in vitro model of human unthelial cell strain 5637 and in vivo model of C57B/L6 mouse. Results: The in vitro adhesion showed that the adhesion rate for the mutant (COTD) was about 60% of the parent strain CFT073 (P < 0.05). For the in vitro invasion assay, the invasion rate of the CFT073 was as 2.5 times as that of the mutant (P < 0.01). For the in vivo invasion assay, the E. coli strains wild-type and mutant (COTD) was inoculated into the bladder of the C57B/L6 mice, respectively. After 12 h of inoculation, the bladder tissues were collected and used for colony counting. The results showed that the colonization number of the mutant (COTD) was significantly fewer than that of the CFT073. The colonization number of the mutants was about 4.0 × 106 cfu, which was also obviously fewer than that of the CFT073 (1.9 × 107 cfu) (P < 0.01). By using the method of ␤-galactosidase in situ staining, we found that the mutant was defective in the ability of intracellular bacterial community (IBC) formation, which is an important indicator of pathogenicity for UPEC. Taken together, this study has suggested that ompT plays an important role of the pathogenesis of uropathogenic Escherichia Coli, however, the detailed regulatory mechanisms between the genes still need further study.

On 31 December 2019, the World Health Organization (WHO) Country Office in China picked up a media statement on the website of the Wuhan Municipal Health Commission on cases of 'viral pneumonia' in Wuhan, Hubei Province, People's Republic of China. The official name of the virus responsible for the outbreak is severe acute respiratory syndrome coronavirus (SARS-CoV-2) according to the International Committee on Taxonomy of Viruses (ICTV), and the disease it causes is named coronavirus disease (COVID-19). WHO, under the International Health Regulations (IHR 2005), declared the emergence of COVID-19 a Public Health Emergency of International Concern on 30 January 2020 and declared the outbreak a pandemic on 11 March 2020. WHO detailed a strategic response and preparedness plan 1 and produced a Research and Development Blueprint research agenda 2 to drive innovation in all aspects of outbreak control, from clinical case management to vaccine development, and developed a master plan for coordinating clinical trials that could lead to potential therapies for patients affected with the COVID-19 disease. Today, different countries and private laboratories are working to develop effective vaccines using state-of-the-art technology, and simultaneously assessing different treatments, including interferon and other pharmaceutical combinations being used to identify effective therapies. However, we are still trusting of reactive strategies to face this new threat for humanity but working in isolated silos.

The epidemiology of bovine and human tuberculosis (TB) was studied in the Federal Capital Territory and Kaduna state of Nigeria using four diagnostic methods; tuberculin test, culture and acid-fast stain of milk, animal (cattle) tissue and human sputum. Two PCR-based molecular techniques (Spoligotyping and Variable Number Tandem Repeat) were used to identify the species and strains of the isolates, while IS61 10-RFLP molecular method was optimised and applied on few samples to deten-nine the efficacy of the method. Of the 967 lactating cows from 57 herds tested for TB, 14.6%, 4% and 81.4% were positive, inconclusive and negative reactors respectively. Tuberculin test also showed that mycobacterial infection was prevalent iii the two management systems studied (nomadic and semi-nomadic), but the effect of management on the prevalence of infection was not significant. However, age was found to play a significant role in the prevalence infection where more positive cases were observed among the older age groups. It was also observed that control policy is either not in place or inadequately implemented in the study area. Of the 156 milk samples collected, 12.6% and 23% were culture and acid-fast positive respectively, while out of the 250 tissue samples 17.3% and 20% were culture and acid-fast positivc respectively. Thi III is finding confirmed a definite relationship between the disease in live and slaughtered cattle. Comparing the three diagnostic methods in List of Contents

Tradicionalmente considerados patógenos oportunistas, cada vez son más los casos descritos de infecciones cutáneas por micobacterias no tuberculosas (MNT) en individuos inmunocompetentes en relación sobre todo con traumatismos que alteren la barrera cutánea, incluidos los procedi-mientos dermoestéticos (mesoterapia¹, acupuntura 2 , tatuajes 3 , manicura 4 y pedicura 5 , etc.) e intervenciones médicas invasivas (inyecciones, bombas de insulina 6 , etc.). Son bacterias saprófitas ambientales que ocasionan infecciones clínicamente muy polimorfas, de curso subagudo y evolución tórpida pese a la antibioterapia empírica.

We are presenting our initial experience with the utilization of the scalp as a donor for split thickness skin grafting in the treatment of massive thermal injuries. Rapid donor reepithelization, absence of hypertrophic scarring in the donor area, inconspicuous donor area and a large area for the procurement of grafts in the pediatric population are the advantages that are emphasized in the literature. The outcome in a 3-year-old boy who suffered a burn injury from an open fire in the family house on the 57% of his total body surface area (48% full thickness burn) showed that the “take rate”, in the absence of a massive local infection, was around 80% and that the scalp can be utilized again as a donor area after a period of 14 days. Folliculitis and alopecia are complications that should be kept in mind when using this technique.

Sažetak. Prikazujemo svoje inicijalno iskustvo u uporabi vlasišta kao davatelja presatka djelomične debljine kože pri liječenju masivnih opeklinskih ozljeda. Brzina cijeljenja donora, odsutnost razvoja hipertrofi čnih ožiljaka na davateljskim regijama, nezamjetne donorske regije te velika površina koja se, posebice u dječjoj dobi, može iskoristiti kao donor prednosti su ove tehnike koje se navodi u literaturi. Ishod kod trogodišnjeg dječaka s opeklinskom ozljedom nastalom u plamenu u obiteljskoj kući pri čemu mu je opečeno 57% tjelesne površine (48% tjelesne površine opeklina pune debljine kože) pokazao je da je prihvat transplantata u odsutnosti masivne lokalne infekcije bio oko 80% te da se vlasište može ponovo iskoristiti kao donorska regija nakon perioda od 14 dana. Folikulitis i alopecija jesu komplikacije o kojima treba voditi računa pri uporabi ove tehnike.

Article type: Case Report Article Background: One of the most serious types of meningitis caused by Mycobacterium tuberculosis (MTB) which involves meningeal layer and is usually associated with high mortality and morbidity. We focused on the significance diagnosis and prompt treatment. Methods: We describe a case of TBM.In a 40-Year-old Asian male. He was no respiratory distress, neck stiffness, constipation, and nausea, but frequent urination. In addition, the patient had a history of drug addiction. Results: His Magnetic Resonance Imaging (MRI) showed hyperintense Lesions. Sputum culture for Mycobacterium tuberculosis (MTB) was found positive and he was given a therapeutic trial of quinolones and Steroids. Conclusion: Observing the principles of biological safety among the personnel of medical centers and screening for TB disease in drug-positive and HIV-positive is essential. Article history: Received: 24 Jun 2019 Revised: 02 Aug 2019 Accepted: 07 Aug 2019 Published: 12 Sep 2019

Johne's disease (JD; paratuberculosis) control programs have been regionally implemented across the globe, but few have successfully eradicated the pathogen (Mycobacterium avium ssp. paratuberculosis; MAP) causing this disease. The limited success may partly be attributed to excluding young stock (calves and replacement heifers or bulls) from testing strategies aimed at identifying MAP-infected cattle. Young stock can shed MAP in feces and can have detectable MAP-specific antibodies in blood, as confirmed in experimentally and naturally infected cattle. Furthermore, MAP transmission causes new infections in young stock. Calves and heifers are often included in JD management strategies on dairy farms but excluded from conventional diagnostic tests due to a presumed lag between infection and detection of MAP shedding and MAP-specific serum antibodies. We summarize evidence of MAP shedding early in the course of infection and discuss promising diagnostics, testing and management strategies to support inclusion of young stock in JD control programs. Improvements in fecal PCR, interferon-gamma release assay (IGRA), and ELISA enable earlier detection of MAP and specific early immune responses. Studies on IGRA and ELISA have focused on evaluation of new antigens and optimal age of testing. New diagnostics have been developed, including phage-based tests to detect viable MAP, as well as gene expression patterns and metabolomics to detect MAP-infected young stock. In addition, refinements in testing and management of calves and heifers may enable reductions in MAP prevalence. We provide recommendations for dairy farmers, researchers, veterinarians, and other stakeholders that may improve JD control programs with an objective to control and potentially eradicate JD. Additionally, we have identified the most pressing gaps in knowledge that currently hamper inclusion of young stock in JD prevention and control programs. In summary, transmission among young stock may cause new MAP infections, and appropriate use of new diagnostic tests, testing and management strategies for young stock may improve the efficacy of JD control programs.

In most proteome mass spectrometry experiments, more than half of the mass spectra cannot be identified, mainly because of various modifications. The open search strategy allows for a larger precursor tolerance to utilize more spectra, especially those with post-translational modifications; however, thorough quality control based on independent information is lacking. Here, we used the "Suspicious Discovery Rate (SDR)" based on translatome sequencing (RNC-seq) as an independent source to reference the proteome open search results in steady-state cells. We found that the open search strategy increased the spectra utilization with the cost of increased suspicious identifications that lack translation evidence. We further found that restricting the peptide FDR below 0.1% efficiently controlled the suspicious identifications of open search methods and thus enhanced the confidence of the peptide identification with modifications comparable to the level of the traditional narrow window search. We then demonstrated the successful and validated identification of 27 single amino acid variations from the spectra of two cell lines using the open search strategy without predefined database. These results validated the proper use of open search methods for higher-quality proteome identifications with information on post-translational modifications and single amino acid polymorphisms.