Impact of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> complex lineages as a determinant of disease phenotypes from an immigrant rich moderate tuberculosis burden country

Background

Growing evidences suggested that the Mycobacterium tuberculosis complex (MTBC) lineages can determine the clinical outcome of pulmonary and extra-pulmonary tuberculosis. However, limited data only available revealing such association of bacterial genotypes and clinical phenotypes from immigrant rich countries.

Methods

A multicenter study has been carried out on a collection of 2092 (1003 extrapulmonary and 1089 pulmonary) MTBC isolates. Genotyping of all the isolates were carried out by spoligotyping and 24 loci based MIRU-VNTR typing.

Results

Demographically domination of young Saudi nationals (61.4%) and men (61.2%) were found in this cohort. Lymph nodes (62.4%) and gastrointestinal sites (16.7%) were the most common anatomical sites of infection. The predominant lineages were Delhi/CAS (26.9%), EAI (14.2%) and Ghana (9.9%). Mycobacterium africanum type I and II were reported for the first time in the country among extrapulmonary cases. ‘Ancestral’ lineages M.bovis (OR-5.22; 95% CI-2.23-8.22, p-?<?0.001) and Delhi/CAS (OR-0.57; 95% CI-0.411-0.734, p-?<?0.001) were directly associated with lymph node tuberculosis and gastrointestinal tuberculosis (M. bovis-OR-0.33; 95% CI-0.085-0.567, p-0.001 and Delhi/CAS-OR-1.87; 95% CI-1.22-2.53, p-?<?0.001) respectively. Among the ‘Modern’ lineages, EAI showed significant association to central nervous system tuberculosis (OR-1.98; 95% CI-0.76-3.19, p-0.04) and Uganda-I to gastrointestinal tuberculosis (OR-2.41; 95% CI-0.77-4.06, p-0.02).

Conclusions

The findings substantially contribute to the emerging evidences that MTBC lineages influence disease phenotypes and epidemiological consequences.

     

Comparison of three pyrethroid treatments of top-sheets for malaria control in emergencies: entomological and user acceptance studies in an Afghan refugee camp in Pakistan

Insecticide-treated bedding materials (sheets and blankets) could be protective against vectors of malaria and leishmaniasis--especially in complex emergencies, epidemics and natural disasters where people are more likely to sleep in exposed situations. Comparison of cotton top-sheets impregnated with different pyrethroids (permethrin 500 mg/m2, deltamethrin 25 mg/m2 or alphacypermethrin 25 mg/m2) for effectiveness against mosquitoes (Diptera: Culicidae) was undertaken in a refugee camp in Pakistan. Predominant species encountered were Anopheles stephensi Liston, An. pulcherrimus Theobald, An. nigerrimus Giles, Culex quinquefasciatus Say, Cx. tritaeniorhynchus Giles and other culicine mosquitoes. All three pyrethroid treatments performed significantly better than the untreated sheets in deterrence and killing of mosquitoes. No significant differences were found between the three insecticides tested in terms of entomological effect. Washing of the treated sheets greatly reduced their effectiveness. In a user acceptance study conducted among 88 families (divided into four groups), six families complained of irritation of the skin and mucous membranes. Of these reports, one was from the placebo group (using untreated sheets) and the other five (5/22=23%) from families using deltamethrin-treated sheets. All families allocated to permethrin and alphacypermethrin groups declared an appreciation for the intervention and reported no side-effects. Ten of the placebo group disliked the intervention, citing no prevention of mosquito biting as the reason. Side-effects associated with deltamethrin indicate that alphacypermethrin and permethrin are more appropriate first choice insecticides for treatment of sheets and blankets.     

Uptake kinetics of arsenic species in rice plants

Arsenic (As) finds its way into soils used for rice (Oryza sativa) cultivation through polluted irrigation water, and through historic contamination with As-based pesticides. As is known to be present as a number of chemical species in such soils, so we wished to investigate how these species were accumulated by rice. As species found in soil solution from a greenhouse experiment where rice was irrigated with arsenate contaminated water were arsenite, arsenate, dimethylarsinic acid, and monomethylarsonic acid. The short-term uptake kinetics for these four As species were determined in 7-d-old excised rice roots. High-affinity uptake (0-0.0532 mM) for arsenite and arsenate with eight rice varieties, covering two growing seasons, rice var. Boro (dry season) and rice var. Aman (wet season), showed that uptake of both arsenite and arsenate by Boro varieties was less than that of Aman varieties. Arsenite uptake was active, and was taken up at approximately the same rate as arsenate. Greater uptake of arsenite, compared with arsenate, was found at higher substrate concentration (low-affinity uptake system). Competitive inhibition of uptake with phosphate showed that arsenite and arsenate were taken up by different uptake systems because arsenate uptake was strongly suppressed in the presence of phosphate, whereas arsenite transport was not affected by phosphate. At a slow rate, there was a hyperbolic uptake of monomethylarsonic acid, and limited uptake of dimethylarsinic acid.     

Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system

Pseudomonas aeruginosa is an important opportunistic pathogen that produces a variety of cell-associated and secreted virulence factors. P. aeruginosa infections are difficult to treat effectively because of the rapid emergence of antibiotic-resistant strains. In this study, we analyzed whether the amoeba Dictyostelium discoideum can be used as a simple model system to analyze the virulence of P. aeruginosa strains. The virulent wild-type strain PAO1 was shown to inhibit growth of D. discoideum. Isogenic mutants deficient in the las quorum-sensing system were almost as inhibitory as the wild type, while rhl quorum-sensing mutants permitted growth of Dictyostelium cells. Therefore, in this model system, factors controlled by the rhl quorum-sensing system were found to play a central role. Among these, rhamnolipids secreted by the wild-type strain PAO1 could induce fast lysis of D. discoideum cells. By using this simple model system, we predicted that certain antibiotic-resistant mutants of P. aeruginosa should show reduced virulence. This result was confirmed in a rat model of acute pneumonia. Thus, D. discoideum could be used as a simple nonmammalian host system to assess pathogenicity of P. aeruginosa.     

The Role of Biological Agents in the Management of Large Vessel Vasculitis (LVV): A Systematic Review and Meta-Analysis

Background

Giant cell arteritis (GCA) and Takayasu''s arteritis (TAA) are large vessel vasculitides (LVV) for which corticosteroids (CS) are the mainstay for treatment. In patients with LVV unable to tolerate CS, biological agents have been used with variable effectiveness.

Objective

To systematically review the effectiveness and safety of biological agents in patients with LVV.

Methods

We searched 5 electronic databases (inception to October 2012) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. Our protocol was registered in PROSPERO.

Results

We included 25 studies (3 RCTs and 22 case series with ≥2 cases). 95 GCA and 98 TAA patients received biological agents. The RCTs using anti-TNF agents (infliximab, etanercept and adalimumab) did not suggest a benefit in GCA. GCA patients receiving tocilizumab, in case series, achieved remission (19 patients) and reduction of corticosteroid dose (mean difference, –16.55 mg/day (95% CI: –26.24, –6.86)). In case series, 75 patients with refractory TAA treated with infliximab discontinued CS 32% of the time. Remission was variably defined and the studies were clinically heterogeneous which precluded further analysis.

Conclusion

This systematic review demonstrated a weak evidence base on which to assess the effectiveness of biological treatment in LVV. Evidence from RCTs suggests that anti-TNF agents are not effective for remission or reduction of CS use. Tocilizumab and infliximab may be effective in the management of LVV and refractory TAA, respectively, although the evidence comes from case series. Future analytical studies are needed to confirm these findings.     

Communities of culturable yeasts and yeast-like fungi in oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar

This report is the first investigation of yeast biodiversity from the oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar. Yeasts and yeast-like fungi, were cultured from seawater sampled at 13 coastal areas surrounding Qatar over a period of 2 years (December 2013–September 2015). Eight hundred and forty-two isolates belonging to 82 species representing two phyla viz., Ascomycota (23 genera) and Basidiomycota (16 genera) were identified by molecular sequencing. The results indicated that the coastal waters of the Qatari oligotrophic marine environment harbor a diverse pool of yeast species, most of which have been reported from terrestrial, clinical and aquatic sources in various parts of the world. Five species, i.e., Candida albicans, C. parapsilosis, C. tropicalis, Pichia kudriavzevii and Meyerozyma guilliermondii (n?=?252/842; 30% isolates) are known as major opportunistic human pathogens. Fifteen species belonging to nine genera (n?=?498/842; 59%) and 12 species belonging to seven genera (n?=?459/842; 55%) are hydrocarbon degrading yeast and pollution indicator yeast species, respectively. Ascomycetous yeasts were predominant (66.38%; 559/842) as compared to their basidiomycetous counterparts (33.6%; 283/842). The most isolated yeast genera were Candida (28%; 236/842) (e.g., C. aaseri, C. boidinii, C. glabrata, C. intermedia, C. oleophila, C. orthopsilosis, C. palmioleophila, C. parapsilosis, C. pseudointermedia, C. rugopelliculosa, C. sake, C. tropicalis and C. zeylanoides), Rhodotorula (12.7%; 107/842), Naganishia (8.4%; 71/842), Aureobasidium (7.4%; 62/842), Pichia (7.3%; 62/842), and Debaryomyces (6.4%; 54/842). A total of eleven yeast species ( n = 38) isolated in this study are reported for the first time from the marine environment. Chemical testing demonstrated that seven out of the 13 sites had levels of total petroleum hydrocarbons (TPH) ranging from 200 to 900 µg/L, whereas 6 sites showed higher TPH levels (>?1000–21000 µg/L). The results suggest that the yeast community structure and density are impacted by various physico-chemical factors, namely total organic carbon, dissolved organic carbon and sulphur.

     

Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study

BackgroundIn developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children.MethodsIn this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline.ResultsThe case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons).

Conclusion and Significance

We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.     

Relationship Between IL-2, IL-17 Concentrations,and Serum Creatinine Levels in Men with Chronic Kidney Diseases

Background:Chronic kidney disease (CKD), is a major public health challenge worldwide. It is more prevalent in developed countries compared with the rest of the world, due to the higher rates of life expectancy and unhealthy lifestyle related factors. This aim of the current study is to evaluate the relationship between interleukins IL-2 and IL-17 concentrations and kidney function markers in men with CKD.Methods:Forty-five men with CKD and seventy controls were enrolled in the current study to assess the relationship between interleukin-2 (IL-2), interleukin-17 (IL-17), and CKD parameters. Fasting blood samples were collected from patients with CKD and their controls at same time. Serum IL-2, and IL-17 were measured in patients with CKD and their controls, and then the relationship between these interleukins and serum creatinine, serum urea, serum uric acid and urine albumin were evaluated.Results:A significant relationship was detected between IL-2 (p< 0.001), IL-17 (p< 0.001) levels and serum creatinine concentrations. The significant increase of IL-2 and IL-17 levels were also paralleled with a significant increase in serum urea (p< 0.001), and urine albumin (p< 0.001) concentrations respectively.Conclusion:IL-2 and IL-17 may play a critical role in the pathophysiology of CKD. The significant increase of IL-2 and IL-17 is associated with significantly high concentrations of creatinine, serum urea and urine albumin suggesting that these interleukins may be used as targets for future biomarkers and molecular therapy. However, due to limited sample size of the current study, larger prospective cohorts are needed to confirm these observations.Key Words: Chronic kidney disease, Interleukins, Serum creatinine, Serum urea, Urine albumin     

On high-cycle fatigue of 316L stents

This paper deals with fatigue life prediction of 316L stainless steel cardiac stents. Stents are biomedical devices used to reopen narrowed vessels. Fatigue life is dominated by the cyclic loading due to the systolic and diastolic pressure and the design against premature mechanical failure is of extreme importance. Here, a life assessment approach based on the Dang Van high cycle fatigue criterion and on finite element analysis is applied to explore the fatigue reliability of 316L stents subjected to multiaxial fatigue loading. A finite element analysis of the stent vessel subjected to cyclic pressure is performed to carry out fluctuating stresses and strain at some critical elements of the stent where cracks or complete fracture may occur. The obtained results show that the loading path of the analysed stent subjected to a pulsatile load pressure is located in the safe region concerning infinite lifetime.