Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov , NCT04327388 ; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 1...

DNA polymorphism analysis and pathogenicity assays were used to characterize strains of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola collected from rice leaves in West Africa. Restriction fragment length polymorphism (RFLP), repetitive sequence-based polymerase chain reaction, fluorescent amplified fragment-length polymorphism (FAFLP) analyses were assessed for molecular characterization, while pathogenicity was tested by leaf clipping and leaf infiltration. Dendrograms were generated for the data sets obtained from RFLP analysis and repetitive polymerase chain reaction suggesting that the interrelationships between strains were dependent on the technique used. In all cases, data showed that African strains of X. oryzae pv. oryzae form a group genetically distant from Asian strains. FAFLP analyses separated the X. oryzae strains into three groups with significant bootstrap values. A specific and intriguing feature of African strains of X. oryzae pv. oryzae is a reduction in the number of insertion sequence elements and transcription activator-like (avrBs3/pthA) effector genes, based on the molecular markers employed in the study. In addition, pathogenicity assays conducted with African strains of X. oryzae pv. oryzae on a series of nearly isogenic lines (NILs) identified three new races. Finally, leaf infiltration assays revealed the capacity of African strains of X. oryzae pv. oryzae to induce a nonhost hypersensitive response in Nicotiana benthamiana, in contrast with Asian X. oryzae pv. oryzae and X. oryzae pv. oryzicola strains. Our results reveal substantial differences between genomic characteristics of Asian and African strains of X. oryzae pv. oryzae.

We detected 10 protozoan and nine helminth species in surveys of 338 5-15 year-old Quechua schoolchildren in three communities of the Asillo zone of the Puno region, located at a very high altitude of 3910 m in the Peruvian Altiplano. The area proved to be hyperendemic for human fascioliasis with a 24.3% overall mean prevalence of Fasciola hepatica, local prevalences ranging between 18.8 and 31.3%, and infection intensities of up to 2496 eggs per gram of faeces (epg), with 196-350 epg (mean: 279 epg) and 96-152 epg (123 epg) as arithmetic and geometric means, respectively. Prevalences did not significantly vary between schools and in relation to sex. No statistical differences were found in intensities between schools, nor according to sex or age groups between and within schools, although the highest overall egg counts were detected in girls and in the youngest age group. Asillo zone is a man-made irrigation area built only recently to which both liver fluke and lymnaeid snails have quickly adapted. The region appears to be isolated from the Northern Bolivian Altiplano natural endemic area. Such man-made water resources in high altitude areas of Andean countries pose a high fascioliasis risk. Significant positive association of F. hepatica with protozooses following a one host life cycle, such as Giardia intestinalis, suggests that human infection mainly occurs through drinking water. This is supported by additional evidence such as the absence of typical aquatic vegetation in the drainage channels inhabited by lymnaeid snails, the absence of aquatic vegetables in the traditional nutrition habits of the Quechua inhabitants, and the lack of potable water systems inside dwellings, which requires inhabitants to obtain water from irrigation canals and drainage channels.

Coprologic surveys were carried out in villages of the Behera Governorate in the Nile Delta region of Egypt to characterize the epidemiologic features of human fascioliasis caused by Fasciola hepatica and F. gigantica in this lowland endemic area by comparison with fascioliasis caused by only F. hepatica in areas hyperendemic for human disease in the Andean highlands of South America. The fascioliasis prevalences detected (range ‫ס‬ 5.2−19.0%, mean ‫ס‬ 12.8%) are the highest obtained in Egypt. The comparison with previous results suggests that in the Nile Delta, fascioliasis is spreading from an original situation of sporadic human cases in well-known endemic foci for animal disease to an endemic distribution in humans, which may be characterized as a mesoendemic region that includes several hyperendemic areas for human disease. As in Andean countries, a relationship with sex was found, although in Egypt prevalences, but not intensities, appeared to be significantly higher in females. All ages appear to be susceptible to liver fluke infection, with prevalences and intensities being lower before and after school age, a situation that is consistent with that detected in Andean countries, although the peak in the 9−11-year-old age group appears less pronounced in Egypt. The intensities were very high when compared with those found in subjects sporadically infected in areas endemic for animal disease, but relatively low for a hyperendemic situation, although the intensities may not be conclusive because of the transmission seasonality of fascioliasis in the Nile Delta. The marked similarities in the qualitative and quantitative spectrums of protozoans and helminths, multiparasitisms, and associations between liver flukes and other parasitic species suggest physiographic-hydrographic and behavioral-social characteristics similar in all areas hyperendemic for human fascioliasis, which are independent of other factors such as climate, altitude, and cultural or religious features. The significant positive association between liver fluke infection and schistosomiasis mansoni detected in one locality has never been described elsewhere, and must be considered relevant from clinical, pathologic, diagnostic, and therapeutic points of view. Interestingly, the relationships of schistosomiasis prevalences and intensities with sex and age follow patterns similar to those found in fascioliasis.

Acid mine drainage (AMD), associated with active and abandoned mining sites, is a habitat for acidophilic microorganisms that gain energy from the oxidation of reduced sulfur compounds and ferrous iron and that thrive at pH below 4. Members of the recently proposed genus “Ferrovum” are the first acidophilic iron oxidizers to be described within the Betaproteobacteria. Although they have been detected as typical community members in AMD habitats worldwide, knowledge of their phylogenetic and metabolic diversity is scarce. Genomics approaches appear to be most promising in addressing this lacuna since isolation and cultivation of “Ferrovum” has proven to be extremely difficult and has so far only been successful for the designated type strain “Ferrovum myxofaciens” P3G. In this study, the genomes of two novel strains of “Ferrovum” (PN-J185 and Z-31) derived from water samples of a mine water treatment plant were sequenced. These genomes were compared with those of “Ferrovum” sp. JA12 that also originated from the mine water treatment plant, and of the type strain (P3G). Phylogenomic scrutiny suggests that the four strains represent three “Ferrovum” species that cluster in two groups (1 and 2). Comprehensive analysis of their predicted metabolic pathways revealed that these groups harbor characteristic metabolic profiles, notably with respect to motility, chemotaxis, nitrogen metabolism, biofilm formation and their potential strategies to cope with the acidic environment. For example, while the “F. myxofaciens” strains (group 1) appear to be motile and diazotrophic, the non-motile group 2 strains have the predicted potential to use a greater variety of fixed nitrogen sources. Furthermore, analysis of their genome synteny provides first insights into their genome evolution, suggesting that horizontal gene transfer and genome reduction in the group 2 strains by loss of genes encoding complete metabolic pathways or physiological features contributed to the observed diversification.