Cryptococcal meningitis : epidemiology and therapeutic options

Cryptococcal meningitis causes morbidity and mortality worldwide. The burden of disease is greatest in middle- and low-income countries with a high incidence of human immunodeficiency virus (HIV infection. Patients taking immunosuppressive drugs and some immunocompetent hosts are also at risk. Treatment of cryptococcal meningitis consists of three phases: Induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine, which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important.Publisher PDFPeer reviewe

Schistosomiasis japonicum diagnosed on liver biopsy in a patient with hepatitis B co-infection: a case report

Introduction Chronic hepatitis B virus and schistosomiasis are independently associated with significant mortality and morbidity worldwide. Despite much geographic overlap between these conditions and no reason why co-infection should not exist, we present what is, to the best of our knowledge, the first published report of a proven histological diagnosis of hepatic Schistosomiasis japonicum and chronic hepatitis B co-infection. A single case of hepatitis B and hepatic Schistosomiasis mansoni diagnosed by liver biopsy has previously been reported in the literature. Case presentation A 38-year-old Chinese man with known chronic hepatitis B virus infection presented with malaise, nausea and headache. Blood tests revealed increased transaminases and serology in keeping with hepatitis B virus e-antigen seroconversion. A liver biopsy was performed because some investigations, particularly transient elastography, suggested cirrhosis. Two schistosome ova were seen on liver histology, identified as S. japonicum, probably acquired in China as a youth. His peripheral eosinophil count was normal, schistosomal serology and stool microscopy for ova, cysts and parasites were negative. Conclusion Hepatic schistosomiasis co-infection should be considered in patients with hepatitis B virus infection who are from countries endemic for schistosomiasis. Screening for schistosomiasis using a peripheral eosinophil count, schistosomal serology and stool microscopy may be negative despite infection, therefore presumptive treatment could be considered. Transient elastography should not be used to assess liver fibrosis during acute flares of viral hepatitis because readings are falsely elevated. The impact of hepatic schistosomiasis on the sensitivity and specificity of transient elastography measurement for the assessment of hepatitis B is as yet unknown

Microscale sulfur cycling in the phototrophic pink berry consortia of the Sippewissett Salt Marsh

Microbial metabolism is the engine that drives global biogeochemical cycles, yet many key transformations are carried out by microbial consortia over short spatiotemporal scales that elude detection by traditional analytical approaches. We investigate syntrophic sulfur cycling in the ‘pink berry’ consortia of the Sippewissett Salt Marsh through an integrative study at the microbial scale. The pink berries are macroscopic, photosynthetic microbial aggregates composed primarily of two closely associated species: sulfide-oxidizing purple sulfur bacteria (PB-PSB1) and sulfate-reducing bacteria (PB-SRB1). Using metagenomic sequencing and 34S-enriched sulfate stable isotope probing coupled with nanoSIMS, we demonstrate interspecies transfer of reduced sulfur metabolites from PB-SRB1 to PB-PSB1. The pink berries catalyse net sulfide oxidation and maintain internal sulfide concentrations of 0–500 μm. Sulfide within the berries, captured on silver wires and analysed using secondary ion mass spectrometer, increased in abundance towards the berry interior, while δ34S-sulfide decreased from 6‰ to −31‰ from the exterior to interior of the berry. These values correspond to sulfate–sulfide isotopic fractionations (15–53‰) consistent with either sulfate reduction or a mixture of reductive and oxidative metabolisms. Together this combined metagenomic and high-resolution isotopic analysis demonstrates active sulfur cycling at the microscale within well-structured macroscopic consortia consisting of sulfide-oxidizing anoxygenic phototrophs and sulfate-reducing bacteria

Microscale sulfur cycling in the phototrophic pink berry consortia of the Sippewissett Salt Marsh

Microbial metabolism is the engine that drives global biogeochemical cycles, yet many key transformations are carried out by microbial consortia over short spatiotemporal scales that elude detection by traditional analytical approaches. We investigate syntrophic sulfur cycling in the ‘pink berry’ consortia of the Sippewissett Salt Marsh through an integrative study at the microbial scale. The pink berries are macroscopic, photosynthetic microbial aggregates composed primarily of two closely associated species: sulfide-oxidizing purple sulfur bacteria (PB-PSB1) and sulfate-reducing bacteria (PB-SRB1). Using metagenomic sequencing and 34S-enriched sulfate stable isotope probing coupled with nanoSIMS, we demonstrate interspecies transfer of reduced sulfur metabolites from PB-SRB1 to PB-PSB1. The pink berries catalyse net sulfide oxidation and maintain internal sulfide concentrations of 0–500 μm. Sulfide within the berries, captured on silver wires and analysed using secondary ion mass spectrometer, increased in abundance towards the berry interior, while δ34S-sulfide decreased from 6‰ to −31‰ from the exterior to interior of the berry. These values correspond to sulfate–sulfide isotopic fractionations (15–53‰) consistent with either sulfate reduction or a mixture of reductive and oxidative metabolisms. Together this combined metagenomic and high-resolution isotopic analysis demonstrates active sulfur cycling at the microscale within well-structured macroscopic consortia consisting of sulfide-oxidizing anoxygenic phototrophs and sulfate-reducing bacteria

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Cryptococcal meningitis:epidemiology and therapeutic options

Cryptococcal meningitis causes morbidity and mortality worldwide. The burden of disease is greatest in middle- and low-income countries with a high incidence of human immunodeficiency virus (HIV) infection. Patients taking immunosuppressive drugs and some immunocompetent hosts are also at risk. Treatment of cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine), which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important

An observational report of universal GeneXpert testing of inpatients with diagnosed or presumptive TB in the Philippines

BACKGROUND: The Philippines is a high TB and multidrug-resistant TB burden country. Although the scale-up of GeneXpert testing is occurring, the benefits of universal Xpert-Mycobacterium tuberculosis/ rifampicin (MTB/RIF) testing in inpatients have not been documented. METHODS: Routine GeneXpert testing irrespective of priority criteria for testing was conducted within a prospective cohort of all adults with known or presumptive TB admitted to a tertiary infectious diseases hospital in Manila. Study-specific TB diagnosis was decided upon bacteriological results, chest x-ray assessment, if already on anti-TB treatment (ATT) at admission and a cough duration of ?2 wk. RESULTS: Of submitted sputum samples, 87.1% (277/318) had valid acid-fast bacilli (AFB) microscopy and XpertR MTB/RIF results. XpertR MTB/RIF was positive in 97.7% (n = 87/89) of AFB-positive patients and 25.5% (n = 48/188) of AFB-negative patients. Bacteriological confirmation in smear negative cases not on ATT prior to admission was 25.2% (34/135). Rifampicin resistance was detected in 26/135 Xpert positive cases (19.3%), including nine who might not otherwise have been detected, representing a 53% increase in yield. CONCLUSION: Universal GeneXpert testing in this setting enhanced the yield of bacterial confirmation, revealing a high incidence of rifampicin resistance and suggesting a need for further investigations in Xpert-negative/smear-positive patients who may not have mycobacterial TB

Microscale sulfur cycling in the phototrophic pink berry consortia of the Sippewissett Salt Marsh.

Microbial metabolism is the engine that drives global biogeochemical cycles, yet many key transformations are carried out by microbial consortia over short spatiotemporal scales that elude detection by traditional analytical approaches. We investigate syntrophic sulfur cycling in the 'pink berry' consortia of the Sippewissett Salt Marsh through an integrative study at the microbial scale. The pink berries are macroscopic, photosynthetic microbial aggregates composed primarily of two closely associated species: sulfide-oxidizing purple sulfur bacteria (PB-PSB1) and sulfate-reducing bacteria (PB-SRB1). Using metagenomic sequencing and (34) S-enriched sulfate stable isotope probing coupled with nanoSIMS, we demonstrate interspecies transfer of reduced sulfur metabolites from PB-SRB1 to PB-PSB1. The pink berries catalyse net sulfide oxidation and maintain internal sulfide concentrations of 0-500 μm. Sulfide within the berries, captured on silver wires and analysed using secondary ion mass spectrometer, increased in abundance towards the berry interior, while δ(34) S-sulfide decreased from 6‰ to -31‰ from the exterior to interior of the berry. These values correspond to sulfate-sulfide isotopic fractionations (15-53‰) consistent with either sulfate reduction or a mixture of reductive and oxidative metabolisms. Together this combined metagenomic and high-resolution isotopic analysis demonstrates active sulfur cycling at the microscale within well-structured macroscopic consortia consisting of sulfide-oxidizing anoxygenic phototrophs and sulfate-reducing bacteria

Draft genomes from uncultured Thiohalocapsa sp. PB-PSB1 and uncultured Desulfofustis sp. PB-SRB1 from the study "Microscale sulfur cycling in the pink berry consortia of the Sippewissett salt marsh"

<p>The pink berries are macroscopic, photosynthetic microbial aggregates composed primarily of two closely associated species: sulfide-oxidizing purple sulfur bacteria (uncultured Thiohalocapsa sp. PB-PSB1) of the family Chromatiaceae and sulfate reducing bacteria (uncultured Desulfofustis sp. PB-SRB1) from the Desulfobulbacaea.  This dataset consists of the near-complete draft genomes for these two bacterial species.  Annotations provieded here were generated by RAST.</p> <p> </p> <p>These genomes were obtained by binning assembled metagenomic data associated with ncbi bioproject: PRJNA214436.  Genomes annotation data presented here was generated by the RAST automated annotation pipeline with frame-shift correction (http://rast.nmpdr.org).  Full description of the methods used to generate this data and analysis of these genomes has been provided in the publication  "A sulfurous symbiosis: microscale sulfur cycling in the pink berry consortia of the Sippewissett salt marsh" (Wilbanks, et al. in preparation).  </p> <p> </p