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Background: Primary intestinal immunity through viral replication of live oral vaccine is key to interrupt poliovirus transmission. We assessed viral fecal shedding from infants administered Sabin monovalent poliovirus type 2 vaccine (mOPV2) or low and high doses of 2 novel OPV2 (nOPV2) vaccine candidates., Methods: In 2 randomized clinical trials in Panama, a control mOPV2 study (October 2015 to April 2016) and nOPV2 study (September 2018 to October 2019), 18-week-old infants vaccinated with bivalent oral poliovirus vaccine/inactivated poliovirus vaccine received 1 or 2 study vaccinations 28 days apart. Stools were assessed for poliovirus RNA by polymerase chain reaction (PCR) and live virus by culture for 28 days postvaccination., Results: Shedding data were available from 621 initially reverse-transcription PCR-negative infants (91 mOPV2, 265 nOPV2-c1, 265 nOPV2-c2 recipients). Seven days after dose 1, 64.3% of mOPV2 recipients and 31.3%-48.5% of nOPV2 recipients across groups shed infectious type 2 virus. Respective rates 7 days after dose 2 decreased to 33.3% and 12.9%-22.7%, showing induction of intestinal immunity. Shedding of both nOPV2 candidates ceased at similar or faster rates than mOPV2., Conclusions: Viral shedding of either nOPV candidate was similar or decreased relative to mOPV2, and all vaccines showed indications that the vaccine virus was replicating sufficiently to induce primary intestinal mucosal immunity., Competing Interests: Potential conflicts of interest. G. A. and R. R. were full-time employees of the study sponsor; A. S. B. and J. M. were full-time employees of the Bill & Melinda Gates Foundation, which financed the study; and N. S. B. was a full-time employee of the vaccine manufacturer. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

In a blinded phase 1 trial (EudraCT 2017-0000908-21; NCT03430349) in Belgium, healthy adults (aged 18-50 years) previously immunized exclusively with inactivated poliovirus vaccine were administered a single dose of 1 of 2 novel type 2 oral poliovirus vaccines (nOPV2-c1: S2/cre5/S15domV/rec1/hifi3 (n = 15); nOPV2-c2: S2/S15domV/CpG40 (n = 15)) and isolated for 28 days in a purpose-built containment facility. Using stool samples collected near days 0, 14, 21, and 28, we evaluated intestinal neutralization and immunoglobulin A responses to the nOPV2s and found that nOPV2-c1 and nOPV2-c2 induced detectable poliovirus type 2-specific intestinal neutralizing responses in 40.0% and 46.7% of participants, respectively., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Dent disease type 1 is suspected in the presence of a complete phenotype of low molecular weight (LMW) proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, nephrolithiasis, haematuria, hypophosphatemia or chronic kidney disease (CKD). We present two brothers who presented with CKD alone. In the absence of typical clinical features, further assessment of LMW proteinuria and hypercalciuria was not undertaken. Whole-genome sequencing revealed hemizygous loss of function mutations in chloride voltage-gated channel 5 ( CLCN5) consistent with Dent disease. Dent disease should, therefore, be considered in patients with an incomplete phenotype, including unexplained CKD alone., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)-immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks., Methods: In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination., Results: After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%-62%) were shedding virus; 9 of 37 (24%; 12%-41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported., Conclusions: High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Quantifying interference of maternal antibodies with immune responses to varying dose schedules of inactivated polio vaccine (IPV) is important for the polio endgame as IPV replaces oral polio vaccine (OPV)., Methods: Type 2 poliovirus humoral and intestinal responses were analyzed using pre-IPV type 2 seropositivity as proxy for maternal antibodies from 2 trials in Latin America. Infants received 1 or 2 doses of IPV in sequential IPV-bivalent oral polio vaccine (bOPV) or mixed bOPV-IPV schedules., Results: Among infants vaccinated with bOPV at age 6, 10, and 14 weeks of age and IPV at 14 weeks, those with type 2 pre-IPV seropositivity had lower seroprotection rates than seronegative infants at 4 weeks (92.7% vs 83.8%; difference, 8.9% [95% confidence interval, 0.6%-19.9%]; n = 260) and 22 weeks (82.7% vs 60.4%; difference, 22.3 [12.8%-32.4%]; n = 481) post-IPV. A second IPV at age 36 weeks resulted in 100% seroprotection in both groups. Among infants vaccinated with 1 IPV at age 8 weeks followed by 2 doses of bOPV, pre-IPV type 2-seropositive infants had lower seroprotection at age 28 weeks than those who were seronegative (93.0% vs 73.9%; difference, 19.6% [95% confidence interval, 7.3%-29.4%]; n = 168). A second dose of IPV at 16 weeks achieved >97% seroprotection at age 24 or 28 weeks, regardless of pre-IPV status. Poliovirus shedding after challenge with monovalent OPV, serotype 2, was higher in pre-IPV seropositive infants given sequential IPV-bOPV. No differences were observed in the mixed bOPV-IPV schedule., Conclusions: The presence of maternal antibody is associated with lower type 2 post-IPV seroprotection rates among infants who receive a single dose of IPV. This impact persists until late in infancy and is overcome by a second IPV dose.

In May 2016, countries using oral polio vaccine for routine immunization switched from trivalent oral poliovirus vaccine (tOPV) to bivalent type 1 and 3 OPV (bOPV). This was done in order to reduce risks from type 2 vaccine-derived polioviruses (VDPV2) and vaccine-associated paralytic poliomyelitis (VAPP) and to introduce ≥1 dose of inactivated poliovirus vaccine (IPV) to mitigate post-switch loss of type 2 immunity. We conducted a literature review of studies that assessed humoral and intestinal immunogenicity induced by the newly recommended schedules. Differences in seroconversion rates were closely associated with both timing of first IPV administration and number of doses administered. All studies demonstrated high levels of immunity for types 1 and 3 regardless of immunization schedule. When administered late in the primary series, a second dose of IPV closed the humoral immunity gap against polio type 2 associated with a single dose. IPV doses and administration schedules appear to have limited impact on type 2 excretion following challenge.

Background: Multiple genes underlying focal segmental glomerulosclerosis (FSGS) and/or steroid-resistant nephrotic syndrome (SRNS) have been identified, with the recent inclusion of collagen IV mutations responsible for Alport disease (AD) or thin basement membrane nephropathy (TBMN). We aimed to investigate the distribution of gene mutations in adult patients with primary FSGS/SRNS by targeted next generation sequencing (NGS)., Methods: Eighty-one adults from 76 families were recruited; 24 families had a history of renal disease. A targeted NGS panel was designed and applied, covering 39 genes implicated in FSGS/SRNS including COL4A3-5., Results: Confirmed pathogenic mutations were found in 10 patients (6 with family history) from 9 families (diagnostic rate 12%). Probably pathogenic mutations were identified in an additional six patients (combined diagnostic rate 20%). Definitely pathogenic mutations were identified in 22% of patients with family history and 10% without. Mutations in COL4A3-5 were present in eight patients from six families, representing 56% of definitely pathogenic mutations, and establishing a diagnosis of AD in six patients and TBMN in two patients. Collagen mutations were identified in 38% of families with familial FSGS, and 3% with sporadic FSGS, with over half the mutations occurring in COL4A5. Patients with collagen mutations were younger at presentation and more likely to have family history, haematuria and glomerular basement membrane abnormalities., Conclusions: We show that collagen IV mutations, including COL4A5, frequently underlie FSGS and should be considered, particularly with a positive family history. Targeted NGS improves diagnostic efficiency by investigating many candidate genes in parallel., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The community response of indigenous sandstone, chalk and limestone groundwater microorganisms to the addition of the commonly used herbicide isoproturon was examined. The addition of 100 microg l(-1) isoproturon generally caused an increase in species diversity determined by chemotaxonomic analysis (fatty methyl ester analysis) of isolates resulting from incubation of cultures at 18 degrees C for 4 days. Amongst the groundwater samples to which isoproturon was added, isoproturon degradation rates were correlated with increasing dominance of a few species. However, the changes in community profile associated with isoproturon degradation varied from site to site. Repeated sub-culturing with 100 microg l(-1) isoproturon and sterile groundwater was carried out to examine whether this level of pesticide could exert a selection pressure, and hence stimulate more rapid degradation. Significantly increased degradation was observed in a groundwater sample from the chalk, but not in sandstone, or limestone samples. The addition of filter-sterilised sandstone groundwater to bacteria on filter paper from slow degrading limestone sites significantly improved their degrading performance. The addition of filter-sterilised limestone groundwater to the sandstone bacteria reduced their degradation rate only slightly. The data suggested that the nature of the indigenous community does influence pesticide degradation in groundwater, but that the groundwater chemistry may also play a role.

Abstract The biodiversity of the pelagic bacterioplankton community of a maritime Antarctic freshwater lake was examined by cultivation-dependent and cultivation-independent techniques to determine predominant bacterioplankton populations present. The culture-dependent techniques used were direct culture and observation, polymerase chain reaction amplification of 16S rRNA gene fragments, restriction fragment length polymorphism (RFLP) analysis followed by selective sequencing and fatty acid methyl ester analysis. The culture-independent techniques used were 16S ribosomal DNA gene cloning, RFLP analysis and sequencing, in situ hybridisation with group-specific, fluorescently labelled oligonucleotide probes and cloning and sequencing of dominant denaturing gradient gel electrophoresis products. Significant differences occurred between the results obtained with each method. However, sufficient overlap existed between the different methods to identify potentially significant groups. At least six different bacterial divisions including 24 genera were identified using culture-dependent techniques, and eight different bacterial divisions, including 23 genera, were identified using culture-independent techniques. Only five genera, Corynebacterium, Cytophaga, Flavobacterium, Janthinobacterium and Pseudomonas, could be identified using both sets of techniques, which represented four different bacterial divisions. Significantly for Antarctic freshwater lakes, pigment production is found within members of each of these genera. This work illustrates the importance of a comprehensive polyphasic approach in the analysis of lake bacterioplankton, and supports the ecological relevance of results obtained in earlier entirely culture-based studies.

The aim of this research was to determine the effectiveness of a strategy for constructing microbial consortia for treating chemically mixed industrial effluent, based on a more thorough understanding of communities within waste metal-working fluids (MWFs). Complementary phenotypic and genotypic methods revealed that the microbial communities in spent MWFs had low diversity and were very similar in species composition in samples originating from different locations and uses. Of 65 bacterial isolates studied, only 9 species were identified using fatty acid methyl ester (FAME) analysis. The results of genotypic analysis by denaturing gradient gel electrophoresis (DGGE) were congruent with observations made using FAME analysis. The metabolic potential of the isolates was assessed in terms of assimilation ability and tolerance of co-contaminants. The three isolates, selected (Clavibacter michiganensis, Methylobacterium mesophilicum, and Rhodococcus erythropolis) to form a consortium, were representative of three of the four most abundant populations and when combined could utilise or tolerate all of the individual MWF components, including the biocide and the recalcitrant compound benzotriazole.

The ecto-5'-nucleotidase activities of highly purified T and B lymphocytes from human peripheral blood have been investigated using biochemical and histochemical techniques. The enzyme activity of the purified B cells was about 3.5 times that of the T cells. Using a histochemical assay, 21--55% of the B cells stained positively for 5'-nucleotidase, but only 2--22% of the T cells were positive. These results are discussed in relation to the low 5'-nucleotidase activities found on peripheral blood lymphocytes from patients with chronic lymphatic leukaemia and some patients with primary hypogammaglobulinaemia.