A systematic review of source attribution of human campylobacteriosis using multilocus sequence typing

This work was supported by the United Kingdom Food Standards Agency [grant number FS101013]; the Wellcome Trust [grant numbers 087622 to M.C.J.M., 072782MA to N.D.M.]; and National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at the University of Oxford in partnership with Public Health England (PHE). The views expressed are those of the author(s) and not necessarily those of the FSA, NHS, the NIHR, the Department of Health or Public Health England.Peer reviewedPublisher PD

<i>Campylobacter jejuni</i> HS:23 and Guillain-Barré Syndrome, Bangladesh

To the Editor: Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy triggered by a preceding infectious illness. Gastroenteritis caused by Campylobacter jejuni is the most frequently reported antecedent event. In Japan, South Africa, China, and Mexico, Campylobacter strains with certain Penner heat-stable (HS) serotypes, including HS:19 and HS:41, are overrepresented among isolates from GBS case-patients, compared with isolates from enteritis case-patients. Several studies indicate that C. jejuni HS:19 and HS:41 have a clonal population structure and suggest that these serotypes might have unique virulence properties that are intricately linked to development of GBS. However, data from the United Kingdom and the Netherlands suggest that such virulence properties may not be restricted to specific HS serotypes because many other serotypes can be cultured from patients with GBS (5). We report a non-HS:19 and non-HS:41 C. jejuni serotype and sequence type (ST)–3219 that are overrepresented among isolates from GBS patients in Bangladesh. [...

<i>Campylobacter jejuni</i> HS:23 and Guillain-Barré Syndrome, Bangladesh

To the Editor: Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy triggered by a preceding infectious illness. Gastroenteritis caused by Campylobacter jejuni is the most frequently reported antecedent event. In Japan, South Africa, China, and Mexico, Campylobacter strains with certain Penner heat-stable (HS) serotypes, including HS:19 and HS:41, are overrepresented among isolates from GBS case-patients, compared with isolates from enteritis case-patients. Several studies indicate that C. jejuni HS:19 and HS:41 have a clonal population structure and suggest that these serotypes might have unique virulence properties that are intricately linked to development of GBS. However, data from the United Kingdom and the Netherlands suggest that such virulence properties may not be restricted to specific HS serotypes because many other serotypes can be cultured from patients with GBS (5). We report a non-HS:19 and non-HS:41 C. jejuni serotype and sequence type (ST)–3219 that are overrepresented among isolates from GBS patients in Bangladesh. [...

A High Throughput Substrate Binding Assay Reveals Hexachlorophene as an Inhibitor of the ER-resident HSP70 Chaperone GRP78

Glucose-regulated protein 78 (GRP78) is the ER resident 70 kDa heat shock protein 70 (HSP70) and has been hypothesized to be a therapeutic target for various forms of cancer due to its role in mitigating proteotoxic stress in the ER, its elevated expression in some cancers, and the correlation between high levels for GRP78 and a poor prognosis. Herein we report the development and use of a high throughput fluorescence polarization-based peptide binding assay as an initial step toward the discovery and development of GRP78 inhibitors. This assay was used in a pilot screen to discover the anti-infective agent, hexachlorophene, as an inhibitor of GRP78. Through biochemical characterization we show that hexachlorophene is a competitive inhibitor of the GRP78-peptide interaction. Biological investigations showed that this molecule induces the unfolded protein response, induces autophagy, and leads to apoptosis in a colon carcinoma cell model, which is known to be sensitive to GRP78 inhibition

Wild bird-associated Campylobacter jejuni isolates are a consistent source of human disease, in Oxfordshire, United Kingdom

The contribution of wild birds as a source of human campylobacteriosis was investigated in Oxfordshire, United Kingdom (UK) over a 10 year period. The probable origin of human Campylobacter jejuni genotypes, as described by multilocus sequence typing, was estimated by comparison with reference populations of isolates from farm animals and five wild bird families, using the STRUCTURE algorithm. Wild bird-attributed isolates accounted for between 476 (2.1%) and 543 (3.5%) cases annually. This proportion did not vary significantly by study year (P = 0.934) but varied seasonally, with wild bird-attributed genotypes comprising a greater proportion of isolates during warmer compared with cooler months (P = 0.003). The highest proportion of wild bird-attributed illness occurred in August (P < 0.001), with a significantly lower proportion in November (P = 0.018). Among genotypes attributed to specific groups of wild birds, seasonality was most apparent for Turdidae-attributed isolates, which were absent during cooler, winter months. This study is consistent with some wild bird species representing a persistent source of campylobacteriosis, and contributing a distinctive seasonal pattern to disease burden. If Oxfordshire is representative of the UK as a whole in this respect, these data suggest that the national burden of wild bird-attributed isolates could be in the order of 10,000 annually

Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci

Juvenile dermatomyositis (JDM) is a chronic inflammatory myopathy and vasculopathy driven by genetic and environmental influences. Here, we investigated the genetic underpinnings of an analogous, spontaneous disease of dogs also termed dermatomyositis (DMS). As in JDM, we observed a significant association with a haplotype of the major histocompatibility complex (MHC) (DLA-DRB1*002:01/-DQA1*009:01/-DQB1*001:01), particularly in homozygosity (P-val = 0.0001). However, the high incidence of the haplotype among healthy dogs indicated that additional genetic risk factors are likely involved in disease progression. We conducted genome-wide association studies in two modern breeds having common ancestry and detected strong associations with novel loci on canine chromosomes 10 (P-val = 2.3X10-12) and 31 (P-val = 3.95X10-8). Through whole genome resequencing, we identified primary candidate polymorphisms in conserved regions of PAN2 (encoding p.Arg492Cys) and MAP3K7CL(c.383_392ACTCCACAAA\u3eGACT) on chromosomes 10 and 31, respectively. Analyses of these polymorphisms and the MHC haplotypes revealed that nine of 27 genotypic combinations confer high or moderate probability of disease and explain 93% of cases studied. The pattern of disease risk across PAN2 and MAP3K7CL genotypes provided clear evidence for a significant epistatic foundation for this disease, a risk further impacted by MHC haplotypes. We also observed a genotype-phenotype correlation wherein an earlier age of onset is correlated with an increased number of risk alleles at PAN2 and MAP3K7CL. High frequencies of multiple genetic risk factors are unique to affected breeds and likely arose coincident with artificial selection for desirable phenotypes. Described herein is the first three-locus association with a complex canine disease and two novel loci that provide targets for exploration in JDM and related immunological dysfunction

Extended Sequence Typing of Campylobacter spp., United Kingdom

Supplementing Campylobacter spp. multilocus sequence typing with nucleotide sequence typing of 3 antigen genes increased the discriminatory index achieved from 0.975 to 0.992 among 620 clinical isolates from Oxfordshire, United Kingdom. This enhanced typing scheme enabled identification of clusters and retained data required for long-range epidemiologic comparisons of isolates

Campylobacter jejuni HS:23 and Guillain-Barré Syndrome, Bangladesh

To the Editor: Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy triggered by a preceding infectious illness. Gastroenteritis caused by Campylobacter jejuni is the most frequently reported antecedent event. In Japan, South Africa, China, and Mexico, Campylobacter strains with certain Penner heat-stable (HS) serotypes, including HS:19 and HS:41, are overrepresented among isolates from GBS case-patients, compared with isolates from enteritis case-patients. Several studies indicate that C. jejuni HS:19 and HS:41 have a clonal population structure and suggest that these serotypes might have unique virulence properties that are intricately linked to development of GBS. However, data from the United Kingdom and the Netherlands suggest that such virulence properties may not be restricted to specific HS serotypes because many other serotypes can be cultured from patients with GBS (5). We report a non-HS:19 and non-HS:41 C. jejuni serotype and sequence type (ST)–3219 that are overrepresented among isolates from GBS patients in Bangladesh. [...

Assessing the impact of aggregating disease stage data in model predictions of human African trypanosomiasis transmission and control activities in Bandundu province (DRC)

Since the turn of the century, the global community has made great progress towards the elimination of gambiense human African trypanosomiasis (HAT). Elimination programs, primarily relying on screening and treatment campaigns, have also created a rich database of HAT epidemiology. Mathematical models calibrated with these data can help to fill remaining gaps in our understanding of HAT transmission dynamics, including key operational research questions such as whether integrating vector control with current intervention strategies is needed to achieve HAT elimination. Here we explore, via an ensemble of models and simulation studies, how including or not disease stage data, or using more updated data sets affect model predictions of future control strategies