Smith, Kirk

Abstract Background No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture–based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. Methods We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. Results Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. Conclusions This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture–based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

AbstractBackgroundThe Rome IV irritable bowel syndrome (IBS) criteria include changes to the description and frequency of abdominal pain. Existing studies have demonstrated a lower prevalence and greater severity in IBS patients identified using Rome IV than Rome III criteria. Our aim was to investigate the prevalence of post‐infection IBS (PI‐IBS) using Rome IV criteria in a population‐based cohort of laboratory‐confirmed C. jejuni infection cases.MethodsThe Minnesota Department of Health (MDH) requires notification of Campylobacter cases and interviews patients to gather information on clinical symptoms. For this study, the Rome IV diagnostic questionnaire was utilized 6–9 months after infection to determine the development of PI‐IBS. The survey responses were analyzed for the prevalence of IBS and symptom severity.Key ResultsSurveys were completed by 391 participants (31% response rate). Twenty‐three patients had pre‐existing IBS, and 18 did not complete enough questions to categorize their case status. Of the 350 remaining participants, 58 (17%) met Rome IV criteria. An additional 47 patients would have met the Rome III IBS criteria for pain frequency, driving the cumulative prevalence to 30%. The mean IBS Symptom Severity Score (IBS‐SSS) in Rome IV patients was significantly higher than in Rome III (p < 0.05). With Rome IV, IBS‐diarrhea was the most common subtype.Conclusions & InferencesRome IV criteria resulted in a 19% lower prevalence of PI‐IBS than earlier reported Rome III‐based prevalence in a similar population. Rome IV defined PI‐IBS patients have greater symptom severity but similar distribution of IBS subtypes.

Abstract Background Gastrointestinal ( GI ) infections resulting from bacterial, viral, and parasitic pathogens predispose to postinfectious irritable bowel syndrome ( PI ‐ IBS ) and other functional GI disorders. Existing literature supports the role of enterochromaffin cell hyperplasia, serotonin synthesis and reuptake, impaired barrier function, altered immune activation, and potentially mast cell activation in the pathophysiology of PI ‐ IBS . Purpose The objective of this review was to summarize from the literature the characteristics of the pathogens commonly implicated in PI ‐ IBS , their acute enteritis phases, and the changes seen in the postinfectious phase that may contribute toward development of IBS . A limitation of our current understanding is that the postinfectious GI sequelae reported in prior studies followed epidemic diarrheal outbreaks often involving more than one pathogen, or the studies focused on highly selected, tertiary referral patients. Understanding the mechanisms, natural history, and optimized management of individuals suffering PI ‐ IBS following the more typical sporadic infection requires larger studies of PI ‐ IBS following GI infections encountered in community settings. These studies should include genetic, physiological, and molecular studies to provide more generalizable information that can ultimately be used to diagnose, manage, and potentially prevent the development of PI ‐ IBS .