Campylobacter infection in adult patients with primary antibody deficiency

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Campylobacter infection in adult patients with primary antibody deficiency

International audiencePrimary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P<.016 was considered significant. Since 2004, 790 patients with PAD were included in the DEFI study, and 51 presented with Campylobacter infection (6.5%). Medical chart was available for review in 45 patients. Characteristics of these patients at the time of enrollment in the DEFI study are detailed in Table E2 (available in this article’s Online Repository at www.jaci-inpractice.org). A total of 97 episodes were recorded (Table I). The overall distribution of Campylobacter species was unremarkable. Antimicrobial susceptibility testing revealed a higher resistance rate than in the general population for each antibiotic tested (see Figure E2, available in this article’s Online Repository at www.jaci-inpractice.org). A comorbidity was present in 55% of Campylobacter episodes, and a coinfection by other enteropathogens in 10%. Most patients were receiving concomitant therapy at the time of episode. One patient with end-stage cirrhosis died with Campylobacter bacteremia. Overall, bacteremia was observed in 24 episodes (13 patients) and was associated with extraintestinal complication in 10 episodes. Nineteen patients (42%) presented with recurrent (2-11) episodes. Factors associated with recurrent episodes were the presence of comorbidity (OR, 3.7 [95% CI, 1.1-13.1]) and undetectable serum IgA (OR, 8.6 [95% CI, 1.1-21.2]). None of these factors remain significant in multivariate analysis. A mo- lecular study of a subset of 18 strains from 5 patients with recurrent infections demonstrated that all strains were different, even when the antimicrobial susceptibility testing was similar and when the episodes occurred closely over time (Figure E3, available in this article’s Online Repository at www.jaci-inpractice.org). Compared with 288 patients with CVID without Campylobacter infection, patients with CVID with Campylo-bacter infection presented a higher prevalence of consanguinity and a more severe CVID phenotype, with more frequent disease- related complications, lower serum immunoglobulin levels, lower B and natural killer (NK) cells, and a trend for lower naive CD4þT cell at the time of enrollment in the DEFI study (Table II). This study is the first description of a large series of patients with PAD and Campylobacter infection. The 6.5% prevalence was probably underestimated because of the retrospective nature of the clinical data collection. In this population, symptoms were mostly restricted to an isolated, frequently severe, chronic watery diarrhea, with associated malnutrition, leading to repeated hospitalizations and impaired quality of life. Other digestive symptoms and fever were less frequent than those observed in the general population. In contrast, bacteremia and extra- digestive localizations were more frequent (25% vs 0.15% to 2%, and 22% vs 7%, respectively). Despite frequent hospitalizations, the overall prognosis was good. Recurrence rate was high (42%) compared with 1.2% in the general population, and was associated with extraintestinal comorbidity and unde- tectable IgA level in univariate analysis. Although limited by the number of available strains, molecular profiles of strains from patients with recurrent infections were all different. Thus, we could hypothesize that reinfection is more likely than persistent colonization, although colonization with multiple strains cannot be excluded. Conditions associated with the occurrence of Campylobacter infection were described in an analysis restricted to a large ho- mogeneous group of 325 patients with CVID. The present data suggest that hypochlorhydria, either proton pump inhibitor (PPI)-induced or associated with autoimmune gastritis, might play an important role in the pathogenesis of this infection. Almost all CVID-associated complications, particularly liver and gastrointestinal disease, were more frequent in patients with Campylobacter infection. A more severe immune deficiency at CVID diagnosis, with a lower serum immunoglobulin level, was also observed. Even in patients with immunoglobulin replacement therapy, IgM and IgA levels remain very low. IgA and IgM, almost absent in immunoglobulin batches, are more important than IgG in Campylobacter immunity. B-cell and specifically switch memory B-cell deficiency was also more severe in patients with CVID with Campylobacter infection than in patients without Campylobacter infection. This is in line with the high prevalence of Campylobacter infection observed in Good syndrome and X-linked agammaglobulinemia, 2 conditions associated with no circulating B cells (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). B cells are also known to be important for the dialogue between the immune system and gut microbiota, whose composition is important for Campylobacter immunity. T cells may also play an important role, with a trend for decreased naive T cells. Indeed, 15 patients (40%) presented with a severe associated T-cell defect and could be considered as late-onset combined im-munodeficiency (data not shown). In patients with PAD, Campylobacter infection is quite frequent and seems to be related to various factors adding up together: severity of the immune deficiency, PAD complication, and associated antibiotics, immunosuppressive therapies, and PPI. It is characterized by a high frequency of recurrence and bacteremia. Recurrence is associated with the presence of comorbidity and IgA defect, and turned out to be due to rein- fection more than to persistent colonization, suggesting a specific susceptibility despite immunoglobulin substitution

A Potential New Human Pathogen Belonging to Helicobacter Genus, Identified in a Bloodstream Infection

We isolated from aerobic and anaerobic blood culture bottles from a febrile patient, a Helicobacter-like Gram negative, rod-shaped bacterium that MALDI-TOF MS failed to identify. Blood agar cultures incubated in a microaerobic atmosphere revealed a motile Gram negative rod, which was oxidase, catalase, nitrate reductase, esterase, and alkaline phosphatase positive. It grew at 42°C with no detectable urease activity. Antimicrobial susceptibility testing showed that the organism was susceptible to beta-lactams, gentamicin, erythromycin, and tetracycline but resistant to ciprofloxacin. Electronic microscopy analysis revealed a 3 × 0.5 μm curved rod bacterium harboring two sheathed amphitrichous flagella. Whole genome sequencing revealed a genome 1,708,265 base-pairs long with a GC content of 37.80% and a total of 1,697 coding sequences. The genomic analyses using the nucleotide sequences of the 16S rRNA gene, hsp60 and gyrB genes, as well as the GyrA protein sequence, and the results of Average Nucleotide Identity and in silico DNA-DNA hybridization suggest evidence for a novel Helicobacter species close to Helicobacter equorum and belonging to the group of enterohepatic Helicobacter species. As soon as the particular peptide mass fingerprint of this pathogen is added to the spectral databases, MALDI-TOF MS technology will improve its identification from clinical specimens, especially in case of “sterile infection”. We propose to associate the present strain with the Latin name of the place of isolation; Caesarodunum (Tours, France) and suggest “Helicobacter caesarodunensis” for further description of this new bacterium