Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Campylobacter fetus bacteremia and meningitis in an acute lymphoblastic leukemia patient undergoing maintenance therapy: a case report.

BACKGROUND: Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures. CASE PRESENTATION: A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae. CONCLUSION: We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.

Guillain-Barré Syndrome Outbreak in Peru 2019 Associated With Campylobacter jejuni Infection.

OBJECTIVE: To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak. METHODS: We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to Campylobacter jejuni and gangliosides. Genomic analysis was performed on 4 C jejuni isolates. RESULTS: The 49 included patients had a median age of 44 years (interquartile range [IQR] 30-54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2-9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent C jejuni infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2-9.2, p < 0.01) had IgM and/or IgA antibodies against C jejuni. Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the C jejuni strains were closely related and had the Asn51 polymorphism at cstII gene. CONCLUSIONS: Our study indicates that the 2019 Peruvian GBS outbreak was associated with C jejuni infection and that the C jejuni strains linked to GBS circulate widely in different parts of the world.

Expression of the Campylobacter jejuni FliD protein and its reaction to chicken sera.

Campylobacter is a leading causative pathogen of acute bacterial gastroenteritis among humans. Contaminated chicken products are regarded as major sources of human infection. The flagellar capping protein (FliD), which plays important roles in colonization and adhesion to the mucosal surface of chicken ceca, is conserved among Campylobacter jejuni strains. In this study, the recombinant C. jejuni FliD protein was expressed, purified and used as a coated protein to examine the prevalence of C. jejuni antibodies in chickens. The anti-FliD antibody was prevalent among chicken serum samples taken from different farms in the diverse regions of Jiangsu province by using enzyme-linked immunosorbent assay. The Campylobacter antibody was present in culture-negative chickens. No strong dose-response relationships were observed between serum FliD antibody levels and Campylobacter cultural status. These results provide a basis for further evaluating FliD as a vaccine candidate for broiler chickens or for examining host-C. jejuni interactions, with implications for improving food safety.

Antecedent infections in Fisher syndrome: sources of variation in clinical characteristics.

The clinical features of Guillain-Barré syndrome (GBS) are highly variable, according to the type of antecedent infection. Although a major GBS phenotype, Fisher syndrome (FS), has been shown to be preceded by infections similar to those preceding GBS, whether or not the clinical features in FS also vary according to antecedent infection remains unclarified. Frequent antecedent infections among this study of 70 FS patients included Haemophilus influenzae [n = 15 (21%)], Campylobacter jejuni [n = 10 (14%)], and cytomegalovirus (CMV) [n = 6 (8.6%)]. Compared with other FS patients, H. influenzae-seropositive FS patients more frequently had a history of prior upper respiratory tract infection; double vision as the initial symptom; and, except for oculomotor disturbance, more rarely showed cranial nerve involvement. C. jejuni-related FS occurred predominantly in younger male patients and characteristically presented with blurred vision. According to GBS disability scale, CMV-related FS tended to be more severe, although every patient received immunotherapy. Serum anti-GQ1b IgG antibodies were detected in most cases, regardless of antecedent infection type. At the nadir of illness, the most frequent diagnosis in H. influenzae-related cases was "pure FS" without limb weakness or central nervous system involvement (71%), in C. jejuni-related cases "incomplete FS" such as acute ophthalmoparesis with or without ataxia (60%), and in CMV-related cases (50%) advanced conditions such as GBS overlap and Bickerstaff brainstem encephalitis. These findings indicate that the type of preceding infection determined the neurological features of FS. CMV-related FS appeared to be similar to H. influenzae- and C. jejuni-related FS regarding anti-GQ1b antibody-mediated pathogenesis, as opposed to CMV-related GBS.

Campylobacter fetus spondylodiscitis in a patient with HIV infection and restored CD4 count.

Campylobacter fetus (C. fetus) is a rare condition and mostly seen in elderly or immunocompromised patients. We present the first case of C. fetus spondylodiscitis in a virologically suppressed HIV seropositive patient with low back pain. MRI was performed and showed spondylodiscitis of the L4-L5 region. Empirical antibiotic therapy with flucloxacillin was started after blood cultures were drawn and an image-guided disc biopsy was performed. Blood cultures remained negative. The anaerobic culture of the puncture biopsy of the disc revealed presence of C. fetus after which the antibiotic treatment was switched to ceftriaxone. Guided by the susceptibility results, the therapy was switched to ciprofloxacin orally for 6 weeks after which the patient made full clinical, biochemical and radiographic recovery. Since no other immune-deficient conditions were noted, it is important to highlight that patients with HIV infection with restored CD4 counts and complete virological suppression can still be susceptible for infections caused by rare pathogens. Low back pain should raise suspicion for these conditions and should be examined properly.

Serological Markers of Recent Campylobacter jejuni Infection in Patients with Guillain-Barré Syndrome in the State of Piauí, Brazil, 2014-2016.

In countries where poliomyelitis has been eradicated, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. The range of infections that precede GBS in Brazil is unknown. Campylobacter jejuni infection is the most frequent trigger of GBS worldwide. Given the lack of systematic surveillance of diarrheal diseases, particularly in adults, the incidence of enteritis caused by C. jejuni in developing countries is unknown. From 2014 to 2016, pretreatment serum samples from 63 GBS patients were tested by immunoglobulin M (IgM) enzyme-linked immunosorbent assay for C. jejuni. Campylobacter jejuni IgM antibodies were detected in 17% (11/63) of the samples. There was no association between serological positivity (IgM) for C. jejuni and the occurrence of diarrhea among the investigated cases (P = 0.36). Hygiene measures, basic sanitation, and precautions during handling and preparation of food of animal origin may help prevent acute flaccid paralysis.

Campylobacter jejuni-associated perimyocarditis: two case reports and review of the literature.

BACKGROUND: Campylobacter spp. are among the most common bacterial causes of gastroenteritis world-wide and mostly follow a benign course. We report two cases of Campylobacter jejuni-associated perimyocarditis, the first two simultaneous cases published to date and the third and fourth cases over all in Sweden, and a review of the literature. CASE PRESENTATION: A previously healthy 24-yo male (A) presented at the Emergency Department(ED) with recent onset of chest pain and a 3-day history of abdominal pain, fever and diarrhoea. The symptoms began within a few hours of returning from a tourist visit to a central European capital. Vital signs were stable, the Electrocardiogram(ECG) showed generalized ST-elevation, laboratory testing showed increased levels of C-reactive protein(CRP) and high-sensitive Troponin T(hsTnT). Transthoracic echocardiogram (TTE) was normal, stool cultures were positive for C Jejuni and blood cultures were negative. Two days after patient A was admitted to the ED his travel companion (B), also a previously healthy male (23-yo), presented at the same ED with almost identical symptoms: chest pain precipitated by a few days of abdominal pain, fever and diarrhoea. Patient B declared that he and patient A had ingested chicken prior to returning from their tourist trip. Laboratory tests showed elevated CRP and hsTnT but the ECG and TTE were normal. In both cases, the diagnosis of C jejuni-associated perimyocarditis was set based on the typical presentation and positive stool cultures with identical strains. Both patients were given antibiotics, rapidly improved and were fully recovered at 6-week follow up. CONCLUSION: Perimyocarditis is a rare complication of C jejuni infections but should not be overlooked considering the risk of heart failure. With treatment, the prognosis of full recovery is good but several questions remain to be answered regarding the pathophysiology and the male preponderance of the condition.

[Bloodstream infection due to Campylobacter fetus subspecies fetus and skin involvement: A case series of three patients]. / Bactériémie à Campylobacter fetus subspecies fetus et manifestations cutanées : à propos de trois cas.

INTRODUCTION: Among the species of Campylobacter, C. fetus subspecies fetus is characterized by extra-intestinal manifestations, including bloodstream and cardiovascular infections, occurring preferentially in the context of immunosuppression. The cutaneous lesions are rarely described but may be underestimated. CASE REPORTS: We report on 3 cases of cellulitis with bloodstream infection due to Campylobacter fetus subspecies fetus, without cardiovascular infection in a 72- and 85-year-old women, respectively, and a 79-year-old man. Outcome was successful in all 3 cases after prolonged amoxicillin-clavulanic acid treatment, without relapse. CONCLUSION: C. fetus subspecies fetus is rarely associated with skin and soft tissue infections. Cardiovascular complications may be searched in such context.

Seroprevalence in Chickens against Campylobacter jejuni Flagellar Capping Protein (FliD) in Selected Areas of the United States.

Campylobacter jejuni is a causative pathogen of human acute bacterial gastroenteritis. Infected poultry products are regarded as a major source for human C. jejuni infection. The flagellar capping protein (FliD) is highly conserved among C. jejuni strains/isolates and is antigenic as analysed by immunoblot. In this study, we used the FliD protein as a probe to survey the prevalence of C. jejuni antibodies in chickens from two areas in the United States. A total of 394 samples were tested. Sera from layer breeders of 44-52 weeks of age tested 100% positive, while 4- to 6-week broilers from 22 premises showed 7-100% positivity. These results demonstrate that anti-FliD antibodies were prevalent in the poultry population in the areas of serum samples collected.

Was the increase in culture-confirmed Campylobacter infections in Denmark during the 1990s a surveillance artefact?

In 1991, 1999 and 2006, randomly selected individuals from the Danish Central Personal Register provided a serum sample. From individuals aged 30 years and above, 500 samples from each year were analysed for Campylobacter IgG, IgA and IgM antibodies using a direct ELISA method. We applied a seroincidence calculator available from the European Centre for Disease Prevention and Control to perform a mathematical back-calculation to estimate the annual Campylobacter seroincidence in the Danish population. The estimated Campylobacter seroincidence did not differ significantly between the 1991, 1999 and 2006 studies although the reported number of culture-confirmed cases of Campylobacter infection increased 2.5 fold from 1993 to 1999 among individuals aged 30 years and above. This suggests that Campylobacter was widely present in the Danish population before the increase in poultry-associated clinical Campylobacter infections observed from 1993 to 2001 among individuals of this age groups.

Association of Anti-GT1a Antibodies with an Outbreak of Guillain-Barré Syndrome and Analysis of Ganglioside Mimicry in an Associated Campylobacter jejuni Strain.

An outbreak of Guillain-Barré syndrome (GBS), subsequent to Campylobacter jejuni enteritis, occurred in China in 2007. Serum anti-ganglioside antibodies were measured in GBS patients and controls. Genome sequencing was used to determine the phylogenetic relationship among three C. jejuni strains from a patient with GBS (ICDCCJ07001), a patient with gastroenteritis (ICDCCJ07002) and a healthy carrier (ICDCCJ07004), which were all associated with the outbreak. The ganglioside-like structures of the lipo-oligosaccharides of these strains were determined by mass spectrometry. Seventeen (53%) of the GBS patients had anti-GT1a IgG antibodies. GT1a mimicry was found in the lipo-oligosaccharides of strain ICDCCJ07002 and ICDCCJ07004; but a combination of GM3/GD3 mimics was observed in ICDCCJ07001, although this patient had anti-GT1a IgG antibodies. A single-base deletion in a glycosyltransferase gene caused the absence of GT1a mimicry in ICDCCJ07001. The phylogenetic tree showed that ICDCCJ07002 and ICDCCJ07004 were genetically closer to each other than to ICDCCJ07001. C. jejuni, bearing a GT1a-like lipo-oligosaccharide, might have caused the GBS outbreak and the loss of GT1a mimicry may have helped ICDCCJ07001 to survive in the host.

[Frequency of antibodies to the recombinant protein P39 of C. jejuni in patients with gastrointestinal disorders and reactive arthritis in Poland]. / Czestosc wystepowania przeciwcial dla rekombinowanego bialka P39 paleczek C. jejuni u wybranych osób z zaburzeniami zoladkowo-jelitowymi oraz z reaktywnym zapaleniem stawów w Polsce.

INTRODUCTION: Campylobacterjejuni is has been found to be the leading cause of bacterial gastroenteritis worldwide. Clinical manifestation on enterocolitis caused by C. jejuni are diarrhea, fever, abdominal pain and in some patients, fecal blood. After C. jejuni infection, squeals may occur such as reactive arthritis. The aim of the study was to investigate the frequency of antibodies to the recombinant protein P39 sticks C. jejuni in patients with gastrointestinal disorders and reactive arthritis in Poland. MATERIAL AND METHODS: Serum samples collected from 46 patients with bacteriology confir- med infection caused by Campylobacter jejuni, 472 sera from patients with gastrointestinal disorders, 97 serum samples obtained from patients with reactive arthritis and 84 sera from healthy adults and children. Sera were screened for anti-P39 C. jejuni recombinant protein IgA, IgG andIgM antibodies by using the home-made ELISA. Protein P39 C. jejuni was expressing in E. coli BL21 (DE3) using the pET-30 Ek/LIC expression vector. Purification was accomplished by immobilized metal (Ni2+) affinity column chromatography (His Bind Resign, Novagen). RESULTS: SDS-PAGE and Coomassie brilliant blue staining confirmed a high purity of the recombinant P39 protein preparation with an expected molecular mass of 39 kDa. The results of ELISA with the P39 recombinant protein revealed that IgA antibodies in diagnostically significant level (x + 2SD) were found in 18.8%, IgM in 14.8% and IgG in 7.8% of sera obtained from patients with of gastrointestinal disorders. On the other hand, antibodies to recombinant P39 protein in sera obtained from patients with reactive arthritis were found in more than twice the percentage than in patients with gastrointestinal disorders (IgA in 34.0%, IgG in 26.8% and IgM in 19.6%). CONCLUSIONS: In conclusion, based on the data obtained, C. jejuni may be important factor in triggering the gastrointestinal disorder and reactive arthritis in humans in Poland.

Clonal distribution and virulence of Campylobacter jejuni isolates in blood.

Campylobacter jejuni bacteria are highly diverse enteropathogens. Seventy-three C. jejuni isolates from blood collected in Finland were analyzed by multilocus sequence typing and serum resistance. Approximately half of the isolates belonged to the otherwise uncommon sequence type 677 clonal complex. Isolates of this clonal complex were more resistant than other isolates to human serum.

Bloodstream infection caused by Campylobacter lari.

We describe a case of bloodstream infection (BSI) caused by Campylobacter lari in a 58-year-old man diagnosed with lumbar pyogenic spondylitis. Anaerobic blood cultures, taken on the day of admission and on hospital day 4, were positive after 30 h of incubation, although no bacteria were detected by Gram staining. After subculture on 5 % sheep blood agar for 2 days at 35 °C in a 5 % CO2 environment, capnophilic, curved, gram-negative bacteria were recovered. The bacteria were identified as C. lari using a combination of phenotypic identification methods and partial 16S rRNA gene sequencing. The BSI was eradicated following combination therapy with intravenous tazobactam/piperacillin, oral erythromycin, and sulfamethoxazole/trimethoprim. These results suggest that accurate identification, to the species level, is important to determine effective treatment of BSI caused by Campylobacter spp. and can help us to understand the epidemiology.

Isolation of Campylobacter from circulating blood of commercial broilers.

Campylobacter spp. are present in organs and tissues of broiler chickens but the dissemination route is unclear. The aim of the current study was to determine Campylobacter prevalence within circulating blood of commercial broilers. Broilers were acquired from 19 flocks originating from three commercial poultry processing companies. Using aseptic blood collection techniques, 5 ml of circulating blood was collected from each bird and the sample analyzed for Campylobacter. The Campylobacter colonization status of each bird was determined by aseptically sampling and analyzing the ceca. Campylobacter was recovered from 58% (11/19) of flocks sampled. From the 248 total birds sampled, 12% and 46% of the birds had Campylobacter in the blood and ceca, respectively. This study documents Campylobacter prevalence in the circulating blood of commercially raised broilers. Campylobacter presence in the circulatory system may indicate the path used by the organism for rapid dissemination to organs and tissues. From a processing viewpoint, Campylobacter presence in circulating blood of market-age broilers may increase the likelihood of cross-contamination between birds during slaughter.

Serological survey of Toxoplasma gondii and Campylobacter fetus fetus in sheep from New Zealand.

AIM: To determine the prevalence of antibody titres to Toxoplasma gondii and Campylobacter fetus fetus in sheep from New Zealand. METHODS: As part of a free screening service, unsolicited blood samples were supplied by veterinarians wishing to gauge the exposure of their clients' ewe flocks to T. gondii and C. fetus fetus. Blood samples were submitted from mixed-age ewes throughout New Zealand, from 2006 to 2009, that had not been vaccinated for T. gondii and C. fetus fetus. A total of 2,254 sera were serologically titrated for T. gondii and 3,429 for C. fetus fetus. A latex agglutination kit available commercially was used to quantify antibodies to T. gondii, and an agglutination test developed in-house was used for C. fetus fetus. For T. gondii, titres of ≥1:16 and ≥1:64 were used to define a positive response, and for C. fetus fetus a titre of ≥1:10 was defined as positive. A flock was defined as positive if ≥1 ewe had a positive titre. RESULTS: Of the sera tested for T. gondii, 1,917/2,254 (85%) were positive, using a titre of ≥1:16, and 1,384/2,254 (61%) with a titre of ≥1:64. All 198 ewe flocks tested were seropositive to T. gondii, at a titre of ≥1:16, and all but three were at a titre of ≥1:64. A bimodal distribution was evident in the prevalence of titres to T. gondii suggesting that a percentage of titres ≤1:64 may have been non-specific. Of the sera tested for C. fetus fetus, 1,644/3,429 (48%) were positive to at least one of the four test antigens at titre of ≥1:10. Only 34/298 (11%) flocks tested for C. fetus fetus were completely seronegative. The percentage of seropositive ewes to both T. gondii and C. fetus fetus was significantly higher in the North Island than the South Island. CONCLUSIONS: The study demonstrated that exposure to these two important infectious abortifacients was both considerable and widespread. Minimum titres were postulated to establish a 'cut-off' for a positive result and to allow comparison with past and future studies. The bimodal distribution evident for T. gondii suggested a titre of 1:64 may be an appropriate cut-off. The widespread on-farm exposure probably stimulates the immune response of vaccinated ewes. CLINICAL RELEVANCE: Further studies are required to confirm the clinical significance of flock-based antibody responses, and to validate their use in identifying recently aborted ewes, especially where there are no aborted fetuses for examination.

Seroepidemiological studies indicate frequent and repeated exposure to Campylobacter spp. during childhood.

The annual number of episodes of clinical gastroenteritis caused by Campylobacter spp. in The Netherlands is estimated to be 75 000, i.e. once per 200 person life-years. This number is based on extrapolation of culture results from population-based studies. The number of culture-confirmed cases of Campylobacter infection peaks in the first 3 years of life and again between the ages of 20 and 25 years. The seroepidemiology of Campylobacter describes the relationship between age and exposure to Campylobacter and reflects both symptomatic and asymptomatic infections. Using a validated ELISA system, antibodies to Campylobacter were measured in an age-stratified sample (n=456) of the PIENTER serum collection of the Dutch general population. The seroprevalence of Campylobacter IgG antibodies increased with age, reaching almost 100% at age 20 years. Antibody levels steadily increased with age until young adulthood, suggesting repeated exposure to Campylobacter. In conclusion, seroepidemiological data demonstrated repeated exposures to Campylobacter throughout life, most of which do not lead to clinical symptoms. From young adulthood, >95% of the population in The Netherlands had serological evidence for exposure to Campylobacter.

Development and evaluation of an indirect enzyme-linked immunosorbent assay for the detection of antibodies against Campylobacter fetus in cattle.

Campylobacteriosis is a zoonosis that occurs worldwide. Infection with Campylobacter fetus (C. fetus) causes infertility and abortion in sheep and cattle. The current study focuses on the SapA gene of C. fetus that encodes surface array proteins and plays an important role in the virulence of C. fetus. The SapA-N (1398bp) and SapA-C (1422bp) fragments were amplified from the C. fetusSapA gene using polymerase chain reaction (PCR), and the corresponding recombinant proteins rSapA-N and rSapA-C were expressed in Escherichia. coli BL21 cells. Results of Western blotting and enzyme-linked immunosorbent assay (ELISA) showed that the immunological activity of rSapA-N was higher than that of rSapA-C (P<0.05). Therefore, rSapA-N was selected to establish an indirect ELISA for detecting antibodies against C. fetus. The diagnostic criteria were as follows: S/P0.45: positive; S/P<0.4: negative; 0.45>S/P0.4: suspected. The specificity and sensitivity of our method were 94.3% and 88.6%, respectively. Moreover, no cross-reactions were observed between rSapA-N and serum samples that were positive for other bovine bacterial pathogens diseases such as Mycobacterium avium subspecies paratuberculosis. One hundred and two serum samples from cows that had experienced abortion were tested. Four and 2 C. fetus-positive serum samples were found among the 70 bovine brucellosis-positive samples and the 32 infectious bovine rhinotracheitis (IBR)-positive samples, respectively. The findings suggest that the rSapA-N-based ELISA method has immense potential in future applications.

Subclass IgG to motor gangliosides related to infection and clinical course in Guillain-Barré syndrome.

In 176 patients with Guillain-Barré syndrome the subclass and cross-reactivity of serum IgG antibodies to motor gangliosides was related to preceding infections and clinical phenotypes. Two subgroups of patients were identified. Presence of only IgG1 antibodies was related to diarrhea, positive Campylobacter serology, cross-reactive antibodies to C. jejuni lipo-oligosaccharides and poor outcome. In contrast, having both IgG1 and IgG3 antibodies was related to upper respiratory tract infections, cross-reactive antibodies to Haemophilus influenzae lipo-oligosaccharides and better outcome. These findings support a model in which C. jejuni and H. influenzae infections induce two distinct patterns of cross-reactive antibodies with different clinical outcome.