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.

Isolation of Campylobacter hepaticus from free-range poultry with spotty liver disease in New Zealand.

Case history: In October 2019, a free-range egg laying flock suffering an outbreak of spotty liver disease was investigated. Eight 32-week-old hens were examined post-mortem. Clinical and pathological findings: Five of the eight hens had sparse, focal, gross hepatic lesions typical of spotty liver disease. Histopathology of the liver showed random, focal hepatic necrosis, lymphoplasmacytic cholangitis/pericholangitis and, in one hen, severe lymphoplasmacytic cholecystitis. Campylobacter-like organisms were grown from all eight bile samples which were confirmed by PCR as Campylobacter hepaticus. The genome of C. hepaticus isolates from the outbreak were sequenced and compared to those of isolates from Australia and the United Kingdom. Phylogenetic analysis based on single nucleotide polymorphisms showed that the C. hepaticus isolates from this outbreak were most closely related to isolates from Australia. Diagnosis: Campylobacter hepaticus focal hepatic necrosis. Clinical relevance: This is the first report of an outbreak of spotty liver disease confirmed to be caused by C. hepaticus in poultry in New Zealand. Therefore infection with C. hepaticus should be considered as a differential diagnosis for mortality in laying hens around peak lay in New Zealand.

Rapid Reduction of Campylobacter Species in the Gut Microbiome of Preschool Children after Oral Azithromycin: A Randomized Controlled Trial.

Campylobacter has emerged as a potential important cause of childhood morbidity in sub-Saharan Africa. Biannual mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. We conducted a randomized controlled trial in Burkina Faso in which children were randomized in a 1:1 fashion to a 5-day course of azithromycin or placebo to investigate the effect of oral antibiotics on the gut microbiome. We evaluated the changes in the gut microbiome of preschool children treated with azithromycin using metagenomic DNA sequencing. We found that three Campylobacter species were reduced with azithromycin treatment compared with placebo. These results were consistent with other studies that have shown decreases in Campylobacter species after azithromycin treatment, generating the hypothesis that a decrease in Campylobacter may contribute to observations of reduction in mortality following azithromycin distribution.

Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution.

The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.

The disease burden associated with Campylobacter spp. in Germany, 2014.

Bacteria of the genus Campylobacter are an important cause of human illness worldwide. Campylobacter infections are expressed as gastroenteritis and can lead to severe sequelae like reactive arthritis, Guillain-Barré syndrome, irritable bowel syndrome and inflammatory bowel disease. In Germany, Campylobacter-associated gastroenteritis cases are notifiable but there is no reporting obligation for the sequelaes and the disease burden is clearly underestimated. The aim of our study was to quantify reliably the current disease burden of all Campylobacter spp.-associated diseases for Germany with the method of disability-adjusted life years (DALYs). DALYs combine mortality and morbidity in a single summary measure, whereby one DALY represents the loss of one year in full health. For acute gastroenteritis, we estimated 967 DALYs of which only 484 DALYs were detected within the reporting system. Overall, we estimated that 8811 DALYs were caused by the campylobacter-related diseases known so far. 98% of the DALYs were associated with morbidity and 2% with mortality. Mortality was caused by the health outcomes Gastroenteritis and Guillain-Barré syndrome exclusively.

Clinical impact of the type VI secretion system on virulence of Campylobacter species during infection.

BACKGROUND: The clinical course of Campylobacter infection varies in symptoms and severity depending on host factors, virulence of the pathogen and initiated therapy. The type VI secretion system (T6SS) has been identified as a novel virulence factor, which mediates contact-dependent injection of enzymes and toxins into competing bacteria or host cells and facilitates the colonisation of a host organism. We aimed to compare the clinical course of Campylobacter infection caused by strains with and without the T6SS and identify possible associations between this putative virulence factor and the clinical manifestations of disease. METHODS: From April 2015 to January 2017, patients with detection of Campylobacter spp. were identified at the University Hospital of Basel and the University Children's Hospital of Basel and included in this case-control study. Presence of the T6SS gene cluster was assayed by PCR targeting the hcp gene, confirmed with whole genome sequencing. Pertinent clinical data was collected by medical record review. Differences in disease- and host-characteristics between T6SS-positive (case) and -negative (control) were compared in a uni- and multi-variable analysis. Hospital admission, antibiotic therapy, admission to intensive care unit, development of bacteraemia and in-hospital mortality were considered as clinical endpoints. RESULTS: We identified 138 cases of Campylobacter jejuni infections and 18 cases of Campylobacter coli infections from a paediatric and adult population. Analyses were focused on adult patients with C. jejuni (n = 119) of which 16.8% were T6SS-positive. Comparisons between T6SS-positive and -negative C. jejuni isolates did not reveal significant differences regarding clinical manifestations or course of disease. All clinical endpoints showed a similar distribution in both groups. A higher score in the Charlson Comorbidity Index was associated with T6SS-positive C. jejuni isolates (p < 0.001) and patients were more likely to have a solid organ transplant and to be under immunosuppressive therapy. CONCLUSIONS: Our study does not provide evidence that T6SS is associated with a more severe clinical course. Interestingly, T6SS-positive isolates are more commonly found in immunocompromised patients: an observation which merits further investigation.

Clinical and microbiological characteristics of patients with bacteremia caused by Campylobacter species with an emphasis on the subspecies of C. fetus.

OBJECTIVES: This study was intended to investigate the clinical and microbiological characteristics of patients with bacteremia caused by Campylobacter species. METHODS: From April 1998 to May 2014, 56 adults with bacteremia caused by Campylobacter species were evaluated. These Campylobacter species isolates were confirmed to the species level using 16S rRNA gene sequencing (all isolates) and multiplex PCR analysis (for C. fetus only). The performance of identification for Campylobacter species by the Bruker Biotyper MALDI-TOF MS was evaluated. The genetic relatedness of C. fetus isolates was analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). RESULTS: The leading underlying medical conditions of these patients were malignancy (46.4%), hypertension (35.7%), and liver cirrhosis (23.2%). The overall 30-day mortality rate was 5.4%. Using 16S rRNA sequencing analysis, 26 isolates of C. coli, 11 of C. jejuni, and 19 of C. fetus, including 15 C. fetus subsp. fetus and five C. fetus subsp. venerealis, were identified. Among the five C. fetus subsp. venerealis isolates recognized by 16S rRNA gene sequencing, only two isolates were C. fetus subsp. venerealis by multiplex PCR method. The Bruker Biotyper MALDI-TOF MS failed to correctly identify C. fetus subsp. venerealis isolates. MLST analysis of C. fetus isolates revealed three STs: ST20 (n = 12), ST11 (n = 5), and ST57 (n = 2), which were compatible with three major PFGE clusters. CONCLUSION: Database expansion of MALDI-TOF MS for the correct identification of C. fetus to subspecies levels is needed. A novel clone of ST57-PFGE Cluster C of C. fetus subsp. venerealis was noted.

Fatal thoracic empyema involving Campylobacter rectus: A case report.

We report the case of a 69-year-old man admitted for septic shock secondary to necrotic pneumoniae complicated by thoracic empyema of fatal issue. Microbiological examination of pleural liquid revealed a mixed anaerobic flora involving Campylobacter rectus and Actinomyces meyeri. Campylobacter rectus is an infrequent anaerobic pathogen of oral origin To our knowledge, this is the first case report of fatal C. rectus - associated thoracic empyema, and only the second reported case in which identification was successfully performed by MALDI-TOF MS.

Using Galleria mellonella as an Infection Model for Campylobacter jejuni Pathogenesis.

Nonmammalian model systems of infection have been employed recently to study bacterial virulence. For instance, Galleria mellonella (the greater wax moth) has been shown to be susceptible to infection by many bacterial pathogens including the enteric pathogen Campylobacter jejuni. In contrast to the traditional animal models for C. jejuni such as the chick colonization model and ferret diarrheal model, the Galleria mellonella infection model has the advantages of lower cost, ease of use and no animal breeding is required. However, injecting the larvae with bacteria requires care to avoid killing of larvae, which could lead to misleading results. Here, we describe the infection of G. mellonella larvae by C. jejuni and how to record/interpret results.

Aspectos epidemiológicos y carga asistencial de gastroenteritis agudas por Campylobacter y Salmonella / Campylobacter and Salmonella acute gastroenteritis: Epidemiology and health care utilization

Fundamento y objetivo: En Cataluña, los sistemas de notificación y vigilancia no permiten conocer la incidencia real ni la carga asistencial de las gastroenteritis agudas (GEA) bacterianas de origen alimentario por Campylobacter ySalmonella, objeto de este estudio. Pacientes y métodos: Estudio descriptivo de los casos de GEA por Campylobacter y Salmonella en los años 2002 y 2012 en una región de Cataluña, España, identificados a partir de cultivos microbiológicos. Resultados: La incidencia estimada de GEA por Salmonella se redujo un 50% en 2012, y la de Campylobacter, un 20%. Los niños entre 1-4 años fueron los más afectados en ambos períodos. Se observaron diferencias significativas según el microorganismo en la presentación clínica de algunos síntomas y en la duración de la enfermedad. Acudieron al Servicio de Urgencias el 63,7% de los casos, y un 15% requirieron hospitalización, siendo más frecuente entre los casos de salmonelosis. Conclusión: La incidencia de GEA por Campylobacter y Salmonella se ha reducido, pero continúa siendo importante, como lo es la carga asistencial para ambas infecciones. El control de estas dolencias requiere una mayor adecuación de los actuales sistemas de vigilancia epidemiológica (AU)

Background and objective: In Catalonia the current surveillance systems do not allow to know the true incidence or the health care utilization of acute gastroenteritis (AGE) caused by Campylobacter and Salmonella infections. The aim of this study is to analyze these characteristics. Patients and methods: Descriptive study of Campylobacter and Salmonella infections reported in 2002 and 2012 in Catalonia, Spain. We included cases isolated and reported by the laboratory to a regional Surveillance Unit. Results: The estimated incidence of Salmonella and Campylobacter AGE decreased by almost 50% and 20% respectively in 2012. Children between one and 4 years old were the most affected in both years. Significant differences in the clinical characteristics and disease duration were observed betweenCampylobacter and Salmonella. Visits to the Emergency Department and hospitalization rates were 63.7% and 15%, being more frequent among salmonellosis cases. Conclusion The estimated incidence of Campylobacter and Salmonella infections has decreased, however rates are still important, as well as it is the health care utilization in both diseases. Current surveillance systems need appropriateness improvements to reach a better control of these infections (AU)

Disease burden of selected gastrointestinal pathogens in Australia, 2010.

OBJECTIVE: To estimate and compare disease burden attributable to six gastrointestinal pathogens (norovirus, rotavirus, Campylobacter, non-typhoidal Salmonella, Giardia, and Cryptosporidium) in Australia, 2010. METHODS: We estimated the number of acute gastroenteritis (AGE) cases and deaths, disability-adjusted life years (DALYs), and DALY/case for each pathogen. We included AGE cases that did not require medical care. Sequelae were included for Campylobacter (Guillain-Barré syndrome, reactive arthritis (ReA), irritable bowel syndrome (IBS)) and Salmonella (ReA, IBS). RESULTS: We estimated 16626069 AGE cases in Australia in 2010 (population 22 million). Of the pathogens studied, most AGE cases were attributed to norovirus (2180145), Campylobacter (774003), and Giardia (614740). Salmonella caused the fewest AGE cases (71255) but the most AGE deaths (90). The DALY burden was greatest for Campylobacter (18222 DALYs) and Salmonella (3856 DALYs), followed by the viral and protozoal pathogens. The average DALY/case was greatest for Salmonella (54.1 DALY/1000 cases), followed by Campylobacter (23.5 DALY/1000 cases). CONCLUSIONS: The pathogen causing the greatest disease burden varied according to the metric used, however DALYs are considered most useful given the incorporation of morbidity, mortality, and sequelae. These results can be used to prioritize public health interventions toward Salmonella and Campylobacter infections and to measure the impact of these interventions.

Mortality attributable to 9 common infections: significant effect of influenza A, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons.

BACKGROUND: Because there may be substantial hidden mortality caused by common seasonal pathogens, we estimated the number of deaths in elderly persons attributable to viruses and bacteria for which robust weekly laboratory surveillance data were available. METHODS: On weekly time series (1999-2007) we used regression models to associate total death counts in individuals aged 65-74, 75-84, and ≥85 years (a population of 2.5 million) with pathogen circulation-influenza A (season-specific), influenza B, respiratory syncytial virus (RSV), parainfluenza, enterovirus, rotavirus, norovirus, Campylobacter, and Salmonella-adjusted for extreme outdoor temperatures. RESULTS: Influenza A and RSV were significantly (P < .05) associated with mortality in all studied age groups; influenza B and parainfluenza were additionally associated in those aged ≥75 years, and norovirus was additionally associated in those aged ≥85 years. The proportions of deaths attributable to seasonal viruses were 6.8% (≥85 years), 4.4% (75-84 years), and 1.4% (65-74 years), but with great variations between years. Influenza occasionally showed lower impact than some of the other viruses. CONCLUSIONS: The number of different pathogens associated with mortality in the older population increases with increasing age. Besides influenza A and RSV, influenza B, parainfluenza and norovirus may also contribute substantially to elderly mortality.

The prevalence of Campylobacter spp. in broiler flocks and on broiler carcases, and the risks associated with highly contaminated carcases.

A baseline survey on the prevalence of Campylobacter spp. in broiler flocks and Campylobacter spp. on broiler carcases in the UK was performed in 2008 in accordance with Commission Decision 2007/516/EC. Pooled caecal contents from each randomly selected slaughter batch, and neck and breast skin from a single carcase were examined for Campylobacter spp. The prevalence of Campylobacter in the caeca of broiler batches was 75·8% (303/400) compared to 87·3% (349/400) on broiler carcases. Overall, 27·3% of the carcases were found to be highly contaminated with Campylobacter (≥1000 c.f.u./g). Slaughter in the summer months (June, July, August) [odds ratio (OR) 3·50], previous partial depopulation of the flock (OR 3·37), and an increased mortality at 14 days (≥1·25% to <1·75%) (OR 2·54) were identified as significant risk factors for the most heavily Campylobacter-contaminated carcases. Four poultry companies and farm location were also found to be significantly associated with highly contaminated carcases.

A nationwide study of Campylobacter jejuni and Campylobacter coli bacteremia in Finland over a 10-year period, 1998-2007, with special reference to clinical characteristics and antimicrobial susceptibility.

BACKGROUND: Campylobacter bacteremia is an uncommon condition, usually diagnosed in elderly and immunocompromised patients. METHODS: Blood culture isolates and clinical information were collected for patients with diagnoses of Campylobacter jejuni or Campylobacter coli bacteremia in Finland from 1998 through 2007. Bacterial species were identified by means of polymerase chain reaction analysis, and minimal inhibitory concentrations for ciprofloxacin, clindamycin, doxycycline, erythromycin, gentamicin, meropenem, and metronidazole were determined with an agar dilution method. Medical records and mortality data within 1 year after the bacteremic episode were reviewed. RESULTS: The study included 76 patients (median age, 46 years), for whom bacterial isolates (C. jejuni in 73, C. coli in 3) and clinical information were available. Most patients (70%) had no significant underlying diseases. The majority (82%) of the isolates were susceptible for all antimicrobial agents tested. However, antimicrobial therapy seemed to have only a limited effect, because no differences could be detected between patients with appropriate empirical antimicrobial treatment and those with delayed appropriate, inappropriate, or no antimicrobial therapy, either in the duration of hospitalization (median, 4 days for both groups) or in attributable mortality. The outcome of the infection was severe in 4 patients infected with C. jejuni; 2 died within 30 days, spondylodiscitis developed in 1, and Guillain-Barré syndrome developed in 1. CONCLUSIONS: C. jejuni and C. coli bacteremia occurred mainly in moderately young individuals without severe underlying diseases. The bacterial isolates were predominantly susceptible to antimicrobial agents, and the outcome of the disease was typically good, regardless of appropriate or inappropriate antimicrobial treatment given in the hospital.

Hospitalization and deaths for select enteric illnesses and associated sequelae in Canada, 2001-2004.

This paper describes morbidity and mortality parameters for Campylobacter spp., Salmonella spp., enterohaemorrhagic Escherichia coli, Listeria spp., norovirus infections and their primary associated sequelae [Guillain-Barré syndrome (GBS), haemolytic uraemic syndrome, reactive arthropathies and Reiter's syndrome]. Data from a period of 4 years were obtained from three national databases to estimate percentage of reported cases hospitalized, mean annual hospitalization incidence rate, frequency of hospitalization by age and sex, and number of deaths. The length of hospital stay, discharge disposition, hospitalization age, and number of diagnoses per case were also extracted and summarized. In addition, we estimated that each year in Canada, there are between 126 and 251 cases of Campylobacter-associated GBS. This study provides morbidity and mortality estimates for the top enteric pathogens in Canada, including their associated sequelae, which can contribute to the quantification of the burden of illness.

Virulence spectra of typed strains of Campylobacter jejuni from different sources: a blinded in vivo study.

Campylobacter jejuni is a major cause of human diarrhoeal disease, but specific virulence mechanisms have not been well defined. The aims of the present blinded study were to measure and compare the in vivo properties of 40 serotyped, biotyped and genotyped C. jejuni isolates from different sources and genetic makeup. An 11-day-old chick embryo lethality assay, which measured embryo deaths and total viable bacteria over 72 h following inoculation of bacteria into the chorioallantoic membrane, revealed a spectrum of activity within the C. jejuni strains. Human and chicken isolates showed similar high virulence values for embryo deaths while the virulence of the bovine isolates was less pronounced. A one-way ANOVA comparison between the capacity of the strains to kill the chick embryos after 24 h with cytotoxicity towards cultured CaCo-2 cells was significant (P=0.025). After inoculation with a Campylobacter strain, mouse ligated ileal loops were examined histologically and revealed degrees of villous atrophy, abnormal mucosa, dilation of the lumen, congestion and blood in lumen, depending on the isolate examined. A 'total pathology score', derived for each C. jejuni strain after grading the pathology features for degree of severity, showed no apparent relationship with the source of isolation. Some relationship was found between amplified fragment length polymorphism groups and total ileal loop pathology scores, and a one-way ANOVA comparison of the mouse pathology scores against total chick embryo deaths after 72 h was significant (P=0.049).

Factors that led to the Walkerton tragedy.

In May 2000, bacterial contamination of municipal water in Walkerton, Ontario, resulted in the worst public health disaster involving municipal water in Canadian history. At least seven people died and 2300 became ill. A public inquiry led by judge Dennis O'Connor examined the events and delineated the causes of the outbreak, including physical causes, the role of the public utilities operators, the public utilities commissioners, the Ministry of the Environment (MOE), and the provincial government. Improper practices and systemic fraudulence by the public utility operators, the recent privatization of municipal water testing, the absence of criteria governing quality of testing, and the lack of provisions made for notification of results to multiple authorities all contributed to the crisis. The MOE noted significant concerns 2 years before the outbreak; however, no changes resulted because voluntary guidelines as opposed to legally binding regulations governed water safety. The inquiry concluded that budgetary restrictions introduced by the provincial government 4 years before the outbreak were enacted with no assessment of risk to human health. The ministers and the cabinet had received warnings about serious risks. Budgetary cuts destroyed the checks and balances that were necessary to ensure municipal water safety.

Are host characteristics or exposure factors mainly involved in the acquisition of zoonotic Salmonella and Campylobacter coinfection in humans?

We hypothesized that patients coinfected with zoonotic Salmonella and Campylobacter were frailer than monoinfected Salmonella or Campylobacter patients. The study cohort included all first-time Salmonella/Campylobacter infections in Aarhus and North Jutland counties, Denmark, from 1991 through 2003. Data on comorbidity, hospitalization in relation to the Salmonella/Campylobacter infection, and 1-year mortality were obtained from electronic registries. Among 13,449 individuals, 114 (0.85%) had Salmonella/Campylobacter coinfection, 6567 (48.8%) had Salmonella monoinfection, and 6768 (50.3%) had Campylobacter monoinfection. There were no major differences in age, gender, comorbidity, hospitalization rates, 1-year mortality, or seasonal variation between coinfected patients on the one hand and each of the monoinfected patient groups on the other. The main difference was encountered between the Salmonella serotype distribution as 49.1% of coinfected patients versus 20.3% of monoinfected Salmonella patients had Salmonella serotypes other than Salmonella Enteritidis and Salmonella Typhimurium (odds ratio [95% confidence interval]: 4.07 [2.73-6.06]). In conclusion, Salmonella/Campylobacter coinfected patients were not frailer than monoinfected patients. The difference in Salmonella serotype distribution was compatible with a higher proportion of coinfections acquired during foreign travel.

Campylobacter bacteremia: clinical features and factors associated with fatal outcome.

BACKGROUND: Campylobacter bacteremia is uncommon. The influence of underlying conditions and of the impact of antibiotics on infection outcome are not known. METHODS: From January 2000 through December 2004, 183 episodes of Campylobacter bacteremia were identified in 23 hospitals in the Paris, France, area. The medical records were reviewed. Characteristics of bacteremia due to Campylobacter fetus and to other Campylobacter species were compared. Logistic regression analysis was performed to identify risk factors for fatal outcome within 30 days. RESULTS: Most affected patients were elderly or immunocompromised. C. fetus was the most commonly identified species (in 53% of patients). The main underlying conditions were liver disease (39%) and cancer (38%). The main clinical manifestations were diarrhea (33%) and skin infection (16%). Twenty-seven patients (15%) died within 30 days. Compared with patients with bacteremia due to other Campylobacter species, patients with C. fetus bacteremia were older (mean age, 69.5 years vs. 55.6 years; P = .001) and were more likely to have cellulitis (19% vs. 7%; P = .03), endovascular infection (13% vs. 1%; P = .007), or infection associated with a medical device (7% vs. 0%; P = .02). Independent risk factors for death were cancer (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-20.8) and asymptomatic infection (OR, 6.7; 95% CI, 1.5-29.4) for C. fetus bacteremia, the absence of prescription of appropriate antibiotics (OR, 12.2; 95% CI, 0.9-157.5), and prescription of third-generation cephalosporins (OR, 10.2; 95% CI, 1.9-53.7) for bacteremia caused by other species. CONCLUSIONS: Campylobacter bacteremia occurs mainly in immunocompromised patients. Clinical features and risk factors of death differ by infection species.