Abstract
Clostridioides (Clostridium) difficile infections (CDI) are considered worldwide as emerging health threat. Uptake of C. difficile spores may result in asymptomatic carrier status or lead to CDI that could range from mild diarrhea, eventually developing into pseudomembranous colitis up to a toxic megacolon that often results in high mortality. Most epidemiological studies to date have been performed in middle- and high income countries. Beside others, the use of antibiotics and the composition of the microbiome have been identified as major risk factors for the development of CDI. We therefore postulate that prevalence rates of CDI and the distribution of C. difficile strains differ between geographical regions depending on the regional use of antibiotics and food habits. A total of 593 healthy control individuals and 608 patients suffering from diarrhea in communities in Germany, Ghana, Tanzania and Indonesia were selected for a comparative multi-center cross-sectional study. The study populations were screened for the presence of C. difficile in stool samples. Cultured C. difficile strains (n = 84) were further subtyped and characterized using PCR-ribotyping, determination of toxin production, and antibiotic susceptibility testing. Prevalence rates of C. difficile varied widely between the countries. Whereas high prevalence rates were observed in symptomatic patients living in Germany and Indonesia (24.0 and 14.7%), patients from Ghana and Tanzania showed low detection rates (4.5 and 6.4%). Differences were also obvious for ribotype distribution and toxin repertoires. Toxin A+/B+ ribotypes 001/072 and 078 predominated in Germany, whereas most strains isolated from Indonesian patients belonged to toxin A+/B+ ribotype SLO160 and toxin A-/B+ ribotype 017. With 42.9–73.3%, non-toxigenic strains were most abundant in Africa, but were also found in Indonesia at a rate of 18.2%. All isolates were susceptible to vancomycin and metronidazole. Mirroring the antibiotic use, however, moxifloxacin resistance was absent in African C. difficile isolates but present in Indonesian (24.2%) and German ones (65.5%). This study showed that CDI is a global health threat with geographically different prevalence rates which might reflect distinct use of antibiotics. Significant differences for distributions of ribotypes, toxin production, and antibiotic susceptibilities were observed.
Highlights
Clostridioides (Clostridium) difficile infections (CDI) have become an emerging health threat; more than 450,000 cases with approximately 30,000 deaths have been estimated to occur every year in the USA alone (Lessa et al, 2015)
Prevalence rates of C. difficile carriage were highest in the participants from the German and the Indonesian study sites compared with the two African study sites (Table 1)
Like in Seesen/Germany, C. difficile was only found in symptomatic patients in the Tanzanian study site but not in the healthy control group. 48.9% of Tanzanian patients with diarrhea were children 12 years of age or younger and five out of seven C. difficile isolates were recovered from children (Seugendo et al, 2015)
Summary
Clostridioides (Clostridium) difficile infections (CDI) have become an emerging health threat; more than 450,000 cases with approximately 30,000 deaths have been estimated to occur every year in the USA alone (Lessa et al, 2015). Strains with modifications in the toxin A and B coding region, the so-called pathogenicity locus (PaLoc), compared to the well-characterized reference strain VPI 10463, are defined as variant strains. They can be differentiated by toxinotyping, a PCR-restriction fragment length polymorphism (RFLP)-based method (Rupnik and Janezic, 2016). The aim of this article is to compare the data obtained from Indonesia and Germany with the previously published data from Ghana and Tanzania and to present this multi-center prospective study as a whole in order to compare prevalence rates, strain distribution and characterization of C. difficile in these four distinct geographical regions
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