Prevalence and Strain Characterization of Clostridioides (Clostridium) difficile in Representative Regions of Germany, Ghana, Tanzania and Indonesia – A Comparative Multi-Center Cross-Sectional Study

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.

Clostridioides difficile ribotypes 001 and 126 were predominant in Tehran healthcare settings from 2004 to 2018: a 14-year-long cross-sectional study

“…However, in the isolates from Ghana (40%, n = 6/15) and Algeria (36.4%, n = 4/11) in Africa, RT 084 was the most prevalent and with an equal distribution between symptomatic patients and asymptomatic controls. In addition, all were found to be nontoxigenic and resistant to erythromycin and ciprofloxacin [45][46][47]. When comparing the age groups, the overall ribotype diversity was higher in patients aged ≥81 years which is consistent with the results from a multicentre study performed in Europe [48].…”

Clostridioides difficile infection in the Asia-Pacific region

“…Less is known of the molecular epidemiology of C. difficile in South America, but RTs 027, 106, 012, 046, and 014/020 are reportedly the most common strains [31,33,34]. Similar to the current study, RT 017 (followed by RT 001) has also been found at high prevalence in South Africa [35], and in Ghana, Malawi, and Tanzania the few studies which performed molecular typing have shown a high prevalence of non-toxigenic strains [36,37], similar to reports from Southeast Asian countries [15].…”

Clostridium difficile shedding by healthy dogs in Nigeria and Malawi

“…This strain has also be reported in humans and animals in different countries, including Africa (Djebbar et al, ; Janezic, Ocepek, Zidaric, & Rupnik, ). This non‐toxigenic ribotype was the 2nd most common strain in Nigerian dogs and was the predominant type in two studies of humans in Ghana, another West African country (Janssen et al, ; Seugendo et al, ). The most common Nigerian strain, AI‐78, has been reported in humans in different countries,(Aschbacher et al, ; Krutova et al, ) but typically at a low prevalence and this strain has received little attention.…”