Africa is a continent with increasing numbers of travellers [15]. When pooling subregion-/country-specific data from three traveller studies [4, 6, 10], we found the risk of contracting ESBL-PE to vary significantly between the various parts of Africa. In addition, comparing our joint data with two recent large reports [7, 11] providing subregion- and country-specific data enabled us to investigate the current subregion- and country-specific knowledge about ESBL-PE acquisition by travellers to Africa.
ESBL-PE colonization rates in northern Africa
Our pooled data showed the highest acquisition rates (12/28; 42.9%) among visitors to Northern Africa, which accords with the results from the study by Arcilla et al. (42.0%) [11]; Ruppé et al. [7] did not report visitors to this subregion. Similar (43–44%) rates have been reported among Swedish travellers [3, 12]. Visitors to Egypt appear to be at particularly high risk; 70.6% (12/17) of our subjects, 80.0% (23/40) of those in a study by Arcilla et al., and 50% (19/38) of those in another by Tham et al. became colonized [11, 14]. Moreover, all 12 travellers colonized by ESBL-PE in Northern Africa had visited Egypt. It is noteworthy that these proportions are as high as those among travellers to India/South Asia in various investigations [4,5,6,7,8, 11]. Bassyouni et al. reported carriage rates as low as 21% among healthcare workers in Egypt [17].
ESBL-PE colonization rates in middle Africa
To our knowledge, only one previous study has reported ESBL-PE acquisition rates among visitors to Middle Africa; Ruppé et al. [7] found 53.3% (24/45) of travellers to be colonized. In our pooled data, colonization rates in Middle Africa ranked second (4/15; 26.7%) among the subregions. In nonclinical samples obtained from local populations, carriage rates as high as 59% have been shown among healthy children in the Central African Republic [18], and 44–57% among inpatient carers, hospital workers and their household members in Cameroon [19].
ESBL-PE rates in eastern Africa
Colonization rates among travellers to Eastern Africa (30/185; 16.2%) were lower than those reported by Arcilla et al. (57/205; 27.8%) [11], Lubbert et al. (12/47; 25.5%) [8], and Ruppé et al. (17/29; 56.8%,) [7]. Our moderate colonization rates are supported by findings among local populations: ESBL-PE carriage rates between 11.6 and 16.5% have been reported for healthy community children in Tanzania, [20, 21] and 5.3% for locals in Uganda, [22].
ESBL-PE colonization rates in western Africa
ESBL-PE acquisition rates in Western Africa appear moderately low, but the results differ between studies: our pooled data showed proportions (11/110; 10.0%) close to those presented by Arcilla et al. (20/106; 18.9%) [11], while higher rates have been found by Ruppé et al. (44/99; 44.4%) [7] and Lubbert et al. (5/12; 38.5%) [8] among German travellers to Western and Middle Africa. Moreover, in the research by Frickmann et al., 27.1% (13/48) of European military personnel with diarrhoea in Mali became colonized by ESBL-PE [23]. As for local populations, colonization rates of 22% have been reported for healthy volunteers in Burkina Faso [24] and 33% for healthy community children in Guinea-Bissau [25].
ESBL-PE colonization rates in southern Africa
Our low rates in Southern Africa (4/58; 6.8%) accord with those found by Arcilla et al. (7/116; 6.0%) [11] and Lubbert et al. (2/18; 11%) [8]. In our pooled data, the vast majority had visited South Africa or Namibia. Consistent with the low ESBL-PE acquisition rates, one study exploring local populations in South Africa reported maternal faecal carriage rates of 4.4% in South Africa [26].
Findings from multivariable analysis
Travellers’ diarrhoea
ESBL-PE acquisition rates among those who contracted TD during travel (31/153; 20.3%) were higher than among those without TD (30/243; 12.3%) (AOR 2.1; 95% CI 1.1–4.1). This was expected, since TD was identified as a risk factor in two of the three original studies [6, 10] and numerous others [1, 3, 7, 8, 11, 12].
Antimicrobial medication
Forty-four (11.1%) travellers had taken antimicrobial medications during travel. Of the Finns, 17.3% (34/196) took antibiotics while this proportion was 5.0% (10/200) among the Dutch. In multivariable analyses, fluoroquinolone antibiotics were an independent risk factor for ESBL-PE colonization (ESBL-PE(+) 40.0%; AOR 4.7; 95% CI 1.5–13.9). Other antibiotic groups did not reach statistical significance in the risk factor analysis, yet the numbers of travellers using each individual antibiotic type were small; eight had taken beta-lactams (ESBL-PE(+) 50.0%; AOR 3.4, CI 0.5–21.9) and 14 other antimicrobials (ESBL-PE(+) 35.7%; AOR 3.8 CI 0.9–14.6). Ruppé et al. found beta-lactam usage to predispose to colonization by ESBL-PE (20/25; 80%) [7].
Even though taken by 34 (8.6%) travellers as an antimalarial, doxycycline was not associated with increased ESBL-PE rates (ESBL-PE(+) 5/34; 14.7%; AOR 0.9, 95% CI 0.4–2.5). This finding accords with other studies [7, 11]. However, these data do not allow conclusions on the total impact of doxycycline on antimicrobial resistance, as these investigations only analysed the ESBL or CPE feature of the Enterobacteriaceae; the potential to select doxycycline-resistant strains in general or other types of multidrug-resistant bacteria was not explored. Indeed, we recently showed that fluoroquinolone intake predisposes selectively to colonization by fluoroquinolone-resistant bacteria [27]. Thus, the effect of doxycycline on other bacteria and travellers’ microbiota deserves further research.
Increasing age as risk factor
Increasing age proved an independent risk factor for ESBL-PE colonization in Africa. Only two earlier reports [3, 6] have described similar results, as opposed to several others [7, 8, 11]. Moreover, in one study conducted among returning travellers with diarrhoea, increasing age even appeared protective [28]. The role of age remains unclear. There may be other factors associated with increasing age, such as co-medications/comorbidities or altered immune response not covered in these studies that interfere with the analyses in either direction. As the risk of bacteraemic infections caused by resistant Enterobacteriaceae increases with age [29], the risk factors in the older age groups warrant further studies.
Overnight hospitalisation
In our joint data, overnight hospitalisation predisposed to colonization with ESBL-PE. Although numerous retrospective studies have shown high colonization rates by multiresistant bacteria among travellers hospitalized in high-prevalence countries [30,31,32], to our knowledge, this is the first study to actually show in a prospective setting hospitalisation abroad as a risk factor for ESBL-PE acquisition. In previous prospective traveller studies, overnight hospitalisations has either not been analysed separately from other health care contacts in the risk factor analyses [7, 11] or the proportion of travellers requiring a stay in hospital for treatment has been small or negligible (0–0.5%) [3, 8]. In our data, six (1.5% of all subjects) needed overnight hospitalisation.
Travel destination
In multivariable analysis, when compared to Southern Africa, travel to Northern Africa was associated with higher colonization rates. The rates presumably vary between subregions and countries according to the background prevalence of the local populations [33]. They may also depend on several other factors, such as local culture-related food production and preparation habits and hygienic conditions and, of course, whether the traveller contracts TD and takes antibiotics (see above).
Other risk factors
Even though multiresistant Enterobacteriaceae have become increasingly prevalent globally [33], colonization rates were not found to increase during the study period (2009–2013). Neither individual studies nor sampling techniques were found statistically significant factors in the multivariable analysis. Travel duration was not seen to be associated with increased risk in univariate or multivariable analysis. This may be explained by a proportion of travellers becoming colonized already on arrival and the carriage resolving while abroad (Professor Kantele, unpublished observation).
Limitations of the study
As the data for the joint risk factor analysis were derived from three separate studies, some data had been collected in differing formats rendering the results incomparable. Moreover, although pooling served to increase the validity and precision of study results, the data remained insufficient in some occasions for analysis in any great detail: In Additional file 1: Table S1, we present the factors available from two out of three studies [4, 6]: purpose of travel, diet (omnivore or vegetarian), type of accommodation, use of medications (antidiarrhoeals, proton-pump inhibitors, and antiemetics) and contact with local health care (other than hospitalisation). The five investigations appeared heterogeneous in the forest plot analysis, however, in the multivariable analysis of the pooled data, the interaction between subregions and studies was not found statistically significant.
Information concerning mild gastrointestinal symptoms in the ‘no TD’ group was only available for the Finnish volunteers (48.8% of all ‘no TD’ cases). To pool the three studies, we had to define TD as three or more stools per 24 h; milder diarrhoea cases were categorised as ‘no TD’, although even mild TD also may predispose to ESBL-PE acquisition.