Search

Additional file 2. Baseline biological results—safety registry of malaria patients treated with artenimol–piperaquine.

Additional file 5. Factors associated with the change in Alanine amino-transferase (ALAT), Aspartate amino-transferase (ASAT) and creatinin from baseline to the final treatment day.

Additional file 1. Illnesses and symptoms at Visit 1 by System Organ Class and Preferred Term—safety registry of malaria patients treated with artenimol–piperaquine.

Antimicrobial resistant (AMR) Enterobacterales are widely distributed among the healthy population of the Indochinese peninsula, including Laos. However, the local reservoir of these pathogens are currently not known and possible sources such as agricultural settings and food have rarely been analyzed. In this work, we investigated the extended-spectrum cephalosporin- (ESC-) and colistin-resistant Escherichia coli strains (CST-R-Ec) isolated from the gut of local people, feces of poultry, and from chicken meat (60 samples each group) in Laos. Whole-genome sequencing (WGS) analysis based on both short- and long-read sequencing approaches were implemented. The following prevalence of ESC-R-Ec and CST-R-Ec were recorded, respectively: local people (70 and 15%), poultry (20 and 23.3%), and chicken meat (21.7 and 13.3%). Core-genome analysis, coupled with sequence type (ST)/core-genome ST (cgST) definitions, indicated that no common AMR-Ec clones were spreading among the different settings. ESC-R-Ec mostly possessed bla CTX-M-15 and bla CTX-M-55 associated to ISEcp1 or IS26. The majority of CST-R-Ec carried mcr-1 on IncX4, IncI2, IncP1, and IncHI1 plasmids similar or identical to those described worldwide; strains with chromosomal mcr-1 or possessing plasmid-mediated mcr-3 were also found. These results indicate a high prevalence of AMR-Ec in the local population, poultry, and chicken meat. While we did not observe the same clones among the three settings, most of the bla CTX-Ms and mcr-1/-3 were associated with mobile-genetic elements, indicating that horizontal gene transfer may play an important role in the dissemination of AMR-Ec in Laos. More studies should be planned to better understand the extent and dynamics of this phenomenon.

Background: Semiquantitative dipstick tests are utilized for albuminuria screening. Methods: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test&reg, and the albumin-specific immunochromatographic assay Micral-Test&reg, for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. Results: In 970 subjects, albuminuria (&ge, 30 mg/g) was detected in 12.7% (95% CI 85.6&ndash, 96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1&ndash, 89.1%) and 91.9% (95% CI 88.7&ndash, 96.9%) and specificity 71.5% (95% CI 68.4&ndash, 74.6%) and 17.5% (95% CI 15.0&ndash, 20.2%) for the Combur9-Test&reg, and Micral-Test&reg, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test&reg, was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and &ge, 300 mg/dL, and with the Micral-Test&reg, it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test&reg, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test&reg, respectively. Conclusion: Compared to the Combur9-Test&reg, the utility of the Micral-Test&reg, is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test&reg, require a subsequent ACR conformation test.

Additional file 3. Overview of adverse events (AE) and serious adverse event (SAE) other than adverse event of special interest (AESI).

Additional file 4. Factors associated with the occurrence of adverse event (AE) including adverse event of special interest (AESI).

OBJECTIVES Many travellers to low-income countries return home colonized at the intestinal level with extended-spectrum cephalosporin-resistant (ESC-R) and/or colistin-resistant (CST-R) Escherichia coli (Ec) strains. However, nothing is known about the local sources responsible for the transmission of these pathogens to the travellers. METHODS We compared the ESC-R- and CST-R-Ec strains found in the pre- (n = 23) and post-trip (n = 37) rectal swabs of 37 travellers from Switzerland to Zanzibar with those (i) contemporarily isolated from local people, poultry, retailed chicken meat (n = 31), and (ii) from other sources studied in the recent past (n = 47). WGS and core-genome analyses were implemented. RESULTS Twenty-four travellers returned colonized with ESC-R- (n = 29) and/or CST-R- (n = 8) Ec strains. Almost all ESC-R-Ec were CTX-M-15 producers and belonged to heterogeneous STs/core-genome STs (cgSTs), while mcr-positive strains were not found. Based on the strains' STs/cgSTs, only 20 subjects were colonized with ESC-R- and/or CST-R-Ec that were not present in their gut before the journey. Single nucleotide variant (SNV) analysis showed that three of these 20 travellers carried ESC-R-Ec (ST3489, ST3580, ST361) identical (0-20 SNVs) to those found in local people, chicken meat, or poultry. Three further subjects carried ESC-R-Ec (ST394, ST648, ST5173) identical or highly related (15-55 SNVs) to those previously reported in local people, fish, or water. CONCLUSIONS This is the first known study comparing the ESC-R- and/or CST-R-Ec strains obtained from travellers and local sources using solid molecular methods. We showed that for at least one-third of the returning travellers the acquired antibiotic-resistant Ec had a corresponding strain among resident people, food, animal and/or environmental sources.

OBJECTIVES Intestinal colonization with extended-spectrum cephalosporin-resistant (ESC-R) and colistin-resistant (CST-R) Enterobacterales (Ent) can be driven by contact with colonized animals and/or contamination of the food chain. We studied the ESC-R-Ent and COL-R-Ent colonizing poultry as well as contaminating chicken meat in Zanzibar (Tanzania). Results were compared with recently published data obtained from rectal swabs of people in the community. METHODS During June and July 2018, we collected poultry faecal material (n = 62) and retail chicken meat (n = 37) samples. ESC-R and CST-R strains were isolated implementing selective approaches and characterized with different molecular methods, including WGS coupled with core-genome analyses. RESULTS The prevalence of ESC-R-Ent and CST-R-Ent, respectively, were: 88.7% and 48.4% in poultry; and 43.2% and 18.9% in chicken meat. Overall, the following strains and main resistance mechanisms were found in the two settings: 69 ESC-R Escherichia coli (CTX-M-15 subgroup, 75%), 34 ESC-R Klebsiella pneumoniae (CTX-M-9 group, 54.5%), 24 non-ESC-R but CST-R E. coli (mcr-1, 95.8%) and 17 non-ESC-R but CST-R K. pneumoniae (D150G substitution in PhoQ). Several clones (differing by only 0-13 single nucleotide variants) were concomitantly and frequently found in human and non-human settings: mcr-1-carrying E. coli ST46; CTX-M-15-producing E. coli ST361; CTX-M-14-producing K. pneumoniae ST17; and CTX-M-15-producing K. pneumoniae ST1741. CONCLUSIONS This is one of the few studies that have assessed the occurrence of identical MDR Enterobacterales in human and non-human settings. The frequent human gut colonization observed in the community might be favoured by the spread of ESC-R-Ent and CST-R-Ent in poultry and chicken meat. Further studies with a One Health approach should be carried out to better investigate this phenomenon.