Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan.

Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.

Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa.

BACKGROUND: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies. METHODS: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence. RESULTS: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78. CONCLUSIONS: This Phase 2b trial is the largest on ETVAX® undertaken amongst travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.

European hospitals as source of multidrug-resistant bacteria: analysis of travellers screened in Finland after hospitalization abroad.

BACKGROUND: As hospitals have a high prevalence of multidrug-resistant organisms (MDRO), hospitalization abroad indicates for travellers an increased risk of acquiring MDRO-and carrying the strains home. Antimicrobial resistance (AMR) rates are highest in the (sub)tropics, whereas Europe is considered a lower risk region. Since AMR prevalences vary within Europe, we aimed to gather country-specific data on the risks for hospitalized travellers. METHODS: At hospitals of the Helsinki and Uusimaa district in Finland, patients hospitalized abroad over the past 12 months are systematically screened for methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), carbapenemase-producing bacteria and vancomycin-resistant Enterococcus spp. (VRE). Among patients screened 2010-19, we selected those hospitalized in Europe, recorded their MDRO findings, infections and mortality, and analysed MDRO-associated risk factors. RESULTS: Of the 1772 patients treated in 41 European countries, 16.6% (295) carried MDRO, 12.5% (221) ESBL-PE, 7.8% (138) solely ESBL-E. coli, 2.6% (46) MRSA, 2.2% (30) of those screened VRE and 2.2% (39) carbapenem-resistant Gram-negatives. Among those colonized, 9.8% (29) had symptomatic MDRO infections and 0.3% (one) died. Colonization was most frequently recorded for those treated in eastern and southern Europe, with Bulgaria, Cyprus and the Russian Federation scoring highest. MDRO colonization was associated with antibiotic treatment and showed a negative correlation with time from discharge to screening. CONCLUSIONS: After hospitalization in European countries, ESBL-PE carriage was relatively common (12.5%), while other MDROs proved less frequent (<5%). Antibiotic treatment and short time since hospitalization abroad increased the risk of MDRO colonization. Clear differences between countries and regions were revealed, with highest rates in the east and the south.

Import of multidrug-resistant bacteria from abroad through interhospital transfers, Finland, 2010-2019.

BackgroundWhile 20-80% of regular visitors to (sub)tropical regions become colonised by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE), those hospitalised abroad often also carry other multidrug-resistant (MDR) bacteria on return; the rates are presumed to be highest for interhospital transfers.AimThis observational study assessed MDR bacterial colonisation among patients transferred directly from hospitals abroad to Helsinki University Hospital. We investigated predisposing factors, clinical infections and associated fatalities.MethodsData were derived from screening and from diagnostic samples collected between 2010 and 2019. Risk factors of colonisation were identified by multivariable analysis. Microbiologically verified symptomatic infections and infection-related mortality were recorded during post-transfer hospitalisation.ResultsColonisation rates proved highest for transfers from Asia (69/96; 71.9%) and lowest for those within Europe (99/524; 18.9%). Of all 698 patients, 208 (29.8%) were colonised; among those, 163 (78.4%) carried ESBL-PE, 28 (13.5%) MDR Acinetobacter species, 25 (12.0%) meticillin-resistant Staphylococcus aureus, 25 (12.0%) vancomycin-resistant Enterococcus, 14 (6.7%) carbapenemase-producing Enterobacteriaceae, and 12 (5.8%) MDR Pseudomonas aeruginosa; 46 strains tested carbapenemase gene-positive. In multivariable analysis, geographical region, intensive care unit (ICU) treatment and antibiotic use abroad proved to be risk factors for colonisation. Clinical MDR infections, two of them fatal (1.0%), were recorded for 22 of 208 (10.6%) MDR carriers.ConclusionsColonisation by MDR bacteria was common among patients transferred from foreign hospitals. Region of hospitalisation, ICU treatment and antibiotic use were identified as predisposing factors. Within 30 days after transfer, MDR colonisation manifested as clinical infection in more than 10% of the carriers.

Acute epiglottitis after COVID-19 infection.

In patients with acute epiglottitis, the possibility of COVID-19 should be ruled out. Repeated nasofiberoscopy examinations or a tracheostomy, which may produce infectious aerosols, may be required.

Louse-borne relapsing fever in Finland in two asylum seekers from Somalia.

We report two cases of louse-borne relapsing fever (LBRF) in young Somali asylum seekers having recently arrived to Finland. They had sought medical attention for a febrile illness. Blood smears were examined for suspected malaria, but instead, spirochete shaped bacteria were observed. The bacteria were confirmed as Borrelia recurrentis by PCR and sequencing. The patients survived, but their treatment was complicated by Jarisch-Herxheimer reaction. We conclude that LBRF must be considered as a diagnostic option in febrile refugees also in the northernmost parts of Europe.

Relapsing fever.

Relapsing fewer is an infection to be considered in the differential diagnosis of an immigrant´s febrile illness. It is a severe, tick-borne or body louse-borne infection caused by the relapsing fever associated borrelia species. The body louse-borne infection is in particular encountered in the Horn of Africa region due to poor hygiene, and has during the past year been described in several European countries as imported by refugees coming from this region. Doctors should thus bear relapsing fever in mind as a differential diagnosis in a febrile refugee having recently arrived in Finland.