Import of community-associated, methicillin-resistant Staphylococcus aureus to Europe through skin and soft-tissue infection in intercontinental travellers, 2011-2016.

OBJECTIVES: Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016. METHODS: Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory. RESULTS: A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus-positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton-Valentine leucocidin (PVL) -positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p <0.001) and was highest in Latin America (16/57, 28%, 95% CI 17.0-41.5) and lowest in Sub-Saharan Africa (4/121, 3%, 95% CI 0.9-8.3). Major epidemic clones (USA300 / USA300 Latin-American Variant, Bengal Bay, South Pacific) accounted for more than one-third (19/51, 37%) of CA-MRSA imports. CA-MRSA SSTI in returnees was complicated (31/51 multiple lesions, 61%; 22/50 recurrences, 44%), led to health-care contact (22/51 surgical drainage, 43%; 7/50 hospitalization, 14%), was transmissible (13/47 reported similar SSTI in non-travelling contacts, 28%), and associated with S. aureus nasal colonization (28 of 51 CA-MRSA cases, 55%; 24 of 28 colonized with identical spa-type in nose and lesion, 85%). CONCLUSIONS: Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host.

Toll-like receptor 9 (TLR-9) promotor polymorphisms and gene expression are associated with persistent Staphylococcus aureus nasal carriage.

OBJECTIVES: Toll-like receptor (TLR) 9 could have importance in human Staphylococcus aureus immunity, but population-level evidence for this hypothesis is missing. METHODS: We phenotyped S. aureus nasal carriage of 603 volunteers using four consecutive swabs, genotyped TLR9 promotor variants in 106 persistent carriers and 219 noncarriers, measured TLR9-mRNA expression in whole blood after stimulation with viable S. aureus and studied mutual associations of carriage, transcriptional activity and single nucleotide polymorphisms while accounting for sex and hormone contraceptive use (HCU). RESULTS: The -1486 (rs187084) and -1237 (rs5743836) CT haplotype was more common in noncarriers (185/438, 42%) than in carriers (63/212, 30%), with the TT haplotype showing a reverse association (noncarriers, 180/438, 41%; carriers 117/212, 55%) (χ2 p 0.001). Mean TLR9 mRNA expression in whole blood was higher in noncarriers (ratiocarriers/noncarriers 0.63; 95% confidence interval, 0.43-0.92; p 0.017). A duplication of TLR9 transcriptional activity lowered the odds of persistent S. aureus carriage by 37% in the overall group (odds ratio = 0.63; 95% confidence interval, 0.42-0.94; p 0.022) and by 54% in women (odds ratio = 0.46; 95% confidence interval, 0.23-0.90; p 0.023). Promotor haplotype and HCU had a combined effect on TLR9 transcription (interaction model): women in the TT (risk) haplotype/HCU- stratum (baseline) had lower mRNA levels than women in the CT (protective) haplotype/HCU- (ratio 1.92; p 0.055), the CT haplotype/HCU+ (ratio 2.02; p 0.032) and the TT haplotype/HCU+ (ratio 2.59; p < 0.004) strata. No such associations were observed in men. CONCLUSIONS: We provide evidence that TLR9 affects human S. aureus immunity and present potential explanations for differences according to sex in S. aureus colonization and infection.

Predominance of dfrG as determinant of trimethoprim resistance in imported Staphylococcus aureus.

To investigate the global occurrence of trimethoprim-sulfamethoxazole resistance and the genetic mechanisms of trimethoprim resistance, we analysed Staphylococcus aureus from travel-associated skin and soft-tissue infections treated at 13 travel clinics in Europe. Thirty-eight per cent (75/196) were trimethoprim-resistant and 21% (41/196) were resistant to trimethoprim-sulfamethoxazole. Among methicillin-resistant S. aureus, these proportions were 30% (7/23) and 17% (4/23), respectively. DfrG explained 92% (69/75) of all trimethoprim resistance in S. aureus. Travel to South Asia was associated with the highest risk of acquiring trimethoprim-sulfamethoxazole-resistant S. aureus. We conclude that globally dfrG is the predominant determinant of trimethoprim resistance in human S. aureus infection.

Postinfectious irritable bowel syndrome after travelers' diarrhea--a cohort study.

BACKGROUND: There is sound evidence for the role of gastrointestinal infections in the development of postinfectious irritable bowel syndrome (PI-IBS), but understanding the interaction between mental factors and the infection remains incomplete. This study aims to (i) assess the occurrence of PI-IBS in a cohort of patients with self-reported travelers' diarrhea (TD), (ii) assess risk factors for PI-IBS development, and (iii) investigate the prognosis of PI-IBS after 1 year. METHODS: Patients consulting the travel clinic at the University Hospital Tuebingen, Germany (in 2009 and 2010) were identified from records and questioned in follow-ups in 2011 and 2012. We used the Rome III modular questionnaire to assess IBS, the Hospital Anxiety and Depression Scale to assess anxiety and depression, and the Patient Health Questionnaire to assess somatization. KEY RESULTS: We identified 529 eligible subjects from the clinical records. Of 135 subjects (age: 36.6 ± 14.6 years, 58.5% female) included in the study sample 6.7% (95% CI 3.0-11.1) had PI-IBS. We found more females (88.9% vs 56.3%, p = 0.08) and younger age subjects (mean 29.3 vs 37.1 years, p = 0.02) among the PI-IBS subjects. A multivariable regression model revealed vomiting at baseline and high somatization scores as strong and independent PI-IBS risk factors. One year later PI-IBS occurrence decreased to 3.3% (three cases of 90). CONCLUSIONS & INFERENCES: Our findings underline the close linkage of mental and somatic processes for the manifestation of PI-IBS. Screening for psychiatric comorbidities in patients with severe gastrointestinal infections may allow identifying groups at high risk for PI-IBS.

Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe.

Staphylococcus aureus is emerging globally. Treatment of infections is complicated by increasing antibiotic resistance. We collected clinical data and swabs of returnees with skin and soft tissue infections (SSTI) at 13 travel-clinics in Europe (www.staphtrav.eu). Sixty-two percent (196/318) SSTI patients had S. aureus-positive lesions, of which almost two-thirds (122/196) were Panton-Valentine leukocidin (PVL) positive. PVL was associated with disease severity, including hospitalization for SSTI (OR 5.2, 95% CI 1.5-18.2). In returnees with SSTI, longer travel and more intense population contact were risk factors for nasal colonization with PVL-positive S. aureus. Imported S. aureus frequently proved resistant to trimethoprim-sulfamethoxazole (21%), erythromycin (21%), tetracycline (20%), ciprofloxacin (13%), methicillin (12%) and clindamycin (8%). Place of exposure was significantly (p < 0.05) associated with predominant resistance phenotypes and spa genotypes: Latin America (methicillin; t008/CC24/304), Africa (tetracycline, trimethoprim-sulfamethoxazole; t084/CC84, t314/singleton, t355/CC355), South Asia (trimethoprim-sulfamethoxazole, ciprofloxacin; t021/CC21/318), South-East Asia (clindamycin; t159/CC272). USA300-like isolates accounted for 30% of all methicillin-resistant S. aureus imported to Europe and were predominantly (71%) acquired in Latin America. Multi-resistance to non-ß-lactams were present in 24% of imports and associated with travel to South Asia (ORcrude 5.3, 95% CI 2.4-11.8), even after adjusting for confounding by genotype (ORadjusted 3.8, 95% 1.5-9.5). Choosing randomly from compounds recommended for the empiric treatment of severe S. aureus SSTI, 15% of cases would have received ineffective antimicrobial therapy. These findings call for the development of regionally stratified guidance on the antibiotic management of severe imported S. aureus disease and put the infected and colonized traveller at the centre of interventions against the global spread of multi-resistant S. aureus.

[Muscular sarcocystosis after travel to Malaysia: a case series from Germany]. / Muskuläre Sarkozystose nach Malaysiareise: eine Fallserie aus Deutschland.

BACKGROUND: Since 2011, about 100 travellers to the island of Tioman, Malaysia, have been diagnosed worldwide with suspected muscular sarcocystosis, a previously only sporadically observed parasitic disease. Source of infection and therapy remain unclear. Final diagnosis requires microscopic identification of cysts in muscle biopsies. The study objective was a systematic description of characteristic symptoms, laboratory investigations and treatment response. METHODS: Systematic case series. RESULTS: The 26 cases of 5 centers for tropical medicine in Germany showed a characteristic biphasic development: symptoms began in general 2 weeks after mid-holidays (min. 7.5, max. 22 days) with unspecific fever and headaches lasting for almost 1 week. After an asymptomatic period of 2 weeks, severe myalgia (6.5, scale 0-10) and fever developed and lasted for about 6 weeks (min. 7, max. 207 days), accompanied by creatin-phosphokinase(CK)-elevation (up to 3.5 times), and eosinophilia (2.9 times). One out of two muscle biopsies revealed a cyst typical for sarcocystosis. In 6 out of 7 patients an increase in Sarcocystis-specific antibody concentration could be demonstrated by ELISA. Treatment with systemic steroids and albendazole, or ivermectin resulted in significant symptomatic improvement in most of the patients. One patient was treated early with cotrimoxazole and subsequently did not develop a second phase of the disease. All patients had stayed in the North-West of the island Tioman. CONCLUSIONS: Muscular sarcocystosis develops in a biphasic pattern with initial fever and later prolonged myalgia, eosinophilia, and CK-elevation. Steroids achieve symptomatic relief in the late phase. Early cotrimoxazole-therapy could possibly prevent parasitic muscle invasion. In fever after travel to Malaysia differential diagnosis should include sarcocystosis. The source of infection appears to be located in North-West of Tioman. Further studies are needed, including addressing early diagnosis and treatment.

Leishmaniasis in the era of tumor necrosis factor alpha antagonist therapy--a research agenda for Europe.

A number of published case reports suggest an association of tumor necrosis factor (TNF) alpha antagonist use and manifest leishmaniasis. Despite increasing popularity of antagonising TNF alpha for the treatment of autoimmune disorders, systematic research on the risk of opportunistic leishmaniasis in patients receiving these drugs is lacking. This perspective identifies areas of uncertainty regarding the safety profile of TNF alpha antagonist drugs and their clinical use in patients at risk of leishmaniasis. Then, we reflect on how current pharmacovigilance activities in Europe could be enhanced to help reduce these uncertainties. Our aim is to stimulate a debate about this important drug safety issue with potential consequences for patients receiving TNF alpha antagonists living in or travelling to areas endemic for leishmaniasis.

Tumor necrosis factor alpha antagonist drugs and leishmaniasis in Europe.

Leishmaniasis is endemic in Europe and the prevalence of latent infection in the Mediterranean region is high. Reports describing opportunistic leishmaniasis in European patients treated with tumor necrosis factor (TNF) alpha antagonist drugs are rapidly accumulating. For other granulomatous infections, risk of opportunistic disease varies by mode of TNF-alpha antagonism. This study explores whether this may also be the case for leishmaniasis. We ascertained the relative frequency of exposure to different TNF antagonist drugs among published cases of opportunistic leishmaniasis in Europe and compared this with the prescription of these drugs in Europe. We found that risk of opportunistic leishmaniasis is higher in patients receiving anti-TNF monoclonal antibodies (infliximab or adalimumab) compared with patients treated with the TNF-receptor construct etanercept. Clinicians may want to consider these observations, which suggest that etanercept should be favoured over anti-TNF monoclonal antibodies in individuals living in or visiting areas endemic for leishmaniasis until evidence from prospective research is available. A European adverse event reporting system is required to identify rare opportunistic infections associated with immunosuppressive and immunomodulatory biotherapies.

Post-infectious irritable bowel syndrome--a review of the literature.

INTRODUCTION: Despite considerable research efforts, the epidemiological characteristics of post-infectious symptoms of the irritable bowel syndrome-type (PI-IBS) are not yet well defined. Estimates of its incidence after gastrointestinal (GI) infection show considerable variation and the number of patients with a history of a GI infection among all patients with IBS is practically unknown. This review aims at summarizing published estimates (i) on the prevalence of PI-IBS among all IBS patients and (ii) on PI-IBS incidence after GI infection, critically discusses methodological differences that may explain the variation of the presented findings and gives an overview on currently identified risk factors for the development of PI-IBS. METHODS: A systematic literature review was perfomed of studies indexed in PUBMED that assessed the epidemiology and risk factors of PI-IBS. RESULTS: The reported incidence of PI-IBS ranges for epidemic infections between 7 and 36 %, for individual infections between 4 and 36 % and for traveller's diarrhea from 4 to 14 %. Estimates of the prevalence of PI-IBS range from as low as 7 % to more than ⅓ of all IBS patients, depending on the study design. The predictors and biomarkers are varying among the studies. CONCLUSION: PI-IBS appears to be common following infectious enteritis and among all IBS patients, but precise estimates are still lacking.

Schistosoma japonicum infection and rectal carcinoid tumour: underreported coincidence or neglected association?

Schistosoma japonicum infection associated with a rectal carcinoid in an asymptomatic 44-year-old female from the Philippines is described. A systematic review of the literature could not identify similar reports, suggesting a rare coincidence. However, epidemiological data on the frequency of both conditions as well as published results of a colorectal screening programme from China indicate that underreporting of this concurrence is likely. Moreover, several studies suggest a causal link between schistosomiasis caused by S. japonicum and more common gastrointestinal malignancies such as colorectal carcinoma. Hence the presented case and the apparent neglect of this observation in the current literature allow speculation on a role of S. japonicum in the pathogenesis of rare gastrointestinal neoplasms such as carcinoid tumours as well. Future reports on similar observations could help to determine the need for systematic investigations and are strongly encouraged.

[Inflammatory myofibroblastic tumor of the pancreas with regional lymph node involvement]. / Inflammatorischer, myofibroblastischer Tumor des Pankreas mit Beteiligung regionärer Lymphknoten.

Inflammatory myofibroblastic tumors (IMT) can be found in virtually any location of the human body. Histologically a mesenchymal aspect predominates and makes these mostly benign tumors apt to be erroneously diagnosed as a soft tissue sarcoma. Cases showing infiltrative growth and local recurrence further complicate the assessment. Localization of an IMT in the pancreas is extremely rare. Clinical investigations regularly lead to the putative diagnosis of a malignant tumor and only subsequent histological examination can establish the correct tumor classification. We present the case of a 62-year-old woman with IMT of the pancreas. Evidence of lymph node involvement has not yet been reported in this setting.