Werner Espelage

Resurgence of Field Fever in a Temperate Country: An Epidemic of Leptospirosis among Seasonal Strawberry Harvesters in Germany in 2007

BACKGROUND Although leptospirosis is a reemerging zoonosis of global importance, outbreaks related to agricultural exposures are primarily situated in tropical countries. In July 2007, a suspected leptospirosis outbreak was recognized among strawberry harvesters from Eastern Europe who were working in Germany. An investigation was initiated to identify the outbreak source and the risk factors for infection. METHODS We conducted a retrospective cohort study with use of a questionnaire administered to harvesters by health authorities in Romania, Slovakia, and Poland. Collected serum samples were tested by microscopic agglutination test and immunoglobulin M enzyme-linked immunosorbent assay. A case patient was defined as a person who worked in the strawberry field during the period 5 June-8 September 2007 and had leptospirosis-compatible symptoms and either an antibody titer 1:800 and a positive immunoglobulin M enzyme-linked immunosorbent assay result (for a confirmed case) or no serological confirmation (for a suspected case). Local rodents were examined for leptospirosis. RESULTS Among 153 strawberry harvesters, we detected 13 confirmed case patients who had test results positive for antibodies against Leptospira species serogroup Grippotyphosa and 11 suspected case patients (attack rate, 16%). Risk of disease increased with each day that an individual worked in the rain with hand wounds (odds ratio, 1.1; 95% confidence interval, 1.04-1.14) and accidental rodent contact (odds ratio, 4.8; 95% confidence interval, 1.5-15.9). Leptospires of the serogroup Grippotyphosa were isolated from the kidneys of 7 (64%) of 11 voles. CONCLUSIONS This is, to our knowledge, the largest leptospirosis epidemic to occur in Germany since the 1960s. Contact between hand lesions and contaminated water or soil and infected voles was the most likely outbreak source. The unusually warm winter of 2006-2007 supported vole population growth and contributed to this resurgence of leptospirosis in Germany. Because of ongoing climate change, heightened awareness of leptospirosis in temperate regions is warranted.

Characteristics and risk factors for symptomatic Giardia lamblia infections in Germany

BackgroundIn developed countries, giardiasis is considered a travel related disease. However, routine surveillance data from Germany indicate that >50% of infections were acquired indigenously. We studied the epidemiological characteristics of symptomatic Giardia infections acquired in Germany and abroad, and verified the proportion of cases acquired in Germany in order to investigate risk factors for sporadic autochthonous Giardia infections.MethodsWe identified Giardia cases notified by 41 local health authorities between February 2007 and January 2008 and interviewed them on their clinical symptoms, underlying morbidities, travel abroad and potential risk factors for the disease. We conducted a case-control-study including laboratory-confirmed (microscopy or antigen-test) autochthonous Giardia cases with clinical manifestations (diarrhoea, cramps, bloating) and randomly selected controls from the local population registry matched by county of residence and age-group (0-5, 6-19, ≥20 years). Secondary cases, controls with diarrhoea and persons who had travelled outside Germany in the three weeks prior to disease onset (exposure period) were excluded. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) using conditional logistic regression.ResultsOf 273 interviewed cases, 131 (48%) had not travelled abroad during the defined exposure period. Of these 131, 85 (65%) were male, 68 (54%) were living in communities with >100,000 inhabitants and 107 (83%) were aged 20 years or older. We included 120 cases and 240 controls in the case-control study. Cases were more likely to be male (aOR 2.5 CI 1.4-4.4), immunocompromised (aOR 15.3 CI 1.8-127) and daily consumers of green salad (aOR 2.9 CI 1.2-7.2). Contact with animals (pets/farm animals) and exposure to surface water (swimming/water sports) were not associated with symptomatic disease.ConclusionsA substantial proportion of Giardia lamblia cases in Germany are indigenously acquired. Symptomatic cases are significantly more likely to be immunocompromised than control persons from the general population. Physicians should consider Giardia infections among patients with no recent history of travel abroad, particularly if they have immune deficiencies. Green salads may be an important vehicle of infection. Information campaigns highlighting this food-borne risk should emphasise the risk to persons with immune deficiencies.

A Survey of Outpatient Antibiotic Prescribing for Cystitis

BACKGROUND In view of the currently increasing rates of antibiotic resistance, we studied the factors that affect the prescribing of specific antibiotics for uncomplicated cystitis in outpatient care. METHODS A nationwide cross-sectional survey of physicians in private practice in various specialties (internal medicine, general medicine, surgery, obstetrics/gynecology, child and adolescent medicine, otorhinolaryngology, dermatology, urology) was carried out in 2008. The sample was derived from the German state directories of medical specialists. RESULTS 1810 (60%) of the physicians surveyed reported that they made decisions about antibiotic treatment every day, with uncomplicated urinary tract infection as the most common diagnosis (715 physicians). The antibiotics that they prescribed most commonly for it were cotrimoxazole (61%) and fluoroquinolones (21%). The following factors were significantly associated with a preference for fluoroquinolones: being a gynecologist (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.80), location of practice in the former East Germany (OR 2.01, CI 1.16-3.46), a treatment strategy incorporating a switch from empirical to targeted treatment (OR 1.72, CI 1.02-2.90), and the stated intention of avoiding inconvenience to the patient (OR 2.14, CI 1.25-3.68). DISCUSSION Fluoroquinolones are no longer recommended as the drug of first choice for uncomplicated urinary tract infections because of the development of resistance, but are still commonly prescribed for it. ARS (Antibiotic Resistance Surveillance in Germany) publishes current regional and patient-group-specific resistance rates to promote good clinical practice and improve prescribing behavior.

Persistence of nasal colonisation with methicillin resistant Staphylococcus aureus CC398 among participants of veterinary conferences and occurrence among their household members: A prospective cohort study, Germany 2008–2014

There are only few data on the persistence and transmission of methicillin resistant Staphylococcus aureus (MRSA) of the clonal complex (CC) 398 among veterinarians and their household members. We therefore investigated the long-term colonisation with MRSA CC398 among participants of veterinary conferences in Germany in 2008/2009 and their household members. Forty-five initially MRSA CC398 positive and 180 initially MRSA CC398 negative conference participants were included in a longitudinal study. These persons and their household members were tested for nasal colonisation in 2011, 2012 and 2014. Of 31 continuously tested and initially MRSA CC398 positive participants only 8 (26%) were colonized with MRSA CC398at all 4 time points, 4 (13%) of them consistently with the same spa type. Among initially MRSA CC398 negative participants, 13 (7%) were tested MRSA CC398 positive at least once during the follow-up period. Data for household members at least at one time point were available for 185 households. Of these 21 (11%) households had one or more household member who tested positive for MRSA CC398at least once. The odds of household members to be MRSA CC398 positive was 12 times higher (95% confidence interval 4-37) when the conference participant tested MRSA CC398 positive in 2008/2009. This association remained strong when household members working in veterinary medicine or livestock farms were excluded. In summary, these data suggest that colonisation with MRSA CC398 is partially transient and that household members of MRSA CC398 colonized persons are at an increased risk of colonisation with MRSA CC398.

Veterinarians Visiting Swine Farms Are at High Risk for Colonization With Livestock-Associated Methicillin-Resistant Staphylococcus aureus

TO THE EDITOR—We congratulate Wardyn et al [1] for a well-conducted study on the association between swine farming and colonization with antibiotic-resistant Staphylococcus aureus. Similar to farmers, veterinarians are exposed to S. aureus in livestock. Several small studies from Europe have found a prevalence for colonization of veterinarians with livestockassociated methicillin-resistant S. aureus (LA-MRSA) between 1.4% and 44% [2]. We conducted a large cross-sectional study among participants of veterinary congresses in Germany in 2008 and 2009. Participants were sampled for LAMRSA colonization (as defined by attribution of isolates to clonal complex 398) by means of nasal swabs and asked to fill out a questionnaire. We calculated univariate and adjusted odds ratios using logistic regression modeling in STATA/SE13.1 (StataCorp, College Station, Texas). We tested all risk factors in the adjusted model that were significantly associated with the outcome in univariate analysis excluding apparently unrelated protective factors (ie, having a dog). We retained those that were significantly associated with LA-MRSA colonization. The study was approved by the ethical review board of the ethics committee of the Charité Hospital (Berlin, Germany) and conducted in accordance with the Helsinki Declaration. The participants provided written consent. Of 1453 participants, we excluded 18 (1%) who had missing questionnaires, 204 (14%) who were not veterinarians, and 536 (37%) who had not worked in herd health management within the previous year. This resulted in a final study population of 695 persons. In 64 (9%) of the participants, we found nasal colonization with LA-MRSA with the following co-resistances: tetracycline (98%), clindamycin (66%), erythromycin (64%), cotrimoxazol (42%), ciprofloxacin (22%), gentamicin (20%) and moxifloxacin (6%). None of the isolates from our study was resistant to glycopepetides, linezolid, or tigecycline. Factors associated with LA-MRSA include a number of occupational exposures, especially working with swine, but also a history of MRSA infection and contact with humanMRSA carriers (Table 1). Living in Lower Saxony, the German State with the highest pig density (http:// www.destatis.de); attending in pig farming; a history of MRSA infection; contact with a human MRSA carrier; and preferential use of tetracycline for group treatment, as well as fluorchinolones for individual animal treatment, remained independently associated with LA-MRSA in adjusted analysis (Table 1).

Molecular phylogeny of a novel human adenovirus type 8 strain causing a prolonged, multi-state keratoconjunctivitis epidemic in Germany

The German infectious disease surveillance system revealed an increase of epidemic keratoconjunctivitis (EKC) from an average of 320 cases/year (2001 to 2010) up to 2146 and 1986 cases in 2012 and 2013, respectively. From November 2011 until December 2013 (epidemic period) 85% of typed isolates were human adenovirus type 8 (HAdV-D8), whereas only low level circulation (19%) of HAdV-D8 was observed outside the epidemic period. In order to investigate whether a novel monophyletic HAdV-D8 strain prevailed during the epidemic period, complete genomic sequences of 23 HAdV-D8 isolates were generated by deep sequencing and analyzed phylogenetically. For comparison, eight HAdV-D8 isolates from outside the epidemic period were sequenced. HAdV-D8 isolates of the epidemic period had a very high sequence identity of at least 99.9% and formed a monophyletic cluster with two subclusters. A single outlier was closely related to HAdV-D8 strains isolated prior to the epidemic period. Circulation of the epidemic strain was detected as early as 2010 but not after the epidemic period in 2014. In conclusion, molecular phylogeny of complete genomic sequences proved a monophyletic HAdV-D8 epidemic. However, co-circulation of other HAdV types as well as better reporting may have contributed to the huge increase of reported cases.

The zoonotic potential of Clostridium difficile from small companion animals and their owners

Background Clostridium difficile infections (CDI) in humans range from asymptomatic carriage to life-threatening intestinal disease. Findings on C. difficile in various animal species and an overlap in ribotypes (RTs) suggest potential zoonotic transmission. However, the impact of animals for human CDI remains unclear. Methods In a large-scale survey we collected 1,447 fecal samples to determine the occurrence of C. difficile in small companion animals (dogs and cats) and their owners and to assess potential epidemiological links within the community. The Germany-wide survey was conducted from July 2012-August 2013. PCR ribotyping, Multilocus VNTR Analysis (MLVA) and PCR detection of toxin genes were used to characterize isolated C. difficile strains. A database was defined and logistic regression used to identify putative factors associated with fecal shedding of C. difficile. Results In total, 1,418 samples met the inclusion criteria. The isolation rates for small companion animals and their owners within the community were similarly low with 3.0% (25/840) and 2.9% (17/578), respectively. PCR ribotyping revealed eight and twelve different RTs in animals and humans, respectively, whereas three RTs were isolated in both, humans and animals. RT 014/0, a well-known human hospital-associated lineage, was predominantly detected in animal samples. Moreover, the potentially highly pathogenic RTs 027 and 078 were isolated from dogs. Even though, C. difficile did not occur simultaneously in animals and humans sharing the same household. The results of the epidemiological analysis of factors associated with fecal shedding of C. difficile support the hypothesis of a zoonotic potential. Conclusions Molecular characterization and epidemiological analysis revealed that the zoonotic risk for C. difficile associated with dogs and cats within the community is low but cannot be excluded.

Human pathogenic Clostridium difficile strains in companion animals detected in a Germany-wide survey

In food and food-producing animals monitoring of antimicrobial resistant bacteria is mostly conducted on commensal E. coli. From 2015 on in the EU also the selective isolation and subsequent resistance testing on ESBL/AmpC-producing E. coli is mandatory (2013/652/EU).Question: Domestic pigs and Eurasian wild boar (Sus scrofa) share several important viral and bacterial pathogens. Therefore, direct and indirect contacts between domestic pigs and wild boar present a risk of pathogen spill-over and can lead to long-term perpetuation of infection. Biological indicators could be a powerful tool to understand and characterize contacts between wild boar and domestic pigs. Here, faecal E. coli were explored as potential biological indicator under experimental conditions. Methods: Within an animal trial domestic pigs (group 2, n=8) were brought into contact with faecal material of wild boar (group 1, n=8). Before and three to five weeks after transmission of faeces fecal samples of both groups were collected, coliforme bacteria isolated, and the bacteria tested by CHEF-PFGE for clonal relatedness. The study was meant as test and calibration phase for potential field studies. Results: Eighty-eight individual E. coli clones were detected by XbaI restriction and PFGE analysis. Selecting only one isolates representing a distinct clone from an individual faecal sample, 123 E. coli isolates were further analysed. Overall, 17 different clones were found in several animals of a group (1 or 2) or both samples from one animal. Additionally, five clones were detected in group 1 as well as in contact group 2. Conclusions: The data gained in our pilot study suggest that faecal E. coli can be used as biological indicator of contact between wild boar and domestic pig. Based on these promising results, future field studies will especially target the practicability of E. coli microbiome molecular typing as surrogate of contacts at the wildlife-livestock interface. This study is funded by the European Unions Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 311931 (ASFORCE).

Survey zur ärztlichen Verschreibung von Antibiotika: Ergebnisse zur akuten Zystitis in der ambulanten Versorgung

BACKGROUND In view of the currently increasing rates of antibiotic resistance, we studied the factors that affect the prescribing of specific antibiotics for uncomplicated cystitis in outpatient care. METHODS A nationwide cross-sectional survey of physicians in private practice in various specialties (internal medicine, general medicine, surgery, obstetrics/gynecology, child and adolescent medicine, otorhinolaryngology, dermatology, urology) was carried out in 2008. The sample was derived from the German state directories of medical specialists. RESULTS 1810 (60%) of the physicians surveyed reported that they made decisions about antibiotic treatment every day, with uncomplicated urinary tract infection as the most common diagnosis (715 physicians). The antibiotics that they prescribed most commonly for it were cotrimoxazole (61%) and fluoroquinolones (21%). The following factors were significantly associated with a preference for fluoroquinolones: being a gynecologist (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.80), location of practice in the former East Germany (OR 2.01, CI 1.16-3.46), a treatment strategy incorporating a switch from empirical to targeted treatment (OR 1.72, CI 1.02-2.90), and the stated intention of avoiding inconvenience to the patient (OR 2.14, CI 1.25-3.68). DISCUSSION Fluoroquinolones are no longer recommended as the drug of first choice for uncomplicated urinary tract infections because of the development of resistance, but are still commonly prescribed for it. ARS (Antibiotic Resistance Surveillance in Germany) publishes current regional and patient-group-specific resistance rates to promote good clinical practice and improve prescribing behavior.