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Background. Traveling the world may result in infection with tropical or other travel-associated diseases. This applies increasingly also to people with immune-compromising and other medical conditions, as well as to elderly individuals. To reduce exposure and susceptibility to health risks, there is a need for appropriate pre-travel advice for these particular groups of travelers. Methods. In this observational study, we analyzed the overall risk of health problems among travelers with underlying medical conditions who attended the University of Amsterdam's Academic Medical Center's (AMC) travel clinic from January to October 2010. Telephone questionnaires were administered to 345 travelers with underlying conditions and 100 healthy travelers. Results. The most common underlying medical conditions studied included: (1) diabetes mellitus; (2) impaired immunity due to use of immune-suppressing medication; (3) reduced gastric barrier; and (4) HIV infection. The overall incidence of travel-related diseases (TRDs) was higher among those patients with underlying medical conditions compared to healthy travelers [incidence rate ratio (IRR) 2.26, 95% CI (1.29–3.98)]. Of all diseases reported, gastrointestinal disease, fever, and respiratory problems were reported most frequently. Travel to Central America, South Central Asia, Northeast Asia, and North Africa was associated with increased risk of contracting TRD. Hepatitis B protection was absent or unknown in 75% of these travelers. Conclusions. Travelers with medical conditions had a higher risk of obtaining TRD, predominantly gastrointestinal in nature.

We encountered a case of severe murine typhus complicated by acute respiratory distress syndrome. To determine worldwide prevalence of such cases, we reviewed the literature and found that respiratory symptoms occur in ≈30% of murine typhus patients. In disease-endemic areas, murine typhus should be considered for patients with respiratory symptoms and fever.

Background. After reports of emerging outbreaks in Canada and the United States, Clostridium difficile-associated disease (CDAD) due to polymerase chain reaction ribotype 027 was detected in 2 medium-to-large hospitals in The Netherlands in 2005. Methods. National surveillance was initiated to investigate the spread and the epidemiology of CDAD. Microbiologists were asked to send strains recovered from patients with a severe course of CDAD or recovered when an increased incidence of CDAD was noted. A standardized questionnaire was used to collect demographic, clinical, and epidemiological patient data. Strains were characterized by polymerase chain reaction ribotyping, toxinotyping, the presence of toxin genes, and antimicrobial susceptibility. Results. During the period from February 2005 through November 2006, 1175 stool samples from 863 patients were sent from 50 health care facilities. Of these patients, 218 (25.3%) had CDAD due to ribotype 027, and 645 patients (74.7%) had CDAD due to other ribotypes, mainly 001 (17.8%) and 014 (7.2%). Polymerase chain reaction ribotype 027 was more frequently present in general hospitals than in academic hospitals (odds ratio [OR], 4.38; 95% confidence interval [CI], 1.60-12.0). Outbreaks of CDAD were observed in 10 hospitals and in 1 nursing home. Patients infected with ribotype 027 were significantly older (OR, 2.18; 95% CI, 1.43-3.33), and significantly more patients used fluoroquinolones (OR, 2.88; 95% CI, 1.01-8.20), compared with those who were infected with other ribotypes. Clear trends were observed for more severe diarrhea (OR, 1.99; 95% CI, 0.83-4.73), higher attributable mortality (6.3% vs. 1.2%; OR, 3.30; 95% CI, 0.41-26.4), and more recurrences (OR, 1.44; 95% CI, 0.94-2.20). Conclusions. Ribotype 027 was found in 20 (18.3%) of 109 hospitals in The Netherlands, with a geographic concentration in the western and central parts of the country. The clinical syndrome in patients with CDAD differed on the basis of ribotype. Thus, early recognition of the ribotype has benefits.

In recent years, requests for rabies immunoglobulin have increased at Amsterdam's Academic Medical Center's travel clinic. Travellers who received rabies pre-exposure prophylaxis (PrEP) before travel departure have immunological memory that can quickly be activated by timely booster vaccinations after possible exposure to rabies. PrEP alleviates the need for costly and scarcely available rabies immunoglobulin in case of exposure. This study describes which travellers are at risk of rabies exposure and would benefit from PrEP. The secondary aim was to specify which factors influence decision-making on taking PrEP. We reviewed electronic patient files of travellers attending our clinic for rabies post-exposure prophylaxis between January 2009 and February 2014. Demographic and travel characteristics were compared with a sample of patients who were seen for pre-travel advice at our clinic. To assess which factors had influenced the decision to take PrEP, a questionnaire survey was conducted. A total of 161 travellers experienced animal-associated injury. Compared with travellers from the pre-travel database, more people travelled to Southeast Asia (49.5% vs. 30.9%, p = 0.035) for comparable time periods (median 21 vs. 21 days, p = 0.083). Transcutaneous injuries (type III) were common (73.9%), most often inflicted by dogs (45%). Only ten travellers (6.2%) had received PrEP. Barriers for PrEP were high costs and a short time interval between consultation and travel departure. Travellers t o Southeast Asia should particularly be informed about rabies and the possibility of PrEP. Long-term travel was not associated with a higher risk of rabies exposure

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis. Although a rare condition among travelers, increased travel and global transportation of food products may result in more cases across non-endemic, developed countries in the future. We here describe two men with headache and painful skin after visiting the Philippines as presenting symptoms. Subsequently, confusion and focal neurologic symptoms developed. Both had increased serum eosinophils; however, CSF eosinophilia was only demonstrated after repeated lumbar puncture. In the CSF of both, Angiostrongylus spp. DNA was detected. Both were treated with albendazole combined with corticosteroids, after which symptoms improved.

Background The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. Conclusions The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added., Daniela Bezemer and colleagues investigate the extent to which the resurgent HIV epidemic in the Netherlands is the result of newly introduced strains, or of growth of already circulating strains., Editors' Summary Background Since the first recorded case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. Now, three and a half decades later, about 35 million people (more than half of whom are women) are infected with HIV, the virus that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner, and, globally, most sexual transmission of HIV occurs during heterosexual sex. Nevertheless, many new HIV infections still occur in men who have sex with men (MSM; homosexual, bisexual, and transgender men, and heterosexual men who sometimes have sex with men), and, in some countries, HIV/AIDS still predominantly affects the MSM community. In the US, for example, 78% of new HIV infections occurred among MSM in 2010 although MSM represent only 4% of the total population, and, in 2011, 54% of all people living with HIV were MSM. Indeed, despite HIV-positive individuals being diagnosed earlier these days and having access to effective combination antiretroviral therapy (cART), which both halts disease progression and reduces the risk of HIV transmission, the HIV epidemic among MSM is resurgent (growing again) in many Western countries. Why Was This Study Done? To control this resurgent epidemic, it is important to know as much as possible about HIV transmission among MSM so that effective prevention strategies can be designed. Here, the researchers use phylogenetic analysis and mathematical modeling to ask whether the introduction of new strains or the spread of already circulating strains is responsible for the resurgent HIV-1 subtype B epidemic occurring among MSM in the Netherlands. Viral phylogenetic analysis infers evolutionary relationships between viral strains by examining their genetic relatedness and can be used to identify HIV transmission clusters. HIV-1 viruses are classified into subtypes based on their genetic sequence and geographical distribution. HIV-1 subtype B is a common subtype that is found in west and central Europe, the Americas, and several other regions. What Did the Researchers Do and Find? The researchers built a phylogenetic tree for the HIV epidemic in MSM in the Netherlands by analyzing HIV-1 subtype B polymerase gene sequences found in 5,852 participants (73% of whom were MSM) in the ATHENA cohort, an observational cohort of all HIV-1-infected patients in care in the Netherlands since 1996 (when cART became available). Examination of this tree identified 106 large transmission clusters (groups of ten or more closely related subtype B HIV-1 strains). Half of the HIV-1 polymerase sequences from HIV-1-positive MSM registered in the ATHENA cohort in the Netherlands were included in 91 MSM-majority clusters: large transmission clusters in which more than half the related sequences originated from MSM. At least 54 of the MSM-majority clusters were circulating before 1996 and have persisted until the present day. Moreover, about a third of new HIV infections diagnosed among MSM since 1996 involve viruses included in these long-lived clusters. The researchers then used mathematical modeling to estimate that the effective reproduction number (the number of secondary infections per primary infection) for all the MSM-majority clusters was around one for the whole study period. Thus, these clusters were self-sustaining and not contracting. Notably, MSM-majority clusters (particularly the newer clusters) tended to have higher reproduction numbers in recent years. Moreover, although the average age at diagnosis within each of the MSM-majority clusters increased over the study period at a rate of 0.45 years/year, the average age at diagnosis was lower at initiation of new clusters and only increased by 0.28 years/year. What Do These Findings Mean? These findings suggest that several large, persistent, and self-sustaining sub-epidemics, many of which have been present since early in the AIDS epidemic, are driving the resurgent HIV epidemic among MSM in the Netherlands, despite the widespread availability of treatment, increasing rates of diagnosis, and earlier treatment initiation. Importantly, however, these findings also suggest that some sub-epidemics have emerged more recently and that some sub-epidemics, particularly the newer ones, are growing and may be preferentially affecting younger MSM. The accuracy of these findings may be limited by some aspects of the study. For example, the reproduction number estimates assume that the time from diagnosis of a case to the diagnoses of secondary cases is similar across clusters. Nevertheless, the new insights provided by this study should help guide the development of strategies to curb the resurgent HIV epidemic that is currently affecting MSM in the Netherlands and elsewhere. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001898. The US Centers for Disease Control and Prevention provides information on all aspects of HIV/AIDS, including information on HIV/AIDS among MSM (in English and Spanish) NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings, including information on HIV and MSM and personal stories from MSM living with HIV Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including MSM and HIV; Avert also provides personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS, including HIV/AIDS and MSM (in several languages) The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it A 2011 World Bank Report The Global HIV Epidemics among Men Who Have Sex with Men is available A PLOS Computational Biology Topic Page (a review article that is a published copy of record of a dynamic version of an article in Wikipedia) about viral phylodynamics is available

Since mid-2015, a rapidly expanding outbreak of Zika virus infection is spreading across Latin America and the Caribbean. Although Zika virus infection usually causes only mild disease, the World Health Organization has declared the epidemiological association with the occurrence of congenital microcephaly and neurological complications a 'Public Health Emergency of International Concern' and urged the international community to mount a coordinated international response aimed to protect people at risk, especially pregnant women. In December 2015, the first case of imported Zika virus infection in the Netherlands was diagnosed in a returned traveler from Surinam. To date, more than 20 cases have been reported in The Netherlands, all imported from Surinam. We describe the epidemiology, clinical aspects, diagnostic challenges and the existing evidence to date that link Zika virus infection to complications

Travellers to tropical destinations who seek medical attention after returning to their home country often present with fever, frequently as a result of an imported infectious disease. For this reason, clinicians initially focus on an infectious cause when a clear relationship in time exists between travel and disease onset. We present a case of a patient, who developed fever 2 weeks after his return from Ghana and who was finally diagnosed with an auto-immune disease: arteritis of the large arteries. This case illustrates that broad differential diagnostic thinking is paramount in the assessment of returned travellers.

Background Hepatitis A vaccines are highly immunogenic in healthy patients, but there is uncertainty about their immunogenicity in immunocompromised patients. Methods Our study included immunocompromised patients who received 1 or 2 hepatitis A vaccinations between January 2011 and June 2013. We assessed factors that influenced the serologic response to vaccination. We performed a literature review of previous studies on hepatitis A vaccination in immunocompromised patients. Results Of 85 immunocompromised patients, 65 used immunosuppressive drugs, 13 had received stem cell transplants, and 7 were infected with human immunodeficiency virus. After vaccination, 65 of 85 (76.5%) developed antibodies. Tumor necrosis factor α blocker use was associated with better serologic responses than other immunosuppressive drugs. Female patients were more compliant than male patients with postvaccination antibody titer measurements. In 11 relevant studies, antibody responses after the first and second vaccination averaged 37% and 82%, respectively. Factors that negatively influenced serologic response rates were high doses of immunosuppressive drugs, fewer hepatitis A vaccinations, and a short interval between vaccination and antibody measurement. Conclusions Immunocompromised patients showed moderate to good serologic responses to hepatitis A vaccination, but may need more time to develop immunity. Tumor necrosis factor α blocker use was associated with better antibody responses than other drugs. Specifically, male patients should be motivated to return for antibody titer measurements.

Rickettsioses are a diverse group of bacterial infections of the genus Rickettsia which are transmitted by arthropods. They are increasingly being recognised as the cause of acute febrile illness in travellers and in the inhabitants of tropical areas. In general, rickettsial disease should be considered if a patient presents with an acutely occurring febrile illness within less than 3 weeks of leaving an area where it is endemic. Other possible symptoms include malaise, myalgia, headache, and skin rash. An inoculation eschar is strongly suggestive of the diagnosis, but is often absent. As antibodies can sometimes only be demonstrated late in the disease process or after recovery, antibiotic therapy should be started as soon as the diagnosis is suspected on clinical grounds.

Background. Mortality among patients with Clostridium difficile infection (CDI) is high. Because of high age and multiple underlying diseases, CDI-related mortality is difficult to estimate. We estimated CDI-related mortality in an endemic situation, not influenced by outbreaks and consequently certain patients and C. difficile strains. Methods. Between 2006 and 2009, 13 Dutch hospitals included all hospitalized CDI patients. Nine hospitals individually matched each CDI patient to 2 control patients, based on ward and time of CDI hospitalization. Survival status was obtained via the Dutch Civil Registration System. Kaplan-Meier and Cox regression were used for survival analysis. Results. We identified 1366 patients with CDI (1.33 per 1000 admissions). All-cause mortality risk was 13% after 30 days and 37% after 1 year. The highest mortality was seen among elderly patients and patients with polymerase chain reaction ribotype 027. Three hundred seventeen CDI patients were matched to 317 patients without diarrhea and 232 patients with diarrhea, with a 30-day mortality risk of 5.4% and 8.6%, respectively. CDI patients had a 2.5-fold increased 30-day mortality rate compared to controls without diarrhea (hazard ratio 2.5 [95% confidence interval, 1.4–4.3]) when adjusted for age, sex, and underlying diseases. CDI-related death occurred mainly within 30 days after diagnosis. Conclusions. Mortality among CDI patients is high, even in an endemic situation. Our results show that CDI is associated with to a 2.5-fold increase in 30-day mortality. This highlights the considerable disease burden and clinical impact of CDI, even in absence of an outbreak.

Background: Blastocystis sp. are among the most commonly observed intestinal parasites in routine clinical parasitology. Blastocystis in humans consists of at least 9 genetic subtypes. Different subtypes of Blastocystis may be associated with differences in pathogenicity and symptomatology.Methods: Advanced microscopy on two samples and sequence-confirmed PCR on a third sample from the same individual were used for Blastocystis diagnosis and subtype analyses on routine clinical samples in a university hospital.Results: With a combined gold standard of sequence-confirmed PCR and positive advanced microscopy, 107 out of 442 (24.2%) patients were diagnosed with Blastocystis. infection, which is a high frequency of detection in comparison to previous reports from industrialized countries. The sensitivity of microscopy and sequence-confirmed PCR was 99.1% (106/107) and 96.3% (103/107), respectively.Among 103 typable samples, subtype 3 was most abundant (n = 43, 42%), followed by subtypes 1 and 2 (both n = 23, 22%), subtype 4 (n = 12, 12%), and single samples with subtypes 6 (1%) and subtype 7 (1%). The prevalence of Blastocystis infection was 38% in patients from the Department of Tropical Medicine and 18% in patients from other departments.Conclusions: A high prevalence of Blastocystis infection was found with both advanced microscopy and sequence-confirmed PCR in our patient population. Most cases were caused by subtypes ST1, ST2, ST3 and ST4. A significantly higher prevalence was found among patients with a history of recent travel to tropical countries. © 2013 Bart et al. licensee BioMed Central Ltd., SCOPUS: ar.j, info:eu-repo/semantics/published

The aim of this study was to assess the applicability and benefits of the new WHO dengue fever guidelines in clinical practice, for returning travellers.We compared differences in specificity and sensitivity between the old and the new guidelines for diagnosing dengue and assessed the usefulness in predicting the clinical course of the disease. Also, we investigated whether hypertension, diabetes or allergies, ethnicity or high age influenced the course of disease.In our setting, the old classification, compared with the new, had a marginally higher sensitivity for diagnosing dengue. The new classification had a slightly higher specificity and was less rigid. Patients with dengue who had warning signs as postulated in the new classification were admitted more often than those who had no warning signs (RR, 8.09 [1.80-35.48]). We did not find ethnicity, age, hypertension, diabetes mellitus or allergies to be predictive of the clinical course.In our cohort of returned travellers, the new classification system did not differ in sensitivity and specificity from the old system to a clinically relevant degree. The guidelines did not improve identification of severe disease.

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.

Background: Clostridium difficile infections (CDIs) are common in developed countries and affect .250000 hospitalized patients annually in the USA. The most important risk factor for the disease is antibiotic therapy. Methods: To determine the period at risk for CDI after cessation of antibiotics, we performed a multicentre case –control study in the Netherlands between March 2006 and May 2009. Three hundred and thirty-seven hospitalized patients with diarrhoea and a positive toxin test were compared with 337 patients without diarrhoea. Additionally, a control group of patients with diarrhoea due to a cause other than CDI (n¼ 227) was included. Results: In the month prior to the date of inclusion, CDI patients more frequently used an antibiotic compared with non-diarrhoeal patients (77% versus 49%). During antibiotic therapy and in the first month after cessation of the therapy, patients had a 7 –10-fold increased risk for CDI (OR 6.7 –10.4). This risk declined in the period between 1 and 3 months after the antibiotic was stopped (OR 2.7). Similar results were observed when the second control group was used. All antibiotic classes, except first-generation cephalosporins and macrolides, were associated with CDI. Second- and third-generation cephalosporins (OR 3.3 and 5.3, respectively) and carbapenems (OR 4.7) were the strongest risk factors for CDI. Patients with CDI used more antibiotic classes and more defined daily doses, compared with non-diarrhoeal patients. Conclusions: Antibiotic use increases the risk for CDI during therapy and in the period of 3 months after cessation of antibiotic therapy. The highest risk for CDI was found during and in the first month after antibiotic use. Our study will aid clinicians to identify high-risk patients.

Background. Clostridium difficile infection (CDI) due to polymerase chain reaction (PCR) ribotype 027 (type 027) has been described worldwide. In some countries, an increase was reported of toxin A‐negative PCR ribotype 017 (type 017). We encountered an outbreak due to these 2 types occurring simultaneously in a 980-bed teaching hospital in the Netherlands. Methods. In a case-control study from May 2005 through January 2007, we investigated general and typespecific risk factors as well as outcome parameters for CDI due to type 027 or 017. Clonal dissemination was investigated by multilocus variable number of tandem repeat analysis (MLVA). Results. We identified 168 CDI patients: 57 (34%) with type 017, 46 (27%) with type 027, and 65 (39%) with 1 of 36 different other types. As controls, we included 77 non-CDI diarrheal patients and 162 patients without diarrhea. Risk factors for CDI were nasogastric intubation, recent hospitalization, and use of cephalosporins and clindamycin. Type-specific risk factors were older age for both types 017 and 027, use of clindamycin and immunosuppressive agents for type 017, and use of fluoroquinolones for type 027. At day 30 of follow-up, the overall mortality among patients with types 017, 027, other types, non-CDI diarrheal patients, and nondiarrheal patients was 23%, 26%, 3%, 2%, and 6%, respectively. MLVA showed persistent clonal dissemination of types 017 and 027, despite appropriate infection control measures. Conclusions. Patients with CDI have type-specific risk factors and mortality rates, with prolonged clonal spread of type 027 or 017.

Since 2002, increasing rates of nosocomial Clostridium difficile infection (CDI) with a more severe course, higher mortality, and more complications have been reported in Canada, USA and Europe. One specific strain (PCR ribotype 027, REA-group BI, PFGE-type NAP1) was identified and accounted for at least half of the isolates. CDI can be prevented by robust infection control practice and prudent antibiotic use. In an outbreak setting it is often practical to combine multiple different CDI interventions which may consist of increased and early case finding, expanded infection-control measures, and antibiotic stewardship. Antimicrobials to be targeted ideally should be based on the local epidemiology and the C. difficile strains present, but restricting the use of cephalosporins and clindamycin have been the most effective. The results of fluoroquinolone restriction have been varied and may be of particular importance for outbreaks associated with the hyper-virulent PCR ribotype 027 strains.

The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case–control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high.

To describe the epidemiological characteristics of Clostridium difficile infection (CDI) in the Netherlands.Descriptive.After the first outbreaks in 2005 of Clostridium difficile infection (CDI) due to the hypervirulent PCR ribotype 027, a national reference laboratory was started in the Leiden University Medical Centre for typing and characterisation of C. difficile. Data were obtained from this national reference laboratory and from a continuous surveillance in 14 Dutch hospitals. The study period was January 2008-June 2009.In 2008, the incidence of CDI was 18 per 10.000 admissions (range: 14-23) in the 14 participating hospitals in the national surveillance study. In the study period, a total of 1867 cases of CDI were reported from 63 centres. The number of CDI outbreaks caused by type 027 decreased in the period January 2008 to June 2009, compared to the preceding years: type 027 was the cause of outbreaks in 4 Dutch hospitals in 2008-2009, whereas all 14 hospitals experienced an outbreak due to this type in the period 2005-2007. Although no systemic surveillance has been carried out in nursing homes, 24 Dutch nursing homes reported outbreaks of C. difficile in the period 2005-2009, in 12 of which type 027 was isolated. There was an increase of CDI detected in patients with diarrhoea outside health care facilities which appeared to coincide with the emergence of other types. In particular, type 078 increased since the end of 2006 and became the third most frequent type in the Netherlands. This type has also been recognised since 2007 as an important cause of CDI infection in animals, especially pigs. Recently there have also been reports that at least a third of the patients with CDI outside health care institutions do not have known risk factors for CDI such as an underlying disease, recent hospitalization or antibiotic use.CDI can also develop in the community The general practitioner should consider C. difficile in the differential diagnosis of elderly patients with diarrhoea.

After the first outbreaks of Clostridium difficile PCR ribotype 027 (North American pulsed-field type 1, restriction endonuclease analysis group BI) in the Netherlands in 2005, a national surveillance programme for C. difficile infection (CDI) was started. Furthermore, national guidelines were developed to rapidly recognise type 027 infections and prevent further spread. The mean incidence of CDI measured in 14 hospitals remained stable throughout the years: an incidence of 18 per 10,000 admissions was seen in 2007 and 2008. Between April 2005 and June 2009 a total of 2,788 samples were available for PCR ribotyping. A decrease was seen in the number and incidence of type 027 after the second half of 2006. In the first half of 2009, the percentage of type 027 isolates among all CDI decreased to 3.0%, whereas type 001 increased to 27.5%. Type 014 was present in 9.3% of the isolates and C. difficile type 078 slightly increased to 9.1%. We conclude that currently there is a significant decrease in type 027-associated CDI in the Netherlands.

Summary In diseased piglets from two Dutch pig-breeding farms with neonatal diarrhoea for more than a year, culture and PCR analyses identified the involved microorganism as Clostridium difficile PCR ribotype 078 harbouring toxin A (tcdA) and B (tcdB), and binary toxin genes. Isolated strains showed a 39 bp deletion in the tcdC gene and they were ermB gene-negative. A number of 11 porcine and 21 human isolated C. difficile PCR ribotype 078 toxinotype V strains were found genetically related by multiple-locus variable-number tandem-repeat analysis (MLVA). Moreover, a clonal complex was identified, containing both porcine and human isolates. The porcine isolates showed an antimicrobial susceptibility profile overlapping that of isolates from Dutch human patients. On the basis of these pheno- and genotypical analyses results, it was concluded that the strains from affected piglets were indistinguishable from increasingly encountered C. difficile PCR ribotype 078 strains of human C. difficile infections in the Dutch population and that a common origin of animal and humans strains should be considered.

BACKGROUND: Since 2005, an increase in the prevalence of Clostridium difficile infection (CDI) due to polymerase chain reaction ribotype 078 has been noticed in The Netherlands. This strain has also been identified as the predominant strain in pigs and calves. METHODS: CDI caused by type 078 was studied in relation to CDI caused by the hypervirulent type 027 and by types other than 027 and 078. Human and porcine isolates were further investigated and characterized by multilocus variable number tandem repeat analysis. RESULTS: From February 2005 through February 2008, the incidence of type 078 among isolates obtained from 1687 patients increased from 3% to 13%. Compared with patients infected with type 027, patients infected with type 078 were younger (67.4 vs. 73.5 years; P < .01) and more frequently had community-associated disease (17.5% vs. 6.7%; odds ratio, 2.98; 95% confidence interval, 2.11-8.02); rates of severe diarrhea (38.9% vs. 40.0%) and attributable mortality (3.8% vs. 4.0%) were similar in both groups. Compared with patients infected with other types, patients infected with type 078 more frequently received fluoroquinolone therapy (29.4% vs. 19.8%; odds ratio, 2.17; 95% confidence interval, 1.06-4.44). Type 078 isolates contained genes for toxin A, toxin B, binary toxin, and a 39-base pair deletion in toxin regulator gene (tcdC), as well as a point mutation at position 184, resulting in a stop codon. Multilocus variable number tandem repeat analysis of 54 human and 11 porcine isolates revealed 4 clonal complexes containing both porcine and human isolates. CONCLUSIONS: CDI due to type 078 and CDI due to type 027 present with similar severity, but CDI due to type 078 affects a younger population and is more frequently community associated. C. difficile type 078 isolates from humans and pigs are highly genetically related.

In a recent paper, Keel and colleagues concluded that Clostridium difficile PCR ribotype 078 was the most common PCR ribotype among isolates from swine (83% of 119 isolates) and isolates from calves (94% of 33 isolates) in The United States ([1][1]). In contrast, only 1 of 23 human isolates

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

1 National Institute of Population Research and Training (NIPORT), Mitra and Associates, ORC Macro. Bangladesh demographic and health survey 1999/2000. Dhaka and Calverton: National Institute of Population Research and Training (NIPORT), Mitra and Associates, and ORC Macro, 2001: 197. 2 Donner A, Klar N. Statistical considerations in the design and analysis of community intervention trials. J Clin Epidemiol 1996; 49: 435–39.

In February 2012 a rabid puppy dog was imported into Amsterdam, the Netherlands from Morocco via Spain. In a joint action between the Netherlands’ Food and Consumer Product Safety Authority, the Public Health Service of Amsterdam and the Centre for Infectious Disease Control all exposed human and animal contacts were traced and, when necessary, provided with post-exposure prophylaxis. During the importation, the international legislations with respect to vaccination requirements were not fully obeyed by veterinarians and custom services.

The emergence of hypervirulent strains of Clostridium difficile causing outbreaks in hospitals and nursing homes may result in a greater than before spread of the bacterium in the community. By consequence, the incidence of community-onset cases of Clostridium difficile-associated diarrhoea (CDAD) may increase outside known risk groups that are currently characterised by prior hospitalisation, prior antibiotic usage, older age and significant comorbidity. Here, we describe two case histories of community-onset CDAD. The first concerns a previously healthy young female with community-acquired CDAD without recent hospitalisation or antibiotic usage. The second patient developed diarrhoea in the community after discharge from a hospital where--in retrospect--an outbreak of CDAD occurred. The cases illustrate that CDAD should be included in the differential diagnosis of patients seeking care for community-onset diarrhoea, even in those without characteristic risk factors for CDAD

M. P. Grobusch, A. Goorhuis, R. W. Wieten, J. D. M. Verberk, E. F. F. Jonker, P. J. J. van Genderen and L. G. Visser 1) Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, 2) Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden and 3) Institute for Tropical Diseases, Harbour Hospital Rotterdam, Rotterdam, the Netherlands E-mail: m.p.grobusch@amc.uva.nl Article published online: 13 July 2013