Eosinophilia à deux: a brain nagging souvenir from the Philippines.

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.

Rabies vaccinations: are abbreviated intradermal schedules the future?

Rabies is a deadly disease, and current preexposure vaccination schedules are lengthy and expensive. We identified nine studies investigating abbreviated schedules. Although initial responses were lower, accelerated adequate immune responses were elicited after booster vaccinations. Lower-dose (and therefore cheaper) vaccination schedules may constitute a valid alternative to current vaccination schedules.

The tropics and the crime they did not commit.

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.

[New infectious diseases in Europe; the effect of climate change, globalisation and human behaviour]. / Nieuwe infectieziekten in Europa.

Climate change directly and indirectly contributes to the emergence of vector and water borne infections. Other infectious diseases may be introduced to new geographical areas as a result of globalisation and changing human behaviour. Despite the still low absolute risk, the pathogenicity of some of these infections creates a significant challenge for clinicians. Awareness of changing disease epidemiology helps in timely recognition of such infections. Vaccination guidelines for emerging vaccine-preventable diseases, such as tick-borne encephalitis and leptospirosis, may need to be updated.

COVID-19 impact on EuroTravNet infectious diseases sentinel surveillance in Europe.

BACKGROUND: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers' health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. METHODS: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). RESULTS: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (-5.3%), rabies post-exposure prophylaxis (-2.8%), and dengue (-2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). CONCLUSIONS: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.

Rabid puppy-dog imported into the Netherlands from Morocco via Spain, February 2012.

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.

[Monkeypox, a new pandemic?] / Uitbraak van monkeypox: een nieuwe pandemie?

Monkeypox (MPX) is a disease caused by the monkeypox virus. It is a viral zoonotic disease, endemic in Central and West Africa. Human-to-human spread also occurs and is a feature of the current global outbreak. As far as we know, exponential transmission during this outbreak is not related to changed viral characteristics but due to multiple high-risk contacts in a subset of people that have contracted the virus, so far almost exclusively affecting men who have sex with men (MSM). Appropriate public health measures and increased alertness of all health care providers is needed to increase case-finding and decrease transmission. There is a real chance of MPX to become endemic in large parts of the world.

Type-specific risk factors and outcome in an outbreak with 2 different Clostridium difficile types simultaneously in 1 hospital.

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 type-specific 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.

Clostridium difficile infection in an endemic setting in the Netherlands.

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.

Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature.

Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.

Relatedness of human and animal Clostridium difficile PCR ribotype 078 isolates determined on the basis of multilocus variable-number tandem-repeat analysis and tetracycline resistance.

Totals of 102 and 56 Clostridium difficile type 078 strains of human and porcine origins, respectively, from four European countries were investigated by an optimized multilocus variable-number tandem-repeat analysis (MLVA) and for tetracycline susceptibility. Eighty-five percent of all isolates were genetically related, irrespective of human or porcine origin. Human strains were significantly more resistant to tetracycline than porcine strains. All tetracycline-resistant strains contained the Tn916-like transposon harboring the tet(M) gene. We conclude that strains from human and porcine origins are genetically related, irrespective of the country of origin. This may reflect a lack of diversity and/or common source.

Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands.

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.

Community-onset Clostridium difficile-associated diarrhoea not associated with antibiotic usage--two case reports with review of the changing epidemiology of Clostridium difficile-associated diarrhoea.

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.

[Epidemiology of Clostridium difficile PCR ribotype 027 in the Netherlands 2005-present and the emergence of other subtypes]. / De epidemiologie van clostridium difficile PCR-ribotype 027 in Nederland sinds 2005 en de opkomst van andere typen.

Outbreaks of Clostridium difficile associated diarrhoea (CDAD) involving the virulent PCRribotype 027, toxinotype III were first reported in the Netherlands in 2005. This ribotype has now been detected in 26 of the 97 hospitals in the Netherlands. In 13 of the hospitals, the introduction of ribotype 027 was linked to increased CDAD incidence; this was found in 2 hospitals since December 2006. Ribotype 027 has also been detected in to nursing homes. In 2007, no evidence of ribotype 27 was found in 6 of the 12 hospitals in which ribotype 027 was confirmed in 2005-2006 and an outbreak of CDAD had occurred. The incidence of CDAD increased again in 2 hospitals that had previously had the epidemic well under control. Meanwhile, other PCR ribotypes appear to be gaining ground in the Netherlands, some of which have the same virulent characteristics as ribotype 027. Notably, ribotype 078, which appears to be associated with livestock, is becoming increasingly common.

Update of treatment algorithms for Clostridium difficile infection.

BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI. AIM: To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies. SOURCES: A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017. CONTENT: We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C. difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n = 2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n = 5) or by capsules (n = 2). IMPLICATIONS: Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy.

Spread and epidemiology of Clostridium difficile polymerase chain reaction ribotype 027/toxinotype III in The Netherlands.

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.

How to: Establish and run a stool bank.

BACKGROUND: Since 2013, several stool banks have been developed following publications reporting on clinical success of 'faecal microbiota transplantation' (FMT) for recurrent Clostridium difficile infections (CDI). However, protocols for donor screening, faecal suspension preparation, and transfer of the faecal suspension differ between countries and institutions. Moreover, no European consensus exists regarding the legislative aspects of the faecal suspension product. Internationally standardized recommendations about the above mentioned aspects have not yet been established. OBJECTIVE: In 2015, the Netherlands Donor Feces Bank (NDFB) was founded with the primary aim of providing a standardized product for the treatment of patients with recurrent CDI in the Netherlands. Standard operation procedures for donor recruitment, donor selection, donor screening, and production, storage, and distribution of frozen faecal suspensions for FMT were formulated. RESULTS AND DISCUSSION: Our experience summarized in this review addresses current donor recruitment and screening, preparation of the faecal suspension, transfer of the faecal microbiota suspension, and the experiences and follow-up of the patients treated with donor faeces from the NDFB.

Monoclonal antibodies for the treatment of Ebola virus disease.

INTRODUCTION: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp™ and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients.

BACKGROUND: The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. MATERIALS AND METHODS: Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0-22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8(+) and CD4(+) T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8(+) T-cells were determined using class I tetramers. RESULTS: The geometric mean titre of neutralizing antibodies was not different between the groups (p = 0.77). The presence of YFV-specific CD4(+) and CD8(+) T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p = 0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8(+) T-cells (r = -0.66, p = 0.0045). Percentages of early-differentiated memory cells increased (r = 0.67, p = 0.017) over time. CONCLUSION: These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains.