Chemokine profiling in children and adults with symptomatic and asymptomatic respiratory viral infections.

Molecular diagnosis; Viral infection; Chemokines; Disease prognosis; CXCL10; CXCL11; CCL3; CCL4; CCL5; Random forest.

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.

[Current dilemmas on the transmission of hepatitis E virus]. / Actuele dilemma's rond de transmissie van hepatitis E-virus.

Immunocompromised patients are especially at risk for developing chronic hepatitis E virus (HEV) infection, which may result in progressive liver disease and cirrhosis. In addition, treatment of chronic HEV infection in these patients often includes dose reduction of immunosuppressive therapy and this may lead to severe flare-ups of the underlying condition or even rejection of transplant material. Therefore prevention of HEV transmission is being more and more recognised as an essential step to stop increasing HEV seroprevalence. The Dutch National Institute for Public Health and the Environment (RIVM) has recently warned immunocompromised patients following haematopoietic stem cell and solid organ transplantations for the risk of infection by HEV through eating of contaminated products from pig meat. Furthermore, the Dutch blood bank recently decided to start screening all blood products for HEV to prevent iatrogenic transmission of HEV. We describe two patients with HEV infection and discuss risk of infection for immunocompromised patients, transmission routes and the importance of prevention of iatrogenic transfusion related transmission.

High-risk human papillomavirus detection in self-sampling compared to physician-taken smear in a responder population of the Dutch cervical screening: Results of the VERA study.

In 2017 the cervical cancer screening program in The Netherlands will be revised. Cervical smears will primarily be tested for the presence of high-risk human papillomavirus (hrHPV) instead of cytology, and vaginal self-sampling will be offered to non-responders. This includes a potential risk that part of the women who would otherwise opt for a cervical smear will wait for self-sampling. However, self-sampling for hrHPV in a responder population has never been studied yet. The aim of this study was to investigate the applicability and accuracy of self-sampling in detecting hrHPV in a screening responder population. A total of 2049 women, aged 30-60years, participating in the screening program in The Netherlands were included from April 2013 to May 2015. After they had their cervical smear taken, women self-collected a cervicovaginal sample with a brush-based device, the Evalyn Brush. Both the cervical smear and self-sample specimen were tested with the COBAS 4800 HPV platform. The hrHPV prevalence was 8.0% (95% CI 6.9-9.2) among the physician-taken samples, and 10.0% (95% CI 8.7-11.3) among the self-samples. There was 96.8% (95% CI 96.0-97.5) concordance of hrHPV prevalence between self-samples and physician-taken samples. Women in our study evaluated self-sampling as convenient (97.1%), user-friendly (98.5%), and 62.8% preferred self-sampling over a physician-taken sampling for the next screening round. In conclusion, self-sampling showed high concordance with physician-taken sampling for hrHPV detection in a responder screening population and highly acceptable to women. Implementation of HPV-self-sampling for the responder population as a primary screening tool may be considered.

Large two-centre study into the prevalence of Mycoplasma genitalium and Trichomonas vaginalis in the Netherlands.

Mycoplasma genitalium and Trichomonas vaginalis are common sexually transmitted infections (STIs). In the Netherlands, testing for M. genitalium and T. vaginalis is not recommended for first-line STI screening. Recent reports about the increasing antimicrobial resistance in M. genitalium raise concern about the adequacy of current empirical treatment regimens. It is necessary to have insight in the prevalence of M. genitalium and T. vaginalis in order to evaluate current first-line STI screening and treatment protocols. During a five-month period, samples sent to two large medical microbiology diagnostic centres in the Netherlands for STI screening (Chlamydia trachomatis and Neisseria gonorrhoeae) were retrospectively tested for the prevalence of M. genitalium and T. vaginalis using the Diagenode S-DiaMGTV kit. A total of 1569 samples from 1188 unique patients (55.4% female) were tested. M. genitalium was the second most prevalent STI detected (4.5% of the patients), after C. trachomatis (8.3%). T. vaginalis was detected in 1.4% of the patients, comparable to the prevalence of N. gonorrhoeae (1.3%). Dual infections were only detected in a small number of patients (1.0%). Incorporation of M. genitalium into routine STI screening should be considered, because of its relatively high prevalence, the consequences of its detection for antibiotic treatment and because of the availability of easy-to-use molecular diagnostic tests. For T. vaginalis, routine screening may be considered, depending on local prevalence and (sub)population.

Rapid detection of a norovirus pseudo-outbreak by using real-time sequence based information.

BACKGROUND: Sequence based information is increasingly used to study the epidemiology of viruses, not only to provide insight in viral evolution, but also to understand transmission patterns during outbreaks. However, sequence analysis is not yet routinely performed by diagnostic laboratories, limiting its use in clinical practice. OBJECTIVES: To describe the added value of sequence based information available within 3 days after the detection of norovirus in fecal samples of patients and personnel during a suspected outbreak on a hospital ward. Results were used to guide the implementation of appropriate infection control measures, in particular closure of the ward. STUDY DESIGN: Observational study. RESULTS: Norovirus infection was detected in seven patients and two health care workers on an oncology ward of the children's hospital. Six of seven patients had a hospital acquired infection defined as a first day of illness more than two days after admission. After notification of the first two patients, supplementary infection control measures were taken to prevent further spread. Despite these measures, three additional patients with norovirus infection were identified. Characterization of the noroviruses of 5 out of 7 patients was available within 7 days after the notification of the first patient. Four different genotypes were detected, providing evidence for multiple introductions of different norovirus strains with only a few secondary cases rather than ongoing nosocomial transmission. Therefore, we maintained the already implemented infection control interventions without closure of the ward. CONCLUSIONS: Sequence based information available in real-time is helpful for understanding norovirus transmission in the hospital and facilitates appropriate infection control measures during an outbreak.

The significance of rhinovirus detection in hospitalized children: clinical, epidemiological and virological features.

Recent developments in molecular diagnostic tools have led to the easy and rapid detection of a large number of rhinovirus (HRV) strains. However, the lack of clinical and epidemiological data hampers the interpretation of these diagnostic findings. From October 2009 to January 2011, we conducted a prospective study in hospitalized children from whom samples were taken for the detection of respiratory viruses. Clinical, epidemiological and microbiological data from 644 patients with 904 disease episodes were collected. When HRV tested positive, strains were further characterized by sequencing the VP4/VP2 region of the HRV genome. HRV was the single respiratory virus detected in 254 disease episodes (28%). Overall, 99 different serotypes were detected (47% HRV-A, 12% HRV-B, 39% HRV-C). Patients with HRV had more underlying pulmonary illness compared with patients with no virus (p 0.01), or patients with another respiratory virus besides HRV (p 0.007). Furthermore, cough, shortness of breath and a need for oxygen were significantly more present in patients with HRV infection. Particularly, patients with HRV-B required extra oxygen. No respiratory symptom, except for oxygen need, was predictive of the presence of HRV. In 22% of HRV-positive disease episodes, HRV infection was hospital acquired. Phylogenetic analysis revealed several clusters of HRV; in more than 25% of these clusters epidemiological information was suggestive of transmission within specific wards. In conclusion, the detection of HRV may help in explaining respiratory illness, particular in patients with pulmonary co-morbidities. Identifying HRV provides opportunities for timely implementation of infection control measures to prevent intra-hospital transmission.

Laboratory-based surveillance in the molecular era: the TYPENED model, a joint data-sharing platform for clinical and public health laboratories.

Laboratory-based surveillance, one of the pillars of monitoring infectious disease trends, relies on data produced in clinical and/or public health laboratories. Currently, diagnostic laboratories worldwide submit strains or samples to a relatively small number of reference laboratories for characterisation and typing. However, with the introduction of molecular diagnostic methods and sequencing in most of the larger diagnostic and university hospital centres in high-income countries, the distinction between diagnostic and reference/public health laboratory functions has become less clear-cut. Given these developments, new ways of networking and data sharing are needed. Assuming that clinical and public health laboratories may be able to use the same data for their own purposes when sequence-based testing and typing are used, we explored ways to develop a collaborative approach and a jointly owned database (TYPENED) in the Netherlands. The rationale was that sequence data - whether produced to support clinical care or for surveillance -can be aggregated to meet both needs. Here we describe the development of the TYPENED approach and supporting infrastructure, and the implementation of a pilot laboratory network sharing enterovirus sequences and metadata.

Sequence-based identification and characterization of nosocomial influenza A(H1N1)pdm09 virus infections.

BACKGROUND: Highly transmissible viruses such as influenza are a potential source of nosocomial infections and thereby cause increased patient morbidity and mortality. AIM: To assess whether influenza virus sequence data can be used to link nosocomial influenza transmission between individuals. METHODS: Dutch A(H1N1)pdm09-positive specimens from one hospital (N = 107) were compared with samples from community cases (N = 685). Gene fragments of haemagglutinin, neuraminidase and PB2 were sequenced and subsequently clustered to detect patients infected with identical influenza viruses. The probability of detecting a second patient was calculated for each hospital cluster against the background diversity observed in hospital and community strains. All clusters were further analysed for possible links between patients. FINDINGS: Seventeen A(H1N1)pdm09 hospital clusters were detected of which eight had a low probability of occurrence compared with background diversity (P < 0.01). Epidemiological analysis confirmed a total of eight nosocomial infections in four of these eight clusters, and a mother-child combination in a fifth cluster. The nine clusters with a high probability of occurrence involved community cases of influenza without a known epidemiological link. CONCLUSION: If a background sequence dataset is available, the detection of hospital sequence clusters that differ from dominant community strains can be used to select clusters requiring further investigation by hospital hygienists before a nosocomial influenza outbreak is epidemiologically suspected.

Influenza in the immediate post-pandemic era: a comparison with seasonal and pandemic influenza in hospitalized patients.

BACKGROUND: Comparative data on severity and treatment of seasonal, pandemic and post-pandemic influenza virus infections are scarce. OBJECTIVES: To systematically analyze characteristics of hospitalized patients with influenza in the post-pandemic period compared to seasonal and pandemic influenza. STUDY DESIGN: Clinical and virological data of patients hospitalized in a tertiary referral hospital with post-pandemic influenza (2010-2011) were compared with those during seasonal influenza epidemics (2007-2009) and the influenza A(H1N1)pdm09 pandemic (2009-2010). RESULTS: 82 patients were admitted during the post-pandemic period, compared to 85 during the pandemic and 60 during seasonal influenza epidemics. No differences were observed in the occurrence of complicated illness and the need for intensive care. However, radiographic pneumonia was significantly more often diagnosed in patients with influenza A(H1N1)pdm09 compared to patients with seasonal influenza A (25% versus 71% in pandemic, p=0.004, and 55% in post-pandemic, p=0.047). Oseltamivir was more frequently prescribed in post-pandemic and pandemic patients compared to previous influenza seasons (48.9% resp. 76.5% versus 6.5%, p<0.0001). During the post-pandemic period, patients with influenza B were significantly less often treated with oseltamivir compared to patients with influenza A (27.0% versus 48.9%, p=0.043), although the course of illness in patients with influenza B was comparable with influenza A. No upsurge of oseltamivir resistance was observed. CONCLUSIONS: In our center, severity of illness was comparable for all influenza seasons, although more radiographic pneumonia was diagnosed in patients with influenza A(H1N1)pdm09. Despite the increased use of oseltamivir, no increase in oseltamivir resistance was detected.

Seasonal patterns in time series of pertussis.

To gain insight into pertussis disease dynamics, we studied age-specific long-term periodicity and seasonality of pertussis in The Netherlands. Hierarchical time-series models were used to analyse the monthly reported pertussis incidence in January 1996-June 2006 by age group. The incidence of pertussis showed a slightly increasing long-term trend with highest incidence rates seen in 1996, 1999, 2001 and 2004. For all age groups the annual peak incidence was found in August, except for the 13-18 years age group where the peak occurred in November. Monthly trends in adults showed high correlation with trends in age groups 0-4 years (0.94) and 5-12 years (0.92). We found no evidence for a relationship between annual rises in pertussis and the opening of schools. Concurrent annual fluctuations of pertussis incidence in adults and infants suggest frequent transmission within and between these age groups. Studying trends offers insight into transmission dynamics and may facilitate decisions on future vaccination strategies.

[Climate change influences the incidence of arthropod-borne diseases in the Netherlands]. / Klimaatverandering beïnvloedt het vóórkomen in Nederland van ziekten overgebracht door teken, muggen en zandvliegen.

Climate change is associated with changes in the occurrence of arthropod-borne diseases. It is difficult to foresee which arthropod-borne diseases will appear in the Netherlands due to climate change. Climate change influences the prevalence of ticks and may lead to a further increase in Lyme disease and an increased risk of the introduction of rickettsioses. With further warming of the climate there is a real possibility of settlement of the mosquito Aedes albopictus and introduction of the sandfly in the Netherlands. Whether this will lead to circulation of micro-organisms transmitted by these vectors (e.g. West Nile virus, Dengue virus, Leishmania) is not clear. Continued vigilance is necessary, even for vector-borne diseases that appear to be less relevant for the Netherlands.

The value of ProMED-mail for the Early Warning Committee in the Netherlands: more specific approach recommended.

This article describes a retrospective and descriptive study into the added value of ProMED-mail--the global electronic reporting system for outbreaks of emerging infectious diseases and toxins maintained by the International Society for Infectious Diseases--as an early warning system for The Netherlands Early Warning Committee (NEWC). Information about infectious disease events in foreign countries originating from ProMED-mail was retrieved from the reports of the NEWC between May 2006 and June 2007. Each event was analysed in depth in order to determine if it could have been a possible threat to public health in The Netherlands. It was determined whether these events were mentioned in other sources of information used by the NEWC besides ProMED-mail. In addition, we assessed the possible consequences of missing an event when not reading ProMED-mail or of being informed of the event with a time delay. Semi-structured interviews with stakeholders were conducted to explore other functions of ProMED-mail besides early warning. Five out of 25 events reported in ProMED-mail were assessed as a potential threat to The Netherlands, mainly because of the known vulnerability of The Netherlands for vaccine preventable diseases: an outbreak of measles in the United Kingdom and Japan, a case of poliomyelitis in Kenya, and two events concerning Highly Pathogenic Avian Influenza (HPAI) H5N1. The outbreak of measles in Japan and one case of HPAI H5N1 infection in a bird in Germany were only reported by ProMED-mail; the other potential threats were mentioned in other sources with a time delay. ProMED-mail has a limited but real added value over other sources in the early warning of threats. A more specific approach of using ProMED-mail by defining vulnerabilities of a country would be useful and efficient. ProMED-mail is appreciated for providing background and preliminary outbreak information.

[Recent changes in the epidemiology of infectious diseases in the Netherlands: the report 'Status of infectious diseases in the Netherlands, 2000-2005']. / Recente veranderingen in de epidemiologie van infectieziekten in Nederland: het rapport 'Staat van infectieziekten in Nederland, 2000-2005'.

Based on the changes in the epidemiology of infectious diseases in the Netherlands in 2000-2005, it is possible to formulate a prediction for the immediate future. Developments that one may expect with a reasonable amount of certainty are a further rise in sexually transmitted diseases, continued vulnerability for infectious diseases for which the State Vaccination Programme distributes vaccines, a slow increase in bacterial resistance, an increase in opportunistic infections, and growing risks for the introduction of new micro-organisms via international travel and trade. Much less certain are the developments surrounding avian influenza A/H5N1, ticks and mosquitoes, the rise and spread of new diseases, and bioterrorism.

Recognition of threats caused by infectious diseases in the Netherlands: the early warning committee.

The early warning committee was established in order to recognise threats to public health caused by infectious diseases in the Netherlands in a timely and complete fashion. This article describes the outcome of a retrospective and descriptive evaluation into the completeness of the recognitions made by the early warning committee. Information about outbreaks of infectious disease in the Netherlands in 2002 and 2003, as reported in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine), and about infectious disease events in other countries, was compared with reports of the regular weekly meetings of the Dutch early warning committee. If an outbreak or a foreign event was not mentioned in the meetings of the early warning committee, the cause for this was established. For events in other countries, it was established on the basis of whether or not the event could have been a threat to public health in the Netherlands. All outbreaks of infectious disease in the Netherlands, published or mentioned in the Nederlands Tijdschrift voor Geneeskunde were discussed by the early warning committee. Three of the events occurring in other countries in 2002 had not been discussed by the committee although, based on the criteria for a potential threat to the Netherlands, they should have been: the outbreak of avian influenza A/H5N1 in domestic fowl in Hong Kong, the increase among hospitalised patients of carriers of extended-spectrum a-lactamase producing micro-organisms in Scotland, and outbreaks of measles in several countries. In 2003, all events in other countries that could have posed a threat to the Netherlands were discussed by the early warning committee. In 2002 and 2003, the early warning committee recognised nearly all threats due to infectious diseases and outbreaks of infectious diseases which were of national importance and published in various sources of literature.

[Recognition of the threats caused by infectious diseases in The Netherlands in 2002 and 2003 by the weekly meetings of the early warning committee]. / Signalering van bedreigingen door infectieziekten in Nederland in 2002 en 2003 door het wekelijkse signaleringsoverleg.

OBJECTIVE: To establish whether the meetings of the so-called 'early warning committee' recognise all the threats to the public health in the Netherlands caused by infectious diseases. DESIGN: Retrospective and descriptive evaluation. METHOD: The information about the outbreaks of infectious diseases in the Netherlands and about events in the area of infectious diseases in foreign countries was compared with the domestic and foreign reports discussed in the regular weekly meetings of the Dutch early warning committee. For this purpose, the authors summarized the outbreaks of infectious diseases in the Netherlands in 2002 and 2003 as reported in articles in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine). This summary was then compared with the domestic reports discussed in the meetings of the early warning committee. If an outbreak was not mentioned in the meetings of the early warning committee, the cause for this was established. For the same period, a summary was made of the foreign events in the area of infectious diseases and this was also compared with the foreign reports mentioned in the meetings of the early warning committee. When an event had not been discussed in the meetings of the early warning committee, it was established on the basis of criteria whether the event could have been a threat to public health in the Netherlands. RESULTS: All outbreaks of infectious diseases in the Netherlands had been discussed in the early warning committee. Of the foreign events in 2002, 3 had not been discussed in the committee although they should have been, based on the criteria for a potential threat to the Netherlands: the outbreak of avian influenza A/H5NI in domestic fowl in Hong Kong, the increase among hospitalised patients of carriers of extended-spectrum 3-lactamase producing micro-organisms in Scotland, and outbreaks of measles in several countries. In 2003, all foreign events that could have been a threat to the Netherlands were discussed in the early warning committee. CONCLUSION: In 2002 and 2003, the meetings of the early warning committee recognised practically all the outbreaks of and threats due to infectious diseases.