Jan Groen

A newly discovered human pneumovirus isolated from young children with respiratory tract disease.

From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.

SACRAL NERVE NEUROMODULATION IN THE TREATMENT OF PATIENTS WITH REFRACTORY MOTOR URGE INCONTINENCE: LONG-TERM RESULTS OF A PROSPECTIVE LONGITUDINAL STUDY

PURPOSE Conservative treatment rarely results in a durable cure of patients with urge incontinence and bladder overactivity. Instrumental and surgical procedures often have significant side effects and less than optimal results. We developed a technique of sacral nerve neuromodulation using chronic unilateral electrical stimulation of the S3 sacral nerve to inhibit the micturition reflex to provide effective nondestructive alternative therapy for patients whose condition is refractory to conservative treatment. MATERIALS AND METHODS Of 85 patients 45 who responded to a test with a temporary electrode underwent implantation of a permanent S3 sacral nerve electrode coupled to a pulse generator. Treatment results were evaluated by urodynamic studies and voiding/incontinence diaries documenting pad use, incontinence episodes, voiding frequency and voided volume. Partial success and cure were defined as 50% to 90% and more than 90% improvement, respectively, in pad use and/or incontinence episodes. RESULTS Of 45 patients 18 (40%) were cured at an average followup of 47.1 months and 9 (20%) achieved partial success. Median number of pads used and median number of incontinence episodes daily had decreased from 5.4 to 1.2 (p = 0.0001) and 7.1 to 1.3 (p = 0.0001), respectively, 6 months after implantation. Subsequently these results remained almost constant for 5 years. Bladder overactivity disappeared in 19 of the 44 patients (43%). The repeat intervention rate was 37.7% and there was no permanent injury or nerve damage. CONCLUSIONS Sacral nerve neuromodulation is safe, effective and durable in patients with urge incontinence refractory to conservative treatment.

Diagnosing visceral leishmaniasis with the recombinant K39 strip test: Experience from the Sudan

We compared a strip test employing recombinant K39 (rK39) antigen and protein A/colloidal gold as read‐out agents with the rK39 ELISA for IgM and IgG antibodies and the direct agglutination test (DAT) using 55 sera from patients with parasitologically confirmed visceral leishmaniasis (VL). The rK39 strip test was positive in 37/55 (67%), the DAT in 50/55 (91%) at ≥ 1 : 1600 cut‐off value and in 47/55 (85%) at ≥ 1 : 6400 cut‐off value. The rK39‐ELISA gave positive IgG results for all sera; those who had a positive strip test had significantly higher IgG levels than those with a negative strip test (31.1 (SD=3.6) and 17.7 U/ml (SD=9.8), respectively, P < 0.0001). A total of 31/55 (56%) sera showed a positive IgM result; of these 27 (49%) had a positive strip test. We tested 115 apparently cured VL patients with the strip test during follow‐up; 68 were also tested with DAT. In the strip test, 25–43% of patients had a positive result at time points 3, 6, 9 and 12 months after treatment; for DAT (cut‐off ≥ 1 : 1600) these results were 67–83%. In neither test did a significant decrease in positivity rates occur over time (P=0.37 for the strip test, P=0.17 for the DAT). No correlation (P=0.33) was found between a positive strip test and a positive DAT result (cut‐off ≥ 1 : 1600), indicating that the strip test and DAT are complementary rather than interchangeable. Of 61 endemic controls two (3%) had a positive strip test result; both had a positive leishmanin skin test. The rK39 strip test has the ideal format for use in the field, but its sensitivity is limited; like DAT, but to a lesser extent, it remains positive after treatment.

Likelihood-Based Cointegration Analysis in Panels of Vector Error-Correction Models

We propose a likelihood-based framework for cointegration analysis in panels of a fixed number of vector error-correction (VEC) models. We obtain likelihood ratio statistics to test for a common cointegration rank across the individual VEC models with both heterogeneous and homogeneous cointegrating vectors. Their limiting distributions are a summation of the limiting behavior of Johansen trace statistics. We extend the asymptotic distribution theory to cover the case of an infinite cross-sectional dimension. We apply the framework to a dataset of exchange rates and appropriate monetary fundamentals. We find evidence for the validity of the monetary exchange rate model within a panel of VEC models for three major European countries, whereas the results based on individual VEC models for each of these countries separately are less supportive.

The Monetary Exchange Rate Model as a Long-Run Phenomenon

Pure time series-based tests fail to find empirical support formonetary exchange rate models. In this paper we apply pooled timeseries estimation on a forward-looking monetary model, resulting inparameter estimates which are in compliance with the underlyingtheory. Based on a panel version of the Engle and Granger (1987) two-stepprocedure we find that the residuals of our pooled estimated modelare stationary. This indicates that on a pooled time series levelthere is cointegration between the exchange rate and themacroeconomic fundamentals of this monetary model.

Protective Immunity in Macaques Vaccinated with a Modified Vaccinia Virus Ankara-Based Measles Virus Vaccine in the Presence of Passively Acquired Antibodies

ABSTRACT Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.

Evaluation of Six Immunoassays for Detection of Dengue Virus-Specific Immunoglobulin M and G Antibodies

ABSTRACT The performance of six commercially available immunoassay systems for the detection of dengue virus-specific immunoglobulin M (IgM) and IgG antibodies in serum was evaluated. These included two IgM and IgG enzyme immunoassays (EIA) from MRL Laboratories and PanBio, a rapid immunochromatographic test (RIT) from PanBio, immunofluorescence assays (IFA) from Progen, a dot blot assay from Genelabs, and a dipstick EIA from Integrated Diagnostics (INDX). For this study a panel of 132 serum samples, including 90 serum samples from patients with suspected dengue virus infection and 42 serum samples from patients with other viral infections, was used. In addition, serial serum samples from two monkeys experimentally immunized and challenged with dengue virus type 2 were used. Results were considered conclusive when concordant results were obtained with four of the six antibody-specific assays. Based on this definition, the calculated overall agreement for the human serum samples for the respective IgM immunoassays was 97% (128 of 132), with 34% (45 of 132) positive serum samples, 63% (83 of 132) negative samples, and 3% of samples (4 of 132) showing discordant results. The calculated overall agreement for the IgG assays was 94% (124 of 132), with 49% (65 of 132) positive, 45% (59 of 132) negative, and 6% (8 of 132) discordant results, respectively. The sensitivities of the dengue virus-specific assays evaluated varied between 71 and 100% for IgM and between 52 and 100% for IgG, with specificities of 86 to 96% and 81 to 100%, respectively. The relative sensitivities of the respective IgM assays measured with the monkey serum samples were comparable with those obtained with 12 serial serum samples from humans. Overall performance, based on the sum of the agreement, sensitivity, specificity, and Kappa statistics of the IgM and IgG immunoassays, showed that the antibody detection systems from INDX and Genelabs and the MRL and PanBio EIA are useful and reliable assays for dengue virus serodiagnosis.

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.

Comparison of two morbilliviruses isolated from seals during outbreaks of distemper in North West Europe and Siberia

SummaryRecently morbilliviruses were isolated from harbour seals (Phoca vitulina) in North West Europe (phocid distemper virus-1: PDV-1) and from Baikal seals (Phoca sibirica) in Siberia (phocid distemper virus-2:PDV-2) during outbreaks of severe disease which resembled distemper in dogs. PDV-1 and PDV-2 were passaged in SPF dogs, in which they caused distemper-like disease symptoms, and were subsequently passaged in Vero cells in which they caused cytopathic changes. PDV-1, PDV-2, and canine distemper virus (CDV) were compared with respect to their biological, morphological, physical, protein chemical, and antigenic properties. It was concluded that PDV-1 should be considered a newly recognized member of the genusMorbillivirus, whereas PDV-2 proved to be quite similar if not identical to CDV.

Respiratory syncytial virus specific serum antibodies in infants under six months of age: Limited serological response upon infection

The decline of maternal respiratory syncytial virus (RSV) specific serum antibodies was studied in 45 children during the first 6 months of life, using a virus neutralization assay and competition ELISAs measring fusion protein and glycoprotein specific antibodies. In all children RSV neutralizing antibodies were demonstrated at birth, with titers ranging from 33 to 1382. The calculated mean half life of these antibodies was 26 days. Furthermore, in a group of 38 children with suspected RSV infection, all younger than 6 months of age on admission, the diagnostic value of serological assays was evaluated. In 32 children RSV infection was confirmed by virus isolation, direct immune fluorescence and RT‐PCR. In 7 patients of this group a significant titer rise in virus neutralization assay was demonstrated. Six additional RSV infected children could be identified by showing the presence of RSV‐specific IgM or IgA serum antibodies or by showing an increase in fusion protein or glycoprotein specific antibodies. All serological tests together identified 13 (41%) of the 32 RSV infected patients. It is concluded that in children of this age group, which represent the majority of patients hospitalized with RSV infections, serological assays not only have a limited diagnostic value but are of limited value for sero‐epidemiological studies. J. Med. Virol. 52:97–104, 1997.