Foekje Stelma

Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009-2010.

Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 2009 and 2010 [A(H1N1) 2009] distributed across this period were analyzed. Of these, 19 cases of oseltamivir-resistant virus harboring the H275Y mutation in the neuraminidase (NA) were detected. The mean 50% inhibitory concentration (IC50) levels for oseltamivir- and zanamivir-susceptible A(H1N1) 2009 viruses were 1.4-fold and 2-fold, respectively, lower than for the seasonal A(H1N1) influenza viruses from 2007/2008; for oseltamivir-resistant A(H1N1) 2009 virus the IC50 was 2.9-fold lower. Eighteen of the 19 patients with oseltamivir-resistant virus showed prolonged shedding of the virus and developed resistance while on oseltamivir therapy. Sixteen of these 18 patients had an immunodeficiency, of whom 11 had a hematologic disorder. The two other patients had another underlying disease. Six of the patients who had an underlying disease died; of these, five had received cytostatic or immunosuppressive therapy. No indications for onward transmission of resistant viruses were found. This study showed that the main association for the emergence of cases of oseltamivir-resistant A(H1N1) 2009 virus was receiving antiviral therapy and having drug-induced immunosuppression or an hematologic disorder. Except for a single case of a resistant virus not linked to oseltamivir therapy, the absence of detection of resistant variants in community specimens and in specimens from contacts of cases with resistant virus suggested that the spread of resistant A(H1N1) 2009 virus was limited. Containment may have been the cumulative result of impaired NA function, successful isolation of the patients, and prophylactic measures to limit exposure.

Has CXCL13 an Added Value in Diagnosis of Neurosyphilis

In patients with syphilis, central nervous system (CNS) involvement is often difficult to determine. In patients who also are infected with human immunodeficiency virus (HIV), this is even more challenging, as cerebrospinal fluid (CSF) pleocytosis can be attributed to HIV, syphilis, or both. Hence, this study investigated (i) CSF chemokine (C-X-C motif) ligand 13 (CXCL13) as a potential marker to diagnose neurosyphilis in HIV-infected individuals and (ii) the added value of CSF CXCL13 to conventional CSF biomarkers, such as the rapid plasma reagin test (RPR), in diagnosing neurosyphilis. We included 103 syphilis patients from two centers in The Netherlands: 47 non-HIV-infected patients and 56 HIV-infected patients. A positive CSF-RPR was regarded as the gold standard for neurosyphilis. CSF CXCL13 levels were significantly higher in neurosyphilis patients when neurosyphilis was diagnosed by CSF-RPR (P = 0.0002) than in the syphilis control group. The sensitivity and specificity of CSF CXCL13 (cutoff of 76.3 pg/ml) to diagnose neurosyphilis by using positive CSF-RPR as the gold standard were 50% and 90%, respectively. CSF CXCL13 had an added value to CSF-RPR positivity in 70% of HIV-positive patients and in 33% of HIV-negative patients. Our data show that CSF CXCL13 might be a potential additional marker in neurosyphilis when other markers are not conclusive. The added value of CSF CXCL13 measurement to the current neurosyphilis gold standard appears to benefit HIV-positive patients more than HIV-negative patients.

The contribution of water contact behavior to the high Schistosoma mansoni Infection rates observed in the Senegal River Basin

BackgroundSchistosomiasis is one of the major parasitic diseases in the world in terms of people infected and those at risk. Infection occurs through contact with water contaminated with larval forms of the parasite, which are released by freshwater snails and then penetrate the skin of people. Schistosomiasis infection and human water contact are thus essentially linked, and more knowledge about their relationship will help us to develop appropriate control measures. So far, only few studies have related water contact patterns to infection levels.MethodsWe have conducted detailed direct water contact observations in a village in Northern Senegal during the first years of a massive Schistosoma mansoni outbreak to determine the role of human water contact in the extent of the epidemic.We quantified water contact activities in terms of frequency and duration, and described how these vary with age and sex. Moreover, we assessed the relationship between water contact- and infection intensity patterns to further elucidate the contribution of exposure to the transmission of schistosomiasis.ResultsThis resulted in over 120,000 recorded water contacts for 1651 subjects over 175 observation days. Bathing was the main activity, followed by household activities. Frequency and duration of water contact depended on age and sex rather than season. Water contacts peaked in adolescents, women spent almost twice as much time in the water as men, and water contacts were more intense in the afternoon than in the morning, with sex-specific intensity peaks. The average number of water contacts per person per day in this population was 0.42; the average time spent in the water per person per day was 4.3 minutes.ConclusionsThe observed patterns of water contact behavior are not unusual and have been described before in various other settings in sub-Saharan Africa. Moreover, water contact levels were not exceptionally high and thus cannot explain the extremely high S. mansoni infection intensities as observed in Northern Senegal. Comparison with fecal egg counts in the respective age and sex groups further revealed that water contact levels did not unambiguously correspond with infection levels, indicating that factors other than exposure also play a role in determining intensity of infection.

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome

BackgroundChronic fatigue syndrome (CFS) is a clinical condition characterized by severe and disabling fatigue that is medically unexplained and lasts longer than 6 months. Although it is possible to effectively treat CFS, the nature of the underlying physiology remains unclear. Various studies have sought evidence for an underlying disturbance in immunity. The aim of this study was to compare the humoral and cellular immune responses upon influenza vaccination in CFS patients and healthy controls.ResultsIdentical antibody titers were observed in CFS patients and healthy controls. Patients and controls demonstrated similar seroprotection rates against all three virus-strains of the influenza vaccine, both pre- and post-vaccination. Functional T cell reactivity was observed in both CFS patients and healthy controls. CFS patients showed a non-significant, numerically lower cellular proliferation at baseline compared to controls. Vaccination induced a significant increase in cellular proliferation in CFS patients, but not in healthy controls. Cytokine production and the number of regulatory T cells were comparable in patients and controls.ConclusionsThe humoral and cellular immune responses upon influenza vaccination were comparable in CFS patients and healthy controls. Putative aberrations in immune responses in CFS patients were not evident for immunity towards influenza. Standard seasonal influenza vaccination is thus justified and, when indicated, should be recommended for patients suffering from CFS.

A Dutch nationwide evaluation of serological assays for detection of Borrelia antibodies in clinically well-defined patients

Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B. burgdorferi antibody assays from 8 laboratories in the Netherlands. The total number of samples was 809. Samples were selected based on clinical and laboratory parameters. We included samples from patients with erythema migrans, acrodermatitis chronicum atrophicans, and neuroborreliosis; cross-reactivity controls; and healthy controls. Data are presented from 10 enzyme-linked immunosorbent assays and 5 immunoblots. For manifestations of B. burgdorferi infection with short disease duration, the positivity rate of the assays varied significantly. In patients with long disease duration, the positivity rate differed only marginally. In cross-reactivity controls, there was significant variation in the reactivity rate. The majority of false-positive reactions are of the IgM isotype.

Amyloid beta-42 (Aβ-42), neprilysin and cytokine levels. A pilot study in patients with HIV related cognitive impairments

HIV-associated dementia (HAD) is associated with amyloid-beta (Aβ) deposition. This study measured CSF and plasma amyloid beta-42 (Aβ-42), neprilysin (NEP) and cytokine levels in HIV-related cognitive impairments (HCI), HIV normal cognitive functioning (NF) and non-HIV controls. Our data showed a trend towards detectable plasma Aβ-42 levels more frequently in HCI (67%), when compared to NF (29%) and controls (10%). We showed elevated IL-8 levels in CSF of HCI compared to NF, although not significant values. The data from this pilot study indicates that CSF IL-8 and plasma Aβ-42 may be interesting biomarkers for the presence of HCI.

Absolute Lymphocyte Count Predicts the Response to New Influenza Virus H1N1 Vaccination in Pediatric Cancer Patients

ABSTRACT We measured the vaccination response to the new H1N1 virus in relation to the lymphocyte count prior to vaccination in pediatric cancer patients. The absolute lymphocyte count above the lower normal limits (LNL) for age prior to vaccination predicts the response to influenza vaccination in pediatric cancer patients treated with chemotherapy.

Humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue.

The aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. Humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. Cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activation assays. Regulatory T cells were measured at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA. Comparable humoral immune responses were observed in fatigued and non-fatigued patients, both pre- and post-vaccination. At baseline, fatigued patients showed a significantly diminished cellular proliferation upon virus stimulation with strain H3N2 (1414 ± 1201 counts), and a trend in a similar direction with strain H1N1 (3025 ± 2339 counts), compared to non-fatigued patients (3099 ± 2401 and 5877 ± 4604 counts, respectively). The percentage of regulatory T lymphocytes was significantly increased (4.4 ± 2.1% versus 2.4 ± 0.8%) and significantly lower amounts of interleukin 2 were detected prior to vaccination in fatigued compared to non-fatigued patients (36.3 ± 44.3 pg/ml vs. 94.0 ± 45.4 pg/ml with strain H3N2 and 28.4 ± 44.0 pg/ml versus 74.5 ± 56.1 pg/ml with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations, post-vaccination cellular proliferation, and post-vaccination cytokine concentrations did not differ between both groups. In conclusion, influenza vaccination is favorable for severely fatigued cancer survivors and should be recommended when indicated. However, compared to non-fatigued cancer survivors, fatigued cancer survivors showed several significant differences in immunological reactivity at baseline, which warrants further investigation.