Measles seroprevalence among Dutch travelling families.

BACKGROUND: While measles vaccination is widely implemented in national immunisation programmes, measles incidence rates are increasing worldwide. Dutch inhabitants who were born between 1965-1975 may have fallen between two stools, lacking protection from a natural infection, and having missed the introduction of the measles vaccination schedule. With this study we aim to find the measles seroprevalence in travellers born between 1965 and 1975, compared to those born before 1965 and after 1975. METHODS: Families travelling to Eastern Europe or outside Europe during the preceding year were recruited via Dutch secondary schools between 2016 and 2018. Their vaccination status was assessed using questionnaires, vaccination records and measles serology in dried blood spot (DBS) eluates. Measles virus antibody concentrations were determined with an ELISA (EUROIMMUNE®) and a subset was retested with a focus reduction neutralization assay (FRNT). RESULTS: In 188 (79%) of the 239 available DBS eluates, the ELISA could detect sufficient measles virus-specific IgG antibodies. Of the negative samples that were retested with FRNT, 85% remained negative, resulting in an overall seroprevalence of 82% [95% CI 76-86]. Children had a lower seroprevalence (72%) than adults (87%). Travellers born between 1965 and 1975 were protected in 89%. CONCLUSIONS: In this study, we report a measles seroprevalence of 82% among Dutch travelling families. Remarkably, seroprevalence rates were lowest in children (12-18 years) instead of travellers born between 1965 and 1975. Although a fraction of people without detectable antibodies may be protected by other immune mechanisms, these data suggest that measles (re)vaccination should be considered for travellers to endemic regions.

B-Cell Immunophenotyping to Predict Vaccination Outcome in the Immunocompromised - A Systematic Review.

Vaccination is the most effective measure to prevent infections in the general population. Its efficiency strongly depends on the function and composition of the immune system. If the immune system lacks critical components, patients will not be fully protected despite a completed vaccination schedule. Antigen-specific serum immunoglobulin levels are broadly used correlates of protection. These are the products of terminally differentiated B cells - plasma cells. Here we reviewed the literature on how aberrancies in B-cell composition and function influence immune responses to vaccinations. In a search through five major literature databases, 6,537 unique articles published from 2000 and onwards were identified. 75 articles were included along three major research lines: extremities of life, immunodeficiency and immunosuppression. Details of the protocol can be found in the International Prospective Register of Systematic Reviews [PROSPERO (registration number CRD42021226683)]. The majority of articles investigated immune responses in adults, in which vaccinations against pneumococci and influenza were strongly represented. Lack of baseline information was the most common reason of exclusion. Irrespective of study group, three parameters measured at baseline seemed to have a predictive value in assessing vaccine efficacy: (1) distribution of B-cell subsets (mostly a reduction in memory B cells), (2) presence of exhausted/activated B cells, or B cells with an aberrant phenotype, and (3) pre-existing immunological memory. In this review we showed how pre-immunization (baseline) knowledge of circulating B cells can be used to predict vaccination efficacy. We hope that this overview will contribute to optimizing vaccination strategies, especially in immunocompromised patients.

Adherence to hepatitis A travel health guidelines: A cross-sectional seroprevalence study in Dutch travelling families - The Dutch travel Vaccination Study (DiVeST).

BACKGROUND: This Dutch travel Vaccination Study (DiVeST) aimed to study adherence or compliance to Dutch travel health guidelines in travelling families and to identify risk groups to provide better advice and protection for international travellers. METHODS: Between 2016 and 2018, family members who travelled to Eastern Europe or outside Europe during the preceding year were recruited via Dutch secondary schools. The vaccination status of the travellers was assessed using questionnaires and vaccination records and hepatitis A virus antibody concentrations in dried blood spot (DBS) eluates. Subgroups of travellers with lower adherence to guidelines were identified. RESULTS: Of the 246 travellers that participated in this study, 155 (63%) travelled to destinations for which the HAV vaccination was recommended. Of these 155 travellers, 56 (36%) said they visited a pre-travel clinic, and 64 of them (41%) showed a valid HAV vaccination in their vaccination records. Of the 145 travellers with available DBS eluates, anti-HAV antibodies were detected in 98 (68%) of them. CONCLUSIONS: We found that adherence to travel health guidelines, in terms of HAV vaccination, was suboptimal. According to our results, specific attention should be paid to children, persons visiting friends and relatives and those who travel relatively short distances.

[Yellow fever in Brazil: the importance of vaccination]. / Gele koorts uit Brazilië.

BACKGROUND: Since 2016 outbreaks of yellow fever are reported in Brazil. This is a risk to unvaccinated travellers in that area. CASE DESCRIPTION: In early January, an unvaccinated traveller returning from São Paulo attended our outpatient clinic complaining of symptoms later diagnosed as yellow fever. The disease manifested itself as fever, lower back pain, nausea and highly elevated liver enzymes. A yellow fever infection has multiple stages. The first stage is acute infection which merges into the second stage which is when improvement occurs. Either improvement continues or transfers into a third stage which is characterized by multi-organ failure. In this particular patient, stage three did not occur. CONCLUSION: The goal of this case report is to show that vaccination against yellow fever is the most important preventive measure when travelling to an area where the yellow fever virus is in circulation. Yellow fever should not be forgotten in the differential diagnosis of a traveller with fever.

[A man with upper abdominal pain and a pancytopenia]. / Een man met pijn in de bovenbuik en pancytopenie.

A 41-year-old man visited his general practitioner because of upper abdominal pain. Physical examination revealed splenomegaly. Laboratory testing showed pancytopenia with a striking monocytopenia with hairy cells. Immunological and molecular analysis confirmed the diagnosis hairy cell leukemia.

Imported scrub typhus in The Netherlands.

Two cases of travel-acquired scrub typhus imported in the Netherlands are described. The characteristic eschar was absent in both cases. One case acquired scrub typhus in non-rural surroundings in India, highlighting that scrub typhus must also be considered a (sub) urban zoonosis.

[Approaches to vitamin B12 deficiency]. / Vitamine B12-deficiëntie.

A 28-year-old female vegetarian was referred to a specialist in internal medicine with persistent iron deficiency. Laboratory analysis revealed microcytic anaemia with low ferritin levels but normal total vitamin B12 levels. The red blood cell distribution width, however, showed a very wide variation in red blood cell sizes, indicating a coexisting vitamin B12 deficiency, which was confirmed by the low concentration of active vitamin B12. Another patient, a 69-year-old woman with a history of previous gastric surgery and renal insufficiency as a complication of diabetes mellitus, was suspected to be deficient in vitamin B12, as she had low total vitamin B12 levels and an accumulation of methylmalonic acid and homocysteine in her blood. Testing the total concentration of vitamin B12 alone has insufficient diagnostic accuracy and no accepted gold standard is available for diagnosing vitamin B12 deficiency. With the development of newer tests, such as measuring holotranscobalamin II (concentration of active vitamin B12), atypical and subclinical deficiency states can be recognized. A new approach to diagnosing vitamin B12 deficiency is presented, based upon these 2 case descriptions.

Prevention of catheter-related bacteremia with a daily ethanol lock in patients with tunnelled catheters: a randomized, placebo-controlled trial.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) results in significant attributable morbidity and mortality. In this randomized, double-blind, placebo-controlled trial, we studied the efficacy and safety of a daily ethanol lock for the prevention of CRBSI in patients with a tunnelled central venous catheter (CVC). METHODOLOGY: From 2005 through 2008, each lumen of the CVC of adult hematology patients was locked for 15 minutes per day with either 70%-ethanol or placebo, where after the lock solution was flushed through. As a primary endpoint, the incidence rates of endoluminal CRBSI were compared. PRINCIPAL FINDINGS: The intent-to-treat analysis was based on 376 patients, accounting for 448 CVCs and 27,745 catheter days. For ethanol locks, the incidence of endoluminal CRBSI per 1000 CVC-days was 0.70 (95%-CI, 0.4-1.3), compared to 1.19 (95% confidence interval, 0.7-1.9) for placebo (incidence rate-ratio, 0.59; 95% confidence interval, 0.27-1.30; P = .19). For endoluminal CRBSI according to the strictest definition (positive hub culture and identical bacterial strain in blood), a 3.6-fold, non-significant, reduction was observed for patients receiving ethanol (2 of 226 versus 7 of 222; P = .103). No life-threatening adverse events were observed. More patients receiving ethanol discontinued lock-therapy (11 of 226 versus 1 of 222; P = .006) or continued with decreased lock-frequency (10 of 226 versus 0 of 222; P = .002), due to non-severe adverse events. CONCLUSIONS: In this study, the reduction in the incidence of endoluminal CRBSI using preventive ethanol locks was non-significant, although the low incidence of endoluminal CRBSI precludes definite conclusions. Therefore, the lack of statistical significance may partially reflect a lack of power. Significantly more patients treated with ethanol locks discontinued their prophylactic treatment due to adverse effects, which were non-severe but reasonably ethanol related. Additional studies should be performed in populations with higher incidence of (endoluminal) CRBSI. Alternative sources of bacteremia, like exoluminal CRBSI or microbial translocation during chemotherapy-induced mucositis may have been more important in our patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122642.

Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: a prospective observational safety study.

BACKGROUND: Guidelines advocate >7d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h. METHODS: Prospective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of 10d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered. RESULTS: One hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced 1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5d, and mean time of treatment with imipenem was 4.7d. In patients without documented infection, mean time of imipenem treatment was only 3.7d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection. CONCLUSION: Discontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.

Comparison of the roll plate method to the sonication method to diagnose catheter colonization and bacteremia in patients with long-term tunnelled catheters: a randomized prospective study.

Diagnosing catheter-related bloodstream infection (CRBSI) still often involves tip culture. The conventional method is the semiquantitative roll plate method. However, the use of a quantitative sonication technique could have additional value, as it may detect endoluminal microorganisms more easily. Because endoluminal infection tends to occur in long-term central venous catheters, we compared both techniques for patients with long-term tunnelled catheters. For 313 consecutive Hickman catheter tips from 279 hematological patients, colonization detection rates were compared by performing both techniques in a random order, using conventional detection cutoffs. Additionally, for the subgroup of patients with clinical suspicion of CRBSI (n = 89), the diagnostic values of both techniques were compared. The overall tip colonization rate was 25%. For each technique, the detection rate tended to be better if that technique was performed first. The diagnostic performance for the subgroup of patients with clinical suspicion of CRBSI was limited and not different for both methods. Sensitivity and specificity were 45% and 84%, respectively, for sonication versus 35% and 90%, respectively, for the roll plate technique. The fact that 35 of 40 patients with CRBSI received antimicrobial therapy before catheter removal and tip culture, in an attempt to salvage the catheter, may partly explain this poor performance. No differences were observed when catheters were stratified according to in situ time below or above the median of 4 weeks. The sonication culture technique was not better than the roll plate method to diagnose tip colonization or CRBSI in patients with long-term tunnelled catheters.

Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study.

BACKGROUND: Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. METHODS: In 269 patients treated for acute myelogenous leukemia-myelodysplastic syndrome (AML-MDS) during 2002-2007, evidence of IA was collected using high-resolution computed tomography and galactomannan measurement in bronchoalveolar lavage fluid specimens. IA was classified on the basis of updated European Organization for Research and Treatment of Cancer/Mycoses Study Group definitions. Outcome of infection was registered. Diagnostic and therapeutic IA-related costs, corrected for neutropenia duration, were comprehensively analyzed from a hospital perspective. Voriconazole treatment was given orally from day 1 if possible. RESULTS: A total of 80 patients developed IA; 48 (18%) had probable or proven infection, and 32 (12%) had possible IA. Seventy-three patients were treated with voriconazole; 55 (75%) took oral voriconazole from day 1. In patients with IA, the mortality rate 12 weeks after starting antifungal therapy was 22% (16 of 73 patients). The overall mortality rate, registered 12 weeks after neutrophil recovery from the last dose of antileukemic treatment, was 26% in patients with IA versus 16% in patients without IA (P = .08), reflecting an IA-attributable mortality rate of 10%. In a Cox regression analysis, IA was associated with an increased mortality risk (hazard ratio, 2.4; 95% confidence interval, 1.3-4.4). Total IA-related costs increased to euro 8360 and euro 15,280 for patients with possible and probable or proven IA, respectively, compared with patients without IA (P<.001). CONCLUSIONS: Early diagnosis and treatment of IA with oral voriconazole result in acceptable mortality rates. Nevertheless, IA continues to have substantial attributable mortality combined with a major impact on hospital resource use, so effective prevention in high-incidence populations has the potential to save lives and costs.

Tolerability of prophylactic aerosolized liposomal amphotericin-B and impact on pulmonary function: data from a randomized placebo-controlled trial.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a leading cause of mortality in immunocompromised patients, with the highest risk observed in patients with acute leukaemia or lung transplantation. IPA-prophylactic strategies include administration of aerosolized amphotericin-B. Liposomal amphotericin-B (L-AmB) is one of the formulations available, although few data exist on safety and tolerability. METHODS: Data on tolerability, systemic toxicity and effects of aerosolized L-AmB on pulmonary function were recorded in a subgroup out of 271 haematological patients enrolled in a placebo-controlled trial on the efficacy of aerosolized L-AmB for the prevention of IPA. Using an adaptive aerosol-delivery system, nebulization of L-AmB or placebo was performed during chemotherapy-induced neutropenia for 30 min/day on 2 consecutive days/week with a maximum of 6 weeks. RESULTS: Thirty-eight patients (41 episodes) received L-AmB, 39 patients (49 episodes) received placebo. Proportions of patients with >20% post-nebulization decline in forced expiratory volume in 1s (FEV(1)) or forced vital capacity (FVC) did not differ between groups. Also 26/38 L-AmB patients (68%) versus 31/39 patients (79%) on placebo had no significant decline during the entire treatment (p=0.20). Coughing was significantly more reported in L-AmB patients (p<0.0001). No differences were observed when baseline and post-nebulization serum levels of renal function and hepatic enzymes were compared. CONCLUSIONS: Short-term prophylactic nebulization of L-AmB was well tolerated and not associated with decline in pulmonary function or systemic adverse effects.

Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. METHODS: We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for >or=10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations. RESULTS: A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P=.005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02-0.66; P=.007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P=.002). CONCLUSION: In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.