Infectious complications in hematology patients: A clinical focus on prevention

The aim of this thesis was to contribute to infection preventive strategies in hematology patients with prolonged neutropenia. Invasive pulmonary aspergillosis (IPA) develops by pulmonary deposition of conidia. A placebo-controlled trial on the efficacy of prophylactic aerosolized liposomal amphotericin-B (L-AmB) was performed in hematology patients during treatment-related neutropenia. For the intent-to-treat analysis, 18 of 132 placebo patients developed IPA, versus 6 of 139 in L-AmB patients (P=.005). Short-term prophylactic nebulization of liposomal amphotericin B was not associated with decline in pulmonary function or systemic adverse effects, only coughing was significantly more reported. In a study among acute leukemia patients, the mortality rate was 26% and 16%, respectively, in patients with and without IPA (P=.08), with corrected additional IPA-related costs of €15280 (P<.001), which makes IPA prevention both efficacious and cost-effective. Current guidelines advocate administration of 7-14 days of broad-spectrum antibiotics for unexplained ferver (UF) in neutropenic hematology patients. Effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. In the Erasmus MC, broad-spectrum antibiotics are initially administered, but discontinued when after 72 hours no bacterial etiology is documented. Among 166 hematology patients on selective antibiotic prophylaxis, 317 febrile episodes were observed; 56% were due to UF. Due to the restrictive antibiotic policy, the mean treatment duration was only 3.7 days. Overall-mortality after neutrophil recovery was 3.6% (6 of 166 patients). No patient died from untreated bacterial infection, suggesting that discontinuation of broad-spectrum antibiotics in this setting is safe, provided that no infectious etiology is documented. Diagnosing catheter-related bloodstream infection (CRBSI) often involves tip culture, using the conventional semi-quantitative roll-plate method. The quantitative sonication technique could have additional value, as it may also detect endoluminal microorganisms. However, in a prospective study of 313 tunnelled catheters from 279 hematology patients, the diagnostic performance in patients with suspected CRBSI was equally limited for both methods. Finally, in a placebo-controlled trial on the efficacy of a daily prophylactic 70%-ethanol lock on the prevention of endoluminal CRBSI in tunneled devices, a 3.6-fold, non-significant, reduction was observed for ethanol-treated hematology patients. Partially, the lack of significance may reflect a lack of power. More patients receiving ethanol discontinued lock-therapy, because of non-severe adverse events

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 t

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 chemotherapyinduced 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 wit

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.</p