Intradermal vaccination to protect against yellow fever and influenza.

The viral infections yellow fever and influenza can lead to large epidemics, which may deplete limited vaccine supplies. The intradermal vaccination route of yellow fever and influenza vaccines has received renewed attention, because it allows dose reduction without loss of efficacy. In this chapter, we review these two vaccines, the history of vaccine development, correlates of protection, immune response to vaccination and current knowledge concerning intradermal vaccination, including the immunological background, both in healthy subjects and immunocompromized individuals.

Soluble CD27 induces IgG production through activation of antigen-primed B cells.

OBJECTIVES: High levels of soluble CD27 (sCD27), a marker of immune activation, are found in several infectious [including human immunodeficiency virus type-I (HIV-1)] and autoimmune diseases; however, a direct biological effect of sCD27 on B cells has not been established. The aim of this study was to investigate whether sCD27, by binding to CD70, can induce immunoglobulin G (IgG) production from B cells. METHODS: B cells from healthy and HIV-1-infected individuals were cultured with recombinant human sCD27 (rhsCD27), and IgG production was measured. The role of rhsCD27 in inducing the expression of transcription factors involved in plasma cell differentiation was evaluated. Furthermore, we investigated the impact of different cytokines on the modulation of CD70 expression on B cells and the relationship between levels of IgG and sCD27 in serum from healthy and HIV-1-infected individuals. RESULTS: We demonstrated that rhsCD27 induced IgG production from antigen-primed (CD27+) B cells. This effect was mediated by rhsCD27 binding to CD70 on B cells leading to activation of Blimp-1 and XBP-1, transcription factors associated with plasma cell differentiation. We found a significant correlation between levels of serum sCD27 and IgG in HIV-1-infected individuals and healthy controls. CONCLUSIONS: sCD27 may act to enhance immunoglobulin production and differentiation of activated memory or recently antigen-experienced B cells, thus providing an activation signal to antigen-experienced B cells. This mechanism may operate during autoimmune and chronic infectious diseases, situations in which continuous immune activation leads to upregulation of CD70 expression and increased sCD27 cleavage.

[Ileocolitis in an immunocompromised patient. Crohn's disease or an infection?] / Ileocolitis bij een immuungecompromitteerde patiënte.

BACKGROUND: Histoplasma capsulatum is an endemic fungus in especially tropical areas. While mostly asymptomatic, histoplasmosis can be life-threatening in immunocompromised patients. CASE DESCRIPTION: A 60-year-old woman of Suriname origin, with a history of renal transplantation and use of mycophenolate mofetil and prednisone, presented with abdominal pain and diarrhea. Colonoscopy revealed ulcerative ileocolitis and biopsy showed active granulomatous inflammation. Morbus Crohn was considered the most plausible diagnosis after ruling out several infectious and pharmacological causes. Despite prednisone treatment, symptoms persisted and infliximab was initiated. The patient developed constitutional symptoms and radiological examination revealed disseminated granulomatous disease. Liver biopsy and re-evaluation of previous intestinal histopathology confirmed suspected histoplasmosis. CONCLUSION: Histoplasmosis should be considered in immunocompromised patients with ileocolitis who have been in endemic regions (South America). Physicians need to assess the risk of previous exposure to histoplasmosis before starting anti-TNF-α therapy.

The effect of anti-tumour necrosis factor alpha treatment on the antibody response to influenza vaccination.

OBJECTIVES: The effect of anti-tumour necrosis factor (TNF) therapy on the antibody responses to vaccines is the subject of ongoing debate. Therefore, we investigated the effect of the three currently available anti-TNF agents on influenza vaccination outcomes in a patient population with long-standing disease. METHODS: In a prospective cohort study, we assessed the antibody response upon influenza vaccination in 112 patients with long-standing autoimmune disease treated with immunosuppressive medication either with anti-TNF (etanercept, adalimumab or infliximab; n = 64) or without anti-TNF (n = 48) and a control group of 18 healthy individuals. Antibody responses were determined by haemagglutination inhibition assay, before and 4 weeks after vaccination. RESULTS: The proportion of individuals with a protective titre (>or=40) after vaccination was large (80-94%) and did not significantly differ between the three groups. Post-vaccination geometric mean antibody titres against influenza (A/H3N2 and B) were significantly lower in the 64 patients treated with anti-TNF compared with the 48 patients not receiving anti-TNF, and the healthy controls. CONCLUSIONS: The antibody response to influenza vaccination in patients treated with anti-TNF is only modestly impaired. The proportion of patients that achieves a protective titre is not significantly diminished by the use of TNF blocking therapies.

[Practical advice for travellers with immune disorders]. / Praktische adviezen voor reizigers met een afweerstoornis.

For patients with immune disorders, the risk of infection during travel depends on the cause and severity of the immune disorder and the type of travel. Immunocompromised travellers experience more severe effects of illness than those without immune disorders. Some risks can be reduced or avoided by taking adequate precautions and, in some cases, modifying travel plans. Ensuring adequate medication use during the trip requires careful planning prior to travel. Regarding vaccination, immunocompromised travellers may have an impaired ability to generate antibodies; live attenuated vaccines are often contraindicated. The treating physician must take a proactive role when an immunocompromised patient indicates that he or she plans to travel. Protocols developed by the Dutch National Coordination Centre for Travellers Health (LCR) provide practical advice regarding a number of situations. Provided that they are given proper individualised advice, there is little concrete evidence to suggest that these patients should not travel anywhere they wish.

Dynamics of colistin and tobramycin resistance among Enterobacter cloacae during prolonged use of selective decontamination of the digestive tract.

Background: A high prevalence of colistin resistance among E. cloacae isolates in two intensive care units (ICU) (of 16 and 6 beds) using selective digestive decontamination (SDD) since 1990 instigated a retrospective and prospective investigation to quantify the role of clonal transmission. SDD is topical application of colistin and tobramycin and systemic use of cefotaxime during the first days of ICU-admission. Methods: Multi-resistant E. cloacae (MREb) was defined as ESBL production and/or tobramycin non-susceptibility and/or colistin non-susceptibility. Incidence of acquisition and prevalence of carriage with MREb was determined from microbiological culture results. Results: Colistin-resistant E. cloacae was first detected in November 2009 and carriage was demonstrated in 141 patients until October 2014. Mean incidence of MREb acquisition was 4.61 and 1.86 per 1000 days at risk in ICUs 1 and 2, respectively, and the mean monthly prevalence of MREb in both ICUs was 7.0 and 3.1%, respectively, without a discernible trend in time. Conversion rates from carriage of colistin-susceptible to resistant E. cloacae were 0.20 and 0.13 per 1000 patient days, respectively. Whole genome sequencing of 149 isolates revealed eight clusters, with the number of SNPs of the largest two clusters ranging between 0 and 116 for cluster 1 (n = 49 isolates), and 0 and 27 for cluster 2 (n = 36 isolates), among isolates derived between 2009 and 2014. Conclusions: This study demonstrates a stable low-level endemicity of MREb in two Dutch ICUs with prolonged use of SDD, which was characterized by the persistent presence of two clusters, suggesting incidental clonal transmission.

A rare case of Waterhouse- Friderichsen syndrome during primary Varicella zoster infection.

Primary Varicella zoster virus infection in adults is associated with a higher risk of complications when compared with the benign disease course of primary infection during childhood. We present a rare complication of adult primary Varicella zoster in the form of acute, irreversible adrenal insufficiency due to bilateral adrenal haemorrhage, which is also known as the WaterhouseFriderichsensyndrome.

[Impaired immunity: risk groups and consequences for general practice]. / Verminderde afweer.

- Due to medication use, comorbidities and/or age, an increasing number of patients have an impaired immunity to infection.- Impaired immunity may lead to an increased risk of (opportunistic) infection, complications from infections, and difficulties in the diagnosis of infections.- Guided by clinical parameters, a general practitioner can classify an impaired immunity as 'clinically irrelevant', 'limitedly relevant' or 'potentially serious'.- Tocilizumab impairs the production of CRP, which makes it unreliable as an infection parameter.- In case of a suspected infection in patients with severe immunosuppression, it will often be necessary to consult a specialist as quickly as possible about further diagnostic procedures and the need for, type and administration route of antimicrobials.- In patients with an impaired immunity, adaptation of the antibiotic policy and prophylactic measures, such as vaccination, may be indicated.- Patients with (functional) asplenia should immediately start antibiotic treatment in case of fever, pending clinical evaluation by a physician.

Intradermal influenza vaccination in immunocompromized patients is immunogenic and feasible.

BACKGROUND: Many strategies, including intradermal vaccination, have been tested to augment antibody responses upon vaccination. This strategy has not been evaluated in different groups of immunocompromized patients. We conducted a prospective, randomized study to compare the humoral response upon standard intramuscular influenza vaccination with the response upon reduced-dose intradermal vaccination in patients treated with anti-tumor necrosis factor (TNF)-alpha, human immunodeficiency virus (HIV)-infected patients, hematologic stem cell transplantation (HSCT) patients, and healthy controls. METHODS: In total 156 immunocompromized patients and 41 healthy controls were randomized to receive either 0.5mL of the 2005/2006 trivalent influenza vaccine intramuscular or 0.1mL intradermal. Humoral responses, determined by hemagglutination inhibition assay, were measured before and 28 days postvaccination. Geometric mean titers (GMTs) and protection rates (PRs) are reported as primary outcomes, adverse events as a secondary outcome. RESULTS: Reduced-dose intradermal vaccination leads to similar GMTs and PRs, within all tested groups, compared to the standard intramuscular vaccination. Healthy controls yielded significantly better GMTs and PRs than immunocompromized patients. Local skin reactions after intradermal vaccination occurred less frequent and were milder in immunocompromized patients than in healthy subjects and were predictive for a positive vaccination outcome for individual subjects. CONCLUSIONS: Intradermal influenza vaccination is a feasible alternative for standard intramuscular vaccination in several groups of immunocompromized patients, including those treated with anti-TNF, HIV-infected patients and HSCT patients. The occurrence of a local skin reaction after intradermal vaccination is predictive of a response to at least one of the vaccine antigens.

Synergistic immunosuppressive effect of anti-TNF combined with methotrexate on antibody responses to the 23 valent pneumococcal polysaccharide vaccine.

INTRODUCTION: The efficacy of the immune response upon vaccination in patients treated with anti-tumor necrosis factor-alpha (anti-TNF) with or without methotrexate is the subject of debate. We studied the effect of immunosuppressive treatment, including anti-TNF and methotrexate, on the response to pneumococcal polysaccharide (PPS) vaccine. METHODS: Fifty-two patients treated with immunosuppressives including anti-TNF (anti-TNF group), 41 patients given a similar immunosuppressive regimen without anti-TNF (no anti-TNF group), and 18 healthy controls were vaccinated with a 23 valent PPS vaccine. The percentage of patients treated with methotrexate in the anti-TNF and no anti-TNF group was 65% and 76%, respectively. Antibodies against four of the vaccine antigens (PPS 6B, 9V, 19F and 23F) were measured before and 4 weeks after vaccination. The primary outcome was the response rate, defined as the percentage with a postvaccination titer 0.35 microg/ml in combination with at least a twofold increase in antibody titer. The protection rate was defined as a postvaccination titer > or = 0.35 microg/ml. RESULTS: The use of methotrexate was the strongest predictor of impaired vaccination outcome. Anti-TNF caused an additional immunosuppressive effect in the presence of methotrexate, leading to the lowest response percentages in patients using the combination of these two drugs. The underlying disease, other immunosuppressives such as prednisone or type of anti-TNF agent used did not influence vaccination outcome. CONCLUSIONS: Patients who were treated with the combination of methotrexate and anti-TNF demonstrated a significantly impaired immune response following pneumococcal polysaccharide vaccination as compared to patients treated with either methotrexate or anti-TNF only or immunosuppressives excluding these two compounds.

Pneumonia involving Aspergillus and Rhizopus spp. after a near-drowning incident with subsequent Nocardia cyriacigeorgici and N. farcinica coinfection as a late complication.

Reported here is the case of a 22-year-old man who developed pneumonia with unusual pathogens after a near-drowning incident. On day 7 following admission, Rhizopus spp. and Aspergillus fumigatus were cultured from the patient's bronchoalveolar lavage fluid. One week later, sputum cultures revealed N. cyriacigeorgici as well as N. farcinica. The patient recovered fully after prolonged therapy with liposomal amphotericin B, amikacin, meropenem and cotrimoxazole.

Detection of the Candida antigen mannan in cerebrospinal fluid specimens from patients suspected of having Candida meningitis.

Cerebrospinal fluid samples from five patients from which Candida cells were cultured were tested for the presence of mannan. Samples from four patients categorized as having proven candidosis reacted positively. Samples from the remaining patient and from patients with other central nervous system infections were negative. Detection of mannan may be valuable in the diagnosis of Candida meningitis.