Search

BackgroundThe COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders.MethodsThe primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity.ResultsOf the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60–66), 86% were male, and median CD4+ T-cell count was 650/μL (IQR, 423–941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/mL (95% confidence interval [CI], 24–46) to 4317 BAU/mL (95% CI, 3275–5360) (P < .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4+ T cells (P = .04) and S-specific B cells (P = .02) was observed.ConclusionsAn additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination.Clinical Trials Registration. EUCTR2021-001054-57-N.

BackgroundThe COVIH study is a prospective SARS-CoV-2 vaccination study in people living with HIV (PLWH). Of the 1154 PLWH enrolled, 14% showed a reduced or absent antibody response after a primary vaccination regimen. As the response to an additional vaccination in PLWH with hyporesponse is unknown, we evaluated whether an additional vaccination boosts immune responses in these hyporesponders.MethodsConsenting hyporesponders received an additional 100 µg of mRNA-1273. Hyporesponse was defined as ≤300 spike(S)-specific binding antibody units [BAU]/mL. The primary endpoint was the increase in antibodies 28 days after the additional vaccination. Secondary endpoints were the correlation between patient characteristics and antibody response, levels of neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity.ResultsOf the 75 PLWH enrolled, five were excluded as their antibody level had increased to >300 BAU/mL at baseline, two for a SARS-CoV-2 infection before the primary endpoint evaluation and two were lost to follow-up. Of the 66 remaining participants, 40 previously received ChAdOx1-S, 22 BNT162b2, and four Ad26.COV2.S. The median age was 63 [IQR:60-66], 86% were male, pre-vaccination and nadir CD4+ T-cell counts were 650/μL [IQR:423-941] and 230/μL [IQR:145-345] and 96% had HIV-RNA 300 BAU/mL in 64/66 (97%) with a mean increase of 4282 BAU/mL (95%CI:3241-5323). No patient characteristics correlated with the magnitude of the antibody response nor did the primary vaccination regimen. The additional vaccination significantly increased the proportion of participants with detectable ancestral S-specific B-cells (p=0.016) and CD4+ T-cells (p=0.037).ConclusionAn additional mRNA-1273 vaccination induced a robust serological response in 97% of the PLWH with a hyporesponse after a primary vaccination regimen. This response was observed regardless of the primary vaccination regimen or patient characteristics.

BackgroundVaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown.Methods and FindingsA prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines in adult PLWH, without prior COVID-19, compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response and reactogenicity.Between February-September 2021, 1154 PLWH (median age 53 [IQR 44-60], 86% male) and 440 controls (median age 43 [IQR 33-53], 29% male) were included. 884 PLWH received BNT162b2, 100 mRNA-1273, 150 ChAdOx1-S, and 20 Ad26.COV2.S. 99% were on antiretroviral therapy, 98% virally suppressed, and the median CD4+T-cell count was 710 cells/µL [IQR 520-913]. 247 controls received mRNA-1273, 94 BNT162b2, 26 ChAdOx1-S and 73 Ad26.COV2.S. After mRNA vaccination, geometric mean concentration was 1418 BAU/mL in PLWH (95%CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV-status remained associated with a decreased response (0.607, 95%CI 0.508-0.725). In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+T-cell counts 250-500 cells/µL (2.845, 95%CI 1.876-4.314) or >500 cells/µL (2.936, 95%CI 1.961-4.394), whilst a viral load >50 copies/mL was associated with a reduced response (0.454, 95%CI 0.286-0.720). Increased IFN-γ, CD4+, and CD8+T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation induced marker assays, comparable to controls. Reactogenicity was generally mild without vaccine-related SAE.ConclusionAfter vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH. To reach and maintain the same serological responses and vaccine efficacy as HIV-negative controls, additional vaccinations are probably required.

Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised.

Distinguishing acute Q fever from respiratory infections, fever, or hepatitis requires serologic testing or PCR., Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised.

Literature-based consensus guideline is more sensitive and easier to use in clinical practice., Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice.

Background. Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIVpositive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections.Methods. Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and after unrestricted DAA availability. We compared the HCV incidence in both years.Results. The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1-7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI,.35-.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation.Conclusions. Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

Contains fulltext : 174731.pdf (Publisher’s version ) (Closed access) Background.: Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS). The objective of this randomized controlled clinical trial was to assess the efficacy of either long-term treatment with doxycycline or cognitive-behavioral therapy (CBT) in reducing fatigue severity in patients with QFS. Methods.: Adult patients were included who met the QFS criteria according to the Dutch guideline: a new onset of severe fatigue lasting >/=6 months with significant disabilities, related to an acute Q fever infection, without other somatic or psychiatric comorbidity explaining the fatigue. Using block randomization, patients were randomized between oral study medication and CBT (2:1) for 24 weeks. Second, a double-blind randomization between doxycycline (200 mg/day, once daily) and placebo was performed in the medication group. Primary outcome was fatigue severity at end of treatment (EOT; week 26), assessed with the Checklist Individual Strength subscale Fatigue Severity. Results.: Of 155 patients randomized, 154 were included in the intention-to-treat analysis (doxycycline, 52; placebo, 52; CBT, 50). At EOT, fatigue severity was similar between doxycycline (40.8 [95% confidence interval {CI}, 37.3-44.3]) and placebo (37.8 [95% CI, 34.3-41.2]; difference, doxycycline vs placebo, -3.0 [97.5% CI, -8.7 to 2.6]; P = .45). Fatigue severity was significantly lower after CBT (31.6 [95% CI, 28.0-35.1]) than after placebo (difference, CBT vs placebo, 6.2 [97.5% CI, .5-11.9]; P = .03). Conclusions.: CBT is effective in reducing fatigue severity in QFS patients. Long-term treatment with doxycycline does not reduce fatigue severity in QFS patients compared to placebo. Clinical Trials Registration.: NCT01318356.

Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positiveCoxiella burnetiiPCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to 1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.

SUMMARYIn May 2008 the Nijmegen Municipal Health Service (MHS) was informed about an outbreak of atypical pneumonia in three in-patients of a long-term psychiatric institution. The patients had been hospitalized and had laboratory confirmation of acute Q fever infection. The MHS started active case finding among in-patients, employees of and visitors to the institution. In a small meadow on the institution premises a flock of sheep was present. One of the lambs in the flock had been abandoned by its mother and cuddled by the in-patients. Samples were taken of the flock. Forty-five clinical cases were identified in employees, in-patients and visitors; 28 were laboratory confirmed as Q fever. Laboratory screening of pregnant women and persons with valvular heart disease resulted in one confirmed Q fever case in a pregnant woman. Of 27 samples from animals, seven were positive and 15 suspect forCoxiella burnetiiinfection. This outbreak of Q fever in a unique psychiatric setting pointed to a small flock of sheep with newborn lambs as the most likely source of exposure. Care institutions that have vulnerable residents and keep flocks of sheep should be careful to take adequate hygienic measures during delivery of lambs and handling of birth products.

Contains fulltext : 154096.pdf (Publisher’s version ) (Open Access) BACKGROUND: Fungal skull base osteomyelitis (SBO) is a severe complication of otitis externa or sinonasal infection, and is mainly caused by Aspergillus species. Here we investigate innate and adaptive immune responses in patients with Aspergillus SBO to identify defects in the immune response that could explain the susceptibility to this devastating disease. METHODS: Peripheral blood mononuclear cells isolated from six patients with Aspergillus SBO and healthy volunteers were stimulated with various microbial stimuli, among which also the fungal pathogens Candida albicans and Aspergillus fumigatus. The proinflammatory cytokines IL-6, TNFalpha and IL-1beta, and the T-helper cell-derived cytokines IFNgamma, IL-17 and IL-22 were measured in cell culture supernatants by ELISA. RESULTS: Proinflammatory cytokine responses did not differ between SBO patients and healthy volunteers. The Candida- and Aspergillus-specific Th17 response (production of IL-17 and IL-22) was significantly decreased in the SBO patients compared to healthy individuals, while Th1 cytokine response (IFNgamma production) did not differ between the two groups. CONCLUSIONS: We show that patients with Aspergillus skull base osteomyelitis infection have specific defects in Th17 responses. Since IL-17 and IL-22 are important for stimulating antifungal host defense, we hypothesize that strategies that have the ability to improve IL-17 and IL-22 production may be useful as adjuvant immunotherapy in patients with Aspergillus SBO.

Contains fulltext : 135900.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for pattern recognition receptors (PRRs) on susceptibility to RVVC. STUDY DESIGN: For the study, 119 RVVC patients and 263 healthy controls were recruited. Prevalence of polymorphisms in five PRRs involved in recognition of Candida were investigated in patients and controls. In silico and functional studies were performed to assess their functional effects. RESULTS: Single nucleotide polymorphisms (SNPs) in TLR1, TLR4, CLEC7A, and CARD9 did not affect the susceptibility to RVVC. In contrast, a non-synonymous polymorphism in TLR2 (rs5743704, Pro631His) increased the susceptibility to RVVC almost 3-fold. Furthermore, the TLR2 rs5743704 SNP had deleterious effects on protein function as assessed by in silico analysis, and in vitro functional assays suggested that it reduces production of IL-17 and IFNgamma upon stimulation of peripheral blood mononuclear cells with Candida albicans. No effects were observed on serum mannose-binding lectin concentrations. CONDENSATION: This study demonstrates the association of susceptibility to RVVC with genetic variation in TLR2, most likely caused by decreased induction of mucosal antifungal host defense. CONCLUSION: Genetic variation in TLR2 may significantly enhance susceptibility to RVVC by modulating host defense mechanisms against Candida. Additional studies are warranted to assess systematically the role of host genetic variation for susceptibility to RVVC.

Background Invasive fungal infections are very severe infections associated with high mortality rates, despite the availability of new classes of antifungal agents. Based on pathophysiological mechanisms and limited pre-clinical and clinical data, adjunctive immune-stimulatory therapy with interferon-gamma (IFN-γ) may represent a promising candidate to improve outcome of invasive fungal infections by enhancing host defence mechanisms. Methods In this open-label, prospective case series, we describe eight patients with invasive Candida and/or Aspergillus infections who were treated with recombinant IFN-γ (rIFN-γ, 100 μg s.c., thrice a week) for 2 weeks in addition to standard antifungal therapy. Results Recombinant IFN-γ treatment in patients with invasive Candida and/or Aspergillus infections partially restored immune function, as characterized by an increased HLA-DR expression in those patients with a baseline expression below 50%, and an enhanced capacity of leukocytes from treated patients to produce proinflammatory cytokines involved in antifungal defence. Conclusions The present study provides evidence that adjunctive immunotherapy with IFN-γ can restore immune function in fungal sepsis patients, warranting future clinical studies to assess its potential clinical benefit. Trial registration ClinicalTrials.gov - NCT01270490

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age ( P = 0.004 and 0.010), proven chronic Q fever ( P = 0.020 and 0.002), vascular chronic Q fever ( P = 0.024 and 0.005), acute presentation with chronic Q fever ( P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever ( P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively.

A 54-year-old woman presented to the emergency department with progressive proximal muscle weakness and a symmetric skin rash. Physical examination demonstrated a heliotrope rash, Gottron lesions, mechanic's hands and symmetrical erythema of the face, neck and upper legs. The diagnosis 'dermatomyositis' was established. Subsequently, the patient was successfully treated with prednisolone 1 mg/kg.

Background Chronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed. Methods Fifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded. Results According to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively. Conclusions If chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions.

In the Netherlands, more than 4000 patient cases of acute Q fever have been reported since 2007. Approximately 20% of these patients subsequently developed long-term fatigue. Such fatigue, as well as other physical symptoms and patient-perceived limitations in social functioning, have been compiled into what is known as the Q fever fatigue syndrome (QFS). The number of Dutch patients having QFS is expected to increase over the next years. The chance of a spontaneous recovery during the first six months following an acute Q fever infection is high. Allowing the fatigue to run its natural course is therefore justified. The diagnosis of QFS is based on history-taking, a physical examination and laboratory test results. The percentage of patients who recover spontaneously from QFS seems low. Data on outcome after treatment are not yet available. The recommendation is to refer patients with QFS to specialists who offer cognitive behavioural therapy for chronic fatigue syndrome or QFS. The objective of the recently published national guideline ‘Q fever fatigue syndrome (QFS)' is to achieve uniformity in its diagnosis and treatment.

Chronic esophageal candidiasis is an infection that is mostly seen in immunocompromised conditions, among which is chronic mucocutaneous candidiasis (CMC). Recently an association between CMC and esophageal carcinoma has been reported. Here we present two patients with chronic esophageal candidiasis who developed esophageal squamous cell carcinoma and we discuss the etiologic role of Candida-induced nitrosamine production, the loss of STAT1 function and impaired tumor surveillance and T-lymphocyte function in the development of esophageal carcinoma.

Item does not contain fulltext Candida species are major causes of mucosal and invasive infections, leading to substantial morbidity and mortality. Despite the development of new classes of antifungal drugs, mortality in patients with systemic candidiasis remains high. Host-Candida interaction plays an important role in effective elimination of the pathogen. Genetic studies have rendered important insights into antifungal host defense and have identified potential targets for adjunctive therapy. In this article, the authors review the genetic variations in the host defense to Candida and their implications for the treatment of mucosal and systemic candidiasis.

Q fever is a worldwide zoonosis, caused by C. burnetii. Infection usually occurs through inhalation of infected aerosols. The reservoir mainly consists of dairy cattle. Clinical symptoms of acute Q fever are non-specific and resemble a mild flu-like illness. Children often present with gastrointestinal symptoms and rash. Rarely, chronic infection develops. This is usually manifested as endo-carditis, vascular infection and, in children, osteomyelitis. Diagnosis is based on serology and nucleic acid amplification (PCR). Doxycycline is the treatment of choice for acute infection. An alternative for young children and pregnant women is cotrimoxazole. Chronic infection requires long term treatment usually with doxycycline combined with hydroxychloroquine.

Q fever is an ubiquitous zoonosis that is caused by Coxiella burnetii. Infection occurs through inhalation of infected aerosols. The main reservoir is dairy cattle. Although understanding of the disease is growing, many questions, including those about optimal treatment, still remain. There are few reports of Q fever in children, although seroepidemiological data suggest that they are often exposed to C. burnetii. Clinical presentation of acute and chronic Q fever seems to be different in children and adults. We present an overview of the epidemiological and clinical features of Q fever, with emphasis on paediatric cases.

Following Coxiella burnetii infection, there is a 1 to 5% risk of chronic Q fever. Endocarditis, mycotic aneurysm, and vascular prosthesis infection are common manifestations. We present three patients with endocarditis by C. burnetii concomitant with another bacterial pathogen. Chronic Q fever should therefore be considered in all endocarditis patients in regions where Q fever is endemic.

Summary Vulvovaginal candidiasis (VVC) is a clinical syndrome due to a vaginal yeast infection with a Candida species (mostly C. albicans ), characterized by itching, soreness, bright red rash, and heavy white vaginal discharge, causing a strong discomfort in patients. Recurrent vulvovaginal candidiasis (RVVC) is defined as the occurrence of at least three episodes per year. Predisposing factors such as pregnancy, the use of antibiotics, contraceptive pills or hormone replacement treatment and diabetes mellitus have been reported to contribute to the susceptibility for RVVC. Nevertheless, in most patients suffering from this debilitating disease, none of these risk factors are present. Therefore, it is believed that genetic predisposition may also play a significant role for the susceptibility to RVVC. The present review summarizes the current knowledge concerning the gene polymorphisms that have been associated with RVVC. Several components of the innate immune system related to the recognition of C. albicans (manose binding lectin, Dectin-1), or the induction of inflammation (the cytokine interleukin-4, the NLRP3 component of the inflammasome) have recently been shown to influence susceptibility to RVVC. However, further studies are warranted in order to understand more thoroughly the spectrum of genetic variation inducing genetic susceptibility to RVVC in otherwise healthy patients.

Contains fulltext : 116709.pdf (Publisher’s version ) (Open Access) BACKGROUND: Q fever is a zoonosis that is present in many countries. Q fever fatigue syndrome (QFS) is one of the most frequent sequelae after an acute Q fever infection. QFS is characterized by persistent fatigue following an acute Q fever infection, leading to substantial morbidity and a high socio-economic burden. The occurrence of QFS is well-documented, and has been described in many countries over the past decades. However, a treatment with proven efficacy is not available. Only a few uncontrolled studies have tested the efficacy of treatment with antibiotics on QFS. These studies suggest a positive effect of long-term treatment with a tetracycline on performance state; however, no randomized controlled trials have been performed. Cognitive behavioral therapy (CBT) has been proven to be an effective treatment modality for chronic fatigue in other diseases, but has not yet been tested in QFS. Therefore, we designed a trial to assess the efficacy of long-term treatment with the tetracycline doxycycline and CBT in patients with QFS. METHODS/DESIGN: A randomized placebo-controlled trial will be conducted. One-hundred-eighty adult patients diagnosed with QFS will be recruited and randomized between one of three groups: CBT, long-term doxycycline or placebo. First, participants will be randomized between CBT and medication (ratio 1:2). A second double-blinded randomization between doxycycline and placebo (ratio 1:1) will be performed in the medication condition. Each group will be treated for six months. Outcome measures will be assessed at baseline and post intervention. The primary outcome measure is fatigue severity. Secondary outcome measures are functional impairment, level of psychological distress, and Coxiella burnetii PCR and serology. DISCUSSION: The Qure study is the first randomized placebo-controlled trial, which evaluates the efficacy of long-term doxycycline and of cognitive behavioral therapy in patients with QFS. The results of this study will provide knowledge about evidence-based treatment options for adult patients with QFS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01318356, and Netherlands Trial Register: NTR2797.