Q fever and spontaneous abortion

Q fever, caused by Coxiella burnetii, may result in abortions in infected animals and pregnant women. However, the role that Q fever plays in spontaneous abortions is still unknown. This study examined the association between Q fever serology and abortion in a region where Q fever is endemic. A case–control population-based study was conducted in General Yagüe Hospital (Burgos area, Spain) between June 2009 and July 2010. A total of 801 samples from 500 pregnant women were tested, of whom 273 had a spontaneous abortion and 227 gave birth. IgG and IgM antibody titres against Q fever were determined in their two phases (I and II) by immunofluorescence assay. Seropositivity (phase I IgG ≥1:16 or phase II IgG ≥1:80) was detected in 88/273 (32.2%) cases and 53/227 (23.3%) controls; p <0.01, OR 1.5, 95% CI 1.0–2.3. Seropositivity for both phases of IgG, compatible with recent or persistent infection, was detected in 55 (20.1%) vs 22 (9.7%); p <0.001, OR 2.3, 95% CI 1.3–3.9. High phase II IgG antibodies compatible with active or recent infection (titres ≥1:160) were detected in 27 (9.6%) vs 7 (3.1%); p <0.002, OR 3.4, 95% CI 1.4–8.0, respectively. Q fever was diagnosed in 14 (5.1%) cases. The risk of abortion associated with serological markers of active or recent Q fever in pregnant women was measurable and noticeable in this population, and accounted for 12% (95% CI 4–21%).     

Association between serological evidence of past Coxiella burnetii infection and atherosclerotic cardiovascular disease in elderly patients

Q fever, caused by Coxiella burnetii, may cause vascular complications, but the role that this infection may play in the development of atherosclerotic cardiovascular disease remains unknown. This study examined the association between Q fever serology and cardiovascular disease in a region where Q fever is endemic. A case-control study was conducted in the Hospital Universitario de Burgos (Spain) between February 2011 and June 2012. A total of 513 samples were tested, from 454 hospitalized patients ≥65 years old, of whom 164 were cases (patients with prevalent or incident coronary heart, cerebrovascular or peripheral artery, disease) and 290 controls (patients without cardiovascular disease). Serum IgG antibody phase II titres against Q fever were determined by immunofluorescence assay. Seropositivity (titres ≥1:256) was detected in 84/164 (51.2%) cases and in 109/290 (37.6%) controls (p = 0.005; OR, 1.7; 95% CI, 1.1–2.5). This ratio increases when adjusted for sex, hypertension, dyslipidaemia, smoking, diabetes and atrial fibrillation (OR, 2.6; 95% CI, 1.5–4.7). The geometric mean titre (GMT) for C. burnetii phase II assay was higher in cases than in controls (p = 0.004). We found no significant relationship between cardiovascular disease and C. pneumoniae, and Cytomegalovirus seropositivity (both determined by the IgG ELISA method). In conclusion, serological evidence of past Q fever is associated with atherosclerotic cardiovascular disease in elderly patients in an endemic region.     

Fluorescence in situ hybridization for detecting Coxiella burnetii in tissue samples from chronic Q fever patients

ObjectiveDetection of the intracellular bacterium Coxiella burnetii, causative agent of chronic Q fever, is notoriously difficult. Diagnosis of and duration of antibiotic treatment for chronic Q fever is partly determined by detection of the bacterium with polymerase chain reaction (PCR). Fluorescence in situ hybridization (FISH) might be a promising technique for detecting C. burnetii in tissue samples from chronic Q fever patients, but its value in comparison with PCR is uncertain. We aim to assess the value of FISH for detecting C. burnetii in tissue of chronic Q fever patients.MethodsFISH and PCR were performed on tissue samples from Dutch chronic Q fever patients collected during surgery or autopsy. Sensitivity, specificity, and overall diagnostic accuracy were calculated. Additionally, data on patient and disease characteristics were collected from electronic medical records.ResultsIn total, 49 tissue samples from mainly vascular walls, heart valves, or placentas, obtained from 39 chronic Q fever patients, were examined by FISH and PCR. The sensitivity and specificity of FISH compared to PCR for detecting C. burnetii in tissue samples from chronic Q fever patients was 45.2% (95% confidence interval (CI), 27.3% – 64.0%) and 84.6% (95% CI, 54.6% – 98.1%), respectively. The overall diagnostic accuracy was 56.8% (95% CI, 42.2% - 72.3%). Two C. burnetii PCR negative placentas were FISH positive. Four FISH results (8.2%) were deemed inconclusive because of autofluorescence.ConclusionWith an overall diagnostic accuracy of 57.8%, we conclude that FISH has limited value in the routine diagnostics of chronic Q fever.     

Single nucleotide polymorphism (SNP) rs3751143 in P2RX7 is associated with therapy failure in chronic Q fever while rs7125062 in MMP1 is associated with fewer complications

ObjectivesChronic Q fever is a persistent infection with the intracellular bacterium Coxiella burnetii. Development of chronic Q fever is associated with single nucleotide polymorphisms (SNPs) in genes encoding for pattern recognition receptors, for phagolysosomal pathway components and for matrix metalloproteinases (MMPs). We evaluated the association of SNPs in these innate-immunity and MMP genes with clinical outcomes.MethodsSNPs were selected from previous association studies and analysed in a cohort of patients with chronic Q fever. The primary outcome was all-cause mortality; secondary outcomes were therapy failure and chronic Q fever–related complications. Subdistribution hazard ratios (SHR) were calculated.ResultsNineteen SNPs were analysed in 134 patients with proven and 29 with probable chronic Q fever. In multivariable analysis, none of the selected SNPs was associated with all-cause mortality. However, SNP rs3751143 located in P2RX7 appeared to be associated with therapy failure (SHR 2.42; 95% confidence interval, 1.16–5.05; p 0.02), which is in line with other reports, showing that a loss of function of the P2X7 receptor leads to inefficient killing of intracellular organisms. In addition, SNP rs7125062 located in MMP1, involved in the cleavage of extracellular matrix, was associated with fewer chronic Q fever–related complications such as acute aneurysms (SHR 0.49; 95% confidence interval, 0.29–0.83; p 0.008).ConclusionsA polymorphism in P2RX7, known to lead to loss of function of the receptor and inefficient killing of intracellular organisms, and a polymorphism in MMP1 were respectively associated with more therapy failures and fewer complications such as acute aneurysms in patients with chronic Q fever.     

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

ObjectivesThis study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cut-off parameters for indirect immunofluorescence assay (IFA).MethodsSequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR.ResultsFor all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to ≥3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36–204 days) and IgG was 177 days (interquartile range 134–355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cut-off reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%–85.2% sensitivity; 89.9%, 95% CI 62.5%–100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%–87.6% sensitivity; 99%, 95% CI 95%–100% specificity).ConclusionsThis study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cut-offs in other geographically diverse locations.     

Serological follow-up in patients with aorto-iliac disease and evidence of Q fever infection

The aim of this study was to provide data on the risk of developing chronic Q fever in patients with aorto-iliac disease and evidence of previous Q fever infection. Patients with an aortic and/or iliac aneurysm or aorto-iliac reconstruction (aorto-iliac disease) and evidence of previous Q fever infection were included. The presence of phase I and II Coxiella burnetii IgG antibodies was assessed periodically using immunofluorescence assay. A total of 111 patients with aorto-iliac disease were divided into three groups, based upon the serological profile [mean follow-up: 16?±?9 months (mean?±?standard deviation)]. Group 1 consisted of 30 patients with a serological trace of C. burnetii infection (negative IgG phase I, IgG phase II titer of 1:32). Of these, 36.7 % converted to serological profile matching past resolved Q fever. Group 2 included 49 patients with negative IgG phase I titer and IgG phase II titer ≥1:64. No patients developed chronic Q fever, but 14.3 % converted to a positive IgG phase I titer. Group 3 consisted of 32 patients with positive IgG phase I and positive IgG phase II titers, of which 9.4 % developed chronic Q fever (significantly different from group 2, p?=?0.039). The IgG phase I titer increased in 28.1 % of patients (from 1:64 to 1:4,096). The risk of developing chronic Q fever in patients with aorto-iliac disease and previous Q fever infection with a positive IgG phase I titer was 9.4 %. The IgG phase I titer increases or becomes positive in a substantial number of patients. A standardized serological follow-up is proposed.     

Efficacy and safety of anti-interleukin-5 therapy in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized,controlled trials

BackgroundAnti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear.MethodsA literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation.ResultsA total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I² = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV₁ from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, ?0.86, 95% CI, ?1.92 – 0.19, I² = 0%; FEV₁, mean difference, 0.01, 95% CI, ?0.01 – 0.03, I² = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo.ConclusionAnti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.     

Detection of phase I IgG antibodies to Coxiella burnetii with EIA as a screening test for blood donations

The presence of a high phase I IgG antibody titre may indicate chronic infection and a risk for the transmission of Coxiella burnetii through blood transfusion. The outbreak of Q fever in the Netherlands allowed for the comparison of an enzyme immunoassay (EIA) with the reference immunofluorescence assay (IFA) in a large group of individuals one year after acute Q fever. EIA is 100?% sensitive in detecting high (≥1:1,024) phase I IgG antibody titres. The cost of screening with EIA and confirming all EIA-positive results with IFA is much lower than screening all donations with IFA. This should be taken into account in cost-effectiveness analyses of screening programmes.     

Antibiotic strategies and clinical outcomes in critically ill patients with pneumonia caused by carbapenem-resistant Acinetobacter baumannii

ObjectivesThis study aimed to investigate antibiotic prescribing patterns and effectiveness of different anti-carbapenem-resistant Acinetobacter baumannii (CRAB) strategies for CRAB pneumonia.MethodsWe conducted a multicentre, retrospective study in three hospitals. During 2010–2015, adult ICU patients with CRAB pneumonia treated with at least one antimicrobial agent covering the CRAB isolate in vitro for more than 2 days were included. We used multivariate logistic regression to analyse the associations of anti-CRAB strategies with ICU mortality and other clinical outcomes.ResultsAmong 238 patients with CRAB pneumonia, tigecycline monotherapy (84, 35.3%) was the most common antibiotic strategy, followed by tigecycline with colistin (43, 18.1%), colistin monotherapy (34, 14.3%), colistin combination without tigecycline (33, 13.9%), tigecycline combination without colistin (32, 13.4%), and sulbactam-based therapy without tigecycline and colistin (12, 5.0%). In multivariate analysis, tigecycline-based therapy was associated with higher ICU mortality than non-tigecycline therapy (adjusted OR 2.30, 95% CI 1.19–4.46). There was no difference between colistin-based therapy and non-colistin therapy. Compared with tigecycline monotherapy, colistin monotherapy was associated with lower ICU mortality (aOR 0.30, 95% CI 0.10–0.88). Treatment failure analyses showed similar trends. Tigecycline-based therapy was associated with higher treatment failure rate than non-tigecycline therapy (aOR 2.51, 95% CI 1.39–4.54), whereas colistin-based therapy was associated with lower treatment failure rate than non-colistin-based therapy (aOR 0.48, 95% CI 0.27–0.86).ConclusionsTigecycline was commonly prescribed for CRAB pneumonia. However, tigecycline-based therapy was associated with higher ICU mortality and treatment failure. Our study suggests that colistin monotherapy may be a better antibiotic strategy for CRAB pneumonia.     

Outbreak of SARS-CoV-2 B.1.617.2 (delta) variant in a nursing home 28 weeks after two doses of mRNA anti-COVID-19 vaccines: evidence of a waning immunity

ObjectivesTo describe a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) variant outbreak among residents (n = 69) and health workers (n = 69) of a small nursing home in northeastern Italy, with full vaccination coverage of 91% and 82%, respectively. Evaluation of the anti-Spike IgG titres 28 weeks after the mRNA vaccine booster dose against SARS-CoV-2 infection and severe coronavirus disease 2019 (COVID-19).Materials and methodsSera were collected within 48 hours from the index case; anti-Spike IgG was determined (expressed as WHO binding antibody units (BAU)/mL) through a commercial quantitative assay; SARS-CoV-2 was diagnosed using RT-PCR, and full-genome sequencing was performed for lineage characterization. Residents were grouped according to anti-Spike IgG titres (≤50, 51–1000 and > 1000 BAU/mL) and the resulting protection against infection and severe disease was measured.ResultsNone of the health workers and 14 of the 59 (24%) residents fully vaccinated and without a previous SARS-CoV-2 infection showed anti-Spike IgG ≤50 BAU/mL (one-sided Fisher exact test, p 0.011). Among these residents, a level of anti-Spike IgG ≤50 BAU/mL resulted in a higher risk of SARS-CoV-2 infection (relative risk 1.55, 95% CI 1.17–2.05) and severe COVID-19 (relative risk 5.33, 95% CI 1.83–15.57).ConclusionLow levels of SARS-CoV-2 neutralizing anti-Spike IgG in serum 28 weeks after the administration of the second dose parallel the waning of vaccine protection.     

Microbiological Challenges in the Diagnosis of Chronic Q Fever

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 positive Coxiella burnetii PCR 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 <60% when cutoff titers of ≥1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff 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.     

Measles seroprevalence in pregnant women in Soweto,South Africa: a nested cohort study

ObjectivesMeasles infection causes particularly severe disease in young children who, prior to vaccination, are dependent on maternal antibodies for protection against infection. Measles vaccination was introduced into the South African public immunization programme in 1983 and became widely available in 1992. The aim of this study was to determine measles-specific immunoglobulin G (IgG) levels in pregnant women living with and without HIV born before and after measles vaccine introduction in South Africa.MethodsMeasles IgG antibody level from blood obtained at the time of delivery was compared between women who were born before 1983 (n = 349) and since 1992 (n = 349). Serum samples were tested for measles IgG antibody using an enzyme-linked immunosorbent assay. Geometric mean titres (GMTs) and the proportion with seronegative (<200 mIU/mL) or seropositive titres (≥275 mIU/mL) were compared.ResultsWomen born since 1992 had lower GMTs [379.7 mIU/mL (95% CI 352.7–448.6)] and fewer were seropositive (55.9%, 195/349) than women born before 1983 [905.8 mIU/mL (95% CI 784.7–1045.5); 76.8%, 268/349], for both comparisons p < 0.001.ConclusionsWe found an association between measles vaccine implementation into the public immunization program in South Africa and peri-partum maternal measles immunity, where women born before vaccine introduction had higher measles IgG antibody titres and were more likely to be seropositive. These findings suggest a need to reconsider the infant measles immunization schedule in settings where women have derived immunity mainly from measles vaccine rather than wild-type virus exposure.     

The combined use of tigecycline with high-dose colistin might not be associated with higher survival in critically ill patients with bacteraemia due to carbapenem-resistant Acinetobacter baumannii

ObjectiveTo assess the association of survival and treatment with colistin and tigecycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.MethodsAn observational cohort study was carried out. Targeted therapy consisted of monotherapy with colistin (9 million UI/day) or combined therapy with colistin and tigecycline (100 g/day). The primary outcome was 30-day crude mortality. The association between combined targeted therapy and mortality was controlled for empirical therapy with colistin, propensity score of combined therapy and other potential confounding variables in a multivariate Cox regression analysis.ResultsA total of 118 cases were analysed. Seventy-six patients (64%) received monotherapy and 42 patients (36%) received combined therapy. The source of bacteraemia was primary in 18% (21/118) of the patients, ventilator-associated pneumonia in 64% (76/118) and other sources in 14% (16/118). The 30-day crude mortality rate was 62% (42/76) for monotherapy and 57% (24/42) for combined therapy. The variables associated with 30-day crude mortality were: Charlson index (hazard ratio (HR) 1.16, 95% CI 1.02–1.32; p 0.028), empirical therapy with colistin (HR 2.25, 95% CI 1.33–3.80; p 0.003) and renal dysfunction before treatment (HR 1.91, 95% CI 1.01–3.61; p 0.045). Combined targeted therapy was not associated with lower adjusted 30-day crude mortality (adjusted HR 1.29, 95% CI 0.64–2.58; p 0.494).ConclusionsCombined targeted therapy with high-dose colistin and standard dose tigecycline was not associated with lower crude mortality of bacteraemia due to carbapenem-resistant A. baumannii in critically ill patients.Trial registrationRegistered in ClinicalTrials.gov. Identifier: NCT02573064.     

Current outcomes of chronic active antibody mediated rejection – A large single center retrospective review using the updated BANFF 2013 criteria

BackgroundThe updated BANFF 2013 criteria has enabled a more standardized and complete serologic and histopathologic diagnosis of chronic active antibody mediated rejection (cAMR). Little data exists on the outcomes of cAMR since the initiation of this updated criteria.Methods123 consecutive patients with biopsy proven cAMR (BANFF 2013) between 2006 and 2012 were identified.ResultsPatients identified with cAMR were followed for a median of 9.5 (2.7–20.3) years after transplant and 4.3 (0–8.8) years after cAMR. Ninety-four (76%) recipients lost their grafts with a median survival of 1.9 years after diagnosis with cAMR. Mean C4d and allograft glomerulopathy scores were 2.6 ± 0.7 and 2.2 ± 0.8, respectively. 53.2% had class II DSA, 32.2% had both class I and II, and 14.5% had class I DSA only. Chronicity score >8 (HR 2.9, 95% CI 1–8.4, p = 0.05), DSA >2500 MFI (HR 2.8, 95% CI 1.1–6.8, p = 0.03), Scr >3 mg/dL (HR 3.2, 95% CI 1.6–6.3, p = 0.001) and UPC >1 g/g (HR 2.5, 95% CI 1.4–4.5, p = 0.003) were associated with a higher risk of graft loss.ConclusionscAMR was associated with poor graft survival after diagnosis. Improved therapies and earlier detection strategies are likely needed to improve outcomes of cAMR in kidney transplant recipients.     

Chronic Q fever-related complications and mortality: data from a nationwide cohort

ObjectivesChronic infection with Coxiella burnetii (chronic Q fever) can cause life-threatening conditions such as endocarditis, infected vascular prostheses, and infected arterial aneurysms. We aimed to assess prognosis of chronic Q fever patients in terms of complications and mortality.MethodsA large cohort of chronic Q fever patients was assessed to describe complications, overall mortality and chronic Q fever-related mortality. Chronic Q fever-related mortality was expressed as a case fatality rate (number of chronic Q fever-related deaths/number of chronic Q fever patients).ResultsComplications occurred in 166 of 439 (38%) chronic Q fever patients: in 61% of proven (153/249), 15% of probable (11/74), and 2% of possible chronic Q fever patients (2/116). Most frequently observed complications were acute aneurysms (14%), heart failure (13%), and non-cardiac abscesses (10%). Overall mortality was 38% (94/249) for proven chronic Q fever patients (median follow-up 3.6 years) and 22% (16/74) for probable chronic Q fever patients (median follow-up 4.7 years). The case fatality rate was 25% for proven (63/249) chronic Q fever patients and 4% for probable (3/74) chronic Q fever patients. Overall survival was significantly lower in patients with complications, compared to those without complications (p <0.001).ConclusionsIn chronic Q fever patients, complications occur frequently and contribute to the mortality rate. Patients with proven chronic Q fever have the highest risk of complications and chronic Q fever-related mortality. Prognosis for patients with possible chronic Q fever is favourable in terms of complications and mortality.     

Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis

ObjectivesDespite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown.MethodsA cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013–2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control.ResultsA total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4⁺ and CD8⁺ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17–6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02–3.57) and MN (3.33, 1.26–9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08–2.63), underlying medical conditions (1.94, 95% CI 1.09–3.46) and lack of antiviral therapy (2.08, 95% CI 1.04–4.17) were predictors for higher T-cell responses.ConclusionsSurvivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.     

Targeted screening as a tool for the early detection of chronic Q fever patients after a large outbreak

In the aftermath of the Dutch Q fever outbreak, an increasing number of patients are being diagnosed with chronic Q fever. Most of these patients are unaware of being infected with Coxiella burnetii, the causative agent of Q fever. To find patients in an earlier, asymptomatic stage, a targeted screening strategy (TSS) for patients with risk factors for chronic Q fever was started in the southeast region of Noord-Brabant. In total, 763 patients were tested using an IgG phase II indirect fluorescent antibody test (IFAT), of which 52 (7 %) patients tested positive. Ten of these 52 patients displayed a chronic Q fever serological profile. All of these 10 patients had a heart valve(s) or (endo-)vascular prosthesis. All except one were asymptomatic. Suggestive signs for chronic infections on positron emission tomography–computed tomography (PET-CT) were demonstrated in 5 (50 %) of these patients. Forty-two out of the 52 patients with a positive screening test showed a past Q fever serological profile. After a year of follow-up (every 3 months), none of these patients showed elevation of antibody titres and no new chronic Q fever patients were found in this group. A targeted screening programme is a useful instrument for detecting patients at risk of developing chronic Q fever.     

Treatment outcomes of multidrug-resistant tuberculosis patients in Zhejiang,China, 2009–2013

ObjectivesTo examine treatment outcomes and factors associated with poor outcome of multidrug-resistant (MDR) tuberculosis (TB) in China.MethodsWe conducted a prospective observational cohort study including consecutive patients with MDR-TB between 2009 and 2013 in six regions of Zhejiang province. Patients were prescribed treatments by infectious disease specialists, and treatment outcomes were recorded. Sociodemographic characteristics were obtained through a structured questionnaire. The primary endpoint was poor treatment outcomes, defined as treatment failure based on microbiologic persistence, default (lost to follow-up) or death at 24 months. We assessed risk factors for poor treatment outcomes using a Cox proportional hazards model.ResultsA total of 820 MDR-TB patients were observed, and 537 with known treatment outcomes were included in our study. Overall, the treatment success rate was 40.2 per 100 years (374/537 participants, 69.6%), while treatment failure, death and default rates were 10.0 per 100 years (101 participants, 18.8%), 3.4 per 100 years (36 participants, 6.7%) and 2.7 per 100 years (26 participants, 4.8%) respectively. Independent predictors of poor treatment outcomes included age >60 years (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2–4.2), patients registered as experiencing relapse (HR 2.2, 95% CI 1.1–4.4), patients registered as receiving treatment after failure (HR 2.4, 95% CI 1.2–4.9), use of standardized MDR-TB regimens (HR 0.6, 95% CI 0.4–1.0), cavitary disease (HR 4.9, 95% CI 2.8–8.6) and adverse events (HR 2.5, 95% CI 1.2–5.5).ConclusionsUnder well-designed treatment and management scheme, high treatment success rates were achieved in a high-MDR-TB-burden country. Antimicrobial susceptibility testing for all second-line drugs should be conducted to further assist in the treatment of MDR-TB.     

Chronic aspirin use and survival following sepsis—A propensity-matched,observational cohort study

ObjectivesThe use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin use leads to improved outcomes in patients with sepsis.MethodsWe conducted an observational cohort study among patients with sepsis, hospitalized in internal medicine wards in a single university-affiliated medical center. A propensity-score model was used to match and compare patients on chronic aspirin use to non-users. Patients with established cardiovascular disease were excluded. The primary outcome was survival rates at 30 days. Secondary outcomes included survival rates at 90 days, days of fever, length of hospital stay, and hospital readmission within 90 days.ResultsA total of 1671 patients fulfilled the inclusion criteria. 533 chronic aspirin users were matched to 533 aspirin non-users. Survival rates were significantly higher among patients on chronic aspirin use (hazard ratio (HR) 0.67; 95% CI, 0.51–0.89)). This effect was highlighted in several subgroups of patients, as patients with chronic obstructive pulmonary disease (COPD) or those with chronic use of beta blockers showed the greatest survival benefit with aspirin use. Patients in the aspirin group also showed significantly higher 90 days survival rates (HR 0.69; 95% CI, 0.57–0.92; p = 0.006) and experienced less days of fever in comparison to the control group.DiscussionPre-hospitalization treatment with aspirin for patients without established cardiovascular disease may be associated with mortality reduction, as shown in this is hypothesis-generating single center observational study.     

A combination of interferon-gamma and interleukin-2 production by Coxiella burnetii-stimulated circulating cells discriminates between chronic Q fever and past Q fever

Infection with Coxiella burnetii may lead to life-threatening chronic Q fever endocarditis or vascular infections, which are often difficult to diagnose. The present study aims to investigate whether measurement of in-vitro interferon-gamma (IFN-γ) production, a key cytokine in the immune response against C. burnetii, differentiates chronic from a past cleared infection, and whether measurement of other cytokines would improve the discriminative power. First, C. burnetii-specific IFN-γ production was measured in whole blood of 28 definite chronic Q fever patients and compared with 135 individuals with past Q fever (seropositive controls) and 908 seronegative controls. IFN-γ production was significantly higher in chronic Q fever patients than in controls, but with overlapping values between patients and seropositives. Secondly, the production of a series of other cytokines was measured in a subset of patients and controls, which showed that interleukin (IL)-2 production was significantly lower in patients than in seropositive controls. Subsequently, measuring IL-2 in all patients and all controls with substantial IFN-γ production showed that an IFN-γ/IL-2 ratio >11 had a sensitivity and specificity of 79% and 96%, respectively, to diagnose chronic Q fever. This indicates that a high IFN-γ/IL-2 ratio is highly suggestive for chronic Q fever. In an additional group of 25 individuals with persistent high anti-Coxiella phase I IgG titres without definite chronic infection, all but six showed an IFN-γ/IL-2 ratio <11. In conclusion, these findings hold promise for the often difficult diagnostic work-up of Q fever and the IFN-γ/IL-2 ratio may be used as an additional diagnostic marker.