Using the Sysmex UF-4000 urine flow cytometer for rapid diagnosis of urinary tract infection in the clinical microbiological laboratory.

BACKGROUND: Urinary tract infections are responsible for a significant worldwide disease burden. Performing urine culture is time consuming and labor intensive. Urine flow cytometry might provide a quick and reliable method to screen for urinary tract infection. METHODS: We analyzed routinely collected urine samples received between 2020 and 2022 from both inpatients and outpatients. The UF-4000 urine flow cytometer was implemented with an optimal threshold for positivity of ≥100 bacteria/µL. We thereafter validated the prognostic value to detect the presence of urinary tract infection (UTI) based on bacterial (BACT), leukocyte (WBC), and yeast-like cell (YLC) counts combined with the bacterial morphology (UF gram-flag). RESULTS: In the first phase, in 2019, the UF-4000 was implemented using 970 urine samples. In the second phase, between 2020 and 2022, the validation was performed in 42,958 midstream urine samples. The UF-4000 screen resulted in a 37% (n = 15,895) decrease in performed urine cultures. Uropathogens were identified in 18,673 (69%) positively flagged urine samples. BACT > 10.000/µL combined with a gram-negative flag had a >90% positive predictive value for the presence of gram-negative uropathogens. The absence of gram-positive flag or YLC had high negative predictive values (99% and >99%, respectively) and are, therefore, best used to rule out the presence of gram-positive bacteria or yeast. WBC counts did not add to the prediction of uropathogens. CONCLUSION: Implementation of the UF-4000 in routine practice decreased the number of cultured urine samples by 37%. Bacterial cell counts were highly predictive for the presence of UTI, especially when combined with the presence of a gram-negative flag.

Cost Effectiveness of Rectal Culture-based Antibiotic Prophylaxis in Transrectal Prostate Biopsy: The Results from a Randomized, Nonblinded, Multicenter Trial.

Background: Culture-based antibiotic prophylaxis is a plausible strategy to reduce infections after transrectal prostate biopsy (PB) related to fluoroquinolone-resistant pathogens. Objective: To assess the cost effectiveness of rectal culture-based prophylaxis compared with empirical ciprofloxacin prophylaxis. Design setting and participants: The study was performed alongside a trial in 11 Dutch hospitals investigating the effectiveness of culture-based prophylaxis in transrectal PB between April 2018 and July 2021 (trial registration number: NCT03228108). Intervention: Patients were 1:1 randomized for empirical ciprofloxacin prophylaxis (oral) or culture-based prophylaxis. Costs for both prophylactic strategies were determined for two scenarios: (1) all infectious complications within 7 d after biopsy and (2) culture-proven Gram-negative infections within 30 d after biopsy. Outcome measurements and statistical analysis: Differences in costs and effects (quality-adjusted life-years [QALYs]) were analyzed from a healthcare and societal perspective (including productivity losses, and travel and parking costs) using a bootstrap procedure presenting uncertainty surrounding the incremental cost-effectiveness ratio in a cost-effectiveness plane and acceptability curve. Results and limitations: For the 7-d follow-up period, culture-based prophylaxis (n = 636) was €51.57 (95% confidence interval [CI] 6.52-96.63) more expensive from a healthcare perspective and €16.95 (95% CI -54.29 to 88.18) from a societal perspective than empirical ciprofloxacin prophylaxis (n = 652). Ciprofloxacin-resistant bacteria were detected in 15.4%. Extrapolating our data, from a healthcare perspective, 40% ciprofloxacin resistance would lead to equal cost for both strategies. Results were similar for the 30-d follow-up period. No significant differences in QALYs were observed. Conclusions: Our results should be interpreted in the context of local ciprofloxacin resistance rates. In our setting, from a healthcare perspective, culture-based prophylaxis was significantly more expensive than empirical ciprofloxacin prophylaxis. From a societal perspective, culture-based prophylaxis was somewhat more cost effective against the threshold value customary for the Netherlands (€80.000). Patient summary: Culture-based prophylaxis in transrectal prostate biopsy was not associated with reduced costs compared with empirical ciprofloxacin prophylaxis.

Rectal Culture-Based Versus Empirical Antibiotic Prophylaxis to Prevent Infectious Complications in Men Undergoing Transrectal Prostate Biopsy: A Randomized, Nonblinded Multicenter Trial.

BACKGROUND: An increase in infections after transrectal prostate biopsy (PB), related to an increasing number of patients with ciprofloxacin-resistant rectal flora, necessitates the exploration of alternatives for the traditionally used empirical prophylaxis of ciprofloxacin. We compared infectious complication rates after transrectal PB using empirical ciprofloxacin prophylaxis versus culture-based prophylaxis. METHODS: In this nonblinded, randomized trial, between 4 April 2018 and 30 July 2021, we enrolled 1538 patients from 11 Dutch hospitals undergoing transrectal PB. After rectal swab collection, patients were randomized 1:1 to receive empirical prophylaxis with oral ciprofloxacin (control group [CG]) or culture-based prophylaxis (intervention group [IG]). Primary outcome was any infectious complication within 7 days after biopsy. Secondary outcomes were infectious complications within 30 days, and bacteremia and bacteriuria within 7 and 30 days postbiopsy. For primary outcome analysis, the χ2 test stratified for hospitals was used. Trial registration number: NCT03228108. RESULTS: Data from 1288 patients (83.7%) were available for analysis (CG, 652; IG, 636). Infection rates within 7 days postbiopsy were 4.3% (n = 28) (CG) and 2.5% (n = 16) (IG) (P value = .08; reduction: -1.8%; 95% confidence interval, -.004 to .040). Ciprofloxacin-resistant bacteria were detected in 15.2% (n = 1288). In the CG, the presence of ciprofloxacin-resistant rectal flora resulted in a 6.2-fold higher risk of early postbiopsy infection. CONCLUSIONS: Our study supports the use of culture-based prophylaxis to reduce infectious complications after transrectal PB. Despite adequate prophylaxis, postbiopsy infections can still occur. Therefore, culture-based prophylaxis must be weighed against other strategies that could reduce postbiopsy infections. Clinical Trials Registration. NCT03228108.

Regional Impact of COVID-19-Associated Pulmonary Aspergillosis (CAPA) during the First Wave.

BACKGROUND: Critically ill COVID-19 patients have proven to be at risk for developing invasive fungal infections. However, the incidence and impact of possible/probable COVID-19-associated pulmonary aspergillosis (CAPA) in severe COVID-19 patients varies between cohorts. We aimed to assess the incidence, risk factors, and clinical outcome of invasive pulmonary aspergillosis in a regional cohort of COVID-19 intensive care patients. METHODS: We performed a regional, multicentre, retrospective cohort study in the intensive care units (ICUs) in North Brabant, The Netherlands. We included adult patients with rt-PCR-confirmed SARS-CoV-2 infection (COVID-19), requiring mechanical ventilation for acute respiratory distress syndrome. Demographics, clinical course, biomarker value, and treatment outcomes were compared between the groups with possible/probable CAPA from the main study centre and the regional centres, and without signs of CAPA from the main study centre as controls. The primary aim was to assess the regional impact of possible/probable CAPA in COVID-19 ICU patients, measured as all-cause mortality at 30 days after ICU admission. Secondary outcomes were risk factors for developing CAPA, based on underlying host factors and to identify the value of the mycological arguments for the diagnosing of CAPA. RESULTS: Between 1 March and 30 April 2020, we included 123 patients with severe COVID-19: 29 patients (30.9%) in the main ICU with possible/probable CAPA, and 65 (69.1%) with no signs of CAPA; 29 patients in the regional ICUs with signs of CAPA. Patients' characteristics and risk factors did not differ for CAPA and non-CAPA patients. Patients with COPD and/or chronic steroid medication developed CAPA more frequently, although this was not statistically significant. CAPA patients were admitted to the ICU earlier, had lower PF-ratios, and more often required renal replacement therapy. All-cause 30-day mortality was significantly higher in mechanically ventilated COVID-19 patients with possible/probable CAPA 39.7% (23/58) compared to patients without evidence for CAPA 16.9% (11/65) (OR 3.2 [95% CI 1.4-7.4] p = 0.005). CONCLUSION: The high incidence of possible and probable CAPA in critically ill COVID-19 patients is alarming. The increase in 30-day mortality in CAPA highlights the need for active surveillance and management strategies in critically ill COVID-19 patients.

The clinical relevance of IgM and IgA anti-pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency.

Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)-antibodies, PnPS IgA and IgM-antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA-PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti-PnPS IgM and IgA-assays in patients with suspected primary immunodeficiency in a large teaching hospital in 's-Hertogenbosch, the Netherlands. Serotype-specific-PnPS IgG assays were performed; subsequently, 23-valent-PnPS IgG assays (anti-PnPS IgG assays), and later anti-PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre- and six of 10 post-immunization samples from good responders to PnPS serotype-specific IgG testing had decreased anti-PnPS IgA and/or IgM titres. Of these, three pre- and no post-immunization samples were from patients previously classified as 'no PAD'. Determination of anti-PnPS IgA and IgM in addition to anti-PnPS IgG did not reduce the need for serotype-specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post-immunization samples: anti-PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63-0.97; anti-PnPS IgM + IgG AUC 0.80, 95% CI = 0.62-0.98; anti-PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51-0.91; anti-PnPS IgG AUC = 0.93, 95% CI = 0.85-1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype-specific PnPS IgG can still display impaired anti-PnPS IgM and IgA responses, and that the additional measurement of anti-PnPS IgA and IgM could not reduce the need for serotype-specific IgG testing. Future studies are needed to investigate the clinical relevance of potential 'specific IgA or IgM antibody deficiency' in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.

Focusing on Good Responders to Pneumococcal Polysaccharide Vaccination in General Hospital Patients Suspected for Immunodeficiency. A Decision Tree Based on the 23-Valent Pneumococcal IgG Assay.

Background and Aim: Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping. Methods: Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC). Results: Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 µg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 µg/ml and/or post-immunization-titer ≥96.1 µg/ml and none with a post-immunization-titer ≤38.5 µg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict poor responders would have been used. Conclusion: In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.

Risk factors for developing acute gastrointestinal, skin or respiratory infections following obstacle and mud run participation, the Netherlands, 2017.

BackgroundIn the Netherlands, obstacle, mud and survival runs are increasingly popular. Although outbreaks of gastroenteritis have been reported following these events, associated health risks have not been systematically assessed.AimTo investigate the incidence of acute gastrointestinal infections (AGI), skin infections (SI) and respiratory infections (RI) among obstacle run participants, as well as risk factors.MethodsBetween April and October 2017, we conducted a retrospective cohort study among 2,900 participants of 17 obstacle runs in the Netherlands. Demographic, symptomatic and behavioural data were collected from participants via an online questionnaire 1 week after participation in an obstacle run. Stool specimens were obtained from respondents for microbiological tests. Adjusted relative risks (aRR) and 95% confidence intervals (CI) using multilevel binomial regression analysis were calculated.ResultsOf 2,646 respondents (median age: 33 years; 53% male), 76 had AGI after the obstacle run; ingesting mud was associated with AGI (aRR: 1.7; 95% CI: 1.2-4.9) and 38 respondents had AGI during or in the week before the obstacle run. Overall, 103 respondents reported SI and 163 RI. Rinsing off in a hot tub was associated with SI (aRR: 2.2; 95% CI: 1.7-2.8). Of 111 stool specimens, 13 tested positive for six different pathogens. No clusters were found.ConclusionThe reported incidence of AGI, SI and RI was low. Risk of these infections could be decreased by informing participants on preventive measures, e.g. showering vs rinsing in the hot tub, avoiding ingesting mud and not participating with symptoms of AGI.

Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers.

In the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak of NDM-1-producing Klebsiella pneumoniae infection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated health care centers (HCCs). Next-generation sequencing was performed on 250 carbapenemase-producing Enterobacteriaceae isolates, including 42 NDM-positive isolates obtained from 29 persons at the outbreak site. Most outbreak isolates were K. pneumoniae (n = 26) and Escherichia coli (n = 11), but 5 isolates comprising three other Enterobacteriaceae species were also cultured. The 26 K. pneumoniae isolates had sequence type 873 (ST873), as did 7 unrelated K. pneumoniae isolates originating from five geographically dispersed HCCs. The 33 ST873 isolates that clustered closely together using whole-genome multilocus sequence typing (wgMLST) carried the same plasmids and had limited differences in the resistome. The 11 E. coli outbreak isolates showed great variety in STs, did not cluster using wgMLST, and showed considerable diversity in resistome and plasmid profiles. The blaNDM-1 gene-carrying plasmid present in the ST873 K. pneumoniae isolates was found in all the other Enterobacteriaceae species cultured at the outbreak location and in a single E. coli isolate from another HCC. We describe a hospital outbreak with an NDM-1-producing K. pneumoniae strain from an unknown source that was also found in patients from five other Dutch HCCs in the same time frame without an epidemiological link. Interspecies transfer of the resistance plasmid was observed in other Enterobacteriaceae species isolated at the outbreak location and in another HCC.

Acute Mono-Arthritis of the Knee: A Case Report of Infection with Parvimonas Micra and Concomitant Pseudogout.

Parvimonas micra is a rare pathogen for septic arthritis and is known for its subacute onset. We report a case of acute arthritis of the knee caused by P. micra and pseudogout. Initially, calcium pyrophosphate crystals were found in the knee, which were successfully treated with a steroid injection. Only anaerobic cultures became positive. A 16S rRNA PCR-analysis was necessary to identify P. micra as causative agent, a method which is never described before in similar cases. The infection was treated with clindamycin for 6 weeks. This is the third case report of a septic arthritis caused by P. micra and the second which also reports concomitant pseudogout.

Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic.

BACKGROUND: Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007-2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever. METHODS: A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever. RESULTS: Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months. CONCLUSIONS: A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever.

Pediatric acute Q fever mimics other common childhood illnesses.

Knowledge of Q fever has increased over the last decades, but research has mainly focused on adults. Data in children are scarce, and current knowledge is mostly based on case reports. The aim of this study was to determine predictors for acute Q fever in children in the general population. We retrospectively studied all children tested for Coxiella burnetii by serology and/or PCR upon request of their general practitioner in the regional laboratory for Medical Microbiology of the Jeroen Bosch during the Q fever outbreak in the Netherlands between 2007 and 2011. A total of 1061 patients was analyzed. Influenza-like illness and respiratory tract infection were the most common presentations of acute Q fever, mimicking other common childhood illnesses. None of the reported symptoms was significantly related to a positive test outcome and therefore presenting signs or symptoms have no predictive value in diagnosing Q-fever in children. Only diagnostic tests are reliable. As the infection generally follows a mild and uncomplicated course, we question if the difficulty of recognizing pediatric Q fever is a problem worth solving.

Epidemic Q fever in humans in the Netherlands.

In 2005, Q fever was diagnosed on two dairy goat farms and 2 years later it emerged in the human population in the south of the Netherlands. From 2007 to 2010, more than 4,000 human cases were notified with an annual seasonal peak. The outbreaks in humans were mainly restricted to the south of the country in an area with intensive dairy goat farming. In the most affected areas, up to 15% of the population may have been infected. The epidemic resulted in a serious burden of disease, with a hospitalisation rate of 20% of notified cases and is expected to result in more cases of chronic Q fever among risk groups in the coming years. The most important risk factor for human Q fever is living close (<5 km) to an infected dairy goat farm. Occupational exposure plays a much smaller role. In 2009 several veterinary control measures were implemented including mandatory vaccination of dairy goats and dairy sheep, improved hygiene measures, and culling of pregnant animals on infected farms. The introduction of these drastic veterinary measures has probably ended the Q fever outbreak, for which the Netherlands was ill-prepared.

Proximity to goat farms and Coxiella burnetii seroprevalence among pregnant women.

During 2007-2009, we tested serum samples from 2,004 pregnant women living in an area of high Q fever incidence in the Netherlands. Results confirmed that presence of antibodies against Coxiella burnetii is related to proximity to infected dairy goat farms. Pregnant women and patients with certain cardiovascular conditions should avoid these farms.

Follow-up of 686 patients with acute Q fever and detection of chronic infection.

BACKGROUND: Recent outbreaks in the Netherlands allowed for laboratory follow-up of a large series of patients with acute Q fever and for evaluation of test algorithms to detect chronic Q fever, a condition with considerable morbidity and mortality. METHODS: For 686 patients with acute Q fever, IgG antibodies to Coxiella burnetii were determined using an immunofluorescence assay at 3, 6, and 12 months of follow-up. Polymerase chain reaction (PCR) was performed after 12 months and on earlier serum samples with an IgG phase I antibody titer ≥ 1:1024. RESULTS: In 43% of patients, the IgG phase II antibody titers remained high (≥ 1:1024) at 3, 6, and 12 months of follow-up. Three months after acute Q fever, 14% of the patients had an IgG phase I titer ≥ 1:1024, which became negative later in 81%. IgG phase I antibody titers were rarely higher than phase II titers. Eleven cases of chronic Q fever were identified on the basis of serological profile, PCR results, and clinical presentation. Six of these patients were known to have clinical risk factors at the time of acute Q fever. In a comparison of various serological algorithms, IgG phase I titer ≥ 1:1024 at 6 months had the most favorable sensitivity and positive predictive value for the detection of chronic Q fever. CONCLUSIONS: The wide variation of serological and PCR results during the follow-up of acute Q fever implies that the diagnosis of chronic Q fever, necessitating long-term antibiotic treatment, must be based primarily on clinical grounds. Different serological follow-up strategies are needed for patients with and without known risk factors for chronic Q fever.

Foam sclerotherapy: investigating the need for sterile air.

BACKGROUND: Sclerotherapy with foam is becoming increasingly popular for the treatment of varicose veins. There is no consensus on the necessity of sterile air or other gases to produce foam. OBJECTIVES: To evaluate the potential risk of bacterial inoculation of polidocanol (POL) foam using room air and the antimicrobial properties of polidocanol. MATERIALS AND METHODS: The amount of airborne microorganisms was quantitatively measured. Four bacterial strains were tested for susceptibility to polidocanol: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Streptococcus pyogenes. RESULTS: Air measurements varied as a result of air movement and the number of people in the room. Although the risk of introducing one colony-formin unit can be calculated as less than 1 in 330, the clinical relevance is still to be determined. No inhibition of bacterial growth was achieved with POL in of any of the tested strains. CONCLUSIONS: Foam sclerotherapy with POL prepared in a standard treatment room is a safe procedure without the risk of introducing a severe bacterial complication. The use of sterile air, nitrogen, or carbon dioxide is unnecessary and will make foam sclerotherapy with POL more elaborate and more expensive to use.

Evaluation of a diagnostic algorithm for acute Q fever in an outbreak setting.

In the peak of the 2009 Q fever outbreak in the Netherlands, we introduced a diagnostic algorithm for acute Q fever with an enzyme-linked immunosorbent assay for immunoglobulin M antibodies to Coxiella burnetii phase II antigens (MII screen) as an initial step. Subsequently, an immunofluorescence assay or PCR was performed depending on the MII screen outcome, date of onset of disease, and inpatient or outpatient setting. The impact of MII screen on the number of immunofluorescence assays performed and the contribution of PCR to diagnosis were retrospectively evaluated in 825 patients referred in a 17-day period. Acute Q fever was diagnosed in 256 patients. The introduction of MII screen reduced the number of immunofluorescence assays performed by more than 80%. In 103 patients, PCR analysis contributed to the diagnosis of acute Q fever. Q fever diagnostics were hampered by the fact that for a high number of patients the date of onset of disease was not provided and the requested follow-up serum samples were not received.

Antibodies against Coxiella burnetii and pregnancy outcome during the 2007-2008 Q fever outbreaks in The Netherlands.

BACKGROUND: Q fever has become a major public health problem in The Netherlands. Infection with Coxiella burnetii (Q fever) during pregnancy has resulted in adverse pregnancy outcome in the majority of reported cases. Therefore, we aimed to quantify this risk by examining the earliest periods corresponding to the epidemic in The Netherlands. METHODS: Serum samples that had been collected from the area of highest incidence by an existing national prenatal screening programme and data from the Netherlands Perinatal Registry (PRN) on diagnosis and outcome were used. We performed indirect immunofluorescence assay to detect the presence of IgM and IgG antibodies against C. burnetii in the samples. The serological results were analyzed to determine statistical association with recorded pregnancy outcome. RESULTS: Evaluation of serological results for 1174 women in the PRN indicated that the presence of IgM and IgG antibodies against phase II of C. burnetii was not significantly associated with preterm delivery, low birth weight, or several other outcome measures. CONCLUSION: The present population-based study showed no evidence of adverse pregnancy outcome among women who had antibodies to C. burnetii during early pregnancy.

[Chronic Q fever during pregnancy]. / Chronische Q-koorts tijdens de zwangerschap.

A 42-year-old woman visited the pulmonologist for follow-up after a pneumonia. In retrospect the pneumonia appeared to be a manifestation of an acute Q fever infection. A few weeks later the patient was found to be unexpectedly pregnant. At the normal serological follow-up six months after the primary infection chronic Q fever infection was diagnosed. Doxycycline and hydroxychloroquine are contraindicated in pregnancy and the patient was found to be allergic to co-trimoxazole. Therefore treatment with erythromycin was chosen on empirical grounds. The patient had many symptoms during pregnancy. After 38 weeks and 2 days amenorrhea labour was induced on maternal indication. Finally a healthy boy of 3850 grams was born by caesarean section. In view of the increased risk of chronic Q fever infection during pregnancy we advise intensified serological monitoring of patients with acute Q fever who subsequently become pregnant.

Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial.

BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov, protocol record NL30340.042.09.