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

Contains fulltext : 87399.pdf (publisher's version ) (Open Access)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

Q fever during pregnancy : lessons from the Dutch epidemic

Van 2007 tot 2010 kampte Nederland met een Q-koortsuitbraak van ongekende omvang, met meer dan 4000 humane gevallen. Q-koorts is een infectieziekte die wordt veroorzaakt door de bacterie Coxiella burnetii. Het is een zoönose, wat betekent dat de bacterie verspreid wordt van dieren op mensen. Met name melkgeiten en –schapen zijn de bron van de humane besmettingen in Nederland. Besmetting van mens-op-mens is zeer zeldzaam. Een acute C. burnetii infectie wordt gekenmerkt door koorts, hepatitis of pneumonie, maar verloopt in 60% van de gevallen asymptomatisch. De incubatietijd is één tot drie weken. Het stellen van de diagnose Q-koorts is lastig, temeer omdat C. burnetii hooginfectieus is en afkapwaarden voor serodiagnostiek niet vaststaan. Bijdragend in de diagnostiek is de antigene variatie die C. burnetii vertoont. Afhankelijk van de duur van infectie produceert het lichaam antistoffen tegen antigenen in een bepaalde fase (eerst tegen fase II antigenen, vervolgens tegen fase I). Hierdoor is er een onderscheid te maken tussen een doorgemaakte infectie, acute infectie of chronische infectie. Na het stellen van de diagnose acute Q-koorts, bestaat de eerste keuze behandeling uit een kuur doxycycline voor minimaal twee weken. Een acute infectie leidt in 1-5% van de gevallen tot een chronisch ziektebeeld, waarbij endocarditis of infecties van vasculaire structuren kunnen ontstaan. De kans op het ontwikkelen van chronische Q-koorts wordt groter geacht bij immuungecompromitteerden, patiënten met pre-existent klep- of vaatlijden en zwangeren. Een langdurige behandeling met doxycycline gecombineerd met hydroxychloroquine is in het geval van chronische Q-koorts aangewezen. Between 2007 and 2010 The Netherlands suffered from on enormous human Q fever outbreak with over 4000 notified cases. Q fever is a zoonosis, caused by the intracellular bacterium Coxiella burnetii. In the Dutch situation, especially infections in dairy goat and sheep are hypothesised to be the main sources of human infection. Peron-to-person spread is rare. Acute C. burnetii infection is characterised by fever, hepatitis or pneumonia, but remains asymptomatic in 60% of the cases. The incubation period is one to three weeks. Since C. burnetii is highly infectious and cut-off values for serodiagnosis are inconsistent, diagnosing Q fever is difficult. Additive in serodiagnosis is the characteristic of C. burnetii of antigenetic phase variation. Depending on the duration of infection, antibodies against two phases of antigens are produced (first against phase II antigen, later against phase I). Therefore a distinction can be made between an acute, previous or chronic infection. Treatment of acute Q fever consists of doxycycline for at least two weeks. After an acute infection 1-5% of the patients develop chronic Q fever which is often complicated by endocarditis or infection of vascular structures. The risk of chronic Q fever has been reported to be increased in immunocompromised patients, patients with underlying cardiac valve or vascular diseases and pregnant women. In case of chronic Q fever long-term treatment with doxycycline in combination with hydroxychloroquine is recommended.

Prevalence and predictors of over-the-counter medication use among pregnant women: a cross-sectional study in the Netherlands

Citation for published version (APA): Verstappen, G. M., Smolders, E. J., Munster, J. M., Aarnoudse, J. G., & Hak, E. (2013). Prevalence and predictors of over-the-counter medication use among pregnant women: a cross-sectional study in the Netherlands. BMC Public Health, Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Background: Over-the-counter-medication (OTC-medication) use during pregnancy can be potentially harmful for the fetus. To successfully counsel the patient it is important to know if the patient is at risk. In this study possible predictors for OTC-medication use were identified and a model was designed to predict OTC-medication use during pregnancy

Prevalence and predictors of over-the-counter medication use among pregnant women:a cross-sectional study in the Netherlands

<p>Background: Over-the-counter-medication (OTC-medication) use during pregnancy can be potentially harmful for the fetus. To successfully counsel the patient it is important to know if the patient is at risk. In this study possible predictors for OTC-medication use were identified and a model was designed to predict OTC-medication use during pregnancy.</p><p>Methods: We performed a post-hoc analysis on data collected for a clustered clinical trial to study a screening strategy for Query fever. Pregnant women under supervision of a midwife were eligible for inclusion. These women filled out questionnaires during their pregnancy and post-partum. These questionnaires were used to determine the prevalence and to select possible predictors for OTC-medication use. These predictors were included in a prediction model using multivariate analysis. The discrimination and calibration of the model were assessed with Receiver Operating Characteristic analysis and the Hosmer and Lemeshow test.</p><p>Results: Of the 1348 women enrolling in the clustered clinical trial, we included 1246 women in this analysis. The prevalence of OTC-medication use was 12.5%. The predictors for OTC-medication use in our cohort were: nulliparity, use of prescription medication, the presence of a comorbidity, Body Mass Index between 26 and 30 kg/m(2) and General Practitioner visits. These predictors were used to design a prediction model for OTC-medication use. The area under the Receiver Operating Characteristic-curve of the prediction model was 0.667 (95% CI 0.620-0.714 P</p><p>Conclusion: It is possible to indicate women at risk for OTC-medication use during pregnancy, using five maternal characteristics that independently contribute to the prediction model. The predictors are easy to estimate and the model is easy to implement in daily practice.</p>

Nationwide registry-based ecological analysis of Q fever incidence and pregnancy outcome during an outbreak in the Netherlands

Objective: Whether areas affected by Q fever during a large outbreak (2008-2010) had higher rates of adverse pregnancy outcomes than areas not affected by Q fever. Design: Nationwide registry-based ecological study. Setting: Pregnant women in areas affected and not affected by Q fever in the Netherlands, 2003-2004 and 2008-2010. Participants: Index group (N=58 737): pregnant women in 307 areas with more than two Q fever notifications. Reference group (N=310 635): pregnant women in 921 areas without Q fever notifications. As a baseline, pregnant women in index and reference areas in the years 2003-2004 were also included in the reference group to estimate the effect of Q fever in 2008-2010, and not the already existing differences before the outbreak. Main outcome measures: Preterm delivery, small for gestational age, perinatal mortality. Results: In 2008-2010, there was no association between residing in a Q fever-affected area and both preterm delivery (adjusted OR 1.01 (95% CI 0.94 to 1.08)), and perinatal mortality (adjusted OR 0.87 (95% CI 0.72 to 1.05)). In contrast, we found a weak significant association between residing in a Q fever-affected area in 2008-2010 and small for gestational age (adjusted OR 1.06 (95% CI 1.01 to 1.12)), with a population-attributable fraction of 0.70% (95% CI 0.07% to 1.34%). We observed no dose-response relation for this outcome with increasing Q fever notifications, and we did not find a stronger association for women who were in their first trimester of pregnancy during the months of high human Q fever incidence. Conclusions: This study found a weak association between residing in a Q fever-affected area and the pregnancy outcome small for gestational age. Early detection of infection would require mass screening of pregnant women; this does not seem to be justified considering these results, and the uncertainties about its efficacy and the adverse effects of antibiotic treatment