Publications by authors named "Wouter Van den Bijllaardt"

13 Publications

  • Page 1 of 1

Evaluation of the test accuracy of a SARS-CoV-2 rapid antigen test in symptomatic community dwelling individuals in the Netherlands.

PLoS One 2021 13;16(5):e0250886. Epub 2021 May 13.

Microvida Laboratory for Medical Microbiology, Amphia Hospital, Breda, The Netherlands.

Background: SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (qRT-PCR) is well suited for the diagnosis of clinically ill patients requiring treatment. Application for community testing of symptomatic individuals for disease control purposes however raises challenges. SARS-CoV-2 rapid antigen tests might offer an alternative, but quality evidence on their performance is limited.

Methods: We conducted an evaluation of the test accuracy of the 'BD Veritor System for Rapid Detection of SARS-CoV-2' (VRD) compared to qRT-PCR on combined nose/throat swabs obtained from symptomatic individuals at Municipal Health Service (MHS) COVID-19 test centers in the Netherlands. In part one of the study, with the primary objective to evaluate test sensitivity and specificity, all adults presenting at one MHS test center were eligible for inclusion. In part two, with the objective to evaluate test sensitivity stratified by Ct (cycle threshold)-value and time since symptom onset, adults who had a positive qRT-PCR obtained at a MHS test center were eligible.

Findings: In part one (n = 352) SARS-CoV-2 prevalence was 4.8%, overall specificity 100% (95%CI: 98·9%-100%) and sensitivity 94·1% (95%CI: 71·1%-100%). In part two (n = 123) the sensitivity was 78·9% (95%CI: 70·6%-85·7%) overall, 89·4% (95% CI: 79·4%-95·6%) for specimen obtained within seven days after symptom onset and 93% (95% CI: 86%-97.1%) for specimen with a Ct-value below 30.

Interpretation: The VRD is a promising diagnostic for COVID-19 testing of symptomatic community-dwelling individuals within seven days after symptom onset in context of disease control. Further research on practical applicability and the optimal position within the testing landscape is needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250886PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118553PMC
May 2021

COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study.

Lancet Infect Dis 2020 11 2;20(11):1273-1280. Epub 2020 Jul 2.

Viroscience, Erasmus MC, Rotterdam, Netherlands.

Background: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers.

Methods: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients.

Findings: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community.

Interpretation: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers.

Funding: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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http://dx.doi.org/10.1016/S1473-3099(20)30527-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332281PMC
November 2020

Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic.

JAMA Netw Open 2020 05 1;3(5):e209673. Epub 2020 May 1.

Department of Infection Control, Amphia Hospital, Breda, the Netherlands.

Importance: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring.

Objective: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms.

Design, Setting, And Participants: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020.

Main Outcomes And Measures: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase-polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19.

Results: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms.

Conclusions And Relevance: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.9673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243090PMC
May 2020

Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands, March 2020.

Euro Surveill 2020 03;25(12)

Amphia hospital, Breda, the Netherlands.

To rapidly assess possible community transmission in Noord-Brabant, the Netherlands, healthcare workers (HCW) with mild respiratory complaints and without epidemiological link (contact with confirmed case or visited areas with active circulation) were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within 2 days, 1,097 HCW in nine hospitals were tested; 45 (4.1%) were positive. Of six hospitals with positive HCW, two accounted for 38 positive HCW. The results informed local and national risk management.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.12.2000334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118342PMC
March 2020

[Gastroenteritis at sporting events with water and mud: an example to illustrate outbreak investigation methods].

Ned Tijdschr Geneeskd 2019 09 9;163. Epub 2019 Sep 9.

GGD Hart voor Brabant, afd. Infectieziektebestrijding, Den Bosch.

OBJECTIVE To determine the size and causative pathogen of the outbreak and to identify risk factors for developing gastroenteritis among participants of the Survivalrun in Udenhout in September 2016. Design Retrospective cohort study. METHODS We sent an invitation to go to an online questionnaire to participants and volunteers of the Survivalrun by email. The link to the questionnaire was also shared on the Facebook page and website of the Survivalrun. We calculated attack rates (AR) and relative risks (RR) for several exposures to identify risk factors for developing diarrhoea and/or vomiting within 3 days after the run. In addition, stool samples of six participants were tested for common gastrointestinal pathogens. RESULTS A total of 444 people completed the questionnaire. Symptoms of gastroenteritis were reported by 163 study participants (37%). Five participants reported symptoms of gastroenteritis in the week before and three participants during the Survivalrun. Multivariate analysis identified the following risk factors for developing gastroenteritis: participation on the second day of the run(RR 2.4: 95% CI 1.1-5.3), ingesting water (RR 1.7: 95% CI 1.3-2.3) and ingesting mud (RR 1.3: 95% CI 1.1-1.6). Four out of six stool samples tested positive for norovirus (various types). CONCLUSION This outbreak investigation shows that pathogens, such as norovirus, can easily spread during sporting events where participants have to move through water and mud. Specific methods and knowledge of the circumstances are essential for a thorough outbreak investigation.
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September 2019

Culturing periprosthetic tissue in blood culture bottles results in isolation of additional microorganisms.

Eur J Clin Microbiol Infect Dis 2019 Feb 14;38(2):245-252. Epub 2018 Nov 14.

Laboratory for Medical Microbiology and Immunology, Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands.

Despite low sensitivity, culture of periprosthetic tissue (PPT) specimens on agars and in broths has traditionally been used for the detection of causative microorganisms in patients suspected for prosthetic joint infection (PJI). The aim of this study was to evaluate the added diagnostic value of culturing PPT in blood culture bottles (BCB) over the conventional combination of standard agar and broth alone. This prospective cohort study was conducted over a 12-month period and included consecutive patients undergoing revision arthroplasty. Overall, 113 episodes from 90 subjects were studied; 45 subjects (50.0%) met the Infectious Diseases Society of America (IDSA) criteria for PJI, of whom the majority (75.6%) had an acute infection. Sensitivity and specificity of culture were assessed using IDSA criteria for PJI as gold standard. Although the increase in sensitivity from 84.44 (CI 70.54; 93.51) to 93.33% (81.73; 98.60) was not significant, added diagnostic value of culturing PPT in BCBs was demonstrated by the significantly higher number of detected pathogens in culture sets with BCBs compared to culture without BCBs (61 pathogens in conventional set versus 89 when BCBs were included for 57 PJI episodes, P = <0.0001). In 17 (29.8%) episodes, microorganisms were cultured from BCBs only, and in 9 (52.9%) of these episodes, virulent pathogens were found. This study demonstrates that PPT culture in BCBs leads to isolation of additional microorganisms, both virulent and low-virulent, which were not cultured with use of agars and broths alone. Isolation of additional causative microorganisms has serious consequences for the treatment strategy in PJI.
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http://dx.doi.org/10.1007/s10096-018-3420-6DOI Listing
February 2019

Susceptibility of ESBL Escherichia coli and Klebsiella pneumoniae to fosfomycin in the Netherlands and comparison of several testing methods including Etest, MIC test strip, Vitek2, Phoenix and disc diffusion.

J Antimicrob Chemother 2018 09;73(9):2380-2387

Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.

Objectives: Fosfomycin susceptibility testing is complicated and prone to error. Before using fosfomycin widely in patients with serious infections, acquisition of WT distribution data and reliable susceptibility testing methods are crucial. In this study, the performance of five methods for fosfomycin testing in the routine laboratory against the reference method was evaluated.

Methods: Ten laboratories collected up to 100 ESBL-producing isolates each (80 Escherichia coli and 20 Klebsiella pneumoniae). Isolates were tested using Etest, MIC test strip (MTS), Vitek2, Phoenix and disc diffusion. Agar dilution was performed as the reference method in a central laboratory. Epidemiological cut-off values (ECOFFs) were determined for each species and susceptibility and error rates were calculated.

Results: In total, 775 E. coli and 201 K. pneumoniae isolates were tested by agar dilution. The ECOFF was 2 mg/L for E. coli and 64 mg/L for K. pneumoniae. Susceptibility rates based on the EUCAST breakpoint of ≤32 mg/L were 95.9% for E. coli and 87.6% for K. pneumoniae. Despite high categorical agreement rates for all methods, notably in E. coli, none of the alternative antimicrobial susceptibility testing methods performed satisfactorily. Due to poor detection of resistant isolates, very high error rates of 23.3% (Etest), 18.5% (MTS), 18.8% (Vitek2), 12.5% (Phoenix) and 12.9% (disc diffusion) for E. coli and 22.7% (Etest and MTS), 16.0% (Vitek2) and 12% (Phoenix) for K. pneumoniae were found. None of the methods adequately differentiated between WT and non-WT populations.

Conclusions: Overall, it was concluded that none of the test methods is suitable as an alternative to agar dilution in the routine laboratory.
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http://dx.doi.org/10.1093/jac/dky214DOI Listing
September 2018

Shortening the incubation time for the combination disk diffusion extended-spectrum β-lactamase (ESBL) confirmation test: how far can we go?

Int J Antimicrob Agents 2017 Sep 6;50(3):473-476. Epub 2017 Jul 6.

Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands; Department of Medical Microbiology, Haaglanden Medical Centre, The Hague, The Netherlands.

The combination disk diffusion extended-spectrum β-lactamase (ESBL) confirmation test (CDT) is used for the confirmation of ESBL production in Enterobacteriaceae and usually takes 16-20 h to results. In this study, we searched for the shortest possible incubation time without a reduction in reliability. A total of 125 ESBL screening-positive isolates were subjected to CDT and were molecularly characterised by microarray. Inhibition zones were read every hour over 6-18 h of incubation. Concordance between earlier and 18-h readings was calculated for each hour. Results were validated on 224 isolates during routine clinical practice. For the initial 125 isolates, concordance (Cohen's κ) between the 6-h and 18-h readings was 0.88 [95% confidence interval (CI) 0.78-0.96; P <0.001]. The earliest time point for full concordance with the 18-h reading was 10 h. Validation of the 10-h reading for 224 clinical isolates resulted in a concordance of 0.99 (95% CI 0.98-1.0) between the 10-h and 18-h readings. Overall concordance on all 349 isolates was 0.99 (95% CI 0.97-1.0). Reading after 10 h of incubation has an excellent correlation with results after 18 h of incubation. This can significantly reduce the turnaround time for ESBL detection in laboratories with long opening hours or providing a 24/7 service. Consequently, there is a potential for implementing infection control measures up to 8 h earlier.
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http://dx.doi.org/10.1016/j.ijantimicag.2017.03.032DOI Listing
September 2017

Shortening the incubation time for antimicrobial susceptibility testing by disk diffusion for Enterobacteriaceae: how short can it be and are the results accurate?

Int J Antimicrob Agents 2017 May 3;49(5):631-637. Epub 2017 Mar 3.

Department of Medical Microbiology, Haaglanden Medical Centre, The Hague, The Netherlands.

The standard incubation time for antimicrobial susceptibility testing (AST) by disk diffusion is primarily based on laboratory working hours rather than growth and kill characteristics of bacteria. Faster AST results could result in better patient outcomes and reduced costs by initiating earlier appropriate therapy. The earliest possible reading moment for disk diffusion using established disk zone diameter breakpoints for Enterobacteriaceae was determined with a special focus on the accuracy of the results. A total of 88 Enterobacteriaceae challenge isolates, including isolates with specific resistance mechanisms such as extended-spectrum β-lactamase (ESBL), were subjected to disk diffusion with 15 antibiotics. Hourly images were automatically produced by an incubator/camera combination from 1 h to 20 h. Disk zones were plotted over time for all combinations. Essential and categorical agreement rates using the final reading after 20 h of incubation as a reference were calculated for every hour. In total, 1320 antibiotic-micro-organism combinations were tested. Clear growth with readable inhibition zones was visible after 6 h of incubation for the majority (95.8%) of plates and after 7 h for all incubated plates. However, zone sizes changed significantly after those time points for a number of strains. After 10 h of incubation, minor, major and very major error rates were 1.6% (n = 21), 0.2% (n = 1) and 0.7% (n = 4), respectively. The results of this study clearly indicate that early reading of inhibition zones to 10 h after incubation is feasible and accurate and thus may save significantly on turnaround time.
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http://dx.doi.org/10.1016/j.ijantimicag.2016.12.019DOI Listing
May 2017

Seroprotection after hepatitis a vaccination in patients with drug-induced immunosuppression.

J Travel Med 2013 Sep-Oct;20(5):278-82. Epub 2013 Jul 9.

Department of Infectious Diseases, Public Health Service (GGD) Gelre-IJssel, Apeldoorn, The Netherlands.

Background: Increasing numbers of travelers using immunosuppressive drugs visit hepatitis A endemic countries. Data on protection rates after hepatitis A vaccination in this group are scarce.

Methods: In this retrospective study, records of subjects with hepatitis A serology taken after vaccination were searched for in travel clinic databases. Relation between immunosuppressive drug use, age, gender, and time between vaccination and serology was evaluated.

Results: Seroprotection rates within 4 weeks after primary vaccination (50%) are lower than after 4 weeks (64%). After the complete series of two vaccinations seroprotection rates reach 95% although success depends on the immunosuppressive drug being used. Subjects under anti-TNF alpha treatment have significantly lower seroprotection rates than subjects using classical immunosuppressive drugs after the second vaccination. There is no influence of age or gender on seroprotection rates.

Conclusions: Last-minute vaccination in subjects using immunosuppressive medication is not reliable, only 60% of our subjects had a protective antibody level after a single vaccination. When serology was done within 4 weeks after a single vaccination, seroprotection rates were only 50%, after 4 weeks this number rose to 64%. When persons visit a travel clinic in time for a complete vaccination series, satisfactory seroprotection rates can be reached. Seroprotection rate depends on the drug being used, persons using anti-TNF alpha are less protected.
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http://dx.doi.org/10.1111/jtm.12050DOI Listing
April 2014

A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania.

Malar J 2011 Aug 24;10:247. Epub 2011 Aug 24.

Kilimanjaro Christian Medical College-Kilimanjaro Clinical Research Institute, Moshi, Tanzania.

Background: Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania.

Methods: In a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1 km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period.

Results: The coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2).

Conclusions: This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity. The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting.

Trial Registration: ClinicalTrials.gov: NCT00509015.
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http://dx.doi.org/10.1186/1475-2875-10-247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169516PMC
August 2011

In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals.

Antimicrob Agents Chemother 2010 May 1;54(5):1762-8. Epub 2010 Mar 1.

Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.

The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the hemolytic effect of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) plus a single dose of primaquine (PQ; 0.75 mg/kg of body weight) in children aged 1 to 12 years. Children were randomized to receive SP+AS+PQ or placebo; those with a hemoglobin (Hb) level below 8 g/dl were excluded from receiving PQ and received SP+AS. The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment. This reduction in Hb was most pronounced in G6PD-deficient (G6PD A-) individuals (-2.5 g/dl; 95% confidence interval [95% CI], -1.2 to -3.8 g/dl) but was also observed in heterozygotes (G6PD A) (-1.6 g/dl; 95% CI, -0.9 to -2.2 g/dl) and individuals with the wild-type genotype (G6PD B) (-0.5 g/dl; 95% CI, -0.4 to -0.6 g/dl). Moderate anemia (Hb level of <8 g/dl) was observed in 40% (6/15 individuals) of the G6PD A-, 11.1% (3/27 individuals) of the G6PD A, and 4.5% (18/399 individuals) of the G6PD B individuals; one case of severe anemia (Hb level of <5 g/dl) was observed. PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis.
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http://dx.doi.org/10.1128/AAC.01135-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863610PMC
May 2010

The suitability of clay pots for indoor sampling of mosquitoes in an arid area in northern Tanzania.

Acta Trop 2009 Aug 11;111(2):197-9. Epub 2009 Apr 11.

Department of Medical Microbiology 268, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Water storage clay pots have been recently explored as method for outdoor mosquito sampling and as novel device for administrating insect-pathogenic fungi to mosquitoes. Their suitability for indoor mosquito sampling in natural conditions is unknown. We tested clay pots as indoor resting sites alongside catches by CDC light trap in an area of low malaria endemicity in northern Tanzania. Mosquitoes were caught by clay pots although the rate of female Anopheles mosquito catches was 22.64 (95% CI 11.26-45.52) times greater for CDC light traps. The proportion of fed female Anophelines was significantly higher for clay pots compared to CDC light trap (p<0.001), indicating these methods sample different populations of mosquitoes. Although we were able to identify households with a consistently higher exposure to mosquitoes by CDC light trap, there was no apparent heterogeneity in mosquito catches by clay pots. We conclude that clay pots are not a reliable tool to sample mosquitoes in the dry season in an area of low transmission intensity with Anopheles arabiensis as principle vector.
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http://dx.doi.org/10.1016/j.actatropica.2009.04.003DOI Listing
August 2009