The effect of measuring serum doxycycline concentrations on clinical outcomes during treatment of chronic Q fever.

Background: First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 µg/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. Objectives: To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. Methods: We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. Results: We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 µg/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 µg/mL before dosage increase, and 5.9 µg/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. Conclusions: SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 µg/mL and <10 µg/mL during treatment of chronic Q fever.

High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia.

Community-acquired pneumonia (CAP) is mostly caused by Streptococcus pneumoniae. Identification of the pathogen causing CAP can be achieved by conventional culture techniques of sputum and/or blood, antigen detection from urine or molecular analysis. However, it remains difficult to determine patients who are at risk of severe disease development (intensive care unit [ICU] admittance and/or death). In this retrospective study, 121 patients admitted to the emergency department with pneumonia symptoms were included. Several markers of infection (pneumococcal DNA load in blood (real-time LytA PCR), white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels) were assessed for their ability to predict severe disease development. Of 121 patients, 6 were excluded from the study because of an alternative diagnosis, whereas 8 were excluded from biomarker analysis because of the presence of co-morbidities. Of the 115 patients analysed by the LytA PCR, 23 were positive. PCR detected S. pneumoniae DNA in 82% of patients with positive blood culture for S. pneumoniae. PCR missed three samples from patients in which S. pneumoniae was recovered by blood cultures. However, eight additional LytA PCR-positive samples were detected from patients whose blood cultures remained negative. Pneumococcal DNA load was also monitored in time for 31 patients, of whom 11 had positive PCR results. For 10 out of 11 (91%) positive PCR patients, a clear increase in Ct-values was observed, indicating a lower pneumococcal DNA load in the blood as a result of antibiotic therapy. Biomarker analysis was performed in 107 patients, of whom 29 showed severe disease development. Pneumococcal DNA load (p = 0.026), PCT (p = 0.046) and suPAR (p = 0.001) levels most reliably predicted severe disease development. In conclusion, in patients with CAP, higher pneumococcal DNA load, PCT and suPAR values are associated with severe disease development (ICU admission and/or death). These biomarkers may be useful tools for triage of patients suspected of having CAP in the emergency department.

Capnocytophaga canimorsus meningitis diagnosed by 16S rRNA PCR.

Capnocytophaga canimorsus is a common Gram-negative anaerobic bacterium from the oral flora of dogs, typically transmitted to humans by dog bites. We report a case of C. canimorsus meningitis where there was (on presentation) no apparent predisposing risk factor and in whom we used 16S rRNA PCR gene sequencing to identify the pathogen quickly and to switch to appropriate antibiotic therapy. Physicians should be aware of potential C. canimorsus meningitis if conventional cerebrospinal fluid bacterial culture is negative but Gram staining identifies bacteria, especially in patients with a recent dog bite or known immunodeficiency.

Vascular chronic Q fever: quality of life.

The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50·6 [95% confidence interval (CI) 46·7-54·4] and 44·6 (95% CI 41·6-47·5), respectively. During treatment, the mean physical health score declined significantly by 1·7 points each 3 months (P < 0·001) to 40·8 (95% CI 34·4-45·1). The mean mental health score significantly and steadily increased towards 51·2 (95% CI 46·9-54·3) during follow-up (P = 0·026). A total of 23% of patients were cured after 18 months of follow-up. In conclusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival.

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.

High Coxiella burnetii DNA load in serum during acute Q fever is associated with progression to a serologic profile indicative of chronic Q fever.

PCR is very effective in diagnosing acute Q fever in the early stages of infection, when bacterial DNA is present in the bloodstream but antibodies have not yet developed. The objective of this study was to further analyze the diagnostic value of semiquantitative real-time PCR (qPCR) in diagnosing acute Q fever in an outbreak situation. At the Jeroen Bosch Hospital, in 2009, qPCR testing for Coxiella burnetii DNA was performed for 2,715 patients suspected of having acute Q fever (positive, n = 385; negative, n = 2,330). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the qPCR assay were calculated for patients with negative qPCR results with a follow-up sample obtained within 14 days (n = 305) and qPCR-positive patients with at least one follow-up sample (n = 369). The correctness of the qPCR result was based on immunofluorescence assay results for samples submitted for qPCR and follow-up testing. The sensitivity of the Q fever qPCR assay was 92.2%, specificity 98.9%, PPV 99.2%, and NPV 89.8%. Patients who later developed serologic profiles indicative of chronic Q fever infection had significantly higher C. burnetii DNA loads during the acute phase than did patients who did not (P < 0.001). qPCR testing is a valuable tool for the diagnosis of acute Q fever and should be used in outbreak situations when the onset of symptoms is <15 days earlier. Special attention is needed in the follow-up monitoring of patients with high C. burnetii DNA loads during the acute phase, as this might be an indicator for the development of a serologic profile indicative of chronic infection.

Time-course of antibody responses against Coxiella burnetii following acute Q fever.

Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases.

Screening for Coxiella burnetii seroprevalence in chronic Q fever high-risk groups reveals the magnitude of the Dutch Q fever outbreak.

The Netherlands experienced an unprecedented outbreak of Q fever between 2007 and 2010. The Jeroen Bosch Hospital (JBH) in 's-Hertogenbosch is located in the centre of the epidemic area. Based on Q fever screening programmes, seroprevalence of IgG phase II antibodies to Coxiella burnetii in the JBH catchment area was 10·7% [785 tested, 84 seropositive, 95% confidence interval (CI) 8·5-12·9]. Seroprevalence appeared not to be influenced by age, gender or area of residence. Extrapolating these data, an estimated 40 600 persons (95% CI 32 200-48 900) in the JBH catchment area have been infected by C. burnetii and are, therefore, potentially at risk for chronic Q fever. This figure by far exceeds the nationwide number of notified symptomatic acute Q fever patients and illustrates the magnitude of the Dutch Q fever outbreak. Clinicians in epidemic Q fever areas should be alert for chronic Q fever, even if no acute Q fever is reported.

Simultaneous increase of Cryptosporidium infections in the Netherlands, the United Kingdom and Germany in late summer season, 2012.

Starting August 2012, an increase in Cryptosporidium infections was reported in the Netherlands, the United Kingdom and Germany. It represented a 1.8 to 4.9-fold increase compared to previous years. Most samples were C. hominis IbA10G2. A case­control study was performed in the Netherlands but did not identify an endemic source. A case­case study in the north of England found travel abroad to be the most common risk factor.

Comparison of ELISA and indirect immunofluorescent antibody assay detecting Coxiella burnetii IgM phase II for the diagnosis of acute Q fever.

A commercially available enzyme-linked immunosorbent assay (ELISA) detecting Coxiella burnetii phase II-specific IgM for the diagnosis of acute Q fever was compared with indirect immunofluorescent antibody assay (IFA). IFA is the current reference method for the detection of antibodies against C. burnetii, but has disadvantages because the judgment of fluorescence is subjective and tiring, and the test is expensive and automation is not possible. To examine whether phase II IgM ELISA could be used as a screening assay for acute Q fever, we compared the sensitivity and specificity of IFA and ELISA. The sensitivity of the IFA and ELISA tests were 100 and 85.7%, respectively, with a specificity of 95.3 and 97.6%, respectively. Because of the high sensitivity and specificity of the ELISA in combination with the practical disadvantages of the IFA, we introduced a new algorithm to screen samples of patients with symptoms of acute Q fever infection.

[COVID-19 in the Emergency Department of Bernhoven hospital]. / COVID-19 op de Spoedeisende Hulp in Bernhoven.

OBJECTIVE: To describe disease presentation and clinical characteristics of patients with COVID-19 presenting to the Emergency Department (ED) of Bernhoven hospital in Uden, the Netherlands. DESIGN: Prospective, descriptive study. METHOD: The registry focused on atypical symptoms and co-infections. We hypothesized that patients older than 70 years more often have atypical symptoms. The number of co-infections is unknown. Therefore, we prospectively registered medical history, duration of symptoms, symptoms, temperature, lab results and co-infections of patients with confirmed COVID-19 in the period March 4-16th. RESULTS: The clinical characteristics of 107 patients were registered. The average age was 71 years and 41% was female. The median duration of symptoms was 5 days. 19% of patients had not been referred to pulmonary or internal medicine. Symptoms were fever (78%), respiratory complaints (78%), chest pain (28%), abdominal pain (13%), and diarrhea (34%). In 54% of the COVID-19 patients at the ED, the temperature was ≥ 38,0°C, CRP ≥ 50 in 51%, leucocytosis in 12% and elevated LD in 61%. Of 31 patients 24 (77%) had an absolute lymphopenia. Co-infections were seen in 16% of patients. The mortality in the ED was 2% and ICU-admission 5%. On March 25th, 2020 the overall mortality was 22% and ICU-admission 15%. CONCLUSION: We have seen patients with a very serious disease resulting in a high mortality and ICU-admission. Over 35% of patient did not have the typical symptoms of fever and respiratory complaints; atypical symptoms like chest pain, abdominal pain and diarrhea are frequently seen. There is no difference between patients over and under 70 years. COVID-19 patients can present with atypical symptoms, co-infections and distributed over various medical specialties.

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.

OBJECTIVES: Chronic 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. METHODS: SNPs 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. RESULTS: Nineteen 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). CONCLUSIONS: A 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.

Legionella pneumophila DNA in serum samples during Legionnaires' disease in relation to C-reactive protein levels.

Legionella pneumophila DNA can be detected in serum from patients with Legionnaires' disease (LD). We explored this observation studying the kinetics of L. pneumophila DNA in serum samples in relation to C-reactive protein (CRP). Eleven hospitalized patients with LD were studied. Diagnosis was made by Legionella urinary antigen test in 8 patients and seroconversion in 3 patients. A macrophage infectivity potentiator (MIP) real-time PCR was performed on 31 serum samples, including 20 follow-up serum samples. Serum samples obtained on the day of admission were MIP PCR-positive in 7 (64%) and MIP PCR-negative in 4 (36%) patients. Three (75%) of the 4 patients with a MIP PCR-negative serum sample on the day of admission became positive during follow-up. Overall, L. pneumophila DNA was detected in serum samples from 10 of the 11 patients (91%). CRP levels in the 7 patients with a positive MIP PCR serum sample on day of admission (499 +/- 144 mg/l; median +/- SD) were significantly higher than those in the 4 patients with a negative MIP PCR serum sample on the day of admission (244 +/- 97 mg/l). No difference in the severity of the disease on the day of admission was found between these patients. The presence of L. pneumophila DNA in serum is a common phenomenon in hospitalized patients with LD, although in some cases it is not yet present on the day of admission. L. pneumophila DNA in serum on the day of admission correlates with high CRP levels, but not with the severity of the disease.

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

OBJECTIVES: Chronic 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. METHODS: A 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). RESULTS: Complications 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). CONCLUSIONS: In 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.

Genetic variations in innate immunity genes affect response to Coxiella burnetii and are associated with susceptibility to chronic Q fever.

OBJECTIVES: Chronic Q fever is a persistent infection, mostly of aortic aneurysms, vascular prostheses or damaged heart valves, caused by the intracellular bacterium Coxiella burnetii. Only a fraction of C. burnetii-infected individuals at risk develop chronic Q fever. In these individuals, a defective innate immune response may contribute to the development of chronic Q fever. We assessed whether genetic variations in genes involved in the killing machinery for C. burnetii by macrophages, contribute to the progression to chronic Q fever. METHODS: The prevalence of 66 single nucleotide polymorphisms (SNPs) in 31 genes pivotal in phagolysosomal maturation, bacterial killing and autophagy, was determined in 173 chronic Q fever patients and 184 controls with risk factors for chronic Q fever and serological evidence of a C. burnetii infection. Associations were detected with univariate logistic regression models. To assess the effect of these SNPs on innate responses to C. burnetii, the C. burnetii-induced cytokine production and basal reactive oxygen species production of healthy volunteers was determined. RESULTS: RAB7A (rs13081864) and P2RX7 loss-of-function SNP (rs3751143) were more common in chronic Q fever patients than in controls. RAB5A (rs8682), P2RX7 gain-of-function SNP (rs1718119), MAP1LC3A (rs1040747) and ATG5 (rs2245214) were more common in controls. In healthy volunteers, RAB7A (rs13081864) and MAP1LC3A (rs1040747) influenced the C. burnetii-induced cytokine production. RAB7A (rs13081864) modulated basal reactive oxygen species production. CONCLUSIONS: RAB7A (rs13081864) and P2RX7 (rs3751143) are associated with the development of chronic Q fever, whereas RAB5A (rs8682), P2RX7 (rs1718119), MAP1LC3A (rs1040747) and ATG5 (rs2245214) may have protective effects.

Epiglottitis in the adult patient.

Epiglottitis is an acute disease, which was predominantly caused by Haemophilus influenzae type b in the pre-vaccination era. In the vaccination era, with waning vigilance, adults remain at risk for acute epiglottitis according to recent Dutch incidence rates. There is more diversity in the cause of epiglottitis in adults. We describe three patients who presented to the emergency ward of a regional teaching hospital with severe epiglottitis. All three patients had stridor at presentation indicating a compromised airway. Emergency intubation was attempted, but two patients required a tracheotomy and one patient died. Patients received fibreoptic nasal intubation, systemic dexamethasone and antibiotics. Stridor is an important acute sign of upper airway obstruction, which requires vigilance for epiglottitis, regardless of the patient's age. Fibreoptic nasal intubation should preferentially be attempted with the possibility of immediate surgical airway on hand. Timely diagnosis and treatment usually results in a complete recovery. In adults, severe acute epiglottitis and stridor can justify early intubation.

Chronic Q fever: patient and treatment-related factors influencing long-term quality of life.

BACKGROUND: Chronic Q fever is accompanied by high mortality and morbidity, and requires prolonged antibiotic treatment. Little is known on long-term quality of life (LQOL) in chronic Q fever patients treated with antibiotics. AIM: To identify patient and treatment-related factors associated with impaired LQOL in chronic Q fever patients treated with antibiotics, and to assess patients' perception on treatment. DESIGN: Cross-sectional study. METHODS: LQOL was assessed with a validated questionnaire from the Nijmegen Clinical Screening Instrument. Patients' perception on treatment was measured with three newly developed questions. RESULTS: We included 64 patients: LQOL was impaired in 55% (n = 35) after a median follow-up of 5 years. Median treatment duration was 27 months. In multivariable analysis, treatment duration was significantly associated with impaired LQOL (OR 1.07; 95%CI 1.02-1.12, P < 0.01 per month increase). Age, gender, number of antibiotic regimens, surgical intervention, complications, diagnostic classification, focus of infection or registration of side effects during treatment were not associated with impaired LQOL. After start of treatment, 17 patients (27%) perceived improvement of their condition. Disadvantages of treatment were experienced on a daily basis by 24 patients (69%) with impaired LQOL and 13 patients (46%) without impaired LQOL (P = 0.04). CONCLUSIONS: LQOL in chronic Q fever patients treated with antibiotics is impaired in more than half of patients 5 years after diagnosis. Antibiotic treatment duration was the only variable associated with impaired LQOL. The majority of patients experienced disadvantages on a daily basis, highlighting the high burden of disease and treatment.

Involvement of matrix metalloproteinases in chronic Q fever.

OBJECTIVES: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. METHODS: We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever. RESULTS: In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p<0.001), individuals with past Q fever (p<0.05, p<0.01, respectively) and of patients with chronic Q fever (both p<0.001). SNPs in MMP7 (rs11568810) (p<0.05) and MMP9 (rs17576) (p<0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL). CONCLUSION: Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.

[Two patients with mumps]. / Twee patiënten met de bof.

Two patients, men aged 17 and 19 years respectively, were admitted with parotitis epidemica and orchitis caused by mumps. The second patient also had meningitis. PCR analysis revealed that, in both cases, the causative agentwas a mumps virus that was genetically related to a wild-type virus responsible for an outbreak in Singapore. This viral strain was also responsible for a mumps outbreak at Hotel School The Hague in September 2004. Both patients were not fully vaccinated. Both patients were from regions in which clustering of patients with clinical signs of mumps has been seen. Interestingly, a number of patients with confirmed mumps had been fully vaccinated. Possible explanations for the increase in mumps cases include low vaccination and immunity levels, primary and secondary vaccine failure and the emergence of genetically disparate mumps viruses.