Q-fever patients suffer from impaired health status long after the acute phase of the illness: results from a 24-month cohort study.

OBJECTIVES: During the largest Q-fever outbreak ever reported, a cohort study was established to assess the health status of Q-fever patients over a 24-month period and to identify factors associated with health status. METHODS: Laboratory-confirmed Q-fever patients participated at six time points after onset of illness. Scores on twelve subdomains from two health status instruments were calculated for each time point to determine progression and compare to reference groups. RESULTS: The study included 336 Q-fever patients. There is a significant linear improvement over time in nine of the twelve health status subdomains. For example, the proportion of patients with severe fatigue improved from 73.0% at three months to 60.0% at twelve months and 37.0% at twenty-four months, but this was still high compared to a healthy reference group (2.5%). For the three most severely affected subdomains -'Fatigue', 'General Quality of Life' and 'Role Physical'- the baseline characteristics significantly associated with a long-term reduced health status were being female, being a young adult and having pre-existing health problems. CONCLUSIONS: Despite a significant linear improvement over time in nine of the twelve health status subdomains, more than one out of three patients still suffered from a reduced health status at 24 months.

Large regional differences in serological follow-up of Q fever patients in the Netherlands.

BACKGROUND: During the Dutch Q fever epidemic more than 4,000 Q fever cases were notified. This provided logistical challenges for the organisation of serological follow-up, which is considered mandatory for early detection of chronic infection. The aim of this study was to investigate the proportion of acute Q fever patients that received serological follow-up, and to identify regional differences in follow-up rates and contributing factors, such as knowledge of medical practitioners. METHODS: Serological datasets of Q fever patients diagnosed between 2007 and 2009 (N = 3,198) were obtained from three Laboratories of Medical Microbiology (LMM) in the province of Noord-Brabant. One LMM offered an active follow-up service by approaching patients; the other two only tested on physician's request. The medical microbiologist in charge of each LMM was interviewed. In December 2011, 240 general practices and 112 medical specialists received questionnaires on their knowledge and practices regarding the serological follow-up of Q fever patients. RESULTS: Ninety-five percent (2,226/2,346) of the Q fever patients diagnosed at the LMM with a follow-up service received at least one serological follow-up within 15 months of diagnosis. For those diagnosed at a LMM without this service, this was 25% (218/852) (OR 54, 95% CI 43-67). Although 80% (162/203) of all medical practitioners with Q fever patients reported informing patients of the importance of serological follow-up, 33% (67/203) never requested it. CONCLUSIONS: Regional differences in follow-up are substantial and range from 25% to 95%. In areas with a low follow-up rate the proportion of missed chronic Q fever is potentially higher than in areas with a high follow-up rate. Medical practitioners lack knowledge regarding the need, timing and implementation of serological follow-up, which contributes to patients receiving incorrect or no follow-up. Therefore, this information should be incorporated in national guidelines and patient information forms.

Specific interferon γ detection for the diagnosis of previous Q fever.

BACKGROUND: Current practice for diagnosis of Q fever, caused by the intracellular pathogen Coxiella burnetii, relies mainly on serology and, in prevaccination assessment, on skin tests (STs), which both have drawbacks. In this study, C. burnetii-specific interferon γ (IFN-γ) production was used as a new diagnostic tool for previous Q fever, circumventing most of these drawbacks. Our aim was to compare this test to serology and ST. METHODS: One thousand five hundred twenty-five individuals from an endemic area with a risk for chronic Q fever were enrolled. IFN-γ production was measured after in vitro stimulation of whole blood with C. burnetii antigens. Various formats using different C. burnetii antigens were tested. Serology and ST were performed in all individuals. RESULTS: In all assay formats, C. burnetii-specific IFN-γ production was higher (P < .0001) in seropositive or ST-positive subjects than in seronegative and ST-negative subjects. Whole blood incubated for 24 hours with C. burnetii Nine Mile showed optimal performance. After excluding subjects with equivocal serology and/or borderline ST results, IFN-γ production was 449 ± 82 pg/mL in the positive individuals (n = 219) but only 21 ± 3 pg/mL in negative subjects (n = 908). Using Bayesian analysis, sensitivity and specificity (87.0% and 90.2%, respectively) were similar to the combination of serology and ST (83.0% and 95.6%, respectively). Agreement with the combination of serology and ST was moderate (84% concordance; κ = 0.542). CONCLUSIONS: Specific IFN-γ detection is a novel diagnostic assay for previous C. burnetii infection and shows similar performance and practical advantages over serology and ST. Future studies to investigate the clinical value in practice are warranted.

Assessing the long-term health impact of Q-fever in the Netherlands: a prospective cohort study started in 2007 on the largest documented Q-fever outbreak to date.

BACKGROUND: Between 2007 and 2011, the Netherlands experienced the largest documented Q-fever outbreak to date with a total of 4108 notified acute Q-fever patients. Previous studies have indicated that Q-fever patients may suffer from long-lasting health effects, such as fatigue and reduced quality of life. Our study aims to determine the long-term health impact of Q-fever. It will also compare the health status of Q-fever patients with three reference groups: 1) healthy controls, 2) patients with Legionnaires' disease and 3) persons with a Q-fever infection but a-specific symptoms. METHODS/DESIGN: Two groups of Q-fever patients were included in a prospective cohort study. In the first group the onset of illness was in 2007-2008 and participation was at 12 and 48 months. In the second group the onset of illness was in 2010-2011 and participation was at 6 time intervals, from 3 to 24 months. The reference groups were included at only one time interval. The subjective health status, fatigue status and quality of life of patients will be assessed using two validated quality of life questionnaires. DISCUSSION: This study is the largest prospective cohort study to date that focuses on the effects of acute Q-fever. It will determine the long-term (up to 4 years) health impact of Q-fever on patients and compare this to three different reference groups so that we can present a comprehensive assessment of disease progression over time.

Why did patients with cardiovascular disease in the Netherlands accept Q fever vaccination?

This study examines patient's reasons for accepting Q fever vaccination, including risk perception, feelings of doubt, social influence, information-seeking behavior, preventive measures taken, and perceptions regarding received information and governmental action. Data was obtained from exit interviews conducted after Q fever vaccination, between January and April 2011. A total of 413 patients with specific cardiovascular conditions in the Netherlands participated in exit interviews; 70% were older than 60 years. Most reported reasons for accepting Q fever vaccination were: "I am at an increased risk for developing (chronic) Q fever" (69%) and "my general practitioner recommends Q fever vaccination for me" (34%). The majority (86%) reported a high perceived severity of Q fever, and only 6% felt vulnerable to Q fever after vaccination. One-third had doubts about getting vaccinated, primarily related to fears of side effects and practical barriers. Fifty-two percent solicited advice from their social networks; of these, 67% reported influence on their vaccination decision. General practitioners and family were the most reported sources of advice. Thirty percent actively sought information about Q fever vaccination. Twenty-two percent of all respondents had taken other preventive measures, such as avoiding contact with goats and sheep (74%), and cancelling or postponing visits to Q fever-affected areas (36%). Almost one-half of all respondents reported negative feelings regarding governmental action to control Q fever. Significant differences were observed regarding feelings of doubt, information-seeking behavior, perceived vulnerability, preventive measures taken, and perceptions regarding received information and governmental action regarding gender, age, educational level, and/or employment status. Vaccination decision-making may differ among socio-demographic subgroups. When preparing future vaccination campaigns, it is important to obtain greater insight into these differences and take these aspects into account in risk communication strategies by tailoring information to specific target groups.

Self-reported sick leave and long-term health symptoms of Q-fever patients.

BACKGROUND: In The Netherlands, 1168 Q-fever patients were notified in 2007 and 2008. Patients and general practitioners (GPs) regularly reported persisting symptoms after acute Q-fever, especially fatigue and long periods of sick leave, to the public health authorities. International studies on smaller Q-fever outbreaks demonstrate that symptoms may persist years after acute illness. Data for the Dutch outbreaks were unavailable. The aim of this study is to quantify sick leave after acute Q-fever and long-term symptoms. METHODS: Our study targeted 898 acute Q-fever patients, notified in 2007 and 2008 residing in the Province Noord-Brabant. Patients from the 2008 cohort were mailed a questionnaire at 12 months and those of the 2007 cohort at 12-26 months after onset of illness. Patients reported underlying illness, Q-fever-related symptoms and sick leave. RESULTS: The response rate was 64%. Forty percent of the working patients reported long-term (>1 month) sick leave. Pre-existent heart disease odds ratio (OR) 4.50; confidence interval (CI) 1.27-16.09), hospitalization in the acute phase (OR 3.99; 95% CI 2.15-7.43) and smoking (OR 1.69; 95% CI 1.01-2.84) were significant predictors for long-term absence. Of the patients who resumed work, 9% were-at the time of completing the questionnaire-still unable to function at pre-infection levels due to fatigue or concentration problems. Of the respondents, 40% reported persisting physical symptoms at the time of follow-up. Fatigue (20%) was most frequently reported. Daily activities were affected in 30% of cases. CONCLUSIONS: Q-fever poses a serious persisting long-term burden on patients and society.

The 2007­2010 Q fever epidemic in The Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming.

We describe the Q fever epidemic in the Netherlands with emphasis on the epidemiological characteristics of acute Q fever patients and the association with veterinary factors. Data from 3264 notifications for acute Q fever in the period from 2007 through 2009 were analysed. The patients most affected were men, smokers and persons aged 40­60 years. Pneumonia was the most common clinical presentation (62% in 2007 and 2008). Only 3.2% of the patients were working in the agriculture sector and 0.5% in the meat-processing industry including abattoirs. Dairy goat farms with Coxiella burnetii-induced abortion waves were mainly located in the same area where human cases occurred. Airborne transmission of contaminated dust particles from commercial dairy goat farms in densely populated areas has probably caused this epidemic. In 2010, there was a sharp decline in the number of notified cases following the implementation of control measures on dairy goat and sheep farms such as vaccination, hygiene measures and culling of pregnant animals on infected farms. In combination with a rise in the human population with antibodies against C. burnetii, these have most likely ended the outbreak. Development of chronic Q fever in infected patients remains an important problem for years to come.

The health status of Q-fever patients after long-term follow-up.

BACKGROUND: In the Netherlands, from 2007 to 2009, 3,522 Q-fever cases were notified from three outbreaks. These are the largest documented outbreaks in the world. Previous studies suggest that symptoms can persist for a long period of time, resulting in a reduced quality of life (QoL). The aim of this study was to qualify and quantify the health status of Q-fever patients after long-term follow-up. METHODS: 870 Q-fever patients of the 2007 and 2008 outbreaks were mailed a questionnaire 12 to 26 months after the onset of illness. We assessed demographic data and measured health status with the Nijmegen Clinical Screening Instrument (NCSI). The NCSI consists of three main domains of functional impairment, symptoms and QoL that are divided into eight sub-domains. The NCSI scores of Q-fever patients older than 50 years (N=277) were compared with patients younger than 50 years (N=238) and with norm data from healthy individuals (N=65) and patients with chronic obstructive pulmonary disease (N=128). RESULTS: The response rate was 65.7%. After applying exclusion criteria 515 Q-fever patients were included in this study. The long-term health status of two thirds of Q-fever patients (both younger and older than 50 years) was severely affected for at least one sub-domain. Patients scores were most severely affected on the sub-domains general QoL (44.9%) and fatigue (43.5%). Hospitalisation in the acute phase was significantly related to long-term behavioural impairment (OR 2.8, CI 1.5-5.1), poor health related QoL (OR 2.3,CI 1.5-4.0) and subjective symptoms (OR 1.9, CI 1.1-3.6). Lung or heart disease, depression and arthritis significantly affected the long-term health status of Q-fever patients. CONCLUSIONS: Q-fever patients presented 12 to 26 months after the onset of illness severe -clinically relevant- subjective symptoms, functional impairment and impaired QoL. All measured sub-domains of the health status were impaired. Hospitalisation and co-morbidity were predictors for worse scores. Our data emphasise that more attention is needed not only to prevent exposure to Q-fever but also for the prevention and treatment of the long-term consequences of this zoönosis.

[Three years of Q fever in the Netherlands: faster diagnosis]. / Drie jaar Q-koorts in Nederland: snellere diagnose.

OBJECTIVE: To assess if more rapid diagnosis and treatment is possible and to assess if this could be improved, since the first outbreak of Q fever in 2007. DESIGN: Retrospective study of secondary data. METHODS: Analysis of surveillance data regarding Q fever over the period 2007 to 2009 and additional information on some patients from 2007 and 2008 obtained from general practitioners. RESULTS: Diagnostic delay fell sharply between 2007 and 2009 and to a lesser extent, so did therapeutic delay from 2007 to 2008. In high incidence areas, diagnosis and treatment was faster with a lower proportion of patients admitted to hospital than in low incidence areas. CONCLUSION: It appears that familiarity with the condition leads to faster diagnosis coupled with a lower percentage of hospital admissions. In order to react quickly it is necessary that doctor and patient should be aware of Q fever, especially in areas of low incidence. Polymerase chain reaction diagnostic techniques should also be available.

High and persistent excretion of hepatitis A virus in immunocompetent patients.

The duration and level of virus excretion in blood and faeces of patients with hepatitis A virus (HAV) infection were studied in relation to levels of alanine aminotransferase (ALT), disease severity and HAV genotype. Clinical data, blood and faeces were collected from 27 patients with acute hepatitis A (median age: 33 years) for a maximum of 26 weeks. Single blood donations from 55 other patients with acute HAV (median age: 32 years) were also used. Virus loads were quantified by competitive nested RT-PCR. HAV was excreted in faeces for a median period of 81 days after disease onset, with 50% of patients still excreting high levels at Day 36 (2 x 10(6) - 2 x 10(8) copies/ml faeces suspension). Viraemia was detected, but not quantifiable, for a median period of 42 days. In the first 10 days of illness, higher ALT levels were correlated with higher viraemia levels. Comparison of patients infected with genotype 1a with those infected with type 1b did not differ significantly in terms of the duration of HAV excretion or jaundice. In conclusion, faecal excretion of HAV is at a high titre in the first month, perhaps making patients infectious for a longer period than assumed currently. Blood banks should be aware that viraemia may be present for more than 1 month, and genotype did not affect the duration of virus excretion or jaundice.

Transmission of hepatitis B virus from a surgeon to his patients during high-risk and low-risk surgical procedures during 4 years.

OBJECTIVE: We investigated cases of acute hepatitis B in The Netherlands that were linked to the same general surgeon who was infected with hepatitis B virus (HBV). DESIGN: A retrospective cohort study was conducted of 1,564 patients operated on by the surgeon. Patients were tested for serologic HBV markers. A case-control study was performed to identify risk factors. RESULTS: The surgeon tested positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) with a high viral load. He was a known nonresponder after HBV vaccination and had apparently been infected for more than 10 years. Forty-nine patients (3.1%) were positive for HBV markers. Transmission of HBV from the surgeon was confirmed in 8 patients, probable in 2, and possible in 18. In the remaining 21 patients, the surgeon was not implicated. Two patients had a chronic HBV infection. One case of secondary transmission from a patient to his wife was identified. HBV DNA sequences from the surgeon were completely identical to sequences from 7 of the 28 patients and from the case of secondary transmission. The duration of the operation and the occurrence of complications during or after surgery were identified as independent risk factors. Although the risk of HBV infection during high-risk procedures was 7 times higher than that during low-risk procedures, at least 8 (28.6%) of the 28 patients were infected during low-risk procedures. CONCLUSIONS: Transmission of HBV from surgeons to patients at a low rate can remain unnoticed for a long period of time. Prevention requires a more stringent strategy for vaccination and testing of surgeons and optimization of infectious disease surveillance. Policies allowing HBV-infected surgeons to perform presumably low-risk procedures should be reconsidered.