Strategies for early detection of chronic Q-fever: a systematic review.

BACKGROUND: Chronic Q-fever, a condition with high morbidity and mortality, may develop after an acute infection with Coxiella burnetii (acute Q-fever). Several strategies have been suggested for early detection of chronic Q-fever, focusing on follow-up of known acute Q-fever patients and detection of asymptomatic or unknown chronic infections. As there is no international standard or consensus, the aims of this study were to summarise the available literature and assess the evidence for different follow-up and screening strategies. DESIGN: We conducted a systematic review by searching PubMed and Embase. Twenty articles were included, of which fourteen only provided information on follow-up of known acute Q-fever cases, four presented data on identification of previously unknown C. burnetii infections, and two had information on both topics. RESULTS: The conversion rate of acute to chronic Q-fever ranged from 0 to 5.0%. Most studies advised serological follow-up of acute Q-fever patients, but without consistent advice on optimum timing and duration. The recommendation to use echocardiography for all acute Q-fever patients to detect valvular damage remains controversial. Screening of high-risk patients in an outbreak setting is advised by studies investigating such strategy. CONCLUSIONS: There is sufficient evidence to support serological follow-up of all known acute Q-fever patients at least once during the first year following the acute infection, and more frequently in patients with known risk factors for chronic disease, such as heart valve- or vascular prosthesis. Screening of risk groups should be considered in outbreaks of Q-fever.

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.

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.

Impact of Q-fever on physical and psychosocial functioning until 8 years after Coxiella burnetii infection: An integrative data analysis.

BACKGROUND: This study aimed to determine short- and long-term physical and psychosocial impact of Coxiella burnetii infection in three distinct entities: Q-fever fatigue syndrome (QFS), chronic Q-fever, and patients with past acute Q-fever without QFS or chronic Q-fever. METHODS: Integrative data analysis was performed, combining original data from eight studies measuring quality of life (QoL), fatigue, physical and social functioning with identical validated questionnaires, from three months to eight years after onset infection. Linear trends in each outcome were compared between Q-fever groups using multilevel linear regression analyses to account for repeated measures within patients. RESULTS: Data included 3947 observations of 2313 individual patients (228 QFS, 135 chronic Q-fever and 1950 patients with past acute Q-fever). In the first years following infection, physical and psychosocial impact was highest among QFS patients, and remained high without significant improvements over time. In chronic Q-fever patients, QoL and physical functioning worsened significantly over time. Levels of fatigue and social participation in patients with past acute Q-fever improved significantly over time. CONCLUSION: The impact differs greatly between the three Q-fever groups. It is important that physicians are aware of these differences, in order to provide relevant care for each patient group.

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.

Enhanced hygiene measures and norovirus transmission during an outbreak.

Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons. However, little is known about their effectiveness in limiting further spread of norovirus infections. We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004. Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%-86.6%) reduction in reproduction number. This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak. Even more stringent control measures are required to break the chain of transmission of norovirus.

Methicillin-resistant Staphylococcus aureus in a beauty salon, the Netherlands.

An outbreak of community-associated USA300 methicillin-resistant Staphylococcus aureus occurred in a beautician and 2 of her customers. Eight other persons, who were either infected (n = 5) or colonized (n = 3), were linked to this outbreak, including a family member, a household contact, and partners of customers.

Fatigue following Acute Q-Fever: A Systematic Literature Review.

BACKGROUND: Long-term fatigue with detrimental effects on daily functioning often occurs following acute Q-fever. Following the 2007-2010 Q-fever outbreak in the Netherlands with over 4000 notified cases, the emphasis on long-term consequences of Q-fever increased. The aim of this study was to provide an overview of all relevant available literature, and to identify knowledge gaps regarding the definition, diagnosis, background, description, aetiology, prevention, therapy, and prognosis, of fatigue following acute Q-fever. DESIGN: A systematic review was conducted through searching Pubmed, Embase, and PsycInfo for relevant literature up to 26th May 2015. References of included articles were hand searched for additional documents, and included articles were quality assessed. RESULTS: Fifty-seven articles were included and four documents classified as grey literature. The quality of most studies was low. The studies suggest that although most patients recover from fatigue within 6-12 months after acute Q-fever, approximately 20% remain chronically fatigued. Several names are used indicating fatigue following acute Q-fever, of which Q-fever fatigue syndrome (QFS) is most customary. Although QFS is described to occur frequently in many countries, a uniform definition is lacking. The studies report major health and work-related consequences, and is frequently accompanied by nonspecific complaints. There is no consensus with regard to aetiology, prevention, treatment, and prognosis. CONCLUSIONS: Long-term fatigue following acute Q-fever, generally referred to as QFS, has major health-related consequences. However, information on aetiology, prevention, treatment, and prognosis of QFS is underrepresented in the international literature. In order to facilitate comparison of findings, and as platform for future studies, a uniform definition and diagnostic work-up and uniform measurement tools for QFS are proposed.

Population Screening for Chronic Q-Fever Seven Years after a Major Outbreak.

INTRODUCTION: From 2007 through 2010, the Netherlands experienced a large Q-fever epidemic, with 4,107 notifications. The most serious complication of Q-fever is chronic Q-fever. METHOD: In 2014, we contacted all 2,161 adult inhabitants of the first village in the Netherlands affected by the Q-fever epidemic and offered to test for antibodies against Coxiella burnetii using immunofluorescence assay (IFA) to screen for chronic infections and assess whether large-scale population screening elsewhere is warranted. RESULTS: Of the 1,517 participants, 33.8% were IFA-positive. Six IFA-positive participants had an IgG phase I titer ≥1:512. Two of these six participants were previously diagnosed with chronic Q-fever. Chronic infection was diagnosed in one of the other four participants after clinical examination. CONCLUSIONS: Seven years after the initial outbreak, seroprevalence remains high, but the yield of screening the general population for chronic Q-fever is low. A policy of screening known high-risk groups for chronic Q-fever in outbreak areas directly following an outbreak might be more efficient than population screening. A cost-effectiveness analysis should also be performed before initiating a population screening program for chronic Q-fever.

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.

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.

[Persistent fatigue following Q fever]. / Aanhoudende vermoeidheid na een Q-koortsinfectie.

In the Netherlands, more than 4000 patient cases of acute Q fever have been reported since 2007. Approximately 20% of these patients subsequently developed long-term fatigue. Such fatigue, as well as other physical symptoms and patient-perceived limitations in social functioning, have been compiled into what is known as the Q fever fatigue syndrome (QFS). The number of Dutch patients having QFS is expected to increase over the next years. The chance of a spontaneous recovery during the first six months following an acute Q fever infection is high. Allowing the fatigue to run its natural course is therefore justified. The diagnosis of QFS is based on history-taking, a physical examination and laboratory test results. The percentage of patients who recover spontaneously from QFS seems low. Data on outcome after treatment are not yet available. The recommendation is to refer patients with QFS to specialists who offer cognitive behavioural therapy for chronic fatigue syndrome or QFS. The objective of the recently published national guideline 'Q fever fatigue syndrome (QFS)' is to achieve uniformity in its diagnosis and treatment.

An outbreak of scabies in multiple linked healthcare settings in The Netherlands.

We report a large scabies outbreak occurring in Tilburg, Netherlands, which affected several different healthcare settings that provide care to the elderly and the mentally disabled. The outbreak demonstrated how the complex system of care provision to vulnerable groups facilitated extensive scabies transmission among multiple linked healthcare settings and the community.