Giardiasis in Bergen. Outbreak and clinical consequences.

Background Giardia lamblia is a common cause of waterborne disease. It is endemic in many parts of the world, especially where sanitation is poor, but in Europe and North America it is most often encountered in outbreaks following contamination of drinking water. The first registered outbreak of giardiasis affecting a large community in Norway happened in Bergen in the autumn of 2004. The reservoir “Svartediket” was the source, and the water probably held Giardia cysts for several weeks. Giardia can cause acute and chronic gastroenteritis. Several drugs constitute effective treatment, and metronidazole is the main drug available in Norway. Prior to the outbreak in Bergen there were no published studies on long term effects after eradication of the parasite. Aims The aim of the studies in this thesis is to investigate the course of giardiasis and its consequences following a large outbreak in an area where Giardia is not endemic. Methods In the first study, we concentrated on patients from general practice. Patients with clinically defined giardiasis were identified through a search in the medical records at two general practice clinics located in the area receiving water from the contaminated reservoir. Of the 7,100 persons registered, 134 fulfilled the inclusion criteria and 119 consented to take part in the study. Data were retrospectively obtained from the medical records. The patients were then requested to complete a mailed questionnaire and submit stool samples six months after the outbreak. A second questionnaire was sent out one year after the outbreak. The main outcome variable was abdominal symptoms that were not present prior to the acute infection. In the second study, we investigated a historic cohort of 1252 patients with giardiasis verified by detection of Giardia in stool samples submitted as part of regular clinical investigations in Bergen during the outbreak. A 2:1 control group matched by age and gender was recruited from the general population of Bergen. This group was later expanded so that the whole control group consisted of 3594 individuals. All participants received a questionnaire by mail three years after the outbreak. Main outcome variables were irritable bowel syndrome (IBS) according to Rome III criteria and “chronic fatigue” as defined by the Fatigue Questionnaire. Results In the group of patients from general practice the majority was between 20 and 39 years of age (51.4%), and there were more women (69.3%) than men. The diagnosis was supported by a positive test for Giardia lamblia in 55% (66/119) of the patients. Treatment with metronidazole was given to 89 (75%), and after initial treatment 36% (32/89) returned to their doctor because symptoms recurred. A second prescription was given to 28% (25/89), after which 16% (14/89) returned once more. 11% (10/89) received a third treatment with metronidazole. Six months after the outbreak stool samples were positive for Giardia in three of 82 patients. At this point 37% (44/118) reported gastrointestinal symptoms related to their Giardia-infection, and after 12 months this proportion was 19% (19/99). In the cohort of patients with laboratory verified giardiasis the prevalence of IBS three years after the outbreak was 46% (355/770), compared to 14% in the control group. The adjusted relative risk (RR) was 3.4 (95% confidence interval (CI) 2.9 to 3.8). The prevalence of chronic fatigue was 46% (366/794) among the Giardiapatients, and 12% among the controls, giving an adjusted RR of 4.0 (95% CI 3.5 to 4.5). IBS and chronic fatigue were associated, but there was also an increased risk of having IBS only (RR 1.8, 95% CI 1.4 to 2.3) or chronic fatigue only (RR 2.2, 95% CI 1.7 to 2.8). Discussion In the study from general practice we identified patients that would have been missed by a strict laboratory based inclusion criterion, either because stool samples were not submitted or due do misclassification when samples were negative. Several patients did not receive treatment and this could suggest that they did not have giardiasis, but another reason could be that they called at the medical centre before the outbreak was known and recovered spontaneously without treatment. After clearance of the parasite a substantial proportion of the patients had persisting symptoms 6 and 12 months after the outbreak, which shows that potential negative health effects of giardiasis was more extensive than first anticipated. In the cohort of persons with verified giardiasis the infection was associated with a high prevalence of IBS and chronic fatigue three years after the outbreak, and the risk was significantly higher than in the control group. This supports the findings in the group from general practice, and shows the consequences in a larger population and over a longer period of time. The prevalence of IBS in this study and gastrointestinal symptoms in the first one differs, but cannot be easily compared. The sample sizes vary, the case definitions are different and the questionnaires used to define the outcomes are not the same. Put together the two studies illustrate a wider range of the clinical consequences after the outbreak. Conclusions These studies show that a considerable proportion of patients consistently had persisting symptoms after giardiasis from the time of the acute infection and up to three years after. The association between acute giardiasis and later gastrointestinal symptoms and fatigue is strong. This calls for more research on the mechanisms for both giardiasis and medically unexplained physical symptoms like IBS and chronic fatigue

Consultations for gastroenteritis in general practice and out-of-hours services in Norway 2006–15

Background: Most of the patients with gastroenteritis seeking health care services are managed in primary care; yet, little is known about these consultations. Syndromic-based surveillance of gastrointestinal infections is used in several countries, including Norway. Aim: To investigate the extent of, and explore characteristics associated with, consultations for gastroenteritis in primary care and to compare consultations in daytime general practice and out-of-hours (OOH) services in Norway. Design and Setting: Registry-based study using reimbursement claims data from all consultations in general practice and OOH services in Norway over the 10-year period, 2006–15. Methods: The main outcome variable was whether the consultation took place in general practice or OOH services. Possible associations with patient age and sex, time and use of point-of-care C-reactive protein (CRP) testing and sickness certificate issuing were investigated. Results: Gastroenteritis consultations (n = 1 281 048) represented 0.9% of all consultations in primary care (n = 140 199 637), of which 84.4% were conducted in general practice and 15.6% in OOH services. Young children and young adults dominated among the patients. Point-of-care CRP testing was used in 36.1% of the consultations. Sickness certificates were issued in 43.6% of consultations with patients in working age. Age-specific time variations in consultation frequencies peaking in winter months were observed. Conclusions: The proportion of gastroenteritis consultations was higher in the OOH services when compared with daytime general practice. Young children and young adults dominated among the patients. The seasonal variation in consultation frequency is similar to that shown for gastroenteritis caused by norovirus.publishedVersio

Consultations and antibiotic treatment for urinary tract infections in Norwegian primary care 2006–2015, a registry-based study

Background Extensive use of antibiotics and the resulting emergence of antimicrobial resistance is a major health concern globally. In Norway, 82% of antibiotics is prescribed in primary care and one in four prescriptions are issued for the treatment of urinary tract infections (UTI). The aim of this study was to investigate time trends in antibiotic treatment following a consultation for UTI in primary care. Methods For the period 2006–2015 we linked data from the Norwegian Registry for Control and Payment of Health Reimbursements on all patient consultations for cystitis and pyelonephritis in general practice and out-of-hours (OOH) services, and data from the Norwegian Prescription Database on all dispensed prescriptions of antibiotics. Results Altogether 2,426,643 consultations by attendance for UTI took place in the study period, of these 94.5% for cystitis and 5.5% for pyelonephritis. Of all UTI consultations, 79.4% were conducted in general practice and 20.6% in OOH services. From 2006 to 2015, annual numbers of cystitis and pyelonephritis consultations increased by 33.9 and 14.0%, respectively. The proportion of UTI consultations resulting in an antibiotic prescription increased from 36.6 to 65.7% for cystitis, and from 35.3 to 50.7% for pyelonephritis. These observed changes occurred gradually over the years. Cystitis was mainly treated with pivmecillinam (53.9%), followed by trimethoprim (20.8%). For pyelonephritis, pivmecillinam was most frequently used (43.0%), followed by ciprofloxacin (20.5%) and sulfamethoxazole-trimethoprim (16.3%). For cystitis, the use of pivmecillinam increased the most during the study period (from 46.1 to 56.6%), and for pyelonephritis, the use of sulfamethoxazole-trimethoprim (from 11.4 to 25.5%) followed by ciprofloxacin (from 18.2 to 23.1%). Conclusions During the 10-year study period there was a considerable increase in the proportion of UTI consultations resulting in antibiotic treatment. Cystitis was most often treated with pivmecillinam, and this proportion increased during the study period. Treatment of pyelonephritis was characterized by more use of broader-spectrum antibiotics, use of both sulfamethoxazole-trimethoprim and ciprofloxacin increased during the study period. These trends, indicative of enduring changes in consultation and treatment patterns for UTIs, will have implications for future antibiotic stewardship measures and policy.publishedVersio

Clinical features of gastroenteritis during a large waterborne Campylobacter outbreak in Askøy, Norway

Purpose: Outbreaks of Campylobacter infection are common, but studies exploring the clinical features of acute illness in the outbreak setting are scarce in existing literature. The main purpose of the present study was to investigate the clinical features of self-reported acute illness in gastroenteritis cases during a large waterborne Campylobacter outbreak in Askøy municipality, Norway, in 2019. Methods: A web-based self-administered questionnaire, and invitation to participate was sent by the municipality of Askøy as text message to mobile phones using the municipality’s warning system to the inhabitants during the ongoing outbreak. Results. Out of 3624 participants, 749 (20.7%) were defined as cases, of which 177 (23.6%) reported severe gastroenteritis. The most common symptoms were loose stools (90.7%), abdominal pain (89.3%) and diarrhea (88.9%), whereas 63.8% reported fever, 50.2% joint pain and 14.2% bloody stools. Tiredness, a symptom non-specific to gastroenteritis, was the overall most common symptom (91.2%). Conclusion: About one in four of the cases reported symptoms consistent with severe gastroenteritis. We found more joint pain and less bloody stools than reported in published studies of laboratory confirmed campylobacteriosis cases. Tiredness was common in the current study, although rarely described in previous literature of acute illness in the outbreak setting.publishedVersio

Antibiotics for gastroenteritis in general practice and out-of-hours services in Norway 2006-15

Background When patients with gastroenteritis (GE) seek health care, they are generally managed in primary care. Little is known about the use of antibiotic treatment in these cases. Objective The aim of this study was to investigate time trends and patient characteristics associated with antibiotic treatment for GE in Norwegian primary care in a 10-year period. Methods We linked data from two nationwide registries, reimbursement claims data from Norwegian primary care (the KUHR database) and The Norwegian Prescription Database, for the period 2006–15. GE consultations were extracted, and courses of systemic antibiotics dispensed within 1 day were included for further analyses. Results Antibiotic treatment was linked to 1.8% (n = 23 663) of the 1 279 867 consultations for GE in Norwegian primary care in the period 2006–15. The proportion of GE consultations with antibiotic treatment increased from 1.4% in 2006 to 2.2% in 2012 and then decreased to 1.8% in 2015. Fluoroquinolones (28.9%) and metronidazole (26.8%) were most frequently used. Whereas the number of fluoroquinolones courses decreased after 2012, the number of metronidazole courses continued to increase until year 2015. The antibiotic treatment proportion of GE consultations was lowest in young children and increased with increasing age. Conclusion Antibiotic treatment is infrequently used in GE consultations in Norwegian primary care. Although there was an overall increase in use during the study period, we observed a reduction in overall use after year 2012. Young children were treated with antibiotics in GE consultations less frequent than older patients.publishedVersio

Risk of miscarriage in women with chronic diseases in Norway:A registry linkage study

BACKGROUND: Increased risk of miscarriage has been reported for women with specific chronic health conditions. A broader investigation of chronic diseases and miscarriage risk may uncover patterns across categories of illness. The objective of this study was to study the risk of miscarriage according to various preexisting chronic diseases. METHODS AND FINDINGS: We conducted a registry-based study. Registered pregnancies (n = 593,009) in Norway between 2010 and 2016 were identified through 3 national health registries (birth register, general practitioner data, and patient registries). Six broad categories of illness were identified, comprising 25 chronic diseases defined by diagnostic codes used in general practitioner and patient registries. We required that the diseases were diagnosed before the pregnancy of interest. Miscarriage risk according to underlying chronic diseases was estimated as odds ratios (ORs) using generalized estimating equations adjusting for woman’s age. The mean age of women at the start of pregnancy was 29.7 years (SD 5.6 years). We observed an increased risk of miscarriage among women with cardiometabolic diseases (OR 1.25, 95% CI 1.20 to 1.31; p-value <0.001). Within this category, risks were elevated for all conditions: atherosclerosis (2.22; 1.42 to 3.49; p-value <0.001), hypertensive disorders (1.19; 1.13 to 1.26; p-value <0.001), and type 2 diabetes (1.38; 1.26 to 1.51; p-value <0.001). Among other categories of disease, risks were elevated for hypoparathyroidism (2.58; 1.35 to 4.92; p-value 0.004), Cushing syndrome (1.97; 1.06 to 3.65; p-value 0.03), Crohn’s disease (OR 1.31; 95% CI: 1.18 to 1.45; p-value 0.001), and endometriosis (1.22; 1.15 to 1.29; p-value <0.001). Findings were largely unchanged after mutual adjustment. Limitations of this study include our inability to adjust for measures of socioeconomic position or lifestyle characteristics, in addition to the rareness of some of the conditions providing limited power. CONCLUSIONS: In this registry study, we found that, although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications

Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: A controlled prospective cohort study

Objectives To investigate whether acute infection with Giardia lamblia is associated with fibromyalgia 10 years after infection and whether fibromyalgia is associated with irritable bowel syndrome (IBS) and chronic fatigue (CF) in this setting. Methods A cohort study was established after an outbreak of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and a matched control group were followed for 10 years. The main outcome was fibromyalgia 10 years after giardiasis, defined by the 2016 revisions of the fibromyalgia diagnostic criteria using the Fibromyalgia Survey Questionnaire (FSQ). Results The prevalence of fibromyalgia was 8.6% (49/572) among Giardia exposed compared to 3.1% (21/673) in controls (p<0.001). Unadjusted odds for having fibromyalgia was higher for Giardia exposed compared to controls (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37). Conclusions We found a higher prevalence of fibromyalgia among Giardia exposed compared to controls 10 years after the acute infection. Fibromyalgia was strongly associated with IBS and CF, and the difference between the exposed and controls can be attributed to the high prevalence of IBS and CF among the Giardia exposed. Notably, this study was not designed to establish causality between Giardia exposure and the outcomes.publishedVersio

Rastløse bein – en studie fra allmennpraksis

BAKGRUNN Forekomsten av rastløse bein er rundt 5–10 % blant voksne i den generelle befolkningen. Få studier er gjort om forekomsten blant pasienter som oppsøker fastlege. Det er også få studier om sammenheng med andre vanlige plager som irritabel tarm, kronisk utmattelse eller kronisk muskel- og ryggsmerte. MATERIALE OG METODE Studien ble gjennomført som en spørreskjemaundersøkelse ved legekontorer på Sør- og Vestlandet høsten 2017 og våren 2018, der pasienter som ventet på time hos fastlegen fortløpende ble invitert til å delta. 2 634 personer deltok (62,2 % kvinner, gjennomsnittsalder 49,6 år). Svarprosenten var 86,8. Rastløse bein ble definert basert på internasjonale kriterier. Assosiasjoner mellom rastløse bein og irritabel tarm, kronisk utmattelse og kronisk muskel- og ryggsmerte ble analysert med khikvadrattester og logistisk regresjon. RESULTATER OG FORTOLKNING Andelen pasienter med rastløse bein var 14,3 %. Blant pasientene med rastløse bein rapporterte 44,8 % at symptomene var moderate til veldig plagsomme, og 85,8 % at de ikke brukte medikamenter for dette. Andelen pasienter med rastløse bein var signifikant høyere blant pasienter med irritabel tarm (21,8 % versus 13,6 %, p = 0,009), kronisk utmattelse (18,2 % versus 13,1 %, p = 0,003) og kronisk muskel- og ryggsmerte (23,2 % versus 12,2 %, p < 0,0005). Fastleger bør være oppmerksomme på at mange pasienter har rastløse bein og at tilstanden er assosiert med andre vanlige plager. HOVEDFUNN Forekomsten av rastløse bein var 14,3 % blant pasienter som oppsøker fastlegen. Rundt halvparten av dem oppga mye og hyppige plager, men et fåtall benyttet medikamentell behandling. Rastløse bein var hyppigere blant pasienter med andre plager som irritabel tarm (justert oddsratio (OR) 1,73), kronisk utmattelse (OR 1,48) og kronisk muskel- og ryggsmerte (OR 2,06), sammenliknet med pasienter uten disse tilstandene.publishedVersio

Risk of miscarriage in women with psychiatric disorders

Background Some psychiatric disorders have been associated with increased risk of miscarriage. However, there is a lack of studies considering a broader spectrum of psychiatric disorders to clarify the role of common as opposed to independent mechanisms. Aims To examine the risk of miscarriage among women diagnosed with psychiatric conditions. Method We studied registered pregnancies in Norway between 2010 and 2016 (n = 593 009). The birth registry captures pregnancies ending in gestational week 12 or later, and the patient and general practitioner databases were used to identify miscarriages and induced abortions before 12 gestational weeks. Odds ratios of miscarriage according to 12 psychiatric diagnoses were calculated by logistic regression. Miscarriage risk was increased among women with bipolar disorders (adjusted odds ratio 1.35, 95% CI 1.26–1.44), personality disorders (adjusted odds ratio 1.32, 95% CI 1.12–1.55), attention-deficit hyperactivity disorder (adjusted odds ratio 1.27, 95% CI 1.21–1.33), conduct disorders (1.21, 95% CI 1.01, 1.46), anxiety disorders (adjusted odds ratio 1.25, 95% CI 1.23–1.28), depressive disorders (adjusted odds ratio 1.25, 95% CI 1.23–1.27), somatoform disorders (adjusted odds ratio 1.18, 95% CI 1.07–1.31) and eating disorders (adjusted odds ratio 1.14, 95% CI 1.08–1.22). The miscarriage risk was further increased among women with more than one psychiatric diagnosis. Our findings were robust to adjustment for other psychiatric diagnoses, chronic somatic disorders and substance use disorders. After mutual adjustment for co-occurring psychiatric disorders, we also observed a modest increased risk among women with schizophrenia spectrum disorders (adjusted odds ratio 1.22, 95% CI 1.03–1.44). Conclusions A wide range of psychiatric disorders were associated with increased risk of miscarriage. The heightened risk of miscarriage among women diagnosed with psychiatric disorders highlights the need for awareness and surveillance of this risk group in antenatal care.acceptedVersio