Transmission and Persistence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus among Veterinarians and Their Household Members

After the first isolation of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in 2003, this MRSA variant quickly became the predominant MRSA obtained from humans as part of the Dutch national MRSA surveillance. Previous studies have suggested that human-to-human transmission of LA-MRSA, compared to that of other MRSA lineages, rarely occurs. However, these reports describe the transmission of LA-MRSA based on epidemiology and limited molecular characterization of isolates, making it difficult to assess whether transmission actually occurred. In this study, we used whole-genome maps (WGMs) to identify possible transmission of LA-MRSA between humans. For this, we used LA-MRSA isolates originating from a 2-year prospective longitudinal cohort study in which livestock veterinarians and their household members were repeatedly sampled for the presence of S. aureus. A considerable degree of genotypic variation among LA-MRSA strains was observed. However, there was very limited variability between the maps of the isolates originating from the same veterinarian, indicating that each of the veterinarians persistently carried or had reacquired the same LA-MRSA strain. Comparison of WGMs revealed that LA-MRSA transmission had likely occurred within virtually every veterinarian household. Yet only a single LA-MRSA strain per household appeared to be involved in transmission. The results corroborate our previous finding that LA-MRSA is genetically diverse. Furthermore, this study shows that transmission of LA-MRSA between humans occurs and that carriage of LA-MRSA can be persistent, thus posing a potential risk for spread of this highly resistant pathogen in the community.     

Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households: A Prospective Cohort Study

Background

The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients.

Methods and Findings

This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases.A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting.

Conclusions

The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.     

Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study

Background

Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.

Methods and Findings

We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.

Conclusions

Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing. Please see later in the article for the Editors'' Summary     

Determinants of Influenza Transmission in South East Asia: Insights from a Household Cohort Study in Vietnam

To guide control policies, it is important that the determinants of influenza transmission are fully characterized. Such assessment is complex because the risk of influenza infection is multifaceted and depends both on immunity acquired naturally or via vaccination and on the individual level of exposure to influenza in the community or in the household. Here, we analyse a large household cohort study conducted in 2007–2010 in Vietnam using innovative statistical methods to ascertain in an integrative framework the relative contribution of variables that influence the transmission of seasonal (H1N1, H3N2, B) and pandemic H1N1pdm09 influenza. Influenza infection was diagnosed by haemagglutination-inhibition (HI) antibody assay of paired serum samples. We used a Bayesian data augmentation Markov chain Monte Carlo strategy based on digraphs to reconstruct unobserved chains of transmission in households and estimate transmission parameters. The probability of transmission from an infected individual to another household member was 8% (95% CI, 6%, 10%) on average, and varied with pre-season titers, age and household size. Within households of size 3, the probability of transmission from an infected member to a child with low pre-season HI antibody titers was 27% (95% CI 21%–35%). High pre-season HI titers were protective against infection, with a reduction in the hazard of infection of 59% (95% CI, 44%–71%) and 87% (95% CI, 70%–96%) for intermediate (1∶20–1∶40) and high (≥1∶80) HI titers, respectively. Even after correcting for pre-season HI titers, adults had half the infection risk of children. Twenty six percent (95% CI: 21%, 30%) of infections may be attributed to household transmission. Our results highlight the importance of integrated analysis by influenza sub-type, age and pre-season HI titers in order to infer influenza transmission risks in and outside of the household.     

Spatiotemporal Determinants of Urban Leptospirosis Transmission: Four-Year Prospective Cohort Study of Slum Residents in Brazil

Background

Rat-borne leptospirosis is an emerging zoonotic disease in urban slum settlements for which there are no adequate control measures. The challenge in elucidating risk factors and informing approaches for prevention is the complex and heterogeneous environment within slums, which vary at fine spatial scales and influence transmission of the bacterial agent.

Methodology/Principal Findings

We performed a prospective study of 2,003 slum residents in the city of Salvador, Brazil during a four-year period (2003–2007) and used a spatiotemporal modelling approach to delineate the dynamics of leptospiral transmission. Household interviews and Geographical Information System surveys were performed annually to evaluate risk exposures and environmental transmission sources. We completed annual serosurveys to ascertain leptospiral infection based on serological evidence. Among the 1,730 (86%) individuals who completed at least one year of follow-up, the infection rate was 35.4 (95% CI, 30.7–40.6) per 1,000 annual follow-up events. Male gender, illiteracy, and age were independently associated with infection risk. Environmental risk factors included rat infestation (OR 1.46, 95% CI, 1.00–2.16), contact with mud (OR 1.57, 95% CI 1.17–2.17) and lower household elevation (OR 0.92 per 10m increase in elevation, 95% CI 0.82–1.04). The spatial distribution of infection risk was highly heterogeneous and varied across small scales. Fixed effects in the spatiotemporal model accounted for the majority of the spatial variation in risk, but there was a significant residual component that was best explained by the spatial random effect. Although infection risk varied between years, the spatial distribution of risk associated with fixed and random effects did not vary temporally. Specific “hot-spots” consistently had higher transmission risk during study years.

Conclusions/Significance

The risk for leptospiral infection in urban slums is determined in large part by structural features, both social and environmental. Our findings indicate that topographic factors such as household elevation and inadequate drainage increase risk by promoting contact with mud and suggest that the soil-water interface serves as the environmental reservoir for spillover transmission. The use of a spatiotemporal approach allowed the identification of geographic outliers with unexplained risk patterns. This approach, in addition to guiding targeted community-based interventions and identifying new hypotheses, may have general applicability towards addressing environmentally-transmitted diseases that have emerged in complex urban slum settings.     

Weight at Birth and Subsequent Fecundability: A Prospective Cohort Study

Objective

To examine the association between a woman''s birth weight and her subsequent fecundability.

Method

In this prospective cohort study, we included 2,773 Danish pregnancy planners enrolled in the internet-based cohort study “Snart-Gravid”, conducted during 2007–2012. Participants were 18–40 years old at study entry, attempting to conceive, and were not receiving fertility treatment. Data on weight at birth were obtained from the Danish Medical Birth Registry and categorized as <2,500 grams, 2,500–2,999 grams, 3,000–3,999 grams, and ≥4,000 grams. In additional analyses, birth weight was categorized according to z-scores for each gestational week at birth. Time-to-pregnancy measured in cycles was used to compute fecundability ratios (FR) and 95% confidence intervals (CI), using a proportional probabilities regression model.

Results

Relative to women with a birth weight of 3,000–3,999 grams, FRs adjusted for gestational age, year of birth, and maternal socio-demographic and medical factors were 0.99 (95% CI: 0.73;1.34), 0.99 (95% CI: 0.87;1.12), and 1.08 (95% CI: 0.94;1.24) for birth weight <2,500 grams, 2,500–2,999 grams, and ≥4,000 grams, respectively. Estimates remained unchanged after further adjustment for markers of the participant''s mother''s fecundability. We obtained similar results when we restricted to women who were born at term, and to women who had attempted to conceive for a maximum of 6 cycles before study entry. Results remained similar when we estimated FRs according to z-scores of birth weight.

Conclusion

Our results indicate that birth weight appears not to be an important determinant of fecundability.     

Obesity,Metabolic Syndrome and Risk of Atrial Fibrillation: A Swedish,Prospective Cohort Study

AimWe aimed to investigate whether different measures of obesity could similarly predict atrial fibrillation, and whether the atrial fibrillation risk associated with obesity is dependent on presence of metabolic syndrome.ResultsDuring a mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were recorded. One standard deviation increment of each obesity measure was associated with increased atrial fibrillation risk as: body mass index 1.25 (1.12 – 1.40), waist circumference 1.35 (1.19 – 1.54) and sagittal abdominal diameter 1.28 (1.14 – 1.44). Compared to normal weight subjects without metabolic syndrome, increased atrial fibrillation risk was noted for overweight subjects with metabolic syndrome, 1.67 (1.16 – 2.41), obese subjects without metabolic syndrome, 1.75 (1.11 – 2.74) and obese subjects with metabolic syndrome, 1.92 (1.34 – 2.74). Compared to subjects with normal waist circumference without metabolic syndrome, subjects with elevated waist circumference and metabolic syndrome suffered increased atrial fibrillation risk, 2.03 (1.44 – 2.87).ConclusionsBody mass index, waist circumference and sagittal abdominal diameter could similarly predict atrial fibrillation. Obesity was associated with an increased atrial fibrillation risk regardless of metabolic syndrome, whereas overweight and elevated waist circumference was associated with increased atrial fibrillation risk only if metabolic syndrome was present.     

Obesity and Cardiovascular Disease Risk Factors in Firefighters: A Prospective Cohort Study

Objective: Obesity, despite being a significant determinant of fitness for duty, is reaching epidemic levels in the workplace. Firefighters’ fitness is important to their health and to public safety. Research Methods and Procedures: We examined the distribution of BMI and its association with major cardiovascular disease (CVD) risk factors in Massachusetts firefighters who underwent baseline (1996) and annual medical examinations through a statewide medical surveillance program over 5 years of follow‐up. We also evaluated firefighters’ weight change over time. Results: The mean BMI among 332 firefighters increased from 29 at baseline to 30 at the follow‐up examination (2001), and the prevalence of obesity increased from 35% to 40%, respectively (p < 0.0001). In addition, the proportion of firefighters with extreme obesity increased 4‐fold at follow‐up (from 0.6% to 2.4%, p < 0.0001). Obese firefighters were more likely to have hypertension (p = 0.03) and low high‐density lipoprotein‐cholesterol (p = 0.01) at follow‐up. Firefighters with extreme obesity had an average of 2.1 CVD risk factors (excluding obesity) in contrast to 1.5 CVD risk factors for normal‐weight firefighters (p = 0.02). Finally, on average, normal‐weight firefighters gained 1.1 pounds, whereas firefighters with BMI ≥ 35 gained 1.9 pounds per year of active duty over 5 years of follow‐up. Discussion: Obesity is a major concern among firefighters and shows worsening trends over time. Periodic medical evaluations coupled with exercise and dietary guidelines are needed to address this problem, which threatens firefighters’ health and may jeopardize public safety.     

Incidence and Treatment of Developmental Hip Dysplasia in Mongolia: A Prospective Cohort Study

Background

In Mongolia, adequate early diagnosis and treatment of developmental hip dysplasia (DDH) have been unavailable and its incidence was unknown. We determined the incidence of ultrasonographic DDH in newborns and established adequate procedures for diagnosis and treatment of DDH at the largest maternity hospital in Ulaanbaatar, Mongolia.

Methodology/Principal Findings

During one year (Sept 2010 – Aug 2011) we assessed the hips newborns using ultrasound and Graf’s classification of DDH. 8,356 newborns were screened; median age at screening was 1 day. We identified 14,873 Type 1 (89.0%), 1715 Type 2a (10.3%), 36 Type 2c (0.2%), 70 Type D (0.4%), 14 Type 3 (0.08%), and 4 Type 4 hips (0.02%). Children with Type 1 hips (normal) were discharged. Children with Type 2a hips (physiologically immature) received follow-up ultrasounds at monthly intervals. Children with Type 2c to 4 (DDH; deformed or misaligned hip joint) hips were treated with a Tubingen hip flexion splint and also followed up. The hip abnormalities resolved to mature hips in all children who were followed up. There was no evidence for severe treatment related complications.

Conclusion/Significance

This study suggests that the incidence of DDH in Mongolian neonates is comparable to that in neonates in Europe. Early ultrasound-based assessment and splinting treatment of DDH led to mature hips in all children followed up. Procedures are feasible and will be continued.     

Plasma Ascorbic Acid,A Priori Diet Quality Score,and Incident Hypertension: A Prospective Cohort Study

Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other’s predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertension-free in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995–1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred-and-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 μmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-adjusted Cox regression models, the hazard ratio of hypertension per 19.6-μmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79–0.92) and per 12-points higher diet score 0.86 (95% CI 0.79–0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion.     

Hypertension Persisting after Pre-Eclampsia: A Prospective Cohort Study at Mulago Hospital,Uganda

Background

Pre-eclampsia/eclampsia usually resolves after delivery but sometimes hypertension persists and cardiovascular disease develops later. Our objective was to determine the incidence and maternal socio-demographic and obstetric risk factors for persistence of hypertension in women with pre-eclampsia/eclampsia.

Methods

This was a prospective cohort study conducted from July 2009 to June 2011 at Mulago Hospital labour ward and postnatal clinics. We followed up 188 women admitted with pre-eclampsia/eclampsia until 3 months after delivery. Data was collected using interviewer-administered questionnaires, examination of participants and review of medical records. Stata (version12) software was used for data analysis. Univariable analysis was used to compute the relative risk of persistent hypertension at the 95% confidence level. This was followed by multivariable logistic regression analysis to determine factors independently associated with persistence of hypertension.

Results

64 (34%) out of the 188 women analysed had persistent hypertension three months after delivery. Maternal age, gestational age at delivery and parity were predictors of persistent hypertension.

Conclusion

The proportion of women with pre-eclampsia/eclampsia at risk of persistent hypertension at three months after delivery was high, with nearly one of three mothers remaining hypertensive. Follow up of mothers who develop pre-eclampsia is important so that early diagnosis and management of chronic hypertension can be made to avoid long term morbidity and mortality.     

Contact Investigation in Households of Patients with Tuberculosis in Hanoi,Vietnam: A Prospective Cohort Study

Setting

Existing tuberculosis control strategies in Vietnam are based on symptomatic patients attending health services for investigation. This approach has not resulted in substantial reductions in the prevalence of tuberculosis disease, despite the National Tuberculosis Program achieving high treatment completion rates. Alternative approaches are being considered.

Objective

To determine the feasibility and yield of contact investigation in households of patients with smear positive pulmonary tuberculosis among household members of tuberculosis patients in Hanoi, Vietnam.

Methods

Household contacts of patients with smear positive pulmonary tuberculosis were recruited at four urban and rural District Tuberculosis Units in Hanoi. Clinical and radiological screening was conducted at baseline, six months and 12 months. Sputum microscopy and culture was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular testing was used to compare the strains of patients and their contacts with disease.

Results

Among 545 household contacts of 212 patients, four were diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000 persons, 95% CI 17–1451) and one was diagnosed with tuberculosis during the subsequent 12 months after initial screening (incidence 180 cases per 100,000 person-years, 95% CI 44–131). Two of these cases were culture positive for M. tuberculosis and both had identical or near-identical MIRU-VNTR strain types.

Conclusion

Household contacts of patients with potentially infectious forms of tuberculosis have a high prevalence of disease. Household contact investigation is feasible in Vietnam. Further research is required to investigate its effectiveness.     

Livestock-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) as Causes of Human Infection and Colonization in Germany

Pigs, cattle and poultry are colonized with MRSA and the zoonotic transmission of such MRSA to humans via direct animal contact, environmental contaminations or meat are a matter of concern. Livestock-associated (LA) MRSA are mostly belonging to clonal complex (CC) 398 as defined by multilocus sequence typing. However, MRSA of other clonal lineages including CC5, CC9 and CC97 have also been detected in livestock animals in Germany. Within the framework of a Dutch-German network project (EUREGIO), 14,036 MRSA isolated from clinical and screening specimens (January 2008 - June 2012) derived from human patients in hospitals as well as general or specialized practices in a German region characterized by a high density of livestock production, were subjected to S. aureus protein A (spa) sequence typing. The prevalence of putative LA-MRSA among the human MRSA isolates was determined by analyzing the detection of livestock-indicator (LI) spa types which had already been reported in German livestock. Overall, 578 spa types were detected among the MRSA isolates. LI spa types t011, t034, t108, t1451, t2011, t571, t1456, t1250, t1255, t1580, t2970, t2346, t1344, t2576, t2330 and t2510 (all of which are indicative for LA-MRSA CC398) accounted for 18.6% of all human isolates. The LI spa types t1430 (CC9), t3992 (CC97), t002 (CC5) and t007 (CC30) were found in 0.14%, 0.01%, 1.01% and 0.04% of all human MRSA isolates, respectively. LI spa types associated with CC398 represented 23% of all MRSA from screening samples and a varying proportion among isolates from clinical specimens ranging between 0% in cerebrospinal fluid, 8% in blood cultures and 14% in deep respiratory fluids. Our findings indicate that LA-MRSA are a major cause for human infection and stress the need for close surveillance. Although LA-MRSA CC398 predominates, the occurrence of putative LA-MRSA from other clonal lineages should be monitored.     

Probiotic Supplement Use among Young Children in Taiwan: A Prospective Cohort Study

Objectives

The objective of this study is to provide details on probiotic supplement use among young children in Taiwan.

Participants and Methods

This study is based on the Taiwan Birth Cohort Study database. We used questionnaires to collect information on probiotic supplement use among young children from birth to 18 months of age, while also considering their demographic characteristics and other covariates. Low-birth-weight infants, preterm infants, those with birth defects, and those with caregivers who returned incomplete questionnaires were excluded. The final valid sample comprised 16,991 cases.

Results

Approximately half the children received probiotic supplements before the age of 18 months. Only 6.3% of the children received probiotic supplements during the two periods of birth to 6 months and 7 to 18 months. Firstborn children, native mothers, mothers with higher educational levels, higher family income, and parents who lead healthy lifestyles were positively related to probiotic supplement use among children. Young children who were breastfed, with eczema, or with gastrointestinal tract problems were significantly positively associated with probiotic supplement use.

Conclusion

The findings show that probiotic supplement usage among young children is associated with a more socially advantaged circumstance and certain child health factors, such as eczema, diarrhea, and constipation. Parents might use probiotic supplements for prevention or treatment of child diseases. The findings of this research could serve as a baseline for future studies, and provide insight into probiotic supplement use behavior for health professionals caring for infants and young children.     

Uremic Pruritus,Dialysis Adequacy,and Metabolic Profiles in Hemodialysis Patients: A Prospective 5-Year Cohort Study

Background

Uremic pruritus is a common and intractable symptom in patients on chronic hemodialysis, but factors associated with the severity of pruritus remain unclear. This study aimed to explore the associations of metabolic factors and dialysis adequacy with the aggravation of pruritus.

Methods

We conducted a 5-year prospective cohort study on patients with maintenance hemodialysis. A visual analogue scale (VAS) was used to assess the intensity of pruritus. Patient demographic and clinical characteristics, laboratory parameters, dialysis adequacy (assessed by Kt/V), and pruritus intensity were recorded at baseline and follow-up. Change score analysis of the difference score of VAS between baseline and follow-up was performed using multiple linear regression models. The optimal threshold of Kt/V, which is associated with the aggravation of uremic pruritus, was determined by generalized additive models and receiver operating characteristic analysis.

Results

A total of 111 patients completed the study. Linear regression analysis showed that lower Kt/V and use of low-flux dialyzer were significantly associated with the aggravation of pruritus after adjusting for the baseline pruritus intensity and a variety of confounding factors. The optimal threshold value of Kt/V for pruritus was 1.5 suggested by both generalized additive models and receiver operating characteristic analysis.

Conclusions

Hemodialysis with the target of Kt/V ≥1.5 and use of high-flux dialyzer may reduce the intensity of pruritus in patients on chronic hemodialysis. Further clinical trials are required to determine the optimal dialysis dose and regimen for uremic pruritus.     

Predictors,Neuroimaging Characteristics and Long-Term Outcome of Severe European Tick-Borne Encephalitis: A Prospective Cohort Study

MethodsA cohort of 111 TBE patients (median age 51, range 17–75 years; 42% females) was analysed prospectively. Data were acquired from the department of neurology, University Hospital Heidelberg, and the infectious diseases registry of the Robert-Koch institute Berlin. Neurological status was ascertained by protocol at admission and discharge and the degree of disability was scored using the modified RANKIN Scale (mRS; clinical score addressing neurological disability, range from 0, healthy to 6, dead) at admission and at follow-up. Follow-up examination was conducted by means of a telephone interview. To identify independent predictors for severe TBE and functional outcome, modelled logistic regression was performed. MRI changes were correlated with infection variants. To assess alpha-motor neuron injury patterns, we used high-resolution magnetic resonance neurography (hrMRN). Analyses were performed at the Department of Neurology, University Hospital, University of Heidelberg from April 2004 through September 2014ResultsAcute course: 3.6% of patients died during the acute infection. All patients with a lethal course suffered from meningoencephaloradiculitis (MER, 14.4% of the cohort), which is associated with a significantly higher risk of requiring intensive care (p = 0.004) and mechanical ventilation (p<0.001) than menigoencephalitis (ME, 27.9% of the cohort). At admission, both MER and ME groups were severely affected, with the MER group having a statistically higher mRS score (median of 5 in the MER groups versus 4 in the ME group; p<0.001). Long-term outcome: outcome for MER was considerably worse (median mRS = 4) than for ME (mRS = 1, p<0.0001) and meningitis (mRS = 0, 57.7% of the cohort). Risk factors: advanced age (p<0.001) and male gender (p = 0.043) are independent risk factors for a severe infection course. Furthermore, we identified pre-existing diabetes mellitus (p = 0.024) as an independent risk factor for MER. In MER, alpha-motor neuron injury accounts for the poor prognosis confirmed by hrMRN.

Conclusion and Relevance

These data provide critical information for neurologists and other health professionals to use in evaluating TBEV patients who live in or travel to endemic areas. This information can be used to classify clinical presentation and estimate infection-associated complications and individual prognosis. Furthermore, the risk for severe, disabling infections in older patients should prompt general practitioners to recommend and encourage vaccination to those patients living in or travelling to endemic areas.     

Obesity and Occupational Injury: A Prospective Cohort Study of 69,515 Public Sector Employees

Background

Obesity and overweight are suggested to increase the risk of occupational injury but longitudinal evidence to confirm this is rare. We sought to evaluate obesity and overweight as risk factors for occupational injuries.

Methodology/Principal Findings

A total of 69,515 public sector employees (80% women) responded to a survey in 2000–2002, 2004 or 2008. Body mass index (kg/m²) was derived from self-reported height and weight and was linked to records of subsequent occupational injuries obtained from national registers. Different injury types, locations and events or exposures (the manner in which the injury was produced or inflicted) were analyzed by body mass index category adjusting for baseline socio-demographic characteristics, work characteristics, health-risk behaviors, physical and mental health, insomnia symptoms, and sleep duration. During the mean follow-up of 7.8 years (SD = 3.2), 18% of the employees (N = 12,204) recorded at least one occupational injury. Obesity was associated with a higher overall risk of occupational injury; multivariable adjusted hazard ratio (HR) 1.21 (95% CI 1.14–1.27). A relationship was observed for bone fractures (HR = 1.37; 95% CI: 1.10–1.70), dislocations, sprains and strains (HR = 1.36; 95% CI: 1.25–1.49), concussions and internal injuries (HR = 1.26; 95% CI: 1.11–1.44), injuries to lower extremities (HR = 1.62; 95%: 1.46–1.79) and injuries to whole body or multiple sites (HR = 1.37; 95%: 1.10–1.70). Furthermore, obesity was associated with a higher risk of injuries caused by slipping, tripping, stumbling and falling (HR = 1.55; 95% CI: 1.40–1.73), sudden body movement with or without physical stress (HR = 1.24; 95% CI: 1.10–1.41) and shock, fright, violence, aggression, threat or unexpected presence (HR = 1.33; 95% CI: 1.03–1.72). The magnitude of the associations between overweight and injuries was smaller, but the associations were generally in the same direction as those of obesity.

Conclusions/Significance

Obese employees record more occupational injuries than those with recommended healthy weight.     

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study

Introduction

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.

Methods and Findings

We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.

Conclusions

Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.     

Psychological Changes following Weight Loss in Overweight and Obese Adults: A Prospective Cohort Study

Background

Participation in weight loss programs is often associated with improved wellbeing alongside reduced cardio-metabolic risk. In contrast, population-based analyses have found no evidence of psychological benefits of weight loss, but this may be due to inclusion of healthy-weight individuals. We therefore examined cardio-metabolic and psychological changes following weight loss in a cohort of overweight/obese adults.

Methods

Data were from 1,979 overweight and obese adults (BMI ≥25 kg/m²; age ≥50 y), free of long-standing illness or clinical depression at baseline, from the English Longitudinal Study of Ageing. Participants were grouped according to four-year weight change into those losing ≥5% weight, those gaining ≥5%, and those whose weight was stable within 5%. Logistic regression examined changes in depressed mood (eight-item Center for Epidemiologic Studies Depression score ≥4), low wellbeing (Satisfaction With Life Scale score <20), hypertension (systolic blood pressure ≥140 mmHg or anti-hypertensives), and high triglycerides (≥1.7 mmol/l), controlling for demographic variables, weight loss intention, and baseline characteristics.

Results

The proportion of participants with depressed mood increased more in the weight loss than weight stable or weight gain groups (+289%, +86%, +62% respectively; odds ratio [OR] for weight loss vs. weight stable = 1.78 [95% CI 1.29–2.47]). The proportion with low wellbeing also increased more in the weight loss group (+31%, +22%, −4%), but the difference was not statistically significant (OR = 1.16 [0.81–1.66]). Hypertension and high triglyceride prevalence decreased in weight losers and increased in weight gainers (−28%, 4%, +18%; OR = 0.61 [0.45–0.83]; −47%, −13%, +5%; OR = 0.41 [0.28–0.60]). All effects persisted in analyses adjusting for illness and life stress during the weight loss period.

Conclusions

Weight loss over four years in initially healthy overweight/obese older adults was associated with reduction in cardio-metabolic risk but no psychological benefit, even when changes in health and life stresses were accounted for. These results highlight the need to investigate the emotional consequences of weight loss.     

Self-Report of Healthcare Utilization among Community-Dwelling Older Persons: A Prospective Cohort Study

Background

Self-reported data are often used for estimates on healthcare utilization in cost-effectiveness studies.

Objective

To analyze older adults’ self-report of healthcare utilization compared to data obtained from the general practitioners’ (GP) electronic medical record (EMR) and to study the differences in healthcare utilization between those who completed the study, those who did not respond, and those lost to follow-up.

Methods

A prospective cohort study was conducted among community-dwelling persons aged 70 years and above, without dementia and not living in a nursing home. Self-reporting questionnaires were compared to healthcare utilization data extracted from the EMR at the GP-office.

Results

Overall, 790 persons completed questionnaires at baseline, median age 75 years (IQR 72–80), 55.8% had no disabilities in (instrumental) activities of daily living. Correlations between self-report data and EMR data on healthcare utilization were substantial for ‘hospitalizations’ and ‘GP home visits’ at 12 months intraclass correlation coefficient 0.63 (95% CI; 0.58–0.68). Compared to the EMR, self-reported healthcare utilization was generally slightly over-reported. Non-respondents received more GP home visits (p<0.05). Of the participants who died or were institutionalized 62.2% received 2 or more home visits (p<0.001) and 18.9% had 2 or more hospital admissions (p<0.001) versus respectively 18.6% and 3.9% of the participants who completed the study. Of the participants lost to follow-up for other reasons 33.0% received 2 or more home visits (p<0.01) versus 18.6 of the participants who completed the study.

Conclusions

Self-report of hospitalizations and GP home visits in a broadly ‘healthy’ community-dwelling older population seems adequate and efficient. However, as people become older and more functionally impaired, collecting healthcare utilization data from the EMR should be considered to avoid measurement bias, particularly if the data will be used to support economic evaluation.