High number of hospitalisations and non-classical presentations: lessons learned from a measles outbreak in 2017, Belgium.

We describe and analyse an outbreak of measles that affected Belgium early 2017. In total, 289 cases were reported, mostly (53%) in people 15 years or older. For 133 (46%) vaccination status was unknown and a further 117 (41%) were not vaccinated. According to national guidelines, 83 of the unvaccinated cases (29% of total cases) should have received minimum one dose of vaccine, but did not. One in five cases (21%) did not present with the classical triad of fever, rash and any of coryza, conjunctivitis or cough. Rash was the most sensitive symptom, being absent in only six cases. A large proportion of cases (125/289, 43%) required hospitalisation. In hospitalised patients, the most commonly observed complications were hepatic disorders (present in 58/125 hospitalised patients, 46%). Thirty-six of the cases (12%) were in healthcare workers and nosocomial spread contributed importantly to the outbreak. Older age at presentation, altered clinical presentations and presence of complications like hepatitis can delay the correct diagnosis of measles. Clinicians should maintain a high index of suspicion in any individual presenting with rash. If the elimination target is to be reached, catch-up vaccination campaigns should be intensified and target young adults and health care workers.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Experience and lessons from surveillance and studies of the 2009 pandemic in Europe.

Surveillance and studies in a pandemic is a complex topic including four distinct components: (1) early detection and investigation; (2) comprehensive early assessment; (3) monitoring; and (4) rapid investigation of the effectiveness and impact of countermeasures, including monitoring the safety of pharmaceutical countermeasures. In the 2009 pandemic, the prime early detection and investigation took place in the Americas, but Europe needed to undertake the other three components while remaining vigilant to new phenomenon such as the emergence of antiviral resistance and important viral mutation. Laboratory-based surveillance was essential and also integral to epidemiological and clinical surveillance. Early assessment was especially vital because of the many important strategic parameters of the pandemic that could not be anticipated (the 'known unknowns'). Such assessment did not need to be undertaken in every country, and was done by the earliest affected European countries, particularly those with stronger surveillance. This was more successful than requiring countries to forward primary data for central analysis. However, it sometimes proved difficult to get even those analyses from European counties, and information from Southern hemisphere countries and North America proved equally valuable. These analyses informed which public health and clinical measures were most likely to be successful, and were summarized in a European risk assessment that was updated repeatedly. The estimate of the severity of the pandemic by the World Health Organization (WHO), and more detailed description by the European Centre for Disease Prevention and Control in the risk assessment along with revised planning assumptions were essential, as most national European plans envisaged triggering more disruptive interventions in the event of a severe pandemic. Setting up new surveillance systems in the midst of the pandemic and getting information from them was generally less successful. All European countries needed to perform monitoring (Component 3) for the proper management of their own healthcare systems and other services. The information that central authorities might like to have for monitoring was legion, and some countries found it difficult to limit this to what was essential for decisions and key communications. Monitoring should have been tested for feasibility in influenza seasons, but also needed to consider what surveillance systems will change or cease to deliver during a pandemic. International monitoring (reporting upwards to WHO and European authorities) had to be kept simple as many countries found it difficult to provide routine information to international bodies as well as undertaking internal processes. Investigation of the effectiveness of countermeasures (and the safety of pharmaceutical countermeasures) (Component 4) is another process that only needs to be undertaken in some countries. Safety monitoring proved especially important because of concerns over the safety of vaccines and antivirals. It is unlikely that it will become clear whether and which public health measures have been successful during the pandemic itself. Piloting of methods of estimating influenza vaccine effectiveness (part of Component 4) in Europe was underway in 2008. It was concluded that for future pandemics, authorities should plan how they will undertake Components 2-4, resourcing them realistically and devising new ways of sharing analyses.

Walking trials in postmenopausal women: effect of low doses of exercise and exercise fractionization on coronary risk factors.

We studied the fractionization of walking training and searched for the minimum dose to affect coronary risk factors in two randomized controlled trials. Altogether 134 (Study I) and 121 (Study II) healthy, sedentary postmenopausal women started the trials, and 130 (Study I) and 116 (Study II) completed them. In Study I the exercise intensity was 65% of the maximal aerobic power (VO2max) and a total of 300 kcal was expended in one (Group W1) or two (Group W2) daily walking bouts. In Study II the exercise was continuous, and the exercise intensity (% of VO2max) and energy expenditure (kcal session(-1)) were 55% and 300 kcal (Group W3), 45% and 300 kcal (Group W4), 55% and 200 kcal (Group W5) and 45% and 200 kcal (Group W6). All the subjects walked 5 days a week. The outcome measures were blood pressure, serum lipoproteins and blood glucose and plasma insulin in fasting state and also during 2-h oral glucose tolerance test in Study I. There was no change in diastolic pressure in the original study groups, but in the combined exercise group (W1+W2) in Study I, the mean diastolic pressure declined by -3.0 mmHg (95% con-fidence interval (CI) -5.5 to -0.4) (P=0.025) in comparison with that of the controls. The mean blood glucose declined by -0.21 mmol L(-1) (CI -0.33 to -0.09) in Group W1 and -0.13 mmol L(-1) (CI -0.25 to -0.01) in Group W2 compared to controls (P=0.03). Also the 2-h glucose concentration decreased in Groups W1 and W2 compared to controls. Systolic blood pressure, serum lipoproteins and insulin levels did not change in Study I or Study II. We conclude that our training program with the greatest exercise dose, exercise intensity 65% of VO2max and weekly expenditure of 1500 kcal had a minimal, positive effect on diastolic pressure and blood glucose, and the effect was similar in one or two daily exercise session groups. This exercise dose is probably close to the minimum to affect coronary risk factors in healthy postmenopausal women. To get a more pronounced and clinically relevant effect, a greater exercise dose is needed.

Walking trials in postmenopausal women: effect of one vs two daily bouts on aerobic fitness.

We compared the effects of one vs two daily bouts of walking on aerobic fitness and body composition in postmenopausal women. One hundred and thirty-four subjects were randomized into exercise groups or a control group and 130 completed the study. The subjects walked 5 d/week for 15 weeks at 65% of their maximal aerobic power expending 300 kcal (1255 kJ) in exercise in one (Group S1) or two daily sessions (Group S2). VO(2max) was measured in a direct maximal treadmill test. Body mass index (BMI) was calculated and the percentage of body fat (fat%) estimated using skinfold measurements. The net change in the VO(2max) was 2.5 mL min/kg (95% CI 1.5, 3.5) (8.7%) in Group S1 and 2.5 mL min/kg (95% CI 1.5, 3.5) (8.8%) in Group S2. The net change in body mass was -1.2 kg (95% CI-1.9, -0.5) in Group S1 and -1.1 kg (95% CI -1.8, -0.4) in Group S2. The net fat% change was -2.1% (95% CI-2.7, -1.4) in Group S1 and -1.7% (95% CI-2.3, -1.0) in Group S2. Exercise improved the maximal aerobic power and body composition equally when walking was performed in one or two daily bouts.

Randomised, controlled walking trials in postmenopausal women: the minimum dose to improve aerobic fitness?

BACKGROUND: The American College of Sports Medicine recommends 20-60 minutes of aerobic exercise three to five days a week at an intensity of 40/50-85% of maximal aerobic power (VO(2)MAX) reserve, expending a total of 700-2000 kcal (2.93-8.36 MJ) a week to improve aerobic power and body composition. OBJECTIVE: To ascertain the minimum effective dose of exercise. METHODS: Voluntary, healthy, non-obese, sedentary, postmenopausal women (n = 121), 48-63 years of age, were randomised to four low dose walking groups or a control group; 116 subjects completed the study. The exercise groups walked five days a week for 24 weeks with the following intensity (% of VO(2)MAX) and energy expenditure (kcal/week): group W1, 55%/1500 kcal; group W2, 45%/1500 kcal; group W3, 55%/1000 kcal; group W4, 45%/1000 kcal. VO(2)MAX was measured in a direct maximal treadmill test. Submaximal aerobic fitness was estimated as heart rates at submaximal work levels corresponding to 65% and 75% of the baseline VO(2)MAX. The body mass index (BMI) was calculated and percentage of body fat (F%) estimated from skinfolds. RESULTS: The net change (the differences between changes in each exercise group and the control group) in VO(2)MAX was 2.9 ml/min/kg (95% confidence interval (CI) 1.5 to 4.2) in group W1, 2.6 ml/min/kg (95% CI 1.3 to 4.0) in group W2, 2.4 ml/min/kg (95% CI 0.9 to 3.8) in group W3, and 2.2 ml/min/kg (95% CI 0.8 to 3.5) in group W4. The heart rates in standard submaximal work decreased 4 to 8 beats/min in all the groups. There was no change in BMI, but the F% decreased by about 1% unit in all the groups. CONCLUSIONS: Walking (for 24 weeks) at moderate intensity 45% to 55% of VO(2)MAX, with a total weekly energy expenditure of 1000-1500 kcal, improves VO(2)MAX and body composition of previously sedentary, non-obese, postmenopausal women. This dose of exercise apparently approaches the minimum effective dose.

Cell-specific expression of manganese superoxide dismutase protein in the lungs of patients with respiratory distress syndrome, chronic lung disease, or persistent pulmonary hypertension.

The developmental profile of manganese superoxide dismutase (MnSOD) and its regulation in hyperoxia vary between species. We hypothesized that MnSOD increases in human lung in response to oxygen treatment, although this response could be restricted to certain cell types and depend on gestational age. Therefore, the cell-specific expression of pulmonary immunoreactive MnSOD protein was investigated during development, and in patients with respiratory distress syndrome (RDS), chronic lung disease (CLD), or persistent pulmonary hypertension (PPHN). Throughout ontogenesis, all cell types expressed MnSOD, but the most intense positivity was found in bronchiolar epithelium and (pre-) type-II pneumocytes. MnSOD protein did not increase during development. The MnSOD staining pattern in arterial endothelium was more intense in RDS patients than in age-matched controls, but this may be related to induction of MnSOD by increased blood flow rather than by oxygen. MnSOD expression in other cell types of RDS, CLD, or PPHN patients did not differ from that in age-matched controls. We conclude that, in terms of mitochondrial enzymatic superoxide scavenging capacity, preterm infants are not more vulnerable than term infants to oxygen-induced lung injury at physiological oxygen concentrations. However, the inability to induce MnSOD in response to oxygen treatment may result in a poor outcome.

Expression and developmental profile of antioxidant enzymes in human lung and liver.

Air breathing, especially oxygen therapy, exposes the lung to reactive oxygen species (ROS). Antioxidant enzymes (AOEs) may protect the lung from ROS-mediated injury. Because expression of the key AOEs increases in several animal species during gestation, we investigated (1) the messenger RNA (mRNA) and activity levels of the key AOEs manganese and copper-zinc superoxide dismutases (MnSOD and CuZnSOD, respectively), catalase (CAT), and glutathione peroxidase (GPx) in adult lung samples and during ontogenesis; and (2) the difference in AOE expression between lung and liver. In the lung, the mRNA expression of MnSOD, CuZnSOD, and CAT increased toward adulthood, and GPx was unchanged. Pulmonary activities of MnSOD and CuZnSOD were unchanged, whereas CAT increased 3-fold from fetuses to adults. In the liver, the mRNA expression of MnSOD, CuZnSOD, and GPx increased, whereas that of CAT decreased toward adulthood. Hepatic activities of MnSOD and CuZnSOD increased 2-fold and 4-fold, respectively, whereas CAT was similar in fetuses and adults. Neonatal GPx activity was 2-fold higher in the lung and 6-fold higher in the liver compared with adults. The mRNA levels of MnSOD correlated positively with those of CuZnSOD and CAT in the lung, and GPx with those of MnSOD and CuZnSOD in the liver. Activities of MnSOD and CuZnSOD correlated positively in the liver. We conclude that the regulation of AOEs differs between human lung and liver, and is not tightly coordinated in either tissue.

Antioxidant enzyme regulation and resistance to oxidants of human bronchial epithelial cells cultured under hyperoxic conditions.

Bronchial epithelial cells are the first cells to encounter high concentrations of inspired oxygen, and their damage is a typical feature in many airway diseases. The direct effect of oxygen on the expression of the main antioxidant enzymes (AOEs) in human bronchial epithelial cells is unknown. We investigated the messenger RNA (mRNA) levels of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the specific activities of MnSOD, CuZnSOD, CAT, GPx, and glutathione reductase, in BEAS-2B bronchial epithelial cells exposed to hyperoxia (95% O2, 5% CO2) for 16 to 48 h. We also assessed the resistance of cells preexposed to hyperoxia to subsequent oxidant stress. Significant cell injury was observed after 72 h exposure to hyperoxia; release of lactate dehydrogenase (LDH) from control cells and cells exposed to hyperoxia for 72 h was 7.0 +/- 1.0% and 22.0 +/- 1.0%, respectively. Hyperoxia for 16 h, 24 h, or 48 h had no effect on the mRNA levels or specific activities of any of these enzymes. Despite their unchanged AOE levels, cells exposed to hyperoxia for 48 h showed increased resistance to H2O2 and menadione. Total glutathione content of the cells increased by 55% and 58% after 24 h and 48 h, respectively, compared with normoxic controls. However, glutathione depletion with buthionine sulfoximine (BSO) did not diminish the oxidant resistance of hyperoxia-exposed cells. We conclude that AOEs in human bronchial epithelial cells are not directly upregulated by high oxygen tension, and that increases in AOE-specific activities or glutathione are not necessary for the development of increased oxidant resistance in these cells.

Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma.

We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significantly. We conclude that MnSOD expression is low in healthy human pleural mesothelium and high in human malignant mesothelioma. The most resistant mesothelioma cells contained coordinated induction of MnSOD and catalase.

Safety and feasibility of a health-related fitness test battery for adults.

BACKGROUND AND PURPOSE: Health-related fitness (HRFI) assessment may be useful in promoting physical activity. Health-related fitness refers to those components of fitness that are related to health status. The safety and feasibility of a test battery designed for the assessment of HRFI were evaluated. SUBJECTS AND METHODS: Middle-aged men (n = 246) and women (n = 254), evenly selected from five age cohorts of a random sample (N = 826), were tested. The subjects had a mean age of 47.0 years (SD = 7.9, range = 37-57). Screening to identify subjects with health limitations was conducted by fitness testers who had master's degrees in sport or health sciences. Safety was assessed in terms of acute complications, delayed-onset muscle soreness (DOMS), and heart rate after each test. Subject exclusion and time costs were evaluated for feasibility. RESULTS: No acute complications occurred. The leg function test caused severe DOMS among inactive women. The overall exclusion rate increased with age. Up to 27% of subjects aged 52 and 57 years were excluded from muscle endurance tests, mainly due to self-reported heart disease or elevated blood pressures. Over 90% of the subjects, however, qualified for balance, flexibility, muscle force, and walk tests. CONCLUSION AND DISCUSSION: The test battery offers a safe and feasible method for the assessment of HRFI in working-aged adults, with the limitation that the one-leg squat function test may cause DOMS, particularly in inactive women.

How to promote physical activity through individual counseling--a proposal for a practical model of counseling on health-related physical activity.

A model was developed to aid practical decision making in the counseling of health-related physical activity. The development was based on the following concepts and theories: (1) A wide concept of physical activity; (2) A logical sequence of the practitioner's work steps; (3) Personal aspect of the client; (4) The client's stages of adoption; (5) Determinants of physical activity; (6) Selected educational concepts; (7) Selected strategies of planned maintenance. The model provides the practitioner the main work steps of counseling to follow and detailed lists of potential factors in each step to be taken into account for effective counseling on health-related physical activity. An illustrative case history is given on the model's application. The model is shown to incorporate central behavioral strategies shown useful in promoting adherence to physical activity.

Hybridization patterns of Actinobacillus actinomycetemcomitans serotypes a-e detected with an rRNA gene probe.

This study reports a genetic characterization of Actinobacillus actinomycetemcomitans strains in relation to serotypes by using rRNA gene restriction patterns. Eighty-eight clinical strains were isolated from 20 unrelated subjects at one or several occasions. The strains were serotyped by using serotype-specific rabbit antisera against serotypes a, b, c, d or e. Three subjects harbored 2 A. actinomycetemcomitans serotypes, 15 subjects 1 serotype and 2 subjects untypable strains. Chromosomal DNA was digested with restriction endonuclease ClaI, BamHI, BglI or HindIII and hybridized to the rrnB ribosomal RNA operon of the Escherichia coli chromosome. Isolates belonging to the same serotype were genetically identical in the same individual but nonidentical if they belonged to different serotypes. Isolates of the same or different serotypes were genetically nonidentical in different individuals. The banding patterns of A. actinomycetemcomitans isolates recovered from the same individuals during several years always remained identical. The hybridization method using pKK3535 as a probe seemed suitable as an epidemiological tool for comparing the clonal identity of A. actinomycetemcomitans strains.