Influenza C virus infection in military recruits--symptoms and clinical manifestation.

Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases.

Decline in temperature and humidity increases the occurrence of influenza in cold climate.

BACKGROUND: Both temperature and humidity may independently or jointly contribute to the risk of influenza infections. We examined the relations between the level and decrease of temperature, humidity and the risk of influenza A and B virus infections in a subarctic climate. METHODS: We conducted a case-crossover study among military conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training period and identified 66 influenza A and B cases by PCR or serology. Meteorological data such as measures of average and decline in ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods, prior and after the onset were obtained. RESULTS: The average temperature preceding the influenza onset was -6.8 ± 5.6°C and AH 3.1 ± 1.3 g/m3. A decrease in both temperature and AH during the hazard period increased the occurrence of influenza so that a 1°C decrease in temperature and 0.5 g decrease per m3 in AH increased the estimated risk by 11% [OR 1.11 (1.03 to 1.20)] and 58% [OR 1.58 (1.28 to 1.96)], respectively. The occurrence of influenza infections was positively associated with both the average temperature [OR 1.10 per 1°C (95% confidence interval 1.02 to 1.19)] and AH [OR 1.25 per g/m3 (1.05 to 1.49)] during the hazard period prior to onset. CONCLUSION: Our results demonstrate that a decrease rather than low temperature and humidity per se during the preceding three days increase the risk of influenza episodes in a cold climate.

Genotypic and phenotypic characterization of carriage and invasive disease isolates of Neisseria meningitidis in Finland.

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.

Bile acid-derived mono- and diketals--synthesis, structural characterization and self-assembling properties.

Three oxo-derivatives of bile acid methyl esters have been used as starting compounds in the preparation of novel bile acid monoketals with 1,2-benzenediol (catechol) and 2,3-naphthalenediol, as well as mono- and diketals with pentaerythritol. Monoketals of pentaerythritol showed a tendency to form thermoreversible gels in many aromatic solvents and the methyl lithocholate derivative proved to be a supergelator able to form a gel with t-butylbenzene at a concentration as low as 0.5% w/v. Whereas the naphthalenediol ketals formed film-type materials in the studied solvents, the catechol ketals underwent rapid crystallization into X-ray quality single crystals. Single crystal X-ray structures of the catechol ketals have been determined. The monoketal obtained from methyl-3,7,12-trioxo-5beta-cholan-24-oate (dehydrocholate) revealed to have an unusual packing pattern in its solid state compared to other bile acid derivatives reported in the literature. The synthesis of diketals from pentaerythritol furnished a mixture of two diastereomers which, in the case of the methyl lithocholate derivative, have been separated and the X-ray crystal structure of one isomer resolved.

Training improves physical fitness and decreases CRP also in asthmatic conscripts.

To study the respiratory and physical health of young men, 224 asthmatic and 668 non-asthmatic military conscripts were recruited from the intake groups of July 2004 and January 2005 in Kajaani, Finland. Factors affecting respiratory health were elicited by a questionnaire at the beginning of the service, and results of high sensitive C-reactive protein (hsCRP) determination, peak expiratory flow (PEF), and 12-minute running test were collected at the beginning and the end of the service. Respiratory infections were diagnosed by a study physician. Upon entering military service, asthmatics had frequent exercise- and cold-related asthma symptoms (69.6% and 76.3%), and 48% of them had no medication for asthma. At the beginning, 25.8% of asthmatics and 19.1% of non-asthmatics had a poor result of less than 2,200 m (p = 0.05) in the 12-minute running test, and after 180 to 362 days of service, the corresponding percentages were 11.7% and 9.7% (p = 0.434). The levels of hsCRP, a marker of low-grade systemic inflammation, decreased significantly among both asthmatics, 1.5 (p = 0.001), and non-asthmatics, 1.6 mg/L (p < 0.001). Asthmatic men had 0.2 and non-asthmatics 0.1 respiratory infections per month (p < 0.001). In summary, asthmatic conscripts can enhance their physical fitness by training similarly to non-asthmatic ones. Their levels of hsCRP also decrease.

Risk factors for acute respiratory tract illness in military conscripts.

BACKGROUND AND OBJECTIVE: Acute respiratory tract infections are the leading cause of missed service days among military conscripts. The aim of this study was to identify factors that possibly predicted and contributed to frequent respiratory tract infections among military conscripts. METHODS: Data on episodes of respiratory illness were collected during the 180-day period of military service in Kajaani, Finland, between July 2004 and July 2005. RESULTS: There were 518 military conscripts recruited, 124 of whom had a diagnosis of asthma. Conscripts with frequent (three or more) infections were more often atopic or suffered from allergic rhinitis or asthma. Overweight (BMI >/= 25 kg/m(2)) and previous respiratory tract infections were the two independent risk factors for frequent respiratory infections. Overall, 4.8% of those who had no risk factors, 10. 3% of those with one risk factor and 35.7% of those with two risk factors suffered from frequent respiratory infections (P for trend < 0.001). CONCLUSIONS: Overweight (BMI >/= 25 kg/m(2)) and previous respiratory tract infections are risk factors for frequent respiratory tract infections in young men during military service.

Asthmatic persons are prone to the persistence of Chlamydia pneumoniae antibodies.

Acute Chlamydia pneumoniae infection may initiate asthma or worsen asthmatic symptoms. In crowded conditions, such as military service, young men are susceptible to respiratory infections, including C. pneumoniae. We recruited 127 asthmatic and 391 nonasthmatic military conscripts, followed up their respiratory tract infections and the kinetics of serum C. pneumoniae antibodies, and assessed the association between C. pneumoniae and asthma during 6 months of military service in 2 intake groups. During the 6-month period, in the July intake group, IgG antibody prevalence decreased from 60.3% to 43.8% in asthmatic and from 55.6% to 22.6% in nonasthmatic conscripts. In the January intake group, IgG antibody prevalence increased from 38.3% to 48.4% in asthmatic and from 37.2% to 43% in nonasthmatic recruits. IgG and IgA antibodies persisted more often in the asthmatic groups. In conclusion, the prevalence of IgG antibodies showed seasonal variation. Military recruits seem to be most vulnerable to C. pneumoniae infections during the period from January to June. The antibody titer changes were more rapid than previously thought.

A Decrease in Temperature and Humidity Precedes Human Rhinovirus Infections in a Cold Climate.

Both temperature and humidity may independently or jointly contribute to the risk of human rhinovirus (HRV) infections, either through altered survival and spread of viruses in the environment or due to changes in host susceptibility. This study examined the relationship between short-term variations in temperature and humidity and the risk of HRV infections in a subarctic climate. We conducted a case-crossover study among conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training and identified 147 HRV cases by real-time PCR. An average temperature, a decline in daily ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods (a week prior and after the onset) were obtained. The average daily temperature preceding HRV infections was -9.9 ± 4.9 °C and the average AH was 2.2 ± 0.9 g/m³. An average (odds ratios (OR) 1.07 (95% confidence interval (CI) 1.00-1.15)) and maximal (OR 1.08 (1.01-1.17)) change in temperature increased the risk of HRV infections by 8% per 1 °C decrease. An average (OR 1.20 (CI 1.03-1.40)) and maximal decrease (OR 1.13 (CI 0.96-1.34)) in AH increased the risk of HRV infection by 13% and 20% per 0.5 g/m³ decrease. A higher average temperature during the three preceding days was positively associated with HRV infections (OR 1.07 (CI 1.00-1.15)). A decrease rather than low temperature and humidity per se during the preceding few days increases the risk of HRV infections in a cold climate. The information is applicable to populations residing in cold climates for appropriate personal protection and prevention of adverse health effects.

Association of IL-6 and IL-6R gene polymorphisms with susceptibility to respiratory tract infections in young Finnish men.

Interleukin-1 (IL-6) is an important mediator of inflammatory response in the respiratory tract during an infection, and the action of IL-6 is mediated by an IL-6 receptor. Several polymorphisms in the IL-6 and IL-6R genes have been associated with different inflammatory disease states. We studied the association between 2 IL-6 (IL6A and IL6B) and 5 IL-6R gene polymorphisms (IL6R1 to IL6R5) and respiratory infections in 511 Finnish military recruits whose respiratory infectious episodes were followed during 6 months of service. A promoter polymorphism of the IL-6R gene, IL6R1 (-183G/A), and two intron 1 polymorphisms, IL6R2 (A/G) and IL6R3 (T/A), were associated with infections. The strongest associations were found for the IL6R1 and IL6R2 polymorphisms, which were in the same linkage disequilibrium block. Conscripts with the A/A (IL6R1), G/G (IL6R2), and A/A (IL6R3) genotypes had an increased risk for respiratory infections during service as follows: odds ratio (OR) 1.72, 95% confidence interval (CI) 1.35-2.19; OR 1.66, 95% CI 1.23-2.26; and OR 1.23, 95% CI 0.98-1.55, respectively. IL-6 gene polymorphism IL6A (-174C/G) was associated with infections only in combination with an IL-6R polymorphism. Our data suggest that polymorphisms in the 5' area of the IL-6R gene may be associated with increased susceptibility to respiratory infections.

Low mannose-binding lectin levels and MBL2 gene polymorphisms associate with Chlamydia pneumoniae antibodies.

OBJECTIVE: Mannose-binding lectin (MBL) has been shown to inhibit infection of host cells by Chlamydia pneumoniae in vitro. We studied if MBL levels and MBL2 polymorphisms associate with the presence of C. pneumoniae antibodies in vivo. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) of the MBL2 gene (promoter alleles H/L, X/Y and P/Q; and exon 1 variant alleles B, C and D and wild-type allele A) were genotyped and serum MBL concentrations and C. pneumoniae IgG, IgA and IgM antibodies were analysed in 889 Finnish military recruits. RESULTS: An MBL level below the median concentration and the MBL2 P/P genotype were significant risk factors of IgG or IgA seroconversions or the presence of IgM antibodies during military service (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.1-2.1 and OR 1.5; 95% CI 1.0-2.2, respectively). In addition, the promoter Y/Y (OR 1.6; 95% CI 1.1-2.3) and exon 1 variant allele genotypes (OR 1.4; 95% CI 1.0-2.0) were possibly associated with elevated antibodies. CONCLUSIONS: These results suggest, for the first time, that low serum MBL levels and MBL2 polymorphisms may associate with elevated C. pneumoniae antibodies and seroconversions and thus support the previous findings in vitro.

Smoking status interacts with the association between mannose-binding lectin serum levels and gene polymorphism and the carriage of oropharyngeal bacteria.

Mannose-binding lectin (MBL) role in the carriage of oropharyngeal bacteria is not known. We investigated the association of smoking, MBL2 polymorphisms, and MBL concentrations with oropharyngeal carriage of respiratory bacteria in young men. Oropharyngeal specimens, MBL concentrations, and MBL2 gene polymorphisms were measured in 124 asthmatic and 394 nonasthmatic Finnish military recruits. The carriage rates of S. pneumoniae (p = 0.002), N. meningitidis (p = 0.005), and beta-hemolytic streptococci (p < 0.001) throughout the military service were significantly higher among smokers than in nonsmokers. An MBL level below the median proved to be a significant risk factor for the carriage of N. meningitidis (odds ratio [OR] = 1.9; 95% confidence interval [CI] 1.0-3.6) and beta-hemolytic streptococci (OR = 2.0; 95% CI 1.2-3.2) in the nonsmokers and a borderline significant risk factor for the carriage of S. pneumoniae (OR = 1.5; 95% CI 0.9-2.6), whereas low MBL levels producing MBL2 haplotypes (LXA/LXA, LXA/O, HYA/O, LYA/O, O/O) seemed to be associated with the carriage of N. meningitidis (OR = 1.8; 95% CI 1.0-3.4) and S. pneumoniae (OR = 1.6; 95% CI 0.9-2.7). Thus, MBL deficiency may predispose nonsmokers to oropharyngeal carriage of these bacteria. We hypothesize that the major factor contributing to elevated bacterial carriage in smokers might be increased bacterial adherence to epithelial cells, which obscures the effect of MBL.

Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.

INTRODUCTION: The aim was to investigate the prevalence of oropharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis and beta-haemolytic streptococci among asthmatic and non-asthmatic young Finnish men and to identify putative risk factors. OBJECTIVES: A total of 224 asthmatics and 668 non-asthmatic men (mean age 19.6 years) from two intakes of conscripts to the Kainuu Brigade, Finland in July 2004 and January 2005 were enrolled upon entering military service. METHODS: Oropharyngeal specimens were examined for bacteria by routine culture methods. All the participants filled in questionnaires concerning risk factors for asthma and respiratory infections. RESULTS: S. pneumoniae (48 cases, 5.4%), Group A streptococci (16, 1.8%), H. influenzae (45, 5.0%), M. catarrhalis (24, 2.7%) and N. meningitidis (20, 2.2%) were isolated from the 892 participants. Ten putative risk factors for oropharyngeal colonization (asthma, atopy, allergic rhinitis, smoking, current use of asthma medication, history of adeno/tonsillectomy, level of highly sensitive C-reactive protein, peak expiratory flow, results of a 12-min running test and body mass index) were evaluated. The only significant risk factor for S. pneumoniae carriage was asthma (OR, 2.04; 95% CI 1.12 to 3.72). CONCLUSIONS: Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.

All known human rhinovirus species are present in sputum specimens of military recruits during respiratory infection.

Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004-2005). The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8%) specimens were HRV-positive and 36 (9.3%) HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%), belonged to HRV-A, while HRV-B strains constituted five (17.2%) of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.

Cold temperature and low humidity are associated with increased occurrence of respiratory tract infections.

OBJECTIVE: The association between cold exposure and acute respiratory tract infections (RTIs) has remained unclear. The study examined whether the development of RTIs is potentiated by cold exposure and lowered humidity in a northern population. METHODS: A population study where diagnosed RTI episodes, outdoor temperature and humidity among conscripts (n=892) were analysed. RESULTS: Altogether 643 RTI episodes were diagnosed during the follow-up period. Five hundred and ninety-five episodes were upper (URTI) and 87 lower (LRTI) RTIs. The mean average daily temperature preceding any RTIs was -3.7+/-10.6; for URTI and LRTI they were -4.1+/-10.6 degrees C and -1.1+/-10.0 degrees C, respectively. Temperature was associated with common cold (p=0.017), pharyngitis (p=0.011) and LRTI (p=0.048). Absolute humidity was associated with URTI (p<0.001). A 1 degrees C decrease in temperature increased the estimated risk for URTI by 4.3% (p<0.0001), for common cold by 2.1% (p=0.004), for pharyngitis by 2.8% (p=0.019) and for LRTI by 2.1% (p=0.039). A decrease of 1g/m(-3) in absolute humidity increased the estimated risk for URTI by 10.0% (p<0.001) and for pharyngitis by 10.8% (p=0.023). The average outdoor temperature decreased during the preceding three days of the onset of any RTIs, URTI, LRTI or common cold. The temperature for the preceding 14 days also showed a linear decrease for any RTI, URTI or common cold. Absolute humidity decreased linearly during the preceding three days before the onset of common cold, and during the preceding 14 days for all RTIs, common cold and LRTI. CONCLUSIONS: Cold temperature and low humidity were associated with increased occurrence of RTIs, and a decrease in temperature and humidity preceded the onset of the infections.

Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men.

BACKGROUND: Mannose-binding lectin (MBL) is an important component of innate immunity, and its deficiency is associated with susceptibility to recurrent infections. METHODS: This exploratory study investigated the association of serum MBL concentrations and MBL2 gene polymorphisms with respiratory tract infections in young men. We genotyped 6 single-nucleotide polymorphisms (SNPs) in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (variant alleles B, C, and D and wild-type allele A) of the MBL2 gene by real-time polymerase chain reaction and measured serum MBL concentrations in 111 Finnish military recruits with asthma and 362 without. RESULTS: An MBL level below the median concentration was a significant risk factor for infections (asthma status-adjusted odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.4-4.5]). Among the 6 SNPs, there was a significant association between the promoter Y/Y genotype and infections (OR, 2.3 [95% CI, 1.2-4.4]) and a borderline significant association between exon 1 variant alleles and infections (OR, 1.7 [95% CI, 0.9-3.1]), after adjustment for asthma status. CONCLUSION: These preliminary results suggest, for the first time, an association between MBL level and respiratory tract infections in young men and a possible association between infections and MBL2 polymorphisms.