Effectiveness of the 2012/13 Trivalent Live and Inactivated Influenza Vaccines in Children and Adolescents in Saxony-Anhalt,Germany: A Test-Negative Case-Control Study

A live attenuated influenza vaccine has been available in Germany since the influenza season 2012/13, which is approved for children aged 2-17 years. Using data from our laboratory-based surveillance system, we described the circulation of influenza and non-influenza respiratory viruses during the influenza season 2012/13 in Saxony-Anhalt. We estimated the effectiveness of live and inactivated trivalent influenza vaccines in preventing laboratory-confirmed cases among children and adolescents. From week 40/2012 to 19/2013, sentinel paediatricians systematically swabbed acute respiratory illness patients for testing of influenza and 5 non-influenza viruses by PCR. We compared influenza cases and influenza-negative controls. Among children aged 2-17 years, we calculated overall and vaccine type-specific effectiveness against laboratory-confirmed influenza, stratified by age group (2-6; 7-17 years). We used multivariable logistic regression to adjust estimates for age group, sex and month of illness. Out of 1,307 specimens, 647 (35%) were positive for influenza viruses and 189 (15%) for at least one of the tested non-influenza viruses. For vaccine effectiveness estimation, we included 834 patients (mean age 7.3 years, 53% males) in our analysis. Of 347 (42%) influenza-positive specimens, 61 (18%) were positive for A(H1N1)pdm09, 112 (32%) for A(H3N2) and 174 (50%) for influenza B virus. The adjusted overall vaccine effectiveness including both age groups was 38% (95% CI: 0.8-61%). The adjusted effectiveness for inactivated vaccines was 37% (95% CI: -35-70%) and for live vaccines 84% (95% CI: 45-95%). Effectiveness for the live vaccine was higher in 2-6 year-old children (90%, 95% CI: 20-99%) than in children aged 7-17 years (74%, 95% CI: -32-95%). Our study of the strong influenza season in 2012/13 suggests a high preventive effect of live attenuated influenza vaccine especially among young children, which could not be reached by inactivated vaccines. We recommend the use of live attenuated influenza vaccines in children unless there are contraindications.     

Clinical Characteristics Are Similar across Type A and B Influenza Virus Infections

Background

Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system.

Methods

The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0–4, 5–14, 15–64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata).

Results

Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003–2004 and 2012–2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0–4 years, those aged 5–14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87–2.47) while those aged 15–64 years were less likely (OR 0.83, 95% CI 0.73–0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses.

Conclusions

Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.     

Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children.

Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double-blind, placebo-controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults.     

Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis

BackgroundThe pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1) virus, and influenza A (H7N9) virus induced severe morbidity and mortality throughout the world. Previous studies suggested a close association between the interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and influenza. Here, we explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis.MethodsRelevant studies published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge, EBSCO, and Cochrane central register of controlled trials databases. Association between rs12252 and influenza susceptibility and severity were determined using statistical analysis of odds ratios (ORs).ResultsA total of four studies consisting of 445 cases and 4180 controls were included in our analysis. Generally, there is increased risk of influenza in subjects carrying rs12252 in the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18–2.22, P=0.003), the homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15–7.84, P<0.001), and the allele contrast (C vs. T: OR=1.67, 95% CI: 1.32–2.13, P<0.001). Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population. SNP rs12252 shows significant impact on severe infections (P<0.05), but not on mild influenza. Besides, our result also associated rs12252 with influenza severity (severe vs. mild: OR=2.37, 95% CI: 1.32–4.25, P=0.004), (severe vs. control: OR=2.70, 95% CI: 1.85–3.94, P<0.001).ConclusionOur meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.     

Acute viral infections of upper respiratory tract in elderly people living in the community: comparative,prospective, population based study of disease burden.

OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home. DESIGN: Prospective surveillance of elderly people. INTERVENTION: None. SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age. MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.     

南京地区2010～2011年度呼吸道感染患儿腺病毒的流行病学研究

本研究为了解南京地区儿童腺病毒(ADV)感染的流行特点及型别,收集2010年8月至2011年7月南京医科大学附属南京儿童医院住院及门诊呼吸道感染患儿的鼻咽抽吸物(NPA)及咽拭子(NPS)共644例,采用巢氏聚合酶链反应法(Nested-PCR)检测ADV hexon基因,将阳性PCR扩增产物进行测序、同源性和进化分析。同时对12种其他呼吸道相关病毒进行PCR检测,包括人博卡病毒(HBoV),呼吸道合胞病毒(RSV),人鼻病毒(HRV),副流感病毒1～4型(PIV1-4),流感病毒A和B(IFVA/B),人偏肺病毒(HMPV),冠状病毒NL63和HKU1(HCoV-NL63和HCoV-HKU1)。结果显示:644例标本中共检出ADV阳性扩增产物171份,检出率为26.55%,3型120例(70.18%,120/171),7型16例(9.36%,16/171),1型12例(7.02%,12/171),2型10例(5.85%,10/171),5型6例(3.51%,6/171),6型3例(1.75%,3/171),57型3例(1.75%,3/171),41型1例(0.58%,1/171)。ADV感染呈全年散发,其发病高峰主要在4～7月。以7岁以下儿童多见(96.49%)。171例ADV感染患儿中有99例(57.89%)存在混合感染,其中以呼吸道合胞病毒(RSV)、人鼻病毒(HRV)多见。ADV阳性患儿诊断以下呼吸道感染为主(63.16%),肺炎占30.41%。结论:ADV是2010年8月到2011年7月南京地区儿童呼吸道感染的重要病原之一,其优势流行株为3型,长期监测其流行型别具有重要意义。     

Population-based case-control study of isolated congenital cataract

BACKGROUND: The aim of this study was to detect possible etiological factors in the origin of isolated congenital cataracts. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contains 111 cases of isolated congenital cataract and 111 matched control pairs without the defect, 37,837 population controls without any defects, and 22,744 malformed controls with other nonocular abnormalities. Exposure data and family history are based on prospective medical records, retrospective maternal information, and information obtained by regional nurses during a home visit with nonrespondent mothers. RESULTS: A positive family history indicated an autosomal-dominant origin in 10% of cases. Rubella infections occurred more frequently in case mothers than in control mothers before vaccination against rubella virus was instituted. A higher prevalence of influenza or common cold during pregnancy was found in the case group (55.9%) than in the population control group (18.5%; adjusted odds ratios [ORs], 5.8; 95% confidence interval (CI), 4.0-8.4) or in the malformed control group (21.7%; adjusted OR, 4.7; 95% CI, 3.2-6.9). The prevalence of acute infectious diseases of the respiratory system during pregnancy was also higher in the case group (26.1%) than in the population control group (9.1%; adjusted OR, 3.8; 95% CI, 2.5-5.8), or the malformed control group (9.3%; adjusted OR, 3.4; 95% CI, 2.3-5.3). The higher risk for isolated congenital cataract in cases of mothers with influenza or common cold and acute infectious diseases of the respiratory system during pregnancy was not found after administration of antifever therapy. CONCLUSIONS: Some isolated congenital cataracts are preventable by rubella vaccination and probably by influenza vaccination in the epidemic period. In addition, our results suggest that using antifever therapy for fever-related respiratory diseases may restrict the teratogenic risk of hyperthermia.     

Prevalence and intensity of infections of Ascaris lumbricoides and Trichuris trichiura and associated socio-demographic variables in four rural Honduran communities

Between January and March 1998, a cross-sectional survey was carried out in four rural communities in Honduras, Central America. We examined the prevalence and intensity of Ascaris lumbricoides and Trichuris trichiura infections among 240 fecal specimens, and the association between selected socio-demographic variables and infection for 62 households. The overall prevalence of A. lumbricoides and T. trichiura was 45% (95% CI 39.0-51.9) and 38% (95% CI 31.8-44.4) respectively. The most intense infections for Ascaris and Trichuris were found in children aged 2-12 years old. By univariate analysis variables associated with infections of A. lumbricoides were: number of children 2-5 years old (p=0.001), level of formal education of respondents (p=0.01), reported site of defecation of children in households (p=0.02), households with children who had a recent history of diarrhea (p=0.002), and the location of households (p=0.03). Variables associated with both A. lumbricoides and T. trichiura infection included: number of children 6-14 years old (p=0.01, p=0.04, respectively), ownership of a latrine (p=0.04, p=0.03, respectively) and coinfection with either helminth (p=0.001, p=0.001, respectively). By multivariate analysis the number of children 2-5 years living in the household, (p=0.01, odds ratio (OR)=22.2), children with a recent history of diarrhea (p=0.0, OR=39.8), and infection of household members with T. trichiura (p=0.02, OR=16.0) were associated with A. lumbricoides infection. The number of children 6-14 years old in the household was associated with both A. lumbricoides and T. trichiura infection (p=0.04, p=0.01, OR=19.2, OR=5.2, respectively).     

A population-based study of coarctation of the aorta: comparisons of infants with and without associated ventricular septal defect.

BACKGROUND: Coarctation of the aorta (CoA) is a congenital cardiovascular malformation (CCVM) sometimes associated with ventricular septal defect (VSD). Although the phenotypic association is well documented, little research exists on the epidemiological features distinguishing CoA with and without VSD. METHODS: The Baltimore-Washington Infant Study (1981-1989), a population-based study of CCVM, evaluated 126 infants with "pure" CoA (free of associated cardiac defects) and 67 infants with CoA and VSD (COA/VSD) in comparison to 3,572 controls. RESULTS: The proportion of infants with associated extracardiac anomalies was greater among CoA/VSD than among pure CoA (31% versus 11%). Infants with CoA/VSD were twice as likely as those with pure CoA to be born small for gestational age (23% versus 12%, respectively, compared with 6% of controls). All-cause mortality during the first year of life was higher in CoA/VSD than in pure CoA (21% vs. 7%). Multiple logistic regression models revealed that family history of CCVM was associated with pure CoA (adjusted case-control odds ratio [OR] = 4.6; 99% confidence interval [CI] = 1.5-13.9) and with CoA/VSD (OR = 5.9, CI = 1.2-23.5); maternal history of organic solvent exposures early in pregnancy was also associated with pure CoA (OR = 3.2, CI = 1.0-10.2) and with CoA/VSD (OR = 3.7, CI 0.9-14.9). Additional risk factors, including maternal epilepsy (OR = 5.3, CI = 0.9-30.6), and use of macrodantin (OR = 6.7, CI = 1.4-31.8) were associated only with pure CoA. CONCLUSIONS: These findings highlight possible genetic and environmental differences between pure CoA and CoA/VSD and may stimulate further investigations of the etiology of CoA.     

Oocyst ingestion as an important transmission route of Toxoplasma gondii in Brazilian urban children

Toxoplasmosis is a cosmopolitan protozoan infection. Data regarding risk factors for the post-natal acquisition of Toxoplasma gondii infection in childhood are limited. We conducted a serological survey for T. gondii IgG antibodies and associated risk factors in 1,217 children 4-11-yr-old from Salvador, Brazil, using a commercial ELISA kit; antibodies were found in 17.5% of the children. Age (OR = 2.18; 95% CI: 1.50-3.17) and maternal schooling level (OR = 0.62; 95% CI: 0.42-0.92) were negatively associated with infection. A greater number of siblings (OR = 1.53; 95% CI: 1.12-2.09), cat at home (OR = 1.54; 95% CI: 1.06-2.24), house with non-treated piped water (OR = 2.54; 95% CI: 1.22-5.31), and the absence of a flush toilet at home (OR = 1.45; 95% CI: 1.04-2.01) were positively associated with T. gondii infection. Our data suggest that low socioeconomic levels and poor hygiene habits are important factors in favoring T. gondii infection.     

Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: A 2-year,randomized, triple-blind,placebo-controlled trial

BackgroundInfluenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years.Methods and findingsIn June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years.Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year.In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted.ConclusionsIn this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children.Trial registrationClinical Trials Registry of India CTRI/2015/06/005902.

Anand Krishnan and co-workers study the efficacy and safety of influenza vaccines for children in India.     

Effectiveness of Seasonal Influenza Vaccines against Influenza-Associated Illnesses among US Military Personnel in 2010-11: A Case-Control Approach

Introduction

Following the 2009 influenza A/H1N1 (pH1N1) pandemic, both seasonal and pH1N1 viruses circulated in the US during the 2010–2011 influenza season; influenza vaccine effectiveness (VE) may vary between live attenuated (LAIV) and trivalent inactivated (TIV) vaccines as well as by virus subtype.

Materials and Methods

Vaccine type and virus subtype-specific VE were determined for US military active component personnel for the period of September 1, 2010 through April 30, 2011. Laboratory-confirmed influenza-related medical encounters were compared to matched individuals with a non-respiratory illness (healthy controls), and unmatched individuals who experienced a non-influenza respiratory illness (test-negative controls). Odds ratios (OR) and VE estimates were calculated overall, by vaccine type and influenza subtype.

Results

A total of 603 influenza cases were identified. Overall VE was relatively low and similar regardless of whether healthy controls (VE = 26%, 95% CI: −1 to 45) or test-negative controls (VE = 29%, 95% CI: −6 to 53) were used as comparison groups. Using test-negative controls, vaccine type-specific VE was found to be higher for TIV (53%, 95% CI: 25 to 71) than for LAIV (VE = −13%, 95% CI: −77 to 27). Influenza subtype-specific analyses revealed moderate protection against A/H3 (VE = 58%, 95% CI: 21 to 78), but not against A/H1 (VE = −38%, 95% CI: −211 to 39) or B (VE = 34%, 95% CI: −122 to 80).

Conclusion

Overall, a low level of protection against clinically-apparent, laboratory-confirmed, influenza was found for the 2010–11 seasonal influenza vaccines. TIV immunization was associated with higher protection than LAIV, however, no protection against A/H1 was noted, despite inclusion of a pandemic influenza strain as a vaccine component for two consecutive years. Vaccine virus mismatch or lower immunogenicity may have contributed to these findings and deserve further examination in controlled studies. Continued assessment of VE in military personnel is essential in order to better inform vaccination policy decisions.     

Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines

BACKGROUND: Vitamin deficiencies induce oral clefts in animal experiments, but the role of specific nutrients in human oral clefts is uncertain. METHODS: Associations between maternal vitamin B-6 and folate status and risk of nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in case-control studies at two sites in the Philippines--Negros Occidental and Davao. Cases were mothers of affected children and control mothers were those who had no children with oral clefts. RESULTS: The risk of having a CL/P-affected child increased with increasing tertile of vitamin B-6 deficiency in both Negros Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51-5.73; OR, 4.98; 95% CI, 2.56-9.67). Poor B-6 status had a stronger association with CL/P among mothers with lower versus higher plasma folate levels. Increasing tertiles of plasma folate were marginally associated with an increased risk of clefts in both sites combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93-2.68; OR, 1.59; 95% CI, 0.94-2.70). Increasing tertiles of erythrocyte folate were associated with a decreased risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13-0.90; OR, 0.46; 95% CI, 0.20-1.09) and an increased risk in Davao (1.0 [reference]; OR, 1.23; 95% CI, 0.54-2.81; OR, 4.85; 95% CI, 2.24-10.50). The inconsistent associations between folate status and CL/P risk appeared to be a result of statistical interaction between folate, vitamin B-6, and case-control status that produced different results in study areas of higher versus lower prevalence of vitamin B-6 deficiency. CONCLUSIONS: Poor maternal vitamin B-6 status was consistently associated with an increased risk of CL/P at two sites in the Philippines. Folate-CL/P associations were inconsistent and may be related to the vitamin B-6 status or other characteristics of the populations under study.     

Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study

Background

There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali.

Methods

A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression.

Results

Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively).

Conclusions

In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.     

Association of TNF-α promoter polymorphisms with the outcome of persistent HBV infection in a northeast Chinese Han population

Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.     

呼吸道病毒感染与慢性阻塞性肺疾病急性加重的关系

目的:探讨呼吸道病毒与慢性阻塞性肺疾病急性加重(AECOPD)的相关性,以期能为AECOPD的诊治提供参考。方法:选取200例AECOPD患者为研究对象,检测患者肺功能,用Luminex xMAP多重分析技术平台,采集患者咽试子建立多重PCR检测技术,对鼻病毒(RHV)、呼吸道合胞病毒(RSV)、流感病毒A(INF-A)、流感病毒B(INF-B)、副流感病毒(PIV)、腺病毒(ADV)进行检测。结果:200例患者肺功能分级I级25例,II级62例,III级96例,IV级17例,其构成比分别为17.50%、31.00%、48.00%、8.50%;咽试子共检出呼吸道病毒116株,检出率为58.00%,其中RHV11株、RSV36株、INF-A37株、INF-B19株、PIV10株、ADV3株,检出率分别为5.5%、18.00%、18.50%、9.50%、5.00%、1.50%;肺功能分级I级患者病毒检出率为20.00%,II级为48.39%,III级为69.79%,IV级为82.35%,病毒检出率在不同肺功能AECOPD患者中比较差异具有统计学意义(P0.05);肺功能分级与病毒检出率直线相关分析结果显示随着肺功能分级的严重程度增加患者咽试子呼吸道病毒检出率明显呈现增高趋势,两者直接具有正相关(r=0.67,P0.05)。结论:COPD患者病情加重与病毒关系密切相关,病毒感染可能参与了COPD患者的病程进展。     

Association of the CYP1B1 Leu432Val polymorphism with the risk of prostate cancer: a meta-analysis

Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates in endocrine-mediated tumors such as prostate cancer. The potential significance of nonsynonymous SNP Leu432Val (rs1056836) as a risk factor in prostate cancer has been extensively studied. The objective of this meta-analysis was to quantitatively summarize the association between CYP1B1 Leu432Val polymorphism and prostate cancer. All eligible studies were searched and acquired from the PubMed and ISI databases. Statistical analysis was performed by using the software STATA 11.0. Ten case-controlled studies from nine eligible publications were identified, which includes 6,668 subjects with 3,221 cases and 3,447 controls. Overall, no significant association was found between the CYP1B1 Leu432Val polymorphism and prostate cancer susceptibility for Val/Val vs Leu/Leu (OR = 1.07; 95% CI: 0.79-1.44; P = 0.67), Leu/Val vs Leu/Leu (OR = 1.05; 95% CI: 0.94-1.17; P = 0.42), Leu/Val + Val/Val vs Leu/Leu (OR = 1.07; 95% CI: 0.91-1.26; P = 0.40) and Val/Val vs Leu/Val + Leu/Leu (OR = 1.11; 95% CI: 0.86-1.44; P = 0.43). However, a higher risk was found among Asians in all genetic models (Val/Val vs Leu/Leu :OR = 2.48, 95% CI: 1.14-5.39, P = 0.02; Leu/Val vs Leu/Leu: OR = 1.40, 95% CI: 1.03-1.89, P = 0.03; Leu/Val + Val/Val vs Leu/Leu: OR = 1.51, 95% CI = 1.14-2.01, P = 0.004; Val/Val vs Leu/Val + Leu/Leu: OR = 2.50, 95% CI = 1.35-4.56, P = 0.004). We were not able to detect any association in the subgroup analysis by source of controls and genotyping method in all genetic models. In conclusion, this meta-analysis provides evidence that CYP1B1 Leu432Val polymorphism is not associated with prostate cancer risk overall with the exception in Asians.     

Is the association between TNF-alpha-308 A allele and DMT1 independent of HLA-DRB1, DQB1 alleles?

The aim of the study was to assess chosen factors of genetic susceptibility to DMT1: DRB1, DQB1, and TNF-alpha polymorphisms-308 (G/A) in children with DMT1 and their up-to-now healthy siblings. Then we tested whether the association between TNF-alpha genes and DMT1 is independent of HLA. 87 diabetic children, their 78 siblings, and 85 persons from healthy control group were followed up. The highest risk of DMT1 was connected with alleles: DRB1*0401 (OR = 3.39; CI: 1.55-7.41), DRB1*0301 (OR = 2.72; CI: 1.48-5.01), DQB1*0201 (OR = 4.04; CI: 2.17-7.52), DQB1*0302 (OR = 5.08; CI: 2.54-10.14), and TNF-alpha-308 A allele (OR = 2.59; CI: 1.23-5.44). Moreover linkage disequilibrium for TNF-alpha-308 A allele with DRB1*0301 and DQB1*0201 was observed in both diabetic children and their siblings. Diabetic children and their siblings present similar genetic risk factors for DMT1. The association between TNF-alpha-308 A allele and DMT1 is dependent of HLA-DRB1 and DQB1 alleles.