Minimum Incidence of Adult Invasive Pneumococcal Disease in Blantyre,Malawi an Urban African Setting: A Hospital Based Prospective Cohort Study

Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect impact of PCV13 introduction to the childhood immunisation program.     

Incidence of H1N1 2009 virus infection through the analysis of paired plasma specimens among blood donors, France

Background

Knowledge of the age-specific prevalence of seroprotection and incidence of seroconversion infection is necessary to complement clinical surveillance data and statistical models. It provides the basis for estimating the future impact of influenza A (H1N1pdm09) and implementing appropriate prevention and response strategies.

Methods

Using a cross-sectional design, two-stage stratified sampling and paired plasma samples, we estimated the age-specific prevalence of a protective level of H1N1pdm09 antibodies in the French adult population before and after the 2009/10 pandemic, and the proportion of those susceptible that seroconverted due to infection, from a single sample of 1,936 blood donors aged 20–70 years in mainland France in June 2010. Samples with a haemagglutination inhibition (HI) titre ≥1∶40 were considered seropositive, and seroconversion due to infection was defined as a 4-fold increase in titre in the absence of H1N1pdm09 vaccination or pre-pandemic seropositivity.

Results

Out of the 1,936 donors, 1,708 were included in the analysis. Seroprevalence before the pandemic was 6.7% (95% CI 5.0, 8.9) with no significant differences by age-group (p = 0.3). Seroprevalence afterwards was 23.0% (95% CI 17.7, 29.3) with 20–29 year olds having a higher level than older groups (p<0.001). Seroconversion due to infection was 12.2% (95% CI 6.9, 20.5). Younger age-group, vaccination against H1N1 and being seropositive before the pandemic were strongly associated with post-pandemic seropositivity.

Conclusions

Before the 2009/2010 winter influenza season, only 6.7% of the French mainland population aged 20–70 had a level of antibodies usually considered protective. During the first pandemic wave, 12.2% of the population seroconverted due to infection and the seroprevalence after the wave rose to 23%, either due to prepandemic seropositivity, infection or vaccination. This relatively low latter figure contributed to an extension of target groups for influenza vaccination for the 2010/2011 season.     

Physical Inactivity and Incidence of Obesity among South Australian Adults

The aim of this paper is to examine the association of physical inactivity with incidence of obesity in the South Australian adult population. Two representative data sources were used – the South Australian Monitoring and Surveillance System (SAMSS), a monthly surveillance system, and the North West Adelaide Health Study (NWAHS), a biomedical cohort study. There were 75.3% (n = 12873) SAMSS participants and 72.8% (n = 1521) of NWAHS participants that were not obese at baseline. The cumulative incidence of obesity for SAMSS participants from the previous year to the current year was 2.7%. The cumulative incidence of obesity for NWAHS participants between baseline and stage 3 was 14.4%. Physical inactivity was associated with incident obesity (RR 1.48, 95% CI 1.14–1.90 [SAMSS] and RR 1.41, 95% CI 1.03–1.93 [NWAHS]). This association remained, but was attenuated after adjustment for chronic conditions, risk factors and socio-demographic factors. However, physical activity should be continued to be encouraged in the population for its known additional health benefits.     

Sexual transmission of hepatitis C virus: cohort study (1981-9) among European homosexual men.

OBJECTIVE--To determine the prevalence, incidence, and persistence of positivity for antibodies to hepatitis C virus (anti-HCV) and the potential for sexual transmission of the virus. DESIGN--A cohort analysis covering 1981-9 comparing estimated cumulative incidences of and seroconversion rates for anti-HCV with those of hepatitis B core antibody (anti-HBc) and antibodies to the human immunodeficiency virus (anti-HIV). SETTING--Copenhagen and Aarhus, Denmark. SUBJECTS--259 Male members of a Danish homosexual organisation. MAIN OUTCOME MEASURES--Correlations of prevalence and incidence with a wide range of sexual lifestyle variables. RESULTS--Only four (1.6%) subjects were positive for anti-HCV in 1981. The estimated cumulative incidence of positivity for anti-HCV was 4.1% in 1984 (seroconversion rate during 1981-4 (2.5%)) and remained at 4.1% in 1989 (seroconversion rate nil during 1984-9). In contrast, positivity for anti-HBC rose from 44.0% in 1981 to 52.7% in 1984 (seroconversion rate 15.5%) and 58.8% in 1989 (seroconversion rate 12.9%), and that for anti-HIV rose from 8.8% to 24.0% (seroconversion rate 16.7%) and 30.1% (seroconversion rate 8.0%) respectively. Three anti-HCV positive patients seroreverted three to five years later. None of the anti-HCV positive subjects had had a transfusion and only one gave a past history of intravenous drug use. Variables in sexual lifestyle correlated with the presence of anti-HBc but not with that of anti-HCV. CONCLUSIONS--In contrast with hepatitis B virus and HIV, sexual transmission of hepatitis C virus seems to be a rare event. Furthermore, antibodies to the virus may become undetectable after several years.     

Cumulative incidence of self-reported diabetes in Croatian adult population in relation to socioeconomic status and lifestyle habits

The aim of this study was to determine the 5-year cumulative incidence of self-reported diabetes mellitus in relation to various socioeconomic and lifestyle factors in Croatian adult population. The analysis included 2909 participants of the Croatian Health Cohort Study (CroHort) aged 20-79 years (median 55, interquartile range 43-67; 69% women) with no history of diabetes. There were 163 new cases of diabetes (5-year cumulative incidence 5.6%), without significant differences according to sex. Significant predictors of diabetes were age, body mass index, waist and hip circumference in bivariate logistic regression, and being married or living in partnership (OR = 1.57, 95% CI 1.08-2.28; p = 0.018), body mass index (OR =1.11, 95% CI 1.07-1.14; p < 0.001) and age (OR = 1.02, 95% CI 1.01-1.03; p = 0.004) in multivariate model. Our results indicate that approximately 1% of the Croatian adult population develops diabetes each year. Association of living in partnership with higher diabetes incidence requires further investigation.     

Recurrent Plasmodium falciparum malaria infections in Kenyan children diminish T-cell immunity to Epstein Barr virus lytic but not latent antigens

Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002-2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5-9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30-0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5-9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology.     

Prevalence of antibodies to 2009 pandemic influenza A (H1N1) virus in German adult population in pre- and post-pandemic period

Background

In order to detect levels of pre-existing cross-reactive antibodies in different age groups and to measure age-specific infection rates of the influenza A (H1N1) 2009 pandemic in Germany, we conducted a seroprevalence study based on samples from an ongoing nationwide representative health survey.

Methodology/Principal Findings

We analysed 845 pre-pandemic samples collected between 25 Nov 2008 and 28 Apr 2009 and 757 post-pandemic samples collected between 12 Jan 2010 and 24 Apr 2010. Reactive antibodies against 2009 pandemic influenza A (H1N1) virus (pH1N1) were detected using a haemagglutination inhibition test (antigen A/California/7/2009). Proportions of samples with antibodies at titre ≥40 and geometric mean of the titres (GMT) were calculated and compared among 6 age groups (18–29, 30–39, 40–49, 50–59, 60–69, ≥70 years). The highest proportions of cross-reactive antibodies at titre ≥40 before the pandemic were observed among 18–29 year olds, 12.5% (95% CI 7.3–19.5%). The highest increase in seroprevalence between pre- and post-pandemic was also observed among 18–29 year olds, 29.9% (95% CI 16.7–43.2%). Effects of sampling period (pre- and post-pandemic), age, sex, and prior influenza immunization on titre were investigated with Tobit regression analysis using three birth cohorts (after 1976, between 1957 and 1976, and before 1957). The GMT increased between the pre- and post-pandemic period by a factor of 10.2 (95% CI 5.0–20.7) in the birth cohort born after 1976, 6.3 (95% CI 3.3–11.9) in those born between 1957 and 1976 and 2.4 (95% CI 1.3–4.3) in those born before 1957.

Conclusions/Significance

We demonstrate that infection rates differed among age groups and that the measured pre-pandemic level of cross-reactive antibodies towards pH1N1 did not add information in relation to protection and prediction of the most affected age groups among adults in the pandemic.     

Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women during the first wave of the 2009 pandemic

Background

Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic.

Methods

Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels.

Results

Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province.

Interpretation

We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.During the first wave of the pandemic (H1N1) 2009, the province of Manitoba was more severely affected than almost any other Canadian province.¹ Pregnant women in particular had higher rates of laboratory-confirmed infection and of severe illness.² However, the number of laboratory-confirmed cases is not an accurate measure of the incidence of influenza in the population. The number and geographic distribution of confirmed cases are influenced by differences in access to medical care, physicians’ practices and other factors.³We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. We did this by measuring the point seroprevalence in random samples of pregnant women presenting for routine prenatal screening before and after the first wave.     

High Incidence of HIV-1 Infection in a General Population of Fishing Communities around Lake Victoria,Uganda

Background

High HIV-1 incidence rates were reported among persons in fisherfolk communities (FFC) in Uganda who were selected for high risk behaviour. We assessed the incidence of HIV-1 and associated risk factors in a general population FFC to determine population-wide HIV rates.

Methods

A community-based cohort study was conducted among a random sample of 2191 participants aged 18–49 years. At baseline and 12 months post-baseline, data were collected on socio-demographic characteristics and risky behaviors (including number of partners, new partners, condom use, use of alcohol and illicit drug use). Venous blood was collected for HIV serological testing. HIV incidence was calculated per 100 person years at-risk (pyar) and adjusted incidence rate ratios (Adj.IRR) were estimated by multivariable Poisson regression.

Results

Overall follow up at 12 months was 76.9% (1685/2191) and was significantly higher among HIV uninfected persons and those with at least 1 year duration of stay in community. Overall HIV-1 incidence was 3.39/100 pyar (95% CI: 2.55–4.49). Among the 25–29 years who drank alcohol, HIV incidence was 7.67/100pyar (95% CI;4.62–12.7) while it was 5.67/100pyar (95% CI;3.14–10.2) for 18–24 year olds who drank alcohol. The risk of HIV infection was higher among 25–29 years (adj.IRR = 3.36; 95% CI: 1.48–7.65) and 18–24 years (adj.IRR = 2.65; 95% CI: 1.05–6.70) relative to 30+ years. Compared to non-drinkers, HIV incidence increased by frequency of alcohol drinking - occasional drinkers (adj.IRR = 3.18; 95% CI: 1.18–8.57) and regular drinkers (adj.IRR = 4.93; 95% CI: 1.91–12.8).

Conclusion

HIV-1 incidence in general fisherfolk population along L.Victoria, Uganda, is high and is mainly associated with young age and alcohol drinking. HIV prevention and control strategies are urgently needed in this population.     

Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

BackgroundBreast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.MethodsBetween April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective).ResultsFour hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005).ConclusionsWithholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity.

Trial Registration

ClinicalTrials.gov NCT01199874     

Serotype distribution of invasive Streptococcus pneumoniae in Canada during the introduction of the 13-valent pneumococcal conjugate vaccine, 2010

A baseline serotype distribution was established by age and region for 2058 invasive Streptococcus pneumoniae isolates collected during the implementation period of the 13-valent pneumococcal conjugate vaccine (PCV13) program in many parts of Canada in 2010. Serotypes 19A, 7F, and 3 were the most prevalent in all age groups, accounting for 57% in <2 year olds, 62% in 2-4 year olds, 45% in 5-14?year olds, 44% in 15-49?year olds, 41% in 50-64?year olds, and 36% in ≥65?year olds. Serotype 19A was most predominant in Western and Central Canada representing 15% and 22%, respectively, of the isolates from those regions, whereas 7F was most common in Eastern Canada with 20% of the isolates. Other prevalent serotypes include 15A, 23B, 12F, 22F, and 6C. PCV13 serotypes represented 65% of the pneumococci isolated from?<2 year olds, 71% of 2-4 year olds, 61% of 5-14 year olds, 60% of 15-49 year olds, 53% of 50-64 year olds, and 49% of the?≥65?year olds. Continued monitoring of invasive pneumococcal serotypes in Canada is important to identify epidemiological trends and assess the impact of the newly introduced PCV13 vaccine on public health.     

A Change in Vaccine Efficacy and Duration of Protection Explains Recent Rises in Pertussis Incidence in the United States

Over the past ten years the incidence of pertussis in the United States (U.S.) has risen steadily, with 2012 seeing the highest case number since 1955. There has also been a shift over the same time period in the age group reporting the largest number of cases (aside from infants), from adolescents to 7–11 year olds. We use epidemiological modelling and a large case incidence dataset to explain the upsurge. We investigate several hypotheses for the upsurge in pertussis cases by fitting a suite of dynamic epidemiological models to incidence data from the National Notifiable Disease Surveillance System (NNDSS) between 1990–2009, as well as incidence data from a variety of sources from 1950–1989. We find that: the best-fitting model is one in which vaccine efficacy and duration of protection of the acellular pertussis (aP) vaccine is lower than that of the whole-cell (wP) vaccine, (efficacy of the first three doses 80% [95% CI: 78%, 82%] versus 90% [95% CI: 87%, 94%]), increasing the rate at which disease is reported to NNDSS is not sufficient to explain the upsurge and 3) 2010–2012 disease incidence is predicted well. In this study, we use all available U.S. surveillance data to: 1) fit a set of mathematical models and determine which best explains these data and 2) determine the epidemiological and vaccine-related parameter values of this model. We find evidence of a difference in efficacy and duration of protection between the two vaccine types, wP and aP (aP efficacy and duration lower than wP). Future refinement of the model presented here will allow for an exploration of alternative vaccination strategies such as different age-spacings, further booster doses, and cocooning.     

The Nicaraguan Pediatric Dengue Cohort Study: Incidence of Inapparent and Symptomatic Dengue Virus Infections, 2004–2010

Dengue, caused by the four serotypes of dengue virus (DENV), is the most prevalent mosquito-borne viral disease of humans. To examine the incidence and transmission of dengue, the authors performed a prospective community-based cohort study in 5,545 children aged 2–14 years in Managua, Nicaragua, between 2004 and 2010. Children were provided with medical care through study physicians who systematically recorded medical consult data, and yearly blood samples were collected to evaluate DENV infection incidence. The incidence of dengue cases observed was 16.1 cases (range 3.4–43.5) per 1,000 person-years (95% CI: 14.5, 17.8), and a pattern of high dengue case incidence every other year was observed. The incidence of DENV infections was 90.2 infections (range 45.2–105.3) per 1,000 person-years (95% CI: 86.1, 94.5). The majority of DENV infections in young children (<6 years old) were primary (60%) and the majority of infections in older children (≥9 years of age) were secondary (82%), as expected. The incidence rate of second DENV infections (121.3 per 1,000 person-years; 95% CI: 102.7, 143.4) was significantly higher than the incidence rate of primary DENV infections (78.8 per 1,000 person-years; 95% CI: 73.2, 84.9). The rigorous analytic methodology used in this study, including incidence reporting in person-years, allows comparison across studies and across different infectious diseases. This study provides important information for understanding dengue epidemiology and informing dengue vaccine policy.     

C. trachomatis pgp3 Antibody Prevalence in Young Women in England, 1993–2010

Seroepidemiology of chlamydia can offer study opportunities and insights into cumulative risk of exposure that may contribute to monitoring the frequency of, and control of, genital chlamydia–the most commonly diagnosed STI in England. We undertook retrospective anonymous population-based cross-sectional surveys using an indirect IgG ELISA for chlamydia Pgp3 antibody. Sera from 4,732 women aged 17–24 years were tested. Samples were taken at 3-yearly intervals between 1993 and 2002, a period during which other data suggest chlamydia transmission may have been increasing, and from each year between 2007 and 2010. Seroprevalence increased in 17–24 year olds over time between 1993 and 2002. Between 2007 and 2010, age-standardised seroprevalence among 17–24 year olds decreased from 20% (95% CI: 17–23) to 15% (95%CI 12–17) (p = 0.0001). The biggest drop was among 20 to 21 year olds, where seroprevalence decreased from 21% in 2007 to 9% in 2010 (p = 0.002). These seroprevalence data reflect some known features of the epidemiology of chlamydia infection, and show that exposure to antibody-inducing chlamydia infection has declined in recent years. This decline was concurrent with increasing rates of screening for asymptomatic chlamydia. Serology should be explored further as a tool for evaluation of chlamydia control, including chlamydia screening programmes.     

Age-dependent methylation of ESR1 gene in prostate cancer

The incidence of prostate cancer increases dramatically with age and the mechanism underlying this association is unclear. Age-dependent methylation of estrogen receptor alpha (ESR1) gene has been previously implicated in other cancerous and benign diseases. We evaluated the age-dependent methylation of ESR1 in prostate cancer. The methylation status of ESR1 in 83 prostate cancer samples from patients aged 49 to 77 years (mean age at 67.4 years) was examined using the bisulfite genomic sequencing technique. The samples were divided into three age groups: men aged 60 years and under (n = 14), men aged 61-70 years (n = 40), and men aged over 70 years (n = 29). Overall, ESR1 promoter methylation was detected in 54 out of 83 (65.1%) prostate samples. The methylation rate of ESR1 increased dramatically with age from 50.0% in patients aged 60 years and under to 89.7% for patients aged 70 years and over. Logistic regression analyses revealed that age and Gleason score were the only variables that affect incidence of ESR1 methylation; other clinical factors such as prostate-specific antigen level and clinical stage did not. We also calculated ESR1 methylation density (the percentage of methylated CpGs among all CpGs within the analyzed region) and severity (the percentage of methylated CpG alleles) for each sample analyzed. Multiple regression analyses showed a positive correlation between age and methylation density (beta, 0.35; P, 0.012; 95% CI, 0.26-2.01); while Gleason score was positively associated with methylation severity (beta, 0.45; P, 0.018; 95% CI, 1.04-4.26). These findings suggest that methylation of ESR1 is both age-dependent and tumor differentiation-dependent and age-dependent methylation of ESR1 may represent a mechanism linking aging and prostate cancer.     

The Association between NQO1 Pro187Ser Polymorphism and Bladder Cancer Susceptibility: A Meta-Analysis of 15 Studies

Background

NAD(P)H:quinone oxidoreductase 1 (NQO1), an obligate two-electron reductase, plays an important role in reducing reactive quinones to less reactive and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its enzyme function may be considered as putative risk factor for cancer. Numerous studies have been performed to investigate the association between NQO1 Pro187Ser polymorphism and bladder cancer risk; nevertheless, the results remain controversial.

Methods

We indentified eligible publications from PubMed, Embase and CBM databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the strength of the associations. False-positive report probability (FPRP) analysis was also performed for all statistically significant findings.

Results

We collected a total of 15 studies including 4298 cases and 4275 controls in the final meta-analysis. Overall, the NQO1 187Ser carriers were associated with an increased bladder cancer risk (homozygous: OR = 1.43, 95% CI = 1.08-1.90; recessive: OR = 1.33, 95% CI = 1.03-1.72; dominant: OR = 1.19, 95% CI = 1.04-1.37, and allele comparing: OR = 1.18, 95% CI = 1.06-1.33). Stratification analyses showed a statistically significant association among Asians (homozygous: OR = 1.82, 95% CI = 1.39-2.38; recessive: OR = 1.52, 95% CI = 1.20-1.93, dominant: OR = 1.40, 95% CI = 1.05-1.88, and allele comparing: OR = 1.35, 95% CI = 1.15-1.58), never smokers (homozygous: OR = 2.30, 95% CI = 1.14-4.65; heterozygous: OR = 2.26, 95% CI = 1.43-3.56; dominant model: OR = 1.59, 95% CI = 1.14-2.21, and allele comparing: OR = 1.72, 95% CI = 1.27-2.33), hospital-based studies (homozygous: OR = 1.46, 95% CI = 1.09-1.94; recessive: OR = 1.32, 95% CI = 1.02-1.69; dominant: OR = 1.28, 95% CI = 1.05-1.56, and allele comparing: OR = 1.24, 95% CI = 1.07-1.43), studies with genotyping performed by PCR-RFLP under all genetic models, and studies with minor allele frequency >0.30 (homozygous: OR = 1.69, 95% CI = 1.25-2.27; recessive: OR = 1.46, 95% CI = 1.10-1.95, and allele comparing: OR = 1.25, 95% CI = 1.04-1.51), respectively.

Conclusions

Despite some limitations, our meta-analysis provides sufficient evidence that NQO1 Pro187Ser polymorphism may contribute to bladder cancer risk. These findings need further validation in well-designed prospective studies with larger sample size and different ethnicities, especially for Asians.     

Temporal trends in incidence of childhood cancer in Switzerland, 1985–2014

BackgroundIncidence of childhood cancer increased in most countries worldwide, but reasons are unclear. This study investigates trends of childhood cancer incidence in Switzerland from 1985 to 2014.MethodsWe extracted data on all childhood cancer cases diagnosed at ages 0–14 years in Switzerland from the Swiss Childhood Cancer Registry. We included ICCC-3 main groups I-XII and calculated age-standardised, cumulative, and age-specific incidence for different diagnostic groups. We analysed trends of annual age-standardised incidence using JoinPoint regression models.ResultsOver the study period from 1985 to 2014, 5104 of 5486 cancer diagnoses (93%) were microscopically verified. The proportion of children treated in paediatric cancer centres increased from 84% during 1985–1994 to 93% in 1995–2004 and 98% in 2005–2014 (p < 0.001). Using the World standard population, age-standardised incidence was 143 in 1985–1994, 154 in 1995–2004, and 162 per million in 2005–2014. Incidence increased by 0.7% (95% confidence interval (CI) 0.5; 1.0) per year for all cancers from 1985 to 2014, 0.8% (95% CI 0.2%–1.4%) for leukaemias over the same period, 3.0% (95% CI 0.2%–1.4%) for CNS tumours during 1985–2002, and 3.8% (95% CI 1.7%–6.0%) for epithelial neoplasms and melanomas over the period 1985–2014.ConclusionTrends in incidence were driven mostly by increases among leukaemias and CNS tumours. For CNS tumours, observed trends may be explained at least partially by diagnostic changes and improved registration. For leukaemias, rising incidence may be real and due to risk factors that experience similar increases in trends.     

Risk factors for elevated HIV incidence rates among female injection drug users in Vancouver

Background

In 1997, we found a higher prevalence of HIV among female than among male injection drug users in Vancouver. Factors associated with HIV incidence among women in this setting were unknown. In the present study, we sought to compare HIV incidence rates among male and female injection drug users in Vancouver and to compare factors associated with HIV seroconversion.

Methods

This analysis was based on 939 participants recruited between May 1996 and December 2000 who were seronegative at enrolment with at least one follow-up visit completed, and who were studied prospectively until March 2001. Incidence rates were calculated using the Kaplan–Meier method. The Cox proportional hazards regression model was used to identify independent predictors of time to HIV seroconversion.

Results

As of March 2001, seroconversion had occurred in 110 of 939 participants (64 men, 46 women), yielding a cumulative incidence rate of HIV at 48 months of 13.4% (95% confidence interval [CI] 11.0%–15.8%). Incidence was higher among women than among men (16.6% v. 11.7%, p = 0.074). Multivariate analysis of the female participants'' practices revealed injecting cocaine once or more per day compared with injecting less than once per day (adjusted relative risk [RR] 2.6, 95% CI 1.4–4.8), requiring help injecting compared with not requiring such assistance (adjusted RR 2.1, 95% CI 1.1–3.8), having unsafe sex with a regular partner compared with not having unsafe sex with a regular partner (adjusted RR 2.9, 95% CI 0.9–9.5) and having an HIV-positive sex partner compared with not having an HIV-positive sex partner (adjusted RR 2.7, 95% CI 1.0–7.7) to be independent predictors of time to HIV seroconversion. Among male participants, injecting cocaine once or more per day compared with injecting less than once per day (adjusted RR 3.3, 95% CI 1.9–5.6), self-reporting identification as an Aboriginal compared with not self-reporting identification as an Aboriginal (adjusted RR 2.5, 95% CI 1.4–4.2) and borrowing needles compared with not borrowing needles (adjusted RR 2.0, 95% CI 1.1–3.4) were independent predictors of HIV infection.

Interpretation

HIV incidence rates among female injection drug users in Vancouver are about 40% higher than those of male injection drug users. Different risk factors for seroconversion for women as opposed to men suggest that sex-specific prevention initiatives are urgently required.Recent reports in Canada and numerous other countries indicate that HIV is increasingly affecting women.¹ Before 1995, adult women in Canada had 9.6% of all positive HIV tests for which the age and sex of the person being tested were known. By 1995, this proportion had increased to 18.5% and reached 23.9% in 2000. In addition, 39% of all new HIV infections among women in 2000 were attributed to injection drug use.² These data are consistent with findings in the United States where, in 1999, women accounted for 23% of all reported AIDS cases in adults, of which 42% were attributed to injection drug use.³These data clearly indicate that the face of the epidemic is changing. Whereas some factors unique to the transmission of HIV to women are known, basic and behavioural research efforts addressing sex-related and drug-related vulnerabilities among female injection drug users (IDUs) are lacking.⁴ At a time when women''s vulnerability to HIV infection is becoming increasingly apparent worldwide,^5,6 a better understanding of the processes and factors that cause drug-related harm among women in industrialized countries is urgently required.Since the mid-1990s, the Downtown Eastside of Vancouver, British Columbia, has experienced an explosive and ongoing HIV epidemic among IDUs with annual HIV incidence rates reaching as high as 19% in 1997.^7,8 When subjects were enrolled in the Vancouver Injection Drug User Study (VIDUS), it was found that the baseline HIV prevalence was higher among women than men (35.2% v. 25.8%).⁷ Follow-up of this cohort now allows an investigation aimed at identifying the predictors of HIV seroconversion among female and male IDUs. Therefore, we sought to compare HIV incidence rates among male and female IDUs in Vancouver and to compare risk factors associated with HIV seroconversion.     

Predicting the epidemic sizes of influenza A/H1N1, A/H3N2, and B: a statistical method

Background

The epidemic sizes of influenza A/H3N2, A/H1N1, and B infections vary from year to year in the United States. We use publicly available US Centers for Disease Control (CDC) influenza surveillance data between 1997 and 2009 to study the temporal dynamics of influenza over this period.

Methods and Findings

Regional outpatient surveillance data on influenza-like illness (ILI) and virologic surveillance data were combined to define a weekly proxy for the incidence of each strain in the United States. All strains exhibited a negative association between their cumulative incidence proxy (CIP) for the whole season (from calendar week 40 of each year to calendar week 20 of the next year) and the CIP of the other two strains (the complementary CIP) from the start of the season up to calendar week 2 (or 3, 4, or 5) of the next year. We introduce a method to predict a particular strain''s CIP for the whole season by following the incidence of each strain from the start of the season until either the CIP of the chosen strain or its complementary CIP exceed certain thresholds. The method yielded accurate predictions, which generally occurred within a few weeks of the peak of incidence of the chosen strain, sometimes after that peak. For the largest seasons in the data, which were dominated by A/H3N2, prediction of A/H3N2 incidence always occurred at least several weeks in advance of the peak.

Conclusion

Early circulation of one influenza strain is associated with a reduced total incidence of the other strains, consistent with the presence of interference between subtypes. Routine ILI and virologic surveillance data can be combined using this new method to predict the relative size of each influenza strain''s epidemic by following the change in incidence of a given strain in the context of the incidence of cocirculating strains. Please see later in the article for the Editors'' Summary