Molecular epidemiology of tuberculosis: achievements and challenges to current knowledge

Over the past 10 years, molecular methods have become available with which to strain-type Mycobacterium tuberculosis. They have allowed researchers to study certain important but previously unresolved issues in the epidemiology of tuberculosis (TB). For example, some unsuspected microepidemics have been revealed and it has been shown that the relative contribution of recently acquired disease to the TB burden in many settings is far greater than had been thought. These findings have led to the strengthening of TB control. Other research has demonstrated the existence and described the frequency of exogenous reinfection in areas of high incidence. Much recent work has focused on the phenotypic variation among strains and has evaluated the relative transmissibility, virulence, and immunogenicity of different lineages of the organism. We summarize the recent achievements in TB epidemiology associated with the introduction of DNA fingerprinting techniques, and consider the implications of this technology for the design and analysis of epidemiological studies.     

Environmental epidemiology: challenges and opportunities

Epidemiology is struggling increasingly with problems with correlated exposures and small relative risks. As a consequence, some scholars have strongly emphasized molecular epidemiology, whereas others have argued for the importance of the population context and the reintegration of epidemiology into public health. Environmental epidemiology has several unique features that make these debates especially pertinent to it. The very large number of environmental exposures require prioritization, and the relative risks are usually very low. Furthermore, many environmental exposures can be addressed only by comparing populations rather than individuals, and the disruption of both local and global ecosystems requires us to develop new methods of study design. The population context is also very important to consider in risk management decisions because of the involuntary nature of most environmental exposures and the diversity of possible outcomes, both health- and nonhealth-related. Studies at the individual or molecular level tend to focus the research hypotheses and subsequent interventions at that level, even when research and interventions at other levels may be more appropriate. Thus, only by starting from the population and ecosystem levels can we ensure that these are given appropriate consideration. Although better research is needed at all levels, it is crucially important to choose the most appropriate level, or levels, of research for a particular problem. Only by conducting research at all these levels and by developing further methods to combine evidence from these different levels can we hope to address the challenges facing environmental epidemiology today.     

Nutritional epidemiology: issues and challenges

Studies of diet in relation to disease raise methodological challenges considerably more complicated than in most epidemiological investigations. Diet is not a single exposure, but rather a complex set of many intercorrelated continuous variables. Moreover, these variables are likely to have non-linear relationships with disease and interact with each other. Many epidemiologists have questioned whether useful measurements of individual diets could be made within populations, due to homogeneity of food intake and imprecision of assessment methods. However, in several recent studies it has been possible to demonstrate reasonable levels of correlation between simple, structured food frequency questionnaires and detailed, weighed assessments of diet. This provides evidence documenting that between-person variation in diet does exist and that simple questionnaires are sufficiently accurate to measure these differences. For a limited set of nutrients, biochemical measurements provide an alternative assessment of exposure. It remains to be seen whether these methodologies can be reliably employed in case-control studies since even small biases due to the presence of illness, which may affect recall of diet or the levels of biochemical parameters, will seriously distort relationships between diet and disease.     

Climate change epidemiology: methodological challenges

Climate change is now thought to be unequivocal, while its potential effects on global and public health cannot be ignored. However, the complexities of the causal webs, the dynamics of the interactions and unpredictability mean that climate change presents new challenges to epidemiology and magnifies existing methodological problems. This article reviews a number of such challenges, including topics such as exposure assessment, bias, confounding, causal complexities and uncertainties, with examples and recommendations provided where appropriate. Hence, epidemiology must continue to adapt by developing new approaches and the integration of other disciplines such as geography and climatology, with an emphasis on informing policy-making and disseminating knowledge beyond the field.     

Systematic review of sexual problems: epidemiology and methodology

We conducted a comprehensive systematic literature review of five sexual problems in order to estimate their population prevalence and to investigate issues arising from the reviewing of epidemiological literature. Two independent reviewers scrutinized abstracts, extracted data, and assessed methodological quality. Twenty-eight relevant studies were identified. Prevalence figures varied considerably, and meta-analysis was not possible because of heterogeneity in study quality and design. Prevalence depends on case definition, characteristics of the study population, and time frame of the prevalence estimates, therefore, design, implementation, and reporting of epidemiological studies needs standardization before systematic reviews and meta-analyses can be carried out.     

早产的预测

早产是围生儿患病和围生儿死亡的最主要因素,因此预测早产具有重要的临床意义.早产往往是一些隐藏的病理情况的具体表现,这些病理情况会导致子宫,特别是子宫颈的生理和生化性的改变.宫颈的生理变化主要表现为宫颈的缩短和宫颈口的扩张,生化改变则比较复杂,有许多生化因子被证实和早产有关,该文就近几年研究比较多、具有一定临床指导意义的一些早产预测指标研究进展作以综述.     

Histologic chorioamnionitis and preterm delivery

Inconsistent findings linking placental histologic chorioamnionitis (HCA) and preterm delivery may result from variations in HCA definition, population studied, and exclusion criteria. This analysis from the 1998-2004 Pregnancy Outcomes and Community Health Study (five Michigan communities) includes the first 1,053 subcohort women (239 preterm, 814 term) with completed placental assessments. Multiple HCA definitions were constructed by 1) varying polymorphonuclear leukocytes/high-powered field thresholds and placenta components included and 2) using polymorphonuclear leukocyte characteristics to assign low/high maternal, fetal inflammation stage and grade. In African Americans, HCA was associated with preterm delivery before 35 weeks. The effect size was modest for polymorphonuclear leukocytes/high-powered field thresholds of greater than 10 and greater than 30 (odds ratios (ORs) = 0.8 and 2.0); larger for greater than 100 (OR = 3.2, 95% confidence interval (CI): 1.4, 7.1); strengthened after excluding medically indicated preterm deliveries (OR = 4.9, 95% CI: 2.0, 11.8); and strongest for high maternal/high fetal HCA (OR = 5.6, 95% CI: 1.4, 22.1). These latter HCA criteria also produced the largest effect size in Whites/others (OR = 2.7, 95% CI: 0.3, 26.9). Among preterm deliveries before 35 weeks excluding those medically indicated, 12% of Whites/others and 55% of African Americans had high maternal HCA. The authors conclude that HCA definition, exclusion criteria, and race/ethnicity influence the HCA-preterm delivery association and that HCA contributes to preterm delivery-related ethnic disparity.     

Stress and preterm delivery: a conceptual framework

Numerous epidemiological studies of various kinds of stress and preterm delivery have produced either negative or weakly positive results. Those inconclusive findings could be either because of the absence of an association or because of recognised methodological problems that may have masked an association. The biological plausibility of the stress hypothesis provides one rationale for continuing stress research, using better study designs. To further this agenda, we propose an epidemiological model, based on the classic 'host, environment, agent' triangle of epidemiological causality. The host is the individual woman, more or less susceptible to stressor-induced pathology. The environment includes the social and cultural conditions that are ongoing stressors as well as social and cultural modifiers of stress e.g. those factors that may influence how a particular stressor is experienced or what the physical response to it may be. The agent is the immediate emotional or physical stressor requiring her response. We draw from recent literature, published principally since 1990, to illustrate this model.
This epidemiological model posits that whether the individual is overwhelmed by stressors depends not only on the strength of the agents but also upon host susceptibility to stress, as well as the background level of acute, environmental and contextual stressors, and the moderating influence of host, environmental and contextual resources for handling stress. Future research needs to be based on stress hypotheses that include all sides of the triangle, data collection instruments that adequately capture relevant stressors and stress responses, and analytical techniques capable of handling complex, multilevel relationships.     

Ethnic differences in preterm and very preterm delivery.

Ethnic differences in preterm (less than 37 weeks) and very preterm (less than 33 weeks) delivery were evaluated in a prospective cohort of 28,330 women. Blacks had the highest rate of preterm and very preterm delivery, followed by Mexican-Americans, Asians, and Whites. Adjustment for maternal age, education, marital status, employment, parity, number of previous spontaneous or induced abortions, smoking and drinking during pregnancy, infant sex, and gestational age at initiation of prenatal care resulted in the following odds ratios for preterm delivery: 1.79 (1.55-2.08) for Blacks, 1.40 (1.19-1.63) for Mexican-Americans, 1.40 (1.16-1.69) for Asians, and 1.00 for Whites. The corresponding odds ratios for very preterm delivery were 2.35 (1.72-3.22) for Blacks, 1.31 (0.88-1.94) for Mexican-Americans, 1.10 (0.67-1.83) for Asians, and 1.00 for Whites. Exclusion of cases of premature rupture of membranes, placenta previa, and abruptio placenta did not explain the large ethnic differences. Although Whites and Mexican-Americans had similar birthweight distributions, Mexican-Americans had an increased risk for preterm delivery. Fifty-five per cent of low birthweight babies in Kaiser were preterm and this fraction did not vary substantially by ethnic group.     

早早产的预测

34周以前终止妊娠的早早产是围产儿病率和围产儿死亡的最主要因素 ,因此预测早早产具有重要的临床意义。该文就近几年来早早产预测指标的研究进展作一综述     

Gestational age reporting and preterm delivery

This study examines recent trends in the reporting completeness and quality of gestational age estimates derived from the date of the last normal menses (DLNM) as reported in South Carolina vital records from 1974 to 1985. Noteworthy improvements in the completeness of reporting emerged during this period with a decline from 31.1 percent missing information in 1974 to 6.6 percent missing in 1985. Completeness of reporting and strategies for imputing values for missing data were analyzed for their impact on the calculation of the percentage of preterm live births. The results indicate that the underreporting of gestational age can lead to marked underestimation of the preterm percentage in a population and to misinterpretation of trends in these percentages. Based on the results of this analysis, it is recommended that preterm percentages be based on cases with DLNM gestational age values between 20 and 50 weeks. Since cases with missing or implausible gestational age data have a greater risk of a poor pregnancy outcome, these findings emphasize the importance of identifying both the completeness of data reporting and the use of imputation and deletion strategies when employing population-based DLNM data to calculate gestational age related indicators.     

Familial patterns of preterm delivery: maternal and fetal contributions

Women who deliver preterm (<37 completed weeks' gestation) are at high risk for recurrence. This has prompted exploration of candidate genes (both maternal and fetal) associated with preterm delivery. Epidemiologists can use recurrence patterns of preterm delivery across generations to assess the relative contributions of maternal and fetal genes. The authors used data from the Medical Birth Registry of Norway (1967-2004) to identify 191,282 mothers and 127,830 fathers who subsequently had at least one singleton offspring. The authors stratified parents according to whether or not they had been born preterm and calculated the risk of preterm delivery among their firstborn. Mothers born preterm had a relative risk for preterm delivery of 1.54 (95% confidence interval (CI): 1.42, 1.67). This association was weaker for fathers born preterm (relative risk (RR) = 1.12, 95% CI: 1.01, 1.25). Among early preterm births (<35 weeks), the effect became stronger for mothers (RR = 1.85, 95% CI: 1.52, 2.27) and weaker for fathers (RR = 1.06, 95% CI: 0.77, 1.44). These data suggest that paternal genes have little, if any, effect on preterm delivery risk. This argues against major contributions of fetal genes inherited from either parent. The increased risk of preterm delivery among mothers born preterm is consistent with heritable maternal phenotypes that confer a propensity to deliver preterm.     

Defining preterm delivery--the epidemiology of clinical presentation

It is possible that preterm delivery is not a single entity but a cluster of conditions with different aetiologies that ultimately result in the delivery of an infant before 37 completed weeks of gestation. Whereas some researchers have reported aetiological heterogeneity, others have found no differences between subtypes or have disputed the desirability and utility of classifying preterm birth into subtypes. This study explores the relationship of maternal risk factors to type of preterm delivery in a cohort of over 7000 black and white women delivering singleton infants at the University of California, San Francisco's Moffitt Hospital between 1980 and 1990. Although the magnitude of the effect of individual risk factors differed between preterm delivery subtypes, the set of risk factors significantly associated with both categories of spontaneous preterm delivery was identical, while that associated with medically indicated preterm births was different. This study indicates that whereas the distinction between spontaneous preterm deliveries and those that are medically indicated seems valid, distinguishing between types of spontaneous preterm births may not lead to useful aetiological inferences.     

Maternal asthma and risk of preterm delivery

PURPOSE: We studied the relation between maternal history of asthma and preterm delivery. METHODS: The 312 preterm delivery cases, studied in aggregate, and in subgroups (spontaneous preterm labor, preterm premature rupture of membranes, medically induced preterm delivery), were compared with 424 randomly selected women who delivered at term. Maternal medical records provided information on maternal lifetime asthma status, pregnancy outcome, and sociodemographic characteristics. Using multivariate logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Maternal history of asthma was associated with an increased risk of preterm delivery overall (OR = 2.37; 95% CI 1.15-4.88). Analyses of preterm delivery sub-groups indicated that maternal history of asthma was associated with at least a doubling in risk of spontaneous preterm labor (OR = 2.35; 95% CI 0.84-6.58) and medically induced preterm delivery (OR = 2.69; 95% CI 1.11-6.53), though only the latter approached statistical significance. There was some evidence of a modest association between maternal asthma and risk of preterm premature rupture of membranes (OR = 1.63; 95% CI 0.50-5.33). CONCLUSIONS: These results support the hypothesis that maternal asthma is associated with an increased risk of preterm labor and delivery.     

Tocolytic therapy for preterm labour: assessing its potential for reducing preterm delivery

Preterm labour (PTL) is a major contributor to preterm delivery (PTD) but delivery is often not preventable by current therapies. We conducted this study to determine the proportion of women with PTL who were and who were not candidates for tocolytic therapy. The cohort comprised residents of Olmsted County, Minnesota who delivered at >20 weeks' gestation in 1985--94 and who experienced PTL. Medical records were abstracted to identify episodes of PTL, its treatment and outcome. We developed an algorithm that accounted for gestation at delivery and pregnancy complications to determine the proportion of pregnancies complicated by PTL that were candidates for tocolytic therapy. Of 651 pregnancies complicated by PTL, a 50% probability sample, stratified by delivery year, were selected and abstracted. The cumulative incidence of PTL ranged from 3.6 to 6.4 per 100 deliveries of live or stillborn infants. Tocolysis was not contraindicated for 49.4% of all women with PTL and for a third of women with only one PTL episode. Delivery was delayed to >35 weeks in 53.8% of candidates for tocolysis. Only an additional 11.7% of women with one or more PTL episodes could have had their PTD delayed beyond 35 weeks if a perfect tocolytic therapy had been available. Many pregnancies complicated by PTL occurred at > or =35 weeks or involved maternal or obstetric factors that contraindicated tocolytic medications. The maximum incremental benefit that could be expected of a new safe and efficacious tocolytic therapy would be to reduce current PTD rates resulting from PTL by about 12%.     

Molecular epidemiology and urothelial cancer

Tobacco smoking is the main cause of human urothelial cancer. It has been suggested that genetic susceptibility may contribute to the risk, because only a small portion of smokers develops urothelial cancer. Tobacco smoke contains many carcinogens which are activated or detoxified by phase-I or phase-II enzymes. The concentration of the ultimate carcinogen, which will react with DNA, is determined by the rate of activation and detoxification. Individuals with an increased rate of activation or a decreased rate of detoxification have a slightly higher level of bulky carcinogen-DNA adduct in the urothelial mucosa. Thus metabolic polymorphisms have been recognized as important determinants of carcinogen susceptibility, and recent efforts have shown that inter-individual differences in specific cytochrome P450 enzymes (CYPs), N-acetyltransferases (NAT), glutathione S-transferases (GST) and sulfotransferases (SULT) are often disproportionately represented in epidemiological studies between urothelial cancer cases and controls. It has been revealed that GSTM1 null genotype or NAT2 slow acetylator genotype may be associated with a small increase in urothelial cancer risk. Associations between other polymorphisms of metabolic enzymes and urothelial cancer are not well-known or are inconsistent. To reveal these associations, further well-designed and large-scale studies are needed.