Annual Review of Public Health - Volume 21, 2000

On exposure to a pathogen, a host may resist infection, become subclinically infected, or progress through several stages from mild to severe infection. Chronic sequelae may or may not occur. Host factors, particularly host genes, influence many of these stages. We have used a model of the continuum of pathogenesis of infectious diseases to consider the effect of host genes on five pathogens of significant public health burden: Mycobacterium tuberculosis, Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio cholerae. The relationships between these infections and polymorphisms in human leukocyte antigen, cytokines, other immune response, or pathogen receptor genes are reviewed. We discuss gene-gene interactions and their effects in complex settings, such as coinfections with several pathogens. Priorities for prevention and control of these pathogens include vaccines and antimicrobial drugs. Research on how host genes can influence vaccine responses and the efficacy of drugs or other interventions, as well as further research into the relationship of host genes to infectious disease outcomes, may lead to new strategies for prevention and control.

Dietary patterns, nutrients, and other constituents of food are major components of the environmental influences that contribute to risk for cancer, and the study of interactions between nutritional and genetic factors is a new and important area of research. This review describes the concepts and principles underlying this area of study and types of relationships between nutritional and genetic factors, and it provides examples of specific diet-gene interactions that are of current interest, with an emphasis on implications for cancer prevention and public health. Polymorphisms exist in the genes for the activating and conjugating metabolizing enzymes, and the induction of metabolizing enzyme activity by nutritional factors may result in either the activation of a carcinogen or the detoxification of a reactive intermediate metabolite. The relationship between the methylenetetrahydrofolate reductase gene and dietary folate is an example of a diet-gene interaction that involves a polymorphism in a vitamin metabolism gene, and the presence of the variant appears to influence both risk for cancer and folate requirements. Diet-gene interactions likely contribute considerably to the observed inter-individual variations in cancer risk in response to exposures to the nutritional factors that have the potential to promote or protect against cancer. Insights into mechanisms by which nutritional factors affect the process of carcinogenesis are provided by knowledge of the targeted gene function and enzyme activity. Increased knowledge in this area will allow a more refined approach to reducing risk for cancer, with diet interventions targeted toward individuals and subgroups that are genetically susceptible and responsive to the effects of nutritional factors.

Investigating the cellular and molecular pathogenesis of cancer is an established and important area of basic science research. Within the past several years, the capability of examining biomarkers of various genetic factors in the development and progression of chronic diseases, such as cancers, has enabled researchers to study these factors in clinical and community-based populations, in which environmental factors can also be measured or even manipulated. Dietary patterns and the nutrients and other co nstituents of food are a major component of the environmental influen ces that appear to contribute to disease risk, and the study of interactions between nutritional and genetic factors is a new and important area of research. This review describes the concepts and principles underlying this area of study, describes types of relationships between nutritional and genetic factors, provides examples of specific diet-gene interactions that are of current interest, and comments on implications for cancer prevention and public health.

Hemochromatosis is a common autosomal recessive condition found in the homozygous state in 1/200–1/400 people of northern-, central-, and western-European origin. It causes increased iron storage, which may lead to liver cirrhosis, liver cancer, heart disease, arthritis, and diabetes in many but not all affected adults, with a higher frequency in males. The condition is easily treated by repeated venesections without side effects but is frequently overlooked. Population screening of adults using iron indices alone or combined with DNA testing has therefore been recommended, but a consensus conference in 1997 recommended that such screening be deferred, owing to uncertainty regarding the extent of clinical disease that may develop in individuals detected by such programs. There was also concern that DNA screening results might be used for discrimination in insurance and occupational settings. Screening family members of patients with evidence of definite iron loading, however, is accepted by all observers. Because serious complications may be overlooked, a more aggressive stance toward case detection in the adult population has been advocated by some observers, realizing that unnecessary treatment might occur. Because additional information regarding the spectrum of clinical disease in homozygotes in now accumulating, a consensus conference in the near future is suggested to consider appropriate policies.

As the target date for the sequencing of the human genome approaches, there is growing recognition that public health practice, research, and education will be impacted by new genetic technologies and information and that a multidisciplinary approach is required. Research in the emerging field of public health genetics encompasses a broad range of disciplines and will increasingly involve the interactions among the investigators in these fields. An overview of these areas of research is provided, with illustrative examples. Education in public health genetics needs to address a variety of audiences, including public health graduate students and practitioners, students from related disciplines, and health care professionals. Two new graduate programs at the Universities of Michigan and Washington and training opportunities for public health professionals are described. These educational efforts must be ongoing so that the potential of genetic technology and information can be appropriately used to benefit the health of all.

It has now been over a quarter of a century since the publication of Mervyn Susser's Causal Thinking in the Health Sciences (1973, Oxford University Press), the first book-length treatment of causal reasoning and inference in our field. Major contributions of this work were its holistic focus on the origins of health outcomes in the context of ecologic systems and its invigoration of the literature on causal criteria in epidemiology. Although a recent resurgence of interest in social context has revivified many points made by Susser, a formal basis for causal analysis consistent with this ecologic perspective has failed to emerge in public health research. Susser's discussion of causal criteria, on the other hand, helped spur a vigorous dialogue that has persisted unabated to the present day. Although the basic outline of the criteria has evolved little, their applications, interrelations, and relative contributions to causal judgments have been the subject of continued and sometimes contentious debate.

A central problem in public health studies is how to make inferences about the causal effects of treatments or agents. In this article we review an approach to making such inferences via potential outcomes. In this approach, the causal effect is defined as a comparison of results from two or more alternative treatments, with only one of the results actually observed. We discuss the application of this approach to a number of data collection designs and associated problems commonly encountered in clinical research and epidemiology. Topics considered include the fundamental role of the assignment mechanism, in particular the importance of randomization as an unconfounded method of assignment; randomization-based and model-based methods of statistical inference for causal effects; methods for handling noncompliance and missing data; and methods for limiting bias in the analysis of observational data, including propensity score matching and sensitivity analysis.

The increased use of rigorous population-sampling methods and the analysis of data from those samples in cross-sectional surveys, case-control studies, longitudinal-cohort investigations, and other epidemiological research efforts have raised important statistical issues for health analysts. We describe the origin, implications, and some plausible resolutions for several of these issues. Some of the main issues we consider include (a) establishing whom the sample represents; (b) using sample weights; (c) understanding the role of other important features, such as the use of sampling stratification and the selection of clustered groups of population members; and (d) finding ways to analyze study data with key sampling features in mind. Ultimately, resolution of all of these issues requires that analysts clearly define a reference population and then understand the role of design features in relating sample results to that population.

Over the past few years there has been growing interest in considering factors defined at multiple levels in public health research. Multilevel analysis has emerged as one analytical strategy that may partly address this need, by allowing the simultaneous examination of group-level and individual-level factors. This paper reviews the rationale for using multilevel analysis in public health research, summarizes the statistical methodology, and highlights some of the research questions that have been addressed using these methods. The advantages and disadvantages of multi level analysis compared with standard methods are reviewed. The use of multilevel analysis raises theoretical and methodological issues related to the theoretical model being tested, the conceptual distinction between group and individual-level variables, the ability to differentiate “independent” effects, the reciprocal relationships between factors at different levels, and the increased complexity that these models imply. The potentialities and limitations of multilevel analysis, within the broader context of understanding the role of factors defined at multiple levels in shaping health outcomes, are discussed.

The first decade of experience with case-crossover studies has shown that the design applies best if the exposure is intermittent, the effect on risk is immediate and transient, and the outcome is abrupt. However, this design has been used to study single changes in exposure level, gradual effects on risk, and outcomes with insidious onsets. To estimate relative risk, the exposure frequency during a window just before outcome onset is compared with exposure frequencies during control times rather than in control persons. One or more control times are supplied by each of the cases themselves, to control for confounding by constant characteristics and self-confounding between the trigger's acute and chronic effects. This review of published case-crossover studies is designed to help the reader prepare a better research proposal by understanding triggers and deterrents, target person times, alternative study bases, crossover cohorts, induction times, effect and hazard periods, exposure windows, the exposure opportunity fallacy, a general likelihood formula, and control crossover analysis.

Growing urbanization accompanying growing population is increasing the demand for water supply in communities throughout the world. Water resources for many cities are already proving inadequate. Additional water resources are inherently more costly and are often not available because other communities and/or land owners have the water rights. Although conservation, particularly through demand management, may delay the need for additional sources for a short period, the need is inevitable. One approach that has been found to provide substantial additional water for communities is the reclamation of wastewaters produced by the communities themselves for unrestricted nonpotable purposes, such as for landscape and market crop irrigation, industry, cooling towers, air conditioning, toilet flushing, construction, vehicle washing, and environmental enhancement. This is done by providing dual distribution systems.

Nonpotable reuse is already widely practiced despite the fact that the reclaimed water distribution systems needed to be installed in existing communities. Inasmuch as additional water is needed for growing populations, the costs would be substantially reduced if the two systems were to be built at the same time in the newly developing areas. Reuse of reclaimed water for potable purposes may be feasible, but it imposes added public health risks that need to be accepted only as a last resort.

In the United States, most adolescents are employed at some time during their teen years. Provisions of the Fair Labor Standards Act, the nation's child labor law, address some of the risks of adolescent employment; however, >70 teenage workers are estimated to die from work-related injuries each year, with greater risk among males, whites, and older adolescents. Furthermore, the nonfatal work-related injuries of the ≥64,000 teens who receive emergency department care each year are believed to significantly undercount actual injuries. Many of these nonfatal injuries are severe, with 15%–45% leading to work restriction or permanent disabilities. Significant methodological issues limit the ability of existing surveillance systems to monitor youth worker injury. Risk factor and intervention research is very limited, but does suggest the role of some worker characteristics, management practices, and training issues. However, these factors need more careful study. This review considers existing information about occupational injuries among adolescents and identifies needs for research and policy attention.

Many diseases are influenced by weather conditions or display strong seasonality, suggestive of a possible climatic contribution. Projections of future climate change have, therefore, compelled health scientists to re-examine weather/disease relationships. There are three projected physical consequences of climate change: temperature rise, sea level rise, and extremes in the hydrologic cycle. This century, the Earth has warmed by about 0.5 degrees centigrade, and the mid-range estimates of future temperature change and sea level rise are 2.0 degrees centigrade and 49 centimeters, respectively, by the year 2100. Extreme weather variability associated with climate change may especially add an important new stress to developing nations that are already vulnerable as a result of environmental degradation, resource depletion, overpopulation, or location (e.g. low-lying coastal deltas). The regional impacts of climate change will vary widely depending on existing population vulnerability. Health outcomes of climate change can be grouped into those of: (a) direct physical consequences, e.g. heat mortality or drowning; (b) physical/chemical sequelae, e.g. atmospheric transport and formation of air pollutants; (c) physical/biological consequences, e.g. response of vector- and waterborne diseases, and food production; and (d) sociodemographic impacts, e.g. climate or environmentally induced migration or population dislocation. Better understanding of the linkages between climate variability as a determinant of disease will be important, among other key factors, in constructing predictive models to guide public health prevention.

The development of air pollution standards ideally involves the integration of data from the disciplines of epidemiology, controlled clinical studies, and animal toxicology. Epidemiological studies show statistical associations between health outcomes and exposure; they cannot establish a definite cause-effect relationship. The utility of toxicological studies is to establish this relationship. Recently, there was simultaneous promulgation of a new National Ambient Air Quality Standard (NAAQS) for particulate matter <2.5 μm in aerodynamic diameter (PM2.5) and a revised NAAQS for ozone (O3). The O3 NAAQS was based, in part, on a sound foundation of toxicological data from controlled exposure studies in humans and animals. It also relied on epidemiological studies of hospital admissions for respiratory diseases. Such studies also served as important bases for the new PM2.5 NAAQS. However, the most influential bases for the PM NAAQS were the numerous and generally consistent epidemiological studies that associated exposure with premature mortality in susceptible subpopulations and the inability of numerous hypothesized confounding factors to negate the associations. Using ozone and PM as examples, this paper discusses the scientific basis for NAAQS promulgations in situations in which the underlying database differed greatly in the extent of toxicological support.

Research examining the relationships between religion and the health of individuals and populations has become increasingly visible in the social, behavioral, and health sciences. Systematic programs of research investigate religious phenomena within the context of coherent theoretical and conceptual frameworks that describe the causes and consequences of religious involvement for health outcomes. Recent research has validated the multidimensional aspects of religious involvement and investigated how religious factors operate through various biobehavioral and psychosocial constructs to affect health status through proposed mechanisms that link religion and health. Methodological and analytical advances in the field permit the development of more complex models of religion's effects, in keeping with proposed theoretical explanations. Investigations of religion and health have ethical and practical implications that should be addressed by the lay public, health professionals, the research community, and the clergy. Future research directions point to promising new areas of investigation that could bridge the constructs of religion and health.

Collaborative partnerships (people and organizations from multiple sectors working together in common purpose) are a prominent strategy for community health improvement. This review examines evidence about the effects of collaborative partnerships on (a) community and systems change (environmental changes), (b) community-wide behavior change, and (c) more distant population-level health outcomes. We also consider the conditions and factors that may determine whether collaborative partnerships are effective. The review concludes with specific recommendations designed to enhance research and practice and to set conditions for promoting community health.

Tremendous strides have been made in reducing the incidence of tooth decay, periodontal diseases, and associated loss of teeth in adults and children since the inception of community water fluoridation programs. Yet the disadvantaged and poor have not fully shared in the benefits. Other challenges to oral health remain. Oral cancer and related smoking and smokeless tobacco use remain major public health problems. Access to preventive and therapeutic dental care is far from universal. Public health programs similar in commitment to the approach of community water fluoridation programs initiated in the 1950s and 1960s are needed to address neglected oral health needs of underserved and high-risk populations in the United States.

In recent years there has been an increasing use of litigation as a public health tool. Litigation has been brought to advance policies concerning such matters as tobacco, gun violence, and lead paint. This article discusses this development and the criticism that can be leveled at using litigation to develop public health policy. The article concludes that, although litigation may not always be successful, it can deter dangerous activities and play an important role in advancing the political and social struggle for public health.

As child morbidity and mortality declined during the twentieth century, a corresponding increase occurred in the relevance of child psychological well-being to public health. Evidence of this trend is the proliferation of programs intended to ameliorate conditions that place children in jeopardy of poor developmental outcome. Most recently, neurobiologic information on brain function and structure has been used to promote strategies for optimizing child development. This review will evaluate the current state of knowledge relating early child development to brain research and illustrate the potential misuse of this information. It will also suggest the following: (a) the extrapolation of neuroscience results to early academic and social enrichment programs obscures the magnitude of potential effects of these programs relative to the vast burden of risk imposed by poverty, and (b) an emphasis on intellectual functioning misses the most compelling evidence on the role of the early social environment in mediating establishment of neural networks that regulate a child's response to stress and capacity for self-control.