Molecular tools have enhanced our understanding of the epidemiology of infectious diseases by describing the transmission system, including identifying novel transmission modes and reservoirs, identifying characteristics of the infectious agent that lead to transmission and pathogenesis, identifying potential vaccine candidates and targets for therapeutics, and recognizing new infectious agents. Applications of molecular fingerprinting to public health practice have enhanced outbreak investigation by objectively confirming epidemiologic evidence, and distinguishing between time-space clusters and sporadic cases. Clinically, moleculartools are used to rapidly detect infectious agents and predict disease course. Integration of molecular tools into etiologic studies has identified infectious causes of chronic diseases, and characteristics of the agent and host that modify disease risk. The combination of molecular tools with epidemiologic methods provides essential information to guide clinical treatment, and to design and implement programmes to prevent and control infectious diseases. However, incorporating molecular tools into epidemiologic studies of infectious diseases impacts study design, conduct, and analysis.
In this volume, the main axis of classification is provided by the predominantly site-based categories of chapter II (Neoplasms) of the 10th Revision of the International Classification of Diseases (WHO, 1992). However, the characteristics of many cancers—with respect to etiology, treatment and prognosis—are also dependent upon their histology. For this reason, the CD-ROM accompanying the volume also includes some cancers classified according to combinations of site and morphology.
The analytical methods for mycotoxin determination used in fully developed countries require sophisticated infrastructure, stable electricity, ready availability of supplies, and qualified and experienced technicians for instrument maintenance. Simple and appropriately validated tools analogous to those used for the management of contaminated bulk commodities at the grain elevator level are needed at the rural level in developing countries. These tools are needed to promote public health and to manage emergency situations in subsistence farming communities with an immediate and severe problem of mycotoxin contamination of food grains, with the goal of working towards feasible reductions in exposure. Two general analytical approaches that require less infrastructure are described here. The first approach is thin-layer chromatography (TLC), which has been used for more than 50 years to analyse mycotoxins. The advantages of TLC include simplicity and proven reliability. Accuracy may be improved by using precision spotters to apply precise amounts of sample to TLC plates and optical readers. The costs of these refinements to TLC are far lower than those of gas or liquid chromatography systems. The disadvantages of TLC include the need for stable supplies of solvents and standards as well as safe conditions for their storage. The second approach described here is based on immunological methods using anti-mycotoxin antibodies. These tests are available as kits, have the necessary standards built in, use little or no organic solvent, and are generally easy to use. The disadvantages of these methods include the need to refrigerate the kits before use and the limited shelf-life. It has been proposed that companies and development agencies could be solicited to develop packages of kits, sampling equipment (e.g. grinders), and training models for deployment in the many areas where mycotoxins are a chronic problem.
Mycotoxins have been investigated in relation to a wide range of adverse human health effects, but the evidence for all but a small number of associations is limited. Thus, the full impact on human health of the widespread exposure to mycotoxins remains to be defined. The main exception is for aflatoxins; epidemiological, experimental, and mechanistic studies have contributed to establishing aflatoxins as a cause of human liver cancer, with a particularly elevated risk in people chronically infected with hepatitis B virus. In addition, acute aflatoxicosis after exposure to high dietary toxin levels has been demonstrated. The impairment of child growth by aflatoxin exposure early in life remains an important subject of study. More information is also required on the potential immune effects of aflatoxins, especially in vulnerable populations. For fumonisins, studies indicate a possible role in oesophageal cancer and in neural tube defects, although no definitive conclusions can be drawn at present. For deoxynivalenol and other trichothecenes, exposure has been linked to acute poisoning outbreaks in large numbers of subjects. For ochratoxin A and zearalenone, the human health effects remain undefined. The limited tools available to accurately assess human exposure to mycotoxins and the relative paucity of epidemiological studies need to be addressed if the full extent of the adverse effects of these common dietary contaminants is to be understood and adequate public health measures taken. In this respect, newly established biomarkers of exposure at the individual level are proving valuable in improving exposure assessment in epidemiological studies.
Molecular tools have enhanced our understanding of the epidemiology of infectious diseases by describing the transmission system, including identifying novel transmission modes and reservoirs, identifying characteristics of the infectious agent that lead to transmission and pathogenesis, identifying potential vaccine candidates and targets for therapeutics, and recognizing new infectious agents. Applications of molecular fingerprinting to public health practice have enhanced outbreak investigation by objectively confirming epidemiologic evidence, and distinguishing between time-space clusters and sporadic cases. Clinically, moleculartools are used to rapidly detect infectious agents and predict disease course. Integration of molecular tools into etiologic studies has identified infectious causes of chronic diseases, and characteristics of the agent and host that modify disease risk. The combination of molecular tools with epidemiologic methods provides essential information to guide clinical treatment, and to design and implement programmes to prevent and control infectious diseases. However, incorporating molecular tools into epidemiologic studies of infectious diseases impacts study design, conduct, and analysis.
This chapter first discusses the urgent need for prevention of childhood diseases that impose a huge and growing burden on families and society. It provides a review of recent research in this area to illustrate both the strengths and limitations of molecular epidemiology in drawing needed links between environmental exposures and illness in children. For illustration, three of the major diseases in children are discussed: asthma, cancer and developmental disorders. All three impose significant difficulties, have increased in recent decades, and are thought to be caused in substantial part by environmental factors, such as toxic exposures due to lifestyle choices (i.e. smoking and diet), pollutants in the workplace, ambient air, water and the food supply. These exogenous exposures can interact with "host" factors, such as genetic susceptibility and nutritional deficits, to cause disease. Molecular epidemiology has provided valuable new insights into the magnitude and diversity of exposures beginning in utero, the unique susceptibility of the young, and the adverse preclinical and clinical effects resulting from the interactions between these factors. However, molecular epidemiology also faces certain constraints and challenges that are specific to studies of the very young, including ethical issues, technical issues due to the limited amount of biological specimens that can be obtained, and communication of results to parents and communities. These challenges are particularly apparent when incorporating the newer epigenetic and "omic" techniques and biomarkers into studies of children's diseases.
The Khon Kaen cancer registry was established in 1984 as a hospital-based cancer registry, and population-based cancer registration started in 1988 with retrospective data collection from 1985. Cancer registration is done by passive and active methods. Data on survival for 13 cancer sites or types registered during 1993-1997 were reported. Follow-up was done by active methods, with median follow-up ranging between 8-32 months for different cancers. The proportion with histologically verified diagnosis for various cancers ranged between 54-100%; death certificates only (DCOs) comprised 0-5%; 85-97% of total registered cases were included for survival analysis. Five-year follow-up ranged from 40-83%. Five-year age-standardized relative survival rates for common cancers were cervix (58%), breast (61%), colon (39%), ovary (43%), non-Hodgkin lymphoma (42%) and rectum (43%). Five-year relative survival by age group portrayed an inverse relationship or was fluctuating. Five-year survival was the highest for localized disease, followed by the regional and distant metastasis categories. Trends in 5-year relative survival in 1993-1997 compared to 1985-1992 showed a marked increase for cancers of the rectum, breast, ovary, Hodgkin and non-Hodgkin lymphomas and decrease for cancers of the lip and larynx.
The Singapore cancer registry is a national registry established in 1968. Cancer registration is done by passive methods. The registry contributed survival data on 45 cancer sites or types registered during 1993-1997. Data on 34 cancers registered during 1968-1997 were utilized for survival trend by period and cohort approaches. Follow-up was done by passive methods, with median follow-up ranging between 2-72 months for different cancers. The proportion with histologically verified diagnosis for various cancers ranged between 27-100%; death certificates only (DCOs) comprised 0-7%; 76-100% of total registered cases were included for the survival analysis. The top-ranking cancers on 5-year age-standardized relative survival rates were nonmelanoma skin (96%), thyroid (90%), testis (88%), corpus uteri (77%), breast (74%), Hodgkin lymphoma (73%) and penis (70%). Five-year relative survival by age group showed either a decreasing trend with increasing age groups or was fluctuating. Localized stage of disease ranged between 18-65% for various cancers and survival decreased with increasing extent of disease. Period survival closely predicted survival experience of cancers diagnosed in that period, and an increasing trend in period survival over different periods indicated an improved prognosis for cancers diagnosed in those calendar periods.
Until recently, the potential relevance of genetic, biochemical and lifestyle factors to coronary heart disease have been studied in relative isolation from one another. Although this approach has yielded some major insights, it has resulted in a fragmented and incomplete understanding of the relative importance and interplay of nature and nurture in the development of coronary risk. New opportunities for more integrated, powerful and comprehensive approaches have been opened by major developments, including: establishment, collation and maturation of relevant population bioresources; emergence of technologies that enable rapid and accurate assessment of many genetic and biochemical factors, without necessitating assumptions about biological mechanisms; and advances in statistical analytical methods. This chapter provides a critical review of the strengths and limitations of established and emerging epidemiological approaches to the study of the separate and combined effects of genetic, biochemical and lifestyle factors in coronary heart disease.
The population-based cancer registry in Manila, Philippines, called the Philippine Cancer Society-Manila Cancer Registry, was established in 1983. Cancer registration is pursued by active methods. The registry contributed survival data on a random sample of total incident cancers of breast (500), cervix (500), colon and rectum (300) registered in 1994-1995. Follow-up has been carried out by passive and active methods, with median follow-up ranging between 15-33 months for different cancers. The proportion of histologically verified diagnosis for various cancers ranged between 78-88%; 74-83% of the total submitted cases were included for survival analysis. Complete follow-up at five years was available in 75-82% of cases. Five-year age-standardized relative survival rates was the highest for cancer of the breast (52%) followed by colon (49%), cervix (36%) and rectum (31%). Five-year relative survival by age group did not display any pattern or trend and was fluctuating. A decreasing survival with increasing extent of disease was noted for all cancers.
The Songkhla registry, besides being hospital-based, has population-based cancer registration data available since 1990. Cancer registration is done by active methods. The registry is contributing data on survival for 36 cancer sites or types registered during 1990-1999. Follow-up has been carried out by passive and active methods with median follow-up ranging from 3-71 months for different cancers. The proportion with histologically verified diagnosis for various cancers ranged between 52-100%; death certificate only (DCO) cases comprised 0-34%; 54-93% of total registered cases were included for survival analysis. Complete followup at five years ranged from 50-85% for different cancers. Five-year age-standardized relative survival rates of common cancers were cervix (59%), lung (7%), breast (59%), thyroid (86%), oesophagus (11%), liver (2%), nonmelanoma skin (75%), colon (45%) and oral cavity (33%). Five-year relative survival by age group did not reveal any pattern or trend and was fluctuating. A majority were diagnosed with regional spread of disease, and survival decreased with increasing clinical extent of disease.
Biomarkers can be used to measure the presence of a wide variety of parent compounds and metabolites in body fluids and excreta, and serve as biomarkers of internal dose. Chemical-macromolecular adducts formed in blood and tissue or excreted in urine serve as biomarkers of exposure as well, and in many instances reflect both exposure and additional relevant biological processes. An assortment of analytical techniques have been developed to identify and measure parent compounds, metabolites, chemical-DNA and protein adducts. This chapter will discuss many analytical techniques that measure biomarkers in molecular epidemiologic studies, including biological, physical, chemical and immunological methods.
