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MODULE OUTLINE
8.1 ENVIRONMENTAL EXPOSURES
8.1.1 The Environmental Problem
8.1.2 Environmental Pollution
8.1.3 Epidemiological Studies
8.1.4 Risk Assessment and Management
8.2 OCCUPATIONAL EXPOSURES
8.2.1 Introduction
8.2.2 Occupational Hazards and Diseases
8.2.3 Occupational Health Studies
8.2.4 Prevention of Occupational Disease
8.3 NUTRITIONAL EXPOSURES
8.3.1 Introduction
8.3.2 Incidence and Prevalence of Malnutrition
8.3.3 Diseases Associated with Malnutrition
8.3.4 Assessment of Nutritional Status
8.3.5 Epidemiological Studies of Nutritional Exposures
8.4 RADIATIONAL EXPOSURES
8.4.1 Over-View
8.4.2 Radiations: Types, Sources, and Measurement
8.4.3 Effects of Radiation
8.5 OTHER EXPOSURES
8.5.1 Biological Markers
8.5.2 Genetic Exposures
8.5.3. Pharmaceutical Agents
UNIT 8.1
Learning Objectives
· Sources of air pollution: indoor pollutants, out-door pollutants
· Sources of water pollution: municipal sewage, industry
· Sources of soil pollution: solid waste, hazardous waste, sewage
· Types of eco-poisons: pesticides and PCB
· Prevention of pollution: primary and secondary
Key Words and Terms
· Acid rain
· Air pollution
· Dental waste
· Drug residues
· Eco-poisons
· Environmental health
· Environmental degradation
· Environmental engineering
· Environmental ethics
· Environmental exposure
· Environmental health
· Environmental impact analysis
· Environmental law
· Environmental medicine
· Environmental monitoring
· Environmental policy
· Environmental pollution
· Environmental protection
· Food microbiology
· Food parasitology
· Green-house effect
· Hazardous substance/waste
· Inhalation exposure
· Maternal exposure
· Maximum permissible exposure level
· Medical waste
· Natural disasters
· Noise and vibration
· Occupational exposure
· Paternal exposure
· Pest control
· Refuse disposal
· Smoke
· Soil pollution
· Vehicle emissions
· Water micro-biology
· Water pollution
UNIT OUTLINE
8.1.1 THE ENVIRONMENTAL PROBLEM
A. Definition and Scope of Environmental Epidemiology:
B. Ecology
C. Population and the Environment
D. Background to the Environmental Problem:
E. Effect of the Environment on Health
8.1.2 ENVIRONMENTAL POLLUTION
A. Air Pollution
B. Water Pollution
C. Soil Pollution
D. Eco-Poisons
E. Others: Food, Animals and Plants
8.1.3 EPIDEMIOLOGICAL STUDIES
A. General
B. Exposure Assessment
C. Measurement of Outcome
D. Confounding
E. Priorities in Environmental Epidemiology Research
8.1.4 RISK ASSESSMENT and MANAGEMENT
A. History
B. Definition of Risk Assessment
C. Risk Management
8.1.1 THE ENVIRONMENTAL PROBLEM
A. DEFINITION AND SCOPE OF ENVIRONMENTAL EPIDEMIOLOGY:
Environmental epidemiology is a sub-discipline that studies environmental causes of human disease and how to prevent those diseases. It seeks to establish exposure-disease relations and to change them. The environment consists of all those substances and phenomena that have an impact on human health and disease at all stages of the human lifespan. The environment can be physical, chemical, biological, social, political, and cultural. Environmental hazards enter the body through the respiratory tract, the alimentary tract, and the skin. Most environmental exposures that have an adverse effect on health are involuntary. The discipline of environmental epidemiology was first concerned with infectious diseases. It later expanded into air, water, and soil pollution. Its scope is now quite wide including: physical and environmental causes of disease, air pollution, water pollution, soil pollution (solid wastes, chemicals, mining, radiological), eco-poisons (e.g. DDT) food toxins, and bacterial infections. The concept of total exposure is used to describe the multi-media exposure in environmental epidemiology i.e. exposures from several and not one source of exposure. Where environmental causes can not be eliminated, environmental epidemiology helps set safe exposure limits. Reducing risk is by restrictions and regulation. Conservation of natural resources may be the definitive approach.
B. ECOLOGY
Ecology is the study of the organism and its environment. The interaction can be described in several modes. Humans interact with energy systems either in the food web or non nutritive energy systems (fossil, electrical, and nuclear). Humans interact with biological systems in the biosphere. They interact with geophysical systems like the earth, water, and the atmosphere. They also interact with biological systems of the biosphere. Human civilization has created systems that were unknown in primitive society and with which humans have to interact such as the built environment (home dwellings, factories, water systems, sewage systems, communication systems, and transport systems), technological activities (manufacturing, mining, energy production), residues and wastes (domestic waste, manufacturing waste, transport waste like CO and HC, and wastes as a result of energy generation). Humans have to interact with environmental hazards that are either natural or are a result ot human activity. Natural disasters may be geophysical such as earthquakes or meteorological such as cyclones, hurricanes, typhoons, and volcanic eruptions. They cause psychosocial stress, and injuries, property losses. The victims are in urgent need of water, food, and shelter. Biological hazards arise as a failure of environmental sanitation. They are disease-causing organisms that may be water-borne, food-borne, or vector-borne. The water borne hazards are polio, HAV, salmonella spp, shigella spp, cholera, E. Histolytica, and G.lamblia. Food-borne outbreaks are caused by viruses, bacteria, or protozoa. Vector borne hazards arise due to conditions that encourage the breeding of vectors (mosquitoes, fleas, lice, ticks, etc): standing water, overloaded sewage, and improper handling of wastes. Mosquitoes in particular thrive in mismanaged irrigation waters, water in discarded automobile tyres. Open drains are breeding places for rodents. Chemical hazards are mostly man-made and may be solid, liquid, or gaseous. Physical hazards are extremes of temperature, humidity, noise, vibration, tools and equipment. Heat causes heat stroke and heat exhaustion. Extreme cold causes hypothermia. Life at high altitude is difficult because of shortage of oxygen. Drowning in water causes death. Electric shocks cause extensive tissue damage. Noise and vibration have physical and psychological effects. Noise is defined as unwanted sound. Noise is annoying. It disturbs sleep, conversation, rest and home life. Besides annoyance, noise impairs hearing, causes stress, causes emotional problems, and reduces concentration which increases the risk of unintentional injury. Construction noise is temporary. Traffic noise is permanent but peak hours vary. Sound meters are used to measure the frequency and amplitude of sound which are expressed in decibels. Noise pollution is controlled by legislation to control sources of noise, education, and environmental change (padding, and ear plugs). Vibration usually accompanies noise. The sources of vibration are: industry, construction, road traffic, and the supersonic boom of aircraft.
C. POPULATION AND THE ENVIRONMENT
Carrying capacity is the amount of resources (air, water, shelter, etc) in a given environment needed to support a population of a given size. Population doubling time is directly proportional to the annual population growth rate. The doubling times in years for various growth rates is as follows: 0.5% - 140 years, 1.0% 70 years, 2.0% 35 years, 3.0% 24 years, and 4.0% 17 years. Population increase can result into environmental degradation if the carrying capacity is not increase proportionately. A higher population is associated with production of more waste and therefore more air and water pollution, higher energy demands which leads to higher fossil fuel use and hence pollution, higher food demand, less land for agriculture, less living space per person, less available resources leading to crime and war, higher health care demand, higher housing demand. Population increase is controlled naturally by starvation, epidemics or wars or artificially by contraceptives.
D. BACKGROUND TO THE ENVIRONMENTAL PROBLEM:
The earth consists of the lithosphere (land mass) and the hydrosphere (water mass). The biosphere is part of the earth in which life exists. The ecosystem is biotic and abiotic. It is dynamic as evidenced by the carbon, nitrogen, phosphorus, and energy cycles. The current problems facing the biosphere are: waste disposal, destruction of ecosystems, and desertification. The ozone layer protects against ultra-violet rays. This protective layer is being depleted by hydrocarbon release into the atmosphere. Environmental health emergencies: chemical spills, earthquakes, floods, forest fires, landslides, and radioactive spills. Population growth leads to environmental degradation unless special measures are taken. More people use more of the natural resources which if not replaced will be deleted. Energy consumption is increasing. Fossil fuels cause air pollution. Alternative fuels such as nuclear power, geothermal power, solar power, and the biomass do also have environmental risks. Industrialized nations have more per capita energy consumption than the less developed countries and hence have more pollution. Increasing industrialization leading to ecological damage, exposure to chemical & physical hazards. Pesticides used in agriculture, noise, and radiation are other causes of the environmental problem. In response to the increasing environmental degradation, special laws have been passed in many countries. An environmental impact statement is now required before approval of new industrial developments.
E. EFFECT OF THE ENVIRONMENT ON HEALTH
Carcinogenesis:
Environmental epidemiology is concerned with investigation of chemicals that are toxic or carcinogenic. Environmental carcinogens are chemical or radiation. They cause mutagenesis by changing the DNA molecule or the DNA structure. The mechanisms of mutagenesis are: break, base substitution, intercalation, and frame shift. DNA repair often repairs the damage but may fail in some cases. Testing of mutagenicity is by in vivo animal tests or in vitro. Reproductive teratogenesis/toxicity: paternal or maternal exposure.
Toxicology operates using three laws: the dose makes the poison, chemical agents have specific effects, and humans are animals. When chemicals come into contact with the human they are absorbed, distributed, metabolized, and excreted. Differences among humans in susceptibility are not understood. Toxicology tests the safety of chemicals and helps set environmental standards.
8.1.2 ENVIRONMENTAL POLLUTION
A. AIR POLLUTION
DEFINITION OF THE PROBLEM
Air pollution is defined as contamination of the air by substances in amounts great enough to interfere with the comfort, safety, and health of living organisms. The three commonest causes of air pollution are automobiles combustion, burning of fossil fuels for energy generation, and industrial plants like refineries and mills. The most pervasive air pollutants are CO, Pb, NO2, SO2, O3, and particulate matters. Air borne pollutants can be gases, vapors, erosols, mist, dust, or smoke.
The problem of air pollution is the result of industrialization. Before the industrial Revolution, the causes of air pollution were all natural phenomena: dust, sand storms, forest fires, volcanic eruptions, gases from the depths of the earth, and gases from decaying organic matter.
There is concern for both indoor and outdoor air quality. Indoor air includes homes, and institutions like hospitals, schools, and prisons. Outdoor air quality is affected by industrialization and the use of automobiles. Developed countries became aware of their air quality problems and started taking measures to control the problems. Developing countries are just becoming aware of an increasing problem for which they do not have the resources to solve. They also face a real moral and economic dilemma. The economic and industrial activities that they need to get out of poverty cause degradation of air-quality and the choice is difficult to make. The problems of air-quality control are no longer national. International cooperative efforts are needed because of the long-range transportation of pollutants. Acid rain, dust storms, radioactive fall-out do not respect national boundaries. The fall-out from the 1954 Bikini island atomic tests, and the 1986 Chernobyl
INDOOR POLLUTION:
The sources of indoor pollutants are either internal or external. The concentration of indoor pollutants is higher than that of outdoor pollutants because pollutants are trapped and are concentrated. Humans spend more than 90% of their time indoors.. There is little information on the chronic effects of indoor pollutants. The internal sources are cigarette smoke, heating and air-conditioning, building materials like asbestos, wood combustion, radon, formaldehyde, and nitrogen dioxide from gas stoves. Carbon monoxide is the most dangerous indoor pollutant. Formaldehyde is from indoor insulating material. The external sources: pollutants entering the house from the external atmosphere. Indoor pollutants include organic and inorganic compounds, viruses, bacteria, and fungi. The problem of indoor pollution has come to prominence only recently with the emergence of a politically-powerful anti-smoking movement. Even non-smoking members of the household suffer from passive smoking. Indoor air quality surveys need to be undertaken. Housing codes should incorporate appropriate measures to prevent such pollution.
OUTDOOR POLLUTION:
TYPES AND SOURCES OF OUTDOOR POLLUTION: The sources of outdoor pollution are: burning of coal or heavy oil, automobile emissions that are products of incomplete combustion of petrol, and emissions from the chemical industry. Control of indoor smoking can increase outdoor pollution with smokers preferring to smoke in the open air rather than drop the habit. Air pollutants may be organic or inorganic. The inorganic are either gases or particles. The commonest gases are: nitrogen oxides NO2, sulfur oxides SO2, carbon monoxide CO, carbon dioxide CO2, ozone O3 and hydrocarbons. The particles are from mining and construction (lead, asbestos, beryllium, cadmium, mercury, iron) or radioactive material. Ozone is a highly reactive oxidant which irritates mucous membranes and causes pulmonary epithelial inflammation. Levels of ozone are high in the summer. Levels are higher in the day than at night. They are highest at mid afternoon. Sulfur dioxide, particles, and erosols are due to burning fossil fuels. Nitrogen oxides due to auto emission systems affect the immune system. Carbon monoxide is due to incomplete combustion of organic matter. Its primary source is auto emission. Acute carbon monoxide exposure is a cause of fatal poisoning. Chronic exposure is associated with angina and myocardial infarction. Asbestos is from insulation materials or from material of clutches and brakes. It is associated with lung cancer, mesothelioma, and asbestosis with smokers being at a higher risk. Auto emissions contain the following carcinogenic substances: benzene, polycystic aromatic hydrocarbons (PAH) and nitro-PAH. Exposure to benzene is from 4 sources: cigarette smoke, home solvents, gasoline, and leaky underground tanks that contaminate water supplies. Benzene is associated with leukemia and aplastic anemia. Diesel exhaust is mutagenic and is associated with lung cancer. Acid erosols increase cancer risk. Lead is found in electric batteries, pipes, paint, plastic pigments and leaded gasoline. Lead poisoning is chronic in nature leading to anemia, birth defects, bone damage, depression of neurological and psychological functions, kidney damage, hypertension, childhood learning disabilities, miscarriage and sterility. Exposure to lead is either by ingestion in food or water or inhalation. Children accidentally ingest lead-containing substances like paint. Adults are exposed at the work place. The whole family is exposed if the home has leaden pipes. Auto emissions containing lead contaminate vegetables and water. Children at a higher risk of developing lead poisoning because of their higher intenstinal absorption. Inhaled lead poses a bigger problem because it goes directly into the blood stream. Lead poisoning is controlled by education, and regulatory ban of lead products. Plumbing in homes should be changed. Stress, boredom, Hypochondriasis, depression, hysteria, and frustration are psychological hazards. War and the urban scourges of overcrowding, traffic jams, isolation, and lack of privacy are sociological hazards.
ENVIRONMENTAL TOBACCO SMOKE (ETS): ETS has two types of effects: mainstream smoke for the smokers themselves and side-stream smoke for the non smokers. ETS is associated with lung cancer, heart disease, fetal & infant effects (intra-uterine growth retardation, low birth weight, preterm delivery, respiratory tract infection, behavioral and cognitive abnormalities). Tobacco smoke contains carcinogenic and mutagenic substances. Control of ETS is by education of smokers and non-smokers about the dangers of tobacco and restriction of smoking places in airlines, public buildings and restaurants.
DEPLETION OF THE OZONE LAYER: Ozone, although a pollutant, has a useful function of filtering out the sun’s UV rays which cause skin cancer, eye problems, genetic mutations, and disruption of the ocean food chains. There is thinning of the ozone layer over the polar regions and the northern mid-latitudes. An ozone hole is developing over the southern hemisphere. The ozone depletion is due to industrial release of chlorofluoro carbons into the atmosphere. The Chlorine reacts with ozone turning it into oxygen.
GLOBAL WARMING DUE TO THE GREENHOUSE EFFECT: There are disputes whether global warming is in fact occurring. Global warming results as a consequence of the greenhouse effects that is when greenhouse gases (CO2, CFC, methane, and Nitrous oxide) prevent the re-radiation of infra-red (heat) into the atmosphere. With global warming, the polar ice masses thaw releasing extra water that causes the sea levels to rise. The rising sea levels will affect coastal dwellers and result in higher demand for electricity for cooling. Agricultural produce is also affected since more irrigation is needed. The most important greenhouse gas is CO2. Carbon dioxide is released in the following ways into the atmosphere: burning of fossil fuels (in electricity generation, gas production, automobiles), deforestation which decreases the number of plants that consume carbon dioxide in photosynthesis, primitive agricultural methods of burning and slashing, and use of wood for home cooking. Control of CO2 is achieved by finding alternatives to fossil fuels and growing more vegetation to absorb released CO2.
PHOTO CHEMICAL SMOG: Photochemical smog is a secondary pollutant that is produced when a primary pollutant like NO2 reacts with sunlight. Photochemical smogs are commoner in valleys surrounded by mountains that prevent winds from blowing away the accumulated smog. Thermal inversion worsens the smog problem. A layer of lighter warm air traps a layer of cooler air below allowing pollutants to concentrate in the cooler air.
ACID RAIN: Acid rain (also called acid snow, acid dew, acid drizzle, acid fog, and acid sleet) is due to sulfur dioxide and nitrogen oxide mixing with water to form acids (sulfuric acid and nitric acid) that fall with the rain. Acid rain acidifies the soil affecting crops and materials. Other effects of acid rain are: killing marine life, erosion of buildings, and causing respiratory problems.
MEASUREMENT OF AIR POLLUTION:
Legislation in several countries has defined acceptable air quality criteria. The ambient air quality standards and indoor air quality standards, permissible exposure limits (PEL), threshhold limit values (TLV), and recommended exposure limits (REL) are special parameters for measuring air pollution. Factories are limited by law to certain air pollutant emission levels. Systems of pollutant measurement have therefore been developed to fulfill regulatory requirements. Pollutant levels are affected by rainfall, wind speed, atmospheric inversion, and human activities. It is almost impossible to measure individual exposure because levels vary throughout the day. What are practical are environmental measurements. Different substances are measured for each type of pollution. Assessment of pollution by reducing pollutants that are produced from fossil fuels is by measuring the concentration of particles in smoke particles, the concentration of sulphur dioxide, and the concentration of sulphuric acid/suplhates. Polycyclic aromatic hydrocarbons are from incomplete combustion of fossil fuels are measured by chromatography. The assessment of photochemical oxidizing pollutants is based on assessing nitrogen oxide (most of it from auto emissions), hydrocarbons (from auto and chemical refinery emissions), and ozone. Carbon monoxide, from auto emissions, cigarette smoking and combustion, is measured by continuous monitoring. Lead (from burning coal, burning heavy oils, factories, and petrol engine vehicles) is measured by spectrophotometry.
EFFECTS OF AIR POLLUTANTS:
Pollutants produce health effects by physically or chemically. Physical effects include injury to skin, irritation & inflammation, gases and asphyxia. Chemical effects include enzymatic damage, and binding to active compounds that impairing or changing their properties. There are controversies about the level at which pollutants are harmful to health. One view is that there is a threshold dose below which a pollutant is not harmful. The alternative view is that pollutants have harmful effects at any dose.
The clinical effects may be acute or chronic. Acute effects occur at high doses of exposure and include: death, pain, irritation, and respiratory disease (asthmatic attacks, wheezing). Chronic effects occur with low continuous doses and include: neurologic disorders, cardio-vascular disorders, genetic disorders, cancer, and respiratory problems. Impaired respiratory function in children can lead to growth failure. Pollution exacerbates existing chronic disease. Lead has neuropsychological effects in young children. Carbon monoxide leads to impaired psychomotor performance, headache, nausea, dizziness, and coma. Suspended particles & sulfur dioxide are responsible for bronchitis, lung cancer, and other respiratory disease. Smoking exacerbates the respiratory effects of air pollution. Aromatic hydrocarbons lead to leukemia. Aromatic hydrocarbons release into the atmosphere has increased. They become trapped in the stratosphere where they react with and deplete the protective ozone layer. This exposes humans to dangerous cosmic ultra-violet radiations with resultant skin cancer and genetic change.
PREVENTION OF AIR POLLUTION
Primary prevention of outdoor air pollution is by controlling or limiting industrial and car emissions. Many countries including US and UK
B. WATER POLLUTION
HYDROLYTIC CYCLE
The water cycle can be described starting from the evaporation of water from the surface into the atmosphere. Water vapor in the atmosphere cools and falls back to earth as rain or as snow. On earth water may be surface water such as in rivers and streams or may be underground water in the soil. Human activity has interfered a lot with the natural hydrolytic cycle.
SOURCES OF WATER
Over 97% of the earth’s water is salty ocean water and only 3% is available as fresh water for normal human use. Desalination of ocean water is very expensive. The distribution of fresh water as a total of all water on earth is as follows: ice sheets and glaciers is 1.9%, ground water 0.5%, non-ocean surface water 0.02%, soil water 0.01%, atmospheric water 0.0001%. The ice glaciers of the north are the largest source of fresh water yet that water is not readily available for human use. Ground water is 96.5% of available freshwater in the world. Thus ground water contamination is a catastrophe of immense proportions.
USES OF WATER
Water is a universal solvent needed for digestion, absorption, and excretion. Humans settle where they can get water for drinking, bathing, and cooking. Water supplies may be private or public. Fresh water resources are limited in many countries. The situation is worsened by water pollution which leads to some of the sources being unusable. In normal circumstances a water cycle operates. Water after use by humans returns to the ecosystem and is used again. Water re-use is complicated by water pollution. Japan
WATER POLLUTANTS
Problem of water pollution: Water is such a good solvent that it is liable to easy contamination by a wide range of substances. Water pollution is both a biological and a chemical hazard. In developing countries contamination by infectious organisms is the main problem. In both developed and developing countries chemical contamination is on the increase. Water pollution affects the natural eco-system affecting both the fishing, agricultural, and recreational industries. Fish and insects are killed. Detergents and petrochemical contaminants affect coastal waters. Organochloride compounds affect under-ground water.
Sources and types of water pollutants: The sources of water pollution may be point sources such as a factory or a non-point source such as a leachate from landfill runoff. The latter is more difficult to identify and correct. The sources of water pollution are municipal sewage or industrial pollutants. Water pollution is by: Organic wastes, Infectious agents, Synthetic organic compounds, Inorganic chemicals, radioactive materials, oil spills, and heat. Contamination can also be by overgrowth of acquatic plants that over consume oxygen.
HEALTH EFFECTS OF WATER POLLUTION
The following pollutants in drinking water are risk factors for cancer: asbestos, radionuclides like radon, inorganic solids (arsenic, nitrites, and fluoride), and organic chemicals. Water pollution has also been associated with adverse pregnancy outcome (LBW, spontaneous abortion, IUGR, congenital malformations) and infectious disease. Water-borne infections cause skin diseases (athlete's foot and warts), otitis externa due to P. eruginosa, GI infections and eye infections. Eye infections are controlled by chlorination. This is however a double-edged sword. Too much chlorine irritates the eyes.
WATER TREATMENT
The objectives of water treatment are to make it bacteriologically safe and esthetically pleasing in taste, odor, color, and clarity. Water treatment is expensive. Much money would be saved if only drinking water was treated since only 2% of treated water is used for drinking purposes. Municipalities use two main sources of raw water: ground water and surface water. Two types of water treatment are known depending on the type of water treated: drinking water purification and waste water treatment. The methods used to purify drinking water are: spray aeration, activated charcoal filtration, coagulation, flocculation, sedimentation, sand filtration, and disinfection. Chlorine, ozone, ultraviolet light, and iodine are used in disinfection. Spray aeration removes organic compounds by oxidation. Care must be taken to prevent contact of drinking water with sewage and infectious agents by ensuring the integrity of the water distribution systems. Break of water pipes near sewage lines can easily lead to admixture of water with sewage. Waste-water treatment is removal of pollution from wastes of industry or domestic sewage. It has three phases: primary, secondary, and tertiary treatment. Primary treatment is physical removal of solids by sedimentation in ponds or tanks. Secondary treatment is when dissolved material is decomposed by micro-organisms followed by chlorination. Tertiary treatment is biological or physicochemical.
MEASUREMENT AND MONITORING WATER POLLUTION
Standards for drinking water are defined by legislation. Regular water sampling and assessment are required by law. Three traditional indicators of water pollution are used: biological oxygen demand (BOD), chemical oxygen demand (COD), and pH measurement. Other methods that are used are: Coliform bacteria concentration, an indicator of fecal pollution, and total suspended solids.
C. SOIL POLLUTION
OVERVIEW
Sewage, and solid or hazardous wastes pollute the soil. Soil can also be polluted by irrigation using contaminated water. Their disposal /management has become an important issue because of the increase in its volume. This has arisen because of industrialization and population increase. Several recent disasters have stimulated interest in waste disposal. In 1979 the Love Canal hazard was declared near Chicago
Solid waste can be organic, inorganic, or radio-active. Its sources may be residential, commercial, mining, industrial, municipal, and agricultural. If solid waste is not properly disposed of it can be the source of offensive odors, a breeding place for insects and rodents, and a cause of loss of amenities and damage to the eshetics of an area. The objectives of solid waste management are (a) minimizing waste by resource recovery and reuse (b) removing harmful material from the ecosystem. The processes of solid waste management consist of collection with some form of compression to reduce the volume. This is followed by disposal which is various types: sanitary land-fill, incineration, composting, recycling, and sea disposal. Integrated solid waste management means using all methods of source reduction and waste disposal. Sanitary land fills are geological formations that do not allow leachates reaching ground water. Waste deposited at a land fill is compressed by a bull dozer and is covered with soil to prevent access by rodents. There are problems with landfills. Landfills in several municipalities are filling up with no new free land available. Some landfills can leak. Fires due to methane gas have occurred. Incineration at waste to energy plants converts some of the waste into steam that drives turbines for electricity generation. Incineration reduces the volume of waste by 80-90%. Incineration is however without its own problems. The residual solid waste still has to be disposed of in some way. Incinerators also worsen air pollution. Composting is is a form of recycling in which organisms are used for biodegradation of waste to become fertilizers or mulch. Recycling (resource recovery) conserves resources, conserves energy, and conserves landfill space. Source reduction involves use of recyclable materials, less packaging, and selling products in a concentrated form that requires less packaging.
HAZARDOUS WASTE
Hazardous waste is dangerous both to health and the environment. Hazardous waste can be ignitable e.g. solvents, corrosives e.g. oxidizers, reactive e.g. explosions, toxic e.g. poisons, radioactive, and biological. Suspected hazardous waste can be tested for ignitability, corrosiveness, reactivity (explosiveness), and toxicity.
Hazardous waste production is very high in industrialized countries. Before environmental awareness, hazardous waste was disposed of on land or was discharged into rivers. Many of such contaminated rivers are now being cleaned up. Hazardous waste dump sites may be near human homes. Studies of angiosarcoma and birth defects have detected an increased risk due to living near a dumping site. Many diseases that are now considered of unknown etiology may be due to hazardous wastes. Hazardous waste is disposed of in secured landfills. It can also be disposed of by deep well injection, incineration (thermal destruction), recycling, and neutralization. Hazardous waste can be reduced by source reduction (product substitution and using new processes) as well as treatment of the hazardous materials (biological, chemical, and physical).
SEWAGE
The sources of sewage are: waste water (domestic and industrial), human and animal waste. The problems in sewage disposal are many. In developing countries there is hardly any disposal system. Where systems exist they are primitive and inefficient: disposal as night soil and use of pit latrines. More affluent communities use septic tanks. Most communities in developed countries have municipal sewage disposal systems. Sewage carries many pathogens. Sewage-borne pathogens may enter ground water and contaminate it. Soil samples must therefore be analyzed on a regular basis to monitor contamination. BOD specifies the strength of sewage in terms of pathogen contamination. Sewage also carries a lot of chemical contaminants from domestic use or from industrial waste.
SEWAGE TREATMENT
Sewage treatment involves removing solids then treating the organic material by microbial decomposition. Primary treatment uses sedimentation tanks to remove large suspended or floating solids, greases, and oils. Secondary treatment involves biological oxidation to reduce solids by use of trickling filter systems, activated sludge processing, contact aeration, intermittent sand filters, and stabilization/oxidation ponds. The resulting sludge is then digested by anerobic organisms to reduce its volume and change it into inert substances. After treatment the solid and liquid effluents are disposed of in 3 ways: spraying or spreading over the ground, burying it underground or in landfills, disposing of it in surface water bodies, or use as fertilizers. Tertiary treatment is recovery of water from the sludge and using it as potable water. This is carried out in countries like Japan
C. ECO-POISONS
OVER VIEW
Eco-poisons contaminate the air, water, food, and the soil. Few studies have been undertaken on the chronic effects of eco-poisons. The following are the types of eco-poisons encountered: (a) medicinal agents, (b) gases and volatile liquids eg co, cyanide, hydrocarbons (c) methanol and ethanol (d) corrosives: acids and alkalis, bleaches, disinfectants (d) insecticides, herbicides, rodenticides, fungicides e.g. organophosphates, DDT (e) poisonous plants and animals e.g. venomous snakes (f) metals. The most important eco-poisons are pesticides.
PESTICIDES
Pesticides are biologically active compounds that kill or modify the behavior of pests: insects, animals, microorganisms, weeds etc. Insecticides were introduced in the 1940s. They are synthetic compounds that kill both target and non target organisms. The commonest used pesticides are herbicides and insecticides. About 50% of pesticides are used in agriculture. Two groups are at high risk of pesticide poisoning: children who ingest the pesticides by accident and farm workers who are exposed in the course of their work. An ideal pesticide must be cheap, specific in action killing only the target organism, short half life, and breakdown into harmless materials. Pesticides are classified as soft or non-persistent and hard or persistent. Non-persistent pesticides last until 12 weeks. Moderately-persisting insecticides last 1-8 months eg DDT, Aldrin, Dieldrin, and HHC. Permanent pesticides are mercury, lead, arsenic and PCB; they persist for a long time. The hard pesticides are preferred by farmers because of their long-lasting effects. They however accumulate in the environment. Pesticides move through the ecosystem to the home an end up in food or water consumed by humans. They also contaminate ground water and the air. The pesticide groups that are of public health importance are: (a) inorganic insecticides like arsenic and lead (b) petroleum products like kerosene and diesel (c) botanicals like pyrethrum (d) chlorinated hydrocarbons like DDT, NHC (benzene hexachloride), lindane, chlordane, heptachlor, endrin, isodrin, and chlordecone (d) bio degradable organophosphates like TEPP, parathion, and diazinon (e) carbamates used as contact insecticides eg sevin, propoxur, and landrin (f) biolarvicides (g) insect growth regulators e.g. methoprene (h) fumigants eg hydrogen cyanide, methyl bromide, carbon disulphide (I) insect attractants and repellents (j) anticoagulant poisons eg fumarin (k) herbicides.
Animal carcinogenicity tests have incriminated some pesticides. Limited epidemiologic studies have focused on occupational groups such as farmers and pesticide applicators. The effects of pesticides may be acute (headaches, rashes, weakness, dizziness, and fatigue. The chronic effects are cancer, mutations, birth defects, respiratory problems, convulsions, coma and death. Control of pesticide poisoning is by education on safe use of pesticides, government regulation to make sure that only safe pesticides are sold, and research to develop better and safer pesticides.
PCBs
Polychlorinated biphenyls (PCB) are wide-spread in the environment. They cause rashes, headaches, nausea, diarrhea, alopecia, loss of libido, menstrual disorders, and fetal malformations. They enter and persist in the food chain.
D. FOOD POISONING/INFECTION
The problems of food pollution are increased by centralized food processing in big facilities, big communal eating facilities, international trade, and tourism. Food is grown in the rural areas and is transported to the urban areas where most people live. This increases the handling time of food thus increasing the risk of pollution in transit. Food can be contaminated by microorganisms, chemicals, food additives, and veterinary drugs. Antibiotics and hormones given to animals eventually reach humans in meat and milk. Antibiotics contribute to growth of bacterial resistance.
Micro-organisms: Any food can serve as a vehicle of transmission. Public eating places are more likely than homes to be sites of transmission of infection. The following factors contribute to food poisoning: improper holding temperature, poor personal hygiene of food handlers, inadequate cooking, contaminated equipment, and food from polluted sources. The following are food-borne infections: S fecalis, S pyogenes, Salmonella spp., shigella spp., cholera, L. monocytogenes, viral hepatitis, and enteroviruses. Bacterial food poisoning is caused by: S aureus, C. perfringes, C. welchii, and C. botulism. Food can also convey parasitic infections like E histolytica, T spiralis, Tenia spp., G lamblia, Toxoplasma spp. Food infection is of two types. Bactaria can be established and replicate in the food. Pre-formed bacterial toxins may contaminate food even in the absence of any active replication.
Chemicals: The following are chemical poisons in food: aluminium, arsenic, cadmium, chlorinated hydrocarbons, copper, lead, mercury, organic phosphates, PCBs, and zinc. Aflatoxins and mycotoxins are from poisonous plants. Food additives could cause cancer.
Control: Food inspection requires clean food service facilities (restaurants, churches, schools, retail outlets) and regular food inspection. Facilities must have clean water supplies, ventilation, good food storage (cold, dry, frozen), clean preparation and serving, cleanliness and sanitation of equipment and utensils, insect and rodent control, and personal hygiene of food workers. Microbial monitoring of food can detect infection. This is however done seriously and consistently only for milk. The following methods in food processing can destroy bacteria: pasteurization, refrigeration, dehydration, and specialized packing. Refrigeration reduces bacterial growth but does not kill bacteria. Adequate cooking is necessary to kill most bacteria. Food workers must be educated that their clothes, hair, and open wounds can harbor bacteria.
E. ANIMALS and PLANTS
INSECT AND RODENT CONTROL
Insects and rodents are vectors of disease. The important insects are: fleas, flies, lice, mosquitoes, cockroaches, and ticks. The important rodents are: rats and mice.
Rodents cause the following problems: psychological stress, sociological, economic, and disease (typhus, plague, rat bite fever, Weil's disease, salmonellosis, trichinosis, and hantoviruses. Rats can infect sewer systems and become very difficult to dislodge. Rodents are dealt with by: (a) poisoning, trapping, food and harborage removal, proper solid waste disposal, and rodent proofing.
HAZARDS FROM PLANTS AND PLANT PRODUCTS
The following plant products can cause hazard to human health: enzyme inhibitors, Phytohemagglutins, Goitregens, Cyanogens, Pressor amines, Oxalates, and fava beans. Enzyme inhibitors disturb body physiology. Trypsin inhibitors are found in soy beans, potatoes, and kidney beans. Amylase inhibitors are found in wheat, beans, and unripe mangoes. Cholinesterase inhibitors are found in solanine from potato. Phytohemagglutins are found in sweat peas, kidney beans, and soya beans. Goitrogens are not well documented. Cyanogens are tropical foods and cause degenerative tropical neuropathy. Pressor amines raise BP and are found in bananas that have high levels of serotonin, nor-adrenaline, and tryptamine. Oxalates are found in spinach, rhubarb, and cocoa; they cause corrosive gastro-enteritis, shock, convulsive syndromes, and renal damage. Favism is caused by products in fava beans.
8.1.4 EPIDEMIOLOGICAL STUDIES
GENERAL
Study of exposure-disease relations is confounded by other geographical factors. Quantifying risk is difficult. Public perceptions are unreliable. The press is biased towards negative and sensational news. Experimental studies, controlled chamber studies, and epidemiological studies are used to study risks of environmental exposure. The relation of environment to disease can be described as time-related disease patters or as mapping/spatial data analysis. The time-related description consists of time clustering like in the thalidomide disaster, cyclic patterns like in respiratory infections, and longitudinal trends.
B. EXPOSURE ASSESSMENT
Exposures can be single or mixed. Exposures can be measured as binary (yes/no) or on an ordinal scale. Exposures are described by their frequency, level of exposure, and whether there is a trend. Exposures can be measured directly by a personal monitor or indirectly by using environmental sampling. Exposures are measured using interview questionnaires, diaries, micro-environmental measurements, macro-environmental measurements, measurement of individual dose, measurement of individual doses, measurement of tissue concentration, and use of bio markers such as urinary metabolites, DNA adducts, and urinary adducts. Exposure is ascertained in the external environment or the internal environment. Residence in an area with the contaminant is a poor measure of exposure. Concentration of the substance can be measured in the ambient atmosphere, in the vicinity of the exposed person, and using a personal biometer. Sampling of persons for environmental measurements can be random, haphazard, or purposive (i.e. a well defined target population). As regards measurement of the substance, sampling can be random or can be integrated. A random sample is suitable for exposures that are homogenous and uniform over time and space but useless for exposures that change their mix or state with time. A random sample is also called a grab sample and it is a snapshot in time and location. Several grab samples can be mixed to give a composite sample. Integrated sampling involves collecting a sample over a timed interval for example 1 day or 1 week. The dose is computed from the exposure data. Stratified and systematic sampling may also be used where appropriate. Measurement of exposure to air pollutants can be carried out in 3 different ways. In personal sampling a person wears a device. In breathing zone sampling, air is sampled within 1 foot radius. Area sampling involves a fixed zone. Sampling can be short term or long term. The concentration of air borne contaminants is measured as volume per volume or weight per volume. In the laboratory pollutants are measured using spectrophotometry, electrode-based methods, gravimetric methods, and titrimetric methods. Exposure can be modeled for better understanding. Dose is measured at the point of contact or within the tissues. Very often direct tissue measurements are not possible and surrogate measures have to be used to tissue-level exposure. The applied dose or potential is the amount of the substance deposited at the point of contact with the body or the absorptive surface. The internal dose is the amount of substance absorbed into organs and tissues. The biologically effective dose is the amount of substance deposited at the biologically significant sites in organs and tissues.
The criteria of a good method of exposure measurement are: sensitivity, selectivity, rapidity, ease of operation, comprehensiveness, portability, and cost
Exposure can be measured prospectively or retrospectively. Microenvironmental exposure assessment. Multi media assessment of exposure.
Assessment of chemical hazards is difficult because of variations in concentration of the chemicals in the microenvironment of the individual, variation in the pharmacodynamics of the chemical among individuals, and variations in the pathogenic process.
MEASUREMENT OF OUTCOME
Health effects can be produced by in an experimental system. Epidemiological studies may show an exposure-disease relation but with insufficient evidence. Some groups of humans have higher susceptibility. Morbidity, mortality, and cost are also measures of outcome.
CONFOUNDING
The environmental effects on human health can be pinpointed accurately for very few exposures for example exposure to UV light causes sunburn and skin cancer; lead poisoning causes brain damage in the young, and the photochemical fog irritates the eyes and the lungs. Confounding by age, gender, personal behavior, genetic makeup, present health status, and exposure to other pollutants, makes it difficult to pinpoint other health effects of specific exposures. Measurement of the level of exposure is not reliable because of heterogeneity in the pollutants and also the places resulting in considerable sampling error. The effect of meteorological coniditions on pollutant levels may not be easily ascertainable. SES and poor prior health are also confounders.
PRIORITIES IN ENVIRONMENTAL EPIDEMIOLOGY RESEARCH
There are outstanding issues in air pollution, water pollution, and ionizing radiations. The health effects of the following air pollutants are a priority for study: asbestos, benzene, CO, lead, NO4, and SO2. The research priorities in the field of water pollution are: arsenic, asbestos, agricultural chemicals, industrial chemicals, domestic chemicals, disinfection by products, fluoride, nitrate, and radionuclides. The major issue in radiation is the effect of electromagnetic fields.
EPIDEMIOLOGICAL STUDIES OF AIR POLLUTION
Epidemiological studies of air pollution episodes provide information about risk and consequences of pollutants. Ecologic studies are used for preliminary study. Exposure-disease association can be explored in cross sectional and case control studies. Prospective cohort studies are difficult because of loss to follow-up. In a few cases intervention studies can be used. Measurement of personal exposure is difficult to measure. Diary methods have been tried. Occupational and biomonitoring studies are an additional source of information. Classical studies include Snow’s study of cholera due to contaminated drinking water in London and the study of various air pollution episodes: Meuse Valley fog in Belgium in 1930, Donora in Pennsylvania in 1948, and the London
8.1.5 RISK ASSESSMENT and MANAGEMENT
HISTORY
Risk assessment became popular in the 1970s due to new laws about the environment: the threshold limit values (TLV), acceptable daily intakes of pesticides and food additives, etc
DEFINITION OF RISK ASSESSMENT
Risk is defined as the probability of an adverse outcome. Risk assessment is an analytic process of combining information on human exposure to environmental agents with data on health effects to produce the probability or frequency of health effects in a population. It is a tool for translating research findings into science-based risk management strategies. It uses both qualitative and quantitative methods. The objective of risk assessment is to find the optimum balance between risk and benefit, set target levels, and set priorities.
Risk assessment / risk characterization has 4 components: hazard identification/assessment, dose response assessment, exposure assessment, and risk determination. Hazard assessment is based on epidemiological studies and toxicological studies. Toxicological studies are carried out in rodents or in humans using both in vitro and in vivo techniques. Data extrapolated from animal studies to humans or that extrapolated from low dose to high dose human exposure leads to dose-response assessments. Hazard characterization involves assessment of dose response and susceptibility. Exposure assessment is carried out in the macro environment (air, water) or the micro environment (diet, smoke, alcohol etc). Risk determination involves prediction of risk beyond of risk beyond the range of empirical observation. Meta analysis and pooled analysis are used widely in risk analysis.
Risk assessment uses both laboratory research data and field epidemiological data. Effects of exposures to specific agents can be observed in the laboratory and in the field. Sophisticated laboratory techniques are used for dose-response and exposure assessment. Epidemiological data is used in addition to toxicological data in risk assessment. Epidemiological data is sometimes superior to animal toxicological data because it is relevant to the human risk in terms of disease and dose response, and is capable of detecting low-dose effects. Epidemiological data makes the following specific contributions to risk assessment: hazard identification, dose response assessment (supra linear non threshold, linear non threshold, sub linear non threshold, linear threshold), exposure assessment, and risk characterization by estimating the potential risk to the exposed population. The field of molecular epidemiology is bound to contribute a lot to risk assessment. Problems and issues are raised about the use of epidemiological data in risk assessment: relevancy, data quality, uncertainty, and variability.
RISK MANAGEMENT
Risk management encompasses scientific input in the form of risk characterization as well as evaluation of public health, economic, social, political, and social aspects of the risk and potential risk management actions. Much debate is usually involved since many stakeholders are involved and the scientific data may not be definitive. The relevant agencies then make the necessary decisions and actions on risk management.
Risk management varies whether it is a single agent toxin or a multi-agent toxin. The concept of tolerance levels or acceptable levels generates a lot of debate. The purists will argue that hazards carry a definitive risk at any level of exposure but this will create a lot of social and economic stress. Others argue that each hazard has a threshold level (tolerable or acceptable level) beyond which it has to be regulated. Macro environmental exposures are easier to control than micro environmental exposures because the latter involve human lifestyle and behavior. Risk management is based on risk assessment reports. Risk assessment reports are speculative but it leads to regulatory action. Steps in the regulation of a hazard are: identification of the hazard, characterization of the hazard, and control of the hazard. Control is either by regulation or substitution. Communication of results of risk assessment to the general public is not easy.
Learning Objectives
· The concept of occupational basis of disease
· Occupational hazards: psychological (stress), physical (electrical, noise, radiological, temperature, vibration), biological, ergonomical
· Major occupational diseases: lung diseases, cancer, skin, infections, reproductive effects, musculoskeletal injury, trauma, noise injury
· Prevention of occupational disease: primary, secondary, tertiary
Key Words and Terms
· ergonomics
· occupational accident
· occupational disease
· occupational exposure
· Occupational hazard
· occupational health
· occupational injury
· occupational medicine
UNIT OUTLINE
8.2.1 INTRODUCTION
A. History of Occupational Medicine
B. Limited and Unreliable Data
C. Job Histories and Exposure
D. Statistical Indicators
E. Legislation
8.2.2 OCCUPATIONAL HAZARDS and DISEASES
A. Types of Hazards:
B. Occupational Diseases:
C. Accidents in the Work Place:
D. Occupational Diseases of the Future
8.2.3 OCCUPATIONAL HEALTH STUDIES
A. Types of Studies:
B. Mortality Studies:
C. Morbidity Studies
D. Outstanding Problems in Occupational Medicine
8.2.4 PREVENTION OF OCCUPATIONAL DISEASE
A. General
B. Primary Prevention:
C. Secondary Prevention:
D. Tertiary Prevention:
E. Surveillance of Occupational Disease
8.2.1 INTRODUCTION
A. HISTORY OF OCCUPATIONAL MEDICINE
Occupational hazards have been known since pre-historic times. In 1561 George Agricola published ‘De Meletellica‘ emphasizing the need to ventilate mines. In 1567 Percellus published ‘On the Miner’s Sickness and Other Miners’ Diseases’. In 1700 Ramazzini published ‘Discourse on the Diseases of Workers’. The industrial revolution gave rise to many occupational diseases that were not common before that. The first occupational diseases were described during the industrial revolution. Percival Pott described scrotal cancer in chimney sweeps. Lung cancer was described in metal miners, bladder cancer in aniline dye workers, and skin cancer in oil shale workers. New diseases are being described at the moment: dermatitis, vibration injury, locomotor problems, and psychological problems. It was observed from epidemiological studies that mortality rates varied by type of occupation and also by social class. Overall mortality and cause-specific varied by the job and SES. Virtually all countries of the world have laws on occupational health. Occupational hazards are moving from developed countries with protective laws to less developed countries where multinational companies are now building their factories. Occupational diseases are more in the less developed than the developed countries.
B. LIMITED AND UNRELIABLE DATA
Workers give poor occupational history. Company records, compensation claims, and reports to OSHA are not usually complete. Laboratory results and physician visits are either not documented or are incomplete. One of the reasons for under reporting of occupational disease is diagnosis; workers may suffer from diseases that are not easily linkable to their occupational exposures. The diagnosis of occupational diseases is not complete or accurate. Fear of litigation discourages companies from keeping complete records or co-operating in occupational studies. There is limited toxicological data on many exposures. The long latency between exposure and disease make study of causes more difficult. There is in general low awareness of occupational disease.
C. JOB HISTORIES AND EXPOSURE
There are changes in exposure or jobs that may not be fully documented. It is difficult to unravel causal relations between health and work. The pre-existing health condition affects the type of job assigned a worker. The work in turn may affect health. The worker is exposed to other environmental pollutants away from the place of work. The sick leave the factory or are not assigned to some jobs making it difficult to relate their illness to the putative exposure. Because of incomplete job histories it is difficult to know whether the cause of disease is the current or the previous job. Even in cases in which the job is known, there may be no measure of the actual pollutant concentration. It is not enough to know the job, the specific department and nature of contact with the pollutant must be known.
D. STATISTICAL INDICATORS
Standardized mortality ratio, SMR, does not separate effects of SES and occupation. Absence from work may not correspond to morbidity.
E. LEGISLATION
In 1835 Massachusetts Maryland
8.2.2 OCCUPATIONAL HAZARDS and DISEASES
A. TYPES OF HAZARDS:
The following are types of hazards (a) psychological stress (b) physical hazards (electrical, noise, radiological, temperature, and vibration), (c) chemical hazards, (d) biological hazards, and (e) ergonomical hazards. The major types of occupational diseases are: lung diseases, cancer, skin diseases, infectious diseases, reproductive disorders, musculoskeletal injuries, trauma, and noise injury. Occupational diseases are recognized and defined using a combination of clinical, epidemiological, and toxicological evaluations.
B. OCCUPATIONAL DISEASES:
Occupational hazards have wide spread health effects: diseases and injuries. Occupational disease is due to cumulative and repetitive exposure to workplace hazards. It may mainifest as acute or chronic disease. Occupational injury results from a work accident or from exposure involving a single incident in the work environment. Occupational disease is a serious issue since workers are usually the healthiest and young members of the community. Occupational diseases can be classified as lung diseases, musculoskeletal injiuries, traumatic injuries, occupational cancers, cardiovascular diseases, reproductive disorders, neurotoxic disorders, noise, dermatological disorders, psychological disorders, and infections.
Occupational lung diseases are of various types: asthma, obstructive airway disease, granulomatous lung disease, chemical pneumonitis, bronchial asthma, and pneumoconiosis (asbrestosis, byssinosis, silicosis, coal miner’s disease). Pneumoconioses are chronic occupational obstructive lung diseases, caused by dust, silicon, carbon, beryllium, asbestos, and cotton. They are described in 4 groups: silicosis due to silica, coal workers' pneumoconiosis due to coal dust, asbestosis is due to asbestos fibers, and berylliosis is due to beryllium and beryllium compounds. Musculoskeletal injuries include back, neck, and trunk disorders, the traumatic Raynaud’s phenomenon, bursitis, tenosynovitis, writer’s cramp, trigger finger, rotator cuff syndrome, carpal tunnel syndrome, and back pain. Traumatic injuries include amputations, fractures, eye loss, lacerations, and traumatic deaths. Occupational cancers, due to radiational or chemical exposure, include lung cancer, leukemia, mesothelioma, bladder cancer, nose cancer, and liver cancer. Cardiovascular diseases include hypertension, coronary heart disease, and acute myocardial infarction. Reproductive disorders include infertility, spontaneous abortion, teratogenesis, and low sperm counts due to exposure to lead and DBCP. Neurotoxic disorders include peripheral nerve injury, toxic encephalitis, psychoses, and personality disorders. Noise can lead to hearing loss and tinnitis. Dermatological disorders include dermatoses, dermatitis, pigmentation changes, spots, scleroderma, skin infections, contusions, and cancer due to chemical irritants, mechanical effects, and physical effects burns (thermal and chemical). Psychological disorders include personality disorders, alcoholism, and drug dependency. Occupational infectious disorders include acute hepatitis due to HBV, HIV, TB, anthrax, leptospirosis, and brucellosis. Occupational eye diseases include soreness, itchiness, or chemical burns due to chemical irritants, acids or alkali. Occupational ENT disease includes rhinits, septal ulceration, and carcinoma. Heavy metals cause neurologic and cardiac toxicity. Liver and kidney damage is caused by organic solvents and chlorinated hydrocarbons.
C. ACCIDENTS IN THE WORK PLACE:
Injuries at the workplace may be fatal or non-fatal. Fatal injuries are motor crash injuries, machine injuries, falls, electrical injuries, and injury due to falling objects. Non-fatal injuries include back injuries due to postural problems, injuries to the hand, fingers, arms, legs, head, eyes, feet, and toes. Injuries with high mortality are in mining, construction, transport, andf agriculture. The factors that determine occurrence of accidents are age, gender, work conditions, and personality. Younger workers are more likely to get accidents than older ones who are more careful. Females have a generally lower risk. Accidents are more common in some seasons and times of the day. Unsafe work conditions increase the risk of accidents. Some personalities are more likely to get into accidents than others. Background psychological problems can predispose to accidents. Prevention requires attitude to safety, safety clothing, and protection e.g. boots & wearing helmets.
D. OCCUPATIONAL DISEASES OF THE FUTURE
New occupational diseases are being described like angiosarcoma of the liver (due to vinyl chloride) and carcinoma of the respiratory tract (due to halo ether). VDTs are likely to lead to new occupational diseases. Occupational hazards are being exported to the developing countries with transfer of hazardous heavy manufacturing jobs there. LDCs are under pressure to industrialize rapidly without time and energy to care about the health of workers. Child labor in LDCs is also an increasing problem.
E.
8.2.3 OCCUPATIONAL HEALTH STUDIES
A. TYPES OF STUDIES:
Three types of occupational health studies can be carried out: clinical, epidemiological, and toxicological. We will concentrate our discussion here on epidemiological studies. The epidemiological investigation of occupational diseases has the objectives: (a) investigate suspected hazards (b) determine the quantitative relation between hazards and disease (c) assess the effectiveness of intervention. The study must start by defining the question or hypothesis of study, definition of the study population, and then a decision is made on the study design: cross-sectional, follow-up, and case control. Follow-up could be prospective or could be study of a historical cohort experience. Besides these studies, epidemiological analysis of population-based health data can be undertaken with useful results.
A complete occupational history consists of: description of all jobs done, exposures at each job, time course of symptoms, similar symptoms in co-workers, and confounding exposures.
B. MORTALITY STUDIES:
Mortality studies are typically retrospective follow-up studies (historical cohort studies). A population of occupationally-exposed persons is assembled on the basis of past records and is followed until the present to determine mortality experience. The total population is used is used as a standard to compute SMR; direct standardization is used only in exceptional cases. Alternatively proportional Mortality Ratios (PMR) may be used. These are prevalence ratios and not rates since they do not have time dimension in the form of person-years. The starting and end-points of the mortality study must be clearly defined. The following must be recorded for use in analysis as potential confounders: gender, age at which work started, and the calendar year work/exposure started. Person-years are allocated to each type of work/exposure. Either of 2 assumptions may be made with regard to loss to follow-up: (a) it occurred at the end of the study (b) it occurred at the time of loss to follow-up. Control for gender, age at start of work, and year work started is carried out since they are confounders; it is however not valid to control for all of the three at the same time. The analysis must be stratified on the basis of retirement. Those who retire may do so because of illness.
C. MORBIDITY STUDIES
Occupational morbidity studies are based on: (a) case reports of acute cases or previous records (b) case control studies for preliminary assessment since they are not much use in occupational epidemiology (c) cross-sectional studies (d) follow-up studies. Occupational health surveys of the health status of workers are undertaken by a surveillance system. Surveillance based on exposure can be passive (is just monitor records), active (look for cases of diseases and exposure), or multi-phasic screening for many diseases. In active exposure-based surveillance the following information is collected: occupational history (all jobs ever held, exposures in each job), non-work exposures, substance exposed to, concentration of the environmental pollutant, health status (measured by symptoms and their duration, hospitalization or hospital treatment, presence of chronic disease, and cause of death), and confounding factors: demographic, smoking, and alcohol consumption. In active surveillance based on disease, the case control study design is used to identify the exposures.
D. OUTSTANDING PROBLEMS IN OCCUPATIONAL MEDICINE
Reproductive effects have been studied in very few compounds. The relation between vinly chloride and fetal death has yet to be elucidated. Also not clear is the relation between paternal exposure and childhood cancer. The following causal relations remain to be elucidated: the role of nickel, coke ovens, asbestos, and beryllium in respiratory cancer. The relation between benzene and leukemia. The high risk of CHD in longshoremen and those exposed to carbon disulfide.
8.2.4 PREVENTION OF OCCUPATIONAL DISEASE
A. GENERAL
Occupational diseases are highly preventable because they arise from man-made conditions that are known and can be changed. Prevention of occupational disease is based on anticipation, recognition, and evaluation. Control of occupational diseases is based on identification and evaluation of the hazardous agents, setting standards, eliminating or substituting the agent, and starting engineering controls. Environmental monitoring/surveillance is then carried out continuously. Control and prevention of occupational diseases involves various types of OSH OSH
B. PRIMARY PREVENTION:
Primary prevention is to reduce exposure. Prevention of chemical hazards is by substitution, enclosure, and removal at source. Work practices can also be made to reduce exposure. These include segregation the workers from the hazards or provide them with personal protection. Ventilation and dilution can decrease the exposure risk. Personal hygiene is important in preventing infectious disease. Administrative controls may reduce individual exposure by job rotation and reducing time of contact with a hazard. Education remains the best approach. For education to be effective it must cover the workers, the management and their families. Information on health hazards must be provided to all workers. Legislation regulates the work-place and defines procedures for protection. On another front there is need to develop biological markers of exposure and disease to allow early detection. Biological markers of geneti c susceptibility to hazardous exposure will also contribute to primary prevention.
Ergonomics is making the job fit the worker such that there is no harm. It is a new discipline frist described on 1949. It was first applied in the military and later in industry and in the home. Future applications of ergonomics will be in the fields of consumer goods, physical disability, mental disability, geriatrics, sports and leisure. It has research and application modes in anatomy, physiology, psychology, and technology. Ergonomics aims at matching human capacities and limitations to work systems and environments. Ergonomically designed furniture, computers, and transportation systems. It has been found that ergonomic design in the workplace increases productivity. Ergonomic considerations of the human cover anatomy, physical working capacity, sensory capacity, and cognitive capacity. Human anatomical considerations are body size and dynamic anthropometric variations. Physical working capacity includes cardiovascular, erobic, and muscular capacity. Maximal working capacity is at ages 20-30 years and gradually falls by 30% at age 60. Women have 30% less erobic power and 30-50% less muscle power than men. Sensory capacity of the vision, hearing, touch, taste and smell also fall with age. Cognitive capacity is capacity to process information and make decisions. It requires both short and long term memory. It decreases progressively with age; noticeable changes occur at age 65 years. Experience can compensate for age –related cognitive decline. Work design can reduce stress on the body. Work stations should be designed in such a way that they avoid bent neck and bent trunk postures and as well as elevation of arms. For standing work, the height of the work station must be commensurate with the height of the person and type of work. Sitting work is less tiring than standing work. Stress-relieving ergonomic design includes avoiding forward bending, a horizontal line of vision, adjustable seat height, and sufficient leg space. Ergonomic design prevents trunk bending and twisting in manual work involving lifting, pushing, and pulling. Pauses are needed for repetitive manual work. Care must be taken to make the work environment safe: good lighting, appropriate temperature and humidity, acceptable levels of vibration and noise, and firm non-slippery ground.
C. SECONDARY PREVENTION:
Secondary prevention is reducing the effects of the exposure. Occupational hygiene involves identification of the hazard, measuring it, implementing controls, and evaluation. Monitoring can be physical, biological, chemical, or radiological. Surveillance (for both the hazard and the disease), sentinel health events, and identification of groups at risk are used. The authorities must be notified of the findings from monitoring as is required by law. A control plan must be made including engineering control, personal protection, standards, isolation, ventilation, and education.
D. TERTIARY PREVENTION:
Tertiary prevention is reducing the effects of disease. This involves prevention of complications and disability. Workmen compensation insurance ensures health care for those injured at work. Workmen compensation is a no-fault system that assures income replacement for those injured and also pays for medical expenses. Compensation is well developed in developed countries and not yet developed in under developed countries.
E. SURVEILLANCE OF OCCUPATIONAL DISEASE
Surveillance of occupational disease consists of occupational hazard surveillance and occupational disease surveillance.
Learning Objectives
· Definition and classification of malnutrition
· Nutritional-related diseases
· Methods of nutritional assessment
Key Words and Terms
· Adolescent nutrition
· Anthropometry
· Avitaminosis
· Body mass index
· Cephalometry
· Child nutrition
· Craniometry
· Crown-rump length
· Dietary supplement
· Food frequency
· Food labeling
· Hypervitaminosis
· Infant nutrition
· Malnutrition
· Nutritional assessment
· Nutritional disease
· Nutritional disorders
· Nutritional requirements
· Nutritional status
· Nutritional surveys
· Nutritional value
· PEM
UNIT OUTLINE
8.3.1 INTRODUCTION
A. Definition of Nutritional Epidemiology
B. Nutritional Requirements
C. Primary Nutritional Disorders: Deficiency
D. Primary Nutritional Disorders: Excess
E. Secondary Nutritional Disorders
8.3.2 INCIDENCE AND PREVALENCE OF MALNUTRITION
A. PEM
B. Vitamins
C. Mineral
D. Obesity
E. Starvation and Famines/Food Security
8.3.3 DISEASES ASSOCIATED WITH MALNUTRITION
A. Cardio-Vascular Disease: HT and CHD
B. Cancer: Esophagus, Stomach, Colon
C. Gastro-Intestinal: Cirrhosis, Liver Cancer, Pancreatitis
D. Dental Caries
E. Others: Dm, Renal Calculi
8.3.4 ASSESSMENT OF NUTRITIONAL STATUS
A. Introduction
B. Biochemical Assessment of Nutritional Status
C. Assessment of Food Intake
D. Anthropometry
8.3.5 EPIDEMIOLOGICAL STUDIES OF NUTRITIONAL EXPOSURES
A. Introduction
B. Experimental Studies
C. Cross Sectional Studies
D. Case Control Studies
E. Cohort Studies
8.3.1 INTRODUCTION
A. DEFINITION OF NUTRITIONAL EPIDEMIOLOGY
Nutritional epidemiology is use of epidemiologic methods to study the relation between diet and disease. Many diseases have dietary causes such as birth defects, cancer, cardiovascular disease, and cataracts.
A. TYPES AND UTILISATION OF FOOD
DEFINITION OF NUTRITION
Nutrition is the process by which food is ingested and utilized by the body.
FUNCTIONS OF FOOD
Food serves three purposes: providing energy, growth and repair, and maintenance of the body in the best physiologic state by providing micro-nutrients needed in metabolic pathways.
Energy expenditure is measured as BMR in a resting subject. The measurement is usually done early in the morning after an overnight fast. The following factors affect energy BMR: age, gender, body size, body composition, physical activity, environmental temperature, physiological state (such as pregnancy or systemic infection). Energy requirements on a per weight basis are highest in infants and young children. There is a steady decline after the age of 20. Energy is required for growth. Energy can be derived from carbohydrates, fats, proteins and alcohol. The proportion of energy from each type of food varies in each country depending on the composition of the diet.
Growth and repair: Proteins when ingested are broken down into amino acids that are utilized in tissue growth and repair. A person is considered in positive nitrogen balance when the dietary intake exceeds losses. A negative balance ensues when losses exceed losses. Infants and young children require more protein because they are growing rapidly.
Body maintenance: Vitamins and minerals are involved as substrates or co-factors in chemical reactions of the body.
TYPES OF FOOD
Carbohydrates: There are three types of dietary carbohydrates: sugars, starches, cellulose and related materials. Sugars are either monosaccharides such as glucose, fructose, and galactose or disaccharides such as sucrose, maltose, and lactose. The monosaccharides are absorbed directly into the jejunum. The disaccharides require digestion and breakdown into their monosacharide components before they can be absorbed. Starches are polysaccharides being built up of several monosaccharide units. They are broken down during cooking and digestion to easily absorbable monosaccharides. The commonest starches are dextrins, amylose, and amylopectin. Cellulose is of plant origin and is not easily digestable by the human intestine. It serves the purpose of providing bulk to the stool thus aiding voiding.
Fat: fats are the chief energy store in the body. They are also essential components in nervous tissue, cell membranes, and some hormones. The most important fat groups are triglycerides, phospholipids, cholesterol, and lipo-proteins. The body can synthethise fats and does not depend wholly on dietary intake. There are a few fatty acids that are called essential because the body can not synthesize them.
Proteins: The body is able to synthesize many amino acids that are the building blocks of proteins. Nine amino acids are essential because they can not be synthesized by the body and have to be taken in the diet.
Micro-nutrients: Carbohydrates, fats, and proteins are required in big amounts and are called macro-nutrients. Vitamins and minerals are required in small quantities and are called micro-nutrients. Vitamin A is involved in the maintenance of mucosal surfaces, production of mucus, the immune system and retinal function. Thiamine (B1) is involved in carbohydrate metabolism, maintenance of cardiac muscle and peripheral nerves. Riboflavin (B2) is involved in intra-cellular oxidation, and maintenance of skin. Nicotinic acid is involved in utilization of energy from food and maintenance of skin. Pyridoxine is involved in the metabolism of amino acids especially tryptophan. Folic acid is involved in cell multiplication especially in the blood and the mucosa. Cobalamine (B12) is involved in cell multiplication, control of fatty acid synthesis in myelin sheaths. Ascorbic acid maintains connective tissue and stimulates intestinal iron absorption. Vitamin D is controls calcium and phosphate metabolism. Vitamin E contributes to anti-oxidant capacity of the body. Vitamin K is involved in the clotting mechanisms.
B. NUTRITIONAL REQUIREMENTS
Food requirements vary by age and physiological condition. Infants and children need more food by weight especially proteins because of rapid growth. Pregnancy and lactation also increase nutritional requirements.
Several countries have worked out levels of intake for each nutrient that are required to prevent malnutrition. These are usually termed recommended daily allowances.
C. PRIMARY NUTRITIONAL DISORDERS: DEFICIENCY
PROTEIN ENERGY MALNUTRITION
PEM is a syndrome of nutritional deficiency common in poor developing countries. It has two extremes and several intermediate steps. Marasmus is due to absolute lack of food. Kwashiokor is due to protein deficiency. Associated deficiencies of zinc, snd vitamin A occur. PEM in children: is due to poverty or ignorance or both. PEM in adults: PEM in adults is common in hospitalized patients due to inadequate intake.
VITAMIN DEFICIENCY
Vitamin A deficiency causes loss of night vision and xerophthalmia. Thiamine deficiency causes neuropathy, Wernicke's encephalopathy, Korsakoff's psychosis, and optic atrophy. Riboflavin deficiency causes mucosal lesions. Niacin deficiency causes Pellagra, glossitis, stomatitis, and dermatitis. Pyridoxine deficiency causes glositis and neuropathy. Folate deficiency is associated with anemia due to megaloblastosis, and villus atrophy. Vitamin B12 deficiency causes megaloblastosis and neuropathy. Vitamin C deficiency causes scurvy. Vitamin D deficiency leads to rickets and osteomalacia. Vitamin E deficiency. Vitamin K deficiency leads to hypo-prothrombinemia.
DEFICIENCY OF MINERALS
Zinc deficiency
Copper deficiency
Iodine deficiency: hypothyroidism
FOOD SENSITIVITY
This causes allergic reactions that may manifest as eczema, GI symptoms, migraine, RTI, and urticaria.
D. PRIMARY NUTRITIONAL DISORDERS: EXCESS
VITAMIN EXCESS
Vitamin A deficiency effects on the nervous system and is involved in teratogenesis. Nicotinic acid deficiency causes vaso-dilation. Pyridoxine deficiency causes peripheral neuropathy. Ascorbic acid deficiency causes increased urinary oxalate. Vitamin D deficiency causes hypercalcemia and renal failure. Vitamin E excess causes nausea. Vitamin K excess causes hyperbilirubinema.
OBESITY
Obesity arises in cases of excessive intake and decreased energy expenditure. The body mass index (BMI) is an objective assessment of obesity. BMI 19-25 is considered normal range. Overweight is 26-29. Obesity is 30-39. Severe or morbid obesity is 40 and above. There are three ways of preventing obesity. Decreasing food intake is the most effective. Exercise increases energy expenditure. Appetite suppressants are of limited value. Thyroxine therapy, jaw wiring, and surgical operations to reduce stomach size have also been tried.
E. SECONDARY NUTRITIONAL DISORDERS
Secondary nutritional disorders arise in disease states. They arise due to inadequate dietary intake, mal-digestion, mal-absorption, increased nutrient requirements, and loss of endogenous nutrients.
8.3.2 INCIDENCE AND PREVALENCE OF MALNUTRITION
A. PEM
Nutritional disorders: PEM: Children in LDC, Adults in hospital. Obesity: Worldwide. More in DC and high SES. Vitamin deficiency: Worldwide. More in LDC. Mineral deficiency: Worldwide. Vitamin excess: Hyper-vitaminosis A and D
B. VITAMINS
C. MINERAL
D. OBESITY
E. STARVATION AND FAMINES/FOOD SECURITY
8.3.3 DISEASES ASSOCIATED WITH MALNUTRITION
A. CARDIO-VASCULAR DISEASE: HT AND CHD
Hypertension is due to high sodium intake
CHD is due to high dietary unsaturated fats, low dietary fiber (leads to high cholesterol and VLDL)
B. CANCER: ESOPHAGUS, STOMACH, COLON
Esophageal cancer is due to preservatives (e.g. nitrosamines), dietary deficiency (zinc, carotenoids, retinol), alcohol, mycotoxins
Stomach cancer is due to nitrosamines and fat
C. GASTRO-INTESTINAL: CIRRHOSIS, LIVER CANCER, PANCREATITIS
Gall stones are due to high cholesterol, high sugar, and low fiber diet
Liver cancer is due to aflatoxin
Pancreatitis is due to PEM
D. DENTAL CARIES
Dental caries are due to prolonged contact of sugar with teeth
E. OTHERS: DM, RENAL CALCULI
Diabetes (type 2) is due to high fat and low fiber diet
Urinary calculi are due to high phosphate
Vitamin deficiency diseases: vitamin A (carotene) deficiency causes xerophthalmia. Vitamin B1 (thiamine) deficiency causes beriberi. Vitamin B3 (niacin) deficiency causes pellagra. Vitamin C (niacin) deficiency causes scurvy. Vitamin D5 deficiency causes rickets. Vitamin K deficiency causes hemorrhage due to clotting failure. Folic acid deficiency in pregnancy causes neural tube defects and iron deficiency anemia.
Mineral deficiency diseases: Iron deficiency causes anemia. Iodine deficiency causes goiter. Fluorine deficiency causes dental caries.
8.3.4 ASSESSMENT OF NUTRITIONAL STATUS
A. INTRODUCTION
Diet is measured as a specific food, a food group, or a nutrient (specific chemical compound in food). Dietary intake can also be measured as its effects either biochemical or anthropometric.
B. BIOCHEMICAL ASSESSMENT OF NUTRITIONAL STATUS
SHORT TERM
Serum analysis is used for vitamins, lipids (albumin, pre-albumin, transferrin, retinol binding globulin, and thyroid binding globulin). Fecal analysis is used for lipids and vitamins. Urine analysis is used for vitamins, minerals and ions, 24-hour urine nitrogen, urea, and creatinine (24-hour urinary creatinine excretion assesses muscle mass). Bile salts are analyzed for cholesterol. Serum is analyzed for vitamins, cholesterol, triglycerides, and fatty acids. There are no low cost measures for energy and fiber.
MEDIUM and LONG TERM MEASURES
Red blood cells are analyzed for vitamins, folic acid, selenium, copper and fatty acids. White blood cells are analyzed for vitamins, zinc, selenium, and fatty acids. Hair, finger nails, and toe nails are used to measure zinc, copper, selenium, and other trace elements. Sub-cutaneous fat is ueed to measure fat soluble vitamins like retinol, carotenoids, and fatty acids.
INTERPRETATION OF BIOCHEMICAL MEASURES
Biochemical measures involve sampling at a point in time and sampling bias may occur especially if the sample is taken shortly after a meal. Chemical interactions, chemical changes, de novo synthesis, and effects of disease may confuse the interpretation of biochemical findings.
B. ASSESSMENT OF FOOD INTAKE
ASSESSMENT OF HOUSEHOLD FOOD INTAKE
Assessment of food intake can be based on the household or on the individual. Assessment of household food intake is carried out in four ways: food accounting, food inventory, household record, and list recall. A food account is a list of all foods entering the household. A food inventory is a record of all food coming into the house in addition to inventory taking at the start and end of the study periods. A household record is recording all food, raw or cooked, available for consumption and estimated in household measures taking care to subtract food eaten by visitors or lost to waste. A list recall is a questionnaire of the amount and cost of food obtained for household use.
ASSESSMENT OF INDIVIDUAL INTAKE
Five methods are available for assessing individual intake: food frequency questionnaires, dietary history obtained by interview, 24-hour recall of types of food and portions, diet history, and diet record/food record/food diary. In the food frequency questionnaire (FFQ) or the food amount questionnaire (FAQ), the respondent is presented with a list of foods and is asked to indicate how often and/or how much of each food item is eaten per day or per week or per month. In the diet recall method the respondent is asked to remember all foods taken in the preceding 24 hours. In the diet history method the respondent is asked about usual types of food taken in a long interview that can last up to 2 hours with the objective of determining an eating pattern over a period of 7 days. The food diary or diet record consists of recording intake by type of food and amount over a period of 3-7 days. It takes about 6 different shapes. A menu record is recording frequency of foods eaten without specifying the amounts. A check-list is a printed list of foods that the respondent ticks off each day as foods are consumed with indication of portion size and record of any items consumed but not n the printed list. An estimated record has portions of food consumed described in household measures such as cups and spoons. A weighed record (weighed inventory technique) is a record with weights of portions as served and the plate waste. A precise weighed record requires that the respondent keep a record of all ingredients used in the preparation of meals including inedible waste, total cooked weight of meals, cooked weight of individual portions, and any plate waste. The photographic record requires taking a photograph of food as served and quantification is made by comparison with reference photographs. In the semi-weighed method, the total quantity of food served to the family is weighed but quantities served to individuals are given in household measures.
ANALYSIS OF FOOD COMPOSITION
There are three approaches for direct analysis of food. In the duplicate diet method, the respondent may keep a duplicate portion of the meal for analysis by the investigator. In the aliquot sampling technique the respondent puts aside small amounts of the food consumed for later analysis. In the equivalent composite technique a combined sample of raw food, equivalent to the mean daily amount of food consumed is made up for the investigator to analyze. Assessment of portions poses special problems. Usually average portions are estimated using household measures such as cups and spoons. Food models or replicas may be shown to the respondent to make a choice of the relevant portion size. The best approach is to weigh the food but this is not very practical.
COMPUTATION OF NUTRIENT CONTENT
The computation of the nutrient content of a food is not easy. The easiest way to measure nutrient intake is to undertake chemical analysis of a duplicate portion. Food composition data-bases are available for commonly used foods. The nutrient score is computed as the product of the food score and the nutrient composition and food score is defined as the product of the frequency of intake and the portion size.
VALIDATION OF DIETARY ASSESSMENT
Several approaches are used to validate dietary intake methods. Biochemical measurement of nutrients in blood and other tissues in invasive, costly, and may not reflect true intake because of confounding effects of digestion, absorption, uptake, utilization, metabolism, excretion and changes due to hemostatic mechanisms. Repeat 24-hour dietary recalls may not be representative of the usual food intake. Diet history suffers from effects of interviewer bias and is not accurate with irregular eating habits. Food records with weighing may be unrepresentative and distort usual eating habits due to presence of the investigator. Urinary nitrogen reflects only protein intake. Doubly-labeled water is useful in assessing energy intake only and is very expensive. It may not be accurate in cases of gross obesity or high alcohol intake that distort the models of body water partitioning.
EVALUATION OF ASSESSMENT METHODS
The method must use instruments pre-tested in the same or similar population. It also must preferably have been validated against another dietary method or an external marker of intake. Its reproducibility must be established. The methods of quantifying portions must be defined. The food composition database used for analysis must be identified and any changes made to it must be mentioned. Interviewers must be trained and methods of data collection must be standardized. Details about interviews must be reviewed for possible bias: place and method of interview, duration, level of detail, probes used to elicit information, follow up on queries, and the informant. Checks for consistency among interviewers and field workers must be carried out.
C. ANTHROPOMETRY
ANTHROPOMETRIC INDICES IN CHILDREN
Several measures of assessment are used for children: weight for age, height for age, weight for height, mid-arm circumference, and skin-fold thickness. Other derived indices are used: such as arm muscle area and arm fat area. Weight and height are basic measurements in anthropometry and are the simplest indicators of nutritional status. Arm and calf circumferences are proxies for soft tissue mass using the assumption that the cross-sectional area of the bones in the upper arm and lower leg are standard across populations and are unaffected by acute nutritional changes. Skin-folds measure subcutaneous fat and are used as proxies for body fatness. Waist and hip circumferences give a composite measure of fatness both subcutaneous and visceral. Measurements of both upper and lower limbs give a more representative picture of the whole body ((page 292 Design Concepts in Nutritional Epidemiology 2nd edition by Barrie M Margetts and Michael Nelson OUP 1997 Oxford, NY, and Tokyo)..
The best measures for ages 0-1 years are weight, length, head circumference, arm circumference, triceps skin-fold, and sub-scapular skin-fold. For ages 1-5 the measures used are weight, length (up to 3 years), height (over 3 years), arm circumference, triceps skin-fold thickness, and sub-scapular skin-fold thickness. For ages 5-20 years the measures used are weight, height, arm circumference, triceps skin-fold thickness, sub-scapular skin-fold thickness, medial calf skin-fold thickness, and calf circumference. Over the age of 20 years the measures used are weight, height, arm circumference, calf circumference, skin-folds (triceps, biceps, sub-scapular, supra-iliac, and medial calf), and for the overweight waist and hip circumferences (page 292 Design Concepts in Nutritional Epidemiology 2nd edition by Barrie M Margetts and Michael Nelson OUP 1997 Oxford, NY, and Tokyo)..
If weight for age is 60-80% of the NCHS with edema the child is diagnosed to have kwashiorkor. If weight for age is 60-80% of the NCHS without edema the child a diagnosis is made of under-nutrition. If weight for age is Less than 60% with edema, a diagnosis of marasmic kwashiokor is made. If weight for age is less than 60% without edema a diagnosis of marasmus is made. Weight or height as a percentage of NCHS ideal for that age can be used to classify children on the stunting/wasting scale as shown below:
Degree | Stunting (height/age) | Wasting (weight/height) |
Over 95% | Over 90% | |
Mild | 87.5 - 95% | 80-90% |
Moderate | 80-87.5% | 70-80% |
Severe | Less than 80% | Less than 70% |
Mid-arm circumference (cm) in children aged 12-60 months: Normal is more than 14.5 cm. Mild/moderate PEM is 12.5 - 14.5 cm. Severe PEM is less than 12.5 cm. Skin-fold thickness assesses subcutaneous fat deposits. It is measured with the Harpender caliper. The arm muscle area is computed as AMA = AC – (p x TRI)2/4p where AC = arm circumference in centimeters and TRI = triceps skin fold thickness. The arm fat area is computed as AFA = {(AC)2/4p} – AMA.
ANTHROPOMETRIC INDICES IN ADULTS
Weight as a percentage of expected body weight and the body mass index are used to assess adult nutritional status. The body mass index (the Quetelet index) is computed as BMI = weight/height2 with weight in kilograms and height in centimeters. Skin fold thickness and the ratio of the hip to waist circumference can also be used as indices of nutritional status.
FACTORS AFFECTING ANTHROPOMERIC ASSESSMENTS
Weight and heigh may be affected by genetic factors, nutritional status, disease especially infections, age, social and psychological stress, and measurement error.
ANTHROPOMETRIC STANDARDS
It is best to use one international reference standard with interpretation of findings being made taking local situations into consideration. The NCHS standard is used in many places although initially developed for American children. If an international standard is not available or is judged unsuitable, a local standard can be developed provided it fulfils the following criteria. It must be based on measurements from a well nourished population. A cross sectional sample is used using well defined sampling procedures. The adequacy of the sample is judged by having at least 200 subjects in each age-sex category. Measuring procedures should be optimal and should include all variables used in nutritional evaluation. Raw data used should be available for inspection later on (page 291 (Design Concepts in Nutritional Epidemiology 2nd edition by Barrie M Margetts and Michael Nelson OUP 1997 Oxford, NY, and Tokyo).
8.3.5 EPIDEMIOLOGICAL STUDIES OF NUTRITIONAL EXPOSURES (Design Concepts in Nutritional Epidemiology 2nd edition by Barrie M Margetts and Michael Nelson OUP 1997 Oxford, NY, and Tokyo).
A. INTRODUCTION
MEASURES OF EXPOSURES and OUTCOME
Dietary habits, anthropometry, and biological assays can be used both as exposure or outcome variables depending on the hypotheses of study. Knowledge about and attitudes to food are used as exposure measures. Morbidity and mortality are used as outcome measures. Both exposure and outcome measures can be assessed as continuous or as discrete. The continous measures of exposure may be based on total cumulative dose, avarage dose per day or month, dose at critical times, and dose as percent of the standard. Discrete measures of exposure may be dichotomized as yes/no responses, or as quartiles, percentiles, or percentage above or below the standard. Discrete measures of outcome may be categorized according to cut-off points such as blood pressure and weight for height below a given level.
DESIGN CHARACTERISTICS
The investigator must have a rationale for choice of variables to be investigated and for choosing among different study designs (ecologic, cross sectional, case control, and cohort). The sampling unit (group or individual), the sampling frame, as well as the sampling method must be defined. The response, non-compliance, and non-completion rates must be anticipated using data from previous studies or from the pre-test. The following sample characteristics must be described: age, gender, social class, clinical diagnoses, and geographical coverage. The power of the study and anticipated duration must be considered.
SOCIODEMOGRAPHIC AND PSYCHO-SOCIAL VARIABLES IN ANALYSIS
Food intake and its effects are confoundable by a large number of social and psychological variables that must be considered in the analysis. The socio-demographic variables are age, gender, ethnicity, social class or occupation, residence, marital status, and size/type of household. The psychosocial variables are knowledge, beliefs, attitudes, norms, values, roles, social pressures, and behavior.
LIMITATIONS OF NUTRITIONAL EPIDEMIOLOGY
All nutritional studies share the problem of imprecise and non specific measurement of food intake. Intakes of various nutrients are highly correlated such that it is difficult to separate the effects of one nutrient from those of another one. The biological measures of nutritional status may not correlate with intake. In most studies the physical state of the food is not considered. The effect of time is difficult to evaluate. Diet may act early or late in the pathogenesis process. The only mitigating factor is that for individuals dietary intake tends to be consistent over time and that intakes at various times are highly correlated.
B. EXPERIMENTAL STUDIES
COMMUNITY INTERVENTION TRIALS
Community intervention trials use populations or households as the unit of measure. They are suitable for common exposures that do not demand high accuracy in measurement, have a high potential for bias in measurement, and are associated with long or short latent periods to disease. They are suitable for common outcomes measured as incidence and mortality. They have high costs and have medium-long duration. Community intervention trials answer a practical question does the nutritional intervention work under the normal conditions in which communities live? They are more concerned with measuring efficacy and assessing implementation than causal mechanisms. They are carried out under conditions of less rigorous control for confounding than clinical trials.
RANDOM CONTROLLED TRIALS
Random controlled trials are based on individuals as units of measure. They are suitable for common or rare exposures that require high accuracy of measurement with low potential for measurement bias and are associated with short latent periods to disease. They are used for common outcomes measured as incidence. They are of short or medium duration and are associated with moderate or high costs. Several ethical problems arise in controlled studies. Subjects may not be compliant or non cooperative. The control group may take the dietary exposure outside the study. Random controlled trials answer the question whether the nutritional intervention works in theory because they are carried out in idealized and not real world conditions. They measure effectiveness and explore causal mechanisms.
C. CROSS SECTIONAL STUDIES
Cross sectional nutritional studies can take various forms: prevalence surveys, description of population characteristics, migrant studies, KAP studies, and ecologic studies. Cross sectional studies can be more meaningful by study of special groups such as migrants, religious groups such as the 7th day Adventists who are vegetarians, groups with distinct behaviors, groups in cultural transition or social upheaval. Cross sectional studies have two major limitations: the time sequence between diet and disease is not clear and there are many confounding factors that cannot be controlled easily. Cross-sectional studies are based on either households or individuals as measurement units. They are suitable for common exposures with high or low accuracy of measurement and high potential for measurement bias and are associated with a short latent period to disease. They are suitable for common outcomes measured as prevalence. They are of short duration and are associated with low costs.
Ecologic or correlational studies, are a special type of cross-sectional study, relating exposures to diseases. They are usually the first stage in nutritional epidemiological studies used to generate hypotheses. They are based on groups as unit of measure. They are suitable for rare exposures with low measurement accuracy, high potential for measurement bias, and are associated with long latent periods to disease. They are suitable for rare or common outcomes measured as prevalence. They are of short duration associated with low cost. They have the advantage of relying on previously collected data. Among the indices of exposure used for ecological studies are the national food supply, the household food budget, household food consumption, per capita food consumption, soil or food micronutrient concentration, and average food or water concentration of toxins. The indices of disease used in ecologic studies are mortality rates, morbidity rates, and biological assessments (serum, feces, urine). Examples of ecological studies are the correlation between national per-capita meat intake and incidence of colon cancer and the relation between GDP and colon cancer incidence. The analytic techniques used in ecologic studies are: disease mapping, simple regression, simple correlation, and time lagging analysis. Ecologic studies can be confounded by genetic, environmental, and lifestyle factors. The results of ecological studies are also difficult to interpret because they relate to groups of persons and not individuals. The ecological fallacy is said to exist if the disease-exposure relation at the group level cannot be found at the individual level. Despite their limitations, ecologic studies are used widely because they are sometimes the only alternative available.
D. CASE CONTROL STUDIES
Case control cases involve comparison of cases of disease with non cases on nutritional exposure parameters. They are based on individuals as unit of measurement. They are suitable for common exposures with low measurement accuracy, high potential for measurement bias and are associated with long latent periods to disease. They are suitable for rare outcomes measured as either prevalence or incidence. They are of short duration and are associated with low/moderate cost. Controls are recruited from patients with diagnoses etiologically unrelated to the disease under study or from the general population. A control could become a case in the course of the study and there are statistical approaches that enable use of information before and after the change. Nested case control studies are those within a follow up study and they rely on biological specimens collected at the start of follow-up for measurement of exposure.
Case control studies suffer from the disadvantage of inaccurate measurement of dietary intake giving rise to inconsistent findings. Another disadvantage is the error in measurement of dietary intake because dietary habits change with onset of disease. The following are common confounders of nutritional case control studies: smoking, physical activity, personal hygiene, and infections. For example the relation between cancer of the pancreas and coffee is confounded by smoking.
E. COHORT STUDIES
Cohort studies involve collecting baseline data on dietary intake and then following up the cohort to detect disease occurrence. Cohort studies are based on individuals. They are suitable for rare exposures with high/low measurement accuracy, low potential for measurement bias and are associated with short latent periods to disease. They are suitable for common outcomes measured as incidence or mortality. They have medium/long duration associated with high costs. Cohorts of children can be followed into adulthood to relate birth weight and childhood growth to adult diseases. Adult cohorts can be followed to relate diet to coronary heart disease. Cohort studies of the elderly can be used to study dietary effects on health in advanced age. Cohort studies have an advantage over case control studies in that dietary intake information is collected prospectively avoiding the problem of recall bias. Their disadvantage are: very large studies are needed to show significant results, dietary habits may change in the course of a long follow-up, loss to follow-up..
UNIT 8.4
RADIATION EXPOSURE
Learning Objectives
· Ionizing radiation as a disease determinant
· Prevention of disease due to ionizing radiation
· Sources of radiation: environmental background radiation: solar, geological, radon), medical (diagnostic, therapeutic), occupational (uranium miners, workers at nuclear plants, military), nuclear fall-out.
· Effects of radiation: acute (acute radiation syndrome) and chronic (cancer, teratogenesis)
Key Words and Terms
· Cosmic radiation
· Dose-response
· Ionizing radiation
· Radiation accident
· Radiation carcinogenesis
· Radiation dose
· Radiation genetics
· Radiation injury
· Radiation measurements
· Radiation monitoring
· Radiation oncology
· Radiation protection
· Radiation safety
· Radiation teratogenesis
· Radiation workers
· Radiochemistry
· Radiometry
· Radionuclide imaging
· Radiotherapy
· Radiation sensitive agents
· Relative biological effectiveness
· Tomography
· Ultrasonography
· Whole body irradiation
UNIT OUTLINE
8.4.1 OVER-VIEW
A. Historical Background
B. Medical Uses Of Radiation
C. Military Uses Of Radiation
D. Industrial Uses Of Radiation
E. Uses Of Radiation In Research
8.4.2 RADIATIONS: TYPES, SOURCES, AND MEASUREMENT
A. Ionizing and Non-Ionizing Radiation
B. Radiation Measurements:
C. Environmental Sources of Radiation:
D. Medical Exposure to Radiation
E. Occupational Exposure to Radiation
8.4.3 EFFECTS OF RADIATION
A. Cellular Effects of Radiation:
B. The Genetic Effects of Radiation
B. Secondary Prevention
E. Legislation and International Cooperation
8.4.1 OVER-VIEW
A. HISTORICAL BACKGROUND
The health effects of radiation were observed in the past. In the 1530s Paracelsus observed high death rates among miners which we know today to be due to radon. Uranium miners have been observed to have elevated lung cancer rates. The wide-spread use of x-rays and radium for diagnosis and treatment exposed many patients and health workers and resulted into injuries and death. Erythema due to x-rays was described in 1896 soon after its discovery. Other effects of radiation were described in due course. The testing of atomic weapons by the US , UK , France , Russia , and China Israel , Pakistan , Iraq , and India Hiroshima and Nagasaki Pennsylvania in the 1970s and Chernobyl in Russia
B. MEDICAL USES OF RADIATION
Radiation is used in various diagnostic procedures. X-rays were the first to be invented. Today more sophisticated methods are used. Some laboratory procedures also rely on radioactive materials. Radiotherapy is now a well established method of treating cancer. Epidemiological studies have established what are safe dosages of exposure to radiation during medical procedures. The risk to patients and medical staff is therefore reduced.
C. MILITARY USES OF RADIATION
D. INDUSTRIAL USES OF RADIATION
E. USES OF RADIATION IN RESEARCH
8.4.2 RADIATIONS: TYPES, SOURCES, AND MEASUREMENT
A. IONIZING and NON-IONIZING RADIATION
Radiations may be ionizing or non-ionizing. Ionizing radiations may be photons ( gamma & x-rays) or particulate (alpha & beta particles). Non-ionizing radiations are UV light, visible light, and infrared light. Other types of radiation are the extremely low frequency electromagnetic fields from power lines and ultra sound.
B. RADIATION MEASUREMENTS:
Two measurements are normally used: the Gray, the Sievert, and REM. The Gray is a measure of the amount of the absorbed radiation dose. One Gray is equivalent to absorption of 1 joule of energy per kilogram of tissue weight. The Sievert, like the Gray, measures energy absorption. It is also described as the effective dose equivalent because it takes into account the variation in the ionizing power of the absorbed radiation concerned which determines the relative biological effect (RBE). The relative biological effect depends on linear energy transfer (LET) of the type of radiation. The Sievert employs a weighing factor that takes into account the variation of the effect of radiation by the tissue. The weighing factors for various organs have been determined as follows: gonads 0.25, breast 0.15, red bone marrow 0.12, lung 0.12, and the thyroid 0.03. REM, the roentgen equivalent man, is a measure of the biological damage to tissues.
C. ENVIRONMENTAL SOURCES OF RADIATION:
There are 2 main sources of radiation in the environment: background natural radiation and man -made radioactive sources. Environmental natural radiation may be cosmic or solar from outer space, geological /terrestrial from the rocks, internal in the form of inhaled radioactive material, and the radio-active gas radon that seeps through the soil. Workers in uranium mines are exposed to radioactive rays. Radiation (ionizing, microwave, and laser) has both acute and chronic health effects. Ultra violet radiation covers wavelengths 0-400 nm. The UV-B type covers wavelengths 290-330 nm and is associated with 2 curable skin cancers (basal cell carcinoma and squamous cell carcinoma) and malignant melanoma which metastasizes early. The warning signs of cancerous melanomas are: asymmetry, irregular borders, non uniform pigmentation, and diameter >6mm. Prevention of cancerous melanomas is by decreasing sun exposure and screening for early detection. Radon deserves special mention because it is a household source of radiation exposure. Radon-222 is an isotope created by radioactive decay of trace uranium in rocks and soils. Radon is colorless tasteless, and odorless gas produced as an intermediate product in the breakdown of uranium-238. It is an inert gas that moves through crevices and cracks to the atmosphere where it has a very low concentration. The escaping radon achieves higher concentrations if it escapes into a confined space such as mines and buildings. Radon-222 decays into daughter radons that emit alpha particles. That is where anti-radon measures in the homes are needed. .It can travel many miles underground and enters buildings through cracks. Some buildings are constructed using radon-releasing rock. Radon concentrates in buildings building up to dangerous levels. Outdoor radon is very diluted and ha slower risk. Radon breaks down into radon daughters that become attached to dust particles and are deposited in the lungs where they release alpha and beta radiation leading to lung cancer. Radon and smoking act synergistically in causing lung cancer. Among control measures against radon is use of home kits to test for indoor radon concentration. If the concentration is found high, cracks in the foundation are filled up
Environmental man-made radiation is from global fall-out or nuclear explosions, or emissions from nuclear power plants. Electromagnetic fields are suspected to cause cancer, adverse reproductive outcomes, and behavioral or neural effects. Residential exposure (from TV, video, and appliances) may lead to childhood and adult malignancy (leukemia and brain cancer). Occupational exposure may also lead to leukemia and brain cancer.
D. MEDICAL EXPOSURE TO RADIATION
Radiation in the medical setting may be due to diagnostic procedures, use of radio-pharmaceuticals, or irradiation for cancer. Both the patients and the medical workers are exposed unless stringent measures are taken to minimize exposure
E. OCCUPATIONAL EXPOSURE TO RADIATION
The following are exposed to radiation: uranium miners, nuclear power plant workers, military personnel handling nuclear weapons, and workers in other industries where radiation is used.
8.4.3 EFFECTS OF RADIATION
A. CELLULAR EFFECTS OF RADIATION:
Ionizing radiations either damage cellular DNA or cause DNA mutations. The effects of radiation are different for somatic and germ cells. Effects on germ cells, unlike somatic cells, can be transmitted to the next generation. The factors influencing biological effects depend on the type of radiation and the target tissue. The effect of radiation depends on the type of radiation and its energy, the time of exposure, and the accumulated dose. Tissues respond differently to radiation. Lymphoid tissue, the intestine, gonads, the respiratory tract, and the lens of the eye are sensitive to radiation. The tissues most affected are the bone marrow, intestine, skin, and lungs.
B. THE GENETIC EFFECTS OF RADIATION
Radiation causes aberrations in chromosomal structure, variation in the number of chromosomes per cell, and point mutations.
Primary prevention is to prevent or limit exposure. The principle of radiological protection is to keep exposures as low as possible and in any case not to exceed the dose equivalent limits. Women at work need special protection because of potential teratogenic effects. Measures to prevent nuclear accidents or avert nuclear war are a primary prevention of massive exposure. Medical exposure must be limited to what is absolutely necessary and within safe limits. The disposal of nuclear waste is a big problem since there are no proper disposal sites for high level radioactive waste much of which is still being stored. Reprocessing of spent fuel is one of the measures of dealing with the problem.
B. SECONDARY PREVENTION
Long-term follow-up is needed for those exposed because effects may appear late. Genetic counseling may be necessary
E. LEGISLATION and INTERNATIONAL COOPERATION
UNIT 8.5
Learning Objectives
- Definition and use of biomarkers
- Genetic anomalies as causes of disease
- Incidence of common chromosomal and genetic anomalies
- Diseases with multi-factorial causes
- Prevention of genetic disorders: primary and secondary
- Definition, classification, and prevention of ADR
- Incidence and prevention of ADR, drug interactions, and drug poisoning
- Prevention of drug poisoning: primary, secondary, tertiary
Key Words and Terms
· Alleles
· Chromosome mapping
· Cloning
· Conjugation
· Gene expression
· Gene frequency
· Gene library
· Genetic algorithm
· Genetic code
· Genetic counseling
· Genetic cross-over
· Genetic engineering
· Genetic markers
· Genetic models
· Genetic predisposition
· Genetic regulation
· Genetic screening
· Genetic transcription
· Genetic vectors
· Genetics dictionary
· Genome library
· Heterozygous
· Homozygous
· Statistical models in genetics
· Mutation
· Non-disjunction
· Operator regions
· Pedigree
· Penetrance
· Polymorphism
· Population genetics
· Promotor region
· Recombination
· Regulatory sequences
· Repressor proteins
· Suppressor region
· Terminator region
· Transduction
· Translation
· Adverse drug reactions
· Drug abuse
· Drug approval
· Drug chemistry
· Drug control
· Drug costs
· Drug design
· Drug incompatibility
· Drug industry
· Drug interactions
· Drug labeling
· Drug poisoning
· Medication abuse
· Medication errors
· Narcotic control
· Pharmaceutical preparation
UNIT OUTLINE
8.5.1 BIOLOGICAL MARKERS
A. Overview
B. Basics of Molecular Biology
C. Characterization of Biomarkers
D. Uses of Biomarkers
E. Study Designs in Molecular Epidemiology
8.5.2 GENETIC EXPOSURES
A. Definition, Scope, and Incidence
B. Biological Basis
C. Genetic Diseases
D. Epidemiological Studies of Genetic Diseases
E. Prevention of Genetic Diseases
8.5.3. PHARMACEUTICAL AGENTS
A. Adverse Drug Reactions (ADR)
B. Drug Interactions:
C. Drug Poisoning
8.5.1 BIOLOGICAL MARKERS
A. OVERVIEW
DEFINITION
Molecular epidemiology is use of biological markers in epidemiological research. To study disease-exposure relations. The biomarkers may be cellular, biochemical, molecular, genetic, immunologic, or physiological. Molecular epidemiology incorporates biomarkers in analytic epidemiology thus making its conclusions more valid and less biased. They also contribute to increasing understanding of disease mechanisms, better disease classification, and individual susceptibility.
HISTORY
Molecular epidemiology has grown with discovery of more techniques of biological analysis. The beginnings were investigations of disease causes carried out by bacteriologists, virologists, immunologists and other scientists interested in infectious disease. Later pathological analyses including clinical chemistry were utilized. Sero-epidemiology was utilized extensively in the study of several diseases and is considered a precursor of modern molecular epidemiology. Recent advances in cancer studies have revealed more biomarkers that are environmental carcinogens or tumor markers. Other markers have been developed in the fields of occupational medicine, toxicology, environmental epidemiology, and genetic epidemiology.
B. BASICS OF MOLECULAR BIOLOGY
STRUCTURE OF DNA
DNA bases are either ….. A & T or ….., C and G. A codon consists of 3 nucleotides that code for 1 amino acid. A gene codes for one protein molecule. The chromosome is the smallest replicating unit. The genome is the complete set of genetic information in an organism. The genome has 100,000 genes only 5,000 – 10,000 of which are normally expressed. Only 30% of DNA is coding and is translated into protein. Regions of DNA that encode proteins are called exons. Intervening regions between exons are non coding and are called introns. Oncogenes are genes that code for proteins that are involved in cell growth. If oncogenes are not properly regulated, inappropriate growth will result eventually leading to neoplasia.
LABORATORY TECHNIQUES
Several laboratory techniques are used in molecular biology. Restriction endonucleases break the DNA chain at specified points. Hybridization is the melting of annealed DNA. Electrophoresis is used to separate RNA, DNA and proteins. Northern blot is used for RNA. Southern blot, named after Edward Souther, is used for DNA. Western blot, the opposite of Souther Blot, is used for proteins. DNA and RNA can be isolated. Synthesis of cDNA is also possible. The polymerase chain reaction, PCR, is used to duplicate RNA and DNA. Cloning is used to isolate and expand cDNA and putting it in a form that can be duplicated. DNA sequencing. Monoclonal antibodies.
BIOLOGICAL SPECIMEN BANKS
The following can be kept in a tissue bank: cells in culture, feces, red blood cells, saliva, serum, tissues, urine, white blood cells, nails, hair, semen, maternal milk, DNA. Bias may arise due selection bias.
C. CHARACTERIZATION OF BIOMARKERS
CLASSIFICATION OF BIOMARKERS
Biomarkers can be markers of exposure or markers of outcome. Markers of exposure serve various purposes: integration of multiple portals of entry, integrating fluctuations in exposure intensity, estimation of exposure time based on the cumulative amount, relating exposure to long term and short term outcome. Markers of outcome serve the purposes of controlling or eliminating pre-clinical disease, estimation of induction periods, identifying the stage of pathogenesis at which the exposure acts, and identify homogenous disease entities based on common exposures. There is a gradation in each of the two categories. Markers may just indicate exposure to an agent. They may also indicate the internal dose or the biologically effective does. Cotinine is an internal dose marker for nicotine. DNA adducts are a marker of the biologically effective dose of benzopyrene exposure. Outcome markers may indicate early biological effects, alteration of structure and function, clinical signs or prognostic signs. Chromosomal anomalies indicate early biological response to exposure. The carcinoembryonic antigen a well as sGOT are markers of sub-clinical disease. Alpha antritrypsine is a susceptibility marker for effects of smoking.
DESCRIPTION OF BIOMARKERS
The properties of biomarkers can be described based on biological characteristics, kinetic behavior, bioassay and variability. Biomarkers may be exogenous biological agents that are non-metabolizable such as PCB or metabolizable such as DDE. They may be endogenously produced biological agents such as a-feto protein and sGOT. They may be molecules that have been changed such as glcosylated hemoglobin. They may also be cells or tissues that are either in their natural state or have been changed. The kinetics of biomarkers can be described as time appearance in the body following exposure, persistence, the peak dose, metabolism, excretion, and storage. Bioassay properties include sensitivity and specificity. Biomarker kinetics can be studied in vitro studies, in vivo studies in animals or humans, and field studies. Variability of the biomarker can be inter-individual, intra-individual, or inter-group. The variation could be due to diet, the diurnal rhythm, biological modifiers such as CSF and the type of tissue in which it is measured.
CRITERIA FOR SELECTING A BIOMARKER
A marker is selected for use in epidemiological studies based on the following considerations: biologic relevance, pharmacokinetics, temporal relevance, background variability, confounding, reproducibility, specificity, sensitivity, and predictive value.
VALIDATION OF BIOMARKERS
Biological markers are validated as correct measures of exposure, disease, and susceptibility. Dose response relations are used to assess validity of the biomarkers. If the level of the marker increases with increase of an exposure then the marker can be considered a valid measure of that exposure. Marker persistence is of great epidemiological importance because it gives information about past exposures. Biomarkers can also be validated by intra-person and inter-person variation. Another way of validating biomarkers is correlation with clinical status or with other biomarkers.
Measurement validity of biomarkers can be visualized as content validity, construct validity, and criterion validity. Construct validity measures the extent to which the marker represents the underlying biological phenomena. Construct validity measures how well the marker corresponds with other relevant characteristics. Criterion validity is asessed as sensitivity, specificity, and predictive value of the test for a marker. Internal validity is lack of misclassification and confounding bias. External validity is extrapolation of the results.
STATISTICAL MODELS IN BIOMARKER MEASUREMENTS
Measurements of biomarkers have to be related to standard measures. Measurements using RIA are related by means of a standard curve or regression. Measurements by ELISA are related to the standard using a standard curve. A linear model is used to relate chromatic data to peak concentrations. A standard sample is used to compare Gels with the test sample.
D. USES OF BIOMARKERS
BIOMARKERS OF CARDIOVASCULAR DISEASE
Cardiovascular markers are of three main classes: lipid-related, markers of thrombosis, and markers of disease outcome. Lipid-related markers are plasma lipids, plasma lipoproteins, or enzymes. The plasma lipids are total cholesterol, triglycerides, low density lipo-proproteins, and high density lipo-proteins. Plasma lipoproteins are Apo B and Apo A1. Lipoprotein lipase is an enzyme. Markers of thrombosis are factor VIII, plasma fibrinogen, platelet counts, and platelet aggregation. Markers of outcome are various serum enzymes in myocardial infarction.
BIOMARKERS IN GENETIC DISEASE
Metabolites such as PKU are used as markers for specific genetic diseases. Common diseases such as IDDM are HLA-related.
USE OF BIOMARKERS IN CARCINOGENESIS STUDIES
Biomarkers are involved in carcinogenesis studies in the measurement of the internal dose, measurement of the biologically effective dose, assessment of early biological effects, measurement of susceptibility, measurement of mutagenicity, and study of oncogenes. Biomarkers are used to measure the internal dose of potential carcinogens such as DDT, PCB, aflatoxin, and nitroso compounds. DNA adducts are biomarkers that can be used to measure the biologically effective dose. Adducts are stable complexes or reactive chemicals with cellular macromolecules such as red blood cells (RBC adducts) or DNA (DNA adducts). They play a role in mutation and carcinogesis. Assays for adducts use red blood cells or lymphoctes. Early biological effects can be measured as using sister chromatid exchanges, micronuclei, or chromosomal aberrations. Sister chromatid exchanges (SCE) are more sensitive markers of chromosomal damage than chromosomal breakage. SCE involve an exchange of DNA material without known change in cell function. They are markers of genetic lesions due to chemical carcinogens, viruses, ionizing radiations, and mutagens. Other causes of SCE that can confound the study are: age, female gender, diet, smoking, drug therapy, radiotherapy, and occupational exposures. Micronuclei arise when chromosomal fragments are not incorporated into daughter nuclei during mitosis. Micronuclei are increased by exposure to agents that damage DNA such as tobacco (smoking and chewing) and alcohol. Micronuclei are assayed in peripheral lymphocytes. Chromosomal damage, assayed in peripheral lymphocytes, can be numerical anomalies or structural abnormalities which lead to carcinogenesis. Age, tobacco, and viral infections cause chromosomal damage. Susceptibility biomarkers are useful in cancer prevention. Biomarkers are also used to screen for mutagenic agents. Urine mutagenicity assays are popular because urine is the final excretory pathway and is so easy to collect. Two urine mutagenicity tests are carried out: the Ames
USE OF BIOMARKERS IN INFECTIOUS DISEASES
Serum antibodies are measured in infectious diseases to monitor evolution of immunity. Susceptibility is measured using immunological markers.
USES OF BIOMARKERS IN RISK ASSESSMENT
Biomarkers can be used to assess relation of dose to disease risk. They can also be used to predict risk.
E. STUDY DESIGNS IN MOLECULAR EPIDEMIOLOGY
Preliminary studies consist of biomarker development studies and biomarker characterization studies. Field studies may be cross sectional, case control, or interventions.
8.5.2 GENETIC EXPOSURES
A. DEFINITION, SCOPE, and INCIDENCE
Genetic epidemiology investigates the role of genetic factors and their interaction with environmental factors in disease etiology
Chronic diseases with a genetic component occur in 5-10% of adults. About 1 in 50 of new borns has a congenital anomaly that may have a genetic basis. Genetic disorders and malformations account for 30% of pediatric hospital admissions in developed countries. Up to 50% of deaths in the first year of life in developed countries are due to genetic disorders. The distribution of genetic disorders is: congenital malformations 45%, single gene defects 20%, chromosomal disorders 15%, and common diseases with a genetic component 20%. Seven (7) out of every 1000 live births have a chromosomal disorder sub-divided as follows: sex chromosomal disorders 3, autosomal disorders 1.5, and chromosomal rearrangements 2.5. There is an ethnic distribution for some disorders. The UK incidence of the following conditions is as follows: Down's Syndrome (trisomy 21), 1/700-1000 live births, Edwards Syndrome (trisomy 18), 1/5000 live births, Patau's syndrome (trisomy 13) 1/8000 live births, Klinefelter Syndrome (47, XXY), 1/1000 live born males; Turner's syndrome (45, X) 1/5000 live births; autosomal recessive phenylketonuria, 1/10,000 infants, and homocystinuria 1/200,000 infants. No information is available for cystinosis and alkaptonuria. Thalassemia is more common in mediterranean and oriental ethnic groups. Sickle cell disease is more common in black Africans.
B. BIOLOGICAL BASIS
GENE and CHROMOSOMES
The human genome has 100,000 genes packed in 23 chromosomes in the nucleus. Human genes have among them 3 billion individual bits of information. Humans of all known races and ethnicities share 99.9% of the 3 billion bits of information. In 1988 scientists announced that all humans are descended from one ancestor. All the diversity seen in the human race is due to a mere 0.1% of the genome. A gene is a length of DNA that codes for one protein molecule. The gene has coding regions, called exons, and non-conding regions, called introns. Each three bases in the gene are called a codon and they code for one amino acid. The sequence of codons makes up what is called the genetic code. A gene has three codons at the end, called stop codons, that determine the end of a protein. A chromosome is continuous molecule of DNA that has thousands of genes. Chromosomes can be identified microscopically and can be counted. A normal human cell has 23 pairs of homologous chromosomes. Chromosomes are divided into two main groups: autosome and sex chromosomes. There are 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes (X and Y). Genes that lie geographically near one another on the chromosome do not get separated during meiosis and tend to be inherited together, a phenomenon called linkage.
DNA and CHROMOSOME ANOMALIES
There are 4 main anomalies of the DNA molecule: deletion of a gene, point mutation involving a single base change, insertion or deletion of nucleotides, and fusion of genes. Deletion of genes occurs in thalassemia. Point mutation occurs in sickle cell disease in which there is a single amino acid substitution in the hemoglobin molecule. In some forms of thalassemia there is frame-shift mutation due to insertion of nucleotides whose number is not a multiple of three. If the number is a multiple of three this effect does not occur. Gene fusion occurs in some forms of thalassemia. The fused genes code for a different protein from the normal one.
Chromosomal anomalies are of 4 types: an abnormal number of chromosomes, translocation of a chromosome from its usual site to a different site, deletion of a chromosome, and insertion of a chromosome. In anomalies of number, the normal haploid number of 23 chromosomes is changed. It may be doubled (diploid), tripled (triploid), or even multiplied by 4 (tetraploid). Trisomy is a situation when an individual carries one extra chromosome. Double trisomy is when an individual is carrying 2 extra chromosomes. Monosomy is a situation in which one chromosome is missing. In translocation anomalies, breakage of a piece of chromosome and its attachment to another chromosome is called translocation. Sometimes there is reciprocal translocation which is exchange of material between 2 non-identical chromosomes. In deletion anomalies there are breakages of the chromosome and loss of some chromosomal material. In inversion abnormalities, the two ends of a chromosome may join forming a ring chromosome
HOMOZYGOUS AND HETEROZYGOUS:
Alleles are genes coding for the same traits on each one of the pair of homologous chromosomes. Alleles of a particular trait are situated at identical points (called loci) on each member of a homologous pair of chromosomes. If the genes of the pair are identical we say they are homozygous. They may both be dominant or recessive. If the genes of the pair are not identical, we say they are heterozygous. One of the heterozygous alleles is dominant whereas the other is recessive (or masked). The theoretical probability of inheriting particular characteristics from parents can be computed using probability formulas. The chances of inheriting one particular allele from a heterozygous parent is 1/2. If both parents are heterozygous the chances are ¼.
The following human characteristics are determined by a single pair of alleles: tongue rolling, attached ear lobes, response to the PTC (phenylthiocarbamide) test, response to the sodium benzoate test, sex determination as male (XX) or female (XY), dimpled cheeks, the widow’s k (a V-shaped downward hairline in the middle of the forehead), bent little finger toward the ring finger, double-jointed thumb, freckles, ABO blood type, and mid-digital hair.
DOMINANT AND RECESSIVE GENES
The genes may be dominant or recessive. The pair of alleles can be both dominant (called co-dominance), or both recessive, or one can be dominant and the other recessive. In dominant disease. An individual will be affected if he/she carries only one abnormal allele. In recessive diseases, both alleles must be abnormal. Dominant genes will exert their effect in both homozygous and heterozygous situations. Recessive genes exert their effect only in the homozygous situation.
GENOTYPE AND PHENOTYPE.
A distinction must be made between genotype and phenotype. Genotype refers to the genetic composition that was inherited from the parents. Gene expression is sometimes not perfect because of the phenomenon of incomplete gene penetrance. Incomplete dominance is a situation of intermediate inheritance in which both alleles express themselves in an offspring such that the phenotype is intermediate between the 2 homozygous individuals.
C. GENETIC DISEASES
CHROMOSOMAL DISORDERS
Autosomal disorders
· Down's syndrome is trisomy 21
· Edward's syndrome is trisomy 18
· Patau's syndrome is trisomy 13
Sex-linked disorders
· Kilnefelter's syndrome (47, xxy)
· Xyy male
· Turner's syndrome (45,x)
· 47, xxx female
Chromosomal aberrations linked to malignancy
· Chronic granulocytic leukemia: t()
· Burkitt's lymphoma: t(8:2), t(), t(8;22)
· Acute myeloblastic leukemia: t()
· Chronic lymphocytic leukemia: trisomy 12
· Retinoblastoma: del
· Wilm's tumor: del
· Acute lymphocytic leukemia: trisomy 21
Genetic disorders associated with chromosomal breakage
· Fanconi's anemia
· Ataxia telengiectasia
· Bloom syndrome
· Xeroderma pigmentosum
SINGLE GENE DISORDERS
Aminoacidopathies
· Phenylketonuria
· Homcystinuria
· Cystinosis
· Alkaptonuria
Transport disorders
· Cystinuria
· Nephrogenic diabetes insipidus
· Hartnup disease
Storage disorders
· Glycogen storage disorders
· Sphingolipidoses
· Gangliosidoses
· Muco-polysaccharidoses
Connective tissue disorders
· Collagen disorders
· Osteogenesis imperfecta
· Marfan's syndrome
MULTIFACTORIAL DISORDERS
· Definition: Both genetic and environmental factors are involved in causation. The genetic component is due to polygenic inheritance
· Common multi-factorial malformations: cleft palate, cleft lip, club foot, dislocation of hip, congenital heart disease, Hirschprung's disease, and pyloric stenosis
· Common disorders of multi-factorial origin with genetic markers: insulin-dependent diabetes (HLA haplotypes eg B8, B15, DW3, DW4), celiac disease (HLA-A1-B8-DW3), ankylosing spondylitis (HLA-B27), peptic ulceration (blood group O), atherosclerosis (apolipoprotein A-1, low density lipoprotein receptors, apolipoprotein E)
D. EPIDEMIOLOGICAL STUDIES OF GENETIC DISEASES
· The traditional genetic epidemiology studies are case control studies, cohort studies, and cross sectional studies with case control studies being the most popular. Molecular analysis can be used in case control studies to explore genetic and environmental interactions.
· New study designs are: family studies, twin studies, adoption studies, migrant studies, affected relative study, and various adaptations of the case control design: case only and case parent studies.
· Family studies include study of first relative disease risk, concordance studies, gene isolation by segregation or linkage. Increased disease risk in a first degree relative points towards a genetic cause. Concordance of certain variables related to disease within the family (between parents and offspring or among siblings) is assessed by using the correlation coefficient. Concordance among spouses indicates environmental causes. Gene isolation involves investigating the relation between an allele and a disease condition by analysis of DNA polymorphism or by family studies to establish segregation of linkage between disease-associated loci. Segregation analysis seeks to determine if the pattern of familial disease is compatible with Mendelian inheritance using statistical methods. Linkage analysis seeks to investigate whether two alleles from 2 loci segregate together in a family as they are passed from parents to child.
· Twin studies may be based on study of monozygotic twins or dizygotic twins. Monozygotic twins share genetic material 100%. Dizygotic twins share only 50% of genetic material. The results of a twin study are set out as shown in the 2x2 contingency table below
Twin 1 + | Twin 1 - | |
Twin 2 + | a | b |
Twin 2 - | c | d |
The concordant rates and discordant rates for disease are computed. The concordant rate is computed as a / (a + b + c) and the discordant rate is computed as (b+c) / (a + b + c). A strong concordance in monozygotic twins suggests a genetic cause of disease.
· Adoption studies are used to evaluate the relative contributions of genetic and environmental factors to disease. Disease risk can be compared in twins adopted by different families. Disease risk is also compared in adopted children and biological children. Disease risk can also be compared in parents and their offspring adopted into other families.
· In affected relative studies, the alleles of the proband are compared to those of a second affected case as well as the parents. The case only study is a simple design that yields the OR; it compares observed genotype with the expected based on the population. The case parent design compares actual with expected genotype based on parental genotype.
· Inbreeding studies: inbreeding increases homozygous sites that results in a higher risk of autosomal recessive disorders. It is possible to compute an inbreeding coefficient and to relate it to disease risk in any given community.
· Admixture studies are used to study the effect of racial mixing. For example in the US
· Genetic mapping in relation to clinical disease: The Human genome project aims at mapping the sequence of the human genome of about 50,000 – 100, 000 genes will contribute new information for genetic studies. Human genes play roles in both rare and common diseases.
· Using genetic distribution to compute disease risk
· Genetic markers: Genetic markers can be gene products such as ABO, HLA, proteins, or enzymes. They can also be based on direct analysis of DNA. These studies suffer from three main disadvantages: confounding bias, misclassification of genotype, and gene-environmental interactions.
· Time trend studies indicate whether disease is biological or environmental. Environmental disease changes with time.
· Migrant studies are also used to evaluate the relative roles of genetic and environmental factors in disease. Interpretation of migrant studies is complicated by three considerations: the migrants are a self-selected group that does not represent the general population, age at migration determines the type and amount length of exposure to environmental causes in the home and migrant countries, and migrants may carry with them some of the cultures and lifestyles of the original country.
E. PREVENTION OF GENETIC DISEASES
PRIMARY PREVENTION
Genetic counseling
· Discouraging consanguinity
· Pre-marital/pre-pregnancy risk assessment is based on a detailed family history, diagnosis of disease in family members
· Pre-natal diagnosis is controversial
Screening
- Screening is available for: phenylketonuria, hypothyroidism, cystic fibrosis, sickle cell disease, Tay-sachs disease, adult-onset polycystic kidney disease, multiple endocrine adenomatosis, familial polyposis coli
SECONDARY PREVENTION
- Surgical correction
- Replacement therapy e.g. give insulin in dm
- Amelioration therapy e.g. restrict diet in phenylketonuria
- Preventive therapy e.g. remove polyposis coli
- Gene therapy
C. TERTIARY PREVENTION
· Supportive
8.5.3. PHARMACEUTICAL AGENTS
A. ADVERSE DRUG REACTIONS (ADR)
HISTORICAL BACKGROUND
ADR has a long history. In 1831 sudden death due to chloroform was described. Agranulocytosis due to amidopyrine was described in 1933. Smallpox vaccination was found associated with jaundice in 1883 and it was not until later that the real cause was identified as viral hapatitis. In 1937 a mistake in mixing reagents led to death of 107 persons because diethylene glycol was used by mistake as a solvent for sulfonamide. Tin used in a skin preparation by mistake killed 100 people in Paris Germany , 500 in UK
DRUGS ASSOCIATED WITH ADR
There has been a dramatic increase in synthetic drugs. In 1936 the British Pharmacopeia listed only 36 drugs. Today it lists thousands. As more drugs are available for use, toxicity incidents also increase. Any drug can cause ARD. The commonest ADRs are due to: anti-HTsives, anti-coagulants, cytotoxics, corticisteroids, and digoxin. Risk of ADR: The young children and the elderly are at higher risk for ADR. Women are at higher risk than men.
TYPES OF ADR
Adverse drug reactions (ADR) are classified as type A and type B. Type A reactions are due to the known pharmacological effects of the drug. They are dose dependent, predictable, and not so severe). Type B reactions are rare idiosyncratic reactions of the drug. They are non-dose dependent, unpredictable and have more mortality.
INCIDENCE OF ADR
In the UK
PREVENTION and SURVEILLANCE
PREVENTION OF ADR: (a) Primary prevention: control of prescription, know allergy, avoid polypharmacy, rational drug use (b) Secondary: stop drug, antidote, monitoring for further side-effects (c) Tertiary:
POST-MARKETING SURVEILLANCE: The process of drug development takes over 10 years. The initial animal studies may fail to detect adverse effects. Clinical trials reveal only the common side effects because they involve only a few patients, they are of limited duration, and exclude some types of patients like pregnant women. Post-marketing surveillance becomes necessary to be able to pick up more ADRs. The following methods are used: (a) non-systematic reporting of anecdotal case history information in medical journals (b) spontaneous reporting of any observed reactions to ADR registers. These registers may be regional or national. Drug manufacturers also maintain registers. The ADR profile of a drug is constructed from studying all these reports. (c) case control studies that retrospectively study the causes of reported reactions. Cases are essentially persons with the observed reaction. They are compared to normal controls regarding use of drugs. (d) prospective studies.
B. DRUG INTERACTIONS:
According to UK
C. DRUG POISONING
INCIDENCE
Drug Poisoning: can be accidental & deliberate (accidental and deliberate). Drug poisoning is on the increase. According to UK
PREVENTION
Primary prevention: keep out of access espp children and the elderly. Child-resistant or child-proof container caps are recommended. Education can be carried out through community outreach seminars, including drug information in school curricula, information at retail outlets, and information through the mass media. Secondary prevention: Remove poison (gastric lavage, induce emesis, adsorbents), anti-dotes, and elimination (forced diuresis, hemoperfusion), support: cardio-vascular, respiratory. Tertiary prevention: prevent complications: skin care, bladder care, anti-convulsants.