WHO responds to Ebola virus disease outbreak in West Africa
Global Alert and Response (GAR) – Ebola virus disease (EVD) WHO
What You Need to Know About the Ebola Virus and Emory University Hospital
On 28 February 2003, the French Hospital of Hanoi, Vietnam, a private hospital of fewer than 60 beds, consulted the Hanoi office of the World Health Organization (WHO). A business traveler from Hong Kong had been hospitalized on 26 February for respiratory symptoms resembling influenza that had started three days before. The WHO medical officer, Dr Carlo Urbani, an infectious diseases epidemiologist and a previous member of Medecins sans Frontieres, answered the call. Within days, in the course of which three more people fell ill with the same symptoms, he recognized the aggressiveness and the highly contagious nature of the disease. It looked like influenza but it wasn’t. Early in March the first patient died, while similar cases started to show up in Hong Kong and elsewhere. Dr Urbani courageously persisted working in what he knew to be a highly hazardous environment. After launching a worldwide alert via the WHO surveillance network, he fell ill while travelling to Bangkok and died on 29 March. A run of new cases, some fatal, was now occurring not only among the staff of the French Hospital, but in Hong Kong, Taiwan, Singapore, mainland China, and Canada. Public health services were confronted with two related tasks: to build an emergency worldwide net of containment, while investigating the ways in which the contagion spread in order to pinpoint its origin and to discover how the responsible agent, most probably a micro-organism, was propagated. It took four months to identify the culprit of the new disease as a virus of the corona-virus family that had jumped to infect humans from wild small animals handled and consumed as food in the Guangdong province of China. By July 2003, the worldwide propagation of the virus, occurring essentially via infected air travelers, was blocked. The outbreak of the new disease, labeled SARS (Severe Acute Respiratory Syndrome), stopped at some 8,000 cases and 800 deaths. The toll would have been much heavier were it not for a remarkable international collaboration to control the spread of the virus through isolation of cases and control of wildlife markets. Epidemiology was at the heart of this effort, combining investigations in the populations hit by SARS with laboratory studies that provided the knowledge required for the disease-control interventions.
Epidemiology owes its name to `epidemic’, derived from the Greek epi (on) and demos (population). Epidemics like SARS that strike as unusual appearances of a disease in a population require immediate investigation, but essentially the same investigative approach applies to diseases in general, whether unusual in type or frequency or present all the time in a population in an `endemic’ form. In fact, the same methods are used to study normal physiological events such as reproduction and pregnancy, and physical and mental growth, in populations. Put concisely, epidemiology is the study of health and disease in populations.
The population aspect is the distinctive trait of epidemiology, while health and disease are investigated at other levels as well. In fact, when `medicine’ is referred to, without specification, one thinks spontaneously of clinical medicine that deals with health and disease in individuals. We may also imagine laboratory scientists carrying out biological experiments, the results of which may hopefully be translated into diagnostic or treatment innovations in clinical medicine. By contrast, the population dimension of health and disease, and with it epidemiology, is less prominent in the minds of most people. In the past, introduced to someone as an epidemiologist, I was not infrequently greeted with the remark `I see you are a specialist treating skin diseases’. (Clearly the person thought of some fancy `epidemiology’, alias dermatology. Now I introduce myself as a public health physician, which works much better.)
A flashback into history
Clear antecedents of contemporary epidemiology can be traced back more than 2,000 years. The writings of the great Greek physician Hippocrates (c. 470 to c. 400 ac) provide not only the first known descriptions, accurate and complete, of diseases such as tetanus, typhus, and phthisis (now tuberculosis of the lung), but also show an extraordinarily perceptive approach to the causes of diseases. Like a modern epidemiologist, Hippocrates does not confine his view of medicine and disease to his individual patients but sees health and disease as dependent on a broad context of environmental and lifestyle factors.
According to Hippocrates:
Whoever wishes to investigate medicine properly should proceed thus: in the first place to consider the seasons of the year, and what effects each of them produces. Then the winds, the hot and the cold, especially such as are common to all countries, and then such as are peculiar to each locality. In the same manner, when one comes into a city to which he is a stranger, he should consider its situation, how it lies as to the winds and the rising of the sun; for its influence is not the same whether it lies to the north or to the south, to the rising or to the setting of the sun. One should consider most attentively the waters which the inhabitants use, whether they be marshy and soft, or hard and running from elevated and rocky situations, and then if saltish and unfit for cooking; and on the ground, whether it be naked and deficient in water, or wooded and well watered, and whether it lies in a hollow, confined situation, or it is elevated and cold; and the mode in which the inhabitants live, and what are their pursuits, whether they are fond of drinking and eating to excess, and given to indolence, or are fond of exercise and labour.
Hippocrates, On Airs, Waters and Places
Many centuries would elapse, however, before epidemiology could move from perceptive observations and insights to a quantitative description and analysis of diseases in populations. The necessary premise was the revolution in science ushered in by Galileo Galilei (1564-1642), who for the first time systematically combined observation and measurement of natural phenomena with experiments designed to explore the underlying regulating laws, expressible in mathematical form (for example, the law of acceleration of falling bodies). The work of John Graunt (1620-74), a junior contemporary of Galilei, is a remarkable example of the general intellectual climate promoting accurate collection and quantitative analyses of data on natural phenomena. In his Natural and Political Observations Upon the Bills of Mortality of London, Graunt uses simple (by our standards) but rigorous mathematical methods to analyse mortality in the whole population, including comparisons between men and women and by type of diseases (acute or chronic). Later progress in epidemiology was made possible by two developments. First, the expansion in collection of data on the size and structure of populations by age and sex, and on vital events such as births and deaths; and second, advances in mathematical tools dealing with chance and probabilities, initially arising out of card and dice games, which were soon seen to be equally applicable to natural events like births and deaths.
By the early 19th century, most of the principles and ideas guiding today’s epidemiology had already been established, as even a cursory look at the subsequent history shows.
In France, Pierre-Charles Alexandre Louis championed the fundamental principle that the effect of any potentially beneficial treatment, or of any toxic substance, can only be assessed by a comparison of closely similar subjects receiving and not receiving it. He used his `numerical method’ to produce statistical evidence that the then widespread practice of bloodletting was ineffective or even dangerous when contrasted with no treatment. In London, John Snow’s research highlighted the idea that insightful epidemiological analyses of disease occurrence may produce enough knowledge to enable disease-prevention measures, even in ignorance of the specific agents at microscopic level. Snow conducted around the middle of the 19th century brilliant investigations during cholera epidemics that led to the identification of drinking water polluted by sewage as the origin of the disease. This permitted the establishment of hygienic measures to prevent the pollution without knowing the specific noxious element the sewage was carrying. That factor, discovered some 20 years later, turned out to be a bacterium (Vibrio cholerae) excreted in the faeces by cholera patients and propagated via the sewage. In Germany, Rudolf Virchow forcefully promoted during the second part of the century the concept that medicine and public health are not only biological but also applied social sciences. Consistent with this inspiration, his studies ranged from pathology – he is acknowledged as the founder of cellular pathology – to epidemiological investigations backed by sociological enquiries. In the United States, the work of Joseph Goldberger demonstrated that epidemiology is equally well suited to identify infectious and non-infectious agents as possible origins of a disease. In the first three decades of the 20th century, he investigated pellagra, a serious neurological disease endemic in several areas of the Americas and Europe, reaching the conclusion that it was due not to an infectious agent, as most then believed, but to poor diet, deficient in a vitamin (later chemically identified and named vitamin PP). In the century spanning Louis to Goldberger, and in fact throughout its history up to the present day, epidemiology has received major support from advances in the contiguous field of statistics, a key ingredient of any epidemiological investigation.
Epidemiology today
Today’s epidemiology developed particularly during the second half of the last century. By the end of World War II, it became apparent that in most economically advanced countries the burden of non-communicable diseases of unknown origin, such as cancer and cardiovascular disease, was becoming heavier than the load of communicable disease due to micro-organisms and largely controllable through hygiene measures, vaccinations, and treatment with antibiotics. These new circumstances provided a strong impetus for epidemiology to search for the unknown disease origins through new as well as established methods of research which soon came to be used beyond their initial scope in all areas of medicine and public health. This is reflected in the concept of epidemiology as the study of health and disease in populations: [Epidemiology is] the study of the occurrence and distribution of health-related states or events in specified populations, including the study of the determinants influencing such states, and the application of this knowledge to control the health problems.
M. Porta, A Dictionary of Epidemiology
All aspects of health when studied at the level of population are the proper domain of epidemiology, which covers not only the description of how diseases and, more generally, health-related conditions occur in the population, but also the search for the factors, as a rule multiple, at their origin. This investigative activity is sustained by scientific curiosity but is firmly directed towards an applied objective: the prevention and treatment of disease and promotion of health. A fascinating and challenging feature of epidemiology is that it explores health and disease in connection with factors which, to take heart attacks as an example, span from the level of the molecule, say blood cholesterol, to the level of society, say loss of employment. This broad perspective makes epidemiology at the same time a biomedical and a social science. Epidemiological studies include both routine applications of epidemiological methods, for example in surveillance of communicable diseases or in monitoring of hospital admissions and discharges, and research investigations designed to generate new knowledge of general relevance.
There may be overlaps and transitions between these two types of studies. When routine surveillance detects an outbreak of a previously unknown disease, like SARS, subsequent investigations produce factual knowledge that is at the same time useful for the local and practical purpose of controlling the disease and for the general scientific purpose of describing the new disease and the factors at its origin. Epidemiology fulfils the same diagnostic functions for the health of a community as a doctor’s consultation does for the individual.
Within epidemiology a clear distinction must be made between observational and intervention, or experimental, studies. Experimental studies are dominant in the biomedical sciences. For example, scientists working in laboratories intervene all the time on whole animals, isolated organs, and cell cultures by administering drugs or toxic chemicals to study their effects. By contrast, within epidemiology, observational studies are by far the most common. Epidemiologists observe what happens in a group of people, record health-related events, ask questions, take measurements of the body or on blood specimens, but do not intervene actively in the lives or the environments of the subjects under study. Intervention studies, for example trials of new vaccines in the population, are an essential but smaller component of epidemiology, representing no more than one-fifth to one-tenth of all epidemiological studies in healthy populations. In populations of patients, however, trials of treatments, from drugs to surgery, are most common. All kinds of studies, whether routine or for research, observational or experimental, stand with their own particularities on the common basis of the epidemiological principles.
Five major areas within epidemiology
1. Descriptive epidemiology: describes health and disease and their trends over time in specific populations.
2. Aetiological epidemiology: searches for hazardous or beneficial factors influencing health conditions (e.g. toxic pollutants, inappropriate diet, deadly micro-organisms; beneficial diets, behavioural habits to improve fitness).
3. Evaluative epidemiology: evaluates the effects of preventive interventions; quantitatively estimates risks of specific diseases for persons exposed to hazardous factors.
4. Health services epidemiology: describes and analyses the work of health services.
5. Clinical epidemiology: describes the natural course of a disease in a patient population and evaluates the effects of diagnostic procedures and of treatments.
Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. Constitution of the World Health Organization, 7 April 1948 One may wonder whether the founding fathers, who in the aftermath of World War II inscribed the definition of health in the World Health Organization (WHO) constitution, unconsciously had in mind happiness rather than health, although even happiness, a changing and intermittent human experience, cannot be accurately described as a heavenly and lasting state of perfect well-being. Abstract as it is, the WHO definition does have the merit of stressing the relevance of the psychological and social dimensions, beyond those purely physiological, of health and disease (social aspects incorporated in a recent WHO classification of disabilities and social determinants of health have been a central theme for the organization in recent years). Even today, for the majority of humankind the basic objective of achieving absence of disease or infirmity, as far as may be possible by current preventive and therapeutic means remains unattainable, nor is it clear when it may be attained. Hence measuring health starting from its negative, the presence of disease, is not only technically easier but also makes practical sense.
Defining disease
For the purpose of epidemiological study, a disease can be defined either by creating a definition and regarding as cases the subjects that fit it or by accepting as cases those subjects that have been so diagnosed by a doctor. In an epidemiological survey of diabetes it may be decided that a study team directly examines a fraction of all adults in a town and regards as diabetic those people who satisfy a pre-fixed set of diagnostic criteria. Alternatively, and much more simply, one can accept as cases the people declared to be diabetic by doctors in the general practices and hospitals of the town. Actually the two approaches may to some extent overlap. When carrying out a direct survey, the study team will in fact come across some subjects already known to be diabetic and for whom further tests may be deemed unnecessary.
Accepting existing diagnoses may, however, result in data perturbed by differences in disease definition and diagnostic practice between doctors in the area, a drawback not shared by a direct full-blown epidemiological survey carried out with a fixed definition and uniform procedures. An intermediate solution between a more reliable but cumbersome survey and a simpler but less reliable face-value acceptance of existing diagnoses may consist of confirming or rejecting the diagnosis only after thoroughly reviewing the medical records in the physician and hospital files. Still, this procedure would not capture, as an epidemiological survey would, the not infrequent cases of diabetes present in the population that do not show up in the files because those affected have no symptoms. Any of these approaches to the definition of diabetes and case identification may be employed to produce figures on the frequency of diabetes in a country, a region, or a particular group of people.
To complicate matters, many disease definitions have changed and continue to change, sometimes even in a major way, with advances in biological and medical knowledge. In the case of diabetes, the threshold levels for sugar in the blood that define diabetes were modified ten years ago taking into account the results of several studies showing that levels previously regarded as `normal’ and safe were in fact associated with an increased frequency of complications. For heart attacks, the different types of myocardial infarction are currently redefined including among the criteria the detection in the blood of some hitherto unmeasurable proteins released by the damaged heart cells. Epidemiology itself may contribute to defining or redefining diseases. Rather than committing himself to a disease definition, the epidemiologist may simply measure individual symptoms such as insomnia, headache, fatigue, tremors, or nausea to see whether they occur jointly, forming a ‘syndrome’ (a cluster of symptoms) in individuals with special personal traits or in particular settings. This paves the way to the investigation of the physiological mechanisms, the external circumstances, and the progress in time of the syndrome; once these elements become clear, the definition of a new disease or a special form of a disease already known may be consolidated.
