Application of Disease Etiology and Natural History to Prevention in Primary Health Care (PDF)

Review Med Princ Pract 2020;29:501–513 Received: December 12, 2019...

Review Med Princ Pract 2020;29:501–513 Received: December 12, 2019 Accepted: May 17, 2020 DOI: 10.1159/000508718 Published online: May 18, 2020 Application of Disease Etiology and Natural History to Prevention in Primary Health Care: A Discourse Franklin White a, b Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 a Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada; b Pacific Health and Development Sciences, Victoria, BC, Canada Highlights of the Study Etiology and natural history are keys to identifying intervention opportunities. Prevention is defined at three levels: primary, secondary, and tertiary. Strategies include health promotion, reducing risk factors, case finding, screening, addressing func- tional health, preventing errors, and integrated models. Health literacy and language are critical considerations for public communication and patient-cen- tered care. Keywords ognized. The distinction between incidence effects and Prevention · Etiology · Natural history · Primary health care · treatment effects of prevention is explored. This review also Health literacy examines the differing roles of language in health science and public communication, aspects of disease classification, related issues in patient-centered care, the prevention para- Abstract dox, and integrated models of disease prevention. The principles of etiology and natural history of disease are © 2020 The Author(s) essential to recognizing opportunities for prevention across Published by S. Karger AG, Basel the illness spectrum. They have a bearing on how illness is experienced, how differently it can be perceived at the time of first contact with the health system, and how it may ap- Introduction pear at later stages. Opportunities for prevention arise at ev- ery stage in the process, and three main levels are described: This review portrays the etiology and natural history of primary, secondary, and tertiary. Prevention strategies in- diseases as essential to primary health care (PHC) in pro- clude health promotion focused on determinants, clinical moting health and preventing disease. Although written for prevention to reduce modifiable risk factors, case finding, health professionals most likely to encounter individuals screening, and addressing functional outcomes relevant to early in the process of seeking help for illness or injury, the quality of life; the importance of preventing errors is also rec- principles are applicable at any stage of a person’s illness. [email protected] © 2020 The Author(s) Franklin White www.karger.com/mpp Published by S. Karger AG, Basel Pacific Health and Development Sciences This is an Open Access article licensed under the Creative Commons PO Box 44125, RPO Gorge Attribution-NonCommercial-4.0 International License (CC BY-NC) Victoria, BC V9A7K1 (Canada) (http://www.karger.com/Services/OpenAccessLicense), applicable to fwhite.pacificsci @ shaw.ca the online version of the article only. Usage and distribution for com- mercial purposes requires written permission.  While no disease model is free from theoretical and Recognizing such variations in perception may help practical limitations, especially considering the vast range practitioners to contextualize how different people inter- of circumstances that affect health, etiology and natural pret seemingly similar afflictions differently, and to un- history provide a robust framework that serves well to con- derstand why some are resistant to adopting approaches ceptualize illness entities, and ways of intervening in them. offered by the formal health system, and to appreciate the Alternative clinical, social, and environmental paradigms role of some alternative models and practices. Even so, that can meet critical scrutiny should also be considered the disease focus remains legitimately at the core of much. Using all applicable frameworks, practitioners must medical and public health practice. respond to the needs of people as they present with illness. Disease itself has enduring value as a sustainable con- The Importance of Language and Health Literacy struct; the most obvious benefit is in making a diagnosis. Before enlarging on aspects of diagnosis, etiology, nat- According to a view expressed in a BMJ debate: “… ac- ural history, and disease prevention, the role of language knowledgement by the medical profession that a patient’s must be recognized, as it is linked to our cognitive ability condition has a name and is a legitimate illness is im- to think, learn, reason, and communicate. Without com- mensely reassuring and enabling… Crudely handled, mon understanding, people may arrive at varying inter- Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 medicalization can perpetuate disability and exclusion. pretations of what is written, read, or said; when this hap- But used constructively and appropriately it is the first pens, it creates confusion across the spectrum from pro- step towards recovery”. fessional to public communication. Core PHC skills It is self-evident that not all diagnosed conditions will therefore include listening, asking questions, diagnosing, reach full recovery, but (at the very least) any person giv- and recommending a course of action. Precision in lan- en a diagnosis will want to know its prognosis (the likely guage is critical for rigorous thought and clarity in ex- course and possible outcomes). Prognoses can vary from pressing an approach to patient care and in providing recovery to death, and a range of intermediate outcomes public health information. However, this linguistic which may impact on function and quality of life. To re- principle does not stop there: rigorous use of language is spond intelligently to this expectation ideally requires never sufficient, as it must be integrated with effective that the natural history of the disease is understood, and knowledge translation to achieve language more readily that intervention efficacies are known. understood by particular patients and the public at large, Detailed knowledge about prognosis (with and with- people mostly not steeped in biomedical science and out intervention) comes mainly from epidemiological technology. This is not a new idea: “…physicians ab- studies that quantify the likelihood of possible outcomes, sorb… diagnostic frameworks and population-based while efficacy estimates generally require the conduct of guidelines, and translate them… to the level of a single randomized controlled trials, and may vary with the char- person whose illness is but one piece of life and whose acteristics of patients selected for study. For potentially profile never quite matches the one in the textbook”. fatal conditions, mortality estimates are calculated, for Also, among health care recipients, health literacy is a example the case-fatality rate (proportion of cases of a variable commodity: “…health literacy includes listening, disease that are fatal within a specified period of time), speaking, and conceptual knowledge that make it possible which is often used for acute infectious diseases (IDs), to understand health interactions, forms, and instruc- and the 5-year survival rate (proportion of people alive 5 tions… health care environments have cultures of their years after diagnosis, or a designated intervention), often own, ways of doing things, and uses of language that are used for cancer. different than what average persons experience in their Despite prognostic implications, there exist more nu- day to day lives… The greater the difference between our anced interpretations. The potential for stigma attached lived experiences and those of others, the more likely our to particular disease labels is long recognized. A diagnosis frames of reference will be different. Therein lies the po- in itself can adversely influence clinical management, if tential for misunderstanding”. driven more by the label than by a patient’s actual needs The transition to a more “patient-centered approach”. Particular diagnoses may affect lifestyle, relation- to clinical management owes much to the emergence of ships, and the ability to earn a living. Aided by the inter- family medicine as a discipline that makes continuing net, people are taking more control over their health, and care its special responsibility. Among the exponents was sometimes perceive the medicalization of some condi- Ian McWhinney (1926–2012), a founder of the specialty tions as unwarranted. when it was launched about half a century ago. He wrote: 502 Med Princ Pract 2020;29:501–513 White DOI: 10.1159/000508718 “An understanding of the meaning of the illness for the straightforward: the meaning of symptoms can vary patient should be as important for the physician as reach- greatly between this first health system contact and the ing a clinical diagnosis”. referral context; for example, the diagnostic spectrum for Linguistic principles apply at all levels from local to in- cough presenting in a community clinic will differ from ternational. Communicating more effectively in local lan- that among patients referred to a specialized chest clinic. guages can help implement public health strategies to sup- Similarly, persons referred with severe headache to a neu- port sick people and prevent transmission. For example, in rology clinic are more likely to have a brain tumor than the Democratic Republic of the Congo, the technical term the much larger number presenting with a similar com- “suspected case” meant “criminal” in the local Nande lan- plaint in an emergency clinic [17, 18]. guage, initially impeding efforts to manage an Ebola virus Furthermore, among the reasons specialists are more disease outbreak. Public perceptions of newly medical- likely to arrive at a valid diagnosis is that their case load ized disorders with accompanying diagnostic terms reveal has been triaged by clinicians in PC: preliminary testing that use of medical language in communication can bias has often been done, and the condition is often further how a condition is perceived: if it is a “disease,” how seri- advanced and easier to diagnose (its “pre-test probability” ous, and how common or rare is it ? The choice of lan- has been elevated). This should come as no surprise: it is Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 guage can influence a patient’s understanding, their deci- predicted by Bayes’ theorem, a mathematical formula for sion to seek care, and whether to comply with prevention applying conditional probability. Bayes’ theorem is or treatment. Patient decision making, or self-triage , now introduced early in medical school and in standard thus has implications for medical care. Over-emphasizing texts, e.g., Chapter 3 in Harrison’s Principles of Internal diagnosis, as distinct from what the illness means to the Medicine. Even so, adherence to Bayes’ principles is patient, therefore requires attention. A rational middle largely absent in clinical practice – low probability dis- ground exists: neither indiscriminate acceptance of medi- eases are still tested for causing unneeded cost and risk, calization nor criticizing new terms just because they are and high probability diseases often ignored when a single medicalized can be justified. negative test result is returned. The broader concept of PHC derives from a societal “Primary Care” or “Primary Health Care”? perspective more aligned with the role of organized pub- The terms “primary care” (PC) and “primary health lic health systems: “Essential health care made accessible care” are sometimes used interchangeably, but are not at a cost that a country can afford, with methods that are identical frameworks. Because they are mutually support- practical, scientifically sound and socially acceptable. Ev- ive and have a similar relationship to the natural history eryone should have access to it and be involved in it, as of disease, both are relevant here. PC is a profession-cen- should other sectors of society beyond health. It should tered concept based on a clinical role: “Health or medical include community participation and education on prev- care that begins at time of first contact between a physi- alent health problems, health promotion and disease pre- cian or other health professional and a person seeking vention, provision of adequate food and nutrition, safe advice or treatment for an illness or an injury”. De- water, basic sanitation, maternal and child health care, scribed by some ethicists as “the traditional medical mod- family planning, prevention and control of endemic dis- el” , this is an inaccurate label. It is not exclusive to eases, immunization against vaccine-preventable diseas- medicine: it applies to many other kinds of service pro- es, appropriate treatment of common diseases and inju- vider. Neither is it inherently “traditional” (taken to im- ries, and provision of essential drugs”. ply “adhering to customs that are respected because they According to the World Health Organization (WHO), are time-honored or integral to a certain culture or his- PHC “provides whole-person care for health needs tory”). To the contrary, although “time-honored,” throughout the lifespan, not just for a set of specific dis- the PC model is used because it works. Evidence shows eases… it is rooted in a commitment to social justice and that it helps to prevent illness and death, and (in contrast equity and in recognition of the fundamental right to the to specialty care) is associated with more equitable distri- highest attainable standard of health, echoing Article 25 bution of health in populations. of the Universal Declaration on Human Rights”. For An important focus of PC is clinical decision making: this review, it is relevant to highlight the phrase “not just any act of diagnosis based on presenting symptoms and for a set of specific diseases.” Yes, PHC is more than this, signs that leads to a decision regarding prognosis, treat- but WHO’s language explicitly includes disease within ment, referral, or counseling. The task is often not PHC, just as it encompasses PC as clinically defined. Etiology and Natural History in Disease Med Princ Pract 2020;29:501–513 503 Prevention DOI: 10.1159/000508718  The Language of Disease and Illness The first International List of Causes of Death, was ad- The term “disease” does not convey the same meaning opted by the International Statistical Institute in 1893. for everyone; it varies with role, context, and perception. Now known as the International Classification of Diseases Those directly affected experience it as “illness.” Informal (ICD), and published under WHO auspices since 1948, caregivers (families, friends, others) become aware at an this goes through successive revisions. For example, early stage. Self-care and mutual support may be suffi- WHO member states will use ICD-11 starting from 2022 cient to navigate the process, but may also be critical, de-. With advances in knowledge and experience, dis- pending on whether the formal health system enables ac- ease taxonomy continues to evolve. cess. From a purely clinical perspective, “illness” has been Reflecting ongoing research and development, the for- oversimplified as “the subjective sensation of experienc- mal integration of psychosocial elements within the bio- ing a diseased state” ; it is more complex when viewed medical model gave rise in 1980 to a supplementary clas- from the patient perspective: “it is possible for an indi- sification of Impairments, Disabilities, and Handicaps to vidual to have a disease, yet be unaware of it and act ac- ICD-9. This subsequently led to widespread adoption of cordingly; it is also possible for people to feel and/or act an International Classification of Functioning, Disability sick without showing evidence of any objectively verifi- and Health (ICF), which was launched in 2001 [26, 27]. Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 able disease. In the former instance there is no illness, The ICF is applicable to functional entities as outcomes or though there may be disease. In the latter case there is as starting points for clinical and public health interven- certainly illness”. tion at the individual or population level. While this was The term “disease” has ancient roots in the English lan- a significant step forward because abilities and par- guage, literally “lack of ease” or “uneasiness.” In the 21st ticipation are context dependent and related to quality of century, it came to be defined as any departure from good life, there are ongoing efforts to improve definitions and health or from normal physiological and/or psychological measurement [29, 30]. As famously stated by Greenwood: function; this definition encompasses “disorders” but must “The scientific purist, who will wait for medical statistics not be misconstrued as referring to natural processes, such until they are nosologically exact, is no wiser than Hor- as normal childbirth, menopause, sexual preference, as- ace’s rustic waiting for the river to flow away”. pects of aging, and bereavement, which require distinct recognition. Nor should it be applied to signs or symptoms Etiology per se, for example a rash, a lump, elevated temperature, The term “etiology” means the science of causes; from cough, pain, nausea, or weakness; although these may be a scientific perspective, all diseases must have causes. A expressions of underlying disease, until adequately inves- cause is something that produces an effect; in epidemiol- tigated they do not in themselves constitute disease. In bio- ogy it is customary to distinguish necessary cause, suffi- medical terminology, disease is defined by clinical, patho- cient cause, proximal cause, and distal cause. A necessary logical, and epidemiological criteria that enable systematic cause is one without which a condition cannot occur. Suf- study and application. At present, four major categories ficient cause is defined as a set of minimal conditions and are commonly recognized: injuries, IDs, non-communica- events that inevitably produce health, disease, and injury. ble diseases (NCDs), and mental and behavioral disorders, A proximal cause is an immediate precipitating factor; a each category comprising many conditions. distal cause is more remote. These concepts are embed- Diseases pass through stages: susceptibility, patholog- ded within epidemiology , the discipline that studies ical onset, pre-symptomatic, clinical, then resolution. the distribution and determinants of health-related states Each may be modifiable by intervention, such as preven- or events in specified populations, including diseases, tion, treatment, and rehabilitation, as well as by self-care causes of death, behaviors, responses to intervention/ and social adjustments. Depending on disease type and non-intervention, and the provision and use of health severity, outcomes vary from recovery to death, with in- services. termediate outcomes such as impairment (a physical or It is now recognized that virtually all diseases have mental defect at the level of a body system or organ), dis- multifactorial causation; in other words, varying combi- ability (temporary or long-term reduction of one’s capac- nations of causes are required to produce the effect. ity to function), or handicap (reduction of one’s capacity This gives rise to a composite framework of health and to fulfill a social role as a consequence of an impairment, illness: tissues and organs operating at biological level, disability, inadequate training for the role, or other cir- perception and experience at psychological level, and at- cumstances). tribution of meaning at social level ; integrating these 504 Med Princ Pract 2020;29:501–513 White DOI: 10.1159/000508718 elements is critical to understanding the clinical picture. egies, and is also utilized by public health organizations While it was once argued that some IDs, genetic disor- within health promotion strategies. In operational terms, ders, and traumatic injuries could be considered unifac- etiology and natural history are interdependent, offering torial, this was only ever true to the extent that the neces- the potential to identify and integrate potential clinical sary cause was a defined microbiological agent, a defec- and public health interventions if properly supported by tive gene, or a singular event such as an explosion. In relevant health systems development. causation as now understood, numerous factors play roles, and some may hold potential for prevention. In 21st Natural History of Disease century medicine, illness is viewed as a continuum that The natural history of disease refers to the progression may flow in either direction, including reversibility in of a disease process in an individual over time, in the ab- many conditions. sence of treatment. Hippocrates (c. 460–375 BC) was Factors relevant to multifactorial causation include the among the first to regard disease as a natural rather than following. Predisposing factors: those that prepare, a supernatural phenomenon, encouraging physicians to sensitize, condition, or otherwise create a state of suscep- look for causes using objective observation and deductive tibility so that the host tends to react in a deleterious fash- reasoning. In modern times, what is known about the Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 ion to a disease agent, personal interaction, environmen- natural history of any disease is constructed largely from tal stimulus, or specific incentive. These factors are “nec- observations of affected persons followed over time. Ide- essary” but rarely “sufficient” to cause the phenomenon ally this requires studies of defined cohorts which com- under study. Enabling factors: those that facilitate the mence with the onset of the condition; however, although manifestation of disease, disability, ill-health, or use of such studies have been carried out for numerous diseases, services or conversely those that facilitate recovery from rigor can be difficult to achieve especially for chronic con- illness, maintenance or enhancement of health status, or ditions with insidious onset that increasingly dominate more appropriate use of health services. These factors the global burden. For example, inception cohorts for may be “necessary” but are rarely “sufficient” to cause the multiple sclerosis are virtually impossible to recruit be- phenomenon under study. Precipitating factors: those as- cause clinical onset is often discordant with biological on- sociated with onset of a disease, illness, accident, behav- set and disease duration may exceed that of an investiga- ioral response, or course of action; usually one factor is tor’s career, even their lifespan. more important or more obviously recognizable than Viewed historically, much of what we know about the others if several are involved and one may often be re- natural history of most diseases has been pieced togeth- garded as “necessary.” Reinforcing factors: those tending er pragmatically, from astute clinical observations as to perpetuate or aggravate the presence of a disease, dis- well as formal studies of defined phases of a condition, ability, impairment, attitude, pattern of behavior, or whether this be studies of etiology, prevention and treat- course of action. They may tend to be repetitive, recur- ment efficacy, or of prognostic outcomes. Thereby, most rent, or persistent and may or may not necessarily be the often from multiple sources, a composite picture of a same or similar to those categorized as predisposing, en- dynamic disease process (its natural history) is con- abling, or precipitating. Risk factors: an aspect of person- structed. Relevant examples exist for all disease catego- al behavior or lifestyle, and environmental exposure, or ries: injuries, e.g., meniscal tears , childhood trauma an inborn or inherited characteristic that, on the basis of ; IDs, e.g., trachoma , human papilloma virus epidemiological evidence, is known to be associated with (HPV) ; NCDs, e.g., type 2 diabetes , Crohn’s health-related condition(s) considered important to pre- disease ; mental and behavioral disorders, e.g., vent. There are several types of risk factor: risk marker; schizophrenia , bipolar disorders. Such knowl- determinant; modifiable risk factor; non-modifiable risk edge is continually reorganized in light of emerging re- factor. search and experience, while management of emerging An understanding of multifactorial causation in itself diseases, e.g., COVID-19, is rendered particularly chal- may be applied to the design of prevention strategies, lenging because so little is known to support initial in- such as the Precede-Proceed model ; this employs an terventions. analysis of predisposing, reinforcing, and enabling fac- There is an honored tradition for such observational tors in the design of behavioral and environmental inter- enquiry in the field of general practice that has strength- ventions across the health spectrum. Similarly, actions on ened with the emergence of family medicine as a specialty. modifiable risk factors is a key to clinical prevention strat- Among its heroes is William Pickles, who wrote a classic Etiology and Natural History in Disease Med Princ Pract 2020;29:501–513 505 Prevention DOI: 10.1159/000508718  Color version available online Natural History of Disease and Prevention in Primary Health Care Prevention Primary Secondary Tertiary level Health Early detection Treatment-rehabilitation promotion and treatment Promote function and risk Restore health Limit disability reduction Reduce barriers Health status Health Disease Health maintained averted restored Clinical threshold Disease Chronicity limited Mortality Disease status Impairment disability Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 handicap pathology Stages of Susceptibility Subclinical, pre and Clinical disease Outcome disease - risk factors and early -functionality Fig. 1. Natural history of disease and determinants symptomatic -residual pathology prevention in Primary Health Care. entitled Epidemiology in Country Practice. His scientific by initial cell changes may become irreversible with pro- contribution was to document, at a level not previously gression to detectable neoplasia). achieved, the development and evolution of ID epidemics. For individuals who cross the clinical threshold to be- He did this by astute observation, charting, and excellent come “sick,” treatment becomes the intervention priori- record keeping. In 1939 he wrote the following: “Let me ty. Nonetheless, opportunities for preventive interven- recommend… particularly to those… entering country tion exist at every stage in the natural history. Treatment practice, this observation of the natural history of epidem- in itself may be preventive, not of the disease as it oc- ic diseases… We… practitioners are in a position to sup- curred but of its consequences in terms of chronicity or ply facts from our observations of nature, and it is, I feel functional outcome; or it may be indirectly preventive most strongly, our plain duty to make use of this unique such as the treatment of individuals with a disease trans- opportunity”. Stemming from such eclectic origins, missible from person to person, which may in turn reduce the discipline of clinical epidemiology has become steadi- the rate of secondary transmission, e.g., individuals on ly formalized, contributing much to the elucidation of eti- antiretroviral treatment with an undetectable virus load ology and natural history of diseases, and to our existing cannot transmit HIV to others; or it may result in a quar- and growing knowledge about disease prevention. antine decision as in the current COVID-19 pandemic for As illustrated in Figure 1 (a generic model), the passage which (at the time of writing) no fully effective drug or of a person through time is represented by the thick line vaccine has been identified. moving left to right. Thus, a healthy person may enter a Any depiction of the natural history of disease has lim- subclinical process which in turn may cross a threshold itations. For example, risk factors and determinants to become recognized as clinical disease. The model shown under the primary prevention column (Fig. 1) may shows how the person may emerge from the clinical situ- also function under subsequent columns dealing with ation with a range of possible outcomes, from death to secondary and tertiary prevention. Also, while the dia- partial or full recovery. This dynamic sequence holds for gram emphasizes prevention in the PHC context, more virtually all conditions: for IDs, transition from subclini- specific diagrams may be applicable for diseases for which cal to clinical disease reflects the incubation period (time the intervention focus is on progression factors. interval between invasion by an infectious agent and the onset of symptoms or signs), while for cancer (for exam- Levels of Prevention ple) it is the latent period or interval between exposure Prevention refers to any intervention intended to stop and manifestations (a complex multistep process where- something from happening. In PHC, this includes poli- 506 Med Princ Pract 2020;29:501–513 White DOI: 10.1159/000508718 cies and actions to reduce the incidence and/or preva- reductions in disease commensurate with the extent of lence of disease, disability, and premature death, to re- coverage. Reducing the incidence in turn leads to reduc- duce the prevalence of disease precursors and risk factors tions in rates of related complications and mortality in the population, and, if none of these are feasible, to which may also be considered an “incidence effect,” keep- slow its progress and reduce associated disability and so- ing in mind the time lag between incidence and the oc- cial impacts. This concept is usefully classified within currence of related outcomes. For example, rubella vac- three major levels: primary, secondary, and tertiary. In cination leads not only to a reduction in its incidence, but epidemiological terms, primary prevention aims to re- also to a secondary reduction in congenital rubella syn- duce disease incidence, secondary prevention aims to re- drome (CRS); a core rationale for rubella vaccination is duce disease prevalence by shortening its duration, and to protect pregnant women from this serious outcome in tertiary prevention aims to reduce the number and/or im- their offspring (CRS outcomes include congenital heart pact of complications. Two other levels are recognized in disease, hearing impairment, cataracts, and developmen- some contexts: “primordial” and “quaternary.” Primor- tal delay). dial prevention aspires to establish and maintain condi- Illustrating a more delayed incidence effect is the use tions that minimize hazards to health (as distinct of vaccine to prevent infection by strains of HPV associ- Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 from dealing with risk factors already present); however, ated with long-term risk of cervical cancer. The Interna- because the aim of such efforts (in epidemiological terms) tional Agency for Research on Cancer recognized HPV as is to reduce disease incidence, it is appropriate to view the “necessary” cause in the natural history of cervical primordial as a form of primary prevention. Quaternary cancer and HPV types 16 and 18 as carcinogenic agents prevention is defined by the World Organization of Fam- based on strong and consistent associations between in- ily Doctors (WONCA) as actions taken to identify and fection and disease. Since 2007, HPV vaccination has protect patients at risk of over-medicalization and to pro- been implemented in many countries; strong evidence of mote ethically acceptable interventions ; this may be protective efficacy against premalignant and cancerous considered a form of tertiary prevention as already de- lesions emerged. Based on such evidence, in 2018 the fined. WHO launched a global goal of eliminating cervical can- While PHC practitioners are generally well versed in cer. aspects of health promotion and prevention, the extent to Incidence effects can also be reversed, as observed in which such measures are incorporated in their practices, the current upsurge of measles in many countries where based on evidence, offers room for improvement. vaccination levels have been allowed to slip ; this is For example, population health might be enhanced by largely a result of anti-vaccination groups disseminating capturing missed screening opportunities, as long as un- misinformation. Comparable events have occurred be- necessary diagnostic tests are avoided, given the potential fore due to failure to promote scientifically reliable public harm that inappropriate testing can give rise to. information. In Britain, a reduction in pertussis vaccina- tion in 1974 was followed by an epidemic of over 100,000 Primary Prevention cases of pertussis and 36 deaths by 1978. In Japan during Primary prevention initiatives vary with the needs of the same period, vaccination rates fell precipitously lead- individuals and populations through the life course, and ing to a jump in pertussis from 393 cases and no deaths include such measures as fortification of staples with in 1974 to 13,000 cases and 41 deaths in 1979. In Sweden, minerals or vitamins, childhood immunization, smoking the incidence rate per 100,000 children aged 0–6 years prevention, contraceptive counseling, nutrition guide- increased from 700 in 1981 to 3,200 in 1985. lines, and eliminating contaminants in air, food and Considered within primary prevention, “primordial drinking water. Primary prevention aims to reduce dis- prevention” refers to measures that address underlying ease incidence by intervening on modifiable risk factors determinants of health that may require policy shifts and or other preventive measures, e.g., health promotion, that related actions. In the language of etiology, this addresses influence the likelihood of disease outcomes. For a classic distal causes, while in terms of natural history it targets example, providing clean water, sanitation, and hygiene the underlying conditions that promote disease onset. As education has been shown to reduce the incidence of di- primary prevention it acts mostly to reduce incidence, but arrheal diseases. does so through more complex chains of causation such Incidence effects are well illustrated by mass vaccina- that its impact is generally less immediate and more dif- tion against childhood infections, which leads typically to fuse. However, all of this can be considered within the Etiology and Natural History in Disease Med Princ Pract 2020;29:501–513 507 Prevention DOI: 10.1159/000508718 operational domain of health promotion, including Secondary Prevention healthy public policy [59, 60]. In many respects, there- This refers to early detection and prompt intervention fore, the distinction between primordial prevention and to control disease and minimize disability. The “iceberg health promotion lies more in its professional constitu- phenomenon” is relevant here, referring to a common ency than its operational approach; thus, the term is en- situation where only a relatively small proportion of cas- countered in some medical specialties, while the term es, the “tip of the iceberg,” comes to the attention of the “health promotion” is more widely understood across health care system. The “submerged portion” includes public health and PHC. The term “primordial preven- disease not medically attended, attended but not accu- tion” is obtuse to the public at large, while the term “health rately diagnosed, and diagnosed but not reported ; it promotion” offers an intuitive meaning to virtually ev- may include inapparent infections (subclinical and incu- eryone. bating cases and carriers, which are significant in the “Health promotion” itself is a broader concept that im- spread of IDs). The proportion of missed cases varies with pinges on all levels of prevention, from primary to ter- disease severity, especially during the early phases of the tiary: “it consists of policies and processes that enable natural history when prevention is more likely to be ef- people to increase control over and improve their health. fective. For examples, the submerged portion for type 2 Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 These address the needs of the population as a whole in diabetes is about 50% in many developed countries; for the context of their daily lives, rather than focusing on psychiatric disorders it may be as high as 80%. Corre- people at risk of specific diseases, and are directed to- sponding estimates are higher for less developed coun- wards action on the determinants of health”. tries. For some conditions such as HIV/AIDS and cancer Much of the current focus of health promotion in- of the cervix, the size of the submerged portion has de- volves a concern for health inequities, and acting on the creased with improved case finding and screening meth- underlying social determinants, e.g., power, money, and ods. resources that give rise to them, e.g., deficits in human The epidemiological outcome of effective secondary rights, literacy, gender equality, opportunity, and related prevention can generally be considered a “treatment ef- needs for a “health in all policies” approach. Keep in fect” – there is no incidence effect, except for reduced mind that, while social determinants are powerful, other secondary transmission of some IDs. The potential for determinants (biological, environmental, health systems) arresting epidemic spread underlies such preventive also influence health and also offer vitally important av- practices as contact-tracing, quarantine, and active treat- enues for intervention. ment. Responsibility for primary prevention is mostly shared Secondary prevention measures fall mostly within two among front-line practitioners and public health staff categories: case finding and screening programs. Such working with communities. It is supported by regulatory practices often include elements of health promotion, for agencies which set standards for air, water, and food qual- example, in child health clinics, in addition to immuniza- ity, and offer specialized functions relating to radiation tion (primary prevention), children may undergo anthro- protection, hazardous products and wastes, and the regu- pometry: parents of children not meeting height and lation of vaccines, drugs, and devices. Similar measures weight norms may then be counseled on aspects of nutri- apply to workplace hazards, their removal, reduction, or tion or referred for assessment. In clinical practice, op- amelioration, e.g., air exchange, temperature control, portunistic case finding during routine or periodic ex- ventilation, protective clothing and equipment, adequate amination may yield previously undetected cases of lighting, and other best practices, thereby comprising a chronic conditions such as hypertension, diabetes, and central role within the discipline of occupational health. cancer, thereby leading to earlier intervention than would They apply in the home: safe handling of food, building otherwise occur. In public health practice case finding is standards, child safety measures, and so on. At times of essential to communicable disease control through “con- threat from epidemic disease and other community expo- tact tracing” individuals who have had close contact with sures, e.g., toxic chemicals, fire, floods, and heatwaves, a diagnosed case of conditions such as tuberculosis, sexu- primary prevention requires timely decisions and prompt ally transmitted infections, COVID-19; it is also em- actions. There is no better example at present than the ployed in investigating foodborne illness to identify those COVID-19 pandemic, where timely action to promote who may be at risk. social distancing has been the most critical step in reduc- While case finding can be considered a normal clinical ing transmission. activity when carried out on the professional judgment of 508 Med Princ Pract 2020;29:501–513 White DOI: 10.1159/000508718 a clinician in consultation with a patient, formal screen- scribed. Selection bias: error due to systematic differences ing programs require a more rigorous decision-making in characteristics between those who take part in screen- process due to ethical, logistical, and natural history con- ing and those who do not: if those differences are associ- siderations. Screening programs are a complex health ated with a better outcome, then the apparent “improve- systems enterprise that may entail significant infrastruc- ment” may be erroneously attributed to the screening ture investment in aspects such as laboratory support, in- program. Lead-time bias: over-estimation of survival formation systems, institutional technologies, and quality time, due to the backward shift in the starting point in assurance. This being so, we must clearly define what is measuring survival, i.e., early diagnosis does not neces- meant by “screening.” Screening is defined as presump- sarily result in improved prognosis. Length bias: selection tive identification of unrecognized disease or defect by of disproportionate numbers of long-duration cases in the application of tests, examinations or other procedures one group (more likely to show up at any point in time, which can be applied rapidly. A screening test is not in- especially if screened) but not in another, i.e., unscreened tended to be diagnostic: it sorts out apparently well sub- people include those with all durations. jects who probably have a disease from those who prob- ably do not. A decision to offer a screening program must Tertiary Prevention Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 be justified in accordance with decision-making rules This consists of measures aimed at mitigating the im- that take into account disease severity and prevalence in pact of long-term disease and disability by: eliminating or a given setting, that the proposed screening test has good reducing impairment, disability, and handicap, minimiz- performance characteristics, e.g., acceptable error rates ing suffering, optimizing function and quality of life, and and predictive values, the feasibility and acceptability of maximizing the potential years of life. Tertiary preven- test procedures including cost and resource implications, tion targets both the clinical and outcome stages of a dis- attributes such as age, sex, family history, and whether ease. It is implemented in symptomatic patients and aims risk factors are present, and evidence of intervention ef- to reduce the severity of disease impacts including associ- fectiveness. Screening programs vary with geographic ju- ated functional sequelae, e.g., diabetic foot care education risdiction depending on epidemiologically defined need and cardiac rehabilitation in post-myocardial infarc- and the availability of technical and financial resources. tion patients. It envisions the preventive act in terms Some are offered to entire cohorts, e.g., antenatal, early of achieving not only a better clinical outcome, but also childhood, occupational groups, while others may be of- in enhancing functional outcomes and restoring social fered to individuals at particular risk, e.g., families with a roles. For example, special care dentistry has emerged as history of particular genetic conditions. a discipline to facilitate oral care for people with intellec- Among the key principles laid out by Wilson and tual and developmental disabilities (IDD) for whom con- Jungner in 1968, in a highly cited document that has ventional dental care presents challenges ; in fact, the stood the test of time, is that “the natural history of the Precede-Proceed model has been applied to an oral health condition, including development from latent to declared strategy for adults with IDD. Thus, tertiary preven- disease, should be adequately understood.” Related to tion aims to encompass broad societal outcomes, e.g., re- this, it has become an ethical requirement of screening ducing stigma in health facilities , harm reduction for initiatives that presumptive identification of disease will addictions , and wheelchair-friendly building designs lead to improved prognosis. Although meeting this over-. More needs to be done in all societies to address such all expectation is a challenging exercise on several fronts, needs in order to improve the quality of life for everyone many screening programs do achieve this status: for ex- affected by functional challenges; while not “treatment” ample, screening for high blood pressure, cervical cancer, in the usual medical sense, the necessary actions at policy and mammography for breast cancer. This duly noted, level require advocacy and leadership from those on the principles for justifying a screening program are not al- front lines of medicine and public health. ways respected by advocates of particular practices for Considering quaternary prevention as a subcategory which the evidence base may be flawed, incomplete, or of tertiary prevention, much of its rationale has emerged controversial; common examples include breast self-ex- from over-medicalization of the elderly [49, 74]. How- amination and PSA testing for prostate cancer. ever, such a perspective is relevant to all patients: people In assessing screening initiatives, the “appearance” of may suffer harm from medical interventions from con- an improved prognosis can arise as a result of bias (sys- ception, through childhood, and indeed during their en- tematic error). The three most common are now de- tire life course. In this broader context, the approach is Etiology and Natural History in Disease Med Princ Pract 2020;29:501–513 509 Prevention DOI: 10.1159/000508718 described as “action taken to protect individuals from vention so far explored has mostly to do with manipulat- medical interventions that are likely to cause more harm ing external environments, while future challenges may than good”. Examples include overtreatment and increasingly turn to human evolutionary biology for a over-diagnosis, and actions include protection from un- more complete understanding. It unlikely that we will necessary and ethically questionable examinations and ever prevent all disease because our capacity to change all interventions. Although the motivation behind this aspects of external environments is limited, as is our ca- movement is to promote best practices, additional impe- pacity to improve the evolved design of the human organ- tus comes from related medical malpractice claims where ism itself. a particular conclusion is of interest: factors that predict Sound preventive approaches tend to build upon one that a patient will resort to litigation include a prior poor another. In fact, the natural history model is compatible relationship with the clinician and a perception that the with other models now in common use, such as Haddon’s patient is not being kept informed. matrix as applied to the design of injury prevention, the Some observers approach these concerns from a sys- Precede-Proceed model that guides health education and tems perspective, focusing on the inevitability of medical promotion initiatives, and the social ecological model errors. By recognizing that such events occur and learning through which strategies are designed, implemented and Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 from them, an effective approach to resolving them re- assessed to ensure that preventive actions are reinforced quires promoting a culture that recognizes safety challeng- at all levels from individual to family, community, and es and implements viable solutions rather than harboring society at large. a culture of blame, shame, and punishment. The Joint Despite the transformation of the model, some bioethi- Commission (a US accreditation body) thereby recognizes cists portray a limited perspective: “…as medicine focuses two major error types: (1) errors of omission as a result of on changing individual’s bodies to reduce suffering, its in- actions not taken e.g., not strapping a patient into a wheel- creasing influence steals attention away from changing the chair, (2) errors of commission due to wrong actions taken social structures and expectations that can produce such e.g., administering a medication to which a patient has a suffering in the first place”. Although the motivations known allergy; stemming from this a typology of errors has behind such a view are no doubt intended to be construc- been developed along with prevention modalities. Be- tive, especially by encouraging attention to the determi- cause errors typically occur from the convergence of many nants of health, such assertions reveal a lack of insight or contributing factors, this builds upon the principle of mul- even awareness of how operational paradigms have already tifactorial causation, where the analysis of modifiable fac- shifted. A basic mischaracterization is to reduce medicine tors may serve as a basis for preventive strategies. to a focus “on changing individual’s bodies.” As discussed earlier, it is the integration across the biopsychosocial spec- trum that completes the clinical picture; while more needs Discussion to be achieved in this direction, this particular assertion is simply archaic, perhaps even a “straw man” – creating a As stated at the outset, etiology and natural history position that is easy to refute, then attributing that position provide a robust framework that serves well to conceptu- to the medical profession. alize illness entities, and ways of intervening in them. More fundamentally, it is incorrect to portray medical Viewing all knowledge as theory, the goal of science is the and public health or health policy interventions as a zero- development of better theories , and research in turn sum game (a situation in which gains to one group or in- is driven by uncertainty surrounding accepted theories. dividual can occur only at the expense of losses else- Thus, the biomedical concept of disease has grown to in- where), and to do so reflects a lack of understanding of clude psychosocial elements critical to functional health. what PHC is actually about. Just because resources are The existence of initially competing paradigms did not allocated to dealing with disease at the level of individuals require that we negate a general theoretical framework does not mean that other disciplines (including public that itself grew out of ancient wisdom and has been health) are thereby impeded from addressing environ- continually modernized. In the 21st century, this evolving mental and social determinants. Although more needs to model remains essential in defining and analyzing illness- be done to address determinants, even with the most op- es, and ways of intervening in them. timal performance of health promotion and prevention This duly stated, what has been reviewed here is by no efforts, people will still need medical care; it is not there- means a unifying theory of disease. The potential for pre- fore a simplistic choice between one or the other ap- 510 Med Princ Pract 2020;29:501–513 White DOI: 10.1159/000508718 proach, but getting the balance right in both developed cades (1972–2014). About two thirds of the mortality de- and developing countries [82, 83]. In support of this, cline was explained by risk factor changes and one third WHO’s Health in All Policies framework emphasizes the by improved treatments. In the contemporary global situ- accountability of policymakers for health impacts at all ation of burgeoning NCDs, the North Karelia experience policy levels, including an emphasis on the consequences offered a powerfully motivating lesson and similar of public policies on health systems, determinants of initiatives were subsequently initiated in some 30 coun- health, and well-being. This in turn contributes to tries of Western Europe and the Americas, and several sustainable development. elsewhere in the world, collectively referred to as the CIN- A core principle underlying population health is that DI-CARMEN-INTERHEALTH network. a large number of people at small risk may generate more Success in creating integrated health promotion and cases of disease than a small number at high risk. Re- disease prevention systems requires vision, leadership lated to this is the “prevention paradox”: a preventive and management skills, and training strategies to support measure that brings large benefits to the community may front-line staff. The process should be guided by evidence offer little to most participating individuals. For example, and supported by monitoring and evaluation. To address to prevent one vehicle accident death, thousands of peo- disease burdens at population level takes vision and long- Downloaded from http://karger.com/mpp/article-pdf/29/6/501/3128006/000508718.pdf by guest on 31 August 2024 ple must wear seatbelts. Applying this principle to cardio- term commitment, measured in decades. All such initia- vascular disease in East Asia, a reduction of just 3% in tives are works in progress, and beyond the scope of this average blood pressure (as might be achieved by sus- review to discuss further; an early review was published tained reductions in dietary sodium or caloric intake) is by the WHO. estimated to reduce the incidence of disease (largely among clinically defined non-hypertensive persons) al- most as much as would hypertensive therapy of all hyper- Conclusion tensive persons in the population. PC medicine, es- pecially in the form of family practice, offers opportuni- Virtually all diseases are the result of interactions ties to improve continuity of care as part of a life-course across our internal and external environments and be- approach to health, where integrated approaches become haviors that may influence the process at any stage from more feasible than with less coordinated and episodic susceptibility and exposure risk to clinical outcome. medical care. It enables people to remain active in the While prevention owes much of its historical success to workforce, helps to sustain household income, and en- the conceptual and applied knowledge that continues to courages people to invest in their own and their children’s flow from the biomedical sciences, as health systems health and well-being. move to address more adequately the spectrum of disor- Integrated approaches may be scaled up to society as a ders now dominating the global burden of disease, we whole, perhaps best illustrated by the North Karelia Proj- must look beyond disaggregated risk factors and determi- ect. Half a century ago, extremely high cardiovascular nants to embrace how these interrelate throughout the mortality in North Karelia (a province in Finland), was of life course, including biological experiences of early life, great concern to its population. In response, the North as well as cultural and social influences. The scientific ap- Karelia project was launched by the Finnish government proach to investigating any condition that affects people’s in 1972. Health policy initiatives included tobacco con- health starts with formulating theories, moves to gather- trol legislation and food industry participation (to reduce ing and analyzing data, then to inferences and interpreta- dietary fat and salt), supported by health education and tions, and closes with knowledge translation to specific promotion, while PC physicians and nurses organized audiences. Constructing and deconstructing, knowledge around detection and intervention on modifiable risk fac- advances in small increments, and so it is with our under- tors at the individual level. After an initial 5 years, this standing of the natural history of disease. strategy was extended to Finland as a whole. The main aims were to reduce extremely high serum cholesterol, blood pressure, and smoking levels with lifestyle changes Acknowledgements and improved drug treatment, especially for hyperten- I thank Debra Nanan for critiquing the manuscript. This review sion. Major declines were observed for serum cholesterol, is dedicated to the memory of our colleague, the late John Murray blood pressure, and smoking. Coronary mortality re- Last (1926–2019) whose epidemiology and public health reference duced in the middle age population by 84% over 4 de- texts are used around the world. His light continues to shine. Etiology and Natural History in Disease Med Princ Pract 2020;29:501–513 511 Prevention DOI: 10.1159/000508718  Conflict of Interest Statement Author Contributions The author has no conflicts of interest to declare. Aside from the references cited, this review is otherwise en- tirely my own work. Funding Sources There was no applicable funding. References 1 White F. 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