R. P. Deolankar

Welcome to the series of lectures on Disease Informatics• Disappointment by research bodies to solve the

real disease problem is because of not having perception of disease complexities

• Diseases have been defined in a simple manner leaving several targets for combating disease unattended

• IT applications simplify complexities and could provide better definition of diseases

• Informatics professionals need to be facilitated for development of software for disease study using standard guidelines

“Clean bowled” is not the complete cricket• Clean bowled: Current – one cause one effect --

disease definition permits dismissal of the batsman (say viral disease) only by the ball bowled by the bowler hitting the wicket (say virus; the component cause of the disease that is considered as the complete cause)

• Out: The treatments given by family physician based on his clinical diagnosis also permit the dismissal of batsman if the ball hit by the batsman is caught, by lbw, run out, stumped etc (described as targeting super-component in later slides)

• Logic: To win the game team must be balanced. Team of only bowlers, only batsman, only wicket keepers, only captains or only umpires is a joke

Prerequisite for this lecture• Lecture no. 25371 DIG for Disease Informatics Group.

Part I • Lecture no. 25381 DIG for Disease Informatics Group.

Part II• Lecture no. 28921 Disease Informatics: Host factors

simplified• Lecture no. 30331 Disease Informatics: Phytates

driving from the back-end to Influenza, Encephalitis, Hepatitis, Anemia at the front-end.

• Lecture no. 31981 Disease Informatics: ICD-11 at the doorstep

• Lecture no. 34011 Disease Informatics: Terms and Jargon to begin with

• Lecture no. 34141: Disease Informatics: Brush up the terms describing techniques and resources

Importance of “Family Physician”

Draws a mental picture of Disease Causal Chain (DiCC) of a patient by:

• Recording clinical history, performing clinical check up and treating individual

• Predicting disease that could occur in future and planning prevention of further disease or complication

• Keeping confidential the diagnostic information of a particular patient

Background begins

Public Health professionalFocuses on community health protection and

improvementHas to define disease broadly and openly Disease definitions should fit to population

and environment rather than individualSubject matter of Epidemiology is covered

under Public Health

Epidemiology and public health• Epidemiologist is an investigator• Investigates Disease Causal Chains of patients

drawn by family physicians (clinicians) to arrive at accord and discord of the disease continuum

• Studies associations and establishes relationship of risk factors of diseases

• On the basis, tries to find out component causes and sufficient causes of the diseases

Genuine epidemiologist interacts with Family physicians (clinicians)• Genuine Epidemiologist keeps rapport with

Clinicians to share inferences drawn from cases and try to understand chain of events of diseases

• Epidemiologist share risk factor information and elaborates which factors drive the disease from backend to frontend

• This interaction permits drawing of hypothetical cause and effect diagrams to be verified by performing experiments

Disease informatics• Disease Informatics is the application of

Information Science in defining the diseases with least error, identifying most of the targets to combat a cluster of diseases (Disease Causal Chain) and designing a holistic solution (Health strategy) to the problem.

• Researchers, Health workers, Clinicians, Epidemiologists and Public Health personnel benefit from and contribute to the Disease Informatics

The first logical step of disease investigation; know the remarkable events• Standard terminology can be used by Setting

aside the combination terms (anatomical + physiopathological) from MeSH database of NCBI to provide the database for events occurring in the Disease Causal Chains

• Identify most of the targets to combat a cluster of diseases in a command area

• Achieve this by horizontally studying the clinical histories of sample cases or by identifying the clinically remarkable events in a cross section of the community

The second step; sequence the events• It needs to be known the sequence in which

events occur• It is also of the interest to know which factors

drive the disease processes from the backend events to the frontend events

• Make cause and effect diagrams (fish bone)• The causal factor components could be pooled

in a pie diagram to explain various sufficient causes of the diseases

What is a case? (In simple words)

Case is a person, case represents some characteristics useful in the investigation

Normal case = Normal personDisease case = A person showing features of

a diseaseNon-case = A person not showing features of

a disease

Case for a Public health studyStudy subjects in a Public Health Study are

casesMight comprises at-least two types of cases;

Normal cases + Disease casesThe normal case is likely to be defined by the

investigatorThe disease case (deviation from normal)

goes naturally

Inclusion and exclusion criteriaWhich cases are to be included in the study?

There are criteria that must be met by the cases for inclusion in the study

Which case is to be excluded?The cases that would be considered as non-cases by a certain criteria

Case definition

Case definition of a disease is a description of diagnostic criteria of the diseaseSometimes required in public health study

Disease in an individual case is:Disease defined by the case definition + “something more”

Disease continuum• How to infer the disease if certain persons show

immunodeficiency syndrome like AIDS without being HIV+ve?

• Generally speaking, Continuum = “case definition” + something more. Continuum is a whole; covers cases sometimes not conforming to the standard case definition.

• Let us call this “set of something more” as a super-component X (that covers component causes of the disease not covered in the case definition)

• Components within super-component-X might vary from an individual to individual

Solution to the disease through Super-component X • It is thought that chicken soup has no antiviral

factor but has natural healing powers for the common cold!!! Does it modulate super-component-X

• Several nutraceuticals and functional foods work in this manner and are broad based treatments

• Disease definition for a disease of an Individual ≠ Disease definition prepared for public health purpose

Ayurveda, Siddha, Unani, Yoga and super-component-X• The Ancient Indian Medicine provides pre-seasonal

treatments (shodhan) to uproot seasonal infections and diseases rather than performing pruning operation on several diseases at the front end during season

• Unlike antiviral Oseltamivir, age-old medicines (like Tribhuvan Kirti) tackling non-viral component causes provide relief in several patients having Flu and Cold

• Daily routine (Dinacharya) and seasonal lifestyle (Ritucharya) recommended in old days to prevent diseases could be redefined to suit modern life

T1 ≠ T2 and also CD1 ≠ CD2 Patient (P1) reports relief from a viral disease

(D1; laboratory diagnosis provided by the super-specialist virologist) through a treatment (T1) given by family physician of P1 on the basis of the clinical diagnosis (CD1);

Patient (P2) exhibiting the disease D1 given T1 by the associate physician of the virologist fails to respond

P2 then also finds relief by another treatment (T2) given by his family physician on the basis of his clinical diagnosis (CD2); why?

Treatment of an individual depends on more elaborate definition of the disease • Treatment of viral encephalitis using

hormones in a case when hormone deficiency is not part of the case definition

• Treatment of viral diarrhea using enkephalinase inhibitor in a case when enkephalin deficiency is not part of the case definition

• Treatment of constipation using prebiotics in a case when dysbiosis is not part of the case definition

Grades of disease definitionUsually case definition describes what is

normal, suspected, strongly suspected, probable and laboratory confirmed case

This description vary from study to study by having or not having certain component causes and also description of the severity of the disease

Effect modificationThe odds ratio between cigarette smoking

and lung cancer may be smaller among individuals who consume large quantities of beta carotene in their food when compared to the analogous odds ratio among persons who consume little or no beta carotene in their food; this modification could be in an additive manner

Multiplicative interaction• Poverty (represented by under-nutrition, unsafe

water and sanitation, and use of solid fuels are more common among poor rural households in developing countries) might interact with infectious etiology in a multiplicative manner; represents statistical interaction

• Mortality attributed to the rotavirus gastroenteritis is largely seen in developing countries rather than developed countries

• Under-nutrition is the single leading global cause of health loss

Complex of risk factorsZinc deficiency affects mortality from diarrhea

directly It also affects mortality by reducing growthIt may also be correlated with underweight,

other micronutrient deficiencies, and unsafe water and sanitation

This might be a combination of effect modification (additive effects) as well as statistical interaction (multiplicative)

By and large effect modification and statistical interaction are used synonymously

What is burden?• Burden is load or taxing on individual or family

or society or Nation or the globe• It could be cultural, chemical, pathological,

economic, social or socioeconomic• Disease burden is judged against disease events• Disease burden could be due to factors driving

from backend to frontend event of a Disease Causal Chain

• Disease investigator needs to understand variety of burdens

The subject begins

Utility of estimating Disease BurdenImportant input to health decision-making and

planning processesProvides a framework for integrating,

validating, analyzing and disseminating information needed to assess the comparative importance of diseases, injuries and risk factors in causing premature death, loss of health and disability in different populations

Body burdenBody burden is the load of foreign chemicals

in the bodyMost of the chemicals could be toxicSome of these chemicals could alter the

functions of genesSome of these could disrupt endocrine system

Burden of disease = Measurement of load or taxing due to disease in a population

Prof. Alan D Lopez

Dr. Colin D. Mathers

Dr. Majid Ezzati

Prof. Dean T. Jamison

Prof. Christopher J. L. Murray

Burden of diseaseUnit of measurement for Burden of disease =

DALYDALY means Disability-Adjusted Live Year

Unit of measurement of benefits from intervention = QALYQALY means Quality-Adjusted Life years

DiseaseHealth is compromised due to diseasesDiseases lead to death and / or disabilityQuality and quantity of life is reduced due to

diseaseMortality + Disability is proportional to the

quantity of disease

Disability

Disability = Shortfall in an ideal health status = an ideal health status – actual health status

DALY

DALY = Life lost due to premature mortality + Years of life lost due to time lived in states of

less than full healthOne DALY = One lost year of "healthy" life

DALYs across the population Sum of these DALYs across the population =

Burden of diseaseTop health = Least burden of diseaseLeast burden of disease → living to an

advanced age, free of disease and disability

YLLYears of Life Lost due to premature mortality in the population YLL = N * LWhere:YLL= Years of Life Lost due to premature mortality in the populationN = number of deaths L = standard life expectancy at age of death in years

Severity of the diseaseSeverity of the disease is to be scaledScale for weight factor for severity of disease isFrom 0 to 10 implies perfect health1 implies death

Disease definitionDisease is usually defined by case definition that depends on

CausationThe disability weightThe population incidence and Prevalence

YLDThe Years Lost due to Disability (YLD)YLD = I * DW * Lwhere: I = number of incident cases DW = disability weight L = average duration of the case until remission or death (years)

Disease mechanismYLD is estimated by causeFor a particular disease there are several

disease mechanismsEach mechanism is composed of several

component causesThere could be several case definitions for a

particular disease

DALY = YLL + YLD

DALY’s are calculated for disease or health condition

It is sum of Years of Life Lost (YLL) due to premature mortality in the population andThe Years Lost due to Disability (YLD) for incident cases of the health condition

DALY = YLL + YLD

Disease eventUsually it is described by signs and symptomsPathophysiological changes at certain

anatomical locationRoot causes are generally categorized as

genetic, environmental or etiological

Clean hands save lives• You may not find Panacea but you could probably

find intervention to prevent several diseases• Hand-washing has been shown to cut the number

of child deaths from diarrhea (the second leading cause of child deaths) by almost half and from pneumonia (the leading cause of child deaths) by one-quarter

• Reference: Global Hand-washing Day: 15 October, Planner’s Guide

• Conclusion: Backend measures uproot the disease while front end measures prune the disease

Interventions against diarrheal disease

Cost in proportion to hygiene promotion

• Cholera immunizations 1655• Rotavirus immunizations 1627• Measles immunization 804• Oral rehydration therapy 450• Hygiene promotion

(including hand washing) 1Reference: Global Handwashing Day, 15 October, Planner’s Guide

Economic developmentHygiene promotion α economic developmentLower infant mortality rates α higher economic growth WHO estimates that a 10 year increase in average life expectancy at birth translates into a rise of 0.3 – 0.4% in economic growth per year

Sanitation and hygiene, and diarrhea vaccine

• Good sanitation and hygiene prevents invasion of several “disease causing microorganisms”

• Monovalent vaccine causes selective invasion to prevent multiplication of a single serotype / species of microorganism in a responsive patient. The commercial life of vaccine may last till the microorganism mutates to gain resistance to vaccine

• Hence, backend measures uproot the disease while front end measures prune the disease

Transmission of the disease (!)

Whatever is transmitted is not the disease but the component cause of the disease in a predisposed patient

The transmission results in specific immunity in resistant individual and subclinical or clinical infection in a susceptible case

SusceptibilityThe susceptibility to the disease is due to the

host and/or environmental factorsNon-response to vaccine could also be due to

the host and/or environmental factorsThe policy of research for so called

communicable diseases should be primarily based on creation of healthy “environment” or healthy “host X environment” interaction

Vaccine policyHence “vaccine” in general is not a substitute

to creating healthy “environment” or healthy “host X environment” interaction; it is complimentary

Poor vaccine policy could be the result of lack of application of disease informatics

Inductors of probiosis provide “environmental vaccines”

• Could reduce hostility of environment (microecology)

• The gut, vaginal or body environment could be altered by induction of probiosis

• Evading the factors that cause dysbiosis could be an inexpensive method in bringing down disease burden

• Should it be part of primary research policy for research?

Oral Polio Vaccine goes oral to environmental• Prepared using a live, attenuated virus, used

during pulse polio campaign• Excreted vaccine virus is expected to spread

through water• Vaccinee potentially precludes transmission of

the wild poliovirus to other hosts • Could an arboviral vaccine virus be

disseminated through mosquitoes for prevention of arboviral diseases?

Thank you