CHAPTER 5

APPLICATION OF NEURAL
NETWORKS IN PREDICTION OF
LEPROSY DISEASE USING
DEMOGRAPHIC AND CLINICAL
DATA
Abstract

Artificial Neural Network model (ANN) is a powerful tool to facilitate,

classify, analyze and predict an outcome for complex data. This network model has

vast application in various fields such as engineering, manufacturing and medicine.

Now-a-days ANN is broadly used in the medical field for early diagnosis of diseases.

This study attempts to make use of Neural Network in Epidemiological field,

especially in anti-leprosy vaccination trail. Multilayer feed forward perceptron

network and Radial Basis Function were used for diagnosis of leprosy disease. This

study facilitates to compare the performance of two neural networks based on its

accuracy on both training and testing data set. For constructing the network, the

whole data set was divided into inputs and outputs. The demographic, physical and

clinical symptoms were considered as inputs and the outputs are identified as cases

with ‘1’ and non-cases with ‘0’. The original data were divided into training and

testing sample. The training sample was used to develop a model to diagnose the

disease.

Keyword: Artificial Neural Network model, Multilayer Layer Perceptron, Radial

Basis Function

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5.1 INTRODUCTION

Artificial Neural Network (ANN) model is a branch of machine learning

method and its architecture imitates the original functioning of biological nervous

system of the human brain. Early diagnosis or prediction of disease is one of the

most important requirements in the medical field. The Neural network models are

broadly used for this purpose throughout the world. It is used not only in the medical

field, but also in engineering, agriculture, education, business and manufacturing. For

the past three decades, the neural network model is depicted as a better predictive

technique. However, it is rarely used in epidemiological research. Application of

ANN models are limited in the field of leprosy, especially in the phases of diagnosis.

However, the main aim to employ such models is to achieve the accuracy in its

prediction and for being easily applicable in the diagnosis of health problems.

The structure of ANN has logical features termed as neurons or Node s which

involve three major layers with feed forward architecture, the input layer (neurons),

hidden layer and output layer. Neurons in each layer describe the connectivity of

inputs and outputs. The input layer is a set of input units, which receives all the

information from various sources. The input units (neurons) are completely linked

to the hidden layer. Similarly, the hidden layer with hidden units (neurons) is

connected to output layer with output units (neurons). The connection between the

neurons (or Node) is made by weights (Fig. 5.1). Each neuron converts the received

information of inputs to output by multiplying the weights and summing up the

weighted inputs. The output layer sends the information to activation pattern applied

to the input layer [Ganesan. N et al. (2010)].

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Thus

∑ ( ) (5.1)

where O denotes the output, W is a weight element and X is an input element andf is

an activation function.

Fig.5.1 Feed Forward Architecture in Decision Making

INPUTS WEIGHTS SUM OUTPUT

5.1.1 Functioning of Neural Network Model

The activation pattern of the input neurons is to transmit input signal to all the

neurons in the consecutive layer (output layer or hidden layer). Fig. 5.2 represents

the actual functioning of neural networks. Input neurons in input layers are identified

based on the number of independent variables; likewise each output neuron in the

output layer corresponds to one dependent variable. Hidden layers are lying between

input and output layer. The output is obtained by computing input vector with

weights which can be determined through the methods like regression coefficients in

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linear regression. The number of neurons and hidden layers play an important role in

the performance of the network model.

Fig. 5.2 Functioning of Neural Network model

HIDDEN
INPUT
OUTPUT

5.1.2 Types of Neural Networks

In general, the architecture of Neural Network consists of single-layer, multi-

layer feed forward, feed backward and lateral connectivity. This study considers two

network designs; Multilayer Perceptron (MLP) and Radial Basis Function (RBF).

The main difference between these two types is that the parameters of MLP are

nonlinear and that of the RBF is linear [Jayawardena A.W et al. (1997)]. The purpose

of utilizing both networks (MLP and RBF) would be same, but their structures of

manipulation are different. However, MLP network design with Back Propagation

(BP) algorithm is commonly used for involving more than one hidden layer in the

prediction of outcome. This study attempts to use both the approaches to determine

the parameter estimates and to compare the performances of these models in the

prediction of disease.

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5.1.3 Multilayer Perceptron (MLP) design

The significant aspect of MLP design is to fix the number of hidden layers

and the number of units in the layers, since determining the appropriate number of

hidden layers is essential to achieve the accuracy in prediction. MLP design with

error back propagation algorithm choose best parameter estimates out of a set of

parameter estimates obtained from each hidden layer. This method performs the

function of fitting and pattern recognition by using the supervised training

method.

5.1.4 The Network architecture of MLP

A simple structure of neuron of MLP networks is shown in Fig 5.3. The

following mathematical expression can be described as the actual functioning of the

above figure

( ) (5.2)

Wherei is the input vector of the neuron, w is the weights between the

neurons, bis the bias, a is the output signal of the neuron and f is the activation

function of each neuron.

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 Fig. 5.3 MLP networkwith inputs

Source: Rejane B. Santos et al. (2013)

The logarithmic and hyperbolic tangent functions are the most important

nonlinear activation functions for MLP and helps to know nonlinear relationships

between input and output vectors.

5.1.5 Radial Basis Function (RBF) design

A Radial Basis Function (RBF) network is a type of two layers feed forward

network. In the input layer, the input neuron is transformed by a basic function to the

hidden layer and a linear combination of the responses of hidden layer neurons is

added to form the output unit at the output layer. The training methods, supervised

and unsupervised method are adopted for the training of RBF networks. The hidden

layers are trained by an unsupervised learning method and determine the Radial

Basis Function for each Node and the output layer is trained in supervised learning

method [Rejane B. Santos et al. (2013)].

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 Fig. 5.4 Radial basis network with i inputs

Source: Rejane B. Santos et al. (2013)

(| | ) (5.3)

Eq. 5.3 represents the numeric expression of the Fig. 5.4, where i is the input

vector of the input layer and w is the weight of activation function, ||dist|| is a vector

of the distance between the weight and the input vector. The hidden layer consists of

Radial Basis Function which is obtained from a distance between its weight (w)

and the input vector (i) and is multiplied by the bias b[Rejane B. Santos et al.

(2013)].

5.1.6 Significance of Statistical approaches on Vaccination trial

The success of vaccination trial can be assessed without using laboratory

facility by estimating potency of vaccine efficacy. Simultaneously, there is a need to

develop the technique to predict the chances of occurrence of the disease after a

certain period of time. The technique discussed below has been applied in anti-

leprosy vaccination trial; nevertheless it may also be applicable in a trial for any

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other diseases. Identification and prediction of disease are also essential in the field

of evaluation during a vaccination trial against any infectious disease.

The diagnosis of leprosy has become quite complex, since symptoms of the

disease appeared 3--5 years after contracting the infection. Due to this long

incubation period, the diagnosis of leprosy has become quite complex for physicians

to determine when a person is infected. Even though many leprosy patients can be

clinically cured, people often suffer with the consequences such as nerve and skin

damages due to late intervention. In addition to this, standard or prompt approach in

the diagnosis of leprosy disease based on physical and clinical examination may lead

to over diagnosis and misdiagnosis of the disease. To overcome this problem, this

study suggested an alternative approach that varies from conventional statistical

methods when data are multivariate with multi-co linearity between factors. ANN is

a non parametric method which does not make any prior assumption about the

distribution and also it provides highly precise results compared to other regression

models. ANN is more flexible to study large, complex and non-linear relationship

between the factors [Irfan Y. Khan et al. (2013)]. Hence, ANN model enables to

assess the relationship between the factors, hidden manipulation among factors and

predict an outcome or diagnosis of the disease.

5.2 RELATED WORK

Numerous studies have used an artificial intelligence method to obtain a

prediction of outcome for complex problems. Ali A. El-Solh et al. (1999) developed

a predictive model known as the General regression neural network (GRNN) and

compared the predictive accuracy of the neural network with Clinician assessment in

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the study “Predicting Active Pulmonary Tuberculosis Using an Artificial Neural

Network”. In the article “Epidemiologic Interpretation of Artificial Neural

Networks”, it is discussed how a neural network could classify the individuals in a

case-control study and intend to provide an idea about the interpretations of

connection weights from the input layers to hidden layer and hidden layer to output

layer by Mei-Sheng Duh et al. (1998). In another study, Yang Benfu et al. (2009)

constructed the diagnostic model of smear negative pulmonary tuberculosis based on

artificial neural network and confirmed its efficiency in the study “Study on the

artificial neural network in the diagnosis of smear negative pulmonary tuberculosis”.

Qeethara Kadhim Al-Shayea and Itedal S. H. Bahia (2010) analyzed the data

obtained from UCI Machine Learning Repository in order to diagnose diseases in the

study “Urinary System Diseases Diagnosis Using Artificial Neural Networks”. In

this article they showed that the neural network provided significant result in the

diagnosis of urinary system disease. Koushal Kumar and Abhishek (2012)

recommended an approach for diagnosis of kidney stone disease by using three

different techniques, Multilayer perceptron (MLP) with back propagation training

algorithm, Radial Basis Function (RBF) and Learning vector quantization (LVQ) in

the article “Artificial Neural Networks for Diagnosis of Kidney Stones Disease”. In

this article, they compare the performance of all three neural networks on the basis of

accuracy, time taken and size of training data. Mohd Khalid Awang and Fadzilah

Siraj (2013) aimed to evaluate the application of Neural network in predicting the

presence of heart disease, in particular the angina in patients in the paper “Utilization

of an Artificial Neural Network (ANN) in the Prediction of Heart Disease”. In this

paper, they revealed that the artificial Neural Network would give a better diagnosis

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incorporated in the current information system. Irfan Y. Khan et al. (2013)

investigated two acute cases, nephritis disease and heart disease and analyzed

dataset by the feed forward, back propagation neural network with supervised

learning to diagnose the disease in the article “Importance of Artificial Neural

Network in Medical Diagnosis disease like an acute nephritis disease and heart

disease”. They also suggested that ANN is a very flexible and powerful tool in

medical diagnosis.

5.3 METHODS

5.3.1 Setting and Procedure

The study was conducted in Tamilnadu where a large prospective anti-

Leprosy vaccination trial was done. Two consecutive resurveys were conducted from

1993 to 1998 with one and half years to two years of gap. Background of vaccination

trial and availability of individuals during vaccination intake and all successive two

resurveys were described in chapter 3 and chapter 4. Various related studies

determined the predictors such as age, sex, region and other physically and clinically

proved symptoms which were the influencing factors for various diseases in

epidemiology studies. Based on this, we constructed Radial Basis Function (RBF)

and Multi-Layer Perceptron feed forward back propagation network for second

resurvey in this study. In second resurvey (table 5.1), out of 1,21,904; 85,322 and

85,311 individuals were randomly assigned in the training set; 36,578 and 36,586

were randomly assigned in the validation set to construct the MLP and RBF neural

networks respectivley . Information regarding demographic (gender, age, duration of

vaccination), clinical symptoms (obtained from previous resurvey), previous intake

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of BCG vaccine, contact of leprosy at home and vaccination status (vaccinated or

unvaccinated) were assigned as the input to the both networks (figure 5.5 and figure

5.6). The input layer (Figure 5.5) is defined by 13 input units, one hidden layer is

formed by 8 numbers of neurons and the output layer is formed by 2 numbers of

neurons which are classified as diseased (incidence=1) or non diseased (incidence=0)

for first resurvey. Similarly, The input layer (Figure 5.7) is defined by 13 input units,

one hidden layer is formed by 9 numbers of neurons and the output layer is formed

by 2 numbers of neurons which are classified as diseased (incidence=1) or non

diseased (incidence=0) for second resurvey. All independent variables (inputs) were

normalized by scaling the value over a range between zero and one.

5.4 THE OBJECTIVE OF THE STUDY

The main objectives of this study are

(1) To construct the MLP and RBF Neural networks to predict the

occurrence of leprosy disease using the combination of factors as an

input data.

(2) To compare the predictive performance of the Radial Basis Function

(RBF) and Multilayer Perceptron (MLP) neural network models in the

diagnosis of leprosy disease.

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5.5 THE METHODOLOGY OF NETWORK MODELS IN DIAGNOSIS

OF LEPROSY

This study facilitates to compare the performance of two neural network

models based on its accuracy on both training and testing data set. For constructing

the network, the variables of whole data set was divided into inputs and outputs. The

demographic, physical and clinical symptoms were considered as inputs and the

outputs are identified as cases with ‘1’ and non-cases with ‘0’. The original data were

divided into training and testing sample. The training sample was used to develop a

model and the testing data could to assess the performance of models in prediction of

the disease.

5.6 STATISTICAL ANALYSIS

Demographic variables, physical and clinical variables from previous and

current resurveys were used for constructing MLP and RBF neural network

separately. The Sensitivity, Specificity and ROC curve were used to assess the

performance models using validation samples. The performance predictive model

resulting from the both Multi layer perceptron and Radial Basis Function was

evaluated based on validation set. The sample of validation set (30%) is randomly

allotted to the entire data set. A receiver operating characteristic curve (ROC) was

generated from both the suggested models and represented by a diagram obtained

from Sensitivity against Specificity for various thresholds that are used to estimate

the diagnostic accuracy of models. Those measures, Sensitivity and Specificity were

evaluated by estimating the probability of occurrence of leprosy correctly for each

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and every individual, whether infected or not. Here the dependent variable has two

categories and each curve represents at subject as the disease versus other category.

5.7 RESULTS

Analysis was carried out for the second resurvey. The whole dataset of

second resurvey (121904) are classified into the training set (around 70%) and the

testing set (around 30%) randomly for MLP and RBF models as mentioned in the

table 5.1. Out of 1,21,904 dataset, 85,467 are allocated into training set, 36,434 are

allocated into testing set and 3 are excluded due to the missing value for constructing

MLP network. Similarly, 85,248 and 36,649 are allocated into training and testing set

respectively ; and 7 are excluded due to the missing value for constructing RBF

network.

Table 5.1 Selection of dataset for MLP and RBF Networks (second Resurvey)

Radial Basis
Multi LayerPerceptron
Case summary of data Function
selection
N Percent N Percent

Sample Training 85467 70.1% 85248 69.9%

Testing 36434 29.9% 36649 30.1%

Excluded 3 7

Total 121904 100.00% 121904 100.00%

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Table 5.2 Network information of Multi layer Perceptron Layer

Number of units in
14
Input Layer
Input Layer
Rescaling Method Standardized
for Covariates

Number of Units in
5
Hidden Layer
Hidden Layer
Activation Function Hyperbolic Tangent

Dependent
1
Variables
Incidence Rate
Number of Units 1

Rescaling Method
Output Layer for Scale Standardized
Dependents

Activation Function Identify

Error Function Sum of Squares

Table 5.2 depicts the network information of Multi Layer Perceptron model

.The 14 independent variables (including Bias) are given in the input layer. The

hidden layer consist 5 number of units. The output layer consist only one unit,

namely, the incidence rate. Table 5.3 represents the model summary of Multi Layer

Perceptron model. It shows that in training set, the sum of square error is 42,768.124

and the relative error is 1. In the testing set, the sum of square is 17,945.82 and

relative error is 1.001, which is mildly higher than training set.

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Table 5.3 Model summary of Multi Layer perceptron model

Sum of Square Error 42,768.124

Training Relative Error 1

Training Time 00:11.1

Sum of Squares Error 17,945.82

Testing
Relative Error 1.001

Table 5.4 depicts the network information of Radial Basis Function model.

The input layer consists 13 independent variables. The hidden layer consists 10

number of units. The output layer consist only one unit, namely, the incidence rate.

The Table 5.5 represents the model summary of Radial Basis Function model. It

shows that in the training set, the sum of square error is 264.999 and the Percent of

Incorrect predictions is only 0.3%. In the testing set, the sum of square is 102.622

and Percent of Incorrect predictions is as same as training set (0.3% ).

The ANN models are constructed ( figure 5.5 and figure 5.6) using the

characteristics such sex, age, symptoms of the previous resurvey (first resurvey),

duration after vaccination (till second resurvey) and contact at leprosy are

represented in the input layer and the models were designed to generate the output

values ranging from 0 (non diseased) to 1 (diseased).

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Table 5.4 Network information of Radial Basis Function

Number of units
13
in Input Layer
Input Layer
Rescaling Method
Standardized
for Covariates

Number of Units
10
in Hidden Layer
Hidden Layer
Activation
Hyperbolic Tangent
Function
Dependent
1
Variables Incidence Rate
Number of Units 1

Rescaling Method
Output Layer for Scale Standardized
Dependents

Activation
Identify
Function
Error Function Sum of Squares

Table 5.5 Model summary of Radial Basis Function model

Sum of Square Error 264.999

Percent Incorrect
0.30%
Training Predictions

Training Time 00:00:11.404

Sum of Squares Error 102.622

Testing
Percent Incorrect
0.30%
Predictions

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Table 5.6 Classification table of observed and predicted outcome of Multi Layer

Perceptron network Model of second resurvey (without Symptoms)

Predicted

Sample Observed Diseased Non diseased Total

Diseased 0 271 271

Training Non diseased 0 85,196 85,196

Total 0 85,322 85,467

Diseased 0 101 101

Testing Non diseased 0 36,333 36,333

Total 0 36,578 36,434

Table 5.7 Classification table of observed and predicted outcome of Radial Basis

Function Model (without Symptoms)

Predicted

Sample Observed Diseased Non diseased Total

Diseased 0 266 266

Training Non diseased 0 84,982 84,982

Total 0 85,248 85,248

Diseased 0 103 103

Testing Non diseased 0 36,546 36,546

Total 0 36,649 36,649

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Table 5.8 Area under the ROC Curve (second resurvey without Symptoms)

MLP RBF
Incidence Rate Others 0.67 0.611
Incidence 0.67 0.611

Classification of observed and expected values of second resurvey without

symptoms of both MLP and RBF neural networks are represented in the table 5.6 and

table 5.7. In which, the suggested models are not able to predict the disease category

in second resurvey. At the same time, we can assess the performance of models

Multi Layer Perceptron and Radial Basis Function models through the values 0.67

and 0.61 respectively (table 5.8) of area under the curves achieved by the ROC

curves (figure 5.6 and figure 5.8).

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 Figure 5.5. The Network diagram obtained using MLP Network for second

resurvey (without symptoms)

Foot note: PP1- Presence of Patches in First resurvey, NP1- Number of Patches in
First resurvey, PLS1-Patchy loss of Sensation at First resurvey, IS1- Infilteration of
Skin in First resurvey, OD1- Overall Deformity in First resurvey, CC0 – Contact
with Leprosy patients at intake, CC1- Contact with Leprosy patients in first
resurvey, CC2- Contact with Leprosy patients in second resurvey, Dur-2, Duration
at resurvey2

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Figure 5.6 Receivers Operating Characteristic Curve obtained for Predicting

performance of MLP network for second resurvey(without Symptoms)

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 Figure 5.7 The Network model obtained using Radial Basis Function of second

resurvey (without symptoms)

Foot note: PP1- Presence of Patches in First resurvey, NP1- Number of Patches in
First resurvey, PLS1-Patchy loss of Sensation at First resurvey, IS1- Infilteration of
Skin in First resurvey, OD1- Overall Deformity in First resurvey, CC0 – Contact
with Leprosy patients at intake, CC1- Contact with Leprosy patients in first resurvey,
CC2- Contact with Leprosy patients in second resurvey, Dur2- Duration at
resurvey2

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 Figure 5.8 Receivers Operating Characteristic Curve obtained for

Predictingperformance of RBF network for second resurvey (without Symptoms)

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5.8 DISCUSSION

According to the available literature, this is the first study endeavored to

utilize the neural network for the diagnosis of leprosy. The review of various

literatures revealed that this predictive model provides a high level of Sensitivity and

Specificity in prediction of various diseases. In one such study, [Ali A. El-Solh

(1999)] a general regression neural network (GRNN) was used to develop the

predictive model in the diagnosis of active pulmonary Tuberculosis that identified

the patients more accurately than clinical assessment. The neural network model had

achieved the Sensitivity of 100% (95% CI, 72--100) and Specificity of 69% (95% CI,

61--78) with the predictor variables, upper zone disease on chest roentgenogram,

fever, weight loss, etc.,. In a similar study, the neural network model was used in

diagnosing smear negative pulmonary tuberculosis (SNPT) and it achieved the

accuracy, Sensitivity and Specificity of 93.10%, 88.89% and 100%, respectively

[Yang Benfu (2009)] . In which, they had defined personal and clinical information,

medical histories, chest X-rays and clinical laboratory results as input variables to

construct the model.

In the same year, two different studies evaluate the performance of neural

network model in prediction of heart disease. In the first study, they identified eight

important variables, including family history of premature CAD, smoking,

cholesterols, hypertension, diabetes mellitus and hyper- chilseteroemia that were the

major risk factors of anginha . In this study, the model achieved the prediction

accuracy of 88.89% [Mohd Khalid Awangand Fadzilah Siraj(2013)]. In the second

study, Feed-forward, back propagation neural network is used as a classifier to

distinguish between infected and non-infected person in acute nephritis disease and

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heart disease. Here also the symptoms such as temperature of patients, occurrence of

nausea, lumbar pain, urine pushing, micturition pains and images of Cardiac Single

Proton Emission Computed Tomography (SPECT) were considered as input

variables for construction of the model [Irfan Y. Khan, P.H. Zope, S.R. Suralkar

(2013)]. However, neural network models performed well when compared with other

predictive models, while predicting or diagnosing of disease and proved physical and

clinical symptoms were playing a vital role in achieving the model’s accuracy.

The scenario of the current study is different from previous mentioned

studies. First point, the majority of the diagnosis of Leprosy is made through the

Physical and Clinical symptoms of disease, the study is not supposed to be

considered the symptoms of the current resurvey. And the second point, the study

consists such a large dataset (1,21,904 in second resurvey) with the meager

occurrence of disease (372 in second resurvey). In this situation, the study had

attempted to generate the models (both MLP and RBF) to the diagnosis of leprosy at

second resurvey. In the case of the constructing the model without symptoms, the

variables such as age, gender, previous intake of BCG vaccine (through the presence

of a scar), vaccination status (either received vaccine or placebo), duration from

vaccination and symptoms (observed of previous resurvey) were assigned as the

input variables into the models.

If the number of occurrence of disease and occurrence of non disease are

equally distributed, the models can predict the leprosy using probability of

occurrence of disease with demographic and clinical variable alone (without

symptoms). Addition to this, as discussed in the previous chapters, some of the

explanatory variables are not seems to be a significant association with the

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occurrence of disease (Leprosy), the suggesting network models also could not give

better prediction ( table 5.6 and the table 5.7) in such a large cohort study with rare

occurrence of diseases. Figure 5.4 and figure 5.6 had shown the structure of

Multilayer Perceptron Layer and Radial Basis Function network model, while we

construct the models without symptoms. Instead of this, if we observe the ROC

curve; it gives us a visual display of the Sensitivity and Specificity. It shows 0.67 and

0.611 (table 5.8) predicted pseudo-probabilities of the area under the curve. The

classification tables showed that the predictive models are considerably better at

predicting non-cases than cases where symptoms were considered as predictor

variables.

5.9 LIMITATION

1. Though the Artificial neural network proved as an efficient model in

prediction of any other diseases, the current study unable to predict the

leprosy without symptoms.

2. The suggested models seem to be insignificant while constructing the model

for large set of data with too little occurrence of disease.

5.10 CONCLUSION

The artificial intelligence approaches do not provide better results in the

prediction of Leprosy, especially the rare occurrence of disease for large datasets.

This study has revealed that the performance of Multilayer perceptron and Radial

Basis Function found to be insignificant in the prediction of leprosy.

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