Accepted Manuscript

Tuberculosis diagnosis support analysis for precarious health

information systems

Alvaro David Orjuela-Cañón , Jorge Eliécer Camargo Mendoza ,

Carlos Enrique Awad Garcı́a , Erika Paola Vergara Vela

PII: S0169-2607(17)31236-1
DOI: 10.1016/j.cmpb.2018.01.009
Reference: COMM 4596

To appear in: Computer Methods and Programs in Biomedicine

Received date: 6 October 2017

Revised date: 15 December 2017
Accepted date: 10 January 2018

Please cite this article as: Alvaro David Orjuela-Cañón , Jorge Eliécer Camargo Mendoza ,
Carlos Enrique Awad Garcı́a , Erika Paola Vergara Vela , Tuberculosis diagnosis support analysis for
precarious health information systems, Computer Methods and Programs in Biomedicine (2018), doi:
10.1016/j.cmpb.2018.01.009

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Highlights

 Data was acquired from a precarious information system of the Hospital

Santa Clara.
 Medical staff worked together to obtain and analyze the models.
 Two models of artificial neural networks were used to detect the disease
and to cluster the data.
 The proposed method obtained interesting results for applications with
the cited conditions.

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Title Page

Tuberculosis diagnosis support analysis for precarious health information systems

Alvaro David Orjuela-Cañón*

Electronics and Biomedical Engineering Faculty,
Universidad Antonio Nariño,
Bogota D.C., Colombia

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Jorge Eliécer Camargo Mendoza

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Systems Engineering Faculty,
Universidad Antonio Nariño,

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Bogota D.C., Colombia

Carlos Enrique Awad García

Tuberculosis Program,
Santa Clara Hospital,
Bogotá D.C., Colombia
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Erika Paola Vergara Vela
Tuberculosis Program,
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Santa Clara Hospital,

Bogotá D.C., Colombia
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*Correspondence Details:
Address: Carrera 3 Este No. 47A – 15 Bloque 4 Piso 1, Bogota D.C., Colombia
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Phone: (+57 1) 3400135 – (+57) 3006095106

E-mail: alvorjuela@uan.edu.co
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Abstract:

Background and objective: Pulmonary Tuberculosis is a world emergency for the World Health
Organization. Techniques and new diagnosis tools are important to battle this bacterial infection.
There have been many advances in all those fields, but in developing countries such as Colombia,
where the resources and infrastructure are limited, new fast and less expensive strategies are
increasingly needed. Artificial neural networks are computational intelligence techniques that can
be used in this kind of problems and offer additional support in the tuberculosis diagnosis process,
providing a tool to medical staff to make decisions about management of subjects under suspicious

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of tuberculosis.
Materials and Methods: A database extracted from 105 subjects with precarious information of

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people under suspect of Pulmonary Tuberculosis was used in this study. Data extracted from sex,
age, diabetes, homeless, AIDS status and a variable with clinical knowledge from the medical

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personnel were used. Models based on artificial neural networks were used, exploring supervised
learning to detect the disease. Unsupervised learning was used to create three risk groups based on

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available information.
Results: Obtained results are comparable with traditional techniques for detection of tuberculosis,
showing advantages such as fast and low implementation costs. Sensitivity of 97% and specificity
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of 71% where achieved.
Conclusions: Used techniques allowed to obtain valuable information that can be useful for
physicians who treat the disease in decision making processes, especially under limited
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infrastructure and data.

Keywords: Tuberculosis Diagnosis, Artificial Neural Networks (ANN), Self-Organizing Maps

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(SOM), Multilayer Perceptron (MLP), Public Health, Diagnosis Support Systems

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1. Introduction

According to the World Health Organization (WHO), tuberculosis (TB) is a disease considered a major
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global health problem. Around 10.4 million of new cases were reported in 2015, with 1.4 million

associated deaths [1]. For the same year, Colombia had a TB incidence of 24.2 cases per 100,000
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inhabitants; 12,978 reported cases of which 90.2% were new cases. Regions with highest incidence were

Amazonas and Chocó with 72.1 and 45.4 cases per 100,000 inhabitants, respectively [2].

It is known that in both cited regions, as in other developing countries where incidence of TB is

high [1], detection tasks are still a hard work. There, hospital and medical infrastructure used to diagnose

TB is limited, and it is not possible to have sophisticated and elaborated laboratories to achieve minimal

requirements to diagnose TB. According to [2], 73.9% of the cases were confirmed by laboratory, making

necessary to get better resources for improving detection and treatment in primary health of TB.
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According to these challenging conditions, demands to propose new alternatives for TB diagnosis are

necessary, offering to reduce the costs and time characteristics, especially in locations with difficulties to

get better facilities.

Computational intelligence techniques are based on models inspired by biology. For instance,

fuzzy logic techniques work with human semantic to be involved in computing processes, genetic

algorithms use evolution theory to find a solution by solving optimization problems, and artificial neural

networks (ANN) use connectionist models emulating the behavior of the brain [3].

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ANN have demonstrated its ability to find solutions in health problems providing support to

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physicians in diagnosis medical tasks. Studies include ANN with supervised learning, where the objective

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is to detect the disease, establishing a nonlinear mapping between input information and the output (TB

positive or negative), for which the network was trained. Also, there is an unsupervised learning approach

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in which the network recognizes similarities in the input data arranging groups, which can be seen as risk

groups [4, 5].

Considering just the TB diagnosis field, many and different applications have been reported
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around the world. One of the first models was sated by El-Solh in USA [6]. For this study, the author

collected enough information from each subject, including clinical variables, laboratory tests and X-Ray
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images of the thorax. Results achieved 100% of sensitivity and 69% of specificity. In Latin America,

Brazil is the leader using these approaches, where different efforts have contributed to dismiss pulmonary
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TB incidence. Proposals with different input information have been exposed, having results with

sensitivity values upper than 80%, reaching rates of 100% in some cases. For specificity, results have
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been less satisfactory, with registered values that have dropped to 40%, in the worst case [7–11]. All

those results show differences according to available information used in each study. Some studies just
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used a couple of variables, and a very few cases used all medical data of patients. It also depends on the

quality of the information system used for such studies.

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Around the world there are some examples of using computational intelligence models,

especially in developing countries [12–16]. Unsupervised methods have been used to train models that

support the diagnosis process; the most representative works are reported in [10, 17–19], from which the

last two address pleural TB. Very few studies have been conducted with low quality data or with small

datasets. This is a common problem in Colombia, where faraway places do not have enough

infrastructure or information systems that allow to collect enough information with the expected quality.
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ANN models can be trained in a supervised way, where an input-output relation is learned to

extract complex non-linear patterns from the dataset. Multilayer perceptrons (MLP) are models composed

by units known as neurons, configuring a neural network with feedforward connections. Unsupervised

learning models of ANN can be implemented using the Self Organizing Maps (SOM), which were

introduced by Kohonen and Somervuo taking as inspiration the functionality of visual, aural and sensory

areas of the brain [5]. A SOM is widely used to visualize relations between variables in high volumes of

data, in which the architecture is used to represent the data into a nonlinear and reduced new space,

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typically of two dimensions (such as a map). This new space has similar characteristics of the input space,

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highlighting patterns that cannot be easily seen in the input space.

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This paper shows a computational intelligence method, based on ANN, as a tool to support the

TB diagnosis process, where resources for medical systems and specialized infrastructure are precarious

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or do not exist, and hostile environments do not allow to get enough data. In the present case, information

extracted from sex, age, status related with diabetes, homeless and immunodeficiency, combined with a

clinical knowledge was used to train the computational intelligence models. Two approaches were used:
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one based on supervised learning, which helps to detect the disease, and the other one based on

unsupervised learning, which is focused on patients and on treatment management.

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2. Materials and Methods

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a) Database
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Database was obtained from the TB Program at Hospital Santa Clara (HSC) in Bogotá D.C. - Colombia.

The HSC is a public institution with patients with a low socioeconomic status. This population is
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vulnerable and belongs to an area of the city with high overcrowding conditions and risk of sexual

transmission diseases. Commonly, medical consultation of these patients is belated and most of them
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arrive to the hospital as emergency cases.

Information from people under suspect of pulmonary tuberculosis in the period of January 2008

to March 2011 was considered. The Ethics and Research Committee of the HSC approved this study. An

informed consent was not needed because all data were obtained in a retrospective and anonymous mode.

Only data from subjects with confirmed diagnostic were considered (using culture and individuals that

finished the anti-TB therapy). At the end, information of 105 subjects was used: 83 subjects (79%) with

TB confirmed and 22 subjects (21%) that were determined without the disease using diagnosis of
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exclusion. An empirical treatment was started with these subjects. Individuals with confirmed TB

previous to the consultation were not included in the study.

Confirmation of the TB cases was achieved using a culture test. For TB negative cases, tests did

not have a positive culture test, other disease was found meanwhile the treatment, and as mentioned, a

diagnosis of exclusion was used.

Considered information was extracted of subjects with suspicion of TB. A first examination of

signs and symptoms was performed by medical personnel, and a clinical suspicion diagnosis was

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determined. This data was represented in an input variable named “Clinical information”, which takes a

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“1” value when just the medical report was considered, and “0” when other test result or additional

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information lead the subject to start the treatment.

Other included variables were extracted from sex, age, homeless and diabetes status, and HIV

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(human immunodeficiency virus)/AIDS (acquired immunodeficiency syndrome) status. This last was

determined using the study of clinical suggestion and confirming the status with exams, but without

complementary information as CD4 cell or load viral. All variables were coded with zeros and ones
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according to negative or positive, respectively (Table 1). Age variable was maintained as numeric, with

its original information, and a normalization given by the maximum value was achieved. This procedure
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was developed to avoid saturation of values in the synaptic weights of network and to avoid a wrong

representation of the information in training.

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Table 1. Variables used in the study.

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Variable Quantity
Male 72 (69%)
Sex
Female 33 (31%)
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Age Mean + std 40.8+17.7

Yes 30 (29%)
Clinical information
No 75 (71%)
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Yes 28 (27%)
HIV/AIDS
No 77 (73%)
Yes 33 (27%)
Homeless
No 72 (72%)
Yes 2 (2%)
Diabetes
No 103 (98%)

For estimating the statistical error and generalization of the models, using the explained dataset,

a technique of cross-validation was employed [4]. In this technique, the dataset was divided into three sets

ensuring that data from people without and with the disease are equitable distributed. This is performed to
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assess the generalization of the trained model, preserving a portion of data that was not used in training.

Table 2 shows these sets and the number of its members.

Table 2. Dataset division for training

Set TB confirmed patients TB negative patients Total
1 28 7 35
2 28 7 35
3 27 8 35
Total 83 22 105

b) Multilayer Perceptrons

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Commonly, one hidden layer and one output layer are enough to solve classification problems [4]. The

ANN used in this work had an input layer composed of seven units, each one for each variable, and one

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output layer composed just of one neuron. Values of +1 and -1 were used to represent if input data

corresponds to a patient with TB or not, respectively. Neurons in the hidden layer were established in an

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experimental way, testing from two to ten neurons. All neurons had a hyperbolic tangent function as

activation function.
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Between different algorithms to train the ANN, resilient backpropagation was used because its

speed and low computational cost [20, 21]. In training, also a cross-validation strategy was considered. In
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each case, training was performed with two sets (see Table 2) and results for validation were computed

with the left out set, maximizing the classification rate between TB and no disease. To avoid overfitting,
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an early stopping procedure was implemented. Performances of the obtained models were evaluated using

sensitivity, specificity, classification rate, positive prediction, and negative prediction measures. The
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different trainings were performed employing MATLAB 2016a (The MathWorks, Inc, Natrick, MA)

through its Neural Networks Toolbox [22].

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As an additional contribution, a relevance analysis was conducted obtaining the best result [23].

This relevance was computed replacing the original value of the input by its mean value. The procedure
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was done for all the input variables, where it was possible to assess the importance of each variable for

the complete classification system represented by the ANN model.

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Figure 1. MLP model used. Number of neurons in the hidden layer is obtained in an experimentally way.
Font: Authors.

c) Self Organizing Maps

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The training of the SOM was performed in an unsupervised manner in a process of three steps: one of
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them competitive, then a cooperative one, and finally, an adaptive. In this case, competition consisted of

an input vector with information of each patient codified as explained before. This vector was presented
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to the map and compared with the information of synaptic weights of each neuron, choosing the best

matched unit (BMU), and finalizing the competitive step. A radio of neurons was taken up to execute the
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cooperative step, and then the adaptive step was performed to change the synaptic weights of the involved

neurons.
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Before training, SOM architecture must be fixed. In the cooperative step, it is necessary to

provide parameters such as number of neurons, size of the map, type of lattice, and neighborhood
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function. All these parameters obey to experimental rules with some initial information. To build the map,

length and width dimensions of the map correspond to the analysis of the inertias in a Multiple

Correspondence Analysis (MCA), where the ratio of the two first inertias is the same as the ratio of wide

and high dimensions. The initial value of these dimensions decreases until most of the neurons are

activated by the data. Finally, a hexagonal topology of the lattice was chosen because the distance

between the centers of the neurons is the same for all of them.
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According to the medical experience and based on previous works [17, 19], three groups were

proposed maintaining correspondence with the risk of having the disease: high, medium and low. This

was adjusted after SOM training, where the k-means algorithm was applied to create the groups of

neurons. This algorithm works based on distances between neurons given by synaptic weights, and

joining the closest neurons based on three groups [24]. To label each group, the trained map was used for

computing the number of activations for every group of neurons, using data from patients with TB and

without TB from the training data. Then, assignation of the risk was determined by the number of

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activations for these both states (high and low risk). A third group was considered when the number of

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activations in the group was similar for the two states previously mentioned, and then a medium risk was

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determined. The used software to implement the described methodology as MATLAB 2016a (The

MathWorks, Inc, Natrick, MA) and the toolbox employed in [25].

3. Results
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Table 3 shows mean and standard deviation of the results for the three sets used in the cross-validation

technique, and then a 95% confidence interval (CI) was computed. For MLP models, the chosen neural

network had six neurons in the hidden layer according to the best obtained results.
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Table 3. Results for best neural networks models

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(%) MLP (%) SOM

Accuracy 77.5 (+0.7) 85.7 (+2.5)
Sensitivity 97.0 (+0.6) 89.3 (+2.6)
Specificity 71.4 (+1.4) 71.4 (+11.2)
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Using the MLP chosen model, the before mentioned relevance study was implemented,
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obtaining the results described in Figure 2. It is possible to see that the variable with the highest impact is

the clinical information. When this input was replaced by its mean value, the classification rate (TB
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positive/negative) dropped under 75% of accuracy using the MLP model. The same procedure using other

input variables did not show major influence in the results, with classification rates higher than 95%.

For SOM models, the map with the best performance in the three sets was chosen. Figure 3

shows the U matrix, visualizing distances between the resultant map with 4 x 3 neurons. Bluish colors

represent closer locations of the neurons and reddish colors represent the largest distances. In a first sight

it is possible to see three regions in the trained map. One of them in the top area, other in the left-bottom

area and the last one in the right-bottom area.

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Figure 2. Relevance analysis using MLP models. Clinical input was the most relevant for the MLP model.
(M = Male, F = Female, Clinical = Clinical Information, HIV = HIV/AIDS status)
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Figure 3. U matrix for the best SOM model. Colorbar on the right side points out the closeness level
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between neurons.

The k-means algorithm was applied with three regions (k=3), and these regions were labeled.

The map with the colored regions according to the risk is displayed in Figure 4. In the left side (Figure

4a), the labeled map was activated just with data of confirmed patients with TB. The number of

activations are shown with numbers in each neuron. For subjects considered as TB negative, this

information is also avaliable (Figure 4b). Table 4 has the summary of the results for this set. Sensitivity
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and specificity were computed taking the high and medium risk as a method to detect the disease (see

Table 3).

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a) Activations with information of TB confirmed b) Activations with information of negative TB
subjects.
subjects.

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Figure 4. Labeled map. Three regions based on risk were obtained: red (high risk), yellow (medium risk)
and green (low risk).
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Table 4. Activations of neurons in each risk group

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Risk Group TB NTB Total

High (Red) 14 (50%) 0 (0%) 14 (40%)
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Medium (Yellow) 11 (39%) 2 (29%) 13 (37%)

Low (Green) 3 (11%) 5 (71%) 8 (23%)
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Other important information provided by the SOM models are the maps for each input (see

Figure 5). This visual tool is useful to relate the labeled map with each variable. From Figure 4, it was
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established that the right-bottom region of the map represents the high risk. When this information is

compared with the maps of the variables, age and diabetes status variables show elevated values in that
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region of the map. HIV/AIDS status variable has a relation with the low risk group, because its maximum

values are in the same region of the map.

4. Discussion

ANN models had comparable result, with sensitivity of 97% for detecting the disease using MLP models.

These results are better than other methods such as sputum smear (20-80%) and Xpert MTB/RIF ® (88%)

[26, 27]. An advantage of ANN models compared with these methods is the reduced demand of
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requirements in time and general costs. Also, it is possible to implement this support tool using paper or

software resources, where its development and replication can happen in an accelerated way. This is

especially relevant when medical infrastructure is insufficient and there are not specific laboratories to

develop a bacteria culture or there are not Xpert ® machines. The presented method represents an

alternative to laboratory examination.

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a) Male b) Female

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c) Age d) Clinical Status

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e) Homeless Status f) HIV/AIDS Status

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g) Diabetes Status

Figure 5. Maps for each input variable. Colorbar on the right side points out the closeness level between
neurons.
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As a support system, results show that these models can contribute to make decisions about

treatment for patients. To make medical decisions using just a clinical suspicious it can be seen as a

system with 36% of sensitivity. The evaluated models can improve this detection rate, avoiding the use of

results of culture, taking less time to make a final decision about treatment anti-TB.

Differences in the CI estimation were observed between supervised and unsupervised models.

This is due to the use of cross-validation. For MLP models, CI was obtained from one hundred

initializations of synaptic weights for each model, and for SOM models, this value was obtained from the

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three sets used in cross-validation, showing a higher dispersion [5]. In SOM models, it is not common to

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see this kind of validation technique. However, to evaluate the clustering in data, this technique was

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employed to avoid the bias caused by just one model. With respect to results found in other studies [17,

28], the obtained performance is comparable with differences in the validation technique.

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For MLP models it was possible to measure the relevance of the input variables, where clinical

information was the most relevant. The information of this variable was suppressed, and results dropped

around 23% (see Figure 3). This result was the expected since the system is generated as a complement to
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the decision making process, where the medical staff has additional information to send the patient to

treatment. It is known that TB diagnosis is a complex task, and it is not limited to information of just one
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variable [6]. In this case, ANN have the capacity to give a solution with a nonlinear processing that

establishes relations between input data and an output for which it has been trained.
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It is difficult to compare our models in a exactly way with respect to previous results [7–9, 14,

15, 17]. These cited studies treat at least ten input variables, some of them with specific radiologic tests,
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and additional information about patients. As mentioned, data were collected retrospectively, and it is

possible to find bias in them. Incomplete information and false data could modify results, however the
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challenging conditions were considered from the beginning. Currently, new studies including a better way

to collect data are being developed.

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About used variables, experiments developed with different codifications for age were

implemented, dividing all range into age intervals (0-15, 15-60, >60 years old) and assigning one-zero

vectors. These results were not shown in this paper because of its similarity with the presented results. It

was preferred to maintain original age information, just with a normalization process as mentioned.

Maps of age, clinical information, homeless, HIV/AIDS and diabetes status variables showed a

vertical division, compared with sex variable, which has a horizontal division. A variable with higher
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relation with the high-risk group is the diabetes status, but the distance between its values in the map is

short. Behavior of clinical and HIV/AIDS information should be topic of a deeper study. This, because

both maps show an inverse relation between elevated values of the variables and the high-risk group, in

spite of previous studies that show the confounding association [26].

Finally, three risk groups in the labeled map can be useful in management of treatment.

Information of patients that activated the medium risk group can be reviewed with more detail.

Activations of the high and low risk groups indicate to send the patient to the beginning of the therapy

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and to send the patient to home, respectively. In the presented case, and for the shown results, 13 of 35

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patients under suspicious needed more special examination, saving around a third part of time.

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5. Conclusions

Models based on ANN are useful to support the pulmonary Tuberculosis under limited

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resources. In a database analyzed with basic information, MLP can detect the disease reaching a

sensitivity of 97%. Clustering studies using SOM networks allowed to find relevant relations between
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input variables and three risk groups previously established. In this last case, the detection reached 89% in

sensitivity. The tool permitted to find 13 of 35 patients without conclusive diagnostic, needing more
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examinations, saving around a third part of time in the diagnosis process.

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Acknowledgements

This work was supported by the Universidad Antonio Nariño under project number 2016207. Authors
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thank the Hospital Santa Clara for the support in the development of this work.
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Conflict of Interest:

A D Orjuela-Cañón and J E Camargo-Mendoza received research funds from Universidad Antonio

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Nariño. Carlos Awad and Erika Vergara declare that they have no conflict of interests.

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