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Screening for Tuberculosis among Household Contacts of Index Patients.

Byline: Rizwan Iqbal, Kashif Munir, Saira Bashir, Ambreen Arif, Masood Hussain Rao, Ahsanullah Mirbahar, Tasleem Akhtar, Rukhsana Firdous and Muhammad Asim

Abstract

Background: Household contacts of sputum positive pulmonary TB cases are at a high risk of getting infected with tuberculosis therefore symptomatic or vulnerable individuals should be screened and treated early.

Objectives: To determine the prevalence of pulmonary tuberculosis in the households contacts of index patients having pulmonary tuberculosis infection using standard diagnostic tests and refer the positive cases to DOTS program for treatment. Study type, settings and duration: This national descriptive study was conducted in seven Centers of PMRC throughout Pakistan form November 2010 to March 2012.

Subjects and Methods: A total of 580 index adult patients suffering from pulmonary tuberculosis, being treated at DOTs Centers of major tertiary care hospitals of Karachi, Lahore, Multan, Peshawar and Quetta living within 5-8 kilometers of the hospital, who consented to participate in the study were selected from the DOTs centres. Generally one but occasionally two close contacts of these index patients (spouses, parents or siblings) were called to the hospital for screening of TB using chest X- ray, smear microscopy and tuberculin skin test.

Results: Out of 800 contacts screened, 125 (15.6%) were positive on sputum smear examination while 113 had infiltration on X-rays along with positive tuberculin skin test (Indurations of greater than 10 mm) making a definitive diagnosis of TB. Calcified lesions were seen on X-rays in another 91 cases giving evidence of past infection, however 26 of these were AFB positive indicating either the relapse of disease or active lesion. Low grade fever and weight loss were the most significant findings in contacts that were positive on sputum smear and radiology.

Conclusion: Almost 15.6% household contacts of pulmonary tuberculosis patients have pulmonary tuberculosis.

Policy message: Health care providers in general and DOTs staff in particular should be trained to inform all index cases that their close contacts especially those suffering from weight loss and fever should be screened for tuberculosis and treated if required.

Key words: Pulmonary tuberculosis, close contacts, sputum smear positive.

Introduction

It is estimated that 8.5 million cases of pulmonary tuberculosis occurred in year 2000 including 3.5 million sputum positive cases with 1.9 million deaths1. Tuberculosis if not diagnosed and treated properly can lead to multi drug resistance tuberculosis (MDR)2. Centre for disease control (CDC) therefore planned for the elimination of TB by reducing it by one case per million populations by the year 20103.

The first priority of tuberculosis control program is to identify and treat all persons with active tuberculosis4. The second priority is search for contacts who were exposed to TB patients. The contacts need to be evaluated for the extent of disease and active treatment of TB if required5. The guidelines for investigation of TB patients were published in 1976 and were updated in 2005 and these provide expanded plan for individuals who are exposed to TB patients and in whom transmission of disease is suspected6,7. Transmission of TB mostly occurs from sputum positive cases of pulmonary tuberculosis, laryngeal TB cases and sputum negative pulmonary tuberculosis patients having cavitatory lesions on radiographs8. Various studies have reported that high smear positivity and cavitatory lesions can more likely transmit infections and thus causing tuberculin skin testing positive in contacts and prevalence of active TB in these suspects is between 1.2% to 1.5%9.

Tuberculin skin testing and clinical evaluation of the contacts should be done promptly after a suspected case of infectious TB is reported particularly in young children, immune compromised patients and others who are at greater risk10. A tuberculin skin testing (TST) was considered positive when an induration equal to or greater than 10 mm diameter was detected. A patient was considered newly infected when there was an increase in the reaction of at least 10mm compared to the previous reaction measurement11.

A household contact was defined as a group of people living within one residence who share meals together, for at least 30 days prior to the diagnosis of tuberculosis in the index case who was defined as the first tuberculosis case identified in the household12.

To generate national data on the disease in the house hold contacts, this study was carried out at seven PMRC Centre's located throughout Pakistan in which 800 contacts of 580 sputum smear positive index patients were studied.

Subjects and Methods

This descriptive study was done over a period of 15 months and was conducted at 7 PMRC Research Centres located in public sector territory care hospitals of Pakistan where TB DOTS Program is available. These included 2 in Lahore (FJMC and King Edward Medical University), 2 in Karachi (JPMC and DMC), one each in Multan (NMC), Peshawar (KMC) and Quetta (BMC).

Patients suffering from pulmonary tuberculosis that were positive on sputum smear microscopy at the above mentioned sites and seeking treatment from DOTS Centers were selected as index case. Contacts were defined as household members living with index cases for more than 30 days and whose age was above 14 years13. One to two close contacts from each index case were screened for TB using X ray chest, sputum microscopy and tuberculin skin test through the research support.

A tuberculin skin test was considered positive if it was 10mm or greater12. X-ray chest showing infiltration along with cavitatory lesions was taken as a positive finding for diagnosing pulmonary tuberculosis. Sputum smear examination was done using Zeihl Nelsen (ZN) method. The study was approved by ethical review board of KEMU/Mayo hospital, Lahore, and written informed consent was taken from contacts. Patients already taking treatment for tuberculosis were not included.

A total of 580 index patients were selected and their distribution all over the country was done using population census (Demographic survey 2002). There were 320(55%) patients from Punjab, 140(24%) from Sindh, 80(14%) from KPK and 40(7%) from Baluchistan. About 800 contacts of these 580 index patients were screened for active and passive tuberculosis their distribution was 450 from Punjab, 200 from Sindh, 100 from KPK and 50 from Baluchistan.

AFB sputum smear positive patients of pulmonary TB were selected as index patients from TBO3 register which is a record of TB patients in DOTS program. Two researchers were recruited from each centre to collect data. One member filled questionnaire of Index and contacts while other injected tuberculin whose results were read after 48 hours. Sputum examination of the contact was done at DOTS centre, and X-ray chest was done at the hospital. Those found positive on sputum smear examination were referred for treatment from DOTS. Questionnaires from all centres along with X-rays were collected at TB research centre, KEMU, Lahore for entry and analysis. Data was entered and analyzed by using Statistical Package for the Social Sciences version 15.0 (SPSS) software.

Results

A total of 580 index patients and 800 close contacts were studied. The average age of index patients was 34.9 +- 17.4 years (range 15 - 85 years). Average age of index patients was slightly younger in the Sindh (30.2 +- 15.3 years) as compared to other provinces but the average age of contacts was almost same in all provinces.

Gender distribution of index patients was almost same in Punjab while, more females were seen in Sindh (60%) and Baluchistan (85%). Same trend was seen for contacts in Baluchistan and KPK.

Table-1 shows that 32% index patients had family history of tuberculosis which was highest in Baluchistan (75%) followed by KPK (47%).

Table 1: Family history of tuberculosis in Index patients.

Family History of Tuberculosis

PMRC Research Centers###Absent###Present

###n###%###n###%

KEMU, Lahore###113###80.7###27###19.3

FJMC, Lahore###88###83.8###17###16.2

NMC, Multan###38###50.7###37###49.3

Punjab###239###74.7###81###25.3

JPMC, Karachi###48###68.6###22###31.4

DMC, Karachi###58###82.9###12###17.1

Sindh###106###75.7###34###24.3

KMC, Peshawar, (KPK)###42###52.5###38###47.5

BMC, Quetta (Baluchistan)###10###25.0###30###75.0

Total###397###68.4###183###31.6

Family history of diabetes was most common in KPK while other medical problems were maximally seen in Baluchistan (72%).

Table 2: Duration of contact in years with index patients by center and province wise.

PMRC Research Centers###Duration of Contact with Index Patient (Years)

###Mean###S.D###Min###Q1###Median###Q3###Max

KEMU, Lahore###18.97###8.15###0.08###15.00###18.00###22.00###50.00

FJMC, Lahore###18.33###12.52###0.17###6.00###19.00###28.00###52.00

NMC, Multan###21.78###9.08###0.08###17.00###20.00###25.50###50.00

Punjab###19.38###10.07###0.08###15.00###19.00###25.00###52.00

JPMC, Karachi###17.96###8.12###0.08###16.00###18.00###21.50###42.00

DMC, Karachi###18.21###8.24###0.17###16.00###18.00###22.00###40.00

Sindh###18.08###8.16###0.08###16.00###18.00###22.00###42.00

KMC, Peshawar, (KPK)###14.14###8.89###0.08###6.50###15.00###20.00###45.00

BMC, Quetta, (Baluchistan)###7.44###9.91###0.08###0.50###1.18###15.00###45.00

Total###17.65###9.96###0.08###13.00###18.00###23.00###52.00

Table 3: Relationship of contacts with index patients by center and province wise.

PMRC Research Centers###Father###Mother###Spouse###Brother###Sister###Son###Daughter###In Laws###Others###Total

KEMU, Lahore###19###36###23###41###28###15###18###6###14###200

FJMC, Lahore###5###12###43###10###11###40###16###10###3###150

NMC, Multan###8###16###21###9###6###17###8###6###9###100

Punjab###32###64###87###60###45###72###42###22###26###450

JPMC, Karachi###14###22###16###8###12###7###7###8###6###100

DMC, Karachi###10###22###22###13###3###12###7###9###2###100

Sindh###24###44###38###21###15###19###14###17###8###200

KMC, Peshawar, (KPK)###8###20###21###10###11###18###3###4###5###100

BMC, Quetta,(Baluchistan) 1###8###7###4###3###5###9###9###4###50

Total###65###136###153###95###74###114###68###52###43###800

Almost 20% index patients were smokers and 13% had other addictions. Cigarette smoking was maximally seen in Punjab and KPK while other addictions were highest in Baluchistan. Most of the index patients (72.4%) were illiterate, with majority belonging to Baluchistan (92.5%) followed by Sindh (52.9%). In KPK 25.1% undergraduates and post graduates were suffering from TB.

The median (Inter-quartile range) family size was 8 (6-10) for index patients. The largest family size was 11 (9-15) in Baluchistan and smallest 7 (5.5 - 9) in Punjab. The minimum family size was 2 and maximum 52 members. Mean duration of contact was 17.56 +- 9.96 months (range 1month to 52 years) with a median of 18 years with inter-quartile range between 13 and 23 years (Table-2).

In Baluchistan 18 persons had history of contact of less than a year. while in all other provinces it ranged between 11 and 25 years. Spouse (husband or wife) was the most common contact followed by mother and son (Table-3).

In the contacts the commonest symptoms were cough (41%) followed by expectoration, low grade fever, anorexia and weight loss (Table-4).

Chest X-ray showed infiltration in 113(14.1%) contacts which was highly suggestive of TB infection, 91(11.4%) had calcified lesions indicating some old infection while remaining 596(74.5%) had normal chest X-rays. The highest X-rays positivity was seen in Baluchistan (Table-5).

Table 4: Tuberculosis related symptoms in contact persons.

###Cough###Expectoration###Low grade fever###Weight Loss###Anorexia

###n###%###n###%###n###%###n###%###n###%

KEMU, Lahore###65###32.5###20###10.0###40###20.0###23###11.5###11###5.5

FJMC, Lahore###29###19.3###24###16.0###27###18.0###13###8.7###12###8.0

NMC, Multan###32###32.0###26###26.0###25###25.0###29###29.0###22###22.0

Punjab###126###28.0###70###15.6###92###20.4###65###14.4###45###10.0

JPMC, Karachi###40###40.0###37###37.0###21###21.0###16###16.0###12###12.0

DMC, Karachi###82###82.0###26###26.0###15###15.0###6###6.0###49###49.0

Sindh###122###61.0###63###31.5###36###18.0###22###11.0###61###30.5

KMC, Peshawar, (KPK)###29###29.0###25###25.0###21###21.0###21###21.0###16###16.0

BMC, Quetta,(Baluchistan)###49###98.0###37###74.0###38###76.0###13###26.0###31###62.0

Total###326###40.8###195###24.4###187###23.4###121###15.1###153###19.1

Table 5: X-ray findings in contacts by centers and provinces.

###Infiltration###Calcification###No Lesion Normal

PMRC Research Centers###Total

###n###%###n###%###n###%

KEMU, Lahore###13###6.5###11###5.5###176###88.0###200

FJMC, Lahore###21###14.0###29###19.3###100###66.7###150

NMC, Multan###30###30.0###13###13.0###57###57.0###100

Punjab###64###14.2###53###11.8###333###74.0###450

JPMC, Karachi###6###6.0###11###11.0###83###83.0###100

DMC, Karachi###5###5.0###13###13.0###82###82.0###100

Sindh###11###5.5###24###12.0###165###82.5###200

KMC, Peshawar, (KPK)###20###20.0###12###12.0###68###68.0###100

BMC, Quetta, (Baluchistan)###18###36.0###2###4.0###30###60.0###50

Total###113###14.1###91###11.4###596###74.5###800

Tuberculin skin test showed an induration of more than or equal to 10 mm in 274(34%) cases which was highest in Baluchistan. Bilateral lung involvement on X-ray was seen in 155(76%) contacts while 17(8%) had left side and 32(16%) right side involvement (Table-6).

Table-6: Radiologic findings on X-ray chest.

Radiologic Findings

Lung###Mild###Moderate

Involved###Infiltration###Infiltration###Cavity###Calcification###Total

Bilateral###34###21###16###84###155

Left###8###4###5###0###17

Right###15###5###5###7###32

Total###57###30###26###91###204

Chi-square = 34.71###p-value Less than 0.001

Table-7 shows province wise distribution of 800 sputum smear results. Overall smear positivity was 15.6% which was 34% for contacts belonging to Baluchistan and 7% for Sindh.

When infiltration and calcification was correlated with Tuberculin Skin Test (TST), it was noted that out of 800 contacts 57 showed mild infiltration and of these 55 also had indurations of equal to or more than 10mm. Among 596 cases with normal radiologic findings 80 had indurations [greater than or equal to]10 mm. The sputum smear positive contacts were compared with radiological findings (Table-8).

Table-7: Province wise distribution of smear results in contacts.

PMRC Research Centers###Smear Positive###Smear Negative###Total

###n###%###n###%

KEMU, Lahore###17###8.5###183###91.5###200

FJMC, Lahore###28###18.6###122###81.3###150

NMC, Multan###27###27.0###73###73.0###100

Punjab###72###16.0###378###84###450

JPMC, Karachi###6###6.0###94###94.0###100

DMC, Karachi###8###8.0###92###92.0###100

Sindh###14###7###186###93.0###200

KMC, Peshawar (KPK)###22###22###78###78.0###100

BMC, Quetta (Baluchistan)###17###34###33###66.0###50

Total###125###15.6###675###84.3###800

When signs and symptoms were correlated with radiological findings it was noted that cough was present in almost all cases having infiltration and cavity (Table-9).

Discussion

In the present study out of 800 contacts screened for pulmonary tuberculosis, 113(14.1%) had infiltration in the lung suggesting pulmonary tuberculosis, 91 had calcified lesions indicating past infection. This positivity rate is higher than other studies from Iran which showed 7.6 % active pulmonary TB in contacts12. Studies from

Table 8: Relation of radiologic findings with Tuberculin Skin Test (TST) and Smear results.

Radiologic Finding###Indurations' Size###Smear Result

###Less than 10.00 mm###10.00 mm###Total###Positive###Negative###Total

Normal###516###80###596###0###596###596

Mild Infiltration###2###55###57###46###11###57

Moderate Infiltration###1###29###30###27###3###30

Cavity###0###26###26###26###0###26

Calcification###7###84###91###26###65###91

Total###526###274###800###125###675###800

Chi-square = 450.88###Chi-square = 509.13

p value Less than 0.001###p value Less than 0.001

Table 9: correlation of signs and symptoms with radiologic findings.

Radiologic

###Mild###Moderate

###Normal###Cavity###Calcification

###Infiltration###Infiltration

###n=576###n=26###n=91###p value

###n=57###n=30

###n###%###n###%###n###%###n###%###n

Cough###223###37.4###33###57.9###17###56.7###14###53.8###39###42.9###0.006

Expectoration###133###22.3###20###35.1###13###43.3###10###38.5###19###20.9###0.007

Low Grade Fever###115###19.3###25###43.9###13###43.3###12###46.2###22###24.2###Less than 0.001

Weight Loss###67###11.2###23###40.4###9###30.0###11###42.3###11###12.1###Less than 0.001

Anorexia###104###17.4###16###28.1###9###30.0###9###34.6###15###16.5###0.046

developed countries show even lesser cases14. Studies from USA15 and Brazil16 reported that household contacts of individuals with TB were at a higher risk of acquiring infection than the general population. Active pulmonary disease in contacts is almost always due to transmission of infection from the index cases17.

Proper access to effective therapy is a challenge for the TB control programs worldwide and it is often suggested that to reconsider the role of active case finding18. The study carried in Peru, performed active case finding among household contacts and neighbours of TB patients and reported high detection rates especially among people exposed to patients having high grade positive sputum smears. The study recommended that combined active and passive case finding in household contacts may detect substantially more cases of TB19. Results of tuberculin skin test in our study showed that all 113 cases having infiltration in their chest x-ray were tuberculin positive (indurations greater than 10 mm). In 91cases who had calcified lesions indicating past infection, also had positive tuberculin skin test. Out of 596 contacts who had normal X-ray chest only 80 cases had positive Monteux test and 516 cases had tuberculin skin test negative (induration less than 10 mm). Similar findings were reported from Iran12.

Traditional tuberculin skin testing for investigating close contacts is from the perspective of the public health service, as it is less expensive than any other procedure used for screening tuberculosis alone20.

Sputum smear positivity in our study was 15.6% which is high and reflects close and overcrowded living style in our community. Similar study from Great Britain showed 12.5% sputum smear positivity in close contacts21 while an Iranian study reported sputum smear positivity in 7.6% contacts as rest of contact cases could not expectorate sputum and therefore sputum smear test for AFB could not be done12. Similar 7% sputum smear positivity in contacts was reported from Hongkong22.

Tuberculosis is a major public health problem in developing countries and Pakistan ranks 8th in the world with a prevalence of 171/100,000 cases. The prevention of active tuberculosis through treatment of latent tuberculosis infection is a major element of national strategy for eliminating tuberculosis23. A study done by Aga Khan University in rural Sindh reported that household contacts of AFB sputum smear positive tuberculosis patients had a high prevalence of tuberculosis infection as determined by tuberculin skin testing24. Another similar study by King Edward Medical University Lahore showed household contacts of patients suffering from active pulmonary tuberculosis had more chances of being infected with Mycobacterium tuberculosis as compared to the healthy non-contact, as shown by the higher levels of anti tuberculosis antibodies and positivity of Montoux test with more than 10mm of induration and erythema25.

Iran reported that majority (86%) of contact population had positive tuberculin skin test reaction of 10 mm or more reflecting latent tuberculosis26. A study from Hong Kong showed that rate of latent tuberculosis was highest among two extremes of age i.e. children less than 5 years and those greater than 60 years of age, and thus recommended that contact investigation is very useful for active case finding in tuberculosis27.

In the present study 32% index patients had a family history of TB and most of the index cases were illiterate. Mother was the most common contact followed by son, brother, husband, wife and sister. The study did not show any predilection for gender or age.

Household contacts of patients suffering from active pulmonary tuberculosis have more chances of being infected with Mycobacterium tuberculosis. All contacts of TB patients should be screened as early as possible to reduce the number of active TB cases. After diagnosis appropriate treatment should be given through TB DOTS program. Since undetected cases continue to spread infection to close contacts, strategies for tuberculosis case detection need to be improved to minimize the mycobacterium tuberculosis transmission.

Acknowledgement

This study was funded by Pakistan Medical Research Council, Islamabad as a multi-centre study. I am thankful to all the centre in charges for providing maximum support to the co-investigators. We also acknowledge index patients along with their contacts who cooperated in this study.

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PMRC TB Research Centre, King Edward Medical University, Lahore1, PMRC Research Centre, Fatima Jinnah

Medical College, Ganga Ram Hospital, Lahore2, PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi3, PMRC Research Centre, Dow Medical College, Karachi4, PMRC Research Centre, Nishtar Medical Collwge, Multan5, PMRC Research Centre, Khyber Medical College Peshawar6, PMRC Research Centre, Bolan Medical College, Quetta7, Statistical Officer, PMRC, National Health Research Complex, Lahore8.

Corresponding Author: Rizwan Iqbal PMRC TB Research Centre King Edward Medical University Lahore. Email: rizwaniqbal1@live.com
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Author:Iqbal, Rizwan; Munir, Kashif; Bashir, Saira; Arif, Ambreen; Rao, Masood Hussain; Mirbahar, Ahsanulla
Publication:Pakistan Journal of Medical Research
Article Type:Report
Geographic Code:9PAKI
Date:Dec 31, 2013
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