Int. J. Life. Sci. Scienti. Res., 4(2): 1707-1712, March 2018

Tuberculosis Among Household Contacts of Multidrug-Resistant Tuberculosis Cases at a Tertiary Hospital in Lucknow, India

 

Rajeev Kumar^1*, RAS Kushwaha¹, Amita Jain², Zameerul Hasan¹, Priyanka Gaur³, Sarika Panday¹ 

¹Department of Respiratory Medicine, King George’s Medical University, India

²Department of Microbiology, King George’s Medical University, India

³Department of Physiology, King George’s Medical University, India

 

^*Address for Correspondence: Mr. Rajeev Kumar, PhD Scholar, Dept. of Respiratory Medicine, King George’s Medical University, UP, Lucknow, India

 

ABSTRACT- Background: Multidrug-resistant tuberculosis (MDR-TB) is caused by strain of Mycobacterium tuberculosis, it is transmitted through air droplets from infected person and Close contacts of MDR-TB patients have a high potential to developing TB. This study aims to determine the profile of TB/multidrug-resistant TB (MDR-TB) among household contacts of MDR-TB patients.

Material and Methods: The cases were recruited from the King George’s Medical University, Lucknow, India. In this cross-sectional study, Close contacts of MDR-TB patients were screened for tuberculosis. clinical, radiological and bacteriological experiments were performed to find out the evidence of TB/MDR-TB.

Results: The cases were enrolled Between December 2015 to December 2016, a total of 100 index MDR-TB patients were recruited which initiated on MDR-TB treatment. A total of 428 contacts who could be studied, 11 (2.57%) were diagnosed with MDR-TB and 4 (0.93%) had TB. The most frequent symptoms observed in patients were cough, chest pain and fever.

Conclusions: Tracing symptomatic contacts of MDR-TB cases could be a high yield strategy for early detection and treatment of MDR-TB cases to contribute to reduced morbidity, mortalityand to cut the chain of transmission of infection in the community. The approach should be bringing about for wider implementation and dissemination.

Keywords: TB, MDR-TB, Symptomatic, Household, Transmission

INTRODUCTION- Multidrug-resistant tuberculosis (MDR-TB) is caused by strain of Mycobacterium tuberculosis that is resistant to at both isoniazid (INH, H) and rifampicin (RMP, R) that are two most powerful 1^st line anti TB drugs, it is transmitted through air droplets from infected person and Close contacts of MDR-TB patients have a high potential to developing TB.

Because of the emergence of resistant nature of Mycobacterium tuberculosis strains, tuberculosis adopted more alarming nature in the form of MDR-TB, is a global occurrence that poses a serious threat to ongoing national TB control programmes. India accounts for about a quarter of the global TB burden. Worldwide India is the country with the highest burden of both TB and MDR-TB ^[1]. There are an estimated 79,000 multi-drug resistant TB patients among the notified cases of pulmonary TB each year. According to WHO. In 2016 an estimated 28 lakh cases occurred and 4.5 lakh people died due to TB. 

According to the 2017 World Health Organization global report, approximately 490000 people were infected by MDR-TB. In addition, there were an estimated 110,000 people who had rifampicin resistant TB (RR-TB). So the number of people estimated to have had MDR-TB or RR-TB in 2016 was 600,000 with approximately 240,000 deaths. Almost half (47%) of these cases were in India, China and the Russian Federation, in which India has highest TB incidence in Asia ^[1].

The prevalence of MDR-TB in India is reported to be around 3% in new cases and 12-17% in retreatment cases ^[2]. Close contacts of MDR-TB cases are expected to be at increased risk of developing TB due to intense and/or prolonged exposure to index cases in the weeks to months before diagnosis and treatment beginning ^[3]. However, contradictory statistics have emerged from different existing studies concerning the risk of TB in close contacts of drug-susceptible and MDR-TB patients. A number of studies have reported a comparable risk of transmission in the two groups ^[4–6], whereas others have not ^[7]..

Global TB Report 2017 released by the WHO, India, along with China and Russia, accounted for almost of half of the 490,000 multi-drug-resistant TB (MDR-TB) cases registered in 2016, but limited data are available from India to date on the occurrence of TB/MDR-TB among household contacts of MDR-TB patients. Contact tracing in general is supposed to provide two functions: (1) identifies contacts with TB disease so that treatment can be initiated early when disease is more restricted- this in addition serves to decrease transmission and (2) identifies high-risk infected contacts who might assistance from either anticipatory treatment or close surveillance ^[8].

The objective of our study was to estimate the incidence of TB in household contacts of MDR-TB patents registered at the DR-TB center KGMU. Many risk factors that are associated to development of MDR-TB have been reported among contacts but have not been concurrently assessed. The present study was carried out to determine the proportion of household contacts, whodevelop active TB due to direct transmission from an index case in that household through the clinical, radiological, and bacteriological profile in household contacts of MDR-TB patients at a tertiary TB care center in Lucknow.

 

MATERIAL AND METHODS

Setting and Study design- A cross-sectional study was conducted at the Department of Respiratory Medicine King George’s Medical University DOTS-PLUS center, which covers 24 Districts of Uttar Pradesh. The study population includes all the house hold contacts MDR-TB patient registered under categary iv drug regimen of DOTS-PLUS program at DR-TB centre were recruited from December 2015 to December 2016. A total of 100 MDR-TB cases were recruited for this study after given inform consent. The study was ethically approved by institutional ethics comitte. All index cases were retreatment patients who had unsuccessful treatment with 1^st line drug regimen. The majority were residing in urban slum areas and were of poorer socio-economic position. After an initial phase of hospitalization of about one month, all index cases received supervised ambulatory treatment with second-line drugs.

 

Screening contact practice at the hospital- At the DOTS-PLUS center, it was a regular work practice to enquire all index cases if any there family member had pulmonary symptoms (fever, weight loos, cough and loss of appetite) suggestive of TB. If any symptomatic family members were recognized, the index case was encouraged to take the family member for further examination at the hospital.

The DOTS-PLUS center team did thorough clinical examination of the symptomatic family member together with detailed history, physical examination, and laboratory work up as per the guideline of Revised National Tuberculosis Control Programme. Close contacts with no active TB disease were monitored carefully for at least two years. It is more important to careful and close follow-up was encouraged for infants and children less than 5 years of age because they are more prone to suffer from the disease. Household contacts with no suggestive signs and symptoms of active TB were aware regarding the signs and symptoms of TB, about their contact with an MDR-TB index case and about the significance of seeking treatment immediately if they develop signs and symptoms of TB disease. Follow up monitoring was done every 1–2 months. Contacts from Lucknow and nearby places, a team composed of community health workers and medical officer conducted home visits after every 1-2 month to trace. Those contacts, who came from outside Lucknow were motivated to visit the DOTS-PLUS center KGMU after every 1–2 months to undergo the study investigations.

 

Data collection- After obtaining informed consent, a standardized case-report form was filled out for all contacts of each index patient. Sex, age, weight clinical examination assessment, radiological assessment, closeness to the index case, bacille Calmette-Guérin (BCG) scar (presence/absence to assess infection rates among vaccinated and unvaccinated groups) and any history of TB (pulmonary/extra-pulmonary) were also recorded.

Socioeconomic status based on education, occupation and family income were classified by using modified Kuppuswamy scale ^[9].. Nutritional status was assessed using the body mass index ^[10].. Sputum examination for acid-fast bacilli (AFB) on two early morning samples on 2 consecutive days was carried out in all contacts and in case of any positive result for sputum microscopy, these cases were referred to Intermediate Reference Laboratory (IRL) for Xpert MTB/Rif resistance testing. On confirmation from IRL for Rifampicin resistance on Xpert MTB, these patients were registered at DOTS-PLUS to start cat 4 treatments. Those cases with no Rif resistant to Xpert MTB although positive for sputum microscopy were referred to respective DOTS centres for registration and treatment initiation. Tuberculin skin testing (TST) using 5 tuberculin units (TU) purified protein derivative (PPD) was performed in all contacts and was recorded after 48-72 h at the study center. A reading of ⩾10 mm was taken as positive. All contacts were also offered human immunodeficiency virus and Diabetes testing.

Some of the Contacts that were not available at the time of home visit for interview, their history were obtained from the index cases or from other relatives of the family. In the case of casualty of any contact members because of TB, a history was obtained from the index patients or from other relatives of the family.

The ‘Index case’ was defined as the first identified case of MDR-TB in the house. All index cases were confirmed by sputum culture as having MDR-TB

A household Contact case was defined as any person who shared the same enclosed living space for least 3 months prior to the identification of the index case and included spouses, children, parents, siblings and other family members (uncles, grandfathers, cousins).

 

RESULTS- Between December 2015 and December 2016, 100 index patients were reviewed that were started Anti-tuberculosis treatment. Their demographic profile is shown in Table 1. Over a 67 (67%) were male and 33% female. 54% index cases belong to urban and 46% belong to rural areas. Out of 100 index cases  Seven (7%) had previous and Nine (9%)  had present history of tuberculosis and majority of index cases were retreatment patients that received treatment either of first line anti TB drugs of WHO treatment category regimen previously. In the study population, 410 (80.7%) were HIV negative, ninety eight (19.3%) of confirmed MDR-TB index cases were also HIV positive.

 

 

 Fig. 1: Flow diagram representing contact tracing and outcomes of household contacts

(TB = Tuberculosis, IC= Index cases, HC= Household contact, KGMU= King George’s Medical University, n= Number of patients)

 

Table 1: Socio Demographic characteristics of Index case (IC)

Variables	Frequency (n=100)	(%)
Sex Male Female	67 33	67 33
Age ≤ 40 >40	58 42	58 42
Residence Urban Rural	54 46	54 46
Personal habit Alcoholic Non alcoholic Smoker Ex-smoker Non-smoker	17 83 27 4 69	17 83 27 4 69
HIV status Positive Negative	22 88	22 88
Contact history Present Past Absent	7 9 84	7 9 84
Smear Grading 3+ or 2+ 1+ or scanty	54 46	54 46
Culture Result Positive Negative	98 2	98 2

 

The household contacts of the index cases were identified using the medical records of the index cases that were present in DR-TB center and through interviews of index cases and their family members; symptomatic contacts or family members recognized on the screening form and attached with the respective index case file.

There were 506 household contacts of 100 index patients were screened for tuberculosis. Their demographic profile is shown in Table 2. Majority of contacts (67.6%) were male and most of them (70.4%) belong to the urban area.

 

Table 2: Socio Demographic characteristics of household contact (HC)

Variables		Frequency (n=506)	(%)
Sex Male Female		342 164	67.6 32.4
Age ≤ 40 >40		318 188	62.8 37.2
Residence Urban Rural		356 150	70.4 29.6
Personal habit Alcoholic Non alcoholic Smoker Ex-smoker Non-smoker		54 401 94 37 375	10.7 89.3 18.5 7.31 74.1
Smear Grading 3+ or 2+ 1+ or scanty		(n=15) 11 4	73.3 26.7
Culture Result Positive Negative		(n=428) 15 413	3.50 96.5
Drug susceptibility testing Resistance          Susceptible	11 4		73.3 26.7
Number of contacts who developed MDR-TB per household   One Two Three	11 3 1		73.3 20 6.7

 

Three hundred eighteen (62.8%) of the contacts have ages bellow to 40 years that are the most susceptible age group of the population. A symptomatic household contact was identified in 15 of 428 (3.50%) index cases. The most common symptoms were a cough followed by fever loss of appetite and haemoptysis. History of loss of weight was also present in all 15 contacts. Sputum specimens were collected and examination was performed for 428 (83.99%) household contacts, whereas the remaining 78 (15.4%) were unable to provide sputum for examination. Chest X-ray was performed in 228 contacts. Sputum for AFB yielded negative result for 413 (96.4%) cases while it was positive in 15 (3.50%), sputum smear positive cases had smear grading  3+ or 2+  for 11and 1+ or scanty for 4.

All sputum positive and other suspected cases were referred to Intermediate Reference Laboratory (IRL) for Xpert testing and Drug susceptibility testing (DST). Xpert and DST results of 11 (73.3%) contacts confirmed MDR-TB while 4 (26.7%) was declared drug-susceptible TB. Four contacts that were diagnosed with pulmonary TB were referred back to their respective district for registration at DOTS center for category first whereas the remaining 11 contacts that were diagnosed as MDR-TB patients were registered for drug resistant TB treatment at DR-TB center KGMU.

DISCUSSION- In India, the main objective of National DOTS-Plus Programme is to reduce tuberculosis transmission by providing early diagnosis and treatment of MDR-TB patients, for that, it follows the entire protocol of MDR-TB to facilitate prevention, diagnosis, treatment, and to cover the entire nation with the scheduling and monitoring in a phased manner.   Household contacts constitute a high-burden group for developing TB and MDR-TB, and the significance of selective case detection in these groups cannot be overemphasized. Recently infected contacts carry an eightfold risk of developing TB compared with persons infected more remotely ^[11]. While not all cases found through household contact tracing are the result of transmission from the index case, early detection and treatment of the contagious cases will greatly reduce the transmission rate in the population ^[12,13]. Because of frequent exposure to index patient, household contacts of MDR-TB have more recurrent threat to developing active TB and MDR-TB. On the other hand, available information on subsequent risk of developing active TB/MDR-TB disease among MDR-TB contacts have not been reliable. There are very few studies reported from India on the burden of disease and infection among contacts of MDR-TB patients. Singla et al reported that TB prevalence among contacts was 5.3%, of whom only 0.7% had MDR-TB ^[2]

 In the present study, we measured the factors that are related to contacts such as residence, any history of TB treatment, HIV status, sex, age, and number of confirmed MDR-TB in the house. In this study, a total 428 contacts of index patient studied, of which, 11(2.57%) contacts developed MDR-TB while 4(0.93%) cases developed drug susceptible TB subsequent to the index case. The Overall rate of disease in the present study was 3.50 % which is very low as compared to an earlier study conducted by Dhingra et al. ^[14] who reported a 53.5% prevalence of TB infection in household contacts. We could not determine that household contact gets infected by transmission from index case as we were not performed genetic study of mycobacterium. However, as we know it is a communicable disease, there is significant proof to support the transmission of MDR-TB strain from person-to-person in the community. It was shown by Bayona et al. ^[15] that over half figure of global MDR-TB cases are thought to result from primary transmission. In addition, the transmission may have taken place previously, when they were drug-susceptible, as most of the index cases were retreatment cases. This study had a number of functioning problems with the simple contact tracing and testing strategies used. Almost a third of close contacts with cough for more than two weeks could not provide sputum samples for smear microscopy. While a number of contacts were unable to produce sputum sample when needed, many others were simply not present at their home at the time of visiting the team of DR-TB  center. There are a number of limitations in our study. First, the small sample size of drug-resistant contact cases due to the inability to trace all the contacts. Second, data on several determinants for the MDR-TB disease were absent from analysis because they were not in the routine registers patients. Third, we considered only household contacts that are living with index patient and not other casual or close contacts.

CONCLUSIONS- Present study highlights the requirement for early detection and treatment of TB in household contacts of MDR-TB, who represent a high-burden group, and also suggest that active tracing of symptomatic contacts; cases contribute to reduced morbidity, mortality and transmission of infection in the society. This could be a very effective approach to saving more people as well as in cutting the chain of the transmission in the community. The conclusions from this study are believed to notify the national MDR-TB treatment carrying out plan as well as other similar countries in their attempt to roll out MDR-TB treatment services.

ACKNOWLEDGMENTS-  We were greatly thankful to Uttar Pradesh Council of Science and Technology (UP-CST), Lucknow for provided funding and department of Respiratory Medicine, King George’s Medical University, Lucknow, India and also appreciates patients participated in this study.

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