Study of Clinico-Radiological Profile in Childhood Tuberculosis

Background: Tuberculosis still is one of the deadliest diseases in the world killing nearly 2 million people every year. In India, two deaths occur every three minutes from tuberculosis. The actual global disease burden of childhood tuberculosis is not known, as childhood Tuberculosis is notoriously difficult to diagnose because of the absence of a ‘gold standard’ as bacteriologic confirmation is rarely achieved. The present study was designed to study clinical profile of various forms of childhood TB. Objective of this study was to study clinic-epidemiological profile of various forms of childhood TB.Subject and Method:Retrospective analysis of clinical profile of 100 patients of childhood TB in the age group of 6 months to 12 years. A detailed clinical history, family history of contact with Koch’s disease, history of BCG vaccination of each child was recorded. A complete examination was carried out and findings regarding the general and systemic examination were recorded. Result:Age distribution in our study showed that 51% cases in the age of 5-12 years, 47% cases in the age group 1-5 years and  2 % cases falling in the age group 0-1 years, with male to female ratio of a 1.27:1. 95% of the patients belonged to the lower socio-economic class. The distribution of TB was- pulmonary tuberculosis(42%),TBME(30%),pleural effusion(12%),abdominal TB (12%), TB lymphadenitis(4%), Osteotuberculosis(2%), miliary TB(2%). 12% of the patients had mild to moderate malnutrition (PEM Grade I, II)and 57 % were severely malnourished. 72% of the patients were BCG vaccinated and history of Koch’s contact were present in 21% of all cases. The most frequently seen symptoms were fever (88%), cough (65%), weight loss in 50%, anorexia in 35% of cases and in physical examination cachexia was the most common (50%) followed by hepatomegaly (40%),lymphadenopathy(16%) and Splenomegaly (8%) of  cases. Conclusion:childhood TB is commonly seen in children more than 1 year, lower socioeconomic class and in severely malnourished children.


Introduction
Tuberculosis is known to exist in India for thousands of years. It has been mentioned in Vedas and Ayurvedic Samhitas regarding its clinical feature. In the Mahabharata by Maharshi Ved-Vyas there is mentioned death of Vichitravirya, the son of king Shantanu. He died of TB. The disease was known as 'Rajyakhsma'. [1] Tuberculosis still is one of the deadliest diseases in the world killing nearly 2 million people every year. [2] Tuberculosis, the only infectious disease to be declared a ' global emergency ' by the WHO , is major cause of death in adult and children worldwide but the brunt is borne by developing countries with 95% of cases and 98% of deaths. [3] In India, two deaths occur every three minutes from tuberculosis. [4] Tuberculosis continues to be an important cause of morbidity and mortality for children. [5] As children acquire infection with Mycobacterium tuberculosis from adults in their environment, incidence of tuberculosis in children therefore reflect the ongoing transmission and, indirectly, efficacy of the control program. [6] The actual global disease burden of childhood tuberculosis is not known, but it has been assumed that 10% of the actual total TB case load is found amongst children. Global estimate of 1.5 million new cases and 1,30,000 deaths due to TB per year amongst children is reported. [5] Childhood Tuberculosis is notoriously difficult to diagnose because of the absence of a 'gold standard' as bacteriologic confirmation is rarely achieved and due to the predominantly paucibacillary nature of childhood TB. Sputum microscopy often the only test available in endemic areas, is positive in less than 10-15% of children with probable TB and culture yields are usually low (30-40%). [7] The situation is not helped by the presence of a large number of fairly expensive 'diagnostic tests' such as ELISA, PCR, Quantification etc. because a positive result does not always signify presence of disease and likewise a negative result does not necessarily mean absence of disease. [8] Primarily, diagnosis of childhood TB is based on a very high index of suspicion and subsequent detailed clinical & laboratory evolution. [9] Though Anti-tuberculosis drugs have been available for fifty years now and efficacy of modern Original Article short-course chemotherapy has been proved beyond doubt, considerable morbidity results from late diagnosis or inadequate treatment, lack of compliance and lack of guidelines for stopping treatment. India had a National Tuberculosis Program (NTP) in place from sixties. In 1992, a joint Government of India / World Health organization review found that despite the existence of the NTP, TB patient did not complete treatment. [10] The WHO recommended treatment strategy for detection and cure of TB is DOTS (Directly observed Treatment Short course. Based on the recommendations of the review, the Revised National Tuberculosis Program (RNTCP), incorporating the internationally recommended DOTS strategy, was developed. The RNTCP, based on the DOTS, began as a pilot in 1993 and was launched as a national program in 1997. Rapid RNTCP expansion began by 1998. By the end of 2000, 30% of the country's population was covered, and by the end of 2002, 50% of the country's population was covered under RNTCP. By 2005, around 97% of the population had been covered, and the entire country was covered under DOTS by 24 th March 2006. [4] The Indian Academy of Paediatrics (IAP) in 1997 recommended standard protocol for treatment of childhood TB. 5 In Gujarat RNTCP was started in 2000 and patients wise boxes were launched in 2007. To seek consensus on improved case detection and improved treatment outcomes for all diagnosed paediatrics TB case, a workshop on the "formulation of guideline for diagnosis and treatment of paediatric TB cases under RNTCP" was held in New Delhi in Aug'2003. [5] Implementation of DOTS under RNTCP for paediatric patients was started in month 2007 at District TB Centre (DTC) in Shri Sayaji General Hospital and Medical College Baroda. There is a total change in the scenario before & after implementation of DOTS and so this study was undertaken when DOTS was newly introduced in our hospital with a view to find out to study the clinicoradiological profile of patients suffering from pulmonary and extra pulmonary tuberculosis in paediatric age group.

subjects and Methods
This study was conducted in the Department of Paediatrics, Shri Sayaji General Hospital and Medical College Baroda, between Oct' 07 to Nov'08 including OPD & ward patients. The total numbers of 100 patients in the age group 6 months to 12 years were included in this study and all of them presented with clinical features of tuberculosis. This is longitudinal study with simple randomization with sample size of 100.

Inclusion criteria
Total numbers of 100 patients in the age group 6month-12 years were included in this study all of them presented with clinico-radiological features of TB.

History and clinical examination
Children and infants attending the out patients department between Oct. 07 to April '08 with clinical symptoms and signs suggestive of tuberculosis were enrolled in the study. A detailed clinical history, family history of contact with Koch's disease, history of BCG vaccination of each child was recorded. A complete examination was carried out and findings regarding the general and systemic examination were recorded. The nutritional status was assessed and classified according to IAP classification of under nutrition. Mantoux test was given to all patients with 10 TU on the left forearm and readings were taken at the end of 72 hours. Relevant pathological and radiological investigations were done to substantiate the diagnosis of tuberculosis. Patients were classified according to RNTCP guideline for diagnosis of childhood tuberculosis. Then the patients were assigned the category by the concerned paediatrician. Then each patient was referred to district tuberculosis centre OPD (17). DTC enrolment was done and patient was allotted nearest DOTS centre, according to the residential area, either urban (Baroda Municipal Corporation) or rural. From the respective DOTS centre, the patients were examined and enrolled by Concerned Medical Officer. After enrollment Medical Officer will demand drug pouches from Suryanarayan baugurban TB centre for the enrolled patient. Patients get drug-pouches from their nearest DOTS center. The patient's belonged to rural areas under district of Baroda are being provided drugs by nearest rural DOTS center. Then regular follow up of the patients was done at frequent interval in paediatric OPD for assessment of improvement or deterioration of general well being and clinico-radiological profile. During this study, frequent visits to DOTS centre were done in rural and urban area, to ensure the provision of drugs to the patients by DOTS provider and to check the compliance of patients under DOTS treatment.

Statistical Analysis
The recorded data was compiled and entered in a spreadsheet computer program (Microsoft Excel 2007) and then exported to data editor page of SPSS version 15 (SPSS Inc., Chicago, Illinois, USA). Descriptive statistics included computation of percentages, means and standard deviations. For all tests, confidence level and level of significance were set at 95% and 5% respectively.

Results & Discussion
The present study was carried out in Department of Paediatrics, Shri Sayaji General Hospital, Medical College, Baroda from October 2007 to November 2008 over a period of 13 months. Total 100 patients were enrolled in the study. Age distribution showed 2 % cases falling in the age group 0-1 years, 47% cases in the age group 1-5 years and 51% cases in the age of 5-12 years. In the study by Anis-ur-Rehman, at Ayub Medical College, Abbottabad, Pakistan, 8% of the patients were below 3 years and 22% of the patients belonged to 3-6 years and 48% of the patients were between 6-12 years. 11 Our study showed that TB infection is common in the infancy and preschool age. Above table and pie diagram shows that 67% of the patients hailed from rural area and 33% were residing in urban areas. Only 7% hailed from tribal area.  Table 2 shows that 95% of the patients belonged to the lower socio-economic class of III, IV, V of Modified Prasad's classification. 73% belonged to lower socioeconomic status in the study of Thilotheammal et al. [12] High incidence of TB in children aged 0-5 years in an area of South Africa correlated with lower level of parental education, low annual household income. [13] Our study showed that TB is more prevalent in lower socio-economic class.   (21). Malnutrition decreases immunity in growing children making them more vulnerable to tuberculosis. [15] [16] However, since extra pulmonary forms of tuberculosis and children less than 10 years of age were not included in the assessment the results of this study cannot be extrapolated to the paediatric population.   [17] Garg p at Agra showed that pulmonary (52.4%) and extra pulmonary TB (47.6%) accounted for almost equal number of cases (52.4%, 47.6%), which matches with our study. Workload from TB clinic (1966-1999) of major tertiary centre in North India, reported extra pulmonary TB in only 17%of total cases. Extra pulmonary TB has been reported among 37% of newly diagnosed cases of TB from 522bedded community Hospital in America. [18] TBME is significantly seen in younger subjects in contrast to pleural effusion, TB lymphadenitis, Ostoetuberculosis which is seen in older age group. Children less than 5 years old and infected with tuberculosis are at higher risk of developing disease probably due to immature immunity. [19,20] Children under the age of 5 years are at higher risk for developing the tuberculous disease after infection; often develop more severe degree of disease. [21,22] Miller F J W et al at London shown that the life time risk for developing tuberculosis after infection is 43% in infants, 24% between 1-5 years of age and 15% in adolescents, compared to immunocompetent adult with lifetime risk of 5-10%. [22] [15] Quadriplegia was the most common neurological defect observed in 30%, followed by Hemiplegia in 26.6% patients. 7 th nerve was the most commonly involved cranial nerve (26.6%) followed by 6 th nerve in 6.6% and 3 rd in 3.3% patients.
Abdominal distension was the most common symptom, present in 83.3% patients; fever was the next frequent complaint present in 58.3% patients. 58.3 % patients had Abdominal discomfort, while 50% had came with history of weight loss. The finding of calcified hilar lymph nodes & calcified paranchymal lesion is known as Ranke complex {Ghon focus or Primary complex}. [24] The above table shows that Primary Pulmonary Complex were present in 50% cases, followed by Progressive Pulmonary Diseases present in 30.8% cases, and 19.2% had showed normal chest X-ray. Evidence of hilar lymphadenopathy is seen up to 83 to 96 % in children with primary TB. [24][25][26] It must be pointed out that over diagnosis of hilar lymphadenitis in childhood with slightly rotated or expiratory films is a common mistake in clinical practice. Thymus, body of manubrium can be mistaken for paratracheal lymphadenopathy.

Conclusion
Childhood TB is commonly seen in children more than 1 year, lower socioeconomic class and in severely malnourished children. 27%patients were having severe malnutrition and 72% patients had BCG vaccination scar. There was association between type of childhood TB and age. Out of 100 patients enrolled in the study 66(66%) were cured/Improved of the disease, 13(13%) patients expired and 20(20%) patients were lost to follow up.