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Spectrum of Tuberculosis in BCG vaccinated and unvaccinated Children in Bangalore, India.

 Dr Vishwanath K G1, Dr.Siddaraju M L2, Jagannatha P S3

Abstract:

One hundred and twelve children (aged 6 months to 14 years) attending TB clinic of pediatric department at vanivilas hospital, Bangalore for a period from May 2000 to April 2001 were analyzed. This study was undertaken to evaluate the clinical spectrum of TB among BCG vaccinated and unvaccinated children. During the study period 89 BCG vaccinated and 23 BCG unvaccinated children were studied to determine the pattern of tuberculosis.  Among the study group 73.2% children were malnourished.  Among malnourished children 76.8% of the children were BCG vaccinated. 73.2% of children were having intrafamilial contact among these 80.5% children were BCG vaccinated. Fourtynine percent in BCG vaccinated and 48% in BCG unvaccinated had pulmonary forms of tuberculosis. Twenty (22.5%) children in BCG vaccinated group and 7 (30.3%) children in BCG unvaccinated group suffered from serious form of tuberculosis including tubercular meningitis, miliary tuberculosis, disseminated and osteoarticular tuberculosis. The difference was not statistically significant (p>0.05).  BCG is not effective in preventing tubercular infection in children of preschool age.  It is effective to a certain extent in localizing the infection to a particular organ. Low socio economic condition, severe form of malnutrition and intrafamilial contact is contributing factor in the genesis of tuberculosis in children vaccinated with BCG.

Key words: Tuberculosis, Children, BCG Vaccination, diagnosis

Introduction:

Tuberculosis has reemerged as a major public health challenge in the world, India accounts for nearly one third of global TB burden. According to the review of global tuberculosis situation by World Health Organization1, India comes under a group of high prevalence country with the Annual Risk of Tuberculosis Infection (ARTI) ranging between 0.6-2.0% per year. There are about 0.9 million incident smear positive cases of pulmonary tuberculosis (PTB) in India every year.  The incidence of smear negative PTB is expected to be similar, with the incidence of extra pulmonary TB cases estimated at about 0.2 million.  Therefore, there are about 2 million new TB cases occurring in the country every year.  The prevalence of smear positive cases would be about 3-4 millions i.e. 3 to 4 the incident cases total2. Overall, 40% of our country's populations are infected with tubercle bacilli. Authentic and reliable information on the magnitude of tuberculosis problem among children in the community is scanty Adult Tuberculosis is the fountain head of the pediatric Tuberculosis (3).

Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis (tubercle bacillus) and occasionally by Mycobacterium bovis.  It affects both the pulmonary and extra pulmonary tissues.  The disease is usually chronic with varying clinical manifestations.  Primary infection can occur at any age, but children are most often affected in areas of high incidence and high population density.  Primary infection may be asymptomatic and often resolves spontaneously. 

In addition to the agent and host factors, socio economic factors (e.g. poverty, illiteracy, ignorance, overcrowding, poor sanitation, large families and some other factors) do play significant role in the outcome of the tuberculosis.  These are non-specific determinants of tuberculosis.  For control of tuberculosis the emphasis is given on early detection and treatment.

The BCG vaccine was discovered in 1924 and is in use for nearly 75 years.  It has not made the impact that was expected.  Several epidemiological studies have shown very wide variations in protection offered by BCG vaccine4. Studies have demonstrated the changing spectrum of tuberculosis in children who have been vaccinated5. 

The tuberculosis disease in adults almost always causes significant symptomatology, childhood symptoms are non-specific and up to 50% of children may be asymptomatic during initial stages of pathogenesis (disease).  Clinicians usually apply a set of criteria rather than a single diagnostic procedure in the diagnosis of tuberculosis in children6.  These commonly include tuberculin skin test (TST), radiological appearance of the patients chest, a history of close contact with tuberculous patient, various clinical signs and symptoms and where possible, bacteriological investigation. Because of the diversity of the criteria mentioned above and their widely differing sensitivities/specificities in diagnosing disease, clinicians often place emphasis on the criteria they believe to be the most useful, and accordingly categorize their diagnosis as suspect, probable or confirmed tuberculosis.

In spite of the fact that each of the above tests can be relatively easy to implement and interpret, they can result in misdiagnosis. In the absence of a simple, single, reliable and inexpensive tool of diagnosis for TB in children, it is prudent not to rely upon single criterion. Applications of a simple, reasonably effective scoring system greatly assist in the selection of suspects for further investigation or for treatment.

This study was undertaken to evaluate the clinical spectrum of TB among BCG vaccinated and unvaccinated children.

Subjects and Methods:

The prospective study was conducted in the pediatric department of the Vanivilas Hospital, Bowring and Lady courzon hospital, attached to Bangalore Medical college, Bangalore from May 2000 to April 2001. Pediatric department of Vanivilas Hospital runs a TB clinic regularly every Monday afternoon between 2 to 4 PM. All new cases in the age group of 0-14 years attending outpatient department or admitted in the wards with symptoms suggestive of tuberculosis disease were evaluated using Kenneth Jones (K.J) criteria for enrolled in the study.

Children were assessed by detailed history, through physical examination and diagnostic investigations.  In the history details’ regarding familial and extra familial contact with TB was enquired apart from the details of the illness.  Socio economic status was assessed by modified method of Kuppuswami7.  Nutritional assessment was done according to IAP classification8.  Mantoux test was done for all study groups by research person and indurations exceeding 10mm after test was considered a positive reaction. Chest X-ray, hemogram and urine routine examination were done for all patients.  Radiologic findings were analyzed with the help of a competent radiologist.  In relevant cases gastric aspirate for AFB smear examination for three consecutive days, lymph node biopsy, cerebrospinal, pleural and peritoneal fluid test were done. Patients were followed up at monthly intervals for a minimum period of 9 months. Chest x-ray was repeated at the end of treatment.  All the family members (adult) were screened with chest x-ray and smear examination to exclude intrafamilial contact. Family members were found positive by examinations were referred to the nearest DOTS center for treatment. Siblings of index cases were screened with Mantoux test and chest x-ray to exclude asymptomatic tuberculous disease. The children (siblings) who were found positive by examination were enrolled in TB clinic and treatment was given. Confirmed cases were treated according to IAP consensus on Treatment of childhood TB8. All this information and type of tuberculosis was recorded in pre tested proforma.

The children satisfying Kenneth Jones score more than 6 are included in the study9. The children with <6 K.J score are excluded from the study. The total number 112 children fulfilled the above condition were studied. Four hundred and eighty nine (489) family members (including siblings) were screened during the study period.

Statistical methods:

Chi-square (c2) test was used to test the significant difference between the proportions. The calculated values of the test criteria were compared with the tabular value at 95% level for ascertaining the significance of the test. The data were analyzed using SPSS software (SPPS, Chicago, IL).

Results:

   Male female ratio in the study group was 1:1.  Maximum number of cases (48.2%) were in the age group of 5-9 years and 31.3% were in the 0-4 year’s age group. Overcrowding was present in 77.3% of the study group. Slightly more than half (57.1%) belonged to low, 29.4% in middle and 13.3% were in upper class socio economic groups. BCG scar was present in 79.5% of the children.  In the study group 73.2% were malnourished. Past history of either Recurrent Respisratory track infection/ measles was observed in 58.9% of the children. History of contact with tuberculosis patient either intrafamilial or extrafamilial was present in 73.2% of the study population. There is no significant difference (p>0.05) between BCG vaccinated and unvaccinated children with respect to age, sex, overcrowding, socioeconomic status, nutritional status, past history and history of contact in the study population.(Table 1).

Clinical Presentation:

The predominant symptoms were fever (78.6%) and cough (50.9%).  More than half of the children had weight loss or poor weight gain.  In addition swelling in the neck (27.1%), abdominal pain (8.9%) was observed in the study population. (Table 2, Figures for various symptoms is not mutually exclusive).

 

Diagnostic Criteria:

Seventy eight children (56.8%) had >10mm tuberculin reaction. Sixty five (73%) children in vaccinated group and 13 (23%) children in unvaccinated group had positive tuberculin test. Abnormal Chest x-ray was seen in 62(70%) cases among BCG vaccinated group and 17 (74%) cases in BCG unvaccinated group.  Details of the other diagnostic examination are given in Table 3.

Clinical Type of TB:

The pattern (clinical spectrum) of tuberculosis in the two groups is depicted in Table 4. Progressive primary complex, pleural effusion and cavitory were diagnosed on the basis of chest radiography.  The 3 cases of disseminated tuberculosis were diagnosed on the basis of clinical signs, radiological appearance. Tubercular lymphadenitis was diagnosed in 17 children based on histopathology.  Glancing at the figure it is apparent that the type (pattern) of tuberculosis including severe forms occurred in almost equal number of vaccinated and unvaccinated children (P>0.05).  In other words, BCG vaccinated children exhibited similar pattern of illness as the BCG unvaccinated.  The clinical presentation of tubercular meningitis in the vaccinated and unvaccinated children was different.  The diagnosis of tuberculous meningitis was based on CSF analysis and CT scan findings.   Disseminated forms TB in this study were seen in children with PEM (68.2%) and those belonging to upper middle class (Not in table).

Discussion:

In the present study 48.2% were in the age group of 5-9 years and 38.2% where in the age group 0-4 years this indicates the high prevalence of childhood tuberculosis in the younger age group. The probable reasons for this may be due to low resistance of host, increased prevalence of moderate and severe malnutrition and close contact with infected adults.  Raj narain et al10 reported 38.9% were in <4 year age group and Chakraborty AK et al11 reported 54.3% cases in 0-4 years and  45.6% in 5-9 years.   The extent of tuberculosis problem in children is a reflection of infectious pool of adult smear positive cases in the community. Prevention and early detection of child cases are essential tasks in tuberculosis control. All children who are vaccinated when they come in contact with the large pool of sputum positive pulmonary tuberculosis adults are likely to be infected. In a study of 2000 BCG vaccinated children; the author has found the incidence to be 91%12. In the present study Prevalence of progressive primary complex among pulmonary form of tuberculosis is 90.9% in the BCG vaccinated group compared to 81% in the BCG unvaccinated group, which is comparable to N.Somu et al study13.   Tuberculous meningitis is the second commonest tuberculous lesion (55%) observed in the present study.  Prevalence of tuberculous meningitis is not statistically significant difference between BCG vaccinated and unvaccinated children.  In Somu N et al study observed that tuberculous meningitis was in the ratio of 1:3 among the BCG vaccinated and unvaccinated children. In our study the ratio of tuberculous meningitis is 3:1 among the BCG vaccinated and unvaccinated children this could be due to less protective effect of BCG and 80.5% of BCG vaccinated children having intrafamilial contact. In  a hospital based study, authors have shown the result of BCG vaccination in malnourished children below 5 years of age getting exposed to infectious cases develop tuberculosis in a moderately sever form14.

   It is very apparent in the resulting data that a vaccinated child also suffers from tuberculosis. The question remains whether BCG is effective? Why children develop tuberculosis despite being vaccinated? What is the alternative we have? There is no ready answer for these questions.  The 15- year follow up of the famous Indian Council of Medical Research (ICMR) BCG trial in Chingleput district, concluded that "BCG offers no protection against adult type bacillary tuberculosis. Consequently, BCG cannot be expected to reduce the transmission of tuberculosis"15. Improved patient care, better BCG immunization coverage and multidrug anti tuberculosis regimen have not created a dent in the mortality due to tuberculosis in children. 

However certain remedial measure can be taken to prevent the tuberculosis in children.  So it must be stressed that the most powerful weapons for controlling tuberculosis and altering the epidemiological situation in a community are case finding and case holding16.  A sincere effort at all levels of health care delivery system is the need of the day.

Acknowledgments:

Authors whole heartedly thank the teaching and non-teaching staff of the pediatric department and vanivilas hospital for their co-operation. We are also grateful to all the study children and their family members for their co-operation without their support the study would not have been possible.

Funding : None

Key Messages:

  1. All types of TB occur in BCG vaccinated children and 22.5% progress to severe disseminated forms.
  2. BCG is not effective in preventing tubercular infection in children of preschool age
  3. Among malnourished children 76.8% of the children were BCG vaccinated.
  4. 73.2% of children were having intrafamilial contact among these 80.5% children were BCG vaccinated.

 

References:

Table 1: General Characteristic of Study population

 

BCG Vaccinated (N=89)

BCG Unvaccinated (N=23)

Total

(N=112)

Age*:

      

0-4

29 (82.9)

6 (17.1)

35 (31.3)

5-9

42 (77.8)

12 (22.2)

54 (48.2)

10-14

18 (78.3)

5 (21.7)

23 (20.3)

Sex*

      

Male

47(85.5)

8 (14.5)

87 [77.7]

Female

42 (73.7)

15 (26.3)

25 [22.3]

Socio economic status*

      

Upper Class

11 (73.3)

4 (26.7)

15 (13.4)

Middle Class

26 (78.8)

7 (21.2)

33 [29.5]

Lower Class

52 (81.3)

12 (18.7)

64 [57.1)

Over Crowding*:

      

Present

69 (79.3)

18 (20.7)

87 [77.7]

Absent

20 (80.0)

5 (20.0)

25 [22.3]

Nutritional Status*

      

Nourished

26 (86.7)

4 (13.3)

30 (26.8]

Malnourished

63 (76.8)

19 (23.2)

82 [73.2]

Past History*

      

Recurrent respiratory infection (RRTI)

37 (88.1)

5(11.9)

42 [37.5]

Measles

9 (81.8)

2(18.2)

 11 [9.8]

Measles + RRTI

11 (84.6)

2(15.4)

13 [11.6]

No Relevant history

32 (68.9)

14(31.1)

46 [41.1]

History of Contact*:

      

With Contact

66 (80.5)

16(19.5)

82 [73.2]

Without contact

6 (60.0)

4(40.0)

10 [8.9]

Doubtful

17 (85.0)

3(15.0)

20 [17.9]

* P>0.05, [ ]Column Percentage, ( ) Row percentage

 


Table 2: Distribution of Symptomatology in Children with Tuberculosis among BCG Vaccinated and unvaccinated group.

 

Symptoms

BCG

Vaccinated

(n=89)

%

Unvaccniated

(n=23)

%

Fever

70

78.7

18

78.3

Cough

46

51.7

11

47.8

Loss of weight

19

21.3

7

30.4

Loss of Appettie

33

37.1

6

26.1

Vomitting

5

5.6

4

17.4

Diarrhoea

3

3.4

1

4.3

Abdominal pain

9

10.1

1

4.3

Swelling neck

19

21.3

8

34.8

Headache

4

4.5

3

13.0

Convulsions

7

7.9

1

4.3

Urninary symptoms

1

1.1

0

0.0

Table 3: Investigation Profile in 122 children by BCG vaccinated status

 

Vaccinated  Group

Unvaccinated Group

Mantoux

n=89

n=23

<10 (negative)

24

10

>10(positive)

65

13

Xray Chest

n=89

n=23

Suggestive(PPC)

37

10

Cavity

1

-

Plueral Effusion

4

3

Unresolving pneumonia

20

4

Not done

8

4

Normal

19

2

CT Scan findings

n=5

n=1

Basal Exudates

2

1

Tuberculoma

3

-

Histopathology

n=14

n=4

Lymphnode

14

4

Fluid Analysis

n=11

n=3

Ascitic

2

-

Plueral Fluid

2

1

CSF

7

2

Acid fast bacilli

n=3

  

Gastric aspirate

3

-
     

Barium Swallow

1

-

Fundal Examination

1

-

Table 4: Clinical Spectrum of tuberculosis among BCG vaccinated and unvaccinated group (n=112)

Type of Tuberculosis

BCG Vaccinated

BCG Unvaccinated

Pulmonary*

n=44

(49.4)

n=11

(47.8)

Progressive Primary Complex

40

9

Plueral Effusion

3

2

Cavitory

1

0
     

Extra Thoracic*

n=20

(22.5)

n=7

(30.3)

Tubercular Meningitis

11

4

Milliary

0

1

Oster Articular

3

1

Abdominal or Pericardial

3

0

Disseminated

2

1

Ileoceacal

1

0
     

TB Lymphadenitis

14

(15.7)

3

(13.0)
     

Aids

1

(0.01)

1

(0.04)
     

Asymptomatic with history of contact

10

1

* p>0.05

 

 

First Published April 28th 2007

Copyright ©Priory Lodge Education 2007

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