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Tubercle (1990) 71, 177-180 0 Longman Group UK Ltd 1990
Evaluation of BCG at birth in the United Arab Emirates M. R. SEDAGHATIAN” Department
and I. A. K. SHANA’A
of Neonatology,
Mafraq Hospital, Abu Dhabi, United Arab Emirates
Summary-A total of 387 healthy full term infants who received BCG vaccination at birth were evaluated by the tuberculin PPD test at 6-8 weeks post vaccination. A total of 92% of these infants had visible BCG scars at that time. All infants were tested with PPD but only 264 returned for the test to be read. The tuberculin test was negative in 37 (14%) and of less than 5 mm induration in another 60 (23%) of the infants. The same pattern was observed in different nationalities. Of 11 infants with no BCG scar after vaccination, 3 had positive PPD reactions of more than 5 mm induration. There was a significant correlation between the size of the BCG scar and induration of tuberculin test P c 0.001. The complications of the vaccination were minimal. We have observed 3 sterile abscesses at the site of BCG vaccination which resolved spontaneously. We think the available vaccine is safe and potent, and that the rate of BCG scar formation and of tuberculin conversion is higher than in most studies.
Introduction
The DurDose of this studv was to evaluate the effectiveness of our neonatal BCG vaccination policy in healthy full term infants by looking at the following criteria I
Tuberculosis is a major public health problem especially in the United Arab Amirates (UAE), because of multinational inhabitants. It is an important cause of childhood morbidity and mortality in many developing countries, the extent of which is often not known in precise terms. BCG vaccination shortly after birth has been shown to protect against tuberculosis in many countries [l, 2, 31. The policy of the Ministry of Health in UAE is to offer BCG vaccination to all babies within the first few days after birth. * Correspondence: Dr M. R. Sedaghatian, Consultant and Head, Department of Neonatology, Mafraq Hospital, P.O. Box 2951, Abu Dhabi, United Arab Emirates.
177
I
,
1. The percentage of negative scars after BCG vaccination. 2. The correlation between the size of the BCG scar and induration of the tuberculin PPD test. 3. The percentage of tuberculin conversion at 6-8 weeks post BCG vaccination. 4. The correlation between negative BCG scars and positive PPD test. 5. The number of complications of vaccination in this age group.
178 Materials and methods According to Ministry of Health policy in UAE, all the full term newborn infants born at Mafraq Hospital were given the BCG vaccine during the first 5 days of life. The vaccine was a heat-stable, freeze-dried glutamatae BCG vaccine from the Japan BCG laboratory. A homogenous suspension in a concentration of 0.5 mg per ml was prepared by the single public health nurse and 0.1 ml was given by intradermal injection, During a period of 8.5 months from 21 September 1986 until 7 June 1987, a total of 1640 live born infants were delivered in Mafraq Hospital. From this group, 387 infants who had documented evidence of having received BCG vaccination in the early neonatal period were returned to the neonatal clinic at the age of 6-8 weeks postvaccination. The site of the BCG vaccination was evaluated and graded as no scar, l-2 mm bud, 34 mm bud, 4-5 mm bud and more than 5 mm bud. The tuberculin PPD test was then performed on the middle third of the flexor surface of the forearm. The PPD was purified lympholized tuberculin from Institute Merieux, Lyon, France. The intradermal injection was performed by a single nurse with 0.1 ml of the solution which contained 10 IU of purified tuberculin. The maximum transverse diameter of induration was measured with a transparent plastic ruler 48-72 h after the test. The test was graded as non-reactive (~1 mm induration), 2-5 mm, 6-9 mm and 210 mm induration. Results During the 8.5 month study period, a total of 387 infants who received BCG vaccination at birth returned to the hospital for evaluation. There was no BCG scar in 30 infants (8%), 1 mm papule in 103 (27%)) 2-3 mm papule in 133 (34%), 4-5 mm papule in 78 (20%) and more than 5 mm papule in 43 (11%). All these infants were tuberculin tested, but only 264 returned for the test to be read. The test was negative in 37 infants (14%), 2-5 mm induration in 60 (23%), 6-9 mm induration in 60 (23%) and 10 mm or more induration in 107 (40%) (Table 1). The same patterns were observed in different nationalities. The sizes of the transverse indurations of the tuberculin tests are shown in Figure 1. There was a significant correlation between
SEDAGHATIAN
AND SHANA’A
Table 1 Correlation between the size of BCG scar and PPD induration in 264 infants (percentages are given in brackets) BCG
. Neg (%)
PPD
I mm (%) papule
2-3 mm 4-5 mm >5 nun papule papule pap&e Total
O-l mrri induration 5 (46) Non-reactive
13 (18)
14 (14)
3 (6)
2 (6)
37
2-5 mm induration
3 (27) (73)
25 (34) (52)
18 (18)
6 (12)
8 (25)
60
(32)
(18)
(31)
6-9 induration
2 (18)
18 (25)
26 (27)
lO(21)
4 (13)
60
l(9)
17 (23)
41 (41)
30 (61)
18 (56)
107
510 mm induration Total
(27) (48) (68) (82) (69) 11 (100) 73 (100) 99 (100) 49 (100) 32 (100) 264
x2 = 37.31654,
P < 0.001
the size of BCG scar and the diameter of the induration of the tuberculin test (Table 1) (P < 0.001): 8 of 11 infants who had no BCG scar also had 5 mm or less induration. As the size of BCG scar increased, the percentage of small or negative tuberculin reactions (5 mm or less) decreased. Of 97 infants with tuberculin reactions of 5 mm or less, 78 (80%) of them had BCG scars of 3 mm or less. We did not test these infants with stronger PPD solutions. Discussion In many developing countries tuberculosis is still a major public health problem. BCG vaccination has been given to very young infants since 1922. The use of this vaccine at birth has been shown to protect against haematogenous spread of primary tuberculosis [3, 4, 51. The effectiveness of BCG vaccination depends on the quality of the vaccine, its transportation and the technique of the vaccination [6]. The recommendation of the Ministry of Health in UAE made in 1986 on neonatal BCG vaccination stimulated us to evaluate the effectiveness of the BCG vaccine in the first week of life by testing tuberculin conversion at 6-8 weeks postvaccination and determining the complication rate of BCG vaccine. The presence of BCG scars was used as one of the criteria to assess the coverage of the vaccination. The absence of a scar after BCG vaccination has been found to be between 3 and
NEONATAL
179
BCG VACCINATION
30%
252.
12
6
--l
t-l
I
12-13 14-15 Fig. 1
The diameters
of the induration
of the tuberculin
t
1.1
16-17
I
I
18-19
7
PPD tests (mm).
25% in different studies [7, 81. In our study 11 (8%) of infants had no BCG scar. Of these, 3 had positive tuberculin reactions of more than 5 mm induration (Table 1). Grindulis [8] found that 25% of 149 Asian neonates who received intradermal injection of BCG vaccine at birth had no BCG scars 22 months after vaccination but, of these, 40% had positive Mantoux tests. It is probable that some of these infants with no visible BCG scars had unsatisfactory vaccinations. The technique of multiple puncture vaccination (DermoJet) which appears to require less skill than an intradermal injection by syringe and needle, especially in newborns, may be advantageous at an early age [2, 61. The size of the tuberculin reaction after vaccination is not generally thought to influence the degree of protection offered by BCG; 38% of our infants, 80% of those in the study of Karalliedde [7] and 50% in that of Grindulis [8] had negative tuberculin tests (less than 5 mm induration) after BCG vaccination. The mean size of induration of the tuberculin test was 3.5 mm at 3 months of age in Karalliedde’s study and 7.7 mm at 6-8 weeks post-vaccination in our study (Fig. 1). In Karalliedde’s study 50% of infants who were examined at 3 months of age had tuberculin anergy (O-l mm
induration) despite the presence of a BCG scar, compared to 14% in our report at 6-8 weeks postvaccination. This could be due to both the quality and the quantity of the BCG vaccine, the nutritional status of the nation, the method of intraderma1 injection of both vaccine and PPD and the time interval between BCG vaccination and the PPD test. In our study, the percentage of negative tuberculin reactors decreased as the size of BCG scar increased and this correlation is significant (P
Tubercle (1990) 71, 177-180 0 Longman Group UK Ltd 1990
Evaluation of BCG at birth in the United Arab Emirates M. R. SEDAGHATIAN” Department
and I. A. K. SHANA’A
of Neonatology,
Mafraq Hospital, Abu Dhabi, United Arab Emirates
Summary-A total of 387 healthy full term infants who received BCG vaccination at birth were evaluated by the tuberculin PPD test at 6-8 weeks post vaccination. A total of 92% of these infants had visible BCG scars at that time. All infants were tested with PPD but only 264 returned for the test to be read. The tuberculin test was negative in 37 (14%) and of less than 5 mm induration in another 60 (23%) of the infants. The same pattern was observed in different nationalities. Of 11 infants with no BCG scar after vaccination, 3 had positive PPD reactions of more than 5 mm induration. There was a significant correlation between the size of the BCG scar and induration of tuberculin test P c 0.001. The complications of the vaccination were minimal. We have observed 3 sterile abscesses at the site of BCG vaccination which resolved spontaneously. We think the available vaccine is safe and potent, and that the rate of BCG scar formation and of tuberculin conversion is higher than in most studies.
Introduction
The DurDose of this studv was to evaluate the effectiveness of our neonatal BCG vaccination policy in healthy full term infants by looking at the following criteria I
Tuberculosis is a major public health problem especially in the United Arab Amirates (UAE), because of multinational inhabitants. It is an important cause of childhood morbidity and mortality in many developing countries, the extent of which is often not known in precise terms. BCG vaccination shortly after birth has been shown to protect against tuberculosis in many countries [l, 2, 31. The policy of the Ministry of Health in UAE is to offer BCG vaccination to all babies within the first few days after birth. * Correspondence: Dr M. R. Sedaghatian, Consultant and Head, Department of Neonatology, Mafraq Hospital, P.O. Box 2951, Abu Dhabi, United Arab Emirates.
177
I
,
1. The percentage of negative scars after BCG vaccination. 2. The correlation between the size of the BCG scar and induration of the tuberculin PPD test. 3. The percentage of tuberculin conversion at 6-8 weeks post BCG vaccination. 4. The correlation between negative BCG scars and positive PPD test. 5. The number of complications of vaccination in this age group.
178 Materials and methods According to Ministry of Health policy in UAE, all the full term newborn infants born at Mafraq Hospital were given the BCG vaccine during the first 5 days of life. The vaccine was a heat-stable, freeze-dried glutamatae BCG vaccine from the Japan BCG laboratory. A homogenous suspension in a concentration of 0.5 mg per ml was prepared by the single public health nurse and 0.1 ml was given by intradermal injection, During a period of 8.5 months from 21 September 1986 until 7 June 1987, a total of 1640 live born infants were delivered in Mafraq Hospital. From this group, 387 infants who had documented evidence of having received BCG vaccination in the early neonatal period were returned to the neonatal clinic at the age of 6-8 weeks postvaccination. The site of the BCG vaccination was evaluated and graded as no scar, l-2 mm bud, 34 mm bud, 4-5 mm bud and more than 5 mm bud. The tuberculin PPD test was then performed on the middle third of the flexor surface of the forearm. The PPD was purified lympholized tuberculin from Institute Merieux, Lyon, France. The intradermal injection was performed by a single nurse with 0.1 ml of the solution which contained 10 IU of purified tuberculin. The maximum transverse diameter of induration was measured with a transparent plastic ruler 48-72 h after the test. The test was graded as non-reactive (~1 mm induration), 2-5 mm, 6-9 mm and 210 mm induration. Results During the 8.5 month study period, a total of 387 infants who received BCG vaccination at birth returned to the hospital for evaluation. There was no BCG scar in 30 infants (8%), 1 mm papule in 103 (27%)) 2-3 mm papule in 133 (34%), 4-5 mm papule in 78 (20%) and more than 5 mm papule in 43 (11%). All these infants were tuberculin tested, but only 264 returned for the test to be read. The test was negative in 37 infants (14%), 2-5 mm induration in 60 (23%), 6-9 mm induration in 60 (23%) and 10 mm or more induration in 107 (40%) (Table 1). The same patterns were observed in different nationalities. The sizes of the transverse indurations of the tuberculin tests are shown in Figure 1. There was a significant correlation between
SEDAGHATIAN
AND SHANA’A
Table 1 Correlation between the size of BCG scar and PPD induration in 264 infants (percentages are given in brackets) BCG
. Neg (%)
PPD
I mm (%) papule
2-3 mm 4-5 mm >5 nun papule papule pap&e Total
O-l mrri induration 5 (46) Non-reactive
13 (18)
14 (14)
3 (6)
2 (6)
37
2-5 mm induration
3 (27) (73)
25 (34) (52)
18 (18)
6 (12)
8 (25)
60
(32)
(18)
(31)
6-9 induration
2 (18)
18 (25)
26 (27)
lO(21)
4 (13)
60
l(9)
17 (23)
41 (41)
30 (61)
18 (56)
107
510 mm induration Total
(27) (48) (68) (82) (69) 11 (100) 73 (100) 99 (100) 49 (100) 32 (100) 264
x2 = 37.31654,
P < 0.001
the size of BCG scar and the diameter of the induration of the tuberculin test (Table 1) (P < 0.001): 8 of 11 infants who had no BCG scar also had 5 mm or less induration. As the size of BCG scar increased, the percentage of small or negative tuberculin reactions (5 mm or less) decreased. Of 97 infants with tuberculin reactions of 5 mm or less, 78 (80%) of them had BCG scars of 3 mm or less. We did not test these infants with stronger PPD solutions. Discussion In many developing countries tuberculosis is still a major public health problem. BCG vaccination has been given to very young infants since 1922. The use of this vaccine at birth has been shown to protect against haematogenous spread of primary tuberculosis [3, 4, 51. The effectiveness of BCG vaccination depends on the quality of the vaccine, its transportation and the technique of the vaccination [6]. The recommendation of the Ministry of Health in UAE made in 1986 on neonatal BCG vaccination stimulated us to evaluate the effectiveness of the BCG vaccine in the first week of life by testing tuberculin conversion at 6-8 weeks postvaccination and determining the complication rate of BCG vaccine. The presence of BCG scars was used as one of the criteria to assess the coverage of the vaccination. The absence of a scar after BCG vaccination has been found to be between 3 and
NEONATAL
179
BCG VACCINATION
30%
252.
12
6
--l
t-l
I
12-13 14-15 Fig. 1
The diameters
of the induration
of the tuberculin
t
1.1
16-17
I
I
18-19
7
PPD tests (mm).
25% in different studies [7, 81. In our study 11 (8%) of infants had no BCG scar. Of these, 3 had positive tuberculin reactions of more than 5 mm induration (Table 1). Grindulis [8] found that 25% of 149 Asian neonates who received intradermal injection of BCG vaccine at birth had no BCG scars 22 months after vaccination but, of these, 40% had positive Mantoux tests. It is probable that some of these infants with no visible BCG scars had unsatisfactory vaccinations. The technique of multiple puncture vaccination (DermoJet) which appears to require less skill than an intradermal injection by syringe and needle, especially in newborns, may be advantageous at an early age [2, 61. The size of the tuberculin reaction after vaccination is not generally thought to influence the degree of protection offered by BCG; 38% of our infants, 80% of those in the study of Karalliedde [7] and 50% in that of Grindulis [8] had negative tuberculin tests (less than 5 mm induration) after BCG vaccination. The mean size of induration of the tuberculin test was 3.5 mm at 3 months of age in Karalliedde’s study and 7.7 mm at 6-8 weeks post-vaccination in our study (Fig. 1). In Karalliedde’s study 50% of infants who were examined at 3 months of age had tuberculin anergy (O-l mm
induration) despite the presence of a BCG scar, compared to 14% in our report at 6-8 weeks postvaccination. This could be due to both the quality and the quantity of the BCG vaccine, the nutritional status of the nation, the method of intraderma1 injection of both vaccine and PPD and the time interval between BCG vaccination and the PPD test. In our study, the percentage of negative tuberculin reactors decreased as the size of BCG scar increased and this correlation is significant (P
