Intradermal BCG Research Articles

Intradermal vs percutaneous BCG in South African infants

Intradermal vs percutaneous BCG in South African infants

Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial

Objective To compare the incidence of tuberculosis over two years in infants vaccinated at birth with intradermal BCG or with percutaneous BCG.Design Randomised trial.Setting South Africa.Participants 11 680 newborn infants.Interventions...

Absence of Relationships Between Tuberculin Responses and Development of Adult Asthma With Rhinitis and Atopy

To investigate the relationship between tuberculin skin responses and the development of adult asthma, rhinitis, and atopy. Two hundred fourteen patients with mild-to-moderate asthma accompanied with rhinitis and 220 normal volunteers underwent a medical history, chest radiography, allergen skin-prick testing (SPT), bovine Mycobacterium tuberculosis vaccine (BCG) scar identification, purified protein derivative (PPD) tuberculin skin testing, serum-total and serum-specific IgE measurements, and bronchial provocation (provocative dose of histamine causing a 20% fall in FEV(1) [PD(20)]). Thirty-one normal volunteers (14.1%) and 168 asthma-rhinitis subjects (78.5%) had one or more positive skin test results (p < 0.0001). Neither the presence of a BCG scar nor a history of BCG vaccination had a significant effect on atopy in either group. The rate of PPD positivity had no statistical difference between atopy and nonatopy in both groups. In multivariate logistic regression analysis, the odds ratio for tuberculin reactivity was not related to the level of serum-total IgE nor to the level of serum-specific IgE to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), skin response to DP and DF, and PD(20). Overall, no significant correlations were found between tuberculin skin reactivity and log serum-total IgE or PD(20). There is no relationship between history of tuberculosis infection, tuberculin responses, and development of adult bronchial asthma, allergic rhinitis, and atopy. Our study suggests that the protection provided by intradermal BCG vaccination in infants to prevent atopic diseases may be limited in early childhood, when a substantial memory of cellular immune modulation still exists.

A case of extensive ulcerating vasculitis following a BCG vaccination

Adverse reactions following BCG vaccination are uncommon, with an estimated prevalance of 0.4 per 1000 vaccines [Lotte A, Wasz-Hockert O, Poisson N, et al. Second IUATLD study on complications induced by intradermal BCG vaccination. Bull Int Union Tuber 1988;63:47-59]. Complications include erythema, blistering, abscess formation, regional lymphadenitis and keloid formation. The onset of cutaneous tuberculosis (TB) has also been reported. We describe the case of 12-year-old girl who developed extensive primary ulceration involving most of her left upper arm at the site of a BCG vaccination. A skin graft to the arm failed to take at the periphery and the ulcerated area increased to involve most of the upper lateral arm. Over a period of 18 months, secondary lesions developed on her forehead prompting further investigation of a systemic disease process. Following extensive immunological and microbiological examination, a diagnosis of vaccine-induced granulomatous vasculitis was made and the patient responded to a combination of antituberculous therapy and steroids. Once the disease process was under control, skin grafting of the ulcerated area was successful in achieving wound closure. Non-healing ulceration may be referred to the plastic surgeon and a diagnosis of vasculitis should be considered in difficult cases. A multidisciplinary team approach involving immunologists, dermatologists and plastic surgeons provides the best opportunity for a successful long-term outcome in terms of disease control as well as immediate skin cover.

Risk and protective factors for leprosy development determined by epidemiological surveillance of household contacts.

Household contacts of leprosy patients are the group with the highest risk of developing the disease, and although many risk or prevention factors have been identified, they have not been employed in leprosy-monitoring programs. This investigation aimed to establish the relative risks or the preventive effects of the presence of BCG vaccination, the Mitsuda test, and the ML-Flow assay. Household contacts (1,396) were monitored for a 5-year period. Twenty-eight contacts (2%) developed leprosy and had their clinical and operational classifications established. All immunological tests were performed, and intradermal BCG vaccination was given after the BCG scar count. Of the affected contacts, 75% developed the disease in the first year, and 71.4% were classified as having paucibacillary forms. Contacts of lepromatous leprosy patients presented a 3.8-fold-higher risk of developing leprosy. BCG vaccination and the Mitsuda test showed a protective effect against leprosy of 0.27 (at least one scar) and 0.16 (>7 mm), respectively, and the positive ML-Flow test indicated a relative risk approximately sixfold higher for occurrence of the disease. All unfavorable combinations of two and three assays generated significant risk values that ranged from 5.76 to 24.47, with the highest risk given by the combination of no BCG scar, negative Mitsuda test, and positive ML-Flow test. We suggest that the BCG vaccination may be given to stimulate Mitsuda test positivity, reducing the patient's risk of developing multibacillary forms. The high significance of these tests may have a great impact on programs to monitor contacts and should be used to improve early detection and treatment.

Robust γδ+ T cell expansion in infants immunized at birth with BCG vaccine

Cell-mediated immune responses to BCG vaccine were evaluated in 7-month-old infants vaccinated with intradermal combined BCG and Hepatitis B or intradermal BCG and intramuscular Hepatitis B at birth. Peripheral blood mononuclear cell cultures from both groups showed CD4(+), CD8(+) and remarkable gammadelta(+) T cell BCG-specific proliferation, without significant differences. Also, IL-10, IL-12, IFN-gamma and TNF-alpha concentrations in culture supernatants, measured by ELISA, were similar. The results suggested that the combined BCG and Hepatitis B vaccine was as immunogenic as BCG separated from Hepatitis B vaccine.

Enquête sur les effets secondaires locaux du vaccin intradermique BCG-SSI ® chez l'enfant de moins de six ans en France

During April 2006, 579 physicians took part in a survey about intradermal BCG SSI ® adverse events (AE) in children less than 6 years old, managed by InfoVac France. Since January 2006, 68% physicians (paediatricians: 73% and general practitioners [GP]: 60%) have vaccinated at least one child. The site of injection is mainly the extern side of the shoulder (72%), according to the recommendations. Systematic vaccination is continued by 54% GP and 26% paediatricians. Others indications are: admission in day care center (33%), admission in day care center associated with risk factors (24%), or only risks factors (8%). Half physicians observed AE and 6% of them reported them at pharmacovigilance centers or pharmaceutical company. AE were mainly inflammations or indurations over 1 cm (for 75% of physicians who observed AE), oozing (73%). Abscesses are notified by 54%, ulcers by 39%, lymphadenopathies over 1 cm by 20%, suppurative lymphadenopathies by 3% and keloid scares by 17% of them, several AE may coexist for some children. Our aim is to start a prospective follow-up of BCG-SSI ® vaccination and its AE; 58% physicians who answered this investigation agreed to participate.

Boosting of Cellular Immunity against Mycobacterium tuberculosis and Modulation of Skin Cytokine Responses in Healthy Human Volunteers by Mycobacterium bovis BCG Substrain Moreau Rio de Janeiro Oral Vaccine

Oral immunization of healthy adults with 10(7) CFU BCG Moreau Rio de Janeiro was well tolerated and significantly boosted gamma interferon responses to purified protein derivative, Ag85, and MPB70 from previous childhood intradermal BCG immunization. Oral BCG offers the possibility of a needle-free tuberculosis vaccine and of boosting the protective immunity from intradermal tuberculosis vaccines.

The use of immunomodulators as an adjunct to antituberculous chemotherapy in non-responsive patients with osteo-articular tuberculosis

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months. The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm(3) (sd 261) and 545 cells/mm(3) (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm(3) (sd 343)) still remained lower than that of group I (1071 cells/mm(3) (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Lymphadenitis following intradermal BCG vaccination

Purpose:Intradermal BCG vaccine has not well been accepted by pediatric practitioners due to BCG lymphadenitis. Therefore, this study was undertaken to find out the incidence of lymphadenitis following intradermal BCG vaccination and its clinical outcome. Methods:One thousand and fifty infants, who received intradermal BCG(French 1173 P2, Korea Tuberculosis Association) vaccination in the Well Baby Clinic of Hanyang University Hospital from July 2001 to January 2004, were included in the study. Severe local reactions at the injection site and any mass noted on surrounding areas were reported to, and evaluated by, pediatricians. Surgical procedures, either surgical resection or needle aspiration, were recommended when lymph nodes progressed to suppurate without regression. Results:Twenty infants(1.9 percent) developed lymphadenitis 2 to 8 months following vaccination. The incidence of BCG lymphadenitis was significantly higher in infants born with intrauterine period of

The effect of local rifampicin instillation on the treatment of suppurative BCG lymphadenitis

Purpose:The purpose of this study was to evaluate the types of lymphadenitis after BCG vaccination and the effect of local rifampicin instillation on the treatment of suppurative BCG lymphadenitis. Methods:A total of 32 otherwise healthy infants with suppurative BCG lymphadenitis, who visited the Department of Pediatrics of Chonbuk National University Hospital, from March 2002 through June 2004, were enrolled in this study. They were treated with needle aspiration and local rifampicin instillation. We investigated the time the lymphadenitis took to be suppurative, accompanying clinical manifestations, and the treatment effects. Results:Of the 32 infants, 19 were male and 13 were female. They were full term babies and one preterm baby with a gestational age of 30 weeks. They received intradermal administration, with the BCG vaccine of PasteurⓇ(French) strain mostly on the left deltoid area(96.9 percent). Regional lymphadenitis occurred in 1 to 11 months after BCG vaccination, mostly 1-5 months after vaccination (78.1 percent). Among the infants, 87.5 percent had unilocular lesion but 12.5 percent had more than one enlarged lymph node cares. Most of the lymphadenitis presented in the left axillary area(77.8 percent), and the left supuraclavicular area(11.1 percent). After one to three times of needle aspiration with rifampin instillation, all infants recovered completely without surgical excision or severe complication. Conclusion:The regional lymphadenitis is the most common complication in infants who receive intradermal BCG vaccination. This study supports that in suppurative BCG lymphadenitis the needle aspiration and local rifampicin instillation is very effective and can be a more economical treatment modality.

BCG vaccine-associated suppurative lymphadenitis

Clusters of BCG vaccine-associated suppurative lymphadenitis (BCG-ASLD) have been reported in many countries. We have observed an increase in BCG-ASLD following the change from the percutaneous Evans vaccine to the intradermal BCG Statens Serum Institute (SSI) vaccine.

Percutaneous or intradermal BCG vaccine?

To compare the intradermal and percutaneous routes of BCG administration. A review of the literature published between 1987 and 2002 was carried out in the MEDLINE and Lilacs databases. The following key words were used: BCG vaccine/administration, adverse effects, efficacy, tuberculosis/prevention and control. Some articles published before 1987 were included because of their relevance to the topic. There are no clinical studies comparing the efficacy of intradermal and percutaneous BCG. Percutaneous BCG causes a weaker reaction, however it is also less efficient in stimulating gamma-interferon production by Th1-lymphocytes, which is considered as the best marker of the anti-tuberculin immune response. In vivo and in vitro studies suggest a better immune response with intradermal BCG. The intradermal method should be recommended for BCG administration.

Percutaneous or intradermal BCG vaccine?

Percutaneous or intradermal BCG vaccine?

The BCG scar after percutaneous multiple puncture vaccination may help establish the nationalities of unidentified cadavers

BCG vaccination using the multiple puncture device (the Heaf gun) has been used in Japan and in the United Kingdom. The appearance of the BCG scars therefore differs from that caused by the conventional intradermal BCG vaccination, which is used throughout the world. The aim of this study was to investigate the usefulness of examining BCG scars to identify the nationalities of unidentified cadavers. We investigated the BCG vaccination program not only in Japan, but also in other countries, along with the relation between the BCG scar and nationality. The results showed that the countries which domestically make and use the Heaf gun are Japan (where it is the only method that has been in use since 1968), the United Kingdom (where it has been used, in part, since 1982), and South Africa (where it has been used, in part, since 1972). In addition, for the past 10 years, the Japanese Heaf gun method has been partially applied in the Republic of Korea and in Brazil. The Heaf gun scar can be clearly distinguished from the intradermal scar, and is visible throughout a person’s life when good technique is used to administer the vaccination. If the Heaf gun scar is found on the left upper arm of an unidentified Asian cadaver, it is sure to be that of a Japanese. The findings of this present study indicate that the Heaf gun scar can be examined to identify the nationalities of unidentified cadavers.

Safety of the intradermal Copenhagen 1331 BCG vaccine in neonates in Durban, South Africa.

To evaluate the safety of the intradermal Copenhagen BCG vaccine in neonates at different levels of delivery and neonatal units of the Durban Functional Region and surrounding regions. A prospective study was carried out over a two-year period between July 1997 and June 1999. All neonates who had been vaccinated with the intradermal vaccine were evaluated at immunization clinics six weeks after immunization, or earlier if adverse effects occurred. In total, 9763 neonates were examined: in 95.4% the vaccination scar had healed and 1.5% had no visible scar. Adverse events occurred in 3.1%. The proportion of neonates with no visible vaccination scars decreased over the study period, as did the number with adverse events. The lowest rate of adverse events and the highest rates of healed vaccination scars were seen in the tertiary hospital and regional and district hospitals that were in close proximity to the academic centre involved in this study. In the study sites, the transition from the percutaneous to intradermal route of administration of BCG vaccine was successful and took place without incurring unacceptably high rates of adverse events. To minimize adverse events, however, it is essential to continue training health personnel involved in implementing intradermal BCG vaccination programmes.

Réaction anaphylactoïde post-BCG : le rôle du dextran ?

The authors describe the case of a 16-year-old male without any medical history who developed anaphylactic shock a few minutes after the injection of the intradermal vaccine BCG Pasteur. Chronology of events, lack of any other drug intake and the dramatic increase of serum tryptase level account for the anaphylactic reaction consecutive to vaccine injection. A few weeks after the accident, the allergic data donˈt reveal much. At this time, serum anti dextran IgG are significantly high (8 mg/L), suggesting the involvement of dextran in this severe adverse reaction.

Comparing the adrenaline–Pirquet test with international PPD tuberculin tests

Several tuberculins, strengths and setting methods are in everyday use. We wanted to compare the Norwegian reference adrenaline–Pirquet test with the internationally recommended Mantoux PPD test and Rhoditest.In responders of a random sample of young adults, with randomization of test subjects, we intra-individually compared the adrenaline-Pirquet (aP) test with Norwegian-produced synthetic medium tuberculin (SMT) with either the Mantoux test with PPD 2 tuberculin units (TU) (M2), the Mantoux–PPD 5 TU (M5) or the PPD 2 TU–Rhoditest (Rh). The criteria for a positive reaction were ≥4 mm for the aP test, ≥10 mm for the M2 test, ≥6 mm for the M5 test and ≥2 mm for the Rh test. Strongly positive reactions were defined as aP test ≥10 mm and M2/M5 test ≥15 mm.One of the tuberculin tests was positive while the comparison test was negative in 14% of the M2 test group (n=236), 15% in the M5 test group (n=162) and 20% in the Rh test group (n=187). The three PPD tests had positive reactions 3–10 times as often, with a simultaneous negative aP test, than vice versa. Strongly positive reactions occurred in 7% of the aP tests (≥10 mm), 32% of the M2 tests (≥15 mm) and in 41% of the M5 tests (≥15 mm). Receiver operating characteristic (ROC) curves gave the best agreement, with aP test ≥3 mm compared with the M2 and the Rh tests. Regression equations are presented for transformations of the Norwegian reference method of adrenaline–Pirquet results to internationally recommended PPD tests.The international recommendations, globalization in general and the skill of Norwegian public health nurses in performing intra-dermal BCG suggest a future shift to the PPD 2 TU Mantoux test in Norway. Due to the lack of sensitivity and specificity of all tuberculin tests they might be used in targeted tuberculin testing and not as a general screening procedure in a low-incidence tuberculosis area with BCG-vaccinated inhabitants.

Administration of the BCG vaccination using the multipuncture method in schoolchildren: a comparison with the intradermal method

BACKGROUNDBCG vaccination using the multipuncture device (the Heaf gun) is recommended in the UK for infants and very small children only. The aim of this study was to investigate the...

Adverse local reactions from accidental BCG overdose in infants.

Local reactions to BCG vaccine depend on the administration technique, the dose, and the type of BCG preparation.1 We report on infants who were accidentally vaccinated intradermally with a percutaneous BCG preparation, receiving about five times the upper limit of the currently recommended intradermal dose of BCG. All infants born at our hospital before November 1994 were routinely given intradermal BCG after written parental consent was obtained. A total of 857 infants were accidentally vaccinated intradermally with the percutaneous BCG (Evans E4981A and E4946B) between July and November 1994. After public announcement of the error, 556 of these infants attended special follow up clinics where they were examined for adverse reactions to BCG. The …