Double BCG vaccination in a neonate: implications, management and prevention

Abstract

Tuberculosis is a common cause of morbidity and mortality especially in low-income and middle-income countries like India. BCG vaccination is recommended for all neonates after birth in areas with a high tuberculosis disease burden. Here, we describe a case where a neonate received two doses of the BCG (Chennai strain) vaccine within a span of 4 days after birth due to a vaccination error. Parents were informed about the event. The infant was managed conservatively and followed up till 12 months of life for any possible complication. There were no serious adverse effects apart from the localised reaction and a double scar on the left arm. Measures to avoid any such error in the future and the need for reporting medication error has been highlighted. Parental concerns are frequent in such scenarios and should be actively addressed.

Background

An estimated 10.6 million people fell ill from tuberculosis (TB) in 2021 globally, out of which 1.6 million people died in the same year.¹ The burden of this disease is highest in low-income and middle-income countries (LMICs) such as India. BCG vaccine is one of the oldest vaccines, first tried almost a century ago² and remains one of the most effective preventive strategies to protect from severe forms of TB. WHO recommends giving BCG vaccine to all healthy neonates at birth or as soon as possible after birth, in countries or settings with a high incidence of TB.³ The efficacy of BCG vaccine has been proven in various studies, especially in reducing severe TB.^4–6 The standard dose of BCG vaccine is 0.05 mL for infants less than 1 year and 0.1 mL for infants more than 1 year, to be given intradermally.³ Here, we describe a case of a neonate who received two doses of BCG vaccine over a span of 4 days due to an error in the documentation and was followed up for 12 months for any adverse effects. Corrective steps that were taken thereafter to prevent such further episodes are also discussed so that at places of high delivery burden, these mistakes can be avoided.

Case presentation

A term neonate, with uneventful antenatal history, was born via a lower segment caesarean section (LSCS) in view of the previous LSCS, at 37 weeks of gestation and birth weight of 2.58 kg, appropriate for gestation age and good APGAR score. Perinatal history was uneventful, and the baby was shifted with the mother in the postnatal ward. The infant received birth dose vaccination of oral polio virus, hepatitis B and BCG within 12 hours of life. The infant again received BCG vaccination after 72 hours in view of inadequate documentation as the immunisation card was not issued during the first vaccination. Before the second dose of OPV and hepatitis B could be given, the error was recognised, and its administration was prevented. Parents were informed about the error and counselled about the possible complications and the need to follow-up for the same. There was no history of immunodeficiency in the family. The mother’s HIV status was negative and was not repeated in the infant. The infant was conservatively managed and was monitored closely for any complications. The infant was discharged on day 6 of life.

Treatment

The infant was managed conservatively, with a close follow-up till 12 months of life. Parents were counselled about the need to follow-up at regular intervals for possible complications. They were explained the possible issues that may occur and how to recognise these and the expected line of management if they occur. Parents needed ongoing counselling due to their concerns.

Outcome and follow-up

The infant was followed up in outpatient department (OPD) monthly until 6 months of life, then once every 3 months till 1 year. With any change in the condition of the infant, extra visits were made to the follow-up OPD. Infant developed local skin reaction in the form of papule formation followed by pustule at both BCG vaccination sites (7 mm and 12 mm in diameter) at 5–6 weeks of age, followed by spontaneous ulceration at both sites at around 7 weeks and scar formation by 9–10 weeks of age (figure 1). The infant is well, developmentally normal with two healed scars over the left upper arm. There were no systemic adverse effects or regional lymphadenitis associated with the double vaccination.

Figure 1.

(A) Local skin reaction—papule followed by pustule formation at both the sites of BCG vaccination at 5–6 weeks of age, (B) spontaneous ulceration at both sites at around 7 weeks, (C) scar formation by 9–10 weeks of age.

Discussion

Globally, TB is the 13th leading cause of death and among the most common infectious causes.¹ Sustainable development goals of the United Nations include ending TB epidemics by 2030 (Goal 3). Pillar 1 of the End TB strategy under the programme includes vaccination against TB as one of its components.⁷ BCG is currently the only available TB vaccine. It is a live attenuated bacterial vaccine derived from Mycobacterium bovis, originally isolated from a tuberculous cow in 1902, after repeated cultures in the ox bile, glycerine and potato medium.² Subsequent repeated cultures resulted in the loss of its virulence. The effectivity of BCG depends on the age of the population being given the vaccine, prior tuberculin skin test (TST) positivity and the type of disease being prevented. The maximum effect is seen in neonates and in school-age TST-negative children, with maximum protection against severe forms of TB, such as TB meningitis and miliary TB.^{4 5 8} Studies have shown that BCG vaccination in neonates can reduce the incidence of pulmonary TB by 59% and severe TB by 90%.⁴

Correct technique and dose of BCG vaccine by trained healthcare workers are important for the maximum benefits and safety. The vaccine is commonly available as lyophilised (freeze-dried) preparation in vacuum-sealed, multidose, amber-coloured ampoules, or 2 mL vials with normal saline as a diluent. The reconstituted vaccine is to be protected from light and stored at 2°C–8°C and discarded within 4–6 hours. The vaccine is given intradermally; in many countries on the lateral aspect of the left upper arm. Correct administration is verified by bleb formation. It is followed by a papule formation within 2–3 weeks, which increases in size up to 4–8 mm within 5–6 weeks. Then it ulcerates and heals with scar formation within 2–5 months of vaccination. Around 10% of those vaccinated may not develop scar formation.⁹ Adverse events following immunisation include large abscess (> 10 mm) at the site of vaccination, severe ulceration or suppurative lymphadenitis usually caused by inadvertent injection of the vaccine subdermally.^{10 11} Disseminated disease and involvement of sites other than the site of inoculation (eg, skin, intestine, bone and bone marrow) after vaccination are rare complications.^{3 12} Disseminated disease is mainly seen in patients with immunodeficiency.¹³

Case reports and series have been published describing inadvertent administration of high doses of BCG vaccine in neonates and adults.^14–18 Though a rare event with an estimated incidence of 2.2 cases per 1 million doses, this number might be an underestimation, due to the lack of reporting of such events.^{17 19} Many cases have been published with reports of high doses of BCG vaccine being given, but to the best of our knowledge, this is the first case where BCG was given twice within a span of 4 days in the neonate after birth. In view of the lack of literature on such cases, the patient was monitored as a case of overdosage of the BCG vaccine. Since BCG is a live attenuated vaccine, its excessive dose has the potential to cause adverse effects. Localised skin lesions followed by regional lymphadenitis are the most common presentation in these patients. Systemic complications are rare events. There are no clear guidelines for the management of such cases. It varies from only observation to aspiration of the abscess or surgical excision of the lump to anti-TB chemoprophylaxis.^13–17

In a case series of an overdose of the BCG vaccine, where 80 times the routine dose was given to 26 newborns, neonates were followed up for the adverse effects.¹⁴ All of them received isoniazid and rifampicin for 3 months as chemoprophylaxis. Local skin lesions were the most common adverse effect with lesions at BCG site observed in around 61% of cases, out of which papule followed by pustule, skin induration and skin erythema were the most common presentation. None of them developed clinical TB. In another case series of five neonates, twice the routine dose of BCG vaccine was given to the newborns. All the infants were managed conservatively, and followed till 12 months, at the end of which, none had any adverse effect attributable to vaccination.¹⁶ Wei et al reported accidental overdose of BCG vaccine to 20 infants aged 15 days to 7 months.¹⁸ Infants were managed conservatively and closely observed for complications. Three infants presented with abscess at the injection site, which resolved spontaneously within 6 weeks. Ritz et al reported an overdosage of the BCG vaccine by 10 times in a 14-year-old girl, who developed subcutaneous fluctuant tender lump at the injection site within few hours, which was surgically excised within 12 hours of immunisation and was given isoniazid and rifampicin for 6 weeks. In the follow-up, the patient did not develop any adverse effects, apart from the surgical scar.¹⁷

We describe a case of double immunisation with low-attenuated BCG Chennai strain vaccine, within a span of 4 days. In our case, since immunodeficiency was not suspected, and only double the routine dose was given, conservative management with close follow-up was planned. Parents were counselled about the error and transparency of the event was maintained throughout. There were no severe adverse effects, apart from the local abscess at injection site, followed by ulceration and scar formation at the two sites of vaccine administration. Follow-up of 1 year is a limitation in our case report. Adverse effects could manifest even later.

To prevent any such episodes in the future, corrective steps were taken. It was decided that an immunisation card would be created at the time of the immunisation, kept with the patient’s records and given to them at time of discharge. Previously, the card was both made and given to them at discharge. Another practice change done was a stamp which was placed on the front cover, indicating whether they had received their vaccinations. This was checked by the nurse before administering vaccine. Ideally, data of all the newborns should be maintained in a central database and vaccination status uploaded at the time of immunisation. Any infant receiving vaccination should first get it verified in the record and then immunisation should be given. In view of lack of resources and absence of any such database, this corrective step could not be done in our case. This case highlights the practical problems being faced in centres with high delivery load in LMICs, where due to inadequate records and manpower, immunisation errors can occur. Few simple steps that can prevent these vaccine errors in a busy birthing centre, are highlighted in this case report.

Learning points.

• Double vaccination of BCG in the index case did not cause any adverse reaction. However, such cases need appropriate follow-up to recognise and treat possible complications.

• Methods to prevent such vaccination errors have been emphasised, which can be followed in low-income and middle-income countries (LMICs).

• There is a need for better reporting of immunisation errors especially in LMICs.

• A policy of transparency should be in place in the event of immunisation mistakes. Parents should be informed about the error and counselled about the same. They may be extremely anxious about the situation and may require repeated counselling.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).