The position paper is intended for use mainly by national public health officials and managers of immunization programmes. They may also be of interest to international funding agencies, vaccine advisory groups, vaccine manufacturers, health professionals, researchers, the scientific media, and the general public.
General considerations on Tuberculosis
Tuberculosis (TB) was declared a global emergency by WHO in 1993, and Mycobacterium tuberculosis (M. tuberculosis) is now considered to be responsible for more adult deaths than any other pathogen. Vaccination with BCG still remains the standard for TB prevention in most countries because of its efficacy in preventing life-threatening forms of TB in infants and young children. It is inexpensive and usually requires only one administration in either newborns or adolescents (7, 8). As there is currently no suitable alternative, BCG will remain in use for the foreseeable future and may continue to be used as a prime vaccine in a prime-boost immunization schedule in conjunction with new TB vaccines.
BCG vaccine contains a live, attenuated strain of M. bovis that was originally isolated from cattle with tuberculosis and cultured for a period of 13 years and a total of 231 passages . The BCG vaccine was first used to immunize humans in 1921. Following its introduction into the WHO Expanded Programme on Immunization (EPI) in 1974, the vaccine soon reached global coverage rates exceeding 80% in countries endemic for TB
WHO position paper – February 2018
This position paper replaces the 2004 WHO position paper on Bacille Calmette-Guérin (BCG) vaccine and the 2007 WHO revised BCG vaccination guidelines for infants at risk for human immunodeficiency virus (HIV) infection. It incorporates recent developments in the tuberculosis (TB) field, provides revised guidance on the immunization of children infected with HIV, and re-emphasizes the importance of the birth dose. This position paper also includes recommendations for the prevention of leprosy.
Background of Tuberculosis
The causative agent of TB is the bacterium Mycobacterium tuberculosis. In children, TB occurs most commonly in those aged <5 years. While TB typically affects the lungs, it may also affect other sites of the body (extrapulmonary TB). HIV infection, malnutrition, tobacco use, and diabetes are predisposing factors for TB. Multi-drug resistant TB (MDR-TB) is caused when bacteria do not respond to the 2 most powerful first line anti-TB drugs. Globally, 1.7 billion people are estimated to be infected with M. tuberculosis and in 2016, 1.7 million people died from TB, including 400 000 among people infected
with HIV.
Leprosy
Leprosy is caused by Mycobacterium leprae and mainly affects the skin and peripheral nerves, if it presents with deformities it can result in lifelong disability. Cases tend to occur in clusters and mainly affect adults but can also occur in children. More than 200 000 cases were reported in 2016, including 12 819 new cases with visible deformities.
Buruli ulcer and other non-tuberculous mycobacterial (NTM) infections Buruli ulcer is caused by Mycobacterium ulcerans. In 2016, 1 864 new cases of Buruli ulcer were reported from 11 countries. Other non-tuberculous mycobacterial infections can cause a wide spectrum of diseases and are treated by combinations of antibiotics.
Bacille Calmette-Guérin (BCG) vaccines
BCG is a live attenuated bacterial vaccine derived from M. bovis. Several BCG vaccines, based on different strains, are available worldwide. While BCG has demonstrated significant effectiveness, protection has not been consistent against all forms in all age groups. BCG has also shown effectiveness in preventing leprosy (RR from 20-80%) and Buruli ulcer (RR of 50% in Africa region).
WHO Recommendations
BCG vaccination is recommended in countries or settings with a high incidence of TB and/or high leprosy burden as well as where Buruli ulcer occurs. A single dose should be given to all healthy neonates at birth. If the vaccine cannot be administered at birth, it should be given at the earliest opportunity thereafter.
Countries with low incidence of TB or leprosy may choose to selectively vaccinate high-risk neonates. Additionally, countries with declining rates of TB are encouraged to evaluate the epidemiology of TB and leprosy and consider a switch to selective risk group vaccination.
The standard dose of BCG vaccine is and intradermal injection of 0.05 mL of the reconstituted vaccine for infants <1 year, and 0.1 mL for those >1 year. BCG vaccine can be safely co-administered with other routine childhood vaccines including the hepatitis B birth dose. BCG multi-dose vials should be used despite any wastage. Studies have shown minimal or no evidence of any additional benefit of repeat BCG vaccination against TB or leprosy.
Therefore, revaccination is not recommended even if the tuberculin skin testing (TST) reaction or result of an IFN-ɣ release assay (IGRA) is negative.
Vaccination of older age groups, special populations, contraindications and precautions
Older age groups -. BCG vaccination of unvaccinated, TST-negative or IGRA-negative school children is recommended for those coming from or moving to high incidence/burden settings, as well as older groups at risk through occupational exposure.
Pregnant – As a precaution, BCG vaccination is not recommended during pregnancy.
Immunocompromised and HIV-infected person – BCG vaccination is contraindicated for
immunocompromised persons and for patients undergoing immunosuppressive treatment. Infants exposed to immunosuppressive treatment in utero or via breastfeeding should not receive BCG.
Children who are HIV-infected should not receive BCG vaccination. However, if HIV-infected individuals, including children, are receiving anti-retroviral therapy (ART), are clinically well and immunologically stable they should be vaccinated with BCG.
Neonates born to women of unknown HIV status should be vaccinated. However, neonates with unknown HIV status born to HIV-infected women should be vaccinated if they have no clinical evidence suggestive of HIV infection, regardless of whether the mother is receiving ART. Additionally, neonates with HIV infection should delay BCG vaccination until ART has been started and are immunologically stable.
Neonates born to mothers with pulmonary TB – BCG vaccination is recommended if an infant is asymptomatic, has no immunological evidence of TB, and is HIV-negative.
Further Monitoring and Research Needs To better understand the safety and effectiveness of BCG vaccination at different ages and in different populations, especially of HIV-infected children including those receiving ART, reporting of TB cases is encouraged. Additionally, further evidence is needed on programmatic strategies of BCG vaccination, such as timeliness of vaccination and wastage.
There is also a need for development of vaccines that provide greater protection than BCG on all forms of TB for all age groups including persons infected with HIV. The development of more effective vaccines against leprosy is also encouraged.
23 FEBRUARY 2018
SOURCE: WHO
