The Tuberculosis Vaccine Pipeline
In addition to the risks for developing BCG disease, evidence suggests that BCG provides little to no protection for HIV-infected infants (Mansoor 2009). The World Health Organization (WHO) revised its guidelines to recommend that infants with a confirmed HIV diagnosis should not receive BCG vaccination. This recommendation is impossible to implement in many high-burden settings because of limited capacity to rapidly confirm diagnosis using HIV RNA testing. Despite its variability and limitations, it is estimated that the BCG vaccine saves the lives of over 40,000 children annually (of over 100 million vaccinated). This makes the decision of whether or not to vaccinate HIV-exposed children where HIV RNA testing is not available a challenge for both parents and health care providers. Without being able to confirm an HIV diagnosis using RNA testing soon after birth, parents and their health care providers are forced to weigh the risks (BCG disease) versus the benefits (protection against severe forms of pediatric TB) of BCG vaccination. Policy makers, clinicians, and researchers are struggling with how to use BCG more effectively and safely and what alternative strategies can be used in its place. There are a few vaccines in preclinical and early-phase clinical studies that may be replacements for BCG. But these constructs are years away from efficacy testing. Delaying BCG vaccination by providing isoniazid preventive therapy (IPT) to HIV-exposed infants as preexposure prophylaxis until HIV status can be confirmed, as well as early initiation of antiretroviral treatment (ART), may be ways to address the challenges of BCG in HIV-exposed infants, but each strategy comes with implementation challenges. HIV RNA testing is not part of regular clinical practice in many high-TB-burden countries and it is unclear how long BCG vaccination can be delayed; studies are underway that hope to answer this question. Because it is difficult to bacteriologically confirm TB diagnosis in infants and young children, and the fact that pediatric TB is often an indication that a close adult contact is sick, IPT is a significantly underused strategy due to the fear of promoting isoniazid resistance. While great progress has been made in scaling up access to HIV treatments, a majority of those in need are still waiting for treatment; therefore, getting infants into treatment earlier may be a significant challenge in places where many people have been waiting for years to get ART. Because BCG is part of the WHO’s Expanded Program on Immunisation schedule of vaccines it is administered in conjunction with a host of other vaccines (including those for measles, polio, and tetanus) throughout the world. Little explanation is given to parents about the vaccines, and many people misunderstand the limitations of protection that BCG provides. Some may incorrectly believe that because they were vaccinated against TB that they are protected against all forms of the disease for their entire lifetime. The lack of community understanding of the limitations of BCG is a major obstacle in creating community demand for a newer, better, and safer TB vaccine.
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