New Drugs for the Treatment of Tuberculosis in Children

In its most recent update of the Model List of Essential Medicines, the WHO has included several new drugs for the treatment of tuberculosis

In its most recent update of the Model List of Essential Medicines, the World Health Organisation has included several new drugs for the treatment of tuberculosis (TB). This list specified the minimum set of essential medicines that should be available in a basic health service and it is used as a guide in many countries where it has improved access to essential drugs.

For the first time, the list includes the use of fixed dose combinations for treating paediatric TB as well as delamanid, a new treatment for multidrug-resistant TB in children

The latest update sees the addition of 30 new medicines for adults and 25 for children, bringing the total to 433 essential medicines for the treatment of priority diseases. For the first time, the list includes the use of fixed dose combinations (FDC) for treating paediatric TB as well as delamanid, a new treatment for multidrug-resistant TB (MDR-TB) in children aged 6 to 17 years. These two essential additions address a global health problem of growing importance: paediatric TB, one of the diseases specifically included in the health targets of the Sustainable Development Goals (SDG).

Every year 1 million children in the world get sick with TB and over 200,000 of them die as a result of this preventable and treatable disease

Every year 1 million children in the world get sick with TB and over 200,000 of them die as a result of this preventable and treatable disease. Children infected with Mycobacterium tuberculosis have a greater risk of developing active disease than infected adults. Any delay in diagnosis and, therefore, in the start of treatment increases the risk of rapid progression of the disease and consequently of a fatal outcome. TB is usually diagnosed by identifying the bacteria in a sputum sample and such identification is particularly difficult in paediatric patients. The probability of identifying the bacteria in children is 20% lower than what can be expected in ideal conditions. The challenges involved give rise to errors in diagnosis and help to obscure the real extent of the epidemic of TB in the paediatric population.  

The good news is that once diagnosed TB can be treated and cured

The good news is that once diagnosed TB can be treated and cured. However, in many settings and for a long time, most children have not had access to treatments designed specifically for children, that is, formulations providing the paediatric doses recommended by the WHO in a child-friendly presentation. Parents and care providers often have to chop and crush pills intended for adults and try to dissolve them in liquid to ensure that the child will swallow the medicine in spite of the bitter taste; and this has to be done every day for the interminable 180 days it takes to complete the course of treatment. 

The availability of these new paediatric formulations developed by the WHO with the support of the TB Alliance and UNITAID represents an unprecedented advance in the treatment of this disease

The availability of these new paediatric formulations developed by the WHO with the support of the TB Alliance and UNITAID represents an unprecedented advance in the treatment of this disease. The new child-friendly medicine, which costs $15.5 for a 6-month course, is manufactured by the Indian pharmaceutical company MacLeods. It is a fixed dose combination of three active ingredients (rifampicin, isoniazid and pyrazinamide) in the correct doses as specified by the most recent WHO recommendations. Moreover, the drug is soluble and has a pleasant flavour.

Kenya was the first country to implement this treatment on the national level, and the new formulas are now recommended in the national guidelines of over 30 countries.

Although the number of TB cases is decreasing worldwide, there is a proportional increase in cases of multidrug-resistant TB (MDR-TB). Cases of MDR-TB do not respond to the usual combination treatments and require treatment with combinations of up to 7 different drugs. Patients on these complex regimens have to take as many as 20 pills a day for 18 months, and treatment is associated with severe side effects that include permanent deafness and psychosis. Almost none of the second-line drugs used to treat these resistant forms of the disease are available in paediatric formulations, and research and development (R&D) into the treatment of MDR-TB is not just urgently needed, it is a moral imperative.

Photo by Andalu Vila San Juan

Advancing the argument that the problem of MDR-TB is adequately addressed in other specific programmes, the WHO excluded TB from the list of antibiotic-resistant ‘priority pathogens’ published earlier this year. The stated purpose of this list is to identify the bacteria that pose the greatest threat to human health for which new antibiotics are urgently needed. The aim is to promote R&D leading to new antibiotics that can combat the growing worldwide problem posed by antimicrobial resistance.

The exclusion of TB from the list of antibiotic-resistant ‘priority pathogens’ is clearly unjustified

The exclusion of TB from this list is clearly unjustified and also contradictory in light of the global epidemiological evidence, which indicates that TB is the leading cause of death worldwide from resistant pathogens. In 2050, TB could account for over 25% of the 10 million deaths caused by resistant pathogens. The exclusion of TB from the WHO list has tangible and harmful effects on an area of research that is already underfunded. Less money is being spent on TB research today than at the height of the last economic recession.  This lack of funding for R&D is reflected in the fact that only two new drugs for TB have been approved in the last almost 50 years (bedaquiline and delamanid). 

The welfare of our children is central to the 2030 Agenda for Sustainable Development and the SDG targets cannot be met without greater political commitment to the R & D urgently needed to address the major health problems that affect the paediatric population. TB is one of those problems.