Tuberculosis in children: a new drug should simplify and facilitate treatment

Publicação: 2 de October de 2019

A single medication against this infection will be given to patients under 10 years old from 2020

The changes involve offering the same drugs available today as a single combined dose in a ‘3-in-1’ tablet

According to the World Health Organization (WHO), each day about 650 children die from tuberculosis worldwide – 80% of them under 5 years of age. The figures show that over 237 thousand children die each year in the world. Administering the treatment currently used is a hindrance and may lead to treatment failures, as the doses administered at home by the parents are not always adequate (there may be errors in cutting the tablets, and drug bioavailability may be uneven). In addition, this difficulty can cause treatment to be interrupted, irregular or abandoned. Currently, child treatment, in the most intense phase, combines three drugs (rifampicin 75mg, isoniazid 50mg and pyrazinamide 150mg). In the maintenance phase, the drugs are two: rifampicin 75mg and isoniazid 50mg. However, only one of these drugs – rifampicin – is currently available in liquid presentation. Pyrazinamide, although existing in solution, is currently missing.

But this reality is about to change. The Ministry of Health announced in September this year a new treatment for children with tuberculosis and a single pill will be used daily for the first two months of the disease (more intense phase) and another for the next four months (maintenance phase), which should facilitate administration and reduce possible dosing errors. In addition, the tablet will also be water soluble and have more palatable flavors. It is expected that the new format will be available in the Unified Health System (SUS) in 2020. According to the board, in 2018, 75 new cases of the disease occurred in Brazil, of which 1,552 were children aging from zero to 10 years.

Dr. Claudete Araújo Cardoso, from the Pediatric Coordination area of the Brazilian Network of Research on Tuberculosis REDE-TB, explains that treatment in children is more complex because at the moment there is no fixed dose of combined medicines as in adults. “The currently available pediatric formulations are more complex to administer if compared to adults, as it is necessary to offer three different types of drugs for treatment. Although the drugs are the same, the different presentation makes the current treatment more complex in children under 10 years if compared to adults”, he emphasizes.

Regarding the effectiveness of the treatment with combined drugs that will be offered next year, Professor Dr. Clemax Couto Sant’Anna, also from the Pediatrics Coordination of the Brazilian Network for Tuberculosis Research Network REDE-TB, ensures that they are as effective as the current ones. “The drugs are the same, what happened was the formulation of a single tablet with dispersible presentation, that is, the tablets can be dissolved in a small amount of water and no longer need to be macerated, and have the advantage of being easy to administer and with doses suitable for children”, he adds.

For Dr. Claudete it is essential to carry out cost-effectiveness and pharmacokinetic studies of the new formulation in the pediatric population with active TB and latent TB in the country. “Only through the results achieved in such studies will it be possible to assess the real impact of the new formulation on anti-TB therapy in children more easily and appropriately, thus increasing the chances of treatment success”, he points out. The expert also considers essential the transfer of information about the new presentation to health professionals who work with children with tuberculosis. “This should precede the implementation of the new formulation, so that its incorporation takes place properly and in an integrated manner”, he notes.

Prior to being offered to children, the single-dose model has been available for adults since 2010, with other formulations and in tablet presentation. Asked why it was almost ten years for the drug to be adapted for children, Dr. Clemax explains that there were some technical difficulties in the production of these drugs by the interested laboratories. “The goal was to ensure that dispersible tablet formulations could maintain WHO-recommended doses of each antimicrobial. In addition, the international advocacy movement was needed for the cause of children with tuberculosis. Several awareness-raising movements of NGOs and health-related parties have influenced the thinking of governments in this sense. The WHO emphasized the importance of childhood tuberculosis as of 2012 and this has greatly contributed to having these dispersible tablets today”, he acknowledges.

WHO data report that in 2017, one million children fell ill with tuberculosis worldwide. Every year, globally, 7,500 children under the age of 15 become infected with the bacillus. These children are at risk of developing the disease at some point in their life. The coordinators of the pediatric area of REDE-TB believe that the incorporation of dispersible tablets in the doses proposed by the National Commission for the Incorporation of Technologies in SUS (CONITEC) in Public Consultation No. 36 of 24/06/2019 will bring significant progress to the treatment of tuberculosis in childhood, increasing treatment adherence.

Tuberculosis kills three people in the world every minute

Regarding the incidence of the disease in childhood, Professor Clemax points out that it cannot be said that the incidence of tuberculosis in children has increased, but rather that there was no significant decrease, especially among the youngest. “The reduction in incidence was not significant. Several social movements, health service management and tuberculosis control programs around the world have been working on this reduction to meet WHO goals for TB elimination by 2050”, he says. In this sense, Brazil develops the “Brazil without Tuberculosis Plan”. For Dr. Claudete, reducing treatment dropout can be achieved with financial support for access to health care when needed, home visits for Directly Observed Treatment (DOT) of TB, and care centers close to the patient’s home. Monthly appointments to reinforce the need for treatment adhesion also contribute to reduce child treatment dropout rates.

According to WHO data, tuberculosis kills three people worldwide every minute. It is one of the top ten causes of death. Brazil is among the 30 countries with the highest incidence of the disease. Making TB care in the health network more effective can change this situation. But, according to Dr. Claudete, this should only happen to the extent that treatment is available in places closer to the patient’s residence. For her, such proximity to home provides better adherence to treatment and therefore a more significant clinical outcome of cure. “Another measure to improve the effectiveness of care is through home visits to the DOT administration, as well as the interdisciplinary approach through the joint evaluation of medical, nursing, pharmacy and social service professionals, which undoubtedly provides more effective care to the patient”, the expert concludes.

Brazil’s achievements in the fight against the disease

Brazil has advanced in its actions against tuberculosis. It has reduced half of the cases and will lead the global disease control strategy over the next three years. The Minister of Health, Luiz Henrique Mandetta, this year takes over the chairmanship of the Stop TB Partnership Council, an international organization that works to eliminate tuberculosis in the world. The institution is linked to the United Nations Office of Project Services (UNOPS/UN) and has about 1,700 representatives in over 100 countries, including governments, international organizations, research and funding agencies, as well as foundations and NGOs.

“We are putting Brazil at the forefront of the fight against the disease because it is a partner of Stop TB. We are leading the world to eliminate tuberculosis, so we are bringing not only the minister of health, with his training and leadership, but also the experience that Brazil has made over so many years in an effort to fight TB and achieve so much in a country with such a high burden”, said Lucica Ditiu, executive director of Stop TB.

This year, Brazil is in the pro tempore presidency of the BRICS (Brazil, Russia, India, China and South Africa) – a group of countries formed by emerging economies. And thus, also chairs the Tuberculosis Research Network, created in 2017, within the scope of the BRICS. By the end of the Brazilian mandate, the Ministry of Health aims to strengthen the work of researchers and countries to advance and develop innovative initiatives in tuberculosis. The BRICS concentrate 40% of tuberculosis deaths worldwide and, therefore, the commitment of the bloc is fundamental to eliminate the disease as a public health problem.

In July, during the opening ceremony of MEDTROP-PARASITO 2019, Luiz Henrique Mandetta announced an investment of R$ 16 million to finance the development of tuberculosis research within the BRICS Economic Group. The idea is to foster new interventions, therapeutic schemes and medications, as well as new methods of diagnosis and access to treatment of the disease. The public call will be launched at the end of the year and should include Brazilian institutions that will work in partnership with at least two other researchers from the bloc’s countries. The results of the Brazilian initiative may contribute to interventions in the BRICS health systems.