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Study shows regimen for short-course preventive therapy for TB for children is valuable alternative

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Results from the TITI Study, published in the IIJTLD, demonstrates that a three-month rifampicin-isoniazid (3RH) regimen was found to be a valuable alternative to the six-month isoniazid (6H) regimen for preventing TB in young children.

Results from the TITI (Transmission Investiguée de la Tuberculose Infantile) Study, published in the April issue of the International Journal of Tuberculosis and Lung Disease (IJTLD),  demonstrate that a three-month rifampicin-isoniazid (3RH) regimen was found to be a valuable alternative to the six-month isoniazid (6H) regimen for preventing tuberculosis (TB) in young children. This shorter regimen can facilitate better adherence and completion and is available as a fixed dose combination tablet that is dispersible and child friendly.

TITI study involved the systematic screening of children under five years living with adults with bacteriologically confirmed pulmonary TB in the largest cities in Benin, Burkina Faso, Cameroon and Central African Republic. The study, which has also shown that contact investigation and preventive therapy were successfully implemented in resource-limited urban settings under programmatic conditions with few additional resources being required, was coordinated by The Union.

According to the World Health Organization (WHO), TB is estimated to have affected 1.1 million children worldwide in 2018, yet significantly less than 50 percent of children with active TB receive appropriate diagnosis and treatment. Around 230,000 children die annually from the disease, and 80 percent of children who die from TB are younger than five years of age.

Dr Kobto G Koura, Programme Coordinator – Africa at The Union, said: “This is the first study using the new fixed dose combination of 3RH as preventive treatment for eligible young child contacts in TB-endemic settings with a one-year post-treatment follow-up. The study showed very low incidence of TB during follow-up, indicating that both 6H and 3RH were effective in preventing TB up to 12 months after treatment completion.”

Isoniazid alone, given daily for a duration of six or nine months (6H or 9H), has been the main regimen for preventive therapy in children for decades, but shorter regimens with similar efficacy are now also recommended. The fact that 3RH demonstrated similar effectiveness and safety to the longer isoniazid regimens offers potential to reduce barriers to treatment completion.

The study showed high rates of uptake (91 percent) and completion (94 percent) of TB preventive therapy. High coverage of contact investigation and high uptake of preventive therapy in this study is likely due to the support provided to staff in the form of training and supervision, alongside good provision of information to the index person with TB about the services and their benefits, and the payment of transportation fees, chest X-rays costs and credits for phone contacts.

In the same issue of the IJTLD, an editorial cited the TITI study as dispelling various myths about contact screening and treatment within TB programmes, namely:

  • it was possible to evaluate most children with few additional resources
  • initiation and completion of preventive therapy was high
  • the number of children treated for TB disease after completion of preventive therapy was far lower than the expected frequency of progression by age.

The proportion of household contacts tested and treated was higher than that reported in other settings, yet the support provided was simpler, with the authors estimating that the support costs were $32 US per child.

The cost associated with providing TB prevention to all children who need it requires an initial investment, but will result in longer-term health gains and savings by preventing subsequent TB disease in the most vulnerable – treatment for which carries a direct medical cost of at least 10 times the cost of prevention.

The Union previously identified Child TB as being a silent epidemic, impacting on the segment of society too young to advocate for themselves. While preventive therapy for young children with TB contacts, even without access to tests for infection, has been a WHO recommendation for high-risk populations since 1998, less than 30 percent of eligible household contacts are started on treatment.

The International Journal of Tuberculosis and Lung Disease (IJTLD) is an official publication of The Union. Further information about the journal and how to take out a subscription is available on The Union website.

Editorial (free to view): Fighting a Hidden Epidemic: Expanding Tuberculosis Preventive Treatment to the Youngest Household Contacts. Andrea Cruz, Kevin Schwartzman, and Ian Kitai.

Original article (for Union members): Tuberculosis contact investigation and short-course preventive therapy among young children in four African countries. Valerie Schwoebel et al.