Working from the premise that when taken daily, Isoniazid or INH prevents the development of tuberculosis in adults who have HIV, the study recruited over 500 HIV-positive children and about 850 HIV-uninfected children that were born to HIV-positive mothers in high-risk TB areas of Johannesburg, Cape Town and KwaZulu-Natal. The study sought to investigate whether the use of Isoniazid at a very early age ‘€“ three to four months – can protect children from developing TB as most infection occurs in children under two years of age. It was a randomised study where one group of children received the actual Isoniazid pill and the other a placebo. The intervention proved to be ineffective. Shabir Madhi is the Director of the National Institute for Communicable Diseases (NICD).    

‘€œUnfortunately, what the study showed is that, firstly, even when HIV-infected children are receiving antiretroviral treatment, as much as 20% of them will actually develop tuberculosis in the first two years of life. So, it tells us that even with antiretroviral treatment HIV-infected children remain highly susceptible to developing tuberculosis’€, says Professor Madhi, Director of the National Institute for Communicable Diseases (NICD).

‘€œThe results of the study, unfortunately, showed as well that the use of Isoniazid prophylaxis aimed at preventing TB, unfortunately did not work in reducing the risk of developing TB infection in the HIV-uninfected children that were born to HIV-infected mothers’€, Professor. Madhi continues.    

In HIV-negative children, it was found that about 4 ‘€“ 5% get infected with TB annually in the first two years of their lives. Professor Madhi says to participate in the study the young ones had to come from a household with no prior history of TB infection. Yet, some of the children did develop TB.      

‘€œWhat we found, subsequently, is that of all of the children that developed tuberculosis in this particular study, only one-third of them actually developed tuberculosis in the presence of another member in that household having TB, which tells us that the majority of children that develop tuberculosis, the exposure to the infectious case is actually unknown. And the frightening part of that is that it goes against the dogma that children usually develop TB mainly because of household contact’€, he says.

‘€œWhat that tells us is that children mainly become infected with tuberculosis because of the adults that are surrounding them. And what it tells us is that we need to basically improve our targeting of the management of tuberculosis in adults to prevent the child from becoming infected because all of this infection and all of this disease that’€™s happening in children is almost a measure’€¦ it’€™s a marker of how well we’€™re doing in terms of controlling tuberculosis in adults because if we’€™re able to control tuberculosis in adults these children won’€™t become infected. The adults are really the sources of infection of tuberculosis for these young children’€, adds Professor Madhi.                    

This means more needs to be done to identify TB cases in communities.

‘€œThat has got extremely important implications in terms of how we need to go about looking out for TB in children, but more importantly, how much more important it is that we actually intervene at the community level amongst adults in preventing TB because unless we’€™re able to reduce that overall community exposure of TB which children are exposed to, we’€™re not going to reduce the burden of TB in children purely by targeting the prophylaxis of children that have a known household exposure’€.                                                                                                                                                                                                                                                                                                                                                                                                                                        

Prof. Madhi says there was a fair amount of confidence that Isoniazid would work as an intervention to protect children against TB when the research was initiated. Now researchers have learned that Isoniazid prophylaxis in children is a quick-fix where long-term solutions are needed. Madhi says he hopes that the Gene-Xpert PCR test which is able to make a TB diagnosis almost immediately instead of in weeks, will be widely used as it will have positive spin-offs.

‘€œNow what that strategy will allow us to do is that it will allow us to basically make sure that we’€™re treating the infectious cases that are coming to our health facilities immediately and, hopefully, reduce the number of people that end up not being treated. But, more importantly, is active surveillance for TB’€¦ going down to the community level’€¦ knocking on doors’€¦ finding anyone that has got a cough, as an example’€¦ getting them to agree to send a sample for testing’€¦ and then identifying these TB cases at a very, very early stage before they start spreading the bug throughout the community. And that’€™s the only way we’€™re going to win this game. We’€™re not going to win the game in South Africa in protecting against TB by trying to prevent it with Isoniazid prophylaxis. There’€™s just too much TB circulating for short-cut interventions’€, he says.