Acute burden of active TB in HIV+ kids
Children under two born to HIV positive mothers are at high risk of getting TB, but the risk doubles if the child is also HIV positive.
This is according to a study involving 1 300 children born to HIV-infected mothers based in Johannesburg, Cape Town and Durban. The sample is divided into two groups ‘ 800 HIV negative and 500 positive kids.
‘The question that we’re faced with is how to actually prevent HIV-infected children as well as children that are born to HIV-infected mothers, but that are not themselves HIV-infected from developing tuberculosis,’ says the study’s lead scientist, Professor Shabir Madhi, Director of Wits University’s Respiratory and Meningeal Pathogens Research Unit (RMPRU).
The aim of the study is to investigate the possibility of preventing primary tuberculosis by giving all the babies Isoniazid (INH), one of two first-line medicines used to treat TB.
‘We’ve got HIV-infected children and HIV-uninfected children that were born to infected mothers’¦ Fifty percent of the children in each of these groups would receive Isoniazid (INH). The other 50% would receive a placebo,’ says Madhi.
‘We are providing them with the drug from three months of age until two years of age. During that time period, if the child manifests any sort of symptoms of TB we would investigate the child. And obviously, we would only know at the end of the study whether this intervention of ours works or not.
‘At two years of age we plan to stop the intervention drug and we would continue following up for another two years in each child just to see whether the effect of the intervention actually endures after the initial two years of prophylaxis. So, in total it would be a four-year period.’
Preliminary results from the study, which started recruiting in November 2004, show that there is a huge burden of TB infection in children with HIV.
‘When we started the study, our estimate was that over a two-year period about 12% of HIV-infected children would actually develop tuberculosis,’ says Madhi.
‘But our preliminary data actually suggests that the incidence (the number of children that actually develop tuberculosis in one year in HIV-infected children) is around 20%. So, we’ve completely under-estimated the burden of tuberculosis that actually exists in HIV-infected children.’
In the uninfected children, the incidence of tuberculosis is about half of what it is in HIV-infected children.
Until now, the strategy to prevent the development of TB, including pulmonary or lung TB in children, has been to vaccinate them early after birth with the BCG vaccine.
However, says Madhi, there are some problems with the vaccine: ‘We know, firstly, that it’s not very effective in preventing pulmonary TB in children. It’s more useful in preventing extra-pulmonary TB, that’s TB meningitis and TB of other areas of the body’¦
‘The next problem is that there’s emerging data which actually shows that a BCG vaccine might actually be harmful to HIV-infected children.’
Even so, kids in Prof Madhi’s study still receive the vaccine as routine. The professor says he has a few good reasons to suspect that the research using chemo-prophylaxis with Isoniazid will prove effective.
‘There’s a study that’s been completed in South Africa on HIV-infected adults with a CD 4 count greater than 200 that have previous evidence of infection by TB. When these adults are actually prophylaxed with INH, we find that, actually, they have a reduced risk of developing TB subsequently.
So, at least, there’s adult data to support the notion that this is the sort of strategy that might work in children. Our study is slightly different in that children that we’re looking at haven’t had previous infection by TB’¦ We’re more interested in actually preventing the primary infection from taking place as well as the subsequent disease from developing.’
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