One in eight children with confirmed TB have drug-resistant TB in Cape Town, South Africa, according to a surveillance study of childhood TB drug-resistance, presented by Professor Simon Schaaf at the 46th Union World Conference on Lung Health held in Cape Town from 2 to 6 December 2015.
Twenty per cent of multi-drug resistant TB cases were also found to be resistant to ofloxacin, which has important implications for the second-line treatment regimen in South Africa, which also contains the drug.
The findings come from a prospective surveillance study conducted from March 2013 to February 2015 at the Tygerberg Children’s Hospital in Cape Town. Drug-sensitivity was conducted using line probe assay for isoniazid and rifampicin on the first isolate from each child under 13 years of age who had culture-confirmed TB. Further phenotypic drug-sensitivity testing was done if rifampicin resistance was found. If an Xpert MTB/RIF test was positive and indicated rifampicin resistance, but culture-negative, no further drug-sensitivity testing was possible. Results were compared with five previous two-year surveys conducted at the same hospital.
Of the 292 children who had culture- or Xpert MTB/RIF-positive results for TB who were included in the study, 16 (5.5%) were found to be Xpert-positive but culture negative and were not included in the analysis. The median age was 35.5 months (IQR: 14-82 months) and 49% (n = 143) were male.
12.7% (n = 35) were diagnosed with drug-resistant TB. Four per cent (n = 11) died while in hospital, eight of whom died within the first week of hospital admission. 15.5% (n = 41) of the 95.7% of the culture-confirmed TB cases that were tested for HIV, were found to be HIV positive.
When comparing the results from the 2013-2015 survey to the five previous drug-resistance surveys conducted at the hospital, of the cases found to be drug-resistant, there was a significant decrease in the proportion of isoniazid mono-resistance from 2.5 % in 2013-2015 compared to 7.7% in 2005-2007 (p = 0.0007).
Rifampicin mono-resistance increase from no cases in 2003-2005 to 2.9% (n = 8) of cases in 2013-2015 (p = 0.002).
Although there has been a significant twofold decrease in the proportion of multidrug-resistant (MDR) cases between 2007-2009 (8.9%) and 2011-2013 (4.6%) [OR: 2.01; 95% CI: 1.04-3.88, p = 0.04], this decrease was not sustained in the latest survey, when it rose to 7.2%.
There had been a significant decrease in the number of cases who had previously been on TB treatment, from 22.3% (n = 65) in 2005-2007 to 10.1% (n = 28) in 2013-2015; OR 2.55 (95% CI: 1.58-4.11, p < 0.0001).
HIV prevalence decreased significantly from 29% to 15.5% between the 2005-2007 survey and the 2013-2015 survey (OR1.56; 95% CI:1.01-4.11, p < 0.05). There was also a significant increase in the proportion of children tested for HIV over the same period from 59% (n = 174) to 95.7% (n = 264).
First availability of appropriate, child-friendly TB medicines in correct doses
Dispersible, palatable, simple to administer and affordable child-friendly tuberculosis (TB) medicines in the correct doses, which are the first to meet the dosage guidelines set by the World Health Organization (WHO) in 2010, are now available, according to an announcement by the TB Alliance and partners ahead of the conference.
Children need different doses of TB medicines to adults. Until now, children with drug-sensitive TB have been typically treated with multiple pills intended for adults that must be split or crushed to try to achieve an appropriate dose for a child. Splitting TB tablets usually results in imprecise dosing. This can make treatment less effective, leading to poor health outcomes and the development of more difficult to treat MDR-TB in children. Crushing tablets also make them taste bitter.
The new TB medicines are fixed dose combinations (FDCs) of the three most commonly used drugs to treat drug-sensitive TB (rifampicin, isoniazid, and pyrazinamide). These are not new drugs, but are improved formulations that are dissolvable and flavoured so that they are simple to administer and easy for children to take.
The formulations are in the process of being prequalified by WHO but are now available under the WHO’s Expert Review Panel mechanism. Initial roll-out of the new medicines, that will be manufactured by the Indian pharmaceutical company Macleods, is expected in early 2016.
WHO revised their guidelines for childhood TB treatment in 2010, recognising that children need higher doses of the medicines than the doses they were receiving. Lacking incentives and clear market information, pharmaceutical companies did not produce any products conforming to the new guidelines.
Over the past three years, TB Alliance has worked with manufacturers to develop properly-formulated TB medicines that are easier to administer in children, which included work to address market barriers to ensure new treatments will reach children in need.
Schaaf S et al. Surveillance of childhood tuberculosis drug resistance in Cape Town, South Africa: increasing rifampicin mono-resistance. 46th Union World Conference on Lung Health, Cape Town, 2015.
TB Alliance and partners announce world’s first availability of appropriate, child-friendly, TB medicines in correct doses. 24 November 2015. Available at: http://www.tballiance.org/news/tb-alliance-announces-worlds-first-appropriate-child-friendly-tb-medicines