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HEALTH: MDR-TB remains a difficult diagnosis for children
Diagnosing MDR-TB in children still difficult
LILLE, 8 November 2011 (IRIN) - Years of treatment and mounds of pills are hard work for older patients with multidrug resistant tuberculosis (MDR-TB), but in children, treatment becomes a minefield for patients and doctors alike.
MDR-TB is resistant to the most powerful drugs used to treat active TB, rifampicin and isoniazid. With weaker immune systems, children who contract TB - most often from parents - progress to active disease in about a year. But just how many children are affected is not known as there is almost no research into children and MDR-TB - and very little useful guidance on how to treat them.
There are only eight studies published on MDR-TB treatment outcomes among children, says Nathan Ford, medical coordinator for Médecins Sans Frontières’ (MSF) Campaign for Essential Medicines. Much of what does exist comes from South Africa's Stellenbosch University, whose researchers work in Cape Town's Tygerberg Hospital. The hospital began collecting data on drug resistant (DR-TB) tuberculosis among children in 2003.
Simon Schaaf, a professor at Stellenbosch, presented the findings of the hospital's latest such survey at the International Lung Health Conference, held recently in Lille, France. Among about 330 children with DR-TB, about 7 percent had MDR-TB - a figure that has remained relatively steady since the hospital began conducting the surveys.
According to Schaaf, paediatric DR-TB cases are often a window on local TB epidemics. In 2010
, the Western Cape confirmed 1,400 MDR-TB cases - the second highest in the country.
The study found very low uptake of isoniazid preventative TB therapy (IPT) among paediatric patients, despite a national IPT policy. About 70 percent of children who would have qualified for IPT were never prescribed the preventative medication, which uses one of the main drugs used to treat active TB, isoniazid. About 5 percent of these children subsequently died.
With a small number of studies indicating the scope of MDR-TB among children, high-level awareness of the problem is lacking, according to Carlos Perez Velez, who is leading a study on new diagnostic methods to improve TB case detection among children in his native Colombia as part of his work with the US-based National Jewish Health respiratory hospital.
"You go to a minister of health and you tell them there's a problem with TB in children and he'll ask you for the data,” Perez Velez told IRIN/PlusNews. "You'll say there's no data. He'll say if there's no data then why are you saying there's a problem. It's the chicken and egg paradigm."
Children who develop the disease in their spinal column are often diagnosed too late, sometimes leading to long-term neurological effects and spinal deformity. Treatment for MDR spinal TB requires a mix of surgery and a long course of drugs.
Marianne Gale, a doctor with MSF, described the realities of diagnosing and treating children with MDR-TB. In 2010, the MSF clinic in the Nairobi slum of Mathare diagnosed a mother with MDR-TB. Her 18-month-old daughter had TB symptoms and a chest X-ray suggested she also had active TB but getting a culture was impossible.
Samples of sputum from suspected DR-TB patients are used to grow bacteria cultures that are then tested for drug resistance - but these are difficult to obtain from children.
"We actually had the capacity to do sputum induction, which in many sites we're not able to do," Gale said. "There were many attempts that were traumatic to the child and perhaps more traumatic to the staff. We managed to get a sample that actually never [developed] on culture."
Given the difficulties of diagnosing children, about half of all children treated for DR-TB in MSF's projects in Swaziland and South Africa are unconfirmed, leaving clinicians to make tough calls to start young patients on long treatment.
Gauging the dosage
Without a culture, Gale said clinic staff reluctantly started the child on MDR-TB medication - a challenge in and of itself.
"This child was 18 months old but only weighed 7.5kg so calculating the dosages and adjusting them as the child grew was a nightmare," said Gale, adding that the MSF clinic - with an in-house pharmacist - was probably better able to do this than most clinics in similar settings. "Manipulating the formulations was challenging and also how to make those drugs acceptable for this young child."
Both mother and child were doing well on treatment after six months but family pressure led both to discontinue treatment. While the clinic learned that the mother had died, they were unable to trace the child.
Almost all MDR-TB drugs are designed for adults. "Almost all children will need these pills broken into bits, sometimes half, sometimes quarters; sometimes medication needs to be ground and most formulations don't dissolve completely in water," James Seddon, a researcher at the Desmond Tutu TB Centre in Cape Town, told IRIN/PlusNews. "Some [liquid forms] are available... but actually in most high TB burden areas they are not incredibly practical because they require refrigeration and also the glass of the bottle is very heavy for [transporting] to [clinics] that need large volumes."
Some children may also need to take vitamins or HIV medication and so may end up taking a large number of pills a day, Seddon added. Many do not taste good and may cause vomiting. MSF has lobbied the World Health Organization (WHO) to produce effective guidelines about the composition of new paediatric fixed-dose combination drugs that would reduce children’s pill burden and have been shown to improve adherence.
Meanwhile, existing guidelines need work. WHO, the UK and US have developed guidelines for paediatric MDR-TB treatment, but these are largely not evidence-based and, in some cases, may have been simply adapted from adult guidelines, noted Seddon.