Children at increased risk

Research, willpower and good administration could help halt the march of a disease that is striking down too many children: multidrug-resistant tuberculosis (MDR-TB).

The roots of tuberculosis (TB) spread back tens of thousands of years. Yet, despite all the research, it remains one of the deadliest infectious diseases, mutating into even more severe versions of itself: drug-resistant TB (DR-TB).

South Africa is up there ahead of much of the global pack in terms of disease rates (we are third behind India and China according to the World Health Organization (WHO) in TB cases). MDR-TB has got to be one of the most alarming emerging health threats facing this country, including in children. It is highly infectious, awkward to diagnose and difficult to treat.

It is also not enough to be aware that this airborne disease is on the move. The basic steps of diagnosis and treatment are, unfortunately, not established enough to ensure control of its rapid spread.

‘[TB] is under-recognised in children,’ warns Professor Simon Schaaf of the Desmond Tutu TB Centre, which is linked to the Department of Paediatrics and Child Health at Stellenbosch University’s Faculty of Medicine and Health Sciences. ‘Of about 40 000 children reported with TB in 2012, 5% of them would have DR-TB. But in South Africa very few places actually diagnose them. That’s the burden of disease we are talking about.’

Recording and reporting of MDR-TB in children in South Africa is also poor, as the diagnosis is often not confirmed by culture and drug susceptibility testing in children. As a result, the estimates are inaccurate of just how heavy the load of paediatric MDR-TB is.

Another spoke in the wheel of progress is that many patients who are diagnosed do not start the correct treatment, and those that do start treatment sometimes stop taking treatment because treatment duration is long, complex and often causes unpleasant side effects. Furthermore, evidence that the MDR-TB threat in children has not been taken seriously in general is that there are no child specific formulations for this disease to date.

What needs to be done is known, but needs to be improved in practice with contact tracing, diagnostic tests, diagnosis, treatment regimens, adherence to treatment and child-friendly medications.

Médecins Sans Frontières (MSF) cautioned in its executive summary last month that TB is ‘one of the gravest public health threats facing the world today and all the more serious as drug resistance takes a grip’. The organisation pointed the finger of blame at ‘an inadequate global response’ that allowed the growing epidemic of DR-TB to take hold. ‘DR-TB originally developed because of improper use of anti-TB medicines, and now these tougher-to-treat DR-TB strains are spreading from person to person, even to people who have never had TB before,’ it warned.

Tracing

Professor Schaaf and many of his colleagues working in the embattled TB arena have urged action, particularly when it comes to the scourge of MDR-TB and children. The latter all too often fall through the cracks of the system: Too many are not traced; too many are not treated.

‘In general, recording and reporting of TB in children is poor and incomplete,’ says Professor Anneke Hesseling, also of the Desmond Tutu TB Centre. ‘It is vital we screen children for MDR-TB when they come in as contacts of infectious adults with the disease.’

The reasons and challenges of identifying children at risk are numerous, many of them due to poor communication
and/or socio-economic conditions:

• Adults often don’t mention there are children in the household.
• Clinics do not have the resources to visit every household.
• A patient may fail to report that there are children in the home if they are not his or hers.
• If a parent is in hospital, there may be no way for children to be brought for testing.
• It may be too expensive to bring children to a clinic or hospital.

The results of a year-long study at three clinics in the Western Cape – regarded as the province with the best resources and procedures when dealing with DR-TB – were disconcerting.

‘We observed for a year to see how many adults were diagnosed at the clinics and how many children got into the system as contacts.’ They only managed to find, and screen for MDR, about 20% of children, according to Professor Schaaf. Approximately 5-7% of young child contacts of MDR-TB cases will develop the disease but of these children, 80-90% will have MDR-TB themselves, as children contract their DR-TB from adults with the disease. If only 20% of the child contacts are screened, one realises just how many are not getting into the treatment system.

Preventive therapy, as opposed to only starting treatment after a positive diagnosis of TB, is providing good results. Implemented by Professor Schaaf, the programme targets those who have been exposed to the disease and are therefore at risk of developing it down the line. ‘This means shorter treatments and fewer drugs,’ he explains. ‘These cases may only need six months of preventive treatment rather than the normal 18 months for MDR-TB disease treatment.’

Even children in contact with MDR-TB cases, who may test culture-negative but are showing symptoms and chest X-ray changes, are managed as if they are MDR-positive. This is because there may not be enough organisms for the culture yet to show a positive result. ‘We are identifying them as MDR-TB contacts earlier and putting them on treatment with early/minimal disease. It is much better for the children.’

Diagnosis

Diagnosis of MDR-TB and XDR-TB remains challenging. The tools are not child-friendly: Getting a sputum sample from a toddler can be traumatic for all involved as the natural reaction is to cough/swallow rather than cough/spit.
Options are to do gastric aspiration or sputum induction. Both involve nil per mouth for a few hours. With the gastric aspirate procedure, a tube is passed through the nose into the stomach to aspirate swallowed sputum. With sputum induction, a cough is stimulated by strong salt-water inhalations, which irritate the airways, allowing a sputum specimen to be suctioned. Both procedures take time and are highly unpleasant for the child.

DR-TB is essentially a microbiological diagnosis, but such confirmation is typically possible in fewer than half of children. ‘A major challenge is that we don’t have diagnostic tools that are sensitive enough for use in children,’ explains Professor Hesseling.

There is excitement in health circles about the phasing in of a rapid molecular diagnostic test (GeneXpert) to replace microscope-based TB diagnoses. This would make South Africa the world’s largest user of the machine, according to Norbert Ndjeka, director of DR-TB, TB and HIV at the South African National Department of Health.

It is, however, not perfect. MSF cautions that it needs electricity to run, so is unsuitable for off-grid rural health centres. Crucially, it does not sufficiently meet the needs of diagnosing TB in children.

“Getting a sputum sample from a toddler can be traumatic for all involved as the natural reaction is to cough/swallow rather than cough/spit.”

‘Education and training of healthcare workers to clinically diagnose and treat children with DR-TB is an absolute priority,’ says Professor Schaaf.

Treatment

Current treatment is double-edged: It is crucial if a patient is to be cured, but it is cruelly difficult to undergo. Once diagnosed, the patient faces a medication onslaught. An adult can face two years of taking 14 600 bitter pills and dozens of painful injections to be rid of MDR-TB.

Child-friendly formulations and dosages are almost non-existent. Horrendous side effects are often reported, including nausea, vomiting, deafness or hypothyroidism. Then there is the emotional trauma of a child being hospitalised for months in an effort to ensure he or she gets the required daily bombardment of medication.

Doctors and humanitarian organisations say new treatment regimens are key to turning the tide on the advance of DR-TB. For the first time in 40 years there is positive movement regarding new anti-TB drugs ‘but it is vital these are tested early in children’, says Professor Schaaf. The top priority is child-friendly palatable dosing, and drugs that shorten the treatment thereby reducing the risk of serious side effects.

A positive note is that, with rapid diagnosis and good clinical attention, outcomes are very good in the majority of children: 90% are cured as opposed to 60% of adults.

‘Tuberculosis is a disease of poverty. It is not the developing world that drives the market,’ says Professor Hesseling. ‘This may be an incentive for companies, especially generic companies, to make drugs that help the developing world.’ This need is underlined by the fact that some of the better drugs are too expensive and inaccessible to much of the developing world. ‘We need to advocate and present good quality data in terms of what we need. Those of us working in this area need to be actively engaged in what is happening.’

The World Health Organization reports that 81% of people with DR-TB do not receive effective treatment and of the 19% who do, only half are cured. Every year there are nearly half a million new cases of MDR-TB worldwide.

While TB may be a disease of poverty it certainly does not stay in poor countries. ‘It spreads worldwide as we are a global village,’ observes Professor Schaaf.