Despite significant momentum to responding to childhood TB in 2013 with launch of first-ever roadmap, are we groping in the dark with very little data on TB in children? Charalambos Sismanidis, a noted expert who was speaking at the 44th Union World Conference on Lung Health, said that childhood TB data was first reported by countries to the WHO in 2012 but this is not enough. There are gaps in surveillance system as childhood TB does get under-reported (and under-diagnosed).
A large number of childhood TB cases are not reported to national TB programmes (NTPs) such as those treated outside of NTPs in private sector and do not end up in national data. So these cases are never found by surveillance system. Childhood TB is also under-diagnosed. Notification is a good proxy for TB incidence but in countries where surveillance systems are weak, then the TB case notifications are much lower, and actual case load might be higher.
Yamuna Mundade of UNITAID said that there is a possibility that instead of 6% incident cases of adult TB cases being in children, actual burden might be as high as 10-15%. Children are often not included in most of TB prevalence studies so no wonder we have very less data on childhood TB. There are very imprecise estimates for child mortality due to TB, said Yamuna.
Challenges in diagnosis, inadequate treatment and control
Yamuna added that diagnosing TB in children is difficult as clinical presentation of childhood TB is atypical most of the times. Children when sick are more likely to report to maternal and child health (MCH) clinics where focus in on acute respiratory infections (ARIs) so diagnosis of TB gets further delayed. Getting specimens from very young children with presumptive TB (such as sputum samples for diagnosing pulmonary TB) is difficult. To add to the woes, sensitivity of sputum is low in children making it even harder to get an accurate confirmed diagnosis. Besides extra-pulmonary TB is commoner in children making it even more difficult to diagnose as symptoms and clinical manifestations both are atypical.
Non-availability of appropriate child-friendly anti-TB drug formulations, dosing, and delivery mechanisms further compound the challenge of treating childhood TB, said Yamuna. UNITAID, an organization where Yamuna works, has prioritized childhood TB for 2013-2016. UNITAID's strategic objectives for 2013-2016 give priority to childhood TB with one of them as follows: increase access to affordable, adapted paediatric medicines to treat HIV, TB and Malaria.
Only half of the childhood TB cases are possibly getting treated with poorly adapted drugs. Responding to childhood TB becomes more of a challenge with weak data. Programming, financing, drug procurement and supply chain issues are some of the key areas adversely affected with weak data on childhood TB.
In high burden TB countries such as Pakistan those dealing with childhood TB could sense the urgency to respond. Children comprise 10% of TB case load (25733 cases of childhood TB out of total 255094 cases reported) said Farhana Amanullah, an expert from Pakistan. Before 2007 childhood TB cases were not being reported in her setting, said Farhana. Pressure to report childhood TB cases had not come first from NTP in Pakistan yet since Farhana and her colleagues thought it is important to do so, they began recording and reporting childhood TB. 34% of childhood TB cases came from just one hospital (Indus Hospital) in Karachi. They responded to the challenge and came up with child TB guidance and desk guide in 2007, which was revised later in 2012. Childhood TB then got included in Joint Monitoring Mission (JMM) too in 2010. JMM recommendations included updating child TB guidelines, training NTP and non-NTP sector in managing childhood TB, introducing DOTS in children's hospital, achieving higher BCG coverage; conducting training of trainers of NTP Pakistan and Stop TB Partnership in Afghanistan; among others.
It is important to raise awareness that accurate recording and reporting data on childhood TB will inform and enable NTP to do optimal drug procurement, argued experts.
Market shortcoming
Drugs for treating childhood TB are more expensive than those for treating adulthood TB. There are fewer manufacturers of paediatric anti-TB medicines may be because of greater perceived manufacturing risk and higher development costs, said experts. Procurers of childhood TB medicines have different quality-requirements which add to the disincentive for the manufacturers.
ACCEPTABILITY AND ADAPTABILITY ARE SPECIFIC FOR CHILDREN
Acceptability and adaptability of anti-TB medicines is also an important consideration when it comes to children. Child-friendly formulations, dosing adjustments, flavour, colour, fixed dose combinations (FDCs) and less pill burden are some of the important criteria to keep in mind while developing medicines for children.
CHILDHOOD TB DRUG PROCUREMENT IS NOT WELL COORDINATED
Unlike drug procurement for anti-TB medicines for adults, the same is happening in less coordinated manner for children. NTPs buy childhood TB drugs from the Global Drug Facility (GDF) and directly from the manufacturers too. Many donors have financed purchase of childhood TB medicines such as UNITAID, Global Fund to fight AIDS, Tuberculosis and Malaria (The Global Fund), United Nations Development Programme (UNDP), Department for International Development (DfID, UK), World Bank, among others.
The GDF has good data over the years of how many quality-assured drugs were distributed for children with TB. The GDF supplied childhood TB drugs to 17% of notified cases in 7 out of 22 high burden TB countries in 2011. In 2007, 139,969 cases of childhood TB were notified and GDF had supplied medicines for 52,128 of them. Notification and GDF’s drug supply for childhood TB both have gone up by 2012. In 2012, 307,964 cases of childhood TB were notified and GDF supplied medicines for 161,329 of them.
Some countries have procured less or more drugs than reported cases of childhood TB between 2007-2012 such as Myanmar, Cambodia, Thailand, Pakistan, etc. In some countries more drugs were procured than childhood TB cases reported. So reporting of childhood TB cases has to catch on with procurement or more investigation is needed for consistent data.
Experts advocated that we should seize every opportunity to consolidate demand for childhood TB formulations, support studies or interventions to improve estimates of childhood TB burden and market dynamics, and accelerate childhood TB research studies. Although diagnosing TB in children is unique yet there is no separately identified childhood TB test. In some cases of childhood TB (such as TB of the brain where cerebro-spinal fluid (CSF) is taken as a sample to test) GeneXpert MTB/RIF has given a very good specificity and sensitivity.
A project that gives hope is underway (2013-2016) which is addressing the public health problem related to lack of access to childhood TB drugs. Formally called STEP-TB project (Speeding Treatments to End Paediatric TB) is being supported by UNITAID and United States Agency for International Development (USAID) and implemented by the Global Alliance for TB Drug Development (TB Alliance), World Health Organization (WHO)’s Global Tuberculosis Programme, WHO Essential Medicines Programme, among others.
This project is aiming to provide better market data on the existing and potential childhood TB landscape to make the business case to manufacturers, donors and governments. It is also collating clinical data necessary for regulatory approval of new childhood TB formulations. It is working to clear regulatory pathways used by manufacturers and regulatory agencies for new and existing paediatric TB medicines. Very importantly this project is also aiming to secure commitment of at least 2 manufacturers to ensure timely and global availability of new childhood TB formulations. It is also helping the countries to treat and to have right policy and practices to help uptake of new paediatric regimens.
Elizabeth Gardiner, Vice President, Market Access, TB Alliance said that people use different languages while speaking about childhood TB, in terms of total cases (treated and untreated), treated cases (NTP & non NTP) or reported cases (NTP including PPM). It is important to understand how the developers 'see the world' in terms of total potential market size, private sector sales, direct NTP procurement and GDF distribution of childhood TB medicines.
TB Alliance assessed to take a quick look on the response to childhood TB outside the NTPs in 3 countries: Pakistan, Indonesia and Nigeria. The study looked at where do children with presumptive TB taken for diagnosis and treatment, how many of these cases are actually reported to NTP and what diagnosis and treatment is given to them.
In Pakistan, 35 child-healthcare facilities were seeing a total 115,000 children in 3 months. 1017 paediatric TB cases were identified (463 unreported). 1.8% additional cases unreported to NTP. In Indonesia, 64 facilities were seeing 65,000 children in 3 months. 985 paediatric TB cases were identiified (929 unreported). 3.5% additional cases were unreported to NTP. This study does not provide information on how many children are correctly diagnosed, identified as those with presumptive TB, or confirmed with active TB disease, but gives a sense of the magnitude of the problem.
This study also identified certain points of care where a large number of children come for seeking healthcare services. In Indonesia, paediatricians were one such group; in Nigeria, private hospitals were one such group; and in Pakistan, private laboratories and diagnostic services was one such group that could be a strong potential ally of paediatric TB care and control.
A call to action to make paediatric TB care more accessible to children in need in immediate time frame was given. It calls upon the TB programme staff to share information on supply chain and be transparent on procurement. It also calls upon the TB programmes to draw in the support of non-NTP sector with a focus to improve quality of care, reporting and recording by care providers of largest number of children with TB.
Bobby Ramakant, Citizen News Service - CNS
November 2013
(The author is supported by the Global Alliance for TB Drug Development (TB Alliance) to provide conference coverage from the 44th Union World Conference on Lung Health)
