The Unmet Needs of Paediatric Therapeutics in Poor Countries

In recent decades, the world has witnessed an unprecedented decrease in child mortality, with numbers halving from the over 12.7 million annual child deaths in 1990 to less than 6 million in 2015 [1]. This decreasing tendency has been confirmed in all areas of the world, although reductions have been rather modest in developing countries and in particular in Sub-Saharan Africa. Neonatal deaths have also decreased but at a much slower rate, and thus account for an increasing proportion of child deaths (37.4% in 1990, 44% in 2013 [2]). The first months of life seem therefore the most vulnerable period for the child’s survival, and the global health community has the responsibility to specifically address major causes of premature death with adequate interventions designed to suit the needs of the younger ones. In low-income settings, however, the availability of specific paediatric formulations tailored to the particular needs of newborns and young children is severely limited [3]. The global scarcity of specific paediatric formulations is a well-recognized problem worldwide [4], but its impact is maximum in the 54 countries of Africa, and more specifically related to the treatment of infections and other diseases endemic to the continent. Indeed, licensing a paediatric-friendly formulation includes the requirement of conducting in infants well-designed clinical trials, to assess the bioequivalence of this new formulation against the original one [5]. Palatability assessments should also be conducted, to understand how the taste of the new formulation may affect its acceptability. These trials are expensive and challenging to do in low-income settings [6], and it does not come as a surprise that trials assessing specific paediatric formulations for ‘tropical’ diseases are only sporadically conducted. The World Health organization (WHO) currently recommends the use of either dispersible tablets or granule sachets adjusted for size and strength as the preferred drug formulation for young children and infants [7]. However, with few exceptions, these types of formulations are hard to find in rural areas of the developing world, where populations seem to be entirely unfamiliar with their use [8]. Other formulations often used in children include liquid formulations (syrups), or oral suspensions (to be mixed with water), and seem to be more readily available and known by the population, but require manipulation or particular storage conditions (refrigeration) after preparation that make their use and stability in hot-climate rural areas particularly challenging. In the absence of adequate paediatric formulations, children in poor settings are often administered oral solid dosage forms originally tailored for adults, crushed and dissolved in water. These practices, and the frequently suboptimal palatability of adult medications, often lead to poor tolerability and compliance, and inaccurate dosing, which may increase the risk of toxicity, reduced efficacy and drug resistance [8]. In recent years, several initiatives have been set up in the Western World to incentivize the specific development of paediatric formulations [9, 10], but progress remains slow, particularly in terms of their translation into better drugs for the children of lowincome countries [11]. The WHO has recently