Some studies suggest that decreasing overall antibiotic use may reverse bacterial resistance in human populations 37 38. One cannot assume from this that combination therapy will have the same effect. It is thus critical to know if using FDCs will prevent the appearance of drug resistance and/or reverse existing rates of drug resistance at both individual and population levels. The primary difficulty in assessing the evidence will be to actually measure developing/ongoing antimicrobial resistance in populations in field situations.
• Recent uses of molecular biology techniques might allow for easier tracking of clinical resistance markers See, for instance,39 40 41 42 although this genotyping must be correlated in the field with clinical outcomes.
• Larger longitudinal and community based studies are needed. An important and potentially significant study was performed by Roper et al. (2003)43 who characterised genetic change in dhfr and dhps genes in the Plasmodium falciparum population of KwaZulu-Natal, South Africa, during 1995-99, a period of rapid deterioration of the effectiveness of sulfadoxine-pyrimethamine. They did the same analysis in P falciparum sampled from communities in northern Tanzania in 2001. The authors found a large genetic change during 1995-99 in KwaZulu-Natal and the determinants of resistance in this province share a common evolutionary origin with those found in Tanzania, even though the two sites are 4000 km apart. Their interpretation is that gene flow rather than new mutations has been the most common originator of resistance in African countries. Nosten et al. 44 studied in vitro susceptibility patterns to mefloquine over a 13 year period in Thailand and found a sustained shift away from P. falciparum resistance, brought about by use of artesunate plus mefloquine.
• Head to head comparisons of blister packs compared to FDCs and/or free combinations are needed with regard to health outcomes, including development of AMR.
• For HIV and malaria, increasing the pace of our understanding of genetic resistance pathways and mutations, since this understanding has not kept up with the increasing number of therapeutic options.