The study was conducted in two hospitals, a government health care facility and a private health care facility. The record keeping at the private health care facility was excellent and permitted a retrospective study over the period chosen. Record-keeping at the government health care facility was quite different with categorization of certain records as secondary records and thus stored away with limited access. This practice did not permit full access to the records required for the retrospective study. Availability of modern medical record system has been identified as a key factor facilitating clinical audit , thus modernizing medical record systems in Nigeria will be valuable in development of clinical auditing. The private sector is a leading provider of malaria case management in many endemic countries , which was also evidenced in this study. The results from the study show that during the pre-resistance years chloroquine was the main drug used in the chemotherapy of malaria in both sectors of health care provision. It was administered as standard doses during this period and anti-histamines, especially promethazine, were routinely co-administered with chloroquine. The practice of prescribing sub-therapeutic doses of chloroquine became prominent between 1992 and 1997 which coincided with the emerging resistance and resistance dissemination phases and revealed deficiencies in the private sector in relation to poor adherence to National and WHO guidelines for malaria. Poor drug use practices such as the use of sub-therapeutic doses, are among factors that can lead to the emergence and spread of drug resistant strains of Plasmodium falciparum ( and this was evident in this study. The government-owned hospital, which is also a tertiary institution, adhered to National and WHO guidelines for malaria treatment. The findings from this study are consistent with previous reports  that prescribers in government health facilities tend to adhere more to national treatment guidelines than private practitioners. These findings pose a huge challenge to national treatment policies which are aimed at improving health care at all levels.
Promethazine and other anti-histamines are routinely used as adjunct to chloroquine in the treatment of malaria in south-west Nigeria to reduce chloroquine-induced pruritus and/or vomiting. The decline in chloroquine efficacy in south-west Nigeria appears to coincide with the period of increased prescription of sub-therapeutic doses of chloroquine and decreased co-administration of anti-histamines with chloroquine. Drug pressure and exposure of parasites to sub-therapeutic concentrations of anti-malarial drugs represent positive inducers of drug resistance.
Although chlorpheniramine or promethazine are routinely used as adjunct to chloroquine in treatment of malaria, the role of this prescription practice in the slow emergence of drug resistant parasites in Nigeria is unknown. Anti-histamines, including chlorpheniramine, promethazine and cyproheptadine, have been shown to enhance chloroquine activity by reversal of chloroquine resistance in vitro and in vivo [14–16]. The efficacy of the combination of chloroquine and chlorpheniramine in the treatment of uncomplicated acute chloroquine resistant P. falciparum infection was confirmed in limited clinical studies in southwest Nigeria [4, 5]. In the present study, there was an association between decreased frequency of use of promethazine and emergence of chloroquine resistance. Thus, inadvertent combination of chloroquine with anti-histamines over the years may have contributed to delay in emergence of resistance to chloroquine in south-west Nigeria. A recent study also described beneficial pharmacokinetic interactions between chlorpheniramine and chloroquine . These observations essentially represent a valuable proof of the principle for clinical application of the reversal of resistance phenomenon.
The Nigerian Government adopted the use of ACT in 2005 and the current guideline for treatment of uncomplicated falciparum malaria in Nigeria is artemether-lumefanthrine or artesunate-amodiaquine . The results from the present studies confirm the influence of prescription of inappropriate doses of anti-malarial drug on dissemination of drug resistance falciparum malaria and the need to improve malaria treatment practices in Nigeria. In the resistance dissemination years, the records show that artemether was prescribed as monotherapy despite the fact that it was not one of the drugs recommended for management of malaria. Furthermore, in Nigeria, anti-malarial drugs are obtainable over the counter without prescription thus there is a potential for monotherapy with the artemisinins and the use of ACT in sub-therapeutic doses. As Nigeria implements the use of ACT, it becomes imperative that sub-standard doses of ACT are not used at any level of health care delivery. Since the private sector is a leading provider of malaria case management in many endemic countries  and responsible for treating over 50% of malaria cases in Nigeria, it is critical that the private sector in addition to government supported health care providers are targeted for training programmes in malaria case management.