Antimicrobial self medication in post conflict northern Uganda: Implications on chloroquine and artemisinin genotypic resistance in the community

Abstract

Background: Antimicrobial self-medication is a common medical action practiced globally. Its use though associated with risks, provides hope of improved access to healthcare for communities especially in resource limited settings who face challenges of inadequate healthcare systems. This therefore, poses a dilemma to the regulators of healthcare systems especially in developing countries who have to ensure that the risks due to antimicrobial self-medication are minimized. Aim: To explore the prevalence of antimicrobial self-medication in post conflict northern Uganda and its implication on chloroquine and artemisinin genotypic resistance in the communities. Method: This was a cross sectional study and was sub-divided into four sub-studies. In sub-study one we performed a systematic review of antimicrobial self-medication in low and middle income countries. In the review we observed the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines and the protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO). In sub-study two we performed a household antimicrobial self-medication survey in northern Uganda. The households were randomly selected using multi-cluster sampling method. One individual in each household who had experienced illness in the three months prior to data collection was interviewed using an interviewer administered questionnaire. In sub-study three, patients reporting to outpatient departments (OPD) of Lira and Gulu regional referral hospitals were randomly recruited using systematic sampling. Data was collected using interviewer administered questionnaires and urine antibacterial activity bioassay performed. In sub-study four, patients reporting to outpatient departments (OPD) of Lira and Gulu regional referral hospitals with symptoms of malaria (fever) were recruited into the study. Malaria screening was done using rapid diagnostic test (HRP-2) and microscopy. For patients with Plasmodium falciparum, capillary blood from finger prick was collected on filter paper, parasite DNA was extracted using chelix-resin method. The parasite DNA was analyzed using restriction fragment length polymorphism (RFLP) and sequencing to establish presence of Pfcrt K76T, Pfmdr-1 and K13-gene polymorphisms respectively. All the results were analyzed using STATA 12.0 at 95% level of significance. xv Results: From the review, the prevalence of antimicrobial self-medication in low and middle income countries was 38.8% (Article I). However, in the communities of northern Uganda, the prevalence of antimicrobial self-medication was 75.7% (Article II). A third of the households (34.6%) in northern Uganda store antimicrobial agents (Article III). Among the patients who presented to hospitals in northern Uganda, 30.4% had used antibacterial agents for the same symptoms before coming to the hospital (Article IV). The most common antimicrobial agents used without a prescription in northern Uganda include coartem, amoxicillin, cotrimoxazole, metronidazole, and ciprofloxacin. Individuals who practice antimicrobial self-medication obtain drug related information on the medicines used from past experiences, old prescriptions, friends/relatives, health professionals, and drug leaflets. The common source of antimicrobial agents used in self-medication include drug shops/pharmacies, hospitals, and leftover agents. The predictors of antimicrobial self-medication in northern Uganda include gender (female), drug knowledge, reading drug leaflets, advice from friends, previous experience, long waiting time in the hospitals, and distance to the health facility. Over half (54.4%: 116/213) of the Plasmodium falciparum DNA samples analyzed had mutant (chloroquine resistant) genotype Pfcrt K76T. Majority, 97% (164/169) of the Plasmodium falciparum DNA samples carry wild type 86N genotype of Pfmdr-1 gene. Two non-synonymous mutations at codon 522 and 533 of the K13-propeller gene (artemisinin resistant) were detected in the samples analyzed. The study also found one synonymous mutation at codon 509 of the K13-propeller domain. Conclusion and recommendation The prevalence of antimicrobial self-medication in northern Uganda is about twice that found in other developing countries. Over a third of out-patients presenting to hospitals in northern Uganda have used antibacterial agents for the same illness prior to hospital visit. Chloroquine sensitive strains of Plasmodium falciparum parasites are re-emerging in northern Uganda at a slow rate than that seen in other sub-Saharan countries. Non-synonymous mutation in K13-gene (codon 533) for artemisinin resistance previously reported in Cambodia is present in northern Uganda. Validation and surveillance for artemisinin resistance gene markers should be considered. Enforcement of regulations on OTC access of antimicrobial agents should be considered in addition to education intervention involving both community members and healthcare professionals.