Combating drug-resistant Salmonella enterica Typhi bacteria responsible for typhoid fever using artesunate and ciprofloxacin combination (360G-Wellcome-351513_Z_26_Z)

Typhoid fever caused by Salmonella enterica serotype Typhi remains a major public health problem in low- and middle-income countries, particularly in West Africa with 762 cases per 100,000 person-years among children in rural areas. Ciprofloxacin has long been an affordable and widely used first-line treatment for typhoid fever. However, the emergence and spread of ciprofloxacin-resistant S. Typhi strains increasingly compromised treatment efficacy. New effective, affordable and accessible treatment strategies are urgently needed to combat drug-resistant bacteria. This project aims to combine ciprofloxacin with artesunate, a safe and widely used antimalarial drug given that current experimental studies have shown that artesunate modulate block the bacteria AcrAB-TolC efflux pump activity and increase intracellular antibiotic accumulation restoring thus optimal bacterial inhibition and ciprofloxacin efficacy against resistant Salmonella. We will evaluate this approach on enrolled patients infected with confirmed ciprofloxacin-resistant bacteria. Participants will be randomly assigned to receive either expensive Levofloxacin as control arm or ciprofloxacin combined with artesunate as experimental arm to assess treatments efficacy in both arms over two years using a randomized controlled clinical trial. The outcomes will include bacteria and fever clearance comparison between treatment arms. Keywords: Typhoid fever, Salmonella Typhi, ciprofloxacin resistance, artesunate, Levofloxacin, efflux pump inhibitor, combination therapy.