RESUMEN
Background: Many sub-Saharan African patients receive clinical care from extramurally-supported research and surveillance. Dur- ing the COVID-19 pandemic, pausing these activities reduces pa- tient care, surveillance, and research staff employment, increasing pandemic losses. In Oyo State, Nigeria, we paused a multi-country invasive salmonellosis surveillance initiative and a rural clinical bac- teriology project. Objective: Working with research partners raises health facility con- cerns about SARS-CoV-2 transmission risks and incurs infection pre- vention costs, so we developed and implemented re-opening plans to protect staff and patients and help health facilities deliver care. Methods: Our reopening plan included appointing safety and per- sonal protective equipment (PPE) managers from existing project staff cadres, writing new standard operating procedures, implement- ing extensive assessed training, COVID-19 testing for staff, procuring and managing PPE, and providing secondary bacteraemia blood culture support for COVID-19 patients in State isolation facilities. Results: Surveillance data showed that the pandemic reduced care access and negatively affected patient unsupervised antibacterial use. The re-opening plan repurposed human and material resources from national and international extramurally-supported programs to mitigate these effects on public health. Conclusions: A structured reopening plan restarted care, surveil- lance, and infection prevention and control.
RESUMEN
Background: The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19. Methods: This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286). Results: There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492-1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2-28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341-2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251-1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797-2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva. Conclusion: Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].
