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Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014–2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage–specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.

BackgroundUrinary tract infections (UTI) are common in clinical practice and empirical treatment is largely employed due to predictability of pathogens. However, variations in antibiotic sensitivity patterns do occur, and documentation is needed to inform local empirical therapy. The current edition of the Uganda Clinical Guidelines recommends amoxicillin or cotrimoxazole as choice drugs for empirical treatment of community-acquired UTI. From our clinical observations, we suspected that this recommendation was not effective in our setting. In order to examine validity, we sought to identify bacteria from community-acquired infections and determine their susceptibility against these antibiotics plus a range of potentially useful alternatives for treatment of UTI.MethodsA cross-sectional study of mid-stream urine collected from 339 symptomatic patients over a three-month period at Gulu regional referral hospital. Qualitative culture and identification of bacteria and antibiotic sensitivity testing using the modified Kirby-Bauer disk diffusion method was done. Participants’ demographic and clinical characteristics were collected using a standard form. Results were analyzed by simple proportions among related variables and confidence intervals computed using binomial exact distribution.ResultsEighty two cultures were positive for UTI. Staphylococcus spp (46.3%) and Escherichia coli (39%) were the most common pathogens. There was high resistance to cotrimoxazole (73.2%), nalidixic acid (52.4%) and amoxicillin (51.2%). The most favorable antibiograms were obtained with gentamicin, amoxicillin-clavulanate and levofloxacin where 85.4%, 72.0%, 67.1% of isolates respectively, were either sensitive or intermediate. Only 51% of isolates were sensitive to ciprofloxacin.ConclusionThere was high resistance to most antibiotics tested in this study. The recommendations contained in the current edition of the Uganda Clinical Guidelines are not in tandem with antibiotic sensitivity pattern of uropathogens seen in our setting. Amoxicillin-clavulanate or gentamicin should be considered for replacement of amoxicillin and cotrimoxazole for empirical treatment of UTI in our setting.

Background: Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods.Methods: Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed.Results: Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC 50 values for chloroquine were persistently low throughout the study period (17.4-24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower IC 50 s to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10 −8 ). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018. Conclusion:This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.

Background Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum parasites, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods Methods Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed. Results Chloroquine resistance (100 nM) was observed in only 3 (1.3%) samples. Average IC 50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harboring p fcrt K76 alleles showed significantly lower IC 50 s to chloroquine than the parasites harboring K76T alleles (21.4 nM vs 43.1 nM, p-value= 3.9×10 -8 ). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018. Conclusion This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.