Salmonella Typhi whole genome sequencing in Rwanda shows a diverse historical population with recent introduction of haplotype H58.

Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, presenting high rates of morbidity and mortality in low- and middle-income countries. The H58 haplotype shows high levels of antimicrobial resistance (AMR) and is the dominant S. Typhi haplotype in endemic areas of Asia and East sub-Saharan Africa. The situation in Rwanda is currently unknown and therefore to reveal the genetic diversity and AMR of S. Typhi in Rwanda, 25 historical (1984-1985) and 26 recent (2010-2018) isolates from Rwanda were analysed using whole genome sequencing (WGS). WGS was locally implemented using Illumina MiniSeq and web-based analysis tools, thereafter complemented with bioinformatic approaches for more in-depth analyses. Whereas historical S. Typhi isolates were found to be fully susceptible to antimicrobials and show a diversity of genotypes, i.e 2.2.2, 2.5, 3.3.1 and 4.1; the recent isolates showed high AMR rates and were predominantly associated with genotype 4.3.1.2 (H58, 22/26; 84,6%), possibly resulting from a single introduction in Rwanda from South Asia before 2010. We identified practical challenges for the use of WGS in endemic regions, including a high cost for shipment of molecular reagents and lack of high-end computational infrastructure for the analyses, but also identified WGS to be feasible in the studied setting and giving opportunity for synergy with other programs.

Community- and Hospital-Acquired Infections in Surgical patients at a Tertiary Referral Hospital in Rwanda.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) are increasing in globally. The aim of this study was to compare community-acquired infections (CAIs) and hospital-acquired infections (HAIs) and determine the rate of third-generation cephalosporin resistance and ESBL-PE at a tertiary referral hospital in Rwanda. METHODS: This was a cross-sectional study of Rwandan acute care surgery patients with infection. Samples were processed for culture and susceptibility patterns using Kirby-Bauer disk diffusion method. Third-generation cephalosporin resistance and ESBL-PE were compared in patients with CAI versus HAI. RESULTS: Over 14 months, 220 samples were collected from 191 patients: 116 (62%) patients had CAI, 59 (32%) had HAI, and 12 (6%) had both CAI and HAI. Most (n = 178, 94%) patients were started on antibiotics with third-generation cephalosporins (ceftriaxone n = 109, 57%; cefotaxime n = 52, 27%) and metronidazole (n = 155, 81%) commonly given. Commonly isolated organisms included Escherichia coli (n = 62, 42%), Staphylococcus aureus (n = 27, 18%), and Klebsiella spp. (n = 22, 15%). Overall, 67 of 113 isolates tested had resistance to third-generation cephalosporins, with higher resistance seen in HAI compared with CAI (74% vs 46%, p value = 0.002). Overall, 47 of 89 (53%) isolates were ESBL-PE with higher rates in HAI compared with CAI (73% vs 38%, p value = 0.001). CONCLUSIONS: There is broad and prolonged use of third-generation cephalosporins despite high resistance rates. ESBL-PE are high in Rwandan surgical patients with higher rates in HAI compared with CAIs. Infection prevention practices and antibiotic stewardship are critical to reduce infection rates with resistant organisms in a low-resource setting.

Widespread antimicrobial resistance among bacterial infections in a Rwandan referral hospital.

BACKGROUND: Resistance among bacterial infections is increasingly well-documented in high-income countries; however, relatively little is known about bacterial antimicrobial resistance in low-income countries, where the burden of infections is high. METHODS: We prospectively screened all adult inpatients at a referral hospital in Rwanda for suspected infection for seven months. Blood, urine, wound and sputum samples were cultured and tested for antibiotic susceptibility. We examined factors associated with resistance and compared hospital outcomes for participants with and without resistant isolates. RESULTS: We screened 19,178 patient-days, and enrolled 647 unique participants with suspected infection. We obtained 942 culture specimens, of which 357 were culture-positive specimens. Of these positive specimens, 155 (43.4%) were wound, 83 (23.2%) urine, 64 (17.9%) blood, and 55 (15.4%) sputum. Gram-negative bacteria comprised 323 (88.7%) of all isolates. Of 241 Gram-negative isolates tested for ceftriaxone, 183 (75.9%) were resistant. Of 92 Gram-negative isolates tested for the extended spectrum beta-lactamase (ESBL) positive phenotype, 66 (71.7%) were ESBL positive phenotype. Transfer from another facility, recent surgery or antibiotic exposure, and hospital-acquired infection were each associated with resistance. Mortality was 19.6% for all enrolled participants. CONCLUSIONS: This is the first published prospective hospital-wide antibiogram of multiple specimen types from East Africa with ESBL testing. Our study suggests that low-resource settings with limited and inconsistent access to the full range of antibiotic classes may bear the highest burden of resistant infections. Hospital-acquired infections and recent antibiotic exposure are associated with a high proportion of resistant infections. Efforts to slow the development of resistance and supply effective antibiotics are urgently needed.