Recurrent spontaneous Escherichia coli meningitis in an adult: a case report.

Objectives: The aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain. Patient and methods: An adult presented to a hospital in Kenya with meningitis symptoms. E. coli was cultured from CSF. Treatment with ceftriaxone was successful; however, the patient relapsed a few days later. E. coli was cultured from CSF and blood during the reinfection episode, though the patient died during admission. We sequenced the isolates using Illumina MiSeq and performed antimicrobial susceptibility testing, fitness and virulence assays on the bacteria. Results: The E. coli isolates from the two episodes were found to be distinct: the initial strain was ST88, serotype O8 H17 while the subsequent episode was caused by an ST167, serotype O101 H5 MDR strain. The ST88 strain was susceptible to all drugs except ampicillin and amoxicillin/clavulanate while the ST167 strain was MDR, including to all ß-lactam drugs due to the presence of the carbapenemase gene bla NDM-5. The hospital-acquired ST167 strain was also resistant to newer drugs such as cefiderocol and eravacycline, which are currently not available locally, and had overall lower fitness and virulence in vitro compared with the initial infecting strain. Conclusions: Though less fit and virulent in vitro, the MDR strain was fatal, suggesting that host factors, rather than bacterial virulence, may have been of greater importance in this patient's outcome.

Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

BACKGROUND: Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. METHODS: We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models. RESULTS: For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73-1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80-1.52). Estimates of mortality impact varied by site without a consistent pattern. CONCLUSIONS: In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates.

Erratum to: Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

[This corrects the article DOI: 10.1093/jacamr/dlaa130.].

Malaria infection, disease and mortality among children and adults on the coast of Kenya.

BACKGROUND: Malaria transmission has recently fallen in many parts of Africa, but systematic descriptions of infection and disease across all age groups are rare. Here, an epidemiological investigation of parasite prevalence, the incidence of fevers associated with infection, severe hospitalized disease and mortality among children older than 6 months and adults on the Kenyan coast is presented. METHODS: A prospective fever surveillance was undertaken at 6 out-patients (OPD) health-facilities between March 2018 and February 2019. Four community-based, cross sectional surveys of fever history and infection prevalence were completed among randomly selected homestead members from the same communities. Paediatric and adult malaria at Kilifi county hospital was obtained for the 12 months period. Rapid Diagnostic Tests (CareStart™ RDT) to detect HRP2-specific to Plasmodium falciparum was used in the community and the OPD, and microscopy in the hospital. Crude and age-specific incidence rates were computed using Poisson regression. RESULTS: Parasite prevalence gradually increased from childhood, reaching 12% by 9 years of age then declining through adolescence into adulthood. The incidence rate of RDT positivity in the OPD followed a similar trend to that of infection prevalence in the community. The incidence of hospitalized malaria from the same community was concentrated among children aged 6 months to 4 years (i.e. 64% and 70% of all hospitalized and severe malaria during the 12 months of surveillance, respectively). Only 3.7% (12/316) of deaths were directly attributable to malaria. Malaria mortality was highest among children aged 6 months-4 years at 0.57 per 1000 person-years (95% CI 0.2, 1.2). Severe malaria and death from malaria was negligible above 15 years of age. CONCLUSION: Under conditions of low transmission intensity, immunity to disease and the fatal consequences of infection appear to continue to be acquired in childhood and faster than anti-parasitic immunity. There was no evidence of an emerging significant burden of severe malaria or malaria mortality among adults. This is contrary to current modelled approaches to disease burden estimation in Africa and has important implications for the targeting of infection prevention strategies based on chemoprevention or vector control.

Diagnostic Accuracy of Unattended Automated Office Blood Pressure Measurement in Screening for Hypertension in Kenya.

Despite increasing adoption of unattended automated office blood pressure (uAOBP) measurement for determining clinic blood pressure (BP), its diagnostic performance in screening for hypertension in low-income settings has not been determined. We determined the validity of uAOBP in screening for hypertension, using 24-hour ambulatory BP monitoring as the reference standard. We studied a random population sample of 982 Kenyan adults; mean age, 42 years; 60% women; 2% with diabetes mellitus; none taking antihypertensive medications. We calculated sensitivity using 3 different screen positivity cutoffs (≥130/80, ≥135/85, and ≥140/90 mm Hg) and other measures of validity/agreement. Mean 24-hour ambulatory BP monitoring systolic BP was similar to mean uAOBP systolic BP (mean difference, 0.6 mm Hg; 95% CI, -0.6 to 1.9), but the 95% limits of agreement were wide (-39 to 40 mm Hg). Overall discriminatory accuracy of uAOBP was the same (area under receiver operating characteristic curves, 0.66-0.68; 95% CI range, 0.64-0.71) irrespective of uAOBP cutoffs used. Sensitivity of uAOBP displayed an inverse association (P<0.001) with the cutoff selected, progressively decreasing from 67% (95% CI, 62-72) when using a cutoff of ≥130/80 mm Hg to 55% (95% CI, 49-60) at ≥135/85 mm Hg to 44% (95% CI, 39-49) at ≥140/90 mm Hg. Diagnostic performance was significantly better (P<0.001) in overweight and obese individuals (body mass index, >25 kg/m2). No differences in results were present in other subanalyses. uAOBP misclassifies significant proportions of individuals undergoing screening for hypertension in Kenya. Additional studies on how to improve screening strategies in this setting are needed.

Effect of strikes by health workers on mortality between 2010 and 2016 in Kilifi, Kenya: a population-based cohort analysis.

BACKGROUND: Health workers' strikes are a global occurrence. Kenya has had several strikes by health workers in recent years but their effect on mortality is unknown. We assessed the effect on mortality of six strikes by health workers that occurred from 2010 to 2016 in Kilifi, Kenya. METHODS: Using daily mortality data obtained from the Kilifi Health and Demographic Surveillance System, we fitted a negative binomial regression model to estimate the change in mortality during strike periods and in the 2 weeks immediately after strikes. We did subgroup analyses by age, cause of death, and strike week. FINDINGS: Between Jan 1, 2010, and Nov 30, 2016, we recorded 1 829 929 person-years of observation, 6396 deaths, and 128 strike days (median duration of strikes, 18·5 days [range 9-42]). In the primary analysis, no change in all-cause mortality was noted during strike periods (adjusted rate ratio [RR] 0·93, 95% CI 0·81-1·08; p=0·34). Weak evidence was recorded of variation in mortality rates by age group, with an apparent decrease among infants aged 1-11 months (adjusted RR 0·58, 95% CI 0·33-1·03; p=0·064) and an increase among children aged 12-59 months (1·75, 1·11-2·76; p=0·016). No change was noted in mortality rates in post-strike periods and for any category of cause of death. INTERPRETATION: The brief strikes by health workers during the period 2010-16 were not associated with obvious changes in overall mortality in Kilifi. The combined effects of private (and some public) health care during strike periods, a high proportion of out-of-hospital deaths, and a low number of events might have led us to underestimate the effect. FUNDING: Wellcome Trust and MRC Tropical Epidemiology Group.