Ferritin and its association with anaemia in a healthy adult population in Kenya.

BACKGROUND: Iron deficiency is the commonest cause of anaemia worldwide. Serum ferritin is the most sensitive non-invasive indicator of iron stores but its utility is compromised in inflammatory states as it is an acute phase reactant. This study sought to estimate the burden of iron deficiency in a healthy adult population residing in Kenya and to determine the association between various ferritin cut-offs and anaemia in a population known to have chronic low-grade inflammation. METHODS: Healthy adults aged 18-65 years were recruited from urban towns in 4 counties in Kenya at average altitudes of 1683-2099m above sea level as part of a global study conducted by the International Federation of Clinical Chemistry (IFCC) to determine reference intervals (RIs) for common laboratory tests. We analyzed complete blood count (CBC), C-reactive protein, iron, transferrin, transferrin saturation and ferritin data. RESULTS: We obtained data from 528 participants. There were 254 (48.1%) males and 274 females (51.9%). Based on a ferritin cut-off of 15 µg/L and Hb cut-offs of 14.5 g/dL and 12 g/dL, the prevalence of iron deficiency anaemia was 0.8% and 7.3% in males and females respectively. The odds of having anaemia was highest if one had a ferritin value less than 15 µg/L with a sensitivity of 28.6% and specificity of 98.4% in males, and sensitivity of 83.3% and specificity of 78.0% in females. CONCLUSION: Only the ferritin cut-off of 15 ug/L had an association with anaemia where it can be used for ruling out iron deficiency as the cause. Sex specific ferritin cut-offs for diagnosing iron deficiency in adults in sub-Saharan Africa need to be derived by comparing ferritin levels to stainable iron in bone marrow aspirates and trephines in order to ensure that we are using appropriate clinical decision limits.

Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

BackgroundMicrobial cultures for the diagnosis of pneumonia take several days to return a result, and are frequently negative, compromising antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. MethodsThe TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results128 stored samples were tested, with sensitivity of 97% (95% CI 88-100%). Prospectively 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (IQR 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (OR 2.9 (95%1.5-5.5). ConclusionsImplementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing. Trial registrationThe prospective study was registered with clinicaltrials.gov NCT03996330

Rapid point of care nucleic acid testing for SARS-CoV-2 in hospitalised patients: a clinical trial and implementation study

BackgroundThere is urgent need for safe and efficient triage protocols for hospitalized COVID-19 suspects to appropriate isolation wards. A major barrier to timely discharge of patients from the emergency room and hospital is the turnaround time for many SARS-CoV-2 nucleic acid tests. We validated a point of care nucleic acid amplification based platform SAMBA II for diagnosis of COVID-19 and performed an implementation study to assess its impact on patient disposition at a major academic hospital. MethodsWe prospectively recruited COVID-19 suspects admitted to hospital (NCT04326387). In an initial pilot phase, individuals were tested using a nasal/throat swab with the SAMBA II SARS-CoV-2 rapid diagnostic platform in parallel with a combined nasal/throat swab for standard central laboratory RT-PCR testing. In the second implementation phase, we examined the utility of adding the SAMBA platform to routine care. In the pilot phase, we measured concordance and assay validity using the central laboratory as the reference standard and assessed assay turnaround time. In the implementation phase, we assessed 1) time to definitive bed placement from admission, 2) time spent on COVID-19 holding wards, 3) proportion of patients in isolation versus COVID negative areas following a test, comparing the implementation phase with the 10 days prior to implementation. ResultsIn phase I, 149 participants were included in the pilot. By central laboratory RT-PCR testing, 32 (21.5%) tested positive and 117 (78.5%). Sensitivity and specificity of the SAMBA assay compared to RT-PCR lab test were 96.9% (95% CI 0.838-0.999) and 99.1% (0.953-0.999), respectively. Median time to result was 2.6 hours (IQR 2.3 to 4.8) for SAMBA II SARS-CoV-2 test and 26.4 hours (IQR 21.4 to 31.4) for the standard lab RT-PCR test (p<0.001). In the first 10 days of the SAMBA implementation phase, we conducted 992 tests, with the majority (59.8%) used for hospital admission, and the remainder for pre-operative screening (11.3%), discharge planning (10%), in-hospital screening of new symptoms (9.7%). Comparing the pre-implementation (n=599) with the implementation phase, median time to definitive bed placement from admission was reduced from 23.4 hours (8.6-41.9) to 17.1 hours (9.0-28.8), P=0.02 in Cox analysis, adjusted for age, sex, comorbidities and clinical severity at presentation. Mean length of stay on a COVID-19 holding ward decreased from 58.5 hours to 29.9 hours (P<0.001). Use of single occupancy rooms amongst those tested fell from 30.8% before to 21.2% (P=0.03) and 11 hospital bay closures (on average 6 beds each) were avoided after implementation of the POC assay. ConclusionsThe SAMBA II SARS-CoV-2 rapid assay performed well compared to a centralized laboratory RT-PCR platform and demonstrated shorter time to result both in trial and real-world settings. It was also associated with faster time to definitive bed placement from the emergency room, greater availability of isolation rooms, avoidance of hospital bay closures, and greater movement of patients to COVID negative open "green" category wards. Rapid testing in hospitals has the potential to transform ability to deal with the COVID-19 epidemic.