Neonatal reference intervals for thyroid stimulating hormone and free thyroxine assayed on a Siemens Atellica® IM analyzer: a cross sectional study.

BACKGROUND: Deriving population specific reference intervals (RIs) or at the very least verifying any RI before adoption is good laboratory practice. Siemens has provided RIs for thyroid stimulating hormone (TSH) and free thyroxine (FT4) determined on their Atellica® IM analyzer for all age groups except the neonatal age group which provides a challenge for laboratories that intend to use it to screen for congenital hypothyroidism (CH) and other thyroid disorders in neonates. We set out to determine RIs for TSH and FT4 using data obtained from neonates undergoing routine screening for CH at the Aga Khan University Hospital, Nairobi, Kenya. METHODOLOGY: TSH and FT4 data for neonates aged 30 days and below were extracted from the hospital management information system for the period March 2020 to June 2021. A single episode of testing for the same neonate was included provided both TSH and FT4 were done on the same sample. RI determination was performed using a non-parametric approach. RESULTS: A total of 1243 testing episodes from 1218 neonates had both TSH and FT4 results. A single set of test results from each neonate was used to derive RIs. Both TSH and FT4 declined with increase in age with a more marked decline seen in the first 7 days of life. There was a positive correlation between logFT4 and logTSH (rs (1216) = 0.189, p = < 0.001). We derived TSH RIs for the age groups 2-4 days (0.403-7.942 µIU/mL) and 5-7 days (0.418-6.319 µIU/mL), and sex specific RIs for males (0.609-7.557 µIU/mL) and females (0.420-6.189 µIU/mL) aged 8-30 days. For FT4, separate RIs were derived for the age groups 2-4 days (1.19-2.59 ng/dL), 5-7 days (1.21-2.29 ng/dL) and 8-30 days (1.02-2.01 ng/dL). CONCLUSION: Our neonatal RIs for TSH and FT4 are different from those published or recommended by Siemens. The RIs will serve as a guide for the interpretation of thyroid function tests in neonates from sub-Saharan Africa where routine screening for congenital hypothyroidism using serum samples is done on the Siemens Atellica® IM analyzer.

Evaluation of the Parasight Platform for Malaria Diagnosis.

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site.

Metabolic syndrome and its predictors in an urban population in Kenya: A cross sectional study.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of interrelated risk factors which doubles the risk of cardio-vascular disease (CVD) in 5-10 years and increases the risk of type 2 diabetes 5 fold. The identification of modifiable CVD risk factors and predictors of MetS in an otherwise healthy population is necessary in order to identify individuals who may benefit from early interventions. We sought to determine the prevalence of MetS as defined by the harmonized criteria and its predictors in subjectively healthy black Africans from various urban centres in Kenya. METHOD: We used data collected from healthy black Africans in Kenya as part of a global study on establishing reference intervals for common laboratory tests. We determined the prevalence of MetS and its components using the 2009 harmonized criterion. Receiver operator characteristic (ROC) curve analysis was used to determine the area under the curves (AUC) for various predictors of MetS. Youden index was used to determine optimum cut-offs for quantitative measurements such as waist circumference (WC). RESULTS: A total of 528 participants were included in the analysis. The prevalence of MetS was 25.6% (95% CI: 22.0%-29.5%). Among the surrogate markers of visceral adiposity, lipid accumulation product was the best predictor of MetS with an AUC of 0.880 while triglyceride was the best predictor among the lipid parameters with an AUC of 0.816 for all participants. The optimal WC cut-off for diagnosing MetS was 94 cm and 86 cm respectively for males and females. CONCLUSIONS: The prevalence of MetS was high for a healthy population highlighting the fact that one can be physically healthy but have metabolic derangements indicative of an increased CVD risk. This is likely to result in an increase in the cases of CVD and type 2 diabetes in Kenya if interventions are not put in place to reverse this trend. We have also demonstrated the inappropriateness of the WC cut-off of 80 cm for black African women in Kenya when defining MetS and recommend adoption of 86 cm.

Comparison of equations for estimating glomerular filtration rate in screening for chronic kidney disease in asymptomatic black Africans: a cross sectional study.

BACKGROUND: Several equations have been developed to estimate glomerular filtration rate (eGFR). The common equations used were derived from populations predominantly comprised of Caucasians with chronic kidney disease (CKD). Some of the equations provide a correction factor for African-Americans due to their relatively increased muscle mass and this has been extrapolated to black Africans. Studies carried out in Africa in patients with CKD suggest that using this correction factor for the black African race may not be appropriate. However, these studies were not carried out in healthy individuals and as such the extrapolation of the findings to an asymptomatic black African population is questionable. We sought to compare the proportion of asymptomatic black Africans reported as having reduced eGFR using various eGFR equations. We further compared the association between known risk factors for CKD with eGFR determined using the different equations. METHODS: We used participant and laboratory data collected as part of a global reference interval study conducted by the Committee of Reference Intervals and Decision Limits (C-RIDL) under the International Federation of Clinical Chemistry (IFCC). Serum creatinine values were used to calculate eGFR using the Cockcroft-Gault (CG), re-expressed 4 variable modified diet in renal disease (4v-MDRD), full age spectrum (FAS) and chronic kidney disease epidemiology collaboration equations (CKD-EPI). CKD classification based on eGFR was determined for every participant. RESULTS: A total of 533 participants were included comprising 273 (51.2%) females. The 4v-MDRD equation without correction for race classified the least number of participants (61.7%) as having an eGFR equivalent to CKD stage G1 compared to 93.6% for CKD-EPI with correction for race. Only age had a statistically significant linear association with eGFR across all equations after performing multiple regression analysis. The multiple correlation coefficients for CKD risk factors were higher for CKD-EPI determined eGFRs. CONCLUSIONS: This study found that eGFR determined using CKD-EPI equations better correlated with a prediction model that included risk factors for CKD and classified fewer asymptomatic black Africans as having a reduced eGFR compared to 4v-MDRD, FAS and CG corrected for body surface area.

The New Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 Equation: Potential Impact on Screening for Chronic Kidney Disease in an Asymptomatic Black African Population.

BACKGROUND: In 2021, a new Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation was introduced that excluded race correction. We set out to compare estimated glomerular filtration rate (eGFR) determined using the creatinine-based CKD-EPI 2009 and 2021 equations and the reclassification of chronic kidney disease (CKD) eGFR staging to explore the potential ramifications of adopting the 2021 equation on reported eGFR and CKD staging. METHODS: We analyzed secondary data previously utilized to determine reference intervals among Black African individuals residing in urban towns in Kenya. Serum creatinine was measured using a standardized modified Jaffé kinetic method on a Beckman AU5800 analyzer. Glomerular filtration rate (GFR) was estimated using both the 2009 and 2021 CKD-EPI creatinine equations. Classification of CKD based on eGFR was performed using the Kidney Disease: Improving Global Outcomes (KDIGO) practice guidelines. RESULTS: Using 533 study samples, the median eGFR was highest when determined using the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation yielded a median eGFR that was similar to the non-race-corrected CKD-EPI 2009 equation. The race-corrected CKD-EPI 2009 equation classified 93.6% of participants into CKD stage G1 compared with 85.6% by the CKD-EPI 2021 equation. The CKD-EPI 2021 equation classified 14.3% of participants into CKD stage G2 compared to 6.4% by the race-corrected CKD-EPI 2009 equation. CONCLUSIONS: The CKD-EPI 2021 equation gave a comparable eGFR to the non-race-corrected CKD-EPI 2009 equation and its implementation in laboratories reporting eGFR in Kenya will help in identifying patients with an appropriate decrease in renal function.

Post-vaccination SARS-CoV-2 IgG spike antibody responses among clinical and non-clinical healthcare workers at a tertiary facility in Kenya.

INTRODUCTION: Following the coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, vaccination became the main strategy against disease severity and even death. Healthcare workers were considered high-risk for infection and, thus, were prioritised for vaccination. METHODS: A follow-up to a SARS-CoV-2 seroprevalence study among clinical and non-clinical HCWs at the Aga Khan University Hospital, Nairobi, we assessed how vaccination influenced SARS-CoV-2 anti-spike IgG antibody responses and kinetics. Blood samples were drawn at two points spanning 6 to 18 months post-vaccination, and SARS-CoV-2 spike antibody levels were determined by enzyme-linked immunosorbent assay. RESULTS: Almost all participants, 98% (961/981), received a second vaccine dose, and only 8.5% (83/981) received a third dose. SARS-CoV-2 spike IgG antibodies were detected in 100% (961/961) and 92.7% (707/762) of participants who received two vaccine doses, with the first and second post-vaccine test, respectively, and in 100% (83/83) and 91.4% (64/70) of those who received three vaccine doses at the first and second post-vaccine test, respectively. Seventy-six participants developed mild infections, not requiring hospitalisation even after receiving primary vaccination. Receiving three vaccine doses influenced the anti-spike S/Co at both the first (p<0.001) and second post-vaccination testing (p<0.001). Of those who tested SARS-CoV-2 positive, the anti-spike S/Co ratio was significantly higher than those who were seronegative at the first post-vaccine test (p = 0.001). Side effects were reported by almost half of those who received the first dose, 47.3% (464/981), 28.9% (278/961) and 25.3% (21/83) of those who received the second and third vaccine doses, respectively. DISCUSSION AND CONCLUSION: Following the second dose of primary vaccination, all participants had detectable anti-spike antibodies. The observed mild breakthrough infections may have been due to emerging SARS-CoV-2 variants. Findings suggest that although protective antibodies are induced, vaccination protected against COVID-19 disease severity and not necessarily infection.

The diagnostic accuracy of an initial point-of-care lactate at the emergency department as a predictor of in-hospital mortality among adult patients with sepsis and septic shock.

Background: In patients with sepsis, elevated lactate has been shown to be a strong predictor of in-hospital mortality. However, the optimal cutoff for rapidly stratifying patients presenting to the emergency department at risk for increased in-hospital mortality has not been well defined. This study aimed to establish the optimal point-of-care (POC) lactate cutoff that best predicted in-hospital mortality in adult patients presenting to the emergency department. Methods: This was a retrospective study. All adult patients who presented to the emergency department at the Aga Khan University Hospital, Nairobi, between 1 January 2018 and 31 August 2020 with suspected sepsis or septic shock and were admitted to the hospital were included in the study. Initial POC lactate results (GEM 3500® blood gas analyzer) and demographic and outcome data were collected. A receiver operating characteristic (ROC) curve for initial POC lactate values was plotted to determine the area under the curve (AUC). An optimal initial lactate cutoff was then determined using the Youden Index. Kaplan-Meier curves were used to determine the hazard ratio (HR) for the identified lactate cutoff. Results: A total of 123 patients were included in the study. They had a median age of 61 years [interquartile range (IQR) 41.0-77.0]. Initial lactate independently predicted in-hospital mortality [adjusted odds ratio (OR) 1.41 95% confidence interval (CI 1.06, 1.87) p = 0.018]. Initial lactate was found to have an area under the curve (AUC) of 0.752 (95% CI, 0.643 to 0.86). Additionally, a cutoff of 3.5 mmol/L was found to best predict in-hospital mortality (sensitivity 66.7%, specificity 71.4%, PPV 70%, NPV 68.2%). Mortality was 42.1% (16/38) in patients with an initial lactate of ≥ 3.5 mmol/L and 12.7% (8/63) in patients with an initial lactate of <3.5 mmol/L (HR, 3.388; 95% CI, 1.432-8.018; p < 0.005). Discussion: An initial POC lactate of ≥ 3.5 mmol/L best predicted in-hospital mortality in patients presenting with suspected sepsis and septic shock to the emergency department. A review of the sepsis and septic shock protocols will help in the early identification and management of these patients to reduce their in-hospital mortality.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

Background: The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. Methods: This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). Results: Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). Conclusion: In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

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.

Seroprevalence, correlates and kinetics of SARS-CoV-2 nucleocapsid IgG antibody in healthcare workers and nonclinical staff at a tertiary hospital: A prevaccine census study.

BACKGROUND: Healthcare workers and nonclinical staff in medical facilities are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS-CoV-2 infection since most infected HCWs and other staff may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions. METHODS: This was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay. RESULTS: One thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted value (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The staff categories with higher prevalence included pharmacy (25.6%), outreach (24%), hospital- based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result after adjusting for age, sex and comorbidities included prior COVID-19 like symptoms, odds ratio (OR) 2.0 [95% confidence interval (CI) 1.3-3.0, p = 0.001], a prior positive SARS-CoV-2 PCR result OR 12.0 (CI: 7.7-18.7, p<0.001) and working in a clinical COVID-19 designated area, OR 1.9 (CI 1.1-3.3, p = 0.021). The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later; OR 0.7 (CI: 0.48-0.95, p = 0.025). CONCLUSIONS: The prevalence of anti- SARS-CoV-2 nucleocapsid IgG among HCWs and nonclinical staff was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.

The impact of i-PUSH on maternal and child health care utilization, health outcomes, and financial protection: study protocol for a cluster randomized controlled trial based on financial and health diaries data.

BACKGROUND: Universal Health Coverage ensures access to quality health services for all, with no financial hardship when accessing the needed services. Nevertheless, access to quality health services is marred by substantial resource shortages creating service delivery gaps in low-and middle-income countries, including Kenya. The Innovative Partnership for Universal Sustainable Healthcare (i-PUSH) program, developed by AMREF Health Africa and PharmAccess Foundation (PAF), aims to empower low-income women of reproductive age and their families through innovative digital tools. This study aims to evaluate the impact of i-PUSH on maternal and child health care utilization, women's health including their knowledge, behavior, and uptake of respective services, as well as women's empowerment and financial protection. It also aims to evaluate the impact of the LEAP training tool on empowering and enhancing community health volunteers' health literacy and to evaluate the impact of the M-TIBA health wallet on savings for health and health insurance uptake. METHODS: This is a study protocol for a cluster randomized controlled trial (RCT) study that uses a four-pronged approach-including year-long weekly financial and health diaries interviews, baseline and endline surveys, a qualitative study, and behavioral lab-in-the-field experiments-in Kakemega County, Kenya. In total, 240 households from 24 villages in Kakamega will be followed to capture their health, health knowledge, health-seeking behavior, health expenditures, and enrolment in health insurance over time. Half of the households live in villages randomly assigned to the treatment group where i-PUSH will be implemented after the baseline, while the other half of the households live in control village where i-PUSH will not be implemented until after the endline. The study protocol was reviewed and approved by the AMREF Ethical and Scientific Review Board. Research permits were obtained from the National Commission for Science, Technology and Innovation agency of Kenya. DISCUSSION: People in low-and middle-income countries often suffer from high out-of-pocket healthcare expenditures, which, in turn, impede access to quality health services. Saving for healthcare as well as enrolment in health insurance can improve access to healthcare by building capacities at all levels-individuals, families, and communities. Notably, i-PUSH fosters savings for health care through the mobile-phone based "health wallet," it enhances enrolment in subsidized health insurance through the mobile platform-M-TIBA-developed by PAF, and it seeks to improve health knowledge and behavior through community health volunteers (CHVs) who are trained using the LEAP tool-AMREF's mHealth platform. The findings will inform stakeholders to formulate better strategies to ensure access to Universal Health Coverage in general, and for a highly vulnerable segment of the population in particular, including low-income mothers and their children. TRIAL REGISTRATION: Registered with Protocol Registration and Results System (protocol ID: AfricanPHRC; trial ID: NCT04068571 : AEARCTR-0006089 ; date: 29 August 2019) and The American Economic Association's registry for randomized controlled trials (trial ID: AEARCTR-0006089; date: 26 June 2020).

The millennial generation plastic surgery trainees in sub-Saharan Africa and social media: A review of the application of blogs, podcasts, and twitter as web-based learning tools.

The delivery of education and training in plastic surgery in Sub-Saharan Africa face increasing challenges. These include endemic shortages of plastic surgeons within postgraduate medical school faculties, the erosion of financial and clinical resources for teaching, and more recently, the millennial generation paradigm shift. It is generally accepted that the millennial generation will be more discerning and comfortable in their requirements for web-based learning content to support their education and training in plastic surgery. We reviewed current literature including original and review articles obtained through a search of PubMed database, Medline, Google Scholar, and hand searching of bibliographies of published articles using the keywords: social media, Blogs, Twitter, plastic surgery, and millennial generation. This article defines and explores Blogs, Podcasts, and Twitter, as web-based learning tools, and discusses how to leverage social media to maximize their educational value and effectiveness.s.

Résumé L'offre d'éducation et de formation en chirurgie plastique en Afrique subsaharienne est confrontée à des défis croissants. Il s'agit notamment de la pénurie endémique de chirurgiens plasticiens au sein des facultés de médecine de troisième cycle, de l'érosion des ressources financières et cliniques pour l'enseignement et, plus récemment, du changement de paradigme de la génération du millénaire. Il est généralement admis que la génération du millénaire sera plus exigeante et plus à l'aise dans ses exigences en matière de contenu d'apprentissage en ligne pour soutenir son éducation et sa formation en chirurgie plastique. Nous avons examiné la littérature actuelle, y compris les articles originaux et critiques obtenus grâce à une recherche dans la base de données PubMed, Medline, Google Scholar, et une recherche manuelle dans les bibliographies des articles publiés à l'aide des mots clés: médias sociaux, blogs, Twitter, chirurgie plastique et génération du millénaire. Cet article définit et explore les blogs, les podcasts et Twitter, en tant qu'outils d'apprentissage basés sur le Web, et explique comment tirer parti des médias sociaux pour maximiser leur valeur éducative et leur efficacité.

Determination of reference intervals for common chemistry and immunoassay tests for Kenyan adults based on an internationally harmonized protocol and up-to-date statistical methods.

BACKGROUND: Due to a lack of reliable reference intervals (RIs) for Kenya, we set out to determine RIs for 40 common chemistry and immunoassay tests as part of the IFCC global RI project. METHODS: Apparently healthy adults aged 18-65 years were recruited according to a harmonized protocol and samples analyzed using Beckman-Coulter analyzers. Value assigned serum panels were measured to standardize chemistry results. The need for partitioning reference values by sex and age was based on between-subgroup differences expressed as standard deviation ratio (SDR) or bias in lower or upper limits (LLs and ULs) of the RI. RIs were derived using a parametric method with/without latent abnormal value exclusion (LAVE). RESULTS: Sex-specific RIs were required for uric acid, creatinine, total bilirubin (TBil), total cholesterol (TC), ALT, AST, CK, GGT, transferrin, transferrin saturation (TfSat) and immunoglobulin-M. Age-specific RIs were required for glucose and triglyceride for both sexes, and for urea, magnesium, TC, HDL-cholesterol ratio, ALP, and ferritin for females. LAVE was effective in optimizing RIs for AST, ALT, GGT iron-markers and CRP by reducing influence of latent anemia and metabolic diseases. Thyroid profile RIs were derived after excluding volunteers with anti-thyroid antibodies. Kenyan RIs were comparable to those of other countries participating in the global study with a few exceptions such as higher ULs for TBil and CRP. CONCLUSIONS: Kenyan RIs for major analytes were established using harmonized protocol from well-defined reference individuals. Standardized RIs for chemistry analytes can be shared across sub-Saharan African laboratories with similar ethnic and life-style profile.

Analysis of Candida auris fungemia at a single facility in Kenya.

OBJECTIVES: Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia. METHODS: Patients with candidemia were identified by the electronic medical record and reviewed for risk factors and outcome. Candida isolates were identified by Vitek2 as Candida haemulonii, but species determinations for 21 of the isolates using published molecular and proteomic methods identified all as C. auris. FINDINGS: From September 2010 to December 2016, C. auris accounted for 38% of 201 patients with candidemia, while C. albicans contributed 25%. C. auris patients had been hospitalized longer (mean 32 days vs. 13 days; p<0.001), were more likely to have central lines preceding candidemia than C. albicans patients (84% vs. 54%; p=<0.001) and had more commonly been treated with carbapenems (83% vs 61% for C. albicans [p=0.01]). The crude mortality was 29%, compared to 36% for C. albicans. CONCLUSIONS: These findings suggest an opportunistic pathogen that may be less virulent, but difficult to eradicate and that control efforts should focus on antimicrobial usage.

Complete blood count reference intervals from a healthy adult urban population in Kenya.

BACKGROUND: There are racial, ethnic and geographical differences in complete blood count (CBC) reference intervals (RIs) and therefore it is necessary to establish RIs that are population specific. Several studies have been carried out in Africa to derive CBC RIs but many were not conducted with the rigor recommended for RI studies hence limiting the adoption and generalizability of the results. METHOD: By use of a Beckman Coulter ACT 5 DIFF CP analyser, we measured CBC parameters in samples collected from 528 healthy black African volunteers in a largely urban population. The latent abnormal values exclusion (LAVE) method was used for secondary exclusion of individuals who may have had sub-clinical diseases. The RIs were derived by both parametric and non-parametric methods with and without LAVE for comparative purposes. RESULTS: Haemoglobin (Hb) levels were lower while platelet counts were higher in females across the 4 age stratifications. The lower limits for Hb and red blood cell parameters significantly increased after applying the LAVE method which eliminated individuals with latent anemia and inflammation. We adopted RIs by parametric method because 90% confidence intervals of the RI limits were invariably narrower than those by the non-parametric method. The male and female RIs for Hb after applying the LAVE method were 14.5-18.7 g/dL and 12.0-16.5 g/dL respectively while the platelet count RIs were 133-356 and 152-443 x10(3) per µL respectively. CONCLUSION: Consistent with other studies from Sub-Saharan Africa, Hb and neutrophil counts were lower than Caucasian values. Our finding of higher Hb and lower eosinophil counts compared to other studies conducted in rural Kenya most likely reflects the strict recruitment criteria and healthier reference population after secondary exclusion of individuals with possible sub-clinical diseases.

Urolithiasis analysis in a multiethnic population at a tertiary hospital in Nairobi, Kenya.

BACKGROUND: Urolithiasis is a global problem whose incidence is reported to be on the rise across the world. Previously, urolithiasis was reported as being rare among the indigenous African population but recent data suggest otherwise. This study reviewed the demographic and clinical characteristics of patients with urolithiasis seen at the Aga Khan University hospital Nairobi (AKUHN) as well as the chemical composition of the stones and the modalities of therapy used. METHODS: This was a retrospective study which utilized patients' clinical and laboratory records from 2013 to 2014. Sixty-seven symptomatic patients with confirmed urolithiasis formed the study. This study aimed to describe the clinical characteristics of patients, modalities of treatment as well as the chemical composition of renal stones from patients diagnosed and managed for urolithiasis during a duration spanning 17 months. Wet chemistry was utilized for analyzing the chemical composition of the urinary calculi. Data on age, sex, symptoms, radiological investigations done, location of the calculi, chemical composition of calculi and therapeutic procedures instituted were extracted and analyzed. RESULTS: Ages ranged from 3 to 87 years with a median of 42; males were the majority (79%) and the commonest presenting symptoms were flank pain (91%) and dysuria (19%). The majority of the stones were located in the ureters (46%) and at the pelvi-ureteric junction (25%). A statistically significant difference in frequency of lodgment at the pelvi-ureteric site between males and females was noted. However, the number of female patients in this study was small and studies with larger numbers of female participants are required to confirm this observation. All stones contained calcium and oxalate, often as the only constituents (72%). In the remainder of the stones, other constituents such bicarbonate, ammonium, phosphorous, magnesium, uric acid and cystine occurred in varying combinations with calcium oxalate. Laser lithotripsy was the most performed therapeutic procedure (77.6%). CONCLUSIONS: Males formed the majority of patient with urolithiasis. Overall, most of the calculi were located in the ureters except in women where the pelviureteric location was commoner. Stones containing calcium oxalate only were predominant across the age groups and in both sexes. Lithotripsy was the commonest mode of management.

Spectrum of Microbial Diseases and Resistance Patterns at a Private Teaching Hospital in Kenya: Implications for Clinical Practice.

BACKGROUND: Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data. METHODS: We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity and susceptibility data captured in hospital and laboratory electronic records between 2010 and 2014. RESULTS: For blood isolates, we used culture collection within the first three days of hospitalization as a surrogate for community onset, and within that group, Escherichia coli was the most common, followed by Staphylococcus aureus. In contrast, Candida spp. and Klebsiella pneumoniae were the most common hospital onset causes of bloodstream infection. Antimicrobial resistance rates for the most commonly isolated Gram negative organisms was higher than many recent reports from Europe and North America. In contrast, Gram positive resistance rates were quite low, with 94% of S. aureus being susceptible to oxacillin and only rare isolates of vancomycin-resistant enterococci. CONCLUSIONS: The current report demonstrates high rates of antimicrobial resistance in Gram negative organisms, even in outpatients with urinary tract infections. On the other hand, rates of resistance in Gram positive organisms, notably S. aureus, are remarkably low. A better understanding of the reasons for these trends may contribute to ongoing efforts to combat antimicrobial resistance globally.

Genotypes and cephalosporin susceptibility in extended-spectrum beta-lactamase producing enterobacteriaceae in the community.

INTRODUCTION: Infections from extended spectrum beta lactamases (ESBLs) producing enterobacteriaceae are increasingly being reported in the community setting. These infections are often multidrug resistant, with clinical and epidemiological implications, and necessitate surveillance measures based on local data. In the present study ESBLs genotypes were correlated with susceptibility to cephalosporins among ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates acquired in the community. METHODOLOGY: We investigated 28 E. coli and 24 K. pneumoniae isolates by PCR for the presence of blaSHV, blaCTX-M, and blaTEM. Minimum inhibitory concentration (MIC) for cephalosporins was determined by use of E-tests. RESULTS: blaCTX-M was detected in 46 (88.5%), blaSHV in 13 (25%) and blaTEM in18 (34.6%) of the isolates. Nineteen (36.5%) isolates had more than one genotype detected. Urine specimens provided most of the ESBL-producing isolates (71%) followed by respiratory specimens (11%). MIC50 for cefotaxime, ceftazidime, and ceftriaxone were at 60 µg/ml, 13 µg/ml, and 139 µg/ml, respectively. There was a statistically significant association (p-value = 0.017) between blaSHV and resistance to ceftazidime. Though other associations could be seen among the genotypes and susceptibility profiles of the three drugs, they were not statistically significant. Twenty-four (52.2%) of the blaCTX-M isolates were sensitive and nine (19.6%) resistant to ceftazidime. For cefotaxime, 29 (63%) of blaCTX-M isolates were resistant and two (4.3%) were sensitive. CONCLUSION: The predominant ESBL genotype in the local community-acquired infections is blaCTX-M , most of which involved the urinary tract. ESBL genes elevated MICs for the cephalosporins, but only blaSHV could predict resistance to ceftazidime.