Vitamin D status in healthy black African adults at a tertiary hospital in Nairobi, Kenya: a cross sectional study.

BACKGROUND: Vitamin D has been known since the twentieth Century for its benefits in bone health. Recent observational studies have demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few with vitamin D deficiency ranging from 5 to 91%. A few cut- offs have correlated vitamin D deficiency to physiological markers such as parathyroid hormone (PTH), calcium and phosphate with varying results. METHODS: This was a cross sectional study carried out among blood donors at Aga Khan University hospital, Nairobi (AKUHN) from March to May 2015. Vitamin D (25(OH)D) levels were assayed and correlated with PTH, calcium and phosphate. RESULTS: A total of 253 individuals were included in the final analysis. The proportion of study participants who had a 25(OH) D level of < 20 ng/ml thus classified as vitamin D deficient was 17.4% (95% C.I 12.73-22.07). The 25(OH) D level that coincided with a significant increase in PTH was 30 ng/ml. Males were less likely to be vitamin D deficient (O.R 0.48 (C.I 0.233-0.993) p 0.04). Sunshine exposure for ≥3 h per day reduced the odds of being Vitamin D deficient though this was not statistically significant after multivariate regression analysis. CONCLUSIONS: We found a much lower prevalence of Vitamin D deficiency compared to many similar studies carried out in sub-Saharan Africa possibly due to the recruitment of healthy individuals and the proximity of Nairobi to the equator which allows for considerable exposure to sunshine. Vitamin D levels below 30 ng/mL was associated with a significant rise in PTH levels, suggesting that this cut off could be appropriate for defining Vitamin D deficiency in the population served by our laboratory.

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.

Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya.

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10-15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously. Methods: A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher's exact test was used to determine the association between the immunophenotypic markers and categorical variables. Results: Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki-67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden. Conclusion: Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies.

Biallelic disruption of DDX41 activity is associated with distinct genomic and immunophenotypic hallmarks in acute leukemia.

Introduction: Inherited DDX41 mutations cause familial predisposition to hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with the majority of DDX41 mutated MDS/AMLs described to date harboring germline DDX41 and co-occurring somatic DDX41 variants. DDX41-AMLs were shown to share distinguishing clinical features such as a late AML onset and an indolent disease associated with a favorable outcome. However, genotype-phenotype correlation in DDX41-MDS/AMLs remain poorly understood. Methods: Here, we studied the genetic profile, bone marrow morphology and immunophenotype of 51 patients with DDX41 mutations. We further assessed the functional impact of ten previously uncharacterized DDX41 variants of uncertain significance. Results: Our results demonstrate that MDS/AML cases harboring two DDX41 variants share specific clinicopathologic hallmarks that are not seen in other patients with monoallelic DDX41 related hematologic malignancies. We further showed that the features seen in these individuals with two DDX41 variants were concordant with biallelic DDX41 disruption. Discussion: Here, we expand on previous clinicopathologic findings on DDX41 mutated hematologic malignancies. Functional analyses conducted in this study unraveled previously uncharacterized DDX41 alleles and further illustrate the implication of biallelic disruption in the pathophysiology of this distinct AML entity.

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.

Plasma Cell Leukemia: A Review of 3 Cases Managed in Kenya.

Plasma Cell Leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia that can arise either de novo (primary plasma cell leukemia) or evolve from previously diagnosed and treated multiple myeloma (secondary PCL). We highlight three clinical cases with very different presentations as a reminder of this diagnosis. The cases also highlight the diversity and variability that cover a patient's journey that is highly dependent on accessibility based on financial capability and social support. The clinical presentation is more aggressive due to the higher tumour burden and more proliferative tumor cells with cytopenias being profound and more organomegaly. The diagnosis is made based on at least 20% of total white blood cells being circulating plasma cells with a peripheral blood absolute plasma cell count of at least 2 × 109/l. Treatment with novel agents followed by autologous stem cell transplant in those who are transplant eligible leads to better outcomes.

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.

Task Sharing and Shifting to Provide Pathology Diagnostic Services: The Kenya Fine-Needle Aspiration Biopsy Cytology and Bone Marrow Aspiration and Trephine Biopsy Training Program.

PURPOSE: Fine-needle aspiration biopsy (FNAB) cytology is a simple, inexpensive, and accurate diagnostic test for benign, infectious, and malignant lesions of the breast, thyroid, lymph nodes, and other organs. Similarly, bone marrow aspiration and trephine (BMAT) biopsy procedures are relatively simple and inexpensive techniques that are important for diagnosing and monitoring many hematologic diseases including leukemias and lymphomas. However, the scarcity of pathologists in Kenya limits patient access to these simple diagnostic tests. We describe a task sharing and shifting program that sought to improve the provision of FNABs and BMAT biopsies in tertiary public hospitals in Kenya. METHODS: Between January 2016 and February 2017, we trained pathologists, pathology residents, and technologists from the University of Nairobi and Aga Khan University Hospital, Nairobi, in FNAB and BMAT biopsies, who in turn trained pathologists, medical officers (MO), clinical officers (CO), and technologists at five tertiary public hospitals. The program involved curriculum development, training workshops, the establishment of new and strengthening existing FNAB and BMAT biopsy clinics, interim site visits, audits, and stakeholder workshops. RESULTS: Fifty-one medical personnel at the tertiary hospitals were trained. The FNAB numbers increased by 41% to 1,681, with 139 malignant diagnoses (7.1%). BMAT biopsy numbers increased by 268% to 140, with 34 malignant cases. Between 60% and 100% of the FNAB and BMAT biopsy procedures were performed by MO and CO over the project period. One new FNAB and two new BMAT biopsy clinics were established. CONCLUSION: This project demonstrates a successful model of task sharing and shifting from specialist pathologists to MO and CO that improved access to important FNAB and BMAT biopsy services in a low-resource setting.