Seroprevalence of SARS-CoV-2 and Hepatitis B Virus Coinfections among Ethiopians with Acute Leukemia.

SARS-CoV-2 and blood-borne viral coinfections are well reported. Nevertheless, little is known regarding the seroprevalence of SARS-CoV-2 and coinfection with blood-borne viruses in hematologic malignancy patients in Ethiopia. We aimed to assess the seroprevalence of SARS-CoV-2 and associated infections with hepatitis B and other viruses among adolescent and adult acute leukemia patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A cross-sectional study was conducted from July 2020 to June 2021. Blood samples were tested for the presence of anti-SARS-CoV-2, HBV, HCV, and HIV with ELISA kits and occult hepatitis B infection with a real-time polymerase chain reaction assay. Out of a total 110 cases, the SARS-CoV-2 seroprevalence was 35.5%. The prevalence showed a significant increment from July 2020 to the end of June 2021 (p = 0.015). In 22.7% and 2.7% of leukemia cases, HBV and HIV, respectively, were detected. No HCV was identified. The rate of SARS-CoV-2 coinfection with HBV and HIV was 28% (11/39) and 2.6% (1/39), respectively; however, there was no statistically significant association between SARS-CoV-2 seropositivity with HBV and HIV (p > 0.05). There is a need for viral screening in leukemia cases to monitor infections and inform management.

Hematological, clinical, cytogenetic and molecular profiles of confirmed chronic myeloid leukemia patients at presentation at a tertiary care teaching hospital in Addis Ababa, Ethiopia: a cross-sectional study.

BACKGROUND: In low-income countries there is insufficient evidence on hematological, clinical, cytogenetic and molecular profiles among new CML patients. Therefore, we performed this study among newly confirmed CML patients at Tikur Anbesa Specialized Hospital (TASH), Ethiopia. OBJECTIVE: To determine the hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at tertiary care teaching hospital in Addis Ababa, Ethiopia. METHODS: A facility-based cross-sectional study was conducted to evaluate hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at TASH from August 2021 to December 2022. A structured questionnaire was used to collect the patients' sociodemographic information, medical history and physical examination, and blood samples were also collected for hematological, cytogenetic and molecular tests. Descriptive statistics were used to analyze the sociodemographic, hematological, clinical, cytogenetic and molecular profiles of the study participants. RESULTS: A total of 251 confirmed new CML patients were recruited for the study. The majority of patients were male (151 [60.2%]; chronic (CP) CML, 213 [84.7%]; and had a median age of 36 years. The median (IQR) WBC, RBC, HGB and PLT counts were 217.7 (155.62-307.4) x103/µL, 3.2 (2.72-3.6) x106/µL, 9.3 (8.2-11) g/dl and 324 (211-499) x 103/µL, respectively. All patients had leukocytosis, and 92.8%, 95.6% and 99.2% of the patients developed anemia, hyperleukocytosis and neutrophilia, respectively. Fatigue, abdominal pain, splenomegaly and weight loss were the common signs and symptoms observed among CML patients. Approximately 86.1% of the study participants were Philadelphia chromosome positive (Ph+) according to fluorescence in situ hybridization (FISH). P210, the major breakpoint protein, transcript was detected by both qualitative polymerase chain reaction (PCR) and quantitative real time polymerase chain reaction (PCR). CONCLUSION: During presentation, most CML patients presented with hyperleukocytosis, neutrophilia and anemia at TASH, Addis Ababa. Fatigue, abdominal pain, splenomegaly and weight loss were the most common signs and symptoms observed in the CML patients. Most CML patients were diagnosed by FISH, and p120 was detected in all CML patients diagnosed by PCR. The majority of CML patients arrive at referral center with advanced signs and symptoms, so better to decentralize the service to peripheral health facilities.

Health-related quality of life and its associated factors among hemophilia patients: experience from Ethiopian Hemophilia Treatment Centre.

BACKGROUND: Hemophilia is a rare genetic condition that is often overlooked and underdiagnosed, particularly in low-income countries. Long-term spontaneous joint bleeding and soft tissues can have a significant negative impact on a patient's health-related quality of life (HRQoL). The objective of this study was to assess HRQoL and its associated factors in Ethiopian patients with hemophilia. METHODS: A cross-sectional survey was conducted among patients with hemophilia at Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. Patients were recruited consecutively during follow-up visits. The European Quality of Life Group's 5-Domain Questionnaires at five levels (EQ-5D-5L) and Euro Quality of Life Group's Visual Analog Scale (EQ-VAS) instruments were used to assess HRQoL. The EQ-5D-5L utility score was computed using the disutility coefficients. We applied the Krukal-Wallis and Mann-Whitney U tests to determine the differences in EQ-5D-5L and EQ-VAS utility scores between patient groups. A multivariate Tobit regression model was used to identify factors associated with HRQoL. Statistical analyses were performed using STATA version 14 and statistical significance was determined at p < 0.05. RESULTS: A total of 105 patients with hemophilia participated in the study, with a mean (standard deviation (SD) age of 21.09 (± 7.37] years. The median (IQR) EQ-5D-5L utility and EQ-VAS scores were 0.86 (0.59-0.91) and 75 (60.0-80.0), respectively. Age was significantly negatively associated with the EQ-5D-5L utility index and EQ-VAS (ß = -0.020, 95 CI = -0.034, -0.007) and ß = -0.974, 95% CI = -1.72, 0.225), respectively. The duration since hemophilia diagnosis (ß-0.011, 95% CI, 0.001-0.023) and living out of Addis Ababa (ß = -0.128, 95% CI, -0.248-, -0.007) were also significantly negatively associated with the EQ-5D-5L utility index.. CONCLUSION: The median EQ-5D-5L utility and EQ-VAS scores of patients with hemophilia were 0.86 (0.59-0.91) and 75 (60.0-80.0), respectively. Older age, living far from the Hemophilia Treatment Center (HTC), and longer duration since diagnosis were significantly negatively associated with HRQoL. HRQoL may be improved by providing factor concentrates, decentralizing HTCs in different parts of the country, increasing awareness of bleeding disorders among health professionals, and providing psychosocial support to affected patients.

Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma.

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

Reliability and validity of the Amharic version of immune thrombocytopenia life quality index tool for assessment of the health-related quality of life in Ethiopian patients of immune thrombocytopenia: Cross-sectional study.

Background: Platelet count and bleeding risk are frequently used in clinical assessments of the severity of immune thrombocytopenia. On the other hand, immune thrombocytopenia also influences patients' health-related quality of life. The immune thrombocytopenia life quality index is a new tool for evaluating health-related quality of life in immune thrombocytopenia patients. Objective: To assess the psychometric properties of the Amharic version of the immune thrombocytopenia life quality index tool for immune thrombocytopenia patients in Ethiopia. Methods: The facility-based cross-sectional study was carried out from 15 September to 30 October 2022. The school of pharmacy institutional ethics review board provided ethical clearance and approval of the study protocol (approval number: ERB/SOP/487/14/2022). Both written informed consent and family or legal guardian consent were obtained for participants aged 14-18 years and informed consent for participants aged >18 years. The tool was forward-backward translated before being pretested on five immune thrombocytopenia patients. Descriptive statistics were used to report sociodemographic and clinical data. The psychometric properties of the immune thrombocytopenia life quality index in Amharic were evaluated for acceptability, reliability, and construct validity. Results: This study included 100 participants, at the age of diagnosis of immune thrombocytopenia, the median with inter-quartile range of platelet count (×109/L) was 15.00 (18.00). The majority of study participants (79, 79%) received prednisolone alone as first-line therapy. The tool psychometric test was reliable; the correlation coefficient between items ranged from 0.147 to 0.956, and the overall Cronbach's alpha coefficient was 0.956. Furthermore, the tool was construct-valid, with factor analysis between components revealing that Item-1 had an eigenvalue greater than one and explained 72.532% of the total variance among all 10 immune thrombocytopenia life quality index domains. The immune thrombocytopenia life quality index total (alternative score) had a strong (r = 0.9) correlation with Item-8 and a moderate (r = 0.317) correlation with Item-5. Conclusion: The Amharic version of the immune thrombocytopenia life quality index tool is a valid and reliable tool that can be used to assess the health-related quality of life of immune thrombocytopenia patients in Ethiopia.

Frequency of viral infections in adolescent and adult in-patient Ethiopians with acute leukemia at presentation to a tertiary care teaching hospital: a cross-sectional study.

BACKGROUND: Leukemic patients are prone to infectious agents such as viruses due to dysregulated immune system resulting from infiltration of the bone marrow by malignant cells, chronic stimulation, reactivation of some viruses and viral pathogenicity as well as rarely from acquisition of a new infections leading to severe complications. However, the prevalence of these infections has not been systematically documented in resource-limited settings such as Ethiopia. OBJECTIVE: To determine the prevalence of HBV, HCV, and HIV among adult and adolescent in-patients with acute leukemia before the administration of chemotherapy, at the Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. METHODS: A cross sectional study was conducted on 176 adult and adolescent inpatient Ethiopians, who were diagnosed with acute leukemia from April 2019 to June 2021. Socio-demographic characteristics and relevant clinical data were collected. Peripheral blood samples were collected and tested for HBV, HIV, and HCV using Enzyme-Linked Immunosorbent Assay (ELISA) and real-time PCR. Chi-square tests were used to assess associations between variables. RESULTS: Of the 176 patients, 109(62%) were males. The median age was 25[IQR,18-35] yr, with a range from 13 to 76 year. The prevalence of HBV (positivity for HBsAg plus HBV DNA), HCV and HIV was 21.6%, 1.7%, and 1.7%, respectively. HBsAg was positive in 19 cases (10.8%). Among 157 HBsAg negative patients, 52(33.1%) were positive for Anti-HBcAg; of these seropositive cases, 47.5% were positive for HBV DNA. Most DNA positive, HBsAg negative cases (79.0%) had DNA concentrations below 200 IU/ml indicating true occult HBV infection (OBI). Of the 176 cases, 122 had a history of blood transfusions, but no statistically significant association was found between HBV infection and blood product transfusion history (P = 0.963). CONCLUSIONS: The prevalence of HBV, HIV and HCV in patients with acute leukemia was similar to the national prevalence level of these infections. Given the HBsAg positivity and the high prevalence of occult hepatitis B infection in our study, these patients may be at increased risk for chemotherapy related hepatitis flares. Hence, clinicians caring these patients are strongly advised to screen their patients for HBV and also for HIV and HCV infections routinely.

Estimating prognostic relevant cutoff values for a multiplex PCR detecting BCR::ABL1 in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy in resource-limited settings.

The prognosis of chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) treatment is based on the quantification of BCR::ABL1 fusion gene transcript copy number, harmonized by an international scale (IS) based on TaqMan-based real-time quantitative PCR (qRT-PCR). In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a "screening tool," offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. We conclude that the relative simplicity and low cost of mpx-PCR and prognostic relevant cutoff values (0.1-0.6% IS) should allow its use in peripheral clinics and thus maximize the positive impact of TKIs made available through GIPAP in most LMICs.

Spectrum of BCR-ABL Mutations and Treatment Outcomes in Ethiopian Imatinib-Resistant Patients With Chronic Myeloid Leukemia.

PURPOSE: Despite the successes achieved in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy, resistance remains an obstacle. The most common mechanism of resistance is the acquisition of a point mutation in the BCR-ABL kinase domain. Few studies have reported African patients with CML in regard to such mutations. We here report the types of BCR-ABL mutations in Ethiopian imatinib-resistant patients with CML and their outcome. PATIENTS AND METHODS: Patients with CML with a diagnosis of imatinib resistance who were tested for BCR-ABL mutation between 2014 and September 2019 were included. RESULTS: A total of 962 cases of CML on imatinib therapy were reviewed and 164 cases of failure were found. Of these, only 31 cases (19%) had mutation analysis performed. Most cases (94%) were secondary failures. At the time of CML diagnosis, the median age was 33 years and the majority presented with features of advanced-phase disease. Of the 31 patients, 22 mutations were found (65%). The types of mutations detected were as follows: non-P-loop mutations 36% (11), P-loop mutations 13% (four), and alternatively spliced BCR-ABL variants 23% (seven). The splice variant frequently detected was BCR-ABL35INS (20%). Twenty-six of the 31 patients (84%) were switched to second-line TKIs, whereas in four patients (13%), imatinib dose escalation was done. Overall, the outcome revealed that 16 patients (52%) were alive with complete hematologic response, whereas 12 patients (39%) had died. All patients who expressed BCR-ABL135INS were treated with second-line TKIs, and two of them (33%) had died because of disease progression. CONCLUSION: In Ethiopia, CML affects the young and point mutations were frequently detected in imatinib-resistant patients. BCR-ABL1 35INS was also prevalent and associated with disease progression.

Clinical Characteristics and Histopathological Patterns of Hodgkin Lymphoma and Treatment Outcomes at a Tertiary Cancer Center in Ethiopia.

PURPOSE: In developing countries, Hodgkin lymphoma (HL) affects the young population. In Ethiopia, nearly 70% of the population are < 35 years of age. Therefore, this study aimed to elucidate the age distribution, histopathologic patterns, clinical characteristics and treatment outcomes of HL in Ethiopia. MATERIALS AND METHODS: Data from clinical records of 133 consecutive patients with HL between 2014 and 2019 were reviewed and collected. Formalin-fixed paraffin-embedded tissue blocks of HL cases were collected and used for subtype classification. RESULTS: A total of 68.4% (91) of the patients were male; male-to-female ratio was 2.2:1. The median age was 22 years. The age distribution was 57.1% (76), 30.8% (41), and 2.3% (3) for the age groups (10-29), (30-59), and (60-69) years, respectively. Thirteen percent (12) were associated with HIV. The majority of the cases, 50.4% (67), were of the mixed-cellularity (MCCHL) subtypes and 30% (40) nodular-sclerosis (NSCCHL). Most HIV-associated cases (60%, 6) were of the MCHL subtype. The 4-year overall survival (OS) was 83.1%. The 4-year OS of early-stage patients was 100% and advanced-stage patients with low-risk (International Prognostic Score [IPS] ≤ 2) and high-risk (IPS ≥ 3) were 94.1% and 62.9%, respectively. All patients who received combined-therapy survived, whereas those who received doxorubicin, bleomycin, vinblastine, and dacarbazine only showed a 4-year OS rate of 77.9%. CONCLUSION: HL affects the youngest and most productive population in Ethiopia. The treatment outcome is favorable in both HIV-associated and non-HIV-associated HL. However, the study population was likely a highly selected group as the majority of the Ethiopian population do not have access to specialized care.

Addis Ababa population-based pattern of cancer therapy, Ethiopia.

Cancer in Sub-Saharan Africa is becoming an important challenge for health services due to rising numbers of patients. In Addis Ababa with around 3.5 million inhabitants, more than 2000 cases are diagnosed annually. In this retrospective population-based cohort study we assessed completeness of and waiting time for cancer-therapy among patients registered in the Addis Ababa City Cancer Registry (AACCR), Ethiopia. Patient hospital files were retrieved to complete the data from AACCR. A total of 588 files were found (51% of those diagnosed from January to March 2012 and 2014). We analyzed completeness and waiting time of chemotherapy and radiotherapy; with completeness defined as ≥85% therapy received according to local guidelines. Analysis was done for the five most common cancer-types commonly treated with chemotherapy (breast, colorectal, non-Hodgkin`s lymphoma, lung and ovarian) and the four most common cancer-types commonly treated with radiotherapy (breast, cervical, head and neck and rectal). In our study, half of the patients (54.1%) received adequately dosed chemotherapy and 24.5% of patients received adequately dosed radiotherapy. The median waiting time was 2.1 months (Range: 0 to 20.72) for chemotherapy and 7 months (Range: 0.17 to 21.8) for radiotherapy. This study underscores the need for health system measures to improve cancer-directed therapy in Ethiopia, especially concerning radiotherapy.

Long-range haplotype analysis of the malaria parasite receptor gene ACKR1 in an East-African population.

The human ACKR1 gene encodes a glycoprotein expressing the Duffy blood group antigens (Fy). The Duffy protein acts as a receptor for distinct pro-inflammatory cytokines and malaria parasites. We determined the haplotypes of the ACKR1 gene in a population inhabiting a malaria-endemic area. We collected blood samples from 60 healthy volunteers in Ethiopia's southwestern low-altitude tropical region. An assay was devised to amplify the ACKR1 gene as a single amplicon and determine its genomic sequence. All haplotypes were resolved at 5178 nucleotides each, covering the coding sequence (CDS) of the ACKR1 gene and including the 5'- and 3'-untranslated regions (UTR), intron 1, and the 5'- and 3'-flanking regions. When necessary, allele-specific PCR with nucleotide sequencing or length polymorphism analysis was applied. Among the 120 chromosomes analyzed, 18 ACKR1 alleles were confirmed without ambiguity. We found 18 single-nucleotide polymorphisms (SNPs); only one SNP was novel. The non-coding sequences harbored 14 SNPs. No SNP, other than c.-67T>C, indicative of a non-functional allele, was detected. We described haplotypes of the ACKR1 gene in an autochthonous East-African population and found 18 distinct ACKR1 alleles. These long-range alleles are useful as templates to phase and analyze next-generation sequencing data, thus enhancing the reliability of clinical diagnostics.

Antioxidant defense and oxidative damage vary widely among high-altitude residents.

OBJECTIVES: People living at high altitude experience unavoidable low oxygen levels (hypoxia). While acute hypoxia causes an increase in oxidative stress and damage despite higher antioxidant activity, the consequences of chronic hypoxia are poorly understood. The aim of the present study is to assess antioxidant activity and oxidative damage in high-altitude natives and upward migrants. METHODS: Individuals from two indigenous high-altitude populations (Amhara, n = 39), (Sherpa, n = 34), one multigenerational high-altitude population (Oromo, n = 42), one upward migrant population (Nepali, n = 12), and two low-altitude reference populations (Amhara, n = 29; Oromo, n = 18) provided plasma for measurement of superoxide dismutase (SOD) activity as a marker of antioxidant capacity, and urine for measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of DNA oxidative damage. RESULTS: High-altitude Amhara and Sherpa had the highest SOD activity, while highland Oromo and Nepalis had the lowest among high-altitude populations. High-altitude Amhara had the lowest DNA damage, Sherpa intermediate levels, and high-altitude Oromo had the highest. CONCLUSIONS: High-altitude residence alone does not associate with high antioxidant defenses; residence length appears to be influential. The single-generation upward migrant sample had the lowest defense and nearly the highest DNA damage. The two high-altitude resident samples with millennia of residence had higher defenses than the two with multiple or single generations of residence.

Alternative hematological and vascular adaptive responses to high-altitude hypoxia in East African highlanders.

Elevation of hemoglobin concentration, a common adaptive response to high-altitude hypoxia, occurs among Oromo but is dampened among Amhara highlanders of East Africa. We hypothesized that Amhara highlanders offset their smaller hemoglobin response with a vascular response. We tested this by comparing Amhara and Oromo highlanders at 3,700 and 4,000 m to their lowland counterparts at 1,200 and 1,700 m. To evaluate vascular responses, we assessed urinary levels of nitrate (NO3-) as a readout of production of the vasodilator nitric oxide and its downstream signal transducer cyclic guanosine monophosphate (cGMP), along with diastolic blood pressure as an indicator of vasomotor tone. To evaluate hematological responses, we measured hemoglobin and percent oxygen saturation of hemoglobin. Amhara highlanders, but not Oromo, had higher NO3- and cGMP compared with their lowland counterparts. NO3- directly correlated with cGMP (Amhara R2 = 0.25, P < 0.0001; Oromo R2 = 0.30, P < 0.0001). Consistent with higher levels of NO3- and cGMP, diastolic blood pressure was lower in Amhara highlanders. Both highland samples had apparent left shift in oxyhemoglobin saturation characteristics and maintained total oxyhemoglobin content similar to their lowland counterparts. However, deoxyhemoglobin levels were significantly higher, much more so among Oromo than Amhara. In conclusion, the Amhara balance minimally elevated hemoglobin with vasodilatory response to environmental hypoxia, whereas Oromo rely mainly on elevated hemoglobin response. These results point to different combinations of adaptive responses in genetically similar East African highlanders.

DYSKERATOSIS CONGENITA IN TWO ETHIOPIAN BROTHERS.

Dyskeratosis congenita (DKC) is a rare, progressive bone marrow failure syndrome that is characterized by the triad of reticulated skin pigmentation, nail dystrophy and oral leukoplakia. Current evidence indicates that DKC is a disease of defective telomere maintenance, ribosome deficiency and protein synthesis dysfunction. Mortality is often associated with bone marrow failure (BMF), development of malignancy and other multisystem complications of the disease. Here we report two Ethiopian brothers with classical signs and symptoms of DKC. The characteristic clinical features, laboratory findings, and clinical course of the two brothers are discussed along with relevant literature review.

How useful are complete blood count and reticulocyte reports to clinicians in Addis Ababa hospitals, Ethiopia?

BACKGROUND: Complete blood count (CBC) and reticulocyte (Retics) are routine hematology tests useful for the differential diagnosis of anemia and other medical conditions. However, it has been presumed that they are not used as regular as they should be in medical practice in Addis Ababa hospitals. METHODS: A hospital-based cross-sectional questionnaire survey was conducted during November-December 2010, in which 408 clinicians participated and their response on the use of CBC and Retics was assessed. The always/frequently (A/F) response was considered to reflect routine use of the CBC/Retics parameters by the clinicians. The Chi square test was used to study statistical associations among different variables. RESULT: Only four of 13 parameters in CBC were frequently or always used by more than 85% of the clinicians. Health Officers were observed to use 12 of the 13 CBC parameters less than the other professional group; interns and residents demonstrated highest use of CBC results. More than a third of clinicians' preferred white blood cell (WBC) differential report in percentages than the more useful absolute number report. Reticulocyte parameters were not being used by majority of clinicians in patient management. Clinicians rated 'average' regarding the adequacy of clinical laboratory methods course they took during medical education. As service users, clinicians indicated mm3 as unit of preference in cell count on the laboratory report form. CONCLUSION: Overall, most clinicians do not use much of the data provided on routine CBC report. Additional research is needed to understand the issue further. Responsible bodies should promote the appropriate use of CBC/Retics reports by clinicians.

The genetic architecture of adaptations to high altitude in Ethiopia.

Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo.

Adaptations to climate-mediated selective pressures in humans.

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans.

The global distribution of the Duffy blood group.

Blood group variants are characteristic of population groups, and can show conspicuous geographic patterns. Interest in the global prevalence of the Duffy blood group variants is multidisciplinary, but of particular importance to malariologists due to the resistance generally conferred by the Duffy-negative phenotype against Plasmodium vivax infection. Here we collate an extensive geo-database of surveys, forming the evidence-base for a multi-locus Bayesian geostatistical model to generate global frequency maps of the common Duffy alleles to refine the global cartography of the common Duffy variants. We show that the most prevalent allele globally was FY*A, while across sub-Saharan Africa the predominant allele was the silent FY*B(ES) variant, commonly reaching fixation across stretches of the continent. The maps presented not only represent the first spatially and genetically comprehensive description of variation at this locus, but also constitute an advance towards understanding the transmission patterns of the neglected P. vivax malaria parasite.