Aisha Indo Mamman

Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria

Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in sub‐Saharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naïve Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity ≥2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were >35 years. Tricuspid regurgitant jet velocity was ≥2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin (P = 0.002), blood urea nitrogen (P = 0.019) and lactate dehydrogenase concentrations (P = 0.026) and with inability to walk >300 m in 6 min (P = 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations (P ≤ 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged. Am. J. Hematol., 2008.

NT-PROBNP AS A MARKER OF CARDIOPULMONARY STATUS IN SICKLE CELL ANAEMIA IN AFRICA

N‐terminal (NT) pro‐brain natriuretic peptide (proBNP) ≥160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross‐sectional study at Ahmadu Bello University Teaching Hospital, Shika‐Zaria, Nigeria, we studied 133 hydroxycarbamide‐naïve Nigerian sickle cell anaemia patients aged 18–52 years at steady‐state and 65 healthy controls. Twenty‐six percent of patients versus 5% of controls had NT‐proBNP ≥160 ng/l (P = 0·0006). By logistic regression among the patients, human immunodeficiency virus seropositivity, higher serum ferritin and lower haemoglobin or higher lactate dehydrogenase independently predicted elevated NT‐proBNP. After adjustment for haemoglobin concentration, elevated NT‐proBNP concentration was associated with an estimated 7·8‐fold increase in the odds of severe functional impairment, defined as an inability to walk more than 300 m in 6 min (95% confidence interval 1·5–32·6; P = 0·005). Similarly, elevated tricuspid regurgitation velocity was associated with an estimated 5·6‐fold increase in the odds of functional impairment (95% confidence interval 1·5–21·0; P = 0·011). In conclusion, NT‐proBNP elevation is common and is associated with markers of anaemia, inflammation and iron status and with severe functional impairment among sickle cell anaemia patients in Nigeria.

Prevalence of HIV-Associated Neurocognitive Disorder (HAND) among Patients Attending a Tertiary Health Facility in Northern Nigeria:

Background: HIV-associated neurocognitive disorder (HAND) is a great source of morbidity in sub-Saharan African region. However, the magnitude of this problem remains largely uninvestigated despite having the largest number of population with HIV/AIDS. The aim of this study is to determine the prevalence of HAND among patients attending a tertiary health facility in Nigeria. Method: We conducted a cross-sectional study among HIV-positive patients on antiretroviral therapy (ART) for at least 1 year. They were assessed using the International HIV Dementia Scale, Word Recall Test, Stick Design Test, Subjective Cognitive Complaint Questionnaire, Alcohol Use Disorder Identification Test, Drug Abuse Screening Test, Center for Epidemiological Study–Depression Scale, Instrumental Activity of Daily Living, and neurological examination. The CD4 count and viral load were determined for all the participants. A consensus diagnosis was made on each case based on the Frascati criteria. Data obtained were analyzed using “SPSS” for Windows version 15. Results: A total of 418 HIV-positive patients participated in the study, of which 325 (77.8%) are females. The mean age (standard deviation) of the participants was 37.2 (9.3) years. The prevalence of HAND was 21.5% (95% confidence interval [CI] = 17.6%-25.4%), of which 9.6% were asymptomatic. The significant predictors of HAND in this study are duration of illness (odds ratio [OR] = 1.33 P < .001), detectable viral load (OR = 0.19, P < .001), CD4 count (OR = 0.99, P < .001), education (OR = 0.94, P = .011), stopping medication (OR = 3.55 P = .01), and severity of illness (OR = 1.24, P = .005). Conclusion: One-fifth of the HIV-positive patients in this study had HAND. Various sociodemographic and clinical features were related to the prevalence of HAND.

Coexistence of JAK2 and BCR-ABL mutation in patient with myeloproliferative neoplasm.

The World Health Organisation (WHO) classifies myeloproliferative neoplasm (MPN) into BCR-ABL positive chronic myeloid leukaemia (CML Ph + ) and Ph− MPN. The JAK2 V617F mutation is specific for Ph− MPN and occurs in approximately 50% of primary myelofibrosis. Earlier reports suggest that the occurrence of JAK2 and BCR-ABL mutations are mutually exclusive. However, recent reports have documented the coexistence of BCR-ABL and JAK2 mutation in the same patient mostly following treatment with tyrosine kinase inhibitors (TKIs). We thus report a 60-year-old male with atypical clinical and laboratory features of MPN and the presence of both BCR-ABL and JAK2 Mutations.

Induction of foetal haemoglobin synthesis in erythroid progenitor stem cells: mediated by water-soluble components of Terminalia catappa

Current novel therapeutic agents for the treatment of sickle cell anaemia (SCA) focus on increasing foetal haemoglobin (HbF) levels in SCA patients. Unfortunately, the only approved HbF‐inducing agent, hydroxyurea, has long‐term unpredictable side effects. Studies have shown the potential of plant compounds to modulate HbF synthesis in primary erythroid progenitor stem cells. We isolated a novel HbF‐inducing Terminalia catappa distilled water active fraction (TCDWF) from Terminalia catappa leaves that induced the commitment of erythroid progenitor stem cells to the erythroid lineage and relatively higher HbF synthesis of 9.2‐ and 6.8‐fold increases in both erythropoietin (EPO)‐independent and EPO‐dependent progenitor stem cells respectively. TCDWF was differentially cytotoxic to EPO‐dependent and EPO‐independent erythroid progenitor stem cell cultures as revealed by lactate dehydrogenase release from the cells. TCDWF demonstrated a protective effect on EPO‐dependent and not EPO‐independent progenitor cells. TCDWF induced a modest increase in caspase 3 activity in EPO‐independent erythroid progenitor stem cell cultures compared with a significantly higher (P˂0.05) caspase 3 activity in EPO‐dependent ones. The results demonstrate that TCDWF may hold promising HbF‐inducing compounds, which work synergistically, and suggest a dual modulatory effect on erythropoiesis inherent in this active fraction. Copyright

Cis-vaccenic acid induces differentiation and up-regulates gamma globin synthesis in K562, JK1 and transgenic mice erythroid progenitor stem cells.

Gamma globin induction remains a promising pharmacological therapeutic treatment mode for sickle cell anemia and beta thalassemia, however Hydroxyurea remains the only FDA approved drug which works via this mechanism. In this regard, we assayed the γ-globin inducing capacity of Cis-vaccenic acid (CVA). CVA induced differentiation of K562, JK1 and transgenic mice primary bone marrow hematopoietic progenitor stem cells. CVA also significantly up-regulated γ-globin gene expression in JK-1 and transgenic mice bone marrow erythroid progenitor stem cells (TMbmEPSCs) but not K562 cells without altering cell viability. Increased γ-globin expression was accompanied by KLF1 suppression in CVA induced JK-1 cells. Erythropoietin induced differentiation of JK-1 cells 24h before CVA induction did not significantly alter CVA induced differentiation and γ-globin expression in JK-1 cells. Inhibition of JK-1 and Transgenic mice bone marrow erythroid progenitor stem cells Fatty acid elongase 5 (Elovl5) and Δ(9) desaturase suppressed the γ-globin inductive effects of CVA. CVA treatment failed to rescue γ-globin expression in Elovl5 and Δ(9)-desaturase inhibited cells 48 h post inhibition in JK-1 cells. The data suggests that CVA directly modulates differentiation of JK-1 and TMbmEPSCs, and indirectly modulates γ-globin gene expression in these cells. Our findings provide important clues for further evaluations of CVA as a potential fetal hemoglobin therapeutic inducer.

Anemia and iron deficiency in pregnant women in Zaria, Nigeria

Introduction: Anemia is common in pregnancy and iron deficiency is a major cause of anemia in pregnant women in Africa. This is due to increased demands of the fetus, growing uterus, placenta, and poor nutritional habits. Objectives: To determine the prevalence of anemia and the role of iron deficiency in causation of anemia in pregnant women attending the antenatal clinic of the Ahmadu Bello University teaching hospital (ABUTH) in Zaria, Nigeria. Materials and Methods: Ninety (90) consenting pregnant women were entered for this study with an equal number of controls. A structured questionnaire was administered to participants. Full blood count, serum ferritin, urine and stool microscopy for parasites were carried out. Results: The mean hematocrit in the pregnant and non-pregnant subjects was 35% (SD ± 3.8; 95 CI = 34.2-35.8) and 39% L/L (SD ± 3.2; 95% CI = 37.3-38.7) with P < 0.001. In the pregnant subjects 11(12.2%) had anemia while none of the controls was anemic. Mean serum ferritin among the pregnant and non-pregnant subjects was 26.0 μg/L (SD ± 35.2; 95% CI = 18.6-33.4) and 70.3 μg/L (SD ± 106.1; 95% CI 48.1-92.5), respectively, with P-value of <0.001. Even though iron deficiency was observed in 68/90 (75.6%) of pregnant women, it was latent in 61/68(89.7%) of the women while it was frank in 7/68 (10.3%). In the non-pregnant subjects, 23/90 (25.6%) had iron deficiency despite a normal hematocrit. Of the 11/90 (12.2%) of pregnant subjects that had anemia 7/11(63.6%) had frank iron deficiency anemia while 4/11 (36.4) had anemia due to other causes. 2/90 (2.2%) of the pregnant subjects had ova of hookworm in their stool samples and both had iron deficiency anemia. Conclusion: Iron deficiency underlies many cases of anemia in pregnancy, thus justifying the use of iron supplementation in pregnancy as is currently practiced. Latent iron deficiency among non-pregnant controls suggests that iron supplementation may benefit non-pregnant women within the reproductive age group could help to improve their iron stores before the contemplation of pregnancy, thereby, reducing the prevalence of pregnancy related anemia in this environment.

Prevalence of Lupus Anticoagulant in Women with Spontaneous Abortion in Zaria

Introduction: Spontaneous abortion (SA) is a common complication of pregnancy. Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, has been associated with SA in many studies, especially in Caucasians. This study was carried out to determine the prevalence of LA in women with SA in ABUTH, Zaria. Materials and Methods: A cohort of 100 consecutive women presenting with SA with no history of thrombotic episodes were enrolled into the study. Prothrombin time (PT), kaolin clotting time (KCT), and activated partial thromboplastin time (APTT) were conducted on samples of all the participants. Eight patients had prolonged APTT, and after a 50:50 mixture of their plasma with pooled control plasma, four (50%) had uncorrected APTT. Staclot® (a hexagonal-phase phospholipid) test and calculated Rosner index for prolonged KCT were used for the confirmation of LA in samples with uncorrected APTT after mixing studies. Results: We analyzed 100 women with one or more SA with a mean age of 31.0 ± 3.8 years. Nearly 4% and 3% of the participants were LA positive with Staclot® and KCT tests, respectively. Patients with LA were more likely to have had a past history of preeclampsia/eclampsia, small for gestational age deliveries, and previous SA (prevalence odds ratio [95% confidence interval]) of 1.9 (0.2, 20.1), 3.2 (0.3, 34.3), and 1.4 (0.1–13.6), respectively. The PT, APTT, and KCT were significantly prolonged in patients with LA (P ≤ 0.001 for each, respectively). Conclusion: LA may be one of the causes of SA and other adverse pregnancy outcomes such as preeclampsia/eclampsia and small for date deliveries. It is recommended that patients with prolonged APTT, uncorrected with 50:50 mixing study with pooled control plasma, should be evaluated further for LA.

Protein C and antithrombin levels in patients with sickle cell anemia in Ahmadu Bello University Teaching Hospital Zaria, Nigeria

Background: Alterations in the components of hemostasis, namely platelet function, the procoagulant, anticoagulant, and the fibrinolytic systems, are observed in sickle cell anemia (SCA) and are in favor of a procoagulant phenotype. Therefore, study of protein C and antithrombin (AT) levels in patients with SCA in steady state may be used in the treatment and/or prevention of SCA-related thrombotic complications. We studied the changes of these naturally occurring anticoagulants in patients with SCA attending the sickle cell clinic in Ahmadu Bello University Teaching Hospital, Zaria. Methods: We conducted a case–control study involving 50 SCA (HbSS) patients in the steady state as cases and 25 healthy volunteers with normal hemoglobin (HbAA) as controls. Protein C and AT levels were estimated by semi-automation using Diagnostica Stago hematology coagulation analyzer. Frequencies, proportions, and independent t test were performed using SPSS version 20. Results: The mean ages of both the patients and controls were 23.80 ± 7.46 and 24.28 ± 3.48 years, respectively, and study participants comprised 40 (53.0%) women between the ages of 15–50 years and 15–34 years (P = 0.76). The mean values of protein C and AT levels in patients with SCA in the steady state and the control group were 60.26 ± 20.58% versus 81.30 ± 19.74%, 95% CI 11.13–30.96, and 42.11 ± 5.01% versus 61.88 ± 11.27%, 95% CI 16.03–23.51 with P values (P < 0.001), respectively. Conclusions: This study showed that there was a significant decrease in the levels of protein C and AT between the SCA patients in the steady state and the controls. We recommend baseline investigations of these naturally occurring anticoagulants in patients with SCA, especially in those with frequent vaso-occlusive crises. This will give us an insight into the additional pathophysiologic mechanism in SCA-related thrombotic complications for better patient management and outcome.

Prevalence and pattern of parasitic infestations among nomadic Fulani children in a grazing reserve in Northwestern Nigeria

Background: Nomadic pastoralists lack access to basic sanitary and health-care facilities mainly because their mode of life makes them a hard to reach group. In the Nigerian context, there is dearth of knowledge about the interplay between their lifestyle and health indices.Therefore, this study is aimed at determining the association between the prevalence of parasitic infestation among nomadic Fulani children in Ladduga grazing reserve, Kaduna, Northwestern Nigeria. Aim: The aim of this study was to assess the prevalence and pattern of parasitic infestation among nomadic Fulani children in Ladduga grazing reserve, Kaduna, Northwestern Nigeria. Materials and Methods: A cross-sectional descriptive study was conducted using questionnaires, physical examination, automated hemocytometry, enzyme-linked immunosorbent assay-based serum ferritin assay, and formol-ether concentration-based stool tests on 337 children (5–15 years) at Ladduga grazing reserve, Northwestern Nigeria. Data were analyzed using SPSS version 20.0. Results: The prevalence of parasitic infestation was 14.4% (49/337). The predominant parasites found were hookworm species, i.e., Necator americanus and Ancylostoma duodenale (46.9%) and Schistosoma mansoni (26.6%) while Ascaris lumbricoides, Hymenolepis nana, and Enterobius vermicularis accounted for 26.6%. Anemia was found in 40.4% (137/340) of the children with a statistically significant difference between younger (5–9 years) and older children (10–15 years; P < 0.05). Of those with parasites in the stools, 53% of children had anemia. Iron deficiency anemia was found in only 8.1% (4/49) of children. Conclusion: The prevalence of anemia was high in the studied population, but iron deficiency was not a major cause despite hookworm infestation, thus necessitating the need for further studies to identify other causes of anemia among this group.