Correlates of transfusion transmissible infections among patients with sickle cell disease in Nigeria: case-control study.

Transfusion transmissible infections (TTIs) such as Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) are among the most frequent complications in individuals with Sickle Cell Disease (SCD). We investigated factors associated with TTIs in SCD patients and controls in South-west Nigeria. A total of 2,034 participants with or without SCD were recruited in a matched case-control study. HIV, HBV and HCV infections were diagnosed using commercialy available ELISA kits (Biorad, Paris). Samples positive for HIV ELISA were further confirmed using Western blot. Data were analyzed using descriptive statistics, paired/independent t-test and logistic regression at p = .05. Proportion with HBV was higher among those with multiple sexual partners (12.7%), tattoo/body incision (11.8%), and sharing of sharp objects (7.3%), but HIV was only higher among participants with history of tattoo/body incision (1.5%). Prevalence of TTIs was similar among participants with or without transfusion. History of sharing sharp objects (adjusted odds ratios (aOR) = 1.72; 95%CI:1.11-2.66) and tattoo/body incision (aOR = 1.89; 95%CI:1.22-2.94) almost doubled the risk of HBV. TTIs are endemic in the studied area. Certain lifestyles predispose people to TTIs than having blood transfusion. Population-based intervention targeting lifestyle changes may reduce the risk of TTIs in the study area.Abbrveviations AA: Hemoglobin AA; AC: Hemoglobin AC; aOR: adjusted Odds Ratios; AS: Hemoglobin AS; CHOP: Children Outpatient; CI: Confidence Interval; EDTA: Ethylenediamine Tetraacetic Acid; GOP: General Outpatient; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; HIV: Human Immunodeficiency Virus; HPLC: High Performance Liquid Chromatography; IAMRAT: Advanced Medical Research & Training; IDU: Injection Drug Use; MOP: Medical Outpatient; SC: Hemoglobin SC; SCD: Sickle cell disease; SD: Standard Deviation; SF: Hemoglobin SF; SS: Hemoglobin SS; STDs: Sexually Transmitted Diseases; TTI: Transfusion transmissible infections; UCH: University College Hospital Ibadan; UI: University of Ibadan.

The Effect of Alpha Thalassemia, HbF and HbC on Haematological Parameters of Sickle Cell Disease Patients in Ibadan, Nigeria.

BACKGROUND: Sickle cell disease is a protean disease with limited data on Nigeria's phenotypic and genetic variants. This study was conducted to provide baseline data on these variants by characterising the existing forms of sickle cell disease and correlating these with basic haematological parameters. METHODS: Adult and paediatric patients with SCD were recruited from a tertiary health centre in Nigeria. Patients were age and sex-matched with healthy controls. Blood samples were obtained for Full Blood Count, phenotyping by High-Performance Liquid Chromatography, and genotyping for alpha thalassemia by multiplex Gap-polymerase chain reaction. Data analysis was done using IBM SPSS statistics version 23. RESULTS: A total of 130 patients with sickle cell disease and 117 controls were studied. Alpha thalassemia in the study population was due to a 3.7kb deletion in the alpha-globin gene cluster at a prevalence of 45.4% in the patients and 47% in the controls. The prevalence of the various existing forms of SCD genotype was: Homozygous S without alpha gene deletion (HbSS)- 39.2%; HbSC - 10.8%; HbSSα+1- 35.4%; HbSSα+2 - 6.9% and HbSF- 7.7%. In the control population, HbAA without alpha gene deletion had a prevalence of 42.7%, HbAAα+1 was 25.6%, HbAA α+2 was 6%, HbAS- 7.7%, HbAS α+1 - 11.1%, HbAS α+2 - 2.6%, HbAC - 2.6% and HbAC α+1 - 1.7%. HbA2 was significantly elevated in HbSS individuals with two alpha gene deletions but reduced in normal controls (HbAA) with alpha gene deletions. HbF and HbA2 were negatively correlated with each other (r= -0.587, p < 0.001). Individuals with the HbSC genotype followed by HbSSα+2 had the best haematological parameters. CONCLUSIONS: Haematological parameters vary with haemoglobin genotype. The C haemoglobin and homozygous alpha-thalassemia deletion had a better ameliorating effect on SCD haematological parameters than the F haemoglobin in this population. The effect of alpha thalassemia on some haematological parameters in SCD patients are reversed in normal controls.

Barriers to Therapeutic Use of Hydroxyurea for Sickle Cell Disease in Nigeria: A Cross-Sectional Survey.

Background: Sickle cell disease, the inherited blood disorder characterized by anemia, severe pain and other vaso-occlusive complications, acute chest syndrome, disproportionate hospitalization, and early mortality, has significant financial, social, and psychosocial impacts and drains individuals, families, and health systems globally. Hydroxyurea could improve the health of the 300,000 individuals born each year with sickle cell disease in sub-Saharan Africa; however, challenges to adoption and adherence persist. This study assessed the barriers to therapeutic use of hydroxyurea for sickle cell disease within the Nigerian healthcare system, specifically from the level of the patient, provider, and health system. Methods: We used purposive sampling to recruit participants from 13 regions in Nigeria. A cross-sectional survey was administered to physicians (n = 70), nurses or counselors (n = 17), and patients or their caregivers (n = 33) at 13 health centers. Findings were mapped onto the appropriate Consolidated Framework for Implementation Research (CFIR) domains. Results: This study was able to identify factors that mapped onto the inner setting, outer setting, and characteristics of individuals domains of CFIR. The majority of physicians (74.3%) prescribe hydroxyurea, and half stated hydroxyurea is the standard of care. Among clinicians, barriers included limited knowledge of the drug, as well as low self-efficacy to prescribe among physicians and to counsel among nurses; perceived side effects; perceived patient preference for traditional medicine; cost for patient and expense of accompanying laboratory monitoring; and limited availability of the drug and equipment for laboratory monitoring. Among patients and caregivers, barriers included lack of knowledge; perceived side effects; cost; religious beliefs of disease causation; and lack of pediatric formulation. Conclusions: Findings suggest that patient, provider, and health systems-level interventions are needed to improve hydroxyurea uptake among providers and adherence among patients with sickle cell disease in Nigeria. Interventions such as patient education, provider training, and policy change could address the disproportionate burden of sickle cell disease in sub-Saharan Africa and thus improve health equity.

Diagnostic Accuracy of HemotypeSC as a Point-of-Care Testing Device for Sickle Cell Disease: Findings from a Southwestern State in Nigeria and Implications for Patient Care in Resource-Poor Settings of sub-Saharan Africa.

This study aimed to determine the performance of a rapid, point-of-care testing device (HemotypeSC)™ for diagnosing sickle cell disease (SCD) relative to 2 commonly-used methods compared to DNA polymerase chain reaction (PCR) as the reference standard. The diagnostic performance of (HemotypeSC)™ in diagnosing SCD and determining various other Hb genotypes relative to high performance liquid chromatography (HPLC) and cellulose acetate Hb electrophoresis in alkaline buffer (CAE) was investigated among 156 participants aged 4 to 23 years in Ekiti, Southwest Nigeria. PCR was considered as the reference method/gold standard. The sensitivity and specificity for SS, SC, AS, AC, and AA genotypes by HemotypeSC and HPLC when compared with PCR, were each 100%. Similarly, their positive and negative predictive values were each 100%. However, sensitivity and specificity for identifying these Hb genotypes by CAE were 100, 100, 96.5, 0, 99.2%, and 99, 100, 92.9, 0, 91.7%. Also, CAE did not identify any of the 2 HbAC individuals that were correctly identified by PCR and both HemotypeSC, and HPLC, thus representing 100% HbAC misdiagnosis. In conclusion, this study shows that HemotypeSC has perfect concordance with PCR and 100% accuracy in diagnosing SCD in the population tested. Its ease of use, accuracy and other attributes make it suitable for use in sub-Saharan Africa for rapid determination of Hb genotypes.

Haematological indices of sickle cell patients with chronic leg ulcers on compression therapy.

BACKGROUND: Recurrent chronic leg ulcers and its are morbidities associated with sickle cell anaemia (SCA). Compression therapy increases the rate of healing of these ulcers and also decreases the rate of recurrence. OBJECTIVE: This study evaluated the haematological parameters of patients with SCA and chronic leg ulcers placed on high compression bandaging to provide data for improved ulcer management and prevention. METHODS: Eighteen patients with SCA and chronic leg ulcers were recruited for treatment by compression therapy in Ibadan, Nigeria, from March to June 2015. Eighteen SCA patients with no history of chronic leg ulcers were age and sex matched and recruited as controls. Blood samples, wound biopsies and swabs were collected at different time points for full blood count, microbiology, culture and antimicrobial susceptibility tests. Haemoglobin variants were quantified by high performance liquid chromatography. Fasting blood sugar was tested for leg ulcer patients to determine diabetic status. RESULTS: Ulcers ranged from 0.5 cm2 to 416 cm2 (median: 38.4 cm2). Post-intervention ulcer size ranged from 0.0 cm2 to 272 cm2 (median: 18.6 cm2, p < 0.001); four ulcers completely healed. Compared to the control group, haematological indices at commencement of treatment were more severe in leg ulcer patients (p = 0.02). No patients with chronic leg ulcer was diabetic. Microorganisms isolated from the leg ulcers include Pseudomonas aeruginosa, Staphylococcus aureus, Proteus sp., Escherichia coli and Klebsiella oxytoca. CONCLUSION: Measures to improve haematological parameters during leg ulcer treatment in SCA patients should be taken to aid wound healing.

Hesperidin, a citrus bioflavonoid, alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster.

Trichloroethylene (TCE) is a chlorinated organic pollutant of groundwater with diverse toxic effects in animals and humans. Here, we investigated the ameliorative role of hesperidin, a citrus bioflavonoid on TCE-induced toxicity in Drosophila melanogaster. Four groups of D. melanogaster (50 flies/vial, with 5 vials/group) were exposed to ethanol (2.5%, control), HSP (400mg/10g diet), TCE (10µM/10g diet) and TCE (10µM/10g diet)+HSP (400mg/10g diet) respectively in the diet for 5days. Then, selected oxidative stress and antioxidant markers were evaluated. The results showed that TCE significantly increased the level of reactive oxygen species (ROS) and inhibited catalase, glutathione S-transferase and acetylcholinesterase (AChE) activities with concurrent depletion of total thiol level. However, co-administration of TCE and hesperidin mitigated TCE-induced depletion of antioxidants, and restored ROS level and AChE activity in the flies (p<0.05). Overall, hesperidin offered protective potency on TCE-induced oxidative stress in the flies via anti-oxidative mechanism.

Acquisition, maintenance and adaptation of invasion inhibitory antibodies against Plasmodium falciparum invasion ligands involved in immune evasion.

Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most individuals, independent of age. Antibodies levels measured by ELISA also varied within and between individuals over time and the antibodies against EBA181, PfRh2 and MSP2 declined more rapidly in younger individuals (≤15 years) compared with older (>15). The breadth of high antibody responses over time was more influenced by age than by the frequency of infection. High antibody levels were associated with a more stable invasion inhibitory response, which could indicate that during the long process of formation of immunity, many changes not only in levels but also in functional responses are needed. This is an important finding in understanding natural immunity against malaria, which is essential for making an efficacious vaccine.