Leveraging deep learning for detecting red blood cell morphological changes in blood films from children with severe malaria anaemia.

In sub-Saharan Africa, acute-onset severe malaria anaemia (SMA) is a critical challenge, particularly affecting children under five. The acute drop in haematocrit in SMA is thought to be driven by an increased phagocytotic pathological process in the spleen, leading to the presence of distinct red blood cells (RBCs) with altered morphological characteristics. We hypothesized that these RBCs could be detected systematically and at scale in peripheral blood films (PBFs) by harnessing the capabilities of deep learning models. Assessment of PBFs by a microscopist does not scale for this task and is subject to variability. Here we introduce a deep learning model, leveraging a weakly supervised Multiple Instance Learning framework, to Identify SMA (MILISMA) through the presence of morphologically changed RBCs. MILISMA achieved a classification accuracy of 83% (receiver operating characteristic area under the curve [AUC] of 87%; precision-recall AUC of 76%). More importantly, MILISMA's capabilities extend to identifying statistically significant morphological distinctions (p < 0.01) in RBCs descriptors. Our findings are enriched by visual analyses, which underscore the unique morphological features of SMA-affected RBCs when compared to non-SMA cells. This model aided detection and characterization of RBC alterations could enhance the understanding of SMA's pathology and refine SMA diagnostic and prognostic evaluation processes at scale.

Equilibration time of haemoglobin concentration after packed red blood cell transfusion in children seen in the emergency unit of a tertiary hospital in Southeast, Nigeria.

Blood transfusion is an important treatment modality for severe anaemia. Monitoring post-transfusion haemoglobin (Hb) concentration helps the clinician in assessing the success of blood transfusion. Previous authors have reported different timings for post-transfusion equilibration using varied time intervals for post-transfusion Hb concentration assessment. This study was therefore aimed at determining the appropriate time to assess Hb concentration after packed red blood cell (pRBC) transfusion in children using 5 different time intervals. It was a longitudinal observational study carried out in a tertiary care hospital in Southeast, Nigeria and involved 108 children aged 1-10 years without active bleeding or significant haemolysis that were transfused with pRBC. The Hb concentration was measured using a portable haemoglobinometer just before the blood transfusion and after the blood transfusion at 1, 6, 12, 24, and 48th-hour. The 1-hour (6.8 ± 1.5 g/dl) post-transfusion Hb concentration was significantly different (p 0.001) from the 6th-hour (10.2 ± 1.5 g/dl), but no further significant (p > 0.05) changes occurred after the 6th-hour till the 48th-hour. This finding suggests that equilibration of Hb concentration had occurred by the 6th hour after blood transfusion. This study, therefore, recommends that Hb concentration assessment in children without ongoing bleeding or haemolysis can be done at the 6th hour after pRBC transfusion.

Low-field magnetic resonance image enhancement via stochastic image quality transfer.

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings.

Detection of acute promyelocytic leukemia in peripheral blood and bone marrow with annotation-free deep learning.

While optical microscopy inspection of blood films and bone marrow aspirates by a hematologist is a crucial step in establishing diagnosis of acute leukemia, especially in low-resource settings where other diagnostic modalities are not available, the task remains time-consuming and prone to human inconsistencies. This has an impact especially in cases of Acute Promyelocytic Leukemia (APL) that require urgent treatment. Integration of automated computational hematopathology into clinical workflows can improve the throughput of these services and reduce cognitive human error. However, a major bottleneck in deploying such systems is a lack of sufficient cell morphological object-labels annotations to train deep learning models. We overcome this by leveraging patient diagnostic labels to train weakly-supervised models that detect different types of acute leukemia. We introduce a deep learning approach, Multiple Instance Learning for Leukocyte Identification (MILLIE), able to perform automated reliable analysis of blood films with minimal supervision. Without being trained to classify individual cells, MILLIE differentiates between acute lymphoblastic and myeloblastic leukemia in blood films. More importantly, MILLIE detects APL in blood films (AUC 0.94 ± 0.04) and in bone marrow aspirates (AUC 0.99 ± 0.01). MILLIE is a viable solution to augment the throughput of clinical pathways that require assessment of blood film microscopy.

Determinants of hydroxyurea use among doctors, nurses and sickle cell disease patients in Nigeria.

BACKGROUND: Hydroxyurea (HU) is an evidence-based therapy that is currently the most effective drug for sickle cell disease (SCD). HU is widely used in high-income countries with consequent reduction of morbidity and mortality. In Nigeria, HU is prescribed by physicians while nurses are mainly involved in counseling the patients to ensure adherence. The extent of utilization and the determinant factors have not been sufficiently evaluated in Nigeria. OBJECTIVE: To assess the frequency of use of HU and factors affecting utilization among healthcare providers, patients, and caregivers for SCD. METHODS: A questionnaire was administered online and in- person to assess the frequency of HU use and the factors that promote and limit its use. The data were analyzed by descriptive statistics using IBM SPSS software version 23 and the result was presented in frequency tables and percentages. RESULT: A total of 137 physicians, 137 nurses, and 237 patients/caregivers responded to the survey. The rate of prescription of HU by doctors in the past 6 months was 64 (46.7%), 43 (31.4%) nurses provided counseling and 36 (15.6%) patients were on HU. Among doctors, adequate knowledge (91.3%), clinical benefits and safety (94.8%), and inclusion of HU in management guidelines (86.9%) were motivators for prescribing it while inadequate knowledge (60.9%) and unawareness of treatment guidelines (68.6%) constituted barriers. Among nurses, reduction of crisis (91.6%) and safety (64.8%) were the major motivators while barriers were high cost (79.1%) and intensive monitoring (63.1%) of HU treatment. Among the patients, the major motivator was the reduction of crises (80.3%) while poor knowledge (93.2%), high cost of the drug (92.2%) while monitoring (91.2%), non-availability (87.7%) and side effects (83.9%) were the major barriers for the utilization of HU. CONCLUSION: HU prescription and utilization are still poor among healthcare providers and patients. Inadequate knowledge, non-availability and high cost of HU as well as unawareness of treatment guidelines constitute major barriers to prescription and utilization.

Content aware multi-focus image fusion for high-magnification blood film microscopy.

Automated digital high-magnification optical microscopy is key to accelerating biology research and improving pathology clinical pathways. High magnification objectives with large numerical apertures are usually preferred to resolve the fine structural details of biological samples, but they have a very limited depth-of-field. Depending on the thickness of the sample, analysis of specimens typically requires the acquisition of multiple images at different focal planes for each field-of-view, followed by the fusion of these planes into an extended depth-of-field image. This translates into low scanning speeds, increased storage space, and processing time not suitable for high-throughput clinical use. We introduce a novel content-aware multi-focus image fusion approach based on deep learning which extends the depth-of-field of high magnification objectives effectively. We demonstrate the method with three examples, showing that highly accurate, detailed, extended depth of field images can be obtained at a lower axial sampling rate, using 2-fold fewer focal planes than normally required.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Optical mesoscopy, machine learning, and computational microscopy enable high information content diagnostic imaging of blood films.

Automated image-based assessment of blood films has tremendous potential to support clinical haematology within overstretched healthcare systems. To achieve this, efficient and reliable digital capture of the rich diagnostic information contained within a blood film is a critical first step. However, this is often challenging, and in many cases entirely unfeasible, with the microscopes typically used in haematology due to the fundamental trade-off between magnification and spatial resolution. To address this, we investigated three state-of-the-art approaches to microscopic imaging of blood films which leverage recent advances in optical and computational imaging and analysis to increase the information capture capacity of the optical microscope: optical mesoscopy, which uses a giant microscope objective (Mesolens) to enable high-resolution imaging at low magnification; Fourier ptychographic microscopy, a computational imaging method which relies on oblique illumination with a series of LEDs to capture high-resolution information; and deep neural networks which can be trained to increase the quality of low magnification, low resolution images. We compare and contrast the performance of these techniques for blood film imaging for the exemplar case of Giemsa-stained peripheral blood smears. Using computational image analysis and shape-based object classification, we demonstrate their use for automated analysis of red blood cell morphology and visualization and detection of small blood-borne parasites such as the malarial parasite Plasmodium falciparum. Our results demonstrate that these new methods greatly increase the information capturing capacity of the light microscope, with transformative potential for haematology and more generally across digital pathology. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Clinicopathologic Features of Childhood Rhabdomyosarcoma and Treatment Outcomes in Ibadan, Nigeria: A 10-year Review.

The objectives of this study were to describe the clinicopathologic features and treatment outcomes of childhood rhabdomyosarcoma in a resource-constrained setting. All cases of childhood rhabdomyosarcoma seen over a 10-year period (July 2006 to June 2016) at the University College Hospital, Ibadan, Nigeria were reviewed. Data were extracted from the database of the pediatric Hematology/Oncology Unit of the hospital and analyzed. Ethical approval was obtained from the Institutional Ethics Committee. Fifty children were seen comprising 30 men and 20 women with bimodal ages of 4 and 5 years. Median duration of illness was 16 weeks and the most common primary tumor site was the head-and-neck region in 27 (54%) of cases. The histologic subtypes were embryonal in 30 (60%), alveolar in 9 (18%), and not specified in 11 (22%). The Intergroup Rhabdomyosarcoma Study group TNM Pretreatment stages were stage I in 15 (30%), stage III in 17 (34%), and stage IV in 18 (36%). Treatment included chemotherapy, surgery, and radiotherapy and abandoned in 20 (40%) cases. Median survival was 45 weeks (95% confidence interval: 16.4-73.6) and 5 (10%) patients were alive and disease free, 4 years or more after diagnosis. Outcome of childhood rhabdomyosarcoma is poor and early diagnosis and improved access to treatment are recommended.

Transcranial Doppler screening in Nigerian children with sickle cell disease: A 10-year longitudinal study on the SPPIBA cohort.

BACKGROUND: Primary stroke prevention programmes for children with sickle cell disease (SCD) have been shown to be feasible interventions in resource-poor countries. Different hydroxyurea (HU) regimens have been utilised in ameliorating the severity of SCD. OBJECTIVE: To determine the long-term outcomes of the stroke prevention programme for children with SCD in Ibadan (SPPIBA), Nigeria. METHODS: A longitudinal study of 396 children with haemoglobin SS disease who had been on the stroke prevention programme for a minimum period of 5 years. All enrollees had nonimaging TCD performed at baseline and thereafter 3-monthly or annually. Children with TCD velocities ≥170 cm/s were treated with HU by dose-escalation regimen. RESULTS: The mean age at first TCD examination was 102 ± 46.7 months and the period of follow-up ranged from 5 to 10 years (mean = 7.2 ± 1.7). Time to significant decline in TCD velocities ranged from 5 to 35 months, (median = 10.0 months). The minimum dose of HU required to achieve significant decline in TCD velocities ranged from 15 to 31 mg/kg/day, mean 23.7 (±3.9). HU dose escalation beyond 20 mg/kg/day was required to attain significant reductions in the time-averaged mean of maximal velocities (TAMMV) in 69.1% of the cases. Two stroke events occurred giving a stroke incidence of 0.08 per 100 patient-years. CONCLUSION: The majority of Nigerian children with SCD and elevated TCD velocities achieved significant decline in TAMMV within the first year of HU therapy but on higher doses of HU. It might be important to individualise HU doses for optimal outcomes in primary stroke prevention.

Paediatric soft tissue sarcomas in a resource constraint setting: Grade and stage at presentation and at oncologic intervention are usually of poor prognostic characteristics.

AIM: To describe the pattern of paediatric Rhabdomyosarcomas (RMS) and Non-Rhabdomyosarcomas (NRMS) with emphasis on the indices that affect survival outcomes. METHODS: We reviewed all patients with histologically confirmed RMS and NRMS in the Departments of Pathology and Paediatrics, University College Hospital (UCH), Ibadan, Nigeria; in children aged 0-14 years. The study period was January 1991 to December 2016. Information obtained included age, gender, morphology and site of the tumours. The tumour grade and pathologic/clinical staging of all patients were also obtained and verified by the clinical records. Tumour grading was carried out using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) Sarcoma group grading system and staging was done using TNM. Follow up, survival information and final outcome were retrieved. RESULTS: The 104 patients included in the study had almost equal male-to-female ratio, age ranged between 5 months and 14 years (median 8.2 years). Rhabdomyosarcoma had mean age of 5.6 (±3.8) years while that of NRMS was 9.2(±4.1) years. Overall, the modal age group was 5-9 years. Rhabdomyosarcoma was the commonest histological type (76%), undifferentiated sarcomas (6.7%), fibrosarcoma (3.8%) and 2.9% each for synovial sarcoma and dermatofibrosarcoma protuberans. The common primary sites were the head and neck (including the orbit) 49 (47.1%), and the abdominopelvic 26 (25%) regions. Majority (89%) had histologic grade 3 at presentation. Seventy per cent and 64% of patients with RMS and NRMS, respectively, had high stage tumour at presentation. Median survival for all patients with Rhabdomyosarcoma was 45 weeks with a 1-year survival of 43% and 2-year survival of 25%. Non-RMS (Dermatofibrosarcoma protuberans and Solitary fibrous tumours) had survival of over 4 year's duration. CONCLUSION: Majority of our patients presented at a late stage with histologic high grade which confers poor prognosis and reduced chances for good overall survival outcome.

Data-driven malaria prevalence prediction in large densely populated urban holoendemic sub-Saharan West Africa.

Over 200 million malaria cases globally lead to half-million deaths annually. The development of malaria prevalence prediction systems to support malaria care pathways has been hindered by lack of data, a tendency towards universal "monolithic" models (one-size-fits-all-regions) and a focus on long lead time predictions. Current systems do not provide short-term local predictions at an accuracy suitable for deployment in clinical practice. Here we show a data-driven approach that reliably produces one-month-ahead prevalence prediction within a densely populated all-year-round malaria metropolis of over 3.5 million inhabitants situated in Nigeria which has one of the largest global burdens of P. falciparum malaria. We estimate one-month-ahead prevalence in a unique 22-years prospective regional dataset of > 9 × 104 participants attending our healthcare services. Our system agrees with both magnitude and direction of the prediction on validation data achieving MAE ≤ 6 × 10-2, MSE ≤ 7 × 10-3, PCC (median 0.63, IQR 0.3) and with more than 80% of estimates within a (+ 0.1 to - 0.05) error-tolerance range which is clinically relevant for decision-support in our holoendemic setting. Our data-driven approach could facilitate healthcare systems to harness their own data to support local malaria care pathways.

Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence.

BACKGROUND: Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis. METHODS: Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort. RESULTS: The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups. CONCLUSIONS: The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM.

Expert-level automated malaria diagnosis on routine blood films with deep neural networks.

Over 200 million malaria cases globally lead to half a million deaths annually. Accurate malaria diagnosis remains a challenge. Automated imaging processing approaches to analyze Thick Blood Films (TBF) could provide scalable solutions, for urban healthcare providers in the holoendemic malaria sub-Saharan region. Although several approaches have been attempted to identify malaria parasites in TBF, none have achieved negative and positive predictive performance suitable for clinical use in the west sub-Saharan region. While malaria parasite object detection remains an intermediary step in achieving automatic patient diagnosis, training state-of-the-art deep-learning object detectors requires the human-expert labor-intensive process of labeling a large dataset of digitized TBF. To overcome these challenges and to achieve a clinically usable system, we show a novel approach. It leverages routine clinical-microscopy labels from our quality-controlled malaria clinics, to train a Deep Malaria Convolutional Neural Network classifier (DeepMCNN) for automated malaria diagnosis. Our system also provides total Malaria Parasite (MP) and White Blood Cell (WBC) counts allowing parasitemia estimation in MP/µL, as recommended by the WHO. Prospective validation of the DeepMCNN achieves sensitivity/specificity of 0.92/0.90 against expert-level malaria diagnosis. Our approach PPV/NPV performance is of 0.92/0.90, which is clinically usable in our holoendemic settings in the densely populated metropolis of Ibadan. It is located within the most populous African country (Nigeria) and with one of the largest burdens of Plasmodium falciparum malaria. Our openly available method is of importance for strategies aimed to scale malaria diagnosis in urban regions where daily assessment of thousands of specimens is required.

Acute leukemia in sickle cell disease patients in a tertiary health facility in Nigeria: a case series.

BACKGROUND AND OBJECTIVES: Sickle cell disease(SCD) is a disorder of red cells resulting from the co-inheritance of haemoglobin S (HbS) with another abnormal haemoglobin. The diagnosis of acute leukaemia is uncommon in our patients with sickle cell disease more so the patients have high morbidity and mortality due to the sickling process. Acute leukemia is a malignant clonal disorder of haemopoietic precursor cells resulting in accumulation of immature blood cells in the bone marrow and blood. The objective of the case series was to highlight the challenges of diagnosis and management of SCD patients with acute leukaemia, the importance of peripheral blood film review and propound a possible risk factor. METHODS: Records of 58 patients diagnosed and managed for acute leukaemia over a 7 year period at the University College Hospital, Ibadan were reviewed. The diagnosis of acute leukaemia was based on clinical features in addition to peripheral and bone marrow smears findings. Microsoft excel version 2013 was used for statistical analysis. RESULTS: Five (8.6%) of the patients with acute leukaemia also had sickle cell disease: 3 males and 2 females were described. Recurrent fever and anaemia were the most consistent presenting features in the patients. All the patients were not on any routine medications meant for SCD patients and had poor history of clinic attendance prior to the diagnosis of acute leukaemia. The diagnosis of acute leukaemia was not made until the patients were seen by a haematologist. The principal tool of diagnosis in all the patients was peripheral blood film review. Two patients were discharged against medical advice. The treatment period ranged between one month and one year in the remaining three patients. CONCLUSION: SCD patients are not exempted from developing acute leukaemias and the diagnoses of the two conditions overwhelms the social and economic support of patients and care givers. The study also underscores the relevance of high level of suspicion and prompt review of peripheral blood film of SCD patients particularly when patients present with unremitting symptoms associated with anaemia and fever.

Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis.

Severe Malarial Anemia (SMA), a life-threatening childhood Plasmodium falciparum malaria syndrome requiring urgent blood transfusion, exhibits inflammatory and hemolytic pathology. Differentiating between hypo-haptoglobinemia due to hemolysis or that of genetic origin is key to understand SMA pathogenesis. We hypothesized that while malaria-induced hypo-haptoglobinemia should reverse at recovery, that of genetic etiology should not. We carried-out a case-control study of children living under hyper-endemic holoendemic malaria burden in the sub-Saharan metropolis of Ibadan, Nigeria. We show that hypo-haptoglobinemia is a risk factor for childhood SMA and not solely due to intravascular hemolysis from underlying schizogony. In children presenting with SMA, hypo-haptoglobinemia remains through convalescence to recovery suggesting a genetic cause. We identified a haptoglobin gene variant, rs12162087 (g.-1203G > A, frequency = 0.67), to be associated with plasma haptoglobin levels (p = 8.5 × 10-6). The Homo-Var:(AA) is associated with high plasma haptoglobin while the reference Homo-Ref:(GG) is associated with hypo-haptoglobinemia (p = 2.3 × 10-6). The variant is associated with SMA, with the most support for a risk effect for Homo-Ref genotype. Our insights on regulatory haptoglobin genotypes and hypo-haptoglobinemia suggest that haptoglobin screening could be part of risk-assessment algorithms to prevent rapid disease progression towards SMA in regions with no-access to urgent blood transfusion where SMA accounts for high childhood mortality rates.

White Paper: Pathways to Progress in Newborn Screening for Sickle Cell Disease in Sub-Saharan Africa.

Sickle Cell Disease (SCD) is among the most common single-gene diseases in the world but evidence-based comprehensive health care has not been implemented where the highest prevalence of SCD occurs, in sub-Saharan Africa (SSA). It represents an urgent health burden, both in terms of mortality and morbidity with an estimated mortality of 8-16% in children under 5 years in SSA. Addressing the high mortality of SCD in SSA and for effective management of SCD, newborn screening (NBS) should be incorporated with prevention of infections (including pneumococcal septicaemia and malaria), parental education and support at all levels of healthcare provision to enable timely recognition. The NBS working group of the Africa Sickle Cell Research Network (AfroSickleNet) collaboration surveyed current projects in NBS in SSA, and current conditions that hinder more widespread implementation of NBS for SCD. Solutions based on new point-of-care testing technology to disseminate education, and implementation science approaches that leverage existing resources are proposed.

A Multi-centre Survey of Acceptability of Newborn Screening for Sickle Cell Disease in Nigeria.

Background Sickle cell disease (SCD) is a major genetic disease that manifests early in life and may lead to significant morbidities. One of the health care services that have been effective in reducing the burden of SCD in developed countries is newborn screening (NBS) followed by pneumococcal vaccines, penicillin prophylaxis, and hydroxyurea treatment. Yet, in sub-Saharan African countries, where about 75% of annual affected babies worldwide are born, NBS programmes are largely unavailable. It is not clear whether this is due to technical challenges associated with setting up such programmes, or significant cultural and social barriers to its acceptance in such settings. Objective Our aim was to ascertain the attitudes to and acceptability of NBS in Nigeria among various socio-demographic groups including health professionals, undergraduate students, parents of children with SCD and SCD patients. Methods Data on socio-demographic characteristics, knowledge of SCD and attitude towards NBS were collected using a semi-structured pre-tested questionnaire from April to July 2014 across 15 health institutions and university campuses in Nigeria. Data were collected from 1,301 respondents across Nigeria. Results There was good knowledge of SCD as an inherited blood disorder. Although 86% of respondents (n = 1,119) supported NBS, there was a statistically significant relationship between support for NBS and age (p = 003), educational status (p = 000) and religion (p = 000). Conclusion This study suggests that there is a good acceptability of NBS across Nigeria. The main barriers to its use are likely to be financial and practical, rather than social or cultural.

A COMPARISON OF RAPID DIAGNOSTIC TESTING (BY PLASMODIUM LACTATE DEHYDROGENASE), AND QUANTITATIVE BUFFY COAT TECHNIQUE IN MALARIA DIAGNOSIS IN CHILDREN.

BACKGROUND: The World Health Organization (WHO) considers early and rapid diagnosis as one of the strategies to control malaria. This study compared the performance of Quantitative Buffy Coat (QBC) test and the Plasmodium lactate dehydrogenase (pLDH) rapid diagnostic test (RDT) with microscopy as the gold standard. MATERIALS AND METHODS: The study involved children ages 0-5 years who presented with a history of fever at the University College Hospital, Ibadan, Nigeria. Blood was collected from each patient and used for RDT, QBC and Giemsa-stained blood films for malaria parasites (MP). Results of QBC and RDT were compared with microscopy results for the diagnosis of malaria. RESULTS: A total of 370 cases (194 boys and 176 girls) were studied giving a male: female ratio of 1.1:1. Of the 370 cases tested using Giemsa-stained thick blood films for MP, 78 (21 %) were positive. For the QBC test, 78 (21%) of the cases were positive with sensitivity, specificity, positive and negative predictive values of 70.5 %, 92.1%, 70.5 % and 92.1 % respectively. Seventy-six (20%) of the cases were positive by RDT with sensitivity, specificity, positive and negative predictive values of 84.2 %, 95.2 %, 82.1 %, and 95.9 % respectively. There was no significant difference in the sensitivity of QBC compared with the RDT. CONCLUSION: Both the QBC and the pfLDH (RDT) performed reasonably well in this study Malaria rapid diagnostic tests are recommended in malaria endemic clinical settings to avoid unnecessary antimalarial treatment. List of Abbreviations: AO: Acridine orange, AIDS: Acquired immunodeficiency syndrome, ACT: Artemisinin-based combination therapy, CM:Cerebral malaria, BCP:Benzothiocarboxypurine, DDT:Dichloro-diphenyl-trichloroethane, DNA:DeoxyriboNucleic Acid, ELAM-1: Endothelial leukocyte adhesion molecule, G6PD: Glucose-6-Phosphate Dehydrogenase, HIV: Human immuno deficiency virus, HRP 2: Histidine Rich Protein 2, ICAM -1: Inter cellular adhesion molecule1, ICER: Incremental cost effectiveness ratio, IL-1: Interleukin -1, IFN-g: Interferon-gamma, IgG: Immunoglobulin G, MP: Malaria parasite, NADP: Oxidised Nicotinamide Adenine Dinucleotide Phosphate, NADPH: Reduced Nicotinamide Adenine Dinucleotide Phosphate, PCV: Packed Cell Volume (haematocrit), P. falciparum: Plasmodium falciparum, PLDH: Plasmodium lactate dehydrogenase, PCR: Polymerase Chain Reaction, PPV: Positive predictive value, QBC: Quantitative Buffy Coat examination, TNF: Tumour necrosis factor, NPV: Negative predictive value, RDT: Rapid diagnostic test, SP: Sulphadoxine -Pyrimethamine, SMA: Severe malarial anaemia, UM: Uncomplicated malaria, USA:United States of America, VCAM-1: Vascular cell adhesion molecule, WBC: White Blood Cell, WHO: World Health Organization.

Preliminary Evaluation of a Point-of-Care Testing Device (SickleSCAN™) in Screening for Sickle Cell Disease.

Sickle cell disease affects about 150,000 births annually in Nigeria. Early diagnosis is hampered by factors such as centralized and urban localization of laboratories, high cost of diagnostic equipment and inadequate skilled manpower to operate them. The need for a low-cost, portable, easy-to-use diagnostic test for sickle cell disease is critical, especially in resource-poor countries. In this study, we evaluated the performance characteristics of a novel point-of-care testing device (SickleSCAN™), and its acceptability and feasibility, as a possible screening tool for sickle cell disease. In the first phase, we assessed the performance characteristics of SickleSCAN™ by evaluating 57 subjects comprising both children and adults attending a primary health center, for Hb SS (ßS/ßS; HBB: c.20A>T), Hb SC (ßS/ßC; HBB: c.19G>A) and Hb AS (ßA/ßS) using SickleSCAN™, cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC). Performance characteristics such as diagnostic sensitivity and specificity were compared to HPLC as a standard method. We subsequently undertook a second phase wherein the acceptability and feasibility of the device for sickle cell disease screening, was evaluated using semi-structured and structured questionnaires among 197 healthcare personnel and 221 subjects, respectively. Sickle cell disease was carried by 3.4% of the subjects. The diagnostic sensitivity, specificity and test efficiency of SickleSCAN™ for sickle cell disease (Hb SS and Hb SC), were 100.0, 98.2 and 98.2%, respectively. Findings from this study showed SickleSCAN™ to be a viable screening tool that can easily be applied in community-based screening for early diagnosis of sickle cell disease with little expertise and low cost.