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Emmanuela E Ambrose,1 Benson R Kidenya,2 Mwesige Charles,3 Joyce Ndunguru,4 Agnes Jonathan,4 Julie Makani,4 Irene K Minja,4,5 Paschal Ruggajo,4,6 Emmanuel Balandya4,7 1Department of Paediatrics and Child Health, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 2Department of Biochemistry and Molecular Biology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 3Department of Laboratory Services, Bugando Medical Centre, Mwanza, Tanzania; 4Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 5Department of Restorative Dentistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 6Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 7Department of Physiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, TanzaniaCorrespondence: Emmanuela E Ambrose, Department of Paediatrics and Child Health, Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania, Tel +255789733833, Fax +255282500799, Email emmanuelaambrose@gmail.comPurpose: To assess clinical and haematological outcomes of Hydroxyurea accessed via various access means and uncover the barriers to its utilization in children with Sickle cell anaemia (SCA), North-western Tanzania.Patients and Methods: A retrospective study was conducted between October 2020 and April 2021 at Bugando Medical Centre (BMC) through review of medical files to compare the clinical and haematological outcomes among children with SCA at baseline and followed up retrospectively for at least one year of hydroxyurea utilization, accessed via cash, insurance and projects. Subsequently, a cross-sectional survey was conducted among parents and caregivers to ascertain the barriers to access of hydroxyurea via the various means. The p-values < 0.05 were considered statistically significant.Results: We identified 87 children with SCA who were on hydroxyurea for at least one year. The median age at baseline (before hydroxyurea) was 99 [78– 151] months, and 52/87 (59.8%) were male. Compared to baseline, there was a significant reduction in proportion of patients reporting vaso-occlusive crisis, admissions and blood transfusions, a significant increase in Haemoglobin and mean corpuscular volume, conversely a significant reduction in absolute neutrophil and reticulocytes to both insurance and project participants. There was no significant change in most of these parameters among patients who accessed hydroxyurea via cash. Further, a total of 24/87 (27.6%) participants reported different barriers to access of hydroxyurea, where 10/24 (41.7%) reported hydroxyurea to be very expensive, 10/24 (41.7%) reported insurance challenges, and 4/21 (16.6%) reported unavailability of the drug.Conclusion: The paediatric patients utilizing hydroxyurea accessed via insurance and projects, but not cash, experienced significant improvement in the clinical and haematological outcomes. Several barriers for access to hydroxyurea were observed which appeared to impact these outcomes. These findings call for concerted efforts to improve the sustainable access to hydroxyurea among all patients with SCA.Keywords: sickle cell anaemia, hydroxyurea, access, outcomes, North-western Tanzania

Introduction: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. Methods: After formal training and certification, local personnel screened children 2–16 years old; those with conditional (170–199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. Results: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8–1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. Conclusion: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.

BackgroundSickle cell disease (SCD) is a severe hereditary form of anemia that contributes between 50% and 80% of under-five mortality in Africa. Eleven thousand babies are born with SCD annually in Tanzania, ranking 4th after Nigeria, the Democratic Republic of Congo and India. The absence of well-described SCD cohorts is a major barrier to health research in SCD in Africa.ObjectiveThis paper describes the Sickle Pan African Consortium (SPARCO) database in Tanzania, from the development, design of the study instruments, data collection, analysis of data and management of data quality issues.MethodsThe SPARCO registry used existing Muhimbili Sickle Cell Cohort (MSC) study case report forms (CRF) and later harmonized data elements from the SickleInAfrica consortium to develop Research Electronic Data Capture (REDCap) instruments. Patients were enrolled through various strategies, including mass screening following media sensitization and health education events during World Sickle Cell Day each June and the SCD awareness month in September. Additional patients were identified through active surveillance of previously participating patients in the MSC.ResultsThree thousand eight hundred patients were enrolled between October 2017 and May 2021. Of these, 1,946 (51.21%) were males and 1,864 (48.79%) were females. The hemoglobin phenotype distribution was 3,762 (99%) HbSS, 3 (0.08%) HbSC and 35 (0.92%) HbSβ +thalassemia. Hemoglobin levels, admission history, blood transfusion and painful events were recorded from December 2017 to May 2021.ConclusionThe Tanzania SPARCO registry will improve healthcare for SCD in Africa through the facilitation of collaborative data-driven research for SCD.

Sickle cell disease (SCD) is a common condition within sub-Saharan Africa and associated with high under-5 mortality (U5M). The American Society of Hematology instituted the Consortium on Newborn Screening in Africa (CONSA) for SCD, a 7-country network of sites to implement standardized newborn hemoglobinopathy screening and early intervention for children with SCD in sub-Saharan Africa. CONSA’s overall hypothesis is that early infant SCD screening and entry into standardized, continuous care will reduce U5M compared with historical estimates in the region. Primary trial objectives are to determine the population-based birth incidence of SCD and effectiveness of early standardized care for preventing early mortality consortium-wide at each country’s site(s). Secondary objectives are to establish universal screening and early interventions for SCD within clinical networks of CONSA partners and assess trial implementation. Outcomes will be evaluated from data collected using a shared patient registry. Standardized trial procedures will be implemented among designated birth populations in 7 African countries whose programs met eligibility criteria. Treatment protocol includes administering antibacterial and antimalarial prophylaxis and standard childhood vaccinations against infections commonly affecting children with SCD. Infants with a positive screen and confirmation of SCD within the catchment areas defined by each consortium partner will be enrolled in the clinical intervention protocol and followed regularly until age of 5 years. Effectiveness of these early interventions, along with culturally appropriate family education and counseling, will be evaluated by comparing U5M in the enrolled cohort to estimated preprogram data. Here, we describe the methodology planned for this trial.

In an effort to explore new knowledge and to develop meaningful collaborations for improving child health, the First Pan African Workshop on Newborn Screening was convened in June 2019 in Rabat, Morocco. Participants included an informal network of newborn screening stakeholders from across Africa and global experts in newborn screening and sickle cell disease. Over 150 attendees, representing 20 countries, were present including 11 African countries. The agenda focused on newborn screening rationale, techniques, system development, implementation barriers, ongoing research, and collaborations both globally and across Africa. We provide an overview of the workshop and a description of the newborn screening activities in the 11 African countries represented at the workshop, with a focus on sickle cell disease.

Background It is evident that renal dysfunction (RD) is associated with unique infectious and non-infectious causes in African children. However, little data exists about the prevalence and factors associated with RD in children admitted to African hospitals. Methods In this cross-sectional study, we enrolled all children admitted to pediatric wards of Bugando Medical Centre (BMC) and Sekou-Toure Regional Referral hospital (SRRH) during a 6 month time period. Socio-demographical, clinical and laboratory data were collected using a structured questionnaire. Estimated glomerular filtration rate (eGFR) was calculated using modified Schwartz equation and those with

Factor VII deficiency is a rare inherited disorder. Clinically the patient presents with bleeding tendencies. Diagnosis is made by prolonged prothrombin time, normal activated partial thromboplastin time and low functions factor VII assay or factor VII antigen. Therapy involves factor VII concentrates, recombinant factor VII, fresh frozen plasma and fibrinolytic inhibitors. We present a 6 years old boy with nose bleed for six months of whom prothrombin time was prolonged with functional factor VII assay of less than 1% confirming factor VII deficiency. He was managed with fresh frozen plasma, blood transfusion, tranexamic acid. Factor VII deficiency even though rare should be sought out in children presenting with bleeding. Keywords: Factor VII deficiency; coagulation; hemorrhage.

We conducted a pilot study to determine the effectiveness of a linkage to care intervention with social workers to improve 12-month post-hospital mortality for children in Tanzania with sickle cell disease. Comparison was done with a historical cohort. Mortality was 6.7% in the interventional cohort compared with 19.2% (adjusted Hazard Ratio, 0.26; 95% CI, 0.08-0.83).

Background: Anemia causes significant morbidity and mortality in low-resource settings and is a common problem in sickle cell disease (SCD). Timely, accurate diagnosis of anemia enables appropriate triage and treatment. In the Bedside Expedited Testing for Anemia and Sickle Cell Disease (BETA) study, we aimed to evaluate the accuracy of two simple point-of-care diagnostic devices in the hands of the intended end-users: one for anemia and one for SCD. Here we present the results of the Anemocheck-LRS assay, a simple, inexpensive, color-based test that quickly quantifies hemoglobin concentration to diagnose anemia. Methods: BETA was performed at …

BACKGROUND/OBJECTIVES: Sickle cell disease (SCD) is an important, hidden cause of childhood mortality worldwide. It is most prevalent in sub-Saharan Africa where national newborn screening programs remain unavailable and most children in rural areas are never diagnosed. We conducted a study at a rural district hospital in northern Tanzania to determine the birth prevalence and community awareness of SCD and to determine the feasibility of using point-of-care testing to enroll newborns in a new SCD clinic for ongoing treatment. DESIGN/METHODS: We screened infants at Shirati KMT hospital for SCD using HemoTypeSC, an inexpensive point-of-care test. Infants who screened positive were enrolled in the SCD clinic and instructed to return at 6–12 weeks for confirmatory testing, counseling, and preventive care. RESULTS: A total of 999 newborns were screened from February to September 2019. Among these, 31.6% (315/999) had sickle cell trait and 3.9% (39/999) had SCD. No hemoglobin C was detected. Very few parents knew their own sickle cell status (0.3%). At 5 months after completion, 12 infants from the screening study and 30 additional children had been seen at the SCD clinic for ongoing counseling and care. CONCLUSIONS: Birth prevalence of SCD in rural Tanzania is extremely high and community awareness is low. Newborn point-of-care testing enhances case finding and enables early enrollment in preventive care for SCD, even in rural sub-Saharan Africa with minimal laboratory capacity. SCD-specific clinical services implemented at the district hospital level could expand access to many children and significantly reduce early SCD morbidity and mortality.

Introduction: Sickle cell anemia (SCA) is highly prevalent in sub-Saharan Africa with >300,000 annual births, and substantial morbidity and mortality due to limited resources. The burden of stroke in this population is of particular concern, given the devastating clinical and neurocognitive sequelae of these events. Hydroxyurea, a potent disease modifying therapy for SCA, is safe and feasible for low-resource and malarial endemic countries within sub-Saharan Africa and when used at maximum tolerated dose (MTD), decreases the incidence of acute painful vaso-occlusive events, infections, malaria, transfusions, hospitalizations, and death. Whether hydroxyurea can prevent primary stroke in SCA within Africa has not yet been determined, due in part to lack of stroke screening programs using transcranial Doppler (TCD) ultrasonography. If effective, hydroxyurea would have even more therapeutic benefits for children with SCA, particularly in settings where blood is not available, affordable, or safe. We designed the Stroke Prevention with Hydroxyurea Enabled through Research and Education (SPHERE) trial to determine the stroke risk among Tanzanian children using TCD screening and to investigate the effects of hydroxyurea to reduce that risk. Methods: The SPHERE trial (NCT03948867) is a single center prospective phase 2 open-label screening and treatment pilot study at Bugando Medical Centre, a teaching and referral hospital in Mwanza, Tanzania. Children 2-16 years old with SCA consented to TCD screening by locally trained and certified examiners; recent febrile illness, red cell transfusion, or hospitalization were temporary exclusions. Study participants with maximum Time-Averaged Mean Velocity (TAMV) on TCD exam categorized as conditional (170-199 cm/sec) or abnormal (≥200 cm/sec) are offered hydroxyurea with escalation to MTD, while those with normal TCD screening exams will be rescreened annually. Hydroxyurea is initiated at ~20 mg/kg/day using 500 mg capsules and a weekly dosing calculator, then escalated every 8 weeks by 5 mg/kg/day up to 35 mg/kg/day. Children on hydroxyurea are seen monthly during dose escalation and every 3 months after reaching MTD. The primary endpoint is change in TCD velocity after 12 months of hydroxyurea therapy. Secondary endpoints include changes in splenic volume and filtrative function; change in renal function; incidence of infection, especially malaria; hydroxyurea pharmacokinetics; and genetic modifiers of disease including pharmacogenomics. Results: From April 2019 to April 2020, a total of 202 children underwent TCD screening, exceeding the projected enrollment pace and goal (Figure). The average age (mean ± SD) at enrollment was 6.8 ± 3.5 years, and 53% were female. A majority had previous dactylitis (75%), painful vaso-occlusive episode (93%), blood transfusion (68%), and malaria (89%). Recurrent hospitalization was common with 30% having >5 previous hospitalizations. Only 4% had previously used hydroxyurea. Baseline labs included hemoglobin = 7.8 ± 1.3 g/dL, HbF = 9.3 ± 5.4 %, and ANC = 5.5 ± 2.4 x 109/L. Baseline assessment revealed a palpable spleen in 46 children (23%), and most of these (29) were ≥5 cm below the costal margin. Abdominal ultrasonography documented splenic tissue in 91% of children with an average volume of 101 ± 123 mL (range 8-1045). TCD examinations were performed in all children at enrollment with average TAMV of 148 ± 27 cm/sec [median 144, IQR 130-169 cm/sec] with 76% normal, 21% conditional, 2% abnormal, and 1% inadequate exams. Of 47 children eligible for hydroxyurea for elevated TCD velocities, 45 successfully initiated treatment, while 1 lived too far away for regular visits, and 1 had low blood counts from acute splenic sequestration and died before initiating study treatment. Conclusion: Children with SCA in Tanzania have a high risk for primary stroke. Identification of elevated TCD velocities through screening by local trained certified examiners, coupled with initiation of hydroxyurea treatment with dose escalation to MTD, offers a feasible and affordable means by which to lower TCD velocities and reduce primary stroke risk. Now fully enrolled, SPHERE has built local clinical capacity, research infrastructure and high-quality TCD screening, and will prospectively determine the benefits of hydroxyurea for stroke prevention, as a prelude for expanding hydroxyurea access for children with SCA in Tanzania. Figure Disclosures No relevant conflicts of interest to declare.

To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania.We repurposed dried blood spot samples from children (aged 0-24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children's Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers.We analysed a total of 17 200 specimens during February 2017-May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD AOur calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.Déterminer la prévalence de la drépanocytose et du trait drépanocytaire chez les nouveau-nés, ainsi que la prévalence de variants d'hémoglobine et de modificateurs génétiques de la drépanocytose dans les neuf régions du nord-ouest de la République-Unie de Tanzanie.Nous avons réutilisé des échantillons de gouttes de sang séché provenant d'enfants (âgés de 0 à 24 mois) nés de mères atteintes du virus de l'immunodéficience humaine (VIH), prélevés dans le cadre du programme de diagnostic précoce de l'infection à VIH chez le nourrisson pour détecter une éventuelle drépanocytose. Nous avons procédé à une focalisation isoélectrique pour savoir si les échantillons présentaient une hémoglobine normale, un trait drépanocytaire, une drépanocytose ou un variant d'hémoglobine rare. Ensuite, nous avons envoyé les échantillons identifiés comme porteurs de la maladie ou d'un variant à l'hôpital pour enfants de Cincinnati, aux États-Unis, afin d'analyser l'acide désoxyribonucléique et de mesurer la prévalence d'une α-thalassémie, d'un déficit en glucose-6-phosphate déshydrogénase (G6PD) ou de modificateurs génétiques de l'hémoglobine fœtale.Nous avons étudié 17 200 spécimens au total entre février 2017 et mai 2018. Nous avons observé une prévalence de 20,3% (3492/17 200) pour la drépanocytose, et de 1,2% (210/17 200) pour le trait drépanocytaire. D'un district à l'autre, la présence du trait variait de 8,6% (5/58) à 28,1% (77/274). Nous avons constaté que 42,7% (61/143) des spécimens chez qui une drépanocytose avait été confirmée étaient privés d'un gène, et 14,7% (21/143) de deux gènes du trait α-thalassémique. Enfin, nous avons répertorié un déficit en G6PD ALa prévalence que nous avons calculée est deux fois supérieure aux chiffres mentionnés précédemment, et souligne la nécessité d'instaurer de meilleurs services de diagnostic de la drépanocytose. Nos données réparties par district fourniront des informations en matière de politique de santé publique, afin que le dépistage et le traitement modificateur de la maladie, à base d'hydroxyurée, se concentrent sur les zones de forte prévalence jusqu'à ce qu'un dépistage universel des nouveau-nés soit disponible.Determinar la prevalencia de la enfermedad y del rasgo de las células falciformes en los recién nacidos a nivel regional y de distrito, y la prevalencia de las variantes de hemoglobina y de los modificadores genéticos de la drepanocitosis en las nueve regiones del noroeste de la República Unida de Tanzania.Se reutilizaron las muestras de las manchas de sangre seca de los niños (de 0 a 24 meses de edad) nacidos de madres que padecían el virus de la inmunodeficiencia humana (VIH); estas muestras se obtuvieron a través del programa de Diagnóstico precoz del VIH en niños para diagnosticar las células falciformes. Se aplicó la técnica del enfoque isoeléctrico para determinar si las muestras tenían hemoglobina, rasgos de células falciformes, drepanocitosis normales o una variante de hemoglobina poco frecuente. Se enviaron muestras diagnosticadas como enfermedad o variante al Hospital Infantil de Cincinnati (Cincinnati Children's Hospital) en los Estados Unidos de América para analizarlas a base de ácido desoxirribonucleico y así determinar la prevalencia de talasemia α, de deficiencia de glucosa-6-fosfato deshidrogenasa (G6PD, por sus siglas en inglés) o de modificadores genéticos de hemoglobina fetal.Se analizaron un total de 17 200 muestras entre febrero de 2017 y mayo de 2018. Se observó una prevalencia del rasgo de las células falciformes y de la drepanocitosis del 20,3 % (3492/17 200) y del 1,2 % (210/17 200), respectivamente. El rasgo a nivel de distrito varió del 8,6 % (5/58) al 28,1 % (77/274). Se observó que en las muestras de drepanocitosis confirmadas, el 42,7 % (61/143) presentaba la eliminación de un gen y el 14,7 % (21/143) la eliminación de dos genes en el rasgo de talasemia α. Se registró una deficiencia de G6PD A- en el 19,2 % (14/73) de los varones.La prevalencia que se calcula aquí es el doble de la que se notificó anteriormente y refuerza la necesidad de mejorar los servicios para el diagnóstico de la drepanocitosis. Estos datos a nivel de distrito contribuirán a la política de salud pública, ya que permitirán que los cribados y la terapia con hidroxicarbamida que modifica la enfermedad se centren en las zonas de alta prevalencia, hasta que se disponga de un cribado universal de los recién nacidos.الغرض تحديد معدل انتشار سمات ومرض الخلايا المنجلية لدى حديثي الولادة على مستوى الأقاليم والمناطق، وانتشار متغيرات الهيموجلوبين والمعدلات الجينية لمرض فقر الدم المنجلي، في المناطق التسع الواقعة شمال غرب جمهورية تنزانيا المتحدة. الطريقة قمنا بإعادة استخدام عينات بقع الدم المجففة من الأطفال (من حديثي الولادة إلى 24 شهرًا) المولودين لأمهات مصابات بفيروس نقص المناعة البشرية (HIV)، والتي تم جمعها كجزء من برنامج التشخيص المبكر لفيروس نقص المناعة البشرية للرضع، لتشخيص مرض الخلايا المنجلية. أجرينا تركيزًا متساوي الجهد الكهربائي لتحديد ما إذا كانت العينات تحتوي على هيموجلوبين طبيعي، أو سمة للخلايا المنجلية، أو مرض الخلايا المنجلية، أو أحد المتغيرات النادرة للهيموجلوبين. كما قمنا بشحن عينات تم تشخيصها على أنها مصابة بالمرض أو أحد المتغيرات، إلى مستشفى سينسيناتي للأطفال في الولايات المتحدة الأمريكية، لإجراء تحليلات باستخدام حمض الديوكسي ريبونيوكليك لتحديد مدى انتشار كل من ثلاسيميا ألفا، أو النقص في نازع هيدروجين الجلوكوز 6 فوسفات (G6PD)، أو المعدلات الوراثية للهيموجلوبين الجنيني. النتائج قمنا بتحليل إجمالي 17200 عينة خلال الفترة من فبراير/شباط 2017 إلى مايو/أيار 2018. ولاحظنا انتشار سمة ومرض الخلايا المنجلية بنسبة 20.3% (3492/17200)، و1.2% (210/17200)، على الترتيب. تنوعت السمات على مستوى المناطق من 8.6% (5/58) إلى 28.1% (77/274). ولاحظنا من بين عينات مرض الخلايا المنجلية المؤكد، أن 42.7% (61/143) قد عانت من حذف جين واحد، و14.7% (21/143) عانت من حذف جينين من سمة ألفا ثلاسيميا. وكما بتوثيق النقص في G6PD A في 19.2% (14/73) من الذكور. الاستنتاج إن معدل الانتشار الذي قمنا باحتسابه هو ضعف ما تم الإبلاغ عنه سابقًا، ويعزز الحاجة إلى خدمات محسنة لتشخيص مرض الخلايا المنجلية. ستؤدي البيانات على مستوى المقاطعات لدينا إلى توجيه سياسة الصحة العامة، مما يسمح لكل من الفحص والمعالجة باستخدام هيدروكسي اليوريا المعدل للأمراض، بالتركيز على المناطق ذات الانتشار المرتفع، حتى يتوفر فحص شامل لحديثي الولادة.确定坦桑尼亚联合共和国西北九个地区，新生儿镰状细胞性状和镰状细胞疾病的患病率，以及血红蛋白变体和镰状细胞疾病遗传修饰因子的患病率。.作为 HIV 早期婴儿诊断计划的一部分，我们将携带人类免疫缺陷病毒 (HIV) 的母亲所生婴儿（0-24 个月）的干血斑样本重新用于诊断镰状细胞。我们对其实施等电聚焦，以确定样本的血红蛋白是否正常、是否具有镰状细胞性状、镰状细胞疾病或罕见的血红蛋白变体。我们将诊断出患有疾病或变异的样本运送到美国辛辛那提儿童医院，进行脱氧核糖核酸分析，以确定α地中海贫血、6-磷酸葡萄糖脱氢酶 (G6PD) 缺失症或胎儿血红蛋白遗传修饰因子的患病率。.我们在 2017 年 2 月至 2018 年 5 月期间共分析了 17200 个样本。我们观察到镰状细胞性状和镰状细胞疾病的患病率分别为 20.3％ (3492/17 200) 和 1.2％ (210/17 200)。区级镰状细胞性状患病率则从 8.6% (5/58) 到 28.1% (77/274) 不等。在确诊的镰状细胞疾病样本中，我们发现 42.7% (61/143) 具有 1 基因缺失型 α 地中海贫血性状，14.7% (21/143) 具有 2 基因缺失型 α 地中海贫血性状。我们注意到 19.2% (14/73) 的男婴患有 G6PD A–缺乏症。.我们计算得出的患病率是先前报道的两倍，这凸显了加强镰状细胞诊断服务的必要性。我们的区级数据将为公共卫生政策提供信息，从而确保在新生儿普查之前，对高发地区集中展开筛查和疾病修饰羟基脲疗法。.Определить на национальном уровне и на уровне районов распространенность среди новорожденных носительства признака серповидно-клеточной анемии и самого этого заболевания, а также распространенность вариантов гемоглобина и генетических модификаторов серповидно-клеточной анемии в девяти регионах на северо-западе Объединенной Республики Танзания.Для диагностики серповидно-клеточной анемии авторы использовали взятые методом высушивания пятна образцы крови детей в возрасте от 0 до 24 месяцев, чьи матери живут с вирусом иммунодефицита человека (ВИЧ); эти образцы были собраны в рамках программы ранней диагностики ВИЧ у детей. Для определения наличия в образцах нормального гемоглобина, носительства признака серповидно-клеточной анемии, собственно серповидно-клеточной анемии или редкого варианта гемоглобина использовался метод изоэлектрической фокусировки. Образцы, которые были диагностированы как соответствующие проявлениям заболевания или как содержащие вариантный гемоглобин, были направлены в Детскую больницу Цинциннати, США, для проведения ДНК-анализа с целью определения распространенности в них α-талассемии, дефицита глюкозо-6-фосфат-дегидрогеназы (Г6ФД) или наличия генетических модификаторов фетального гемоглобина.Авторы проанализировали 17 200 образцов в период с февраля 2017 г. по май 2018 г. Носительство признака серповидно-клеточной анемии было обнаружено в 20,3% случаев (3492 из 17 200 образцов), а серповидно-клеточная анемия — в 1,2% (210 из 17 200 образцов). Наличие признака в разных районах варьировалось от 8,6% (5 из 58 образцов) до 28,1% (77 из 274 образцов). Среди образцов с подтвержденным диагнозом серповидно-клеточной анемии в 42,7% случаев (61 из 143) наблюдался признак α-талассемии с делецией 1 гена и в 14,7% (21 из 143) — с делецией 2 генов. Дефицит Г6ФД был зафиксирован у 19,2% (14 из 73) мальчиков.Рассчитанная авторами распространенность заболевания вдвое превышает опубликованные ранее значения и еще раз указывает на необходимость укрепления и расширения услуг по диагностике СКА. Полученные данные по районам станут основой для выработки политики в области общественного здравоохранения, которая бы позволяла сосредоточить скрининговое обследование и лечение гидроксимочевиной (изменяющее течение заболевания) в областях с высоким распространением заболевания до тех пор, пока не станет возможным всеобщее скрининговое обследование новорожденных.

BackgroundAfrica has the highest rates of child mortality. Little is known about outcomes after hospitalization for children with very severe anemia.ObjectiveTo determine one year mortality and predictors of mortality in Tanzanian children hospitalized with very severe anemia.MethodsWe conducted a prospective cohort study enrolling children 2-12 years hospitalized from August 2014 to November 2014 at two public hospitals in northwestern Tanzania. Children were screened for anemia and followed until 12 months after discharge. The primary outcome measured was mortality. Predictors of mortality were determined using Cox regression analysis.ResultsOf the 505 children, 90 (17.8%) had very severe anemia and 415 (82.1%) did not. Mortality was higher for children with very severe anemia compared to children without over a one year period from admission, 27/90 (30.0%) vs. 59/415 (14.2%) respectively (Hazard Ratio (HR) 2.42, 95% Cl 1.53–3.83). In-hospital mortality was 11/90 (12.2%) and post-hospital mortality was 16/79 (20.2%) for children with very severe anemia. The strongest predictors of mortality were age (HR 1.01, 95% Cl 1.00–1.03) and decreased urine output (HR 4.30, 95% Cl 1.04 – 17.7).ConclusionsChildren up to 12 years of age with very severe anemia have nearly a 30% chance of mortality following admission over a one year period, with over 50% of mortality occurring after discharge. Post-hospital interventions are urgently needed to reduce mortality in children with very severe anemia, and should include older children.

Tanzania has the third highest number of infants in the world born annually with sickle cell disease (SCD). Tanzania lacks a national newborn screening program, and a large majority of the clinical care, resources, and research for SCD are located in the coastal city of Dar es Salaam. Previous

Tanzania has the third highest birth rate of sickle cell anaemia (SCA) in Africa, but few studies describe severity of complications or available treatments, especially in Northwest Tanzania around Lake Victoria where the sickle gene is most prevalent. This is a report of the spectrum of clinical disease and range of interventions available at Bugando Medical Centre (Bugando) in Northwest Tanzania in Africa.A cross-sectional study was carried out in Bugando between 1 August 2012 and 30 September 2012. Children (15 years old) with SCA attending Bugando were sequentially enrolled. A trained research assistant completed a Swahili questionnaire with the parent or guardian of each participant concerning demographic information, clinical features of disease, and treatments received.Among the 124 participants enrolled, the median age was 6 years (interquartile range [IQR] 4-8.5), and only 13 (10.5%) were3 years old. Almost all participants (97.6%) had a prior history of a vaso-occlusive episode, 83 (66.9%) had prior acute chest syndrome, and 21 (16.9%) had prior stroke. In the preceding 12 months, 120 (96.8%) had been hospitalized, and a vaso-occlusive episode was the most common reason for hospitalization (35.5%). Prescriptions for folic acid (92.7%) and malaria prophylaxis (84.7%) were common, but only one had received a pneumococcal vaccine, and none had received hydroxyurea or prophylactic penicillin.Children with SCA receiving care in Tanzania are diagnosed late, hospitalized frequently, and have severe complications. Opportunities exist to improve care through wider access to screening and diagnosis as well as better coordination of comprehensive care.

Parvovirus B19 (B19) can cause transient aplastic crisis and lead to acute severe anemia. This study investigated the relationship between B19 and anemia among children

Both anemia and sickle cell disease (SCD) are highly prevalent across sub-Saharan Africa, and limited resources exist to diagnose these conditions quickly and accurately. The development of simple, inexpensive, and accurate point-of-care (POC) assays represents an important advance for global hematology, one that could facilitate timely and life-saving medical interventions. In this prospective study, Robust Assays for Point-of-care Identification of Disease (RAPID), we simultaneously evaluated a POC immunoassay (Sickle SCAN™) to diagnose SCD and a first-generation POC color-based assay to detect anemia. Performed at Bugando Medical Center in Mwanza, Tanzania, RAPID tested 752 participants (age 1 day to 20 years) in four busy clinical locations. With minimally trained medical staff, the SCD POC assay diagnosed SCD with 98.1% sensitivity and 91.1% specificity. The hemoglobin POC assay had 83.2% sensitivity and 74.5% specificity for detection of severe anemia (Hb ≤ 7 g/dL). Interobserver agreement was excellent for both POC assays (r = 0.95–0.96). Results for the hemoglobin POC assay have informed the second-generation assay design to be more suitable for low-resource settings. RAPID provides practical feasibility data regarding two novel POC assays for the diagnosis of anemia and SCD in real-world field evaluations and documents the utility and potential impact of these POC assays for sub-Saharan Africa.

Background Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub-Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource-limited settings. Methodology This was a prospective cohort study. Newborns (aged 0–7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high-performance liquid chromatography. Clinical and laboratory follow-up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies. Results A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/β0-thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/β+ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had β+-thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3- and 6-month follow-up. Febrile episodes were more common for children with Hb FS at 3- and 6-month follow-up. Conclusion The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.

Introduction. Based on sparse historical data, Tanzania ranks fourth globally for the estimated number of annual births with sickle cell disease. Northwest Tanzania is projected to have an especially high burden of sickle cell disease, but no contemporary surveillance data exist to verify this projection. We designed a large prospective study to determine the prevalence of both sickle cell trait and sickle cell disease in northwest Tanzania. Additional objectives included an analysis of two known genetic modifiers of sickle cell disease [alpha thalassemia trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency], as well as genetic variants affecting fetal hemoglobin (HbF) expression and characterization of hemoglobin variants. Methods. The Tanzania Sickle Surveillance Study (TS3) is a prospective cross-sectional study to determine the prevalence of sickle cell trait and disease in an area projected to be at high risk. Dried blood spots (DBS) from all children born to HIV-infected mothers in the 9 regions across northwest Tanzania were collected by the HIV Early Infant Diagnosis (EID) program and transported to a central laboratory at Bugando Medical Centre, a teaching and consultancy hospital in Mwanza. DBS were tested by isoelectric focusing and scored as normal, trait, disease, or variant. Samples scored as disease or variant were retested for confirmation, and then frozen for subsequent genetic analysis. In the US, genomic DNA was extracted from each DBS, and sickle cell disease status was confirmed by PCR and TaqMan genotyping. All confirmed samples were then analyzed for alpha thalassemia trait (rightward -3.7 gene deletion) using quantitative real time PCR, and for G6PD deficiency using three real time PCR probes to distinguish A and B G6PD isoforms, to identify the G6PD A- variant, and to confirm the sex, respectively. Single nucleotide polymorphisms within 3 quantitative trait loci [BCL11A, the HBS1L-MYB intergenic polymorphism (HMIP) region, and the gamma-globin promoter XmnI site] that modify baseline HbF were analyzed using TaqMan genotyping. DBS with hemoglobin variants were investigated for the presence of common variants found in East Africa. Results. Between February 2017 and May 2018, a total of 232 IEF gels were completed by local staff in Tanzania. Among EID samples from children Conclusion. The prevalence of sickle cell trait and disease among infants in northwest Tanzania is very high, exceeding 20% trait and 1.2% disease. Regional prevalence data paired with region-specific crude birth rates predict 10,055 births annually in the northwest regions, more than doubling previous estimates. Concomitant alpha thalassemia trait and G6PD deficiency are frequently co-inherited and may affect the phenotype, as well as common genetic modifiers of HbF expression. Our detailed genetic analysis of a geographically representative surveillance cohort provides a foundation for future targeted screening and the introduction of hydroxyurea for treatment of sickle cell disease in northwest Tanzania. Disclosures Ware: Bristol Myers Squibb: Other: Research Drug Donation; Addmedica: Other: Research Drug Donation; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: DSMB.

Tanzania ranks third in Africa for the estimated number of annual births with sickle cell disease, but these estimates are based on sparse data from small studies reported over the past 50 years. A recently completed surveillance study from Uganda documented substantial variation in the prevalence of sickle cell trait and disease across the country. Tanzania lacks a national newborn screening program, and no contemporary multi-regional screening of infants has been undertaken. We designed and conducted a prospective study to determine the prevalence of sickle cell trait and disease by region and district in northwest Tanzania, where the prevalence of sickle cell is thought to be highest. The study used existing public health infrastructure while building local capacity for accurate diagnosis of sickle cell disease. Secondary objectives included characterization of hemoglobin variants and exploration of associations between sickle cell trait, sickle cell disease, malaria, and HIV. The Tanzania Sickle Surveillance Study (TS3) is a prospective cross-sectional study of HIV-exposed infants born in 9 regions across the Lake Zone of northwest Tanzania. In Tanzania, the HIV early infant diagnosis (EID) program collects dried blood spots (DBS) from all children born to HIV-infected mothers. DBS are transported to a central laboratory for prompt detection of HIV vertical transmission. In northwest Tanzania, the DBS are transported to Bugando Medical Centre, a teaching and consultancy hospital in Mwanza, where they are tested for HIV and then stored on-site, and thus available for further testing. Isoelectric focusing (IEF) equipment was donated to Bugando Medical Centre along with reagents and supplies. Two laboratory staff were trained by a board certified hematologist, and then attended a two day seminar by the IEF manufacturer. One pediatrician completed a 2-month observership at Cincinnati Children's Hospital. All DBS samples were tested by IEF using appropriate controls. Completed gels were scored independently by two Tanzanian staff members as normal, disease, trait, variant, or uninterpretable. DBS samples scored as disease or variant were repeated for confirmation and preserved for later genotyping. Regular Skype calls were convened with US-based collaborators to improve quality and interpretation. HIV test results were obtained from the local EID program. Between February 2017 and May 2018, 232 IEF gels were completed by the local staff. After children >24 months of age were excluded to obtain a more accurate newborn prevalence, the median age of children tested was 52 days (IQR 41-93 days), and a total of 17,278 unique DBS samples were scored. The quality of laboratory testing was extremely high with only 20 samples scored as uninterpretable and 54 with missing results, and the primary analysis was performed on the 17,204 remaining samples. The overall prevalence of sickle cell trait and disease in the entire cohort was 20.3% and 1.2%, respectively, with a 0.1% prevalence of hemoglobin variants. This corresponds to an allelic frequency of 0.114 for the sickle gene mutation and demonstrates perfect Hardy-Weinberg equilibrium. No HbC or other common beta-globin variants were identified. Geospatial mapping revealed some variation across regions, with sickle trait ranging from 16.6% to 22.5% and disease ranging from 0.5% to 1.5%. Analysis of individual districts with >100 samples revealed wider geographic variability, with sickle trait ranging from 15.2% to 27.8% and disease ranging from 0.0% to 4.3%. Co-morbidity between HIV and sickle cell disease was analyzed to compare it with the effect on mortality previously observed in Uganda. The prevalence of sickle cell disease was the same among HIV-infected and HIV-negative children (1.2%), suggesting no difference in mortality. The prevalence of sickle cell trait and disease among infants born in northwest Tanzania is very high, exceeding 20% trait and 1.2% disease. All regions in the Lake Zone are affected possibly due to lack of immigration to the area and similar environmental exposures. Targeted newborn screening can be started in high prevalence districts, using existing public health infrastructure with minimal start-up cost and training. Future work will evaluate the correlation between historical malaria prevalence and sickle cell prevalence, and identify hemoglobin variants. Disclosures Ware: Addmedica: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Agios: Other: advisory board; Global Blood Therapeutics: Other: advisory board; Biomedomics: Research Funding; Nova Laboratories: Consultancy.

Parasitic infectious agents in endemic African countries including Tanzania rarely occurs in isolation and co-infections within a single host in populations are norms rather than exceptions (Brooker et al., 2007; Mazigo et al., 2010a; Mboera et al., 2011). Coinfection refers to a situation in which an individual harbours two or more infections from different species simultaneously, where as mono-infection refers to a situation in which an individual harbours only one infection from a single species (Brooker et al., 2007). Several factors determines the wide geographical distributions of helminth and protozoan parasites and they include climate, environment, socio-economic status, human behaviour and host-specific factors such as genetics, host physiology, host immunological status and population dynamics (Mwangi et al., 2007).

BACKGROUND: Sickle cell disease (SCD) describes a group of inherited red blood cell disorders. People with SCD have abnormal haemoglobin (Hb), called Hb S. In all forms of SCD, at least one of the two abnormal genes causes a person's body to make Hb S. In countries with limited resources, diagnostic technique should be simple and easy to perform with high sensitivity and specificity. METHODS: This study compared the paperbased sickle cell test and sodium metabisulfite sickling test using Hb electrophoresis as a gold standard. It was a crosssectional hospitalbased study which was conducted from July to October 2017 involving a total of 140 blood samples of under 10 years children presumed to have SCD. Blood samples in ethylenediaminetetraacetic acid anticoagulantcontaining vacutainers were used for SCD diagnosis by using paperbased and sodium metabisulfite sickling tests then confirmed by Hb electrophoresis as the gold standard. RESULTS: Blood specimens were from individuals aged 4 years ranged from 2 to 9 years. Slightly majority of blood specimens belonged to males, 54.3% (76/140) while the majority was from inpatients, 82.9% (116/140). Paperbased sickle cell test identified 46/140 (32.9%) Hb AA, 81/140 (57.9%) Hb, and 6/140 (4.3%) Hb AS. Sickling test identified 50/140 (35.7%) Hb AA and 87/140 (62.1%) Hb SS. Hb electrophoresis identified 50/140 (35.7%) Hb AA, 83/140 (59.3%) Hb SS, and 7/140 (5%) Hb AS. The paperbased sickle cell test had a sensitivity of 97.8% and specificity of 96.7% while the sickling test had the sensitivity of 96.7% and specificity of 100%. CONCLUSION: Paperbased sickle cell test was able to detect sickle cell carriers, Hb AS and shown high sensitivity and specificity; therefore, it can be used as a substitute for sickling test in countries with limited resource. However, paperbased sickle test is suitable for adults' population.

To improve control measures against malaria, Tanzania has increased the distribution of free and subsidized insecticide-treated mosquito nets (ITNs) to pregnant women. However, data on knowledge, attitudes and practices of these women regarding malaria are scarce. This study was carried out to describe knowledge, attitudes and practices towards malaria, mosquito net ownership and use among women seeking antenatal care at Iringa Regional Hospital in south-western Tanzania . The study involved women attending the antenatal clinic of the hospital. A pre-tested structured questionnaire was applied to collect information on socio-demographic characteristics, mosquito net ownership and use, as well as knowledge, attitudes and practices about malaria and its control. Among the 222 pregnant women included, 173 (78%, 95%CI, 72-84.2) owned a mosquito net, and 150 (68%, 95%CI, 61-75) reported to sleep always under a mosquito net. The use of mosquito nets was mentioned by 142 (64%, 95%CI, 56.2-72). Of the 46 women who did not own a mosquito net, seven (15.2%) reported cost as the main obstacle for owning one. About 53% (95%CI, 44-62) preferred to use mosquito nets they bought rather than the one provided for free. Several factors such as gravidity, fearing of getting malaria, knowledge on the cause, marital status, and ways used to prevent malaria were significantly associated with mosquito net ownership (all P P

Early diagnosis and prompt treatment is the recommended management for febrile illness among underfives. However, improper home management may be the cause of delay in seeking professional health care. This cross-sectional study was conducted at the outpatient department of Buzuruga Health Centre in Mwanza, Tanzania and involved 372 children5 years of age. Socio-demographic data of caregivers and children, type and source of treatment, and duration of fever were recorded. A total of 283 (76.1%) febrile underfives had received different types of treatment at home, before presenting at the hospital. The majority received antipyretics (204; 72.1%), and only a few (31; 10.9%) received antimalarials. The major sources of drugs were local drug stores (270; 94.7%). Duration of fever1 day (OR = 2.69; 95% CI: 1.95-3.70; P0.001), low grade fever (OR = 4.37, 95% CI: 2.60-7.35; P0.001) and fever accompanied with other major complaints (OR = 1.14, 95% CI: 1.05 - 1.23; P = 0.002) were significantly associated with prompt home medication before presenting to the health centre. In logistic regression analysis, duration of fever, low-grade fever and the presence of other symptoms remained significant predictors to receive antimalarial and or antipyretic drugs. In conclusion, home treatments with antipyretics and antimalarials in preschool children are common in Mwanza. Management of fevers may be improved by educating caregivers on community standard case definition of malaria while emphasizing the importance of early seeking of health facility services.

In Plasmodium falciparum malaria and intestinal helminth infections are among the most common infections in the tropics and they share the same spatial distribution. The objective of this study was to explore the association between infections with intestinal helminths and P. falciparum infection as single helminth infections or co-infections among school children. A cross-sectional study was conducted among 400 school children in Nyamtongo, Sengerema District in Tanzania. The study involved examination of single stool and finger prick blood samples for intestinal helminths and malaria parasites. A Kato-Katz technique was employed to screen for intestinal helminths and Giemsa stained thin and thick blood smears were used to screen for malaria parasites. The results of logistic regression model adjusted for age and sex indicated no association between P. falciparum and S. mansoni (OR= 0.749, 95%CI 0.418-1.344), P. falciparum and hookworm (OR= 0.885, 95%CI 0.489-1.605) and P. falciparum and co-infection of S. mansoni and hookworm (OR=0.859, 95%CI 0.422-1.745). Using multinomial regression model adjusted for age and sex, no association was observed between P. falciparum with Schistosoma mansoni [Ratio of Relative Risk (RRR) = 0.651, 95% Confidence Interval (CI) 0.331-1.363] and hookworm (RRR=0712, CI 0.280-1.765). Similarly, no association was observed between co-infections of S. mansoni + hookworm (RRR=0.635, CI 0.268-1.504) with P. falciparum infection. Co-infections of S. mansoni, hookworm and P. falciparum among school children is common in the Nyamatongo ward, Sengerema District. We recommend prospective longitudinal studies to elucidate the interactions of malaria and helminths and its health impact in risk groups.