Where will pediatric praziquantel be needed in Tanzania? Geographical variation in prevalence, and risk factors of Schistosoma mansoni in pre-school aged children in southern and north-western Tanzania.

Background: Pediatric schistosomiasis has been recognized as a public health concern in schistosomiasis endemic areas of sub-Saharan Africa, including Tanzania. However, there is limited epidemiological information relating to pediatric schistosomiasis in Tanzania. Therefore, this current focused on assessing the geographical prevalence of S. mansoni infection and its associated risk factors in pre-school children (PreSAC) in southern and north-western Tanzania. Methods: A total of 1585 PreSAC aged 1-6 years were enrolled in a cross-sectional study. A single urine and stool sample were obtained from each child and processed using point-of-care circulating cathodic (POC-CCA) antigen and Kato Katz (K-K) technique. The overall prevalence of S. mansoni infection based on K-K technique and POC-CCA test were 18.6% (95%CI:16.7-20.6) and 28.3% (95%CI:26.1-30.6), respectively. The overall geometrical mean eggs per gram of faeces was 110.38epg (95% CI:97.3-125.3). The age group 4-6 years had the highest prevalence (P < 0.01) of S. mansoni in both diagnostic tests and infection intensity (t = -2.8398, P < 0.005) using K-K technique. On multivariable analysis, only Ukerewe district was associated with S. mansoni infection based on K-K technique (aOR = 2.8 (95%CI:2.1-3.9), P < 0.001). Based on POC-CCA test, age group (4-6 years), aOR = 1.7, 95%CI:1.3-2.2, P < 0.001), Nyasa (aOR = 6.2, 95%CI:3.0-12.5, P < 0.001), Geita (aOR = 4.2, 95%CI:2.1-8.2, P < 0.001) and Ukerewe (aOR = 28.9, 95%CI:15.0-55.8, P < 0.001) districts remained independently associated with S. mansoni infection. Conclusion: Schistosoma mansoni is a public health concern among PreSAC in the study districts and its prevalence varies from one geographical setting to another. These findings strongly support the need to include pre-school aged in preventive chemotherapy.

Hydroxyurea pharmacokinetics and precision dosing in low-resource settings.

Introduction: Hydroxyurea is effective disease-modifying treatment for sickle cell anemia (SCA). Escalation to maximum tolerated dose (MTD) achieves superior benefits without additional toxicities, but requires dose adjustments with serial monitoring. Pharmacokinetic (PK)-guided dosing can predict a personalized optimal dose, which approximates MTD and requires fewer clinical visits, laboratory assessments, and dose adjustments. However, PK-guided dosing requires complex analytical techniques unavailable in low-resource settings. Simplified hydroxyurea PK analysis could optimize dosing and increase access to treatment. Methods: Concentrated stock solutions of reagents for chemical detection of serum hydroxyurea using HPLC were prepared and stored at -80C. On the day of analysis, hydroxyurea was serially diluted in human serum, then spiked with N-methylurea as an internal standard and analyzed using two commercial HPLC machines: 1) standard benchtop Agilent with 449 nm detector and 5 micron C18 column; and 2) portable PolyLC with 415 nm detector and 3.5 micron C18 column. After validation in the United States, the portable HPLC and chemicals were transported to Tanzania. Results: A calibration curve using hydroxyurea 2-fold dilutions ranging from 0 to 1000 µM was plotted against the hydroxyurea:N-methylurea ratio. In the United States, both HPLC systems yielded calibration curves with R2 > 0.99. Hydroxyurea prepared at known concentrations confirmed accuracy and precision within 10%-20% of the actual values. Both HPLC systems measured hydroxyurea with <10% variance from the prepared concentrations, and paired analysis of samples on both machines documented <15% variance. Serial measurements of 300 and 100 µM concentrations using the PolyLC system were precise with 2.5% coefficient of variance. After transport to Tanzania with setup and training, the modified PolyLC HPLC system produced similar calibration curves with R2 > 0.99. Conclusion: Increasing access to hydroxyurea for people with SCA requires an approach that eases financial and logistical barriers while optimizing safety and benefits, especially in low-resource settings. We successfully modified a portable HPLC instrument to quantify hydroxyurea, validated its precision and accuracy, and confirmed capacity building and knowledge transfer to Tanzania. HPLC measurement of serum hydroxyurea is now feasible in low-resource settings using available laboratory infrastructure. PK-guided dosing of hydroxyurea will be tested prospectively to achieve optimal treatment responses.

Hydroxyurea with dose escalation for primary stroke risk reduction in children with sickle cell anaemia in Tanzania (SPHERE): an open-label, phase 2 trial.

BACKGROUND: Transcranial Doppler screening with chronic transfusions reduces stroke risk in children with sickle cell anaemia but is not feasible in low-resource settings. Hydroxyurea is an alternative treatment to decrease stroke risk. We aimed to estimate stroke risk in children with sickle cell anaemia in Tanzania and to determine the efficacy of hydroxyurea to decrease and prevent stroke. METHODS: We did an open-label, phase 2 trial (SPHERE) at Bugando Medical Centre, Mwanza, Tanzania. Children aged 2-16 years with a diagnosis of sickle cell anaemia confirmed by haemoglobin electrophoresis were eligible for enrolment. Participants had transcranial Doppler ultrasound screening by a local examiner. Participants with elevated Doppler velocities, either conditional (170-199 cm/s) or abnormal (≥200 cm/s), received oral hydroxyurea starting at 20 mg/kg once daily and escalated every 8 weeks by 5 mg/kg per day to the maximum tolerated dose. Participants with normal Doppler velocities (<170 cm/s) received usual care from the sickle cell anaemia clinic and were rescreened after 12 months to determine whether they qualified for treatment on trial. The primary endpoint was change in transcranial Doppler velocity from the baseline visit to after 12 months of hydroxyurea treatment, analysed in all patients who had paired baseline and follow-up measurements collected after 12 months of treatment. Safety was analysed in the per-protocol population (all participants who received study treatment). This study is registered with ClinicalTrials.gov, NCT03948867. FINDINGS: Between April 24, 2019, and April 9, 2020, 202 children were enrolled and had transcranial Doppler screening. Sickle cell anaemia was confirmed by DNA-based testing in 196 participants (mean age 6·8 years [SD 3·5], 103 [53%] were female, and 93 [47%] were male). At the baseline screening, 47 (24%) of 196 participants had elevated transcranial Doppler velocities (43 [22%] conditional, four [2%] abnormal); 45 initiated hydroxyurea at a mean dose of 20·2 mg/kg per day (SD 1·4) with escalation to a mean dose of 27·4 mg/kg per day (5·1) after 12 months. Treatment response was analysed after 12 months (± 1 month; median 11 months, IQR 11-12) and 24 months (±3 months; median 22 months, 22-22). Transcranial Doppler velocities decreased to a mean of 149 cm/s (SD 27) compared with 182 cm/s (12) at baseline, which was significantly lower than baseline (p<0·0001), with an average decline of 35 cm/s (SD 23) after 12 months of treatment in 42 participants with paired results available at baseline and 12 months. No clinical strokes occurred, and 35 (83%) of 42 participants reverted to normal transcranial Doppler velocities. Clinical adverse events were mild, and dose-limiting toxicities were uncommon. The most common grade 3 adverse events were malaria (12 [29%] episodes in 45 patients) and sepsis (13 [32%] episodes). There were three serious adverse events, none of which were treatment-related, and no treatment-related deaths occurred. INTERPRETATION: Children with sickle cell anaemia in Tanzania have a high baseline stroke risk. Hydroxyurea at the maximum tolerated dose significantly lowers transcranial Doppler velocities and reduces primary stroke risk. Transcranial Doppler screening plus hydroxyurea at the maximum tolerated dose is an effective stroke prevention strategy, supporting wider hydroxyurea access for patients with sickle cell anaemia across sub-Saharan Africa. FUNDING: American Society of Hematology, National Institutes of Health, Cincinnati Children's Research Foundation.

Outcomes of Hydroxyurea Accessed via Various Means and Barriers Affecting Its Usage Among Children with Sickle Cell Anaemia in North-Western Tanzania.

Purpose: 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.

Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa.

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.

The Consortium on Newborn Screening in Africa for sickle cell disease: study rationale and methodology.

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.

Association between antenatal corticosteroids use and perinatal mortality among preterm singletons and twins in Mwanza, Tanzania: an observational study.

OBJECTIVES: To examine the association between antenatal corticosteroids (ACS) use and perinatal mortality in singletons and twins delivered before 35 weeks of gestation. DESIGN: Secondary analysis of data from an observational prospective chart review study that investigated if exposure to ACS was associated with lower rates of perinatal mortality in preterm infants. SETTING: This study was conducted in four hospitals located in Mwanza region, Tanzania. PARTICIPANTS: The study population included all preterm singletons and twins delivered at these hospitals between 24 weeks 0 days and 34 weeks 6 days of gestation from July 2019 to February 2020. OUTCOME MEASURES: The primary outcome was perinatal mortality; the secondary outcome was respiratory distress syndrome (RDS). RESULTS: The study included 844 singletons and 210 twin infants. Three hundred and fourteen singletons (37.2%) and 52 twins (24.8%) were exposed to at least one dose of ACS. Adjusted multivariate analyses revealed that among singletons' exposure to ACS was significantly associated with a lower likelihood of perinatal mortality, adjusted relative risk (aRR) 0.30 (95% CI 0.22 to 0.40) and RDS, aRR 0.92 (95% CI 0.87 to 0.97). In twin infants, exposure to ACS was associated with a reduced risk of RDS only, aRR 0.87 (95% CI 0.78 to 0.98). CONCLUSION: The use of ACS between 24 weeks 0 days and 34 weeks 6 days of gestation in both singletons and twins in low-resource settings is associated with positive infant outcomes. No adverse effects were noted. Further research that examines the benefits of ACS for twin infants is needed.

Enablers and barriers to newborn screening for sickle cell disease in Africa: results from a qualitative study involving programmes in six countries.

OBJECTIVES: Given the fundamental role of newborn bloodspot screening (NBS) to enable prompt diagnosis and optimal clinical management of individuals with sickle cell disease (SCD), we sought to systematically assess enablers and barriers to implementation of NBS programmes for SCD in Africa using established qualitative research methods. SETTING: Childbirth centres and NBS laboratories from six countries in East, West and Southern Africa. PARTICIPANTS: Eight programme leaders involved with establishing and operating NBS programmes for SCD in Angola, Democratic Republic of Congo, Ghana, Liberia, Nigeria and Tanzania. PRIMARY AND SECONDARY OUTCOME MEASURES: Data obtained through a structured, phased interview approach were analysed using a combination of inductive and deductive codes and used to determine primary themes related to the implementation and sustainability of SCD NBS programmes. RESULTS: Four primary themes emerged from the analysis relating to governance (eg, pragmatic considerations when deploying overcommitted clinical staff to perform NBS), technical (eg, design and execution of operational processes), cultural (eg, variability of knowledge and perceptions of community-based staff) and financial (eg, issues that can arise when external funding may effectively preclude government inputs) aspects. Key learnings included perceived factors that contribute to long-term NBS programme sustainability. CONCLUSIONS: The establishment of enduring NBS programmes is a proven approach to improving the health of populations with SCD. Organising such programmes in Africa is feasible, but initial implementation does not assure sustainability. Our analysis suggests that future programmes should prioritise government partner participation and funding from the earliest stages of programme development.

Prevalence and outcome of HIV infected children admitted in a tertiary hospital in Northern Tanzania.

BACKGROUND: Provider Initiated Testing and Counseling (PITC) among hospitalized children have shown to increase the probability of identifying HIV-infected children and hence be able to link them to HIV care. We aimed at determining the prevalence, clinical characteristics and outcome of HIV-infected children admitted at Bugando Medical Centre (BMC) after active provision of PITC services. METHODS: A cross-sectional study with follow up at three months post enrollment was done. Children with unknown HIV status were tested for HIV infection as per 2012 Tanzanian algorithm. Questionnaires were used to collect demographic, clinical and follow up information. Data was statistically analyzed in STATA v13. RESULTS: A total of 525 children were enrolled in the study. Median [IQR] age was 28 [15-54] months. Males consisted of 60.2% of all the participants. HIV prevalence was 9.3% (49/525). Thirty-three (67.3%) of HIV-infected children were newly diagnosed at enrolment. Thirty-nine (79.6%) of all HIV-infected patients had WHO HIV/AIDS clinical stage four disease, 10 (20.4%) had WHO clinical stage three and none qualified in stage one or two. About 84% (41/49) of HIV infected children had severe immunodeficiency at the time of the study. Factors that were independently associated with HIV infection were, cough (OR 2.40 [1.08-5.31], p = 0.031), oral thrush (OR 20.06[8.29-48.52], p < 0.001), generalized lymphadenopathy (OR 5.61 [1.06-29.56], p = 0.042), severe acute malnutrition (OR 6.78 [2.28-20.12], p = 0.001), severe stunting (OR 9.09[2.80-29.53], p = 0.034) and death of one or both parents (OR 3.62 [1.10-11.87], p = 0.034). The overall mortality (in-hospital and post-hospital) was 38.8% among HIV-infected children compared with 14.0% in HIV-uninfected children. Within three months period after discharge from the hospital, 71.4% (25/35) of discharged HIV-infected children reported to have attended HIV clinic at least once and 60.0% (21/35) were on antiretroviral medications. CONCLUSION: PITC to all admitted children identified significant number of HIV-infected children. Mortality among HIV-infected children is high compared to HIV-uninfected. At the time of follow up about 30% of discharged HIV-infected children did not attend to any HIV care and treatment clinics. Therefore effective efforts are needed to guarantee early diagnosis and linkage to HIV care so as to reduce morbidity and mortality among these children.

Health Related Quality of Life among Children with Sickle Cell Anaemia in Northwestern Tanzania.

Background: Sickle cell anaemia (SCA) is a serious, multisystem, genetic disorder affecting millions of children worldwide. The disease causes numerous complications that interfere with the health-related quality of life (HRQoL) of these children including an impact on educational, physical and psychosocial development. Few studies have described the clinical spectrum and quality of life of children with SCA living in a low-resource area. Objectives: This study aimed to determine the clinical spectrum and HRQoL among children living with sickle cell anaemia (SCA) in northwest Tanzania. Methods: This hospital-based cross-sectional study took place at Tertiary and teaching hospital, Bugando Medical Centre, Mwanza Tanzania. The study enrolled children ages 2 - 12 years old with SCA attending the Bugando Medical Centre sickle cell clinic. Health related quality of life was measured using the Pediatric Quality of Life, Brief Generic Core Scale after translating from English into a Swahili version. Important SCA complications were assessed using a structured questionnaire. Results: From October 2016 to March 2017, 204 children were enrolled. Participants presented at a median age of 6 years [IQR 4 - 9]. Among children with SCA the most common clinical signs at the time of enrolment were pale in 69.6% (142/204), jaundice in 65.9% (134/204), oxygen saturation < 90% in 25% (51/204) and splenomegaly in 19% (39/204). Severe anaemia was observed in 30.9% (63/204). A majority reported vaso-occlusive crisis (166/204, 81.4%), and very few had experienced a prior stroke (5/204, 2.5%). Using a modified Likert scale, a total of 41/204 (20.1%) children had poor HRQoL indicated by low scores on PedsQL™ and 163/204 (79.9%) children had high scores, indicating good HRQoL. On multivariate analysis, age ≥ 5 years (p-value < 0.001), haemoglobin < 7 g/dl (p-value = 0.001) and >3 hospitalizations per year (p-value = 0.008) were associated with poor HRQoL. Conclusion: SCA complications, negatively impact the HRQoL of children living with the disease. Severe anaemia, older age and frequent hospitalizations were highly associated with poor HRQoL. Comprehensive management is needed beginning at diagnosis to identify these children early and provide them with adequate support.

Linkage to Care Intervention to Improve Post-Hospital Outcomes Among Children with Sickle Cell Disease in Tanzania: A Pilot Study.

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).

Surveillance for sickle cell disease, United Republic of Tanzania.

OBJECTIVE: 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. METHODS: 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. FINDINGS: 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 A- deficiency in 19.2% (14/73) of males. CONCLUSION: Our 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.

Extremely high birth prevalence of sickle cell disease in rural Tanzania.

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.

Empowering newborn screening programs in African countries through establishment of an international collaborative effort.

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.

Prevalence and intensity of Schistosoma mansoni infection in pediatric populations on antiretroviral therapy in north-western Tanzania: a cross-sectional study.

BACKGROUND: In areas where HIV and intestinal schistosomiasis are highly endemic, co-infections of the two diseases in a single human host are frequent. Evidence in adult populations indicates that HIV and intestinal schistosomiasis are associated with negative health impacts. However, the topic of HIV and schistosomiasis in paediatric populations has received little attention. The present study determined the prevalence and intensity of Schistosoma mansoni infection in a paediatric population on antiretroviral therapy (ART) in north-western Tanzania. DESIGN, SETTINGS AND PARTICIPANTS: A cross-sectional study was conducted among HIV-infected children aged 1-16 years on ART attending a Care and Treatment Clinic at Ukerewe Designated District Hospital, north-western Tanzania. MAIN OUTCOME MEASURES: Single stool and urine samples were collected and screened for S. mansoni eggs and circulating cathodic antigen (CCA), using the Kato-Katz (KK) technique and point-of-care CCA (POC-CCA) rapid urine test, respectively. RESULTS: A total of 134 children with a median age of 10 years (IQR 7-12 years) participated in the study. Of these, 44.8% (60/134) and 55.2% (74/134) were female and male, respectively. The overall prevalence of S. mansoni based on the KK technique and POC-CCA rapid test were 10.7% (95% CI 5.9% to 18.4%) and 33.8% (95% CI 26.2% to 42.4%), respectively. The overall geometrical mean eggs per gram of faeces was 293.9 GM-epg (95% CI 123.3 to 700.9). A small proportion of the children had moderate (4.9%, 5/103) and heavy (3.8%, 4/103) intensity of infection. CONCLUSION: Paediatric populations on ART are co-infected with S. mansoni infection. Screening and treatment of intestinal schistosomiasis at initiation of ART is recommended to reduce the risk of developing hepatosplenic disease, schistosomiasis-related immune reconstitution inflammatory syndrome and the possible adverse effect of schistosomiasis on outcome of ART.

Very severe anemia and one year mortality outcome after hospitalization in Tanzanian children: A prospective cohort study.

BACKGROUND: Africa has the highest rates of child mortality. Little is known about outcomes after hospitalization for children with very severe anemia. OBJECTIVE: To determine one year mortality and predictors of mortality in Tanzanian children hospitalized with very severe anemia. METHODS: We 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. RESULTS: Of 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). CONCLUSIONS: Children 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.

Prevalence and factors associated with renal dysfunction in children admitted to two hospitals in northwestern Tanzania.

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 < 60 ml/min/1.73m2were considered to have RD. Data analysis was done using STATA version 13 and considered significant when p-value was < 0.05. RESULTS: A total of 513 children were enrolled, of which 297 (57.9%) were males. Median age of children with and without RD was 34 months (27-60) and 46.5 (29-72) respectively. Prevalence of RD was 16.2%. Factors associated with RD were herbal medication use (p = 0.007), history of sore throat or skin infection (p = 0.024), sickle cell disease (SCD) (p = 0.006), dehydration (p = 0.001), malaria (p = 0.01) and proteinuria (p = < 0.001). CONCLUSIONS: High prevalence of RD was observed among children admitted to referral hospitals in Mwanza. Screening for RD should be performed on admitted children, particularly those with history of herbal medication use, sore throat/skin infection, SCD, dehydration and malaria. Where creatinine measurement is not possible, screening for proteinuria is a reasonable alternative.

Simultaneous point-of-care detection of anemia and sickle cell disease in Tanzania: the RAPID study.

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.