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.

BackgroundSub-Saharan Africa has the highest rates of child mortality worldwide. Little is known about post-hospital outcomes after an index hospitalization for older children. We determined 12-month post-hospital mortality rate and identified factors associated with higher mortality.MethodsIn this prospective cohort study, we enrolled children 2–12 years of age admitted to the pediatric wards of two public hospitals in northwestern Tanzania. Participants or proxies were contacted at 3, 6 and 12 months post-hospitalization. The primary outcome measured was mortality. Factors associated with mortality were determined using Cox regression analysis.ResultsA total of 506 participants were enrolled. In-hospital mortality rate was 7.7% (39/506). Of the 467 participants discharged, the post-hospital mortality rate was 10.1% (47/467). Sickle cell disease (Hazard Ratio (HR) 3.32, 95% CI 1.44–7.68), severe malnutrition (HR 3.19, 95% CI 1.18–8.57), neurologic diseases (HR 3.51, 95% CI 1.35–9.11), heart disease (HR 7.11, 95% CI, 2.89–17.51), cancer (HR 11.79, 95% CI 4.95–28.03), and septic shock (HR 4.64, 95% CI 1.42–15.08) had higher association with mortality compared to other diagnoses. The risk factors significantly associated with mortality included older age (HR 1.01, 95% CI 1.00–1.08), lower hemoglobin level (HR 0.83, 95% CI 0.76–0.90), lower Glasgow Coma Scale (HR 0.66, 95% CI 0.59–0.74), history of decreased urine output (HR 2.87, 95% CI 1.49–5.53), higher respiratory rate (HR 1.02, 95% CI 1.00–1.03), estimated glomerular filtration rate less than 60 ml/min/1.73m2 (binary) (HR 1.84, 95% CI 1.10–3.10), and lower oxygen saturation (HR 0.96, 95% CI 0.92–0.99).ConclusionsPost-hospital mortality is disturbingly high among children 2–12 years of age in Tanzania. Post-hospital interventions are urgently needed especially for older children with chronic illnesses.

Background There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Methods and findings Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1—Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2—“Low” Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3—“Medium” Watch), 18.0% (n = 566) started a carbapenem (Group 4—“High” Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Conclusion Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. Trial registration ClinicalTrials.gov, (NCT03721302).

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.

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/1.73m 2 were 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.

Background Little is known on how the interaction between Sickle Cell Disease (SCD) and renal insults caused by other coexisting conditions in Sub Saharan Africa such as urinary schistosomiasis, malnutrition and HIV affect the prevalence of renal dysfunction in children with SCD. Objectives To determine the prevalence and factors associated with renal dysfunction among children with SCD aged 6 months to 12 years attended at a tertiary hospital in Northwestern Tanzania. Methods A cross sectional hospital-based study with a short follow up component of 3 months for 153 children with SCD was done to document demographics, clinical characteristics and features of renal dysfunction including urine dipstick albuminuria (>20mg/l) and eGFR (<60ml/ml/min/1.73m 2 ). Other potential renal insults such as HIV infection and Schistosomiasis were also evaluated. Results At enrollment, 48/153(31.37%) children had renal dysfunction declining to 31(20.3%) at 3 months follow up. Acute chest syndrome (OR 3.04, 95% CI [1.08–8.96], p = 0.044), severe anemia (OR 0.44, 95% CI [0.26–0.76],p = 0.003), urinary schistosomiasis (OR 7.43, 95% CI [2.10–26.32] p<0.002) and acute malnutrition (OR 4.92, 95% CI [1.29–18.84], p = 0.020). were associated with renal dysfunction. Conclusion Where prevalent, urinary schistosomiasis and acute malnutrition increase the risk for renal dysfunction in children with SCD. We recommend albuminuria routine screening in children with SCD especially those presenting with acute chest syndrome, severe anemia and features of acute malnutrition for early detection of renal dysfunction among children with SCD.

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IntroductionThe provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward.MethodsContact tracing was conducted following the diagnosis of SARS-CoV-2 in a mother lodging in the KMC ward. All mother-newborn dyads in the KMC and healthcare workers (HCW) were tested for SARS-CoV-2 within 24–72 h of diagnosing the index case. Nasopharyngeal swab samples were obtained and tested from contacts, with a nucleic acid amplification test (NAAT) assay. Next-generation sequencing was done on positive samples. The secondary attack rate (SAR) was calculated assuming that the mother who presented with symptoms was the source of infection.ResultsTwelve (70.6%) of 17 mothers and 8 (42.1%) of 19 neonates who were in the KMC ward with the index case were found to be positive with SARS-CoV-2. Seven (87.5%) of the 8 neonates who tested positive had mothers who also tested positive. Seventy-five percent (9/12) of the mothers and 62.5% (5/8) of the neonates who tested positive were asymptomatic. Eight (27.6%) of 29 HCW were found to be positive and were all asymptomatic. One neonate died from Acinetobacter baumannii sepsis, and his post-mortem lung histopathology showed features compatible with SARS-CoV-2 pneumonia. The sequencing of 13 specimens, which included 1 mother-newborn dyad, indicated clustering to the same phylogenetic lineage with identical mutations. In assessing for factors contributing to this outbreak, it was found that spaces between beds were less than 1 m and mothers had their meals around the same table at the same time.ConclusionWe report on a nosocomial outbreak of SARS-CoV-2 in a KMC ward, affecting a high number of mothers and neonates, and to a lesser extent HCWs. Although it is difficult to point to the index case as the source of this outbreak, as asymptomatic individuals can spread infection, the inadequate adherence to non-pharmaceutical interventions was assessed to have contributed to the spread of infection. This highlights the need for awareness and adherence to mitigation strategies to avoid SARS-CoV-2 outbreaks.