Transcranial Doppler ultrasound velocities in a population of unstudied African children with sickle cell anemia.

The greatest burden of sickle cell anemia (SCA) globally occurs in sub-Saharan Africa, where significant morbidity and mortality occur secondary to SCA-induced vasculopathy and stroke. Transcranial Doppler ultrasound (TCD) can grade the severity of vasculopathy, with disease modifying therapy resulting in stroke reduction in high-risk children. However, TCD utilization for vasculopathy detection in African children with SCA remains understudied. The objective was to perform a prospective, observational study of TCD findings in a cohort of children with SCA from the Democratic Republic of the Congo, Zambia, and Malawi. A total of 770 children aged 2-17 years without prior stroke underwent screening TCD. A study was scored as low risk when the time-averaged maximum of the mean (TAMMX) in the middle cerebral artery or terminal internal carotid artery was <170 cm/s but >50 cm/s, conditional risk when 170-200 cm/s, and high risk when >200 cm/s. Low-risk studies were identified in 604 children (78%), conditional risk in 129 children (17%), and high risk in three children (0.4%). Additionally, 34 (4%) were scored as having an unknown risk study (TAMMX <50 cm/s). Over the course of 15 months of follow-up, 17 children (2.2%) developed new neurologic symptoms (six with low-risk studies, seven with conditional risk, and four with unknown risk). African children with SCA in this cohort had a low rate of high-risk TCD screening results, even in those who developed new neurologic symptoms. Stroke in this population may be multifactorial with vasculopathy representing only one determinant. The development of a sensitive stroke prediction bundle incorporating relevant elements may help to guide preventative therapies in high-risk children.

Point-of-care Ultrasound to Assess Hemodynamic Contributors to Acute Kidney Injury in Pediatric Patients With Cerebral Malaria: A Pilot Study.

BACKGROUND: Acute kidney injury is common in severe malaria and is independently associated with mortality. The pathogenesis of acute kidney injury (AKI) in severe malaria remains incompletely understood. Ultrasound-based tools such as point-of-care ultrasound (POCUS), ultrasound cardiac output monitors (USCOMs) and renal arterial resistive index (RRI) can be used to detect hemodynamic and renal blood flow abnormalities contributing to AKI in malaria. METHODS: We conducted a prospective study of Malawian children with cerebral malaria to determine the feasibility of using POCUS and USCOM to characterize hemodynamic contributors to severe AKI (Kidney Disease: Improving Global Outcomes stage 2 or 3). The primary outcome was feasibility (completion rate of study procedures). We also assessed for differences in POCUS and hemodynamic variables for patients with or without severe AKI. RESULTS: We enrolled 27 patients who had admission cardiac and renal ultrasounds and USCOM. Completion rates were high for cardiac (96%), renal (100%) and USCOM studies (96%). Severe AKI occurred in 13 of 27 patients (48%). No patients had ventricular dysfunction. Only 1 patient in the severe AKI group was determined to be hypovolemic ( P = 0.64). No significant differences in USCOM, RRI or venous congestion parameters were detected among patients with and without severe AKI. Mortality was 11% (3/27) with the 3 deaths occurring in the severe AKI group ( P = 0.056). CONCLUSIONS: Ultrasound-based cardiac, hemodynamic and renal blood flow measurements appear to be feasible in pediatric patients with cerebral malaria. We were unable to detect hemodynamic or renal blood flow abnormalities contributing to severe AKI in cerebral malaria. Larger studies are needed to corroborate these findings.

Transcranial doppler velocities in a large healthy population of African children.

Background and purpose: Transcranial doppler ultrasound (TCD) is a tool that diagnoses and monitors pathophysiological changes to the cerebrovasculature. As cerebral blood flow velocities (CBFVs) increase throughout childhood, interpretation of TCD examinations in pediatrics requires comparison to age matched normative data. Large cohorts of healthy children have not been examined to develop these reference values in any population. There is a complete absence of normative values in African children where, due to lack of alternate neuroimaging techniques, utilization of TCD is rapidly emerging. Materials and methods: A prospective study of 710 healthy African children 3 months-15 years was performed. Demographics, vital signs, and hemoglobin values were recorded. Participants underwent a complete, non-imaging TCD examination. Systolic (Vs), diastolic (Vd), and mean (Vm) flow velocities and pulsatility index (PI) were calculated by the instrument for each measurement. Results: Vs, Vd, and Vm increased through early childhood in all vessels, with the highest CBFVs identified in children 5-5.9 years. There were few significant gender differences in CBFVs in any vessels in any age group. No correlations between blood pressure or hemoglobin and CBFVs were identified. Children in the youngest age groups had CBFVs similar to those previously published, whereas nearly every vessel in children ≥3 years had significantly lower Vs, Vd, and Vm. Conclusions: For the first time, reference TCD values for African children are established. Utilization of these CBFVs in the interpretation of TCD examinations in this population will improve the overall accuracy of TCD as a clinical tool on the continent.

Delayed presentation to hospital care is associated with sequelae but not mortality in children with cerebral malaria in Malawi.

BACKGROUND: Cerebral malaria is still a major cause of death in children in sub-Saharan Africa. Among survivors, debilitating neurological sequelae can leave children with permanent cognitive impairments and societal stigma, resulting in taxing repercussions for their families. This study investigated the effect of delay in presentation to medical care on outcome in children with cerebral malaria in Malawi. METHODS: This retrospective study included participants enrolled in a longstanding study of cerebral malaria between 2001 and 2021 and considered coma duration prior to arrival at hospital (with or without anti-malarial treatment), HIV status, blood lactate levels at admission and age as factors that could affect clinical outcome. Outcomes were categorized as full recovery, sequelae at the time of discharge, or death. A multinomial regression was fit and run controlling for coma duration, HIV status, lactate levels and age, to determine the association between each explanatory variable and outcome. RESULTS: A total of 1663 children with cerebral malaria, aged 6 months to 14 years were included. Longer coma duration (in hours) was associated with greater odds of developing sequelae (OR = 1.023, 95% CI 1.007-1.039, p = 0.006) but not death (OR = 1.00, 95% CI 0.986-1.015, p = 0.961). Younger age (in months) was also correlated with higher rates of sequelae, (OR = 0.990, 95% CI 0.983-0.997, p = 0.004) but not with increased mortality (OR = 0.998, 95% CI 0.993-1.003, p = 0.335). Blood lactate levels on admission were correlated with mortality (OR = 1.125, 95% CI 1.090-1.161, p < 0.001) but not associated with increased rates of sequelae (OR = 1.016, 95% CI 0.973-1.060, p = 0.475). Positive HIV status and treatment with an anti-malarial (artemisinin or non-artemisinin-based) prior to arrival at the hospital were not significantly associated with either adverse outcome. CONCLUSIONS: In Malawian children with cerebral malaria, higher rates of sequelae were significantly associated with extended coma duration prior to admission and younger age. Mortality rates were correlated with increased lactate levels on admission. The differential effects of variables on clinical outcomes suggest that there may be different pathogenic pathways leading to sequelae and death. Actions taken by parents and health care professionals are critical in defining when patients arrive at hospital and determining their ultimate outcome.

Transcranial Doppler Ultrasonographic Evaluation of Cerebrovascular Abnormalities in Children With Acute Bacterial Meningitis.

Introduction: Bacterial meningitis (BM) is a global public health concern that results in significant morbidity and mortality. Cerebral arterial narrowing contributes to stroke in BM and may be amenable to intervention. However, it is difficult to diagnose in resource-limited settings where the disease is common. Methods: This was a prospective observational study from September 2015 to December 2019 in sub-Saharan Africa. Children 1 month-18 years of age with neutrophilic pleocytosis or a bacterial pathogen identified in the cerebrospinal fluid were enrolled. Transcranial Doppler ultrasound (TCD) of the middle cerebral arteries was performed daily with the aim to identify flow abnormalities consistent with vascular narrowing. Results: Forty-seven patients were analyzed. The majority had Streptococcus pneumoniae (36%) or Neisseria meningitides (36%) meningitis. Admission TCD was normal in 10 (21%). High flow with a normal pulsatility index (PI) was seen in 20 (43%) and high flow with a low PI was identified in 7 (15%). Ten (21%) had low flow. All children with a normal TCD had a good outcome. Patients with a high-risk TCD flow pattern (high flow/low PI or low flow) were more likely to have a poor outcome (82 vs. 38%, p = 0.001). Conclusions: Abnormal TCD flow patterns were common in children with BM and identified those at high risk of poor neurological outcome.