Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

Background: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019.

Protocol for a Magnetic Resonance Imaging (MRI) Study of Participants in the Fever Randomized Controlled Trial: Does fever control prevent brain injury in malaria?

Background: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019.

Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria.

Microvascular thrombosis and blood-brain barrier (BBB) breakdown are key components of cerebral malaria (CM) pathogenesis in African children and are implicated in fatal brain swelling. How Plasmodium falciparum infection causes this endothelial disruption and why this occurs, particularly in the brain, is not fully understood. In this study, we have demonstrated that circulating extracellular histones, equally of host and parasite origin, are significantly elevated in CM patients.

Nontraumatic Myelopathy in Malawi: A Prospective Study in an Area with High HIV Prevalence.

Nontraumatic myelopathy causes severe morbidity and is not uncommon in Africa. Clinically, patients often present with paraplegia, and extrinsic cord compression and transverse myelitis are most common causes. Data on exact pathogenesis are scanty because of limitations in diagnostic methods.

Neurodevelopmental Impairments 1 Year After Cerebral Malaria.

Unlabelled: : media-1vid110.1542/5972295739001PEDS-VA_2018-1026 BACKGROUND AND OBJECTIVES: Cerebral malaria (CM) causes significant mortality and morbidity in sub-Saharan African children. Reliable morbidity estimates are scarce because of methodological variability across studies.

Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria.

Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM.

Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria.

Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling.

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke.

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms.

Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011.

Cognitive Outcomes and Psychiatric Symptoms of Retinopathy-Positive Cerebral Malaria: Cohort Description and Baseline Results.

Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM.

Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain.

The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume.

Safety of lumbar puncture in comatose children with clinical features of cerebral malaria.

Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM).

Methods: This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness.

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults.

Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons.

Brain MRI of children with retinopathy-negative cerebral malaria.

Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with retinopathy-negative cerebral malaria (CM) and investigate whether any findings on acute MRI were associated with adverse outcomes. We performed MRI scans on children admitted to the hospital in Blantyre, Malawi with clinically defined CM. Two hundred and seventeen children were imaged during the study period; 44 patients were malarial retinopathy-negative; and 173 patients were retinopathy-positive.

Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis?

Understanding the mechanisms underlying the pathophysiology of cerebral malaria in patients with Plasmodium falciparum infection is necessary to implement new curative interventions. While autopsy-based studies shed some light on several pathological events that are believed to be crucial in the development of this neurologic syndrome, their investigative potential is limited and has not allowed the identification of causes of death in patients who succumb to it. This can only be achieved by comparing features between patients who die from cerebral malaria and those who survive.

NeuroInterp: a method for facilitating neuroimaging research on cerebral malaria.

Radiologic data are increasingly important in clinical care guidelines for neurologic disorders and in the conduct of clinical trials assessing novel therapies. The infrastructure and expertise for neuroradiologic evaluations remain scarce in resource-limited settings, but where available, MRI and CT capacity can offer new insights into common, globally devastating diseases. In vivo data for frequently fatal tropical conditions such as cerebral malaria have been largely limited to autopsy studies, which only provide information on nonsurvivors at a single point in time.

Utilization of ultrasound in medical inpatients in Malawi.

Background: Ultrasound utilization studies in the developing world are important to support appropriate use.

Methods: A prospective, cross-sectional study in the medical wards at Queen Elizabeth Central Hospital, Blantyre, Malawi, was performed which aimed to assess referrals, reports and usefulness of scans to develop local recommendations. The primary outcome of a 'useful scan' was based on scan results and utilization of the report.

MRI findings in a cohort of brain injured survivors of pediatric cerebral malaria.

Abstract. A prospective cohort study of retinopathy-confirmed cerebral malaria (CM) survivors identified 42 of 132 with neurologic sequelae. The 38 survivors with sequelae who were alive when magnetic resonance imaging (MRI) technology became available underwent brain MRIs.

Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: an epidemiologic investigation.

Background: The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness.

Objective: Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique

Methods: Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture.

SIOP PODC: clinical guidelines for the management of children with Wilms tumour in a low income setting.

Wilms tumour is a relatively common and curable paediatric tumour. Known challenges to cure in low income countries are late presentation with advanced disease, malnutrition, failure to complete treatment and limited facilities. In this article, management recommendations are given for a low income setting where only the minimal requirements for treatment with curative intent are available (setting 1).

Central nervous system lesions in Malawian children: identifying the treatable.

In Malawi, children with central nervous system (CNS) tumours are seldom able to be treated with curative intent. A study was undertaken of 29 children who underwent CNS MRI during a two year period. A combination of neoplastic and non-neoplastic diagnoses were noted, seven of which were revised on review.

Stroke outcomes in Malawi, a country with high prevalence of HIV: a prospective follow-up study.

Background: Stroke contributes significantly to disability and mortality in developing countries yet little is known about the determinants of stroke outcomes in such countries. 12% of Malawian adults have HIV/AIDS. It is not known whether having HIV-infection alters the outcome of stroke.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

Background: Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border.

Methods: The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing.

Alternative oblique head CT scanning technique reduces bone artifact and improves interpretability of brainstem anatomy.

Brainstem pathology due to infections, infarcts and tumors are common in developing countries, but neuroimaging technology in these resource-poor settings is often limited to single slice, and occasionally spiral, CT. Unlike multislice CT and MRI, single slice and spiral CT are compromised by bone artifacts in the posterior fossa due to the dense petrous bones, often making imaging of the brainstem non-diagnostic. With appropriate head positioning, the petrous ridges can be avoided with 40° sagittal oblique scans parallel to either petrous ridge.

Neuroimaging findings in children with retinopathy-confirmed cerebral malaria.

Purpose: To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria.

Materials And Methods: In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT.