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Publications (80)
Background: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute br...
Determining the likelihood of causation by a pathogen in brain infections such asencephalitis and meningitis is challenging. While case definitions published forencephalitis causation for a UK-based study in 2010 have been used widely, there havebeen advances in diagnostic methods and clinical understanding since then, and theywere not designed for...
Background
Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries.
Methods
We evaluated growth following hospitalization among children...
Background: A better understanding of which children are likely to die during acute illness will help clinicians and policy makers target resources at the most vulnerable children. We used machine learning to characterise mortality in the 30-days following admission and the 180-days after discharge from nine hospitals in low and middle-income count...
Objectives:
To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa.
Study design:
One hundred thirty-four children (6 months to 18 years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical...
Background
Mortality among children with acute illness in low-income and middle-income settings remains unacceptably high and the importance of post-discharge mortality is increasingly recognised. We aimed to explore the epidemiology of deaths among young children with acute illness across sub-Saharan Africa and south Asia to inform the development...
Background
Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions.
Methods
Secondary analyses of the trial examined 3894 c...
Objectives
Mortality during acute illness among children in low- and middle-income settings remain unacceptably high and there is increasing recognition of the importance of post-discharge mortality. A comprehensive understanding of pathways underlying mortality among acutely ill children is needed to develop interventions and improve guidelines. W...
Background
We sought to identify perceptions of neurorehabilitation challenges for paediatric cerebral malaria (CM) survivors post-hospital discharge at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi.
Methods
An exploratory approach was used to qualitatively investigate the perceived neurorehabilitation challenges for paediatric CM su...
Background
In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling.
Methods
We used retinal angiography to study blood-retinal barrier integrity. We a...
Background:
In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling.
Methods:
We used retinal angiography to study blood-retinal barrier integrity....
Background: We sought to identify perceptions of neurorehabilitation needs and challenges for paediatric cerebral malaria (CM) survivors post-hospital discharge at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi.
Methods: An exploratory approach was used to qualitatively investigate current available neurorehabilitation services; invest...
Background: We sought to identify perceptions of neurorehabilitation challenges for paediatric cerebral malaria (CM) survivors post-hospital discharge at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi.
Methods: An exploratory approach was used to qualitatively investigate the perceived neurorehabilitation challenges for paediatric CM s...
Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with...
We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38...
Background:
Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital.
Methods:...
Streptococcus agalactiae (Group B streptococcus, GBS) is a coloniser of the gastrointestinal and urogenital tracts in adults, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterised by a series of Clonal Complexes (CCs) with different invasive potentials. CC17 for example is commonly associated with neo...
Intestinal pathology in children with complicated severe acute malnutrition (SAM) persists despite standard management. Given the similarity with intestinal pathology in non-IgE mediated gastrointestinal food allergy and Crohn’s disease, we tested whether therapeutic feeds effective in treating these conditions may benefit children with complicated...
Objective
To assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children.
Design
Prospective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domai...
Background:
The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment of infants with sepsis in low income settings (LICs), and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 LICs, Staphylococcus aureus, Klebsiella spp. and E.coli accounted for 55% of infants with sepsis. In a revi...
Background
Progress has been made in tackling malaria however there are still over 207 million cases worldwide, the majority in children. As survival rates improve, numbers of children with long-term neurodisabling sequelae are likely to increase. Most outcome studies in cerebral malaria (CM) have focused only on body function and structure and les...
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 o...
Kaplan–Meier curve showing similar mortality outcome in HIV-infected and HIV-uninfected children (Time in days, 0 is the time of admission): Survival profile was not significantly different between HIV-infected and uninfected children. Hazard ratio 1.10, 95% confidence interval 0.65–1.89, p = 0.72.
Study of the effect of HIV on disease progression in heterogeneous severe malaria syndromes with imprecise diagnostic criteria has led to varying results. Characteristic retinopathy refines cerebral malaria (CM) diagnosis, enabling more precise exploration of the hypothesis that HIV decreases the cytokine response in CM, leading to higher parasite...
HIV-1 Tat protein is implicated in HIV-neuropathogenesis. Tat C31S polymorphism (Tat CS ) has been associated with milder neuropathology in vitro and in animal models but this has not been addressed in a cohort of HIV-infected adults or children.
HIV viral load (VL) in plasma and cerebrospinal fluid (CSF) were determined and plasma HIV tat gene was...
Background. The Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) has routinely collected specimens for blood culture from febrile patients, and cerebrospinal fluid from patients with suspected meningitis, presenting to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, since 1998.
Methods. We present bloodstream infection (...
Importance:
HIV-1 typically replicates in CD4+ T cells. However, HIV-1 can evolve to infect macrophages, especially within the brain. Understanding how CCR5-using macrophage-tropic viruses evolve and differ from CCR5-using T cell-tropic viruses may provide insights into viral evolution and pathogenesis within the central nervous system. We charact...
In 1891, Winter(1) described the first 4 cases of tuberculous meningitis (TBM), in which paracenteses of the theca vertebralis was performed to relieve cerebrospinal fluid (CSF) fluid pressure. Since this original description of the lumbar puncture (LP) procedure, neurologists worldwide have relied on LPs for both diagnostic and therapeutic purpose...
Aims To assess the perceptions and experiences of families and community workers who manage children with disabilities in rural Malawi to enable the cultural adaptation of a training intervention. Disability information and advice services in this setting are limited despite the burden of paediatric disability on many families in Malawi. The study...
Rates of childhood disability are estimated to be high in African settings; however, services to provide information and support are limited. This study aims to explore perspectives and experiences of caregivers of children with disabilities (CWD) from acquired brain injury to inform the development of training packages for health-workers (HW) in h...
Cerebral palsy is the most common cause of physical disability in children worldwide. However, little is reported on this condition in the African context. Doctors from 22 countries in Africa, and representatives from a further 5 countries outside Africa, met to discuss the challenges in the evaluation and management of children with cerebral palsy...
Paediatric Disability in Malawi: Exploring information and advice needs at community level
Orla Shanahan1, Mac Mallewa2, Margaret Wazakili3, Josephine Chimoyo2 Melissa Gladstone4
1. Liverpool School of Tropical Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
2. Malawi Liverpool Wellcome Trust, Blantyre, Malawi...
Infections of the central nervous system are a significant cause of neurologic dysfunction in resource-limited countries, especially in Africa. The prevalence is not known and is most likely underestimated because of the lack of access to accurate diagnostic screens. For children, the legacy of subsequent neurodisability, which affects those who su...
Malnutrition and neurodisability are both major public health problems in Africa. This review highlights key areas where they interact. This happens throughout life and starts with maternal malnutrition affecting fetal neurodevelopment with both immediate (eg, folate deficiency causing neural tube defects) and lifelong implications (eg, impaired co...
Neurodevelopmental delay, neurodisability, and malnutrition interact to contribute a significant burden of disease in global settings. Assessments which are well integrated with plans of management or advice are most likely to improve outcomes. Assessment tools used in clinical research and programming to evaluate outcomes include developmental and...
In addition to encountering most of the conditions treated by clinicians in the West, clinicians in the tropics are faced with unique tropical encephalopathies. These are largely but not entirely infectious in nature. Despite the relatively low cost of EEG technology, it remains unavailable in many low-income tropical settings even at the tertiary...
Background: Fever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an importan...
High mortality burden from Acute Bacterial Meningitis (ABM) in resource-poor settings has been frequently blamed on delays in treatment seeking. We explored treatment-seeking pathways from household to primary health care and referral for ABM in Malawi.
A cross-sectional qualitative study using narrative in-depth interviews, semi-structured intervi...
Aims
Rehabilitation services in Malawi are limited despite the burden of paediatric neurodisability secondary to conditions such as cerebral malaria, meningitis, encephalitis and traumatic brain injury. This hospital-based study aims to explore the perceptions and experiences of parent/carers and health-workers caring for children with neurodisabil...
This article presents key findings from the International Child Neurology Association/African Child Neurology Association Workshop. The viability of international guidelines for the management of children with epilepsy should be reviewed within each African country, and adapted to comply with the regional capacity. Such recommendations can be used...
Cerebral malaria, defined as an otherwise unexplained coma in a patient with Plasmodium falciparum parasitemia, affects up to 1 million people per year, the vast majority of them being children living in sub-Saharan Africa. Despite optimal treatment, this condition kills 15% of those affected and leaves 30% of survivors with neurologic sequelae. Th...
No relationship between viral load and subject classification. Relationships between blood or CSF viral loads and virological classifications were assessed using the Mann-Whitney test in GraphPad Prism 4. Horizontal bars represent median values. (a) Comparisons between blood viral load and CSF compartment classification (Eq, equilibrated; Inter, In...
Intermediate subject 3017 exhibiting two transmitted viruses. Phylogenetic and sequence analysis of plasma and CSF HIV-1 populations for subject 3017. (a) Neighbor-joining tree. Sequences from the CSF are labeled with solid blue circles, and plasma sequences (PL) are labeled with solid red triangles. Bootstrap values ≥40 are indicated (*) at the ap...
Intermediate subject 4048 exhibiting greater than two transmitted viruses. Phylogenetic and sequence analysis of plasma and CSF HIV-1 populations for subject 4048. (a) Neighbor-joining tree. Sequences from the CSF are labeled with solid blue circles, and plasma sequences (PL) are labeled with solid red triangles. Bootstrap values ≥40 are indicated...
Equilibrated subject 4055 exhibiting two transmitted viruses. Phylogenetic and sequence analysis of plasma and CSF HIV-1 populations for subject 4055. (a) Neighbor-joining tree. Sequences from the CSF are labeled with solid blue circles, and plasma sequences (PL) are labeled with solid red triangles. Bootstrap values ≥40 are indicated (*) at the ap...
Compartmentalized subject 4004 exhibiting three or more transmitted viruses. Phylogenetic and sequence analysis of plasma and CSF HIV-1 populations for subject 4004. (a) Neighbor-joining tree. CSF sequences are labeled with solid blue circles, and plasma sequences (PL) are labeled with solid red triangles. Bootstrap values ≥40 are indicated (*) at...
No contamination was observed between subjects. Neighbor-joining phylogenetic tree (radial topology). env sequences from the CSF are labeled with solid blue circles and env sequences from the blood plasma are labeled with solid red triangles. Genetic distance is indicated at the bottom of the figure and indicates the number of nucleotide substituti...
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.
Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique
Persons...
18-year old female with typhoid-associated neurologic illness demonstrating severe truncal and appendicular ataxia and facial masking.
(WMV)
Initial pathogen testing among ill persons during outbreak of typhoid fever, Malawi – Mozambique, 2009
(DOC)
HIV-1 subtype B replication in the CNS can occur in CD4+ T cells or macrophages/microglia in adults. However, little is known about CNS infection in children or the ability of subtype C HIV-1 to evolve macrophage-tropic variants. In this study, we examined HIV-1 variants in ART-naïve children aged three years or younger to determine viral genotypes...
We describe five children who died of clinical rabies in a three month period (September to November 2011) in the Queen Elizabeth Central Hospital. From previous experience and hospital records, this number of cases is higher than expected. We are concerned that difficulty in accessing post-exposure prophylaxis (PEP) rabies vaccine may be partly re...
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.
The investigation included active surveillance, interviews, examinat...
The first African Child Neurology Association meeting identified key challenges that the continent faces to improve the health of children with neurology disorders. The capacity to diagnose common neurologic conditions and rare disorders is lacking. The burden of neurologic disease on the continent is not known, and this lack of knowledge limits th...
Plasmodium falciparum and other human malaria parasites can cause a variety of life-threatening syndromes. Diagnosis is difficult because none of these syndromes is unique to malaria, and parasitemia may be incidental rather than responsible for the illness. Malaria must be considered in the differential diagnosis of each of the severe syndromes it...
In this article, British neurologists share their experiences of neurology in Malawi--as educators and researchers. Malawi is a resource-poor country in Central Africa. The spectrum of neurological illnesses is varied and primarily related to HIV and neuroinfections. Structured overseas training programmes for residents can lead to academic exchang...
Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises
morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and
insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocyt...
This chapter discusses the pathogenesis and clinical features of the major viral causes of acute flaccid paralysis. Many viruses that infect the human nervous system will occasionally cause lower motor neuron disease. However, for some viruses, the infection of lower motor neurons is an especially common and/or important clinical problem. Polioviru...
In a malaria-endemic area of Africa, rabies was an important cause of fatal central nervous system infection, responsible for 14 (10.5%) of 133 cases. Four patients had unusual clinical manifestations, and rabies was only diagnosed postmortem. Three (11.5%) of 26 fatal cases originally attributed to cerebral malaria were due to rabies.
In a region of Africa where malaria is common, rabies was a significant contributor to fatal central nervous system infections, accounting for 14 (10.5%) of 133 cases. Four patients presented with peculiar clinical symptoms, and rabies was only identified postmortem. Rabies was the cause of three (11.5%) of the 26 fatal cases that were initially as...
Rabies is an acute infection of the central nervous system (CNS) and caused by rabies virus or related members of the genus Lyssavirus , family Rhabdoviridae.1 The virus is usually transmitted through a dog bite and produces one of the most important viral encephalitides worldwide, with at least 40 000 deaths reported annually.2 However, it is rare...
Emerging diseases include new diseases caused by previously unknown organisms, and old diseases that are increasing in incidence or geographical area. Emerging viral infections can be divided into those that are transmitted by insects (the arthropod-borne viruses, or arboviruses) and those that are transmitted directly from animals or humans. Clini...
Although West Nile encephalitis is yet to spread to the United Kingdom, it is becoming more prevalent in the rest of the world. This article reviews the recent outbreaks and examines the current methods of diagnosis, treatment, and prevention.
A patient was initially treated with oral carbamazepine (CBZ) and oral phenobarbitone (PB) with incomplete seizure control. The patient subsequently developed persistent vomiting due to marked gastro-oesophageal reflux, which necessitated treatment with rectal CBZ and intravenous PB for the subsequent 10 weeks. There was no difference in seizure co...
