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Papers by Tom Solomon

Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport ... more Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise. J. Appl. Physiol. 85(4): 1218-1222, 1998.-The purpose of this study was to determine whether the increase in insulin sensitivity of skeletal muscle glucose transport induced by a single bout of exercise is mediated by enhanced translocation of the GLUT-4 glucose transporter to the cell surface. The rate of 3-O-[ 3 H]methyl-D-glucose transport stimulated by a submaximally effective concentration of insulin (30 µU/ml) was approximately twofold greater in the muscles studied 3.5 h after exercise than in those of the sedentary controls (0.89 Ϯ 0.10 vs. 0.43 Ϯ 0.05 µmol · ml Ϫ1 ·10 min Ϫ1 ; means Ϯ SE for n ϭ 6/group). GLUT-4 translocation was assessed by using the ATB-[2-3 H]BMPA exofacial photolabeling technique. Prior exercise resulted in greater cell surface GLUT-4 labeling in response to submaximal insulin treatment (5.36 Ϯ 0.45 dpm ϫ 10 3 /g in exercised vs. 3.00 Ϯ 0.38 dpm ϫ 10 3 /g in sedentary group; n ϭ 10/group) that closely mirrored the increase in glucose transport activity. The signal generated by the insulin receptor, as reflected in the extent of insulin receptor substrate-1 tyrosine phosphorylation, was unchanged after the exercise. We conclude that the increase in muscle insulin sensitivity of glucose transport after exercise is due to translocation of more GLUT-4 to the cell surface and that this effect is not due to potentiation of insulin-stimulated tyrosine phosphorylation. insulin receptor; insulin receptor substrate-1; tyrosine phosphorylation Address for reprint requests: P. Hansen, Washington

Implementation science : IS, 2015

Central nervous system infections can have devastating clinical outcomes if not diagnosed and tre... more Central nervous system infections can have devastating clinical outcomes if not diagnosed and treated promptly. There is a documented gap between recommended and actual practice and a limited understanding of its causes. We identified and explored the reasons for this gap, focusing on points in the patient pathway most amenable to change and the development of a tailored intervention strategy to improve diagnosis and treatment. Using theoretically-informed semi-structured interviews, we explored barriers and enablers to diagnosing and managing patients with suspected encephalitis, specifically performing lumbar punctures and initiating antiviral therapy within 6 h. We purposively sampled hospitals and hospital staff in the UK. We audio recorded and transcribed all interviews prior to a framework analysis. We mapped identified barriers and enablers to the patient pathway. We matched behaviour change techniques targeting clinicians to the most salient barriers and enablers and embedde...

A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal

PloS one, 2015

Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is c... more Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, ...

Japanese journal of infectious diseases, 2009

Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotropic flavivirus, may c... more Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotropic flavivirus, may cause acute encephalitis in humans. Recombinant Salmonella typhimurium BRD509 was constructed to display domain III of the envelope (E) protein of JEV (JEDIII) on its surface with the N-terminal domain of ice nucleation protein (INPN) as the display motif. Bacterial cell surface display was confirmed by Western blot analysis and immunohistochemical staining. Binding of recombinant INPN-JEDIII and JEDIII proteins to three mammalian cell lines was compared using a cell-binding ELISA; the human neuroblastoma cell line SK-N-SH, which had a low level of binding, was selected for further studies. The display of JEDIII on the surface of BRD509 did not significantly influence its invasiveness was confirmed by measuring released bacterial antigen using whole-cell ELISA. The relative expression of an apoptosis-related gene and total DNA damage were assessed to investigate the effects of infection o...

Practical neurology, 2007

The management of patients with suspected viral encephalitis has been revolutionised in recent ye... more The management of patients with suspected viral encephalitis has been revolutionised in recent years with improved imaging and viral diagnostics, better antiviral and immunomodulatory therapies, and enhanced neurointensive care. Despite this, disasters in patient management are sadly not uncommon. While some patients are attacked with all known antimicrobials with little thought to investigation of the cause of their illness, for others there are prolonged and inappropriate delays before treatment is started. Although viral encephalitis is relatively rare, patients with suspected central nervous system (CNS) infections, who might have viral encephalitis, are not. In addition, the increasing number of immunocompromised patients who may have viral CNS infections, plus the spread of encephalitis caused by arthropod-borne viruses, present new challenges to clinicians. This article discusses the Liverpool approach to the investigation and treatment of adults with suspected viral encephal...

Japanese encephalitis

Journal of neurology, neurosurgery, and psychiatry, 2000

Solomon, Tom; Dung, Nguyen Minh; Kneen, Rachel; Gainsborough, Mary; Vaughn, David W; Khanh, Vo Thi.

Background: Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children... more Background: Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases.

British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children

SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evide... more SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).

A Survey of UK Healthcare Workers’ Attitudes on Volunteering to Help with the Ebola Outbreak in West Africa

PLOS ONE, 2015

To understand the barriers and enablers for UK healthcare workers who are considering going to wo... more To understand the barriers and enablers for UK healthcare workers who are considering going to work in the current Ebola outbreak in West Africa, but have not yet volunteered. After focus group discussions, and a pilot questionnaire, an anonymous survey was conducted using SurveyMonkey to determine whether people had considered going to West Africa, what factors might make them more or less likely to volunteer, and whether any of these were modifiable factors. The survey was publicised among doctors, nurses, laboratory staff and allied health professionals. 3109 people answered the survey, of whom 472 (15%) were considering going to work in the epidemic but had not yet volunteered. 1791 (57.6%) had not considered going, 704 (22.6%) had considered going but decided not to, 53 (1.7%) had volunteered to go and 14 (0.45%) had already been and worked in the epidemic. For those considering going to West Africa, the most important factor preventing them from volunteering was a lack of information to help them decide; fear of getting Ebola and partners' concerns came next. Uncertainty about their potential role, current work commitments and inability to get agreement from their employer were also important barriers, whereas clarity over training would be an important enabler. In contrast, for those who were not considering going, or who had decided against going, family considerations and partner concerns were the most important factors. More UK healthcare workers would volunteer to help tackle Ebola in West Africa if there was better information available, including clarity about roles, cover arrangements, and training. This could be achieved with a well-publicised high quality portal of reliable information.

The Lancet. Neurology, 2014

Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree... more Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would benefit from routine screening for cognitive difficulties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated.

Management of suspected viral encephalitis in adults–Association of British Neurologists and British infection Association national guidelines

In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramaticall... more In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramatically improved with aciclovir treatment. Delays in starting treatment, particularly beyond 48 h after hospital admission, are associated with a worse prognosis. Several comprehensive reviews of the investigation and management of encephalitis have been published. However, their impact on day-to day clinical practice appears to be limited. The emergency management of meningitis in children and adults was revolutionised by the introduction of a simple algorithm as part of management guidelines. In February 2008 a group of clinicians met in Liverpool to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.

Chapter 10 Viral infections of lower motor neurons

Handbook of Clinical Neurology, 2007

ABSTRACT

PLoS Neglected Tropical Diseases, 2014

Background: Japanese encephalitis (JE) is a major cause of mortality and morbidity for which ther... more Background: Japanese encephalitis (JE) is a major cause of mortality and morbidity for which there is no treatment. In addition to direct viral cytopathology, the inflammatory response is postulated to contribute to the pathogenesis. Our goal was to determine the contribution of bystander effects and inflammatory mediators to neuronal cell death.

PloS one, 2014

Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) ... more Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART. HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery. One hundred and six HIV positive patients, with median (range) age 39 (18-71) years, 73% female and median (range) CD4 count 323.5 (68-1039) cells/µl were studied. Symptomatic neurocognitive impairment...

The evaluation of a tailored intervention to improve the management of suspected viral encephalitis: protocol for a cluster randomised controlled trial

Implementation Science, 2015

BackgroundViral encephalitis is a devastating condition for which delayed treatment is associated... more BackgroundViral encephalitis is a devastating condition for which delayed treatment is associated with increased morbidity and mortality. Clinical audits indicate substantial scope for improved detection and treatment. Improvement strategies should ideally be tailored according to identified needs and barriers to change. The aim of the study is to evaluate the effectiveness and cost-effectiveness of a tailored intervention to improve the secondary care management of suspected encephalitis.Methods/designThe study is a two-arm cluster randomised controlled trial with allocation by postgraduate deanery. Participants were identified from 24 hospitals nested within 12 postgraduate deaneries in the United Kingdom (UK). We developed a multifaceted intervention package including core and flexible components with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. The primary outcome will be a composite of the proportion of patients with suspected encephalitis receiving timely and appropriate diagnostic lumbar puncture within 12 h of hospital admission and aciclovir treatment within 6 h. We will gather outcome data pre-intervention and up to 12 months post-intervention from patient records. Statistical analysis at the cluster level will be blind to allocation. An economic evaluation will estimate intervention cost-effectiveness from the health service perspective.Trial registrationControlled Trials: ISRCTN06886935.

The American journal of tropical medicine and hygiene, 2004

Classification of dengue using the current World Health Organization (WHO) system is not straight... more Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of ...

Interactive clinical case reports

Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000

In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is gener... more In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in addition to standard chemotherapy. Such removal is commonly achieved by exchange transfusion but this procedure is time-consuming and may be associated with haemodynamic disturbance. Current-generation automated cell-separator hardware and software allows prompt red cell exchange, erythrocytapheresis, in a

The Lancet, 2003

Background Japanese encephalitis virus (JEV), although confined to Asia, causes about 35 000-50 0... more Background Japanese encephalitis virus (JEV), although confined to Asia, causes about 35 000-50 000 cases and 10 000 deaths every year, and is the most important cause of encephalitis worldwide. There is no known antiviral treatment for any flavivirus. Results from in-vitro studies and work in animals have shown inteferon alfa has antiviral activity on Japanese encephalitis and other flaviviruses; therefore, we aimed to assess the efficacy of inteferon alfa-2a in Japanese encephalitis.

Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport ... more Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise. J. Appl. Physiol. 85(4): 1218-1222, 1998.-The purpose of this study was to determine whether the increase in insulin sensitivity of skeletal muscle glucose transport induced by a single bout of exercise is mediated by enhanced translocation of the GLUT-4 glucose transporter to the cell surface. The rate of 3-O-[ 3 H]methyl-D-glucose transport stimulated by a submaximally effective concentration of insulin (30 µU/ml) was approximately twofold greater in the muscles studied 3.5 h after exercise than in those of the sedentary controls (0.89 Ϯ 0.10 vs. 0.43 Ϯ 0.05 µmol · ml Ϫ1 ·10 min Ϫ1 ; means Ϯ SE for n ϭ 6/group). GLUT-4 translocation was assessed by using the ATB-[2-3 H]BMPA exofacial photolabeling technique. Prior exercise resulted in greater cell surface GLUT-4 labeling in response to submaximal insulin treatment (5.36 Ϯ 0.45 dpm ϫ 10 3 /g in exercised vs. 3.00 Ϯ 0.38 dpm ϫ 10 3 /g in sedentary group; n ϭ 10/group) that closely mirrored the increase in glucose transport activity. The signal generated by the insulin receptor, as reflected in the extent of insulin receptor substrate-1 tyrosine phosphorylation, was unchanged after the exercise. We conclude that the increase in muscle insulin sensitivity of glucose transport after exercise is due to translocation of more GLUT-4 to the cell surface and that this effect is not due to potentiation of insulin-stimulated tyrosine phosphorylation. insulin receptor; insulin receptor substrate-1; tyrosine phosphorylation Address for reprint requests: P. Hansen, Washington

Implementation science : IS, 2015

Central nervous system infections can have devastating clinical outcomes if not diagnosed and tre... more Central nervous system infections can have devastating clinical outcomes if not diagnosed and treated promptly. There is a documented gap between recommended and actual practice and a limited understanding of its causes. We identified and explored the reasons for this gap, focusing on points in the patient pathway most amenable to change and the development of a tailored intervention strategy to improve diagnosis and treatment. Using theoretically-informed semi-structured interviews, we explored barriers and enablers to diagnosing and managing patients with suspected encephalitis, specifically performing lumbar punctures and initiating antiviral therapy within 6 h. We purposively sampled hospitals and hospital staff in the UK. We audio recorded and transcribed all interviews prior to a framework analysis. We mapped identified barriers and enablers to the patient pathway. We matched behaviour change techniques targeting clinicians to the most salient barriers and enablers and embedde...

A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal

PloS one, 2015

Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is c... more Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial. We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, ...

Japanese journal of infectious diseases, 2009

Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotropic flavivirus, may c... more Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotropic flavivirus, may cause acute encephalitis in humans. Recombinant Salmonella typhimurium BRD509 was constructed to display domain III of the envelope (E) protein of JEV (JEDIII) on its surface with the N-terminal domain of ice nucleation protein (INPN) as the display motif. Bacterial cell surface display was confirmed by Western blot analysis and immunohistochemical staining. Binding of recombinant INPN-JEDIII and JEDIII proteins to three mammalian cell lines was compared using a cell-binding ELISA; the human neuroblastoma cell line SK-N-SH, which had a low level of binding, was selected for further studies. The display of JEDIII on the surface of BRD509 did not significantly influence its invasiveness was confirmed by measuring released bacterial antigen using whole-cell ELISA. The relative expression of an apoptosis-related gene and total DNA damage were assessed to investigate the effects of infection o...

Practical neurology, 2007

The management of patients with suspected viral encephalitis has been revolutionised in recent ye... more The management of patients with suspected viral encephalitis has been revolutionised in recent years with improved imaging and viral diagnostics, better antiviral and immunomodulatory therapies, and enhanced neurointensive care. Despite this, disasters in patient management are sadly not uncommon. While some patients are attacked with all known antimicrobials with little thought to investigation of the cause of their illness, for others there are prolonged and inappropriate delays before treatment is started. Although viral encephalitis is relatively rare, patients with suspected central nervous system (CNS) infections, who might have viral encephalitis, are not. In addition, the increasing number of immunocompromised patients who may have viral CNS infections, plus the spread of encephalitis caused by arthropod-borne viruses, present new challenges to clinicians. This article discusses the Liverpool approach to the investigation and treatment of adults with suspected viral encephal...

Japanese encephalitis

Journal of neurology, neurosurgery, and psychiatry, 2000

Solomon, Tom; Dung, Nguyen Minh; Kneen, Rachel; Gainsborough, Mary; Vaughn, David W; Khanh, Vo Thi.

Background: Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children... more Background: Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases.

British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children

SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evide... more SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).

A Survey of UK Healthcare Workers’ Attitudes on Volunteering to Help with the Ebola Outbreak in West Africa

PLOS ONE, 2015

To understand the barriers and enablers for UK healthcare workers who are considering going to wo... more To understand the barriers and enablers for UK healthcare workers who are considering going to work in the current Ebola outbreak in West Africa, but have not yet volunteered. After focus group discussions, and a pilot questionnaire, an anonymous survey was conducted using SurveyMonkey to determine whether people had considered going to West Africa, what factors might make them more or less likely to volunteer, and whether any of these were modifiable factors. The survey was publicised among doctors, nurses, laboratory staff and allied health professionals. 3109 people answered the survey, of whom 472 (15%) were considering going to work in the epidemic but had not yet volunteered. 1791 (57.6%) had not considered going, 704 (22.6%) had considered going but decided not to, 53 (1.7%) had volunteered to go and 14 (0.45%) had already been and worked in the epidemic. For those considering going to West Africa, the most important factor preventing them from volunteering was a lack of information to help them decide; fear of getting Ebola and partners' concerns came next. Uncertainty about their potential role, current work commitments and inability to get agreement from their employer were also important barriers, whereas clarity over training would be an important enabler. In contrast, for those who were not considering going, or who had decided against going, family considerations and partner concerns were the most important factors. More UK healthcare workers would volunteer to help tackle Ebola in West Africa if there was better information available, including clarity about roles, cover arrangements, and training. This could be achieved with a well-publicised high quality portal of reliable information.

The Lancet. Neurology, 2014

Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree... more Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would benefit from routine screening for cognitive difficulties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated.

Management of suspected viral encephalitis in adults–Association of British Neurologists and British infection Association national guidelines

In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramaticall... more In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramatically improved with aciclovir treatment. Delays in starting treatment, particularly beyond 48 h after hospital admission, are associated with a worse prognosis. Several comprehensive reviews of the investigation and management of encephalitis have been published. However, their impact on day-to day clinical practice appears to be limited. The emergency management of meningitis in children and adults was revolutionised by the introduction of a simple algorithm as part of management guidelines. In February 2008 a group of clinicians met in Liverpool to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.

Chapter 10 Viral infections of lower motor neurons

Handbook of Clinical Neurology, 2007

ABSTRACT

PLoS Neglected Tropical Diseases, 2014

Background: Japanese encephalitis (JE) is a major cause of mortality and morbidity for which ther... more Background: Japanese encephalitis (JE) is a major cause of mortality and morbidity for which there is no treatment. In addition to direct viral cytopathology, the inflammatory response is postulated to contribute to the pathogenesis. Our goal was to determine the contribution of bystander effects and inflammatory mediators to neuronal cell death.

PloS one, 2014

Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) ... more Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART. HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery. One hundred and six HIV positive patients, with median (range) age 39 (18-71) years, 73% female and median (range) CD4 count 323.5 (68-1039) cells/µl were studied. Symptomatic neurocognitive impairment...

The evaluation of a tailored intervention to improve the management of suspected viral encephalitis: protocol for a cluster randomised controlled trial

Implementation Science, 2015

BackgroundViral encephalitis is a devastating condition for which delayed treatment is associated... more BackgroundViral encephalitis is a devastating condition for which delayed treatment is associated with increased morbidity and mortality. Clinical audits indicate substantial scope for improved detection and treatment. Improvement strategies should ideally be tailored according to identified needs and barriers to change. The aim of the study is to evaluate the effectiveness and cost-effectiveness of a tailored intervention to improve the secondary care management of suspected encephalitis.Methods/designThe study is a two-arm cluster randomised controlled trial with allocation by postgraduate deanery. Participants were identified from 24 hospitals nested within 12 postgraduate deaneries in the United Kingdom (UK). We developed a multifaceted intervention package including core and flexible components with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. The primary outcome will be a composite of the proportion of patients with suspected encephalitis receiving timely and appropriate diagnostic lumbar puncture within 12 h of hospital admission and aciclovir treatment within 6 h. We will gather outcome data pre-intervention and up to 12 months post-intervention from patient records. Statistical analysis at the cluster level will be blind to allocation. An economic evaluation will estimate intervention cost-effectiveness from the health service perspective.Trial registrationControlled Trials: ISRCTN06886935.

The American journal of tropical medicine and hygiene, 2004

Classification of dengue using the current World Health Organization (WHO) system is not straight... more Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of ...

Interactive clinical case reports

Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000

In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is gener... more In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in addition to standard chemotherapy. Such removal is commonly achieved by exchange transfusion but this procedure is time-consuming and may be associated with haemodynamic disturbance. Current-generation automated cell-separator hardware and software allows prompt red cell exchange, erythrocytapheresis, in a

The Lancet, 2003

Background Japanese encephalitis virus (JEV), although confined to Asia, causes about 35 000-50 0... more Background Japanese encephalitis virus (JEV), although confined to Asia, causes about 35 000-50 000 cases and 10 000 deaths every year, and is the most important cause of encephalitis worldwide. There is no known antiviral treatment for any flavivirus. Results from in-vitro studies and work in animals have shown inteferon alfa has antiviral activity on Japanese encephalitis and other flaviviruses; therefore, we aimed to assess the efficacy of inteferon alfa-2a in Japanese encephalitis.