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Biomedical subjects

Tom Solomon

Publications and source records attributed to Tom Solomon.

At least 19 recordsLinked to original sources
PubMed2025

Microbiological Investigations for Chikungunya Virus in Children With Acute Encephalitis Syndrome in a Non-Outbreak Setting in Southern India.

Chikungunya virus (CHIKV) is an emerging cause of acute encephalitis syndrome (AES) in India, with limited data on its role in childhood AES in southern India. We systematically evaluated children with AES in southern India during a non-epidemic period for CHIKV. Serum and cerebrospinal fluid (CSF) samples were tested for CHIKV using IgM ELISA and real-time reverse transcriptase PCR. Amplicon sequencing was performed on PCR-positive samples. Clinical and laboratory features were compared between children with and without CSF CHIKV positivity (PCR/IgM antibodies). Of 376 children with AES, 20 (5.3%) had positive CHIKV tests. Co-infections were common, particularly with scrub typhus. Children presented with diverse symptoms affecting various organ systems. Neurological manifestations included meningism, seizures, cerebellar signs, behavioral abnormalities, cranial nerve involvement, involuntary movements, and hemiparesis/hemiplegia. Children with CSF CHIKV positivity showed more focal neurological deficits and transaminitis, and less musculoskeletal symptoms. Sequencing confirmation of CHIKV was made in all patients with positive CHIKV PCR, revealing a close relationship with 2016 Kenyan and Indian strains, albeit in a different clade within the East/Central/South African genotype. Along with important mutations known to impact CHIKV infectivity, four novel amino acid substitutions were detected in envelope protein coding regions. Our findings underscore the importance of routine and comprehensive CHIKV testing for children with AES, irrespective of season/outbreak. The high rate of co-infections warrants further research. Continued genomic surveillance is essential to monitor emerging mutations with epidemic potential, increased severity and the risk of neurological disease.

Humans↗
PubMed2006

A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model.

Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, beta-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation.

Adolescent↗
PubMed2005

Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2-3 September, 2004.

The World Health Organization (WHO) is undertaking consultations on immunological responses as parameters for evaluation and licensure of new Japanese encephalitis (JE) vaccines. Immunological markers could be used by vaccine developers and regulatory authorities to assess vaccine efficacy in absence of clinical efficacy data. The consultation which is reported here reviewed current data on mechanisms of protective immunity gathered from animal experimentation, clinical data from licensed vaccines and from vaccine candidates still in clinical development. Immunological assays and readouts for use in evaluation of candidate vaccines were also discussed. The consultation made a series of recommendations for specifications on immunological criteria to assess JE vaccine efficacy. More detailed recommendations will be drafted following further consultations to serve as WHO guidelines for evaluation and licensure for new JE vaccines.

Antibodies, Viral↗
PubMed2004

Clinical features and predictors of diphtheritic cardiomyopathy in Vietnamese children.

BACKGROUND: Despite the availability of antitoxin and antibiotics, the mortality rate for diphtheria remains high, mostly because of cardiac complications. METHODS: During 1 year, 154 Vietnamese children with diphtheria admitted to a referral hospital were studied prospectively with clinical examination, including a simple pseudomembrane score, 12-lead and 24-hour electrocardiography, measurement of serum cardiac enzyme levels, and estimation of troponin T levels. RESULTS: Thirteen children had diphtheritic cardiomyopathy on admission, and 19 developed it subsequently. Twelve children (8%) died. The combination of pseudomembrane score of >2 and bull neck predicted the development of diphtheritic cardiomyopathy, with a positive predictive value of 83% and a negative predictive value of 93%. Administration of 24-hour electrocardiography on admission improved the ability to predict diphtheritic cardiomyopathy by 57%. Fatal outcome was best predicted by the combination of myocarditis on admission and a pseudomembrane score of >2. Of the cardiac enzyme levels measured, an elevated aspartate aminotransferase level was the best predictor. The presence of troponin T identified additional children with subclinical cardiac damage. CONCLUSIONS: The development of diphtheritic cardiomyopathy can be predicted by means of simple measures.

Adolescent↗
PubMed2004

Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.

BACKGROUND: Japanese encephalitis virus (JEV), the mosquito-borne flavivirus, annually causes an estimated 35,000-50,000 encephalitis cases and 10,000-15,000 deaths in Asia, and there is no antiviral treatment. The role played by the immune response in determining the outcome of human infection with JEV is poorly understood, although, in animal models of flavivirus encephalitis, unregulated proinflammatory cytokine responses can be detrimental. METHODS: We studied the innate, cellular, and humoral immune responses in 118 patients infected with JEV, of whom 13 (11%) died. RESULTS: Levels of interferon (IFN)- alpha , the proinflammatory cytokine interleukin (IL)-6, and the chemokine IL-8 were all higher in the cerebrospinal fluid (CSF) of the nonsurvivors than of the survivors (P=.04, P=.006, and P=.04, respectively), as were both the IL-6 : IL-4 ratio in CSF (a marker of the balance of pro- and anti-inflammatory cytokines) and the level of the chemokine RANTES (regulated on activation, normally T cell expressed and secreted) in plasma (P=.03). In contrast, levels of immunoglobulin (Ig) M and IgG in CSF and of IgM in plasma were higher in the survivors (P=.035, P=.003, and P=.009, respectively). Levels of IFN- gamma and nitric oxide did not vary with outcome. CONCLUSIONS: During JEV infection, elevated levels of proinflammatory cytokines and chemokines are associated with a poor outcome, but whether they are simply a correlate of severe disease or contribute to pathogenesis remains to be determined.

Adolescent↗
PubMed2004

Evaluation of an algorithm for integrated management of childhood illness in an area of Vietnam with dengue transmission.

OBJECTIVES: To determine whether nurses, using the WHO/UNICEF algorithm for integrated management of childhood illness (IMCI), modified to include dengue infection, satisfactorily classified children in an area endemic for dengue haemorrhagic fever (DHF). METHODS: Nurses assessed and classified, using the modified IMCI algorithm, a systematic sample of 1250 children aged 2 months to 10 years (n = 1250) presenting to a paediatric hospital in Dong Nai Province, Vietnam. Their classification was compared with that of a paediatrician, blind to the result of the nurses' assessment, which could be modified in the light of simple investigations, e.g. dengue serology. RESULTS: In children aged 2-59 months (n = 859), the nurses were able to classify, using the modified chart, the presenting illness in >99% of children and found more than one classification in 70%. For the children with pneumonia, diarrhoea, dengue shock syndrome, severe DHF and severe disease requiring urgent admission, the nurse's classification was >60% sensitive and >85% specific compared with that of the paediatrician. For the nurse's classification of DHF the specificity was 50-55% for the children <5 years and in children with definitive dengue serology. Alterations in the DHF algorithm improved specificity at the expense of sensitivity. CONCLUSION: Using the IMCI chart, nurses classified appropriately many of the major clinical problems in sick children <5 years in southern Vietnam. However, further modifications will be required in the fever section, particularly for dengue. The impact of using the IMCI chart in peripheral health stations remains to be evaluated.

Algorithms↗
PubMed2004

Clinical diagnosis and assessment of severity of confirmed dengue infections in Vietnamese children: is the world health organization classification system helpful?

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 disease, it is essential that some measure of capillary leak is included in any classification system, with less emphasis on bleeding and a specific platelet count.

Adolescent↗
PubMed2003

Natural and nosocomial infection in a patient with West Nile encephalitis and extrapyramidal movement disorders.

Since its first recognition in North America in 1999, West Nile virus (WNV) has spread rapidly across the continent, but in many communities, rapid diagnostic tests for detection of WNV infection are not fully available. We describe a patient with extrapyramidal movement disorders and changes in the basal ganglia noted on magnetic resonance images that are characteristic of other flavivirus encephalitides and may help in the recognition of patients with West Nile encephalitis. Detailed molecular analysis suggested that, although our patient received a blood transfusion infected with WNV, the virus that caused his initial infection and encephalitis was probably acquired naturally from a mosquito.

Animals↗
PubMed2003

Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial.

BACKGROUND: Japanese encephalitis virus (JEV), although confined to Asia, causes about 35000-50000 cases and 10000 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. METHODS: We did a randomised double-blind placebo-controlled trial of interferon alfa-2a (10 million units/m2, daily for 7 days) in 112 Vietnamese children with suspected Japanese encephalitis, 87 of whom had serologically confirmed infections. Our primary endpoints were hospital death or severe sequelae at discharge. Analysis was by intention to treat. FINDINGS: Overall, 21 children (19%) died, and 17 (15%) had severe sequelae. Outcome at discharge and 3 months did not differ between the two treatment groups; 20 children in the interferon group had a poor outcome (death or severe sequelae), compared with 18 in the placebo group (p=0.85, difference 0.1%, 95% CI -17.5 to 17.6%), there were no long-term side effects of interferon. INTERPRETATION: The doses of interferon alfa-2a given in this regimen did not improve the outcome of patients with Japanese encephalitis.

Adolescent↗
PubMed2003

Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-and-mouth disease in Sarawak, Malaysia.

We report the virological and clinical features of 8 children who presented with adenovirus-associated acute flaccid paralysis (AFP) during an epidemic of enterovirus type 71 (EV71)-associated hand-foot-and-mouth disease (HFMD) in Sarawak, Malaysia, in 1997. Neutralization tests and phylogenetic analysis revealed adenovirus type 21 (Ad21), although DNA restriction digests suggested that this virus was different from the prototype Ad21. Four children had upper-limb monoparesis, 2 had lower-limb monoparesis (one of whom had changes in the anterior spinal cord noted on magnetic resonance imaging), and 2 had flaccid paraparesis. At follow-up, 4 children were noted to have made full recoveries and 3 had residual flaccid weakness and wasting. Neurophysiological investigation revealed a mixture of axonal and demyelinating features in motor and sensory nerves, with denervation. These findings suggest that Ad21 might cause AFP by anterior horn cell damage or neuropathy of the brachial or lumbosacral plexus. The occurrence of these unusual adenovirus infections during an outbreak of EV71-associated HFMD suggests that an interaction between the 2 viruses may have occurred.

Acute Disease↗
PubMed2003

Recent advances in Japanese encephalitis.

Japanese encephalitis (JE), the most important cause of epidemic encephalitis worldwide, is confined to Asia, but its geographical area is spreading. West Nile virus, and other closely related flaviviruses, cause similar disease elsewhere. Recent cryoelectron microscopic studies have characterized the flavivirus envelope protein as a new class of viral fusion protein (class II), and examined its arrangement on the virion surface. Changes in the envelope protein's hinge region, or its putative receptor-binding domain, are associated with changes in neurovirulence in animal models of JE. Clinically, JE causes a wide range of presentations, including a poliolike flaccid paralysis. Seizures and raised intracranial pressure are associated with a poor outcome, and may be potentially treatable. A safe efficacious formalin-inactivated vaccine against JE has been available for many years, but is too expensive for use in most Asian countries. A newer live attenuated vaccine has been used in China, but its use elsewhere has been restricted by regulatory concerns. A chimeric vaccine in which JE structural proteins are inserted into the 17D yellow fever vaccine backbone is one of several vaccines in development. There are no established antiviral treatments against JE. Interferon alpha was the most promising drug in small open trials, but a recent double-blind placebo controlled trial showed that it did not affect the outcome in children with JE.

Animals↗
PubMed2003

Infectious causes of acute flaccid paralysis.

PURPOSE OF REVIEW: Although acute flaccid paralysis (AFP) is more frequently seen in the tropics than in temperate regions, recent outbreaks of West Nile virus (WNV) in North America have drawn attention to this important presentation. Starting with anatomical and neurophysiological considerations, this article examines data on AFP caused by WNV, and considers recent data on paralysis caused by enteroviruses, and Guillain-Barré syndrome (GBS). RECENT FINDINGS: Neurophysiological, radiological and pathological studies suggest WNV causes AFP by damaging anterior horn cells in the spinal cord. The clinical presentation is probably best described as a 'poliomyelitis-like illness', and the disease as 'WNV myelitis'. Other findings during the recent outbreaks include increasing recognition of a Parkinson's-disease like presentation, and descriptions of virus transmission in blood transfusions and transplanted organs. GBS is now recognized as several disorders characterized by immune-mediated attack on peripheral nerves: in acute inflammatory demyelinating polyneuropathy the myelin sheath and Schwann cell of sensory and motor nerves are targeted; acute motor axonal and acute motor and sensory axonal neuropathy often follow Campylobacter jejuni enteritis and are associated with antibodies against the ganglioside component of the nerve axolemmal membrane. In Asia-Pacific, enterovirus 71 has caused outbreaks of neurological diseases with AFP and encephalitis, but no single genogroup of virus appears responsible for severe disease. SUMMARY: Despite the near eradication of poliomyelitis, AFP caused by viruses remains an important clinical presentation. Distinguishing direct viral causes from GBS is important for public health reasons, and to avoid inappropriate therapies.

Acute Disease↗