Fatal Coxsackie B meningoencephalitis diagnosed by serology and in-situ nucleic acid hybridisation.
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Biomedical subjects
Publications and source records attributed to E J Bell.
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The role of coxsackie B viruses (CBV) in myo/pericarditis has been well documented; however, interpretation of static high neutralising antibody titres in individual patients has always been difficult. In introducing the mu-antibody capture ELISA test for the detection of CBV-specific IgM, we hoped to overcome this problem. A regimen for the routine serological diagnosis of CBV infections was introduced, using the CBV IgM ELISA as a screening test, followed by neutralisation tests (NT) to confirm the positive results. Seven hundred and sixty patients and 304 healthy adult controls were tested. The percentage CBV IgM positive in each of the clinical categories myo/pericarditis (33%) chest pain (22%), myalgic encephalomyelitis (31%), myalgia/Bornholm (19%) and controls (9%) was similar to those found in previous studies using NT alone. Cross-reactions with other enteroviruses, including hepatitis A (Enterovirus 72), were observed but did not prove to be a problem in the illness studied, since most involved adults. Both homotypic and heterotypic CBV IgM responses were found. Matching IgM and NT indicated a recent CBV infection. Positive IgM with negative NT titres suggested a recent infection with an enterovirus other than a CBV.
Between August and November 1985, 45 patients with suspected aseptic meningitis were investigated using conventional virus isolation procedures and the mu-antibody capture Coxsackie B IgM enzyme-linked immunoabsorbent assay (ELISA) test, which is well known to cross-react with other members of the enterovirus group. An enterovirus was isolated from 22% of patients compared with 67% who were positive in the ELISA test. Not only was the rate of enterovirus detection increased by using this ELISA method, the clinician received a result within 2 days of submission of serum to the laboratory. A positive result was reassuring to the patient and helpful in clinical management. The main disadvantage of this test was its cost since Coxsackie B1-5 virus antigens were essential. Development of a single inexpensive enterovirus-specific antigen is thus desirable.
The clinical, pathological, electrophysiological, immunological and virological abnormalities in 50 patients with the postviral fatigue syndrome are recorded. These findings confirm the organic nature of the disease. A metabolic disorder, caused by persistent virus infection and associated with defective immunoregulation, is suggested as the pathogenetic mechanism.
A study of 370 holidaymakers returning from Romania revealed that 279 (75%) reported illness. Alimentary symptoms predominated and were recorded either alone or along with other symptoms by 71 per cent of the tourists. The highest illness rate (82%) occurred in those under 39 years of age and those over 60 years had least illness (38%). Most of the tourists attributed their illnesses to the supply, handling or preparation of food and drink. Twenty-six (21%) tourists had serological evidence of typhoid immunisation out of 121 from whom blood samples were obtained. Most of the tourists studied (85%) were immune to poliomyelitis.
Paralytic poliomyelitis is now unusual in developed countries following the success of vaccination programmes. This paper reports a case of poliomyelitis in a patient with incomplete vaccination where the source of infection is unclear.
The results of a twelve-year study of Coxsackie B virus (CBV) infections in patients with a variety of acute and chronic illnesses are reported. CBVs were isolated from only 123 patients most of whom were children with respiratory illness. Virus diagnosis in adults was based mainly on the detection of significant rising or static high neutralizing antibody titres. Between 1972 and 1979 most investigations centred on patients with suspected viral heart disease, 12% of whom were found to have diagnostically significant CBV titres. In studies on patients with definite myo-pericarditis the number positive increased to 33%. In 1980 clinical interest switched to the possible role of CBV in myalgic encephalomyelitis (ME), an illness of diverse symptomatology. Investigation of suspected cases of ME in 1983 showed that 16% were serologically positive compared to 4% of normal adults in the West of Scotland. In patients with well-documented ME this figure rose to 41%. The demand by clinicians for CBV neutralizing antibody tests has increased over the past twelve years and continues to escalate annually, especially in patients with chronic relapsing illness.
Enterovirus 70 has recently emerged as a causative agent of epidemic acute haemorrhagic conjunctivitis ( AHC ). This paper is a report of the first association of enterovirus 70 with epidemic AHC in Nigeria. Despite numerous symptoms, including reduction in visual acuity, eventual recovery in 2 to 3 weeks with no functional loss was the rule except in 11 patients. Five of these patients ended up with superficial corneal scarring. Two had evisceration for unresolving panophthalmitis, while 4 went blind from ruptured corneal abscesses or ulcers. All the 11 patients had treated themselves or used traditional medications. None of the patients had signs of involvement of the central nervous system.
Irreparable damage to the anterior horn cells of the cervical and thoracic cord was found in a 20-week-old fetus whose mother was immune to poliomyelitis before conceiving but who was inadvertently given oral polio vaccine at 18 weeks gestation. Polio neutralizing antibody titres in sera, taken before and after pregnancy, were identical and were at levels normally regarded as providing protection. Unsuccessful attempts were made to isolate poliovirus from extracts of fetal brain, lung, liver and placenta. Fluorescent antibody tests were performed on various levels of the central nervous system and on the left and right extensor forearm muscles. Specific positive fluorescence to poliovirus 2 and 3 antigens was detected at dorsal spinal cord level only. One positive result was seen with Coxsackie A9 antiserum and fresh guinea-pig complement in the inflammatory cells in the right extensor forearm muscles.This experience, as yet unexplained, underlines the importance of ensuring that women are not pregnant prior to oral polio vaccination.
From January 1979 until December 1980, neutralizing antibody titres to Coxsackie B1-6 viruses were measured in sera from 220 patients presenting to a general medical unit, the majority of whom had chest pain. No four-fold or greater rises in antibody titre were detected in these hospital patients. However, 49 per cent had titres of greater than or equal to 256 to one or more Coxsackie B virus types compared with 10 per cent of the 950 persons studied during a 'normal population' survey in the West of Scotland. When a more rigorous threshold was adopted, titres greater than or equal to 512 were found in 33 per cent and 4 per cent respectively. We conclude that Coxsackie B infections are not uncommon in the practice of a general medical unit and that they may account for more cases of both acute and subacute left chest pain than is usually realised.
The relationship between the group B Coxsackieviruses and a wide variety of illnesses, particularly pleurodynia and myo/pericarditis, is already well established. The detection of raised levels of neutralizing antibody to these viruses in a group of patients in a rural practice presenting with an illness resembling myalgic encephalomyelitis (ME) was therefore unexpected. This is a most distressing and debilitating illness for the patient and the affected family. What is the immunological failure in these patients which apparently allows this virus to persist causing such unusual and bizarre illness? At present ME is probably much commoner than is realized, the majority of patients being given the dismissive diagnosis of psychoneurosis.
Twenty patients presenting with chronic ill-defined illnesses in a rural practice were investigated virologically. The only positive finding was the detection of elevated Coxsackie B titres in 16 of these patients. Three had experienced mainly cardiovascular symptoms; the remaining 13 are thought to have suffered from myalgic encephalomyelitis. This is a distressing and often prolonged illness, the cause of which is as yet unknown but is suspected of having a viral aetiology.
A total of 109 travelling people (people with a nomadic lifestyle), living on 8 separate sites in central and south Scotland, were examined for neutralizing antibodies to poliovirus types 1, 2, and 3. Of those studied, 10% had no detectable antibody to poliovirus type 3 while 7% had no antibody to type 1, the types most commonly associated with outbreaks of paralytic poliomyelitis. Only one subject, a child aged 9 years, had no detectable poliomyelitis antibody; he had no history of poliomyelitis immunization. The best protected groups of travellers were those located on sites with good facilities.As far as poliomyelitis is concerned, we conclude that travelling people in Scotland who live on well equipped sites do not pose a hazard to nearby settled populations and, indeed, are no more vulnerable to infection than members of those communities.
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For many years a substitute cell line has been sought to replace monkey kidney cell cultures for the diagnosis of enterovirus infections. Reports by various workers have shown that the RD cell line, derived from a human rhabdomyosarcoma, will support the replication of most of the prototype strains of enterovirus. The present study shows that, with the exception of the group B coxsackieviruses, RD cells are more sensitive than cynomolgus monkey kidney cultures for the isolation of a wide variety of enteroviruses from clinical specimens. Since regular access by many diagnostic laboratories to supplies of primary cell cultures is often difficult because of distance from source or cost factors, a simple cell culture system is proposed which should prove useful for the diagnosis of most of the important enterovirus infections.
Four ethnic groups of children from the Glasgow area--155 Asians, 85 Africans, 85 Chinese, and 93 Scots--were examined for neutralising to poliovirus types 1, 2, and 3. Only seven of the 418 children had no detectable antibody, and of these, four were aged less than 7 months; none had received polio vaccine. The best-protected children were the Chinese (93% with antibody to all three poliovirus types), followed by the African (81%), Scottish (78%), and Asian children (77%). We conclude that children of immigrants are no more vulnerable to poliovirus infection than their Scottish counterparts.