SEMINAR PAPER R Kay Infections of the nervous system: an A Wu update on recent developments ○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○ !"#$%&'()"*& The past decade has seen major changes in the field of infectious diseases. In particular, many new infections of the nervous system have been recognised, including the lethal infections of Enterovirus 71, and the Nipah and West Nile viruses. Increased interest in prion diseases has occurred, following the recognition of animal-to-human transmission in Europe. Familiar bacteria such as the pneumococcus continue to cause problems due to increasing resistance to multiple antibiotics. Furthermore, human immunodeficiency virus–infected and other immunocompromised patients are under the constant threat of opportunistic infections, many of which are targeted towards the brain and spinal cord. This paper reviews the changing world of nervous system infection, highlighting some of the most significant recent developments. !"#$%&'()*+,-./01234567 89:;< !"#$%&'()*71 !"# $%&'()*+,-. !"#$%&'()*+,-'./0123456*789:; !"#$%& '()*+,-./0123#415'6789 !"#$%&'()*+,-./01)2'(3456789: !"#$%&'()*+,- #./0123456789:; !"#$%&'()*+,-./0123-4&5678 Key words: Introduction Central nervous system infections/ diagnosis; To many physicians, the possibility of encountering a nervous system Central nervous system infections/ infection is always a source of anxiety. Not only are the physical signs treatment; of such infections often non-specific, but also the consequences of over- Opportunistic infections/ looking a treatable condition can be devastating. Moreover, the means epidemiology of making a rapid diagnosis may be limited. The recognition in the past 2 decades of a number of new infectious agents, some of which are potentially lethal, adds further uncertainty to this difficult area of medicine. ! !"#$%&'() The purpose of this paper is to highlight some of these newer nervous !"#$%&'() system infections which are of regional or global interest. Recent devel- !"#$%&'! opments in the management of older infections and opportunistic infec- tions affecting human immunodeficiency virus (HIV)–infected individuals HKMJ 2001;7:67-72 are also addressed. Department of Medicine and Therapeutics, Bacterial infections The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Pyogenic meningitis R Kay, MD, FRCP Pyogenic meningitis continues to be an important disease worldwide. A Wu, MB, ChB, MRCP (UK) Despite the availability of modern medical care, acute bacterial meningi- Correspondence to: Prof R Kay tis still carries a mortality rate for adults of 25%, which is similar to HKMJ Vol 7 No 1 March 2001 67 Kay et al the experience of the pre-antibiotic era.1 Historically, averted by the early introduction of corticosteroids.6 the three most important pathogens are Streptococcus Of more topical interest, is the concurrent 1998 out- pneumoniae, Neisseria meningitidis, and Haemophilus break of meningitis in previously healthy adults, caused influenzae. In North America and Europe, owing partly by the group B streptococcus, in Singapore and Hong to immunisation practices, the incidence of meningitis Kong. This pathogen normally only causes meningitis caused by H influenzae has declined but S pneumoniae in neonates.7 Unlike S suis meningitis, no particular and N meningitidis remain important pathogens in chil- risk factor was noted for this streptococcal meningitis; dren and young adults. In newborns, group B strepto- nor was it confined to women, whom group B strepto- coccus is the most common pathogen associated with cocci normally inhabit. It remains to be seen whether meningitis. Listeria monocytogenes, transmitted by this neonatal pathogen will emerge as a significant contamination of processed food, is also recognised cause of meningitis in Asia or elsewhere. as a significant cause of meningitis in newborns and the elderly in the United States.2 Tuberculous meningitis Tuberculous meningitis (TBM) is common in the Asian Of particular interest to Southeast Asian physicians region. The annual incidence of TBM in Hong Kong 8 is the fact that the common bacteria causing meningitis is estimated at 1.8 per 100 000 population. Although in this region are somewhat different from those reported classically described as an indolent disease, with a in the West. There are relatively few reports of mening- prodromal illness of malaise, headache, and fever itis caused by N meningitidis and H influenzae in this for 2 to 3 weeks, it is important to realise that TBM region and infections caused by L monocytogenes are can present acutely with disease progression occur- also uncommon. In contrast, Gram negative bacilli such ring within a few days. The diagnosis of TBM is not as Klebsiella pneumoniae and Pseudomonas aeruginosa always straight-forward. Although imaging or cerebro- are increasingly recognised as important pathogens, spinal fluid (CSF) findings are helpful, definitive both in the context of community-acquired meningitis diagnosis can only be made if Mycobacterium tuber- and nosocomial meningitis. This is particularly the case culosis is found in the CSF. Unfortunately, acid-fast stain- among the elderly and individuals with chronic debilitat- ing of the CSF is only 5% to 30% sensitive, and culture ing diseases such as diabetes, cirrhosis, and malignancy. has a sensitivity of only 20% to 50%.9 Since isolation of M tuberculosis usually requires several weeks, various Antibiotic-resistant strains of S pneumoniae, which tests have been developed for rapid diagnosis of TBM. remains the most important pathogen in community- At present, the most promising is the polymerase chain acquired meningitis, are also increasingly recognised. reaction (PCR) assay for DNA fragments of the myco- For nosocomial meningitis (mainly related to head in- bacterium in the CSF, with a sensitivity close to or better jury or neurosurgery), antibiotic-resistant strains of than culture (50% to 85%).10 In this era of increasing Staphylococcus aureus and Acinetobactor baumanii drug resistance, however, culture and sensitivity testing are causing problems for management.3 Empirical remains the cornerstone of management. treatment of community-acquired meningitis should include a third generation cephalosporin plus peni- Lyme disease cillin or ampicillin. For suspected penicillin-resistant Lyme disease, like syphilis, is a multisystem disease S pneumoniae, however, vancomycin should be used with variable neurological manifestations. It is caused in place of penicillin. In the treatment of neurosurgi- by a spirochaete, Borrelia burgdorferi, and transmitted cal or immunocompromised patients, vancomycin plus by ticks. In the United States, Lyme disease is of great ceftazidime are the recommended agents.4 interest, as it accounts for over 90% of vector-borne infections. Although the disease is more prevalent in Uniquely in Hong Kong, two species of strepto- North America and Europe, it has also been seen in cocci other than S pneumoniae have been identified as Japan and northeast China, and should be considered causes of community-acquired meningitis in adults. for patients returning from endemic areas with un- Meningitis caused by Streptococcus suis, once reported explained neurological syndromes. Diagnosis is often as the commonest cause of meningitis in Hong Kong, difficult as the CSF may be normal or show non-specific classically affects patients with occupational exposure findings, and antibody tests vary in sensitivity and to pigs or pork and causes early sensorineural hearing specificity. A prolonged course of antibiotic therapy loss.5 The incidence of this disease has declined in re- (such as ceftriaxone 2 g/d for 2 to 6 weeks) is required cent years and now only isolated cases are seen. None- for treatment. The prognosis is generally good and mor- theless, a high index of suspicion for this condition tality rare, although some late neurological sequelae should be maintained since the hearing loss may be may persist.11 68 HKMJ Vol 7 No 1 March 2001 Infections of the nervous system Whipple’s disease spread to abattoir workers in Singapore. Nipah virus Whipple’s disease is a much rarer systemic disorder is a novel paramyxovirus similar to, but distinct from, which also has a variety of central nervous system the Hendra virus which has caused several deaths (CNS) manifestations, including dementia, ophthal- among Australian racehorse workers. moplegia, and myoclonus. It can also present as aseptic meningitis with CSF findings showing mild Likewise, there was an outbreak of West Nile virus lymphocytic pleocytosis and elevated protein. infection in New York, in 1999.15 Initial cases were reported by a physician who noted the unusual Until recently, the diagnosis of Whipple’s disease features of the disease, including encephalitis as well has depended on the demonstration of macrophages as profound weakness. The virus is now identified as containing periodic acid Schiff positive material in an arbovirus belonging to the group of flaviviruses intestinal and other biopsies. Recently, however, a (other members include St. Louis and Japanese B PCR technique for detection of the causative agent, encephalitis viruses), transmitted by mosquitoes from Tropherema whippeli, has been developed and success- birds to humans. This viral infection had not been fully applied to the CSF. Treatment of Whipple’s dis- seen in the United States prior to 1999 and it has been ease consists of intravenous ceftriaxone for a month, postulated that the