High tuberculosis transmission rate in children with nursery exposure to undetected pulmonary tuberculosis.

SETTING: Nursery for newborns in Busan, Republic of Korea. OBJECTIVE: To evaluate tuberculosis (TB) transmission from a health care worker with active pulmonary TB to neonatal contacts. DESIGN: For the first investigation, infants who had been in the nursery 3 months before the index patient was diagnosed with pulmonary TB were enrolled. After a child who had stayed in the nursery 10 months before the diagnosis of the index patient was diagnosed with tuberculous meningitis, a second contact investigation was conducted. RESULTS: Respectively 315 and 1334 children participated in the first and second investigations. The mean age of the contacts was 66.3 days; the rate of latent tuberculous infection (LTBI) at the first investigation was 42.5% (134/315). Only one infant had an abnormal chest X-ray, and was thought to have pulmonary TB. In the second investigation, the mean age of the participants was 17.6 months. The proportion of children with LTBI was 18.7% (249/1334). CONCLUSIONS: The LTBI rate in the present study was much higher than that estimated from other contact investigations. To minimise the risk of nosocomial TB transmission to neonates, screening and management of TB in health care workers should be strengthened.

Tuberculosis outbreak in a primary school, Milan, Italy.

Investigation of an outbreak of tuberculosis (TB) in a primary school in Milan, Italy, found 15 schoolchildren had active TB disease and 173 had latent TB infection. TB was also identified in 2 homeless men near the school. Diagnostic delay, particularly in the index case-patient, contributed to the transmission of infection.

Efficient diagnosis of tuberculous meningitis by detection of Mycobacterium tuberculosis DNA in cerebrospinal fluid filtrates using PCR.

Tuberculous meningitis (TBM) is the most devastating form of meningitis and prompt diagnosis holds the key to its management. Conventional microbiology has limited utility and nucleic acid-based methods have not been widely accepted for various reasons. In view of the paucibacillary nature of cerebrospinal fluid (CSF) and the recent demonstration of free Mycobacterium tuberculosis DNA in clinical specimens, the present study was designed to evaluate the utility of CSF 'filtrates' for the diagnosis of TBM using PCR. One hundred and sixty-seven CSF samples were analysed from patients with 'suspected' TBM (n=81) and a control group including other cases of meningitis or neurological disorders (n=86). CSF 'sediments' and 'filtrates' were analysed individually for M. tuberculosis DNA by quantitative real-time PCR (qRT-PCR) and conventional PCR. Receiver-operating characteristic curves were generated from qRT-PCR data and cut-off values of 84 and 30 were selected for calling a 'filtrate' or 'sediment' sample positive, respectively. Based on these, TBM was diagnosed with 87.6% and 53.1% sensitivity (P<0.001) in 'filtrates' and 'sediments', respectively, and with 92% specificity each. Conventional devR and IS6110 PCR were also significantly more sensitive in 'filtrates' versus 'sediments' (sensitivity of 87.6% and 85.2% vs 31% and 39.5%, respectively; P<0.001). The qRT-PCR test yielded a positive likelihood ratio of 11 and 6.6 by analysing 'filtrate' and 'sediment' fractions, respectively, which establishes the superiority of the 'filtrate'-based assay over the 'sediment' assay. PCR findings were separately verified in 10 confirmed cases of TBM, where M. tuberculosis DNA was detected using devR PCR assays in 'sediment' and 'filtrate' fractions of all samples. From this study, we conclude that (i) CSF 'filtrates' contain a substantial amount of M. tuberculosis DNA and (ii) 'filtrates' and not 'sediments' are likely to reliably provide a PCR-based diagnosis in 'suspected' TBM patients.

Simultaneous tuberculous meningoencephalitis in two siblings.

UNLABELLED: The high morbidity and mortality of tuberculous meningoencephalitis (TBM) warrants an early diagnosis and treatment. BCG vaccine has been proven to reduce the incidence of disseminated disease in children. We report on two siblings (2-year-old boy and 4-year-old girl) with simultaneous TBM, whose parents originated from Kosovo, Albania, but presently reside in Germany. Early diagnosis of TBM was delayed, and at first the misdiagnosis of viral meningoencephalitis was made. Antituberculosis treatment was not initiated despite profound hyponatremia, hydrocephalus, and signs of inflammatory cerebral disease. After establishing the diagnosis of TBM, the boy died from antituberculosis, drug-induced hepatic failure; the sister survived with severe neurological deficits. Contact tracing revealed that TB had been transmitted by a household contact person with proven pulmonary TB who had refused antituberculosis treatment. A thorough contact investigation including tuberculin skin testing to identify children at risk for TB in the vicinity of this patient was not carried out. These case reports demonstrate an unusual simultaneous occurrence of TBM in a brother and sister. It draws attention to the importance of TBM as a differential diagnosis in children with suspected viral meningoencephalitis. CONCLUSIONS: To prevent severe neurological sequelae, early antituberculosis therapy should be considered in infants and children with a clinical impression of meningitis in the context of cerebrospinal fluid white blood cell count of less than 500 cells/microl and lymphocytic predominance, hyponatremia, and possible hydrocephalus. This notion is especially true for children originating from high-endemicity countries for TB. A rigid implementation of antituberculosis treatment of infected individuals and contact tracing is mandatory in order to prevent dissemination of TB in the community. The use of BCG vaccine should be considered in children at high risk for TB infection because of its potential to reduce disseminated TB.

Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis.

Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well documented in human immunodeficiency virus (HIV) positive subjects, but it is not fully recognised in HIV-negative subjects in the familial environment. We report three cases of MDR-TB in three young HIV-negative subjects from the same family. All the patients showed signs of meningitis during the course of their disease, and in two cases a resistant strain of Mycobacterium tuberculosis was isolated in cerebrospinal fluid. Two of the three subjects died from neurological complications; the other was successful treated utilising both systemic and intrathecal therapy for tuberculous meningitis. By a retrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoniazid, and were closely related in the two cases where specimens were available for analysis. The resistance was acquired in two patients initially infected with a susceptible strain; in the other patient, the resistance was present on the first sensitivity test for which results were available. This report demonstrates the high risk of fatality from MDR-TB for HIV-negative subjects in the absence of reliable early diagnostic and preventive tools. It also reinforces the concept that genetic susceptibility to M. tuberculosis may be an important factor in the clinical presentation and outcome of MDR-TB.

Tuberculous meningitis in children: problem to be addressed effectively with thorough contact tracing.

UNLABELLED: Worldwide, tuberculosis is the most common cause of death from a single infectious agent in children. There has been an increase in its incidence in Europe in recent years. Early diagnosis of tuberculous meningitis in children is extremely difficult because of its nonspecific early presentation and it is universally fatal if not recognised and treated. Young children are at increased risk of acquiring tuberculosis and it is more likely to be disseminated in neonates. In summarising the cases of three children with tuberculous meningitis admitted to our centre, we highlight the importance of diagnosis and contact tracing of the source case. CONCLUSION: Diagnosis of tuberculous meningitis requires a high index of suspicion, thorough contact tracing, and appropriate investigations with early treatment as the key to reducing morbidity and mortality.

Issues arising from two related cases of childhood tuberculous meningitis.

Two cases of childhood meningitis occurred in the same school within two weeks. The cases were cousins. The first case died and the aetiology was confirmed as tuberculous following a gene probe of a culture from the meningeal tissues at postmortem. The second case, with similar life threatening clinical features compatible with tuberculous meningitis, recovered. Seventy-seven contacts of the two cases among the immediate and extended families were screened. The adult sources of the infection were found to be two aunts of the second case, who were nurses working in the same nursing home. A further 73 contacts of the adult cases were identified. A total of eight close contacts to the aunts were given chemoprophylaxis and three were treated for tuberculosis. Contact tracing was also undertaken in the nursing home but no further cases were identified. These two cases highlight the difficulties in making a rapid diagnosis in tuberculous meningitis, the difficulties in handling media and public concern with limited information, and deciding on the appropriate level of contact tracing in special circumstances.

Tuberculous meningitis in a Filipino maid.

Tuberculous meningitis, while not uncommon in Taiwan, has not been reported among foreign workers. We report the first case of tuberculous meningitis in a 37-year-old Filipino maid in Taiwan, who presented with headache, fever and vomiting. She had been well before this episode and the small screening films of the chest radiograph obtained on her arrival in Taiwan 15 months previously, and every 6 months thereafter showed no evidence of tuberculosis. The suspicion of tuberculous meningitis was delayed until disturbance of consciousness manifested and a standard chest radiograph showed a diffuse miliary pattern in both lung fields. A cerebrospinal fluid sample that was sent for a polymerase chain reaction-based assay specific for Mycobacterium tuberculosis showed a positive result. The patient recovered with sequelae of mildly incoherent speech and urinary incontinence after antituberculous medication and short-course steroid treatment. Clinicians should be aware of the possibility of tuberculous meningitis in foreign workers with complaints of fever and headache. Because high-quality chest radiographs are a prerequisite for early detection of pulmonary tuberculosis, we recommended that standard posterior-anterior chest radiographs should be obtained as part of the routine health examination for foreign workers.

Sporadic tuberculous meningoencephalitis.

Tuberculous meningoencephalitis in a 24-month-old boy is reported. He contracted the infection from his apparently healthy grandfather with unnoticed pulmonary tuberculosis, as suggested by restriction fragment length polymorphism analysis of the isolated pathogen.

Use of DNA fingerprinting in international source case finding during a large outbreak of tuberculosis in The Netherlands.

SETTING: Tuberculosis outbreak in a low prevalence country. OBJECTIVE: Description of an international source tracing process in which restriction fragment length polymorphism (RFLP) analysis played an essential role. DESIGN: In 1993 a large scale source tracing process was initiated in Harlingen, a harbour town in the north of The Netherlands, after a child with tuberculous meningitis was reported for which no source could be identified. Traditional contact tracing followed the detection of sources of infection. RFLP was used to map the tuberculosis transmission and identify the source case. RESULTS: The investigation extended from the north to several places in the west of The Netherlands. In total 6519 persons were screened; there were 276 infections, among which 49 cases of active tuberculosis were identified. RFLP analysis of Mycobacterium tuberculosis isolates from all 28 culture positive patients showed the 'Harlingen' type DNA fingerprint. After 5 months source tracing led to the identification of the source case in the United Kingdom. Up to June 1996 altogether 37 patients (The Netherlands 28; the UK 7; Surinam 1; Morocco 1) were found to have isolates with the Harlingen type DNA pattern. Despite a thorough evaluation, in 5 of the 37 patients no relation to the source case or the outbreak in Harlingen could be established. CONCLUSION: RFLP typing proved a very useful instrument in guiding the process of international source tracing and contact investigation.

Intracranial tuberculosis in The Netherlands: four paediatric cases.

UNLABELLED: Since 1987 a resurgence of tuberculosis is occurring in the Netherlands in analogy to the situation in other industralised countries. So far this has not been associated with an increased incidence of tuberculous meningitis, which is still a rare complication of the disease. Four cases of intracranial tuberculosis were recently diagnosed in our hospital. All children were from middle-class Dutch families with no identified risk for tuberculosis. An extensive contact identification search could identify a contact in two patients. Two children were in an advanced stage of disease before diagnosis. Skin tests were repeatedly negative in all cases which delayed treatment in two cases for almost 2 weeks. One patient developing a cerebral tuberculous focus during therapy responded well to a second course of corticosteroids. Three children developed severe neurological sequelae. CONCLUSION: This report illustrates that suspicion of intracranial tuberculosis is warranted in the case of an ill-defined inflammatory neurological syndrome.

[Clinical and radiographic characteristics of tuberculosis in infants]. / Kliniko-rentgenologicheskaia kharakteristika tuberkuleza u detei rannego vozrasta.

Epidemiological and BCG vaccination background and clinicoroentgenological signs of tuberculosis were analysed with reference to epidemiological and BCG vaccination background in 177 infants. In infants tuberculosis was represented primarily by intrathoracic lymph node tuberculosis running as infiltrative, tumorous and minor. Disseminated tuberculosis and meningitis occurred as a rule within the first year of life. The disease most frequently arose due to tuberculosis contact. More than half of the children from the infection foci developed complications. In conditions of massive exogenic superinfection BCG vaccination fails to prevent infection and further progression of the disease.

[Extrapulmonary tuberculosis in childhood. Case reports from a pediatric specialty hospital]. / Extrapulmonale Tuberkulose im Kindesalter. Fallberichte aus einem pädiatrischen Schwerpunktkrankenhaus.

The immigration of people from countries with high incidence of tuberculosis has led to an increased number of cases of tuberculosis in Austria. The number of cases of extrapulmonary tuberculosis has increased too. The variability of the clinical presentation of extrapulmonary tuberculosis which can affect almost every organ system makes it essential to include it in the differential diagnosis of any infectious disease. Early identification and rapid onset of therapy are most important for recovering without complications and avoidance of longterm sequelae. 9 cases of extrapulmonary tuberculosis in the Gottfried von Preyer Children's hospital from 1989 to 1992 show the different clinical features of this disease. 3 cases of tuberculous lymphadenitis, 1 case of tuberculosis of the adenoids, 1 case of tuberclulous pleurits, 3 cases of gastrointestinal tuberculosis and 1 case of a tuberculous meningitis and osteomyelitis are described. All 9 children recovered with antituberculous treatment without complications or sequelae.

Evidence of transmission of tuberculosis by DNA fingerprinting.

OBJECTIVE: To determine whether a subject who had died of tuberculous meningitis had been infected by a neighbour. DESIGN: Retrospective comparison of isolates of Mycobacterium tuberculosis from the two cases and from 10 controls by DNA fingerprinting. SETTING: Public Health Service Reference Laboratory for Mycobacteria and bacterial molecular genetics unit of the London School of Hygiene and Tropical Medicine. SUBJECTS: Deceased and neighbour; 10 controls from the same city, from whom isolates had been collected over three months before the subject's death. MAIN OUTCOME MEASURES: Identity and similarity values (SAB) between fingerprint patterns from different isolates obtained by hybridisation of restriction fragments produced by PvuII with a probe from the insertion element IS6110/986, present in multiple copies throughout the genome of M tuberculosis. RESULTS: Isolates from the two cases under investigation had identical fingerprints whereas those from the controls were all distinct. Two clusters of isolates with a similarity coefficient > 0.25 were identified: in one, four out of five patients were born in the midlands (the birth place of the fifth was not known) and in the other all three patients were born in the Indian subcontinent. CONCLUSIONS: The data are consistent with, but do not prove, transmission of tuberculosis from the neighbour to the deceased. Geographical separation of the pools of infection may have led to the evolution of distinct clusters of fingerprint patterns. DNA fingerprinting of M tuberculosis is a powerful new tool for study of the epidemiology and pathogenesis of tuberculosis.