Tuberculous broncho-esophageal fistula in children: a description of two cases.
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Biomedical subjects
Publications and source records attributed to N Beyers.
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A re-emergence of tuberculosis (TB) is occurring world wide in both developed and developing countries. The clinical picture caused by infection with M. tuberculosis may simulate many other disease entities and may result in unnecessary investigations with a delay in diagnosis and treatment. Skeletal TB tends to be isolated to one anatomical site. We report a 6-year-old boy with disseminated skeletal TB with dactylitis resembling sickle cell anaemia and lytic lesions similar to those which are often seen in neuroblastoma, Langerhans' cell histiocytosis and leukaemia. The clinician should be aware that TB can mimic almost any disease and recognise the radiographic appearances of skeletal tuberculous lesions.
OBJECTIVE: To develop a scoring system for screening children for tuberculosis (TB) and for selecting suspects for further investigation in tuberculosis control programmes. Application of the score model, which would not require sophisticated or expensive technology, would be directed towards resource-poor countries with high prevalences of tuberculosis, where health care workers have to deal with diagnostic problems away from district hospitals or diagnostic facilities. DESIGN: Based on contributions from members of an IUATLD task group from 10 countries on the use of diagnostic criteria in childhood tuberculosis, criteria were selected to be used as elements in a score model. Data were collected by standardised questionnaire on 879 subjects aged under 15 years. Of these, 794 were considered probable or confirmed cases of tuberculosis by the diagnosing doctors. From each record, the criteria/procedures used in the diagnosis of probable/confirmed TB and regarded by the doctors as relevant criteria were selected. Bacteriology, histology and chest radiography were used either singly or collectively as the definitive reference (gold standard) against which the more subjective criteria (symptoms, clinical signs, skin test) would be evaluated. The latter criteria cited as relevant were then ranked and further explored for inclusion in the score model. The relative importance of each criterion to every other criterion on the list was expressed as weights, determined by employing a logarithmic least squares method to solve the ratio scale estimation problem which underlies decision-making involving more than one criterion. The resultant values were then assigned to each criterion in the final score model. RESULTS: The five clinical criteria thought to be most relevant as predictors of disease in children were history of contact with a case of tuberculosis, positive skin test, persistent cough, low weight for age, and unexplained/prolonged fever. In selecting the optimal cut-off points for the model at which tuberculosis would be suspected, low sensitivity and specificity (below 70%) but reasonably good positive predictive values (60%-77%) were obtained, depending on age group and epidemiological setting. In low tuberculosis prevalence settings, heavy reliance is placed by the model on a history of contact with a household case of tuberculosis and on a positive skin test, both of which have to be true. For high prevalence settings, more or less equal weighting is assigned to all five elements. Case contact and skin tests are less important, with low body weight, prolonged fever and cough being more indicative of tuberculosis. CONCLUSION: The model provides for epidemiological differences between target populations and should prove successful as a screening tool to select children for further investigation by radiography and bacteriology.
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Cerebrospinal fluid (CSF) adenylate kinase activity was determined in 88 children (mean age 32.6 months) at stage II (n = 40) and stage III (n = 48) tuberculous meningitis (TBM) at, or shortly after, the initiation of treatment, and at weekly intervals thereafter for the first month of treatment, and in 60 children (mean age 40 months) investigated for, but later considered not to have meningitis. CSF adenylate kinase activity in this latter group ranged from 0 to 1.27 u/l (mean 0.59 u/l). Mean CSF adenylate kinase activity during the first week of therapy in children at stage II TBM (2.95 u/l; range 0-9.22 u/l) differed significantly (p = 0.03) from that in children at stage III TBM (5.62 u/l; range 0-18.93 u/l). CSF adenylate kinase activity did not differ between children at stage II and stage III TBM during any of the 3 subsequent weeks. CSF adenylate kinase activity was not related to CSF cell count, total protein or glucose concentration or intracranial pressure at any point during the first month of treatment, but was related to CSF lactate during the first week of therapy (p = 0.001). Consecutive determinations of CSF adenylate kinase activity were available in 34 children. Although CSF adenylate kinase activity tended to increase or decrease in keeping with changes in clinical condition this was not always the case. The close relationship of CSF adenylate kinase activity and lactate concentrations suggests that adenylate kinase activity reflects hypoxic cerebral metabolism and it was unusual for children with increased CSF adenylate kinase activity at the time of diagnosis to be clinically normal on completion of 6 months of antituberculosis treatment. Any treatment modality which significantly reduced CSF adenylate kinase activity in children early in the course of TBM would probably be of clinical benefit to the patients.
The treatment of tuberculosis (TB) is a major challenge throughout the world. The Western Cape Region of South Africa has the highest occurrence of TB in the world. Here, TB is increasing due to improperly managed treatment programmes and inadequate facilities. The development of rules to aid medical practitioners in the early and accurate diagnosis of tuberculosis should prove worthwhile. A method to extract such diagnostic rules from an artificial neural network is presented. These rules accurately represent the knowledge embedded in the "raw" TB data.
OBJECTIVE: To determine the sociocultural understanding of tuberculosis among patients and their household members. DESIGN: Qualitative descriptive study. SETTING: Two adjacent Western Cape suburbs with a population of approximately 35,000, a tuberculosis incidence of > 1,000/100,000 and a surface area of 2.42 km2. SUBJECTS: Twenty-three adult patients on treatment for tuberculosis and their adult household members. INTERVENTIONS: None. METHODOLOGY: Consecutive selected adult tuberculosis patients and their household members were interviewed with an open-ended interview schedule. General household and community conditions and non-verbal responses were recorded. RESULTS: There were relatively affluent but also severely deprived households with severe overcrowding. Substance abuse was common. Patients had limited understanding and knowledge about health, hygiene and the cause of tuberculosis. There was a perception of both physical and social distance between patients and health care providers. All patients relied exclusively on the conventional biomedical curative approach of the medical system to deal with tuberculosis.
SETTING: A South African suburb with a high tuberculosis incidence (> 800/100,000). OBJECTIVE: To determine the prevalence of tuberculosis infection and disease in children less than 5 years of age who were in close household contact with adults with pulmonary tuberculosis. DESIGN: Prospective clinical study. SUBJECTS: Children under 5 years of age (of whom > 98% had been BCG vaccinated in the neonatal period) in household contact with an adult with tuberculosis. INVESTIGATION: Clinical investigation, Mantoux skin testing, chest radiography, gastric aspirate culture for Mycobacterium tuberculosis. RESULTS: Of 155 children younger than 5 years in contact with 80 index cases (83% smear positive), 14% were infected and 34% diseased. Children aged under 2 years had more severe disease (endobronchial tuberculosis and bronchial compression). Of 154 household members aged over 5 years who were assessed, 17 had culture proven pulmonary tuberculosis (13 smear positive) and a further 16 were placed an antituberculosis treatment on the basis of radiological evidence. CONCLUSION: In a high tuberculosis incidence area evaluation of and chemoprophylaxis for childhood contacts of adults with pulmonary tuberculosis is a rewarding procedure. The detection of culture and smear positive pulmonary tuberculosis amongst adolescent and adult household contacts emphasizes the role of contact tracing in the detection of infectious cases of pulmonary tuberculosis and the prevention of the spread of tuberculosis.
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SETTING: A tertiary care hospital in the Western Cape Province of South Africa from November 1983-October 1993. OBJECTIVE: Evaluation of the source of all cultures of Mycobacterium tuberculosis from children aged < 13 years and documentation of the mean time for culture with Löwenstein-Jensen (LJ) medium and a radiometric method (Bactec). RESULTS: One thousand six hundred and sixty cultures of M. tuberculosis were obtained from 1204 children (638 (53%) males and 566 (47%) females). The median time to a positive culture result was 65 days with LJ medium and 23 days with Bactec (P < 0.0001). Gastric aspirate provided 1298 cultures (78%) from 983 children (82%) of whom 52% were aged < 2 years. Ninety-six positive sputum specimens were from 79 children (7%) of whom 70% were > 5 years. Significantly more positive cultures were obtained during the late winter and early spring (P < 0.001), and a similar trend was found for tuberculous meningitis. CONCLUSION: The use of a radiometric culture method has expedited the confirmation of tuberculosis in childhood in our hospital. Even in children < 3 months of age the diagnosis of tuberculosis can often be confirmed by culture. The documented increase in childhood tuberculous disease in spring suggests an increased transmission of tuberculous infection in autumn and winter in our community.
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Little is known about the outcome of multidrug resistant (MDR) tuberculosis (TB) in developing countries. In this study, 443 patients with MDR-TB, defined as resistance to two or more antituberculosis drugs, were identified over the 2-year period 1987 and 1988 in the Cape Province of South Africa. The 5-year outcome of the 343 (77%) patients that could be traced by questionnaire was evaluated retrospectively during 1992 and 1993. Of these, 240 (70%) were resistant to both isoniazid (H) and rifampicin (R) with or without resistance to other first-line antituberculosis drugs and 103 (30%) were resistant to H or R and/or other antituberculosis drugs. Mortality was 116 (48%) and 28 (27%) in these groups respectively with a significantly greater risk of death in the first group. Only 114 (33%) of all the MDR-TB patients were cured after 5 years, 50 (15%) were respiratory disabled and 44 (13%) were still bacteriology positive. Twenty-four (7%) patients were lost during follow-up. Taking into account the high costs involved in treating MDR-TB patients and the scarce resources available in developing countries, more emphasis should be placed on direct observed therapy to cure newly diagnosed infectious drug sensitive tuberculosis patients, thus preventing MDR-TB rather than treating it.
Two highly polymorphic Mycobacterium tuberculosis genomic domains, characterized by hybridization to the oligonucleotide (GTG)5, were identified as potential DNA fingerprinting probes. These domains were cloned [pMTB484(1) and pMTB484(2K4), respectively] and shown to be useful for genotype analysis by Southern blotting. These probes were used to genotype geographically linked strains of M. tuberculosis previously shown to have identical IS6110 fingerprints. Subsequent DNA fingerprints generated with MTB484(1) and MTB484(2K4) showed a high degree of polymorphism, allowing subclassification of IS6110-defined clusters into composites of smaller clusters and unique strains. Correlation of the molecular data with patient interviews and clinical records confirmed the sensitivity of these probes, as contacts were established only within subclusters. These findings demonstrate the requirement for multiple probes to accurately classify M. tuberculosis strains, even those with high copy numbers of IS6110. The enhanced accuracy of strain typing should, in turn, further our understanding of the epidemiology of tuberculosis.
OBJECTIVE: To determine the geographical distribution of tuberculosis in the two Western Cape suburbs with the highest reported incidence of tuberculosis. DESIGN: Descriptive illustrative study. SETTING: Two adjacent Western Cape suburbs covering 2.42 km2 with a population of 34,294 and a reported tuberculosis incidence of > 1,000/100,000. SUBJECTS: All patients notified as having tuberculosis over a 10-year period (1985-1994). INTERVENTIONS: None OUTCOME MEASURE: The geographical distribution of the cases was determined using a geographical information system (GIS) and the National Population Census (1991). RESULTS: One thousand eight hundred and thirty-five of the 5,345 dwelling units (34.3%) housed at least 1 case of tuberculosis during the past decade and in 483 houses 3 or more cases occurred. These cases were distributed unevenly through the community, with the tuberculosis incidence per enumerator subdistrict (ESD) varying from 78 to 3,150/100,000 population. CONCLUSION: In a small area with a high incidence of tuberculosis, the cases are spread unevenly through the community and there are certain houses where tuberculosis occurs repeatedly. This information should be used to direct health services to concentrate on certain high-risk areas.
OBJECTIVE: To characterise Mycobacterium tuberculosis strains present in a community experiencing an epidemic, in order to establish whether a high rate of transmission results in low strain diversity. DESIGN: Sputum specimens collected for 18 months; IS6110-based DNA fingerprinting. SETTING: The communities of Ravensmead and Uitsig, Cape Town, South Africa. PARTICIPANTS: Three hundred and thirty-four pulmonary tuberculosis patients attending the Local Authority Health Care Clinic. MAIN OUTCOME MEASURE: DNA fingerprinting. RESULTS: A total of 334 M. tuberculosis isolates were characterised by IS6110-based DNA fingerprinting; 209 strains were identified, 199 having 5 or more insertions. Forty of these strains were present in 2 or more patients (clustering--126 patients in total), which indicates a recent transmission rate of 30%. The 163 unique strains suggest reactivation of latent infections. Computer analysis showed a high degree of strain diversity, and a common progenitor could only be linked to 33% of the strains. Clustering was shown in 50% of drug-resistant isolates. CONCLUSIONS: The low rate of transmission (30%) and the high degree of strain diversity (209 strains) was unexpected and unexplained, given the high burden of disease in this community. The clustering of drug-resistant strains suggests that transmission, rather than lack of compliance, drives the spread of antibiotic resistance in this community. Preliminary indications are that BCG vaccination, while having little effect on the incidence of tuberculosis in this community, may have altered the strain dynamics.
Concentrations of interferon gamma (IFN-gamma) in the lumbar cerebrospinal fluid (CSF) of 30 children (mean age, 27 months) being treated for stage III (16 children) and stage II (14 children) tuberculosis meningitis (TBM) were determined by ELISA. Nine children with stage III TBM and six with stage II TBM received prednisone (4 mg/kg). Concentrations of IFN-gamma in 73 CSF specimens (18 from the first week of therapy, 20 from the second, 19 from the third, and 16 from the fourth) were determined. The mean concentrations were 780 pg/mL in the first week of therapy and 554 pg/mL, 529 pg/mL, and 269 pg/mL in the second, third, and fourth weeks, respectively. Tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in 56 specimens from 23 of these same children were determined by ELISA. The mean CSF TNF-alpha concentration in 12 specimens obtained during the first week of therapy was 17 pg/mL, and the mean was 11 pg/mL during each of the subsequent weeks (14 specimens were evaluated in the second week and 15 specimens in the third and fourth weeks of therapy). Mean IL-1beta concentrations in these same groups of specimens were 52 pg/mL, 43 pg/mL, 42 pg/mL, and 18 pg/mL. No correlation could be shown between cytokine concentration and stage of disease, and no differences existed between those who did and those who did not receive prednisone. A significant decline in IL-1beta concentrations was shown during the 4-week period, but none in TNF-alpha or IFN-gamma concentrations was noted. Persistently high CSF INF-gamma concentrations in cases of TBM (as in cases of aseptic meningitis but not bacterial meningitis) at the time of diagnosis suggest an immune response fundamentally different from that in bacterial meningitis.
OBJECT: The aim of the study was to identify diagnoses that are confused with pulmonary tuberculosis in children. DESIGN: Prospective, investigative clinical study. SETTING: Tertiary care teaching hospital and an urban tuberculosis clinic in an area with a very high incidence of pulmonary tuberculosis (> 800 new cases/100,000/year). PATIENTS: Children suspected of having tuberculosis, children followed up for pulmonary infiltrates with eosinophilia and children with congenital pulmonary anomalies were investigated. INTERVENTION(s). None. OUTCOME MEASURE: Pulmonary tuberculosis was diagnosed using modified World Health Organisation criteria and the diagnoses of those children not suffering from pulmonary tuberculosis were analysed. RESULTS: Of the 354 children initially suspected of suffering from tuberculosis 71 (20%) were found to be suffering from other pulmonary disease, viz. pneumonia or bronchopneumonia (29%), bronchopneumonia with wheezing (18%), and asthma with lobar or segmental collapse (12%). Of 14 children suffering from pulmonary infiltrates with peripheral eosinophilia 6 (43%) were initially incorrectly diagnosed and treated for tuberculosis. Of 54 children with congenital pulmonary anomalies, 8 (15%) were treated for tuberculosis before the correct diagnosis was made. Congenital anomalies most often confused with tuberculosis were unilateral lung hypoplasia, bronchogenic cyst and tracheal bronchus with an anomalous lobe. CONCLUSIONS: The criteria for diagnosing tuberculosis in children is complicated in areas with a high incidence of tuberculosis and poor socio-economic circumstances where many children presenting with conditions other than tuberculosis will be in contact with an adult case of pulmonary tuberculosis. The commonest conditions confused with tuberculosis are pneumonia, bronchopneumonia and asthma. Pulmonary infiltrates with peripheral eosinophilia and congenital lung abnormalities should be considered especially if the children have an atypical clinical picture or do not respond to tuberculosis treatment.