Transmission of multidrug-resistant strains of Mycobacterium tuberculosis in a high incidence community.
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DNA Fingerprinting↗
Biomedical subjects
N Beyers
Publications and source records attributed to N Beyers.
Adenylate kinase activity in the cerebrospinal fluid of children with tuberculous meningitis and its relationship to neurological outcome.
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.
Adenylate Kinase↗
Extraction of rules for tuberculosis diagnosis using an artificial neural network.
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.
Diagnosis, Computer-Assisted↗
Sociological and anthropological factors related to the community management of tuberculosis in the Western Cape communities of Ravensmead and Uitsig.
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.
Adult↗
Identification of C to T mutation at position -236 bp in the human NRAMP1 gene promoter.
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Base Sequence↗
A decade of experience with Mycobacterium tuberculosis culture from children: a seasonal influence on incidence of childhood tuberculosis.
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.
Age Distribution↗
Stool microscopy and culture to assist the diagnosis of pulmonary tuberculosis in childhood.
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Child↗
The 5-year outcome of multidrug resistant tuberculosis patients in the Cape Province of South Africa.
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.
Adolescent↗
Genotyping of Mycobacterium tuberculosis with additional markers enhances accuracy in epidemiological studies.
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.
Bacterial Typing Techniques↗
The use of a geographical information system (GIS) to evaluate the distribution of tuberculosis in a high-incidence community.
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.
Adolescent↗
Unexpectedly high strain diversity of Mycobacterium tuberculosis in a high-incidence community.
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.
Adolescent↗
Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis.
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.
Child↗
TB or not TB? An evaluation of children with an incorrect initial diagnosis of pulmonary tuberculosis.
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.
Child↗
Respiratory tuberculosis in childhood: the diagnostic value of clinical features and special investigations.
During a 16-month period children presenting to a pediatric outpatient facility from an area with a high tuberculosis incidence (> 400/100,000) and suspected of having respiratory tuberculosis (TB) were evaluated for close contact with adult pulmonary tuberculosis, weight loss, symptom duration, respiratory signs, lymphadenopathy and hepatosplenomegaly and by chest radiography and tuberculin testing (Mantoux or tine). Probable tuberculosis was diagnosed in 258 children and was confirmed in 109 (42%) patients with a mean age of 31 months by culture of Mycobacterium tuberculosis from gastric aspirate or another source. Eleven children with confirmed TB had a normal chest radiograph. After review of special investigations, clinical course and follow-up of the remaining 149 children, 86 children (58%) with a mean age of 32.4 months were considered to have probable TB and 63 (42%) with a mean age of 27 months not to have TB. Significantly fewer children in the "not TB" group than in the confirmed and probable TB groups had a close adult pulmonary tuberculosis contact (13 (21%) and 95 (49%), respectively; P < 0.01). There was no difference between the "not TB" group and the confirmed and probable TB groups in the proportion presenting with weight loss, cough or other respiratory symptoms, a symptom duration > 2 weeks, the presence of bronchial breathing, wheeze, hepatomegaly or splenomegaly or peripheral lymphadenopathy. Final diagnoses in the "not TB" group included bacterial or viral pneumonia or bronchopneumonia in 37, asthma often accompanied by segmental collapse in 9 and cavitating pneumonia in 3 children.(ABSTRACT TRUNCATED AT 250 WORDS)
Child↗
Value of the lateral chest radiograph in tuberculosis in children.
The value of the lateral chest radiograph, often considered a useful adjunct in the detection of hilar adenopathy, was evaluated in a prospective study of 449 children assessed for tuberculosis. Of these children 298 presented to the hospital with signs and symptoms suggestive of tuberculosis, while 151 were investigated in a regional clinic solely because they were in close contact with an adult household member on treatment for tuberculosis. Tuberculosis was confirmed by culture in 176 of the 449 children (39%). In 40 of these (23%) hilar adenopathy was visible on frontal and lateral view, in 19 of the 176 confirmed cases (11%) only on a frontal view and in 22 (13%) on a lateral view only. Probable tuberculosis was diagnosed in a further 140 of the 449 children (31%), and hilar adenopathy was visible on frontal and lateral views in 39 of these children (28%), on the frontal view only in 8 (6%) and on the lateral view only in 27 (19%). In the symptomatic children investigated in the hospital, and the asymptomatic children investigated in the clinic, hilar adenopathy was detected on the lateral chest radiograph only in 36 (12%) and 14 (9%) cases respectively. Lateral chest radiographs will considerably improve the accuracy of the diagnosis of childhood tuberculosis.
Child↗
Delay in the diagnosis, notification and initiation of treatment and compliance in children with tuberculosis.
SETTING: The mortality and morbidity from childhood tuberculosis may be influenced by the delay from the time of first symptoms until the start of and compliance with treatment. OBJECTIVE: This study investigated these delay periods and the compliance with therapy in children with tuberculosis. DESIGN: During the study period there were 49 children with probable and 123 with confirmed pulmonary tuberculosis (WHO criteria). The mean period from first symptoms until presentation was 4.3 weeks, from presentation until notification 5 weeks and from notification until therapy 0.9 weeks. 16% of children notified as having tuberculosis never received therapy. Significantly fewer children in the urban squatter communities received therapy than in urban settled (P = 0.02), rural agricultural (P = 0.0001) and rural settled (P = 0.09) communities. 12% of children did not complete their therapy. CONCLUSION: The delay in presentation ('patient delay') was shorter than the delay in diagnosis ('doctor delay'). Failure to trace children and to complete therapy was particularly likely to occur in urban squatter communities. Easier access to health care facilities may shorten the 'patient delay' while greater awareness of tuberculosis and proper investigation of children may shorten the 'doctor delay'.
Child↗
Oligonucleotide (GTG)5 as a marker for Mycobacterium tuberculosis strain identification.
Culture of Mycobacterium tuberculosis provides no information on the identity of a strain or the distribution of such a strain in the community. Strain identification of M. tuberculosis can help to address important epidemiological questions, e.g., the origin of an infection in a patient's household or community, whether reactivation of infection is endogenous or exogenous in origin, and the spread and early detection of organisms with acquired antibiotic resistance. To research this problem, strain identification must be reliable and accurate. Although genetic identification techniques already exist, it is valuable to have genetic identification techniques based on a number of genetic markers to improve the accurate identification of M. tuberculosis strains. We show that oligonucleotide (GTG)5 can be successfully applied to the identification of M. tuberculosis strains. This technique may be particularly useful in cases in which M. tuberculosis strains have few or no insertion elements (e.g., IS6110) or in identifying other strains of mycobacteria when informative probes are lacking.
Adult↗