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Biomedical subjects

P R Donald

Publications and source records attributed to P R Donald.

At least 19 recordsLinked to original sources
PubMed2001

Tuberculous granulomas in childhood tuberculous meningitis: radiological features and course.

The clinical course and serial cranial computerized tomographic (CT) findings of 202 children with tuberculous meningitis (TBM) admitted to Tygerberg Hospital between 1985 and 1994 were reviewed with regard to the incidence, CT appearance and clinical course of associated intracranial tuberculous granulomas. Thirty-four patients (16.85 per cent) had associated intracranial granulomas. Thirty-eight individual lesions were analysed and classified as meningeal, parenchymal or ependymal according to their central nervous system (CNS) location. Twenty-five patients had round to irregular, brain iso-, hypo- or hyperdense meningeal granulomas with variable degrees of enhancement and peri-lesional hypodensities. Four patients had diffusely enhancing, brain isodense, enplaque-like ependymal granulomas associated with the ventricular ependymal lining. Four patients with miliary tuberculosis and TBM showed multiple small diffusely enhancing, brain iso- or hyperdense parenchymal lesions and associated hypodensities on initial CT. Although granulomas in the meningeal and ependymal group had the propensity to paradoxically enlarge or appear on standard four-drug antituberculosis therapy, the majority resolved uneventfully. Rapid resolution of small parenchymal granulomas associated with miliary tuberculosis occurred in all cases. Most granulomas in this series were co-incidental, asymptomatic CT findings. In rare cases, the development or enlargement of a strategically located granuloma may result in complications.

Child↗
PubMed2000

Preventing tuberculosis in childhood.

Almost half of the cases of tuberculosis requiring treatment may arise in children. The strategies to control tuberculosis in developing countries remain firmly focussed upon adults who are smear positive. The prevention of tuberculosis in childhood has two aspects: prevention of infection and management of infection once it has occurred. The steps for prevention of infection include early diagnosis of adults with tuberculosis who are culture positive but not yet smear positive. Use of ultraviolet lighting or at least large windows and ventilation in the area where patients are kept may reduce the infection rate. An appropriate regimen and supervised chemoprophylaxis to ensure good compliance may be an important step towards control of tuberculosis infection.

Adolescent↗
PubMed2000

Serial lumbar CSF presure measurements and cranial computed tomographic findings in childhood tuberculous meningitits.

Intracranial pressure (ICP) was monitored in 218 consecutive children with hydrocephalus secondary to tuberculous meningitis (TBM). All children underwent cranial computerized tomographic (CT) scanning and continuous lumbar cerebrospinal (CSF) pressure monitoring on admission. Noncommunicating hydrocephalus (37 children), as determined by air encephalography, was treated by ventriculoperitoneal (VP) shunting and communicating hydrocephalus (181 children), by means of daily acetazolamide and frusemide. Response of ICP to treatment in the group with communicating hydrocephalus was assessed by means of repeated CSF pressure monitoring and CT scanning. One hundred and eighty-five of the 218 patients survived the 1st month of treatment. The aim of this study was the retrospective determination of (1) the relationship between ICP measurements and CT findings on admission and (2) the characteristics of the ICP recording which correlated best with the CT criteria of compensated hydrocephalus after the 1st month of treatment. No relationship was found between the level of baseline CSF pressure and the degree of hydrocephalus, as demonstrated by CT scanning, on admission. Seventy-five per cent of the patients with communicating hydrocephalus that survived the 1st month of treatment complied with the CT criteria for compensated hydrocephalus. All these patients had a baseline CSF pressure below 15 mmHg and absence of high-amplitude B waves on the pressure recording done at the end of the 1st month. In this study repeated lumbar CSF pressure monitoring proved to be an effective instrument to assess the response of communicating tuberculous hydrocephalus to medical treatment and also accurately predicted the timing of compensation of the hydrocephalus.

Acetazolamide↗
PubMed2000

The clinical and radiological features of tuberculosis in adolescents.

This retrospective review of clinical records and chest radiographs (CR) of adolescents aged 10-18 years was designed to determine age and sex differences in the clinical and radiological features of adolescent tuberculosis (TB). Records of adolescents who were admitted to Brooklyn Hospital for Chest Diseases (BCH) or who were treated at local authority health clinics were screened. Data from 324 adolescents (male:female ratio 1:1.2) were studied. Intra-thoracic lesions were present on CR in 306 (94%). Primary TB with mediastinal adenopathy was present in 32 (10%). Cavitation was present in 180 (56%), 16% at 10 and 73% at 18 years of age. Cavitation occurred in 55% of males and in 56% of females with increasing frequency from 15 years of age in the former and from age 14 in the latter. Microbiological confirmation of diagnosis was obtained in 254 (78%) cases, 52% in those aged 10-13 years and 86% in those > or = 14 years. Pleural effusion was present in 42 (13%), 26 males and 16 females (p < 0.05). Thirteen (7%) of the 182 hospitalized adolescents and 27 (19%) of the ambulant group did not complete therapy. The nature of tuberculous disease in adolescents changed dramatically with increasing age.

Adolescent↗
PubMed2000

A multicentre study of the early bactericidal activity of anti-tuberculosis drugs.

The early bactericidal activities (EBAs) of 300 mg isoniazid, 18.5 mg isoniazid, 600 mg rifampicin and 800 mg ofloxacin given daily to 262 patients with newly diagnosed pulmonary tuberculosis in Cape Town, Nairobi, Madras and Hong Kong were measured by counting cfu and total acid-fast bacilli in sputum collections taken pre-treatment (S1), at 2 days (S3) and at 5 days (S6). In Cape Town, Nairobi and Madras, the cfu findings suggested that isoniazid produced a massive kill, perhaps of actively growing organisms, during the first 2 days (mean S1-S3 EBAs of 0.636-1.006) but was almost inactive thereafter (mean S3-S6 EBAs of 0.000-0.081), whereas rifampicin maintained moderate activity against slowly growing organisms throughout the 5 days (mean S3-S6 EBAs of 0.242-0.305). This finding suggests that EBAs measured during the 2-5 day interval might be able to assess the sterilizing activity of drugs. Ofloxacin had moderately high mean S1-S3 EBAs of 0.130-0.391. However, in Hong Kong rifampicin appeared to be the most bactericidal drug from the start, possibly because patients had more chronic disease. A method of adjusting the cfu EBAs using total counts was devised which decreased the variability between patients within a treatment group without altering the mean cfu EBA. This resulted in a large gain in precision in Hong Kong, suggesting that their estimates were greatly affected by type II variation, due to dilution of pus by saliva and bronchial secretions, whereas small or no gains were obtained in the other three centres, suggesting that the main cause of variability was type I, due to other factors.

Adult↗
PubMed2000

Twice weekly vs. daily chemotherapy for childhood tuberculosis.

BACKGROUND: Treating childhood tuberculosis places a large burden on health services, and ways of lessening this were sought. METHODS: A randomized controlled trial was conducted to determine the effectiveness of fully intermittent twice weekly treatment for intrathoracic childhood tuberculosis and its effect on adherence to treatment, in comparison with daily (weekday) treatment. The setting was a district of Cape Town, South Africa, an area of high incident tuberculosis. We randomized 206 children with confirmed (4%), probable (94%) and suspected (2%) intrathoracic tuberculosis: 89 (median age, 25 months) received intermittent treatment; and 117 (median age, 28 months) received daily treatment. Intermittent treatment (twice weekly for 6 months) was isoniazid 15 mg/kg/dose, rifampin 15 mg/kg/dose and pyrazinamide 55 mg/kg/dose for 2 months, followed by isoniazid and rifampin only for 4 months. Daily treatment was isoniazid 10 mg/kg/day, rifampin 10 mg/kg/day and pyrazinamide 25 mg/kg/day on weekdays for 6 months. RESULTS: At 6 months 97% of subjects were discharged, with treatment outcomes in the two groups equivalent at that time (P = 0.90) and at the 18- to 30-month follow-up. One relapse occurred in the twice weekly group (P = 0.25). Adherence was equivalent; 70 children (79%) on intermittent and 90 (77%) on daily treatment took 75% or more of the prescribed doses (P = 0.90). Nonadherence over the full course of therapy was significantly associated with nonadherence during the first month of treatment (P = 0.0002) and household crowding (P = 0.002). CONCLUSIONS: Six month fully intermittent antituberculosis treatment is an effective and acceptable alternative to daily treatment.

Antitubercular Agents↗
PubMed2000

Transmission of multidrug-resistant tuberculosis.

AIM: To compare the Mycobacterium tuberculosis isolates of adult index cases with multidrug-resistant (MDR) tuberculosis to the isolates obtained from their child contacts. PATIENTS AND METHODS: A 4-year prospective study in the Western Cape Province of South Africa. We evaluated 149 child contacts of 80 adult MDR pulmonary tuberculosis cases. This report includes those cases where a culture for M. tuberculosis was obtained from both the adult source case and the child contact. Isolates were compared by drug susceptibility pattern and restriction fragment length polymorphism analysis. RESULTS: Six adult-child pairs with cultures for M. tuberculosis were identified. Two children had contact with more than one adult tuberculosis case. One child received previous isoniazid prophylaxis. Drug susceptibility pattern and restriction fragment length polymorphism analysis were identical for five adult-child pairs. One child, with no other known source case, had a strain different from that of the identified source case, but the MDR M. tuberculosis strain with which he was infected was prevalent in the community in which he resided. All children responded well to treatment. CONCLUSION: This study confirms that most of the childhood contacts of adults with MDR tuberculosis are likely to be infected by these MDR source cases despite their exposure to other drug-susceptible adults with tuberculosis in some instances. Child contacts of adults with MDR tuberculosis should be treated according to the drug susceptibility patterns of the likely source cases' M. tuberculosis strains unless their own strain's susceptibility testing indicates otherwise. Contact tracing remains of fundamental importance in identifying children at risk.

Adolescent↗
PubMed2000

Childhood tuberculosis.

Childhood tuberculosis will reflect the incidence of cavitating pulmonary tuberculosis in adults and will consequently be encountered most frequently in those areas with a high incidence of tuberculosis. Problem areas include our continuing inability to confirm the diagnosis of tuberculosis in many children, the escalating interaction of the human immunodeficiency virus (HIV) pandemic and tuberculosis, which is now evident with greater frequency in childhood, and the scarcity of data relating to antituberculosis therapy in childhood, which necessitates reliance on adult studies in many cases. This review highlights several options for obtaining material for culture of Mycobacterium tuberculosis in children, aspects of tuberculin testing, which remains one of the cornerstones supporting a diagnosis of tuberculosis in childhood, the potential importance of therapeutic drug monitoring in problem cases, new data giving epidemiologic and clinical details of the interaction of HIV infection and tuberculosis in children, and studies describing the epidemiology of tuberculosis in the developed and developing world.

AIDS-Related Opportunistic Infections↗
PubMed2000

Early bactericidal activity of paromomycin (aminosidine) in patients with smear-positive pulmonary tuberculosis.

The early bactericidal activity of the aminoglycoside paromomycin (aminosidine) in doses of 7.5 and 15 mg/kg of body weight was measured in 22 patients with previously untreated smear-positive pulmonary tuberculosis. The fall in log(10) CFU per milliliter of sputum per day during the first 2 days of treatment for 7 patients receiving a paromomycin dosage of 7.5 mg/kg/day was 0.066, with a standard deviation (SD) of 0.216 and confidence limits from -0.134 to 0.266, and that for 15 patients receiving 15 mg/kg/day was 0.0924, with an SD of 0.140 and confidence limits from 0.015 to 0.170. The difference between the mean and zero was not significant for the 7. 5-mg/kg dose group but was significant for the 15-mg/kg dose group (t = 2.55, P = 0.023). Since paromomycin has no cross-resistance with streptomycin and has no greater toxicity than other aminoglycosides, these results suggest that it has the potential to substitute for streptomycin in antituberculosis regimens and may be a particularly valuable addition to the drug armamentarium for the management of multidrug-resistant tuberculosis.

Adolescent↗
PubMed2000

Adjunctive thalidomide therapy of childhood tuberculous meningitis: possible anti-inflammatory role.

The objective of this study was to determine the safety and tolerability of the immunomodulatory agent thalidomide as adjunct therapy in children with tuberculous meningitis. Children with stage 2 tuberculous meningitis received oral thalidomide for 28 days in a dose-escalating study, in addition to standard four-drug antituberculosis therapy, corticosteroids, and specific treatment of complications such as raised intracranial pressure. Clinical and laboratory evaluations were carried out. Fifteen patients (median age, 34 months) were enrolled. Thalidomide was administered via nasogastric tube in a dosage of 6 mg/kg/day, 12 mg/kg/day, or 24 mg/kg/day. The only adverse events possibly related to the study drug were transient skin rashes in two patients. Levels of tumor necrosis factor-alpha in the cerebrospinal fluid decreased markedly during thalidomide therapy. Clinical outcome and neurologic imaging showed greater improvement than that experienced with historical controls. Thalidomide appeared safe and well tolerated in children with stage 2 tuberculous meningitis and could have important anti-inflammatory effects. These promising results have led us to embark on a randomized, double-blind, placebo-controlled trial of the efficacy of thalidomide in tuberculous meningitis.

Adjuvants, Immunologic↗
PubMed2000

Primary drug-resistant tuberculosis in children.

SETTING: The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence where initial isoniazid (INH) resistance and multidrug resistance (MDR) among adults was 3.9% and 1.1%, respectively, during 1992-1993. OBJECTIVE: To determine the drug resistance incidence among children as compared to adults, to compare the clinical features of drug-resistant and drug-susceptible TB, and the degree of INH resistance in isoniazid-resistant isolates. METHODS: All Mycobacterium tuberculosis cultures obtained from children (0-13 years) at a regional hospital were prospectively collected from August 1994 to April 1998 and susceptibility testing done on each child's specimens. Degree of INH resistance was determined in available resistant isolates. The children's clinical records were reviewed. RESULTS: Susceptibility results were available in 306/338 children with cultures of M. tuberculosis; 21 isolates (6.9%) were INH-resistant, and seven were MDR. Taking into account study limitations, the incidence of INH resistance was 5.6% and MDR 1% in children aged <5 years. Clinical features were similar in children with drug-susceptible and drug-resistant TB. CONCLUSION: The incidence of drug resistance in childhood tuberculosis in Western Cape is low, and probably reflects the level of primary drug resistance amongst organisms currently circulating in the community.

Adolescent↗
PubMed1999

Haematological abnormalities in children with tuberculosis.

Over a 16 month period 307 children with suspected tuberculosis (TB) and an available full blood count (FBC) seen at Tygerberg Hospital in South Africa were evaluated and categorized as confirmed (A), probable (B), and no TB (C) according to WHO criteria. There was no difference in the mean age of the 168 group A (33.6 months), 83 group B (34.4 months), and the 56 group C (31.6 months) children. A lower mean haemoglobin (Hb 10.2 vs. 10.8 g/dl) was the only significantly different haematological parameter in children with TB compared with the comparison group (Group C). There were no differences in median total white cell count, neutrophils, lymphocytes, monocytes, platelets, or the proportion of children in each group with anaemia, microcytosis, neutrophilia, neutropenia, lymphocytosis, lymphopenia, monocytosis, thrombocytosis or thrombocytopenia. The most common haematological abnormalities in children with TB were the presence of anaemia, neutrophilia, and monocytosis but these changes were found with equal frequency in control patients. Although haematological abnormalities are fairly common in children with TB, in a developing country these abnormalities also occur frequently in children with other non-tuberculosis respiratory infections. An FBC has no diagnostic predictive value when investigating a child for TB.

Child, Preschool↗
PubMed1999

Evaluation of young children in household contact with adult multidrug-resistant pulmonary tuberculosis cases.

BACKGROUND: The prevention and management of multidrug-resistant (MDR) tuberculosis has received much attention, but little attention has been given to children with MDR tuberculosis or children in contact with adults with MDR tuberculosis. The aim of this study was to determine the prevalence of tuberculous infection and disease in childhood contacts of adults with MDR pulmonary tuberculosis. METHOD: All children <5 years of age in household contact with 75 recently diagnosed adults with MDR pulmonary tuberculosis were evaluated. Evaluation included clinical examination, tuberculin skin test, chest radiography and culture for Mycobacterium tuberculosis from gastric aspirates. RESULTS: One hundred twenty-eight children, median age 27 months, were evaluated. Fifty children had recent contact with other adult tuberculosis cases. Sixty-six children previously had chemoprophylaxis or treatment of whom 36 defaulted treatment or received insufficient chemoprophylaxis. One child had HIV infection. Forty-seven children were classified as noninfected, 66 were considered infected only (Mantoux test, > or = 15 mm) and 15 had disease. Three children, who had not previously received antituberculosis drugs, had positive cultures for M. tuberculosis; all were multidrug-resistant. CONCLUSION: This study documents the transmission of multidrug-resistant M. tuberculosis to childhood contacts, the development of disease in these contacts and the importance of knowing the index case's M. tuberculosis susceptibility pattern in choosing a proper treatment regimen for the childhood contact.

Adult↗
PubMed1999

Childhood tuberculosis in an urban population in South Africa: burden and risk factor.

AIM: To study the epidemiology of childhood tuberculosis (TB) in a developing country. SETTING: Two urban communities of Cape Town, South Africa with a TB case notification rate of 1149/100 000. DESIGN: Retrospective descriptive study using the national population census (1991), 10 year official TB notification records, and a geographical information system. RESULTS: The case notification rate of TB in children 0-5 years old was 3588 cases/100 000 children aged 0-5 years, 3.5 times the case notification rate in adults. Children (0-14 years) accounted for 39% of the total case load. Childhood TB case notification rate correlated with parental education (r = -0.64), annual household income (r = -0.6), and crowding (r = 0.32). CONCLUSION: Children, especially those living in poor socioeconomic conditions, form an important epidemiological group and account for a notable proportion of the morbidity caused by TB. Efforts to improve TB control must therefore not only target adults (case detection and cure of infectious cases) but also children (screening of child contacts of adult cases) and the socioeconomic living conditions.

Adolescent↗
PubMed1998

The epidemiology of tuberculosis in South Africa.

Reports by reliable observers indicate that tuberculous disease did not occur to any great extent amongst South Africa's indigenous peoples prior to European colonization. Colonization introduced sources of infection and caused rapid urbanization for purposes of commerce and trade. By the start of the 20th century tuberculosis was recognized as a common health problem amongst the Black and Coloured peoples of South Africa. National notification commenced in 1921 and an incidence of 43 per 100,000 rose to 365 per 100,000 in 1958 and declined to 162 per 100,000 in 1986 before rising again to 221 per 100,000 in 1993. High incidences have been consistently recorded amongst the Coloured population of the Western Cape Province: in 1993 713 per 100,000 compared to the national incidence of 225 per 100,000. Using a computerized geographical information system the precise distribution of tuberculosis in two adjacent underprivileged, mainly Coloured communities, with a combined population of 34,000, is being studied. From 1985 to 1994 4044 notified tuberculosis cases gave an incidence of about 1200 per 100,000, varying from 78 to 3150 per 100,000 for the 39 enumerator subdistricts used for census purposes, and was highest in those with the lowest income. Of 5345 housing units 1835 (34%) housed at least one case of tuberculosis and 483 (9%) three or more cases. IS6110 DNA fingerprinting of strains from this community has shown a high degree of strain diversity (209 out of 334 strains evaluated). Clustering, indicative of recent transmission, was found in only 30% of isolates in this high tuberculosis incidence community.

Age Factors↗