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Biomedical subjects

Peter R Donald

Publications and source records attributed to Peter R Donald.

17 recordsLinked to original sources
PubMed2006

Tuberculous encephalopathy: a reappraisal.

Forty years ago Dastur and Udani described a form of diffuse cerebral damage in tuberculosis, which they called tuberculous encephalopathy. Their pathological and clinical observations led them to propose an immune pathogenesis. Although there have been no convincing independently reported series, the entity is now established in the tuberculosis literature. We review the literature on tuberculous encephalopathy, and suggest alternative aetiopathogenetic explanations for the appearances of the brain in these cases. We propose that tuberculosis is one of many infections which may be associated with a range of immune, drug-related, hypoxic-ischaemic and toxic diffuse brain pathologies.

Brain Diseases↗
PubMed2006

Brainstem tuberculoma presenting as eight-and-a-half syndrome.

We present a case of a young child who developed eight-and-a-half syndrome following a pontine tuberculoma, an unusual complication of central nervous system tuberculosis not previously described in an immunocompetent child. The combination of clinical findings allowed for precise localization of the lesion whilst magnetic resonance T1 weighted imaging with contrast provided valuable etiological information. We also discuss the management and outcome of the case.

Antitubercular Agents↗
PubMed2006

Childhood pulmonary tuberculosis: old wisdom and new challenges.

Childhood tuberculosis is neglected in endemic areas with resource constraints, as children are considered to develop mild forms of disease and to contribute little to the maintenance of the tuberculosis epidemic. However, children contribute a significant proportion of the disease burden and suffer severe tuberculosis-related morbidity and mortality, particularly in endemic areas. This review provides an overview of well-documented concepts and principles, and demonstrates how this "old wisdom" applies to current and future challenges in the field of childhood tuberculosis; the aim was to articulate some of the most pressing issues, to provide a rational framework for discussion, and to stimulate thought and further scientific study. The prechemotherapy literature that described the natural history of disease in children identified three central concepts: (1) the need for accurate case definitions, (2) the importance of risk stratification, and (3) the diverse spectrum of disease pathology, which necessitates accurate disease classification. The relevance of these concepts and their application to pertinent issues such as the diagnosis of childhood tuberculosis are discussed. The concepts are also linked to the basic principles of antituberculosis treatment, providing a simplified approach to the diagnosis and treatment of childhood tuberculosis that is independent of resource constraints. The main challenges for future research are highlighted and in conclusion it is emphasized that the infrastructure provided by the directly observed therapy, short-course strategy, combined with well-targeted interventions, slightly improved resources, and greatly improved political commitment, may lead to a dramatic reduction in tuberculosis-related morbidity and mortality among children.

Age Factors↗
PubMed2006

A critical look at the diagnostic value of culture-confirmation in childhood tuberculosis.

OBJECTIVES: To describe the clinical presentation, delay in diagnosis and treatment initiation, and outcome of culture-confirmed childhood tuberculosis. METHODS: Retrospective study of children<13 years of age at Tygerberg Children's Hospital, Cape Town, South Africa with culture-confirmed tuberculosis seen January 2002-June 2003. Data were collected by review of hospital and clinic records. RESULTS: Culture-confirmed tuberculosis was diagnosed in 184 children, median age 36 months; 26 (14.1%) were diagnosed clinically and treatment was started before admission. Tuberculosis was newly diagnosed in 158 children; 127 (80.4%) were clinically diagnosed and 31 (19.6%) were diagnosed only after culture result was known (culture-diagnosed). The median time from admission to diagnosis was 1 day (1-21 days) for clinically diagnosed, and 73 (34-178 days) for culture-diagnosed children. Treatment was initiated by hospital physicians in all 127 clinically diagnosed and 14/31 culture-diagnosed children. Of the 17 culture-diagnosed children not started on treatment, 4 were subsequently diagnosed on clinical grounds and treated at clinic level, 8 were found in good health, 4 failed to follow-up and 1 neonate died before the culture result was known. CONCLUSIONS: In symptomatic children, the vast majority could be confidently diagnosed on clinical grounds. However, culture-confirmation remains valuable to establish drug susceptibility.

Child↗
PubMed2006

Childhood drug-resistant tuberculosis in the Western Cape Province of South Africa.

AIM: Continued surveillance of drug resistance amongst children presenting with culture-confirmed tuberculosis to a tertiary care hospital and to community clinics. METHODS: Drug susceptibility testing for isoniazid and rifampicin was prospectively done on all children presenting with culture-confirmed tuberculosis from three study populations: children diagnosed at Tygerberg Children's Hospital in the Western Cape Province, South Africa, between March 2003 and February 2005 (recent survey, hospital-based group), and August 1994 and April 1998 (previous hospital-based survey), and a community-based group from five clinics during the recent survey. RESULTS: Isoniazid resistance increased significantly from 6.9% (21/306 children) in the previous survey to 12.8% (40/313 children) in the recent survey (odds ratio (OR) 1.99, 95% confidence interval (CI) 1.11-3.59). Resistance to isoniazid and rifampicin (multidrug resistance) did not increase significantly between the surveys (7/306 in previous survey vs 17/313 in recent survey; OR 2.45, 95% CI 0.94-6.62). All resistance (isoniazid and/or rifampicin) was 18/127 (14.2%) in the community-based group compared to 23/192 (12.0%) in the hospital-based group (OR 0.82, 95% CI 0.41-1.68). CONCLUSION: The prevalence of drug-resistant tuberculosis in this setting is increasing, reflecting ongoing transmission of drug-resistant Mycobacterium tuberculosis.

Adolescent↗
PubMed2006

Comparison of diagnostic criteria of tuberculous meningitis in human immunodeficiency virus-infected and uninfected children.

INTRODUCTION: Tuberculous (TB) meningitis is sometimes difficult to diagnose in young children. The decision to start anti-TB treatment of TB meningitis is usually made on clinical grounds and results of special investigations, such as cerebrospinal fluid examination and cranial computerized tomography (CT), because bacteriologic yield is low and the results delayed. AIM: To determine whether the clinical, laboratory, and radiologic criteria used in the diagnosis of TB meningitis in human immunodeficiency virus (HIV)-uninfected children apply to HIV-infected children. METHODS: Retrospective, case-control study. Clinical, laboratory, and radiologic features of TB meningitis were compared in 34 HIV-infected and 56 HIV-uninfected patients matched for age and stage of TB meningitis. RESULTS: All clinical differences found between the 2 groups at admission were related to the underlying HIV disease. Neurologic presentation and cerebrospinal fluid findings at admission did not differ significantly between the 2 groups. Significantly more HIV-infected than HIV-uninfected children had evidence of TB on chest radiography. The classic CT signs of TB meningitis (obstructive hydrocephalus and basal enhancement) were significantly less prominent in the HIV-infected group (P < 005). CONCLUSION: The diagnostic criteria for clinical diagnosis of TB meningitis apply to HIV-infected children. However, cranial CT findings in this group may be misleading and delay the diagnosis of TB meningitis.

Case-Control Studies↗
PubMed2006

Antimicrobial resistance in tuberculosis: an international perspective.

Drug-resistant tuberculosis is a threat to tuberculosis control programs and community health. This growing problem mirrors the increasing incidence of tuberculosis in general. Public health problems include the absence of early diagnosis and effective treatment. The real need is to identify tuberculosis patients far earlier, particularly those with drug-resistant strains, and to begin appropriate therapy, which is of the shortest possible duration with minimal risk of acquiring further drug resistance or permitting further transmission. This article will address the epidemic of drug resistance and discuss some of the inherent difficulties in the treatment of drug-resistant tuberculosis. We highlight some of the controversies and new findings in this area, as well as future perspectives requiring more active interventions, in addition to new technology and developments.

Antitubercular Agents↗
PubMed2005

The early bactericidal activities of rifampin and rifapentine in pulmonary tuberculosis.

RATIONALE: Comparison of the early bactericidal activity (EBA) of rifapentine and its pharmacokinetics with those of rifampin to determine the cause of poor clinical response and regrowth between doses, leading to rifamycin monoresistance at relapse. OBJECTIVES: Determination of the dose size of rifapentine that gives sufficient drug exposure to prevent regrowth. METHODS: EBA study over initial 5 days of treatment of 123 patients, half at Durban and half at Cape Town, who received single rifapentine doses of 300, 600, 900, or 1,200 mg rifapentine or five daily doses of 150, 300, or 600 mg rifampin, with a pharmacokinetic study on 58 patients measuring standard parameters for each dose size of rifamycin and their desacetyl metabolites. RESULTS: The EBAs for both rifamycins were similar, with a linear relationship to log dose at lower doses and a curvilinear response at higher doses giving a plateau at 1,136 mg rifapentine. The area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) agreed well for both rifamycins on the assumption that the only free 2% of free rifapentine and the 14% of free rifampin after plasma binding were active in the lesions. CONCLUSIONS: Only the free proportions of the rifamycins were active in lesions. From consideration of the pulse size and the duration of the postantibiotic lag, a 1,200-mg dose of rifapentine seemed necessary to improve response and to prevent regrowth between doses, and hence rifamycin monoresistance.

Adolescent↗
PubMed2005

Recurrent culture-confirmed tuberculosis in human immunodeficiency virus-infected children.

INTRODUCTION: Recurrent tuberculosis (TB) is more common among human immunodeficiency virus (HIV)-infected than HIV-uninfected adults. There are limited data regarding recurrence of TB in children. OBJECTIVE: To determine the occurrence of recurrent TB in HIV-infected children with culture-confirmed tuberculosis. METHODS: HIV-infected children with culture-confirmed TB, identified from 1992 to 2000, were followed until February 2004 for further confirmed TB episodes 6 months or more after completion of previous antituberculosis therapy. Clinical data and results of special investigations were recorded. Restriction fragment length polymorphism (RFLP) analysis of Mycobacterium tuberculosis isolates was done when possible. RESULTS: Of 87 children, 9 had a second episode; 2 of these had a third episode of confirmed TB. Adherence to treatment was good in 8; 2 experienced hepatotoxicity, and regimens were changed. Chest radiographs were normal in only 2 children after first treatment completion. Bacteriologic cure was documented in 7 episodes before recurrence. RFLP analysis showed 3 children infected with the same strain (relapse) and 1 child with a different strain between episodes 1 and 3 (reinfection). Two further cases had reinfection based on epidemiologic data and drug susceptibility test results. Full comparison of strains by RFLP was not possible because of the unavailability of isolates of the first episode in 5 cases. CONCLUSION: Recurrent TB in HIV-infected children is common in a high burden TB setting. Both relapse and reinfection occur.

Child↗
PubMed2005

Clinical features and outcome in children admitted to a TB hospital in the Western Cape--the influence of HIV infection and drug resistance.

BACKGROUND: The Western Cape has a high incidence of tuberculosis (TB) and a rising prevalence of HIV infection. Children form 15-20% of this TB burden. OBJECTIVE: To document the clinical features and outcome of TB among children admitted to a regional TB hospital. METHOD: A retrospective, descriptive study was undertaken of children under 15 years of age admitted to Brooklyn Hospital for Chest Diseases from January 2000 to December 2001. Demographic and clinical details of children were recorded routinely in a register that formed the basis of this review. RESULTS: Two hundred and thirty-eight of the 250 children admitted had TB, of whom 120 (50.4%) were boys. The median age was 25 months. Reasons for admission were disease severity in 99 cases, social reasons in 36, and a combination in 103. Adult source cases were identified in 138 instances; 9 had drug-resistant TB, 31 drug-susceptible TB and in 98 cases susceptibility was unknown. TB was confirmed by culture in 119 children. Of 79 in whom susceptibility testing was done, 10 had isoniazid-resistant TB and 8 multidrug-resistant TB. HIV serology was positive in 43 of 138 children tested (31%). Previous antituberculosis treatment, severe malnutrition and weight under the 3rd percentile for age, a negative Mantoux test, and mortality were significantly more common in the HIV-infected children. Twenty-two of 41 previously negative Mantoux tests (< 5 mm induration) were positive on retesting. CONCLUSIONS: HIV infection is common in children with TB and malnutrition, and mortality in this group is high. Repeat Mantoux tests may show an increased number of positive results.

AIDS-Related Opportunistic Infections↗
PubMed2004

A proposed radiological classification of childhood intra-thoracic tuberculosis.

One of the obstacles in discussing childhood tuberculosis (TB) is the lack of standard descriptive terminology to classify the diverse spectrum of disease. Accurate disease classification is important, because the correct identification of the specific disease entity has definite prognostic significance. Accurate classification will also improve study outcome definitions and facilitate scientific communication. The aim of this paper is to provide practical guidelines for the accurate radiological classification of intra-thoracic TB in children less than 15 years of age. The proposed radiological classification is based on the underlying disease and the principles of pathological disease progression. The hope is that the proposed classification will clarify concepts and stimulate discussion that may lead to future consensus.

Adult↗
PubMed2002

Childhood tuberculosis: out of control?

Because of the difficulty of confirming the diagnosis of childhood tuberculosis and because children do not make a significant contribution to the spread of tuberculosis, the burden of childhood tuberculosis in the world is uncertain. Several estimates make use of an arbitrary calculation assigning 10% of the tuberculosis burden to children. Available data linking the incidence of tuberculosis to the proportion of the tuberculosis caseload represented by children suggest an exponential rise in the proportion of the tuberculosis caseload caused by children as the tuberculosis incidence rises so that children may constitute nearly 40% of the caseload in certain high incidence communities. This review discusses the global burden of childhood tuberculosis and attempts to quantify this, the role of HIV/AIDS and tuberculosis in children, the problems this creates for diagnosis, and the occurrence of drug resistant tuberculosis in children. In the developing world, childhood tuberculosis is not under control, and, despite its importance as a child health problem, remains a neglected orphan disease.

Adolescent↗
PubMed2002

Human immunodeficiency virus infection in children hospitalised with tuberculosis.

The impact of HIV infection on clinical presentation and outcome of tuberculosis (TB) was studied in children hospitalised at the Brooklyn Hospital for Chest Diseases (BCH), Cape Town over the 2-year period January 1998 to December 1999. Clinical data were extracted from a prospectively compiled patient register. Of 261 children with TB, 114 (median age 24 mths) were not HIV-infected and 36 (median age 23 mths) were HIV-infected. The HIV status of 111 children (median age 37 mths) was not determined. Pulmonary TB with or without extrapulmonary TB occurred in 97 (85%) children who were not HIV-infected, 35 (97%) HIV-infected children and 87 (78%) of those not tested (p = 0.025). A tuberculin reaction > or = 15 mm was elicited in ten (31%) of 32 HIV-infected children, 76 (72%) of 106 non-HIV-infected and 62 (71%) of those not tested (p < 0.001). Mycobacterium tuberculosis was cultured from 116 (49%) of 238 children and drug sensitivity was evaluated in 79. Nine isolates (11%) were resistant to isoniazid (INH) and 11 (14%) to INH and rifampicin (RMP). Two HIV-infected children treated previously in BCH for drug-sensitive TB were re-admitted with INH and RMP resistance. Two (2%) non-HIV-infected children, six (17%) HIV-infected children and one (1%) child with undetermined HIV status died (p < 0.001).

AIDS-Related Opportunistic Infections↗
PubMed2002

Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up.

SETTING: The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence, where initial multidrug resistance (MDR) among adult TB cases was 1.1% during 1992-1993. OBJECTIVE: To determine the long-term prevalence of TB infection and disease in children in household contact with adults with MDR pulmonary TB, and to establish the efficacy of chemoprophylaxis in preventing disease in these children. METHOD: Children <5 years old in contact with 73 MDR TB adults were evaluated. Disease was treated by prescribing at least 2 drugs to which the adult's strain was susceptible. The remaining children were classified as infected or noninfected and received chemoprophylaxis according to the index's strain susceptibility or were followed up and treated when indicated. All were followed up for 30 months. RESULTS: At the initial evaluation 125 children were seen, median age 27.5 months. Of these, 119 were followed up. Fourteen (12%) had disease, 61 (51%) were infected only, and 44 (37%) were noninfected. By 30-month follow-up, 29 (24%) had developed disease and 64 (54%) were infected only. Four adult-child pair Mycobacterium tuberculosis isolates were compared by DNA fingerprinting; 3 were identical. All children who developed TB disease were clinically cured. Two (5%) of 41 children who received appropriate chemoprophylaxis and 13 (20%) of 64 who did not, developed TB during follow-up (odds ratio: 4.97). CONCLUSION: The study confirms MDR TB transmission to childhood contacts. Seventy-eight percent of children were infected or developed disease. Appropriate chemoprophylaxis may prevent disease in these children.

Adult↗