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Nulda Beyers

Publications and source records attributed to Nulda Beyers.

At least 19 recordsLinked to original sources
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

Tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy in children from a tuberculosis-endemic area.

BACKGROUND: Cervical lymphadenitis is the most common form of extrapulmonary tuberculosis in children, although its relative contribution as a cause of persistent cervical adenopathy is not well-documented. The aim of this study was to determine the relative contribution of tuberculous lymphadenitis as a cause of persistent cervical adenopathy in a tuberculosis-endemic setting and to document its clinical presentation at the primary health care level. METHODS: A prospective descriptive study was conducted from February 2003 through October 200 at 5 primary health care clinics in Cape Town, South Africa. The study included all children younger than 13 years presenting with persistent cervical adenopathy to the local primary health care clinic. RESULTS: A total of 158 children were evaluated of whom 35 (22.2%) were diagnosed with tuberculous lymphadenitis. Bacteriologic confirmation was achieved in 27 of 35 (77.1%) children; all 35 responded to standard antituberculosis treatment. The majority of those without tuberculous lymphadenitis (105 of 123, 85.4%) had a visible superficial lesion in the area drained by the affected nodes. In children with persistent lymphadenopathy > or =2 x 2 cm, tuberculosis lymphadenitis was diagnosed in 31 of 33 (93.9%); specificity was 98.4%, sensitivity was 88.6% and the positive predictive value was 93.4%. CONCLUSION: Children commonly present with persistent cervical adenopathy to the primary health care clinic. The use of a simple clinical algorithm provided an accurate diagnosis of tuberculous lymphadenitis in the study setting. Fine needle aspirations provided a rapid and definitive diagnosis in the majority of children and will have added diagnostic value in settings where alternative diagnoses are more likely.

Algorithms↗
PubMed2006

Radiographic signs and symptoms in children treated for tuberculosis: possible implications for symptom-based screening in resource-limited settings.

BACKGROUND: The World Health Organization advises active tracing of children younger than 5 years old in household contact with a sputum smear-positive tuberculosis index case. This study compared radiographic disease manifestations in 2 groups of children treated for tuberculosis in an endemic setting: those who presented with suspicious symptoms; and those actively traced as household contacts of an adult index case. METHODS: We conducted a prospective descriptive study from February 2003 through October 2004 at 5 primary health care clinics in Cape Town South Africa, including all children (younger than 5 years old) treated for tuberculosis (TB). RESULTS: A total of 326 children (younger than 5 years old) received antituberculosis treatment; 190 (58.3%) presented with suspicious symptoms, and 136 (41.7%) were actively traced contacts. Children were categorized as; "not TB" 71 (22%), intrathoracic tuberculosis 230 (70%) and extrathoracic tuberculosis 25 (8%). Significantly more actively traced contacts were categorized as "not TB" (odds ratio, 7.4; 95% confidence interval, 3.8-14.3), or demonstrated elements of the primary complex only on the chest radiograph (odds ratio, 26.2; 95% confidence interval, 8.6-89.2), compared with children who presented with suspicious symptoms. Of all children diagnosed with intrathoracic tuberculosis, 20 of 230 (9%) reported no symptoms, all of whom demonstrated elements of the primary complex only. CONCLUSIONS: The majority of actively traced contacts had minimal disease. Symptom-based screening would have identified all but 9% of children diagnosed with intrathoracic tuberculosis, all of whom demonstrated elements of the primary complex only. Further investigation is required to establish whether symptom-based screening can be justified to improve access to preventive chemotherapy in resource-limited endemic settings.

Antitubercular Agents↗
PubMed2005

Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns.

RATIONALE: Multiple infections with different strains of Mycobacterium tuberculosis may occur in settings where the infection pressure is high. The relevance of mixed infections for the patient, clinician, and control program remains unclear. OBJECTIVES: This study aimed to describe reinfection and mixed infection as underlying mechanisms of changing drug-susceptibility patterns in serial sputum cultures. METHODS: Serial M. tuberculosis sputum cultures from patients diagnosed with multi-drug-resistant (MDR) tuberculosis were evaluated by phenotypic drug-susceptibility testing and mutation detection methods. Genotypic analysis was done by IS6110 DNA fingerprinting and a novel strain-specific polymerase chain reaction amplification method. MEASUREMENTS AND MAIN RESULTS: DNA fingerprinting analysis of serial sputum cultures from 48 patients with MDR tuberculosis attributed 10 cases to reinfection and 1 case to mixed infection. In contrast, strain-specific polymerase chain reaction amplification analysis in 9 of the 11 cases demonstrated mixed infection in 5 cases, reinfection in 3 cases, and laboratory contamination in 1 case. Analysis of clinical data suggests that first-line therapy can select for a resistant subpopulation, whereas poor adherence or second-line therapy resulted in the reemergence of the drug-susceptible subpopulations. CONCLUSIONS: We have shown that, in some patients with MDR tuberculosis, mixed infection may be responsible for observations attributed to reinfection by DNA fingerprinting. We conclude that treatment and adherence determines which strain is dominant. We hypothesize that treatment with second-line drugs may lead to reemergence of the drug-susceptible strain in patients with mixed infection.

Antitubercular Agents↗
PubMed2005

Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis.

RATIONALE: In a high-tuberculosis (TB) incidence area of Cape Town, South Africa, there is a very high rate of unexplained recurrent TB. The incidence of new bacteriologically confirmed disease in the area is 313 per 100,000 individuals. OBJECTIVE: To estimate the rate of recurrent TB attributable to reinfection after successful treatment. METHODS: All patients with reported TB in the area between 1993 and 1998 were followed up to 2001 for disease needing retreatment (recurrences). Patients who were multi-drug-resistant or who had treatment failure, were transferred, or died during treatment were excluded. Analysis was restricted to patients for whom DNA fingerprinting of their Mycobacterium tuberculosis isolates was obtained. Reinfection TB was defined as a recurrent TB episode in which the strains of the separate episodes differed by more than four bands. MEASUREMENTS AND MAIN RESULTS: 612 of 897 (68%) patients had a DNA fingerprint available at enrollment. Median duration of follow-up was 5.2 years. Recurrent TB occurred in 108 of 612 (18%) patients, of whom 61 of 447 (14%) experienced recurrence after successful treatment, and 47 of 165 (28%) experience recurrence after default. Of the 108 patients with recurrent TB, 68 (63%) had a DNA fingerprint in the second episode. Among these patients, 24 of 31 (77%) recurrences after successful treatment and 4 of 37 (11%) recurrences after default were attributable to reinfection. The reinfection disease rate after successful treatment was estimated at 2.2 per 100 person-years. CONCLUSIONS: The age-adjusted incidence rate of TB attributable to reinfection after successful treatment was four times that of new TB. People who had TB once are at a strongly increased risk of developing TB when reinfected.

Adolescent↗
PubMed2005

TB: a partnership for the benefit of research and community.

A public-private partnership (PPP) involving Stellenbosch University in South Africa and GlaxoSmithKline (GSK) has benefited both research and a local community where tuberculosis (TB) is endemic. The venture, part of GSK's Action TB programme, enabled the University's Desmond Tutu TB Centre to establish an epidemiological field site in two suburbs of Cape Town where the annual risk of TB infection is 3.5%. Collaboration between the centre and GSK focused on the development of a surrogate marker model able to predict patient outcome with relative accuracy. Such models may be useful tools for diagnosis/prognosis and for shortening clinical trials of novel TB agents. Other research findings stemming from the Action TB partnership suggest that exogenous reinfection is responsible for the majority of relapse cases and that adults often have infection with multiple strains. The local community has been empowered by the implementation of the Directly Observed Treatment, Short-course (DOTS) programme and benefited from improved education about health in general and TB in particular. The centre has also provided employment for many local people in field work and other roles. Meanwhile, national and international publicity about the centre's work has aided in generating the essential political will to allocate resources and shape healthcare priorities, benefiting this impoverished community.

Adult↗
PubMed2005

Adult-type pulmonary tuberculosis in children 10-14 years of age.

We report 8 children (10-14 years of age) who were diagnosed with tuberculosis at their local primary health care clinic from July to September 2004, after routine sputum testing was extended to all children older than 10 years of age with suspected tuberculosis. This case series emphasizes that older children develop adult-type cavitating disease, which can be diagnosed by sputum smear microscopy, in contrast to younger children for whom smear microscopy has very little diagnostic value.

Adolescent↗
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↗
PubMed2004

Proportion of tuberculosis transmission that takes place in households in a high-incidence area.

The prevalence of infection among household contacts of people with tuberculosis is high. This information frequently guides active case finding. We analysed DNA fingerprints of Mycobacterium tuberculosis from 765 tuberculosis patients in Ravensmead and Uitsig, adjacent suburbs of Cape Town, South Africa. In 129 households in which DNA fingerprints were available for more than one patient, we identified 313 patients, of whom 145 (46%) had a fingerprint pattern matching that of another member of the household. The proportion of transmission in the community that took place in the household was 19%, and therefore, in this high-incidence area, tuberculosis transmission occurs mainly outside the household.

Adult↗
PubMed2004

Transmission of tuberculosis in a high incidence urban community in South Africa.

BACKGROUND: The objective of this study was to identify risk factors for ongoing community transmission of tuberculosis (TB) in two densely populated urban communities with a high incidence rate of TB in Cape Town, South Africa. METHODS: Between 1993 and 1998 DNA fingerprints of mycobacterial isolates from TB patients were determined by restriction fragment length polymorphism (RFLP). Cases whose isolates shared identical fingerprint patterns were considered to belong to the same cluster and to be attributable to ongoing community transmission. RESULTS: The average annual notification rate of new smear positive TB was 238/100000. In all, 1023/1526 reported patients were culture positive, and RFLP was available for 768 (75%) of the isolates from these patients. Since some patients experienced more than one infection during the study period, 797 cases were included in the analysis. Of the cases, 575/797 (72%) were clustered. Smear-positive cases and those who were retreated after default were more likely to be clustered than smear-negative and new cases, respectively. Patients from Uitsig were more often part of large clusters than were patients from Ravensmead. Age, sex, year of diagnosis, and outcome of disease were not risk factors for clustering, nor for being the first case in a cluster, although various analytical approaches were used. CONCLUSIONS: The incidence and proportion of cases that are clustered in this area are higher than reported elsewhere. An overwhelming majority of TB cases in this area is attributed to ongoing community transmission, and only very few to reactivation. This may explain the lack of demographic risk factors for clustering.

Adolescent↗
PubMed2004

Resistant Mycobacterium bovis Bacillus Calmette-Guérin disease: implications for management of Bacillus Calmette-Guérin Disease in human immunodeficiency virus-infected children.

Guidelines for the diagnosis and management of Bacillus Calmette-Guérin (BCG) disease in children are lacking, and there are limited data on drug resistance of Mycobacterium bovis BCG. A 6-month-old HIV-infected infant presented with right axillary adenitis ipsilateral to the site of BCG immunization. M. tuberculosis complex was cultured from axillary lymph nodes and gastric aspirates, and M. bovis BCG was isolated. Susceptibility testing before initiation of therapy demonstrated inherent resistance to isoniazid. The organism acquired rifampin resistance during therapy. This was confirmed by the presence of a mutation in codon 531 (Ser531Tyr) of the rpoB gene. Treatment guidelines for BCG disease with consideration of inherent and possible acquired drug resistance should be established in settings with high rates of vertical HIV transmission and routine BCG vaccination.

Animals↗
PubMed2004

Stability of polymorphic GC-rich repeat sequence-containing regions of Mycobacterium tuberculosis.

Mycobacterium tuberculosis cultures were subjected to DNA fingerprinting with IS6110- and polymorphic GC-rich sequence (PGRS)-containing probes. The PGRS banding patterns remained highly stable during multiple cultures of specimens from one disease episode (0.5% changed) and during transmission in patients with close contact (1.9% changed). Characteristic PGRS-restriction fragment length polymorphism motifs for different strain groupings may indicate distant evolutionary events leading to the differentiation of M. tuberculosis strain lineages.

Cytosine↗
PubMed2003

Patients with active tuberculosis often have different strains in the same sputum specimen.

It is generally accepted that tuberculosis results from a single infection with a single Mycobacterium tuberculosis strain. Such infections are thought to confer protective immunity against exogenous reinfection. In this study, a novel polymerase chain reaction method was developed to specifically identify M. tuberculosis strains belonging to the Beijing and non-Beijing evolutionary lineages in sputum specimens collected from tuberculosis patients resident in an epidemiologic field site in Cape Town, South Africa. The sensitivity and specificity of the polymerase chain reaction-based strain classification method were 100% (95% confidence interval, 85-100%) when compared with DNA fingerprinting and spacer oligotyping (spoligotyping). Application of this method showed that 19% of all patients were simultaneously infected with Beijing and non-Beijing strains, and 57% of patients infected with a Beijing strain were also infected with a non-Beijing strain. Multiple infections were more frequent in retreatment cases (23%) as compared with new cases (17%), but were not associated with sex, age, or smear grading. These results suggest that multiple infections are frequent, implying high reinfection rates and the absence of efficient protective immunity conferred by the initial infection. This finding could influence our understanding of the epidemiology of disease in high-incidence regions and our understanding for vaccine development.

Adult↗
PubMed2003

World TB Day 2003.

Explore the source record for details and available documents.

Antitubercular Agents↗
PubMed2002

Fine mapping of a putative tuberculosis-susceptibility locus on chromosome 15q11-13 in African families.

Host genetics plays an important role in individual susceptibility and resistance to infectious diseases, but no genes have yet been identified using genome-wide screens. Twin studies have indicated that tuberculosis susceptibility has a significant host genetic component, and several genes appear to be involved. Recently, a genome-wide linkage analysis of 136 African families identified chromosome 15q11-13 as a region with suggestive evidence of linkage, with a LOD score of 2.0. We tested 10 microsatellite markers and 5 positional candidate genes in this chromosomal region for deviation from random transmission from parents to affected offspring. The polymorphisms, lying in a region of 14 cM, were initially typed in the same 79 Gambian families used in the genome screen. A borderline significant association with a 7 bp deletion in UBE3A (P = 0.01) was found. This polymorphism was then evaluated further in a larger series of families with tuberculosis, including 44 Guinean families and 57 families from South Africa. Testing for association between the deletion and tuberculosis across all the families using the exact symmetry test further supported the association (overall P = 0.002). These fine-mapping data suggest that UBE3A or a closely flanking gene may be a tuberculosis-susceptibility locus.

Black People↗
PubMed2002

Tuberculosis in the tropics.

Tropical countries bear the brunt of the global TB burden. Young children are at high risk and suffer the most severe forms of TB; adults with pulmonary cavities are the main sources of transmission. The incidence in sub-Saharan Africa is increasing as a consequence of the HIV pandemic. Smear-negative TB, which is common in children and patients who have HIV infection, is becoming a major problem in resource-poor settings where access to mycobacterial culture and histopathology is limited. Clinical case definitions are being developed to address this problem. Short courses of rifampin-based therapy are not universally available, but access is increasing. DOTS is the main strategy that the WHO is promoting to improve TB control. This is particularly important for sputum smear-positive patients. Unfortunately, the DOTS targets set by the WHO have not yet been met. Innovative, low-cost ways of supervising therapy have been developed using family members or lay supervisors. Preventive therapy in tropical countries is limited to high-risk cases (young children and HIV-infected patients who are tuberculin skin test-positive). An improved TB vaccine would dramatically improve TB control.

Humans↗