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Biomedical subjects

N Beyers

Publications and source records attributed to N Beyers.

At least 37 records · Page 2Linked to original sources
PubMed2005

Diversity of disease in childhood pulmonary tuberculosis.

Many factors can influence the dynamic balance that exists between the host and the pathogen (M. tuberculosis), but the host immune response seems to be the most important. This is illustrated by the vulnerability of immune-compromised individuals to develop tuberculosis and by the age-related spectrum of disease witnessed in immune-competent children. This age-related spectrum of disease reflects the ontogeny of the host immune response towards M. tuberculosis. Renewing our focus on the ontogeny of the immune response in children might provide valuable insights to direct future research regarding tuberculosis prevention, vaccine development and treatment.

Aging↗
PubMed2005

The association of prolonged breastfeeding and allergic disease in poor urban children.

The fact that breastfeeding may protect against allergic disease remains controversial, with hardly any reports from developing countries. This study investigated the association between allergic disease in children and prolonged breastfeeding. Data were collected from a 15% random sample of households from two poor suburbs of Cape Town, South Africa. Parents completed a validated International Study on Asthma and Allergies in Childhood questionnaire on allergic diseases for children aged 6-14 yrs. Other questions included breastfeeding duration, maternal smoking and parental allergy. Results were adjusted for possible confounders and for possible clustering within the household. Out of the 861 children included in the study, allergic disease in general, and hay fever in particular, were significantly less frequent in those with prolonged (> or =6 months) breastfeeding. There was a significant linear inverse association between breastfeeding duration and allergic disease in children without allergic parents, but not in children with an allergic predisposition. In conclusion, these results from a developing country suggest a protective effect of prolonged breastfeeding on the development of allergic disease, particularly hay fever, in children born to nonallergic parents. This protective effect was not found in children with an allergic predisposition.

Adolescent↗
PubMed2005

Development and evaluation of a new chest radiograph reading and recording system for epidemiological surveys of tuberculosis and lung disease.

OBJECTIVE: The development and evaluation of a new chest radiograph reading and recording system (CRRS) for community surveys of tuberculosis (TB) and lung disease. DESIGN: An experienced pulmonologist read 2608 chest X-rays (CXRs) performed as part of a TB prevalence survey using the newly developed CRRS. The kappa (kappa) for inter-reader agreement was calculated after a second reader reported on a stratified random sample of 810 (31%) of the 2608 CXRs. The kappa for intra-reader agreement was calculated from the repeated reporting of a stratified random sample of 104 CXRs. RESULTS: The kappa agreement between the two readers was 0.69 (95%CI 0.64-0.74) for abnormalities consistent with TB and 0.47 (95%CI 0.42-0.53) for any abnormalities. The kappa for intra-reader agreement was 0.90 (95%CI 0.81-0.99) for abnormalities consistent with TB and 0.85 (95%CI 0.74-0.95) for any abnormalities. CONCLUSION: This standardised method for CXR reading and recording provides satisfactory inter- and intra-reader agreement, making it suitable for surveys of TB and other forms of lung disease in the community. Its use will permit comparisons of results obtained in different surveys.

Epidemiologic Methods↗
PubMed2005

Criteria used for the diagnosis of childhood tuberculosis at primary health care level in a high-burden, urban setting.

BACKGROUND: Children contribute a significant proportion of the total tuberculosis (TB) case load in high-burden settings and present a major diagnostic challenge. OBJECTIVE: To document the criteria used at primary health care level to diagnose childhood TB in a high-burden, urban setting. METHODS: This retrospective descriptive study was conducted at two primary health care clinics in Cape Town, South Africa. Information on all children (<15 years of age) entered into the TB register from January 2002 through December 2003 was retrieved for analysis. RESULTS: During the study period, 1277 cases of TB were entered into the TB register, of which 268 (21.0%) were children. Information on 256 (95.5%) children was available for analysis. The majority (206, 80.5%) had intrathoracic TB, of whom 107 (51.5%) had uncomplicated lymph node disease, 79 (38.3%) complicated lymph node disease, 8 (3.9%) a pleural effusion and 12 (5.8%) adult-type cavitating disease. According to modified WHO criteria, the diagnosis of TB was confirmed in 27 (10.5%), probable in 193 (75.4%) and suspect in 36 (14.1%). DISCUSSION: The diagnostic criteria used at primary health care level demonstrated good agreement with current guidelines, but depended heavily on chest radiograph interpretation.

Adolescent↗
PubMed2004

Expansile pneumonia in children caused by Mycobacterium tuberculosis: clinical, radiological, and bronchoscopic appearances.

A cohort of 24 children with expansile pneumonia caused by Mycobacterium tuberculosis is described in mostly HIV-noninfected children (n = 22). The children presented with nonresolving pneumonia and a swinging fever (83%). On chest radiography, they had dense opacification with bulging fissures mainly in the upper lobes (75%). On computed tomography, the lobes are consolidated, with areas of liquefacation. Other features visible are enlarged mediastinal lymph adenopathy with ring enhancement (100%), cavities (63%), and tracheal compression (71%). On bronchoscopy, bronchi were obstructed by more than 75% in 20 (83%) of cases. Lymph gland enucleation was required in 42% of cases. Phrenic nerve palsy was present in 3 children, of whom 2 underwent diaphragmatic plication. The children received standard antituberculous therapy, to which prednisone (2 mg/kg/day) was added for 1 month. The mortality was 4% after 6 months of therapy.

Bronchoscopy↗
PubMed2004

Childhood tuberculosis: clinical research needs.

Childhood tuberculosis (TB) is common in the developing world, where over 90% of global TB cases occur, and has increased in human immunodeficiency virus (HIV) endemic regions. Most children with TB are not infectious, and so, from a public health perspective, are not afforded the same priority by TB control programmes as older age groups in settings of limited resources. In addition, the diagnosis of pulmonary TB is particularly difficult in young children. This has resulted in TB being a neglected disease in children, although it causes substantial morbidity and mortality. This review summarises the current knowledge of clinical aspects of childhood TB management, and aims to identify priority areas for future research. The most critical need is for improved capability to confirm diagnosis. This would lead to better management of childhood TB and would greatly enhance our ability to conduct meaningful research in many related areas, including immunological studies which could lead to a more effective vaccine. Also important are a better understanding of risk factors for infection and disease, including the impact of HIV, and operational research to improve treatment outcomes and management of well childhood contacts.

Adolescent↗
PubMed2004

The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era.

The pre-chemotherapy literature represents an impressive body of evidence that clarifies important epidemiological concepts in childhood tuberculosis. Reports describe the major transitions in tuberculosis, from exposure to infection and from infection to disease (morbidity and mortality), without the influence of chemotherapy. Children with household exposure to a sputum smear-positive source case experienced the greatest risk of becoming infected and of developing subsequent disease. Household exposure to a sputum smear-negative source case or non-household exposure still posed an appreciable, although greatly reduced, risk. Infection in children less than 2 years of age indicated a probable household source case. The majority of older children who were infected did not have a household source identified, and presumably became infected in the community. The annual risk of infection (ARI) was not constant across all ages, but seemed to increase during periods of widening social contact. Infants and adolescents were the groups at highest risk for disease development and death following primary infection.

Adolescent↗
PubMed2004

The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era.

The pre-chemotherapy literature documented the natural history of tuberculosis in childhood. These disease descriptions remain invaluable for guiding public health policy and research, as the introduction of effective chemotherapy radically changed the history of disease. Specific high-risk groups were identified. Primary infection before 2 years of age frequently progressed to serious disease within the first 12 months without significant prior symptoms. Primary infection between 2 and 10 years of age rarely progressed to serious disease, and such progression was associated with significant clinical symptoms. In children aged >3 years the presence of symptoms represented a window of opportunity in which to establish a clinical diagnosis before serious disease progression. Primary infection after 10 years of age frequently progressed to adult-type disease. Early effective intervention in this group will reduce the burden of cavitating disease and associated disease transmission in the community. Although the pre-chemotherapy literature excluded the influence of human immune deficiency virus (HIV) infection, recent disease descriptions in HIV-infected children indicate that immune-compromised children behave in a similar fashion to immune immature children (less than 2 years of age). An important concept deduced from the natural history of tuberculosis in childhood is that of relevant disease. Deciding which children to treat may be extremely difficult in high-prevalence, low-resource settings. The concept of relevant disease provides guidance for more effective public health intervention.

Adolescent↗
PubMed2004

SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa.

SETTING: Stellenbosch University Faculty of Health Sciences, and metropolitan Cape Town, Western Cape, South Africa. OBJECTIVE: To investigate whether the reported association between SLC11A1 (also NRAMP1) polymorphisms and susceptibility to tuberculosis (TB) can be confirmed in a different population, and whether polymorphisms in SLC11A2 (also NRAMP2, DCT1, DMT1) are associated with TB. DESIGN: A case-control study design was used to compare the frequencies of five polymorphisms in SLC11A1 and three in SLC11A2 between a group of bacteriologically confirmed TB patients and healthy community controls. RESULTS: The 5' (GT)9 allele in the promoter of SLC1A1 was found at significantly higher frequencies among 265 controls than in 224 pulmonary TB (PTB) patients (P = 0.002; OR 0.6; 95% CI 0.43-0.83). Homozygotes for the TGTG deletion (1729+55del4) in the 3'UTR of SLC11A1 were over-represented among PTB patients (P = 0.013; OR 5.19; 95% CI 1.42-18.94). Stepwise logistic regression analysis indicated that the 5' and 3' polymorphisms contribute separate main effects. Tuberculous meningitis patients (n = 22) showed the same allele and genotype frequency as PTB patients. No SLC11A2 polymorphisms tested were associated with TB. CONCLUSION: The 5' (GT)n allele driving the highest rate of transcription of SLC11A1 appears to be associated with protection against TB in the majority of the populations studied.

Adult↗
PubMed2003

Danish bacille Calmette-Guérin vaccine-induced disease in human immunodeficiency virus-infected children.

An analysis of isolates of Mycobacterium tuberculosis complex was performed to determine the prevalence of bacille Calmette-Guérin (BCG) disease among human immunodeficiency virus (HIV)-infected children. Speciation was done with polymerase chain reaction; 183 isolates from mycobacterial cultures for 49 HIV-infected patients were analyzed. The Danish Mycobacterium bovis BCG strain was isolated from 5 patients. No cases of Tokyo M. bovis BCG strain disease were detected. All patients were asymptomatic at birth, <12 months of age, and severely immunodeficient at presentation. Four patients had regional axillary adenitis ipsilateral to the vaccination site, and 2 had pulmonary BCG disease. Two patients with regional BCG disease had simultaneous pulmonary M. tuberculosis infection. Although chest radiographic features were similar to those seen in patients with tuberculosis, BCG disease should be considered in HIV-infected infants with right axillary adenitis ipsilateral to the vaccination site. Young, symptomatic, HIV-infected infants are at risk for BCG-related complications. Controlled, population-based studies are needed to assess the risk of BCG in HIV-infected children.

AIDS-Related Opportunistic Infections↗
PubMed2003

Use of genetic distance as a measure of ongoing transmission of Mycobacterium tuberculosis.

The stability of the genotypic marker IS6110, used to define the epidemiology of Mycobacterium tuberculosis, is one of the most important factors influencing the interpretation of DNA fingerprint data. We propose that evolved strains should be considered together with clustered strains to represent chains of ongoing transmission. For the present study we used a large set of fingerprint data for strains collected between 1992 and 1998 from residents of a community with a high incidence of tuberculosis in Cape Town, South Africa. Interstrain genetic distances were calculated by counting the banding pattern mismatches in the IS6110 DNA fingerprints of different isolates. These data demonstrate that the propensity to change by one or two bands is independent of the IS6110 copy number. Hence, the genetic distance between pairs of isolates can be simply expressed as the number of differences in the banding patterns. From this foundation, a data set which identifies newly evolved strains has been generated. Inclusion of these evolved strains into various molecular epidemiological calculations significantly increased the estimate of ongoing transmission in this study setting. The indication is that nearly all cases of tuberculosis in this community are due to ongoing transmission. This has important implications for tuberculosis control, as it indicates that the control measures used at present are unable to reduce the level of transmission. This technique may also be applicable to the study of low-incidence tuberculosis outbreaks as well as the analysis of epidemiological data from other disease epidemics.

DNA Fingerprinting↗
PubMed2003

Tuberculosis transmission patterns in a high-incidence area: a spatial analysis.

SETTING: In the Cape Town suburbs of Ravensmead and Uitsig, tuberculosis has reached epidemic levels, with notifications of 1340/100,000 in 1996. These suburbs are characterised by overcrowding, high unemployment and poverty. It is traditionally believed that tuberculosis transmission takes place mainly in households after close contact with an infectious person. Studies have recently linked tuberculosis transmission to locations outside the household, and have associated these places with a particular high-risk lifestyle. Anthropological studies in some suburbs of Cape Town, in which a very high number of local drinking places (shebeens) were identified (17 per km2), have suggested that social drinking is part of such a lifestyle. OBJECTIVE: To investigate various risk factors and places of transmission of tuberculosis using a geographical information system (GIS). RESULTS AND CONCLUSION: The 1128 bacteriologically-proven cases of tuberculosis studied over the period 1993-1998 were investigated using spatial epidemiological techniques of exploratory disease mapping. Point pattern analysis and spatial statistics indicated clustering of cases in the areas of high incidence. Significant associations of tuberculosis notifications were found with unemployment, overcrowding and number of shebeens per enumerator sub-district. High tuberculosis notifications with unemployment and its associated poverty emerged as the strongest association.

Adult↗
PubMed2003

Adult-to-child transmission of tuberculosis: household or community contact?

SETTING: If a child develops tuberculosis, it is assumed that the source was an adult infectious case, usually living in the same house. Restriction fragment length polymorphism (RFLP) was used in this study to establish transmission from source cases to children. DESIGN: Adult and child tuberculosis cases were prospectively identified from 1993 to 1998 and cultures of Mycobacterium tuberculosis collected. Interviews and RFLP analysis of M. tuberculosis strains were performed to establish epidemiological links and to confirm household transmission. RESULTS: Tuberculosis was confirmed by culture in 1139 (91%) of 1291 adults and 65 (16%) of 417 children. Due to problems in recovering specimens or extracting DNA, RFLP analysis was done in 832 adults and 35 children: 19 (54%) children had household members identified with tuberculosis, 12 with the same strain as the child. Twenty-nine (83%) strains from children formed part of community clusters, but definite contact with source cases was established in only 15. CONCLUSION: The presence of an adult with infectious tuberculosis in the same house as a child with tuberculosis does not necessarily imply adult-to-child transmission. Young children may be infected in the community or in the household. These findings have implications for contact tracing and treatment strategies in high incidence areas.

Adult↗
PubMed2002

Evolution of the IS6110-based restriction fragment length polymorphism pattern during the transmission of Mycobacterium tuberculosis.

Interpretation of the molecular epidemiological data of Mycobacterium tuberculosis is dependent on the validity of the assumptions that have been made. It is assumed that the IS6110 banding pattern is sufficiently stable to define epidemiological events representing ongoing transmission. However, molecular epidemiological data also support the observation that the IS6110 banding pattern may change over time. Factors affecting this rate may include the nature and duration of disease in a host and the opportunity to experience different host environments during the transmission cycle. To estimate the rate of IS6110 change occurring during the process of transmission, M. tuberculosis isolates from epidemiologically linked patients were genotypically characterized by restriction fragment length polymorphism (RFLP) analysis. The identification of IS6110 banding pattern changes during ongoing transmission suggested that a rate could be estimated. IS6110 change was significantly associated with strains with >5 IS6110 elements (P = 0.013) and was not observed in low-copy-number isolates. The minimum rate of appearance of variant strains was calculated to be 0.14 variant cases per source-case per year. This data suggest that clustering of isolates based on identical RFLP patterns is expected to underestimate transmission in patients infected with high-copy-number isolates. A model based on the rate of appearance of both variant and invariant strains demonstrates that the genotypically defined population structure may change by 18.6% during the study period of approximately 6.5 years. The implications for the use of RFLP data for epidemiologic study are discussed.

Adult↗
PubMed2002

Calculation of the stability of the IS6110 banding pattern in patients with persistent Mycobacterium tuberculosis disease.

The interpretation of molecular epidemiologic data of Mycobacterium tuberculosis infection is dependent on the understanding of the stability and evolutionary characteristics of the DNA fingerprinting marker used to classify clinical isolates. This study investigated the stability of the IS6110 banding pattern in serial tuberculosis isolates collected from patients resident in an area with a high incidence of tuberculosis. Evolutionary changes were observed in 4% of the strains, and a half-life (t(1/2)) of 8.74 years was calculated, assuming a constant rate of change over time. This rate may be composed of a high rate of change seen during the early disease phase (t(1/2) = 0.57 years) and a low rate of change seen in the late disease phase (t(1/2) = 10.69 years). The early rate probably reflects change occurring during active growth prior to therapy, while the low late rate may reflect change occurring during or after treatment. We demonstrate that the calculation of these rates is strongly influenced by the time interval between onset of disease and sputum sampling. These calculations are further complicated by partial replacement of the original strain population, resulting in the sporadic appearance of clonal variants in sputum specimens. Therefore, the true extent of genetic diversity may be underestimated within each host, thereby influencing molecular epidemiological data used to establish transmission chains.

Adult↗
PubMed2002

Historic and recent events contribute to the disease dynamics of Beijing-like Mycobacterium tuberculosis isolates in a high incidence region.

SETTING: A retrospective study in an urban setting with a high tuberculosis incidence. OBJECTIVE: To study the molecular epidemiology and disease dynamics of a prevalent Mycobacterium tuberculosis strain family, F29, a subset of the Beijing strains. DESIGN: Multi-locus DNA fingerprinting and genomic analysis was used to characterise F29 isolates. Demographic and molecular epidemiologic data were correlated with those of other isolates from the setting. The geographic locations of five F29 strain clusters were plotted using a geographic information system (GIS) and an index for geographic distribution was calculated. Their cumulative temporal occurrence was also plotted. RESULTS: The genomic similarity of F29 to the Beijing-strains was confirmed. A high degree of clustering predicted high disease transmission. Spatial distribution was mostly widespread except for one cluster. Smaller foci of transmission were observed. The temporal spread showed ongoing transmission. CONCLUSION: F29 belongs to the Beijing strain group. The prevalence and high degree of strain clustering, with limited geographic clustering, indicates that F29 strains are endemic in the study community. However, recent epidemiologic events also contributed to the disease spread. The combination of molecular epidemiologic, spatial and temporal data has enhanced our understanding of the disease dynamics of Beijing strains in our study community.

Adolescent↗