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Biomedical subjects

N Beyers

Publications and source records attributed to N Beyers.

At least 19 recordsLinked to original sources
PubMed2001

Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community.

Correct and rapid diagnosis is essential in the management of multidrug-resistant tuberculosis (MDR-TB). In this population-based study of 61 patients with drug-resistant tuberculosis, we evaluated the frequency of mutations and compared the performance of genotypic (mutation analysis by dot blot hybridization) and phenotypic (indirect proportion method) drug resistance tests. Three selected codons (rpoB531, rpoB526, and katG315) allowed identification of 90% of MDR-TB cases. Ninety percent of rifampin, streptomycin, and ethambutol resistance and 75% of isoniazid resistance were detected by screening for six codons: rpoB531, rpoB526, rrs-513, rpsL43, embB306, and katG315. The performance (reproducibility, sensitivity, and specificity) of the genotypic method was superior to that of the routine phenotypic method, with the exception of sensitivity for isoniazid resistance. A commercialized molecular genetic test for a limited number of target loci might be a good alternative for a drug resistance screening test in the context of an MDR "DOTS-plus" strategy.

Bacterial Proteins↗
PubMed2000

Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Adolescent↗
PubMed2000

Classification of drug-resistant tuberculosis in an epidemic area.

BACKGROUND: Traditionally, patients with drug-resistant tuberculosis are classified as having acquired drug-resistant or primary drug-resistant disease on the basis of a history of previous tuberculosis treatment. Only cases of primary drug resistance are assumed to be due to transmission of drug-resistant strains. METHODS: This descriptive study of 63 patients with drug-resistant tuberculosis assessed the relative contribution of transmission of drug-resistant strains in a high-incidence community of Cape Town, South Africa, by restriction-fragment length polymorphism (RFLP). The RFLP results were compared with the results obtained by traditional classification methods. FINDINGS: According to RFLP definitions, 52% (33 cases) of drug-resistant tuberculosis was caused by transmission of a drug-resistant strain. The proportion of cases due to transmission was higher for multidrug-resistant (64%; 29 cases) than for single-drug-resistant (no cases) tuberculosis. By the clinical classification, only 18 (29%) patients were classified as having primary drug-resistant tuberculosis (implying transmission). The clinical classification was thus misleading in 25 patients. INTERPRETATION: The term acquired drug resistance includes patients infected with strains that truly acquired drug resistance during treatment and patients who were initially infected with or reinfected with a drug-resistant strain. This definition could lead to misinterpretation of surveillance studies, incorrect evaluation of tuberculosis programmes, and delayed diagnosis and treatment of patients with multidrug-resistant disease. The clinical term acquired drug resistance should be replaced with the term "drug resistance in previously treated cases", which includes cases with drug resistance due to true acquisition as well as that due to transmitted drug-resistant strains.

Adolescent↗
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

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

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

Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment.

BACKGROUND: For decades it has been assumed that postprimary tuberculosis is usually caused by reactivation of endogenous infection rather than by a new, exogenous infection. METHODS: We performed DNA fingerprinting with restriction-fragment-length polymorphism analysis on pairs of isolates of Mycobacterium tuberculosis from 16 compliant patients who had a relapse of pulmonary tuberculosis after curative treatment of postprimary tuberculosis. The patients lived in areas of South Africa where tuberculosis is endemic. Medical records were reviewed for clinical data. RESULTS: For 12 of the 16 patients, the restriction-fragment-length polymorphism banding patterns for the isolates obtained after the relapse were different from those for the isolates from the initial tuberculous disease. This finding indicates that reinfection was the cause of the recurrence of tuberculosis after curative treatment. Two patients had reinfections with a multidrug-resistant strain. All 15 patients who were tested for the human immunodeficiency virus were seronegative. CONCLUSIONS: Exogenous reinfection appears to be a major cause of postprimary tuberculosis after a previous cure in an area with a high incidence of this disease. This finding emphasizes the importance of achieving cures and of preventing anyone with infectious tuberculosis from exposing others to the disease.

Adult↗
PubMed1999

Decline in total serum IgE after treatment for tuberculosis.

BACKGROUND: Infection with Mycobacterium tuberculosis induces a type-1 immune response, whereas intestinal parasites elicit a type-2 response. Given that type-1 and type-2 responses inhibit each other, we investigated if M tuberculosis downregulates serum IgE, a marker of a type-2 response. METHODS: A prospective study was done in the Western Cape Province of South Africa, where tuberculosis and intestinal-parasite infection are common. Total serum IgE was determined for 37 controls and for 33 adolescent patients at presentation with tuberculosis and after successful completion of treatment. IgE specific for ascaris and allergens were measured in a subset of these individuals. Mantoux skin tests were done on 35 controls and on 31 patients at diagnosis. FINDINGS: Total IgE concentrations were high in controls (mean 313 kU/L) and in patients before treatment (mean 457 kU/L, p=0.085) and declined in all patients following successful treatment (mean 175 kU/L, p<0.0001). Posttreatment IgE concentrations did not differ from concentrations in controls. Ascaris-specific IgE was lower in controls (mean 1.73 kU/L) than in patients before treatment (4.62 kU/L, p=0.023) and was 2.39 kU/L in patients after treatment (p=0.0625). Tuberculin induration correlated inversely with IgE in patients but not in controls. INTERPRETATION: Infection with M tuberculosis as such is not incompatible with a prominent IgE response. IgE concentrations decreased after successful treatment of tuberculosis, showing that IgE concentrations in human beings can be downregulated under these circumstances, presumably due to enhancement of a type-1 response.

Adolescent↗
PubMed1999

DNA fingerprinting and molecular epidemiology of tuberculosis: use and interpretation in an epidemic setting.

Tuberculosis (TB) is still a major cause of morbidity and mortality. It is clear that control requires more than simple availability of antibiotics. In order to gain insight into the disease, DNA fingerprinting has been applied to the study of bacterial population structure. This technology has been used to quantitate various components of the disease in a high-incidence community, viz. recent transmission (RT) and reactivation (RA) and to monitor these over time as a tool to quantitate changes in the epidemic. In our high-incidence community, we find unexpectedly high strain diversity, lower than predicted RT, and that reactivation disease dominates. This technology can be used to examine and challenge traditional dogmas. Quantitative measure of RT varies over time, using a two-year sliding window for estimation as a useful period. The results show that the "epidemic" consists of subepidemics characterized by strain families that wax and wane in the community of TB patients. The technology is shown to be a useful and quantitative tool to assess disease status and can therefore be used to monitor intervention strategies and refine and monitor results of new control measures.

DNA Fingerprinting↗
PubMed1999

Transmission of a multidrug-resistant Mycobacterium tuberculosis strain resembling "strain W" among noninstitutionalized, human immunodeficiency virus-seronegative patients.

Since 1990, several outbreaks of multidrug-resistant tuberculosis (MDR-TB) have been described among institutionalized patients infected with human immunodeficiency virus (HIV). We describe a community MDR-TB outbreak among HIV-seronegative patients in Cape Town, South Africa. Isolates were characterized by restriction fragment length polymorphism (RFLP) analysis and dot-blot hybridization analysis of mutations conferring resistance for isoniazid, rifampin, streptomycin, and ethambutol. All isolates were identical on RFLP analysis. In 2 patients, RFLP analysis showed exogenous reinfection during or after treatment for drug-susceptible TB. Mutation analysis confirmed the genotypic identity of the isolates. The infecting strain was genotypically related to strain W, which is responsible for the majority of MDR-TB outbreaks in New York City. Transmission of MDR-TB is thus not limited to HIV-seropositive patients in an institutional setting but occurs within a 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↗
PubMed1999

Impact of social interactions in the community on the transmission of tuberculosis in a high incidence area.

BACKGROUND: Tuberculosis (TB) is transmitted by close contact with an infectious person. It is assumed that close contact occurs amongst household members and that contact outside the house is "causal" and does not play a major role in the transmission of TB. METHODS: This study was conducted in an impoverished area with a high incidence of TB and a low HIV seropositive prevalence. Thirty three households with 84 TB patients were identified between February 1993 and April 1996 and the transmission of TB was studied by combining Mycobacterium tuberculosis fingerprinting with in depth sociological interviews. RESULTS: Forty two strain genotypes were identified in the 84 patients. In 15 households all the patients had identical strains, in nine households all the patients had different strains, and in nine households some patients had identical strains and one had a different strain. In 26 houses at least one patient had a strain which formed part of a larger community cluster and in 12 of these households the patient(s) had contact with a community member who had the identical strain. In 58% of the cases the contact took place while drinking in social groups. CONCLUSION: In high incidence areas contact outside the household may be important for the transmission of TB. This contact often takes place during recreation which, in the case of this study of impoverished people, consisted of drinking in social groups. Social interaction patterns should be studied and understood for effective implementation of control strategies.

Disease Transmission, Infectious↗
PubMed1999

Mannose-binding protein B allele confers protection against tuberculous meningitis.

Inhalation is the principal mode of entry for Mycobacterium tuberculosis in humans. Primary infection is usually restricted to the lungs and contiguous lymph nodes. In a subset of infected individuals, predominantly children, the infection is spread hematogenously to the meninges. The host factors that influence the development of tuberculous meningitis have not been well elucidated. The mannose-binding protein (MBP), a serum protein, is considered as an "ante-antibody." MBP has been shown to bind mycobacteria and acts as an opsonin in vitro. Although MBP plays a role in first-line host defense, it may under certain circumstances be deleterious to the host. In tuberculosis (TB), MBP may assist the spread of this intracellular pathogen. Therefore, we hypothesized that MBP genotypes that result in a phenotype of low MBP levels might be protective. We studied a well-defined South African population in which TB has reached epidemic levels. We found that the MBP B allele (G54D), which disrupts the collagen region of the protein and results in low MBP levels, was found in 22 of 79 (28%) of the TB-negative controls from the same community, compared with 12 of 91 (13%) of the patients with pulmonary TB (p < 0.017), and 5 of 64 (8%) of patients with tuberculous meningitis (p < 0.002). In addition, we found significantly lower serum MBP concentrations in TB-negative controls compared with postacute phase, fully recovered TB patients (p < 0.004). These findings suggest that the MBP B allele affords protection against tuberculous meningitis.

Adult↗