Gian D. van der Spuy
Stellenbosch University
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Featured researches published by Gian D. van der Spuy.
The Lancet | 2004
Suzanne Verver; Robin M. Warren; Zahn Munch; Madalene Richardson; Gian D. van der Spuy; Martien W. Borgdorff; Marcel A. Behr; Nulda Beyers; Paul D. van Helden
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.
Molecular Microbiology | 2003
Philip Supply; Robin M. Warren; Anne-Laure Bañuls; Sarah Lesjean; Gian D. van der Spuy; Lee-Anne Lewis; Michel Tibayrenc; Paul D. van Helden; Camille Locht
Deciphering the structure of pathogen populations is instrumental for the understanding of the epidemiology and history of infectious diseases and for their control. Although Mycobacterium tuberculosis is the most widespread infectious agent in humans, its actual population structure has remained hypothetical until now because: (i) its structural genes are poorly polymorphic; (ii) adequate samples and appropriate statistics for population genetic analysis have not been considered. To investigate this structure, we analysed the statistical associations (linkage disequilibrium) between 12 independent M. tuberculosis minisatellite‐like loci by high‐throughput genotyping within a model population of 209 isolates representative of the genetic diversity in an area with a very high incidence of tuberculosis. These loci contain variable number tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed repetitive units (MIRUs). Highly significant linkage disequilibrium was detected among the MIRU‐VNTR loci in this model. This linkage disequilibrium was also evident when the MIRU‐VNTR types were compared with the IS6110 restriction fragment length polymorphism types. These results support a predominant clonal evolution of M. tuberculosis.
Journal of Clinical Microbiology | 2001
Annelies van Rie; Robin M. Warren; Idris Mshanga; Annemarie M. Jordaan; Gian D. van der Spuy; Madalene Richardson; John Simpson; Robert P. Gie; Donald A. Enarson; Nulda Beyers; Paul D. van Helden; Thomas C. Victor
ABSTRACT 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.
Journal of Clinical Microbiology | 2002
Evgueni Savine; Robin M. Warren; Gian D. van der Spuy; Nulda Beyers; Paul D. van Helden; Camille Locht; Philip Supply
ABSTRACT Variable number tandem repeats (VNTRs) of elements named mycobacterial interspersed repetitive units (MIRUs) have previously been identified in 12 minisatellite loci of the Mycobacterium tuberculosis genome. These markers allow reliable high-throughput genotyping of M. tuberculosis and represent a portable approach to global molecular epidemiology of M. tuberculosis. To assess their temporal stability, we genotyped 123 serial isolates, separated by up to 6 years and belonging to a variety of distinct IS6110 restriction fragment length polymorphism (RFLP) families, from 56 patients who had positive sputum cultures. All 12 MIRU VNTR loci were completely identical within the groups of serial isolates in 55 out of 56 groups (98.2%), although 11 pairs of isolates from the same patients with conserved MIRU VNTRs displayed slightly different IS6110 RFLP profiles. In a single case, serial isolates with an unchanged IS6110 RFLP profile showed a change in 1 out of 12 MIRU VNTR loci. These results indicate that MIRU VNTRs are stable over time and therefore are suitable for reliable follow-up of patients chronically infected with tuberculosis over long periods. Moreover, they support MIRU VNTR genotyping as a powerful first-line method followed by subtyping by IS6110 RFLP to define ongoing transmission clusters.
Journal of Clinical Microbiology | 2002
Madalene Richardson; Nora M. Carroll; Erica Engelke; Gian D. van der Spuy; Faeeza Salker; Zahn Munch; Robert P. Gie; Robin M. Warren; Nulda Beyers; Paul D. van Helden
ABSTRACT In an ongoing molecular epidemiology study, human immunodeficiency virus-negative patients with first-time pulmonary tuberculosis from a high-incidence community were enrolled. Mycobacterium tuberculosis strains were identified by restriction fragment length polymorphism analysis with two fingerprinting probes. Of 131 patients, 3 (2.3%) were shown to have a mixture of strains in one or two of their serial cultures. This study further investigated these cases with disease caused by multiple M. tuberculosis strains in the context of the molecular epidemiology of the study setting.
Electrophoresis | 1999
Robin M. Warren; Madalene Richardson; Gian D. van der Spuy; Thomas C. Victor; Samantha L. Sampson; Nulda Beyers; Paul D. van Helden
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.
Clinical Infectious Diseases | 2014
Florian M. Marx; Rory Dunbar; Donald A. Enarson; Brian Williams; Robin M. Warren; Gian D. van der Spuy; Paul D. van Helden; Nulda Beyers
BACKGROUND There is increasing evidence from tuberculosis high-burden settings that exogenous reinfection contributes considerably to recurrent disease. However, large longitudinal studies of endogenous reactivation (relapse) and reinfection tuberculosis are lacking. We hypothesize a relationship between relapse vs reinfection and the time between treatment completion and recurrent disease. METHODS Population-based retrospective cohort study on all smear-positive tuberculosis cases successfully treated between 1996 and 2008 in a suburban setting in Cape Town, South Africa. Inverse gaussian distributions were fitted to observed annual rates of relapse and reinfection, distinguished by DNA fingerprinting of Mycobacterium tuberculosis strains recultured from diagnostic samples. RESULTS Paired DNA fingerprint data were available for 130 (64%) of 203 recurrent smear-positive tuberculosis cases in the 13-year study period. Reinfection accounted for 66 (51%) of 130 recurrent cases overall, 9 (20%) of 44 recurrent cases within the first year, and 57 (66%) of 86 thereafter (P < .001). The relapse rate peaked at 3.93% (95% confidence interval [CI], 2.35%-5.96%) per annum 0.35 (95% CI, .15-.45) years after treatment completion. The reinfection tuberculosis rate peaked at 1.58% (95% CI, .94%-2.46%) per annum 1.20 (95% CI, .55-1.70) years after completion. CONCLUSIONS To our knowledge, this is the first study of sufficient size and duration using DNA fingerprinting to investigate tuberculosis relapse and reinfection over a lengthy period. Relapse occurred early after treatment completion, whereas reinfection dominated after 1 year and accounted for at least half of recurrent disease. This temporal relationship may explain the high variability in reinfection observed across smaller studies. We speculate that follow-up time in antituberculosis drug trials should take reinfection into account.
PLOS ONE | 2012
Novel N. Chegou; Paulin N. Essone; Andre G. Loxton; Kim Stanley; Gillian F. Black; Gian D. van der Spuy; Paul D. van Helden; Kees L. M. C. Franken; Shreemanta K. Parida; Michèl R. Klein; Stefan H. E. Kaufmann; Tom H. M. Ottenhoff; Gerhard Walzl
Background Recent interferon gamma (IFN-γ)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-γ, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-α were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions Multiple cytokines other than IFN-γ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays.
The Journal of Infectious Diseases | 2014
Muneeb Salie; Lize van der Merwe; Marlo Möller; Michelle Daya; Gian D. van der Spuy; Paul D. van Helden; Maureen P. Martin; Xiaojiang Gao; Robin M. Warren; Mary Carrington; Eileen G. Hoal
BACKGROUND The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process. METHODS Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping. RESULTS We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen. CONCLUSIONS This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.
Journal of Clinical Microbiology | 2001
Samantha L. Sampson; Robin M. Warren; Madalene Richardson; Gian D. van der Spuy; Paul D. van Helden; Nancy E. Dunlap; William H. Benjamin
We read with interest the recent publication by Benjamin et al. ([2][1]) regarding the characterization of IS 6110 insertion sites in the direct repeat (DR) region of Mycobacterium tuberculosis . This topical and relevant study described the dissection of a single molecular event leading to an