Cornelis Clay - Academia.edu (original) (raw)
Papers by Cornelis Clay
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2011
The New Delhi Metallo-β-lactamase (NDM) resistance mechanism in Enterobacteriaceae threatens to r... more The New Delhi Metallo-β-lactamase (NDM) resistance mechanism in Enterobacteriaceae threatens to render serious Gram-negative infections untreatable. The NDM-1 enzyme hydrolyses all available penicillin, cephalosporin and carbapenem antibiotics, and is commonly accompanied by additional resistance mechanisms to multiple antibiotic classes. Initially identified as a significant healthcare risk on the Indian sub-continent, it has rapidly become a global problem, posing significant diagnostic and management challenges. Here we report the first laboratory-confirmed case of NDM-1 in South Africa.
Mammalian neocortex is important for conscious processing of sensory information with balanced gl... more Mammalian neocortex is important for conscious processing of sensory information with balanced glutamatergic and GABAergic signaling fundamental to this function. Yet little is known about how this interaction arises despite increasing insight into early GABAergic interneuron (IN) circuits. To study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex, specifically the role of INs in early speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity and showed refinement over the period leading to active whisking onset. To test the contribution of IN subtypes, we conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations inf luenced both spontaneous and sensory-evoked cortical activity in an age-and layer-dependent manner. Silencing SST + INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP + IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results show that these IN subtypes contribute to early sensory processing over the first few postnatal weeks.
Create a successful workflow for PCR ◦ Earlier years – contamination of PCR rxn,s with amplificat... more Create a successful workflow for PCR ◦ Earlier years – contamination of PCR rxn,s with amplification product from previous PCR was a potential problem To Combat contamination – ◦ Three separate rooms Preparing the reaction Amplification Analysis of amplified products New instruments – closed systems – less contamination risk Facilities still need to be well designed No inflexible guidelines in molecular lab design – primary emphasis is avoidance of contamination with each step of the workflow
Journal of clinical …, 2000
In a study carried out in small-town and rural primary health care centers in southwestern Nigeri... more In a study carried out in small-town and rural primary health care centers in southwestern Nigeria, 330 Escherichia coli strains isolated from 187 children with diarrhea and 144 apparently healthy controls were examined for virulence traits. Based on the results of colony blot ...
Background: Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are imp... more Background: Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are implicated in the pathogenesis of gastric adenocarcinoma (GCA), but have not been investigated together, in the South African context of low GCA incidence and high H pylori prevalence. Aims: To determine, based on these factors, the potential for developing GCA in a local cohort with H pylori-associated dyspepsia. Methods: Seventy-nine patients underwent gastroscopy and biopsy. Helicobacter pylori-positive biopsies were analysed for virulence factors; cytotoxin-associated antigen (CagA) and vacuolating toxin (VacA) and mosaics (Vac A m1/m2, Vac A s1/s2 or combinations). Host DNA was analysed for targeted regions in IL-1B and IL-1RN genes, to determine polymorphisms of IL-1B-511*T and IL-1RN (variable number tandem repeat [VNTR]). Results: The mean age was 43 years (SD ±11.7), 66% were female. Forty-eight patients (60%) were H pylori positive, 50% (24/48) demonstrated a virulent organism and 42% (20/48) of these demonstrated the most virulent carcinogenic combination; VacA m1/s1 and CagA. IL-1RN VNTR was sequenced in 25 specimens and IL-1B511 polymorphisms in 48 patients; the high-risk IL-1B511 TT allele was present in 52% (25/48) and TC allele in 33% (16/48). Overall, 85% (41/48) of patients demonstrated high-risk genetic polymorphisms. The highest risk associated with GCA, a combination of H pylori VacAm1/s1 virulence factor and IL-1B511 TT or TC allele, was demonstrated in 42% (20/48). Conclusion: Almost half the patients have a combination of virulent H pylori and carcinogenic IL polymorphism. The implication of these observations on the risk of developing GCA requires further elucidation. How to cite this article: Rush CJ, Hoosien E, de Villiers N, et al. Helicobacter pylori virulence factors and host genetic polymorphisms in a low gastric cancer incidence and high H
Bulletin of the World Health Organisation
WHO considers that environmental surveillance for wild-type polioviruses is potentially important... more WHO considers that environmental surveillance for wild-type polioviruses is potentially important for surveillance for acute flaccid paralysis as a means of confirming eradication of poliomyelitis. The present study investigated methods for detecting polioviruses in a variety of water environments in South Africa. Most polioviruses were isolated on L20B mouse cells, which, however, were not selective: 16 reoviruses and 8 enteroviruses, apparently animal strains, were also isolated on these cells. Vaccine strains of polioviruses were isolated from surface waters during and shortly after two rounds of mass vaccination of children in an informal settlement where there was no sewerage. The results demonstrated the feasibility of poliovirus surveillance in such settlements. It was also evident that neither poliovirus vaccine strains nor other viruses were likely to interfere significantly with the detection of wild-type polioviruses. Optimal isolation of polioviruses was accomplished by ...
Viral infections have a long history of association with drinking water supplies. Evidence of wat... more Viral infections have a long history of association with drinking water supplies. Evidence of water-borne transmission is predominantly based on epidemiological data. Water-borne transmission has only in exceptional cases been confirmed by direct detection of viruses in drinking water supplies. This is because the majority of viruses typically transmitted by water (enteric viruses) are not detectable by conventional methods. However, molecular techniques based on the reverse transcriptase-polymerase chain reaction (RT-PCR) available now, have made it possible to detect low levels of a wide variety of enteric viruses. This preliminary study deals with 411 analyses of drinking water supplies carried out over a period of two years. The drinking water supplies were derived from acceptable quality surface water sources using generally accepted treatment and disinfection processes. Glass wool filters were used for the on-site and in-line recovery of viruses from 100 to 1000 litre volumes ...
In view of the major health impact of enteroviruses, sensitive and reliable techniques for the de... more In view of the major health impact of enteroviruses, sensitive and reliable techniques for the detection and identification of this large group of closely related viruses are essential. To date enteroviruses have generally been isolated by cell culture propagation and typed by neutralization tests using specific antisera. Inoculation of newborn mice remains the most common procedure to distinguish between Coxsackie
Water science and technology : a journal of the International Association on Water Pollution Research, 2001
The objective of this study was to assess the application and efficiency of molecular techniques ... more The objective of this study was to assess the application and efficiency of molecular techniques for the detection and serotyping of enteroviruses from environmental water samples. Samples of water were collected at regular intervals upstream and downstream of an informal settlement. Techniques for the detection of enteroviruses included a reverse transcription polymerase chain reaction (RT-PCR), nested PCR (n-PCR) and Sabin-specific triplex PCR. A specific 297 bp fragment was amplified by the n-PCR and subjected to restriction enzyme (RE) analysis to differentiate between various serotypes of prototypical enteroviruses. Enteroviruses that gave inconclusive restriction patterns were typed by partial sequencing of the VP1 region. Results indicated a high incidence of enteroviruses, predominantly coxsackie B viruses. The results on polioviruses, as well as other enteroviruses, contributed valuable information on enteroviruses circulating in the community. The molecular approach descri...
Zentralblatt für Hygiene und Umweltmedizin = International journal of hygiene and environmental medicine, 1999
The elimination of human viruses, phages, bacteria and Cryptosporidium oocysts by a new generatio... more The elimination of human viruses, phages, bacteria and Cryptosporidium oocysts by a new generation commercial Aquaguard purifier for the domestic treatment of drinking water, has been evaluated. The unit basically consists of a candle prefilter, activated carbon filter and ultraviolet irradiation compartment. Drinking water seeded with selected laboratory test strains of resistant micro-organisms was passed through the unit. Similar tests were carried out with sewage-contaminated river water and secondary treated waste water containing naturally occurring organisms. Test procedures were based on internationally accepted principles for the evaluation of point-of-use water treatment units, including a standard test protocol of the United States Environmental Protection Agency. Reduction in numbers of seeded test organisms at several log levels higher than those expected in water for which the unit is intended, was determined by the cultivation of viable organisms. In the case of seede...
Clinical Microbiology Newsletter, 2008
BMC Research Notes, 2012
Background: The presence of multi-drug resistant Acinetobacter baumannii raises a big therapeutic... more Background: The presence of multi-drug resistant Acinetobacter baumannii raises a big therapeutic challenge in our hospital. Tigecycline, a new glycylcycline with expanded broad spectrum of activity against multi-drug resistant organisms was recently licensed in South Africa. Aim: The aim of this study was to evaluate the in vitro activity of tigecycline against carbapenem resistant A. baumannii complex. Methods: Consecutive clinical isolates of carbapenem resistant A. baumannii complex were collected between February and July 2010. Species identification and susceptibility testing was performed by Vitek-2 colorimetric compact system with Advanced Expert System (AES). Strains were tested for carbapenemase production by the modified Hodge test, according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: A total of 232 carbapenem resistant clinical isolates of A. baumannii complex were collected over the six months study period; 217 (93.5%) of these were modified Hodge test positive. All isolates were susceptible to colistin and 174 (78%) susceptible to amikacin whilst 20 (9%) were susceptible to ciprofloxacin. For tigecycline 169 (75.8%) were fully susceptible, 37 (16.6%) intermediately resistant and only 17 (7.6%) were fully resistant. None of the carbapenem resistant isolates were susceptible to ampicillin, amoxicillin/clavullanic acid, piperacillin/tazobactam, cefuroxime, cefuroxime axetil, cefoxitin, cefepime or nitrofurantoin. Conclusion: All carbapenem resistant isolates were found to be fully susceptible to colistin; amikacin and tigecycline susceptibility was 78% and 76% respectively. Treatment options for infections due to carbapenem and multi-drug resistant A. baumannii organisms are limited and hence tigecycline and amikacin may be considered. The properties of tigecycline i.e. stability, safety, low toxicity, non cross-resistance with other antibiotics and its efficacy against multi-drug resistant A. baumannii isolates make it a good choice. However, ongoing monitoring of A. baumannii susceptibility to tigecycline is needed.
Journal of Clinical Microbiology, 2013
This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteri... more This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteriaceae in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged. CASE REPORTS
Journal of Clinical Microbiology, 2012
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2012
New, effective antibiotics are only likely to become available in 15 - 20 years. To prevent death... more New, effective antibiotics are only likely to become available in 15 - 20 years. To prevent deaths from untreatable Gram-negative infections in South Africa, the rights of any doctor, whether in general or in hospital practice, to indiscriminately prescribe whatever antibiotic they wish, and in whatever fashion, must be challenged. Furthermore, although prevention of the emergence and subsequent spread of carbapenem-resistant Enterobacteriaceae (CRE) has focused on acute and chronic care facilities and inter alia on antibiotic exposure in these institutions, CRE may soon become an issue within entire communities, highlighting a role for public health authorities in CRE prevention efforts.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2011
The New Delhi Metallo-β-lactamase (NDM) resistance mechanism in Enterobacteriaceae threatens to r... more The New Delhi Metallo-β-lactamase (NDM) resistance mechanism in Enterobacteriaceae threatens to render serious Gram-negative infections untreatable. The NDM-1 enzyme hydrolyses all available penicillin, cephalosporin and carbapenem antibiotics, and is commonly accompanied by additional resistance mechanisms to multiple antibiotic classes. Initially identified as a significant healthcare risk on the Indian sub-continent, it has rapidly become a global problem, posing significant diagnostic and management challenges. Here we report the first laboratory-confirmed case of NDM-1 in South Africa.
Mammalian neocortex is important for conscious processing of sensory information with balanced gl... more Mammalian neocortex is important for conscious processing of sensory information with balanced glutamatergic and GABAergic signaling fundamental to this function. Yet little is known about how this interaction arises despite increasing insight into early GABAergic interneuron (IN) circuits. To study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex, specifically the role of INs in early speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity and showed refinement over the period leading to active whisking onset. To test the contribution of IN subtypes, we conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations inf luenced both spontaneous and sensory-evoked cortical activity in an age-and layer-dependent manner. Silencing SST + INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP + IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results show that these IN subtypes contribute to early sensory processing over the first few postnatal weeks.
Create a successful workflow for PCR ◦ Earlier years – contamination of PCR rxn,s with amplificat... more Create a successful workflow for PCR ◦ Earlier years – contamination of PCR rxn,s with amplification product from previous PCR was a potential problem To Combat contamination – ◦ Three separate rooms Preparing the reaction Amplification Analysis of amplified products New instruments – closed systems – less contamination risk Facilities still need to be well designed No inflexible guidelines in molecular lab design – primary emphasis is avoidance of contamination with each step of the workflow
Journal of clinical …, 2000
In a study carried out in small-town and rural primary health care centers in southwestern Nigeri... more In a study carried out in small-town and rural primary health care centers in southwestern Nigeria, 330 Escherichia coli strains isolated from 187 children with diarrhea and 144 apparently healthy controls were examined for virulence traits. Based on the results of colony blot ...
Background: Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are imp... more Background: Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are implicated in the pathogenesis of gastric adenocarcinoma (GCA), but have not been investigated together, in the South African context of low GCA incidence and high H pylori prevalence. Aims: To determine, based on these factors, the potential for developing GCA in a local cohort with H pylori-associated dyspepsia. Methods: Seventy-nine patients underwent gastroscopy and biopsy. Helicobacter pylori-positive biopsies were analysed for virulence factors; cytotoxin-associated antigen (CagA) and vacuolating toxin (VacA) and mosaics (Vac A m1/m2, Vac A s1/s2 or combinations). Host DNA was analysed for targeted regions in IL-1B and IL-1RN genes, to determine polymorphisms of IL-1B-511*T and IL-1RN (variable number tandem repeat [VNTR]). Results: The mean age was 43 years (SD ±11.7), 66% were female. Forty-eight patients (60%) were H pylori positive, 50% (24/48) demonstrated a virulent organism and 42% (20/48) of these demonstrated the most virulent carcinogenic combination; VacA m1/s1 and CagA. IL-1RN VNTR was sequenced in 25 specimens and IL-1B511 polymorphisms in 48 patients; the high-risk IL-1B511 TT allele was present in 52% (25/48) and TC allele in 33% (16/48). Overall, 85% (41/48) of patients demonstrated high-risk genetic polymorphisms. The highest risk associated with GCA, a combination of H pylori VacAm1/s1 virulence factor and IL-1B511 TT or TC allele, was demonstrated in 42% (20/48). Conclusion: Almost half the patients have a combination of virulent H pylori and carcinogenic IL polymorphism. The implication of these observations on the risk of developing GCA requires further elucidation. How to cite this article: Rush CJ, Hoosien E, de Villiers N, et al. Helicobacter pylori virulence factors and host genetic polymorphisms in a low gastric cancer incidence and high H
Bulletin of the World Health Organisation
WHO considers that environmental surveillance for wild-type polioviruses is potentially important... more WHO considers that environmental surveillance for wild-type polioviruses is potentially important for surveillance for acute flaccid paralysis as a means of confirming eradication of poliomyelitis. The present study investigated methods for detecting polioviruses in a variety of water environments in South Africa. Most polioviruses were isolated on L20B mouse cells, which, however, were not selective: 16 reoviruses and 8 enteroviruses, apparently animal strains, were also isolated on these cells. Vaccine strains of polioviruses were isolated from surface waters during and shortly after two rounds of mass vaccination of children in an informal settlement where there was no sewerage. The results demonstrated the feasibility of poliovirus surveillance in such settlements. It was also evident that neither poliovirus vaccine strains nor other viruses were likely to interfere significantly with the detection of wild-type polioviruses. Optimal isolation of polioviruses was accomplished by ...
Viral infections have a long history of association with drinking water supplies. Evidence of wat... more Viral infections have a long history of association with drinking water supplies. Evidence of water-borne transmission is predominantly based on epidemiological data. Water-borne transmission has only in exceptional cases been confirmed by direct detection of viruses in drinking water supplies. This is because the majority of viruses typically transmitted by water (enteric viruses) are not detectable by conventional methods. However, molecular techniques based on the reverse transcriptase-polymerase chain reaction (RT-PCR) available now, have made it possible to detect low levels of a wide variety of enteric viruses. This preliminary study deals with 411 analyses of drinking water supplies carried out over a period of two years. The drinking water supplies were derived from acceptable quality surface water sources using generally accepted treatment and disinfection processes. Glass wool filters were used for the on-site and in-line recovery of viruses from 100 to 1000 litre volumes ...
In view of the major health impact of enteroviruses, sensitive and reliable techniques for the de... more In view of the major health impact of enteroviruses, sensitive and reliable techniques for the detection and identification of this large group of closely related viruses are essential. To date enteroviruses have generally been isolated by cell culture propagation and typed by neutralization tests using specific antisera. Inoculation of newborn mice remains the most common procedure to distinguish between Coxsackie
Water science and technology : a journal of the International Association on Water Pollution Research, 2001
The objective of this study was to assess the application and efficiency of molecular techniques ... more The objective of this study was to assess the application and efficiency of molecular techniques for the detection and serotyping of enteroviruses from environmental water samples. Samples of water were collected at regular intervals upstream and downstream of an informal settlement. Techniques for the detection of enteroviruses included a reverse transcription polymerase chain reaction (RT-PCR), nested PCR (n-PCR) and Sabin-specific triplex PCR. A specific 297 bp fragment was amplified by the n-PCR and subjected to restriction enzyme (RE) analysis to differentiate between various serotypes of prototypical enteroviruses. Enteroviruses that gave inconclusive restriction patterns were typed by partial sequencing of the VP1 region. Results indicated a high incidence of enteroviruses, predominantly coxsackie B viruses. The results on polioviruses, as well as other enteroviruses, contributed valuable information on enteroviruses circulating in the community. The molecular approach descri...
Zentralblatt für Hygiene und Umweltmedizin = International journal of hygiene and environmental medicine, 1999
The elimination of human viruses, phages, bacteria and Cryptosporidium oocysts by a new generatio... more The elimination of human viruses, phages, bacteria and Cryptosporidium oocysts by a new generation commercial Aquaguard purifier for the domestic treatment of drinking water, has been evaluated. The unit basically consists of a candle prefilter, activated carbon filter and ultraviolet irradiation compartment. Drinking water seeded with selected laboratory test strains of resistant micro-organisms was passed through the unit. Similar tests were carried out with sewage-contaminated river water and secondary treated waste water containing naturally occurring organisms. Test procedures were based on internationally accepted principles for the evaluation of point-of-use water treatment units, including a standard test protocol of the United States Environmental Protection Agency. Reduction in numbers of seeded test organisms at several log levels higher than those expected in water for which the unit is intended, was determined by the cultivation of viable organisms. In the case of seede...
Clinical Microbiology Newsletter, 2008
BMC Research Notes, 2012
Background: The presence of multi-drug resistant Acinetobacter baumannii raises a big therapeutic... more Background: The presence of multi-drug resistant Acinetobacter baumannii raises a big therapeutic challenge in our hospital. Tigecycline, a new glycylcycline with expanded broad spectrum of activity against multi-drug resistant organisms was recently licensed in South Africa. Aim: The aim of this study was to evaluate the in vitro activity of tigecycline against carbapenem resistant A. baumannii complex. Methods: Consecutive clinical isolates of carbapenem resistant A. baumannii complex were collected between February and July 2010. Species identification and susceptibility testing was performed by Vitek-2 colorimetric compact system with Advanced Expert System (AES). Strains were tested for carbapenemase production by the modified Hodge test, according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: A total of 232 carbapenem resistant clinical isolates of A. baumannii complex were collected over the six months study period; 217 (93.5%) of these were modified Hodge test positive. All isolates were susceptible to colistin and 174 (78%) susceptible to amikacin whilst 20 (9%) were susceptible to ciprofloxacin. For tigecycline 169 (75.8%) were fully susceptible, 37 (16.6%) intermediately resistant and only 17 (7.6%) were fully resistant. None of the carbapenem resistant isolates were susceptible to ampicillin, amoxicillin/clavullanic acid, piperacillin/tazobactam, cefuroxime, cefuroxime axetil, cefoxitin, cefepime or nitrofurantoin. Conclusion: All carbapenem resistant isolates were found to be fully susceptible to colistin; amikacin and tigecycline susceptibility was 78% and 76% respectively. Treatment options for infections due to carbapenem and multi-drug resistant A. baumannii organisms are limited and hence tigecycline and amikacin may be considered. The properties of tigecycline i.e. stability, safety, low toxicity, non cross-resistance with other antibiotics and its efficacy against multi-drug resistant A. baumannii isolates make it a good choice. However, ongoing monitoring of A. baumannii susceptibility to tigecycline is needed.
Journal of Clinical Microbiology, 2013
This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteri... more This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteriaceae in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged. CASE REPORTS
Journal of Clinical Microbiology, 2012
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2012
New, effective antibiotics are only likely to become available in 15 - 20 years. To prevent death... more New, effective antibiotics are only likely to become available in 15 - 20 years. To prevent deaths from untreatable Gram-negative infections in South Africa, the rights of any doctor, whether in general or in hospital practice, to indiscriminately prescribe whatever antibiotic they wish, and in whatever fashion, must be challenged. Furthermore, although prevention of the emergence and subsequent spread of carbapenem-resistant Enterobacteriaceae (CRE) has focused on acute and chronic care facilities and inter alia on antibiotic exposure in these institutions, CRE may soon become an issue within entire communities, highlighting a role for public health authorities in CRE prevention efforts.