Linda de Gouveia | University of the Witwatersrand (original) (raw)

Papers by Linda de Gouveia

Research paper thumbnail of Microbiological investigation of Bartholin' s gland abscesses in urban women in Johannesburg

... of N. gonorrhoeae, C.trachomatis, Ureaplasma urealyticum and Mycoplasma hominis, using thin c... more ... of N. gonorrhoeae, C.trachomatis, Ureaplasma urealyticum and Mycoplasma hominis, using thin calcium alginate swabs (Calgiswab:Medical Wire & Equipment, Wilshire, UK). ... Sofer Y, Zmira S, Amir J. Brevundimonas vesicularis septic arthritis in an immunocompitent child. ...

Research paper thumbnail of An Unusual Pneumococcal Sequence Type Is the Predominant Cause of Serotype 3 Invasive Disease in South Africa

Journal of Clinical Microbiology, 2010

We reviewed pneumococcal serotype 3 cases reported from 2000 through 2005 to a laboratory-based s... more We reviewed pneumococcal serotype 3 cases reported from 2000 through 2005 to a laboratory-based surveillance system for invasive pneumococcal disease in South Africa. The prevalence of serotype 3 invasive isolates was compared to their prevalence in carriage isolates to determine the odds of invasiveness due to serotype 3 among South African children. Three groups of serotype 3 strains were characterized by pulsed-field gel electrophoresis (PFGE) or Box element PCR (BOX-PCR), randomly selected invasive isolates from one province, isolates from a carriage study involving children in the same province, and antimicrobial-resistant invasive isolates collected nationally. Examples of the PFGE types identified were further characterized by multilocus sequence typing. In total, 15,980 viable isolates causing invasive disease were submitted, of which

Research paper thumbnail of Molecular Characterization of Emerging Non-Levofloxacin-Susceptible Pneumococci Isolated from Children in South Africa

Journal of Clinical Microbiology, 2009

Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, n... more Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, nonlevofloxacin-susceptible Streptococcus pneumoniae (NLSSP) has emerged in South Africa among children receiving treatment for multidrug-resistant tuberculosis. This study aimed to genotypically characterize NLSSP isolates. Invasive isolates were collected through active national laboratory-based surveillance for invasive pneumococcal disease (IPD) from 2000 through 2006 (n ‫؍‬ 19,404). Carriage studies were conducted at two hospitals for patients with tuberculosis in two provinces. Phenotypic characterization was performed by determination of MICs and serotyping. Fluoroquinolone resistance mutations were identified, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Twelve nonlevofloxacin-susceptible cases of IPD were identified, and all were in children <15 years of age. Ten isolates were serotype 19F and formed two clusters according to their PFGE profiles, antibiogram types, and fluoroquinolone resistance-conferring mutations. All nine carriage isolates from children in hospital A were NLSSP, serotype 19F, were indistinguishable by PFGE, and were related to invasive isolates in cluster 2. Of 26 child carriers in hospital B, 22 (85%) were colonized with NLSSP. The isolates were indistinguishable by PFGE, although they displayed two serotypes, serotypes 19F and 23F. The isolates were related to invasive isolates in cluster 1; however, higher levofloxacin MICs and different fluoroquinolone resistance mutations were suggestive of horizontal gene transfer. A serotype 23F carriage isolate displayed increased fitness compared with the fitness of an otherwise indistinguishable serotype 19F carriage isolate. These data suggest that a low-level non-levofloxacin-susceptible strain transformed into a highly resistant strain under antibiotic pressure and underwent capsular switching in order to have increased fitness.

Research paper thumbnail of Serotype 6C is associated with penicillin-susceptible meningeal infections in human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal isolates previously identified as serotype 6A in South Africa

International Journal of Antimicrobial Agents, 2008

a b s t r a c t A newly described pneumococcal serotype (6C) is indistinguishable from serotype 6... more a b s t r a c t A newly described pneumococcal serotype (6C) is indistinguishable from serotype 6A when using the conventional Quellung serotyping method. Serotype 6A isolates were screened by polymerase chain reaction (PCR) for the wciN region of the capsular locus. This study detected serotype 6C among invasive pneumococcal disease (IPD) isolates from national laboratory-based surveillance (2005)(2006) in South Africa. No serotype 6C isolates were identified among 23 serotype 6A cases from children enrolled in a 9-valent pneumococcal conjugate vaccine trial (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005). Of 8167 IPD cases reported nationally, viable isolates were available for serotyping in 87% of cases (n = 7080). Quellung serotyping identified 608 serotype 6A isolates, of which 606 were further tested for serotype 6C. PCR confirmed serotype 6C in 5% (30/606) of the isolates tested. Serotype 6C isolates were: less likely than 6A to cause disease in children compared with adults (6/30 (20%) vs. 311/550 (57%); P < 0.001); more likely to cause laboratory-confirmed meningitis (15/30 (50%) vs. 167/578 (29%); P = 0.01); and more likely to demonstrate susceptibility to penicillin (nonsusceptibility 0/30 vs. 129/578 (22%); P = 0.004). No association with gender, human immunodeficiency virus (HIV) co-infection or case fatality rate was observed. Although serotype 6C prevalence was low, its epidemiology may differ from the other serogroup 6 pneumococci. Our data from the vaccine efficacy trial suggest that cross-protection of the conjugate vaccine is against true serotype 6A strains.

Research paper thumbnail of Invasive Neisseria meningitidis with decreased susceptibility to fluoroquinolones in South Africa, 2009

Journal of Antimicrobial Chemotherapy, 2010

Research paper thumbnail of Increased incidence of meningococcal disease in HIV-infected individuals associated with higher case-fatality ratios in South Africa

Aids, 2010

We aimed to compare the incidence of meningococcal disease amongst HIV-infected and uninfected in... more We aimed to compare the incidence of meningococcal disease amongst HIV-infected and uninfected individuals and to evaluate whether HIV is a risk factor for mortality and bacteremia amongst patients with meningococcal disease. Cohort surveillance study. We conducted laboratory-based surveillance for meningococcal disease in Gauteng Province, South Africa. HIV status and outcome data were obtained at sentinel sites. Incidence in HIV-infected and uninfected persons was calculated assuming a similar age-specific HIV prevalence in tested and untested individuals. Risk factors for death and bacteremia (as compared with meningitis) were evaluated using multivariable logistic regression. From 2003 to 2007, 1336 meningococcal cases were reported. Of 504 patients at sentinel sites with known outcome, 308 (61%) had HIV serostatus data. HIV prevalence amongst cases of meningococcal disease was higher than the population HIV prevalence in all age groups. The incidence of meningococcal disease in HIV-infected individuals was elevated in all age groups with an age-adjusted relative risk of 11.3 [95% confidence interval (CI) 8.9-14.3, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001]. The case-fatality ratio (CFR) was 20% (27/138) amongst HIV-infected and 11% (18/170) amongst HIV-uninfected individuals [odds ratio (OR) 2.1, 95% CI 1.1-3.9]. On multivariable analysis, CFR was greater amongst patients with bacteremia (35%, 29/82) compared with meningitis (7%, 16/226) (OR 7.8, 95% CI 3.4-17.7). HIV infection was associated with increased odds of bacteremia (OR 2.7, 95% CI 1.5-5.0). HIV-infected individuals may be at increased risk of meningococcal disease. The increased CFR in HIV-infected patients may be explained by their increased odds of bacteremia compared to meningitis.

Research paper thumbnail of Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro

Journal of Antimicrobial Chemotherapy, 2007

Objectives: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, a... more Objectives: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin, ciprofloxacin, moxifloxacin, tobramycin and doxycycline on pneumolysin production by a macrolide-susceptible strain and two macrolide-resistant strains [erm(B) or mef(A)] of Streptococcus pneumoniae.

Research paper thumbnail of Antimicrobial susceptibility of pneumococcal isolates causing bacteraemic pneumococcal pneumonia: analysis using current breakpoints and fluoroquinolone pharmacodynamics

International Journal of Antimicrobial Agents, 2010

Research paper thumbnail of Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae

Journal of Antimicrobial Chemotherapy, 2006

Objectives: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination ... more Objectives: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination with ceftriaxone (0.1 and 0.25 mg/L) on pneumolysin production by both macrolide-susceptible and -resistant [2 erm(B) positive and 2 mef(A) positive] strains of Streptococcus pneumoniae.

Research paper thumbnail of Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005

Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, ... more Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 g/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed. A total of 1,897 cases of invasive meningococcal disease were reported, with an average annual incidence of 0.83/100,000 population. Of these cases, 1,381 (73%) had viable isolates available for further testing; 87 (6%) of these isolates tested intermediately resistant to penicillin (Pen i ). Pen i meningococcal isolates were distributed throughout all provinces and age groups, and there was no association with outcome or human immunodeficiency virus infection. The prevalence of Pen i was lower in serogroup A (7/295; 2%) than in serogroup B (24/314; 8%), serogroup C (9/117; 8%), serogroup Y (22/248; 9%), or serogroup W135 (25/396; 6%) (P ‫؍‬ 0.02). Pulsed-field gel electrophoresis grouped 63/82 Pen i isolates into nine clusters, mostly according to serogroup. The clustering of patterns from Pen i isolates was not different from that of penicillinsusceptible isolates. Twelve sequence types were identified among 18 isolates arbitrarily selected for multilocus sequence typing. DNA sequence analysis of the penA gene identified 26 different alleles among the Pen i isolates. Intermediate penicillin resistance is thus widespread among meningococcal serogroups, has been selected in a variety of lineages, and, to date, does not appear to be associated with increased mortality. This is the first report describing the prevalence and molecular epidemiology of Pen i meningococcal isolates from sub-Saharan Africa.

Research paper thumbnail of Molecular Characterization of Emerging Non-Levofloxacin-Susceptible Pneumococci Isolated from Children in South Africa

Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, n... more Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, nonlevofloxacin-susceptible Streptococcus pneumoniae (NLSSP) has emerged in South Africa among children receiving treatment for multidrug-resistant tuberculosis. This study aimed to genotypically characterize NLSSP isolates. Invasive isolates were collected through active national laboratory-based surveillance for invasive pneumococcal disease (IPD) from 2000 through 2006 (n ‫؍‬ 19,404). Carriage studies were conducted at two hospitals for patients with tuberculosis in two provinces. Phenotypic characterization was performed by determination of MICs and serotyping. Fluoroquinolone resistance mutations were identified, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Twelve nonlevofloxacin-susceptible cases of IPD were identified, and all were in children <15 years of age. Ten isolates were serotype 19F and formed two clusters according to their PFGE profiles, antibiogram types, and fluoroquinolone resistance-conferring mutations. All nine carriage isolates from children in hospital A were NLSSP, serotype 19F, were indistinguishable by PFGE, and were related to invasive isolates in cluster 2. Of 26 child carriers in hospital B, 22 (85%) were colonized with NLSSP. The isolates were indistinguishable by PFGE, although they displayed two serotypes, serotypes 19F and 23F. The isolates were related to invasive isolates in cluster 1; however, higher levofloxacin MICs and different fluoroquinolone resistance mutations were suggestive of horizontal gene transfer. A serotype 23F carriage isolate displayed increased fitness compared with the fitness of an otherwise indistinguishable serotype 19F carriage isolate. These data suggest that a low-level non-levofloxacin-susceptible strain transformed into a highly resistant strain under antibiotic pressure and underwent capsular switching in order to have increased fitness.

Research paper thumbnail of Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study

Lancet, 2008

Background Use of fl uoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis... more Background Use of fl uoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could aff ect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fl uoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.

Research paper thumbnail of Increased Risk of Death in HIV-Infected Patients with Pneumococcal Meningitis, South Africa, 2003–2005

International Journal of Infectious Diseases, 2008

Research paper thumbnail of Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005

Journal of Clinical Microbiology, 2008

Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, ... more Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 g/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed. A total of 1,897 cases of invasive meningococcal disease were reported, with an average annual incidence of 0.83/100,000 population. Of these cases, 1,381 (73%) had viable isolates available for further testing; 87 (6%) of these isolates tested intermediately resistant to penicillin (Pen i ). Pen i meningococcal isolates were distributed throughout all provinces and age groups, and there was no association with outcome or human immunodeficiency virus infection. The prevalence of Pen i was lower in serogroup A (7/295; 2%) than in serogroup B (24/314; 8%), serogroup C (9/117; 8%), serogroup Y (22/248; 9%), or serogroup W135 (25/396; 6%) (P ‫؍‬ 0.02). Pulsed-field gel electrophoresis grouped 63/82 Pen i isolates into nine clusters, mostly according to serogroup. The clustering of patterns from Pen i isolates was not different from that of penicillinsusceptible isolates. Twelve sequence types were identified among 18 isolates arbitrarily selected for multilocus sequence typing. DNA sequence analysis of the penA gene identified 26 different alleles among the Pen i isolates. Intermediate penicillin resistance is thus widespread among meningococcal serogroups, has been selected in a variety of lineages, and, to date, does not appear to be associated with increased mortality. This is the first report describing the prevalence and molecular epidemiology of Pen i meningococcal isolates from sub-Saharan Africa.

Research paper thumbnail of Emergence of Endemic Serogroup W135 Meningococcal Disease Associated with a High Mortality Rate in South Africa

Clinical Infectious Diseases, 2008

In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of e... more In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described.

Research paper thumbnail of Molecular basis and clonal nature of increasing pneumococcal macrolide resistance in South Africa, 2000–2005

International Journal of Antimicrobial Agents, 2008

The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa wa... more The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa was investigated. Minimum inhibitory concentrations and serotypes of pneumococcal isolates causing invasive disease from 2000-2005 (n = 15 982), collected through a national laboratory-based surveillance system, were determined. Randomly selected isolates from 2005 (51%; 260/508) had resistance mechanisms determined, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) (n = 64) and multilocus sequence typing (n = 7). Macrolide resistance increased from 9% (160/1828) in 2000 to 14% (508/3656) in 2005 (P < 0.001). Serotype 14 was the most common macrolide-resistant serotype (40%; 760/1921). The majority of macrolide-resistant isolates (75%; 1437/1921) displayed the macrolide-lincosamide-streptogramin B (MLS B ) phenotype. Of the strains screened genotypically, 57% (147/260) contained erm(B), 27% (71/260) contained mef(A) and 15% (40/260) contained erm(B) and mef(A); 1% (2/260) contained ribosomal mutations. Macrolide-resistant isolates were predominantly penicillin-non-susceptible and multidrug-resistant. Isolates clustered according to serotype by PFGE, and 22% (14/64), 11% (7/64) and 5% (3/64) of isolates were related to the Taiwan 19F -14, England 14 -9 and Spain 9V -3 global clones, respectively. Routine use of the 7-valent pneumococcal conjugate vaccine (PCV-7) could reduce the burden of macrolide-resistant pneumococcal disease in South Africa.

Research paper thumbnail of Microbiological investigation of Bartholin' s gland abscesses in urban women in Johannesburg

... of N. gonorrhoeae, C.trachomatis, Ureaplasma urealyticum and Mycoplasma hominis, using thin c... more ... of N. gonorrhoeae, C.trachomatis, Ureaplasma urealyticum and Mycoplasma hominis, using thin calcium alginate swabs (Calgiswab:Medical Wire & Equipment, Wilshire, UK). ... Sofer Y, Zmira S, Amir J. Brevundimonas vesicularis septic arthritis in an immunocompitent child. ...

Research paper thumbnail of An Unusual Pneumococcal Sequence Type Is the Predominant Cause of Serotype 3 Invasive Disease in South Africa

Journal of Clinical Microbiology, 2010

We reviewed pneumococcal serotype 3 cases reported from 2000 through 2005 to a laboratory-based s... more We reviewed pneumococcal serotype 3 cases reported from 2000 through 2005 to a laboratory-based surveillance system for invasive pneumococcal disease in South Africa. The prevalence of serotype 3 invasive isolates was compared to their prevalence in carriage isolates to determine the odds of invasiveness due to serotype 3 among South African children. Three groups of serotype 3 strains were characterized by pulsed-field gel electrophoresis (PFGE) or Box element PCR (BOX-PCR), randomly selected invasive isolates from one province, isolates from a carriage study involving children in the same province, and antimicrobial-resistant invasive isolates collected nationally. Examples of the PFGE types identified were further characterized by multilocus sequence typing. In total, 15,980 viable isolates causing invasive disease were submitted, of which

Research paper thumbnail of Molecular Characterization of Emerging Non-Levofloxacin-Susceptible Pneumococci Isolated from Children in South Africa

Journal of Clinical Microbiology, 2009

Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, n... more Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, nonlevofloxacin-susceptible Streptococcus pneumoniae (NLSSP) has emerged in South Africa among children receiving treatment for multidrug-resistant tuberculosis. This study aimed to genotypically characterize NLSSP isolates. Invasive isolates were collected through active national laboratory-based surveillance for invasive pneumococcal disease (IPD) from 2000 through 2006 (n ‫؍‬ 19,404). Carriage studies were conducted at two hospitals for patients with tuberculosis in two provinces. Phenotypic characterization was performed by determination of MICs and serotyping. Fluoroquinolone resistance mutations were identified, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Twelve nonlevofloxacin-susceptible cases of IPD were identified, and all were in children <15 years of age. Ten isolates were serotype 19F and formed two clusters according to their PFGE profiles, antibiogram types, and fluoroquinolone resistance-conferring mutations. All nine carriage isolates from children in hospital A were NLSSP, serotype 19F, were indistinguishable by PFGE, and were related to invasive isolates in cluster 2. Of 26 child carriers in hospital B, 22 (85%) were colonized with NLSSP. The isolates were indistinguishable by PFGE, although they displayed two serotypes, serotypes 19F and 23F. The isolates were related to invasive isolates in cluster 1; however, higher levofloxacin MICs and different fluoroquinolone resistance mutations were suggestive of horizontal gene transfer. A serotype 23F carriage isolate displayed increased fitness compared with the fitness of an otherwise indistinguishable serotype 19F carriage isolate. These data suggest that a low-level non-levofloxacin-susceptible strain transformed into a highly resistant strain under antibiotic pressure and underwent capsular switching in order to have increased fitness.

Research paper thumbnail of Serotype 6C is associated with penicillin-susceptible meningeal infections in human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal isolates previously identified as serotype 6A in South Africa

International Journal of Antimicrobial Agents, 2008

a b s t r a c t A newly described pneumococcal serotype (6C) is indistinguishable from serotype 6... more a b s t r a c t A newly described pneumococcal serotype (6C) is indistinguishable from serotype 6A when using the conventional Quellung serotyping method. Serotype 6A isolates were screened by polymerase chain reaction (PCR) for the wciN region of the capsular locus. This study detected serotype 6C among invasive pneumococcal disease (IPD) isolates from national laboratory-based surveillance (2005)(2006) in South Africa. No serotype 6C isolates were identified among 23 serotype 6A cases from children enrolled in a 9-valent pneumococcal conjugate vaccine trial (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005). Of 8167 IPD cases reported nationally, viable isolates were available for serotyping in 87% of cases (n = 7080). Quellung serotyping identified 608 serotype 6A isolates, of which 606 were further tested for serotype 6C. PCR confirmed serotype 6C in 5% (30/606) of the isolates tested. Serotype 6C isolates were: less likely than 6A to cause disease in children compared with adults (6/30 (20%) vs. 311/550 (57%); P < 0.001); more likely to cause laboratory-confirmed meningitis (15/30 (50%) vs. 167/578 (29%); P = 0.01); and more likely to demonstrate susceptibility to penicillin (nonsusceptibility 0/30 vs. 129/578 (22%); P = 0.004). No association with gender, human immunodeficiency virus (HIV) co-infection or case fatality rate was observed. Although serotype 6C prevalence was low, its epidemiology may differ from the other serogroup 6 pneumococci. Our data from the vaccine efficacy trial suggest that cross-protection of the conjugate vaccine is against true serotype 6A strains.

Research paper thumbnail of Invasive Neisseria meningitidis with decreased susceptibility to fluoroquinolones in South Africa, 2009

Journal of Antimicrobial Chemotherapy, 2010

Research paper thumbnail of Increased incidence of meningococcal disease in HIV-infected individuals associated with higher case-fatality ratios in South Africa

Aids, 2010

We aimed to compare the incidence of meningococcal disease amongst HIV-infected and uninfected in... more We aimed to compare the incidence of meningococcal disease amongst HIV-infected and uninfected individuals and to evaluate whether HIV is a risk factor for mortality and bacteremia amongst patients with meningococcal disease. Cohort surveillance study. We conducted laboratory-based surveillance for meningococcal disease in Gauteng Province, South Africa. HIV status and outcome data were obtained at sentinel sites. Incidence in HIV-infected and uninfected persons was calculated assuming a similar age-specific HIV prevalence in tested and untested individuals. Risk factors for death and bacteremia (as compared with meningitis) were evaluated using multivariable logistic regression. From 2003 to 2007, 1336 meningococcal cases were reported. Of 504 patients at sentinel sites with known outcome, 308 (61%) had HIV serostatus data. HIV prevalence amongst cases of meningococcal disease was higher than the population HIV prevalence in all age groups. The incidence of meningococcal disease in HIV-infected individuals was elevated in all age groups with an age-adjusted relative risk of 11.3 [95% confidence interval (CI) 8.9-14.3, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001]. The case-fatality ratio (CFR) was 20% (27/138) amongst HIV-infected and 11% (18/170) amongst HIV-uninfected individuals [odds ratio (OR) 2.1, 95% CI 1.1-3.9]. On multivariable analysis, CFR was greater amongst patients with bacteremia (35%, 29/82) compared with meningitis (7%, 16/226) (OR 7.8, 95% CI 3.4-17.7). HIV infection was associated with increased odds of bacteremia (OR 2.7, 95% CI 1.5-5.0). HIV-infected individuals may be at increased risk of meningococcal disease. The increased CFR in HIV-infected patients may be explained by their increased odds of bacteremia compared to meningitis.

Research paper thumbnail of Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro

Journal of Antimicrobial Chemotherapy, 2007

Objectives: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, a... more Objectives: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin, ciprofloxacin, moxifloxacin, tobramycin and doxycycline on pneumolysin production by a macrolide-susceptible strain and two macrolide-resistant strains [erm(B) or mef(A)] of Streptococcus pneumoniae.

Research paper thumbnail of Antimicrobial susceptibility of pneumococcal isolates causing bacteraemic pneumococcal pneumonia: analysis using current breakpoints and fluoroquinolone pharmacodynamics

International Journal of Antimicrobial Agents, 2010

Research paper thumbnail of Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae

Journal of Antimicrobial Chemotherapy, 2006

Objectives: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination ... more Objectives: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination with ceftriaxone (0.1 and 0.25 mg/L) on pneumolysin production by both macrolide-susceptible and -resistant [2 erm(B) positive and 2 mef(A) positive] strains of Streptococcus pneumoniae.

Research paper thumbnail of Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005

Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, ... more Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 g/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed. A total of 1,897 cases of invasive meningococcal disease were reported, with an average annual incidence of 0.83/100,000 population. Of these cases, 1,381 (73%) had viable isolates available for further testing; 87 (6%) of these isolates tested intermediately resistant to penicillin (Pen i ). Pen i meningococcal isolates were distributed throughout all provinces and age groups, and there was no association with outcome or human immunodeficiency virus infection. The prevalence of Pen i was lower in serogroup A (7/295; 2%) than in serogroup B (24/314; 8%), serogroup C (9/117; 8%), serogroup Y (22/248; 9%), or serogroup W135 (25/396; 6%) (P ‫؍‬ 0.02). Pulsed-field gel electrophoresis grouped 63/82 Pen i isolates into nine clusters, mostly according to serogroup. The clustering of patterns from Pen i isolates was not different from that of penicillinsusceptible isolates. Twelve sequence types were identified among 18 isolates arbitrarily selected for multilocus sequence typing. DNA sequence analysis of the penA gene identified 26 different alleles among the Pen i isolates. Intermediate penicillin resistance is thus widespread among meningococcal serogroups, has been selected in a variety of lineages, and, to date, does not appear to be associated with increased mortality. This is the first report describing the prevalence and molecular epidemiology of Pen i meningococcal isolates from sub-Saharan Africa.

Research paper thumbnail of Molecular Characterization of Emerging Non-Levofloxacin-Susceptible Pneumococci Isolated from Children in South Africa

Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, n... more Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, nonlevofloxacin-susceptible Streptococcus pneumoniae (NLSSP) has emerged in South Africa among children receiving treatment for multidrug-resistant tuberculosis. This study aimed to genotypically characterize NLSSP isolates. Invasive isolates were collected through active national laboratory-based surveillance for invasive pneumococcal disease (IPD) from 2000 through 2006 (n ‫؍‬ 19,404). Carriage studies were conducted at two hospitals for patients with tuberculosis in two provinces. Phenotypic characterization was performed by determination of MICs and serotyping. Fluoroquinolone resistance mutations were identified, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Twelve nonlevofloxacin-susceptible cases of IPD were identified, and all were in children <15 years of age. Ten isolates were serotype 19F and formed two clusters according to their PFGE profiles, antibiogram types, and fluoroquinolone resistance-conferring mutations. All nine carriage isolates from children in hospital A were NLSSP, serotype 19F, were indistinguishable by PFGE, and were related to invasive isolates in cluster 2. Of 26 child carriers in hospital B, 22 (85%) were colonized with NLSSP. The isolates were indistinguishable by PFGE, although they displayed two serotypes, serotypes 19F and 23F. The isolates were related to invasive isolates in cluster 1; however, higher levofloxacin MICs and different fluoroquinolone resistance mutations were suggestive of horizontal gene transfer. A serotype 23F carriage isolate displayed increased fitness compared with the fitness of an otherwise indistinguishable serotype 19F carriage isolate. These data suggest that a low-level non-levofloxacin-susceptible strain transformed into a highly resistant strain under antibiotic pressure and underwent capsular switching in order to have increased fitness.

Research paper thumbnail of Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study

Lancet, 2008

Background Use of fl uoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis... more Background Use of fl uoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could aff ect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fl uoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.

Research paper thumbnail of Increased Risk of Death in HIV-Infected Patients with Pneumococcal Meningitis, South Africa, 2003–2005

International Journal of Infectious Diseases, 2008

Research paper thumbnail of Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005

Journal of Clinical Microbiology, 2008

Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, ... more Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 g/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed. A total of 1,897 cases of invasive meningococcal disease were reported, with an average annual incidence of 0.83/100,000 population. Of these cases, 1,381 (73%) had viable isolates available for further testing; 87 (6%) of these isolates tested intermediately resistant to penicillin (Pen i ). Pen i meningococcal isolates were distributed throughout all provinces and age groups, and there was no association with outcome or human immunodeficiency virus infection. The prevalence of Pen i was lower in serogroup A (7/295; 2%) than in serogroup B (24/314; 8%), serogroup C (9/117; 8%), serogroup Y (22/248; 9%), or serogroup W135 (25/396; 6%) (P ‫؍‬ 0.02). Pulsed-field gel electrophoresis grouped 63/82 Pen i isolates into nine clusters, mostly according to serogroup. The clustering of patterns from Pen i isolates was not different from that of penicillinsusceptible isolates. Twelve sequence types were identified among 18 isolates arbitrarily selected for multilocus sequence typing. DNA sequence analysis of the penA gene identified 26 different alleles among the Pen i isolates. Intermediate penicillin resistance is thus widespread among meningococcal serogroups, has been selected in a variety of lineages, and, to date, does not appear to be associated with increased mortality. This is the first report describing the prevalence and molecular epidemiology of Pen i meningococcal isolates from sub-Saharan Africa.

Research paper thumbnail of Emergence of Endemic Serogroup W135 Meningococcal Disease Associated with a High Mortality Rate in South Africa

Clinical Infectious Diseases, 2008

In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of e... more In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described.

Research paper thumbnail of Molecular basis and clonal nature of increasing pneumococcal macrolide resistance in South Africa, 2000–2005

International Journal of Antimicrobial Agents, 2008

The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa wa... more The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa was investigated. Minimum inhibitory concentrations and serotypes of pneumococcal isolates causing invasive disease from 2000-2005 (n = 15 982), collected through a national laboratory-based surveillance system, were determined. Randomly selected isolates from 2005 (51%; 260/508) had resistance mechanisms determined, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) (n = 64) and multilocus sequence typing (n = 7). Macrolide resistance increased from 9% (160/1828) in 2000 to 14% (508/3656) in 2005 (P < 0.001). Serotype 14 was the most common macrolide-resistant serotype (40%; 760/1921). The majority of macrolide-resistant isolates (75%; 1437/1921) displayed the macrolide-lincosamide-streptogramin B (MLS B ) phenotype. Of the strains screened genotypically, 57% (147/260) contained erm(B), 27% (71/260) contained mef(A) and 15% (40/260) contained erm(B) and mef(A); 1% (2/260) contained ribosomal mutations. Macrolide-resistant isolates were predominantly penicillin-non-susceptible and multidrug-resistant. Isolates clustered according to serotype by PFGE, and 22% (14/64), 11% (7/64) and 5% (3/64) of isolates were related to the Taiwan 19F -14, England 14 -9 and Spain 9V -3 global clones, respectively. Routine use of the 7-valent pneumococcal conjugate vaccine (PCV-7) could reduce the burden of macrolide-resistant pneumococcal disease in South Africa.