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ABSTRACT: INTRODUCTION: Dynamics of pneumococcal disease incidence and serotype distribution prior to introduction of pneumococcal conjugate vaccines (PCV) will assist in understanding effects of the vaccine over time and will be important in choosing the optimal PCV formulation. METHODS: We conducted active, laboratory-based, national surveillance for invasive pneumococcal disease (IPD) through the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) from 2003 through 2008. Over 130 laboratories report to this system. Pneumococci were serotyped using Quellung and isolates screened for resistance by disk diffusion; minimum inhibitory concentrations were determined on potentially resistant isolates. We used univariate and multivariable multinomial regression models to assess differences between serotypes. RESULTS: GERMS-SA identified 8674 cases among children <5 years. Overall, 58% (3849/6668), 65% (4314/6668), and 85% (5669/6668) of cases and 61% (455/751), 64% (482/751), 82% (616/751) of deaths were due to serotypes included in 7-valent PCV, 10-valent PCV and 13-valent PCV, respectively. Serotypes 6A and 19A accounted for 16% (527/3252) of penicillin non-susceptible disease. In 2008, reported incidence of IPD was 6-fold higher in children <1 compared to children 1-4 years of age: 87 per 100,000 population and 14/100,000, respectively. The relative risk of IPD was 21-fold (95% CI, 19-24) and 34-fold (29-41) greater in HIV-infected compared to HIV-uninfected children in the <1 year and 1-4-year-old age groups respectively. On multivariable analysis serotypes 6B (RRR 0.7; CI 0.5-0.9), 18C (RRR 0.3; CI 0.1-0.5), 1 (RRR 0.2; CI 0.1-0.4) and 8 (RRR 0.2; CI 0.1-0.4) were significantly less common in HIV-infected individuals than serotype 14. CONCLUSIONS: All vaccine formulations have the potential to prevent most cases and deaths from IPD in children in South Africa. Vaccines with protection against 19A would be advantageous in South Africa.
Vaccine 05/2013; · 3.77 Impact Factor
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Marta C Nunes,
Tinevimbo Shiri,
Nadia van Niekerk,
Clare L Cutland,
Michelle J Groome,
Anthonet Koen,
Anne von Gottberg, Linda de Gouveia,
Keith P Klugman,
Peter V Adrian,
Shabir A Madhi
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ABSTRACT: BACKGROUND:: Pneumococcal nasopharyngeal colonization is a pre-requisite to developing pneumococcal-disease. We investigated the dynamics of pneumococcal colonization in peri-natal HIV-unexposed and HIV-exposed children and their mothers, and risk-factors associated with new serotypes acquisition. METHODS:: 243 mother/child pairs (120 HIV-infected, 123 HIV-uninfected mothers) were studied at 4.4, 7.2, 9.4, 12.3 and 16.0 months of the child's age. Demographic data, nasopharyngeal swabs, as well as oropharyngeal swabs from mothers were collected for pneumococcal conventional culture and serotyping by the Quellung method. RESULTS:: The rate of new serotype acquisition during the 16 months did not differ between HIVexposed (49.1%) and HIV-unexposed (52.0%) children, or between HIV-infected (18.9%) and HIV-uninfected (19.5%) mothers. Serotypes included in the 7-valent pneumococcal conjugate vaccine (PCV7) were acquired more often by HIV-infected (10.0%) compared with HIVuninfected mothers (6.4%; p=0.03). On multivariate analysis, day-care attendance (adjusted odds ratio (AOR) 1.80, p=0.02) and maternal pneumococcal colonization (AOR 1.54, p=0.01) were positively associated with pneumococcal acquisition in the child, whereas breastfeeding had a protective effect on PCV7-serotype acquisition in HIV-uninfected children. New acquisition of 7- and 13-valent PCV serotypes in the mother was positively associated with colonization in the child (AOR 2.01, p=0.006 and AOR 2.04, p=0.002; respectively). CONCLUSIONS:: There is an association of acquisition of 7- and 13-valent PCV serotypes between young children and their mothers. The higher prevalence of PCV7 serotype in HIV-infected mothers suggests that they may be a reservoir for transmission of these serotypes, which could delay indirect effects of PCV in settings with a high HIV burden.
The Pediatric Infectious Disease Journal 01/2013; · 3.58 Impact Factor
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ABSTRACT: From August 1999 through July 2002, hyperinvasive Neisseria meningitidis serogroup B (MenB) clonal complexes (CCs), namely, ST-32/ET-5 (CC32) and ST-41/44/lineage 3 (CC41/44), were predominant in the Western Cape Province of South Africa. This study analyzed MenB invasive isolates from a national laboratory-based surveillance system that were collected from January 2002 through December 2006. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) (n = 302), and multilocus sequence typing (MLST) and PorA and FetA typing were performed on randomly selected isolates (34/302, 11%). In total, 2,400 cases were reported, with the highest numbers from Gauteng Province (1,307/2,400, 54%) and Western Cape Province (393/2,400, 16%); 67% (1,617/2,400) had viable isolates and 19% (307/1,617) were identified as serogroup B. MenB incidence remained stable over time (P = 0.77) (average incidence, 0.13/100,000 population [range, 0.10 to 0.16/100,000 population]). PFGE (302/307, 98%) divided isolates (206/302, 68%) into 13 clusters and 96 outliers. The largest cluster, B1, accounted for 25% of isolates (76/302) over the study period; its prevalence decreased from 43% (20/47) in 2002 to 13% (8/62) in 2006 (P < 0.001), and it was common in the Western Cape (58/76, 76%). Clusters B2 and B3 accounted for 10% (31/302) and 6% (19/302), respectively, and showed no significant change over time and were predominant in Gauteng. Randomly selected isolates from clusters B1, B2, and B3 belonged to CC32, CC41/44, and the new CC4240/6688, respectively. Overall, 15 PorA and 12 FetA types were identified. MenB isolates were mostly diverse with no single dominant clone; however, CC32 and CC41/44 accounted for 35% and the new CC4240/6688 was the third most prevalent clone.
Journal of clinical microbiology 09/2012; 50(11):3678-86. · 4.16 Impact Factor
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ABSTRACT: The emergence of multidrug-resistant (MDR) Streptococcus pneumoniae complicates disease management. We aimed to determine risk factors associated with MDR invasive pneumococcal disease (IPD) in South Africa and evaluate the potential for vaccination to reduce disease burden. IPD data collected by laboratory-based surveillance from 2003 through 2008 were analyzed. Multidrug resistance was defined as nonsusceptibility to any three or more different antibiotic classes. Risk factors for multidrug resistance were evaluated using multivariable logistic regression. Of 20,100 cases of IPD identified, 3,708 (18%) had MDR isolates, with the proportion increasing from 16% (461/2,891) to 20% (648/3,326) (P < 0.001) over the study period. Serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) accounted for 94% of MDR strains. Significant risk factors for MDR IPD included PCV13 (1,486/6,407; odds ratio [OR] of 6.3; 95% confidence interval [CI] of 5.0 to 7.9) and pediatric (3,382/9,980; OR of 12.8; 95% CI of 10.6 to 15.4) serotypes, age of <5 (802/3,110; OR of 2.0; 95% CI of 1.8 to 2.3) or ≥65 (39/239; OR of 1.5; 95% CI of 1.0 to 2.2) years versus age of 15 to 64 years, HIV infection (975/4,636; OR of 1.5; 95% CI of 1.2 to 1.8), previous antibiotic use (242/803; OR of 1.7; 95% CI of 1.4 to 2.1), previous hospital admissions (579/2,450; OR of 1.2; 95% CI of 1.03 to 1.4), urban location (883/4,375; OR of 2.0; 95% CI of 1.1 to 3.5), and tuberculosis treatment (246/1,021; OR of 1.2; 95% CI of 1.03 to 1.5). MDR IPD prevalence increased over the study period. The effect of many of the MDR risk factors could be reduced by more judicious use of antibiotics. Because PCV13 serotypes account for most MDR infections, pneumococcal vaccination may reduce the prevalence of multidrug resistance.
Antimicrobial Agents and Chemotherapy 07/2012; 56(10):5088-5095. · 4.84 Impact Factor
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ABSTRACT: South Africa started routine infant immunization against Haemophilus influenzae serotype b (Hib) disease in 1999 with an accelerated three-dose schedule of Hib conjugate vaccine (HibCV) without a booster dose. Following initial declines in Hib disease, national surveillance has identified increasing numbers of Hib disease episodes in fully vaccinated children.
We reviewed national laboratory-based surveillance data from 2003 through 2009 for invasive Hib disease episodes among children <5 years, including HIV status and vaccination histories. We defined HibCV failures as invasive Hib disease in children at least four months of age who had received all recommended doses of HibCV.
Despite high HibCV vaccination coverage, detection rates of Hib disease in children <5 years increased from 0.7 per 100,000 population in 2003 to 1.3/100,000 in 2009 (p<0.001). Among 263 episodes of invasive Hib disease among children with known vaccination status, 135 (51%) were classified as vaccine failures. Of vaccine failures, 55% occurred among case patients ≥18 months old. HIV status was documented for 90 children with vaccine failure; 53% were not HIV infected.
Vaccine failures, which occurred in both HIV-infected and -uninfected children, comprised half of the rise in invasive Hib disease detected in South African children 10 years after national introduction of Hib vaccine. These findings suggest that HibCV recommendations may require revision. In November 2010, children in South Africa began receiving a booster dose of HibCV as part of a pentavalent vaccine.
Vaccine 11/2011; 30(3):565-71. · 3.77 Impact Factor
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ABSTRACT: Pneumococcal disease is a major global cause of morbidity and mortality. This study evaluated risk factors for mortality in children with pneumococcal meningitis and other invasive pneumococcal diseases (IPD).
The study population included patients <15 years of age with laboratory-confirmed IPD and available outcome data between January 1, 2003 and December 31, 2005 as reported to a national laboratory-based surveillance program. Meningitis was defined by having pneumococcus identified from cerebrospinal fluid culture, while other IPD included patients with pneumococci identified from other normally sterile site specimens. Risk factors for mortality were evaluated using multivariable logistic regression.
A total of 2251 patients with IPD were reported from sentinel sites: 581 with laboratory-confirmed meningitis and 1670 with other IPD. The case-fatality ratio was 35% (205/581) among meningitis cases and 18% (300/1670) among other IPD cases (P < 0.001). Among individuals with available human immunodeficiency virus (HIV) status data, HIV coinfection was less likely among patients with meningitis compared with other IPD (74% [244/328] vs. 82% [880/1067] P < 0.001). On multivariable analysis, HIV-infected status (odds ratio [OR]: 5.34, 95% confidence interval [CI]: 2.32-12.29), Pitt bacteremia score ≥4 (OR: 3.08, 95% CI: 1.21-7.83) and age group <1 year (OR: 2.58, 95% CI: 1.21-5.51) were independent predictors of death among patients with meningitis. Among children with other IPD, malnutrition was an independent predictor of death while HIV infection was not independently associated with increased risk of death.
Pneumococcal meningitis is associated with a high case-fatality ratio among South African children and this is increased by HIV coinfection. Increasing access to antiretroviral therapy and a catch-up program for pneumococcal conjugate vaccine among HIV-infected and malnourished children could reduce this excess mortality.
The Pediatric Infectious Disease Journal 07/2011; 30(12):1075-80. · 3.58 Impact Factor
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ABSTRACT: HIV infection is a major risk factor for invasive pneumococcal disease (IPD). A national antiretroviral program was initiated in South Africa in 2004. This study evaluates the impact of the highly active antiretroviral therapy (HAART) treatment program on the burden of IPD among African children.
Retrospective analysis of laboratory-confirmed IPD among children under 18 years of age, from 2003 to 2008.
The periods 2003-2004, 2005-2006 and 2007-2008 were defined as the early, intermediate and established HAART eras, respectively. Pneumococcal conjugate vaccine was not introduced into public immunization during this period.
One thousand, one hundred and seventy-one episodes of IPD were identified over the study period. Among HIV-infected children under 18 years, the burden of IPD decreased by 50.8% [95% confidence interval (CI) 41.5-58.7] and the incidence of IPD-related mortality declined by 65.2% (95% CI 47.2-77.0) from the early compared to the established HAART era. This decline in HIV-infected children was evident for pneumococcal bacteremia and pneumococcal meningitis. In addition, similar reductions were observed for serotypes included in a 7-valent pneumococcal conjugate vaccine and nonvaccine serotypes. The burden of IPD remained unchanged in HIV-uninfected children under 18 years of age over these periods. The risk of IPD, however, remained 42-fold greater in HIV-infected compared to HIV-uninfected children in the established HAART era.
Although the HAART program has been associated with significant declines in IPD morbidity and mortality, HIV-infected African children with access to HAART remain a high-risk group for IPD. These children should therefore be prioritized in the prevention of IPD.
AIDS (London, England) 02/2011; 25(4):453-62. · 4.91 Impact Factor
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ABSTRACT: All fully sequenced strains of Streptococcus pneumoniae possess a version of the blp locus, which is responsible for bacteriocin production and immunity. Activation of the blp locus is stimulated by accumulation of the peptide pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The blp locus is characterized by significant diversity in blpC type and in the region of the locus containing putative bacteriocin and immunity genes. In addition, the blpA gene can represent a single large open reading frame or be divided into several smaller fragments due to the presence of frameshift mutations. In this study, we use a collection of strains with blp-dependent inhibition and immunity to define the genetic changes that bring about phenotypic differences in bacteriocin production or immunity. We demonstrate that alterations in blpA, blpC, and bacteriocin/immunity content likely play an important role in competitive interactions between pneumococcal strains. Importantly, strains with a highly conserved frameshift mutation in blpA are unable to secrete bacteriocins or BlpC, but retain the ability to respond to exogenous peptide pheromone produced by cocolonizing strains, stimulating blp-mediated immunity. These "cheater" strains can only coexist with bacteriocin-producing strains that secrete their cognate BlpC and share the same immunity proteins. The variable outcome of these interactions helps to explain the heterogeneity of the blp pheromone, bacteriocin, and immunity protein content. IMPORTANCE: Streptococcus pneumoniae resides in a polymicrobial environment and competes for limited resources by the elaboration of small antimicrobial peptides called bacteriocins. A conserved cluster of genes in the S. pneumoniae genome is involved in the production of bacteriocins and their associated protective immunity proteins through secretion of a signaling pheromone. In this study, we show that a significant number of strains have lost the ability to secrete bacteriocins and signaling pheromones due to a specific mutation in a dedicated transporter protein. Because the regulatory and immunity portion of the locus is retained, these "cheater" strains can survive in the face of invasion from a bacteriocin-producing strain without the cost of bacteriocin secretion. The outcome of such interactions depends on each strain's repertoire of pheromone, immunity protein, and bacteriocin genes, such that intrastrain competition drives the diversity in bacteriocin, immunity protein, and pheromone content.
mBio 01/2011; 2(5). · 5.31 Impact Factor
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ABSTRACT: Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008.
Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005-06 as the intermediate-HAART era and 2007-08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and-uninfected individuals.
A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods.
Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults.
PLoS ONE 01/2011; 6(11):e27929. · 4.09 Impact Factor
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Journal of Antimicrobial Chemotherapy 10/2010; 65(10):2258-60. · 5.07 Impact Factor
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ABSTRACT: 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 < 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.
AIDS (London, England) 06/2010; 24(9):1351-60. · 4.91 Impact Factor
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ABSTRACT: 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 661 (4%) were serotype 3, mostly from adults (85% [489/575]). Fewer serotype 3 isolates were nonsusceptible to antimicrobial agents tested (40/661 [6%]) than non-serotype 3 isolates (8,480/15,319 [55%]) (P < 0.001). Compared to non-serotype 3 cases, there was no association with HIV coinfection (2,212/2,569 [86%] versus 72/78 [92%]; P = 0.1) or increased case fatality ratio (1,190/4,211 [28%] versus 54/154 [35%]; P = 0.7). Serotype 3 in children had a low but statistically insignificant invasive disease potential (odds ratio [OR] of 0.15; 95% confidence interval [CI] of 0.01 to 1.06). Strains were grouped into 3 PFGE clusters, with the largest, cluster A, representing 54% (84/155), including 14 isolates confirmed as sequence type 458 (ST458). It was confirmed that 3 isolates from cluster B, which represented only 12% (18/155) of the isolates, were the serotype 3 global strain, ST180. We have therefore identified ST458 as predominating in South Africa, but with an invasive potential similar to that of the predominant global clone ST180.
Journal of clinical microbiology 11/2009; 48(1):184-91. · 4.16 Impact Factor
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ABSTRACT: Fluoroquinolones are not indicated for use for the treatment of pneumonia in children; however, non-levofloxacin-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 non-levofloxacin-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.
Journal of clinical microbiology 03/2009; 47(5):1319-24. · 4.16 Impact Factor
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ABSTRACT: Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 microg/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 penicillin-susceptible 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.
Journal of clinical microbiology 10/2008; 46(10):3208-14. · 4.16 Impact Factor
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ABSTRACT: 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 (1998-2005). 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 (non-susceptibility 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.
International Journal of Antimicrobial Agents 09/2008; 32 Suppl 1:S66-70. · 4.13 Impact Factor
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ABSTRACT: 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=15982), 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.
International Journal of Antimicrobial Agents 07/2008; 32(1):62-7. · 4.13 Impact Factor
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Anne von Gottberg,
Keith P Klugman,
Cheryl Cohen,
Nicole Wolter, Linda de Gouveia,
Mignon du Plessis,
Ruth Mpembe,
Vanessa Quan,
Andrew Whitelaw,
Rena Hoffmann,
Nelesh Govender,
Susan Meiring,
Anthony M Smith,
Stephanie Schrag
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ABSTRACT: Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect 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 fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.
21,521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19,404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected.
12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35.78, 95% CI 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin.
Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.
The Lancet 04/2008; 371(9618):1108-13. · 38.28 Impact Factor
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ABSTRACT: 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.
We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005. The system was enhanced in 2003 to include clinical data collection of cases from sentinel sites. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing.
A total of 2135 cases of invasive meningococcal disease were reported, of which 1113 (52%) occurred in Gauteng Province, South Africa. In this province, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 persons in 2005; the percentage due to serogroup W135 increased from 7% (4 of 54 cases) to 75% (221 of 295 cases). The median age of patients infected with serogroup W135 was 5 years (interquartile range, 2-23 years), compared with 21 years (range, 8-26 years) for those infected with serogroup A (P<.001). The incidence of W135 disease increased in all age groups. Rates were highest among infants (age, <1 year), increasing from 5.1 cases per 100,000 persons in 2003 to 21.5 cases per 100,000 persons in 2005. Overall case-fatality rates doubled, from 11% in 2003 to 22% in 2005. Serogroup W135 was more likely to cause meningococcemia than was serogroup A (82 [28%] of 297 cases vs. 11 [8%] of 141 cases; odds ratio, 8.9, 95% confidence interval, 2.2-36.3). A total of 285 (95%) of 301 serogroup W135 isolates were identified as 1 clone by pulsed-field gel electrophoresis; 7 representative strains belonged to the ST-11/ET-37 complex.
Serogroup W135 has become endemic in Gauteng, South Africa, causing disease of greater severity than did the previous predominant serogroup A strain.
Clinical Infectious Diseases 02/2008; 46(3):377-86. · 9.15 Impact Factor
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ABSTRACT: We describe the epidemiology of invasive meningococcal disease in South Africa from August 1999 through July 2002, as reported to a laboratory-based surveillance system. Neisseria meningitidis isolates were further characterized. In total, 854 cases of laboratory-confirmed disease were reported, with an annual incidence rate of 0.64/100,000 population. Incidence was highest in infants < 1 year of age. Serogroup B caused 41% of cases; serogroup A, 23%; serogroup Y, 21%; serogroup C, 8%; and serogroup W135, 5%. Serogroup B was the predominant serogroup in Western Cape Province, and disease rates remained stable. Serogroup A was most prevalent in Gauteng Province and increased over the 3 years. On pulsed-field gel electrophoresis analysis, serogroup A strains showed clonality, and serogroup B demonstrated considerable diversity. Selected isolates of serogroup A belonged to sequence type (ST)-1 (subgroup I/II) complex, serogroup B to ST-32/electrophoretic type (ET)-5 complex, and serogroup W135 to ST-11/ET-37 complex.
Emerging infectious diseases 03/2007; 13(2):273-81. · 6.17 Impact Factor
