Serotype 6C Research Articles

Identification of natural pneumococcal isolates expressing serotype 6D by genetic, biochemical and serological characterization

The recently discovered pneumococcal serotype 6C was created when the original wciN gene in the 6A capsule gene locus was naturally replaced with a new gene. Since the capsule gene loci of 6A and 6B serotypes may differ by only one base pair in the wciP gene, it was speculated that a new serotype '6D' would be possible if the new wciN gene were inserted into the 6B capsule gene locus. Although pneumococci expressing serotype 6D could be produced in the laboratory, initial searches for natural pneumococcal isolates expressing serotype 6D were unsuccessful. However, we now report the discovery of two naturally occurring pneumococcal isolates from Korea that have the serological, genetic and biochemical features predicted for serotype 6D.

Changes in pneumococcal serotypes and antibiotypes carried by vaccinated and unvaccinated day-care centre attendees in Portugal, a country with widespread use of the seven-valent pneumococcal conjugate vaccine

The seven-valent pneumococcal conjugate vaccine (PCV7) has been available in Portugal since June 2001, but is not included in the National Vaccination Plan. Its impact on colonization is unknown. A point-prevalence study to evaluate PCV7 usage was carried out in 2006 among day-care centre attendees from the Lisbon area. Pneumococcal carriage rates, serotypes, and antibiotypes were determined and compared with results from a similar study conducted in 2001 before vaccine approval. In 2001 and 2006, 717 and 571 children, respectively, were enrolled. In 2006, 45.9% of the participants were appropriately vaccinated and 11.5% were incompletely vaccinated. Carriage of pneumococci remained stable (64.9% in 2001; 68.7% in 2006). Vaccine types (VT) decreased from 53.1% of all pneumococci to 11.2% (p <0.001). Serotype replacement was observed among vaccinated and unvaccinated children. Non-vaccine types (NVT) 1, 6C, 7F, 15A, 16F, 21, 23A, 29, and non-typeable (NT) strains increased significantly; serotype 19A increased, but not significantly. Rates of resistance to penicillin, erythromycin, clindamycin and tetracycline remained stable (p >0.05) due to significant increases in intermediate resistance to penicillin (from 5.5% to 17.8%), erythromycin (from 9.2% to 21.8%), clindamycin (from 6.4% to 19.3%) and tetracycline (from 8.3% to 15.8%) among NVT. Whereas in 2001 resistance among NVT was mostly associated with serotype 19A and NT strains, in 2006 resistance was also found among serotypes 6C, 15A, 24F and 33F. In conclusion, dramatic shifts in serotypes of colonizing pneumococci were observed among vaccinated and unvaccinated children. Rates of antibiotic resistance remained unchanged due to a balance between reduction in VT and an increase in antimicrobial-resistant NVT.

Prevalence of Streptococcus pneumoniae serotype 6C among invasive and carriage isolates in metropolitan Salvador, Brazil, from 1996 to 2007

The newly described Streptococcus pneumoniae serotype 6C accounted for 2.3% (16/709) of meningitis cases and 3.2% (3/95) of nasopharyngeal isolates from healthy individuals in Brazil. The strains were multidrug resistant (18.8%) and genetically diverse. Despite low serotype 6C prevalence, continuous surveillance is necessary to guide vaccine strategies.

PP-039 Determine the new serotype 6C Streptococcus pneumoniae by serological method

PP-039 Determine the new serotype 6C Streptococcus pneumoniae by serological method

High prevalence, low counts and uncommon serotypes of Listeria monocytogenes in linguiça, a Brazilian fresh pork sausage

Linguiça is a highly popular and appreciated pork product in Brazil, frequently consumed undercooked. Aiming at collection of data for a future risk assessment, this study evaluated the prevalence and counts of Listeria monocytogenes in linguiça samples collected at retail level in Sao Paulo, SP, Brazil. ISO methods were used for detection and enumeration of the pathogen (11290-1 and 11290-2, respectively). Isolates were submitted to Simplex-PCR for hlyA gene and those with biochemical features of L. monocytogenes and hlyA positive were serotyped using a Multiplex PCR. Ninety percent of the samples were positive for Listeria spp., and L. monocytogenes was detected in 42% of the samples, with counts below 10 2 CFU/g in all samples. A prevalence of uncommon serotypes 4a and 4c was observed.

Simple, Accurate, Serotype-Specific PCR Assay To Differentiate Streptococcus pneumoniae Serotypes 6A, 6B, and 6C

In this study, we developed a simple, reliable, serotype-specific PCR method to differentiate Streptococcus pneumoniae serotypes 6A, 6B, and 6C. It was more efficient and practical than the assays currently being used to identify serotypes 6A, 6B, and 6C. Of 120 selected serogroup 6 isolates from subjects with invasive (n = 101) and noninvasive (n = 19) pneumococcal disease, most of which were collected after 2003 in New South Wales, 45 had been identified as 6A and 75 had been identified as 6B by the Quellung reaction. PCR analysis confirmed the results for serotype 6B isolates and identified two different subtypes. Fourteen of 45 isolates that had been identified as serotype 6A actually belonged to serotype 6C.

Identification of a Simple Chemical Structure Associated with Protective Human Antibodies against Multiple Pneumococcal Serogroups

Streptococcus pneumoniae, a major human pathogen, expresses at least 91 serologically distinct carbohydrate capsules. Since pneumococcal vaccines are designed to elicit antibodies against many different capsular polysaccharides (PSs), it is important to identify the epitopes involved in eliciting anti-capsular PS antibodies. We investigated the epitopes recognized by Dob1, which is a hybridoma-secreting human immunoglobulin G2 antibody to the PS of serotype 6B (Y. Sun et al., Infect. Immun. 67:1172-1179, 1999). We found that Dob1 bound synthetic capsular carbohydrates Gal(1-->3)alpha-d-Glcp(1-->3)alpha-l-Rhap(1-->3)Rib-ol and alpha-d-Glcp(1-->3)alpha-l-Rhap(1-->3)Rib-ol but did not bind alpha-l-Rhap(1-->3)Rib-ol. The critical epitope alpha-d-Glcp(1-->3)alpha-l-Rhap is found in the capsular PSs of serotypes 6A, 6B, 6C, and 19A but not in the 19F PS. Consistent with this observation, Dob1 bound to the PSs of serotypes 6A, 6B, 6C, and 19A but did not bind the 19F PS and 23 additional unrelated pneumococcal capsular PSs. Also, Dob1 could opsonize pneumococci expressing serotypes 6A, 6B, 6C, and 19A but did not opsonize 19F pneumococci. In addition, ca. 7% of immune sera (12 of 175 sera) had significant amounts of Dob1-like antibodies, i.e., reacted with 6B and 19A PSs, but not with 19F PS. Humans can produce antibodies to the Dob1 epitope and the antibodies to that epitope cross-react with the four serotypes 6A, 6B, 6C, and 19A that belong to different serogroups. This epitope may be useful for producing a totally synthetic, simple chemical structure that is capable of generating protective antibodies to multiple pneumococcal serogroups.

“Dodgy 6As”: Differentiating Pneumococcal Serotype 6C from 6A by Use of the Quellung Reaction

The Quellung reaction has long been the standard method for pneumococcal serotyping ([7][1]); however, the new serotype 6C is reportedly indistinguishable from serotype 6A using this method ([8][2]). We report an anomalous Quellung reaction associated with serotype 6C, which may aid in diagnostic

The 10-Valent Pneumococcal Non-typeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Coadministered With DTPw-HBV/Hib and Poliovirus Vaccines: Assessment of Immunogenicity

Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was evaluated when coadministered with DTPw-HBV/Hib and OPV at 6, 10, and 14 weeks of age in the Philippines, or with DTPw-HBV/Hib and IPV at 2, 4, and 6 months of age in Poland. In this double-blind, controlled study (107007/NCT00344318), 400 Filipino and 406 Polish infants 6 to 12 weeks of age were randomized (3:1) to receive either PHiD-CV or the 7-valent pneumococcal conjugate vaccine (7vCRM). Immune responses were assessed 1 month post-dose III. Percentages of infants with anti-pneumococcal antibody concentrations >or=0.2 microg/mL (GSK's 22F-inhibition ELISA) were within the same range for both pneumococcal conjugate vaccine groups, with the exception of serotypes 6B and 23F for which lower percentages were observed in the PHiD-CV group in Poland. At least 98.2% of PHiD-CV vaccinees had antibody concentrations >or=0.2 microg/mL against pneumococcal serotypes 1, 5, and 7F. In both countries, anti-pneumococcal antibody geometric mean concentrations against serotypes 18C and 19F were higher in the PHiD-CV group than in the 7vCRM group. Antibody geometric mean concentrations for most of the other common serotypes were within the same range for both groups in the Philippines and were lower in the PHiD-CV group in Poland. Functional responses (opsonophagocytic activity [OPA]) were observed for all vaccine serotypes in both countries. PHiD-CV was immunogenic against each of the 10 pneumococcal vaccine serotypes when coadministered with DTPw-HBV/Hib and poliovirus vaccines.

Immunogenicity of Routinely Used Childhood Vaccines When Coadministered With the 10-Valent Pneumococcal Non-typeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV)

The choice of non-typeable Haemophilus influenzae Protein D as main carrier protein in the candidate 10-valent pneumococcal conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals), was driven in part to avoid carrier-mediated suppression and possible bystander interference with coadministered vaccines. Immunogenicity data from 3 primary and 2 booster vaccination studies were assessed for possible impacts of PHiD-CV coadministration on immune responses to routinely administered childhood vaccines, in comparison to 7-valent pneumococcal conjugate vaccine (7vCRM) coadministration. Randomized, controlled studies in which PHiD-CV or 7vCRM vaccines were coadministered with DTPa-[HBV]-IPV/Hib, DTPa-[HBV]-IPV, DTPw-HBV/Hib, IPV, and OPV, combined Hib-Neisseria meningitidis serogroup C vaccine (Hib-MenC-TT), standalone MenC-TT or MenC-CRM vaccines. One month after primary vaccination, >96% of PHiD-CV recipients had seroprotective antibody concentrations against diphtheria, tetanus, poliovirus types 1 and 3, Hib (>or=0.15 microg/mL), SBA-MenC (>or=1:8), and >94% were seropositive for antibodies against pertussis antigens. Somewhat lower responses against poliovirus type 2 in study A (compared with poliovirus type 1 and 2 responses) and hepatitis B in the 6-, 10-, and 14-week schedule in the Philippines (compared with hepatitis B responses in the other studies) were observed after coadministration of both PHiD-CV and 7vCRM vaccines. Antitetanus and anti-PRP antibody geometric mean concentrations (GMCs) tended to be higher after PHiD-CV coadministration, probably because of the TT carrier protein for serotype 18C in PHiD-CV. Booster vaccination induced substantial increases in antibody GMCs for all coadministered antigens. These responses were generally within the same range in PHiD-CV and 7vCRM groups. Observed anti-PRP responses remained higher in PHiD-CV recipients after the booster dose. Coadministration of PHiD-CV with commonly used childhood vaccines induced high levels of seroprotection/seropositivity against all targeted diseases. No evidence of negative interference on the immune response to any of the coadministered vaccine antigens was observed when compared with the current routine practice of 7vCRM coadministration.

Characterization of fluoroquinolone-resistant Shigella flexneri in Hangzhou area of China

The aim of this study was to characterize fluoroquinolone-resistant Shigella and determine whether the qnr and aac(6')-Ib-cr genes could contribute to sporadic shigellosis at the clinic in the Hangzhou area of China. A total of 202 strains of Shigella (79 Shigella sonnei and 123 Shigella flexneri ) isolated from sporadic cases of shigellosis from 1998 to 2007 were analysed for their antimicrobial susceptibility. The gyrA, gyrB, parC, parE, qnr and aac(6')-Ib-cr genes and the profiles and incompatibility of plasmids were characterized. Chromosomal DNA fingerprinting was determined by XbaI-based digestion and PFGE. All strains of S. sonnei were susceptible to fluoroquinolones (ciprofloxacin and levofloxacin) while 15 out of 123 strains of S. flexneri were resistant. All of the 15 resistant strains displayed common mutations in the gyrA and parC genes and formed eight distinct groups with unique molecular characteristics. Notably, 10 isolates showed mutations at codon 87 of gyrA, and the other 5 were qnrS-positive. Two strains were positive for the aac(6')-Ib-cr gene. Importantly, this is the first report of qnrS- and aac(6')-Ib-cr-positive Shigella in China, the qnrS-positive S. flexneri serotypes 1a, 2a and 4c and the aac(6')-Ib-cr-positive S. flexneri serotypes 2a and 4c worldwide. The common mutations at position 83 of gyrA and position 80 of parC were crucial for resistance to nalidixic acid in S. flexneri. The mutation at position 87 of gyrA or the presence of the qnrS gene is necessary for high-level resistance to fluoroquinolones in Shigella isolates from China.

Increase in the Prevalence of the Newly Discovered Pneumococcal Serotype 6C in the Nasopharynx after Introduction of Pneumococcal Conjugate Vaccine

Because pneumococcal serotype 6C was previously not distinguished from serotype 6A, the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on the carriage of serotype 6C is unknown. The nasopharyngeal (NP) prevalence of the 6C serotype was determined using 1326 pneumococcal isolates collected from 7 cohorts of Massachusetts children between 1994 and 2007. Initially, the isolates were serotyped using the quellung reaction; subsequently, stored specimens of all putative 6A isolates were tested for 6C using monoclonal antibodies. The opsonophagocytic and antibiotic susceptibilities of the isolates were determined. The prevalence of 6A was 9.6% (33/343) before 2001, 8.0% (18/226) in 2004, and 2.9% (12/416) in 2007. In contrast, the prevalence of 6C was 0.6% (2/343) before 2001, 2.2% (5/226) in 2004, and 8.7% (36/416) in 2007 (P<.001 for 2/343 vs. 36/416). 6C isolates from 2007 were more susceptible to antibiotics than were 6A isolates. PCV7 induced a low ability to opsonize different isolates of 6C. Among NP isolates, the prevalence of 6C isolates has increased and the prevalence of 6A isolates has decreased since the introduction of PCV7 in Massachusetts in 2000. The observed increase in serotype 6C prevalence may be explained by the induction by PCV7 of low amounts of functional anti-6C antibody, compared with anti-6A and anti-6B antibodies.

Genetic characteristics of pneumococcal disease in elderly patients before introducing the pneumococcal conjugate vaccine

Streptococcus pneumoniae strains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.

PCR-Based Quantitation and Clonal Diversity of the Current Prevalent Invasive Serogroup 6 Pneumococcal Serotype, 6C, in the United States in 1999 and 2006 to 2007

Following introduction of the 7-valent pneumococcal conjugate vaccine to the United States, rates of invasive pneumococcal disease (IPD) caused by serotype 6A declined among all age groups, while rates of IPD caused by newly identified serotype 6C increased slightly among persons 5 years of age and older. Conventionally serotyped 6A isolates (CS6As) from active population-based surveillance during 1999 and 2006 to 2007 were classified as serotypes 6A and 6C by an expedient and highly accurate serotype 6C-specific PCR assay developed during this study. PCR testing of 636 year 1999, 2006, and 2007 CS6As revealed 6C proportions of 35/214 (16.4%), 141/218 (64.7%), and 141/204 (69.1%), respectively. These results agreed with those from a previously devised monoclonal antibody-based serotyping system (346 CS6As compared). Type 6C IPD incidence significantly increased during 2006 and 2007 compared to during 1999 (0.57 to 0.58 cases per 100,000 and 0.22 cases per 100,000, respectively; 164% increase from 1999 to 2007 [95% confidence interval, 87 to 270%]), while rates of IPD due to types 6A and 6B markedly decreased. In 2007, 31.2% of 6C isolates were not susceptible to penicillin. Serotype 6C is now the predominant serotype associated with serogroup 6 IPD in the United States and is often penicillin nonsusceptible. We performed multilocus sequence typing (MLST) on a limited sampling of 6C isolates with different antimicrobial susceptibility profiles. MLST of 42 6C isolates revealed 12 genotypes distributed among six distinct genetic groups. Fifteen 6C isolates shared one of four different MLST types with 6C-negative CS6As. MLST results suggest 6C strains arose from independent recombination events involving only serotype 6A and 6C parental strains.

Differential Effects of Pneumococcal Vaccines against Serotypes 6A and 6C

Because classic pneumococcal serotyping methods cannot distinguish between serotypes 6A and 6C, the effects of pneumococcal vaccines against serotype 6C are unknown. Pneumococcal vaccines contain serotype 6B but not serotypes 6A and 6C. We used a phagocytic killing assay to estimate the immunogenicity of the 7-valent conjugate vaccine (PCV7) in children and the 23-valent polysaccharide vaccine (PPV23) in adults against serotypes 6A and 6C. We evaluated trends in invasive pneumococcal disease (IPD) caused by serotypes 6A and 6C in the United States, using active surveillance. Serum specimens from PCV7-immunized children had median opsonization indices of 150 and < 20 for serotypes 6A and 6C, respectively. Similarly, only 52% of adults (25 of 48) vaccinated with PPV23 showed opsonic indices of > 20 against serotype 6C. During 1999--2006, the incidence of serotype 6A IPD decreased by 91% (from 4.9 to 0.46 cases per 100,000 persons; P < .05) among individuals aged < 5 years and by 58% (from 0.86 to 0.36 cases per 100,000 persons; P < .05) among those aged > or = 5 years. Although the incidence of 6C IPD showed no consistent trend (range, 0-0.6 cases per 100,000 persons) among individuals aged < 5 years, it increased from 0.25 to 0.62 cases per 100,000 persons (P < .05) among those aged > or = 5 years. PCV7 introduction has led to reductions in serotype 6A IPD but not serotype 6C IPD in the United States.

Age‐ and Serotype‐Specific Pediatric Invasive Pneumococcal Disease: Insights from Systematic Surveillance in Santiago, Chile, 1994–2007

We monitored pediatric invasive pneumococcal disease (IPD) in Santiago, Chile, from 1994 to 2007. Three related data sets were generated: (1) IPD cases requiring hospitalization, 1994--2007; (2) cases of bacteremia detected among febrile patients aged 0-35 months seen in emergency departments, 2000--2007; and (3) nasopharyngeal carriage of pneumococcal serotypes, determined from repetitive culturing, among 524 newborns followed up through age 23 months. Of 2369 IPD cases requiring hospitalization, 1878 (79.3%) occurred in those aged 0-59 months, and 1200 (50.7%) occurred in those aged 6-35 months. Among infants aged 0-5 months, meningitis and sepsis comprised 48.4% of all IPD cases (serotype 5 predominated); among those 6-35 months old, 522 (43.5%) of 1200 cases were bacteremic pneumonia (serotype 14 predominated). Serotype 1 peritonitis was common among 5-14-year-old girls. Meningitis and sepsis exhibited high case fatality rates (14%-29%) among all ages. Remarkably, 34 (28.8%) of 118 children with sepsis died, versus 1 fatality (0.4%) among 276 children hospitalized with bacteremia without a focus (P < .001, Fisher's exact test). Serotype 5 was significantly more common among hospitalized patients < 36 months of age, whereas serotype 18C was overrepresented among ambulatory patients. The annual incidence of serotype 14 was stable; those of serotypes 1 and 5 fluctuated markedly. Serotypes 14, 5, and 1 were overrepresented among invasive compared with nasopharyngeal isolates. Clinical syndromes of IPD and predominant serotypes vary with age.

Temporal Trends and Molecular Epidemiology of Recently Described Serotype 6C of Streptococcus pneumoniae

We studied the epidemiology of the recently described serotype 6C of Streptococcus pneumoniae among a collection of carriage isolates recovered between 1996 and 2007 in Portugal. Of 4,064 isolates, 106 (2.6%) were of serotype 6C, 17.9% of which were multidrug resistant. The strains were genetically diverse.

Emergence ofStreptococcus pneumoniaeSerotypes 19A, 6C, and 22F and Serogroup 15 in Cleveland, Ohio, in Relation to Introduction of the Protein‐Conjugated Pneumococcal Vaccine

A 7-valent conjugate pneumococcal vaccine (PCV7) was introduced in 2000. We determined serotypes and assessed antimicrobial susceptibility of 1235 invasive and noninvasive isolates of Streptococcus pneumoniae recovered from children and adults at University Hospitals Case Medical Center (Cleveland, OH) during the period 1999-2007. The annual number of cases of S. pneumoniae infection decreased from 218 in 2000 to 86-130 during the period 2002-2007, with the number of cases involving invasive strains decreasing from 96 to 18-35. For 1999 versus 2005-2007, the annual incidence of vaccine serotypes decreased by 92% (95% confidence interval [CI], -96.3% to -87.0%), whereas that of vaccine-related and nonvaccine serotypes increased 207.4% (95% CI, 135.0%-297.7%) and 18.4% (95% CI, -10.0% to 52.3%), respectively. Serotypes 19A, 6C, and 22F and serogroup 15 accounted for most of these increases. For the period 2005-2007, antimicrobial susceptibility testing revealed that ceftriaxone was the most active parenteral beta-lactam for both meningeal and nonmeningeal infections (72% and 88% of isolates, respectively, were susceptible to this agent); only 52% were susceptible to penicillin G at the meningeal breakpoint, whereas 77% were susceptible at the new nonmeningeal breakpoint of 2 microg/mL. Amoxicillin was the most active oral beta-lactam (72% of isolates were susceptible), whereas 53% of isolates were susceptible to azithromycin, 69% to clindamycin, 63% to trimethoprim-sulfamethoxazole, and 100% to levofloxacin. This study documents decreases in the incidence of infections involving vaccine serotypes, increases in infections involving other serotypes, and decreases in the activity of macrolides and clindamycin after conjugate vaccine introduction.

Occurrence, Distribution, and Origins of Streptococcus pneumoniae Serotype 6C, a Recently Recognized Serotype

The prevalence of Streptococcus pneumoniae serotype 6C, a recently recognized serotype that cross-reacts serologically with serotype 6A, was investigated. Isolates of serotype 6A in various collections were recovered, and serotype 6C was differentiated from 6A by multiplex PCR of DNA extracts by using appropriate primers. Antimicrobial susceptibility was performed by Clinical and Laboratory Standards Institute broth microdilution, and selected isolates were typed by pulsed-field gel electrophoresis, repetitive sequence-based PCR typing, and rapid multilocus sequence typing (MLST) by electrospray ionization mass spectrometry of PCR products. A total of 60 serotype 6C isolates were found: 30 of 122 Cleveland isolates collected from 1979 to 2007, 19 of 39 pediatric isolates collected nationwide in 2005 and 2006, and 11 pediatric isolates from Massachusetts collected in 2006 and 2007. Only four isolates were recovered prior to introduction of the conjugate pneumococcal vaccine in 2000; the earliest isolate was recovered in 1989. The sources of the isolates included blood (n = 5), the lower respiratory tract (n = 27), the sinus (n = 5), the ear (n = 2), and the nasopharynx (n = 18); isolates were recovered from 49 children and 11 adults. Pediatric isolates were found in all six major U.S. geographic regions. Antimicrobial susceptibility showed that 22 isolates were nonsusceptible to penicillin, macrolides, and trimethoprim-sulfamethoxazole, 8 had other resistance patterns, and 30 were fully susceptible. The three typing methods used showed similar clusters of up to eight isolates per cluster. MLST showed five clusters related to serotype 6A, two clusters related to serotype 6B, one cluster related to serotype 3, and one cluster related to serotype 34. This study documents the occurrence, nationwide distribution, diversity, likely origins, and increasing incidence after 2001 of this recently recognized serotype. Serotype 6C warrants consideration for addition to future conjugate pneumococcal vaccines.

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

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.