Genomic analysis of nontypeable pneumococci causing invasive pneumococcal disease in South Africa, 2003-2013.

BACKGROUND: The capsular polysaccharide is the principal virulence factor of Streptococcus pneumoniae and a target for current pneumococcal vaccines. However, some pathogenic pneumococci are serologically nontypeable [nontypeable pneumococci (NTPn)]. Due to their relative rarity, NTPn are poorly characterized, and, as such, limited data exist which describe these organisms. We aimed to describe disease and genotypically characterize NTPn causing invasive pneumococcal disease in South Africa. RESULTS: Isolates were detected through national, laboratory-based surveillance for invasive pneumococcal disease in South Africa and characterized by whole genome analysis. We predicted ancestral serotypes (serotypes from which NTPn may have originated) for Group I NTPn using multilocus sequence typing and capsular region sequence analyses. Antimicrobial resistance patterns and mutations potentially causing nontypeability were identified. From 2003-2013, 39 (0.1 %, 39/32,824) NTPn were reported. Twenty-two (56 %) had partial capsular genes (Group I) and 17 (44 %) had complete capsular deletion of which 15 had replacement by other genes (Group II). Seventy-nine percent (31/39) of our NTPn isolates were derived from encapsulated S. pneumoniae. Ancestral serotypes 1 (27 %, 6/22) and 8 (14 %, 3/22) were most prevalent, and 59 % (13/22) of ancestral serotypes were serotypes included in the 13-valent pneumococcal conjugate vaccine. We identified a variety of mutations within the capsular region of Group I NTPn, some of which may be responsible for the nontypeable phenotype. Nonsusceptibility to tetracycline and erythromycin was higher in NTPn than encapsulated S. pneumoniae. CONCLUSIONS: NTPn are currently a rare cause of invasive pneumococcal disease in South Africa and represent a genetically diverse collection of isolates.

Clinical and Microbiological Features of Salmonella Meningitis in a South African Population, 2003-2013.

BACKGROUND: The clinical and microbiological characteristics of nontyphoidal Salmonella (NTS) meningitis in South Africa, where human immunodeficiency virus (HIV) prevalence is high (approximately 15% in persons ≥15 years of age), were reviewed. METHODS: From 2003 through 2013, 278 cases were identified through national laboratory-based surveillance. Clinical information (age, sex, outcome, Glasgow Coma Scale [GCS], and HIV status) was ascertained at selected sites. Isolates were serotyped; susceptibility testing and multilocus sequence typing on Salmonella enterica serovar Typhimurium isolates was performed. Multivariable logistic regression was used to determine factors associated with mortality outcome, using Stata software, version 13. RESULTS: Where age was ascertained, 139 of 256 (54.3%) patients were <15 years. Males represented 151 of 267 (56.6%). Mortality outcome was recorded for 112 of 146 (76.7%) enhanced surveillance patients; 53 of 112 (47.3%) died. Death was associated with GCS ≤13 (adjusted odds ratio [OR], 18.7; 95% confidence interval [CI], 3.0-118.5; P = .002) on multivariable analysis. Where data were available, all 45 patients aged >15 years were HIV infected, compared with 24 of 46 (52.2%) patients aged <5 years. Neonates were less likely to be HIV infected than infants aged 2-12 months (OR, 4.8; 95% CI, 1.1-21.1; P = .039).Salmonella Typhimurium represented 106 of 238 (44.5%) serotyped isolates: 65 of 95 (68.4%) were ST313 vs ST19, respectively, and significantly associated with HIV-infected patients (P = .03) and multidrug resistance (OR, 6.6; 95% CI, 2.5-17.2; P < .001). CONCLUSIONS: NTS meningitis in South Africa is highly associated with HIV in adults, with neonates (irrespective of HIV status), and with Salmonella Typhimurium ST313. GCS is the best predictor of mortality: early diagnosis and treatment are critical. Focused prevention requires further studies to understand the sources and transmission routes.

Anxiety and depression symptoms in the 2 years following diagnosis of breast or gynaecologic cancer: prevalence, course and determinants of outcome.

PURPOSE: The purposes of this study are to examine the course and prevalence of anxiety and depression over 24 months in women with newly diagnosed breast and gynaecologic cancer and, controlling for demographic and clinical confounders, to test the role of neuroticism and psychiatric history in determining outcome 6, 12, 18 and 24 months post-diagnosis. METHODS: Participants completed the Hospital Anxiety and Depression Scale-anxiety subscale and Centre for Epidemiological Studies Depression Scale on an 8-weekly basis from diagnosis until 96 weeks. Changes over time were analyzed with repeated measures ANOVA. Hierarchical linear regression, adjusted a priori for age, chemotherapy and radiation treatment, living alone, education and tumour stream were used to predict anxiety and depression. RESULTS: Participants were 105 women (66 breast, 39 gynaecologic). Rates of anxiety (18.1 %) and depression (33.3 %) were highest at diagnosis. Average rates of anxiety and depression were 5.9 and 22.4 %, respectively. Average scores of anxiety and depression were highest at diagnosis, with improvement at 8 and 40 weeks, respectively, subsequently maintained. Morbidity at diagnosis was particularly acute among women with a treatment history of anxiety/depression or with high neuroticism. These three variables were the best and only predictors over 24 months. CONCLUSIONS: Women are most vulnerable to anxiety and depression at diagnosis, with improvement over time. Morbidity rates are lower than reported elsewhere. Women with high neuroticism and a psychiatric history are at greatest risk for future morbidity after adjusting for confounders. Early identification of these women plus heightened surveillance or early referral to psychosocial services may protect against longer-term morbidity.

Comparison of the acceptability and benefits of two mindfulness-based interventions in women with breast or gynecologic cancer: a pilot study.

PURPOSE: The aim of this study was to compare the relative benefits and acceptability of two different group-based mindfulness psychotherapy interventions among women with breast and gynecologic cancer. METHODS: Data from 42 women who completed an 8-week mindfulness-based cognitive therapy (MBCT) program comprising 22 contact hours were compared to data from 24 women who completed a 6-week mindfulness meditation program (MMP) comprising 9 contact hours. Distress, quality of life (QOL), and mindfulness were evaluated pre- (T1) and post-intervention (T2). ANCOVA was used to analyse the relationship between intervention type and T1 score on outcome variable change scores. Participants' perceptions of benefit and acceptability were assessed. RESULTS: The participants did not differ on clinical or demographic variables other than MBCT participants were more likely than MMP participants to have a past history of anxiety or depression (p = .01). Scores on distress, QOL, and mindfulness improved from T1 to T2 with medium to large effect sizes for the MMP (p=.002, d=.7; p=.001, d=.8; p=.005, d=.6, respectively) and MBCT (p<.001,d = .6; p=.008, d = .4; p<.001, d=.9, respectively) interventions. [correted]. ANCOVA showed no main effect for intervention type on outcome change scores and no interaction between intervention type and respective T1 score. Distress and mindfulness scores at T1 had a main effect on respective change scores (p = .02, ηp (2) = .87; p = .01, ηp (2) = .80, respectively). Both programs were perceived as beneficial and acceptable with no differences between the intervention types. CONCLUSIONS: Within the limits of a small, non-randomized study, these findings provide preliminary support for the utility of a brief mindfulness intervention for improving distress and QOL in a heterogeneous group of women with cancer. Abbreviated interventions are less resource intensive and may be attractive to very unwell patients.

Screening for depression and anxiety in women with breast and gynaecologic cancer: course and prevalence of morbidity over 12 months.

OBJECTIVE: This study aims to investigate the course and prevalence of anxiety and depression symptoms over 56 weeks in women with newly diagnosed breast and gynaecologic cancer and determine the acceptability and efficiency of incorporating routine screening into practice. METHODS: Participants completed the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) and Centre for Epidemiological Studies Depression Scale (CES-D) at diagnosis and again every 8 weeks for 56 weeks. Changes over time were analysed with repeated measures ANOVA adjusted for post hoc comparisons. Thresholds for caseness/referral to mental health were ≥ 11 and ≥ 16 on the HADS-A and CES-D, respectively. RESULTS: Participants were 167 women (101 breast, 66 gynaecologic). Mean ± SD age was 57.63 ± 22.66 years. Rates of anxiety (17.7%), depression (32.5%) and combined anxiety and depression (35%) symptoms were highest at diagnosis. Mean ± SD scores of anxiety (6.43 ± 3.83) and depression symptoms (12.68 ± 9.47) were highest at diagnosis with significant improvements observed by 8 and 24 weeks, respectively, and maintained thereafter. Overall rates of anxiety, depression and combined symptoms were 7.5%, 23.4% and 24.1%, respectively. Patients with breast and gynaecologic cancer did not differ. Referral was offered at least once to 94 women (56.3%), of whom 45 (47.9%) declined, 23 (24.5%) accepted and 26 (27.7%) were already receiving treatment. Patient evaluation was favourable. CONCLUSIONS: Women are most vulnerable to psychological morbidity at diagnosis. Symptoms improve significantly over time. Reported rates are lower than those in the literature. Regular screening by self-report is acceptable to patients but may not be the most efficient method of improving patient outcomes.

Mindfulness-based cognitive group therapy for women with breast and gynecologic cancer: a pilot study to determine effectiveness and feasibility.

PURPOSE: Group-based mindfulness training is frequently described in psycho-oncology literature, but little is known of the effectiveness of mindfulness-based cognitive therapy (MBCT). We investigated the effectiveness and acceptability of MBCT for women with breast and gynecologic cancer. METHODS: Fifty women were recruited to participate in eight weekly 2-h mindfulness sessions. Outcomes of distress, quality of life (QOL), post-traumatic growth, and mindfulness were assessed pre-intervention, post-intervention, and again 3 months later using validated measures. Data were analyzed with repeated measures ANOVAs with a Bonferroni correction. Participant satisfaction and evaluation were also assessed. RESULTS: Forty-two women completed the program, and complete data were available for 36 women. Significant improvements with large effect sizes (ηρ(2)) were observed for distress (P < 0.001; ηρ(2) = 0.238), QOL (P = 0.001; ηρ(2) = 0.204), mindfulness (P < 0.001; ηρ(2) = 0.363) and post-traumatic growth (P < 0.001; ηρ(2) = 0.243). Gains were maintained 3 months post-intervention. Improvements in outcomes did not differ based on diagnostic group, psychological status, or physical well-being at entry. Change indices further support these findings. Scores on measures of distress, QOL, and post-traumatic growth decreased as a function of increased mindfulness at each time point (all P < 0.05). Participants reported experiencing the program as beneficial, particularly its group-based nature, and provided positive feedback of the therapy as a whole as well as its individual components. CONCLUSIONS: Within the limits of a non-randomized trial, these findings provide preliminary support for the potential psychosocial benefits of MBCT in a heterogeneous group of women with cancer. Future, more comprehensive trials are needed to provide systematic evidence of this therapy in oncology settings.

Systemic shigellosis in South Africa.

BACKGROUND: Systemic disease due to shigellae is associated with human immunodeficiency virus (HIV), malnutrition, and other immunosuppressed states. We examined the clinical and microbiologic characteristics of systemic shigellosis in South Africa, where rates of HIV infection are high. METHODS: From 2003 to 2009, 429 cases of invasive shigellosis were identified through national laboratory-based surveillance. At selected sites, additional information was captured on HIV serostatus and outcome. Isolates were serotyped and antimicrobial susceptibility testing performed. RESULTS: Most cases of systemic shigellosis were diagnosed on blood culture (408 of 429 cases; 95%). HIV prevalence was 67% (80 of 120 cases), highest in patients aged 5-54 years, and higher among females (55 of 70 cases; 79%) compared with males (25 of 48 cases; 52%; P = .002). HIV-infected people were 4.1 times more likely to die than HIV-uninfected cases (case-fatality ratio, 29 of 78 HIV-infected people [37%] vs 5 of 40 HIV-uninfected people [13%]; P = .008; 95% confidence interval [CI], 1.5-11.8). The commonest serotype was Shigella flexneri 2a (89 of 292 serotypes [30.5%]). Pentavalent resistance occurred in 120 of 292 isolates (41.1%). There was no difference in multidrug resistance between HIV-infected patients (33 of 71 [46%]) and uninfected patients (12 of 33 [36%]; 95% CI, .65--3.55). CONCLUSIONS: Systemic shigellosis is associated with HIV-infected patients, primarily in older girls and women, potentially due to the burden of caring for sick children in the home; interventions need to be targeted here. Death rates are higher in HIV-infected versus uninfected individuals.

Risk factors for multidrug-resistant invasive pneumococcal disease in South Africa, a setting with high HIV prevalence, in the prevaccine era from 2003 to 2008.

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.

Assessment of childhood obesity in secondary care: OSCA consensus statement.

This expert opinion provides detailed guidance on assessing obesity in secondary paediatric practice. This guidance builds on existing recommendations from National Institute of Health and Clinical Excellence in the UK, and is evidence based where possible. Guidance is provided on which obese children and young people are appropriate to be seen in secondary care and relevant history and investigations, and guidance on when further investigation of causes and obesity-related comorbidity is appropriate.

Experiences and interpretations of BRCA1/2 testing among women affected by breast or ovarian cancer who received a negative result.

The aim of this study was to retrospectively describe the genetic testing motives and experiences of women with a previous breast and/or ovarian cancer diagnosis, who received negative BRCA1/2 results including variants of unknown significance and no pathogenic variant detected. One hundred and thirteen women (mean age 56.17 years) were recruited from a familial cancer centre in metropolitan Australia, an average 3.4 years after undergoing testing. Participants completed a self-report questionnaire focusing on the retrospective experience of and motives for undergoing BRCA1/2 testing. The study found that the primary motives for undergoing BRCA1/2 testing were (a) to know more about whether their cancer was hereditary, and (b) to have more certainty about the risk of their children developing cancer. In terms of perceptions of personal risk, 35% of women perceived that their risk of breast cancer to be the same or lower than the general population and 80% believed the negative test result to mean that a risk-conferring gene had not been detected. Yet, the average estimate of the likelihood that their cancer was hereditary was 48 out of a possible 100. Psychologically, women did not interpret the negative BRCA1/2 result as a positive outcome. Half were not relieved by the result and were as or more worried than before. Psychological morbidity was high with 17%, 100%, and 36% experiencing clinically significant depression, anxiety, and cancer-specific distress, respectively. Self-ratings of the likelihood that their cancer was hereditary were more closely associated with their personal family cancer histories than with measures of psychological distress. These results have implications for adherence to risk-reducing behaviours and quality of life. Given that these women are not routinely followed up in clinical practice, these findings highlight the importance of post-test genetic counselling and longer-term follow-up for women with negative BRCA1/2 results. Additional time and emotional support from genetic counsellors may help this group of women make sense of the meaning of their test result and adjust psychologically, particularly to uncertainty around the cause of their family history.

Can pneumococcal meningitis surveillance be used to assess the impact of pneumococcal conjugate vaccine on total invasive pneumococcal disease? A case-study from South Africa, 2005-2016.

INTRODUCTION: South Africa introduced seven-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. We aimed to compare the estimated impact of PCV on pneumococcal meningitis (PM) to impact of PCV on total invasive pneumococcal disease (tIPD) based on risk reduction after PCV introduction. METHODS: We conducted national, laboratory-based surveillance for tIPD during 2005-2016. We estimated and compared rates of PCV13 and non-PCV13 serotype disease among tIPD and PM in individuals aged <5 years and ≥5 years, and compared these rates between the 2005-2008 pre-PCV introduction period and two time points after PCV introduction, 2012 and 2016. RESULTS: We enrolled 45,853 tIPD cases; 17,251 (38%) were PM. By 2016, IPD caused by all serotypes decreased 55% (95%CI -57% to -53%) for tIPD, and 54% for PM (95%CI -58% to -51%), 0.7% difference between estimates (p = 0.7). No significant differences were observed between PCV7-serotype disease reduction in tIPD and PM in both age groups or the additional 6 serotypes included in PCV13 in <5 year olds in 2012 and 2016. In 2012 there was a significant difference between increases in non-PCV13 serotype disease in those ≥5 years for tIPD and PM (32% greater increase in PM, p < 0.001), but this difference was absent by 2016. There was a significant difference between the estimated decrease in additional PCV13 type disease in 2016 between tIPD and PM for those aged ≥5 years (28% greater reduction in PM, p = 0.008). CONCLUSION: PM showed similar reductions to tIPD seven years after PCV introduction in vaccine serotype disease in those <5 years, and increases in non-vaccine serotype disease in all ages.

Invasive Pneumococcal Disease in Neonates Prior to Pneumococcal Conjugate Vaccine Use in South Africa: 2003-2008.

BACKGROUND: Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. We provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009. METHODS: Data from children (age ≤ 2 years) with IPD (pneumococcus identified from a normally sterile specimen) from January 2003 to December 2008 were extracted from a national laboratory-based surveillance database. Clinical and laboratory characteristics of IPD among neonates (0-27 days old) was compared with IPD among young children (≥ 28 days ≤ 2 years). Early-onset IPD (0-6 days old) was compared with late-onset IPD (≥ 7-27 days old). Isolates were serotyped using the Quellung reaction. RESULTS: Overall 27,630 IPD cases were reported. Of the 26,277 (95%) with known ages, 6583 (25%) were ≤ 2 years of age, of which 4.5% (294/6583) were neonates. The estimated annual incidence of neonatal IPD in 2008 was 5 per 100,000 live births. Fifty-one percent of neonates with IPD presented with early-onset IPD. Case fatality ratios (CFRs) were high in both groups, 31% (28/89) in neonatal IPD versus 26% (614/2383) in non-neonatal IPD (P = 0.18). Among neonates, the meningitis cases (15/37, 41%) were associated with the highest CFR. The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes accounted for 69% (134/194) of neonatal IPD isolates. CONCLUSIONS: Pneumococcal neonatal disease in South Africa was not uncommon before PCV introduction and is associated with a high CFR. The indirect effect on neonatal IPD of PCV rollout requires further evaluation.

Predictors of depression and anxiety symptom trajectories in the 24 months following diagnosis of breast or gynaecologic cancer.

OBJECTIVE: To identify predictors of anxiety and depression symptom trajectories, as distinct from general distress, in the 96 weeks following diagnosis of breast or gynaecologic cancer. METHODS: Participants completed the Hospital Anxiety and Depression Scale anxiety subscale (HADS-A) and Centre for Epidemiological Studies Depression Scale (CES-D) at diagnosis and at 8-weekly intervals for 96 weeks. Linear mixed models were used to determine the effects of age, relationship status, tumour stream, cancer stage, living situation, residential area, educational status, current and previous anxiety/depression treatment and neuroticism on symptom trajectories. RESULTS: Participants were 264 women with a mean (SD) age of 54 (12) years. Compared to non-treatment-receiving counterparts, women who received anxiety/depression treatment in the past had depression and anxiety symptom severity scores that were 4.58 and 1.24 higher, respectively. Women receiving such treatment at cancer diagnosis had depression and anxiety scores that were 4.34 and 2.35 points higher, respectively, than their counterparts. Compared to women with the lowest neuroticism scores, women with the highest scores scored 8.48 and 3.82 higher on the CES-D and HADS-A, respectively. Depressive severity remained stable but anxiety severity decreased as a function of neuroticism. CONCLUSIONS: In settings with limited resources, women with high neuroticism or a depression/anxiety treatment history should be the initial target of psychological screening. Identification of women with these characteristics at the earliest point of entry into the oncology service followed by heightened surveillance and/or referral to psychosocial services may be useful to prevent chronic psychological morbidity.

Comparison of the hospital anxiety and depression scale and the center for epidemiological studies depression scale for detecting depression in women with breast or gynecologic cancer.

OBJECTIVE: Depression is common in cancer patients but frequently undetected. Consensus regarding validity and optimal thresholds of screening measures is lacking. We investigated the validity of the Hospital Anxiety and Depression Scale (HADS-D) and Center for Epidemiological Studies Depression Scale (CES-D) relative to a referent diagnostic standard in women with breast or gynecologic cancer. METHOD: Participants were 100 patients who completed the CES-D and HADS-D within a larger study. The Mini International Neuropsychiatric Interview was the criterion standard. Sensitivity, specificity, predictive values and likelihood ratios for various thresholds were calculated using receiver operating characteristics. Participants were assigned to two diagnostic groups: 'major depressive disorder' or 'any depressive disorder'. RESULTS: Separate analyses were conducted whereby participants found to be receiving depression/anxiety treatment at the time of validation (n=28) were excluded. Both measures had good internal consistency and criterion validity. There were no statistical differences in global accuracy between the measures for detecting either group. For optimal sensitivity and specificity in both groups, generally recommended thresholds were lowered for the HADS-D. For the CES-D, the threshold was lowered for 'any depressive disorder' and raised for 'major depressive disorder'. Negative predictive values associated with our recommended cutoffs were excellent, but positive predictive values were poor. CONCLUSIONS: The HADS-D and CES-D have acceptable properties and are equivalent for detecting depression in this population. Depending on the purpose of screening, the CES-D may be more suitable for identifying major depression. Threshold choice may have serious implications for screening program effectiveness, and the use of generally recommended thresholds should be cautious.

Meningococcal serogroup Y lpxL1 variants from South Africa are associated with clonal complex 23 among young adults.

OBJECTIVES: To determine the genotypes of serogroup Y meningococcus (MenY), and to determine the prevalence of and identify factors associated with MenY lpxL1 variants. METHODS: Isolates, collected from 2003 to 2007 through national surveillance for invasive meningococcal disease, were characterized by multilocus sequence typing and screened for interleukin-6 induction. LpxL1 genes were sequenced from low IL-6 inducers. RESULTS: MenY represented 13% (n = 219/1702) of meningococcal disease. Clonal complex (cc) 175, ST-23/Cluster A3 (cc23), cc11 and cc167 accounted for 82% (176/214), 11% (24/214), 3% (6/214) and 3% (7/214) respectively. Low cytokine induction was evident in 15% (32/218). Cc23 isolates (24/24) had an lpxL1 mutation, while among the remaining isolates the proportion of lpxL1 variants was 4% (8/189, p < 0.001), and these were all cc175. Compared to wild type isolates, lpxL1 variants were associated with patients aged 5-14 years [unadjusted OR (95% CI): 4.3 (1.5-12)] or 15-24 years [unadjusted OR (95% CI): 9.1 (2.8-29)] compared to children <5 years; and were more likely have been isolated from CSF than blood [unadjusted OR (95% CI): 3.5 (1-11.9)]. On multivariable analysis, age remained significant [adjusted OR (95% CI), 5-14 years: 4.2 (1.5-12); 15-24 years: 8.9 (2.7-29)]. CONCLUSION: LpxL1 variants were associated with cc23 among young adults.

Epidemiology of invasive pneumococcal disease in the pre-conjugate vaccine era: South Africa, 2003-2008.

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 (relative risk ratio (RRR) 0.7; confidence interval (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.