Peter V Adrian

Chris Hani Baragwanath Hospital, Johannesburg, Gauteng, South Africa

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Publications (44)235.39 Total impact

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    ABSTRACT: Background: Quantitative lytA realtime (rt) PCR from nasopharyngeal (NP) swabs distinguishes pneumococcal pneumonia (CAP) from asymptomatic colonization. Use of an optimized cut-off increased pneumococcal etiology compared to traditional diagnostic methods. Here we compare the utility of lytA rtPCR from induced sputum and from NP swabs. Methods: Pneumococcus was considered the cause of CAP in HIV-infected South African adults, if any of blood culture, induced sputum culture or Gram stain, urine antigen, whole blood lytA rtPCR revealed pneumococcus or if NP lytA rtPCR was >8000 copies/ml. lytA rtPCR was also performed on induced sputum. Results: 149 (67.1%) of 222 patients with available induced sputum had pneumococcus detected by lytA rtPCR from sputum, whereas either sputum Gram stain or culture were positive in 105 of 229 patients (45.9%; p<0.001). Mean copy numbers from sputum were higher if sputum cultures were positive than if sputum cultures were negative (7.9 vs. 5.6 log10 copies/ml; p<0.001). Against the composite diagnostic standard, a 10000 copies/ml cut-off for good quality sputum lytA rtPCR had a sensitivity of 78.1% and a specificity of 80.0%. This cut-off performed similarly well as the previously identified 8000 copies/ml cut-off for NP swab lytA rtPCR (AUC-ROC: 80.4% for any quality sputum vs. 79.6% for NP swab). The AUC-ROC for good quality sputum was 83.2%. Conclusions: Overall lytA rtPCR performs similarly well on induced sputum as on NP in most patients, but slightly better if good quality sputum can be obtained. Due to the ease of specimen collection, NP swabs may be preferable for the diagnosis of pneumococcal pneumonia.
    Journal of clinical microbiology. 09/2014;
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    ABSTRACT: There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants.
    New England Journal of Medicine 09/2014; 371(10):918-31. · 54.42 Impact Factor
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    ABSTRACT: A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome.
    BMJ Open 08/2014; 4(8):e005953. · 1.58 Impact Factor
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    ABSTRACT: We studied the effect of maternal HIV-exposure and timing of antiretroviral treatment (ART) in HIV-infected infants on antibody responses to combined diphtheria-toxoid-tetanus-toxoid-whole cell pertussis and Haemophilus influenzae type b conjugate vaccine (HibCV) and monovalent hepatitis B vaccine (HBV). HIV-uninfected infants born to HIV-infected (HEU) or HIV-uninfected (HUU) mothers were enrolled in parallel with HIV-infected children with CD4 ≥25%, who were randomized to initiate ART immediately upon confirmation of HIV-infection (ART-Immed) or when clinically and/or immunologically indicated (ART-Def). Infants received three doses of diphtheria-toxoid-tetanus-toxoid -wP-HibC/HBV at 7.3, 11.4 and 15.4 weeks of age. Antibody to diphtheria-toxoid, tetanus-toxoid, pertussis toxin, filamentous hemagglutinin (FHA) and hepatitis B surface antigen (HBsAg) were measured by Luminex multiplex-immunoassay and polyribosyl-ribitol phosphate (PRP) antibodies by standard ELISA and bactericidal assay. Prevaccination antibody geometric mean concentrations (GMCs) were higher in HUU than HEU infants for tetanus-toxoid, but lower for HBsAg, diphtheria-toxoid and FHA. Postvaccination GMCs and proportion with seroprotective antibody levels or sero-conversion rates were similar between HUU and HEU infants for all vaccines. Postvaccination GMCs were higher in HUU for tetanus-toxoid, diphtheria-toxoid, HBsAg and FHA than ART-Immed infants; and for tetanus-toxoid, HBsAg and pertussis-toxoid than ART-Def infants. Nevertheless, there was no difference in proportion of HUU and HIV-infected infants who developed sero-protective vaccine-specific antibody levels postvaccination. The timing of ART initiation generally did not affect immune responses to vaccines between HIV-infected groups. Vaccination with DTwP-HibCV/HBV of HEU and HIV-infected infants initiated on early-ART confers similar immunity compared with HUU children.
    AIDS (London, England) 02/2014; 28(4):531-41. · 4.91 Impact Factor
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    ABSTRACT: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and -KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and -uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and influenza A/B. At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and -uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than -uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV-uninfected children). We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.
    PLoS ONE 01/2014; 9(2):e86448. · 3.53 Impact Factor
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    ABSTRACT: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are pathogens commonly associated with infectious diseases in childhood. This study aimed to develop a fluorescent multiplexed bead-based immunoassay (FMIA) using recombinant proteins for the quantitation of serum IgG antibodies against these bacteria. Eight pneumococcal proteins (Ply, CbpA, PspA1, PspA2, PcpA, PhtD, SP1732-3 and SP2216-1), 3 proteins of H. influenzae (NTHi Protein D, NTHi0371-1, NTHi0830), and 5 proteins of M. catarrhalis (MC Omp CD, MC_RH4_2506, MC_RH4_1701, MC_RH4_3729-1, MC_RH4_4730) were used to develop the FMIA. Optimal coupling concentrations for each protein, comparison of singleplex and multiplex assays, specificity, reproducibility, and correlation to ELISA for six pneumococcal antigens were determined for validation. FMIA was then used to analyze acute and convalescent paired serum samples of 50 children with non-severe pneumonia. The coupling concentrations varied for different antigens, ranging from 1.6 to 32 μg of protein/million beads. Correlation between singleplexed and multiplexed assays was excellent, with R ≥ 0.987. The FMIA was specific, reaching > 92% homologous inhibition for all specificities; heterologous inhibition ≥ 20% was found only in six cases. The assay was repeatable, with averages of intra-assay variation ≤ 10.5%, day-to-day variation ≤ 9.7% and variation between technicians ≤ 9.1%. Comparison with ELISA for pneumococcal antigens demonstrated good correlation with R ranging from 0.854 (PspA2) to 0.976 (PcpA). The samples from children showed a wide range of antibody concentrations and increases in convalescent samples. In conclusion, the FMIA was sensitive, specific, and repeatable, using small amounts of recombinant proteins and sera to detect antibodies against S. pneumoniae, H. influenzae and M. catarrhalis. The methodology would be suitable for studies investigating etiological diagnosis and in experimental vaccine studies.
    Journal of immunological methods 01/2014; · 2.35 Impact Factor
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    ABSTRACT: Maternal recto-vaginal colonization with Group B Streptococcus (GBS) and consequent vertical transmission to the newborn predisposes neonates to early-onset invasive GBS disease. This study aimed to determine the acquisition and loss of serotype-specific recto-vaginal GBS colonization from 20-37+ weeks of gestational age.
    PLoS ONE 01/2014; 9(6):e98778. · 3.53 Impact Factor
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    ABSTRACT: A high prevalence of bacterial nasopharyngeal (NP) co-infections has been reported in children, however, there is limited such data in adults. We examined the interaction of Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae pharyngeal colonization in mother-child dyads. Pneumococcal-vaccine naive children and their mothers had pharyngeal swabs undertaken at 1.6, 2.5, 3.5, 4.5, 7.4, 9.5, 12.5, 16.2 and 24.2 months of child's age. Swabs were cultured for S. pneumoniae, H. influenzae and S. aureus using standard microbiologic methods. Multivariate generalized estimating equation-models were used to explore the associations of the three bacteria within and between children and their mothers. In children, the observed probability of co-colonization was higher than expected. Well-defined associations in colonization between the bacteria were observed in children but not among mothers. In children, a synergistic association was observed between S. pneumoniae and H. influenzae (Adjusted odds ratio (AOR):1.75, 95%CI:1.32-2.32) and a negative association between S. pneumoniae and S. aureus (AOR:0.51, 95%CI:0.39-0.67) or H. influenzae and S. aureus (AOR:0.24, 95%CI:0.16-0.34) colonization. Additionally, all three bacteria had a higher likelihood of concurrent colonization. There was a strong association in colonization by the bacteria in children and their mothers, including increased likelihood of maternal colonization if the child was colonized by S. pneumoniae (AOR:1.84, 95%CI:1.28-2.63) and H. influenzae (AOR: 6.34, 95%CI:2.24-18.0). The effects of immunization of children with pneumococcal-conjugate-vaccine in settings such as ours needs monitoring with regard to potential changes of pharyngeal bacterial ecology which could occur in vaccinated and --unvaccinated age-groups.
    BMC Infectious Diseases 10/2013; 13(1):483. · 3.03 Impact Factor
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    ABSTRACT: Pneumococcal vaccine-naïve mother-child dyads in South Africa had nasopharyngeal swabs taken 9 times within the first 2 years of the children's lives between January 2007 and May 2009. To quantify the strength of the association of serotype-specific carriage in mother-child dyads, a stochastic transmission model was fitted to the data. Children were more susceptible to individual serotypes included in the 7-valent pneumococcal conjugate vaccine (PCV7) transmitted by their mothers than vice versa; however, children infected their mothers with these serotypes more frequently than mothers infected children. The child-to-mother steady-state forces of pneumococcal acquisition were between 0.36 and 3.29 (per 1,000 days) compared with 0.06-0.51 for mother-to-child transmission. Although children of mothers infected with human immunodeficiency virus were more often exposed to PCV7 serotypes by their mothers, their risk of acquisition remained low compared with the risk of child-to-mother transmission. Mothers acquired pneumococci at lower rates (per 1,000 days) from unmeasured exposure within families and in the wider community (range, 0.12-1.69 per 1,000 days) than did children (range, 1.10-5.21 per 1,000 days). Pneumococcal immunization of young children is expected to have an indirect effect of reducing PCV7 serotype maternal colonization and possibly disease even in settings such as ours, in which there is a high prevalence of human immunodeficiency virus-infected mothers.
    American journal of epidemiology 10/2013; · 5.59 Impact Factor
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    ABSTRACT: Background: We recently reported a critical nasopharyngeal colonization density cut-off as a diagnostic for pneumococcal pneumonia. Here we analyzed the serotype-specific genomic pneumococcal density in blood with regards to colonization density. Methods: Quantitative realtime (rt) PCR for the 40 most prevalent pneumococcal serotypes was performed in the cps locus and lytAPCR was used as internal control on whole blood and nasopharyngeal washes (NW) in adults hospitalized for pneumonia in Soweto, South Africa. For serotyping 11 series of quadruplex rtPCR were performed. Results: Of 514 patients with pneumonia, lytA and serotyping rtPCR were positive from 82 (16.3%) and 49 (9.8%) of 502 available blood and from 226 (56.8%) and 179 (45.0%) of 398 available NW specimens. At least 2 different pneumococcal serotypes were detected in 34 (19.0%) NW and in 2 (4.1%; p=0.02) blood specimens; 3 (4.5%) serotypes in 8 NW and in 0 (0%; p=0.29) blood specimens. At least 1 identical serotype was found in 37 (9.5%) of 390 patients with both specimens available (75.5% of patients with serotype from blood). The bacterial genomic load was at least as high in the NW (0 to 104cfu/ml higher) as in blood. This difference was only significant for serotype 1 (p=0.012). There was a trend for higher pneumococcal density of NW in patients with a simultaneous positive blood specimen for serotypes considered “invasive”. If there was more than one serotype in the NW, the serotype detected in blood corresponded to the NW serotype with the higher genomic count. Conclusion: A quantitative serotyping PCR found at least one identical serotype in NW and blood in most cases. Our results provide important insight into pneumococcal pathogenesis. While the frequency of multiple serotype carriage is high, usually only the dominant serotype with the highest colonization density was detected in blood.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
  • Z Ditse, P V Adrian, L Kuwanda, S A Madhi
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    ABSTRACT: Due to the high cost and limited serotype coverage of pneumococcal conjugate vaccines (PCV), pneumococcal common protein antigens (CPAs) are being investigated as potential vaccine candidates. CPAs are likely to be immunogenic in infants and could confer serotype-independent protection. There are limited data on natural antibody kinetics against CPAs in African populations. We aimed to determine the prevalence of naturally acquired antibody titres to 15 CPAs and explore their association to concurrent pneumococcal nasopharyngeal colonization in children aged 4-7 years with and without underlying HIV-infection and/or previous PCV-vaccination. A 15-plex Luminex assay was established to measure serum IgG titres against "cell-wall associated or surface-exposed" proteins (PspA, PspC, LytB, IgA1-proteinase, SP0082, PdB and PcsB), "membrane-associated" proteins (PsaA, SP0609, SP0749, PpmA, SlrA, StkP and SP2194) as well as the hypothetical protein, SP2027. Archived serum samples from HIV-uninfected (n=212) and HIV-infected (n=74) children were analyzed. Concurrent pneumococcal nasopharyngeal colonization was determined with standard microbiological methods. HIV-uninfected children had significantly higher antibody titres against PspA, PspC, PdB, SP0082, LytB, IgA1 proteinase and PcsB compared to HIV-infected children. In contrast, antibody titres against membrane associated proteins (PsaA, SP2027, PpmA and SlrA) were significantly lower in HIV-uninfected compared to HIV-infected children. Higher antibody titres against PdB, and PcsB were associated with the absence of pneumococcal colonization. There was no association between anti-CPA titres and PCV vaccination. In conclusion PdB and PcsB antigens are potential vaccine-candidates which may protect against pneumococcal colonization and consequently pneumococcal disease.
    Vaccine 07/2013; · 3.77 Impact Factor
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    ABSTRACT: The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We evaluated the effect of in-utero HIV-exposure and antiretroviral treatment (ART) strategies on measles antibody kinetics prior and following measles vaccination. Infants aged 6-12 weeks were enrolled. This included HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU). Additionally, we enrolled perinatal HIV-infected infants with CD4% equal or greater than 25% randomized to deferred-ART until clinically or immunologically indicated (Group-3) or immediate-ART initiation (Group-4). Group-4 was further randomized to interrupt ART at 1 year (Group-4a) or 2 years of age (Group-4b). Additionally, a convenience sample of HIV-infected infants with CD4 less than 25% initiated on immediate-ART was enrolled (Group-5). Measles immunoglobulin-G antibodies were quantified by an indirect enzyme immunoassay with titers 330 mIU/ml or more considered 'sero-protective'. The referent group was HUU-children. The proportion with sero-protective titers at 7.3 weeks of age was higher in HUU (65.2%) compared with any HIV-infected group (range: 16.7-41.8%), but dropped to less than 17% in all groups at age 19.6 weeks. Twenty-eight weeks following the first measles vaccine, Group-4a was less likely to have sero-protective titers (79.3%) as compared to HUU (91.1%; P < 0.0001), Group-3 (95.7%; P = 0.003) or Group-4b (92.1%; P = 0.018). Although the proportion with sero-protective levels were similar between groups immediately postbooster dose, this was lower in HEU (79.6%; P = 0.002) and Group-4a (80.3%; P = 0.010) compared with HUU (94.3%) 41-weeks later. Greater waning of immunity among HIV-infected children in whom ART was interrupted and in HEU following a booster-dose, indicate the possible need for further measles-booster doses after 2 years of age in these children.
    AIDS (London, England) 06/2013; 27(10):1583-1591. · 4.91 Impact Factor
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    ABSTRACT: Maternal vaginal colonization with Group B Streptococcus (GBS) is a major risk factor for invasive GBS infection in newborns. The CDC recommended method for detecting GBS colonization is to culture vaginal and rectal swabs in selective broth followed by subculture on blood agar or selective media. A high incidence of antimicrobial resistance in faecal microflora can compromise the recovery of GBS from selective broth. We compared CHROMagar StrepB (CA), Columbia colistin and nalidixic agar (CNA) and Trans-Vag selective broth enrichment for the isolation of GBS from 130 vaginal and 130 rectal swabs from pregnant women. Swabs were randomized to be plated first on either CA or CNA, following which the swab was inoculated in Trans-Vag broth. GBS was cultured from 37.7% of vaginal swabs and 33.1% of rectal swabs. There were no differences in the detection rate from vaginal swabs between CA (31.5%), CNA (26.2%) and selective broth (30.0%). The sensitivities in relation to a composite score were 83.7%, 69.4% and 79.6% respectively. However, recovery of GBS from rectal swabs was significantly higher from CA (29.2%; p<0.0001) and CNA (23.8%; p=0.002) than from selective broth (9.2%). The sensitivities were 88.4%, 72.1% and 27.9% respectively. The order of plating on solid medium was significant (p=0.003), with GBS detection rates of 30.8% and 24.6% when plated first and second respectively. These findings show that selective broth is not suitable for the recovery of GBS from rectal swabs in settings such as ours, due to masking of GBS colonies by persistent microflora.
    Journal of clinical microbiology 05/2013; · 4.16 Impact Factor
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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; · 3.57 Impact Factor
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    ABSTRACT: In 2003 the World Health Organization (WHO) convened a working group and published a set of standard methods for studies measuring nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus). The working group recently reconvened under the auspices of the WHO and updated the consensus standard methods. These methods describe the collection, transport and storage of nasopharyngeal samples, as well as provide recommendations for the identification and serotyping of pneumococci using culture and non-culture based approaches. We outline the consensus position of the working group, the evidence supporting this position, areas worthy of future research, and the epidemiological role of carriage studies. Adherence to these methods will reduce variability in the conduct of pneumococcal carriage studies undertaken in the context of pneumococcal vaccine trials, implementation studies, and epidemiology studies more generally so variability in methodology does not confound the interpretation of study findings.
    Vaccine 01/2013; 32:165-179. · 3.49 Impact Factor
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    ABSTRACT: INTRODUCTION: The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We evaluated the effect of in-utero HIV-exposure and antiretroviral treatment (ART) strategies on measles antibody kinetics prior and following measles vaccination. METHODS: Infants aged 6-12 weeks were enrolled. This included HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU). Additionally, we enrolled perinatal HIV-infected infants with CD4% equal or greater than 25% randomized to deferred-ART until clinically or immunologically indicated (Group-3) or immediate-ART initiation (Group-4). Group-4 was further randomized to interrupt ART at 1 year (Group-4a) or 2 years of age (Group-4b). Additionally, a convenience sample of HIV-infected infants with CD4(+) less than 25% initiated on immediate-ART was enrolled (Group-5). Measles immunoglobulin-G antibodies were quantified by an indirect enzyme immunoassay with titers 330 mIU/ml or more considered 'sero-protective'. The referent group was HUU-children. RESULTS: The proportion with sero-protective titers at 7.3 weeks of age was higher in HUU (65.2%) compared with any HIV-infected group (range: 16.7-41.8%), but dropped to less than 17% in all groups at age 19.6 weeks. Twenty-eight weeks following the first measles vaccine, Group-4a was less likely to have sero-protective titers (79.3%) as compared to HUU (91.1%; P<0.0001), Group-3 (95.7%; P=0.003) or Group-4b (92.1%; P=0.018). Although the proportion with sero-protective levels were similar between groups immediately postbooster dose, this was lower in HEU (79.6%; P=0.002) and Group-4a (80.3%; P=0.010) compared with HUU (94.3%) 41-weeks later. CONCLUSION: Greater waning of immunity among HIV-infected children in whom ART was interrupted and in HEU following a booster-dose, indicate the possible need for further measles-booster doses after 2 years of age in these children.
    AIDS. 01/2013; 27(10):1583-91.
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    ABSTRACT: The high cost of pneumococcal conjugate vaccine (PCV) and local epidemiological factors contributed to evaluating different PCV dosing-schedules. This study evaluated the immunogenicity of seven-valent PCV (PCV7) administered at 6-weeks; 14-weeks and 9-months of age. 250 healthy, HIV-unexposed infants were immunized with PCV7 concurrently with other childhood vaccines. Serotype-specific anti-capsular IgG concentrations were measured one-month following the 1(st) and 2(nd) PCV-doses, prior to and two-weeks following the 3(rd) dose. Opsonophagocytic killing assay (OPA) was measured for three serotypes following the 2(nd) and 3(rd) PCV7-doses. Immunogenicity of the current schedule was compared to a historical cohort of infants who received PCV7 at 6, 10 and 14 weeks of age. The proportion of infants with serotype-specific antibody ≥0.35 µg/ml following the 2(nd) PCV7-dose ranged from 84% for 6B to ≥89% for other serotypes. Robust antibody responses were observed following the 3(rd) dose. The proportion of children with OPA ≥8 for serotypes 9V, 19F and 23F increased significantly following the 3(rd) PCV7-dose to 93.6%; 86.0% and 89.7% respectively. The quantitative antibody concentrations following the 2(nd) PCV7-dose were comparable to that after the 3(rd) -dose in the 6-10-14 week schedule. Geometric mean concentrations (GMCs) following the 3(rd) PCV7-dose were higher for all serotypes in this study compared to the historical cohort. The studied PCV7 dosing schedule induced good immune responses, including higher GMCs following the 3(rd-)dose at 9-months compared to when given at 14-weeks of age. This may confer longer persistence of antibodies and duration of protection against pneumococcal disease.
    PLoS ONE 01/2013; 8(8):e72794. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: The immunogenicity of pneumococcal conjugate vaccine (PCV) has not been evaluated in HIV-infected infants following the first and second PCV-doses. We studied antibody kinetics of serotypes included in 7-valent PCV in HIV-infected and HIV-uninfected infants prior to and following each of three PCV-doses. METHODS: HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU); and perinatal HIV-infected children with CD(4+)<25% randomized to initiate antiretroviral treatment (ART) when clinically and/or immunologically indicated (ART-) or immediately (ART+) were enrolled. Vaccination occurred at approximately 7.4, 11.5 and 15.5 weeks of age. Serotype-specific antibody was measured by ELISA following each PCV-dose and opsonophagocytic activity (OPA) to three serotypes following the second and third doses. RESULTS: Pre-vaccination, antibody geometric mean concentrations (GMCs) were higher in HUU compared to HIV-exposed groups for most serotypes. GMCs and proportion of infants with antibody ≥0.35μg/ml were similar in HUU compared to other groups following the second PCV-dose. In all groups, GMCs were greater following the third compared to post-second dose; and a higher proportion within each group had antibody ≥0.35μg/ml to 6B and 23F. OPA GMTs increased after the third compared to post-second dose for studied-serotypes; as did the proportion with OPA ≥8 to 23F. CONCLUSION: A two-dose primary-series of PCV probably confers similar protection against invasive pneumococcal disease in HIV-infected compared to HUU children. The inferior response to serotypes 6B and 23F, and lower GMCs and OPA GMTs, following two compared to after three PCV-doses may have implications in the prevention of pneumococcal disease in high-burden countries.
    Vaccine 12/2012; · 3.77 Impact Factor
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    ABSTRACT: Group B streptococcus (GBS) is a leading cause of neonatal sepsis. Sortase dependent pilus like structures have been identified on the surface of GBS, and have been found to be important in the adhesion and attachment of GBS to the host cells. Three pilus island alleles, PI-1, PI-2a, and PI-2b have been described and their proteins are being explored as vaccine candidates. The pilus islands from 541 colonization isolates and 284 invasive isolates were characterized by PCR. All isolates carried at least one pilus island, and they were identified alone or in combinations at the following overall frequency PI-2a (29.8%), PI-2b (0.2%), PI-1+PI-2a (24.8%) and PI-1+PI-2b (45.1%). A combination of PI-1+PI-2a (28.7% vs. 17.6%) was more common among colonizing compared with invasive isolates. Conversely, a combination of PI-1+PI-2b (37.2% vs. 60.2%) was more frequently associated with invasive disease compared to colonization. There was a strong association between pilus islands when adjusted for serotype distribution, PI-2a was identified in 82.5% of colonizing and 79.4% of invasive serotype Ia isolates, whereas serotype III was associated with co-expression of a PI-1 and PI-2b among 84.6% of colonizing and 96.5% of invasive isolates. Based on this homogeneity of pilus island distribution, a pilus based vaccine developed for Europe and the United States will have similar coverage in South Africa.
    Journal of Medical Microbiology 10/2012; · 2.30 Impact Factor
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    ABSTRACT: HIV-exposed newborns may be at higher risk of sepsis because of immune system aberrations, impaired maternal antibody transfer and altered exposure to pathogenic bacteria. We performed a secondary analysis of a study (clinicaltrials.gov, number NCT00136370) conducted between April 2004 and October 2007 in South Africa. We used propensity score matching to evaluate the association between maternal HIV infection and (1) vaginal colonization with bacterial pathogens; (2) vertical transmission of pathogens to the newborn; and (3) sepsis within 3 days of birth (EOS) or between 4-28 days of life (LOS). Colonization with group B Streptococcus (17% vs 23%, P = .0002), Escherichia coli (47% vs 45%, P = .374), and Klebsiella pneumoniae (7% vs 10%, P = .008) differed modestly between HIV-infected and uninfected women, as did vertical transmission rates. Maternal HIV infection was not associated with increased risk of neonatal EOS or LOS, although culture-confirmed EOS was >3 times higher among HIV-exposed infants (P = .05). When compared with HIV-unexposed, neonates, HIV-exposed, uninfected neonates (HEU) had a lower risk of EOS (20.6 vs 33.7 per 1000 births; P = .046) and similar rate of LOS (5.8 vs 4.1; P = .563). HIV-infected newborns had a higher risk than HEU of EOS (134 vs 21.5; P < .0001) and LOS (26.8 vs 5.6; P = .042). Maternal HIV infection was not associated with increased risk of maternal bacterial colonization, vertical transmission, EOS, or LOS. HIV-infected neonates, however, were at increased risk of EOS and LOS.
    PEDIATRICS 08/2012; 130(3):e581-90. · 4.47 Impact Factor

Publication Stats

615 Citations
235.39 Total Impact Points

Institutions

  • 2014
    • Chris Hani Baragwanath Hospital
      Johannesburg, Gauteng, South Africa
  • 2008–2014
    • University of the Witwatersrand
      • Faculty of Health Sciences
      Johannesburg, Gauteng, South Africa
  • 2009
    • Emory University
      Atlanta, Georgia, United States
  • 2007
    • Erasmus MC
      • Pediatrics Laboratory
      Rotterdam, South Holland, Netherlands
  • 2004
    • Paul Sabatier University - Toulouse III
      • Laboratoire de Microbiologie et Génétique Moléculaire - UMR 5100 - LMGM
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2003
    • University of Glasgow
      Glasgow, Scotland, United Kingdom