Dataset Information

Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.

ABSTRACT:

Introduction

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women.

Methods

A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age.

Results

We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94-386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44-49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17-10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95) greater in cases (13.2%) than controls (0.4%).

Discussion

The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting.

SUBMITTER: Dangor Z

PROVIDER: S-EPMC4388823 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.

Dangor Ziyaad Z Lala Sanjay G SG Cutland Clare L CL Koen Anthonet A Jose Lisa L Nakwa Firdose F Ramdin Tanusha T Fredericks Joy J Wadula Jeannette J Madhi Shabir A SA

PloS one 20150407 4

<h4>Introduction</h4>Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women.<h4>Methods</h4>A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 mon ...[more]

PMID: 25849416

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Project description:BackgroundStreptococcus agalactiae or group B Streptococcus (GBS) has emerged as an important cause of invasive disease in adults, particularly among the elderly and those with underlying comorbidities. Traditionally, it was recognised as an opportunistic pathogen colonising and causing disease in pregnant women, neonates, and young infants. Reasons for the upsurge of invasive GBS (iGBS) among the elderly remain unclear, although it has been related to risk factors such as underlying chronic diseases, immunosenescence, impaired inflammatory response, and spread of virulent clones. Antibiotics are successfully as treatment or prophylaxis against iGBS. Several candidate vaccines against iGBS are under development.ObjectivesTo conduct a systematic review of the current literature on invasive GBS in order to determine disease incidence and case fatality ratio (CFR) among non-pregnant adults. Additionally, information on risk factors, clinical presentation, serotype distribution, and antimicrobial resistance was also retrieved.MethodsBetween January and June 2020, electronic searches were conducted in relevant databases: MEDLINE, EMBASE, Global Health, and SCOPUS. Studies were included in the systematic review if they met the inclusion/exclusion criteria. The authors assessed the selected studies for relevance, risk of bias, outcome measures, and heterogeneity. Meta-analyses on incidence and CFR were conducted after evaluating the quality of methods for assessment of exposure and outcomes.ResultsPooled estimates of iGBS incidence in non-pregnant adults 15 years and older were 2.86 cases per 100.000 population (95% CI, 1.68-4.34). Incidence rates in older adults were substantially higher, 9.13 (95%CI, 3.53-17.22) and 19.40 (95%CI, 16.26-22.81) per 100.000 population ≥50 and ≥ 65 years old, respectively. Incidence rates ranged from 0.40 (95% CI, 0.30-0.60) in Africa to 5.90 cases per 100.000 population (95% CI, 4.30-7.70) in North America. The overall CFR was and 9.98% (95% CI, 8.47-11.58). CFR was highest in Africa at 22.09% (95% CI, 12.31-33.57). Serotype V was the most prevalent serotype globally and in North America accounting for 43.48% (n = 12926) and 46,72% (n = 12184) of cases, respectively. Serotype Ia was the second and serotype III was more prevalent in Europe (25.0%) and Asia (29.5%). Comorbidities were frequent among non-pregnant adult iGBS cases. Antimicrobial resistance against different antibiotics (i.e., penicillin, erythromycin) is increasing over time.ConclusionsThis systematic review revealed that iGBS in non-pregnant adults has risen in the last few years and has become a serious public health threat especially in older adults with underlying conditions. Given the current serotype distribution, vaccines including serotypes predominant among non-pregnant adults (i.e., serotypes V, Ia, II, and III) in their formulation are needed to provide breadth of protection. Continued surveillance monitoring potential changes in serotype distribution and antimicrobial resistance patterns are warranted to inform public health interventions.

Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927

Dataset Information

Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.

Introduction

Methods

Results

Discussion

Publications

Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.

Similar Datasets

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