Abstract Group B streptococcus (GBS) is a leading cause of neonatal sepsis, with the highest incidence (1.3 per 1000 live births) reported from Africa. Although the incidence of invasive GBS disease ...is reportedly low in South Asia, there is disconnect between prevalence of maternal recto-vaginal colonization and the incidence of early-onset disease (EOD). This is possibly due to case-ascertainment biases that omit investigation of newborns dying on day-0 of life, which accounts for >90% of EOD. Furthermore, GBS is associated with approximately 15% of all infection related stillbirths. Vaccination of pregnant women with a serotype-specific polysaccharide epitope vaccine could possibly protect against EOD and late-onset disease (LOD) in their infants through transplacental transfer of serotype-specific capsular antibody. Furthermore, vaccination of pregnant women might also protect against impaired neurodevelopment following GBS associated neonatal sepsis, and fetal loss/stillbirths. Licensure of a GBS vaccine might be feasible based on safety evaluation and a sero-correlate of protection, with vaccine effectiveness subsequently being demonstrated in phase IV studies. A randomized-controlled trial would, however, be best suited as a vaccine-probe to fully characterize the contribution of GBS to neonatal sepsis associated morbidity and mortality and adverse fetal outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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.
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.
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%).
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In 2010, an estimated 393,000 infection-related neonatal deaths occurred worldwide with Group B streptococcus (GBS) being a leading cause. Prevention of early-onset disease (0–6 days; EOD) is ...currently focused on intra-partum antibiotic prophylaxis to mothers identified as being at risk; such strategies reduce EOD by 75–80% but are resource-intensive and logistically-difficult to implement in developing countries. Vaccination of pregnant women is an alternate strategy for preventing both EOD and late-onset disease (7–89 days; LOD). A trivalent GBS polysaccharide-protein conjugate vaccine (GBS-CV) composed of capsular epitopes from serotypes Ia, Ib and III is undergoing phase-II evaluation among pregnant women in Europe, North America and Africa. These serotypes cause 70–80% of all invasive GBS disease in early-infancy. Maternal anti-GBS antibodies are associated with protection from EOD, however, since a correlate of efficacy has not been defined, a phase III efficacy trial may be required for licensure. Criteria for selecting appropriate sites include sufficiently high GBS incidence in large birth cohorts, as well as adequate clinical and microbiological diagnostic skills and capacities. Alternate pathways to licensure should be explored, e.g. identification of serological correlates of protection with subsequent phase IV studies establishing vaccine-effectiveness against invasive GBS disease. Conducting a randomized, placebo-controlled efficacy trial, however, has the additional advantage of also being able to evaluate the role of GBS contributing to neonatal culture-negative sepsis, stillbirths, prematurity and low-birth weight.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Invasive group B Streptococcus (GBS) remains a leading cause of illness and death among infants globally. We conducted prospective and retrospective laboratory-based surveillance of GBS-positive ...cultures from infants <3 months of age in 18 hospitals across China during January 1, 2015-December 31, 2017. The overall incidence of GBS was 0.31 (95% CI 0.27-0.36) cases/1,000 live births; incidence was 0-0.76 cases/1,000 live births across participating hospitals. The case-fatality rate was 2.3%. We estimated 13,604 cases of GBS and 1,142 GBS-associated deaths in infants <90 days of age annually in China. GBS isolates were most commonly serotype III (61.5%) and clonal complex 17 (40.6%). Enhanced active surveillance and implementation of preventive strategies, such as maternal GBS vaccination, warrants further investigation in China to help prevent these infections.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Globally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to ...determine incidence and etiology of community-acquired early-onset (<72 hours age) sepsis (EOS) using culture and molecular diagnostics.
This was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates.
We enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6-8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1-5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS.
Using a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluated the association between early-onset sepsis and neonatal encephalopathy in a low-middle-income setting.
We undertook a retrospective study in newborns with gestational age ≥35 weeks ...and/or birth weight ≥2500 grams, diagnosed with neonatal encephalopathy. Early-onset sepsis was defined as culture-confirmed sepsis or probable sepsis.
Of 10,182 hospitalised newborns, 1027 (10.1%) were diagnosed with neonatal encephalopathy, of whom 52 (5.1%) had culture-confirmed and 129 (12.5%) probable sepsis. The case fatality rate for culture-confirmed sepsis associated neonatal encephalopathy was threefold higher compared to neonatal encephalopathy without sepsis (30.8% vs. 10.5%, p < 0.001). Predictors of mortality for culture-confirmed sepsis associated neonatal encephalopathy included severe neonatal encephalopathy (aOR 6.51, 95%CI: 1.03-41.44) and seizures (aOR 10.64, 95%CI: 1.05-107.39).
In this setting, 5% of neonatal encephalopathy cases was associated with culture-confirmed sepsis and a high case fatality rate.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
International guidelines recommend a multi-faceted approach for successful diagnoses of primary ciliary dyskinesia (PCD). In the absence of a gold standard test, a combination of genetic ...testing/microscopic analysis of structure and function/nasal nitric oxide measurement is used. In resource-limited settings, often none of the above tests are available, and in South Africa, only transmission electron microscopy (TEM) is available in central anatomical pathology departments. The aim of this study was to describe the clinical and ultrastructural findings of suspected PCD cases managed by pediatric pulmonologists at a tertiary-level state funded hospital in Johannesburg.
Methods
Nasal brushings were taken from 14 children with chronic respiratory symptoms in keeping with a PCD phenotype. Ultrastructural analysis in accordance with the international consensus guidelines for TEM-PCD diagnostic reporting was undertaken.
Results
TEM observations confirmed 43% (6) of the clinically-suspected cases (hallmark ultrastructural defects in the dynein arms of the outer doublets), whilst 57% (8) required another PCD testing modality to support ultrastructural observations. Of these, 25% (2) had neither ultrastructural defects nor did they present with bronchiectasis. Of the remaining cases, 83% (5) had very few ciliated cells (all of which were sparsely ciliated), together with goblet cell hyperplasia. There was the apparent absence of ciliary rootlets in 17% (1) case.
Discussion
In resource-limited settings in which TEM is the only available testing modality, confirmatory and probable diagnoses of PCD can be made to facilitate early initiation of treatment of children with chronic respiratory symptoms.
There is a paucity of longitudinal data on the serotype-specific burden of invasive group B Streptococcus (GBS) disease from low-middle income countries, which could inform selection of vaccine ...epitopes.
From 2005 to 2014, infants less than 90 days of age with invasive GBS disease were identified through sentinel laboratory and hospital admission surveillance at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa.
We identified 820 cases of invasive GBS disease, including 55% among newborns <7 days age (i.e. early-onset disease; EOD). The overall incidence (per 1,000 live births) of invasive GBS disease was 2.59 (95% CI: 2.42-2.77), including 1.41 (95% CI: 1.28-1.55) for EOD and 1.18 (95% CI: 1.06-1.30) in infants 7-89 days age (late-onset disease). Year-on-year, from 2005 to 2014, we observed a 9.4% increase in incidence of serotype Ia invasive disease (RR: 1.09; 95% CI: 1.04-1.15; p<0.001), and a 7.4% decline in serotype III invasive disease (RR: 0.93; 95% CI: 0.90-0.96; p<0.001). Overall, serotypes Ia (28.2%), III (55.4%) and V (7.9%) were the commonest disease causing serotypes.
The incidence of invasive GBS disease has remained persistently high in our setting, with some changes in serotype distribution, albeit mainly involving the same group of dominant serotypes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Invasive group B streptococcal (GBS) disease is the commonest perinatally-acquired bacterial infection in newborns; the burden is higher in African countries where intrapartum antibiotic prophylaxis ...strategies are not feasible. In sub-Saharan Africa, almost one in four newborns with GBS early-onset disease will demise, and one in ten survivors have moderate or severe neurodevelopmental impairment. A maternal GBS vaccine to prevent invasive GBS disease in infancy is a pragmatic and cost-effective preventative strategy for Africa. Hexavalent polysaccharide protein conjugate and Alpha family surface protein vaccines are undergoing phase II clinical trials. Vaccine licensure may be facilitated by demonstrating safety and immunological correlates/thresholds suggestive of protection against invasive GBS disease. This will then be followed by phase IV effectiveness studies to assess the burden of GBS vaccine preventable disease, including the effect on all-cause neonatal infections, neonatal deaths and stillbirths.
Background Antenatal care remains critical for identifying and managing complications contributing to maternal and infant mortality, yet attendance among women in South Africa persists as a ...challenge. Aim This study aimed to understand the challenges faced by women attending antenatal care in Soweto, Johannesburg, using the three-delay model. Setting This study was conducted in Soweto, Johannesburg. Methods An exploratory, descriptive and qualitative research design was used, and in-depth interviews were conducted with 10 pregnant women and four women who had recently given birth. Results Findings indicate delays in seeking care due to factors such as pregnancy unawareness, waiting for visible signs, and fear of human immunodeficiency virus (HIV) testing. Challenges such as transportation difficulties, distance to clinics, and facility conditions further impeded the initiation of antenatal care. Late initiation often occurred to avoid long waits, inadequate facilities, language barriers and nurse mistreatment. Conclusion From this study, we learn that challenges such as unawareness of pregnancy, cultural notions of keeping pregnancy a secret, fear of HIV testing, long waiting lines, high cost of transportation fees, clinic demarcation, shortage of essential medicines, broken toilets and verbal abuse from nurses have delayed women from initiating antenatal care early in Soweto, Johannesburg. Contribution Challenges of women with antenatal care attendance in South Africa must be addressed by implementing community-based health education interventions, institutionalising HIV psycho-social support services and improving quality of antenatal care services in public health facilities.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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