Prevalence of Bloodstream Pathogens Is Higher in Neonatal Encephalopathy Cases vs. Controls Using a Novel Panel of Real-Time PCR Assays

Abstract

BackgroundIn neonatal encephalopathy (NE), infectious co-morbidity is difficult to diagnose accurately, but may increase the vulnerability of the developing brain to hypoxia-ischemia. We developed a novel panel of species-specific real-time PCR assays to identify bloodstream pathogens amongst newborns with and without NE in Uganda.MethodologyMultiplex real-time PCR assays for important neonatal bloodstream pathogens (gram positive and gram negative bacteria, cytomegalovirus (CMV), herpes simplex virus(HSV) and P. falciparum) were performed on whole blood taken from 202 encephalopathic and 101 control infants. Automated blood culture (BACTEC) was performed for all cases and unwell controls.Principal FindingsPrevalence of pathogenic bacterial species amongst infants with NE was 3.6%, 6.9% and 8.9%, with culture, PCR and both tests in combination, respectively. More encephalopathic infants than controls had pathogenic bacterial species detected (8.9%vs2.0%, p = 0.028) using culture and PCR in combination. PCR detected bacteremia in 11 culture negative encephalopathic infants (3 Group B Streptococcus, 1 Group A Streptococcus, 1 Staphylococcus aureus and 6 Enterobacteriacae). Coagulase negative staphylococcus, frequently detected by PCR amongst case and control infants, was considered a contaminant. Prevalence of CMV, HSV and malaria amongst cases was low (1.5%, 0.5% and 0.5%, respectively).Conclusion/SignificanceThis real-time PCR panel detected more bacteremia than culture alone and provides a novel tool for detection of neonatal bloodstream pathogens that may be applied across a range of clinical situations and settings. Significantly more encephalopathic infants than controls had pathogenic bacterial species detected suggesting that infection may be an important risk factor for NE in this setting.

Prognostic value of amplitude‐integrated EEG in neonates with high risk of neurological sequelae

“…Neonatal encephalopathy (NE) is a clinical constellation of neurological dysfunctions in infants born at or beyond 35 weeks of gestation and that occur secondary to peripartum or intrapartum insult . NE encompasses not only hypoxic‐ischemic encephalopathy (HIE) but also bilirubin encephalopathy (BE), intracranial hemorrhage (ICH), hypoglycemia encephalopathy, purulent meningitis, and epileptic encephalopathies . NE is often complicated with different congenital and metabolic diseases, and it manifests as difficulty with initiating and maintaining respiration, altered mental status, changes in tone, depressed primitive reflexes, and seizures.…”

Maternal colonization with Streptococcus agalactiae and associated stillbirth and neonatal disease in coastal Kenya

“…Stillbirths likely equal neonatal deaths in number, and infections are a major contributor 23 and possibly contributes to preterm birth4 and neonatal encephalopathy,5 from ascending maternal genito-urinary colonisation (Supplementary Table 1 gives definitions). Whilst GBS emerged as the leading cause of EOD in the United States in the 1960s6 and subsequently in Europe, in sSA, there remain major questions as to whether GBS commonly colonises pregnant women, causes stillbirth, or is an important cause of neonatal disease.…”

Group A streptococcal endophthalmitis complicating a sore throat in a 2-year-old child

“…The benefits of a rapid test such as real-time PCR cannot be underestimated. This real-time PCR was an inhouse assay that allowed the results to be communicated to the treating clinicians within one working day 7. For external samples, the turn around time is 24 h from receipt of sample.…”