BIRC6 modifies risk of invasive bacterial infection in Kenyan children.
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ABSTRACT:
SUBMITTER: Gilchrist JJ
PROVIDER: S-EPMC9391038 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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<i>BIRC6</i> modifies risk of invasive bacterial infection in Kenyan children.
Gilchrist James J JJ Kariuki Silvia N SN Watson James A JA Band Gavin G Uyoga Sophie S Ndila Carolyne M CM Mturi Neema N Mwarumba Salim S Mohammed Shebe S Mosobo Moses M Alasoo Kaur K Rockett Kirk A KA Mentzer Alexander J AJ Kwiatkowski Dominic P DP Hill Adrian V S AVS Maitland Kathryn K Scott J Anthony G JAG Williams Thomas N TN
eLife 20220722
Invasive bacterial disease is a major cause of morbidity and mortality in African children. Despite being caused by diverse pathogens, children with sepsis are clinically indistinguishable from one another. In spite of this, most genetic susceptibility loci for invasive infection that have been discovered to date are pathogen specific and are not therefore suggestive of a shared genetic architecture of bacterial sepsis. Here, we utilise probabilistic diagnostic models to identify children with a ...[more]
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Project description:HIV infection is an established risk for diarrhoeal severity, less is known about specific enteric pathogens associated with HIV status. We determined associations of selected enteric pathogens with HIV infection and HIV exposure among Kenyan children.A cross-sectional study among 6 months to 15 year olds presenting to two Western Kenya District hospitals with acute diarrhoea between 2011 and 2013.Stool was tested using standard bacterial culture and microscopy for ova and parasites. HIV status was obtained from children and mothers. Enteric pathogen prevalence was compared between HIV-infected and HIV-uninfected children and between HIV-exposed uninfected (HEU) and HIV-unexposed. Unadjusted and adjusted prevalence ratios for selected pathogens by HIV status were estimated using relative risk (RR) regression. Age, site, income, household crowding, water source/treatment, anthropometrics, cotrimoxazole use and breastfeeding history were accounted for in multivariable models.Among 1076 children, median age was 22 months (interquartile range: 11-42 months), 56 (5.2%) were HIV-infected and 105 (11.3%) of 926 HIV-uninfected children in whom maternal HIV status was obtained were HIV-exposed. The following organisms were most frequently isolated from stool: enteroaggregative Escherichia coli (13.3%), Giardia species (spp.) (11.1%), Campylobacter spp. (6.3%), enteropathogenic E. coli (EPEC) (6.1%) and Cryptosporidium spp. (3.7%). Accounting for age, HIV-infection was associated with typical EPEC infection (prevalence ratio 3.70, P?=?0.002) while HIV-exposure was associated with Cryptosporidium among HIV-uninfected children (prevalence ratio 2.81, P?=?0.005).EPEC and Cryptosporidium infections were more common in HIV-infected and HIV-exposed children, respectively. This could explain the increased mortality attributed to these pathogens in other studies. Interventions targeting EPEC and Cryptosporidium may reduce morbidity and mortality in high HIV-prevalence settings.
| S-EPMC4346243 | biostudies-literature
Project description:BackgroundSevere malaria remains a major cause of pediatric hospital admission across Africa. Invasive bacterial infection (IBI) is a recognized complication of Plasmodium falciparum malaria, resulting in a substantially worse outcome. Whether a biological relationship exists between malaria infection and IBI susceptibility remains unclear. We, therefore, examined the extent, nature and evidence of this association.MethodsWe conducted a systematic search in August 2012 of three major scientific databases, PubMed, Embase and Africa Wide Information, for articles describing bacterial infection among children with P. falciparum malaria using the search string '(malaria OR plasmodium) AND (bacteria OR bacterial OR bacteremia OR bacteraemia OR sepsis OR septicaemia OR septicemia).' Eligiblity criteria also included studies of children hospitalized with malaria or outpatient attendances in sub-Saharan Africa.ResultsA total of 25 studies across 11 African countries fulfilled our criteria. They comprised twenty cohort analyses, two randomized controlled trials and three prospective epidemiological studies. In the meta-analysis of 7,208 children with severe malaria the mean prevalence of IBI was 6.4% (95% confidence interval (CI) 5.81 to 6.98%). In a further meta-analysis of 20,889 children hospitalised with all-severity malaria and 27,641 children with non-malarial febrile illness the mean prevalence of IBI was 5.58 (95% CI 5.5 to 5.66%) in children with malaria and 7.77% (95% CI 7.72 to 7.83%) in non-malaria illness. Ten studies reported mortality stratified by IBI. Case fatality was higher at 81 of 336, 24.1% (95% CI 18.9 to 29.4) in children with malaria/IBI co-infection compared to 585 of 5,760, 10.2% (95% CI 9.3 to 10.98) with malaria alone. Enteric gram-negative organisms were over-represented in malaria cases, non-typhoidal Salmonellae being the most commonest isolate. There was weak evidence indicating IBI was more common in the severe anemia manifestation of severe malaria.ConclusionsThe accumulated evidence suggests that children with recent or acute malaria are at risk of bacterial infection, which results in an increased risk of mortality. Characterising the exact nature of this association is challenging due to the paucity of appropriate severity-matched controls and the heterogeneous data. Further research to define those at greatest risk is necessary to target antimicrobial treatment.
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Project description:BackgroundThe 2 cofactors in the etiology of Burkitt lymphoma (BL) are Epstein-Barr virus (EBV) and repeated Plasmodium falciparum malaria infections. This study evaluated EBV loads in mucosal and systemic compartments of children with malaria and controls. Age was analyzed as a covariate because immunity to malaria in endemic regions is age dependent.MethodsChildren (2-10 years) with clinical malaria from Western Kenya and community controls without malaria were enrolled. Saliva and blood samples were collected, EBV viral load was assessed by quantitative polymerase chain reaction, and EpiTYPER MassARRAY was used to assess methylation of 3 different EBV genes.ResultsRegardless of the compartment, we detected EBV more frequently in malaria cases compared to controls, although the difference was not significant. When EBV was detected, there were no differences in viral load between cases and controls. However, EBV methylation was significantly lower in the malaria group compared to controls in both plasma and saliva (P < .05), indicating increased EBV lytic replication. In younger children before development of immunity to malaria, there was a significant effect of malaria on EBV load in peripheral blood mononuclear cells (P = .04).ConclusionsThese data suggest that malaria can directly modulate EBV persistence in children, increasing their risk for BL.
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Project description:ObjectiveTo investigate the prevalence, risk factors, clinical features, and neurobehavioral comorbidities of epilepsy and acute symptomatic seizures in school-aged children in Kilifi, Kenya.MethodsRandomly selected children (N = 11,223) were screened for epilepsy and other neurodevelopmental disorders. Those who screened positive were invited for further clinical, electroencephalographic (EEG), and neuropsychological evaluations. Prevalence was measured by dividing cases by screened population, providing Agresti-Coull confidence intervals (CIs). Prevalence ratios were computed using log binomial regression, and odds ratios (ORs) were computed using logistic regression; both were implemented with generalized linear models. Attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other neurodevelopmental impairments were assessed in cases and controls.ResultsPrevalence of lifetime epilepsy was 20.9 per 1,000 (95% CI = 18.4-23.7), and that of active epilepsy was 11.5 per 1,000 (95% CI = 9.7-13.6). Prevalence of acute symptomatic seizures was 68.8 per 1,000 (95% CI = 64.2-73.6). Acute symptomatic seizures preceded a diagnosis of epilepsy in 8% of children. Of 98 children diagnosed with epilepsy, focal seizures were seen in 79%, abnormal EEG was seen in 39%, and 83% were not receiving antiepileptic drugs. Childhood absence epilepsy and Lennox-Gastaut epilepsy were the most easily identifiable epilepsy syndromes. Perinatal complications, previous hospitalization, geophagia, and snoring were risk factors for epilepsy. Family history of seizures, abnormal pregnancy, previous hospitalization, and snoring were risk factors for acute symptomatic seizures. Neurobehavioral comorbidities were present in 54% of subjects with lifetime epilepsy and in 3% of controls, with associations for individual comorbidities being statistically significant: ADHD (OR = 14.55, 95% CI = 7.54-28.06), ASD (OR = 36.83, 95% CI = 7.97-170.14), and cognitive impairments (OR = 14.55, 95% CI = 3.52-60.14).SignificanceThe burden of seizure disorders in this area is higher than in locations in high-income countries, and can be reduced by preventing risk factors. A comprehensive management plan for neurobehavioral comorbidities of epilepsy should be incorporated into standard epilepsy care.
| S-EPMC5862110 | biostudies-literature
Project description:Background. Hematopoietic cell transplantation (HCT) is a potentially curative therapy for a wide range of pediatric malignant and nonmalignant diseases. However, complications, including blood stream infection (BSI) remain a major cause of morbidity and mortality. While certain bacteria that are abundant in the oral microbiome, such as S. mitis, can cause BSI, the role of the oral microbial community in the etiology of BSI is not well understood. The finding that the use of xylitol wipes, which specifically targets the cariogenic bacteria S. mutans is associated with reduced BSI in pediatric patients, lead us to investigate dental caries as a risk factor for BSI. Methods. A total of 41 pediatric patients admitted for allogenic or autologous HCT, age 8 months to 25 years, were enrolled. Subjects with high dental caries risk were identified as those who had dental restorations completed within 2 months of admission for transplant, or who had untreated decay. Fisher’s exact test was used to determine if there was a significant association between caries risk and BSI. Dental plaque and saliva were collected on a cotton swab from a subset of 4 high caries risk (HCR) and 4 low caries risk (LCR) children following pretransplant conditioning. 16SrRNA sequencing was used to compare the microbiome of HCR and LCR subjects and to identify microbes that were significantly different between the 2 groups. Results. There was a statistically significant association between caries risk and BSI (p<0.035) (Fisher’s exact test). Multivariate logistic regression analysis showed children in the high dental caries risk group were 21.39 times more likely to have BSI, with no significant effect of age or mucositis severity. HCR subjects showed significantly reduced microbial alpha diversity as compared to LCR subjects. LEfse metagenomic analyses, showed the oral microbiome in HCR children enriched in order Lactobacillales. This order includes Streptococcus and Lactobacillus, both which contain bacteria primarily associated with dental caries. Discussion. These findings support the possibility that the cariogenic microbiome can enhance the risk of BSI in pediatric populations. Future metagenomic analyses to measure microbial differences at, before, and after conditioning related to caries risk, may further unravel the complex relationship between the oral microbiome, and whether it affects health outcomes such as BSI.
2022-04-05 | GSE199991 | GEO
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Project description:BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency state in humans. The clinical phenotype is variable and includes asymptomatic individuals, episodic hemolysis induced by oxidative stress, and chronic hemolysis. G6PD deficiency is common in malaria-endemic regions, an observation hypothesized to be due to balancing selection at the G6PD locus driven by malaria. G6PD deficiency increases risk of severe malarial anemia, a key determinant of invasive bacterial disease in malaria-endemic settings. The pneumococcus is a leading cause of invasive bacterial infection and death in African children. The effect of G6PD deficiency on risk of pneumococcal disease is undefined. We hypothesized that G6PD deficiency increases pneumococcal disease risk and that this effect is dependent upon malaria.MethodsWe performed a genetic case-control study of pneumococcal bacteremia in Kenyan children stratified across a period of falling malaria transmission between 1998 and 2010.ResultsFour hundred twenty-nine Kenyan children with pneumococcal bacteremia and 2677 control children were included in the study. Among control children, G6PD deficiency, secondary to the rs1050828 G>A mutation, was common, with 11.2% (n = 301 of 2677) being hemi- or homozygotes and 33.3% (n = 442 of 1329) of girls being heterozygotes. We found that G6PD deficiency increased the risk of pneumococcal bacteremia, but only during a period of high malaria transmission (P = 0.014; OR 2.33, 95% CI 1.19-4.57). We estimate that the population attributable fraction of G6PD deficiency on risk of pneumococcal bacteremia in areas under high malaria transmission is 0.129.ConclusionsOur data demonstrate that G6PD deficiency increases risk of pneumococcal bacteremia in a manner dependent on malaria. At the population level, the impact of G6PD deficiency on invasive pneumococcal disease risk in malaria-endemic regions is substantial. Our study highlights the infection-associated morbidity and mortality conferred by G6PD deficiency in malaria-endemic settings and adds to our understanding of the potential indirect health benefits of improved malaria control.
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Project description:Human immunodeficiency virus (HIV) infection is known to be associated with EBV shedding in saliva suggesting an increased risk of EBV transmission to infants born to mothers with HIV at an earlier age. In this study we investigated (i) whether maternal HIV status was a risk factor for EBV in blood at delivery or for shedding in saliva and breast milk of 6- and 10-weeks post-partum mothers, (ii) if there was a difference in EBV strains shed between HIV+ and HIV- mothers, and (iii) if maternal HIV status was a determinant of EBV viral load in their infants. Samples were collected as part of a prospective cohort study that followed HIV-positive (HIV+) and HIV-negative (HIV-) pregnant women in Western Kenya through delivery and post-partum period. EBV viral load in blood was found to be significantly higher in mothers with HIV (p-value = 0.04). Additionally, a statistically significant difference was observed between EBV viral load in saliva samples and HIV status where HIV+ mothers had a higher EBV viral load in saliva at 6-weeks post-partum compared to HIV- mothers (p-value < 0.01). The difference in EBV shedding in breast milk was not found to be statistically significant. Furthermore, no difference in frequency of EBV strain was attributable to HIV- or HIV+ mothers. Interestingly, we found that infants born to HIV+ mothers had a higher EBV viral load at the time of their first EBV detection in blood than infants born to HIV- mothers and this was independent of age at detection. Overall, our study suggests that HIV infected mothers shed more virus in saliva than HIV-negative mothers and infants born to HIV+ mothers were at risk for loss of control of primary EBV infection as evidenced by higher EBV viral load following primary infection.
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Project description:Viral infections are among the most common causes for fever without an apparent source (FWS) in young children; however, many febrile children are treated with antibiotics despite the absence of bacterial infection. Adenovirus, human herpesvirus 6 (HHV-6) and enterovirus are detected in children with FWS more often than other viral species. Virus and bacteria interact with pattern recognition receptors in circulating blood leukocytes and trigger specific host transcriptional programs that mediate immune response, and unique transcriptional signatures may be ascertained to discriminate between viral and bacterial causes for children with FWS. Microarray analyses were conducted on peripheral blood samples obtained from 51 pediatric patients with confirmed adenovirus, human herpesvirus 6 (HHV-6), enterovirus or bacterial infection. Whole blood transcriptional profiles could clearly distinguish febrile children from healthy controls, and febrile children with viral infections from afebrile children carrying the same virus. Molecular pathways regulating host immune response were the most affected in febrile children with infection. Pattern recognition programs were prominently activated in all febrile children with infection, while differential activation of transcriptional programs was observed among viral species. Interferon signaling pathway was uniquely activated in children with febrile viral infection, while a different set of pathways was uniquely activated in children with bacterial infection. Transcriptional signatures were identified and classified febrile children with viral or bacterial infection with 87% overall accuracy, an improvement from the current clinical practice of deducing from white blood cell (WBC) count status. Similar degree of accuracy was observed when we validated the signature probes on data sets from an independent study with different microarray platforms. The current study confirms the clinical utility of blood transcriptional analysis, suggests the composition of transcriptional signatures which can be used to ascertain the infectious etiology of febrile young children without an apparent source, thus limit the overuse of antibiotics on febrile children presenting with this common clinical complaint.
2012-10-15 | GSE40396 | GEO