Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis. METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes. RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

Endoscopic Treatment versus Shunting for Infant Hydrocephalus in Uganda.

BACKGROUND: Postinfectious hydrocephalus in infants is a major health problem in sub-Saharan Africa. The conventional treatment is ventriculoperitoneal shunting, but surgeons are usually not immediately available to revise shunts when they fail. Endoscopic third ventriculostomy with choroid plexus cauterization (ETV-CPC) is an alternative treatment that is less subject to late failure but is also less likely than shunting to result in a reduction in ventricular size that might facilitate better brain growth and cognitive outcomes. METHODS: We conducted a randomized trial to evaluate cognitive outcomes after ETV-CPC versus ventriculoperitoneal shunting in Ugandan infants with postinfectious hydrocephalus. The primary outcome was the Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score 12 months after surgery (scores range from 1 to 19, with higher scores indicating better performance). The secondary outcomes were BSID-3 motor and language scores, treatment failure (defined as treatment-related death or the need for repeat surgery), and brain volume measured on computed tomography. RESULTS: A total of 100 infants were enrolled; 51 were randomly assigned to undergo ETV-CPC, and 49 were assigned to undergo ventriculoperitoneal shunting. The median BSID-3 cognitive scores at 12 months did not differ significantly between the treatment groups (a score of 4 for ETV-CPC and 2 for ventriculoperitoneal shunting; Hodges-Lehmann estimated difference, 0; 95% confidence interval [CI], -2 to 0; P=0.35). There was no significant difference between the ETV-CPC group and the ventriculoperitoneal-shunt group in BSID-3 motor or language scores, rates of treatment failure (35% and 24%, respectively; hazard ratio, 0.7; 95% CI, 0.3 to 1.5; P=0.24), or brain volume (z score, -2.4 and -2.1, respectively; estimated difference, 0.3; 95% CI, -0.3 to 1.0; P=0.12). CONCLUSIONS: This single-center study involving Ugandan infants with postinfectious hydrocephalus showed no significant difference between endoscopic ETV-CPC and ventriculoperitoneal shunting with regard to cognitive outcomes at 12 months. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01936272 .).

Infection diagnosis in hydrocephalus CT images: a domain enriched attention learning approach.

Objective. Hydrocephalus is the leading indication for pediatric neurosurgical care worldwide. Identification of postinfectious hydrocephalus (PIH) verses non-postinfectious hydrocephalus, as well as the pathogen involved in PIH is crucial for developing an appropriate treatment plan. Accurate identification requires clinical diagnosis by neuroscientists and microbiological analysis, which are time-consuming and expensive. In this study, we develop a domain enriched AI method for computerized tomography (CT)-based infection diagnosis in hydrocephalic imagery. State-of-the-art (SOTA) convolutional neural network (CNN) approaches form an attractive neural engineering solution for addressing this problem as pathogen-specific features need discovery. Yet black-box deep networks often need unrealistic abundant training data and are not easily interpreted.Approach. In this paper, a novel brain attention regularizer is proposed, which encourages the CNN to put more focus inside brain regions in its feature extraction and decision making. Our approach is then extended to a hybrid 2D/3D network that mines inter-slice information. A new strategy of regularization is also designed for enabling collaboration between 2D and 3D branches.Main results. Our proposed method achieves SOTA results on a CURE Children's Hospital of Uganda dataset with an accuracy of 95.8% in hydrocephalus classification and 84% in pathogen classification. Statistical analysis is performed to demonstrate that our proposed methods obtain significant improvements over the existing SOTA alternatives.Significance. Such attention regularized learning has particularly pronounced benefits in regimes where training data may be limited, thereby enhancing generalizability. To the best of our knowledge, our findings are unique among early efforts in interpretable AI-based models for classification of hydrocephalus and underlying pathogen using CT scans.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Preoperative risk and postoperative outcome from subdural fluid collections in African infants with postinfectious hydrocephalus.

OBJECTIVE: This study investigated the incidence of postoperative subdural collections in a cohort of African infants with postinfectious hydrocephalus. The authors sought to identify preoperative factors associated with increased risk of development of subdural collections and to characterize associations between subdural collections and postoperative outcomes. METHODS: The study was a post hoc analysis of a randomized controlled trial at a single center in Mbale, Uganda, involving infants (age < 180 days) with postinfectious hydrocephalus randomized to receive either an endoscopic third ventriculostomy plus choroid plexus cauterization or a ventriculoperitoneal shunt. Patients underwent assessment with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III; sometimes referred to as BSID-III) and CT scans preoperatively and then at 6, 12, and 24 months postoperatively. Volumes of brain, CSF, and subdural fluid were calculated, and z-scores from the median were determined from normative curves for CSF accumulation and brain growth. Linear and logistic regression models were used to characterize the association between preoperative CSF volume and the postoperative presence and size of subdural collection 6 and 12 months after surgery. Linear regression and smoothing spline ANOVA were used to describe the relationship between subdural fluid volume and cognitive scores. Causal mediation analysis distinguished between the direct and indirect effects of the presence of a subdural collection on cognitive scores. RESULTS: Subdural collections were more common in shunt-treated patients and those with larger preoperative CSF volumes. Subdural fluid volumes were linearly related to preoperative CSF volumes. In terms of outcomes, the Bayley-III cognitive score was linearly related to subdural fluid volume. The distribution of cognitive scores was significantly different for patients with and those without subdural collections from 11 to 24 months of age. The presence of a subdural collection was associated with lower cognitive scores and smaller brain volume 12 months after surgery. Causal mediation analysis demonstrated evidence supporting both a direct (76%) and indirect (24%) effect (through brain volume) of subdural collections on cognitive scores. CONCLUSIONS: Larger preoperative CSF volume and shunt surgery were found to be risk factors for postoperative subdural collection. The size and presence of a subdural collection were negatively associated with cognitive outcomes and brain volume 12 months after surgery. These results have suggested that preoperative CSF volumes could be used for risk stratification for treatment decision-making and that future clinical trials of alternative shunt technologies to reduce overdrainage should be considered.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC.

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children's Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO2), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Brain growth after surgical treatment for infant postinfectious hydrocephalus in Sub-Saharan Africa: 2-year results of a randomized trial.

OBJECTIVE: Hydrocephalus in infants, particularly that with a postinfectious etiology, is a major public health burden in Sub-Saharan Africa. The authors of this study aimed to determine whether surgical treatment of infant postinfectious hydrocephalus in Uganda results in sustained, long-term brain growth and improved cognitive outcome. METHODS: The authors performed a trial at a single center in Mbale, Uganda, involving infants (age < 180 days old) with postinfectious hydrocephalus randomized to endoscopic third ventriculostomy plus choroid plexus cauterization (ETV+CPC; n = 51) or ventriculoperitoneal shunt (VPS; n = 49). After 2 years, they assessed developmental outcome with the Bayley Scales of Infant Development, Third Edition (BSID-III), and brain volume (raw and normalized for age and sex) with CT scans. RESULTS: Eighty-nine infants were assessed for 2-year outcome. There were no significant differences between the two surgical treatment arms in terms of BSID-III cognitive score (p = 0.17) or brain volume (p = 0.36), so they were analyzed together. Raw brain volumes increased between baseline and 2 years (p < 0.001), but this increase occurred almost exclusively in the 1st year (p < 0.001). The fraction of patients with a normal brain volume increased from 15.2% at baseline to 50.0% at 1 year but then declined to 17.8% at 2 years. Substantial normalized brain volume loss was seen in 21.3% patients between baseline and year 2 and in 76.7% between years 1 and 2. The extent of brain growth in the 1st year was not associated with the extent of brain volume changes in the 2nd year. There were significant positive correlations between 2-year brain volume and all BSID-III scores and BSID-III changes from baseline. CONCLUSIONS: In Sub-Saharan Africa, even after successful surgical treatment of infant postinfectious hydrocephalus, early posttreatment brain growth stagnates in the 2nd year. While the reasons for this finding are unclear, it further emphasizes the importance of primary infection prevention and mitigation strategies along with optimizing the child's environment to maximize brain growth potential.

Assessing the utility of low resolution brain imaging: treatment of infant hydrocephalus.

As low-field MRI technology is being disseminated into clinical settings around the world, it is important to assess the image quality required to properly diagnose and treat a given disease and evaluate the role of machine learning algorithms, such as deep learning, in the enhancement of lower quality images. In this post hoc analysis of an ongoing randomized clinical trial, we assessed the diagnostic utility of reduced-quality and deep learning enhanced images for hydrocephalus treatment planning. CT images of post-infectious infant hydrocephalus were degraded in terms of spatial resolution, noise, and contrast between brain and CSF and enhanced using deep learning algorithms. Both degraded and enhanced images were presented to three experienced pediatric neurosurgeons accustomed to working in low- to middle-income countries (LMIC) for assessment of clinical utility in treatment planning for hydrocephalus. In addition, enhanced images were presented alongside their ground-truth CT counterparts in order to assess whether reconstruction errors caused by the deep learning enhancement routine were acceptable to the evaluators. Results indicate that image resolution and contrast-to-noise ratio between brain and CSF predict the likelihood of an image being characterized as useful for hydrocephalus treatment planning. Deep learning enhancement substantially increases contrast-to-noise ratio improving the apparent likelihood of the image being useful; however, deep learning enhancement introduces structural errors which create a substantial risk of misleading clinical interpretation. We find that images with lower quality than is customarily acceptable can be useful for hydrocephalus treatment planning. Moreover, low quality images may be preferable to images enhanced with deep learning, since they do not introduce the risk of misleading information which could misguide treatment decisions. These findings advocate for new standards in assessing acceptable image quality for clinical use.

Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection.

Inflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was a Paenibacillus species, with frequent cytomegalovirus co-infection. A proteogenomic strategy was employed to confirm host immune response to Paenibacillus and to define the interplay within the host immune response network. Immune activation emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization. The innate immune system response included neutrophil activity, signaling via IL-4, IL-12, IL-13, interferon, and Jak/STAT pathways. Platelet-activating factors and factors involved with microbe recognition such as Class I MHC antigen-presenting complex were also increased. Evidence suggests that dysregulated neuroinflammation propagates inflammatory hydrocephalus, and these pathways are potential targets for adjunctive treatments to reduce the hazards of neuroinflammation and risk of hydrocephalus following neonatal sepsis.

Vaginal microbiome topic modeling of laboring Ugandan women with and without fever.

The composition of the maternal vaginal microbiome influences the duration of pregnancy, onset of labor, and even neonatal outcomes. Maternal microbiome research in sub-Saharan Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. Here we aimed to illustrate the relationship between the vaginal microbiome of 99 laboring Ugandan women and intrapartum fever using routine microbiology and 16S ribosomal RNA gene sequencing from two hypervariable regions (V1-V2 and V3-V4). To describe the vaginal microbes associated with vaginal microbial communities, we pursued two approaches: hierarchical clustering methods and a novel Grades of Membership (GoM) modeling approach for vaginal microbiome characterization. Leveraging GoM models, we created a basis composed of a preassigned number of microbial topics whose linear combination optimally represents each patient yielding more comprehensive associations and characterization between maternal clinical features and the microbial communities. Using a random forest model, we showed that by including microbial topic models we improved upon clinical variables to predict maternal fever. Overall, we found a higher prevalence of Granulicatella, Streptococcus, Fusobacterium, Anaerococcus, Sneathia, Clostridium, Gemella, Mobiluncus, and Veillonella genera in febrile mothers, and higher prevalence of Lactobacillus genera (in particular L. crispatus and L. jensenii), Acinobacter, Aerococcus, and Prevotella species in afebrile mothers. By including clinical variables with microbial topics in this model, we observed young maternal age, fever reported earlier in the pregnancy, longer labor duration, and microbial communities with reduced Lactobacillus diversity were associated with intrapartum fever. These results better defined relationships between the presence or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial topics, and expanded our understanding of the impact of the microbiome on maternal and potentially neonatal outcome risk.

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants.

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

Infection risk for Bactiseal Universal Shunts versus Chhabra shunts in Ugandan infants: a randomized controlled trial.

OBJECTIVE Clinical and economic repercussions of ventricular shunt infections are magnified in low-resource countries. The efficacy of antibiotic-impregnated shunts in this setting is unclear. A previous retrospective cohort study comparing the Bactiseal Universal Shunt (BUS) and the Chhabra shunt provided clinical equipoise; thus, the authors conducted this larger randomized controlled trial in Ugandan children requiring shunt placement for hydrocephalus to determine whether there was, in fact, any advantage of one shunt over the other. METHODS Between April 2013 and September 2016, the authors randomly assigned children younger than 16 years of age without evidence of ventriculitis to either BUS or Chhabra shunt implantation in this single-blind randomized controlled trial. The primary outcome was shunt infection, and secondary outcomes included reoperation and death. The minimum follow-up was 6 months. Time to outcome was assessed using the Kaplan-Meier method. The significance of differences was tested using Wilcoxon rank-sum, chi-square, Fisher's exact, and t-tests. RESULTS Of the 248 patients randomized, the BUS was implanted in 124 and the Chhabra shunt in 124. There were no differences between the groups in terms of age, sex, or hydrocephalus etiology. Within 6 months of follow-up, there were 14 infections (5.6%): 6 BUS (4.8%) and 8 Chhabra (6.5%; p = 0.58). There were 14 deaths (5.6%; 5 BUS [4.0%] vs 9 Chhabra [7.3%], p = 0.27) and 30 reoperations (12.1%; 15 BUS vs 15 Chhabra, p = 1.00). There were no significant differences in the time to primary or secondary outcomes at 6 months' follow-up (p = 0.29 and 0.17, respectively, Wilcoxon rank-sum test). CONCLUSIONS Among Ugandan infants, BUS implantation did not result in a lower incidence of shunt infection or other complications. Any recommendation for a more costly standard of care in low-resource countries must have contextually relevant, evidence-based support. Clinical trial registration no.: PACTR201804003240177 (http://www.pactr.org/)

The Incidence of Postoperative Seizures Following Treatment of Postinfectious Hydrocephalus in Ugandan Infants: A Post Hoc Comparison of Endoscopic Treatment vs Shunt Placement in a Randomized Controlled Trial.

BACKGROUND: There are currently no published data directly comparing postoperative seizure incidence following endoscopic third ventriculostomy (ETV), with/without choroid plexus cauterization (CPC), to that for ventriculoperitoneal shunt (VPS) placement. OBJECTIVE: To compare postoperative epilepsy incidence for ETV/CPC and VPS in Ugandan infants treated for postinfectious hydrocephalus (PIH). METHODS: We performed an exploratory post hoc analysis of a randomized trial comparing VPS and ETV/CPC in 100 infants (<6 mo old) presenting with PIH. Minimum follow-up was 2 yr. Variables associated with and the incidence of postoperative epilepsy were compared (intention-to-treat) using a bivariate analysis. Time to first seizure was compared using the Kaplan-Meier method, and the relative risk for the 2 treatments was determined using Mantel-Haenszel hazard ratios. RESULTS: Seizure incidence was not related to age (P = .075), weight (P = .768), sex (P = .151), head circumference (P = .281), time from illness to hydrocephalus onset (P = .973), or hydrocephalus onset to treatment (P = .074). Irritability (P = .027) and vision deficit (P = .04) were preoperative symptoms associated with postoperative seizures. Ten (10%) patients died, and 20 (20%) developed seizures over the follow-up period. Overall seizure incidence was 9.4 per 100 person-years (9.4 and 9.5 for ETV/CPC and VPS, respectively; P = .483), with no significant difference in seizure risk between groups (hazard ratio, 1.02; 95% CI: 0.42, 2.45; P = .966). Mean time to seizure onset was 8.5 mo for ETV/CPC and 11.2 mo for VPS (P = .464). As-treated, per-protocol, and attributable-intervention analyses yielded similar results. CONCLUSION: Postoperative seizure incidence following treatment of PIH was 20% within 2 yr, regardless of treatment modality.

Renal Outcomes in Children with Operated Spina Bifida in Uganda.

BACKGROUND: To describe the extent of renal disease in Ugandan children surviving at least ten years after spina bifida repair and to investigate risk factors for renal deterioration in this cohort. PATIENTS AND METHODS: Children who had undergone spina bifida repair at CURE Children's Hospital of Uganda between 2000 and 2004 were invited to attend interview, physical examination, renal tract ultrasound, and a blood test (creatinine). Medical records were retrospectively reviewed. The following were considered evidence of renal damage: elevated creatinine, hypertension, and ultrasound findings of hydronephrosis, scarring, and discrepancy in renal size >1cm. Female sex, previous UTI, neurological level, mobility, detrusor leak point pressure, and adherence with clean intermittent catheterisation (CIC) were investigated for association with evidence of renal damage. RESULTS: 65 of 68 children aged 10-14 completed the assessment. The majority (83%) reported incontinence. 17 children (26%) were performing CIC. One child had elevated creatinine. 25 children (38%) were hypertensive. There was a high prevalence of ultrasound abnormalities: hydronephrosis in 10 children (15%), scarring in 42 (64%), and >1cm size discrepancy in 28 (43%). No children with lesions at S1 or below had hydronephrosis (p = 0.025), but this group had comparable prevalence of renal size discrepancy, scarring, and hypertension to those children with higher lesions. CONCLUSIONS: Incontinence, ultrasound abnormalities, and hypertension are highly prevalent in a cohort of Ugandan children with spina bifida, including those with low neurological lesions. These findings support the early and universal initiation of CIC with anticholinergic therapy in a low-income setting.

Quality of life among children with spina bifida in Uganda.

BACKGROUND: Children surviving after spina bifida repair often have significant disability, the consequences of which may be more profound in low-income countries. The aim of this cross-sectional study was to measure quality of life (QOL) reported by children with spina bifida in Uganda, and to define factors associated with QOL. METHODS: QOL was measured using both the Health Utilities Index (HUI3) Tool and a visual analogue scale (VAS) marked from 0 to 10. In keeping with the WHO definition of QOL, further analysis was conducted using subjective QOL scores (using the VAS). Multivariate regression was used to investigate the association between VAS scores and prespecified variables: age, sex, hydrocephalus, mobility, urinary continence, school attendance and family size. RESULTS: Sixty two of 68 surviving children aged 10-14 were able to complete all aspects of the assessment. There was poor correlation between the VAS and HUI3 Tool (Pearson correlation 0.488). On multivariate regression, the following variables were associated with a significant change in the 10-point VAS (change in score; 95% CI): male sex (-1.45; -2.436 to -0.465), urinary continence (1.681; 0.190 to 3.172), large family size (-1.775; -2.773 to -0.777) and hydrocephalus (-1.382; -2.374 to -0.465). CONCLUSIONS: Urinary continence and family size are potentially modifiable, the former by simple and inexpensive medical management. Enhanced investment in community-based rehabilitation and support is urgently needed. Delivery of family planning services is a national priority in Uganda, and should be discussed with families as part of holistic care.