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.

Analysis of association of sensory and laboratory assessments for quality and consumer acceptability of steamed East Africa highland bananas.

BACKGROUND: The relevance of several characteristics for the acceptability of steamed East Africa bananas (matooke) was assessed using consumer-preferred characteristics, the overall liking scores, check-all-that-apply (CATA) and the Just About Right scale. The study was conducted in rural and urban locations in three banana growing regions of Uganda. Two landraces and two hybrids were processed into matooke. Twelve trained panellists evaluated color, taste and texture sensory characteristics. RESULTS: Consumers scored matooke from landraces as the most liked. The CATA test showed that the most important characteristics were: smooth mouthfeel, soft to the touch, not sticky, moldable, deep yellow color, attractive, good matooke taste and smell. Principal component analysis confirmed that most of the preferred sensory characteristics were associated with the local genotypes, whereas the less preferred characteristics were associated with hybrids. Correlation analysis revealed strong positive correlations between the consumer assessed characteristics, hardness by touch, softness to touch and yellowness, as well as quantitative laboratory characteristics (moldable, hardness by touch, softness and yellowness) of the steamed matooke. Color assessed by consumers was strongly correlated with the laboratory-assessed color indicators. CONCLUSION: The strong associations observed between laboratory-assessed and consumer-based characteristics (moldable by touch and yellowness) suggest the possibility of predicting consumer characteristics using quantitative laboratory sensory assessments. Matooke taste as assessed by consumer panel is strongly associated with smooth texture and deep yellow color, which were the characteristics associated with landraces in the laboratory sensory assessment. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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 .).

Unifying Children's Surgery and Anesthesia Stakeholders Across Institutions and Clinical Disciplines: Challenges and Solutions from Uganda.

BACKGROUND: There is a significant unmet need for children's surgical care in low- and middle-income countries (LMICs). Multidisciplinary collaboration is required to advance the surgical and anesthesia care of children's surgical conditions such as congenital conditions, cancer and injuries. Nonetheless, there are limited examples of this process from LMICs. We describe the development and 3-year outcomes following a 2015 stakeholders' meeting in Uganda to catalyze multidisciplinary and multi-institutional collaboration. METHODS: The stakeholders' meeting was a daylong conference held in Kampala with local, regional and international collaborators in attendance. Multiple clinical specialties including surgical subspecialists, pediatric anesthesia, perioperative nursing, pediatric oncology and neonatology were represented. Key thematic areas including infrastructure, training and workforce retention, service delivery, and research and advocacy were addressed, and short-term objectives were agreed upon. We reported the 3-year outcomes following the meeting by thematic area. RESULTS: The Pediatric Surgical Foundation was developed following the meeting to formalize coordination between institutions. Through international collaborations, operating room capacity has increased. A pediatric general surgery fellowship has expanded at Mulago and Mbarara hospitals supplemented by an international fellowship in multiple disciplines. Coordinated outreach camps have continued to assist with training and service delivery in rural regional hospitals. CONCLUSION: Collaborations between disciplines, both within LMICs and with international partners, are required to advance children's surgery. The unification of stakeholders across clinical disciplines and institutional partnerships can facilitate increased children's surgical capacity. Such a process may prove useful in other LMICs with a wide range of children's surgery stakeholders.

Subspecialty pediatric neurosurgery training: a skill-based training model for neurosurgeons in low-resourced health systems.

There is inadequate pediatric neurosurgical training to meet the growing burden of disease in low- and middle-income countries (LMIC). Subspecialty expertise in the management of hydrocephalus and spina bifida-two of the most common pediatric neurosurgical conditions-offers a high-yield opportunity to mitigate morbidity and avoid unnecessary death. The CURE Hydrocephalus and Spina Bifida (CHSB) fellowship offers an intensive subspecialty training program designed to equip surgeons from LMIC with the state-of-the-art surgical skills and equipment to most effectively manage common neurosurgical conditions of childhood. Prospective fellows and their home institution undergo a comprehensive evaluation before being accepted for the 8-week training period held at CURE Children's Hospital of Uganda (CCHU) in Mbale, Uganda. The fellowship combines anatomy review, treatment paradigms, a flexible endoscopic simulation lab, daily ward and ICU rounds, radiology rounds, and clinic exposure. The cornerstone of the fellowship is the unique operative experience that includes a high volume of endoscopic third ventriculostomy with choroid plexus cauterization, myelomeningocele closure, and ventriculoperitoneal shunting, among many other procedures performed at CCHU. Upon completion, fellows return to their home institution to establish or rejuvenate a robust pediatric practice as part of a worldwide network of CHSB trainees committed to the care of underserved children. To date, the fellowship has graduated 33 surgeons from 20 different LMIC who are independently performing thousands of hydrocephalus and spina bifida operations each year.

SIOP PODC adapted treatment recommendations for standard-risk medulloblastoma in low and middle income settings.

Effective treatment of children with medulloblastoma requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition the treating centre should have the capacity to effectively screen and manage any tumour and treatment-associated complications. These requirements have made it difficult for many low and middle-income countries (LMIC) centres to offer curative treatment. This article provides management recommendations for children with standard-risk medulloblastoma (localised tumours in children over the age of 3-5 years) according to the level of facilities available.

Presentation, pathology, and treatment outcome of brain tumors in 172 consecutive children at CURE Children's Hospital of Uganda. The predominance of the visible diagnosis and the uncertainties of epidemiology in sub-Saharan Africa.

OBJECT: This study reviews the first operative series of pediatric brain tumors from Uganda, the largest series from Sub-Saharan Africa, and explores the challenges to progress in pediatric neuro-oncology in the region. METHODS: This is a retrospective operative series of brain tumors in 172 children at Cure Children's Hospital of Uganda over 10 years. Demographics, clinical presentation, lesion location, histopathology, operative management, and outcome were investigated. Survival was assessed using Kaplan-Meier method. Log-rank test and p value with Bonferroni correction were used to determine significance of survival differences. RESULTS: There were 103 males (59.9 %) and 69 females (40.1 %; mean age at diagnosis 6.5 years with 29 % < 2 years). The most common histologic types were pilocytic astrocytoma (23.2 %), ependymoma (16.3 %), craniopharyngioma (9.9 %), choroid plexus papilloma (9.3 %), and medulloblastoma (8.1 %). Supratentorial tumors (62.2 %) were more common. Symptomatic hydrocephalus predominated at presentation (66.9 %). In 71 (41.3 %), the presentation was macrocephaly or a visible mass. Estimated 5-year survival was 60 %. CONCLUSIONS: The majority of pediatric brain tumors in the region likely go unrecognized. Most that do come to attention have a "visible diagnosis." Unlike operative series from developed countries, information about the incidence, prevalence, and overall burden of disease for different tumor types cannot be deduced from the various operative series reported from limited resource countries because of the selection bias that is unique to this context. Delayed presentation and poor access to adjuvant therapies were important contributors to the high mortality. The epidemiology of pediatric brain tumors in sub-Saharan Africa is obscure.

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.

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.

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.

Needs of Young African Neurosurgeons and Residents: A Cross-Sectional Study.

Introduction: Africa has many untreated neurosurgical cases due to limited access to safe, affordable, and timely care. In this study, we surveyed young African neurosurgeons and trainees to identify challenges to training and practice. Methods: African trainees and residents were surveyed online by the Young Neurosurgeons Forum from April 25th to November 30th, 2018. The survey link was distributed via social media platforms and through professional society mailing lists. Univariate and bivariate data analyses were run and a P-value < 0.05 was considered to be statistically significant. Results: 112 respondents from 20 countries participated in this study. 98 (87.5%) were male, 63 (56.3%) were from sub-Saharan Africa, and 52 (46.4%) were residents. 39 (34.8%) had regular journal club sessions at their hospital, 100 (89.3%) did not have access to cadaver dissection labs, and 62 (55.4%) had never attended a WFNS-endorsed conference. 67.0% of respondents reported limited research opportunities and 58.9% reported limited education opportunities. Lack of mentorship (P = 0.023, Phi = 0.26), lack of access to journals (P = 0.002, Phi = 0.332), and limited access to conferences (P = 0.019, Phi = 0.369) were associated with the country income category. Conclusion: This survey identified barriers to education, research, and practice among African trainees and young neurosurgeons. The findings of this study should inform future initiatives aimed at reducing the barriers faced by this group.

The CURE Protocol: evaluation and external validation of a new public health strategy for treating paediatric hydrocephalus in low-resource settings.

Introduction: Managing paediatric hydrocephalus with shunt placement is especially risky in resource-limited settings due to risks of infection and delayed life-threatening shunt obstruction. This study evaluated a new evidence-based treatment algorithm to reduce shunt-dependence in this context. Methods: A prospective cohort design was used. The CURE Protocol employs preoperative and intraoperative data to choose between endoscopic treatment and shunt placement. Data were prospectively collected for 730 children in Uganda (managed by local neurosurgeons highly experienced in the protocol) and, for external validation, 96 children in Nigeria (managed by a local neurosurgeon trained in the protocol). Results: The age distribution was similar between Uganda and Nigeria, but there were more cases of postinfectious hydrocephalus in Uganda (64.2% vs 26.0%, p<0.001). Initial treatment of hydrocephalus was similar at both centres and included either a shunt at first operation or endoscopic management without a shunt. The Nigerian cohort had a higher failure rate for endoscopic cases (adjusted HR 2.5 (95% CI 1.6 to 4.0), p<0.001), but not for shunt cases (adjusted HR 1.3 (0.5 to 3.0), p=0.6). Despite the difference in endoscopic failure rates, a similar proportion of the entire cohort was successfully treated without need for shunt at 6 months (55.2% in Nigeria vs 53.4% in Uganda, p=0.74). Conclusion: Use of the CURE Protocol in two centres with different populations and surgeon experience yielded similar 6-month results, with over half of all children remaining shunt-free. Where feasible, this could represent a better public health strategy in low-resource settings than primary shunt placement.

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.

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.

Learning Based Segmentation of CT Brain Images: Application to Postoperative Hydrocephalic Scans.

OBJECTIVE: Hydrocephalus is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid (CSF) in the brain. Segmentation of brain imagery into brain tissue and CSF [before and after surgery, i.e., preoperative (pre-op) versus postoperative (post-op)] plays a crucial role in evaluating surgical treatment. Segmentation of pre-op images is often a relatively straightforward problem and has been well researched. However, segmenting post-op computational tomographic (CT) scans becomes more challenging due to distorted anatomy and subdural hematoma collections pressing on the brain. Most intensity- and feature-based segmentation methods fail to separate subdurals from brain and CSF as subdural geometry varies greatly across different patients and their intensity varies with time. We combat this problem by a learning approach that treats segmentation as supervised classification at the pixel level, i.e., a training set of CT scans with labeled pixel identities is employed. METHODS: Our contributions include: 1) a dictionary learning framework that learns class (segment) specific dictionaries that can efficiently represent test samples from the same class while poorly represent corresponding samples from other classes; 2) quantification of associated computation and memory footprint; and 3) a customized training and test procedure for segmenting post-op hydrocephalic CT images. RESULTS: Experiments performed on infant CT brain images acquired from the CURE Children's Hospital of Uganda reveal the success of our method against the state-of-the-art alternatives. We also demonstrate that the proposed algorithm is computationally less burdensome and exhibits a graceful degradation against a number of training samples, enhancing its deployment potential.

Head and neck neurovascular trauma: Clinical and angiographic correlation.

A retrospective review of all angiograms done for craniocervical trauma, over an eight-year period at Groote Schuur Hospital identified 61 patients out of 823 angiographically studied who had extradural vascular injury and required endovascular treatment. Multiple lesions were identified in nine (14,8%) patients and associated injuries were found in 23 patients (37%). The mechanism of injury was blunt in nine (14.8%) patients and penetrating in 52 (85.2%). There was a statistically significant correlation between the presenting clinical feature and the underlying angiographic lesion. Patients with active bleeding were more likely to have a vessel laceration, an expanding hematoma was associated with false aneurysm and a pulsatile mass with arteriovenous fistula. Endovascular treatment with emphasis on vessel occlusion rather than preservation was successful in all cases except one which required surgical vessel ligation.