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.

Paradata analyses to inform population-based survey capture of pregnancy outcomes: EN-INDEPTH study.

BACKGROUND: Paradata are (timestamped) records tracking the process of (electronic) data collection. We analysed paradata from a large household survey of questions capturing pregnancy outcomes to assess performance (timing and correction processes). We examined how paradata can be used to inform and improve questionnaire design and survey implementation in nationally representative household surveys, the major source for maternal and newborn health data worldwide. METHODS: The EN-INDEPTH cross-sectional population-based survey of women of reproductive age in five Health and Demographic Surveillance System sites (in Bangladesh, Guinea-Bissau, Ethiopia, Ghana, and Uganda) randomly compared two modules to capture pregnancy outcomes: full pregnancy history (FPH) and the standard DHS-7 full birth history (FBH+). We used paradata related to answers recorded on tablets using the Survey Solutions platform. We evaluated the difference in paradata entries between the two reproductive modules and assessed which question characteristics (type, nature, structure) affect answer correction rates, using regression analyses. We also proposed and tested a new classification of answer correction types. RESULTS: We analysed 3.6 million timestamped entries from 65,768 interviews. 83.7% of all interviews had at least one corrected answer to a question. Of 3.3 million analysed questions, 7.5% had at least one correction. Among corrected questions, the median number of corrections was one, regardless of question characteristics. We classified answer corrections into eight types (no correction, impulsive, flat (simple), zigzag, flat zigzag, missing after correction, missing after flat (zigzag) correction, missing/incomplete). 84.6% of all corrections were judged not to be problematic with a flat (simple) mistake correction. Question characteristics were important predictors of probability to make answer corrections, even after adjusting for respondent's characteristics and location, with interviewer clustering accounted as a fixed effect. Answer correction patterns and types were similar between FPH and FBH+, as well as the overall response duration. Avoiding corrections has the potential to reduce interview duration and reproductive module completion by 0.4 min. CONCLUSIONS: The use of questionnaire paradata has the potential to improve measurement and the resultant quality of electronic data. Identifying sections or specific questions with multiple corrections sheds light on typically hidden challenges in the survey's content, process, and administration, allowing for earlier real-time intervention (e.g.,, questionnaire content revision or additional staff training). Given the size and complexity of paradata, additional time, data management, and programming skills are required to realise its potential.

Electronic data collection in a multi-site population-based survey: EN-INDEPTH study.

BACKGROUND: Electronic data collection is increasingly used for household surveys, but factors influencing design and implementation have not been widely studied. The Every Newborn-INDEPTH (EN-INDEPTH) study was a multi-site survey using electronic data collection in five INDEPTH health and demographic surveillance system sites. METHODS: We described experiences and learning involved in the design and implementation of the EN-INDEPTH survey, and undertook six focus group discussions with field and research team to explore their experiences. Thematic analyses were conducted in NVivo12 using an iterative process guided by a priori themes. RESULTS: Five steps of the process of selecting, adapting and implementing electronic data collection in the EN-INDEPTH study are described. Firstly, we reviewed possible electronic data collection platforms, and selected the World Bank's Survey Solutions® as the most suited for the EN-INDEPTH study. Secondly, the survey questionnaire was coded and translated into local languages, and further context-specific adaptations were made. Thirdly, data collectors were selected and trained using standardised manual. Training varied between 4.5 and 10 days. Fourthly, instruments were piloted in the field and the questionnaires finalised. During data collection, data collectors appreciated the built-in skip patterns and error messages. Internet connection unreliability was a challenge, especially for data synchronisation. For the fifth and final step, data management and analyses, it was considered that data quality was higher and less time was spent on data cleaning. The possibility to use paradata to analyse survey timing and corrections was valued. Synchronisation and data transfer should be given special consideration. CONCLUSION: We synthesised experiences using electronic data collection in a multi-site household survey, including perceived advantages and challenges. Our recommendations for others considering electronic data collection include ensuring adaptations of tools to local context, piloting/refining the questionnaire in one site first, buying power banks to mitigate against power interruption and paying attention to issues such as GPS tracking and synchronisation, particularly in settings with poor internet connectivity.

Birth, stillbirth and death registration data completeness, quality and utility in population-based surveys: EN-INDEPTH study.

BACKGROUND: Birth registration is a child's first right. Registration of live births, stillbirths and deaths is foundational for national planning. Completeness of birth registration for live births in low- and middle-income countries is measured through population-based surveys which do not currently include completeness of stillbirth or death registration. METHODS: The EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). In four African sites, we included new/modified questions regarding registration for 1177 stillbirths and 11,881 livebirths (1333 neonatal deaths and 10,548 surviving the neonatal period). Questions were evaluated for completeness of responses, data quality, time to administer and estimates of registration completeness using descriptive statistics. Timing of birth registration, factors associated with non-registration and reported barriers were assessed using descriptive statistics and logistic regression. RESULTS: Almost all women, irrespective of their baby's survival, responded to registration questions, taking an average of < 1 min. Reported completeness of birth registration was 30.7% (6.1-53.5%) for babies surviving the neonatal period, compared to 1.7% for neonatal deaths (0.4-5.7%). Women were able to report age at birth registration for 93.6% of babies. Non-registration of babies surviving the neonatal period was significantly higher for home-born children (aOR 1.43 (95% CI 1.27-1.60)) and in Dabat (Ethiopia) (aOR 4.11 (95% CI 3.37-5.01)). Other socio-demographic factors associated with non-registration included younger age of mother, more prior births, little or no education, and lower socio-economic status. Neonatal death registration questions were feasible (100% women responded; only 1% did not know), revealing extremely low completeness with only 1.2% of neonatal deaths reported as registered. Despite > 70% of stillbirths occurring in facilities, only 2.5% were reported as registered. CONCLUSIONS: Questions on birth, stillbirth and death registration were feasible in a household survey. Completeness of birth registration is low in all four sites, but stillbirth and neonatal death registration was very low. Closing the registration gap amongst facility births could increase registration of both livebirths and facility deaths, including stillbirths, but will require co-ordination between civil registration systems and the often over-stretched health sector. Investment and innovation is required to capture birth and especially deaths in both facility and community systems.

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.

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.

An assessment of non-communicable disease mortality among adults in Eastern Uganda, 2010-2016.

BACKGROUND: There is a dearth of studies assessing non-communicable disease (NCD) mortality within population-based settings in Uganda. We assessed mortality due to major NCDs among persons ≥ 30 years in Eastern Uganda from 2010 to 2016. METHODS: The study was carried out at the Iganga-Mayuge health and demographic surveillance site in the Iganga and Mayuge districts of Eastern Uganda. Information on cause of death was obtained through verbal autopsies using a structured questionnaire to conduct face-face interviews with carers or close relatives of the deceased. Physicians assigned likely cause of death using ICD-10 codes. Age-adjusted mortality rates were calculated using direct method, with the average population across the seven years of the study (2010 to 2016) as the standard. Age categories of 30-40, 41-50, 51-60, 61-70, and ≥ 71 years were used for standardization. RESULTS: A total of 1,210 deaths among persons ≥ 30 years old were reported from 2010 to 2016 (50.7% among women). Approximately 53% of all deaths were due to non-communicable diseases, 31.8% due to communicable diseases, 8.2% due to injuries, and 7% due to maternal-related deaths or undetermined causes. Cardiovascular diseases accounted for the largest proportion of NCD deaths in each year, and women had substantially higher cardiovascular disease mortality rates compared to men. Conversely, women had lower diabetes mortality rates than men for five of the seven years examined. CONCLUSIONS: Non-communicable diseases are major causes of death among adults in Iganga and Mayuge; and cardiovascular diseases and diabetes are leading causes of NCD deaths. Efforts are needed to tackle NCD risk factors and provide NCD care to reduce associated burden and premature mortality.

Randomised comparison of two household survey modules for measuring stillbirths and neonatal deaths in five countries: the Every Newborn-INDEPTH study.

BACKGROUND: An estimated 5·1 million stillbirths and neonatal deaths occur annually. Household surveys, most notably the Demographic and Health Survey (DHS), run in more than 90 countries and are the main data source from the highest burden regions, but data-quality concerns remain. We aimed to compare two questionnaires: a full birth history module with additional questions on pregnancy losses (FBH+; the current DHS standard) and a full pregnancy history module (FPH), which collects information on all livebirths, stillbirths, miscarriages, and neonatal deaths. METHODS: Women residing in five Health and Demographic Surveillance System sites within the INDEPTH Network (Bandim in Guinea-Bissau, Dabat in Ethiopia, IgangaMayuge in Uganda, Matlab in Bangladesh, and Kintampo in Ghana) were randomly assigned (individually) to be interviewed using either FBH+ or FPH between July 28, 2017, and Aug 13, 2018. The primary outcomes were stillbirths and neonatal deaths in the 5 years before the survey interview (measured by stillbirth rate [SBR] and neonatal mortality rate [NMR]) and mean time taken to complete the maternity history section of the questionnaire. We also assessed between-site heterogeneity. This study is registered with the Research Registry, 4720. FINDINGS: 69 176 women were allocated to be interviewed by either FBH+ (n=34 805) or FPH (n=34 371). The mean time taken to complete FPH (10·5 min) was longer than for FBH+ (9·1 min; p<0·0001). Using FPH, the estimated SBR was 17·4 per 1000 total births, 21% (95% CI -10 to 62) higher than with FBH+ (15·2 per 1000 total births; p=0·20) in the 5 years preceding the survey interview. There was strong evidence of between-site heterogeneity (I2=80·9%; p<0·0001), with SBR higher for FPH than for FBH+ in four of five sites. The estimated NMR did not differ between modules (FPH 25·1 per 1000 livebirths vs FBH+ 25·4 per 1000 livebirths), with no evidence of between-site heterogeneity (I2=0·7%; p=0·40). INTERPRETATION: FPH takes an average of 1·4 min longer to complete than does FBH+, but has the potential to increase reporting of stillbirths in high burden contexts. The between-site heterogeneity we found might reflect variations in interviewer training and survey implementation, emphasising the importance of interviewer skills, training, and consistent implementation in data quality. FUNDING: Children's Investment Fund Foundation.

"Every Newborn-INDEPTH" (EN-INDEPTH) study protocol for a randomised comparison of household survey modules for measuring stillbirths and neonatal deaths in five Health and Demographic Surveillance sites.

BACKGROUND: Under-five and maternal mortality were halved in the Millennium Development Goals (MDG) era, with slower reductions for 2.6 million neonatal deaths and 2.6 million stillbirths. The Every Newborn Action Plan aims to accelerate progress towards national targets, and includes an ambitious Measurement Improvement Roadmap. Population-based household surveys, notably Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys, are major sources of population-level data on child mortality in countries with weaker civil registration and vital statistics systems, where over two-thirds of global child deaths occur. To estimate neonatal/child mortality and pregnancy outcomes (stillbirths, miscarriages, birthweight, gestational age) the most common direct methods are: (1) the standard DHS-7 with Full Birth History with additional questions on pregnancy losses in the past 5 years (FBH+) or (2) a Full Pregnancy History (FPH). No direct comparison of these two methods has been undertaken, although descriptive analyses suggest that the FBH+ may underestimate mortality rates particularly for stillbirths. METHODS: This is the protocol paper for the Every Newborn-INDEPTH study (INDEPTH Network, International Network for the Demographic Evaluation of Populations and their Health Every Newborn, Every Newborn Action Plan), aiming to undertake a randomised comparison of FBH+ and FPH to measure pregnancy outcomes in a household survey in five selected INDEPTH Network sites in Africa and South Asia (Bandim in urban and rural Guinea-Bissau; Dabat in Ethiopia; IgangaMayuge in Uganda; Kintampo in Ghana; Matlab in Bangladesh). The survey will reach >68 000 pregnancies to assess if there is ≥15% difference in stillbirth rates. Additional questions will capture birthweight, gestational age, birth/death certification, termination of pregnancy and fertility intentions. The World Bank's Survey Solutions platform will be tailored for data collection, including recording paradata to evaluate timing. A mixed methods assessment of barriers and enablers to reporting of pregnancy and adverse pregnancy outcomes will be undertaken. CONCLUSIONS: This large-scale study is the first randomised comparison of these two methods to capture pregnancy outcomes. Results are expected to inform the evidence base for survey methodology, especially in DHS, regarding capture of stillbirths and other outcomes, notably neonatal deaths, abortions (spontaneous and induced), birthweight and gestational age. In addition, this study will inform strategies to improve health and demographic surveillance capture of neonatal/child mortality and pregnancy outcomes.