The Impact of an Intervention to Improve Malaria Care in Public Health Centers on Health Indicators of Children in Tororo, Uganda (PRIME): A Cluster-Randomized Trial.

Optimizing quality of care for malaria and other febrile illnesses is a complex challenge of major public health importance. To evaluate the impact of an intervention aiming to improve malaria case management on the health of community children, a cluster-randomized trial was conducted from 2010-2013 in Tororo, Uganda, where malaria transmission is high. Twenty public health centers were included; 10 were randomized in a 1:1 ratio to intervention or control. Households within 2 km of health centers provided the sampling frame for the evaluation. The PRIME intervention included training in fever case management using malaria rapid diagnostic tests (mRDTs), patient-centered services, and health center management; plus provision of mRDTs and artemether-lumefantrine. Cross-sectional community surveys were conducted at baseline and endline (N = 8,766), and a cohort of children was followed for approximately 18 months (N = 992). The primary outcome was prevalence of anemia (hemoglobin < 11.0 g/dL) in children under 5 years of age in the final community survey. The intervention was delivered successfully; however, no differences in prevalence of anemia or parasitemia were observed between the study arms in the final community survey or the cohort. In the final survey, prevalence of anemia in children under 5 years of age was 62.5% in the intervention versus 63.1% in control (adjusted risk ratio = 1.01; 95% confidence interval = 0.91-1.13; P = 0.82). The PRIME intervention, focusing on training and commodities, did not produce the expected health benefits in community children in Tororo. This challenges common assumptions that improving quality of care and access to malaria diagnostics will yield health gains

The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda

Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus , upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus . In mice, this isolate designated strain Mbale , was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections. One Sentence Summary We have discovered a novel strain of bacteria upon a frequent viral background underlying postinfectious hydrocephalus in Uganda

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

The embodiment of low-field MRI for the diagnosis of infant hydrocephalus in Uganda

Compared to other parts of the world, the incidence of hydrocephalus in children is very high in sub- Saharan Africa. Magnetic resonance imaging (MRI) would be the preferred diagnostic method for infant hydrocephaleus. However, in practice, MRI is seldom used in sub-Saharan Africa due to its high prize, low mobility, and high power consumption. A low-cost MRI technology is under development by reducing the strength of the magnetic field and the use of alternative technologies to create the magnetic field. This paper describes the embodiment design process to match this new MRI technology under development with the specific characteristics of thehealthcare system in Uganda. A context exploration was performed to identify factors that may affect the design and implementation of the low-field MRI in Ugandan hospitals and Ugandan healthcare environment. The key-insights from the technology- and context-exploration were translated into requirements which were the starting point for the design process. The concept development did have a focus on Cost-effective design, Design for durability &amp; reliability, and Design for repairability. The final design was validated by stakeholders from the Ugandan Healthcare context Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Design for SustainabilityNumerical Analysi

EMR adoption in Dhaka, Bangladesh: A template to index pediatric central nervous system tumor care and a review of preliminary neuro-oncologic observations

Purpose: To describe the design, implementation, and adoption of a simplified electronic medical record (EMR) and its use in documenting pediatric central nervous system (CNS) tumors at a tertiary care referral hospital in South-East Asia.Methods: A novel EMR, cataloguing pediatric CNS tumors was used to collect data from August 2017 to March 2020 at National Institute of Neurosciences and Hospital (NINS&H) in Dhaka, Bangladesh.Results: Two hundred forty-nine pediatric patients with a CNS tumor were admitted to NINS&H. Fifty-eight percent of patients were male, and the median age was 8 years. A total of 188/249 patients (76%) underwent surgery during their index admission. Radiographic locations were known for 212/249 (85%) of cases; the most common radiographic locations were infratentorial (81/212; 38%), suprasellar (45/212; 21%), and supratentorial (29/212; 14%). A histopathological classification was reported on 156/249 (63%) of patients\u27 cytology. The most common infratentorial pathologies were medulloblastoma (22/47; 47%) and pilocytic astrocytoma (14/47; 30%). The median time between admission and surgery was 36 days, while the median post-operation stay was 19.5 days.Conclusions: The feasibility of a basic EMR platform for a busy pediatric neurosurgery department in a lower-middle income country is demonstrated, and preliminary clinical data is reviewed. A wide variety of pediatric CNS tumors were observed, spanning the spectrum of anatomic locations and histopathologic subtypes. Surgical intervention was performed for the majority of patients. Barriers to care include limited molecular diagnostics and unavailable data on adjuvant therapy. Future targets include improvement of clinical documentation in the pre-operative and post-operative period

Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda.

BACKGROUND: The distribution of the enzymopathy glucose-6-phosphate dehydrogenase (G6PD) deficiency is linked to areas of high malaria endemicity due to its association with protection from disease. G6PD deficiency is also identified as the cause of severe haemolysis following administration of the anti-malarial drug primaquine and further use of this drug will likely require identification of G6PD deficiency on a population level. Current conventional methods for G6PD screening have various disadvantages for field use. METHODS: The WST8/1-methoxy PMS method, recently adapted for field use, was validated using a gold standard enzymatic assay (R&D Diagnostics Ltd ®) in a study involving 235 children under five years of age, who were recruited by random selection from a cohort study in Tororo, Uganda. Blood spots were collected by finger-prick onto filter paper at routine visits, and G6PD activity was determined by both tests. Performance of the WST8/1-methoxy PMS test under various temperature, light, and storage conditions was evaluated. RESULTS: The WST8/1-methoxy PMS assay was found to have 72% sensitivity and 98% specificity when compared to the commercial enzymatic assay and the AUC was 0.904, suggesting good agreement. Misclassifications were at borderline values of G6PD activity between mild and normal levels, or related to outlier haemoglobin values (14 gHb/dl) associated with ongoing anaemia or recent haemolytic crises. Although severe G6PD deficiency was not found in the area, the test enabled identification of low G6PD activity. The assay was found to be highly robust for field use; showing less light sensitivity, good performance over a wide temperature range, and good capacity for medium-to-long term storage. CONCLUSIONS: The WST8/1-methoxy PMS assay was comparable to the currently used standard enzymatic test, and offers advantages in terms of cost, storage, portability and use in resource-limited settings. Such features make this test a potential key tool for deployment in the field for point of care assessment prior to primaquine administration in malaria-endemic areas. As with other G6PD tests, outlier haemoglobin levels may confound G6PD level estimation

Vaginal Microbiome Topic Modelling of Laboring Ugandan Women With and Without Fever

The composition of the maternal vaginal microbiome may influence 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. We examined the vaginal microbiome composition of 99 laboring Ugandan women using routine microbiology and 16S ribosomal DNA sequencing from two hypervariable regions (V1-V2 and V3-V4), using standard hierarchical methods. We then introduce Grades of Membership (GoM) modeling for the vaginal microbiome, a method often used in the text mining machine learning literature. Leveraging GoM models, we create a basis composed of a small number of microbial ‘topic’s whose linear combination optimally represents each patient yielding more accurate associations. We identified relationships between defined communities and the presentation or absence of intrapartum fever. Using a random forest model we showed that by including novel microbial topic models we improved upon clinical variables to predict maternal fever. We also show by integrating clinical variables with a microbial topic model into this model found young maternal age, fever report earlier in the current pregnancy, and longer labors, as well as a more diverse, less Lactobacillus dominated microbiome were features of labor associated with intrapartum fever. These results better define relationships between presentation or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial communities, and improve our understanding of the impact of the microbiome on maternal and neonatal infection risk