Derivation and Internal Validation of a Clinical Prediction Model for Diagnosis of Spotted Fever Group Rickettsioses in Northern Tanzania.

Spotted fever group rickettsioses (SFGR) pose a global threat as emerging zoonotic infectious diseases; however, timely and cost-effective diagnostic tools are currently limited. We used data from 449 patients presenting to 2 hospitals in northern Tanzania between 2007 and 2008, of which 71 (15.8%) met criteria for acute SFGR based on ≥4-fold rise in antibody titers between acute and convalescent serum samples.

Healthcare utilisation for febrile diseases in northern Tanzania: a randomised population-based cluster survey.

Background: We conducted a randomised population-based cluster survey in northern Tanzania to assess care-seeking behaviours in the context of a febrile illness. Our objectives were to determine the most effective points for intervention during initial fever case management and to characterise factors associated with care-seeking.

Methods: The primary sampling unit, or cluster, was the village, and the secondary sampling unit was the household.

Evolutionary origin of lubricated joints at the dawn of jawed vertebrates.

The evolutionary origin of the lubricated joints that allow our interconnected skeleton to swivel, rotate, and bend has remained a mystery. A new comparative study of joints in PLOS Biology points to lubricated joints arising in the earliest jawed vertebrates.

Sepsis in Northern Tanzania: A Prospective Observational Study of Clinical Characteristics, Management, and Outcomes for Adolescents and Adults With Sepsis.

Background: Despite a high burden of sepsis in Sub-Saharan Africa, clinical data for adolescent and adult sepsis in this setting are limited. We sought to describe clinical characteristics, management, and outcomes in adolescents and adults with sepsis in northern Tanzania. We also assessed for clinical associations with in-hospital mortality.

Repurposing of a gill gene regulatory program for outer-ear evolution.

How new structures emerge during evolution has long fascinated biologists. An example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones. By contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, partly because it is supported by non-mineralized elastic cartilage, which is rarely recovered in fossils.

Seroprevalence and risk factors for Crimean-Congo hemorrhagic fever virus exposure among febrile patients in northern Tanzania.

Background: Crimean-Congo hemorrhagic fever is a tick-borne zoonotic disease that may be severe and is present in many African countries. We aimed to understand the seroprevalence and risk for Crimean-Congo hemorrhagic fever virus in Tanzania by testing archived serum samples from patients enrolled in a prospective cohort study.

Methods: We prospectively enrolled febrile inpatients and outpatients from 2012 through 2014 at two referral hospitals in northern Tanzania.

Comparison of Paired Immunofluorescent Antibody Serology and Real-Time Polymerase Chain Reaction Testing for the Detection of Acute Q Fever among Febrile Patients in Kilimanjaro, Tanzania, 2012-2014.

Acute Q fever diagnosis via paired serology is problematic because it requires follow-up for convalescent sample collection; as such, it cannot provide a diagnosis to inform a treatment decision at the time of acute presentation. Real-time polymerase chain reaction (PCR) may be a useful approach for the diagnosis of acute Q fever in endemic settings. Among febrile patients enrolled in a sentinel surveillance study for Q fever at two referral hospitals in Moshi, Tanzania, from 2012 to 2014, we analyzed those with paired sera for IgG to Coxiella burnetii (C.

TaqMan Array Card real-time polymerase chain reaction panel to detect pathogens in whole blood of febrile inpatients in northern Tanzania, 2016-2019.

Background: Acute febrile illness is a common reason for seeking healthcare in low- and middle-income countries. We describe the diagnostic utility of a TaqMan Array Card (TAC) real-time polymerase chain reaction (PCR) panel for pathogen detection in paediatric and adult inpatients admitted with febrile illness.

Methods: In this prospective cohort study, we screened medical admissions for a tympanic temperature ≥38.

Long-range enhancers maintain competency for hair cell regeneration in the inner ear.

During tissue regeneration, lineage-related cells can switch their fate to replace missing cells. This cell plasticity is particularly prominent in more regenerative vertebrates such as zebrafish, yet the molecular basis by which cells transdifferentiate into another cell type upon injury remains unclear. Here, we investigate the epigenetic basis of regenerative transdifferentiation in the inner ear, where supporting cells (SCs) generate mechanosensory hair cells (HCs) upon damage.

Origin of Ewing sarcoma by embryonic reprogramming of neural crest to mesoderm.

Ewing sarcoma is a malignant small round blue cell tumor of bones and soft tissues caused by chromosomal translocations that generate aberrant fusion oncogenes, most frequently EWSR1::FLI1. The cell of origin and mechanisms of EWSR1::FLI1-driven transformation have remained unresolved, largely due to lack of a representative animal model. By developing a zebrafish Ewing sarcoma model, we provide evidence for a neural crest origin of this cancer.

Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease.

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD.

Epidemiologic and genomic characterization of an outbreak of Rift Valley fever among humans and dairy cattle in northern Tanzania.

Background: A peri-urban outbreak of Rift Valley fever virus (RVFV) among dairy cattle from May through August 2018 in northern Tanzania was detected through testing samples from prospective livestock abortion surveillance. We sought to identify concurrent human infections, their phylogeny, and epidemiologic characteristics in a cohort of febrile patients enrolled from 2016-2019 at hospitals serving the epizootic area.

Methods: From September 2016 through May 2019, we conducted a prospective cohort study that enrolled febrile patients hospitalized at two hospitals in Moshi, Tanzania.

Predicting mortality in febrile adults: comparative performance of the MEWS, qSOFA, and UVA scores using prospectively collected data among patients in four health-care sites in sub-Saharan Africa and South-Eastern Asia.

Background: Clinical severity scores can identify patients at risk of severe disease and death, and improve patient management. The modified early warning score (MEWS), the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and the Universal Vital Assessment (UVA) were developed as risk-stratification tools, but they have not been fully validated in low-resource settings where fever and infectious diseases are frequent reasons for health care seeking. We assessed the performance of MEWS, qSOFA, and UVA in predicting mortality among febrile patients in the Lao PDR, Malawi, Mozambique, and Zimbabwe.

Environmental contamination with carbapenem resistant in healthcare settings in Fiji: a potential source of infection.

Introduction: There are multiple ongoing outbreaks of carbapenem resistant (CR) infection in Fiji's hospitals. CR is able to colonize and persist on various hospital surfaces for extended periods. We conducted a study to understand the extent of hospital environmental contamination and phylogenetic links with clinical isolates.

Cellular transitions during cranial suture establishment in zebrafish.

Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion.

A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells.

Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells.

Metagenomic Detection of Bacterial Zoonotic Pathogens among Febrile Patients, Tanzania, 2007-2009.

Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007-April 2009.

Vaccine value profile for invasive non-typhoidal Salmonella disease.

Invasive non-typhoidal Salmonella (iNTS) disease is an under-recognized high-burden disease causing major health and socioeconomic issues in sub-Saharan Africa (sSA), predominantly among immune-naïve infants and young children, including those with recognized comorbidities such as HIV infection. iNTS disease is primarily caused by Salmonella enterica serovar Typhimurium sequence type (ST) 313 and 'African-restricted clades' of Salmonella Enteritidis ST11 that have emerged across the African continent as a series of epidemics associated with acquisition of new antimicrobial resistance. Due to genotypes with a high prevalence of antimicrobial resistance and scarcity of therapeutic options, these NTS serovars are designated by the World Health Organization as a priority pathogen for research and development of interventions, including vaccines, to address and reduce NTS associated bacteremia and meningitis in sSA.

Molecular and clinical epidemiology of carbapenem resistant , and Enterobacterales in Fiji: a multicentre prospective observational study.

Background: Carbapenem resistant organisms (CROs) such as (CR), (CR), (CR), and (CR) have been identified by the World Health Organization (WHO) as global priority pathogens. The dissemination of these pathogens and clonal outbreaks within healthcare facilities are of serious concern, particularly in regions with limited resources. In Fiji, where healthcare services are primarily provided by public hospitals, understanding the extent and nature of this problem is essential for the development of effective patient management, prevention interventions and control strategies.

Examining geospatial and temporal distribution of invasive non-typhoidal disease occurrence in sub-Saharan Africa: a systematic review and modelling study.

Background: Invasive non-typhoidal (iNTS) disease is a significant health concern in sub-Saharan Africa. While our knowledge of a larger-scale variation is growing, understanding of the subnational variation in iNTS disease occurrence is lacking, yet crucial for targeted intervention.

Method: We performed a systematic review of reported occurrences of iNTS disease in sub-Saharan Africa, consulting literature from PubMed, Embase and Web of Science published since 2000.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

Background: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines.

Methods: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa.