The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

IntroductionCommunicable diseases are the leading causes of death in Tanzania despite the existence of effective treatment tools. We aimed to assess the sociocultural and health system factors associated with mortality from febrile illness in northern Tanzania.MethodsWe interviewed febrile inpatients to determine prevalence of barriers in seeking or receiving care and grouped these barriers using the Three Delays model (delays at home, in transport and at healthcare facilities). We assessed 6-week mortality and, after matching on age, gender and severity of illness, measured the association between delays and mortality using conditional logistic regression.ResultsWe enrolled 475 children, of whom 18 (3.8%) died, and 260 adults, of whom 34 (13.0%) died. For children, home delays were not associated with mortality. Among adults, a delay in care-seeking due to not recognising severe symptoms was associated with mortality (OR: 3.01; 95% CI 1.24 to 7.32). For transport delays, taking >1 hour to reach a facility increased odds of death in children (OR: 3.27; 95% CI 1.11 to 9.66) and adults (OR: 3.03; 95% CI 1.32 to 6.99). For health system delays, each additional facility visited was associated with mortality for children (OR: 1.59; 95% CI 1.06 to 2.38) and adults (OR: 2.00; 95% CI 1.17 to 3.41), as was spending >4 days between the first facility visit and reaching tertiary care (OR: 4.39; 95% CI 1.49 to 12.93).ConclusionOur findings suggest that delays at home, in transport and in accessing tertiary care are risk factors for mortality from febrile illness in northern Tanzania. Interventions that may reduce mortality include community education regarding severe symptoms, expanding transportation infrastructure and streamlining referrals to tertiary care for the sickest patients.

Fever is one of the most common reasons for healthcare seeking globally and the majority of human pathogens are zoonotic. We conducted a systematic review to describe the occurrence and distribution of zoonotic causes of human febrile illness reported in malaria endemic countries. Articles included in the review yielded data from 53 (48•2%) of 110 malaria endemic countries. The 244 articles included described diagnosis of 30 zoonoses in febrile people. The majority of zoonoses were bacterial (n=17), with viruses (n=9), protozoa (n=3) and helminths (n=1) also identified. Leptospira spp. and nontyphoidal Salmonella serovars were the most frequently reported pathogens. Despite evidence of profound data gaps, this review reveals widespread distribution of a diverse range of zoonotic causes of febrile illness. Greater understanding of the epidemiology of zoonoses in different settings is needed to improve awareness and management of the multiple zoonotic causes of febrile illness. Introduction Fever is one of the most common symptoms prompting healthcare seeking globally. 1-3 Fever has myriad causes and their non-specific clinical presentation means that clinical history and physical examination are often insufficient to accurately identify causal pathogens. 1 Limitations in laboratory services and available diagnostic tools further contribute to diagnostic challenges. 4 In malaria-endemic countries, fever is often assumed to be due to malaria. 5 The mortality and morbidity attributable to malaria remains considerable, but there is also evidence of widespread over-diagnosis within malaria-endemic areas. 6-8 The recognized over-diagnosis of malaria together with declines in malaria incidence since the peak in global malaria deaths in 2004 9,10 have prompted attention to non-malaria causes of fever in malaria-endemic areas. 11,12 Zoonotic pathogens are likely to play a substantial role as causes of fever globally. Almost two-thirds of all human pathogens are zoonotic, 13 and there is growing evidence that many zoonoses cause more cases of human febrile illness than previously appreciated. 12,14-20 Improved understanding of the impacts and burdens of zoonotic causes of fever in malaria-endemic countries would provide the epidemiological evidence base for disease control program development and also influence diagnostic and treatment algorithms for fever, with the potential to improve clinical outcomes. The aim of this study was to systematically review the published literature to describe the occurrence and distribution of reported zoonotic causes of human febrile illness in countries where malaria is endemic. Methods Search strategy and selection criteria The target literature for this systematic review was peer-reviewed published articles that described the testing of one or more febrile person from malaria-endemic countries for one or more zoonotic pathogen using robust diagnostic testing criteria to demonstrate acute infection. Literature searches of the Medline and Embase databases were run using the OvidSP gateway....

Infectious diseases are a leading cause of mortality in low-and middle-income countries (LMICs) despite effective treatments. To study the sociocultural and health system barriers to care, we conducted a qualitative social autopsy study of patients who died from febrile illness in northern Tanzania. From December 2016 through July 2017, we conducted in-depth interviews in Arusha and Kilimanjaro regions with a purposive sample of 20 family members of patients who had died at two regional referral hospitals. Of the deceased patients included in this study, 14 (70%) were adults and 10 (50%) were female. Patients identified their religion as Catholic (12, 60%), Lutheran (six, 30%), and Muslim (two, 10%), and their ethnicity as Chagga (14, 70%) and Sambaa (two, 10%), among others. Family members reported both barriers to and facilitators of receiving health care. Barriers included a perceived lack of capacity of local health facilities, transportation barriers, and a lack of formal referrals to higher levels of care. Family members also reported the cost of health care as a barrier. However, one facilitator of care was access to financial resources via families' social networks-a phenomenon we refer to as social capital. Another facilitator of care was families' proactive engagement with the health system. Our results suggest that further investment in lower level health facilities may improve care-seeking and referral patterns and that future research into the role of social capital is needed to fully understand the effect of socioeconomic factors on healthcare utilization in LMICs.