Numerous studies highlight the essential role of type I interferon (IFN) responses in type 1 diabetes. The absence of type I IFN signaling is associated with a partial reduction of autoimmune diabetes incidence in LEW.1WR1 rats. We sought to delineate type I IFN-independent mechanisms that drive diabetes using type I IFN alpha/beta receptor (IFNAR) knockout rats. Rats were treated with polyinosinic:polycytidylic acid plus Kilham rat virus to induce diabetes. Single-cell RNA-sequencing of islets and cytokine measurements in blood and spleen from prediabetic Ifnar1- /- rats were employed to identify factors driving insulitis in the global absence of IFNAR signaling. Islet immune cells were enriched for Ccl4, Ccl5, and Ifng. In addition, interleukin-1 (IL-1) was increased in spleen, and IFN-gamma was increased in serum from prediabetic Ifnar1- /- rats. Based on these findings, rats were treated with a CC chemokine receptor type 5 inhibitor, an IL-1 receptor antagonist, or a nucleotide-binding oligomerization domain-like receptor family pyrin-domain containing 3 inhibitor, none of which prevented diabetes. The Janus kinase inhibitor ruxolitinib, which blocks both type I and II interferon-driven signaling, completely prevented diabetes, but only when given for a sustained period starting from the time of induction. The tyrosine kinase 2 inhibitor deucravacitinib also prevented diabetes to a significant degree. We conclude that type I and II IFNs act in concert as the main drivers of autoimmune diabetes and that inhibition of downstream signaling events for both is required for disease prevention.

Background:In resource-poor settings, perinatal infections contribute significantly to maternal and neonatal deaths, and the use of clean delivery kits (CDKs) has been proposed as a tool to reduce the risk of infection-related deaths. This study aims to assess the acceptability and effectiveness of CDKs in preventing infections in deliveries attended by traditional birth attendants (TBAs) in Abeokuta, Nigeria.Methods:The study was a cluster-randomized trial with 67 birth centres/clusters, 453 births/mothers, and 457 babies randomized to intervention or control arms; intervention involved supplementation of delivery with JANMA CDKs. Interviews were conducted at the birth homes, and the primary outcomes were neonatal infection and puerperal fever. The association between infection and perinatal risk factors was tested using the Chi-square and Fisher's exact tests.Results:CDKs were well accepted by TBAs. The incidence of puerperal fever and neonatal infection was 1.1% and 11.2%, respectively. Concurrent infection was found in 1 (0.22%) of the mother-neonate pair. There was no significant association between any of the sociodemographic factors and infection for both mothers and neonates. PROM and prolonged labour were significantly associated with puerperal infection. All mothers with puerperal fever were from the control group. Compared to the control group, the relative risk of puerperal infection and neonatal infection in the intervention group was 0.08 (0.004 -1.35, p = 0.079) and 0.64 (0.37 to 1.1, p = 0.10), respectively.Conclusion:CDKs hold promising results in attenuating maternal infections in resource-poor settings. Larger studies with greater statistical power are required to establish statistically reliable information.

Identifying the early islet cellular processes of autoimmune type 1 diabetes (T1D) in humans is challenging given the absence of symptoms during this period and the inaccessibility of the pancreas for sampling. Here, we study temporal events in pancreatic islets in LEW.1WR1 rats, in which autoimmune diabetes can be induced with virus infection, by performing transcriptional analysis of islets harvested during the pre-diabetic period. Single-cell RNA-Seq and differential expression analyses of islets from pre-diabetic rats reveal subsets of β and a cells under stress as evidenced by heightened expression, over time, of a transcriptional signature characterized by interferon-stimulated genes, chemokines including Cxcl10, major histocompatibility class I, and genes for the ubiquitin-proteasome system. Mononuclear phagocytes show increased expression of inflammatory markers. RNA-in situ hybridization of rat pancreatic tissue defines the spatial distribution of Cxcl10+ β and a cells and their association with CD8+ T cell infiltration, a hallmark of insulitis and islet destruction. Our studies define early islet transcriptional events during immune cell recruitment to islets and reveal spatial associations between stressed β and a cells and immune cells. Insights into such early processes can assist in the development of therapeutic and prevention strategies for T1D.

To investigate hand‐dug well water used for drinking and domestic purposes in a rural community in Southwest Nigeria for water safety and fungal presence as well as to determine the antifungal resistance and aflatoxigenic potentials of isolated fungi.

Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing β cells of pancreatic islets. Essential components of the innate immune antiviral response, including type I IFN and IFN receptor (IFNAR)–mediated signaling pathways, likely contribute to human type 1 diabetes susceptibility. We previously showed that LEW.1WR1 Ifnar1−/− rats have a significant reduction in diabetes frequency following Kilham rat virus (KRV) infection. To delineate the impact of IFNAR loss on immune cell populations in KRV-induced diabetes, we performed flow cytometric analysis in spleens from LEW.1WR1 wild-type (WT) and Ifnar1−/− rats after viral infection but before the onset of insulitis and diabetes. We found a relative decrease in CD8+ T cells and NK cells in KRV-infected LEW.1WR1 Ifnar1−/− rats compared with KRV-infected WT rats; splenic regulatory T cells were diminished in WT but not Ifnar1−/− rats. In contrast, splenic neutrophils were increased in KRV-infected Ifnar1−/− rats compared with KRV-infected WT rats. Transcriptional analysis of splenic cells from KRV-infected rats confirmed a reduction in IFN-stimulated genes in Ifnar1−/− compared with WT rats and revealed an increase in transcripts related to neutrophil chemotaxis and MHC class II. Single-cell RNA sequencing confirmed that MHC class II transcripts are increased in monocytes and macrophages and that numerous types of splenic cells harbor KRV. Collectively, these findings identify dynamic shifts in innate and adaptive immune cells following IFNAR disruption in a rat model of autoimmune diabetes, providing insights toward the role of type I IFNs in autoimmunity.

Background Poor environmental conditions and hygiene practices at the time of childbirth is linked to life-threatening infections and death in mothers and babies. Improvements in water, sanitation, and hygiene (WASH) have been identified as a means through which the lives of mothers and babies could be saved. This study was carried out to explore WASH conditions and infection prevention and control (IPC) practices in traditional birth homes/centers in Abeokuta, Southwest Nigeria. A total of 50 traditional birth centers and attendants (TBAs) were enrolled in the study. Sociodemographic characteristics of the TBAs and features of the birth centers were obtained using a semi-structured questionnaire. Assessment of WASH conditions and IPC practices was based on established protocols. Results Findings revealed that majority of the centers operated under poor WASH conditions and IPC practices; none met with the WHO minimum standards for environmental health. Conclusions Adequate WASH facilities and IPC practices remain a critical component of maternal and child health even in non-facility birth. As the transition to facility births continues in many countries, the large number of non-facility births demands their inclusion in WASH-related strategies, if global goals of reducing deaths of newborns and women deaths will be achieved.

Neonatal sepsis, a bacterial infection of blood in the first month of life is a common cause of morbidity and mortality in developing countries and factors associated with positive blood culture and perinatal deaths among neonates are rarely described. This study was conducted at the Special Baby Care Unit of Federal Medical Centre, Abeokuta (FMCA), Southwest Nigeria, to identify the predictors of positive blood culture and deaths due to neonatal sepsis among neonates admitted with clinical diagnosis of septicemia between January and April 2013. Data on socio-demographic characteristics, peripatal events and clinical characteristics of neonates were collected on proforma designed for the study. Blood culture was done on Brain Heart Infusion broth and Thioglycolate broth followed by identification of isolates using conventional methods. Serum Procalcitonin (PCT) and Serum C reactive protein (CRP) Levels were determined by immunochromatographic and immuno-turnidimetric assay respec-tively. The neonates were monitored until discharge from the hospital. Among 180 neonates admitted during the study period, there were 85 cases of clinically suspected sepsis. Forty (47.1%) were males and 45(52.9%) were females while 55 (63.5%) neonates and 30 (36.5%) neonates presented with early and late onset sepsis respectively. Positive blood culture was found in 19 (22.4%) of the neo-nates; 14 (73.7%) of neonates with positive blood cultures had early onset neonatal sepsis and 5 (26.3%) had late onset sepsis. Factors that predicted positive blood culture in both early and late onset neonatal sepsis were mode of delivery (p=0.033), estimated gestational age (p=0.039), and CRP (p=0.000). None of the clinical characteristics was found to be statistically significant with positive blood culture. Deaths occurred in 27 (36%) of neonates. The case-fatality rate was 29%. Predictors of death were booking status (p=0.011), birth after prolonged labour (p=0.014), place of delivery (p=0.001), place of antenatal care (p=0.021), respiratory distress (p=0.034), poor cry (p=0.040), con-vulsion (p=0.011) and PCT (p=0.001). Our findings suggest that mode of delivery and estimated ges-tational age are significantly associated with positive blood culture in both early and late onset neona-tal sepsis. Mortality from neonatal sepsis is high in this study. Booking status, place of delivery, place of antenatal care significantly contributed to mortality suggesting that antenatal and perinatal care remains associated with neonatal mortality.

Background: Neonatal sepsis is a significant cause of neonatal mortality in developing countries. The aetiological agents and their antimicrobial susceptibility patterns are dynamic. Objectives: This study determined clinical features, aetiology, antimicrobial susceptibility and clinical outcome of neonatal sepsis in a Nigerian Tertiary Hospital. Methods: Neonates undergoing sepsis evaluation at a Nigerian Tertiary Hospital were included in the study. Demographic and clinical information were obtained using standard questionnaires. Blood samples were cultured on MacConkey, Blood and Chocolate agar. Isolated bacteria were identified based on morphology, Gram stain appearance and standard commercially prepared biochemical tests. Antimicrobial susceptibility testing was performed on Mueller-Hinton agar using the Kirby-Bauer method. Results: Eighty-five of the 180 neonates admitted during the study period were recruited. Fifty-five neonates presented with early-onset sepsis and 30 with late-onset sepsis. Culture-proven sepsis was detected in 19 (22.4%) neonates. The incidence of culture-proven sepsis in the hospital was 2.8/100 live-births. The most common clinical feature at presentation was respiratory distress. Gram-negative bacteria accounted for 78.9 percent of all isolates and were the only organisms encountered in earlyonset sepsis. Isolated pathogens were predominantly Klebsiella spp (31.6%), Enterobacter spp (21.1%) and coagulase-negative Staphylococci (15.8%). The isolates were most sensitive to ofloxacin. Gram-negative bacteria showed high resistance to cefuroxime and ampicillin. The case-fatality rate was 26%. Conclusion: Gram-negative bacilli, especially Klebsiella spp, was predominant. Neonatal sepsis persists as a cause of mortality in this region. Regular antimicrobial surveillance for empirical treatment remains an important component of neonatal care.